Anti-Social Media (2009, Jun 26, Leicester)

Talk tomorrow in Leicester for Social Media: Uses and Abuses will mention the ZX Spectrum, Flickr, Dopplr, Facebook, Twitter, Google, Bing, iPhone, Second Life, The Sims, World of Warcraft, and much, much more.

Have you experienced anti-socia behaviour in social media environments?

http://www2.le.ac.uk/ebulletin/bulletin-board/2000-2009/2009/06/nparticle.2009-06-17.3587483528

http://usesandabuses.wordpress.com/

Centre for Cultural Policy Research (2005, Glasgow)

CCPR seminar PSB and CultureC Chair: Christine G

Speakers:

Dr Vicki Nash, OfCOM Prof. Philip Schlesinger Bobby Hain Allan Jack

Comm, culture and convergence: prospects for thefuture Vicki Nash

65.9% now digital

4.0% household spend on comms 3.4% in 2000

3G from 0.2-3.5% since 2003

virgin takeover of ntl - 4 components

interest in dedicated gaelic channel

bbc remain cornerstone of psb 10-yr charter w mid-point review should have licence fee

Public Service Publisher - new

in scot, high use of local newspapers, but not eally met by psb

will publish digital localcontent report in new year

regional radio conference, may 2006, geneva - spectrum use in europe awaiting conclusions from there

PSP - not a tradl tv channel - provider for digita and bb world - uk originated content - on demand - new interactive formats - across all comm platforms

ME: Technology, Culture & Society

media literacy -access, ustd, and create commms

nations and regions audit - look at ranges of access

review of tv prodn sector broadcast traininfg and skills regulator digital dividend review - options for release of spectrum - eg high quality video on mobile devices

future

Philip Schelsinger

era of econ andtechl rationalisation statist ideology of competitive nation rhetorics of digital and creative britain

galbraith - ideas esteemed at any time for their acceptabitliyu

parameters incly set, but somee particulars

along with rationalisation is formalisation

Comm Act 2003 - convergence  as ttechl theme - consolidation as econ theme

through policy intervention, changed

ofcom child of comm act

regulation of comms incl bbc

lord currie  - if pressed, shouuld regulate bbc

green paper

jowell: pistachio ripple - some white paperr status

dcms rev of royal charter 4 reviews -building public value - HoL select comm report

instit frameorks of broadcasting

bbc

downsizing of itv psb obligs

role of PSP contingent on bbc

scotland's voice? - devolution not provided focus for  debate - market and reg trends likely to decrease interest

what are relevant terms of informed debate?

formalisation of PSB:

no attempts to define before ofcom dom defn from ofcoms psb reeviews, which have shaped debate intellectual style shaped by passion for evidence based audit society across al public policy

finance, governance and critical mass, and scope of PSB

conception - in bbc building pub vlaue - promoting citzienship, creratively, representing uk - how ofcomhas  redefined purpose of psb - public value in economic terms - measured by market, but defiend in citizenship,etc

gavin davies -purpose of digital britain, is econ and techl goal,with cultural and poplitical conseqs, never thought of as public

pushing forward of digital agenda central to ofcom

licence fee seen as least worse solution

language ofgreen paper - licence fee as venture capital for creative prodn - tied to suport for strong prodn centre

conflicts bw bbcs lang and capital market?

building public value not carte blanche for wasting resouorces

green paper aergues ofcom should look at bbcs efficiency

governance - hutton -sep govertnors from exec

new trust of bbc, quasi regulatory role bow to ofcom in comp matters

bbc estab by statute rather than charter reinforce independence

lords fail to recog polecon of independence, not just a tidying exc

territorial represn?

propopsal to recast exec comm of bbc

q of bbcs scope and scale - legit to considerwhat  we shouls pay for

bbc is downsizing

25% of prodn outsources

effects on critical mass at bbc?

q of decentralisation -regional flavours - scot: building up of manchesterr will pose challenge to indep prodn north of border

not necessarily decentralising, but recentralising

future balance of psb - subject to parlity test

as commercial broadcast retreats from psb

ch4 repositioning itself in market

cultural commission relevance to scot debates

'our next major enterprise...'

report was resounding challenge to scope of devolved broadcasting

XXXScot ACt 1998

reeport is nationalist report

premised on assumptions of buttressing scot national idt

confidence building

bolstering econ devel thro creative and cult inds

imposs to avoid trope of creativity

devolved v reserve powers

if take creative inds as object of policy, they include broadcast and screen inds, which are less distinct in digi era

Annex G - recalibrate broadcast priorities - constituent part of scot cult - asked to introduce element of devol in  broadcassting - what this should be is unclear - ambition lacking in tv and radio - to keep talent in scot, need serious prodn capavbilities - how about uk channel based in scot for commissioning purposes?

other agenda - if psb is propeerly sbordinate to cult policy, pose serious challenge to present powers

Discussion

AllanJack, bbc scotland

construct and creativity

it is agiven that there is a national psychology

an opp

creativity is used in slightly spinning  way, butencompasses all aspects of bbc - expressing themselves

digital media is here and broadcasting landscape is coming

must adapt to it

task for psb

(Carina Wilson - delegate)

4 things bbc is trying to devel and use new enviro

1. be aware that there is sucha thing as public electronicspace. must estab and protect

ME: is bbc relevant in this space?

2. specific job to promote self expression i. island blogging - homes in northern argyle are wired and website created. now exchange,etc. become electronic noticeboard

ME: still disconnected from major digital movements, such as flickr,etc

ME: evaluation of these?

ii. tales from the edge - allow people to make documentariess of own lives. genuinely spontaneous. people marginal to mainstream expressed selves in highly effective way. eg. radio - past lives. listeners contact to say what they would like to hear about. digital has potential to be more democratic

ME: can PSB remain competitive?

efficiency and creativity not opposites eff is imp constitutent of being creativity

developing and keeping talent

river city - made in dumbarton - is way of developing talent

cultural distinctiveness

being scottish is what we are all about

gaelic

network

The Culture Show - half made from glasgow, half from london - first time that a bbc network has been produced out side of london

Bobby Hain, SMG Broadcasting

not enough of these meetings

v interesting for commercial broadcasters particularly

grampian now mandated to prod scot content

committed to regional news

exporting national outside of scot

otherwise, cannot produce networked prodn

welsh market produces in wales,but in scot more active in uk wide

yes taggart, etc location, location , location monarch of the glen

challenges

barb - how deal w multiset households?

17-20 yr olds have no conception of how bbc and itv were once only channels

convergence of tes

now appointed ecommerce director to look at broadcasting and online

while ofcom has reduced licence terms, now we pay less and entire value lost throgh prodn of revenue

we are no better off!

what can we do?

Questions and Answers

Q: are we more meritocratic? which is why ntions contrib only 2%.drop in qual of nations? what has changed?

Bobby: we dont know. commercial imperative will req best ideas. not sure why from 8% to 2%. 2 issues: itvs commercial imperative and ofcoms desire to see more prodns in regions and nations

Vicki: are we geared up?

Dave Rushton: funl prob that wout devol of indep for Scot Exec, cannot address. spectrum not about to be commercialised, but only operates at regional level. should it be deveoled to scot to devel regional services? v little talent employed in scot to look at these issues. need  engineers, etc to have debate.

Philip SChesl: serious challenges of econ for local tv.

Vicki: devol of spectrum: put in a response to ofcom.use for wireless bb, more channels,etcc is open. ofcom still trying to deal w speed of change. if this debate leads to strategy for scot ,thaht would be useful.

Q, highlands and islands: 65% take up for freeview and digi, doubt is as high in scotland

Christine G: robostnes of figures

Vicki: 82% of households have terretrial, compared w 72% in uk. real issue for switchover. she lives 20 miles from glsgow). there are advs to switching first. 3g and bb also prob.

David Hutchison: back to Phil's talk. natuer of discourses need more discussion. comp driven syst. difc bw market syst and market soc has been eroded. risk taking in broadcasting going to decline.  in itv seems true. what about bbc? dump on bbc4? cultural diminuition.

Allan Jack: of course should be. no quota for risk taking in bbc. but pushing boundaries ,new formats. such as

David: progs about  50s should be on bbc2

Allan: not a q of dumping. cant get eth onto one channel. q is how arrange channels

Bobby: commercial imperative of share of impacts  - share of revenue - conspires against taking risks. scotsport - was taking risk. mon 11pm. spelling ,dancing and singing as prime sat night seems surprising, but that's it.

CG: biggest risk was river city. supporting young talent.bet nobody in this audience  watches it

Sarah Oates: russia,america and uk comparative research. but bbc provides unique opp in world. hope that model provides quirkiness of cult and ability to take risks

Iseult: risking if variety prior to proliferation of channels, was done. is arg that wee dont put onto bbc1 and bbc2

Allan: should not use in lazy way, but try to challenge

Wendy, SCA: efficiency and creativ not exclusive, i agree, but  arguable that processes and emphasis on new te have eclipsed climate of debate. how prov space for creativity?? now seeing less risk taking , more box-ticking.

CG: this asks q that vicki asked us. perhaps we need to consider.

Allan: i ustd what you are saying. must pay for thinking space. need exptl space.

John Ar.. indep producer: interesting ways of getting new things .how can prodn in scotland get noticedin such comp environment. 4docs - make film and download to weebsite. q for allan. many indies could not survive wout bbc commisions.ambition is to be on network andachieve 17% prodn, but can we without prodn. nobody in scot can say ' i like thism, it will be on the network' huge chalenge for ofcom is to see if this can change.

Allan: bbc comiteed to moving commissioners outside of scotland. move to manchester moves closer to scotland. common way of thinking - regional.

Vicki: not ofcoms role to decide which programmes, but yes....

Ed Mac... indep consultant: one of realities is lack of buy in from politicians. 3 diff orgs asked mcconnell to attend debates on cultural, but did not attend. cultural planning group scotland - conduit for pub sect sustainabiilty. new area - community broadcasting sector - what is devel interface bw community and psb

Vicki: ofcom has licensed a nmumber of community radio

Bobby: this is abouot bb. link bw people and tradl broadcasters. will see growth of community portals. those sector sthat have managed to integrate sense of community more succesful than just selling .ebay or craigslist more succesrful because ofcommunity.

Allan:bbc trying to devel that part of sector

Q: do we need ofcom and if so why?

Philip: because social balance would not let commerce rip, would want an instit like ofcom. it is written into the game. it is going to be indispensible. issue is how ofcom fns and balance of arg about this. some of this is unpredictale. i am extremely committed to debate on qs of principle and policy. there are just things instits do if they are not challenged.

Vicki:ofcom more efficent. we need because itis trying to make sense of converged world.

Allan: yes need regulators. tv in uk like hollywood in usa (quoting)

Bobby: yes need. otherwise chaos. too many bad channels . do we need them to do eth theydo? perhaps not. we do have intell voice from them that was not present before.

Morgan, Scottish SCreen: where user generated, now multi-casting, psp now blown out of the water

Philip: ofcom doesntthinkso.

Morgan: but was a space. 4docs now changing what psp could have been

Philip: would watch this space. not over yet. other ideas will attach themselves to psp.

Paul Thornton: philip -reconciling public w economic, and impc of tv. how reconcile public w market, but maintain sense of responsibilites?

Philip: compromises, another is about to be worked out. what will be scope and scale? how pubilc value is talked about is neces'y derived from market.

Andrew, ACE: vicki said that audiences req in genre of arts, third from bottom. what is take on this? south bank show.

Allan: need to know more about survey.

bobby: has led ofcom away from box-ticking. theirdefn of genre needs clarification

Philip: underlying q is whether is hierarcy of value. clear that ofcoms is intervention of policy, premised that preferences are real and have conseqs that ought to inform priorities .is qable whether snapshot is adequate basis.

Simon Smith: 2000 people on telephone interview was the stat. 2 terms from ofcom: convergence. but what is this? look at what hasnt changed as mch as what has. tv screen changing doesnt change reason for watching  same. convergence shouldnt take away from factthat this is what drives audience.2. way in which tv is form of comm, there are many other forms .is also a medium for artists. worries when they see that tv is merely comm.

CG: their defn of psb applies better to news than,saym, drama

Summary

Pihilip: if look at hist of media comm, always reevolusions that involve displacement, but rarely disappearance. are signif generational changes of media use. techl convergence has been hyped. serious qs ofmarket sustainability of range of distrib systsms. second point about what do we regulate? we are v selective. we do not regulate press by statutory means. fears of politicians of conseqs. broadcasting has been key sector for reg, along w telecomms for reasons of state as much as identity. what are going to be t marginal inrcements . next thing is content.

World Anti-Doping Agency Gene Doping Symposium (2005)

WADA gene doping Symposium4-5 Dec, 2005, Karolinska Institutet

Welcome

improve people's health. misuse of medical tes

Richard Pound

banbury conference

wada

OM contributions shared by NOCs - but..

gene doping research $3m

gene doping panel in WADA, help with detection

new results - WADC, mar 2003 -

ME: who are stakeholders of gene doping?

Olympic charter amended stating that only countries signed to  WADC can participate in Olympics

UNESCO convention Oct 19 2005 120 supporting states, observed by all 191 states

gov actions - now wider gov support

gov can do sth sports cannot sports cannot address trafficking, seizing, regulation of med professionals

trying to widen network of stakeholders recently, an athlete committee athlete outreach committee

gene doping inevitable

athletes believe they are immune to risk and their entourage seem not to care

New Trends in Anti-Doping Arne Ljungqvist

need to be ahead of the game first time in history

purpose - describe recent developments

some key years 1960 olympic games in rome - danish cyclist died in 100km road race. ioc took action, as first televised Olympics. athlete dying in front of ioc 1961 ioc mc 1964-72 testing for stimulants 1972 munich first serious case, us athlete ephedrine, controversial, still claims medal 1974 testing for AAS - tentative for 76 games in montreal 1983 IOC labs 1988 seoul -arne gave press  conference in rel to  johnson's positive. huge press. death of sport question. response was that this should be stopped. led to unified global effort. iron curtain drop changed this. 1999 ioc code, wada - changed med code into antidoping code 2004 wada code 2005 unesco convention

arne was olympian in1952 and nothing then,

doping code explanation

doping is definedas...

violation new 4. inadequate whereabouts information 8. administration, assisting, encouraging

prohibited list - wada publish each year

criteria - enhance, health risk, spirit of sport

(two of three)

doping need not be cheating to be banned

could say that any substance could be on list, and this is a legal prob

need common sense

substances w similar structures likewise banned, but legal difficulty to try

prohib method enhancement of oxygene trtansfer

distrib of substances 2004 - 36% anabolic 0.1% oxygen transfer enhancement

TUE

anti-doping strategy - info, educatioo, doping control,research

wada allocates 25-30% of budget to research vasst improvement since 2000

ioc never took this responsibility

strategy of doping controls - in comp - unanncounced out of comp - random - targeting (intelligence)

ME: what is current status of intelligence on gene doping?

need to improve intell

ME: how?

recent negative envts

- salt lake city experience, tendency  to make use of most recent advancements. 3 cross country skiers on aranesp - The Sweeney Experience' 2002: first reported that athletes had been contacting him to see how they could benefit; - The BALCO affair 2003; shows illegal production jsut for doping - The Athens experience 2004; first olympics at whch people banned for non-analytic positive; greek athletes; were using artif device for urine - Further designer drugs 2005; don catlin found further egs

The maked Machine false urine

REcent positive evens

SLC2002 -showed that we are close to athletes; these were subsrtances that had been on market for some months - Athens - pursued cheats successfully - WADA Code - UNESCO convention - Research fund - Proactive initiatives

whycontinue fight? - in ethics session. must be unbiased ME: this is too far. to pose all or nth is mistaken.

funl facts must be mentioned 1. no support for such an idea in t sports communioty - there was a debate. but it no longer exists. everyone agrees 2. wada andunesco convention, political estab has reinforced support 3. athletes themselves dont want it. athletes commisions are strongest

ME: when asking athletes about their feelings, hat do you think they are rejecting?

President of K: what are legal conseqs for med professionals?

AL: any person assisting may be banned. will not receive accreditation to be Olympic doctors. but we have limited legal action in civ law. at World Championships some years ago, some finnish professionals weree encouraging, investigation into law. found that action could not be taken. no legal ground .this changed the law.

The Irrefutable Success of Gene Transfer for Therapy of Human Disease) Concepts and techniques of gene therapy - applicationsv to doping in spoprt Ted Friedmann

give overview of underlying baasis of justif for potential of gene doping

rationale is direct outgrowth of gene therapy itself a controversial and difficult field

now a real area of cliincal research basis to think that direct attack can be and has been therapeutic

gene based doping - realstic poss imminent threat to sport - same pressure  that sustain drug doping  will lead to gene doping - based on advances in gene therapy

Evol and current state of gene therapy -controversial history - tools and concepts still immature - clinical reality, effective treatment, poss  cure -- serious risks, tolerable in context of therapy -- still subject to oversight and regulation

gene therapy for human genetic disease science, 1972, mar 3, 172, n 4205 friedman and robin

Proposal for human gene theerapy - needed - technically diffi -use disabled viruses as gene transfer vectors - many ethical and policy problems - reqs local and nationaal oversight - likely to be used for non-therapeuticapplics (enhnacmenet)

dark side broader than gene doping - enhancement of human traits in a eugenic sense.

LeRoy Walters, Kennedy Institute, Georgetown - somatic cell - germ cell

two major technical advances

recombinant DNA -cohen and boyer, 1973 - first efficient transfer tools (engineered viruses), 1981-1982; retrovirus vectors - Temin, Weinberg, Scolnick

retrovirus 1981-2 random integratioon, insertional mutagenesis adenovirus adeno-associate virus liposomes naked dna

ref: j biological chemistry; 1984, 25 12, 7842-9 - restored gene function and reversed phenotype

optimisms - beginnings of human clinical studies - 1989-90 - high expectations - exaggerated promises

gene transfer trials by year crash in 2000

ME: why? at the time of HGP completion

photo of jesse gellsinger

gene directly injected into liver

3 or 4 days later after injection, died react to vector not gene

Uni of Pennsylvania OTC study - a patient death -1999 - adenovirus vector to transfer ornithine transcarbamylase gene (OTTC) directly to liver - patient (JG) developed explosive

visible depression in Society of Gene Therapy

yet, heard of a diff technique

Paris study, Fischer, Great Ormond St LondonX- SCID

photo of Bubble Boy syndrome child - protect from inections

X-linked SCID,sevcombined immunodef dise - mutations in..

ex vivo study

introduiced to bone marrow cells

REF: NEJM article ,Fischer, Alain, lead Hacein-Bey-Abina, S -sustained correction of X-linked severe combined immuno

complete recovery - complete immunecorection 14 patients - some >6 yrs

but at high cost - 3 cases of T-cell leukemia -direct result of treatment - responsive to chemotherapy but reqd eventual one marrow transplantation - one death 2004

other two aree still alive and no evidence of residual disease. but diff to ustd

three cases of leukemia during effective treatment of x-scid deficiency

LMO2 oncogene has been disrupted - this is why we have leukemia

Why is this result imp? - proof - can be therapeutic - all previous studies ,potential or marginal benefits ,theoretical risks - no risk/benefit -X-SCID -quantifiable beenfits - gene transferrresearch becomes gene therapy - opens new era for med

legitmately therapy not just gene transfer

current successful therapies - X-SCID - q14 patients ,3 leuk, 1 death - ADA-SCID - 4 patients - prolonged - chronic grnaulomatous disease -2 patients

addl imminent and probable successes - cancer vaccines - introdcue genes (GM-CSF, CD40) to cancer cells to enhnace immune response (melanoma, CML, others) - restore tumour suppressor fn (p.53) - some photoreceptor degeneration andblindness -restored sight in blind dogs by gene transfer into retina - coronary artery disease

intra-tumoral...

CNS prophylaxis, new chemo agents

additional info into genome, which maintains mutant gene

now, te to fix defect - to change to wildtype gene from mutant

emerging tes - siRNA for gene modulation -especially for dominant diseasee - vector targeting -gene deliv - targetd gene modifi -zinc finger delivery of transcription factors ,transgenes

so, darker side -therapy is poss, what about enhnacement?

socially and ethically 'acceptable' enhnacement -we already do pharma, so why not gene - reelvant genes are becoming identified - tf, applic of gene tools to non-disease traits seem inevitable -

extension to sport - one of most imminent - unlikely to conform to standards of human clinical research -safety, informed voluntary consent

ME: why is informed vol consent unlikely?

sport or bioengineering? is it still sport?

ME: yes ,good photo, the q might be whether he would have been ahigh jumper if he had info about his genes

germ cell -therapy or enhance?

eugenics - old eugenics of late19th and early  20th C - new eugenics based on genetics - new potential for restrictive ,discrimintory

conclusions - all human gene transfer  -immature ,exptl clinical research, not standard of care -but if i had a child with X-SCID, i would opt for genetic approach - proven concept ,truly therapeutic - many dangers, known and unknown,reqs oversight

risks tolerable in light of disease ,but for healthypeople?

conclusion -sport may lead the way - opp to define social atts and responses

in US, not entertaining proposals for enhancement

discussion

how is read out monitored ?/ dosage? how follow efficacy of therapy? if so, might be poss to detect.

ME: what lev of cooperation is expected from biotech industry?

change position but

Goldspink Kathy Howe, killing off cells. factor 9 expt study shelved becuse of immune response to vector

holy grail is sequence correction

goldspink:

tom: surprised by one thing, which  was your optimism. I sat on FDA committe which looked at gene transfer when French study began.  what is your assessment of the science. is it  likely that LMO2 will not be repeated.

Ted: it hasnt in

Olivier: you refereed to over 700 studies, by RAC. do we have idea of success rate? are we aware of  some genes, neverr been poss to transfer. some genes more capable of expression than others. how long to go from animal model to human.

Ted: not all of 700 studies led to clinical. need to learn much more about how to turn genes on and off.

Olivier: side effects?

Ted: dont see them until you see effect.

Olivier: procedure itself not harmful?

Ted: in Gelsinger it did. will not see ath going wrong until see sth happening

Q: state for muscular.

Q: leukemia. single gene as key factor .also v shiort period - 3-4 years. usually cancer 10yrs. sth peculiar of case , it is activation of agene. are ways to avoid activation.

Ted: but not activitation, but disruption

Q: 3rd case special since dif

Odile: transgene role is enormous. cannot claim thatt there are no te that could counteract potential activations.

Chair: what is view on detection of gene transfer? willl this stop? or need legislation on other level?

Ted: no, wont be enough ,but will be strong deterrent.

Coffee

Effects on organ systems/tissues

Heart -    bigger, greater stroke vol -    inc maximal cardiac output

Blood vessel (heart and trained skel musc) -    more capillaries -    improved dilatory capacity

Blood -    ic total amount of red blood cells -    evevn larger expansion of plsma vol, reduced blood count in a blood sample

Adipose tissue -    reduced amount

Connective tissue/bone cartilage -    inc amount/strengthened

efects on organs systs

endocrine system -    insulin sensitivity -    catecholamine and gH response to ex

skin

imune systt

lungs

nervous system/brain -    inc capillaries more utilised

what factors influe performance

bouchard, C. et al 2005 -    gene map -    summarise what has happened in last year -    prediction of health or fitness -    no agreement yet on ‘key genes’ using popn genetics -    difficult to validate – separate population studies reqd

how study human muscle ‘phenotype’? -    skeletal muscle. -    How dna, to mRNA to protein -    Strength and endurance mapped to samples

Considerations -    species -    type/duration/intensity of intervention o    aerobic, resistance, inactivityy -    acute or repeated -    sampling site and time(s) -    amount needed -    mRNA and/or protein -    localisation -    housekeeping genes/normalization procedures o    complicates, regulation -    method – broad or narrow?

ReF: fluck et al 2005,

REF: Mahoney FASEBJ 2005 -    after acute ex, more genes activated in sets -    limited by number of biopsies you can take. Scientists would ilke one every hour -    but used 3h and 48hr

Generating a human endurance ‘transcriptome’ -    24 sedentar subjects -    240 musc biopsies -    24hr post ex -    measured phenotypic by important

500 genes ‘activated’ by ex in humans - COL3A1, FABP4, IGF-1, TGFBR2

what prdicts for improved cycle performance following 6 weeks training?

What genes regulate -    better oxy deliv

Timmons et al FASEB K, 2005

Gene ontology analysis

PGC-1 inc by training in following hours

Ameln et al FASEBJ 2005 -    HIF-1 drives expresion of epo. -    And VEGF -    At protein levvel, was regulated by acute ex, bound more to Dna, drives target genes,

Does epo play role in muscle? -    perhaps, protective or androgenic -    thus, epo might have systemic and local eeffects beneficial for performance

receptors of VEGF go up – inc to manipulate receptor side

5wks of training, VEGF goes up

to develop gene therapy fully, must understand cocktail of things that are going on

in gene therapy, CV side things are going on, but must know more to grow complex structues such as vessels

Targets of interest at geen level -    transcription factors, angiogenic, mit biogenesis, hypertrophyt

cell doping -    naked cells -    encapsulated – put into tissue, then remove. – safe for cheater, since no trace. Can be done with epo and inserted anywhere. -    sooner than one might expect. As many cell trials. And move towards gene modified cells. -    Yesterday, venture capitalist in san diego, using fibroblaysts, for parkinsons

Questions and Answers

Question: focused on up regulation, but what was freq v down reg

A: usually more up regulated, but perhaps a quarter, 3-4times more up than down

Question: how do trained, elite athletes differ?

A: some surprising, some expected. Not easy to predict.

Question: can distinguish

A: no of subjects needed to study polymorphisms v high, often differe considerably. W n24, impossible

Question: important?

A: extremely. But every thousand base is … bypassed polymorphy by looking at integrated response

Question: study in male, not female? Same for female? Each react differently to training

A: what would you expect?

REsponse:

Response: total of 16mins, can dramatically inc endurance performance, no gender related differences. Might depend on ex mode.

Olivier: concern of cell therpay, problem earlier than gene doping. Today, company proposing use of tendon cells to strengthen repair of horses. So is coming at commercial level soon. One key element in detection is time window we have. You have observed some transformation at mRNA level. What is order of magnitude of change?  Concern that signature will be lost.

A: presume that gene copying intensively is more stable and chronic than when you train. I would guess there is an elevation of gene doping product.

Olivier: what level should we detect?

A: problem is legal. Ban people that have strange pattern? Cell therapy been around for long while. Blood transfusion for over 100yrs. Bone marrow transplant since 70s, skin transplant, etc. cell therpay not new, but gene modified cells is novel and cells that are hidden.

Olivier: cells that grown and reinjected

A: yes, like cell

Andren Sandberg is rapporteur

Lunch

Session 2

Chair: Odile Cohen-Hagenauer

Vectors and Delivery Methods C. I Edvard Smith, Karolinska

Gene therapy -    gene could be 10,000 base pairs -    virus contains maybe 3,000 base pairs -    human genome, thousand books with thousand pages

today, cannot fix gene, but put in an extra one

concept oif a gene

if cell goes through many divisions and gene is in episome, will be lost. So if need to put in cells that divide many times must go for integration. Only way to ascertaint hat will be in cell.

Problem with going from outside of cell to nucleus

Local and systemic gene therapy

Gene transfer techniques -    non-biol methods (plamids, oligonueclotides) o    liposomes and polycations (lipofections) o    electroporation o    in situ naked dna injection o    gene gun (biolistics) -    biol methods o    transduction (virus-mediated transfer, most efficient)

drawbacks to viruses

DNA complexes – plasmids or oligonucleotides -    insert size no limit (can use long stretch of DNA, makes possible sequences, marker of normal) -    episomal – normally this; outside chromosome -    short-term expression -    broad host range -    unstable in vivo

is possible to remove all foreign elements. Ie design genes that do not carry any foreign elements, so  harder to trace

Virus as a vector for therapeutic genes, eg hiv

How use a virus?

Concept: the packaging cell line

IMAGE

Empty particles – allow introduction

Packing cell line 2nd generation

There are a number of viruses that can be used -    ecah has benefits and drawbacks

Concept: RNAi – how does it work?

IMAGE

Recent phenomenon, a decade, first observed in plants. If introduce double stranded rna has different features

In mammalian cells, if, instead of long dsRNA sequence, use short siRNA molecule, can have same effect. Si = short interferring

Regulates gene expression

Can achieve stable expression – deliver shRNA

Vectors contain unique sequences that can be trace Provided you know where and how to look Apart from t vectors there are their products

Questions and Answers

A: when expresss siRNA, is v short.

Question: if do cell culture, get up to 10,000 fold interference.

Question: will day come when can do entirely in vitro?

A: yes, should be. But viruses also have problems. They rely on cellular machinary, so good but also limitations – must use normal process of making proteins. If do invitro can avoid regulatory problems.

Vectors and delivery methods – vector and transgene vector detection H. Haisma

www.rug.nl/farmacie/tgm

in non-viral vectors, mostly have much chemical stuff added to them to allow entry to cell

adenovirus

shedding data, gene therapy stdies

shedding

excreta – semen, stool, saliva, urine, blood germ line – sperm, ovum

environmnent – next of kin

if people treated with gene therapy, can find vectors in almost any of tissues

do not find anything in germ line - ie no transfer to next generation

Gene doping detection

IMAGE OF TABLE

Dna – muscle – no shedding - months For adenovirus, shed in serum, saliva and urine, but only last days AAV – muscle – serum saliva urine – weeks Retrovirus – iv blood – semen (probably through prostate) – weeks

Vector: -    protein – no, requires biopsy -    dna, rna – yes, blood, urine -    chemicals – no, requires biopsy -    antibody response – yes, blood

clearance of free dna IMAGE OF GRAPHS

Even if inject into muscle and leaks into circulation, no way of finding. -    goes to liver and is broken down – perhaps find 10% of it in blood, after 30mins

dna detection?

Baterial is immunogenic

CpG dna: -    unmethylated CpG motifs are abundant in bacterial DNA -    the frequency of t CpG motif is supporess and highly methylated in mammalian DNA

detection?

Transgene -    protein o    human original, yes, elevated blood, urine o    new modified, yes if in blood, urine o    human modified, yes if in blood urine -    effect – yes, if in blood, urine

use effect as most promising

specific detection?

IMAGE

Isoelectric patterns of epo

REF: Lasne F et al Mol Ther 2004, 10:409-10 -    can see difference in number of glucose; same gene, same protein looks different from muscle or kidney -    possible fror detection

detection?

Specific – every potential drug needsa  specific sampling and analysis method – also detect other doping General – profiling allows t determination of (major) changes in gene expresion pattens by: gene array or proteomics

Genetic interventions IMAGE

Serum Protein Pattern diagnostics IMAGE

DETECT MAJOR CHANGE

Proteomics IMAGE

Establshes normalised picture of sports people on proteomic level, then look for major changes

Detection by proteomics

May be indication of gene doping – ME: WHAT else might it be

Post translation modifs

Mann and Jensen, Nature Biotech, 21, 255 (2005)

Gene expression profiles

IMAGE

Alreay used for cancer patients -    sample from tumour, isolate its rna, then matched on a chip, comparative analysis from arrays -    in sport, chip would convey change, 25,000 patterns on chip

Gene Array

IMAGE OF CHIP

Discussion -    gene doping vectors will be undetectable -    proteomics and gene expression profiling are powerful generally applicable methods and will be part of diagnosis and therapy in t future -    requires fresh tissue, urine or blood sample of good (RNA or protein) quality -    logistic (handlig, storage) -    global change in sampling handling is needed

Questions and Answers

A: once gene is active, no way of shutting it down.

Chair: Problem, because need 100% proof to commit someone

A review of current gene transfger models relevant to athletic performance

Haematological system and red cells in particular O. Cohen-Hagenauer

Launched European Society of Gene Therapy

Mainly deal with EPO

What matters, detection of EPO or that carry more level of EPO than rules permit? -    v costful

do you want to detect exogenous and transgeneand rEPO, or have world athlete not go beyond a certain threshold

Epo gene transfer -    can easily be monitored in vivo (hematocrit) – as hematocrit will just increase -    not supposed to induce an immune reaction -    therapeutic indications: epo sensitive anemias, eg chronic renal failure

epo gene transfer 1.    state of t art of vector systems 2.    regulatable expression – pharmacological control 3.    adverse effects – alluded to by haisma 4.    detection of abuse and gene doping

state of art of vector stys

state of art of vector systs 1.    dna electroctransfer of plasmid dna in rate muscle- just need needle, introduce gene in muscle, then electric field and dna will stay in. 2.    polymer encapsulation of xenogrenic or allogenicc fibroblasts or myoblsasts engineered to secrete epo 3.    sub-cutaneous implantation of microdermis biopump 4.    IM injection of epo-recombinnt AAV

IMAGES

AAV-mediated epo gene transfer 1.    long term expression (over 6 yrs) 2.    fatal polycythemia (excessive levels) 3.    regulatory system reqd – pharmacological control by an orally administered drug 4.    adverse event: auto-immune anemia 5.    detection of abuse and gene-doping

regulatable expressoin (3)

companies now investing into this sector

Questions and Answers

Coffee

Gene doping and the regulation of skeletal muscle hypertrophy Lee Sweeney

Skeletal muscle

Gene delivery into muscle -    primary targets are post-mitotic (non-dividing) nuclei of mature muscle fibers -    gene delivery vectors o    naked (plasmid) o    virus •    aav serotypes 6 and 8 are most efficient •    capsule modified lentiviruses o    non-viral dna conjugates o    adult stem cells •    muscle and bone marrow derived

adeno-assoviated virus mediateed gene transfer -    readily infects skel musc -    accommodates <4.7kb synthetic gene -    delayed onset of expression (Biut self compleent and high titrs decreates) -    no viral gene expressio -    no immune response in mice /capsid immune response in larger animals -    no integration (?) into post-mitotic nuclei – better for FDA safety -    long duration of xpression (likel years to decades) – but depends on usage, since only hitting postmitotic. Eg. Normal sedentary mouse loses no expression, but if hypertrophy, then lose in matter of months o    in monkeys that are not exercising, expression remains

efficiency of aav gene transfer -    50-95% of fibers show expression of reporter gene (LacZ) delivered by AAV1 -    transduction of -200% of all muscle in mouse possible w high levels -    looks possible for dogs now.

So, enhancement?....

potential appliocs for sskel musc -    primary musc diseases, duchenne beckeer, muscl dyst -    loss of muscle function during aging -    secration of therpaeutic proteins into t blood (factor 9 for haemophilia)

loss of muscle function during aging (sarcopenia) -    progressive loss of muscle mass and force beginning in fourth decade of life -    slowed, but not prevented by exerccise -    negatively impats health and quality of life -    occurs in all mammals -    may be due to progressive failure of skel musc to repair damage (decline in regenerative capacity) o    prob with ageing when satellite cell fusion doesn’t occur as well

Muscle Growth and regeneration. -    Various growth factors, HGF (hamatocrit) -    IGF-1 one of key factors – imp property (most inhibit maturation of muscle cells, so if over express, would inhibit muscile) but igf-1 drives proliferation, then XXXX

IGF-1 -    drieves protein synth -    reduces protein degred -    stimulates sat cell different

GH-IGF-1 axis - local synthesis decreases with ageing

Will inc IGFF-1 expression im muscl promote growth and refgernation pathways?

IGF-1 expression targetd to muscle -    utilize aav to achieve efficient skel musc delivery -    utilize musc specific promoter (MLC1/3) to limit expression to skel -    igf-1 over exzpresiosn should promote growh -    injected legs did not have age related loss -    also stopped loss of power

hyp -    igf1 overexpres should promote musc growth ad repair leading to t following outcomes

IGF-1

Conclusions – -    igf1 ocer express prevents age-relationship atrophy and loss of skel musc function -    skel musc regen i\

20% or more depending

prevented fibrosis due to severe injury

would it lead to enhanceemnt for athletes? If combined w trainig?

IMAGES

Igf-1 effect local- -    avoids harmful side effects, since blood levels of igf-1 not eleveanted -    decteion difi or impossible without biopsy, unless surrogate markers. -    But difficult to seee surrogate

Could systematic delivery of any ageny provide a similar effect to that achieved w local prodn of igf-1?

-    a TF-beta family membner, myostain antagonise igf-1 action, limiting skeltal musc growht. With igf-1 trying to create a balance. So knock down myostat to create effect on igf-1 -    possible cardiac toxicity -    relatively speciic to skeletal musc -    decreases fat -    loss or inhjib or myostat inc musc mass -    wyeth is in phase 2 clin trials w anti-myosttin antibodies for multiple types of muscle dystrophy – scarey note: all have dlated cardiomyopathy – could exacerbate cardiac condition, but speculative at this stage. Beginning to see effects. In obse patient, marked decrease in fat

Muscle growth and regen -    would inhibit prolif of sat cells, igf inrceases

myostatin inhib could allow systemic delivery -    antimyostat antibody injections into t blood of mice result in muscle hypertrophy -    viral delivery to liver or peripheral skel musc could generate screaion of anti-myostatin inhib in blood o    could look in blood for trace -    should result in inc growth and repair -    not clear if harmful side effects. Not clear would prov all benefits of igf-1 especially during senesence

gene doping could be detected by screening

myostatin KO Mouse -    wild type v myostatin null -    in any athlete, would not want total knock out

belgian bull

young child -    parents, mother is competitive athlete

conclusion -    gene transfer could be used for skel musc

nuber of properties could be changed -    strength, but repair, better muscle mass, strength and speed, maintainence of mass and strangth during disue, inc endurance

is genetic enhancement going to be a reality? -    inevitable -    banned on safety and fairness o    but safety sufficient -    if used in widespread for preventing aging, then harder to ban in athletic population. Especially when earlier better for intervention. -    Genetic profiling of athletes ‘ raise issues of genetic ‘fairness’ -  If someone has genetically decreawed myostatin, then is also unfair

Where are we now? -    can do this today o    naked dna o    direct injection o    vasula injection o    regulated gene expression

acknowledgement -    elizaeth barton, linda morris, rosenthal, farrar

Questions and Answers

Question: these are small animals. But how many injections for thigh muscle of human?

A: we are moving away from injection, rather vascular delivery. But problem is immune response in vector

Geoff Goldspink

Animal gene transfer model Interested in musc regulation

Looking at XXX, derived from IGF-1

IMAGES

Biol actions of gh/igf1

Mgf seems to cause sat cells to inc in no –then goes away

Igf1 also involved, but later in process

Damage

Real outcome is muscle force

With knockout myostatin not strong – lacking in functionality

35% inc in mujscle strength within 3 weeks

already company on internet creating mgf – Phoenix pharmaceuticals

ME: how did you find this?

Splicing can be induced by siRNA

Prediction

IMAGE

Put

Detection -    rapid screen mas spec

confirmatory tests -    antibody methods and o -    cell signalling using differeential gene expression

Questions and Answers

Tom: difference of view about what happens to myostatin knockout. Does it give strenght or not?

A: JHU argue that 17% increase in Arnold Schwarzenegger mice. Not a good balance in extra weight.

Lee: agree, if knockout altogether then not much strength .

