How corrupt is sport? #AntiCorruption

Last night, I took part in the Grayson Debate, an annual event of the British Association for Sport and Law. I was asked by Dan Saoul, for whom I have spoken before at the BASL conference. The other speakers were the world leading sports lawyer Michael Beloff QC and former elite cyclist David Miller. 

The event operated by Chatham House rules, as much of what was said was of an extremely sensitive nature, but here's the skeleton of my talk, which covers some of the main points. I focused on the processes that enable corruption and attempts to mitigate against them. 

I don't know how corrupt sport is, but we have to assume that corruption is a feature of any institutional system and constantly work towards improving checks and balances to diminish its occurrence and impact. 

My Position

“Sport’s still haven’t come to terms with what kinds of entities they are and this catastrophically restricts their ability to function as ethically conscientious entities (support from EU). Until every single member of a sports club gets to vote on the position of their global leaders in their sport, these organizations will not be in a position to act in accordance with the ethical standards they require, and will remain organizations highly vulnerable to corruption.”

Improving Football Governance through Supporter Involvement and Community Ownership

-       12,000 grassrootssurveyed, 73% feel completely ignored at national level, 39% at local club level

Vulnerabilities in Sport

• Power $150b value ($700b betting market)
• Reliance on good will / volunteerism
• Life course of individuals in power – fragility of athletic career and national interests eg. Son of Saddam Hussain was IOC President.
• Global community – collapse of common ethical framework.
• Ambiguous bottom lines – enhancing performance / keeping athlete healthy
• Corruption News (corruption sells news)
• Stakeholder ambivalence eg. One athlete falls, just sponsor another)

Forms of corruption

• Cheating (doping, max fixing)
• Governance (contracts, nepotism, conflicted interests, training eg. referees)
• Political (human trafficking, quiet diplomacy, domestic interests)

Solutions

Transparency International recommendations:

• o   Anti-corruption guidelines and appropriate responses
• o   Ethical compliance
• o   Independent non-executive directors
• o   Due diligence and transparency on appointments/partners
• o   Implement multilateral agreements
• o   Whistleblower system
• o   Stakeholder involvement
• o   Bidding standards
• o   Budget transparency

-       Big data – performance tracking to identify unusual behaviours

In 2013, the EU’s Expert Group on Good Governance produced their own version of Principles of good governance in sport, which included this definition:

The framework and culture within which a sports body sets policy, delivers its strategic objectives, engages with stakeholders, monitors performance, evaluates and manages risk and reports to its constituents on its activities and progress including the delivery of effective, sustainable and proportionate sports policy and regulation.”

Is the Corinthian spirit dead?

I don’t believe in ghosts, but a traffic light system may be appropriate to identify risk of corruption, a bit like investment risks. If you are AAA then you are in good shape.

What will virtual reality sport experiences feel like?

This week, I was over in Dublin for a Virtual Reality conference organized by Professor Timothy Jung in collaboration with the Dublin Institute of Technology. I covered all things virtual and sport, here's what I said....

In the future, all sports will be e-sports #SAC2016

My talk at the Sport Accord in Lausanne this year focused on e-sports, an area of focus for my forthcoming book for The MIT Press, out later this year. My talk was followed by a panel debate with Patrick Nally (President, International Federation of Poker), Alex Lim (Sec Gen, International e-Sport Federation), and Chris Osborne (BBC Sport).

Here's the livestream recording

Here's the prezi...

How will virtual reality change watching and playing sport?

Last week, I interviewed for BBC's Chris Osborne on the use of virtual reality in sport. A great article followed.

DIY Steroid Labs

A big story broke this week on Sky News, which has been investigating the rise of DIY steroid labs around the UK. It tells a story of how body building and performance/image enhancement is not just a matter for the world of elite sport to address.

My arguments focused on the cultural shift towards enhancement and the need to re-appraise the morality and law surrounding such practices. If so many people are doing it, it's hard to still claim them as morally bankrupt.

If we can just address the health risks more effectively, then we need not worry. This means a harm reduction model and supervised doping.

eSport Summit

This week, I was in Seoul for the 7th eSport World Championships. Recently, I have begun working with the International eSport Federation and they ran their 1st eSport summit during the champs. It was a great chance to air some ideas I have about the field, many of which are in a book I have coming out next year with MIT Press. Here's what happened.

Sport 2.0

Salford University's Creative Entrepreneur event has become a huge success, with over 400 delegates registered over 1 day. I took part in a panel this year focused on Sport Business 2.0, at which I spoke about the game development community around sports and the growing mobile health market. 

Pitch to Pixel

Opening at the National Football Museum this week is a new exhibition I was involved with producing, through my relationship with the museum's artistic director, John O'Shea.

I have worked with John for many years now and he has done amazing work in bioart and new media art. He has brought together an extraordinary exhibition of the last 40 years of football computer games to show how much gaming has evolved and how close art and life now come together.

The exhibition is on until June, so plenty of time to see it. It's worth spending a whole day at least, just to experience the different kinds of game interfaces and appreciate how they have changed over the years.

The Sporting Future Today

Wearable Technology, Augmented Reality, & Drone Cameras

Today's talk at #SportAccord went really well. It was the first time I'd used flight within a lecture and fortunately nobody got hurt. In actual fact, it was all very safe and I think it made much more real the way in which drone technology is becoming a part of the fabric of our lives.

Here are the slides from the talk

and finally, the lecture itself

eSports

This question frames a @BBC5Live debate tomorrow night I took part in @MediaCityUK . The show was in front of a live audience and went out on @BBC1 'red button' and Twitch, where it had 83,000 concurrent viewers. You can also tune in through the BBC Radio 5 Live channel. If you are nearby and would like to come to the live show, email me and let me know. I can put you on the audience list.

Here's the full brief and deets:

We have a special programme tomorrow night which you can hear on BBC Radio 5 live and watch via the BBC Sport website and Twitch, as we explore Gaming, and the Rise of the Cyber Athlete. With computer game events now attracting thousands of spectators, the industry has teams, managers, star players, they compete in the X Games, and there's even a transfer window - so is it a sport? We'll be debating that question with those involved in eSports on Thursday 15 January from 8.30-10pm.

We’ll be broadcasting from the Blue Room at Quay House in MediaCity, Salford, in front of a live audience. It’ll have a Top Gear feel to it – with refreshment provided to all

Take a look at this cool new tech from RideOn, which I mentioned in the prog, showing how augmented reality is fusing with real world sport experience to create a hybrid gaming experience.

Uploaded by Alon Getz on 2014-12-04.

Social Media & Radio: A Natural Born Partnership?

This week, I a gave a talk for the European Broadcasting Union at their HQ in Geneva. Here's the manuscript: Are Social Media and Radio Natural Born Partners?

by Professor Andy Miah

My starting point for answering this question is to think about the term ‘listening technology’, which has become a crucial concept within the field of social media. Anyone who is doing serious social media work is likely to have purchased some kind of listening technology and some of it is not cheap.

You can pay anything from nothing to tens of thousands of pounds for this software and it provides the most comprehensive means through which you can discover what takes place across your social media channels. The software allows you to understand how audiences engage, what they like, what they don’t like, and what you can do to improve the impact of what you share.

