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World Anti-Doping Agency Gene Doping Symposium (2005)

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


improve people's health. misuse of medical tes

Richard Pound

banbury conference


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


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


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


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


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.


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


imune systt


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: 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


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


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?


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

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


shedding data, gene therapy stdies


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


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


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?


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


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


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


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


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


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


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


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?


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


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


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




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


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 ….?


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


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.


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


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


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


Session 4

Tom murray

Screening a worry


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


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


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

Technology and Sport (2004, San Sebastian)

San SebastianDec, 2004


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


Xtema… - golfer


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 -

Technology pushes sporting boundaries (25 March, 2007)

Interview by Australian Associated Press while in Brisbane last week. Here's the outcome:

Technology pushes sporting boundaries

Dozens of leading professional golfers, including Tiger Woods, have had eye surgery to improve their vision. Some believe it gives them "better than perfect" eyesight and makes the tricky business of reading greens far easier.

Hundreds of American major league baseball pitchers have had surgery to implant stronger tendons from elsewhere in their bodies into their elbows. Many of them testify that they can throw the ball harder and faster than they could before the operation.

Now the day may not be far away when athletes have microscopic-sized devices implanted in their brains to help them perform better.

According to Dr Andy Miah, a British bioethicist, the line between using technology to improve sporting equipment and using it to improve the bodies of its practitioners is becoming increasingly blurred.

"Sports are technologically enabled practises," Miah said.

"We are pushing the limits of the body technologically and creatively - and I think the relationship between those two is quite close.

"People are fascinated with what the body can do in various kinds of performances."

Miah, who was in Brisbane this week to address a conference organised by the Australian Sports Commission, said functional elective surgery in sport is a more immediate issue than the
long-feared emergence of genetically manipulated athletes.

While the World Anti-Doping Agency concentrates on performance-enhancing drugs and worries about so called "gene-doping", it has no provision in its code for surgically enhanced athletes.

Woods, who was so short-sighted his doctor said he could barely count fingers held in front of his face, wore contact lenses early in his career.

He had laser surgery on his eyes in late 1999. After the surgery, which gave him vision rated at 20-15, Woods said the hole looked bigger to him.

Whether or not the surgery had anything to do with it, Woods won seven of the next eight PGA tour events he played in. The following year he began the "Tiger Slam" in which he became the first man to hold all four Majors at the same time.

Woods' surgeon, Dr Mark Whitten, says the eyesight produced by surgically altering the shape of the cornea gives golfers an enhanced three-dimensional view of the shot confronting them. "It
may be better than normal vision," he says.

Others who have had the surgery include Retief Goosen, Vijay Singh, Scott Hoch, Jesper Parnevik, Lee Westwood and Mike Weir.

Around 10% of major league baseball pitchers in the US have had surgery to strengthen their elbows, which come under enormous strain from repeatedly hurling baseballs at 150 kilometres an hour.

The procedure, called ulnar collateral ligament reconstruction (UCR), is widely know as Tommy John surgery after the pitcher who first had it done in 1974.

According to a report published in USA Today, it involves taking a tendon, usually from the wrist or leg, and grafting it into the elbow in a figure-of-eight pattern through tunnels drilled in the
humerus and ulna bones.

The surgery has saved the careers of hundreds of pitchers, and there is evidence that its success rate is encouraging younger pitchers with only minor elbow injuries to seek the surgery to help their careers.

Some pitchers say they come back better than ever.

"I hit my top speed (in pitch velocity) after the surgery," said Kerry Wood, who had the procedure five years ago and now pitches for the Chicago Cubs. "I'm throwing harder, consistently."

Miah believes there is now a new frontier in sporting technology, driven by the convergence of nanotechnology, biotechnology, information technology and cognitive science.

All of these have profound implications for technological and medical developments generally, as well as within sport.

"It seems likely to me that sports will confront the implications of this convergence quite soon.

"We can imagine nanotechnological devices being utilised by athletes to keep them fit ... these are molecular-sized devices that could be inserted into the brain to elicit certain kinds of
physiological modifications."

The technique has already been used to implant molecular-sized devices into the brains of people suffering from Parkinson's disease.

The implants alter the brain's electrical output to help cure the  uncontrollable shaking that is the main symptom of the disease.