Odile: but mujst increase other body parts

Lee: bones do compensate, do get larger. But not looked at tendons. But would assume they would hypertrophy as well

Geoff: myostatin KO; if keep putting into req state, can activtate w mgf, but if keep knocking out myostatin, energy pool diminishes over time. Athletes might use on short term, .

Lee: child born with KO liely to have problems, but mother doesn’t.

Question: shown that athletes using steroids get inc in sat cells, so can detect by muscle biopsy.

Geoff: butler brown in paris when taking biopsy from steroid using athletes, telelle length – life of sat cells – diminished – whereaas we might live to 180 efore run out of sat cells, athletes and exessive exercise might run out

Mitochondrian power plants: target for performance enhancing gene therapy Doug Wallace

Mit genome -    1500 chromosomes, 37mtdna genes -    all key energy genes

african

expressed through oocyte

males do not contribute

life = structure + energy

Schriner s et al 2006, science, 308, 5730, 11… -    increased lifespan by 20%, assoc w marked decrease in mtDNA

mtDNA, since maternally inherited, can only change over long period of time -    difference between everyone in room influences level

women started in africa about 200,000 years ago move to asian then to northern and then to americas

highly correlated w geographic origin – specifically latitude – because of temperature

mtDNA have specific point mutations that change coupling from ATP to decreasing work efficiency, hbut increaseing heat efficiency

changing of coupling efficiency

excess calories burned as heat

A nieme and k majamaa, 2005 Euro j hum gen 13 965-969 - mt dna genotypes correlates w finnish elite endurance versus sprinter athletes - functional difference between type one or two nucleotides

can radically change performance

possible that might be strand invasion of nucleiotide -    if switch from tightly to loosely coupled, would introduce muation, change 1 polymorphic base, inrcease performance 5-10%

Questions and Answers

Question: what is importance of mt ….?

A:

PPAR and the creation of the Marathon Mouse Ronald M. Evans, Salk Institute

What are they? -    peroxisome proliferator-activator receptors, comprise set of three related nuclear hormone receptors, that control broad aspects of lipid metabolism -    expresed in different tissues and are naturally activated

Fat storage and burning -    determined by relative levels of ppars,

revving up metabolism -    synthetic ligand GW1516

created marathon mouse (ppar)

transgenic mouse -    now expresses ppar-delta

muscling in on endurance -    will also treat wildtype (ie. Normal) littermates w orally active PPARd specific rdug

red muscle increased transgenic mice -    pink – glycolytpic fast twitch type ii -    - suggest switch to type 1 myosin rich fibres (slow twitch) -    from carbo burning to fat burning

A – better B – worse C – same

?

treadmill challenge

improved exercise performance in transgenic mice -    80% more time and distance capacity what about ppard null mice? -    Total running time only 20min, compared to wildtype of over 1hr and transgenic of more than 2hrs

Under study – does GW1516 enhance performance in mice?

Future – magic pill?

Clinical -    muscle wasting -    weight loss mec related to inc oxidative meabolism

opp for abuse -    inquiries from athletes, coaches, a horse trainer

conclusions -    ppar-delta directed metabolic changes produces a mouse w a long distance running phenotype -    possible to alter single component of compplex system –ie muscle fiber en burning ) to enttrain t rest of physiologic network -    genetically produced ‘delta’ muscle fibers confer high performance even in absence of exercise (training) -    exercise physiology can be predictively manipulated -    ppar-delter receptor

lead by Yongxu Wang – now running own lab at U Mass.

Gene Doping -  possible orthopedic applications Chris Evans, Harvard Medical School, Boston, MA, USA

Inflammation/arthiritis – phase I

And repair of: Bone Cartilage Ligament and tendon

Arthiritis is chronic, requiring long term gene expression, the other 3 are not – repair, then stop

Gene tansfer to the synovial fluid of joint

ex vivo and in vivo

Some success with ex-vivo

ex-vivo preclinical -    safe feasible in rabbits, rats, dogs, mice horses -    levels of expresion sufficient to inhiit animal models of RA

use retrovirus

phase 1 study in knuckle joint w rhumatoid arthiritis

put into joints that were due for removal

PAHSE I RA STUDY conclusion  (N=2) -    gene transfer to human joints is safe and feaible -    intra-articular gene expresion occurs -    patients accept procedure well -    reported relief, but not fully documented -    phase II studies merited    , BUT which vector

not progressed due to lack of funding. Big pharma wont touch it, small biotech don’t have enough money, millions just to treat small number f patients, but made progress by going around with it.

REF: Evans et al PNAS 102 8698-8706,2005

Targetted genetics company in seattle study.

Also in dusseldorf on modifications to determine clinical response. First year patients respnonded dramatically.

Horses Colorado state uni collab Experimental study in horse wrist joint, experimental model. Remove cartilage and inntroduce chip, measure effects of XX.

Induced disease at day 0, introduced vector after 2 weeks, disease under way, therapeutc not prophlyactivc, at end of experiment untreated joint shows erosion of articular cartilage

Absent from horse who recent therapy

Now bone

Direct injection of adenovirus – BMP-2

V responsive to gene transfer

Do this by making hole in animal’s bone and intro virus (BMP-2)

Rate undergo surgery, where femur exposed and external XX attached 5mm defect in femur would not heal if now use adenovirus and inject 40micro ltirs

after 8 weeks,good healing

Wolf’s law – how bone responds to load

After pins removed normal mineral content returns

Effectively repairing bone that would otherwise not occur

Concluding that we can do this

Cartilage

No intrinsic ability to heal

If partial injury to articular cartilage will not repair

If goes through to bone bone marrow defect

Trying to take adv of fact

Use with rabbit

ligament and tendon -    healing initiated by forming of blood clot -    gene transfer to healing ligament

see if enhance healing

gel-mediated gene transfer -    ad GFP placed into migration model gel -    1 week -    after 3 seeks more cells transduced

Presnet status

Indication – status – relevance to doping Inflam/arthiritus – phase1 clinical – high Bone – advanced preclin - ? Cartilage – preclin - ? Tendon/ligament – experimental – high tendon-muscle

If uses it when injured, then goes back to track, is horse doping?

Overlap between legit medical use – do have arthiritis – but overlaps with doping, since reason for arthiritis is due to over-traiing, so we increae their ability to train

Questions and Answers

Arne: Different between doping and treatment is already in use as TUE. Sports peple should be able to benefit. Problem is when it may go beyond.

Monday

Chair: Friedmann Standard in medical doping involves looking for assays

Don’t worry about looking for epo if you are interested in finding it

Look for local effects Systemic Homeostatic

Need un-biased global assays Changes in gene expression patterns in distal non-target tissues

WADA Perspectives on Gene Doping in Sport Olivier Rabin

Anti-doping analyses started in 60s based on detection of drugs in urine (stimulants and anabolic steroids) Progressive incorporation of -    immunassays: hcG (1987); LH (1997); hGh (2004) -    electrophoresis/focusing: EPO (2000); HBOCs (2004) – human blood oxygen carriers -    flow cytometry: blood transfusions in 2004 trend evolving from pure chemical analysis to incorporate more biochemistry and biology

evolution of rules -    from imperative need to detect and characterize t doping substance(s) in athlete’s biol specimen -    to -    possibiilty to use markers of abuse of substances to report doping -    as long as scientifically validated (concept and method)

markers approach already in final development phase for hGh detection: -    IGF-1 (liver) -    P-III-P (bone) Abnormal markers variation are used to qualify doping Hwr, almost 10 yrs of research and more than $4m

Fundamental concept

Abuse: substance – extra gene -    non physiological modification (imbalance) – change in homeostasis -    detection: where to look? o    Genomic o    Transcriptomic o    Proteomic o    Meabonomic

What to look for? -    signatures of changes unique to doping classes of substances

cannot say one substance equals one specific signature, but can make claims about relationships

limits in -    interpretation of gene modifications -    protein and peptide knowledge -    interpretation of metabolic changes

some gene regulations not fully understood

where to look? -    accessible cells or biol fluids w minimal invasiveness (urine? Blood cell lines, buccal cells; ) -    imaging (changes, markers, radiolabeled tracers)

challenges faced -    identification of right target: where, what how, interpret? -    Accessibility to measurable modifications (invasiveness, time window, ethical methods) -    Eliminate other explanations than doping (gender, age, diseases, enviro, ethnicity) -    Development of specific tools for anti-doping -    Extremely sophisticated constructs w fine modulation already in animal models -    Approaches may well work for gene doping or some substances, but what about cell therapy, in partic autoloous cell transplants – eg. Tendon strengthening in horses – extremely difficult to monitor. Looking for same cells in same organ. Already in application -    Costs. o    Money we can invest has limits. o    Also limit of cost we can ask for analysis. -    Layman accessible! – particularly lawyers.

Hope -    epo study in monkey showed genetically transferred epo still detectable o    not endog -    microarrays and SAGE appear to reveal target genes or mRNA. Proteins are promising. Metabonomics will grow. -    Combination of discriminant factors o    Projects ongoing on physiological markers that can be followed by biochem o    Have longitudinal XXX of athletes and detect unusual variations o    Doubt in future that can test every athlete for gene doping. Must start

Pragmatism -    science is likely to deeliver the antidote. When and how? -    Resources can be v demanding on anti-doping and beyond capability. Need to partner. -    Anti-doping market is limited. -    Partner with academic or private org -    Hope for some large scope methods, not too narrow in application -    Even if gene doping applied, limited chance of success, delay in significance impact in sport, though success will come…

DHEA is an anabolic steroid like testosterone and THG: Global gene expression analysis F Labrie

Use of microarrays applied to DHEA (hormone mutant)

Thg includes a genomic signature typical of a potent anabolic steroid J of Endocrinology 2005, 184, 427-33 Labrie, …. Claude Labrie

What is DHEA? -    precursor of all androgens -    from adrenal or food supplement (will argue against food supp) -    dhydroepiandrosterone (DHEA) -    leads to DHT dihydrotestosterone

The anabolic steroid control Act of 2004 has amended the US controlled substant act to include androstenedione, but it excluded DHEA.

‘ther term anabolic steroid means any drug or hormonal substance chem or pharm relationship to testost (other than estrogenes, progestins, cortico…’

JAMA 280, 1565-1566, 1998 -    qual control of DHEA dietary supplement products

HFL Jane Roberts

Difficulties, always new pharma drugs

Current methods cannot detect gene therapy

But if devevlop, perhaps could apply to other things, proteins/peptides, etc

Gene therapy to gene doping -    non-therapeutic use of genes, genet elements, and/or cells that have capacity to enhance -    muscular, anaemia, pain relief

alternative testing strategy -    surrogate marker approach (biomarker)

cell tissue, organ, organism -    complete ensable of biomolecules -    reflects influecnes of t enviro introduce exogenous substance

biomarkers -    transcripts -    proteins -    metabolites

transcriptomics vs proteomics

transcrcipts (mRNA) -    cellular material o    white blood cells o    urine epithelial cells -    differential gene expression -    complementary to proteomics

proteins -    serum/plasma -    secreted proteins -    includes PTM -    simpler assay -    sample stability?

Surrogate marker approach

Screening approaches

1.    pattern recog (uncharac markers) a.    transcriptomics i.    microarrays ii.    PCA, PC-DA b.    Proteomics i.    Gels, mass spectra ii.    ANNs (WADA Grant) – artif neural networks

2.    biomarkers assays (charac markers) a.    transcriptomics, proteomics b.    characterise proteins c.    development panel assays (multiplexing)

1.    pattern recog

sample prep is key- proteins in serum

Questions and Answers

Question: 4% cvould make world performance difference. Can array technology detect sorts of changes to give improvements of performance. Also legal issues – if athlete tested with array, about 36% of affeymetrix, not confident.

A: at proof of principle stage. Relies on probability

Proteomics J Yates, The Scripps Research Institute

Used for biol discovery

Ideas have been to apply technology to understand how proteins come together

Achieve total protein charcaterisation

Driven by mass spec

Single protein vs shotgun proteomics

Quantification

Global method: Would not stand up in court of law

Questions and Answers

Question: mentioned 20-30% SD, how about if shipped around world?

A: 20-30 is within sample.

Question: what preventive measures to keep stable.

Question; had possible to look at disease or treatment?

A: if biomarker, than one that shows dramatic. PSA doesn’t show much variation across sick and normal.

Question: Haima – not easy to detect in mass spec because some proetins don’t fly very well

A: at peptide level are problems

Proteomics as a tool to tdetect gene doping: intro to protein profiling C C King, San Diego, UoCalif, dept of pediatrics

How can embryonic SCs be used for …

Proteome complete set of proteins in a defined cell type, their relative quantitiates…

Outline -    2D electrophoresis: analysis and pitfalls -    establishing positional databases of proteins for analywsis -    frcaction -    applics for wada

2D gel electrophoresis -    few do this, since pattern recog alone does not give much diagnostic information -    but does offer possible to analyse specific proteins

coffee

Research Report on studies Geoff Goldspink

Exercise -    knee extensor weightlifting exercise -    3 sessions per week

using muscle biopsy

with elderley people

if give growth hormone and then exercise, leads to substantial inc in MGF -    related to inc in cross-sectional area of muscle fibres -    these old people are hormone deficient (drop by 2/3 from teenage to 70+)

relationship between MGF and muscle

studied young people next -    n16 -    give growth hormone, then 4 week washout, then placebo -    take biopsies before and at wk2 and wk8 with blood samples -    untrained indviduals

repeated with trained athletes -    blood levs went up considerably

been taking muscle cells in culture and putting serum on them

use muscle cells in culture

IGF-1 gene transfer

3 Different types of IGF-1 in muscle tissue

actually 6 types (2 classes of 3)

with placebo, inc in class 2 with Gh wen down

with MGF of Class 2,

can now purchase human muscle cells

with GH, get inc in Class II with MGF, mainly class 2

Class II MGF trascripts in cells treated w Human Serum Samples -    clear distinction

Present project with NHFL Newmarket and Nott Trent Uni -    human and murine serium samples for o    biosensor o    other markers o    proteomics – mass spec/neural network

Study 2 Trained Subjects Experimental protocol -    n15 -    from uni exercise science dept -    in training -    randomised o    GH + training o    or Placebo + training,

concern that they might be disqualified from sport

Currently collab

1.    mice receiveing hgh delivered using a mini osmotic pump

mass spec can distinguish

detection -    rapid screening using mass spec -    confirmatroy w o    antibody o    cell signalling using differential gene expression

present and future challenges in detecting enhacneing substances -    synthetic/recombinant analogues -    generic sbstances -    new methods of admin -    gene doping

providing we have good methods, it’s almost immaterial whether gene doping or not

Transcriptional and proteomic effects of IGF-1 Ted Friedmann

Does igf-1 casue sig molecular changes useful for detecion? -    changes? Basis for detection?

Model systems – in vitro and in vivo -    initial studies in in-bred mice – avoid problem of indivd variability, polymorphisms -    cultured murine and human muscle cells o    C2C12 o    Primary human muscle cell -    In vivo, IGF-treated mice o    Muscle, blood, urine, saliva, other organs

Exptl design – short term

I. transcriptional response to IGF-1 - microarray, affymetrix

candidate of genes that can be used to detct

approach to screening for IGF-1 -    identify genes most markedly regulated by IGF-1

Application of microarray technology for the detection of changes in gene expression after doping w recombinant human growth hormone Rene Stempfer…. Christa Nohammer

Goal: development of target dna microarray to identify specific change sin blood cell gene expression related to t admin of hgh

Present project -    feasibility study o    in vitro – different blood cells o    in vitro -  peripheral blood mononuclear cells

microarray procedure

Application of cellular chemistry and proetomic approaches to t detection of gene doping Jane roberts

Objectives -    identify and validate protein expression patterns (fingerprints) o    GH IGF-1 protein gene construct o    Mouse model o    Applic to humans y2-3

Yr1 -    show that genetic manipulation results in change in genetic fingerprint -    can detect w pattern recog

Doping analysis relevant for potential application to gene doping detection James Segura, Biomedical Research Park, PRBB, Barcelona

Oxymoron -    a thetorical figure in which an epigrammatic effect is created by t conjunction of incongrous or contradictory terms -    eg. Not-for-profit drugs; research and physician

detection of doping substacnes -    problem w substances identical to t endogenous ones (endogenous-like substances) is it possible to detect non-natural traits in natural substances?

Gene doping makes this problem harder

Peptide hormones

Indirect markers -    physiological effects -    popn studies: probability

direct markers -    subtle chemical difference between t admin drug and t natural hhormne produced by t b -    difficult to find direct markers

indirect dtection of GH

liver metabolism -    igf-1, igfbp-2 and 3, als

bone metab -    osteocalcine, p-III-p ; picp; ictp

gene expression of gh isoforms

need further verificaiton that change derives from gene therapy and not something else -    use non invasive imaging that shows expression in an unexpected tissue o    IMAGENE

A long way to go before detection

Potential for non-invasive imaging in anti-doping efforts Kurt Zinn

Outline -    background -    imaging -    potential -    points for consideratoin

potential imaging targets -    direct o    transferred genee o    products from gene -    indirect o    change in metab due to chronic exposure to transferred gene products o    changes in anatomy due to chronic exposure to transferredgene products o    inflamm arising from gene transfer or expresed gene product o    reporters of pathway activation

imaging modalities -    radioactive-based -    gamma-ray imaging -    posittron empission tomography -    xray computer tomography -    magnetic resonance imagine -    light-based imaging -    ultrasonography

imaging that maybe immediately applicable to gene doping

Roussel et al, Fig1, J app physio, 94, 1145-1152, 2003

Richardson et al Biochem Soc Trans, 30, 2002 232-237

Potential methods -    direct o    imaging gene transfer agent o    imaging protein gene product o    eg

meausrement of firefly gene for light if mouse produces light, then gene is being expressed

Imaging tc-99m-ad-luciferase

Particle goes to liver

Shows light ommision from liver of mouse

Questions and Answers

Lunch

Session 4

Tom murray

Screening a worry

Matt

T culture of sport Natural talent and effort Natural variation of talent is intrinsic to sport – if your body doesn’t fit, then do something else

New types of sport have developed that appreciate natural talents – where certain body types suit

Equal opportunities -    not part of culture of sport

cannot complain that

does not imply that sport activity is result of genetic lottery -    there is no genetic lottery, but evolution of natural talent combined with effort

fair chance – if different heights where height is relevant, then is unfair – so we divide in groups -    age differences, sex

limits of accessibility on fair innings argument

need sufficient number of competitors to make it worthwhile

natural variation –s mostly self-regulation

people w extreme gene mutations not become elite athletes

limits of genetic screening

gene doping for improvement talent and level of effort -    opening for fair innings – set up games where GM athletes complete, but should we?

The phenotype routlette -    natural phenotype is t result of a delicate balance in order to master o    genetic program o    epigenetic instabilities o    biological chance o    environmental challenges

for safety reasons -    major reason against -    keepin athletes healthy is difficult enough at such extremes of performance. With gene doping more complicated -    delivery, expression and safety -    protect athletes from their own winner instincts -    protect next generation from manipulating their health -    health expenss for sports moveement will likely sky rocket

if we assume safety? -    natural mutations have many advantages appreciated and accepted -    some can be screened for -    hwe, where draw line, w gene doping, one has to screeen for many genetic variants in order to meet t same requirement

snowballing inflation -

rules of fair play -    sport activities presume a pre-competition agreement about rules -    winning is essnetial but so is also fair play

fairness as equal opp not part of sport

as fair share of innings – part of sport with rough measures

as fair play – intrinsic

protecting privacy -    can we protect, with testing -    it can, if understand what privacy is all about -    often willing to give up privacy in certain conditions o    enjoying sport activities is one of those conditions

gene testing – includeed in rules of fair play -    accepted part of different practices -    research, medical treatment, sport activities -    need to regulate. How reliable? Who has access? How handle safely

yes to gene technology -    no to gene doping is consistent w a yes to medical treamtnet

aging of muscles problem – fear that cannot set limits -    distinc between gene transfer in care of patient, always balancing – benefits v risk -    patients are closely mointored to correct for unforeseen -    v different thing to do this on healthy people, where not monitoring closely

these questions not new, many drugs that used on old people that we would not use on younger

eg. Morphine good for people at end state, does not mean that give to anyone in pain

ethics and t challenge of t potential use of genetic technology in sport. Angela Schneider

Summary of effort, talent and fair play -    sport is rule governed -    action against rule is cheating -    should thre be a rule against – yes -    hwr, important practical and ethical problems

Winning the genetic lottery -    is it fair to compensate for those who have lost t genetic lottery from a sport perspective but still wish to compete in elite sport by enhazncing -    Hannson ‘why not allow gene doping’

Need to answer some important concepts

Contested distinctions -    natural and unnatural (artif) -    point of sport is to measure difference o    we have allow naturally differences to affect outcomes o    hwe, we wil not allow t potentially fairere gnetic equalization that would occur through enhancement. Do we have good grounds?

Ethical foundation -    preventing avoidable harm -    paternalism -    performance enhancement -    vision of sport and how gene doping fits within this context -    sport for humans not humans fro sport -    contested

do not design humans for sport

ME: but we do

Sport exhibits values -    leadership must choose which values -    eg. Equity of access; implications of genet therapy for those who currently live with disease or disability; specific sport oriented issues

Laser eye surgery -    language is intructive – if describe as removing normal variation, status as enhancement clear. But if removing abnormalities, more like correction

LASIK -    used in some sports. Should it be? -    Enhances

Comparison w rules against doping -    one point of rules is to limit risk -    risk of laser eye, 5-10%, possible risk -    how much risk is too much? -    Not clear why sport should accept any degre of risk for beyond performance – ie enhancement -    Most relevant value is definition of health

Consistency and credibility of rules In anti-doping have analogous substances

Principle at stake

Distinction between enhancement and repair -    restorative and addtive distinction (fost)

repair is unprobc

incidental improvement -    Tommy John elbow injjury – generalyl accepted

Surgery in absense of defect is enhancement

But Tiger Woods – laser eye

Laser correction public use now

Not like cheating in way that steroid use is

Practice doesn’t cause sufficient harm But this sets bar high

Things that are acceptable elsewhere, not aceptable elsewhere

What do with grey zones? -    arbitrary, but

with strict liability

privacy issues and access to genetic information -    genetic information especially private -    indicative of identities in special way -    puzzle – genetic make up not indicative

social question -    maintaining privacy of personal genetic information  vs potential role of sport community becoming wedge used to derive greater geneal

wituhout moral support, sport will not be able to preserve humanizing influecnce s if sport recognises and re

genetic modification and improving humans -    enhancement

sport conflronst problems

if sport faces problems

who decides?

Sport is leading by saying we will regulate

Ethics, enhancement and sport Tom Murray

Meaning of soprt as a human activity: why the world loves the olympic games

Excellence in sport as expression of -    natural talents -    virtuous perfection of those talents

Aristotle – eudamonia -    full good natual ilfe

there are unvirtuous ways of getting these

objections to doping control in sport -    claim of incoherency -    line drawing problem -    resistance Is futile -    appeal to individual liberty -    romantic/promethean view

ME: but this ignores game theory. It’s not about the rules. It’s about the intended test.

incoherency claim -    no cnpcetual ethical or practical distinction among different means of enhancement sport performance o    the marathoner’s shoes

response -    hypothetical

Line Drawing problem -    all possible lines are arbitary -    aribtrariness is fatal flaw

conflates two meaning of arbitrary -    as unprincipled, indefensible -    as reasonable response when o    drawing SOME line is defensible o    placing line IN THIS PLACE likewise

athletic virtues – fast.

Why 5 players Why not 50 players, look like rugby -    ME: not really. Dimensions of playing field,

But this would not have any of the characteristics of bball

Why draw in this place? -    why not 6 in team? Or 4? No 1 on 1

would not have a game of bball

ME: tom is not distinguishing different kinds of rules – he is talking about constitute rules, not regulative rules

Resistance is Futile -    not a first-order ethical claim -    primarily two empirical predictions o    control will be impossible o    bad conseques ensue -    control is never perfect -    depends upon o    public consensus o    effetive enforcement

ME: he is now switching to regulative rules

ME: breaking some rules is not bad in intelf

there are silly rules – prohibition in us

So must have a public consensus in support of rules

In sport, if ban certain things but do not enfocre

Argument from Individual Liberty

Presumption in favour of liberty Paternalism difficult to defend w adult athletes Hasting Center project -    coercive impact of drugs in sport: the unlevel field

doping control done well provides level playing field

argument from liberty fails to

romantic/promethean view -    humans as self-creators -    understand cultural and philosophical context and implications -    valorizes unfettered will and self-manipulation -    relation to human flourishing? -    Case of anorexia o    ‘anorexia is t cultivation of a specific image as an image – it is purely artficial rceation and that is why it is so admired. Will alone produces it and maintains against considerable odds’ noelle casky, 2003, 129

Triump of Performance Principle -    max performance by any means at any cost -    power lifting: drug free and? -    Unavoidable conseq of refusing to set limits o    Greatly increased risk    rules governing a practice not equal indefensible parternalism -    Threat to spirit of sport

No longer throw people to lions

ME: so the level of risk in sports is just right?

Ethics of enhancement in context -    non-trembling neurosurgeon -    point of practice: spirit of sport -    not t means per se, rather their relationship to t goals of t practice, values and human flourishing

imagine drug with no side effect

imagine drug diminishes hand tremour and neurosurgeons see benefit

let’s also assume that mperson you love most in world needs operation

2 surgeons, one says biomedical enhancement always ethically wrong, never use tremour reducing, and second says, I use it all the time

you would choose one w best results

first surgeon missed practice of surgery

point of sport is natural excellence

point of surgery is to make well

different kinds of human activity calls for different kinds of rules -    partic to circum of relevance

not bad to prevent muscle wasting , but still suspect as use in sport

because of goals and values of practice

challenge of genetic enhancement in sport

what do we value in sport? -    natural talents -    virtuous perfection of talents

what do we disvlaue -    distortion of relationship between natural talent, virtue

what makes a talent natural?

Complex phenotypes -    genome as ecosyst o    genes interact complexly w each other genes, w external environment -    genetic difference in general not rigidly determinative for human behaviour o    see behavioural genetics report at hastings center website

child who has been engineered prenatally, natural?

ME: ecosyst argument – just a complexity argument?

Differences in natural talents? -    as vicious inequalities to be redressed? 1.    Vonnegut’s ‘handicapper general’ •    Disable smart -    As expression of human of human variaton to be celebrated? -    Olympic movement opts for t latter? 1.    Alternative romantic/promtehan, triumph of performance principle

ME

Final session

Jacque Rogge

Test to check for drugs for neurosurgeon

Need clear rules for world of sport

Fairness – but is life fair?

Sport is arbitrary in some ways

Can this be accepted?

Is it fair that kenyan athlete born at 2000m of altitutde has special diet, runs 10km twice a day? Fair to compare with swedish athlete

Laser eye surgery, but would any physician accept to do that? Any ethical physician would refuse operation without pathology

Look at high-jumpers

Achilles tendon most fragile for fosbury

If in 10-15yrs, cell therapy to heal tendon and grow by 10% more and allow better training, forbid? – yes it should, but I need advice.

Paternalism -    we cannot have been told to decide for -    gov put strong warnings on sale of tobacco. But athletes do not know what is dangerous for their health.

Basis of beliefs

850million people practcising sport, 750million recreational

every recreational is competing with self

only 150million in sports contest

we believe that this pyramid provides great educational tool, for body and mind

sport taches social sskills- achieve more in a team, than alone

respct sport, respect society

sport integrates

sport brings health

sport shapes identity

we know life and soc is unfair, but social value of hierarchy – doping destroys ranking system

we believe that protect health, even if paternalism

believe in one example – that fight against doping is important for keeping explemar of sport

different between nature and nurture -    virtuous perfection is essence of sport -    everyone wants to reach limits – leaves sense of accomplishment -    important anser against existential fear that everyone has – who am i?

recruitment -    social aspect -    champion is admired -    not everyone born with talents, but way athlete behaves and lead life is important to protect. Genetic doping would destroy

doping rules are imperect

compensation theory -    compensate up to normal level, but then are cheating, but allowing less effort athlete to be compensated, then penalising the champion

my plea is please give us clear rules – must be crystal clear

enhancement not be allowed

where draw line must be done with ethicists and scientists

Stockholm Declaration Arne Ljungqvist

Composed of olivier, ted, and arne

Today, several human genetic diseaes can be succesffuly reated by gene transfer Gene transfer is still a very immature and it is still an exptl field of human medicine

Challenge?

Change serveal to  ‘a few’

Extensive and rigorous regulatory mechanisms need to ensure safety of research subjects and patients

Gene transfer procedures must -    follow code and principles of human exptn and clinical research -    be performed strictly in accord w local and national rules and regulations for gene transfer in clinical research

Comment: these are more general reseacrh

Tom: human beings?

Lee: clinical trials

Tom: clinical research aimed at dealing with human disease, but some of this will not be about disease. ‘Follow codes and principals governing research to human subjects’

Matt: follows nuremberg, etc

Tom: these are minimal conditions, we can elaborate

Lack of compliane w standards an rules of gene trasnfer procedures must be considered as medical malpractice and/or professional mis-conduct

Development appropriate sanction mechanism for illegal application of gene transfer in sport

Gary: who will develop?

Comment: since no legal, ma

Maybe unethical or illicit

Illegal implies court of law

Unethical and/or illegal

Promote public discussion issues on THE PROSPECT OF gene based enhancement and develop education progrms

Be developed

Comment: this implies it exists

Olivier: can argue this in animal models

Odiele: reservations, since education can be spreading

scientficic progress made through resarch projects supported by WADA and others suggest that new detecion and screening methods are likely to emerge in t near future, which will help to keep sport untainted by gene based doping methods

Cell doping? It is covered if we move entirely towards gene.

Delete ‘near’?

Lee: must emphasise need for research

Support research programs instituted by WADA and other anti-doping organizations

Comment: ‘should be supported’ at end remove support

academic and private research organizations to dedicate resources to further progress in gene doping research should be encouraged

Larry: deter, not just detect – progress to ‘deter’ gene doping

Gary:  government?

Academic, government and private research

Genetic and denomic charcaterisation of athletes to determine genetic traits is contrary to the principles of sport

Rogge: contradiction with screening

Odiele: when speak of genetic trait, must speak of interited trait

Dave: might be reasons to screen for genetic traits in medicine

Tom: say something about unwise nature, but not sure contrary to principles of sport. Not because against principle of sport, but because of potential harm

Lee: must specify athletic traits, not genetic

Ted: not determination of trait, but use of it to exclude. Ie. To determine eligibility

Peter Fricker: this research has been done. Issue here is about discrimination. Need to look at genes and risk of illness.

Tom: use of genetic information about putative athletic ability to discriminate against athlete, should be strongly discouraged.

Add to ‘select’ or discriminate

Peter: must allow ethical reseearch must proceed to validate role of genetic information

Enhance awareness of potentiall illicit use of gene transfer techniques in sport

Promote knowledge on medical and physical dangers associated with gene doping

Odiele: woiuld we like to put forward idea that there are dangers?

Olivier: dangers alone?

Odiele: why not ‘misuse of gene transfer’

Olivier: risks or dangers?

How about potential risks?

Olivier Rabin

ME: why not inter-governmental rules and regulations? As well as local and national

Mitochondrial Disease Research: Social and Ethical Considerations (2005)

Mitochondrial Disease Research:Social and Ethical Considerations

Workshop at Lancaster University, October 28-29, 2005 sponsored by The Wellcome Trust

Friday 28th October 2005

1p.m. to 2 p.m.  Lunch: Conference Centre

2 p.m.  Welcome by Ruth Chadwick, Lancaster University, Director of the Centre for Economic and Social Aspects of Genomics (CESAGen)

Eumitocombat

Rationale treatment strats combating mito oxidative phosphorylation (OXPHOROS) disorders

www.eumitocombat.org

obj

charac genes and proeins involves in formation and reg

SEAC

Carlos, Ruth, Bert, Henk, Ysbrand Poortman, Urban Wiesing

Another euro project separate from this (more reprod than disease)

First Session:  Chair:  Carlos Alonso Bedate,  Madrid

2.15 p.m.  Peter Whittaker, CESAGen, Lancaster University. Mitochondria: structure, function and assembly.

Mito have a critical function in all cells T mechs for carrying out this function are extremely  complex T process for assembling mitochondria is also v complex There are many things that might go wrong If something goes wrong, t effects seen in all organs and systs

What are Mito

Organelees found in cells (other than bacteria) whose primary role is t formation of ATP (adenosine triphosphate)

Mito use t energy madde availale in t breakdown of foodstuffs to make ATP – oxidative phosophorylation (OSphos)

Importance of ATP energy of cell movement synthesis of complex molecules transport of material into and out of cells and within cells

What else do mito do? help regulate cytoplasmic calcium levels – important for control sev cellular activities important role in apoptosis

how do mito make atop?

- 2 stages

Protoon motive force -    drive atp synthesis

synth of atp -    proton motive force now provs t en for t enzyme complex ATP synthase to bring about t synth of ATP

2.4 – dinitrophenol (DNP)

in us was used as a drug for slimming, which led to eye problems too

re-appared in 1990s as slimming divice for body builders

Sean Zhang, 24, of Bloomington

If look for this on internet, still offered for sale in body building sites

Division of mitochondria (assembly)

(mito are scaled down bacteria)

mitochondrial dna looks v much like bacterial dna

they have ribosomes, different from regular, protein making ones – more like bac

mitochondrial rna and protein synth -    mito make rna copies of t genes on t mito dna and these are translated to give proteins on special mitol ribosomes. Most of these are delivered to t inner membrane as parts of t OxPhos syst

a lot can go wrong in the functioning and assembly of mito

Muscle mito from mitol disease patient

Question&A

Question: neurological dysfunction?

Turnbull: not clear.

Blue: but the debilitating effects are precursor to psych cond

Mark: does it spread

Turnbull:  some segregation;

Donald: function of energy production main or only function?

Peter: main, but not only critical function

Donald: diotriphenol, where originate?

Peter: synthetic. Tried as possible uncoupler, use of slimming aid was before observation of coupling.

Donald: not naturally occurring product in body

Doug: are now natural uncoupling proteins in the body, linked to energy metabolism, eg, in brown fat, requires uncoupling

Donald: these are nuclear?

Doug: yes, and protein specific

Donald: mito performance radically affected by hings going on around

Doug: 2,00 proteins in mito, only 30 by XXX;

Bert: agreed upon classif of mito diseases? If so, basis? Genetic defect or clnical?

Doug: no, because of complic of new diseases and complexity of mito genome. There are consensus genome classifs.

3.00 p.m.  Doug Turnbull, Mitochondrial Research Group, Newcastle University Reproductive options for women with mitochondrial DNA disease

Clinical features and reproductive options for mitochondrial dna disease

Defects of mito genome -    need to be clear on perspective -    majority of adult patients with mito disease seem to have primary mutations in genome, rather than nuclear genetic mutations

problem majority of mito diseases due to nuclear genetic mutations -    one or two nuclear are v common among certain populations

nuclear mutations might affect mito dna or can affect nuceucide metab

nuclear make up bulk of resp chain individual components mito replic and repair

nucleus dominates mito

no evidence that mito feedbacks to nucleus- perhaps switches on transcription factors

NOT TALK ABOUT NUCLEAR

Focus on mito disorder

Mito dna is tiny piece, 16,500 basis (32 rows on sequence); not a big task to sequence

Human mtDNA -    located ONLY in mitol matrix -    circular genoome w short non-coding region (Dloop) -    multiple copies in single cells approx 700 in fibroblasts to >200,000 in mammalian oocytes -    maternally inherited o    important in charting evol of species. Eve of Africa based on mito dna patterns; o    until 1988 when first diseases found, already used for evol studs -    genetics of populatins -    no redundancy of dna (introns) in mito genome. Very compact full of genes -    unusual piece of dna

as clinicians/scientists, need to think differently from other diseases, such as huntingtons, duchennes,etc

Human mtDNA -    >50 different mt DNA point muitations -    100 different deletions -    are some common mutations, but mostly irregular – throughout genome

Mito genetics different nucl gen

Homoplasmic wild-type HETEROPLASMIC – most patients w mt dna mut have normal mix Homoplasmic mutant – in some w mt dna mutations, all copies abnormal

Heteroplasmy -    link between mutation patient -    wild-type phenotype o    scientists name for normal -    mutant phenotype o    symptoms occur only when large amount of mutant dna o    many people can be perfectly fine w low level •    mother could have low, child could have high

influ of mt dna

if mutation in genome, affects respiratory chain produces all kinds of disease

Non-neuro -    resp failure -    cardiomy -    liv failure -    shortstature, marrow failure -    diabetes -    thyroid

Neuro (any bit of neurosystem affected) -    optic atrophy, -    CVA, eixure -    Deafness -    Peripheral neuro

CLiniacal mito disease “may affect patients of any age and any tissue of t body”

Adult mito disease Neurol – migraine, strokes, epilepsy, dementia, myopathy, perio, neuro, dip

Acute medicine - seizures and stroke - increasing coma

Cardiology - quite a few myopathies - heart gets big, or abnormal beats - common problem

Gastroen - smooth muscle of gut affected

neurol - drooping of eyelid - not turning eyes properly - involuntary movement (posture) affects all muscles

how patients felt about it - when made diagnosis, was not only affected familymember - investigated family members - in family, aunt has diabetes and eafness, other aunt has cognitive impairment, nephew at 9yrs old first stroke like episode – remarkable variation in family - can we understand anything by looking at family?

Can we understand anything about nature of sisters - each have different conditions or none - look at lev of mutant acquired from mother, does it correlate w clinical symptoms? -  normal – nearly no - second sister 30-40% - most affected sister 80%

important to know when advising on reproductive options….

Patients with high levels of mutations have most disease

Mt DNA disorders

Clinically affected 9.18 (141) – 1 in 10,000 affected At risk 16.49 (335) Total: 25.67 (476) – 25 per 100,000 affected

Newcastle - not much movement of popn within Newcastle)

Looked at all patients that have been referred to us

Common for a genetic disease

Reproductive options fro women w mtDNA mutations

How do we treat patients with mtDNA mut?

We are a long way from this. No drugs in double blind clin trials that

Patrick Chinery

V little drug trial info - part due to clinical heterogeneity

if inherit, how likely to find agent that would help?

While cant cure, we can do a lot to help - Eg. Treat cardiac, diabetes, etc

women were requesting info on reprod options

MtDNA disease

Approx 4.5 per 100,000 clinically affected females (Caucasian popn in uk) Approx 8 per 100,000 at risk females (adult females due to cohort) Counselling and options for 13 per 100,000 females or 6500 females in uk (not neces’y that thes people are wanting children)

Mito DNA Diease -    mt DNA diease is maternally inheritated o    a margin of dount. One single case that questions. •    ME: more info -    MtDNA mutations may be homoplasmic or hetero -    Htero -    Bottleck important for hetero mtdna disorders

Egs

Homoplasmic mutations C1624T in mt-trnavl

Genome sequencing Mt tRNAVal

All children of Sharon have same mt mutation

Why Sharon is unaffected, we do not know.