Yet, there is something ironic about the way this concept disregards what may be considered the first form of listening technology – radio. It is as if radio is seen simply as old media or that it has nothing to offer the dynamic world of social media. Radio was the first media technology to provide a direct, bi-directional communication between producers and audiences. Its content and its values became shaped by this ability and, arguably, so did the entire history of media culture that followed in its wake.

Are things different now? If radio was so influential to the way we think about the values of media culture today, then why does it seem that radio is treated as an outdated mode of communicating, unable to monetize its content to a level that is anywhere near television or film? Is radio’s distinguishing feature still its capacity to listen to people? Is it still the exemplary form of listening technology?

To answer this, I think we have consider what are the distinguishing features of radio today? However, this is no easy task to resolve in a world of complex transmedia experiences, where even our understanding of how people consume media is complicated and dynamic. We don’t even fully understand how people use media across devices and across formats. For example, consider the following media consumer, lets’ call him Andy. Andy loves radio, tv, and social content. He consumes a lot of it, particularly through social media and online television.

Now picture Andy jumping on board an underground train in London. It’s a busy, crowded train and he has on his headphones and decides to open up his download of the latest episode of Homeland, a show of which is starting to tire. The train pulls into Covent Garden and he has to now make the dash through the crowd to the elevator and up into the street. What does he do at this point? He can’t continue watching the screen, it’s too busy. The episode of Homeland is meandering a bit - he’s not very impressed with the latest series – and, instead of switching off the device, he puts the phone into his pocket and continues consuming the content using just the audio track. Instead of watching television now, he is listening to it.

Suddenly, this tv series has become a radio drama and has switched into becoming a different kind of product. He finishes the episode and makes a decision that he may go back to the content later to see the visual version, or he may not. I am not sure how typical this example is, but it is one of many ways in which the conventions around consuming media are changing.

It works the other way around too and this is why many radio shows are producing visual content around their production. The example reminds us that it's not just the technology that is transforming the medium, it is also the way in which the technology interacts with peoples lives and how it forms new habits. So, my first headline is quite startling: I propose to you that we still don’t really know what is radio. With this in mind, how do we begin to theorize radio’s relationship to social media when, in fact, most professionals and commentators would argue that we live in times of transmedia experiences - where the distinctions between types of media content experience is being altered.

Yet, this kind of conversation is all very abstract still, so let’s make it more concrete. Consider the daily media journey of another typical consumer, John. When John wakes up, he often begins his media experience by opening up his BBC news app on his mobile phone, checking the news of the day, before even getting out of bed. This is principally a reading experience, but it’s not deep reading, just quick skim reads. The whole experience may last just 3 minutes. He then get’s up and, while getting ready – still with mobile in hand - click’s the ‘live’ button on the BBC news app, which then opens up the BBC News 24 tv channel on his phone. However, he doesn’t watch it, he just listens. It is the background audio company to his daily routine. Is this a radio experience?

After getting dressed, John goes downstairs and switches on his radio but, while listening to the BBC Today Show, he also reads the BBC News app again and, quite quickly, is reminded of how the content on those two platforms are related - the stories on his BBC News app are quite closely connected to what the BBC Radio 4 programme is discussing, but he is getting more depth from the radio.

If he really likes something he hears on the radio, he might decide to tweet about it and tag it with the @BBCRadio4 account handle or #BBCtoday tag. Within seconds, friends of his - who are also having their breakfast while listening to the show - will favorite his share and this tells him that they are each listening to the show at the same time. They are connected. This has now become a communal media experience.

This example reveals how the first part of our answer to the question about how radio relates to social media requires taking on board the idea that social media has changed how people consume media and, crucially, that the catchall term ‘social media’ is actually part of a broader set of changes to media consumption that emerge around ‘mobile media’ - consuming media on the move. Mobility then, is a decisive factor here, perhaps even more than social media.

Yet, none of this is completely new. Radio has already made inroads to social media integration. So what do we know about how social media is changing how radio producers think about their content? We know mostly that social media creates a change in how people work. People stop chasing web traffic and instead focus on engagement and dialogue. We know also that social media users include a core group who quickly become co-producers of content. We also know that the ethos of social media can change an organization’s working life and how it relates to its audience. We also know that radio listeners do go to social media platforms after listening to content to find more and they want to comment on that content. We know also that young people especially are engaged by the social media content emerging from radio. Other key principles that social media content creators advocate is a 30/70 split, where 30% of what you ahre is yours, while 70% is other things that will interest your followers. Where you can, it is also a good idea to attach an image or video to content, to promote engagement.

However, there is a lot we still don’t know about this world. For example, we know that different audiences in different countries do different things. They don’t consume social media content that relates to radio in the same way. Back in 2007, TIME magazine’s Person of the Year was ‘You’ – it came at the height of the YouTube growth and the decision speaks to the importance of authorship, participation, ownership, matters which social media users care about, and there are some great radio examples of this.

My favorite radio show is a US program called 99% Invisible, part of the Radiotopia programme. At the beginning of this year, they launched a kickstarter campaign to get their program to a weekly schedule. They made a lot of money, easily reaching their targets, because audiences want to feel invested in the media they consume. This goes beyond co-production, it has something to do with co-authorship - the desire to feel invested intellectually or creatively into something. This kind of desire underpins the citizen journalism movement. It explains why we have such phenomena as CNN’s iReport, or the Huffington Post, or Sound Cloud.

So, my answer to the question is that radio is optimally designed to maximize the benefits of social media. It was the first direct form of social media, bringing listeners into contact with presenters and giving live air space to audiences. However, I think there is one other important factor to bear in mind here.

As various media formats converge and has habits of media consumption fragment, there is a need to re-think what we understand as any singular format and, in the end, what may distinguish radio from other media is what may be described as the 'art of radio’ In a world of pervasive user generated content, the distinguishing factor is no longer the platform, it’s not having a channel, since everyone has a channel. Everyone can edit, create, and publish. What’s left, in my view, is something to do with creativity and, to be novel in this social media age, radio producers need to think about their medium as an art form, not as just a communication device. Understood in this way, social media isn’t simply a mode of rethinking how you distribute content. It isn’t even just a context for thinking about how you connect with audiences. It is about allowing your organization and your medium to re-think its values, its purpose, and its contribution to people’s lives.

As a final comment, I want to think specifically about the applications of radio to sport. I recall being at the Vancouver 2010 Olympic Games and having taken a train to Whistler, which was quite a trek. On the way back, people in the carriage were anxious to know what was happening in the ice hockey match - USA vs Canada of course. I remember people would be checking social media to find out what was happening, but actually the place where they should have been is radio. The technology is at a point now where, as a radio commentator, you can deliver 10 second live clips - with minimal delay - across social media platforms.

This capacity requires radio producers to re-think how they relate to platforms - the radio waves are part of a wider ecosystem of audio distribution and engaging people differently with audio becomes all the more important in a mobile world where we struggle to ‘watch’. Even technologies like Google Glass are unlikely to change that situation. In an entirely screen based world, the importance of listening becomes all the more distinct and valued and this is why radio, perhaps more than any other format, has the capacity to really innovate with social media.

