Gene Doping, Doping & the Future of Sport (2008, Dec 18, American Enterprise Institute, Washinton DC)

American Enterprise Institute
18.12.2008
Gene Doping, Doping & the Future of Sport

Introduction
Jon Entine

Travis Tygart
Doping creates atmosphere of coercion
Athletes don’t want it
Public harmed by fraudulent activity
Teenage pregnancy less for girls who play sports
Ethical crisis
Josephson institute of ethic – 24% admit have cheated on a test in school
30% have stolen from a store.

ME: who are they trying to convince, if this is so persuasive?

Gene enhancement is banned
Should play by the rules

THG nearly identical to gestrinone
-    yet it is unhealthy, untested

ME: drugs are bad – ie. They don’t work, they have unknown side effects.

Photos of body builders who use drugs

Organized doping can be sophisticated
-    provides image of a calendar with notes about when to take the drug

liquid, cream

Kelly White – smiling faces on her calendar

ME: ridiculous to claim that this is sophisticated

The shame she faced is important

ME: Health risks are real, but the shame is not

ME Why was victor conte emailing advice? I’m not sure I would have done this.

Education
-    athletes need to know why healthy comp is important.
-    Achievements in sport should be result of hard work, commitment and dedication.

Been in the public domain for many years

This fight is for the soul of sport

Question about facts and values
-    some of what you explained was factual

Jean: doping starts in high-school – beyond elite sport

Rule bound

High-school testing – we support, but need preventative methods.

ME: Youth Olympic Games?

Nanotechnology for human growth hormone

Ed Moses: don’t understand how athletes can run 800m without putting in miles; coaches have changed parameters of athletes.

Panel 1: Athletes under the microscope

John Ruger, Athlete Ombudsmen for USOC
A federally mandated position – Bill Clinton signed it

I don’t represent athletes. I advise them of their rights
But I do help with process
No collective bargaining agreement

3 really important things that an anti-doping prog must have
1.    must succeed if will prosper. People cheat, there’s no doubt about it.

Not much down side to getting caught
Addition of USADA – single most important thing we have done

Every case is publicised – USADA policy

2.    methodologies must be secure, scientifically sound; when lab says you’re guilty, very little you can do to fight that.

Test for gene doping must be absolutely sound
Don Catlin – THG – needed test to be robust for legal defence

Athletes who got a raw deal in doping process

Luge athlete – used propecia – TUE – banned list 2005 – Zak did not check list – he was tested 8 times in 2005, listed propecia in each sheet, and in December 2005 tested positive – went to Torino 2006 and 1-year ban – was that fair? I think arbitrators had second thoughts and changed rules

3.    athletes must believe that process is open and fair

athletes must tell WADA where they are every day 3 months in advance – must live by this standard

IOC supplements test – 15% positive substance without listing on label –

Marion Jones said: I’m worrid about kangaroo court if I were found guilty – we changed rules to make open to public – first was Floyd Landis, who had sympathetic press – but case went against him -  process shown to be fair

Kicker Vencill – had supplement positive – technically guilty – but not guilty of cheating, because of contaminated supplement

Kicker Vencill
Concerns about process
First, I believe in clean sport and relies on anti-doping
Must list a one hour window each day 365 days for when we would be available
I had to update this online
I’ve complied since 2001
Held at high standard

I tested positive for steroid – 4 yr ban – arbitration ruled to 2 yrs, since adopted in fall 2003 – positive test was from contaminated multi-vitamin
Civil lawsuit against company – lawyer said no performance enhancement – my results were not nullified – strict liability – WADA Code 1.5 shows possible of reduction in exceptional circumstances – so best case scenario is 1 yr suspension, but always been more – supplement contamination is a huge culprit – why do anti-doping agencies refuse XXX athletes – lot of discussion about spirit of sport – this would be beneficial info to athletes – hypocritical to be aware of problem and not enough to give general warnings about supplements – I would like to know which supplements or companies that supply them are under investigation, but I’m not given this info

Anti-doping – guilty until prove innocence, contrary to law of land: innocent until proven guilty

Civil case went in my favour – but strict liability still applied – 2 yr penalty – death penalty in my career – strict liability allows ADOs to treat all case the same – for consuming supplement –

I have a huge problem being classed as same as ‘hard’ dopers
Doesn’t seem ethical to me

We are human beings before athletes – must respect
Not much evolution in this

Imperative that athletes and ADOs are more symbiotic
Unethical for only one of parties to be held accountable