Heteroplasmic 3243A>G -    commonest mt mutatin in uk -    woman 2 children

bottleneck -    suppose mother had 50% mt molecules -    what happens in development of primary oocyte -    molecules go down to tiny number (bottleneck) -    then expands again -    bottleneck seems reasonable hypothesis for why, if go down to small, then when expands can lead to more affected

it happens in real terms mother 36% son 95% daughter 0% undetectable

13513 G>A ND5

45% 13513G>A mother, normal, 3 pregnancies, still birth, child dying shortly after birth 85% 13513 G>A (third child) since then, child has died

mother has been incredibly unlucky, or perhaps in some mutations it is forcing to mutant form. We don’t know why all 3 affected given mothers stats

What can be done? -    counselling – limited knowledge -    oocyte donation – limited availability, not own o    sensible options, since would be normal mito o    few taken up ption, due to limited availability, need non-maternal friend; also, mothers want to have their own children; for some, mothers reluctant, -    oocyte sampling -    chorionic villus sampling and amniocentesis – termination o    potentially harmful -    PGD o    Major possibility

Stages of oocyte maturation

No of mt genomes – 1milion

No effective mt replication during embryogenesis

Becoming diluted from 1million

Can look at embryo and transfer back to mother with less mutated mt dna

Current genetic techniques, relatively straight forward to do this rather than

Not much point in PGD for Sharon (homoplasmic)

So what else could we do?

Prevent transmission of t disease

Roberts RM (Prevention of n AM J Medicine Genetic 1997 -    technique will not work because no nucleus, no nucleus membraine -    not a practical soln, would have to stain chromosomes and would be worried about transferring chromes

sensible thing to do is at GV egg stage -    people have done GV transfers

there are ethical issues perhaps, but no legal

why don’t we do that? Because GV egg is v immature To get from GV to fertilised is different Chances of genetic transfer to fertilisation, v difficult, no successful examples

If cant do it at different stages, why not at the Fertilised Oocte stage

Laurance Smith – in mice -    taken two strains of mice (inbred mice have v little mt difference) -    take out pronuclei and swap them over

transfer pronuclei

will it carry any mt?

yes, about 16%

when mice developed had between 10-37% in tissue

threshold for diease is over 50%

so in mouse expt, shown technique is feasible, can have live births of mice

Lawrence Smith – taken to 20 generations and no defect

Potentially valuable technique to stop transmission

No point in further animal work, since inherent difference between human and mouse oocytes and embryos

Press coverage Ethics of tabloid news!?

MTDNA

Applying for research license

Approx 2% of all uk ivf pregnancies are abnormal – 2 or 3 pronuclei - oocytes are not used

Tripronucleate zygotes

Take abnormally fertilised

Take out all pronuclei Transfer back 2 pronuclei into oocyye with different mt Make best use by doing reciprocal transfers

Then culturefor a couple of days, then embryo biopsy to conduct mito

Look at proportion of embryos developing to blastocyst

Look at cytogenetic, epigenetic, and mito dna analysis to see how much carried over

One of reasions for difficulty in obtaining license MT dna disorders

MTDNA

LREC (Local research ethics comm.) applic april 2005 HFEA applic license committee april – turned down HFEA appeal – rejected on same grounds HFEA authority itself sept 2005 -    employed barrister and solicitor to represent -    people writing letters to support -    5 members of authority listening to arguments vs legal expert from licensing -    challenged in high court by prolife -    act is being reviewed – asking for views on act -    gov guidelines are supportive

prob

HFEA - embryo is an egg undergoing fertilisation - “a licence under this paragraph cannot authorise alteration t genetic structure of any cell while it forms part of an embryo” (HFEA Act)

members of Committee - sharmila nebrajani -hossam abdalla - prof iain Cameron - rt rev Richard harries - Jennifer

Question&A

Doug: Warnock – act talks about genetic composition, and discuss genetic structure in relation to designer babies – this was their concern. Was not to stop research in this area. No actual prohibition about changing genetic omposition. Genetic structure not a defined . in 1989, were trying to stop characteristics of people, so that true designer babies. Warnock always in favour preventing dieases.

Peter: can you extrapolate from this to genetic modif on nucleus to prevent disease

Doug: we were not altering genetic structure – ie. Not cutting dna backbone when trying to correct nuclear gene, would have to cut backbone and insert dna . we are not doing that. Were trying to prevent disease, not changing characteristics of self. Like changing batteries in the radio.

Donald: making a value judgement.

Doug: we can transfer less mt

4.00 p.m.  Tea/Coffee

4.30 p.m  Jo Poulton, Nuffield Dept Obstetrics and Gynaecology, University of Oxford Does Genetic Counselling Help Families with mtDNA Disease?

Disagree with doug that nuclear mutation is going to be common

Clinician Started in field in 1986

What can a geneticist offer? Predict transmission risks based -    published cass -    pre-conception oocyte sampling prenatal diagnosis -    ? CVS- technical difficulties – might not be getting representative dose, or what a level of mutant is going to mean to a patient (thresholds) -    ? Pre-implantation diagnosis (trying to develop) Nuclear transplant on single cell embryos -    lots of biological questions The A3243G mutant load in blood declines over t time period between t 2 samples -    if sample heteroplasmic in blood at two different ties, level of mutant in blood can fall to 15% over 18 yrs -    counselling difficult, Chinnery Brain (1998) 121, 1889-1894 -    suppose woman 30% mutant, if met 18yrs later, would have halfed to 15%, so 25% recurrence risk -    difficult to counsel on basis of samples

why study germline segregation?

To help - need clear threshold - need criteria to ensure tha  sample would be representative

load of 9176 mutant mtDNA increases w severity - lev of mutant correlates w severity - lev in blood and other tissues similar - no sequential data to know – ie start with low to high

NOW NORMAL 3 YEAR OLD.

Refined genetic risk by samplinyg oocytes

No one in uk that have license to do it for patients

A3252G - Rory

what can we offer? - recurrance estimates? - not much info - Oocyte sampling? – possibly - oocyte donation? Availability?? Need donor. But all sisters could have been carrying variant - PGD - availability? - concordance testing > 2 blastomees (NOT JUST ONE) - low pregnancy rate: Mother 40y (do not take on over 35), D banked sperm - CVS - problem lack of info on threshold - No intervention

need to know what lev of mutant is below which might not have problems

nightmare to do CVS and having no idea about likelihood

PGD then CVS

Offered oocyte sampling, pgd, then cvs

Couple chose no intervention

Have we helped or hindered this family?

Mrs O: My opinion is that you must absolutely give people the choice

Nuclear transplant -    we must be allowed to research t interactions between mtDNA and t embryonic nucelus -    essential for understanding how mtDNA diseases o    are transmitted, cause disease -    mito abnorm likely to play role in infertility (male and female) and development anomalies -    too early toknow wether will be useable as therapy for patients with mtDNA

Sun, YH, Chen SP, Wang, YP .. Biol Reprod 2005; 72, 510-515 -    carp and goldfish -    cloned fish looked like carp -    nucleus not determining vertebrae -    in fish fertilised egg, enough cytoplasmic of rna to deterine

Question&A

Jo: batteries? Well, cytoplasm contains more

Doug: we want to transfer as little cytoplasm as possible. Mouse: Laurance Smith has done hemotyping of mice. Are they batteries?  Yes. Evidence that they are not batteries is flimsy.

Carlos: but if interacting with dna of nucleus, no evidence

Jo: mt dna must interact with…

?: question of donation. If do nuclear transplant, who?

Doug: presently, using 10%of IVF have abnormal embryos; using  these; many ivfs don’t put back normal embryos; would a mother be prepared to donate one of healthy embryos for treatment? No idea. Once people have gone through ivf, there are many that are not transferred.

Donald: not many.

?: can we freeze them?

Jo: stem cells – unfertilised egg, donor nuclei; stem cells for treat disease, could use to put into mt; expts on this could tell us a lot about early development and help focus what expts we do;

?: big demand on these embryos

Doug: consent procedure – funded by MRC – Alison Murdoch. Question is availability of oocytes.

5.00 – 6.00 p.m.  General Discussion.  Chair: Bert Gordijn, Nijmegen

Bert: study is complex; interactions are numerous. Many things can go wrong. Clinical manifestations highly varied. Disease classifications still being discussed. Treatment possibilities are v limited. Social ethical issues needs classification.

Trichotomy -    in-vitro -    animal research -    clinical trials -    clinical practice

state of the art of these different contexts

in-vitro -    can take from patients and look at cells -    take cells from patients and grow cells and look at effects on cells -    or make cells cybrids -    now looking at pluripotent cells -    ethical question: o    best way is using SL lines. o    Currently using embtyonic carconoma, but not as pluripotent as other cells o    Issues is not around these expts but using human ES cells -    In-vitro do not draw out unique ethical issues

Mark: issues with how HFEA – problem of foreseeability – science canot tell us what is trying to do

Peter: problems with taking biopsies from patients who are somewhat handicapped already?

Doug: Koreans are setting up centres around the world to do this, for motor neuron, or other

Carlos: problem is that cells do not have the disease. May analyse and find biochemical alterations, but this says nothing about phenotype. Phenotypic. This is why need to do expt in humans. Animal models are not going to help.

Doug: this is what we normally do: we have clinical trials.

Animal Research

Jo: people are trying to make mouse models of mito disease, but v difficult. Some given up. Where nuclear gene mutation, mutate mouse then clone out offspring. Japanese have mouse model.

Doug: model never been shared outside of Japan. No pathogenic that have been passed through germline.

Jo: if we can get decent animal models that is very good.

Doug: animal models would be helpful.

Kevin: other animals

Doug: mouse useful for trying treatments, but not for understanding how it would work in humans. Are free radicals ,…..

Clinical Trials

Doug: recent review of published clin trials on mt disease. There is a Cockran collaboration – visual way of assessing clinical trials. Despite fact that diseases wellknown, limited number that are accepted by Cockran. Still only a few number of patients.  For most of diseases, have around 40 people. Not large scale. How assess benefit of any agent. Is benefit because of treatment? Need clinical end points. No good rating scale for mt disease.

Special ethical trials?

Peter: maybe go back to animal trials. Do we need to return?

Doug: people are looking at effects of antioxidants on animal models. If one of antoxidents proves to be good, we still need to trial in humans.

Dog: Exercise might change mt genotype

Ruth: how?

Doug: when you exercise, you increase no. of mt. if looking at muscle when exercising, does it change proportion of wild-type to mutant? Might be able to change mt genotype by ex? Strength training – destroy muscle fibre, and stem cell grows in.  stem cells have low levels of mutation. Change in mt genotype. If we can think of an agent to bring about controlled destruction, might be able to do something.

How high a proportion of

ME: does this alter on trained or untrained?

Doug: if controse muscles in controlled way and let stem cells grow in, could be a treatment.

Jo: stem cell therapy overhyped.

Doug: more sensible to use exogenous stem cells.

Mark: similarity between mt dna

?: patient organisation

Doug: difficult problem in mtl disease. Big part is caring and sharing exp. Duchenne has similar course in many of children affected. For mtDNA, totally varied. Makes it harder to generate community. Limited develop of patient organisations. To do this properly, requires great amount of …. Problem of giving wrong information. If people just don’t understand that this varies so much, then can misinform. In US, is United MT Organisation – for parents.  Has been putting money into research. Mt disease is oft misdiagnosed, so many people go to meeting who do not have the condition. In US, has been big expansion of mt research w little clinical imput. Europe is stronger due to org of health care syst.  Not been a development of good parent patient org.

ME: because of nature of this condition, does this mean that counselling is more important.  If so, how does this inform the counselling process?

Doug: if you go on internet to find mt disease

Doug: considerable under diagnosis

ME: does this radically transform the estimated

Ubiquinone

Little evidence that you get super mitochondria -    endurance athletes – needs more studies

ME: are some batteries better than others?

Genetically influencing by using third source?

Influencing disease likelihood

7.30 p.m. Dinner in Lancaster House Hotel.

Saturday 29th October 2005

Second Session: Chair: Doug Turnbull, Newcastle

9.15 a.m.  Carlos Alonso Bedate, Universidad Autónoma de Madrid, Spain. Handling of complex diseases. An ethical and social viewpoint.

What does it mean to be complex?

If concept not well defined, can be abused. This is partic true of complexity, a concept that has penetrated a range of intelligence fields from physicas, biomed to linguistics Complexity has become a popular word that in many cases is ambiguous Complex is not similar to complicated or multiple A syst if called complex when emerges from the interaction of multiple factors and it can only be explained by that interaction (The bigger picture, tamas vicsek, july 2002)

analysis of t simple or complex - who can tell from studying single or sev neurons what laws describe intricate flow patterns of electrical activ produced by brain? Reason is that randomness and determinism are both relevant to t systs overall behjav Identical systs may exhibit almost regular behav (determ) but because they exist on edge of chaos, can also change dramatically as a result of small changes in conds

Because of Epigenesis: impossible to predict which alternative pathway will be used in a partic case but by analysis of syst possible to determine potential for adaptive change under precisely defined intial conditions It would be possible to alter

Complex systsm in physics, - knowledge of elementary particles for interpreting behav on larger scales because each new lev or scale is charac by new, emergent laws that govern it - t behav of t complex cannot be explained by t sum of t behaviour of each element taking indep - t complex phenotype is nothing more than t sum of t elements of t path but something else (health or disease)

In a new context - disease or health understood as a complex system that emerges from t interaction of simple elements that disrupt t homeostasis of t whole (disease) or maintains homeostatis (health) - in some way then t resulting phenomenon (disease or health) is an epiphenomenon

In many cases treatment (Symptomatic treat) of epiphenomena (disease ) is not going to restore t homeostasis unless we remove t insult BEFORE disruption of homeostatis or by altering some elements of the path - even in that case: the organism wil be able to heal himself only is t insult is limited and no pathogenesis occurred

the crucial thing is to understand t rules and to know t simple elements hat disrupt homeostasis - nin this view early diagosis and treatment critical

at present biomed sci are based mostly on genetic paradigm commited to idea that major diseases will be diagnosed and treated through genee technology because t disease results from genetic changes in thje key ‘rate-controlling enczyme or signal

this approach is, in theorty, applicable to true monogenic diseases only about 1.5% of total disease load

we are told to enter a new golden period of medical discovery

but since a change in evniro may alter t final phenotype it is becoming clear that geneticc analysis in itself will not serve to predict diagnos or treat disease like polygeneic cancer , or hypertension or other complex human complex multifactorial disease

medical research todat dominated by genome-centred view. Clnical discovery and patient-oriented research less common

Jonathan Res

The assumptions of tradl molecular medicine summarised as follows

Assumption has been a paradtim in

- medical genetics - molecular boil - development boil

Brenner and Wilkins, the uniqueness assumption of genetic determ

Unique genes – unique effects

Is undermined by an emerging body of evidence showing functional informational redundancy in cell regulation

1. more than one gene may specify any given function

2. single gene may specify more than one function

Drosophilia (Pumilio) bind to hunchback – induce patterning bind to Ciclin B – remain pole cells

identical genes have opposite effects on germ cell survival when expressed in t germline and soma

it is proposed that germ cell survival is controlled through comp between somatic and germ cell cWunens for an extracellular lipid phosphate

Renault et al. science, 2004, sept 24; 305 (5692): 1963-6 Epub, 2004, Aug 26

Disease

4 modes of activity that are operative 1. monogenic 2. polygenic 3. epigenetic 4. epigenesic –

conclusion -    genetic pathways specify organismal fns only in rare casese (monogenic diseases) where mutation produces dysfunction in a protein of crucial importance. In these rare cases t cell

identical genotpes may produce different phenotypes different genotypes may result in identical phenotypes

Hsp70, 83 and 90 proteins are crucial to maintain homeostasis ion perturbed conditions even in t presence of gene muitations that induce abnormal phenotypes

When t conditions are severly peru drosophilia -    stress to flies leads to different phenotypes among population -    this transferred to subsequent generations

Importance for clnical assays

1.    different genotypes bay be hidden in an homogenous popn: genotypic variation does not neces’y lead to phenogypic varation 2.    t enviro may modulate t effect of a therapy

t mapping of genotypes into phenotypes in one enviro is often completely unpredictable from their mapping in another enviro (Lewontin and Goss, 2004)

The results of a therapy in one enviro could not correlate w its effect in another

what we thought was homogenous popn was NOT

ME: does this bring into question other medical developments we currently accept

medicine research has grown as never before:

we have solved t easy problems we need new post-genomic stratic procedures to solve ‘complex disease’ can these strats be based on DNA or proteomic analysis ? – no

are these thoughts relevant for mt Diseases? -    yes o    no lineal relationship between disorder and phenotype o    no lineal inheritance -    2. Mt disease are rare

1.25% of all genetic disorders may derive from t mtl genome

-    BUT THIS IS A LOW estimate

My proposal

1.    careful mt control analysis 2.    carry out controlled transnational clinical trials used commonly used pharmaceuticals in a.    Patients w clinical mt diseases b.    In defined genetically diagnosd asymptomatic patients

All proposals raise ethical issues

Harmonization requires -    common guideline at international level for transfer of data and boil materials, sharing of biological samples, unified conditions for sample preparation and management; sharing of personal and clnical data -    open and transparent comm. Between researchers and clinicians regarding clinical and research data and their publication; start from simple and go to complex -    estabb unified protocols for transnaitional trials -    estab criteria for quality assessment and consistency -    estab scientific and ethical review boards -    admin, political and ethical consensus

ME: what bodies would you see as bringing about this consensus?

Adequate and fair human subjects selection

Prior decisions

Registration of boil materials to be used -    who is going to register t material to be used? -    Is there going to be a centralised site? A biobank? -    Unified procedures? -    Use of human biological material o    By partners only? o    Other labs outside of program? o    Who is going to control mamangement of material and exchange of this material? o    How? -    Data management – will data be open? -    Anonymous linked or/and unliked from beginnings (Pros and cons) -    Data anonymous to lab doing analysis (pros and cons) -    Each lab maintain code of their own data? (pros cons) -    Who is going to control exchange of material and how? -    Who wil correlate t data obtained w patient -    Favourable risk-benefit ratio

Questions and Answers

Carlos: 40% of genes do not have function- redundancy. PKU. Function of gene supplied by another gene.

Donald: not looking at specific effect

Carlos: yes, no specific effect. But not completely true, since with knockout mice, if infect mice, will get tremendous infection – even though not clear phenotype, not

Beard: Richard Strobeman, common conditions such as asthma, where issues about enviro factors where are then larger scale issues on public health. Where focus limited resources to control incidents of conditions.

Carlos: disease found in the phenome. Most of common diseases enviro.

Celia: what is environment?

Carlos: v grey area. Concentrate on internal factors, such as stress for metabolism. If have cells from PKU. If culture cells at 37% different from at 25%. At 37% will produce HSP, 90, 70, etc which creates correct enzyme.

Peter: need individualised medicine, ie for privileged?

Carlos: perhaps not. Perhaps common elements.

Doug: much of what you have proposed is sensible. Over last 4 yrs, EU has successfully funded two aspects of work you discuss – EUMITOCOMBAT – develop database.  Funding of clinical trials is incredibly expensive. And if most tend to be either MRC funded or EU, or many are drug companies – many of organisations are out of license. Need mechanism to fund activity, which is v expensive.

Carlos: if we don’t do this, forget about treating mt disease.

Doug: yes, but we need political will to allow us to do it.

Carlos: from Chinnery ‘ a deep understanding of t pathological….’

Doug: political side needs considerable financial input

10.00 a.m.  Ruth Chadwick, CESAGen, Lancaster University. Mitochondrial exceptionalism?

Genetic exceptionalism -    Genetic info demands special protection (cambon Thomsen et al) -    T ethical issues in genetics are different explained in relation to features of the differences) o    Nature of t info o    Predictive o    Time-indep o    Shared w blood relatives -    These critier have been advanced to support idea that is special -    But has been criticised – these features not specific to genetics -    Another version – weaker – is that has been perceived as different -    If we look at these criteria in relationship to mt, is complicated o    No time independence – relevant info can change w time o    Extent to which is predictive is v complicated o    Shared with blood relatives is v complicated

Genomic exceptionalism (look at extent to which featrures of susceptibility testing are different from genetic testing as conventionally understood) -    dhuman genome project and after o    SNPS o    Susceptibility testing o    Pharmacogenetics and nutrigenetis o    Pharmaacogenetic exceptionalism •    Allan Rose claims is much less sensitive than other genetic, because to tell someone ‘you should not take that drug’ is different from saying ‘you have a predisposition to…’

In mt genome, not a big discussion about that as there was for HGP, exception for HGDP.

In context of medicine, not same discussion about exceptionalism as there has been about gneomic and genetic

What are we looking for? -    potential conflicts of interests o    hallmark of ethical issue is conflict of interest, but ethics not reduced to this -    could be competing interests of different indivs or troups;; or different interests of t same indivs or groups o    each competing for same resource o    or different interests and cant both be satisfied, eg conflict between interest in getting some  benefit and not being harmed, cant have one without the other, need tradeoff -    vulnerabilities -    …and possible resolutions/processes of resolution

another way in which issues might be exceptional might not just be different conflicts of interest, but that require new ways of looking at problem or processes to deal with.

Prevailing individualism of tradl biomedical ethics not been adequate to deal with sorts of conflicts of interest coming up in genetics, partyl because of genetic exceptionalism because interests of people connected in specific ways. Need ethical frames that take into account these connections

In context of mt disease, ways in which interests of different family members are connected is particularly interesting, because even people with same mutation are affected differently

How are interests identified? -    Empirically o    Social science research identifying what people perceive as their interests -    Legally o    Eg. Hfea on what interests are to be protected as matter of law -    Conceptually o    What kind of being can be bearer of interest? o    Embryo, but also ‘interests’ of children as opposed to adults. L o    Logical questions of activity involve partic interests

Generic issues -    consent -    benefit sharing -    resources

Mitochondrial genome -    possible areas of exceptionalism o    nature of diseases o    research – process and implics o    diagnosis and treatment issues o    nuclear transplantation o    databases o    identity and difference o    ‘blaming it on the mother’ (gender issues)

Diseases -    OXPHOS disorders -    Assoc w diverse array of multisystem diseases – problem of variable expression – conceptual issues about how classify -    Rare – or not? -    mtDNA versus nuclear DNA involvement o    mutations in nuclear dna seems potential for massive confusion in terms of thinking about and understand the field

ME: what theory of normal underpins this classif?

Treatment strategies It is exceptional the treatment of mt disease, potential for cutting edge treatmetnts -    genetic strategies -    pharmaceutical strategies -    transplantation strategies -    germline gene therapy -    potential for novel therapies

what are t interests involved? -    what counts as success? -    Indicators – how determined?

Database issues -    different kinds of database involved: eg to facilitate associations (as in Mitokor database) o    PPP – Public Population Project in genomics. How facilitiate datasharing between biobanks in different countries. Includes debates about social/ethical o    Question for us is whether anything exceptional about mt database -    info databasese, publicly accessible o    purpose of database? To inform ,for consult?

Nuclear transplantation - HUGH Ethics Committee recognised mt diseae as an exception in 1999 - ‘given appropriate technology t avoidance of disease by…nuclear transfer may be supported provided that it is certain that a disease is caused by an error in the mt (non-nuclear) DNA’ - interesting to hear about problem of ‘where is the nuclear’. Although jo was talking about nuclear

this year, another statement on stem cells, currently considering amendment to that to deal with mt disease, but no work done on it yet.

Identity and difference -    role of mt dna in identity o    human diversity o    ancestry tracing -    what makes me me or a child one’s own? -    Difference o    Identical twins vs reproductive cloning

Yesterday, interest that Doug said about what makes children your own insofar as related to genes is nuclear dna that is important, rather than mt -    is important since mt dna inherited only from mother -    interesting to research people’s perceptions of that issue -    this is eg of exceptional mt dna has played important role in reproductive cloning debate because in somatic cell transfer (dolly) wasn’t exact copy of donor, because she had different mt dna -    important different between reproductive twins and reprod twins, commonly ignored. People oft say ‘its’ only same as identical twins’, but it isn’t

Gender -    mtl inheritance -    blame it on mother -    mother blaming self in terms of inheritance -    potential for confusions, since many diseases are nuclear rather than mt dna origin -    gender issues particularly interesting in this field -    whether people feel differently about them in relationship to other gen diseases would be interesting

Summary

What is Exceptional? -    complexity -    severity -    strategies -    symbolic importance o    identity and gender – meaning ascribed to mt dna, its role in either evol etc

Questions and Answers

Donald: why frame question as ‘exceptionalism’? can be a means of obscuring or dismissing. GM was seen as selective breeding early on. If GM crop product seemed to have no detectable difference, they were substantially equivalent. Only question is ‘is it different?’, but this obscures other issues. Why ‘excpeiotnalism’ rather than just ‘what issues does it raise’. Eg. Nanotechnology issues similar to other things, but let’s look at them anyway. Why start with exceptional case.

Ruth: I accept what you say. I don’t think identifying what is special about an area excludes looking at other aspects. At practical level, if want to research issues, need to estab what needs to be done.

Donald: question is research funding generated – show ‘we need to do this, because it’s different’

Ruth: would not have got funding if was nothing different about it. Approach includes presenting ‘what is special’ and ‘what is different’.

Doug: gender issue. I seee what happens to mothers who have children who die. Do they feel different from mothers of children who die from other genetic disease? I don’t know. A lot of mothers who feel tremendous guilt. Is it more, less, different?

Carlos: two cases in spain, tremendous depression because they know they have transmitted disease to children.

Doug: but is it different?

Celia: been talking to people going through PGD. True in general that women feel more guilt about children dying. Women take more responsibility. Patients make distinct between children they knew had genetic disease and future children. People that end up in pgd are people who would find prospect of same situation worrying

Doug: any difference between relative consequences of different genetic disease (autosomal or x linked)  for mothers

Celia:

Peter: mt might not be an exception

Celia: might make men feel different

Beard: comparative point. Charles Rosenberg – in 19th c, inheritance environment debate placyed completely different fashion – inheritance as a given – nothing for which you took responsibility. Samuel Smiles self help was focus of responsibility. Attachments of responsibility completely opposite

Doug: but now we have more control over genetic factors. Debae over whether should do pgd for mt disease. I feel v strongly that we should. Guilt of leaving it to chance.

Celia: guilt is produced by chance.

Doug: but making diagnosis produces the guilt.

ME: but guilt is only one condition that can make people feel bad. Fate. From Chance to Choice, or From Fate to Guilt. How do patiens reconcile the inexplicable? (as fatalistic, bad luck)

Ruth: informed consent functions in different ways.

Doug: what interest of animal has

Carlos: since many of mt are late onset, but can be diagnosed genetically, we have case where can predict, this makes special case. By modulating biochemical phenotype, could prevent onset. This is particular in mt. no other diseases, where person genetically diagnosed can be homogenised as well.

Doug: but for huntingtons,e tc, basis of therapy is to treat early.  Treat asymptomatic

Carlos: but maybe Huntington will be mt.

Glasses: how move towards harmonisation?

10.45 a.m.  Tea/Coffee

11.15 a.m.  Donald Bruce, Society, Religion and Technology Project, Edinburgh "Have you been talking to one of your mothers again?” – Mitochondrial Nuclear Transfer, Identity and Ethics.

Quote is taken from a song ‘the reluctant cannibal’ ‘(flanders and sawnn, circa 1956) -    expresses media fears -    child with three mothers -    makes a very good headline -    ignites ethical flashmpoint

Donald Bruce -    Society, Religion and Technology Project -    Set up in 1970, Church of Scotland, working ecumenically -    Full time scientific director -    Exploring ethical issues in current and future technology -    Engaging technologists w ethical/social implications -    Informed and independent assessment to policy makers -    Stimulating balanced public debate -    Discussion and policy making within the churches

Dolly: an icon for biotech -    promise and threat of biotech o    potential of what we could do o    fears about what we might do -    Roslin focus: cloning as tool for animal GM -    Media focus: human reproductive cloning o    Associations from scifi – good story lines -    Scientists insisted – not what cloning was for o    Vocal in protecting any ‘therapeutic’ uses (Winston, BMJ, 1997) o    Especially treating mt diseasee

MTl transfer: a daunting ethical cocktail? -    exptn on embryos -    nuclear transfer: cf reprod cloning -    multiple genetic identities in reprod -    genetic modification of human germline -    risk of nuclear transfer -    who/what drives research – need or technique? -    Accountability – should HFEA have consulted public or parliament before licensing?

Basic ethical questions raised -    when does human life begin? -    Limits to reprod intervention? -    What is nature of a human being and identity? o    Eg genetic or holistic -    Should we change human genome or untouchable -    To what ends? -    Social ethics, justice, drivers, powers, winners, individual/social

Mitochondrial tansfer: expt on embryo -    embryo status is critical issue -    if fertilised egg has moral status of person, then procedure completely unacceptable -    if embryo has ‘special statu’s research is not ‘anything goes’ but ‘no, unless…’ – cannot research, except for… -    two embryos to produce one baby o    putting an embryo to a different use than reproduction o    sacrificing t potential of one – non-trivial -    beware reducing human embryonic life to a status less than lab mice

mitochondrial transfer: nuclear transfer -    nuclear transfer but not reproductive cloning o    manipulation of eggs already fertilised o    not asexual reproduction of existing person o    Dawson report – not the same thing as cloning -    More like IVF w modification than ‘cloning’ o    Swapping cytoplasm and nuclei o    Still radical -    Confusion identity -    Significant risks -    Confused perceptions also?

ME: do confused perceptions warrant prohibition?

Mitochondrial transfer: multiple identities in reproduction -    embryo w genetic material from three people o    compared w sperm or egg donation? o    3rd party intervention in genetic bond or parents (chutch Scotland worried about osing bond) -    how much do mt constitute identity? o    Are these 37 genes common to all o    are we merely changing batteries o    matter of degree or absolutes? ME: I still struggle with the idea that my batteries are not my identity

-    how much do genes constitute identity? o    Reductionist or holistic accounts or identity

Not as big an issues

-    identity more than genes, but where draw line?

Mitochondrial transfer: human germline GM -    germline therapy highly controversial in bioethics -    1992 Clothier Report: UK says ‘no’ for time being -    nuclear transfer cloning provides new route o    Polly (July, 1997) – nuclear transfer + GM in sheep o    Target GM and gene knockout possible (sheep, pig) -    Human germline by nuclear transfer? o    Feb 2004: Ian Wilmut speculates future use of reproductive cloning for germline gene therapy o    Mitochondrial transfer as potential applic (1996)

Mitochondrial transfer: germline therapy ethical problems -    permanent inheritable genetic change o    informed consent impossible; inter-generational issue o    no right to force genetic change on all future offspring o    deep concerns about non-medical human GM o    does extreme genetic disease make an exception? •    Would future person say ‘why didn’t you’, rather than ‘how dare you’? -    High risks involved o    Micro-injecting human embryo; germline DNA intervention -    Clothier (ethical’ committee judges solely on risk, not  ethics -    Expt to solve t risk would be unethical o    Would need to make future humans research subjects

Is mitochondrial transfer a germline change? -    yes, it changes inheritable dna -    it is not nuclear dna – does that make a difference? o    If mt not tied to identity, does it matter? o    ‘relatively modest’ change to human genome (Donaldson) -    What is t ethical issue? o    Making permanent change? o    Degree of change o    Type of change?

Mt transfer: is it just changing batteries? -    reductionist claim o    makes a (hidden) value judgement o    changes t discourse from inherent to functional o    is CF gene therapy ‘just changing chemical signals in t lung’? o    is athletic enhancement just functional? -    Is it ‘just’ batteries – if mt do moer than make ATP? -    Beware of so focusing on t medical/technical objective that close mind to wider issues  cf. GM – saw what gm was for and neglect wider issues -    Case for mitochondrial germline change not yet proven

Mitochondrial transfer: other issues -    risks of nuclear transfer o    IF mt are box of genes o    Is it safer/riskier to change complete gene set than 1 gene? o    Risk of nuclear transfer procedure – serious issue o    Do you know t quality of donor egg? o    Unpredictiability of effect? o    Is it possible to anser risks without running them? -    Who/What drives research – need or technique? o    If for people withj condito, is it best way to address need? o    Or is it technique driven? -    Animal research issues -    Acccountability o    Should HFEA have consulted public or Parliament before licensing? o    Cf sex selection.

Questions and Answers

Carlos: in conversation with Wilmut, Dolly not perfect copy, since variation occurs. Dolly was not at all  a copy – nuclear genes were not the same. So, careful with nuclear transfer – which cell is used? Because mutations can be tremendous, compared with mutations in early embryo. If take from fibreblast, thousands of mutations which do not influ function of fibreblast, but not embryo.

Kevin: any position on the ethics of mt?

Donald: not yet. Question of identity

ME: what do you think would have happened? Question about public consultation? What should be the criteria/mechanism for establishing whether public consultation is required and what structure should establish that? Ok, perhaps the HFEA, but if they all agree?

Is the division of opinion within the HFEA the justification for public consultation, or is it questioning the foundation of the HFEA legal authority to make this decision? If the latter, then what form should public consultation take?

Doug: encourage to engage with public consultation predominantly through the media. Pressure for patients to tell story to the media.

Doug: doesn’t have to be germline gene therapy. Could stop this by just allowing male births. With sex selection being allowed.

Glasses: may not happen in uk, but will be done elsewhere. If perfected elsewhere where lower ethical standards, then this is going to become used in Europe.

Donald: is this a thought expt? Will germline be so thoroughly explored.

Glasses: if look at importance of biotech in south east asia, then likely that will.

Donald: from UNESCOs point of view, is degree of international pressure. If some country presents it

Doug: some techniques are being developed in other countries.

12.00 to 1.00 p.m.  Discussion. Planning for the future.  Chair: Ruth Chadwick.

Promised scoping paper on social and ethical issues.

EU project (EUMITOCOMBAT). Will report back to coordinator on proceedings of the seminar.

www.eumitocombat.org

potential for doing something else. Setting up a project, for which we might seek further funding.

Develop cesagen project linked to European project and other interested parties

Scoping paper -    have made progress on the issues -    New Jersey version of the therapy (cytoplasm) o    Doug: Jack Cohen – improve fertility of oocytes of women. Injected cytoplasm, children born with lower amount of affected. But evidence base and ethical base lacking. Banned by FDA. Don’t think this would work, since would not be able to transfer enough cytoplasm o

Mark: can mt dysfunction be desirable

Doug: some evidence that allows us to adapt to cold.

Workshop will prove to have been useful.

European project

Ruth: are there particular issues with European. Eg. Euroean database.

Doug: what information should go on the website? Eg. Information for patients, families, access, etc. language? Basis of information?

Celia: dipex website – putting online social scientific interviews with patients, video and audio files.  For patients and social researchers.

Donald: engaging w media – can do nothing with tabloids,

Beard: but cannot assume that is such a big deal

Doug: relate to Carlos and clinical research. Needs to be continued. Are centres that specialise in …..  until understand more about disease and patients, cannot understand. Need to continue EU funded projects where we have…

Mark: jurisdiction shopping in science. Need review of ethical frameworks and regulation of this area of science across nations.

Ruth: for mt disease?

Mark: question of regulation and transfer.

Ruth: HUGO ethics committee wants to do some work on nuclear transfer. From Doug Wallace.

Carlos: CoE approved popn biobanks exchange last week. Minister still have to approve, but big consensus. Disagreement regarding scope of recommendation. Some delegations wanted to include biological materials for embryo and foetus.

GlasseS: will there be a European wide regulatory body

Carlos: v difficult. Even in spain difficult. Next week, in London meeting of represn of national ethics committee.

Donald: unesco docs from ibc may have covered some of these questions

Donald: my presentation was on the assumption on therapy, rather than research towards therapy – important to make distinction.

Specific recommendations - patient information - regulative - distinction between research and therapy - gender/identity issues -

Doug: big push now is to find nuclear dna mitochondrial mutations. We focused too much on mt dna. Patrick searching for nuclear/mito interactions. Mt genetics is very different. Need cohorts of patients regardless whether nuclear mt or mt dna.

Bert: orphan disease and justice.

1.00 p.m. to 2.00 p.m.  Lunch

Damian Sutton, BADIOU, RANCIÈRE AND THE POLITICS OF AESTHETICS (2005, Glasgow School of Art)

Damian sutton, glasgow Art School26102005.

The Event of Photography and the Betrayal of Art

BADIOU, RANCIÈRE AND THE POLITICS OF AESTHETICS

Damian Sutton

Glasgow School of Art

ALL WELCOME

Wednesday 26th October 2006

4.30pm

Design School Seminar Room,

Grnd Floor, Foulis Building

The Glasgow School of Art

Abstract:

The philosophy of Alain Badiou has recently gained much publicity as more of his work is translated into English and many of his ideas resonate with a popular dissatisfaction with both left and right politics (a translation of his Being and Event is out in late-2005). His Ethics (1993) is an often vituperative attack on the lack of faith that left-wing politics has with the major political events of the twentieth century, and on the descent of the left into self-interest. Fidelity must be kept, Badiou suggests, with the truths of art, love, politics and science which puncture all knowledge and opinion.

This paper considers Badiou's attack and its potential for reviewing modernity, modernism, and art's adherence to the destiny of its technologies. Furthermore, the paper uses Badiou's ideas to understand why other scholars of modernism, such as Jacques Rancière, have similarly attacked what they see as the 'legislative reign' of poetics over art. Finally, the paper will examine how the photographic media came to be seen as modernism's Veil of Veronica, and why they can be seen to have squandered the political potential that had garnered photography axiomatic claims to 'democracy', 'truth' and 'the real'.