I met a man recently who has a hearing limitation and wears a hearing aid, which he has hacked to allow him to hear the presence of a wifi signal. He played the sound to us, which was a kind of crackling noise, fluctuating in volume. It might turn out that the social media trend leads us to think about our sensory capacity to hear in different ways and this may be the most exciting thing of all for people working in radio.

So as a concluding point, the power of radio – the art of radio – may not be found in its history, but in the way that social media is compelling it to re-think its future. The kinds of sounds we have typically heard from radio may be quite different from what we hear in the future and sports are fantastic contexts in which to explore this world.

Thank you.

Sport, Technology, & Social Media

This week, I was in Plymouth giving a public lecture on social media and sport. The lecture spanned wearable technology such as Google Glass to virtual reality simulations.

Sport Accord Convention: Youth Club [VIDEO]

The Sport Accord Convention is talked about as the United Nations of Sport, where all Federations come together. This was my second year of being a speaker at the Convention and I chaired a session called the 'Youth Club'. It was the first time ever that the Convention had put together something like this and the average age of panel members was approximately 23 years old. It was a great session and the feedback was awesome.

Congress of Brilliant Minds

I was in Madrid last week for the Congress of Brilliant Minds. Some really amazing other speakers were there, including Steve McCurry, Teresa Morales, David Peterson, and Steve Wozniak Here are the slides from my talk

Oscar Pistorius is more than just a fallen hero

This entry was initially published as a blog piece, but later in the Huffington Post

It was only a few days ago that the world of sport was talking about nothing but Lance Armstrong. However, the case surrounding Oscar Pistorius dwarfs any kind of doping scandal, past or present.

A lot has been written about how the tragedy will mean the loss of a hero for the sports world and for people with disabilities. But, Pistorius isn’t just any old sporting hero. He is the most important athlete of the 21^st Century and this fallen idol will mean that our social world will suffer a little longer from prejudice than it would otherwise have. Unlike most athlete superstars, Pistorius transcended what happens on the field. Debates about him were of significance for society at large.

His capacity to rival the speeds of so-called able-bodied athletes brought into question the use of that term at all and made us believe that a bionic Games that was faster and better than today’s was just around the corner.

In this world, it would be the technologically modified athlete we celebrate and it would be a world where disability no longer mattered. Everybody could compete on a level playing field and sponsors would fund Paralympic sport as much as Olympic. There may even no longer be a division between the two. There would be only one Olympic Games and only the best athletes competing.

This is now all jeopardized by the fact that Oscar was the only Paralympian campaigning to bridge the two Games. No other athletes have made this case and so the issue may simply disappear from the headlines. The IAAF may have an easier time because of these events and the world of sport may generally breathe a silent sigh of relief that there is nobody else pursuing the same campaign.

Just before the London 2012 Olympics, I wrote an article saying that Pistorius would be the most remembered athlete of the entire Games. I think this is even more likely now, but obviously for very different reasons

This is the second most tragic element of the circumstance, after the loss of a human life. An athlete whose entire future was still yet to be written, but which promises so much, seems like it is now etched in stone.

Unless Pistorius finds a way to redeem himself through the trial, then we may never know how much the world has lost by his absence in public life. It wouldn’t be the first time that a celebrity has later found sympathy from the public and managed to recover their place as a role model.

Oscar Pistorius is so young, with so much still ahead of him -  as an athlete, an advocate, and an ambassador - the entire world will be made worse of by this recent, horrific event, if no recovery is possible.

American College of Sports Medicine (2006, May, Denver)

ACSM Eduacting Physicians to Combat Doping: a key step in the fight Dr Alain Garnier, WADA Medical Director

Not responsibility to educate physician, not funds. But to educate.

What is dopng for physicians? -    ethical perspective – cheating -    juridicial perspective – rules violation -    medical perspective – therapeutic use in intentionally diverted into misues or abuse by athlete or entourage

athlete needs a neutral and well informed advisor

program for physician: proposed content -    introduction: rationale to ban doping -    the reality of doping – comeporary doping practices -    athletic entouerage – responsibilities -    vulnerability – critical periods, personalities at risk -    alternatives to doping – training and nutrition -    statute of a drug -    prhiobted list and TUE -    practical issues

aims of program -    to achieve common medical aproacht  in sport medcicine  (harmoniation/best practices) -    to explain t content of the list and TUE process -    encourage use of non prohibited alternatives -    to share exp and knowl

advisor and confidante an advocate for t health of the athlete not providing help in overtaing or supra physio

fight against doping is part of physicians role

Simulating Altitude Training Don McKenzie, UBC, Canada

Principles Does it work What are the effects? Is it safe? What’s new?

Simulated altitude environments -    hypobaric chambers -    normobaric hypoxic systems

when go to altitude, invoke changes across oxoygen cascade

Townsend, N E et al  JAP 93, 1498-1505, 2002 -    from AIS study

Voster, Glan, E et al jP 567(20) 689-699, 2005.

Sheel, A With et al JAP, 100: 1204-1209, 2006.

Lusina S et al, J Physio, (submitted 2006) -    1hr a day, 12 days, signify upregulation

thus, when exposed to chamber, more than sleep happens

Periodic Breathing in sleep -    intermittent hypoxemia -    periodic arousals -    loss of total, slow wave and REM sleep -    excessive daytime sleepiness -    carryover of sympathoexitation?\ -    vascular vasoconstriction during ex?

T Kinsmane, et al JAP, 92, 2114-2118, 2002

Brugniaux, JV ert al JAP, 100: 203-211, 2006

Katayama, K. et al, High Alt Med Biol, 4: 291-304, 2003

Safety -    companies say that they are safe.

What’s newL: the ‘normobaric oxygen paradox’

Balestra, c et al  JAP 100: 512-518, 2006.

Does it work? -    probably -    Levine, etc suggest dose response -    Periodization schedule? -    Nutrition -    Training?

Placebo effect?

Effects? -    alters chemosensitivity/respoiratory control -    alters cardiovascular regulation -    inc sympathetic ns activity -    alters sleep pattern -    potentiation of training post exposure

what do I think? -    it’s a training tool -    complex integrate physiology -    as effective as t scientist, coach and athlete who use it -    demonstrable, signif, pyhysio effects, some of which may influence performance

The Ethics of Altitude Trianign D.C. Malloy, University of Regina, Canada

Training -    ‘the basic goal of training is to use a variety of external stimuli (ex, environment, ..’ (Burke,2006) -    outcome is improved performance

Ethical Training – theory and practice

What is ethical traiiung? – that which results in the best performance? (Teleology – the good) That which employs acceptable means? (Deontology – the right) That which is genuine to the indiv ontologically and physiologically? (existential – the authentic)

The Good: performance outcomes -    goodness of act measured by outcome in producing ‘pleasure’ -    does act avoid pain?

The Right: deontology -    the right o    divine o    social contract •    does training regime X satisfy critieria set by govern bodies? •    Often where debate ends in sport o    intuitive – how we reason.

The Authentic: existential good and bad faith -    authentic physiologiy -    authentic philosophy -    existential – a philosophy of genuineness, freedom and responsibility

adaptation of t human body to a stimulus that does not exceed genetical optential moving t body outside its normal (geuine) physio range -    tf, training regime is authentic if introduces substant that does not bypass training stimulus or beyond range -    eg. Altitude training and nitrogen tents stim prodn of epo within indiv’s normal physio range/genetic potential

inauthentic physio - adaptation of t human body tro stimulus that EXCEEDs genetic potential

inauthentic physiology training

authentic philosophy -    good faith – I am what I am becoming -    bad faith – a way of estalibhins that I am not nwhat I am

Can athlete look in mirror and say ‘this is me’

Is this making me someone I’m not?