Technology such as this could have implications in shooting, snooker, archery and other disciplines requiring steady aim.

Miah, who believes genetic manipulation of athletes is not necessarily a bad thing, says the march of technology is throwing up some crucial philosophical questions.

"The development of biotechnology, stem cell research, cloning technology and the like has provoked a kind of moral encounter with what it means to be human and what technology might be doing to alter that.

"If we can develop devices that make it difficult to say these are external to the body, if they're implantable into the body then it becomes much harder to say that they are artificial."

Centre for Olympic Studies and Research, Loughborough University (1 Dec, 2006)

Research seminar for the Center for Olympic Studies Research: 'Human Enhancement Technologies and the Bio-Politico-Ethics of Sport'

Over the last 5 years, the world has encountered considerable developments in human enhancement technologies. Yet, beyond their techical successes and failures, stem-cells, genetics, nanotech, and information technologies have all featured in the everyday sociologies of the future that abound within media and scholarly texts. The world of sport has encountered a wide range of these applications and the positioning of sports medicine in relation to experimental medical technologies invites rich and complex speculations on the development of performance in elite sport. In this paper, I discuss the role of bio(ethics) in cultural studies and its bearing on the human enhancement debate by drawing on Zylinska (2005). Within the UK, the most recent instantiation of this debate is through the public inquiry into Human Enhancement Technologies in Sport (Science and Technology Select Committee, 2006), the first evidence session of which heard from former 100m Olympic chamption Linford Christie. I discuss the political positioning of sports insitutions in relation to these technologies and how they reflect a broader bio-politico-ethical stance against human enhancement (Garnier, 2006; WADA, 2006).  Moreover, I suggest that this positioning is broadly indicative of a fundamental tension within the world of medicine over its legitimate role, and the ends of a commercial model for  human modification. These circumstances limit the possibility of open debate about the relevance and merit of anti-doping programmes and weaken the credibility of sport's judicial ethos, the latter of which is highlighted by responses from athletes to Linford Christie's involvement with the public inquiry. Finally, I conclude that these characteristics of sport's political economy inhibit nations from developing technoprogressive approaches to the human enhancement debate. References

Garnier, A. (2006). An Open Letter to Those Promoting Medical Supervision of Doping. Lausanne, Switzerland, World Anti-Doping Agency.

Science and Technology Select Committee (2006, March 1). New Inquiry: Human Enhancement Technologies in Sport. Select Committee for Science and Technology, British Government.

World Anti-Doping Agency (2005). The Stockholm Declaration [on Gene Doping], World Anti-Doping Agency.

Zylinska, J. (2005). The Ethics of Cultural Studies. London, Continuum.

Digital era taking fans closer to action (The Times, 18 October, 2006)

Article published in the Times today with Matthew Syed Digital era taking fans closer to action By Matthew Syed and Andy Miah

VIRTUAL reality is upon us. Computer games in the high-street arcade are beginning to resemble exercise machines and an increasingly lucrative cyber-athlete professional league has been established.The United States bobsleigh team used a sled simulator to practice the Olympic run in Turin this year in their search for a critical edge in a competition in which it is almost impossible to practice on new and unfamiliar slopes.

More innovations are in the pipeline, with golf and motor sport leading the way. Fancy playing Augusta, Matrix-style? Digital technologies are increasingly influential on the playing field. Third-eye technology is transforming how events are officiated — Hawk-Eye is set to be used at Wimbledon next summer and cricket is debating whether to equip umpires with hand-held monitors to give them access to technologies familiar to armchair fans.

Radio frequency identification tagging will mean an even greater capacity to monitor and evaluate the actions of athletes on the pitch, including real-time judgments on such things as offside and whether contact has been made between players. Avoidable mistakes by officials could soon be a thing of the past.

The proliferation of mobile digital systems will soon close the gap between athletes and their spectators, where the latter will be able to immerse themselves virtually within the competition zone alongside their favourite athlete.

It is not inconceivable that we will see football teams managed by democratic voting systems.