Biography:

Dr Damian Sutton is Lecturer in Historical and Critical Studies at The Glasgow School of Art. He has recently published on cinema and computer generated imagery, on cinema and theories of memory, and he is a co-editor of The State of the Real, forthcoming from I. B. Tauris. He is currently preparing a book for the University of Minnesota Press on photography, cinema, and time, and 'The Event of Photography' is a paper drawn from this project.

the event of photography and the betrayal of art

badiou, ranciere and t politics of aesthetics

rethink photog and time

rosa parks death - refused togve her seat up for white man - used by civ rights mkvement

t convergent image

vidoc

old and new image

rethink event

manovich

digi image in film

photog rel

technology at arts disposal not as impin velief off poss

change of ideas signif point

struggle of old and new is temporal

first fifty yrs of film, poetic

schema of time

convergence remonds us that photog is idea

event of photog

apparatus and spectatorship

cinema rooted toideals

films purified ideal

phto as mythological

invention of cinema1895when first pubkicly shpwn

first as med observation confirms event

effiiency of seeing

mother temporality

exposure time reduced to kodak moment not technological change but idea of photo as event

the pose

common understanding of event is cause of radical change

naming of event, people must live an actas if it occurred

instit theory, as jolts

internet  change away from pose

delete without  conscience

print in home reinforce family

but theory of event underpins

industry looking for event to orient itself around it

style columns - is technology diff

process o inteest and surveillance

latour - trapped into it

event as jolt

badiou - ethics - p of t event - devel of theory of event -

digitise everything

connectivity -

me-digital as urban , orange arctic co presence

hp - family mobility

badiou

event as uncovering of event as truth badiou said 911 not event since nth changed

conversion of st paul on road to damascus

revol in france as all events

moment that all see themselves as part of rev

void - in whose name event occurs

photog

art testifies of pasing of idea . all art risks being mere piecework

sep act of making from passing of ideas

art as invention

imagine invent of photog

talbot 1832 no clerer to invent

void

talbot married love and idea came to him

xcamera lucida

sawaerad scene and tracd image

bad at drawing led to creation

invent conceptual

art is thought process

phto rel to sci phto as sci event of art

fidelity to photo badiou is central to ethics

art sci politics love

laziness

sci s body of fodelity, selling sci to state betrays truth

badiou -truth forces knowl gallileon event

event as two destinies - - truth ot other

truth of photo as democratic never true always surveillebce

photogs sci value s truthmaker

style is arts betryal of sci

betrayal f art

acculumation of photo for state

new represn of soc

blackbox

kodak, u push button, well do rest

classif of instit memory

subject thus comes into being

bettion - for recording people idt

me - dna database

criminality diff then

police and physician - photo to assign idt

how can art be culpable

art as regime

political potential of modernism lost

but photog caught in

veronicas veil - christ image on cloth

technicism - poetic over form/

ranciere   ethics -whtherartshould be part of good soc

politic and art

singular event dominates

cannot demonstrte fidelity by repeating

fidelity as ethical process

badiou -orthodoxy

badiou and ranc are ambiv about artist

only the work is relevant

role of artist is to lookout for event tat ill make practice obsolete

me  - of surveillence, seems to betray sponeneity

strictly poetic

but reflction of politics

not enough to say eth is political

me –role of instit

ranciere - regime of poetic

fidelity nowtostyleof image, rather than repres soc/

academicism clear eg of stgnation

tag 1982year after first electroniccamera

me -  rel be institut and surveil, seems away from image

Questions and Answers

gibson sci fi , street fjnds a use

home prining and digi - mundane -

d badiou said events are necesily good

connecivity as central to techl basic q is wheth world changes

irreevant whethr mass response, critical is temporal

badiou - sci truth

true event forcea itself into knowl

becomex truth when confirmed ina partic way

reaches eventful status

event as multiple irreducible intervention

fairground - momentus

International Association for the Philosophy of Sport (2005, Czech Republic)

IAPS2005, Czech Republic Friday morning

Doping

Dehumanisation -    Schneider and butcher consider incomplete, since do not know what humanness is

Paper on philosophy of language

4. could a human being ever not be or be less human?

Miah -    “concluding what is ethical about what is ethical….what is valuable about being human….human dignity…autonomy….capacity for being persons…strong evaluations….’ -    Central claim about personhood – measure of individuals…personhood ….. humanness as personhood responds to Schneider and butcher that no …. .persons need not be humans (McNamee – OK, but this is not Mike’s idea. Tooley wrote about this and Singer )

Metaphysical conception of humanness is a mistake

Miah -    Warnock – personhood takes direct route

ME: but Warnock was engaged in various processes – a working legal document

What gives sport value?

For whom?

Which sport, what level, etc?

Dehumanise is dominant concept, rather than human

No need for metaphysical conception of humanness

Charles Travis

What is a greyhound?

Fathers method of developing sense of greyhoundnes is useless

Mother is better – point to different dogs and call them

ME: but what would the mother say?

If we can identify conception of contrast, creates apparent philosophical problem

Baker on Wittgenstein – we get in trouble when picture associated with concept is incompatible

Moral particularism

Account of humanness appears necessary

Need disappears

Approach from concrete use in language

ME: when you begin to ascribe rights and freedoms, you need a metaphysical definition that allows you to make distinctions

Contrasts are drawn in general way

Drawing a line -    in moral judgements creates misleading picture -    leads us to want to say that everything on one side is ok and on other is objectionable -    generalisation is misake

ME: but line drawing is not really used as moral judgment, but to enable a judicial (rule-based) system to function

Degrading v dehuman

Decomposed, demobilised, decapitated

De indicates a lack of something

ME: why are we talking about dehumanising?

The blood is human

Lack of feeling was inhuman – does not mean person not a human, more to do with lack of moral characteristics of human

We know what’s at stake

Schneider and Butcher use humanness rather than moral agency, this is a mistake

Use of language is more complicated than

Not simply GM or performance enhancing drugs that dehumanising, but also other entities

Dehumanise does not mean no longer human

Metaphysical used as basis for grounding moral judgements cannot work

ME: So humanness as personhood doesn’t help?

Bill: ‘a woman is less than a human, so I can do something to her that I would not do to a man’ often used to treat universal in principle vs universal in reach start with relevant similarities what it means to be human is certain relevant similarities

ME: but there are other considerations – rationing, for example, but not only. Dignity functions in a contested manner when dealing with PVS – where one has to assume interest (UK law substituted judgement)

Bill: Rawls: suffering – of course occasion sensitive

Jim: Do animals suffer? What is a supplement? Difference between sup and dope? How classify things on earth? Birds, fish, mammals. Difference between a definition and a clarification of a term. What Schneider and butcher get wrong is that their conceptual analysis is that they think necessary and sufficient conditions define humans – that last bit is wrong!

Leon: Do not need to go to specifics of a case

ME: how specific is a case? What constitutes a case?

ME: What if I am a giant?

Friday 1030-1200

Philosophy of Extreme Sports

Adventurous Changes: Rethinking sport in the age of the extreme Kevein Krein

Best – aesthetic sports – closer to extreme sport

Aesthetic sport and art difference is art = self expression, sport not

Booth – translate philosophy into movement Really?

Cannot represent such abstract ideas through surfing

Discussion:

Extreme correct term? -    death sport or high-risk?

ME: so is sport!

Concept of extreme diminishes with skill

Still a performance for others – but peers, not personal

Photography

The very act of being on the wave is the articulation of a philosophical or perhaps in the case of some sports an ideological premise, eg. Skateboarding and the urban (Dogtown).

Danger of relying on the athlete’s articulation of what they are.

The Intelligibility of Suits: Scott Kretchmar

Reply to Thompson, JPS

Thompson – utopia is conceptually incoherent, implodes because of own contradiction -    welll rid of it

suits is constrained utopia, but not coherent

Thompson -    in utopia, Suits says is no suffering, but in sport there is plenty

thompson’s concern about utopia

suits and play

suits agreed that ideal of existence revolves around those things the sake of which we do other things

suits accepts play as intrinsic, but interested in games

did not praise play over work

not like Huizinga

suits wanted to make a claim about games

utopia populated w activities like baseball and crosswords

game thesis, not play commitment that caught attention of skepticus

why only games?

Knowing what the game is

In utopia, Suits puts games on high normative pedestal -    effort and striving would no longer make sense

instrumentally free mode of living

games give us something to do when there is nothing to do (said the Grasshopper)

ant existence predicated on scarcity

for ants, often too much to do

grasshopper unimpressed w mandate of scarcity umoved my moral pressure of prudence

living life predicated on plenty, even if foolish

presents himself as future harbinger of….

For grasshopper, often too little to do

Suits: Game playing only remaining candidate for utopian occupation. Game playing makes utopia intelligible

Intrinsically valuable No further end Games meet this requirement Must have obstacles to overcome Game playing makes it possible

Argument fails because suits’ utopia is an ideal existence. Needs all intstrum activities save one do not exist

If one is living in bliss, who cares if there is nothing to do?

Cannot be a place where all needs have been met, though work meets a logical conclusion – human basic needs met But larger problem of boredom is left

Suis conclusion that there is nothing to do must be false

Problem w Suits ‘nothing to do’ He actually means, no probs to solve – work/natural probs

Having no probs to solve does not mean nothing to do

Countless things left to do – eg eating, listening to music, sitting in sun, etc

Suits does not answer question by Prudence and Skepticus – why free from work = games

Why liken to game playing rather than trumbone playing?

Suits has only shown us that nothing to do relating to problem solving, not that there is nothing to do

We are inherently problem solving creatures and he neglects this

Partial answers from anthrop -    contemporary human beings are product of millions of years of successful problem solving ancestors met obstacles

lesser problem solvers died off

good problem solvers populate t earth

Suits: many of us are in game denial!

Article 6yrs after grasshopper -    utopia need not be tiddley winks, but grandiose games Suits leaves us w questions about future.. -    utopia comprised as intrinsically satisfied games might be bleak or beautiful, but need to address

humans are made game ready

The Devoted Athlete: An Examination of Seriousness in Competitive Sport Peter Hager, SUNY

330-5pm Friday

Mark Hamilton

LASIK – shown to be beneficial for baseball Tommie John surgery – UCL 10% better for all baseball players -    when elective? – but wasit?

ME: why doesn’t  it happen?

Inevitable

ME: but contingent on physician position

ME: Why care? -    if medical standard, no issue – except diminished autonomy which we cannot possibly pursue

should it be banned?

ME: can it be banned? No, because first outside of sport too

Transsexuals -    Renee Richards – see reassignment surgery 1975 -    1976 US open denied access -    1977 US supreme court ruled in favour

USPGA on ladies prohibits -    Charlotte Wood, finished 3rd 1987 -    Led to ‘female at birth’ clause intro

3 options - let them (transhuman – Julien Huxley - surgical analogous to equipment changes

Anger Jeff Fry

Execessively high display of anger leads to aggressive play

ME: doesn’t anger/aggression win games?

Aristotlte: man angry at right things should be praised, if not angry, coward, etc – slavish

Robert Thurman

Coaching anger relevance? -    caring deeply? -    Justifiable – if injustice – eg cheating by officials -    Pressures coaches face

Anything in sport worth getting angry about?

Why coach?

What is appropriate display of anger?

Can debate value of anger

Donald Jones? – role-differentiated ethics -    take into account special circums

coaches cultivate passion

ME:: but is thi a flaw?

ME: compare w politician – should they get angry

Suits Doug McLaughlin

Elucidation on game playing for understanding utopian lure

3 aspects - utopia - lusory att as unifying aspect of game playing - dream and vision of grasshopper

purpose of grasshopper -    utopia -    theory of games

formulation of games not most important aspect

game v the good life

relationship between games and utopia

grasshopper -    life most worth living -    not exemplar of game playing

we find significance in problem solving -    utopia wout problems would not be a utopia

Thompson article -    does not recog move from play to game playing in suits

Fair is Fair, or is it? Bill Morgan

Both dopers and dopers claim they make the playing field level They are both wrong

Rawls -    justice as reciprocity

doping is a moral offence that affects fairness

WADA and USADA within moral rights to test, but recent efforts they have made are also unfair and morally problematic

Deep seated complex moral problem and looking for easy technical fix

Elliott Better than Well – double standard – we expect athletes not to take drugs, but not in everyday life

Drug rules are not constitutive – not athletically relevant

2 kinds of rule violation - offensive: break rule to gain adv - defensive: occur when v little compliance w rules. Break rules to protect oneself

not persuasive

2 problems

1.    protecting self-interest, no concern about fairness, main concern is not being taken adv of – not being a sucker 2.    everyone’s doing, so ok for me to do it

v difficult to know how many athletes are doping

from 5% to 95% but who knows?

Significant number who don’t dope

Cannot assume that all are, so looks like offensive rather than defensive rule violation

Idea that everyone’s doing it means overestimating no of people doing it, so am overestimating my reaction

Doping claim to level playing field does not work, so authorities have moral right to test

What about WADA and USADA? Fair?

Standard way is drug test -    objectve, impartial, at first glance

devil in detail

1.    even though tests are getting better, still easy to get around test. 2.    False positives as well as false negatives (Tyler Hamilton)

Only people who get caught are dumb or unlucky

Biowash – shampoo

Flush mouth solution

Urinator –

Whizzinator – prosthetic penis (ME: see article in endnote)

Analytic techniques largely failed

Crackdown by legal

Balco – coop w criminal courts

Michelle Collins – never tested positive disqualified for 8 years

Non-analytic attempts along with analytic

Gary Wadler – favourable article on WADA, they willl catch dopers and standardised rules across sports. New world order ‘commiteed to fair play and ethical values’

Not so!

Problems:

WADA has changed burden of proof -    to comfortable satisfaction

raises social justice issue

treating similar cases dissimilarly

violation of mutual reciprocity

ME: but they could not win – burden of proof was too high

Justification has been ‘righteous indignation’

American Arbitration has resisted, but not for much longer

Classic problem of fairness

Not a concern for moral integrity of sport

Problem 2:

Circumstantial criminal cases against dopers

Criminalisation of street drugs and doping -    difference is that former kill each other

dopers will rat each other out

end up with Hobbesian all against all

BALCO

ME: what is a designer drug? – a product that never made the market, but is in the journals

AAP

Three approaches to Pain in Sport – a critical review Sigmund Loland

Background

Phenomenon of pain -    significance in sport – ethical challenges -    ambiguous – epistemological crossroads

a critical review and comparison of 3 ideal-typical approaches

research strategies

Ethics and Philosophy of Future Medical Technologies (2005, Barcelona)

Ethics and Philosophy of Future Medical Technologies, Aug 2005, BCN. Thursday 2pm

Life Extension Session

What does the community think? An Empirical base for philosophical and ethical debates about life extension Lucy Carter, Jayne Lucke, Bree Ryan & Wayne Hall (Australia)

T science - successful life extension in model organisms - suggestion of human applications within 10-20 - possible of pharma therapies to extend life span (strong life extension) - biomedical advances to treat disease and maintain health (weak life extn)

caloric constriction – reduce calories by 30-50% extn life by up to 30% in mice -    if we promote thi, not good for adolescents -

maximum life expectancy has not advanced at all

Policy implics -    global, popn and fertility control, work and employment, superannuation and pensions, health and life insurance, regulation of antiageing industry, health and social (disability) services, end of life issues

Public Opinion

Assumptions -    people are repulsed by the prospect -    huge demand for life extn

no empirical data available despite t importance of public opinion in policy development

this study -    examined public ustdgs of life extn -    aiomed to provide empirical data to controbitute..

Questions

How do members of t public understand t possible for inc life expecracny How likely is gen publ likely to take up What are the mpotivations that influence intentions

Method

Structured indiv interviews

Sample -    31 men and women, research registrer for over 50s -    11male, 20 female -    18 aged 50-65, 13 over 65; -    14 had tertiary ed

Do you think that new technology will be successful in extending life span? -    ‘Yes’ this has already occurred o    sources: •    biomedical devevlops eg spare body parts •    research eg. Genetics, applic of model org findings •    lifestyle improvements, eg diet and activity

Limit to life extn? ‘ as a mortal being you are programmed to die at a certain time. Despite what technology might b able to do wof you to make you healthier, there comes a cetain point where that’s it”

Concern about cost “ I would be concerned abgout being a drain on t economy of t country – living on handouts – and this is t b

influ of family and friends ‘ I would like to extend my life because I married late and I’m not going to see my grandchildren;…

If you were offred some technology that made you live longer, would you use it -    95% declined

ME: what comparative qs and studies could be used here?

Comments from older pop seemed more concerned about quality, younger still concerned about the way they looked

Qual of Life -    health is paramount

looks not a high priority -

findings show 1.    people are concerd about issues to do w life extension and eager to talk 2.    range of opinions, but QoL paramamount 3.    intervention that did not enhance health less popular 4.    looks not important

Limitations -    small sample, characs of sample, exploratory qualitative study -    confirmation reqd in larger study

Who wants to live forever? 3 args against interventions in biological ageing Carlo Leget nd Martien Pijenburg Radboud University Medical Centre, Nijmegen, NL

Distinctions

Chronological ageing – calendar time Biological ageing – process of decline

Goals 1.    prolonging natural life span 2.    combating defects and disease that re intrinsically connected  w biological ageing

Args so far

1.    risks/dangers 2.    financial burden 3.    social injustice 4.    risks of overpopulation 5.    societal side-effects (medicalisation, pressure, evasion, genetics)

observations

never positive args, only rebuttal of negative args treat of args is separate ‘more of the same’

this paper: coherent alternative viewpoint – 3 args against

1.    dimension of time 2.    social nature of human 3.    value of global justice

1.    the time dimensions

time is seen as an object – more one has, happier one is

but time is not an object

we do not exp time, merely ourselves and the world around us

ME: no, it is brought into being – revealed – through systems of measurement. We do have these systems

Paradox: more life is expd as meaningful, more one’s perception of time vanishes – when completely absorbed, time flies

We don’t seek more time, only more meaningful experiences

ME: who needs to many os?

Spiritual

Decentrered self

Meaaningufl life as eternal

Decentred = no interest

2.    the social nature of human

life = living w others meaning of ‘with’? -    indep, stand-alone indivs (liberalism) -    members of a community (communitarianism)

liberal -    negative freedom ‘absence of barriers’ -    self-interest -    negotiations -    instrumental value of t other / t community -    goof life FOR ME

communitarian -    positive freedom: possibilities to act -    common good -    social context as precondition for a human life -    t good for me includes for us

ethical justif -    liberal: autonomous choice -    communitarian o    social network as condition sine qua non for human life o    morally good life includes living in communities and meaningful relations

quality v quantity

- life-extending e only valuable if it benefits all – our – networks - unrealistic perspective since networks exist in diversity and worldwide

‘People do not want to bury their children, so should be  open to all!!’ -    ME: this statement draws from a well known popular view and completely takes it out of context so as to be meaningfless

3.    ethical dimension: global justice

expectancy

Canada: 80; Malawi: 40 -ME : yes, but Malawians have sex a lot more! Under-five mortality Norway: 4/1000; sierra leone: 316/1000 75% HIV infected in Africa (more than 27 milions) 12 million orphans

What moral obligations follow from justice?

“If immortality or increased life is a good it is doubtful ethics…. Harris, 2004)

Objections -    immortality only a good as a life in meaningful time and relations -    life extending technology is not an available benefit yet -    question is whether we should choose to develop it

Global justice -    including equitable access for all and promotion of the common good -    broadinig t moral agenda towards justice of institutions

life expectancy as a moral challenge

discussion

1.    to improve t life expectancy of millions that die at 40 outweights by far t relevance of expanding t life o 80yrs old people 2.    how balance between broading and limiting t agenda of bioethics

Conclusions -    3 args against, stressing social nature of humans -    args against interventions in biological aging -    also relevant for other medical technologies

Living LongeR: Ethical aspects of age retardation

Elisabreth Hildt

Intro Age-retard ethics Age retard and autonomy -    informed consent -    self-creation -    determ of course of ones life conclusion

Intro Age-retard ethics -    risk benefit ratio, beneficience snd non-mal -    autonomy and freedom from time constraints -    biological life cycle -    atts towards ageing, death and morality -    chang in family rels -    aging of soc -    justice

Age retard and autonomy -    informed consent o    info transfer; freedom of choice o    adult and competent persons -    self-creation o    transformation of the self o    personality traits and personal identity o    authenticity -    determ of course of ones life o    creation of a full and active life o    some drawbacks •    sense of time •    extended period of old age •    implics of widespread use o    family structure •    growing up and role of family •    formative influ of older generations •    role of trads •    independence o    structure of soc •    concentration of power and authority •    flexibility to change •

Age retard and autonomy -    autonomy does not solve question, might even be arg against techniques -

Controlling Human Ageing: Alternative Rationales and Impications Robert Binstock, Jennifer Fishman, Eric Jeungst

Grant from NIH on implics of anti-ageing interventions

The Politics of Presentation -    how one presents what one is upto in antiageing science can shape regulation/funding/priority

The Fountain of Youth: A Perennial -    today: o    anti-aging entrepreneurs and longevity practitioners (medicine) o    biogerontologists (science)

why is antiage med flourishing? -    Post WWIII baby boom -    Only light regulation on anti-aging prods and services -    Internet sites for marketing -    Dozens of antiaing how to -    Market 64bilion in 2007

Youngevity.com -    the anti-aging -    Patenting Antiaging miracle minerals are called -    ‘The Vlicabamba mineral essence’

American Academicy of Anti-Ageing Medicine (A4M) -    provides board certif. for practitioners of longevity med -    13000 members -    70 international and national conferences -    2million hits per month on website -    net asserts from $65k to $3.5m

RRonald M Klatz ‘Ten Weks to a Younger You’

Biogerontologists -    40% extn In av life expect and mx life in dietary caloric restrictuions (CR) expts -    development of CR mimetics -    genetic interventions

scientific legitimacy of biogerontologists is shakey -    little better than charlatans -    gerovital, anna aslant and nikita kruschev -    in US, National Instititue on Ageing (NIA) in mid-1970s path to legitimacy, but still fragile

War by gerontologists on Anti-Aging Medicine -‘No truth to the fountain of youth’ - published online (CHECK!) - SILVER FLEECE AWARDS TO A4M – for misleading public - continuing publications and media appearances - boundary work to disting themselves from t illegitimate antiaging med movement ‘Those who have legitimate…. R. Miller’

Similarly A4M seeks legit -    denigrates ‘gerontologist estab’ -    files lawsuits against specific …

Ideal models of aging seniors

Imagery beyond boundary work -    the politics of presentation has important social implics -    3 rhetorial strates for defining aims of anti-aging prods, etc o    1. Med tratement o    2. Enhancement o    3. Prevention

1.    med treatment

eg. A4m: reating maldadeies of aging -    moral authority and prof autonomy of med prof

renews debate over whether aging pathological or risk factor

2.    enhancements

‘stay young’ restore mental and phys capacities that decline w age politically, this rhetoric takes enterprise out of biomed realm -    outside of med prof and gov reg

provokes criticism from bioethicists’not natural’ and tf unethical

beyond therapy (2004)

3.    prevention

forestall chronic health probs, associated w aging for as long as possible strategy avoids criticisms of unethical enahcnement skirts debate over whether aging is a disease

embraced by gerontologists

want to be seen as ‘the good buys who favor…..R.Miller essential for maintaining and enhancing funding for further research

internecine warfare against propoent of enhamcenent – Aubrey de Grey, ‘virtual immortality’ is achievable – claims possible to only die from apoptosis - European Journal of ‘Resistance to debate on how to postpone ageing’

‘We are gradually, much too gradually ….’

The Politics of Presentation: Issues for Empirical Research

Tretment -    will treatment rhetoric by anti-aging entrepreneur and clinicians lead to control by org med? -    Or, will org med engage in boundary work, as t biogeront

Enhancement -    will enhance rhetoric lead to political movement to curtail interventions?

Prevention - does prev rhet succeed in strengthening scientific status of bioger

Friday 26 Aug

Therapy & Enhancement Ruth Chadwick

Disagree with Bayliss definition of enhancement, must disting between improvement

Inevitability thesis is incomplete

Moral argument fails to account for context

Instead, improvement should be focus, but wheth enhancement is improvement depends on context

Eugenics revisited

Negative v positive

Enhancement just eugenics repackaged

Disting between germline and non

Eubionics: the pursuit of bodily perfection – negative and positive -    McNally

Negative eubionics – elimination of body Positivev – pursuit of bodily perfections

Case by case?

Beyond therapy US Pres council -    argue for case by case

enhancements 4 approaches -    beyond therapy -    additionality view -    improvement view o    if qualitative, but if enhance to such an extent that X (human) no longer exists as a category -    umbrella view – enhancement just convenient label for number of interventions

limitations of enhancement/therapy distinct -    enhancements likely to arise from therapeutic med -    this will be difficult o    ME: why?  Drug regulation

Beyond therapy probc definition -    Therapeutic intentions? -    Therapeutic effects -    Evidence based therapy -    Proper scope of medicine -    Indiv vs species issue

Norman Daniels: eliminating shyness relies on understanding cause, which is complex

Why should we be more concerned w cause of condition than suffering

Enhnancement and the self

Baylis and Robert -    ‘the resulting alterations may be conservative (ie used to normalise the self), liberal (i.e used to liberate the self) or radical (used to fashion a self that effectively challenges others’ conception of oneself)’

what would count as a preventive therapeutic intervention? -    preventive mastectomy for woman with strong family history -    since we don’t know whether it would arise, can argument is therapeutic, but also as reassurance -    main aim is to reduce risk status -    counterintuitive to speak of mastectomy as enhancement -    need more to concept of enhancement that just beyond therapy

Norman Daniels, Species typical functionign

While enhancement is always characteristic specific, whether something is improved or not requires a judgement -    good eg. Is height -    depends on what we are trying to achieve – context

improvement should not be included in any definition of enhancement

the inevitability thesis

baylis and roberts -    contemporary Western democracies have no experience with permanently halting the development and use of any enhancement technology on ethical grounds.

What doesit mean that it is inevitable -    if simply that someone will try it, not interesting -    ‘despite the likely failure of particular genetic enhancements, there are some among us who will inevitably attempt to engineer the human genome8 for the purpose of improving Homo sapiens.’ Bayliss and Robert

rape and murder doesn’t stop but doesn’t mean not worth trying

they distance themselves from empirical slippery slope argument -    not clear that views will become more liberal

Ithe future is ours for the shaping, tf genetic enhancement inevitable -    an ‘avant garde’ portayal of human nature o    ME: what not merely health improvement?

Perfectibility different from enhancement

Moral Arguments -    boutique model (individual) -    species approach (collective)

boutique model -    Abdul Adah

Central question is whether medicine resources should be used here

Spectrum of positions -    wrong in itself -    injustice arises -    not a priority -    morally required

Habermasian concern not mentioned

My view is that enhancement permissible in certain conditions

From an impartial position, if can improve, we should make it -    but judgement about what is improvement not easy

no gains without compensating losses

consider context

sport

Aristotle -    if ten pounds are too much for a particular person to eat and two too little, it does not ffollow that t trainer will order six pounds; for this is perhaps too much for the person who is to take it, or too little too little – too little for Milo, too much for the beginner in athletic exercises

whether improvement first depends on context of sport, then internal good of sport

with human ‘improvement’ overall

3 areas in need of consideation

1.    enhancements which undermine t possible of moral agency are not morally permissible

but does either the fact of design or the nature of a given enhancement have this effect?

2.    wht si the relationship between moral permissibility and improvement

is improvement a necessary and/or sufficient condition -    if enhancement did not improve, but did not worsen, might also be permissible -    not sufficient, since issues about distrib

3.    priority should be given to enhancements which reduce existing inequalities

morally required?

Important issue not disting between therapy and enhancement, but whether is improvement -    depends on context and purposes

does thinking about whether it is an improvement overall contradict the context specific position?

There has been a huge trend towards public engagement about ethics -    ME: what does she mean by this?

Nordenfelt, L Honorary Session

Nordenfelt

Health goal as medicine

Edmund Pellegrino and David Thomasma in their book Philosophy as t basis of medicine 14, p.26 -    medicine is an activity whose essence lies in t clinical event, which demands that scientific and other knowl be particularised in t lived reality of a particular human for t purpose of attaining health or curing illness through the direct manipulation of t body and in a value-laden decision matrix

other goals exist – saving lives and QoL, health is central goal

task of interpreting health remains

contemporary philosophy of health determ from scientific point of view -    some argue they are value free and descriptive

Christopher Boorse and Thomas Schramme

BST -    ‘a disease is a type of internal state which is eitheran impairment of normal functional ability, eie a reduction of one or more functional abilities below typical efficiency, or a limitation on functional ability caused by environmental agents’ Health is identical w t absense of disease (Boorse, 1997). -    Ill if probability of survival lowered, or…..

‘health is a state in which we neither suffer from any evil nor are prevented from t functions of daily life’ (galen Ars Medica 193AD)

main rivals – in positive tersms

boorse health bst -    A is completely health, iff , all organs of A function normally, ie if they, given a statistically normal enviro, make at least their statistically normal conttrb to t surviaal of a -    A has a disese, iff, there is at least one organ o As which fns subnormally, given a statistically normal enviro

Holistic theory -    A is completely health, iff, a has t ability given standard cicrcums, to reach all his or her vital goals -    Notion of a vital goal is crucial -    Standard circumstance = different from statistical o    related to a cultural norm -    ‘A has a disease, iff, A has at least one organ which is involved in such a state or process as tends to reduce t health of A. t disease is identical w t state or process itself.’ -    Tends to reduce t health of A – sleected since not all diseases compromise health in relationship to vital goals -    Some maladies can be aborted before they have influenced the bearer

How reconcile these defns?

2 stories

genuses of probable health by considering illness and disting between illness and disease -    percevived problem

in the beginning…

illness recognitionand illness communication the illness language illness experts – doctors did not rely on stories from people who were ill, but looked for causes doctors found regular connections between states and symptoms and fourmed hypotheses designates causes as diseases

disease recognition

a quasi-historical sketch

concept of illness primary to disease

problem to be solved

causes assumed to exist within b or m

illness need not entail threat to reproduction

often concerns pain, suffering or disability subject often believes internal cause thus, human disease relationship to suffering and disability, not inc probability of death

3.    standard medical encounter today

john, pain stomach, sees doctor, presumes illness, pain  indicates this, and observes he is prevented from working

doctor examines, when convinced of nature, will find cause in organic function – organic disease, but not for own seek, not any old malady, needs cause of problem, then treats it in relationship to contemporary art, when successful john is healthy – no longer feels pain and can work as usual

thus: health concept used is variant of holistic – -    estab of fact that he is ill does not rely on diagnosis, john can establish through his own exp of illness -    ME: is he not doing what the doctor does? -    In favour of hgh

Endorse idea of reverse theory of disease XXXX - Josh Congilen? 1943 – Wilford 1989

illness recognition essential, but to avoid misunderstanding, illness need not have occurred in individual case, but disease not discovered unless someone in history who had similar case

Disease (holistic) = bod or ment process which is such rthat it tends to cause an illness (understood as a state of suffering or disability expd by the subject)

ME: presumes sincerity on behalf of subject

Gaylin and Resnik – illness caused by suffering or disability

Ability/disability relevant concepts than well-being/suffering -    pluralist notion of health? -    Do not deny relevance of well-being or suffering, but philosophical technique requires that Ockham’s razor (simple and as universal as possible), ability and disability most potent

Differences

In bst, health is entirely internal In holistic (hth) – goals and other abilities (not just intentional), but ability to perceive, feel, etc

In bst

In hth – extr

In bst – health identical w absence of disease, hth health is compatiable w t presence of disease. T concept of disease is, however, logically related to t concept of ill health (or illness) and also according to t hth. A malady is defined as a state or process which tends to reduce its bearer’s health

Hth – whether person as whole, whether can achieve goals -    goals differ: survival, QoL,

Thomas Schamme

2 theories of health of importance to philosophy of medicine, nordenfelt and boorse

defence of naturalist is critical discussion of nordenfelt

nordenfelt includes too many phenomena in definition of ill health

conclusion: analytical framework of naturalistic view should obtain conceptual priority

nordenfelt focus on concept of health, instead of its contraries – illness, etc

starts with health, which is unusual since typically easier to agree on disease, whereas health more contested

Fullfort focuses on illness, Nordenfelt on health

Cannot identify illnesss unless have view of positive health (nordenfelt)

Critique of N, say something of conceptual priority, but Fulford’s argument is non-starter

Fact that we usually observe illness before seeking explanation has no bearing, merely epistemological effect, -    priority in this case not about temporarlityu

dubious to ground medicine on particular goal (individual health) without idea bout what that signifies

must disting between fullfulling positive health

we might mean positive or direct definition of health – not a lack of something

eg. Boorse says absence of disease, but also positive definition of health

or give more than minimum

other examples, such as freedom – different between positive or negative -    state an ideal, not just minimum -    or ideal/true freedom

if apply this to health, WHO definition states both positive definition and positive conception

nothing depends on wherther we give a positive definition of term -    eg. WHO definition as negative, does not lose positive ideal definition o    ie. Health is merely t absence of disease and infirmity, disease and infirmity are states when complete phys and mental .. is lacking’

common mistake to want to talk about positive health, but then people talk about ideal health, which is different

is N ideal or positive?

N might open way to positive, because includes criterion of individual goals, but he adds a restriction by clarification – ‘vital goals whose aspiriation for minimum happiness…so to count as healthy…good health does not imply ability to become completely happy’ – is less extensive than WHO

But still too wide since coveres disabilities that are not ill health

Paradigmatic eg. – -    Lily, an athlete who struggles to becom accomplished high jumper, but does not succced, wants to jump over 2m, not to succeed means not minimally happy, but even sad, though N says minimal happiness not sufficient, but disability is crucial. Lily is unable to realise at least one vital goal. Still, we would not call her unhealthy or in state of ill health, since not a disease, which would be indep of ambitions.

3 possible responses from N - 2 ambitious goals are ruled out by theory. If goal is unreasonable, cannot count as necessary. N opts for objective accounts, but discusess counter productive and trivial goals. - ME: doesit change if Lily wants to be a doctor? - 2. Must lack a second order ability,ie. We could help her by training or education. - 3. Let’s accept she is not unhealthy. But must not discuss as counter intuitive, because is a welfare theory. Nothing left to argue about. Nothing wrong with this definition, but state reluctance to accept. Welfare theory not approp since health is a medical term – end up with medicalisation of all problems

cannot refer to all people who are unhappy just because cannot fulfil goals as ill

must rely on medical normality

we need distinc between 2 interprets of health 1.    taking account medical science (boorse) 2.    grasping eval of medical conditions (normativism)

since normative is logically prior for N, cannot understand why healthXX

from perspective of medicine science people w same condition are both unhealthy

N proposes ideal which leads to medicalisation

We need scientific perspective to restrict

Defence of naturalism qualified by restriction of particular perspective of science -    naturalism must be supplemented by normative, but cannot be removed

G Khushf

Situate health concepts debate in slightly different state

Beginw observation of the debate which is puzzling -    urge to return to Boorse -    Boorse’s work seems to be situated in theoretical biology, but in theoretical biology, nobody cites boorse -    Why does Boorse play such a role in this debate

Need to see how health concepts have been a lens for models in medicine science

Use debate as a lens and look at background context, to suggest that we have real traction.

It is now moving forward

N has made t contribution that enables us to go forward

Rather than argue with Boorse, argue w N.

Science depends on social conditions, but these conds remain implicit

Division of labour between administrators and practitioners of science

Sustain myth of fact/value divide -    colour all features of scientific landscape

medicine not immune to this divide -    in hyperform

consider division between clinical practitoeners and adminitstrators of health care

inc role of administrators

implied that scientifically based practitioners determine what is medically indicated, then negotiate treatment in accord w patients values – this is essential

contrast, admin provide economic circums – estab the conditions

but they are not supposed to influence

these are manifest in ethical deliberations

eg. How are patient’s views Integrated in medical decision making

patient autonomy does not mean equality with physician’s view

physicians are masters of means

eg. Medical futility – approp and inapprop domains of patient autonomy

thus, fact value divide in 2 features of modern medicine -    admin (value)/physician (fact) -    patient autonomy (value)/clinical interaction (fact)

health and disease

appreciate importance of boorse

examine core features of boorse account -    value free and scientific -    broad social and individual patient values are second strand influencing treatment -    socio-economic factors should not play rolein determining disease o    historically problematic: eg masturbation, etc

if focus on these rubricks, we find his position compelling

Nordenfelt -    appreciated predicament fasced by critics of Boorse -    shows why disease canot be value free, but understand sympathy for Boorsian project -    not coincidental that Boorse has taken the BST term from N and uses it to characterise his own theory

focus on deep resonance between Boorse and N and suggest they are much closer

N view of medical science - health concepts tied to human ends, not survival and reproduction - both he and boorse share fundamental assumptions - both think we can tease out the factual and evaluative and applied science involves reasoning and guard against values - N argues health conceptsa re PARTLY evaluative so must speific where they end - onec we do this, can use as basis for empirical eval - does not question purely empirical investigation what marks of end of the domain -    once end is given can apply to realise that end

can understand why health concept is primary -    allows clarification of the end, which is necessary tyo estabg proper role of medicine

health concepts functional analogue of medicine -    mark of legit from illegit

N’s wants based notion of happiness -    focus on: ends integral to medicine are individually relative -    approp values are thus this or that patient, not patients in general -    ends of clinical encounter specified by patient/physician interaction – allows specification approp treatment -    health concept specifies role of…. -    N upholds core features of Boorse, but sustain value ladenness of Health and disease

Nordenfelt should be seen as biomedical ideal

1.    contrast classes for situating the debate

in one of Boorses early aarticles, presents naturalist, weak naturalist, and strong normativist (pure constructivists) -    these are linked to Boorses health concept -    wanted to disting legit (weak) from illegit (storng

but this clouds the debate hard to find anyone that does not have no descriptive -    everyone is a weak normativist

core difference between N and B

new definition of weak and strong -    weak: can disting between fact and eval components (medical v non-medical), while see values as integral, share w naturalist role of descriptive -    strong: not possible to disentangle fact and value in this way. Seek to show how diverse values configure health concepts

Conclusion: new context

In current context, see shift in whatmakes debate important Until now, has been disconnected from trends in medical practice Health concepts incl’y important

Changes in medicine

Eg. Manage care and total quality review

Now being incorporated into standards of care Overlap between admin and pract

Some see as distortion of medicine – economic

Challenge to classical jurisfictions of medical practitioners

Debate also reframed -    is it possible to disting sociopoliticaland economic from microethic of clinical encounter?

Strong normativist is best? (ME: did he say this?)

Cannot sustain neat fact/value distinc in classical form

How to appropriately address in management strategies?

Nordenfelt Reply

Reply to Schramme -    priority of health -    S says order is solely epistemological not logical priority, so fact that we observe before diagnosis says little. Hwr, purpose was not about logical priority, it is health that is logically prior. The observation temporal priority that Bill fulford has argued, not just epistemology, also bearing on conceptual substance. In doctor patient case, we have paradigm case of HC. Tells us what is at stake in the encounter  - patient’s disaibity and suffering. Fact that we label that as disease, tells us something about concept of disease. -    2 arguments: o    1. Ought to be able to explain why someone canbe medically abnormal, without being badly off •    answer: do not claim that all diseases produce suffering. Consider various stages of disease. But for it to be called a disease in the first place, must in some if not most, result in some suffering. o    2. Must be able ot explain why someone is ill and not simply sufferinf from other impairments, such as loneliness, etc. idfs that we include too much. Someone hwo is sad or unhappy will be labelled ill. EG. Lily the athlete, who cannot jump 2ms. She is obviously healthy, says Schramme, so theory inadequate •    answer: talks about health and illness in contradictory, but also in complete. He also says it is a dimension. So when lily does not achieve and when this is a vital goal, it is not automatically that she is ill. It is merely that her complete health is reduced. She can realise her basic vital goals.  Though S would not admit that her health is somewhat reduced, he would maintain that she is completely healthy. Her is an unrealistic goal. If she should be helped, cure is not to turn to orthopaedics, but in ‘goal care’. We should try to convince lilly about the unrealistic nature of her goal. She can set a utopian goal, but be emotionally prepared for its failure. She has a hidh degree of health. Do not enter into people’s lives when they do not call for it. Unrealistic goal setting.