Ethical Decision Tree

Questions and Answers

Question: WADA talks about banning hypoxic, are they concenred about ethics or long term effects?

Olivier: must take into account fact that some athletes try to make those devices.

British Association of Sports Exercise Medicine (2006, March, The Belfry)

BASEM, 2006.The Belfry

Alfredson Vacularisation Management

Treatment-Difficult! -    where does the pain come from? -    mid-portion -    insertion -    proximal (patellar Tendon)

Questions and Answers

Question: how much pain warrants injection?

A: pain that interferes with your daily life

Question: cynical about 70% success rate.

Cathy Speed Extracorporeal Shock Wave Therapy (ESWT)

‘if a lot of cures are suggested for a disease, it means that the disease is incurable’ (The Cherry Orchard (1904) Act 1, Chekov)

therapeutic ultrasound

Low Intensity Ultrasound

Standard

Shock Wave -    initially lithotripsy

Non Union

Rotator Cuff!

ESWT

Technical issues Dosage Proposed  mechanism Clinical evidence and interpretation Advers

Does it work? What would it mean to prove to you that it works? People don’t understand economics particularly well, but they value being part of the conversation about the budget. Better and worse systems

The difficult models I presented actually articulate a set of political relationship -    the professions

it is part of your job to do this. Currently, you can take it or leave it, but not for long

stem cells pregnancy magazine

Motto

how evaluate -    eg. Science cafes – their existence proves the need, it is irrelevant whether you can prove people understand

you don’t need to ensure we all undersand the science

pyramid -    controlling information -    promoting healthing

Psychology confounding variables increase with chronicity

PEMT:, miuscle pain and gender difcs Eugene lyskow, nebojsa kalezic -    gender deifferences in pain sensations

lunch

tissue engineering -    mesenchymal stem cells -    in vivo

currently not a clinical tool

using post-natal – adult (haemopoietic) stem cells from bone marrow

(other methods: from fat or tissue (endogenous activation in tissue itself)

are there stem cells in tendon -    tendon-derived cels have poorer differentiation potential than MSCs -    Strassburg et al (Peter Clegg’s work at Uni of Liverpool) -    Explains whyt equine tendone injuiries fail tot repair adequately

Hypothesis -    implanting stem cells wold provide cell source capable of synthesising a matrix more like tendon and less like scar tissue

action? – orchestra -    musician: stem cells -    conductor: orchestrates formation of tendon-like matrix

characs of mscs -    in vitro

differentiation of MSCs -    stem cells implanted systemicall in foeti populated all mesenchymal tissues (Liechty et al, 2000) o    differentiated into target cell popn in each case

stimulus for diffn? – -    mechanical load -    contact with cells -    contact with matrix -    growth factors

put undifferentiated into tendon

Differentiation potential of MSCs cultured on tendon matrix: an in vitro model -    mscs capable of migrating, proliferating, expressing ecm proteins found in tendon

experimental models -    surgical models o    rabbit tendon (young et al, 1998) o    rat patellar tendon (Hankemeier et al, 2005) o

Roger Highfield ‘ have we oversold the stem cell dream? ‘Daily Telegraph, 2005) -    field is high on emotion

‘Cool! Ground breaking stem cell science could reduce… -    newspaper article on stem cell and horses

Sports Injury and HBOT Jules Eden London Diving Chamber

All info on website

Set up online medical company called eMed

Based in St Johns Wood

HBOT has been used to treat: joint, muscle, ligment, tendon injuries

When used with physio time of recovery reduced by 70%

Definition: wher a patient breaths 100% osygen intermittently while the pressure in t treatment chamber is increased to a point higher than sea level ie. >1abs

Various names: hyperbaric, recompression, decompression

Monoplace or multiplace

Not used as much as it should be

UHMS – society for hboc - to use hbo, need

effects -    air/gas embolism -    co poisoning -    crush injury, compartment syndrome and other acute traumatic ischemia -    enhancement of healing in problem wounds

Princoples

Boyle’s Law – bubble crusshing Dalton’s Law – gt thje ppo2 up Henry’s Law

So,

Exposure to 2-3 times normal atmospheric

People believe just binding more o2 to haemoglobin Actualloy, you are pushing it into plama A quantity great enough to sustain life in the total absence of hemoglobin

At point of injury, when you need most o2 to promote repair

Time is the greatest factor athletes -    this is different outside of sport

ME: not sure this holds. Most people will want it asap.

Medical Mantra Medical treatment is the balance of benefits for the symptoms versus the side effects to the rest of the body

Does hboc have any side effects? Yes, but rare -    middle ear barotraumas (must pop your ears) -    claustrophobia – people have impression they are about to go into a coffin -    oxygen toxicity – you get this if you breath pure o2 at 3x, for a couple of hours. Not with this! -    Boredom -    NO (problem with) DOPING

Scottish Study – with Celtic

Who cant go in -    untreated pneumothorax

relative contraindication

www.londondivingchamber.co.uk www.uhms.org www.hboevidence.com

Lance Armstrong used to recover

Questions and Answers

Evidence of enhanced performance?

No trials to suggest this

Mesotherapy

Discovery of mesotherapy Dr pistor – discovered

Polyvalent therapy

Anti-doping control -    used lidokane, was prohibited some years ago, not allowed intravenously -    when controlled, could not conclude whether intra or local -    nothing in urine after 4hrs

Brian English Arsenal chief medical officer

Nuscle Injury

‘the only predictive factor for a hamstrong injury is a previous hamstring injury’ Karim Khan

(Is there a genetic predisposition?)

8 days back to playing field, rather than 16 is a big deal

coach can influ number of soft tissue injuries

some athletes just seem more susceptible – thus, genetic?

‘anything extra that may help, I’m pretty inclined to use it’ -    providing nothing banned within it

WADA – if stimulates natural growth factor should be banned substance – but I continue to use it.

Tour de France -    actovegin use, become a little addiction -    WADA said intravenous actovegan will look into it, banned for now. Now, cant have without medical justification ‘massive loop hole’

Not accelerate repair, but prevent the delay

Perhaps employers in the future will expect return from injury quicker

As medical practitioner, you are allowed to inject substances of your choice.

Actovegin banned intravenously during pre-competition, but not banned outright

Everything geared to recovery

Questions and Answers

Do you treat elite as non-elite?

A: yes.

Question: French diff from English. Would there be a role of these treatments in uk

Brian: we are cautious than some of European doctors. Some think we are needle phobic.

Chair: if have 3 kids and 3 weeks off work, then v serious; perhaps more than the elite athlete who loses £60,000 for three weeks, so sure should be entitled.

Cathy: most common question I hear is there anything in it that could dope positive? It has many things in it

Brian: Maximuscle …. Is pharmaceutically produced, so what is says on it, it has, nothing more.

Cathy: side effect of actovegin

Brian: hypertensive when intravenously.