Dionne Koller
Uni of Baltimore, School of Law

Intro by Jon: Teaches civil procedure – Sport and law – health and law – nationalism

Move from individual stories to bring government into conversation
Deconstruct fight against doping

Government support crucial to fairnesss of process
Ensure viability of anti-doping initiatives
Starting point is common wisdom that Olympic sport is private enterprise and doping is an individualized problem – athlete is moral actor in doping equation – focus on individual why we have calls for gov to get involved

I see doping as cheating – and indiv is actor – but not just athlete – much bigger – temptatin to cheat and ability to pull it off well beyond indiv athlete – indiv connected to national community – nationalistic – above all else values ‘winning for the country’

Promote national prestige – sportive nationalism – GDR and now China – intro itself to world through pageantry of sport – How can it maximise nation’s prestige – How does doping fit into that paradigm? – Incentive for nation to allow or encourage doping – Link between medals and doping not hard to appreciate – using drugs greatly increases chance of winning  – Doping is an easy way to get there? – US interested in winning in sport

Doping use rampant – reasons why athletes dope: athletics should be defined by indiv, but seems to be a structure that requires to win for country – now, paradigm shifted, worldwide consensus that doping is wrong and should be stopped and winning in and of itself not enough – winning with morality matters – use athletes to show that can punish if necessary

What does this all mean for doping today? – gov has recalculated to lead fight on world stage – Is this a good thing? Of course, but not convinced that this fight is for the long run – or about fairness and integrity of sport

ME: seems to me that it’s about politics

need incentives – need to show world that we’re tough   – kicker evidences that – important to understand – cold war athletes different from world today – athletes have much more opportunity today to earn money – what is at stake?   – USA no longer letting doping go on – can be doomed to fail – ignore basic fairness in pursuit of athletes can undermine legitimacy – what happens if prestige benefits for fighting doping are not apparent – are we at a place where winning not the only goal – are we at point where win at all costs is dead? – we hear that some countries are not on board.

Questions & Answers

Jon: doping and china
John: indicated that there would be no doping from China athletes – 3 things filtered from my emails in Beijing – Tibet, smog, protest – after games closed had the milk scandals –
Dionne: China is the big question  – 16 yr old faked passports – raises q about process.

John: believe that there has been genetically enhanced athletes in previous games. I’ve spent time in China since 1996 – Chinese coaches involved with genetic enhancement – world class result from genetic enhancement – mitochondrial enhancement – as ageing – young athlete – achieved times that were impossible – 6 months later was gone – one Chinese athlete was genetically enhanced – mitochondria enhancement – very niave to believe that china is only – scientists will tell us rightly that cannot do it safely but many places will do it anyway.

Q: US Olympic Festival – better to have athlete as certified nutritionist to help with healthier lifestyle –

John Ruger: can we get suppliers who guarantee products – some believe we should have USOC nutritional provider – to make money from – sends mixed message when USADA says don’t take supplements and then have a provider that we endorse

Jean: there is no oversight on dietary supplements – not sure how can control a dietary supplement

John Ruger: yes, so this is why should be a good diet – rather than supplement

Edwin: my programme based on natural food. I cook all from scratch – I didn’t take any vitamins – Olympic athletes have some of the worst diets – Daley Thompson: terrible eater and now says he doesn’t know how he made it and could have been better if had a better diet –

Kicker: I have medal winning friends who would not stop taking supplements

Panel II: Drug Testng and Policy

Randy Mayes (moderator)
Intro by Jon: triple helix – science writer – cybergenetics of Kenyan running – genetics in historical context – explains genetics nanotechnology –

Critical analysis of sports enhancements – gene doping – detection –

Ted Friedmann
Clarify the terminology on gene doping – role of genetics in a variety of areas -

Use justified for serious disease – but for more trivial use such as sport, not justifiable

Washington post article

The science of doping
Donald a berry
-    ‘anti-doping authorities have fostered a sporting culture of suspicion, secrecy and fear’

general tenets of doping
-    protecting excellence – whose excellence?

Nature article – surprising position that anti-doping is the cause.