S accuses of including too much, I say he includes too little

Response to George

Constructivist strong normativism

Present concrete eg to test

Need there be a profound shift in concept of health or that we will constantly reconstruction

Distinc between reconstruction and operationalisation

Eg. If clinic accepts ground of someone as unhealthy because cannot go to work – this is operational

What could be reconstructions of health concept

Eg. Measuring health and divising instruments for such measurements. E. sickness impact profile, euroqual, Nottingham health profile -    all contain critieria for measuring health -    they indicate concepts of health -    perhaps the instrument makers construct different concepts of health -    these are postmodern measures of health -    we might have 1000 withiin a decade -    a good state of affairs? I doubt it, descriptively and normatively -    descriptive: o    instrument makers might claim they are merely trying to describe an aspect of health, eg. Mental or dental, or to measure technologies, so not all aspects are accounted for – practical purpose. o    Evaluative: doubt hey would be happy that theya re constructing new concepts of health. They want to measure ordinary understanding – just a partic way of measuring o    May be 150 defns, but from this does not follow that there are 150 good or adequate concepts. Few have derived from careful conceptual analysis o    Thus, maqy find dubious claims within them. Eg Nottingham health profile ‘I lie awake for most of the night’ – explanation? Not just ill health o    We have some intuitive understanding of health and make good judgements. But this does not mean we or they are constructing new concepts of health o    But is there only one concept of health? •    No. like all abstract concepts, health vague. Borders fuzzy. From conceptual analysis only, cannot define sharply.  Must stipulate minimal. But is, at least, a conceptual torso that is given in conceptual language which tells us what dimensions are relevant to health. •    Cconsider Aristotle or gaylen.

Debate

ME: If I cannot work, I am ill. If I cannot be the best worker, I am not ill.

4.2 Future of Medicine

The moral significance of future ‘persons’ G. Papagounous

Question: role of personhood in ethics in relationship to specific entities, namely human beings

In ethics, should not evaluate natural phenomena -    eg. Earthquake, tsunami are neither good nor bad, but consequences can be described in such terms

what is the different between a pilot and a volcano?

Person

Personhood delimintes 2 things

1.    limits of the act. 2.    Allocatrion of the possibility of an act

Warnock – personhood – consciousness, reasoning, self-motivated, communication, self-awareness

Not complete -    if replace ‘raven’ with 2 yr old child, stil theft of ring? – fits personhood as Warnock

must modify personhood

ME: not harm to future persons – they are not harmed. Rather, environmental actions are worsening the conditions within which future persons will exist

Is transferred parental responsibility legitimately enforceable. Matti Hayry matti.hayry@manchester.ac.uk

Premises -    You have (or want to have ) children -    I do not -    You have not been coerced into having (or wanting to have) children by force, threats, deception, or lack or competence or info -    Your children can have children of their own, and so can your possible grandchildren, and so on

Questions

Are you responsible forr t wellbeing of your progeny, including t future generations in your direct family line Are you resposnib for t ewellbeing of other members of t future gen Ami i Are you entitled to coerce me into securing t wellbeing of t future gens?

Are you respon sible for your own? -    box of surprises o    inherited sealed box, cannot open, may contain valuable material or explosive, but smaller chance for latter. Choice: never open box, or give to stranger as give. If give it away, can open it, but no knowledge of contents. Should you give box to stranger

are you responsible for your own?

Conditions for giving t box -    if ou can you can ask t potential recipient. Free informed consent might provide justif -    if not, consider her current sitn. Abject povery might be a factor -    you should be prepared to assume responsib for t conseqs if they are adverse.

Are you responsible for your own? -    the gift of life o    when consider having children, you consider creating indivdwho does not exist yet and giving her a box of surprises o    you  have metaphorically inheretned t gift of life as an heirloom, and you are thinking of

received cannot but open box life might be good or bad

are you responsib for your own conditions for passing on gift -    cannot seek consent of receiver, can only assume -    cannot argue for t situation of t receiver – can only assume life’s value -    must recog your responsib for wellbeing of the (non-voluntary) receiptients -    you must try to guarantee that t lives of your children etc are as good as they can be

are oyu responsib for your own -    answer to first question o    you are responsib for wellbeing of progency, because commitment to this responsib is moralc ond of having kids

are you responsib for others?

How t parental contract comessa bout -    as a prarent you must ask yourself: o    ‘who will take care of my children and my children’s children if I cannot? o    And the natural answer is o    ‘parents of other children. We make a deal. They take care of my progeny if I cannot and I take control of theirs -    how t parental contract is binding o    because by reproducing you have taken on duty to guarantee wellbeing of offspring o    your mutuial contract is not morally binding to anyone else (nonparents) -    answer to this question: o    ou are responsib to other members o t future generations beasides yourown

am I responsib for your children? -    why would I be? o    Because I have made a parental commitment? NO o    Parental contract? No o    Because a need exists, and I should respond to it? •    3 layers •    immediate need in an emergency sitn: your existing child drawoning in a pond? Only I can help. Should i?-yes •    longer term, non-emergency needs: your children need an education, should I contribuite? – probably (prudential), but you first: ME: WHY? SO, REJECT A NATIONAL EDUCATION SYSTEM? •    the needs of your non-existing progeny: why would I sacrifice my worthwhile goals to promote your reproductive aspirations? •    INVOLUNTARY PRODUCED OFFPSRING: should I respond to needs of future children whose existence is due to force, devception or lack or competence or info, of course, but you should join me in preventing such reproduction •    Saving resources to future generations: 5 generations down t line you have burdened t natural enviro 5 units against my one. Could I have double portions, please? •    ME: is he setting up an us and them that is false? •    Answer to 3rd question o    I am not responsib for wellbeing of your distant progeny, or for t wellbeing of other voluntarily produced members of the future gens because I am in no way responsible for their existence

Can you justifiably coerce me? -    possible grounds o    do I have moral duty that you re entitled to make me dispense by coercion or force? No o    have I made a commitment that you are entitle to hold b to by coercion orfoce? No o    have I entered a contract that you are entitled ot make me honour, by coercion or force? No

possible grounds for coercion? -    doyou represent a dominant protective agency which is entitled to coerce me? NO -    if everyone acted like me humanitiy would cease to exist. NO CHANCE. (and voluntarily, what’s the problem) -    if many peoplea cted like me there would be too few tax payers (MOST UNLIKELY) (revise immigration policies)

answer? -    not entitled to coerce me because no valid moral, social or political grounds for such an entitlememnt (I may chip in from time to time voluntarily)

Soren response -    everyone might trace their roots to involuntary creation -    contractarianism: why no contract between procreator and non-procreator to take care of latter

reply -    yes, some involuntariness, but my first duty as non-reproducer is to change world where every reprod choice is voluntary -    wider contract issue with society? Yes, perhaps, but I acknowledged that immediate needs will be met.

Question: the discourse is liberal, but narrow concept of responsibility -    alternative: necessity of action in face of evil.thus responsible for future generations, because the evil exists. Eveil is beginning of responsibility

Question: if you don’t want responsibility, you don’t have responsib for others and if you have your own, you have sole responsibility. But this is not true. Even if you

ME: parental responsibility does not convey, in its entirety, responsiibilty towards children. Parents do not have sole responsibility over their children.

Responsibility for future generations F. Turoldo (Italy) university of Venice.

Why is t term responsibility not t common term in ancient and modern philosophy? -    why contemporary?

Rotation of meaning of responsibility

Initially a juridicial concept – a consequent way – I am responsible for an action and its consequences

2 conditions 1. individuality (I am responsible) 2. consequent (towards past actions)

respondre – to answer for

moral concept of responsibility -    inner judge

T problem of allocating health care resources considering future generations M Igoumenidis

Is it fair to spend mony on moon trips and cloning sheep when could use money to save present people’s lives?

6

European College of Sport Science (2005, Belgrade)

ECSS 2005, Belgrade, Serbia Post Race Rectal HGH

ACE, ACtN3, AMPDI

1 allele of ACE = endurance

D allele of ACE = Sprint

Some studies show assoc

1 acele of ACE overrepresented in SA Ironman - Collins et al Medicine Sci Sport Medicine

suggested this ACE gene other gene with close prox of ACE gene on chromosone 17q23 may encode for a protein directly involved w t athlete phenotype

Growth Hormone (GH1) gene -    17q 24 2 -    encodes for family of GH -    anterior pituity -    IGF-1

Is growth H involved?

GH, little or no beneficial effect on GH on health indivs -    but GH might phys role in carotic metab and enhance tissue repair post ex

ex induced GH secretion stimulates -    swet secretion -    heat XXX through sweat -    influ heat loss during ex

GH1 gene

155 subjects 104 post rectal 55 control subj – no ultra XXX blood sample and geoXXX

triathlete group significance older than control

significance dif in post-ran rectal temp for gh1 genotype

Conclusion -    GH1 not assoc w endurance performance -    Unlikely that any of t genes are aassoc w performance

But temp lower for TT athletes

Exchange Symposium, Fri 5pm

Chair: Emin Eren (TUR)

Sport, Medicine and Scie hist roots -    MEDICINE: fundamental o    Disease – injury o    Healing + prevention

Medicine is sci of diagnosis, treating, and preventing disease

Hist  backg -    priest – magic – physician -    men-nefer -    Met – Sunu – Metsunu = medicine

Medicine and Magic

Ancient Greek

From magic and religion to secular practice Need to understand physics Study of matter and energy -    metaphysics

science -    latin – scientic – knowledge of something -    scive – to know (disting) -    scindere – to cut/divide -    sci – systematic

Is medicine a sci discipline? -    clinical medicine yes -    medicine as ‘art’ of healing using sci method -    ‘doctor’ = teacher

3 pillers of medicine - Claudius Galen – father of sport medicine

Sport Medicine progs around Europe not UK

What is sports medicine -    therapeutic -    team doctor -    sports physician 1904 germany -    dept 1911 dresden -    congress 1912 -    uni course 1919 -    journal 1924 -    institute 1945 prague

scope of sport medicine -    sci, moral, legal, health issues -    enhance qual of life

sci and sport -    ancient

hist of sport sci -    rise of physiology links -    Pierre-Jean Cabani (1757-1808) -    AV Hill -    Edward Muybridge – motion photo -    Ergometry 1790

Sci in Coaching

Coaching – art of sci to better performance

Conclusion

Stimulants – human

Scope -    sport sci – pushing limits -    sport medicine – protecting within limits

brotherhood not rivalry

Pres 2

Fabi Pigouazi

Sport medicine – from biological to clinical

Founded FIMS 1928, 19 feb -    2nd Olympic winter games

IOC MC 1967

Essentials of sport medicine

Ex as essential

ME: ethics in sport medicine at the time?

Ex as component of health -    ex for prevention – treatment, education

specialists -    athlete, coach, team physician, physio – need good relationship

Future development -    sport performance will increase -    av life span will rise -    sport medicine widely used

ME: wat formal structures protect integrity of physican decision making?

ME: ECSS needs a session on science communication

Biol limit of life

115 yrs - goal of 3rd millennium is inc quant and qual of life

heed to change ‘value of soc’

WHO – health definition

Lifestyle changes

Principles of wellness

State of sm in Euro -    euro won 50% of medal sin Athens

Gene doping -    Problem: lack of control of gene expression

FIMS – 200,000 physicians

Vassilis Klissourus

Unifying Sport Medicine and Sport Science: Paradigm of Sport Genetics

Goals – sci – push limit -    medicine-protect

but ultimate goal of both is to optimise human performance

there is no division between sci and medicine challenges

1.    grasp interplay between genes and enviro 2.    bioethic problem of genetic enhancement

Physio Basis of Records -    athlete v non-athlete difference = former learned to close gap between phsych and physio -    drives closer to limits (AV Hill 1925)

Sport Performance Determinant

Phenotype variation -normal distrib - what is relative power of genes and enviro in development of phenotype

2 stages 1. measured genotype 2. unmeasured

JAP, 1971, 31: 338, 344 -    Klissourus twin study -    Max aerobic power -    Almost identifical for twin -    93% heritability -    all genes for VO2Max

Max aerobic for non and identifcal twins -    supp hyp that gen is important for VO2 max

Perth Genetic Analysis

Maes et al JAP, 28 1479, 1996 Genetic and Envirol Sources of Variation in Vo2peak in 105….

Twin research -heritability estimate - conclude genes dominate - for max aerobic power -for max aerobic cap

But phenotype not predetermined or unchangeable -    training changes -    genes not like switches

Reserch direction -    to what extent can modify phenotype? -    A genotype intention modified? -    How genetic is process I change? -    perXX and cognitive?

Klissourus, Interest J Sport Medicine, 2002 Genes and Olympic Performance -    interpret difference were not significance, except for personality (behav)

Behaviour Determines Performance

Identify specific genes -    got to find t many genes relationship to partic att state

Walfarth, et al Medicine Sci Sport Ex, Jan 2005 -    T uHuman Gene Map for Performance Phenotype -    ACE – but siXXX

ME: Include co-presenters on Website of abstracts

Nanga Parbut – 8125m Climbing Beyond the Limits Peter Bartsch JAP 63 752-757, 1987 Bender PR, JAP 1989, 66, 2733 -    ventilation increases over 2wks at a given altitude

1m of o2 of blood -    decrease of plasma vol -    inc of EPO

inc of capillary of fibre

M. Redge West and West, High Alt Physio and Medicine, Chapman and Hall

Calbet AJP 184,304-16, 2003

Performance gets better -    Fulco, JAP in press -    But VO2max decreases, stable

Cenbelli 1889 cited in High Alt Medicine and Physio (Ward, Miledge and West) 2000

1% decrese per 100m over 1500m

Calbet, Am J Physio 284, R302-16, 2003 -    no eeffect because

above 500m -    reduced inoXXX uptake -    24% en deficient at 6452 -    Westertop JAP 1994 -    40% @ 5300-8800m -    Westertop JAP 1993 -    43% during OE11 -    Rose, JAP 1988, find deficit not t issue

Anholm, Am Rev Respir Dis 1992 -    breaking pattern at everest

Sutton JAP, 1988 -    Work on cap of everest

Cognitive function remains impaired 1yr after expedition

RB Huey, JAMA 284, 181, 2000

Mie

Thomas Scasz 1973, 115

Medicine and magic -    formerly when religion was strong and sci weak, men mistook magic for medicine, now when sci is strong and religion weak, men mistake medicine for magic

2 assumpt - sport has relationship lack of governance elite sport susceptible to enhancement

Borgmann – t Baconian/Cartesian project -    man goal dominance of nature – athleteic 1984: 36)

Brown-snout.com/cycling/misc

Ex Dict Sport Sci and Medicine, 1994, 29-30

Biotech – instrum structure -    neither good nor bad -    depend on use

Cuttler et al 1998 – nontherap use of HGC

Kass classif of biomed technology -    control of death and life -    irrelevant except: astr: genetic selection -    Control of H potentialities -    Control of h achievements

Elite sport involves/needs suffering

Medicine not about PERFORMANCE ENHANCING, but sports

Juengst – getting back to normal - telos of med

appeal to normality is problematic in elite sport

Boorse 1997 -    abnormal enhanced health?

Normally as constructed or enhanced

Wollheim, 1984, XIV -    without psych, normality is t name for a ill-defined and tortousuly effXX achievement

3 conceptions of norm

1.    BST 2.    Social construct 3.    Psych/psychoanalyt

Sports medicine need to disting between these ideas -    problem in principle -    can we choose?

Tim Noakes – dis H view of lactate paraxoc

Poster -    detect blood doping through comparison of change in RBC and reticulocyte count

cardiac regenerative capacity -    stem cells

new view of how heart responds to injury

a heart is significance myocyte regeneration - new myocyte formuation

post London

apoptosis – prog cell death necrosis – through injury

why only slow fibres affected -    presence of phosophic -    not present in fast twitch

The Future of Our Memories (2005, Royal Institution of Great Britain)

The Future of Our MemoriesRoyal Institution of Great Britain 23 June, 2005

Wendy -    Bruce Almighty, God digitised? ‘file cabinet’ of memorie -    Share v private

Various Jim Carey movies

Neil

Hartley et al 2003 -    VR – ask neil -    Functional magnetic resonance imaging

Graham et al 2003 -    memory related dementia -    Alzeimers -    Factual memory (Semantic dementia)

Vanneber Bush, 1945 – see Bergire (d-Lib), may) -    www.memoriesforlife.org

AR/VR -    mixed reality lab, Singapore

Alan Nevell (dunde, social memory)

Miniature recording device

48 hrs of video – reality tv – dull – audience

Rugge et al

Hans Berger 1929

Quroga et al 2005 – face recog

Kriema et al 2000

|

Sport Medicine Ethics (2005, Stockholm)

Sport Medicine Ethics, Stockholm,May 2005-05-24

Christian Munthe Sport, Med and HC

HC goods -    securing certain lev of health (prevention, restoration, ailment) -    in a just way

SM goods – secure health conducive to athletic performance -    beyond HC lev ofhealth and goals, also enhancmenet not approach reqt of justive

dual influences of SM -    ethos of trad med (life and qual, autonomy, justice) -    ethos of sports (supreme performance and excellence), autonomy, fairness

Rationing HC -    HC: need paramount (and prognosis); prov for worse off upto a level; contested ideas about relevance of numbers;l contested ides about relevance of merit/desert -    SM: unclear about what is paramount; resource not limted by same funds; numbers probc; merit desert can work both ways (sports injuries, self inflicted, heroes benefit soc)

Conested procedures – 4 args (doping, etc)

1.    SM should adapt to ethos of HC (either prob: goals different; or: reason for revising 2.    HC adapt to ethos of Sports (excellence, fairness): either: prob: rules and goals of sport arbitrary from medical view, or: recom for breaking SM out of HC 3.    Sports should adapt to ethos of HC (but: safety or justice arg) 4.    HC should adapt to ethos of SM (safet, justice) Either: probc, due to dit; radical revision of HC

Remarks: -    what ethos is relevant for ethos of SM? -    ‘place’ of SM? -    Basic prob for ethos based ethics – virtue sport philosophy, or communitarian theories of justice -    Challenge for medical ethics – sm/sport -    There is no archimedian point -    Inquiries into concrete, partic issues needed

Claudio Tamburini

No difference view – between med everything and sport med ethics – latter only more specific applic of normative framework in med ethics generally – NOT TRUE – eg. Autonomy/privacy function/meaning in different way in sport – sport med more paternalistic – eg. Training technique – athletes are not protected -, must subit to rules, - testing = privacynot same – no difference view obviously wrong

But should they be different? – yes: athletes are not sick – wrong to giv medicine for sick – Lyjungqvist = doping is medicine – ‘athletes are healthy’ – thus athletes are not patients – not general rights of HC system  - what’s wrong w athletes using med (prov not state funded) – athlete are patients – meaning of patient – suffer from pathology – too narrow – today healthy people give treatment – not clear where to draw t line – healthy people already consume – WHO – well-being – dependence of medical prof for (non(athlete – exposure to effect of medicine makes vulnerable and this vuln indicates patient status , regardless of whether customer – athlete? – are patients – conclusion: recog as patient

ME: ethos of medicine is that absence of proof does not mean absence of reasonable expectation or evidence; cannot refer to WHO for support for an ethical view same for anti doping code

Anders Sandberg

Health consumerism – what are enhancement treatments? – alcohol caffeine, etc – st johns wort – ginseng – positive psych – beta blockers (musicians) – growth hormone – since it is an enhanceent(?) – IGF – improved elasticity – cognitive enhancement – social (prozac -= leadership) – acceptance is complex =- is morphological freedom a right? – functional food yes, GM less, but dfferes in culture – Japan 50%, would consider, 66% would for … therapy – Thaliand, India, yes, if adv – WHO – health as optimal but function relation to ones own cgoals – conclusion: doping and enhancement  - performance artists: how they change their body

ME: only medical intervention reqd ; modafinial, global GM same?

Question&A

JS: by allowing enhancement, implies coercion

MMc: autonomy – inc vulnerability = higher standard SH: sm goal fro physiocan as not ‘excelelnt’, but goal of employer – make sure team wins CL: health definition tooo wide – who – boorse – too narrow Tomas (athlete): paternalism – we let athlete do unhealthy things, so not too paternalistic – wada: not prov risk to health – Is pressure on autonomy so freat for an athlete? CT: as patient more exposed to med prof – athlete can choose not to expose themselves JP: beta-blockers not analogous – art and creaft

REF: MIGUEL NICOLELI – NEUROSCIENCE, CHIPS IN ARMS, MAGNETIC

Susan Sherwin

Should we welcome/resign/resist – social polic y or indiv choice? – Francoise Bayliss/ - oppose – to pursue GE = research prog – sports req different kinds of body type – enthusiasm for GE = popular reductionism – avoid enthusiasm welcome – also reject 2nd (resign) – beleief in efficacy will lead to demand (!) – resigned acceptance is self-fulfilling- reject inevitability – opt for resistance – social policy, not indiv choice – indiv choice: autonomy as informed choice – prog grants to challenge rights based – for some implices reduced autonomy – must include right to refuse – but in sport not possible – broader implic for young athletes – most likely to be applied in adolesecenc, this is bad time – cannot claim ‘iformned’ – challenge indiv – reject trad economy defences – reject indiv autonomy and personhood and supplement w relational theory – persns as partially contested by social relations – liberal theorie treat self-hood as indiv, relations -= selfhood as ongoing project – wht are t proceses by which a person holds certain prefers – fem theory – irrationality based on consensus (irrational to resist conformity – become irrational NOT to select enhancement – excellence as GM conveys something to those who are genetically deficitine – new expctation for improvement – entrenches legitimacy of comp (social Darwinism) – precautionaryu princip0le needed – excellence is not GM, but social programes – less sexy perhaps

ME: what else shouldn’t we have done based on this model?

Sarah Teeztsel

Adam Moore – unexamined life..open to inspection – proivacy and tech – gene doping – uise of legl gene theory for sport not acceptable – banning just -    drug testing in sport (Canada report) – invasion of privacy - acknowleged

Nick Bostrom

(w Toby Ord) – good or bad – double epistemic prob – 1. radical disagreement about conseqs, 2. Eval of consqs: even if we know what would happen, diffi to say whether, on balance, is good orbad – double epistemic chance of only major reform – eg implic of abolishing slavery, rely on stat and subj intuitions judgement – biases – ‘status quo’ bias – doc by exptl economits – defined as inapprop or irrational pref for state, just because it is XX – ‘mug’ experiment – choc bar or nice mug – predict that 50% would get what they wantede, but 90% choose to return item – ‘endowment’ effect – place value on something just because given to us – irrational? – but status quo bias clear explanation in bioethics, definition of judgmeent for this

how elminate bias? – hypothetical enhancement of cognitve (eg. Memory) – conseq: should we think enhancenment would have good/bad oconseqs? – oft doubts about this (fear of unknown) – how adjudicate between opposing views – ask counter intuitive: what if did opposite? – decrease human cognitive capacity – clearer agreement that bad – those who also bad must judge why ‘current’ level is optimal – burden of proof is on those who make these claims – seems implausible that isat peak – reversal test –doesn’t say is wrong, but that burden of proof on ‘status quo’ – cognitive enhancement: arg from ‘evol adaptation’ reg ratio of heart size to body size – w cognitive enhancements, arg doesn’t work, since eg enviro different now than was previously (ie now cognitive society, previously physical soc);  - if human cog cap corresponded w brain size, then might be good – preventing costs to bigger brain – now less – now less – what evol optimises, so inclusive fitness, but human sep side undermine this – eg. Intell – 2. Arg from transition costs: (do not sxXX, kust because implies t difficult – cost to great - - 3. Arg from risk – but this works both ways – riskness doesn’t imply anything specific -  cognitive benefits enormous – 4. Arg from ‘persons affecting’ – consier not likely to effect – 2nd reason of reversal – imagine – double reversal – more powerful heuristic – as takes into account these other args – toxin in water, reduce cog, intro therapy to water – then toxin removes, then cog enahncenemts above optimal (double reversal test) – reverswal and double reversal best comforts to status quo bias – it extent bias – must interpolate  2 versions of status quo – can take into account genesis choices , deontological considerations, and social policy – intuition about ‘natural ‘ prevalent in bioethics – natural = good – intuition about natural more properly about ‘status quo’

Mike McNamee Slippery Slope

Half-baked HN – witnessin convergence of system – no human or postmodern consition – but convergenet – views of transhumanism not clear – ‘transcend limits’ of HN is wrong – ‘features? Is more approp – reduce vulnerability to human – posthuman? – use to enahncene H choices – no need to shed HN, but augment – in favour: facilitate 2 aims: use technology to improve Hs – transhumanism: ‘ideal blue print’ – personhood: if indep of species, then moral status maintained – arg: 2 types of being|: human and posthuman – Buchanan et al: found on category of H – no longer common H – expand inequalities – genetically deficient – autonomy as RRATIONAL CHOICE THEORY – DEMOcratic technology is naïve and idealistic – surely coomerce will govern – in elite sport prevalent – double blind: poor pay for pleasure of envy – for other transhuman 0 engineer resistance – what is idal type? – criteria of THN – affront to morality – eg. HR, tranhusmanist might be beyond human – why moved by approach of ‘solidarity’ – life span: agening as a creapping evil – woody allen: ‘immortal not by doing great deeds, but by not dying’ – burden of proof should be on transhumanist – transhumanist has no limits and thi is a prob – eg. Bod transplant – burden of proof is on ‘us’ – t human is ‘repugnant (Kass) – proof of transhumanist (HE!) – misuse of drugs for sport enhancement – genetic enhancement – approach to therapy first and subjective normalise these – Kant’s ‘dove’ – preconditions of dyling – should celebrate human vulnerability

For NB : does arg depend on stable conseqs? Different versions of autonomy

Jared Diamond – h not changed much in thouse years, but h can find new ways of re-working hu  limits – intell  (rather acculating of cuilture allows more effective development )

Kate fox book – ‘what do we want, gradual chance, when do we want it, in due course’

NB: Asian disease prob –

600 will die without intervention

A  - 200 saved 75% B – 1/3 600 saved, 2/3 0 saved 28%

C 400 die 22% D 1/3 0 die, 2/3 600 die %78%

A and C are same

B and D are same People overweigh losses in decision making

JS: satuat quo not irrational -    if neither v good nor v bad, then not irrational -    - if chose for 150 age, but might me 40 yr, stick w 80 -    in absence of giving people choice to change, giv opp to do that o    if has rich, then prob not whether conformist – cosmetic surgery entrenches norms

Jim Parry –

Supplements – rusedski – defence – supplement – is suppleenmt controlled Different between an orange or taking vitamin pill – ME: an orange is more (still don’t really know what foos is) – foods are unknown ssubstances

Soren Holm -    new drugs – social position  - should not expect sports doctors to prov good advice -    no reason to beloieve that no ban would lead to open safer doping

should not pressure people finto taking big risks

sociall construction of rules – and arbitrariness of rules

MMc: autotelicity – have own rules

British Philosophy of Sport Association (2005)

BPSA2005 Conference Notes Sigmund Loland

From morals to medicine – a justification

DISPOSITION Why sport? T values of sport to t indiv and soc A selective, critical review of answers from the past and t current A sketch of a possible justification Some implications

MORALITY Arnold and muscular Christianity Coubertin’s ilympism Nansen: avoid sport and practice idrett – body culture of sports (or rather: skiing, the idrett of idretts) Camus: everything I know about ethics I’ve learned from sports

MORALITY II Doxa: sport is good! Children and youth sport -    a safe enviro -    sport as a tool in socialization elite sports -    the system -    the athlete

BUT Children’s sport and moral development (Bredemaier & Shields; Olweus) Elite sports and the society of the spectacle (Gebauer) The fascistoid roots of our admiration for sport heros (Tannsjo)

No obvious connection between sport and morality

How?

Prevalent ideas related to sport:

HEALTH I 1700s, French Encyclopedie (de Wachter) 1800s: t development of applied physiology and medicine (Hoberman) the workers’ sport movement of the mid war period (AIF) -    picked up idea of sport as health

HEALTH II WHO: overweight a global epidemic 1985-2004: av weight increase in adults +5-6kg 1993-2000: overweight 14yrs old from 7.5%-11.5% (Andersen et al, 2004) SDS: sedentary death syndrome

The hegemonic discourse

But… Crude instrumntalism and sociological naivete Individualization in a visual culture Medicalizartion (Zola, Waddington) Strong paternalism (hidden paternalism) ‘revenge of the body’

how?

Sport as a tool

Experiential qualities I Direct and sensual v win and lose Mastery and failure v cooperation and conflict Pleasure and pain v us and them

Experiential qualities II -    a concrete, embodied and sensual quest for answers to existential questions -    what can I/we do? What are my/our possibilities in time and space? What can i/we do as compared to others? Who am i/we?

Sport: testing out of our possibilities as embodied, sensual I’s

Normative anchoring -    Aristotelian eudaimonism: a holistic theory of ends -    Life as a web of values -    Neo-aristotelian virtue ethics (MacIntyre, McNamee) -    Standards of excellence – internal goods – virtues – moral virtue – the/a good life

CONCLUSION Morality and health as integrated values of variable significance Critique: high strung idealism versus practical knowledge Politics of justification and the unity and diversity of life

Could you imagine a version of boxing that did not fall prey to your sorts of concern – is it the ethos you reject or the activity -    critique is buying into the society of the spectacle thesis, rather than the activity

he is talking about the minds of people who watch

Mike McNamee

Polemical philosophy

‘human nature itself lies on the operating table, rdy for alteration, for eugenic and neuropsychic ‘enhancement’, for wholesale design. In leading laboratories, academic and industrial, new creators are condiently amassing their powers, while on the street their evangelists are zealously prophesying a posthuman future’ (Kass, L, 2002)

motivational set of technology intro -    baconian/Cartesian conceptions of science and its powers -    to question their instantation in a new modern ideology ‘transhumanism’sport medicines, genetics and t ‘enhancement’ ideology -    which Prometheus? Hesoid versus Aeschylus -    from athletic to medical hubris (mortality & Mortality)

technology to control nature -    ME: THIS IS NOT THE WAY THEORISTS OF Philosophy AND TECHNOLOGY ARTICULATE TECHNOLOGY

Nuances of myths of Prometheus – lens for hubris of genetic medicine -

science after bacon -    obsession w physical perfectioniams arises as a moral imperative, as sociologists of body have noted, w increasing pervasiveness of modern technology. Roots oder -    Bacon and Descarte emerges t impulse not merely to describe mechanically t operation of nature, but to control it

Moral topography -    Charles Taylor on moral sources of modern identity -    In sport med, might be about drawing relief, natural and artif of work of scientists therein -    As a metaphor for what I take to be t natural work of medicine in the relief of suffering and t artificiality of perf enhancement or t augmentation of natural abilities as opposed to t tradl therapeutic role of medicine

Physicians often sucked into ‘enhancement’

Nature and purposes of medicine hotly contested Roots in healing tradition Assist in presence of someone who suffers Telos of medicine This is lost to sports medicine

Kass’ classification of biomedical technology -    control of death and life -    control of human potentialities -    control of human achievements -    Kass, L.. (1985, 19-24) -    IVF – redefines life and death (not for this paper – ME: YES IT IS!)

Control of human potentialities

Genetic engineering wields 2 powers not shared by medical practice 1.    medicine treats exiting indivs and corrects deviations from health norms 2.    genetic engineering promises alterations to future generations (germ line therapy) and may create new capacities (hence new norms of health/fitness)

ME: HE PRESENTS A CRITIQUE ON GERMLINE ONLY

Changing germline is new.  – ME: NOT REALLY

Not merely to restore, but to augment -    ME: MEDICINE ALWAYS AUGMENTS

Contrl of human capacities -    the limits of many capacities and powers of an idiv are indeed genetically determined, but t nurturing and perfection of these capacities depends upon other influences’ (Kass, 23) (eg. Neurological and psychological manipulation -    ‘from its inception, modern science has been especially interested in finding reliable biological means-means more effective than exhortation or praise or blame-to attain t ends of sensible, decent, human conduct and peace of mind’ (ibid)

new ethics for new  biology. But not sure -    ME: WHEN PEOPPLE ARGUE THIS, THEY DO NOT MEAN THAT WE NEED NEW WAYS OF DOING ETHICS, OR NEW THEORISTS, BUT THAT THE RELATIONSHIPS UPON WHICH ETHICS ARE PREMISED, PARTIC IN MEDICINE, HAVE CHANGED. ALBERT JONSEN’S CASUISTRY, TOD CHAMBERS ‘NARRATIVE’ - New biology: old ethics -    Edelstein (1967: 357-9) notes t ancient greek philosophers task of undermining t glorification of t body -    McKenny cites pplat’s questions in t Republic when..

Plato’s questions -    how much attention should we dvote t our bodies in t effort to optimize our capacities? -    How much control should? -    What endsw? -    What limits …remove causes of suffering?

Scientist – reductionism -    ME: CANNOT ARGUE THIS.

New biology: new ethics? -    ideology – transhumanism -    strong transhumanism – -    weak transhumanism – human nature is a half-baked project o    no respect for sanctity of life

Sports medicine and scientism -    formerly when religion was storng and science weak, men mistook magic for medicine; now, when science is strong and religion weak,

anti-ageing main concern -    we should shed human nature -    taylor ‘we are vulnerable’ -    we should do everything we can to stop it

ME: critique of sci fi!?

Concern about ‘ideal blueprint’

Habermas, jonas, kass, macintryre,

ME: chris gray – cyborg -    sex alteration surgery -    disability

TRANSHUMANISTS UNDER NO ILLUSION

‘Natural is meaningless’ (miah) -    not meaningless, but you might disagree with it

Prometheus (2 versions) – THIS MYTH IS NOT HELPFUL. WHY PICK THIS MYTH? -    overpower god -    cunning of human to be as good as god

ME A WIDE RANGING THESIS – TOO AMBITIOUS DISAGREE WITH THEORY OF SCIENCE/MEDICINE/TECHNOLOGY – PHILOSOPHY OF BIOLOGY CERTAINLY REFLECTS HOBERMAN’S EXPRESSION OF PAST DISAGRE WITH REPRESENTATION OF TRANSHUMANISM DISAGREE W DIPICTION OF GENETICS

IVF – SAME KINDS OF ARGUMENT – NOW WE HAVE, JUST THIS WEEK, LAW LORDS PERMITTED ‘SAVIOUR SIBLINGS’

VIRTUOUS ROBOT?

FRIDAY AM

Anna

Corporeality

Heidegger

Man is man as far as is hand can reach, as far as the purpose of his world extend

Become corporeal by means of hand and speech

Why the hand and not the leg?

Corporeality process

Man assumes emotional figures – existence

Postmodern

We don’t understand ourselves

Universal values have vanished

Gypsies of Europe

Predicated by Nietzsche

Great strength is greatest priority

Speech is essential part of our corporeality Doesn’t pertain only to doctors or semiology, or grammarians, literates, etc

Speech is only an extn of the hand

When hand no longer writes through hand, but through speech, what will happen -    breaking of art, where hand forms meaningful words

what will happen with speech and words -    changed only into symbols

speech taken over by semiology

profound meanings of words will dwindle

transformed into a machine, tool?

Production merely

Physical education responsibility for speech

Hand and words are only means to transcendence

What will happen with the hand?

Managed by computers

Transcendence by sport is victory over self

What about a typing competition -    give someone a title and ask them to write it

LEON CULBERTSON

Hoberman – dehumanisation- ME:  but  he meant alienation (and he is right)

ME: do we need a precise notion of human? (I think he is also arguing for this)

Warnock – embryo rights – she - we don’t need to get into humanness (ME: but that agrees w Warnock!)

humans – as homo sapiens (strong) -    dignity persons (weak)

we are all human – product of our actions

ME: prob is that we do operationalise human!

Dehuman, not less than human Use to work human in weak sense, but not humanness

Edgar – dignity – undignified – don’t talk about dignity when feel undignified

Human definition arises out of sense of being dehumanised

Persons need not be human (McNamee? ME: no!)

What gives sport value?which sport, for whom, etc?

Contextual

Clear view of t misunderstanding Terms such as dehuman used in specific kinds of context

Contrasts – different beings -    prob is that they are oft drawn in way -    drawing t line – ME: we don’t like it, but this is how people conceptualise issues!

Degrading – lack of feeling is inhuman, but not non-human

GEOFF PARSONS

Selection as a vehicle – throughout sport and elsewhere

Conflict of differing philosophy in sport

Different between objectively measured sports and subjectively measured (team sports)

Gov policy driven by sports councils – uk sport

New athlete contract just published -    given to 16yr old, 17p document -    says: we all agree that the overriding thing is to win medals at Olympic championships

institutions of sport act as guardians

performance directors in governing bodies – their job is to win medals – they now have subjective method by which to select people – Olympic profiling – to receive funding and stay in programme, reqs to meet perf directors assessment of what is Olympic profiling -    is asked ‘if athlete wins championship for 3 years, would they get on programme’ – performance  dir says no. -    creates biased selection policies

In objective sport, should be no selectors – performance  on day matters only

Blame governing bodies – complicit, rejected commerce, thirst for resources,

Government role -    top down agenda in very item -    UK Sport cd: seeking perfection

Performance director should be tied to the performance of the athletes for which they make selection

When threatened, sports institutions act like nation states

British sport should celebrate process, rather than medals

WHAT ARE GOVERNING BODIES FOR YOU? WOULD YOU REPLACE THEM WITH SOMETHING ELSE? DIFFERENT PEOPLE?

BIOETHICS AND DOPING

Definition of sport – psychophysio sphare

Doping in sport relationship – if doping is alteration in different relational spheres -    intra personal – relationship betweenathlete and body o    doping – loss of develo of personality o    limit – surpass oneself -    inter personl – negation of propium over sport -    doping compression of games diemsion o    not charac by gratuitousness o    perversion

doping = rejectiung principle outlayed breq to entre into comp

Dr Giovanni Franchi Universita di Teramo giovfranchi@libero.it

ALUN HARDMAN

Different kinds of injury -    injury prior to contest -    iinjury sustained to non-contXX -    injurie sustained as reslt of actions from non-contestant -    injuries sustained as result of foul play

referee must top t game – ME: t player should adopt some referee status -    t rule is badly formulated -    self-offciating/governing -    is it fair only if we interpret t incorrect reading of the rule?

Fraleigh Right Actions -are players following guiding of principleof equal of opp intentionality is imp non-moral principle

health/well being not only concern -    do not stop player if ‘normal injury

ME: if injured player is on attacking team?

Principle of voluntary and dual assessment

Permit medical team to attend to athlete without ceasing play

Is guilt approp response to injury? McNamee, EJSS 2002 -    shame and moral failing, guilt and shame – guilt proper respons to transgress of code, shame is not reaching an ideal -    -if harm unintntionly, rawls says subjective guilt – guilt sign of virtue – causally responsible but not morally

GRAHAM MCFEE

Popper – overstaed claimn of sci method rejected

Account of science -    Popper? -    Creation science -    If meet Popper

Kuhn – different between natural nad social science -    truth denied, t pomo -    natural sci – 2 phases: normal sci – unpacking of past insight, paradigm in place – crisis and revolution when absence of single paradigm – makes no sense -    physics etc failure to invoke conXX over fundamentals -    sociology always contested  - Kuhnan explans why

limitations – socio,psych have competing view of social world Kuhn – how align?

But should be – social world – perspective dependent

question about why in social science you have paradigm claim as barrier to conversations between subject areas?