Autologous Blood Injection for the Treatment of Tendinopathy David Connell Consultant Musculoskeletal Radiologist Royal National Orthopaedic Hospital London

www.devilsfun.nl

angiofibrolastic degeneration

tendon healing

3 phases - brief period of acute inflammation – but not cause of pain

after 6 weeks, remodelling – cell to fibre

physio very important

over a year, fibrous to scar-like tendon over 1 year

treatment

while steroids relieve, no evidence that promote healing

steroids act on the pain fibres -    only on a delta fibres

Cryriax, J, J  Bone Joint Surg 1936

Surgery most effective, but considerable postop downtime

Dry Needling

Bathe in local anaesthetic -    dry-needle x2 -    3 weeks apart -    rehab/physio

nothing in lit stating efficacy, but perhaps 65%

autologous blood injections

treatment for refractory tendinopathy -    fail to respond to rest/physio/ cellular and humoral mediators -    stimulate -    pgdf/egf/fgf refractory tennis elbow -    28 patients o    blind solitary injections o    22 pain free

objective to report findigs in a group of patients

david.connell@rnoh.nhs.uk -    trial for test

blood spinning injection of platelets we did try that , centrifuging blood and taking the surface platelets – which is where best is located but haven’t needed to do this. Just use whole blood.

Prolotherapy = ligament schlerosant injections John Tanner

World anti-doping agency Brian English -    wada have said blood spinning is definitely doping

Are WADA?

Richard Budgett: They are not concerned about autologous blood But if treat blood to concentrate, then it would be injected growth factors, so break rules, but no way they could find that out. So if you do this, you need a TUE.

A: we have had standard TUE and had them approved, but not for spinning or intravenous. Also tried serum.

Cryochamber

Tendinopathy: NSAIDs, GTN, RF, others and, why not, surgery! Nicola Maffulli Keele University

Most athletes do not want to become healthy, just to be well [fit]

As doctors, want to promote repair, but patient only wants to return to competition

World Anti-Doping Agency Gene Doping Symposium (2005)

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

Welcome

improve people's health. misuse of medical tes

Richard Pound

banbury conference

wada

OM contributions shared by NOCs - but..

gene doping research $3m

gene doping panel in WADA, help with detection

new results - WADC, mar 2003 -

ME: who are stakeholders of gene doping?

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

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

gov actions - now wider gov support

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

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

gene doping inevitable

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

New Trends in Anti-Doping Arne Ljungqvist

need to be ahead of the game first time in history

purpose - describe recent developments

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

arne was olympian in1952 and nothing then,

doping code explanation

doping is definedas...

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

prohibited list - wada publish each year

criteria - enhance, health risk, spirit of sport

(two of three)

doping need not be cheating to be banned

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

need common sense

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

prohib method enhancement of oxygene trtansfer

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

TUE

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

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

ioc never took this responsibility

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

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

need to improve intell

ME: how?

recent negative envts

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

The maked Machine false urine

REcent positive evens

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

two major technical advances

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

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

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

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

gene transfer trials by year crash in 2000

ME: why? at the time of HGP completion

photo of jesse gellsinger

gene directly injected into liver

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

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

visible depression in Society of Gene Therapy

yet, heard of a diff technique

Paris study, Fischer, Great Ormond St LondonX- SCID

photo of Bubble Boy syndrome child - protect from inections

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

ex vivo study

introduiced to bone marrow cells

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

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

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

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

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

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

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

legitmately therapy not just gene transfer

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

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

intra-tumoral...

CNS prophylaxis, new chemo agents

additional info into genome, which maintains mutant gene

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

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

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

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

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

ME: why is informed vol consent unlikely?

sport or bioengineering? is it still sport?

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

germ cell -therapy or enhance?

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

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

risks tolerable in light of disease ,but for healthypeople?

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

in US, not entertaining proposals for enhancement

discussion

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

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

change position but

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

holy grail is sequence correction

goldspink:

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

Ted: it hasnt in

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

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

Olivier: side effects?

Ted: dont see them until you see effect.

Olivier: procedure itself not harmful?

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

Q: state for muscular.

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

Ted: but not activitation, but disruption

Q: 3rd case special since dif

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

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

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

Coffee

Effects on organ systems/tissues

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

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

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

Adipose tissue -    reduced amount

Connective tissue/bone cartilage -    inc amount/strengthened

efects on organs systs

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

skin

imune systt

lungs

nervous system/brain -    inc capillaries more utilised

what factors influe performance

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

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

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

ReF: fluck et al 2005,

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

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

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

what prdicts for improved cycle performance following 6 weeks training?

What genes regulate -    better oxy deliv

Timmons et al FASEB K, 2005

Gene ontology analysis

PGC-1 inc by training in following hours

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

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

receptors of VEGF go up – inc to manipulate receptor side

5wks of training, VEGF goes up

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

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

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

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

Questions and Answers

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

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

Question: how do trained, elite athletes differ?

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

Question: can distinguish

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

Question: important?

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

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

A: what would you expect?

REsponse:

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

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

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

Olivier: what level should we detect?

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

Olivier: cells that grown and reinjected

A: yes, like cell

Andren Sandberg is rapporteur

Lunch

Session 2

Chair: Odile Cohen-Hagenauer

Vectors and Delivery Methods C. I Edvard Smith, Karolinska

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

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

concept oif a gene

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

Problem with going from outside of cell to nucleus

Local and systemic gene therapy

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

drawbacks to viruses

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

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

Virus as a vector for therapeutic genes, eg hiv

How use a virus?

Concept: the packaging cell line

IMAGE

Empty particles – allow introduction

Packing cell line 2nd generation

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

Concept: RNAi – how does it work?

IMAGE

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

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

Regulates gene expression

Can achieve stable expression – deliver shRNA

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

Questions and Answers

A: when expresss siRNA, is v short.

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

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

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

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

www.rug.nl/farmacie/tgm

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

adenovirus

shedding data, gene therapy stdies

shedding

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

environmnent – next of kin

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

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

Gene doping detection

IMAGE OF TABLE

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

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

clearance of free dna IMAGE OF GRAPHS

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

dna detection?

Baterial is immunogenic

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

detection?

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

use effect as most promising

specific detection?

IMAGE

Isoelectric patterns of epo

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

detection?

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

Genetic interventions IMAGE

Serum Protein Pattern diagnostics IMAGE

DETECT MAJOR CHANGE

Proteomics IMAGE

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

Detection by proteomics

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

Post translation modifs

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

Gene expression profiles

IMAGE

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

Gene Array

IMAGE OF CHIP

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

Questions and Answers

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

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

A review of current gene transfger models relevant to athletic performance

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

Launched European Society of Gene Therapy

Mainly deal with EPO

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

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

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

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

state of art of vector stys

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

IMAGES

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

regulatable expressoin (3)

companies now investing into this sector

Questions and Answers

Coffee

Gene doping and the regulation of skeletal muscle hypertrophy Lee Sweeney

Skeletal muscle

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

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

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

So, enhancement?....