  • Andy Miah is lecturer in media, bioethics and cyberculture at the University of Paisley and author of Cyber Sport, due out next year
  • University of Glasgow, Physiological Society (4 October, 2006)

    Last week, I gave a presentation at the invitation of Dr Yannis Pitsiladis, whom I have got to know quite well over the last few years. It was a pleasure to come and give another lecture to science students in GU. I've given so many classes here in the Postgrad school,I was left feeling a little nostalgic! Title of paper: Posthuman Enhancement Technologies in Sport

    International Conference on Sport Technology and Development (Shah Alam, Malyasia, Sept 2006)

    Andy Miah in Shah AlamThis was a wonderful meeting where I had a chance to taste a little of the Malaysian lifestyle. It was a bit of a flying visit, but thoroughly worthwhile. The conference was the first major conference of this department, which is very well positioned withiin the university (of over 100,000 students!).

    Conference website available online. My paper was titled Posthuman Sport

    Shah Alam, Malaysia

    This week I gave a keynote at the first international conference on sport technology and develoment at the lovely city of Shah Alam. The Universiti Teknologi Mara did a great job with this meeting and it was fascinating to spend some time around Kuala Lumpur and the neighbouring regions (just dont take any food if you visit the Batu Caves)

    BBC Radio 4

    Last week, I gave an interview for Radio 4 on the ethical issues related to developments in golf technology. Below are the details:

    The Sports Programme

    Mondays, 23:00 - 23:30

    Listen to the latest programme

    John Wilson

    John Wilson

    John Wilson brings you the best of the sports stories

    The  programme was on:

    When does technology cross the line between making sport a better spectacle and undermining the nature of the game? Tim Yeo MP and philosopher Andy Miah discuss speedy golf balls and other gizmos.


    View information on all The Sports Programme programmes

    Craig Heller

    The next stop on my whirlwind meeting run today was also set up just today. I can't believe how lucky I have been to hook up with these people at Stanford Uni. They have been so generous with their time and at such short notice. So, the next meeting today was with Craig. On the flight down to San Jose, the airline magazine had an article about his 'cooling device', the RTX Core Control system, which seems to be producing extraordinary results. The magazine article talked about its application for athletics where overheating impedes performance. This system seems to cool in ways that can yield an enormous performance gain. It was lovely to meet Craig and he kindly showed me a few of the designs that had gone into this 10 year project development. Here's a reference to one of their recent publications: Grahn DA, Cao VH, Heller HC "Heat extraction through the palm of one hand improves aerobic exercise endurance in a hot environment." J Appl Physiol 2005;

    Humanistic Olympics Studies Center

    On July 9-10 this year, the Humanistic Olympics Studies Center in Beijing hosts its 4th meeting. The Beijing Games is particularly interesting for my own research as it has signalled that it will be a 'Hi-Tech Olympics'. Professor Jin Yuanpu from Renmin university of China recently submitted a paper for the programme of the University of East London meeting on the Olympics, which details some of these points. The manuscript of this paper presents an advanced thesis on the various uses of technology in sport, its challenges and potentials.  The theme for this year's meeting is cities and this will be particularly interesting for London 2012, which just this week signed agreements with Beijing to promote exchange and collaboration. As part of this, there is also interesting news for us academics. Quoting from the BOCOG site press release:

     "Livingstone will promote London as a tourist destination and academic center during his three-day visit to China"

    Edward Tenner

    I first encountered Tenner's work 10 years ago, when I was studying for my undergraduate. In his book, 'Why Things Bite Back: Technology and the Revenge of Unintended Consequences', he considers a number of cases related to sport and technology, which informed my own work. I have been reminded of his work again through the Hastings Center's Bioethics Forum, for which he writes. I will next visit the Hastings Center in May for a project meeting.

    Wonderland Magazine and This Sporting Life

    A month or so back, I interviewed for Wonderland magazine for a feature on Sport and Technology. At the time, it felt like just another interview, but I have now learned that Wonderland exists as a result of funding from the tv programme The Dragon's Den. If you take a look at the magazine's website, it really looks like a wonderful piece of work with great attention to design. Having seen one episode of The Dragon's Den, it makes it all the more interesting to have been a part of this one!