State of Play Conference (2005, April, Preston)

‘State of Play’ Conference UCLAN 27-28th April 2005 Day 1: Programme for Wednesday 27th April (revised)

Arrive UCLAN Foster Car Park/Reception

Registration and Buffet Lunch 10am -12.40 Foster Building Scholars Restaurant and Bar

Opening Plenary 12.55 - 1.25 Ian Blackshaw The Court of Arbitration for Sport Comes of Age Adelphi TVI Lecture Theatre

Panel 1: Doping 1.30 – 3.30pm Richard Cramer Hazel Hartley John O’Leary Andy Miah Adelphi TVI Lecture Theatre Chair: Hilary Findlay

Panel 2: Civil/Criminal Liability 1.30 -3.30pm Dave McArdle Mark James Viv Ivins Adam Pendlebury Adelphi LT 114 Chair: Simon Boyes

Coffee: 3.30 - 3.45pm

Panel 3: Image and Spectacle 3.45 - 4.45pm Susan Fletcher Sefletcher2@uclan.ac.uk Paul Boylan Adelphi TVI Lecture Theatre Chair: YvonneWilliams

Panel 4: Post -Fandom 3.45 – 4.45 pm Simon Gardiner Robin Manser Jonnny Magee Adelphi LT 114 Chair: Paul Wilson

Close of Day 1: Deepdale Wine Reception 6.30pm –Dinner 7.30pm

Day 2: Programme for Thursday 28th  April (revised)

Panel 5: E.U Freedoms 9am – 10-15am Geoff Pearson Clifford Stott Simon Boyes

Adelphi Conference Room Chair: Steve Cornelius

Coffee: 10-15am -10-30am

Panel 6: Discrimination 10-30am -11-55am John Wolohan Yvonne Williams Steve Cornelius Adelphi Conference Room Chair: Mark James

Closing Plenary 12- 1pm

Hilary Findlay

Adelphi TVI Lecture Theatre

Weds

Image and spectacle

Sports celebrities

Golfer Doug mccormack

Justification for right of privacy in US

Tort of passing off in uk (since 2002, before ‘deformation’ only course of action, and relies on negative), protects (no right of privacy in uk)

2 types of practice - product endorsement (celeb assoc w product) character merchandising (product is about celeb buut not clear whether endorsed, not protected by copyright – de minimus principle – too trivial to be protected) need to register celeb name as trademark as early as possible

trademarks -    photos and other portraits (is possible to register as a trademark) – image that I registered is trademarked, not all images of that face – must be capable of distinction

photos of people at work – eg cantona scoring goal – diffi to estab, since other traders might want to use them

justice lavey – elvis presley case – where there is trade….that person has no right to stop others..legit trading in image

must use images that are distinctive

with endorsements -    goal of advertiser is to use recognition factor to draw on ‘halo’ effect – eg. Because beckham is brilliant footballer, if used for Gillette, tht must be brilliant too

talksport commissioned agency to produce 3 box sets – shorts w skidmarks eddie Irvine on front – without permission – no issue w photo, since itw as purchased from agency, photo had also been changed – mobile phone transformed to radio – justice lalley decided it was passing off – ref mccullock v may (where same line of business imp) – ‘common for famous people to exploit their images….reason why large sums are paid for…those in .believe that..endorsee takes benefit – upheld by Court of Appeal, despite criticisms on judgement

need to clarify whether good will

need to show actual damage

diffi to bring action on passing off

in this case, it increased pay off from £2000 to £20000 because Irvine said that was minimum he would accept for this kind of endorsement – often, ends up this way, so can take the risk

David Bedford – 2 lookalike figures- directory inquiries service 818 – he had not endorsed. But if he had tried this on passing off, would have had problems – that image is no longer viable, and it wasn’t actually his image that was good, it was look-alikes

If you had personality rights, it would have a remedy

Justice Lalley in Talksport and Irvine talked about modern commerce, but Art 8 of ECHR might have worked – celeb endorsements: any negative publicity, might be transferred back to product, thereby reducing brand equity, so imp that reputation be maintained.

HRA came into force -    Art 8 and 10, -    Does not fully incorporate ECHR (incl privacy right) -    Though courts have interpreted them in context of eCHR8 and 10

Court considered both 8 and 10 in separation, since neither had priority -    court of appeal found in favour of defendant, The Mirror

A & B and C – footballer – newspaper published details about his relationship Lord Wolf ‘ where an indiv is a public figure, he is entitled to privacy in appropriate circums..though must accept that will be subject to scrutiny by media’

Justice Langley, no interim injunc to publish rev of beckham’s former nanny -    story in clear public interest -    nanny ‘fortune based on them having successful marriage’

are we all entitled to t same degree of privacy? -    athletes, politicians?, is it relevant that sports stars often treated as role models?

Other issues Deformation Data protection

Beckham in junction – analogy w Naomi Campbell case – mirror found out she had taken drugs, when she claimed she had not

V fact that beckhams are unique is because of this marriage, so perhaps it is in public interest

Q&A

Athletes as role models? Evidence? -

negotiator

licensing of computer programming

language concerned – English or Japanese – French as comprormise

spectacle of the sport

the spectacle has become international big money

so much money involved in org sport

challenged by Internet

essence of spectacle is money (as control of spectacle)

control by contract (player contracts in particular)

3 parties to every player contract - player, organisation, trade union

baseball, prob not steroid use, but that contracts arranged by trade unions prohibit testing -    eg of how powerful union can be: unfair labour practice claim -    john mcgee – player contracts out of control – to detriment of players themselves

in each contract, because dealing w people, not product like any other – need meaningful relationship

research opponents

confidentiality agreement essential -    between player and association -    do not want others to know what you are paying -    nobody knows what other players are getting -    to avoid constant battles

other aspects to spectacle -    beckham nanny: she breached confidentiality agreement, failure of lawyer o    lawyer did not write contract to convince nanny that disclosing would be risky o    why did she go to paper? They promised her indenification – paper knew she would breach agreement and they agreed to pay it o    could have used liquidated damages conract – give incentive to her not to go to paper o    lawyers should have realised that someone would come forward

fantasy sports -    who owns statistics? British law says no. US authority say the people who manufacturerd it have a right to exploit it -    in US fantasy football worth $3billion dollars in profit -    it wil not end up before court, because too much to lose for both, so negotiation inevitable -    in UK, says this is public info stats

Q&A

Motorola downloading info, creating more info out of raw data – breach of copyright issue failed -    unjust enrichment for US, not similar to Motorola

for fantasy football – is it fair for someone to profit from something they did not produce -    implied license, so will compromise

Thursday

EU Freedoms

Simon Boyes, SL at NTU Law School Caught behind or following on?

Cricket

Kulpak

English cricket system now moved to permitting 2 overseas players in county teams

Implications -    oppo to play against intnational players, but result is fewer opps for local players to get into team -    lottery funding goes to overseas players

bosman case 2key elements -    transfer fee at end of contract, now in breach of Euro articles treaty (restrtc freedom) -    abolished discrim on basis of nationality on limitations to foreign (EU) players

for cricket, transfer fee not relevant really

player quotas has had a relevance

kolpak, analogous to second part of bosman – right not to be discrim against, once in employment – he was a Slovak handball player and was goalkeeper in second division – was subject to quota inquiry

euro court of justice – if association agreement, gives right not to be discrim against based on nationality –

cottonow agreement – similar to kolpak - kolpack does not give right of access to employment, but merely, once in employment ,not to be discrim against

recent change I work place employment

used to be case that commonwealth citizen could obtain working holiday permit – now changed – acting as sports person is not ok – implic for west Indian states and south Africa – but if can satisfy criteria and state no interest to play test cricket, is relatively easy to get in –

EC sees as imp – new strategy, continue w rules but use incentive scheme – give counties £200 per player per day for evry English player  = £20,000 per year perhaps – trying to drive foreign players out

Not appropriate, since tends towards discrim

Has the effect of discouraging teams to not employ foreign players

Cricket is different and this is making a wrong choice

Symptomatic of sports

Assumes can transplant bosman to other sports

Cricket can argue for some level of discrim

Uk only member state that offers opp to play pro cricket

For bosman, argued would diminish opp for pro players, but dismissed because of reciprocal opps

For cricket, this reciprocation not possible

Structure of cricket different from football, impc of test game cannot be overstated – test deal with ECB and sky – stated they needed to do this because test game provides money for grassroots –

Health of England team signif to sport, so more worthy of protection

English high court since 1978 kerry pakka case – test cricket a value worth protecting

Describe as a structural rule

Geoff Pearson, Liverpool Uni, Management School Football related Legal responses to football holiganism, policing of football grounds

Keeping a sense of proportion: Football banning orders and the fundamental freedoms of ‘known’ hooligans

Problem -    English fans reputation for disorder -    40,000 english fans in 1998 -    60,000 man u fans in 1999 -    euro 2004, upto 250,000 attended

serious disorder at france 1998 965 arrests at Euro2000

probs w previous Banning order legislation

Football Disorder Acts -    banning order for hooligans, known to cause trouble -    not new, first introduced in1986, Public Order Act, sect 30 -    Football Spectator’s Act o    If convicted of crim offence relationship to football, prevented from travel when game takes placeabroard

1999 legislation unsuccessful

Football (Disorder) Act 2000 -    Schedule, Sction 14B, new type of banning order to be more effective o    Banning order on complaint (as opposed to conviction) o    If suspected hooligan – big leap! -    If suspected to have contributed to violence, and if court satisfied, magistrate must impose order -    Police watching suspected hooligans, compiling evidence, and proceeding on civil procedure -    ME: how long?

Civil Libertarian concerns w baning orders on complaint -    treaty of EU – right to leave one’s territory -    ECHR – Art 4 liberty and Art 6 fair trial (because introducting punative criminal penality on civil stat case)

Gough a Smith v Chief Constable of Derbyshire (202) QB 1213 -    ECHR (was banning order contravion on Art 6? -    EU treaty (was it proportional) (Does it apply in this case?)

was it applied in gough and smith, and are banning orders on complaint a proprtioanl response?

Proportionality Principle -    must be suff imp to justify limiting a fundamental right o    how serious a prob is football hoolianism? Court don’t like it, though not sure it is really so signif •    every week English fans travel abroad, so number of incidences is quite small •    media hype-up, we don’t see much of uk violence o    Statistics of arrest, conviction, death and injury •    Suggest prob is reducing, no stats on death or injury (1 per year for 25million spectators) •    For Euro2000 arrests, only one was charged w an offence o    Comparison w other cross-border crime (paedophiles, etc) -    measures must be rationally connected o    how imp are banning orders on complaint to t control of football crowds? o    Are those involved in disorder known hooligans? o    Does preventing known hooligans travelling to matches necessarily prevent crowd disorder o    Not actually known hooligans gathering together that causes probl; if properly policed, no probs; but where not policed well, problems arise -    no more than is necessary o    are there other ways to control problem rather than infringing these rights? •    Banning orders on conviction (ME: but can they get convictions? Otherwise, why so few cases?) •    Policing tactics •    More efforts on Fan Policing (support legit expectation of fans) (typically, where a few incidents of violence, police go straight in to entire crowd, rather than select few) • -    De Freitas v Perm Sec of ministry of Agriculture (1999) 1 AC 69 o    This test not thoroughly applied in Gough o    Infringements of civil libs are out of proportion

On strictest version, talks about least restrictive alterantive -    not just whether connected or necessary, but whether is less restrict alternative

ME: what is basis for concluding that courts are so influenced (out of proprtion) by hooligans on tv?

Clifford Stott, Uni of Liverpool

Proportionality in psych of riot

Science of crowd dynamics

Football crowds not just hooligans

Crowd dynamics and riots at international tournaments -    those arrested and convicted are not known hooligans -    identity based processes involving intergroup interrels -    police play pivotal role in structuring these rels

category of being an English fan affects way they are policed -    creating enviro empowers those seeking to create disorder -    they are facilitated by the form of policing -    level forceful and indiscrim forms of policing, based on reputation, rather than behaviour -    English fans arrive and begin to perceive form of policing as illegitimate – see this as affront to rights

When fans perceive policing as legit, then changes dynamics -    eg Scotland fans, emerging sense of leigitmacy in police and self-policing

absense of disorder has little to do with fans, more to do w rels

implics for policing

Euro 2004

collab w PSP (one of portugal’s two forces) create enviro consistant w research

risk is dynamic risk emerges, not fixed interaction of groups influences level of risk

‘balance’ in risk scenario -    police in balance implies low profile deployments, results in spych and behav different

ME: is it difficult for police to target arrest in big crowds?

Discrimination

? South Africa

Chances of aids transmission in sports arena v slim so not subject to compulsory testing, since is unnecessary and in legal context of south Africa, is v precise about rights to eg human dignity, privacy, equality, choice of profession

Chalk v California -    Judge: plaintiff will have to estab that defendent sporting body is receiving funding from gov and that enjoys public patronage

Aids now (since last week) considered a form of disability, which changes sitn somewhat.  Justice jones: confidentiality vital to public and private health

Recog right to dignity, intrinsic value of human – respect and concern

Diffi to force athlete to undergo a test

X v Y and Another

Cf hiv testing and doping? -    hiv more invasive and less accurate

Steve Cornelius, Uni of Johannesburg, Centre for Sport Law

South African Measures to Combat Unfair Discrimination in Sport

Assumed that in SA apartheid implied merely racial, but also concern about gender and disability

Bill of Rights (starting point for all law in SA) -    s 8.2 – binds everybody -    matter of public law

right to non-discrim -    s 9.4 -    no person may unfairly discrim -    not all discrim is bad o    s9.4 prohibits unfair discrim (implies that there is fair discrim) -    s 36.1 – limitations clause (law of gen applic; based on human dignity, equality and freedom, in democratic soc) -    s9.2 – affirimative action measures

legislation -    prom of equality and prevention of unfair discrim act o    if unfairly refuse to consider applic, then unfair •    provides for action, do not need to show actual harm o    denying access to club o    failure to promote diversity in selection of rep teams

SA Sports Comm Act -    coordinate provision and upgrade of facilities in disadvantaged areas -    assist in development (lot of emphasis on women in sport)

Yvonne Williams

Do volunteer coaches have right to refuse responsib to coach people w disabilities?

DDA1999, part 3 – sports coaching is a service, so cannot discrim against a disabled person by refusing to coach or way they do it.

Direct discrim  - treat less favourably then how treats/would treat others

Indirect discrim – same activ offered to all, but disabled treated less favourably or put at disadv

Case in US, using computer aids to hunt

John Wolohan

Discrim laws in us

Racketball player w disability, wants to play w able bodied, and instead of one bounce in the game, he wants to have two – adjust t rules to accommodate a disability

Child w disability takes longer through highschool – rule that only under 19 can play in school sports – so cannot play – but rule is discrim disability?

Casey martin – pro golfer, trying to qual for PGA tour, to get card need to go to qualifying school – he has made it to stage 5 until which he has been allowed to ride a cart – requested for final stages and pga tour – pga tour reject request –

Supreme court grant right to use cart

Walking in golf not really fatiguing and deven if it is casy martin’s fatigue getting in and out of cart is greater than well-athlete

Decided that essence of golf was shot making

Does pga have right to set rules? If pga says it is essential, who is the court to say otherwise?

Asking to modify game just so you can play is not reasonable – it is creating a new game -    able bodied player will have to learn how to play you in different ways, this is not fair

is it a ‘reasonable accommodation’?

Closing Plenary

Hilary Findlay

Canadian Independent Dispute Resolution Programme

Genevieve Turninkey? -    ‘dispute resolution’ ‘real growing activity’

ian blackshaw author of book on ‘mediation in sport’

rules of an arbitration process as instrument of sport policy

what is approp scope of review for sport dispute? -    how broad are grounds of review? -    What is standard of review? -    What scope of authority, when error found?

Appeal layer

If appeal panel has made error, then judicial review (v narrow)

April 2004, dispute res intro to canadian sport

Doping infraction for horse, trainer acknowl that horse given substance by vet that was prohib – this was not raised in hearing, since accepted by all – rules state where horse doped, trainer responsib – but held that vet responsib – strict liability, so trainer liable – parties waived internal appeal process – q about scope of arbitration – hearing de novo (everything relevant should be seen – argued this was too broad –

Second athlete not selected – went directly to arbitration – include first and second round or only second, where issue

Broader scope of review, further usurps authority of sport org

What standard of review to determine whether error?

Human Enhancement Technology (2005, Harvard Law School)

Dan Brock Positional / competitive enhancements Relative enhancement or intrinsic

Many enhancements Ritalin ‘Enhancement v treatment’ v ‘enhancement v achievement’ surgeon  using drug to steady hand – enhancement? But a good thing! Special diet? – training, tf natural -    distiction – conventiona

natural means, effort, etc -    basis for merit

but use other things – natural talent natural – not what we can take credit for

natural – brings out potential enhancement – changes potential

but flawed! No such thing as a fixed potential

Olivier

Rules for technology -    icu – rules on bikes

press on doping often biased – in what way? -    media over simplify -    sometimes good that not public

record number of positive cases in Athens -    more than history of Games

Misuse of medicine

They are fighting ‘mafia’ of sport – illegal market of drugs -    ME: what is incentive pf pharma to work with WADA?

Protect ‘ future health’ of athletes -    ME: mmm, future health, what does it mean to protect this? – if gene profiling shows I will die at 30, then?

More public exposure than ever before

Anti-doping comes from the Athletes, who do not want to jeopardise future -    athletes want to be natural

standardised v personalised technology

Q&A

Power patches used by athletes – lifewave technology Acupuncture?

Different kinds of technology

polevault -    accessibility

Is there any incentive for Pharma to work with WADA?

If all enhanced, sport no more interesting -    al athletes running 100m at 8seconds, no more interesting than 9secs

not all risks are acceptable, if come with harms that

Olivier: we are in a ‘risk reduction’ society. -    ME: mmm, not that sure! Risk calculating perhaps.

Next generation of EPO -    company who develop panicked, since worried about its use in sport

genetic technology as therapy and enhancement, then is it ok?

Technology and Sport (2004, San Sebastian)

San SebastianDec, 2004

Basque

Thank you very much -  Milaesker Hello – Kaixo

Regards - gorantziak

Zer moduz – how are you

Aldor Cobanera

Edurne Pasaban – Alpinista (athlete?) elite,  Mountain Climber -    only woman on opening panel -    since 1998, major changes in technology -    in climbing, far better known thanks to technology -    materials, but also other technology connected with communication -    ICT to stay in touch through mobile phone technology -    Telephoning from summit -    Breakthrough in medicine and technology o    Can contact physicians  when injured in mountain -    Even more important in a minority sport -    Now when on expedition, now take laptop, mobile phone, web access -    It is still difficult to peak -    Technology does not help that much

Victor M. Izquierdo Loyola, Subdirecter General of the Info Soc Enterprises, Ministry of Industry, Tourism and Trade -    ministry of trade -    EC paper on IT o    Talks about how applics and experience should be present from beginning of research design o    Users must be the consideration of a product development

Noberto Santiago Elustondo, President of GAIA -

Jaime Lissavetzky Diez,  Sec of State for Sports and President of the Higher Council for Sport -    subjects have economic and social impact -    physical activity,  and doping -    which is most important? – boosting of physical activity, particularly interesting. -    Enormous amount of consumption

Juaqin Villa, Dept of Innovation and t Knowledge Society -    need to create social network for innovation -    innovation broader than technical and corporate o    also management, services, o    not just in company enviro o    society in general o    innovation as a social phenomenon o

ME: Nobody yet has actually addressed the social concerns, but they have been intimated.

Kim Blair Technology and Sports: Developing Consumer Products

2000 Olympics -    Speedo Fastskin – received tremendous pulblicity, Speedo said, anyone can have one, so was ok. -    Sydney pool was state of the art – hardly discussed -    Reason why records broken in Sydney, was because of the pool o    Though did not have the political resonance

Trek Madone 5.9 Bicycle – I used by Lance Armstrong in Tour de France

Technology and Golf -    1920s Steel Shafts replace hickory shafts -    1960s: fiber glass, aluminium titanium shafts – never made it to market

change was an ‘accident’ -    material not caused change, but that titanium springs -    St Andrews changed spirit of rules – face of club has spring like effect -    In golf industry, believe that curve will flatten out -    When technology introduced, see sudden change, then flattens out and comes back to athleticism

Sports Producct Industry

Attitude to risk -    nuclear, civil engineering and aerospace industry o    slow to adopt new technologies o    whether or not technology is viable o    high regulatory climate -    sporting goods manufacturer - o    Marketing and fashion driven •    Marketing often head of product development •    Signif vol of product sold by brandingt •    Signature products, star endorsement •    Need to seel your vision and the ‘wow’ factor o    Time to market is fast •    Typical small changes on seasonale schedule •    Continuous product intro o    Research horizon •    5 yrs is long •    less than two years typical o    Personnel •    Closed network o    Highly secretive •    Technology barriers are low •    Extremely high lev of secrecy on new products •    Control ofIP is reqd by sports company

No innovation infrastructure in US -    nothing llike SPORTIS

Before 2004 Tour de France, Lance Armstrong called sponsors wanting to put together F1 team – Trek Nike Oakley, Giro and HED – to form collab effort between them

USOC -    relies on product sponsors for nearly all product R&D

Developing Sport Products: Product Attributes -    need to understand all -    aesthetic -    attributes of association -    perceived attributes -    emotional attributes -    style

User-Centred Focus -    talk with lead users – passionate sports people o    understand what they like in their product o    understand why they are passionate about sport o    understand how sport influences daily lives o    understand how daily lives influ their sport -    understand core market o    development surveys o    validate t data o    typically use demographic data -    understand own business o    innovation/product needs to send right message about company’s vision

Cost Sensitivity -    eg. Consider cost of raw materials o    golf tee about 2x cost of materials •    change in material has huge impact on cost o    Golf club about 20x cost of materials •    Change in material has small impact on final cost •    Can change to more expensive…

Heart Rate monitors – 20yrs ago, people did not understand it. Now a company come out with a product and lot of effort in training consumers in using that tool. Plan for and expect slow product adoption

Never underestimate challenge of changing consumer behaviour

Capturing Product Value

Limiting comp -    retain control of IP -    retain key assets o    people, trade secrets, licensing, partnership agreements -    typically, technical barriers are low – easy to copy something new

Developing Alliances - Large multi-nationals -    have patents in place -    development clear vision for product from customer’s viewpoint -    more complete t concept t better

Universitie -    useful for product testing -    can be useful for prototype development -    due diligence required on IP ownership

Venture backed efforts -    develop venture division of your company -    solicity ideas from inventors (internal or external)

consultants -    highly recommended to have ‘insiders’ on team -    provide industry expertise -    prodide industry introductions

Rene Eijlens Innovation for Gold

Beat the heat Clothjing -    hat used to remove heat from head.

European Paralympic Committee -    from therapeutic to elite -    technology central to this development

LUNCH

Xtema… - golfer

FRIDAY MORNING

Xabeir Azkargorta -    medico y entrenador de futbol

En busa del futbolista excelente Luis Fradua Universidad de Granada

Nestor Lucas Cairos System: the intelligent football

Radio based tracking system that analyses data of ball and players in real time

Useful for referee, for graphical presentation of replay

Xabier Azkargorta -    technology is leading to an easier contest and reluctance to train as hard -

Digital Games Research Association Scotland (2004, Dec)

Digra ScotlandDec, 2004-12-14

James Carse – game theorist at NYU – ‘finite and infinite games’

Sutton-smith – the ambiguity of play -    seven rhetorics of play -    modern o    play as freedom o    play as development o    play as imagination and creativity (arts, media, science) -    ancient o    play as power and contest o    play as group identity o    fate and chaos o    play as laughter, subversion

prodigy90_med – advert on gaming – sport related narrative

relationship between ethics and gaming

aint misbehaving: play in organisations, matt statler et al, imagilab, 2002

Daniel Livingstone

AI in Games -    ai = adding behaviour or character -    not officially AI -    e.g. Guard State Machine o    player, guard, player doesn’t want to be seen by guard. o    Basic programming is using a ‘state machine’, not really AI, but creates illusion of AI. o    If we make a noise, guard will ‘hear’ and investigate

Natural problem solving systes -    brains, evol, -    immune syst -    artif o    – artif neural networks o    genetic algorithms (and evolstrategies) o    artif immune sytems

The Genome -

Justice, Healthcare and the Trend Towards Predictive Medicine (2004, Brussels)

Conference NotesJustice, Healthcare and the Trend Towards Predictive Medicine 22 & 23 November, 2004.

Intro

M-J Simoen Background on Foundation.

Cecille…. Brocher foundation aim to provide place for research, linked to medical and scientific: socio-political implications of progress. Mr and Mrs Brocher interested in links between science and law.

Is medical care a service like any other?

Alex Mauron Scientific and social aspects focus Access to health care should not just be for determining individual predisposition, but social solidarity – linked to justice.

Importance of Europe. Genomic and medical progress – impc placed on difc between individuals and risk profiles and tendency people have to be affected by certain medical conditions – pharmacogenetics.

First analyse from philosophical perspective (first session) – regulatory concepts.

Bernard Baertschi, Uni of Geneva – philosopher of bioethics One of most signif authors in francophone world

Bernard Baertschi Norman Daniels was student of John Rawls

Sustaining a right to health care Norman Daniels, ndaniels@hsph.harvard.edu Harvard School of Public Health

Can (should) t tradl Euro view of health care as a basic, universal right be sustained in t face of t challenges posed by advances in predictive medicine and t emergence of a more diverse Euro Union and Market

I focus on ‘should’ more than ‘can’, though should presupposes can, so cannot escape feasibility

Small Irony

You should sustain right to health care 45million people uninsured in US –  they get care, but get too little too late

mentions Bush prob

Promise from more competition: more efficiency -    US as model – expts in comp at various levels: hospitals, insurer, managed comp o    Early Rand study evidence: cited as main evidence, but negative effects on patient health not given much attention o    Prob with export of US strategies for health care – led to following bad models o    Era of managed comp – 1990s ‘backlash’ o    ‘consumer driven’ health plans in US – newest phase -    Economists: failures to lower unit costs, to lower rates of cost increase are evidence that ideal market conditions not approximated, try harder

RAND HIE: 1974 (CLOSE READING IN AN AGE OF EVANGELICIALISM – LATER) -    RANDOM CONTROLLED EXPT REGARDING FREE CARE V DIFFERENT LEVS

Appeal to markets: empirical not principled issue -    not in principe against using market forces – if it could be shown that comp worked to make system yield more value per euro and could be channelled to do so equitably through proper reg, I would embrace integrating marketing mechs -    BUT: US unit prices highest in world, despite more market mechs, no evidence of greater value per doller – indeed contrary evidence, and worst outcomes (return to this later) -    Caution

Promise of Predictive Medicine -    early, low cost predictive profile of health risks – through extensive genetic testing o    assumes low cost, good predictive value for more than straightforward genetic diseases eg. Applicability to high prevalence, chronic conditions o    assume privacy issues addressd -    Promise from (hype from?) genomics, proteonomics,- specifically tailored drugs for safe, effective treatment of indiv depending on genotype -    This technology is a mismatch with existing economic incentives for medicine -    Every drug will become orphan drug – only treat a few people, so why develop o    Many economic and oscila probs before

Predictive Med: two paths -    make syst work better, sustain equity o    idf those at risk o    respond better to identified needs •    indiv medicines? But more orphan drugs o    allocate fairly across competing needs -    divid and conquer: undermine equity o    stratify risk pools •    us v them ideology o    shift costs to those at greater risk (poss to identify those at risk and better respond to needs)

overview of argument -    special moral impc of health o    opp range, capabilities •    connected to Rawls’ theory •    from several philosophical perspectives, if one could devel claim that funl right to protect opp range of indivs (Raels ‘equality of opp’), then argument that way to think about healthcare is protection of opp range… -    obligations of justice to protect health o    obligation to promote fair equality of opp -    use predictive medicine to better protect health, not shift costs or deny coverage -    beware temptations of market – evidence, not ideology -    intergenerational equity/justice and sustainability of transfer schemes o    shrinking working age population makes more difficult to finance health care syst in Europe

FEO Account of moral impc of HC -    disease and disability are epartures from normal function

Justice as Fairness -    hypothetical contract (Orignial posn) -    simplifying assumption o    normal functioning over lifespan -    index of primary social goods -    three principles o    equal basic liberties, fair value of political liberties o    fair equality of opp o    difference principle (restricting range of inequalities permissible in soc)

Extending JAF to healthcare -    JAF simplied to case when there is no disease, disabilityt or premature death -    Open to criticism: - arrow sen, others

Whitehalll study (Marmot and Shipley, 1996) -    all-casue mortality by grade of employment – whitemall men 25 year followup -    socio-economic gradient of health -    not explained by health risk factors we usually talk about (such as lifestyle choices) -    hypothesis

(Justice as fairness) JAF flattens gradient

Compliance with 3 Principles of Rawls -    flatter than

theory extends in surprising way as to why justice is good for health

Accountability fo reasonableness -    four conditions of fair process o    publicity: reasons or rationales for imp decisions and indirect limit-setting structures publicly available o    Relevance: fair minded people (relevant stakeholders) agree rationales are aimed at pursuing appropriate patient care under resource constraint o    Revisability/appeals: fair appeals procedure o    Enforcement/regulation

-    REF: Daniels, Sabin Setting Limits Fairly, OUP 2002 o    Moral disagreements surround many decision, don’t have agreement on moral principles that resolve these disputes, so must fall back on account of fair process that minimises choices that are made

Shifting costs to ill or high risk -    argument for Actuarial Fairness – purchase health security at actuarially fair cost o    US substitute insurance concept for moral concept o    People should buy security that reflects real risks o    It should not apply in health setting -    Actuarial fairness is not fair – if protecting health is social obligation -    Burdens according to ability to pay, not need: principle violated

RAND HIE: SOME NEGATIVES DAVIS, J. HSR 2004, 29: 1219:33. -    Adverse effects on low income and high risk indivs (Rassell, 1995, NEJM) -    Lowincome high BP: better control with free care:; lower risk of death for high risk

Risk Stratification: other costs -    culture is created by institutions, instits can encourage or discourage and reduce mutual support – what’s in it for me, rather than us’ spreads like cancer -    stratifying insurance schemes not only shifts costs to ill but undermines more gen concerns for social justice -    not only will access and burden be modified, but content and quality of benefits will stratify

In Europe, 50 yrs of sharing and caring, in US has promoted division and self-interest. Contributory factor to recent US election as well as others. In US until now, one of good thiungs has been universal health care provision for elderly – not sure whether will continue

Use predictive power to improve health for all – other parth -    respects social obligation, equity -    estab priorities using accountability for reasonableness -    improved preditctive power may have efficiency gains -    evidence based improvements, compatible with market

Challenge to sustainability -    societal aging, changing worker to elderly ratios o    China most rapidly aging popn in world o    Dramatic societal aging in Several Euro countries – shrinking workforce in Italy, elsewhere threat to pay as you go financing of universal health care -    Technological cost drivers – medicine is not what it used to be, costs more everywhere

Challenge not from predictive medicine, but promoted as challenge, by rise of aging popn and reduction of ratio.

Jean-Francois Mattel University of Nice

Devel of health care since mediaeval system intended to take careof needy – workers -    was a social issue, now political

hospitals previously funded by charity -    now funded through solidarity

why is there a philosophical issue? -    defn of man, solidarity -    moral prob on defining human and fair sharing in terms of human dignity -    different to compare health care systems around world o    instruments used o    current used indicators are infant mortality and life expectancy – which relies more on social conditions -    health care system o    defn: range of techniques/practices intended to produce health in same way as we produce wealth o    metaphysical/ontological: what is health? •    Material asset or something different

Can health be seen as industrial product – something that can be traded

Syst wich distribs health – hc systm –more different to control, since has many parts and increasingly economic, indl, and financial components -    which is wher political comes into play

central Q: equality of access for patients and legality of assumption of HC costs

perhaps 3 main axes: liberal (US egaltarian / Euro), inegalitarian

tendency in Europe to think syst is preferable to US, since has concept of solidarity that underpins it -    link to historical idea of charity

society has moved HC into social space, rather than religious space -    social spaces collective, whereas religious spaces are individual

Durkheim – collective concept of solidarity

How can justify solidarity and influ in HC?

Imp in HC since calls into q, social prof and human dimension, but also biological and physical concept of human.

For first time in history, biology become social concept in terms of how society assumes costs of HC

Can bring demands of health into HC and move beyond idea of HC as idea of solely doctor to patient. Horison of perfect health – Utopian society – everyone perfectly attended to. – to allow maximum of solidarity

Increased medical component of science and way that HC incly based on technology, gives new way of analysing human and providing HC.

Belief in indiv dimnison that is absolute – human dignity

Need some distance – philosophical q

Requirement for human dignity and solidarity is devel of human beings over 300 hrs.

Anthrop sense – modernity – (not go into postmod) – converging processes -    new kind of socialised human being -    First charact: progressive secularisation of religious concepts o    eg. Religion based on Judaism or Greece, man only perceived of own existence through religion. No right to health care. -    Second charca: de Toqueville – inc socialisation of man, led to tensions between social and moral requirements. Political arena where they are reconciled -    Third charc: social reqs of today, express on individual needs, rel between individual and social sphere – social demand as collective -    Fourth charac: technical development leading society. We ask sci and tech to solve social and medical problems

Change to modern sense of man

Second of these claims is that concept of man incly reduced – focus on body reduced – what the body requires

Think philosophically, but also consider human dignity and relationship to body

Does a dead body have dignity or is there a higher concept in play here?

Here we talk about dignity of socialised man

Tension between ethical concept of dignity which, to some extent, has metahistorical/metaphysical concept and need for using body, which means that it naturally comes to disappear

Need medical correctness as equal distrib of care to whole of body or to whole of society

Problem: right to medical care nothing more than political right

Rawls: Demand for right is political demand

In 21st century, law is social demand

Mankind today and societies are trying to provide medicality

2 rights: medicality and sociality

people seem to want a perfect health or life

to have this is to put of death entirely

best to have perfect qualities as human being and to have medical care as close to perfection as possible

producing health as producing products

want a body that will never break down

cannot have perfect mental states, but people want perfect physicality – beauty (ME: not easy)

WHO defined health as ideal health -    state of complete well-being physical. -    Can we attain perfect well-being?

Corpus sanum, not necessarily linked to mens sana

Demands of society a great deal.

Body as product

Product of medicine – from birth onwards, medicine acts on body With GM goes beyond that

Locke distinc between ‘property in’ – obligation to respect people and ‘property on’ – material goods

This health is material property in Locke’s terms – not an inalienable right, like freedom, more like commercial article – privileged to have

But cannot say that a body is good or bad in pure ethical terms

Is it better to die as soon as possible after born to avoid suffering, or the contrary

Our societies are no longer tragic societies, but rational

Philosophical question: can we eliminate all tragedy from human life? -    only way out is death

need to avoid tragic dimension to life

we want perfect mental health and bodily health

we want to look death in the face

and look tragedy of life in death

Aristotelian problem: act of living..

Can we have a happy life in which we aim towards living together in a society, moving forward as society?

In third millennium societies, we are trying to make the challenge of taking biological life and giv it good life in Aristotelian terms -    begins with the body and medicalisation of body

socialisation of medicine is medicalisation of the body

man’s body is locus for application of our technologies

economic dimension as healthcare costs

politics makes final decision on this

fact that man becoming instrument, not just medical or social problem, but a moral problem

if man no longer thinks of self as divine create or natural product or man, but part of social mechanism, how is he then to have a body that no longer belongs to natural world?

The body is more and more a technical object. It is something mediated through the technology.  So man becoming something that technology acts upon. Benson: man is constructing himself nowadays and constructing new way of making himself. The body is something we build. Try to give it perfect life/health.

Back to solidarity – guiding threat.

Justice and solidarity: what are they? No longer religious, even if religion is background to all moral thinking. Morality is articulated through society. No greek term for society. Greek words that come close talk about relationship between people. Our modern world needs more solidarity – and more demand.  This means that individuals often unhappy, when they don’t get what they want.

Is our modern societies, whatever decisions, whether will, in allowing soc to determine way medicine acts on body, whether will regulate that or leave it to the market.

Are we going to see market acting in way that Adam Smith described – hand of market – or hand of politics making sure everyone gets health care.

Remarkable that our society is having to deal with this challenge. Not only recognising everyone’s equality before the law – as political, social terms, - but everyone’s equality in medical/bodily terms.

Can our modern societies, where popn aging, can they give healthcare?

Will Genetic Predictive Testing increase inequalities? The Psychl Theresa Marteau Healthy Psych Section, Guy’s Campus, IoP, KCL

How do people respond to predictive genetic testing Must understand something of context where will be introduced We all know that the rich live longer than the poor. This is likely to increase.

Self-efficacy to stop smoking.

Hall and Marteau, in prep – people of lower education, feel less confident to stop smoking

Genetic Predictive Testing for Heart Disease -    websites sell this, but little available from health service

Anticipated that gen test incorporated into HC syst in 5-20 yrs.

Imp to consider now, how people will respond on impact to justice of implementing tests.

Huge expectation that will impact people Gramling et al. 2003 – Exepcted motivational impact of predictive genetic testing for cancers -    asked what they expected to see in their patients, if they underwent testing -    expected that those with risk would be likely to attend screeing, likely to change diet and stop smoking

Will gen pred test inc inequal? -    depends on social patterning of uptake and motivn to change behav o    uptake 1: hypothesis: t difference in uptake between those who are leadst and those who are most deprived is larger for gen predictive test than other pred test (given preexisting socially patenting of expectations and need for informed choice with gen testing) o    hypothesis 2: motivn to change behhav following testing will be lower in those who are most deprived (due to pre-existing socially patterning of fatalism)

role of media in creating hype -    Dobias et al 2001 – womens magazines – mammography messages in women’s magazines aimed at different education levels o    In magazines asso with low education, more likely to be persuasive and less likely to discuss uncertainties

Domenighetti et al 2000 – impact of info on willingness to accept screening -    more we talk about people of uncertainty, less interest they havein attending screening -    when discussing gen screening, emphasis on informed -    those most deprived, less interested

Schwartz et al. 1999 -    mammography ptake in women at high risk for breast cancer (US based study) -    randomly allocated women who were high risk for breast cancer, to receive counselling session or Control o    found that high educated, risk counselling had no impact, but for low level of education, learning in detail mammography rates went down.

Will gen pred test inc inequal? -    hyp1 o    Evidence to support •    Expectations of t benefits of screening higher in those who are more socially deprived -    Hyp 2

Cartoon caption: “Because my genetic programming prevents me from stopping to ask directions – that’s why!”

Perceived controlover causes of illnesses -    Shiloh, Rashuk-Rosenthal and Benyamini, 2002 -    People feel can control, if perceived behavioural and progresses lower to enviro and finally genetic

For chronic gen conditions, gen part only one aspect

Multi-factorial condition emphasse gen component

Senior, Marteau and Peters, 1999 -    parents perceived casues of raised cholestoral in their newborn babies, deterred during screening -    where parents thought was genetic problem, far more fatalistic about the problem -    whereas when not perceived as genetic, felt that was something not of concern

Debate

For Norman Daniels -    2 complexes of ethical principles: Rawls justice and 4 conditions of fair processes -    are they separate?