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

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

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

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

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

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

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

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

IGF-1

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

20% or more depending

prevented fibrosis due to severe injury

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

IMAGES

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

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

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

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

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

gene doping could be detected by screening

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

belgian bull

young child -    parents, mother is competitive athlete

conclusion -    gene transfer could be used for skel musc

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

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

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

acknowledgement -    elizaeth barton, linda morris, rosenthal, farrar

Questions and Answers

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

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

Geoff Goldspink

Animal gene transfer model Interested in musc regulation

Looking at XXX, derived from IGF-1

IMAGES

Biol actions of gh/igf1

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

Igf1 also involved, but later in process

Damage

Real outcome is muscle force

With knockout myostatin not strong – lacking in functionality

35% inc in mujscle strength within 3 weeks

already company on internet creating mgf – Phoenix pharmaceuticals

ME: how did you find this?

Splicing can be induced by siRNA

Prediction

IMAGE

Put

Detection -    rapid screen mas spec

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

Questions and Answers

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

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

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

Odile: but mujst increase other body parts

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

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

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

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

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

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

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

african

expressed through oocyte

males do not contribute

life = structure + energy

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

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

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

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

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

changing of coupling efficiency

excess calories burned as heat

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

can radically change performance

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

Questions and Answers

Question: what is importance of mt ….?

A:

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

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

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

revving up metabolism -    synthetic ligand GW1516

created marathon mouse (ppar)

transgenic mouse -    now expresses ppar-delta

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

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

A – better B – worse C – same

?

treadmill challenge

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

Under study – does GW1516 enhance performance in mice?

Future – magic pill?

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

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

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

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

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

Inflammation/arthiritis – phase I

And repair of: Bone Cartilage Ligament and tendon

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

Gene tansfer to the synovial fluid of joint

ex vivo and in vivo

Some success with ex-vivo

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

use retrovirus

phase 1 study in knuckle joint w rhumatoid arthiritis

put into joints that were due for removal

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

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

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

Targetted genetics company in seattle study.

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

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

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

Absent from horse who recent therapy

Now bone

Direct injection of adenovirus – BMP-2

V responsive to gene transfer

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

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

after 8 weeks,good healing

Wolf’s law – how bone responds to load

After pins removed normal mineral content returns

Effectively repairing bone that would otherwise not occur

Concluding that we can do this

Cartilage

No intrinsic ability to heal

If partial injury to articular cartilage will not repair

If goes through to bone bone marrow defect

Trying to take adv of fact

Use with rabbit

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

see if enhance healing

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

Presnet status

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

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

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

Questions and Answers

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

Monday

Chair: Friedmann Standard in medical doping involves looking for assays

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

Look for local effects Systemic Homeostatic

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

WADA Perspectives on Gene Doping in Sport Olivier Rabin

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

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

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

Fundamental concept

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

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

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

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

some gene regulations not fully understood

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

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

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

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

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

Use of microarrays applied to DHEA (hormone mutant)

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

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

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

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

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

HFL Jane Roberts

Difficulties, always new pharma drugs

Current methods cannot detect gene therapy

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

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

alternative testing strategy -    surrogate marker approach (biomarker)

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

biomarkers -    transcripts -    proteins -    metabolites

transcriptomics vs proteomics

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

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

Surrogate marker approach

Screening approaches

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

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

1.    pattern recog

sample prep is key- proteins in serum

Questions and Answers

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

A: at proof of principle stage. Relies on probability

Proteomics J Yates, The Scripps Research Institute

Used for biol discovery

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

Achieve total protein charcaterisation

Driven by mass spec

Single protein vs shotgun proteomics

Quantification

Global method: Would not stand up in court of law

Questions and Answers

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

A: 20-30 is within sample.

Question: what preventive measures to keep stable.

Question; had possible to look at disease or treatment?

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

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

A: at peptide level are problems

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

How can embryonic SCs be used for …

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

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

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

coffee

Research Report on studies Geoff Goldspink

Exercise -    knee extensor weightlifting exercise -    3 sessions per week

using muscle biopsy

with elderley people

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

relationship between MGF and muscle

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

repeated with trained athletes -    blood levs went up considerably

been taking muscle cells in culture and putting serum on them

use muscle cells in culture

IGF-1 gene transfer

3 Different types of IGF-1 in muscle tissue

actually 6 types (2 classes of 3)

with placebo, inc in class 2 with Gh wen down

with MGF of Class 2,

can now purchase human muscle cells

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

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

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

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

concern that they might be disqualified from sport

Currently collab

1.    mice receiveing hgh delivered using a mini osmotic pump

mass spec can distinguish

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

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

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

Transcriptional and proteomic effects of IGF-1 Ted Friedmann

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

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

Exptl design – short term

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

candidate of genes that can be used to detct

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

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

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

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

microarray procedure

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

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

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

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

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

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

Gene doping makes this problem harder

Peptide hormones

Indirect markers -    physiological effects -    popn studies: probability

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

indirect dtection of GH

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

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

gene expression of gh isoforms

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

A long way to go before detection

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

Outline -    background -    imaging -    potential -    points for consideratoin

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

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

imaging that maybe immediately applicable to gene doping

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

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

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

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

Imaging tc-99m-ad-luciferase

Particle goes to liver

Shows light ommision from liver of mouse

Questions and Answers

Lunch

Session 4

Tom murray

Screening a worry

Matt

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

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

Equal opportunities -    not part of culture of sport

cannot complain that

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

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

limits of accessibility on fair innings argument

need sufficient number of competitors to make it worthwhile

natural variation –s mostly self-regulation

people w extreme gene mutations not become elite athletes

limits of genetic screening

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

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

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

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

snowballing inflation -

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

fairness as equal opp not part of sport

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

as fair play – intrinsic

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

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

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

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

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

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

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

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

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

Need to answer some important concepts

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

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

do not design humans for sport

ME: but we do

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

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

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

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

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

Principle at stake

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

repair is unprobc

incidental improvement -    Tommy John elbow injjury – generalyl accepted

Surgery in absense of defect is enhancement

But Tiger Woods – laser eye

Laser correction public use now

Not like cheating in way that steroid use is

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

Things that are acceptable elsewhere, not aceptable elsewhere

What do with grey zones? -    arbitrary, but

with strict liability

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

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

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

genetic modification and improving humans -    enhancement

sport conflronst problems

if sport faces problems

who decides?

Sport is leading by saying we will regulate

Ethics, enhancement and sport Tom Murray

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

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

Aristotle – eudamonia -    full good natual ilfe

there are unvirtuous ways of getting these

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

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

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

response -    hypothetical

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

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

athletic virtues – fast.

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

But this would not have any of the characteristics of bball

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

would not have a game of bball

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

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

ME: he is now switching to regulative rules

ME: breaking some rules is not bad in intelf

there are silly rules – prohibition in us

So must have a public consensus in support of rules

In sport, if ban certain things but do not enfocre

Argument from Individual Liberty

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

doping control done well provides level playing field

argument from liberty fails to

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

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

No longer throw people to lions

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

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

imagine drug with no side effect

imagine drug diminishes hand tremour and neurosurgeons see benefit

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

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

you would choose one w best results

first surgeon missed practice of surgery

point of sport is natural excellence

point of surgery is to make well

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

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

because of goals and values of practice

challenge of genetic enhancement in sport

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

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

what makes a talent natural?

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

child who has been engineered prenatally, natural?

ME: ecosyst argument – just a complexity argument?

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

ME

Final session

Jacque Rogge

Test to check for drugs for neurosurgeon

Need clear rules for world of sport

Fairness – but is life fair?