    Doping in Torino

    I am writing from the Torino Media Centre within the City after having read and heard a lot more about Repoxygen. Over the last few days, there have been a number of journalists getting in touch wanting to find out about this. On Thursday, I interviewed for the Canadian Broadcast Corporation's evening news. I spoke with Tom Harrington, whom I first met in Toronto when Genetically Modified Athletes came out. It's so good to speak to Tom, as he is genuinely interested in the broader philosophical questions that the development in technology provokes. I am also interviewing for CBC's The Hour on Monday, which will take place at the Main Media Centre in Torino. From what I have seen, doping has been high on the news agenda for Torino. There still seems a lot of confusion about whether genetic doping is taking place and there are no confirmed cases. However, there does seem to be a lot of uncertainty about the circumstances here, which is quite different from Athens where nearly no discussions emerged during Games time about whether gene doping might be happening.

    From what I have read, there is also less clarity about how best to deal with genetic doping. While WADA and others wish to treat it as just another form of doping, i believe that there is also a philosophical uncertainty about the future of doping and its bearing on humanity. This ambiguity relates to the broader changes within society through technology. In the end, we appear to live within a culture of enhancement and, in this environment, the relevance of prohibiting genetically modified athletes is weakened. All that remains is the medical interest to protect its integrity and the safety of athletes.

    If any journalist would like to call me for interview while in Torino, I can be contacted on:

    0034 6365 0302

    Making Sports Virtual

    How long will it be before we ditch the sports arena and compete as athletes - or view as spectators - within an entirely virtual reality? This is the subject of a new book I am writing for The MIT Press, tentatively titled 'CyberSport: Digital Games, Ethics and Cultures'. It will be written with a colleague of mine in Australia, Dr Dennis Hemphill. The subject of this book will feature in a Sky One (television) production to be broadcast on December 2 in the United Kingdom. The programme is about sport and technology generally, and it rounds off with a segment about the prospect of making sports virtual.

    This project develops some thoughts that have been hanging around for the last five years. An early example of how they work out can be found in this piece:

    Miah, A. (2002) Immersion and Abstraction in Virtual Sport, Research in Philosophy and Technology, 21, 225-233

    Andy MIah Sky One Documentary on Digital Technology and Sport (2005, Dec)

    The Beam in Your Eye - LASIK

    Here is an news article about the use of laser-eye surgery on athletes, in this case the golfer Tiger Woods. The basic premise of this piece is that laser eye surgery is also a performance enhancement for athletes, but it is not banned. why not? "A week ago, Tiger Woods was celebrated for winning golf's biggest tournament, the Masters, with the help of superior vision he acquired through laser surgery." (link)

    Here is an extract from an article I have written on this theme, which will be published in a Dutch book on gene doping (edited by Bernike Pasveer and Ivo Van Hilvoorde):

    "To articulate the differences between the various uses of medical technology for sport, one can draw three categories of human modification: therapy, non-therapy, and enhancement. To understand the conceptual differences between these categories, it is useful to consider an example of medical intervention where these boundaries appear to be blurred. Laser eye surgery is a medical intervention intended to relieve the deterioration of eyesight. If this technique is applied to someone who has severe or even mild eyesight problems, then it can be considered therapeutic, since it will rectify any imperfection that might inhibit vision. In this capacity, it is tempting (and usual) to describe this as a ‘therapeutic’ medical intervention. It also matters that the definition is underwritten by the existence of a physician’s authority here. Yet, what are the defining characteristics of this ‘therapeutic’ guise? Is it important that the individual’s eyesight is being restored to a previous level of vision? If this were true, then we might wonder about the relevance of this conclusion. How would we feel if the intervention were applied to a person who was born without eyesight? The surgery would not return the individual to any previous state and, in that sense, s(he) would not be restored. In this case, the person would be restored only in the sense that there exists some species-typical state of function, where the treatment is characterised as therapeutic based on some typical functionality that a given species should possess. It could be said that humans have evolved to utilise the capacity for vision. This could also account for an individual who is born with partial vision – for whom we might also argue that restoration to perfect human vision is justified on account of a species-typical level of functioning to which we are comparing the said capability.