Answer: -    work of philosophers in 1990s, unsolved problem of rationing, how much to give to specific groups? -    When should we trade best outcomes in the use of a resource, in favour for just outcome? -    Do not have philosophical framework of consensus -    Need to suplemetn gen framing of problem of distributive justice with fair process -    Gen framework of fair process

Question: Alex Mauro -    for Norman Daniels -    in view of B Baertschi, process is to flatten gradient, but process is tricky since, if some screening is efficient and if implemented in context of gradient, then expected to steepen. It is as if good quality screening is especially prone to being egalitarian. How can we bring in a correcting factor in name of flattening gradient?

Answer: -    gen law in HC research that medical technology are taken up in proportion to socio-economic status -    Marteau argued that predictive testing might be even worse than established knowl -    The response: more institutional effort from within and outside HC syst to educate people about false aspects of genetic determinism. – health literacy programmes -    This would be consistent with view of health as social product, not just as medicalisation of body -    Evidence from social epidemiology is that health in distrib of populations is primarly effect of social determinants and public health measures -    Couple of other comments on prof Mattei’s paper

Marteau -    if you don’t formulate something, then you don’t set out to try to find it. Solutions in many places, but what one wants is an inequality of resource, when setting up programmes o    spend more resource on those who are more deprived -    education is umbrella term. We know self-efficacy much lower in these groups, so need more help.

Daniels -    Prof Martau focus on threat of inequalities -    Much as I am interested in reducing health inequalities, especially when produced by many unjust XXX, always complex normative problem as to how much to give to worse-off peoplee. We do not have social agreement on this. Itself calls for fair process. Supplement gen view that inequalities are bad, because always faced with specific problem with how much benefit you give up for some people to reduce benefits for others

Ruth Chadwick -    for Marteau on evidence on fatalism -    statement ‘if I have familiar hyper….’ How can one distinguish within that between those who think that’s just what it means to have that condition and a fatalistic attitude, which could be quite different

Response: Mareau -    yes, might be a lack of understanding. -    Was not my study! Similar criticism I have -    One would want to have more than one measure, interview people and understand how that statement is ustod. Better defn of fatalism and use range of measures. -    Was only study that measured education.

Question: Mattei -    diffc between solidarity and charity -    seemed to imply that religious spaces were individual, but lose out on a lot of judeo-christian trad with God’s relationship with individuals -    misses fundamental idea of church -    interested to hear Prof Daniels response too

Answer: Mattei -    distinction isn’t just a reflection on Christianity, but type of help can give to others. True that Christianity has community dimension – caritas – love for other people. What history has show is that when first establishments set up for needy and sick, did supply solidarity, but based on Christian idea of charity. Did welcome non-christians, but nonetheless something that happened within religious sphere -    social sphere has taken over. In a religious relationship between different groups or person and group, are different relationship to ones they have in impersonal relationship between person and group under solidarity. -    In modern societies, have hundreds or thousands of indivs, different to develop social network. -    Prof. Daniels said that social but also political forces directing what goes on.

Norman Daniels -    Agree that religious traditions have community value. Hebrew for charity ‘sadaca’ – righteousness. But is different. If I don’t give charity to some individual, they don’t necessarily have a claim against me, it is at discretion of charity giver, whereas rights involve reciprocal duties. Domain of justice a little different from charity. -    Framework of rights reveals that where diverse popn, merely as citizens, we owe each other as deserving of basic cares.

Question: -    charity and solidarity – one of imp aspects is that solidarity comes from workers movement. Autonomous action in charity, not in solidarity. -    Moving towards individualist soc and lost some value -    Difference in some charities – Muslim: fundamental value -    Careful of Eurocentric view -    Question for Daniels: mentioned market aspect and solidarity system, question about pharmaceutical market. -    Given that market is maximising profits, down side. Taking an outside regulatory sphere. Not helping to modulate practices for access

Answer: Daniels -    complex problem with pharma -    have hd this issue close on pricingof endoretro viral treatments. -    Pharma made concession by providing generics -    Decided to lower prices. -    What drugs get developed and for who? -    Njeed to be revisited

MATTEI -    would all like to see most egalitarian distribution of justice -    this is something inalienable, cannot talk about justice without fairness. -    Can we have justice really or is it just utopian ideal? -    Is it something we can concretely have? -    Saying that market is selfish, must ask whether is individuals are selfish -    Niave to say we have some magic wand to solve this problem

Question for Marteau -    data suggests that more detail of info, the more it risks to increase t inegality -    to poor people give simple messages, to richer, give sophisticated, which also increases inegality of knowl? How deal with this problem of communication?

Answer -    this is one of tensions in this field -    magazine analysis shows that simplistic messages to lower levels of education -    highlights tension between individual autonomy and realising public health outcomes

Daniels -    what we owe each other, not just what it would be nice to have -    connected to broad and confused defn of WHO on health -    real people in HC don’t worry about that defn, they look at morbidity -    protecting health and not all aspects of human well-being -    I don’t think talking about groups is an abstraction -    Markets are not simply individuals, they are shaped by rules and regulations to ensure they avoid certain failures -    One of problems with pharma is that IP law may be stacked in favour of houw drugs get developed

Access to healthcare, in particular new medical technology

Yvon Englert

Thoas Perneger

Imagine trying to screen for cancer in over 50s, test A = cheap and available to everyone, avoid 1000 deaths; or test B = more sensitive, can only give it to 1 in 2, save 1,100 lives. Which would be preferable? -    thi was asked to doctors in private practice and public and asked how they would choose for test B – eg lottery, or medical orgs, only a minority choosing test B -    Med Decis Making, 2002, 21: 3-8 -    Doctors were prepared to lose 100 lives in order to preserve fairness -    BMJ 2004; 329, 425-8 o    Would you allow XX into intensive care? o    Woman in A&E and feels bad o    Do we do it? o    Might depend on disease o    Only one bed available in intensive care, or only 3 o    Describe personality of patient. o    Whether is anxious or not o    Swiss doctors split down middle o    Asked 200 doctors and 55% said they would send patient to intensive care. If 3 beds available, 59% if 1, 45% o    Somebody who is being brave is twice as likely to be admitted to intensive care as someone who is anxious and depressed

10% of doctors said did not want to answer the question

Telemedicine, virtual reality and robotics, new technologies for an optimised health care. Luc Soler

The First Keyhole surgery course

Is patient clinical case or a person? How teach future surgeons if don’t really have contact with patients? When dealing with patients, you might see inturns who are with head doctor and some consideration not given to patient Reduction of surgical nature of medicine – smaller incisions. Direct contact between surgeon and patient, beginning to diminish Operate using tv screens or robotics New imaging technology – MRI scanner Helps for greater communication with patient Reaching areas where human patient becomes digital data Technological developments -    Virtual Reality for Tumour Analysis -    Take 3d medical image – computer tomography, magnetic resonancing, set up digital clone -    No risk to patient since working on virtual patient -    Prepare surgery on this basis -    Simulation of surgery -    Pre-op phase helps for actual op, since info can be superimposed onto patient. So , through robotics, willl get to point where levels of care will rely on these procedures and can rely on qual of care too Medical Imaging -    from CT-scan or MRI of a patient -    better tools for visual

Using algorithms, can build up representation -    allows 3D model to be visualised -    software name: Cult3D (works with IE)

made poss by advances in video games and computer games -    computers now have 3d imaging cards within them

used for explaining condition to patient WebSurg – www.web-surg.com -    World Electronic book of surgery -    Financed by various people. Only free site -    This software is freeware

ME: v intrereting software. Look into

Capacity to go backwards within a procedure and start again

Being used in Geneva and Zurich for surgery planning

Also exists as network system – can be shared with various experts

Helped for info sharing

Real time force feedback simulation -    probe includes feelings of resistance -    INRIA – link again with computer games – Project EPIDAURE

Intra-operative VR surgery

Interactive Augmented Reality

JAMA November 2004

Superimposes image of surgery procedure so can see that eth is being done correctly

Huge surgical advance

3D image doesn’t move when patient breathes – current limitation being dealt with

fully automated augmented reality

LNCS vol 3150

Robot: Telesurgery -    2 robots, 1 society : intuitive surgical -    Da Vinci and Zeus machines, now merged -    New solutions: Artemis, Hitashi, Sinters… -    Extremely expensive $1m (access issues) -    Surgeon can be decoupled from OS -    Robot controlled by -    Lindbergh Surgery, sept 7, 2001, Nature -    Idea not to replace local surg team, but support -    V expensive, since fibre optic transmission time across atlantic costs a lot, so not really poss at mo

Visual Servoin -    increased automation -    control instrument remotely -    can take into account t breathing of patient -    instrument moves to follows beat of heart -    microrobotics and nanorobotics – Norika3 – swallow a pill that will look at what the body doess -    Toshiba (Japan) 5 cm tube trying to make smaller -    Intelligent Microsystem Center (Korea) - biomimetic

ME: this is a good argument to reject naturalness of human

Future of surgery?

Automated procedure -    mistakes of movement can be re -    Robot for a better control of the surgery -    Under the control of surgeons! -    Cartoon: robot surgeon

Acess to health care: Patients rights as a tool for priority setting in Norway Ole Norheim, Uni of Bergen Part 1: background -    priority setting in practice: experience from Norway -    assessement according to t ideals of deliberative demorcaty o    Norheim OF: Report on Norway in Eds Ham and Robert, Reasonable rationinign, OUP, 2003

Part 2: recent development -    patient rights as a tool for priority setting

A short history of priority setting in Norway -    1987: the Lonning I-commission and waiting list guarantee o    set priorities according to severity of disease -    1990: expert group developing national clinical guidelines for bone marrow transplantion o    practical priority setting o    was emerging new technology, costing a lot o    many patients competing for this scarce resource o    principle of evidence as basis for rationing o    where firm evidence, priority stronger o    received supp from ministry and health council -    The Sandberg case, 1993\ o    System broke down. Said no to a patient, whjo happened to be brother of a TV personality in Norway, led to media storm, decision challenged, and minister for health backed down. Several cases like this in 1990s. -    1993: publication of national guidelines for anti-hypertensive treatment informed by cost-considerations o    arguing that not all prevention of CV disease should be provided – higher threshold, based on cost and personal resources to screen and treat -    1997: controversies encompassing new prescrip drugs o    Aricept for Alzheimers disease o    Forsamax for primary osteoporosis -    1997: The Lonning II-commission o    adjustment of criteria for waiting list guarantee •    severity of disease cannot be main concern •    Rawls difference principle: distribution favour the worse-off – easy to see cannot follow this principle extensively in special cases. Eg. Terminally ill cancer patients should not have high priority. Medical outcomes also considered and balanced against needs. Cost-effectivenesss introduced. o    proposed procedures for defining core services o    based on t principles of Accountability for Reasonableness o    compromise between competing values: severity, cost-effectiveness, medical outcomes. o    Inspired by Norman Daniels work o    Ministry of health did not takeup idea of implementing procedures -    1997:Philosophy Norwgian centre for health technology assessment estab -    1999: Norwegian govl appeal board regarding medical treatement abroad established o    as a result of lobbying minister of health on specific cases -    1999: Patient Rights Act o    specialized care

Evaluation -    what procedures are used to determine whether health technologies should be funded? o    No estab procedures o    Highly specialised interventions centralised o    Diffusion of technologies is the rule

Government isn’t actually regulating things

Fear that new technology is being easily introduced, might replace other important services that our HC syst should provide

What is t role of t different instits in these procedures? -    rationing was almost a non-existing health policy issue -    regulation is centralised, funding is decentralised -    little research from Norway on houw such decrentralised decisions are made -    centre for HTA: evidence based assessment of new technologies -    Norwegian Medicines Control Authority: Reimbursement drugs, evidence from cost-effectiveness studies are required

What knids of evidence do these institutions expec, req, or consider in making funding decisions? -    exptl or investigational treatment vs established treatment -    t evidence hierarchy: evidence from randomised clinical trials, systematic reviews and meta-analyses -    evidence from cost-effectiveness studies seldom cited

What ‘standard of proof’ do t institutions expect to be demonstrated in agreeing funding? -    no govl institutions have explicitly formulated ‘standards of proof’ -    Oncology: two or moroe RCTs before a new treatment modality is regarded as ‘established’ -    This standard was challenged by Matheson case, 1996 o    Woman aged 50, breast cancer with metastasis o    Received high-dose chemo with stem cel support in Sweden o    Evidence: Bezwoda et al 1995 o    Demined reimburesment from National Insurance Adminsitration o    Appealed to Minister of Health, appeal accepted o    But only in this case, not for comparable cases o    Oncologists objected: violation of t principle for equal treatment for equals

What appeals mechs ar avaialbe or reviewing decisions? -    appeals mechs for coverage decisionwihtin con

Eval of pririy setting in Norway –prior to 2003 -    much high level activity – principles well established -    political and admin reluctance to introduced proceduires and institutions with a mandate to make explicit coverage decisions -    Patients Rights Act not really implemented o    Now change in Legal system -    Appeals mech estab -    Technology assessment playing minor role -    Conclusion o    Stronger institutions will inc demand for more and relevant info o    Implementin right to necessary health care, a way forward?

Part II

Implementing patients rights as tool for priority setting in Norway Experience from Bergen: largest uni hospital Bottom u

Norwegian Patients Rights act 1999 -    obje: ensure pop equal access -    no sepecifiction on right

Financial sanctions -    since Sep 1, 2004, every patient has right, if not patient free to seek service at other hospital or abroad and regional health authorities wil reimburse t expenses

Implementation -    Wstern health region, -    Consensus based guidance for patients rights -    - based on accepted criteria -    Development by specific group -    Output: rough ‘guidelines’ for all relevant patient groups and interventions with recommended max approp waiting time -    Process:

Aim of project -    strengthen provision of well documented and reasonable cost eeffective health services to all patients with serve conditions

Priority setting model -    core services that should be provided -    elective necessary with right

Results so far -    16 guidelines from different specialistes

-    available for all health professionals on intracnet of hospitals

egs. -    rheumatology

next steps

1. evaluation, adjudtement and comparative analysis

1.    severity of diseas 2.    effectivness of technology 3.    reasonablness

2. Hearing process

3. revision 4.  publication: internet (accessible)

Conclusion: -    rights to core services can be defined through delib open process -    requires consider of who is worst off, clinical outcome,s cost-efectiveness, and qual of evidence -    but leaves room for indivd deiscretion -    openand explicit guidelines prov an opp for starting process toward fair and legit priority -    though not yet evaluated

Genes, food and drugs Ruth Chadwick

Outline -    new technologies have led to revisitng of t individual-collective relation in public health -    and to questions of their impact on health inequalities

related to political will and underlying presuppositions and inconsistencies in policy that can affect whether new technology can inc or dec equality

partic ref to individual choice

Issues -    opp costs: what else could we do with the money? -    access and benefit-sharing Choice? -    upholding of choice coincides with new forms of stratification -    no consistency in argument -    examples: nutrigenetics, obesity, and fnl foods

Two white papers (UK two strategies -    “we will learn more about t genetic featuresof common diseases, such as heart disease and diabetes and t way exeternal factors such as diet and smoking interact with our genes to increase t likelihood of developing a given diease” -    “There will then be t option to test peopole for a predisposition to diesae or a higher than normal risk. Trreatment, lifestyle advice and minotriing aimed at diease prevention could then be tailed appropy to suit each iniv, “Our inhertance, our future” -    Choosing health (2004) o    Sets out stratefy for action based on principles of informed choice….identifies how people can be empowered to make health choices. It sets out how health can be supported and improved in jey environments such as restail outlets local

First white paper, might have thought wil get individual advice in continuing to smoke, more rrecent one is to try to prevent them from smooking

Pulblic engagement -    2003 – traces of deficit model in public understanding o    people don’t understand, but if they had, they would be able to make approp choices -    2004 White paper – shaped by public consultation o    so that individual preferences have influenced development of policy document, but still hang on to view that info will empower people to make healthy choices. Though recog that not simple matter of giving people info and then make healthy choices, because of complecity of people’s lifves Key question -    how do these strategies relate -    impact on health inequalities -    what notions of perosnalised health care and choice are at stake -    2004 white paper talks about false dichotomy ‘nanny state’ – ‘freedom’ can imply neglect

Key example -    food and diet -    nutrigenetics -    food labelling -    obesity, diabetes

Nutrigenetics -    study of individual differences at genetic level (SNPs) influencing response to diet (whole genes or part)

Nutrigenomics -    aplic of genomics in nutrition research enabling assocationbw nutrients and genomic factors

info leading to applic -    understand how nutrition influ metabolic pathways -    understand how this goes way in diet -    understand how individual genotypes are influencing factors

Context -    public perceptions of genetics -    novel foods, eg gm -    prevailing ethical paradigms o    individualism and choice

Public health -    will nutrigenomics have signif public health benefits -    different between nutrigenomics and pharmacogenomics o    the other great promise in the 2003 white paper

pharmacogenomics promises individualised presecribing on basis of genotype -    enable avoidance of adverse reactions -    genetically informed prescribing (type of drug and amount -    greater safety and efficacy -    patient stratification -    signif differences to nutrigenomics o    food stuffs have many different effective ingredients, drugs are much greater characterised, acting on particular pathways o    more diffi to predict effect of specific foods o    promises of nutrigenomics more diffi to establish

testing – empowerment? -    single gene disorders (huntingtons) -    suspectiability testing o    idf recessive genes o    idef genetic makeuip which may increase risk of developing common diseases (heart disease and some cancers) -    pharmacogenetics testing o    medicine response test -    nutrigenetic testing (a form of suscpet test) -    empowerment depends on number of factors (partly due to interpretation, options, and whether people want them or not – right not to know)

Screening -    testing versus screening o    testing: of an individual through referral or self-referral o    screening: ascertaining of prevelance of genes in popn -    criteria for introducting screening o    important condition o    acceptable and reliable test o    scope for action

conditions -    PKU for newborns good example o    Phenylketonuria allows diagnosis to be made and if positive, diet can be adjusted o    However, is single gene disorder and nutrigenetics wont offer that sort of info. -    Diabetes o    Better candidtate -    Obesity o    Genetic Factor A – predisposition to obesity with food X o    Case for screening? o    Importance/scope for action?

Individualism and public health -    personal pills and personalised diets? -    More individualised t promise, t more collective action is required

Acquisition of info -    association studies o    popn groups o    specific disorders -    national dietary surveys o    established for many years, but new twist with genetic element, require setting up large genetic databases -    genetic databases

WHO (on genetic datbaseS) -    ‘..t justification for a database is more likely to be grounded in communal value, and less on individual gain….it leads to t question whether t individual can remain of paramount importance in this context’ -    ‘the achievement of optimal advances in t name of t collective good may require a reconsideration…

Alternative in 2004 whitepaper -    ‘environmental’ approach o    healthy choices (encourage people) o    labelling (Clear) o    restrictions on advertising (of junk food) o    children as a special group -    undelyin principle o    informed choice o    two qualifications •    children •    responsibilities to others (smoking) Inequalities? -    how this approach deal with? -    Increase buren of responsibility for health? -    Whose choice and for what?

Autonomy and choice

Identity – Individual autonomy –    utility – responsibility

White paper operates with notin of ‘responsible choice’ -    if people have info, they will b helped to make those choices -    though antoher notion, which does not arise o    choosing one’s identity: the sort of life one wants to live – which might include not wanting not to know genetic info, or choosing particualrl food style or lifestyle

implics for info -    food, body and self -    what sort of person do I want to be? (eg. Vegetarianism)

Fnl foods -    specific health-promoting or enhancing foods -    regulatory appracoh – highlights importance of freedom to market, subject to safety o    allows rejection in euro, if unsafe, though not whether effective (drugs must prove safety and effectiveness) o    problem: fnl foods targeted at partic audience,s but not like drugs prescribed by professionals, are available in shops; can be bought by anyone who might not benefit -    case by case approach o    tf. No mechanism for looking at… -    potential problem identified with fnl foods – target groups and overdosing -    e.g. cholestoral lowering margarines and yogurts – if same ingredients in many foods, poss to overdose – risk assessed on product alone -    cannotbe solved by labelling alone -    plus or minus nutrigenetics? -    For fnl foods, no drive to protect children as sep group -    Fnal food might be GM

Benefit-sharing -    turn towards sharing benefits of genomics (HUGO 2000, 2002) -    what counts as benefit? -    added value? -    Sharing of burdens? -    Return to issues of class

We are seeing, despite explicit ref to informed choice, return to class divisions

Rights and class -    financial times 20-11-4: ultimately, t worldwide reg push against smoking is being driven by a rev not just in rights but in calss… a class syste is solely being reereced on new bassis, brining with it a new and narrowe understand of rights o    by trying to persuade people to give up smoking, is disproportionately targeted against poort. Same can be said about food styles. – less affluent groups are targeted in strategy. o    By looking at extent to which these policy development will inc/dec inequalities, must look at other strategies, which say certain food choices have to be made. o    Not that people will make more informed choices

It widens genomics divide, but need for joined=up thinking in the two polices

Debate

Question: Norman Daniels -    to all 3 presenters -    first, Norheim, Matteson case, where min of healh backed down, the Bazooda study was later proven to be a fraudulent manipulation of evidence, and was a case that was reviewed in US, Blue Cross, Blue Shield debate – split decision 8 to 7 (scientists voted against it and managers voted for it) – when one capitulates to public, politically manipulated demand, often have signif harms to popn and huge costs. In this case, survival not increased by bone marrow transplant, but decreased -    hype of nutrigenomics might lead to experimentation on popn based on prospect for benefits -    Soler’s presentation was innovative, but problem of distincc between human subject research (requires clinical review and IRBs) and innovative therapies, which do not. o    The 3D tech does not require procedures -    What is case for ethical review for innovative technology

Response

Ruth Chadwick -    agree: fnl foods introduced on case by case basis and nobody is thinking about overall consq of mass consumption -    for nutrigenomics, willl not have enough added value to deliver and wil become fashion accessory for few, real agenda is to get people to make responsible choices -    pharmacogenomics big demand, so bigger issue

Norheim -    medical truth have a half life of five years: be sceptical of medical evidence. -    High standards of evidence a wise approach

Soler -    already performed some evaluation -    ethics: new technology bringing separation of physician and patient -    cannot forget patient is still there, so must see them

Comment rrom Y Englert: Daniels claim v important, current distinc between pharmacology (strict exptn) and expt of therapies -    in Europe, reimbursement for

Question: fro Y Englert: -    poss risk in strategy of prioritising by structure of health care (for Norheim) -    diffi and dangerous for minister to be the one to decide -    also risk that political decision that places framework

Question: for Norheim -    high standard for evidence, reasonable to prefer benefit with high certainty than low, but assumes that research questions are equitably distributed -    research questions are inequitable -    link between framework and research agenda

Response: -    might have problem -    acknowl different criteria in law would be need to be interepreted differently. -    Acknowled different equal disttrib in funding for research -    Framework of accountability – give reasons (scientific) -    Ethical arguments on severity of disease is another argument

Question: -    context in which people make decisions on food important -    food deserts – areas where no food shops and some less than optimal foods -    option for healthy choices has gone down -    changing the context?

Answer: Ruth -    reliance on labelling totally insufficient -    person that eats, not always person who buys -    gov white paper does recog that labelling not suff -    though not clear how help people to make choices -    bear in mind that eveidence of healthy choices is always years out of date – national dietary surveys – produced 5 a day policy – took place in mid-1990s.

Question: Theresa Marteau -    for norheim -    extent to which there is a tension between informed choice and thinking in those providing health care that there is a right choice -    nobody wants to talk about weaknesses in medicine –s ometimes doesn’t work -    people offered pills and potions, but chances are will not benefit -    if there was more of an informed choice, people less interested in choices people made, might be less demand for things

Response: Norheim -    studies on giving info -    BMJ some years ago on managing market -    Prostheic problems -    Prov info about risks/benefits of different interventions, changed demand for the services

Question: Euopean Commission: Health Technology and Informatics -    we are more and more influ by genomics -    interested in projects on popn data -    Question for Chadwick o    Puzzled by dichotomy o    enviro approach sounds like eastern religions. Don’t go into level of atoms, just believe in holistic truth that there are good and bad foods o    other view that analyse to level of gene o    why are we being put in this dilemma o    we have indogenous and exogenous determiniant s(nature/nurture), need to understand from level of cell and synthesise. We have v different worlds with different ontologies, which are sep: molecular biologist, clinicians, and health care people o    each live in their own worlds o    need vertical integration o    seems like policy based evidence, rather than evidence based policy

Response: Chadwick -    need for joined up thinking -    should not look at these things in isolated way -    these 2 policy documents have done that -    not either or, hwr, in case of nutrition, serious question about whether could get suff added value, by going down that research route, over and above generliased dietary advice -    not an argument against genomics approach per se, but in nutrition much more diffi to be clear about cause and effect

Question: Precise philosophical model being discussed on patients -    autonomous informed indivs, but implies info supplied in good faith and checked by publishers -    closer look at accuracy of that info -    problem not having access to it, but having too much info -    in  NEJM article on access to health care, something Clinton admi had raised – access to Hc discrim -    report rewritten twice by next admin in US and new version said something completely different – political interference -     also market interference on report, not pharma industry, which had right not to publish resultst hat didn’t suit them, rather, where info is a merchandise, new info sells best -    eg. New diets being sold to us -    should be talking about autonomous and correctly informed citizen -    Question: how you manage access to info for citzen and make sure is correct?

Response: Chadwick -    serious problem -    diet: one week red wine is good for you, next week it is not -    channels of info need to be examined -    issue about scientific responsib in communicating with public 0 increasingly addressed -    media responsibility -    different for citizen to know where to turn

Question: -    for Ruth -    issue about return of class -    what kind of class is this -    have mentioned various sorts of social stratification -    eg daniels – if genetic diversity is treated only through an actruarial model, might have unwanted genetic stratification. Marteau described social stratification in atts to genetic testing -    so what dimension of class is particuarlly concerned about?

Response: -    different interventions could impact on this in different ways -    social stratify: policy is reinforcing social stratify, since health behavious are those associated with poorer groups of soc -    problem with this is that, if you take this approach, - voting against lifestyle choices – sits uneasily with purported unholding of individual choice assoc with genetic testing, since suggests that indivdiualised medicine approach willl not be to support particular choices -    both strategies wil reinforce social stratify, though one explicitly claims to allow individual choice

Response Norheim -    ban on smoking in restaurants and bars since Jan and argument was about workplace rights -    this might also be a classist debate

Response Ruth -    this argument also used in UK debate, but proposal is that will still be allowed in private clubs, so employees in private clubs not protected

Response Norman Daniels -    availability of info -    Ministerial sumit in Mexico, WHO health systems research -    One of proposals is interenational registryo fo all clinical trials and public assurance of acess to all clinical trials -    Could not have propriety management over info – couldnot manipulate clinical trial info -    Establish a public goods environment for management of these Its.

Response: Englert -    Registry of medicines to provide all data available -    Cannot be some parts left out for negative result -    Transparency issues about study itself and decisions taken over results orientation -    These are difficult to monitor

Question thereas Mareau -    changes in UK trying to improve, where might be divisive -    partly a semantic issue -    choice socially patterned and behaviour socially patterned -    just because people are engaging in behaves doesn’t mean is a choice -    in UK at any one time 70% of smokers would like to stop smoking. While engaging in behaves, perhaps would like to stop.

Response: Ruth -    worth some consideration, but main concern is not reasons why people make certain choices, but view that policy has about what choices people ought to make -    must look at what policy makers mean when they mean choice and upholding choice

Protection of medical and genetic data Heidi Diggelmann Olivier Guillod

Dilemma of Predictive Medicine Y Englert

Medicine evolve to predictive and to collective Move from single gene to multi gene Pre-clinical diagnosing been around for decade or so, since being able to detect for unborn child More complex when trying to deal with diagnosis of illness, which hasn’t yet appeared, but feared by patient or family

If we look at diseases that come later on, more difficult Access to jobs, insurance and social organisation

Pre-clinical screening as starting point, must first consider whether test straightaway and influence of that. Often no symptoms.

Poss of testing raises number of people who want test by 50%. If poss during pregnancy, number raises to 98%. Thus, predictive medicine provides reassurance, rather than distress

For someone with Duchenne syndrome, can avoid no of tragedies

Importance of genetic counselling before test, but not enough – need info for everybody – education programmes. Avoid stigmatisation of people

Not much use for employment purposes

Insurance implications clear

Key issue is data protection

Most sensitive of all data, because of predictive power and shared in specific group of individuals

Goes beyond individualistic approach

Can be used exclusively for identification purposes

INTERNET AVAILABLE GENETIC TESTS

Who owns genetic info?

Council of Europ recommendation 97.5 -

Stefano Rodota

Legit of tests only for health or research Therapeutic model Conference Review: Justice, healthcare and the Trend Towards Predictive Medicine For British Medical Journal

Thus week, Brussels held a symposium on the future of health care, which aimed to bring young and senior scholars to question the ends of current trends in medicine. In particular, the symposium focused on ‘predictive medicine’ and the emerging opportunities for working towards a more just healthcare system. The symposium was supported through the Brocher Foundation, a research foundation interested in questions concerning the socio-political context of science and medicine. It was a relatively small meeting, though the kinds of guests reflected key authors and speakers in bioethics.

The symposium began with a lecture from Norman Daniels, whose work on XXX

Norman Daniels drew attention to the inadequacies of the US model and the worry of exporting its medical models to other countries. His Rawlsian approach to healthcare justice reflected the social obligation to provide socially just …. He also spoke about the challenges faced by the emergence of predictive medicine as a moment of opportunity for requestioning how medicine takes place. Acknowledging that predictive medicine will raise challenging economic realities for the medical industries, Daniels argued that this can be seen as a chance to provide greater justice in healthcare, or it can be used to exacerbate the needs and lack of the most vulnerable people.

Rawlsian ideas were taken up in the subsequent presentation byXX. However, the focus was significantly different, raising questions about the body-as-product both commercially and ideologically. XXX addressed the challenge of Utopian medicine, the prospect of which seems wholly inadequate even in best-case scenarios. The acceptance of tragedy in life is considered indicative of the human condition and the rejection of this circumstance can be seen as socially divisive. It is not that people should not seek to optimise their health, but that the process towards realising that will be to the detriment of those who have the most need.

Neither of the speakers fully addressed the difficulty with limiting individual desires to pursue health at all costs. Indeed, there was lmite

Sports and Genes (2004, Geneva)

Sports and GenesAISTS 2004-09-22

Bengt Kayser

Rankinin, Perusse, Rauramaa, Rivera, Wolfarth, Bouchard – Human gene map for performance and health related fitness phenotypes: the 2003 update Med, Sci. Sport, Ex, vol 36 9 1451-69,

Altitude tents, induce endogenous production of red blood cells

Marathon mice engineered for extra endurance CNN Aug 23

Schuelke et al. Powerful Genes – myostatin rgulation of human muscle mass, Journal p..2682-88 Mcnally, e.m. -    four year old child with unusually large muscle mass

should we exclude this person from comp?

Geneticists engineer marathon mice Helen pearson news@nature.com 2 strains – one dies, the other runs faster for longer

Bob Goldman, 1984, Death in the Locker room

Lane, T. www.theage.com A future of jocks, genes and jingoism Peter fricker – Athens Olympic Team -    identifying athletic genes

Iannis Pitsalidis International Centre for East African Running Science

Why do Kenyans and Ethiopians Win all the time?

Why do Kenyans and Ethiopians win Most of the Time!

Last time an African won marathon was in 1968

Though performances are remarkable

Can genetics explain t dominance of east Africans in world athletics?

Scott,  … and Pitsiladis Med, and Science in Sports and Ex 35 (102) 1727-1732, 2003

Heile Gebraselasie I’ve been running since I was 4 or 5, for us life was a kind of sport

Methodology

Environmental Analysis -    place of birth -    lang -    distance oand method of travel to school

Genetic analysis: mtDNA -    mitochondria are major energy producers of t body -    mitochond fn imp in ex

MtDNA useful in popn genetics -    maternal inheritance, no recombination -    ….

Wildman, DE, Uddin, M., Liu, G, Grossman, Goodman Prot Natl Acad SCi 100 12  7181-8, 2003 -    genetic difc between humans and chimps

Demographic expansion analysis

Peter Forster (2004) Ice ages, and mtDNA chronology of human dispersals Phil Trans R. Soc. Lond. B -    origins of mitochorndria and movement of genes around world

Human mtDNA tree -    many branches of tree, various mitochondrial types and we want to see whether African athletes are part of one branch specifically

MtDNA qs If mt DNA polymorp im in enduance performance..

Contral mtDNA tree -    all different types in Ethiopia – tf. Heterogenous popn -    but did not find that – no common mtDNA -    remarkable distribution -    some amazing athletes who  have genes common among Europeans, than Africa

Conclusions (mtDNA studies) -    Ethiopian athletes distinct enviro relative to ethipian -    Deep commn maternal ancestry

Human karyotype – chromosomes

Why Y? -    patrilineal inheritance -    never 2 ys in 1 cell o    fnal changes immediately subject to selection o    no recombination

Conclusions -    like mtDNA y haplotypes spread throughout tree -    ethiopian y haplotypes show assoc with elite athlete status -    how can t y be having such an effect? -    Direct effect of a genen on t y chromosome? -    Unknown subgroup of popn?

Can genetics explain dominance? -    no genetic evidence found to date! o    So far have not looked too far

They have to run back to school, otherwise they would be caned -    mm

Alex Mauron Sports, Genes, Brains and Ethics

Thomas Murray

Just deserts (1) Purely scholastic process not sport – gambling not sport Largely predictable process not a sport – treadmill test

Nothing more basic to idea of sport than notion that successs or failure ‘sufficiently’ reflects inherent merit of indiv athletes or teams

Ethics of spectator sports -    must be fun to watch in market economy -    needs to be ‘sufficiently’ fair to satisfy yearning for justice

conventional ethics of sports -    let best win -    talent, effort luck

what it means for doping -    chemistry or genetics moral shortcut -    doping disturbs ‘level playing field’

doping immemorial (iliad, chapt 23)

sport has always attracted cheating

‘Citius Altius Fortius…Purius?’ NY Acad Sci, Mgazine, aug, sept 2004-09-22- race between doping and testing

Dilemmas in doping ethics -    prevention best with practical and conceptual difficulties

doping vs honest medical treatment

increasingly doping -    uses substance naturally present in human body -    involves substances also need in bona fide medical treatment -    involves methods that are synergistic with, not alternative o, intensive training

one of major intuitions against dopingis that we substitute something easy – doping – with something that is difficult – training -    may not be true now -    requires sophisticated knowledge

doping vs honest medical treatment not possible

doping vs privacy -    doping prevention requires all-round surveillance of athletes and invasion of privacy -    incly resembles crime control, except in sport you are guilty until proven innocent

The Red Queen -    in Alice’s wonderland you have to run fast just to stay where you are, because landscape moves with you. In fact, t evolutionary arms race between predator and prey is called t Red Queen phenomenon by biologists o    used as metaphor for c-evolution of predator and prey -    sport is full of Red Queen phenomena

running 100m I less than 3 sconds -    thre is arguably an asymptotic levelling-pff of certain sports achievements, as basic human limits are increasingly tested -    puts prob of enhancement in radical light -    will  enhancement of natural hman performance become necessary to remain interesting Red Queen race between dopers and testers -    increasingly costly -    National Centre of Addiction and Substance Abuse (CASA) at Columbia Uni calls for research effort for doping prevention costing hundreds of millions of dollars -    Unforeseen ethical dilemma: would they divert funds from health-related research? If so, is sport so imp?

Mans sana (?) in corpore not so sano perhaps -    sports turned into another health problem, when sport was supposed to be health promoting

health vs hyperhealthTM -    doping prevention relies on conventional distinction between o    medical treatment – restoration of normal species-typical functioning o    enhancement – augment bodily functions (beyond normal)

distinc between therapy and enhancement in bioethics -    asked in rel to gene therapy

gene therapy – initial debate 1980s -    somatic : ok -    germline: not ok -    therapeutic: ok -    enhancement: not OK

1990s -    gene therapy failures -    normalisation of somatic gene therapy – similar to other innovative chemotherapy (pradigm of AND medicament – axel kahn) -    but normal doesn’t mean harmless (see Gelsinger)

gene doping and gene therapy -    debate concludes that somatic gene therapy on same footing as pharma therapy -    same apply to gene doping v pharma doping -    tf gene doping objectionable on same grounds

treatment ok, enhancement not ok -    no need for genetic exceptionalism

gene doping to neurodoping -    other form of doping, such as neurocognitive could becme practical before gene doping

mens ampilificata in coropre amblificato -    one of promising avenues for sports o    eg modafinil – anti-sleeping pill o    for sports involving complex tactical tasks with motor performance (tennis), neurocog enhancement (of woring memory, executive functions, motivation) by pharma means may become incly appealing neurophilosophy

3 years ago – san Francisco – neuroethics

another basic problem -    common unreflected intuition that natural = good, artificial  = bad o    fuels some of the disapproval -    does not help – sports science is highly technicised

sociologists in france – Andrieu, Rauch) -    ritual nture of intensive training -  less to do with health

another problem -    success in sports depends on talent -    first order capacitites (musculation potential, bone structure, lung capacity, etc) -    second order capacities (somatopsychic characrs such as relative intensivity to pain, endurance and the like) -    such capacities are undeserved and unequally distributed, almost by defn -    level playing field problematic

skating on thin ice- thick conceptual distinc be treatment and enhacement probc, emphasis on fairness as THE ethical motivn for doping prevention become less persuasive -    equal doping for all not appealing proposition

real reason for doping prevention less to do with fairness -    has to with health (more of a threat than intensive sports training)

Enjoy the freaks -    mark Lawson, guardian, june 7, 2003

Non-cynical -    need a more secure basis for ethics of sport -    ethical basis of doping position, relies on ethical framework for sport

Q&As

Redefine health and disease How notion of performance has evolved through time?

Whose responsibility is sport ethics?

Dietary supplements

Mattias Kamber Instit of Sport Science, Federal office of sports, Magglingen switzerland Anti-(gene)doping: The Swiss and WADA’s approach He is member of ethics and education working committee

Voices of gene doping

Devel of doping -    1807: arsenic, strychnine, opiate, alcohol, cocaine, cannabis, hypnosis -    1936: stimulants (amphetamine, ephedrine) -    1958: anabolic steroids (dianabol, testosterone) -    1968: diuretics (chlorthaldone, furosemide) -    1976:betablockers (atenolol, propranolol) -    1980: peptide hormones (HCG, hGH, EPO, insulin) -    20XX: gene doping?

Why be concerned? -    misuse of therapeutic medicine

are we ready? -    current anti-doping tools based on science applied to urine o    non-invasive o    concentration of substances (but limited info) -    anti-doping labs started biochemical methods (EPO and HGHG) and new matrix (blood)

not yet ready for genomic or proteomic analyses

challenges -    organisations and governments -    detection and research -    athletes and support personal -    pharma companies and ‘back yard labs’ -    defn and refulations

same topics as ever but more challenges

governments -    misuse of undemocratic states – need instruments – we have this from other aspects of politics – e.g. arms control,

ME: if I am an athlete who uses doping and tries to get around the rules, is that wrong? Sport relies on this

Detection and reearch -    took more than 10 yrs to develop a test for EPO from urine -    break through for hGH and blood doping in short time (blood samples)

more research (and grants) are needed -    what type of biological samples?