Sport is arbitrary in some ways

Can this be accepted?

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

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

Look at high-jumpers

Achilles tendon most fragile for fosbury

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

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

Basis of beliefs

850million people practcising sport, 750million recreational

every recreational is competing with self

only 150million in sports contest

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

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

respct sport, respect society

sport integrates

sport brings health

sport shapes identity

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

we believe that protect health, even if paternalism

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

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

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

doping rules are imperect

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

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

enhancement not be allowed

where draw line must be done with ethicists and scientists

Stockholm Declaration Arne Ljungqvist

Composed of olivier, ted, and arne

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

Challenge?

Change serveal to  ‘a few’

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

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

Comment: these are more general reseacrh

Tom: human beings?

Lee: clinical trials

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

Matt: follows nuremberg, etc

Tom: these are minimal conditions, we can elaborate

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

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

Gary: who will develop?

Comment: since no legal, ma

Maybe unethical or illicit

Illegal implies court of law

Unethical and/or illegal

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

Be developed

Comment: this implies it exists

Olivier: can argue this in animal models

Odiele: reservations, since education can be spreading

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

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

Delete ‘near’?

Lee: must emphasise need for research

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

Comment: ‘should be supported’ at end remove support

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

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

Gary:  government?

Academic, government and private research

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

Rogge: contradiction with screening

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

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

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

Lee: must specify athletic traits, not genetic

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

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

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

Add to ‘select’ or discriminate

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

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

Promote knowledge on medical and physical dangers associated with gene doping

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

Olivier: dangers alone?

Odiele: why not ‘misuse of gene transfer’

Olivier: risks or dangers?

How about potential risks?

Olivier Rabin

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

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

IAPS2005, Czech Republic Friday morning

Doping

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

Paper on philosophy of language

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

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

Metaphysical conception of humanness is a mistake

Miah -    Warnock – personhood takes direct route

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

What gives sport value?

For whom?

Which sport, what level, etc?

Dehumanise is dominant concept, rather than human

No need for metaphysical conception of humanness

Charles Travis

What is a greyhound?

Fathers method of developing sense of greyhoundnes is useless

Mother is better – point to different dogs and call them

ME: but what would the mother say?

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

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

Moral particularism

Account of humanness appears necessary

Need disappears

Approach from concrete use in language

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

Contrasts are drawn in general way

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

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

Degrading v dehuman

Decomposed, demobilised, decapitated

De indicates a lack of something

ME: why are we talking about dehumanising?

The blood is human

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

We know what’s at stake

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

Use of language is more complicated than

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

Dehumanise does not mean no longer human

Metaphysical used as basis for grounding moral judgements cannot work

ME: So humanness as personhood doesn’t help?

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

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

Bill: Rawls: suffering – of course occasion sensitive

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

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

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

ME: What if I am a giant?

Friday 1030-1200

Philosophy of Extreme Sports

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

Best – aesthetic sports – closer to extreme sport

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

Booth – translate philosophy into movement Really?

Cannot represent such abstract ideas through surfing

Discussion:

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

ME: so is sport!

Concept of extreme diminishes with skill

Still a performance for others – but peers, not personal

Photography

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

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

The Intelligibility of Suits: Scott Kretchmar

Reply to Thompson, JPS

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

suits is constrained utopia, but not coherent

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

thompson’s concern about utopia

suits and play

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

suits accepts play as intrinsic, but interested in games

did not praise play over work

not like Huizinga

suits wanted to make a claim about games

utopia populated w activities like baseball and crosswords

game thesis, not play commitment that caught attention of skepticus

why only games?

Knowing what the game is

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

instrumentally free mode of living

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

ant existence predicated on scarcity

for ants, often too much to do

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

living life predicated on plenty, even if foolish

presents himself as future harbinger of….

For grasshopper, often too little to do

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

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

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

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

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

Suis conclusion that there is nothing to do must be false

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

Having no probs to solve does not mean nothing to do

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

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

Why liken to game playing rather than trumbone playing?

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

We are inherently problem solving creatures and he neglects this

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

lesser problem solvers died off

good problem solvers populate t earth

Suits: many of us are in game denial!

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

humans are made game ready

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

330-5pm Friday

Mark Hamilton

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

ME: why doesn’t  it happen?

Inevitable

ME: but contingent on physician position

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

should it be banned?

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

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

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

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

Anger Jeff Fry

Execessively high display of anger leads to aggressive play

ME: doesn’t anger/aggression win games?

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

Robert Thurman

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

Anything in sport worth getting angry about?

Why coach?

What is appropriate display of anger?

Can debate value of anger

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

coaches cultivate passion

ME:: but is thi a flaw?

ME: compare w politician – should they get angry

Suits Doug McLaughlin

Elucidation on game playing for understanding utopian lure

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

purpose of grasshopper -    utopia -    theory of games

formulation of games not most important aspect

game v the good life

relationship between games and utopia

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

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

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

Fair is Fair, or is it? Bill Morgan

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

Rawls -    justice as reciprocity

doping is a moral offence that affects fairness

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

Deep seated complex moral problem and looking for easy technical fix

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

Drug rules are not constitutive – not athletically relevant

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

not persuasive

2 problems

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

v difficult to know how many athletes are doping

from 5% to 95% but who knows?

Significant number who don’t dope

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

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

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

What about WADA and USADA? Fair?

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

devil in detail

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

Only people who get caught are dumb or unlucky

Biowash – shampoo

Flush mouth solution

Urinator –

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

Analytic techniques largely failed

Crackdown by legal

Balco – coop w criminal courts

Michelle Collins – never tested positive disqualified for 8 years

Non-analytic attempts along with analytic

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

Not so!

Problems:

WADA has changed burden of proof -    to comfortable satisfaction

raises social justice issue

treating similar cases dissimilarly

violation of mutual reciprocity

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

Justification has been ‘righteous indignation’

American Arbitration has resisted, but not for much longer

Classic problem of fairness

Not a concern for moral integrity of sport

Problem 2:

Circumstantial criminal cases against dopers

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

dopers will rat each other out

end up with Hobbesian all against all

BALCO

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

AAP

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

Background

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

a critical review and comparison of 3 ideal-typical approaches

research strategies

European College of Sport Science (2005, Belgrade)

ECSS 2005, Belgrade, Serbia Post Race Rectal HGH

ACE, ACtN3, AMPDI

1 allele of ACE = endurance

D allele of ACE = Sprint

Some studies show assoc

1 acele of ACE overrepresented in SA Ironman - Collins et al Medicine Sci Sport Medicine

suggested this ACE gene other gene with close prox of ACE gene on chromosone 17q23 may encode for a protein directly involved w t athlete phenotype

Growth Hormone (GH1) gene -    17q 24 2 -    encodes for family of GH -    anterior pituity -    IGF-1

Is growth H involved?