    Each of these methods of intervention is generally considered acceptable. While there is some disagreement about the legitimacy of interventions that appear to suggest certain ways of being human are preferable over others, let us assume for the moment that eliminating dysfunction, however troubling we might find its definition, is ideologically sound. So, the interest to ensure deafness is corrected is defended on account of it offering an ‘open future’ (Feinberg, 1980), where this entails maximising the possibilities any individual might encounter (for further elaboration see Savulescu, 2001 and Shakespeare, 2001). These examples can be contrasted with an intervention that would raise the level of capability beyond both an individual and species-typical level of normal or even perfect function. So, if laser eye surgery leads to better than perfect vision, we might have quite different concerns and feelings about it.

    Yet, it is also possible to think of circumstances where there is not much resistance to such super-human capacities. For example, there do not seem to be particularly strong moral convictions about the use of binoculars, telescopes, magnifying glasses, or even satellites and cameras, which radically re-define our capacity to see beyond our physical constraints. Yet, how would we feel about super-human vision? What if laser eye surgery could enable humans to enjoy the vision of, say, birds of prey. Alternatively, what if it enabled some additional functionality, such as a zoom capability? What should be our moral stance to such modifications and would such modifications be accepted in competitive sporting cultures? (FN: while not specifically tied to a sporting example, ‘super vision’ has been discussed in the context of sport recently (Alderson, 2001))

    In the world of sport, the ethical reaction to such innovations would be clearly expressed by a certain moral community, which argues that the ‘natural’ athlete must prevail in sports contests. Where a modification places an athlete over and above their natural level of functioning or some species-typical level of functioning, this constitutes doping and is considered to be unacceptable because it provides an enhancement of the natural. On one level, it is possible to understand why anti-doping exists and why some would seek to justify such rules on the basis of naturalness. In some sports, an athlete with the capacity to ‘zoom’ their vision would be at a considerable advantage to an athlete who does not have such capacity (though in others it might actually be an inconvenience and a skill to be able to modify one’s eyesight to optimise performance). In one very important sense, a contest between two athletes would not be of much interest where one of them has super-vision, since the enhanced athlete will be more successful. However, from another perspective, sport intends to reveal the most capable human. An athlete born with some ‘zoom’ capability is, in one very important sense, the most capable human. Why should an athlete not receive their gold medal, if they are the most capable? These matters raise questions about what is just in sport and the legitimacy of enhanced capabilities."

    LifeWaves - Not Doping?

    One of the questions at the Harvard symposium was about the ethical status of LifeWaves, the new technology that is designed to boost energy. There is no official WADA position on this one yet, but it is unlikely that it will be considered a method of doping. However ,it is performance enhancing and does offer a 'short-cut' to better performances. To that extent, one might argue (mistakenly) that is compromises the 'spirit of sport'. Here we have a further indication that there is a need for more joined-up thinking in the world of sport, about performance. In a paper I am due to have published in the Journal of Sport Sciences, I argue that it is necessary to ditch the anti-doping framework and replace it with a 'Performance Policy', which makes clear the connections between a range of technologies and how they challenge the ethical status of performance in sport. Here are some details about the LifeWave patches from The California Aggie:

    "The product consists of two patches, which the company claims will boost energy by 20 to 40 percent, and contains a vague list of ingredients known as 'orthomolecular compounds.' The NCAA and the U.S. Anti-Doping Agency tested the patches and found no illegal substances. The NCAA went a step further by announcing that the patches do not fall under the category of nutritional substances because nothing is ingested.

    While LifeWave's patent is still pending, and no details can be given about the composition of the patches, it is important to note the overall trend that is taking place in sports: an increase in cases of performance-enhancing products or supplements on the market. The fact that athletes at the collegiate and professional levels are looking for any advantages they can gain over their opponents is a distressing sign.

    Gone are the days when athletes gained their advantage by just working harder than their competitors. In today's era of sports, money and results are what matter and some athletes seem to be willing to accomplish their goals by any means necessary.

    While very few collegiate athletes gain the notoriety that often accompanies professional sports, it is important to note that Davis youths admire UCD athletes. Youngsters often emulate what they see performers doing and it is not far-fetched to believe kids will start using supplements in their adolescent years when given their favorite athletes as examples of a product's success.

    LifeWave seems to be the latest in a string of performance-enhancing products. With the rise of such products, athletes are often faced with the tough decision: losing the competitive edge or compromising their athletic integrity."

    Of course, I totally reject the stance of this paper, but what's new!?