Athlete and support personnel -    Victor Comte, BALCO -    THG

We do not know if it is a safe drug or not?

ME: but no form of clinical trial will tell us, since ‘enhancements’ are not studied

Pharma Companies -    detection of ARANESP at OG in Salt Lake withhelp of AMGEN -    new drugs are in devel and clinical studies e.g. RSR13, CERA, DYNEPO -    pharma compnies not forthcoming in assisting sports world

early cooperation with pharma companies is essential

Laws and regulations

Gene doping has been on list since 2003. International conventions Defn of gene doping and medical application will be challenging

Pillar principle

Controls, education and information, research Doping statut of swiss Olympic Law promoting gym and sport

The government fights against doping It promotes doping prevention Formulates a doping list Trafficking, distributing, prescribing…of medication and methods for use are forbidden -    but not easy to apply -    if trafficker claims they are not elite athlete, then not legally compromised Government supports Swiss Olympic financially to carry controls Minimal standards for controls are formulated

Swiss Workshop 2002 -    create an observatory for scientific research results and its possible application for doping -    national level, we are aware of it

WADA -    now doping is most prominent threat -    no structured independent anti-doping organisation until recently -    Council of Europe was not sufficient – not international -    Banbury conference o    Conclusions and recommendations •    Gene transfer technology is beginning to show results •    Potential for misuse in sport •    Collective efforts required •    Compliance with international standards involving human subjects that prevent unethical research is essential •    Broad public discussion and devel of social and policy frameworks before abuse occur, not after •    After Tour de France, survey whether should ban it? 34% suggest we should liberalise it under medical supervision o    Swiss Assoc of Medical Doctors developed code of conduct, now for 1year, doctors have regulations for treating athletes

WADA sport specific conclusions -    if therapy, then ok

WADA calls on govs to consider: -    req detailed record-keeping in respect of all applications of gene transfer technology with independent audit -    expand standards of medical and professional behav to prohibit improper use of gene transfer -    extend civil criminal limitation periods in respect

Legislation -    close rel with govs and international orgs (Unesco, WADA) to adapt internatona and national laws to prohibit gene doping

CCES\ -    if magic pill, what would be point of sport? -    But it is not a magic pill -

ME: what should be role of ethics committee, what political importance does it have in WADA – how do others perceive its role, what is it doing?

Cost of urine test – out of comp: 200CHF, 300CF in comp – depending on substance

Sandro Rusconi Gene Doping: Not yet possible?

Now, gene doping can be used to improve performance

What is a gene? -    one gene = many functions

what is therapeutic ‘gene trasnfer’? -    transfer of functions(s), ‘somatic’ rather than germline, targeting

how far has gene therapy progressed?

Which possibilities would exist for doping with gene transfer? Conclusions and perspectives

Elite sport has become a job with dangerous side effects

Mythos ‘gene’ in good or bad sense

It has become difficult to frankly and objectively discuss about real perspectives of gene technology

Myths -    only against hereditary disease -    transmission gene alteration -    transfer must reach 100% of cells

myths gene doping -    better than conventional doping -    transmissible gene modification -    prenatal design of athletes

DNA – RNA – Protein

Genes ‘segments’ of DNA

1cm3 = 1,000,000,000 cells

the motto ‘one gene one function’ is outdated -    2-5 functions?

100,000 genes = 300000 functions

side effects of gene transferdepend on number of alternative functions of gene product -    for most cases not known

what is a gene: a regulatable nano-device for the production of RNA and proteins -    to be effective gene segment shall include o    sequences for gene regulation o    signas for manipulation/transport of RNA o    signals for translation into protein

space – regulatory – coding spacer –

reductionist paradigm of molecular biologists

gene transfer can imply- transfer of new fn or -    transfer of a compenasating, f -    or transfer of an interfering function

4 big eras of molecular medicine

1980s – genes as probes -    prenatal diagnostics -    is someone predisposed to something?

1990s – genes as factories -    biopharmaceuticals -    take segments of genome and place into cell cultures (e.g. epo)

2000s -    genes as drugs

2000 + post genomic improvements of former technologies

gene transfer – logical consequence of former progress

somatic gene therapy NFP37 somatic gene therapy www.unifr.ch/nfp37

definitions of SGT correction disoreer by somatic gene transfer -    in gene therapy genes are used directly as drugs

Pharmacological considerations difcs conventional and moleculartherapy

Classical drugs -    mw 50-500 daltons -    synthetically prepared -    rapid diffusion/action -    oral -    cellular delivery -    readily revesible

Protein drugs – from genes as factories -    mw 20000 – 100000 DA -    biologically prepared -    slower diffusion -    oral delivery not possible -    cellular delivery o    act extra cellularly -    reversible

Nucleic acids -    mw n x 1000000 Da -    biological -    slow diffusion -    slowly or not reversible

Therapies with nucleic acids (DNA) -    req special formuation -    morec complicated than conventional

Risk / benefit balance -    depends on adopted therapy and targeted disease

why somatic? -    germ line cells: hereditary -    somatic: all other cells

4 qs about gene therapy -    efficiency of gene transfer -    specificity og gene transfer -    persistence of gene transfer -    toxicity of gene transfer

variables? -    which disease/gene/vector/organ/tissue/delivery method

3 main anatomical

ex-vivo -    bone marrow (allows to reconstitute immune system)

in-vivo -    local delivery o    cancers o    e.g. brain, muscle, eye, joints, tumors -    systematic delivery o    egs intravenous, intra-arterial, intra-peritoneal

2 classes of vector -    non-viral o    transfection o    nuclear envelope barrier! -    Viral o    Infection

Why viruses so attractive? -    they know better how to transfer DNA than us

Efficiency of transfection with recombinant DNA compared to infection with recombinant viruses

Mini-list of popular gene transfer vectors -    adrenovirus -    adreno-associated v -    retrovirus -    lentivirus -    Naked DNA o    Liposomes

Recap: limitations of current transfer vectors - can contain only certain amount of DNA in virus

there is no perfect vector

costs of each path through to clinical phase III to registration $80m -    still don’t know if would be registered – only 1 in 4 is registered

trends of clinical GT experimentation -    as of june 2003, 918 cumulative protocols -    4500 treatments -    www.wiley..com/genetherapy

1990, 1993, 2000 / ada deficiency f Anderson, m blasé, c bordignon

1997, 2000 j isner, I baumgarter, 1998, 2000

1998 restenosis v dzau

2000 hemo.. m kaey Jan 2004 – first product gendicine, by Sibiono inc 2004

No god medication without side effects

Most feared side-effects -    immune response to vector -    immune response to new or foreign gene product -    gen toxicity of viral vectors -    adventitos contambinants in recomb viruses -    random intergration in genome (inserational mutagenesis = cancer risk) -    side effects of newly acquired gene products -    contamination of germ line cells

material side effects still virtual when GT was in early phase

5 bitter adverse situations, still only one certified deat

NY ma, 1995, R Ccrystal

Upenn, sept 199 j Wilson Jesse gelsinger

Paris oct 2 2002 a fischer Retro virus x-SCID

Paris jan 14 2003 a fishcer

Pittsburgh, may 2004 K high Aav treatment factor IX hemofphilia, patients develop anti-fix antibodies

Acculutatio of hypes and loaws: roller-coaster drive

Gene doping possible? -    gene therapy o    treatment not heritable principle works o    not yet generally available o    high risk for virtually all  types of diseases

still unreachable

3 levels of doping -    before comp (anabolic) -    during comp (performance enhancers) -    after comp (repair)

which gene transfer? -    ex vivo hematopietic -    invivo – example muscle – growth factor, anti-myostatin

doping with gen transfer, many concrete possibilities

Lee Sweeny, J. App Physiology, 96, 1097 ff (2004) – march publication -    transferred gene method -    igf-1 growth factor -    aav vector,, intra muscular -    rat model

Is rat easily transferable to humans?

Side effects of gene transfer?

Short term -    autoimmunity -    hyperimmunity -    toxic shock

long term -    fibrosis -    cancer, conventional side effects of admin factors, inaccessibility to future gene therapy interventions

Specially dangerous: -    improper procedure (unsuitable vector, insuff competence) -    inapprop material (not GMP (good manufacturing practice) conform) -    insufficient follow-up

objective limitations -    viral gene transfer (immune probs, lmited readmin, gen toxicity) -    n

most likely will not be effective and harmless

Detection? -    antibody detection -    r-nucleic acids detection -    anatomically difficult to detect, but leaves permanent genetic marking -    might require tissue biopsy

foreign gene traces short-lived in body fluitds foreign genes can be in biopsies abnormal gene products oft detectable -    if expressed in wrong tissue, can be seen

adv/disadv of gene

gene doping loses

Is big talk about gene doping just one of many psych bluffs to intimdate lower-tech adversies?

Conclusions -    gebe doping higher health risks -    biggest problem is not intrinsic to technology but bears as usual on human greed and over-ambition

sanro.rusconi@unifr.ch

Prf. Dr. Hidde J Haisma Gene doping is possible? University Center for Pharmacy Rijksuniversiteit Groningen www.rugnl/farmacie/tgm

gene therapy is protein therapy, but using genes -    when give epo as gene or protein, is same thing

genomics -    identification of genes and gene expression -    caterpiller and buttergly – have same genome, but expression is different -    same with human variation – 99% we are all same

genetic manipulation -    GMOs -    Modern biotechnology

Genetic Manipulation Herman (1989-2004) -    dutch transgenic bull -    transgene = lactoferrine to be secretedin milk

genetic manipulation of humans -    delivery for therapeutic purposes -    we don’t have pills yet – and probably would not have this

good news and bad news on gene therapy -    gene therapy works on some patients

FDA stops researchers human gene therapy expt, by deb nelson and rick weiss, wash post, marc 2 200, pa08

December7 1999, Nytimes Successful gene therapy on hemophilia

March 2 200 Nytimes Hint of success indicated in gene therapy

2982000

indications addressed by gene therapy clinical trials J Gene Medicine www.wiley.co.uk/genmed/clinical monogeneic diiseas 9.8 (n=90)

requirements

genetic material to treat disease -    dna, rna

method of delivery -    viral or nonviral

how to get the dna? – internet!

How to get dNa of erythropoietin Go to anymolecular boil sites and it tells you Chromosome 7, location 7q22, geneID 2056

Gene therapy vectors

Vector – adv – diasdv Naked dna – no limitation on size – low transduction efficiency, no integr Liposomes – no lim on size – low trans and eff, no integration Retro

Gene therapy vectors Non-viral

Monogenic diseases

Factor IX in haemophilia B 9 different factors to induce clotting -    one missing or too many cause problems

Kay et al nature genetics, 2000 -    intro of Factor IX into muscle -    shows that it leaves the muscle cells and goes into the blood -    muscle secretes factor IX into blood -    (if this hormone like treatment occurs, you cannot tell where we injected this factor – detection not possible)

Use in sport – increased healing after trauma -    muscle injuries -    ligament and tendon ruptures -    meniscal tears -    cartilage lesions -    bone fracture

this would not be gene doping

misuse -    alternative to protein drugs -    protein identical to human endogenous protein (not possible to detect) -    gene therapy vector present locally

gene doping -    inc hematocrit, by epo -    increase blood flow by vegf -    inc muscle strength using igf-1 -    inc mucle size by inhibition of moystatin -    decrease pain by endorphins o    ME: check his refs

Some things we cannot do -    steroids not on list, since no steroid gene o    steroids made by many genes, not that far yet -    can only make proteins

Gene Doping

gene – potential – risk controlled – risks uncontrolled

epo- ++++ - +/- - ++++ IGF-1 = ++ - - - ++++ VEGF, FGF - + - /- ++++ Growth hormone - + - - - ++++ Myostatin / follistatin - ++++ - ? - ++++ Endorphins, enkephalins - + - ? - ++++

Very easy to make DNA, but might not be safe if uncontrolled

Epo -    glycoprotein hormone that stimulates production of red blood cells -    used to treat anemia resulting from o    cancer chemo o    chronic renal failure -    boost red blood cells prior to elective surgery -    is a gene we produce ourselves -    produced in kidney – stim bone marrow – inc red blood cells -    if you put in a gene, the signalling doesn’t take place -    need to ensure signalling to regulate

ye et al, science, 283:88, 1999 -    epo

IGF-1 -    greatly improved repair fn of dystrophic muscles -    promote skeletal muscle hypertrophy in young mice -    prevents muscle loss in old mice -    synergistic effects with weight-training -    rat ran up ladder, with weights on tale -    improve muscle force by 30-40%, combined with weight training, even more

Can IGF-1 over expression enhance athletic muscle performance? -    inc even without ex -    inrease rate and extent of repair following injury -    better maintenance of muscle mass, strength and speed during ex, during aging -    inc end of skeletal muscle, speed of skeletal muscle

how can we deliver this? -    inject our muscles?

Some vectors show it is possible -    systmetic delivery AAV-6 -    Anti-dystrophin lavelled muscles ffrom mice adminisrtered 1x 10E13 vector genomes of rAAV6-CK6 -    Microdystrophin and VEGF, mice we examined at 6 weeks after treatment -    Gregorevic et al, Nature Medicine, 2004

Gene therapy – risks

Person risks -    disease (vector, transgene), mutagenesis -    offspring

Mileu risks -    people: spouse, next of kin -    environment: infectious disease

as long as we treat somatic cells, no transfer to offspring

gene therapy and doping risks -    vector (contamination, replication competent virus) -    transgene (duration, amount of gene expression, auto-immune response)

detection? -    vector o    vector constitutents – requires biopsy o    vector dna – requires biopsy

-    transgene o    protein (e.g. epo, unless natural product) – yes, if in blood o    effect  - yes, if in blood

detection by proteomics -    physiological profiling o    serial blood sampling o    assessment of protein markers o    using protein maps, can see if changes have occurred o    people are within a certain range

WADA currently do not see drugs they are not looking for – profiling could help Rather than develop new assay for each new potential drugs, profiling could highlight anomalies

Preventatve measures

Regulation (gov, IOC, WADA) Codes of conduct (pharma ind, scientists) Education (athletes, supp staff, public) Detection (assay development)

When and where? -    genes and vectors are available -    plain dna is easily produced -    illlegal drugs produced and used

where? -    human and animal sports

can make epo DNA for €10-€25 -    quality control and marketing much more

ICSSPE Pre-Olympic Congress (2004, Thessaloniki)

ICSSPE Pre-Olympic Congress,Thessaloniki, August, 2004-08-07

Bengt Saltin Energetic limits to performance

Leo Hsu

Concept of the good foul Bsketball Soccer

Good foul unethical -delib interfere - no equal opp for contest -    not agreed on

good foul not cheating -    cheating: intention to deceive and unfair adv -    good foul: intention to break rules  plus unfair adv

simon ‘strategic foul’ -    intention and action -    penalty might become adv cheating\break rules deilib avoid penalty inend to deceive win or gain adv

good foul breaking written rules delib expect to accept penality win and gain adv

a good player… -good intention act rightly keep spirit

concl good foul -    not cheating -    against purpose of sport -    morally wrong act -    indicates deficiency of rules -    violates spirit

Q&A Scott: opponent stalling – good player wants to play good game, so breaks a rule in order to create a good game. Is this good foul? -    response: NO

Sigmund: Good foul morally wrong act, but ethos

Leo: depends on defn of morally right: - if ethos is morally justified, then ok, but if not, then is morally wrong.

Heather

Beauty of Olympic sport typically allow more than one way of playing the game Not clear whether poss to decide between beautiful and corrupt -    elitism, sexism, racism

need to estab criteria for changing sports practices

set out Rawls’ method reflective  equilibrium

narrow -    justif ororig posn, if match -    choose strongest convictions as fixed points then work backwards

wide -    demonstrate why justified to apply in  specific contexts, by increasing breath of test

benefits -    clarification, systematic, democratic

going through process of wide refl equilib help clarify views

can uncover more systematic

democratic: in context of other beliefs. Where conflicts with other values, then indication of problem

disadv with this method -    uniersal and cross Cultural undemocratic -    indivs and their interests

diving or shirt pulling in elite soccer, decision could include everyone in debate as to whether is acceptable – these people unlikely to be aware of internal goods of game -    they’re likely to have limited knowl of game (HMMM) -    to follow wide refl  equilib

abstraction is undemocratic, since must disconnect from cultural context

democracy not about truth

while wide refl equilib is useful – it is too thin, since too far removed from sports practices to have any normative force -    could not determine which ethos is most justified.

Tradition practice bound reasoning: -    Which criteria? -    Who ought to evaluate?

Liberal interpret of practice community allows spectators, etc -    only views about goods internal to game count -    a limited  democracy, providing correct credentials

Gunnar: -    would work in new sports, with fast developing ethos -    would rely on imagination of people to a much higher degree

Mike -    liberalism v communitarianism

Sigmund Loland Fairness in spor t- critical comments on Olympic competitions

Not Fairness as indiv obligation, but ‘structural’ fairness -    when is a competition fair,not when is a competitor fair

fairness in sport -    competitions -    relevant and non-relevant inequalities -    fairness ideal -    implementation of fairness in practice

gen principles of fairness -    eliminate or compensate for inequals that exert SIGNIF influ on performance o    indivds cannot control and influt o    for which cannot be held responsible

-    conseqs for Olympic  sport?

Inequalities -    ext conditions -    person-dependent inequalities: INCLUDING GENETIC MAKEUP, BODY SIZE, ETC -    system inequalities

ext cond -    direct competition – standardisation -    indirect comp (outdoor) – seeded groups, drawing of positions

person depdendent -    sex and age, over-clasficiation (sex classification seems reasonable in some sports – where biological differences are significan, though in others, they are not justified) o    – ME: interesting analogy for genetics, would we seek to ensure athletes are all the same age? To what degree? Where it seems to have some influence on performance, we should. -    body weight – under classification

CAN SPORT SUPPORT ADDITIONAL CLASSES AND DISTINCTIONS AND DO YOU THINK IT POSSIBLE TO LOOK TOWARDS PARALYMPIC DISTINCTIONS TO IMAGINE HOW IT MIGHT FUNCTION? - A QUESTION ABOUT THE SPORTING SPECTACLE AND ITS VALUES

TALENT IDENTIFICATION IN SPORT

What makes a Champion?

Talent -    natural endowment or superior ability -    single most imp factor contributing to achievement -    other factors include

identified developed selected science or art?

Intuition, rolling dice, magic, sport science (multidisciplinary, evidence based)

Nature v nurture

Genetic endowment -    intrinsic potential 46xy -    structure, function, behav -    genetic manipulation -    next doping frontier?

Environmental influence -    extrinsicfactors

Suzuki Method -    all  Japanese children speak Japanese -    inborn greatness or mediocrity not known -    advanced ability can be nurtured  in any child

Why does it matter? -    parental imperative -    Olympic imperative -    Financial imperative

Jason Gulbin -    South Australian Sports Institute -    AIS -    National Coordinator of Talent Search -    Published on athlete profiling, ex induced muscle damage

Thomas Reily -    Liv John Moores -    President-elect of Int. Soc Adv. Kinanthropometry

Darlene Kluka -    Grambling State University -      Volleyball talent

Jason Gulbin Paradigm Shifts in Talent Identification National Talen Search Coordinator, AIS

Concerned about young athlete and talent identification – but much of the work is also on older athlete

Terminology Talent (identification/detection) – athletes from outside of the sport (non-specialist, quasi scientific approach, to examine predisposition for a specific sport) Talent Selection (within the sport, watching athletes) Talent Development (vital to process)

Intentiaonal Search for answers Ireland (NCTC) 2001 -    factors prpmoting and inhibiint  success of H Performance players and athletes n=207

USOC 2002 Talent id and devel of US Olympians

AIS 2003 How do elite Athlete develop n=681

NZAS 2004 Linking promise to t podium taskforce report

Why such a focus on this area?

Australian Typical spending patterns ($AUS)

Costs $37m for a gold medal

$8m for any medal

(Hogan and Norton, 2000)

reducing costs isa  huige bonus

US Census Bureau 2000

Population for Oz significantly less than other countries, so identification critical

National Talent Search Program 10 yr programme www.ais.org.au/talent in each academy, talent search coordinator phase 1: ask pe teachers in highschools to collect data for basic phys test phase 2: submitted to talent search coordinator phase 3: if athlete good, invited to talent devel programme

program  issues -    growth and devel conundrum (too much to measure, children of same age too different) -    labour intensive  (reject around 95% of data from schools) -    athlete acceptance uncertainty (not all kids want to do selected sport) -    variable enthusiasm of schools/teachers -    information privacy concerns (now, they use id numbers, rather than names) -    inability to respond to immediate needs of coaches in age group ( -    emerging adulthood and retention

paradigm shifts -    broad – focussed -    young – older -    novice – experienced -    schools - public domain -    TID

e.g Cycling -    ad in paper for talented female cyclists for 500m event -    females 18-26 -    non-cyclists -    explosive leg power -    competition history -    recruitment via the media -    initial screening n=247 applicants -    peak power, 30 sec av power, vertical jump test -    selected 26 girls -    age 16-29 (played various sports: bball, rock climbing, athletics, rowing, netball) -    lab performance: peak power: (1300w, av power: 700w; 10+yrs),  these athletes peak power: 1134W, av power: 625W – after 6weeks (gardner et al, 2002) -    performance in less than two years, 5 athletes when on to win national comps

Paradigm shifts -    simple – complex models -    from physical to physiological -    focused cohort of 32 selected, based on: o    water ‘feel’ o    school grades o    parental background (molecular biological approach will be critical in advancements)

paradigm shift -    centralised – decentralised -    generalist – specialist

Regional postgrads -    offer maters by research (cycling) – fee-free position plus stipend, to assist talent search coordinators and also develops local support

Summary Consider maximising talent harvest by supplementing traditional TID approaches

KIM SCHIMMEL Deep Play – political hierarchies  in  new Olympics

Reconstitution of Olympic space -    nato resources -    70000 troops -    greek forces -    us coast guard -    us special forces

private security entitites and gov alliances

eyes and ears of the games

cancellation insurance -    first time in Olympic history -    $170m coverage/$6.8m premium  usd -    terrorism, earthquake, landslides (not construction delay)

Olympic Spirit -    if terrorism threat to Olympics real, then why stage it in  modern world (july 26, 2004, b KI Angelopoulous)

www.anti2004.net

current cost of Athens 2004  6billion euros, 1% of Greece gross product

Beijing 2008

Kristine Toohey -    (Sporting) Legacy of Sydney (Cashman) -    economic (direct and indirect) -    vbuilt environment (nonsport) -    info and education -    public life, politics and culture -    sport o    elite, mass (FOCUS ON MASS SPORT IN THIS PRESENTATION), financial, built infrastructure -    symbols memory history

Mass particpation as Olympic legacy (grassroots sport) – theory/intent -    de Coubertin -    Olympic Charter -    IOC invlve with sport for all, since 1983 (samaracnch) -    IOC Sport for aLL commission -    IOC WHO 5th World SFA congress 1994 -    SFA congress declarations sponsored by IOC, Seoul, 1996, bcn 1998, quebec 2000 -    IOC Legacy symposium 2002 (Hein Vergruggen) – to remain educational -    55 papers: mass participation addressed in 3 (2 winter sports)

Ressearch Q -    given intent, does hosting OG boost mass sport particpation in host communities?

Past Olympics -    international conf held in late 1980s in seoul, korea -    reps from 5 previous Olympics -    agreed that mass participation most imp -    but little evidence that actually happens -    2 exceptions o    LA 1984: AAFLA – runs number of programmes o    BCN (Truno, 1995) o    Sport paritipation in BCN •    1+ per week •    1983 36%

Sydney 2000 -    in aus $60m dollars per gold medal

Houlihan from ASC

Centre for East African Running (2004, Glasgow)

Glasgow University Symposium Possible Causes of Success of East African Distance Runners March 8, 2004.

Keith Johnson – genetics dept

‘Off the track, in the field’ Yannis Pitsiladis

Dr. Bezabeh Wolde, Sec Gen Ethiopian Olympic Committee

Sampled entire Olympic team Team trains together

Kotebe College of Teacher Education, Addis Most of athletes from Shewa and Arsi (central part of Ethiopia) -    altitude 3000m (Addis Ababa is 2400m) Bekohi, Aris Province -    deratu tulu -    kenenisa bekele children’s journeies to school by foot/running/cycling World Champs Paris, 10000m -    gold, silver, bronze all Ethiopian

Kenyan First Olympic Gold – Neftali Temu, Mexico Olymmpics Mike Boit, bronze medal 800m 1972 Munich, Olympics Commonwealth Gold, Edmonton, 1978 Nambi? Nandi? province Rift Valley St. Patrick’s High school – boys school -    many Olympians from here tea break – important? Itigo Girls High School Pupils running to school Morning, for lunch, and afternoon (parents must find food for them) Kaptagat Training Camp – Patrick Sang -    Global sport sponsorship -    Joseph Chelimo, Head Coach -    Eliud Kipchoge – gold 5000m World Champs, Paris 2003 -    Richard Limo – Gold 5000m, Edmonton 2001 -    Camp has no electricity -    Cooking fone in pots

IOC Consensus Statement on Sport Nutrition 2003 All cooking done on fires, very precisely

Daily diet -    average carbo 606g -    body weight on average 58.6 -    near perfect ratio

Fluid intake

Eliha Lagat (boston marathon)

IOC Camp – Kipchoge Keino (most well known of Kenyan athletes)

Chirchir training camp -    sampled athletes -    tea important again -    ran in morning without breakfast, and return to have tea with 3 slices of bread

Chepkoilel Stadium Kaptagat Camp (FILA) -    moses tanui -    unpasteurised milk for tea

Amos Biwott (3000m gld, Mexico 1968)

Fatwell Kimaiyo Gold 110m 1976, hurdles

Commonwealth games perth 1962, seraphina antao, gold

“whether there is money in it or not, running is in the children’s blood” school teacher

Acknowls John robertson bequest, uni of glasgow EOC, EAF, Wellcome Royal Soc Carnegie Scotland Event sponsored by Glasgow City Council, Abgene, WWR International, Cranlea

Used Bleep test – had not heard of this test before. -    results under analysis -    1000 kids tested in Nairobi

no obese kids in nandi, but plenty in nairobi

agali (staple part of diet) -    similar structure to rice

John Bale

Pre-colonial period Cultures of running Myth of natural athlete

FAM Webster arranged comp between spear throwing and javelin

Modern period When running became racing Refute idea that these Kenyans emerged in 1972 from nowhere those performances had roots in 1900s earliest recording sportised event was in 1902 one of first timed events – modern notin of recording

influence from Muscular Christianity through missionaries 1924 bureaucratisation of Kenyan running organised African Olympics records from the 1930s best performance for mile measured to second 1951 formation of African Amateur athletic federation

joy adamson – anthropoligist, research on athletic body, Masai

1954 kenyan began to engage with international comp, NOT 1968 Mexico Olympics

Kenyan Olympics, won medals in high jump, javelin, and sprinting Diversification of athletic production imp At Vancouver Empire Games, team was 2 runners in 440m, 1 in 880m, 1 in 3, 6 miles, … -    no suggestion that this was a running team at all went on into 1960s

present time… -    how does this history help explain Kenyan running? -    Need to take a global perspective -    Can Kenyan running be partly explained by the absence of success in the West -    As West declines in interest in this kind of activity, for various reasons – range of alternative activities, which has led to diminution of people taking part in long distance events. In part, this explains the success of Kenyans. -    There are poor results in these events in the west Has slope in improvement of these records declined? Things are slowing down in those events in the west

Interesting to examine how Kenyans react to this running phenomenon and how Kenyans view the western view of this -    neo-colonialism -    need a Kenyan voice

mtDNA Haplotypes and Demographics f Elite Ethiopian Athletes Robert Scott

Why do some people perform better than others?

Proposed explanations for greater success -    favourable physiology -    altitude adaptation -    running long distances to school -    psychl advantage (and cultural = ME: but actually doesn’t mean this) -    favourable genetic endowment

believes tha genetics is important, but not in way that people have considered

Majority of human genetic diversity is within populations rather than between -    more within East Africa than in Europe

more than skin colour needs to be considered -    ok, so what then?

Ethiopia

Methodology

Enviro analysis -    place of birth -    language -    distance and method of travel to school

genetic analysis: mtDNA -    mitco are major energey producers -    mito function imp in ex

mtDNA useful in population genetics -    maternal inheritance: no recombination -    fast mutation rate (D-loop) -    Maternal ancestry can be traced through branches of tree

MtDNA genome separate from

Buccal swabs from 109 control and 114 elite athletes MtDNA extracted and classifieid -    HVS-1 polymorphism -    Coding region polymorphism

Compare distrib of mtDNA types amongst athletes and controls

Ethiopian Regions -    arsi is over-represented in succeses

Place of birth results

Slightly more from Assis Ababa for elite athletes Large increasee for 18%

Might show that athletics is more prevalent in Arsi

Language Results

Possible that different ethinic goups have different frequencies of gene variant

Might be to do with popularions

Distance travelled to school results

Evidence that this might be influential

Students running some 5-10km to school, and even some running marathon distances.

MtDNA questions -    if mtDNa polymorphisms are imp in endurance performance, will t linage on whch they occur be more common amongst t athletes? -    Might this explain t dominance of East African athletes in distance running?

Contrls’ mtDNA tree -    Mitochondrial Eve

Athletes’ mtDNA tree -    relatively similar distribution -    not significantly different

Conclusions -    Ethiopians are of a distinct enviro background relative to Ethiopian popn -    Athletes have a very deep common maternal ancestry -    Athletes are not a genetically distinct population as defined by mtDNA

How does the ACE I/D polymorphism affect athletic performance, especially in East African athletes? Richard Wilson, Molecular Genetics, IBLS, Glasgow University of Paisley

Why t ACE gene? -    is a major target for blood pressure controlling therapies, and has other less well-understood activities

Why geontype athletes? -    athletes with extremes of physiological performance may help elucidate t physiological variation of normality

why genotype Africans? -    African populations contain more genetic variation than European-derived populations

What does ACE I/D do?

Lots apparaetly -    publications showing effects ranging through, o    – muscle performance in response to training skeletal muscle fibre type (in young Japanese), endurance performance (UK Olympians), high altitude adaptation, survival to 100yrs old (in France); kidney responses, insulin sensitivity, etc

How does ACE (I/D) do all this?

ACE -    activates Angiotensinl to AngiotensinII (which raises blood pressure) -    inactivates Bradykinin (removing a factor which lowers blood pressure) -    Two ACE activities so far, is it all this simple?

ACE is DCP1

ACE is a dipeptidase, cutting two amino acids off peptide hormones -    angiotensiI DRVYIHPF HL -    Bradykinin RPPGFSP – FR -    Haemoregulatory peptide AcSD – KP

Ace is an enxzyme that clips other peptide hormones

High affinity for hameo

Ace is found attached to endothelial cells and soluble in blood plasma Form of ACE is found in sperm -    In mice, where have engineered out sperm type, but not other, sperm no longer functions properly, no longer capable of fertility -    Link to cleaning vaginal secretions, which kill sperm (possible fertility link)

Functional genomics of the human ACE / DCP1 gene -    t full ACE protein has two active sites -    33 ACE isoforms o    som – DCPi – link – DCPi – anchor o    som – DCPi – link I DCPii o    tes – DCPii – anchor (male form)

ACE can do a range of things and is collecticated

Variations in the Human ACE gene -    over 70 common variants (SNPs) in 30000 DNA bases of human ACE Gene -    less than 10 of these ACE SNPs chang t functioning of the ACE gene -    human ACE gene shows t signature of recent natural selection (haplotypes / linkage disequilibrium) -    The famous ACE I/D polymorphism is almost certainly non-functional o    Is in region of gene that is removed

The ACE I/D polymorphism -    is easy to test for -    in Caucasians, ACE I/D is associated with 40% of opulation variation in circulating ACE levels (I low, D high) -    Is ace I/D hitch-hiking with t real functional change? (haplotypes) -    if look for other markers on ACE gene, knowing that how different versions have been shuffled around 22982AG is t best functional candidate, I is always found with 22982A in Caucasians, D with 22982G

DNA sampling at Kaptagat Training camp -    sample using swabs -    can diagnose people’s genotype, to carry out genotyping

An ACE blood sampler -    removed from Kenyan population, -    Kenyan, no longer regulated in same way that they are in Caucasians

ACE I/D PCR -    Extract DNA, and amplify small pieces of it

Can genotype for most markers in the ACE gene -    Roberts and others have set-up assays

ACE activity and I/D -    ethio: 40% variation -    Kenyan: 7%

ACE activity and 22982AG -    real causative agent for circulating ACE levels

Conclusions -    22982AG (not I/D) is t functional polymorphism regulating circulating ACE levels -    Kenyan / African population genetics have modified t assoc between ACE i/D and 22982AG

Few people who came out of africa historically, cold not carry the level of variation that existed in Africa -    expains why we do not see this variance in other locatioes

Is ACE I/D asoc with excelenct in Ethopian -    genotyped 114 (… -    no strong assoc with ACE I/D or 22982AG

Ethiopian ACE/ID data -    not clear that ID is solution for talent searching.

ACE I/D might work differently in males and females

Little effect of ACE ID and other polymorphisms on elite endurance Cannot use it as predictive test, May subtly affect training response Tell everyone they’ve got the ACE gene (placebo effect)!

Any evidence that ACE gene involve with other aspect of performance

Best studies are small groups of people, where have looked at small aspects of physiology , rather than assoc with large athlete cohorts.

Y Chromosome haplotypes and the African endurance Athlete Colin Moran

Overview Existing theories (including genetics) Why Y? -    what is t Y chromosome? -    Y chromosome consortium YCC) tree -    Global distrib

Techniques and subject groups Analysis -    by major clades -    by haplotypes

In the beginning -    Rome Olympics, 1960s -    Atlanta Olympics 1996 -    Sydney Olympics 2000 -    37 of top 40, 10k times

Explanations for Success -    diet -    culture -    genetics o    mtDNA o    ACE o    Alpha-actinin 3 (ACTN3) o    Y chromosome

Now around 100 genes associated with human performance

Human Karyotype -    picture of chromosomes -    23rd ppair of chromosomes are sex chromosomes (smallest) why Y? -    patrilineal inheritance -    never 2 y’s in 1 cell o    functional changes immediately subject to selection o    no recombination

haploid (because only one copy of it)

different types of y chromosome in different proportions around the world, because it is a dynamic chromosome

Summary -    Group analysis: o    Control groups not different o    Some difcs between athlete groups and control groups

-    indiv haplotype anaylsis o    4 haplotypes showed as o    sev haplotypes that we may have expected to showed no assoc •    African specific clades, A and B •    E3b*/E3b4 similar to E3b1 •    J(xJ2) which had apparent

Conclusions -    some Ethiopian Y haplotypes show assoc with elite athletes status, though not really a predictor -    Athletes are more distinct from the Arsi control population than the Addis control o    Arsi control truly representative? •    Town v country?

-    how can t y be having such an effect? o    Direct effect of a gene on the Y chromosome o    Unknown subgroup of the population?

Thanks LeicesterUniversity of Paisley    - mark jobling

Demographic characs of elite Kenyan endurance runners Vincent Ochieng Onywera

The Kenyan Runners: In search of Olympic Glory Mike Boit, Kenyatta University

Olympic boycotts and lack of exposure, performance in Kenya declined significantly

Top runners left or stopped

Kenyan Athletes in top ten of world 1968-72: 1 73-76: 4 77-80: 3 81-84: 1 85-88: 4 89-92: 9 93-96: 6

we are still not at human potential in sport – still not training enough

set backs -    inadequate facilities -    less than minimum sports funding -    lack of sophistication in coaching -    lack of expertise in nutrition -    lack of institutional training -    lack of systematic talent identification plans and implementation programme

CULTURAL traditions -    cattle radigin expedition practices (hugh demand for endurance), suallly taken as sports for the young warriers -    male circumsision (process of instilling high discipline, agresiveness, etc; ability to withstand pain)

would be prudent to assist athletes in providing alternative to taking drugs that could enhance their performance

European Federation of Sexology (2004, Brighton)

European Federation of SexologyMay, 2004, Brighton.

Monica Whitty - cyber infidelity -    check 2003 paper in CyberPsych and Behav

Kitzinger and Powell (1995) story completion method Representations of internet infidelity Gender differences -    Taylor (1986) men judge husbands affair as more justiable -    Sheppared nelson, andreoli-Mathie (1995) men rate infidelity as more acceptable -    Women more unset by emotional -    Sex intercourse main act to case jealousy

Content analysis on hypothetical situation

Is it betrayal? -    51% betrayal as unfairful -    84% act of betayal

reasons for why scenario not infidelity -    just friends -    just flirtatious and fun -    it’s a computer -    don’t know person will never meet -    no physical sex -    person cheating with is of same sex

why wrong? -    emotional infidelity o    “it Is cheating” -    sexual infidelity o -    secrets -    cant have relationship wit more than one person o    “not prepared to ‘share’ him with someone else”

impact on relationships: -    aggrieved feelings -    break-up -    loss of trust -    revenge stories -    betrayer feels hurt/depressed/upset/anger -    less time together -    shock -    sexuality inadequate -    self-esteem

Griffiths and Young – online addiction

Conclusions -    limited to a hypothetical sitn -    cyber-affairs potential serious impat on relationship -    equal important given to emotional and sexual infidelity

Rules of acceptability in relation to online acts not clear defined. We know more clearly about this offline.

Louise Madden www.cardiff.ac.uk/socsi/ICT Locating t social in lang of computer mediated sexuality: case of sexualised spamming in realtime chat.

All messages are initial messages,

ME: what kind of utopia?

Trudy Barber

Brief history of technosex -    erotic imagery from China -    1734: mechanical vibrator -    1880: romantic novel -    1900: electrical vibrator for self tratement -    Rachel Maines: the Technology of Orgasm -    Devel of orgasm influ emancipation project

Vulcanisation of rubber – originally for industry, now a fetish -    unforeseen conseqs of technology -    covered in their technology of choice -    gas mask

new sexual expt with new digital technologies -    minority report: Pleasure emporium -    PVC Trinity – in matrix o    Whole of matrix is about fetishism (wanting to be in computer, computer in you)

Electro Stimulation -    electro sex pack

ET-312B – 100% Digital ecstasy -    programmes that can let you – Phaser – connect body to musical track that will let you decide when to have the orgasm -    technological determ or mediation?

Online we become subject and object of desire

www.fuckingmachines.com -    website for technology

mechanical metaphor (Brooke 1991)

technologies are mechanical ext of penis or clitoris

Master R’s Willing ‘victim’ – one of her subjects, (amazing fetishes, also loves artwork, critcket, etc) -    ‘intel inside’ -    possibly find him online -    cost and battery life main hurdles to this being possible -    Master R’s postmodern harem -    Adult digiplay -    Postmodern masturbation -    www.televibe.com o    can plug into -    do not have to be a bodiless entity in cyberspace.