GH, little or no beneficial effect on GH on health indivs -    but GH might phys role in carotic metab and enhance tissue repair post ex

ex induced GH secretion stimulates -    swet secretion -    heat XXX through sweat -    influ heat loss during ex

GH1 gene

155 subjects 104 post rectal 55 control subj – no ultra XXX blood sample and geoXXX

triathlete group significance older than control

significance dif in post-ran rectal temp for gh1 genotype

Conclusion -    GH1 not assoc w endurance performance -    Unlikely that any of t genes are aassoc w performance

But temp lower for TT athletes

Exchange Symposium, Fri 5pm

Chair: Emin Eren (TUR)

Sport, Medicine and Scie hist roots -    MEDICINE: fundamental o    Disease – injury o    Healing + prevention

Medicine is sci of diagnosis, treating, and preventing disease

Hist  backg -    priest – magic – physician -    men-nefer -    Met – Sunu – Metsunu = medicine

Medicine and Magic

Ancient Greek

From magic and religion to secular practice Need to understand physics Study of matter and energy -    metaphysics

science -    latin – scientic – knowledge of something -    scive – to know (disting) -    scindere – to cut/divide -    sci – systematic

Is medicine a sci discipline? -    clinical medicine yes -    medicine as ‘art’ of healing using sci method -    ‘doctor’ = teacher

3 pillers of medicine - Claudius Galen – father of sport medicine

Sport Medicine progs around Europe not UK

What is sports medicine -    therapeutic -    team doctor -    sports physician 1904 germany -    dept 1911 dresden -    congress 1912 -    uni course 1919 -    journal 1924 -    institute 1945 prague

scope of sport medicine -    sci, moral, legal, health issues -    enhance qual of life

sci and sport -    ancient

hist of sport sci -    rise of physiology links -    Pierre-Jean Cabani (1757-1808) -    AV Hill -    Edward Muybridge – motion photo -    Ergometry 1790

Sci in Coaching

Coaching – art of sci to better performance

Conclusion

Stimulants – human

Scope -    sport sci – pushing limits -    sport medicine – protecting within limits

brotherhood not rivalry

Pres 2

Fabi Pigouazi

Sport medicine – from biological to clinical

Founded FIMS 1928, 19 feb -    2nd Olympic winter games

IOC MC 1967

Essentials of sport medicine

Ex as essential

ME: ethics in sport medicine at the time?

Ex as component of health -    ex for prevention – treatment, education

specialists -    athlete, coach, team physician, physio – need good relationship

Future development -    sport performance will increase -    av life span will rise -    sport medicine widely used

ME: wat formal structures protect integrity of physican decision making?

ME: ECSS needs a session on science communication

Biol limit of life

115 yrs - goal of 3rd millennium is inc quant and qual of life

heed to change ‘value of soc’

WHO – health definition

Lifestyle changes

Principles of wellness

State of sm in Euro -    euro won 50% of medal sin Athens

Gene doping -    Problem: lack of control of gene expression

FIMS – 200,000 physicians

Vassilis Klissourus

Unifying Sport Medicine and Sport Science: Paradigm of Sport Genetics

Goals – sci – push limit -    medicine-protect

but ultimate goal of both is to optimise human performance

there is no division between sci and medicine challenges

1.    grasp interplay between genes and enviro 2.    bioethic problem of genetic enhancement

Physio Basis of Records -    athlete v non-athlete difference = former learned to close gap between phsych and physio -    drives closer to limits (AV Hill 1925)

Sport Performance Determinant

Phenotype variation -normal distrib - what is relative power of genes and enviro in development of phenotype

2 stages 1. measured genotype 2. unmeasured

JAP, 1971, 31: 338, 344 -    Klissourus twin study -    Max aerobic power -    Almost identifical for twin -    93% heritability -    all genes for VO2Max

Max aerobic for non and identifcal twins -    supp hyp that gen is important for VO2 max

Perth Genetic Analysis

Maes et al JAP, 28 1479, 1996 Genetic and Envirol Sources of Variation in Vo2peak in 105….

Twin research -heritability estimate - conclude genes dominate - for max aerobic power -for max aerobic cap

But phenotype not predetermined or unchangeable -    training changes -    genes not like switches

Reserch direction -    to what extent can modify phenotype? -    A genotype intention modified? -    How genetic is process I change? -    perXX and cognitive?

Klissourus, Interest J Sport Medicine, 2002 Genes and Olympic Performance -    interpret difference were not significance, except for personality (behav)

Behaviour Determines Performance

Identify specific genes -    got to find t many genes relationship to partic att state

Walfarth, et al Medicine Sci Sport Ex, Jan 2005 -    T uHuman Gene Map for Performance Phenotype -    ACE – but siXXX

ME: Include co-presenters on Website of abstracts

Nanga Parbut – 8125m Climbing Beyond the Limits Peter Bartsch JAP 63 752-757, 1987 Bender PR, JAP 1989, 66, 2733 -    ventilation increases over 2wks at a given altitude

1m of o2 of blood -    decrease of plasma vol -    inc of EPO

inc of capillary of fibre

M. Redge West and West, High Alt Physio and Medicine, Chapman and Hall

Calbet AJP 184,304-16, 2003

Performance gets better -    Fulco, JAP in press -    But VO2max decreases, stable

Cenbelli 1889 cited in High Alt Medicine and Physio (Ward, Miledge and West) 2000

1% decrese per 100m over 1500m

Calbet, Am J Physio 284, R302-16, 2003 -    no eeffect because

above 500m -    reduced inoXXX uptake -    24% en deficient at 6452 -    Westertop JAP 1994 -    40% @ 5300-8800m -    Westertop JAP 1993 -    43% during OE11 -    Rose, JAP 1988, find deficit not t issue

Anholm, Am Rev Respir Dis 1992 -    breaking pattern at everest

Sutton JAP, 1988 -    Work on cap of everest

Cognitive function remains impaired 1yr after expedition

RB Huey, JAMA 284, 181, 2000

Mie

Thomas Scasz 1973, 115

Medicine and magic -    formerly when religion was strong and sci weak, men mistook magic for medicine, now when sci is strong and religion weak, men mistake medicine for magic

2 assumpt - sport has relationship lack of governance elite sport susceptible to enhancement

Borgmann – t Baconian/Cartesian project -    man goal dominance of nature – athleteic 1984: 36)

Brown-snout.com/cycling/misc

Ex Dict Sport Sci and Medicine, 1994, 29-30

Biotech – instrum structure -    neither good nor bad -    depend on use

Cuttler et al 1998 – nontherap use of HGC

Kass classif of biomed technology -    control of death and life -    irrelevant except: astr: genetic selection -    Control of H potentialities -    Control of h achievements

Elite sport involves/needs suffering

Medicine not about PERFORMANCE ENHANCING, but sports

Juengst – getting back to normal - telos of med

appeal to normality is problematic in elite sport

Boorse 1997 -    abnormal enhanced health?

Normally as constructed or enhanced

Wollheim, 1984, XIV -    without psych, normality is t name for a ill-defined and tortousuly effXX achievement

3 conceptions of norm

1.    BST 2.    Social construct 3.    Psych/psychoanalyt

Sports medicine need to disting between these ideas -    problem in principle -    can we choose?

Tim Noakes – dis H view of lactate paraxoc

Poster -    detect blood doping through comparison of change in RBC and reticulocyte count

cardiac regenerative capacity -    stem cells

new view of how heart responds to injury

a heart is significance myocyte regeneration - new myocyte formuation

post London

apoptosis – prog cell death necrosis – through injury

why only slow fibres affected -    presence of phosophic -    not present in fast twitch