Obligation is hard to understand

Gene modification of athletes is coming

World of pro-doping is off track

Paul Haagen

Intro to Paul: sports law book for OUP;

Series of matters where universal agreement: sport rule based activity – clarity to rules are essential to reality – sport central form of intercultural exchange because of clarity of rules and goals – second thing:  sport exists in social and political context – can influence – had worked out a conference with Bei Da – but this was prohibited – was told though that USA was still main culprit of doping – as critical is nationalism and – have a culture of performance enhancement – business people fly from North America to Asia, they are taking various supplements to deal with jet lag – ethical issues  – ADA – accommodations on tests when sufficiently test – Oscar Pistorius – what is baseline for performance aid? –

Sporting rules are artificial – so argument that line-drawing is artificial doesn’t get us far – first base is 90ft, could be100ft, if change, it would change the sport – fact that we draw a line at a particular place or that this is artificial is not a serious objection

If doping is ineffective will self-regulate – people will stop doing it – in absence of effective regulation, a significant number of competitors will be winners – can take a mediocre athlete and make them win – detection more difficult

ME: what would come first, the knowledge to gene dope safely or the knowledge to test for it effectively and are the two related?

Can an agency both police and promote/educate to certain kinds of goals? – if WADA etc promote anti-doping agency, then will be v powerful tendency to exaggerate quality of testing, to create rules that make it harder to challenge, conflate rule of ethical goal – some in doping are interested in seeking of potential – what is inherent in persons – clearly different levels of culpability –

Can enforcement mature to a point where admit that uniformity is a highly ineffective regulatory structure – try to keep people out, like Andy – very difficult to enforce – another is English property crime when inadequate resources to control – so made everything a hanging offence and caught nobody – other possibilities – real danger in change – fight for soul of sport – WADA and anti-doping have been a PR and political success of incredible propositions, close to unique – enforcement mechanisms that are made to work and if you move from moral clarity, it could unravel – failure to change though: maybe signif misdirection of resources particularly moral outrage: at persons who make mistakes, demonizing of them is a real problem – hand checking in bball not same as deliberate attempts to maim and injure – any other possibilities? USADA has strated t work on these – one is criminal law enforcement – if criminal authorities cannot be brought into this world, will be involved in significant underenforcement – BALCO track and field athletes had been pervasively tested and were not caught, but were once criminal authorities involved, same in cycling – GDR when Stasi file opened – who should be the target – coaches, suppliers? So much on athletes best approach? – need to look at creation of safe harbours – or limited safe harbours – Kelly White claims initial doping was unknowing, but current rules do not allow her to get out of it – pleas is to think about problem as regulatory – some things you let slide for good reason and direct resources to most interest

Questions & Answers

Randy: 2009 Code says –

Ted: PPAR – alter way your own endogenous genes are expressing – it is a gene manipulation of a sort as effects your own genes – no gene transfer – a pharmacological agent that is candidate for gene manipulation –

Jean: mitochondria gene enhancement

Ted: putting genes into mitochondria not well developed

Paul: as a society, we are going to massively reconsider role of regulation – moral imperative – but v hard to regulate – success period so narrow – if cheat on law school exam, might get a slightly better job – but if fail to cheat at Olympic trials, you’re probably going home.

Questions of Sport, Edinbugh Law School (2008, Nov 07)

Questions of Sport
Edinburgh Law School
07 Nov, 2008

Sporting Brands & Reputations

13.30        Introduction
Abbe Brown SCRIPT, University of Edinburgh

13:35        The Olympics & the Brand
Farisha Constable, Brand Protection Manager, London Organising Committee of the Olympic Games & Paralympic Games,

Sponsor protection / ambush marketing  – Linford Christie contact lenses /
Unofficial merchandise – bicycle – as rings / pin trading  – counterfeit pins / business names / integrity of brand / IOC/IPC / Olympic condom – ‘for the man that doesn’t mind ‘cuming’ second’ – class action from IOC / how protect: educate, existing laws (passing off, copyright, trade marks), contractual clauses, working with other agencies, special statutory protection / when athletes in Olympics, their image cannot be used by any commercial / marketing rights / working with advertising agencies / joint trading standards unit for the 2012 Games – newham home authority, 5 boroughs, good practice, consistency, planning / London 2012 anti-counterfeiting working group – multi-agency, collaborate and share info, consider and implement education and enforcement strategies, raising awareness and leaving a legacy for brand protection / Olympic Symbols etc (Protection) Act 1995 / London Olympic Games and Paralmpic Games Act 2007 (advertising and street trading – allow framework for regulation (purpose: clean venues, allow sponsors some exposure, prevent ambush marketing)  / regulations made c2010 / Advertising and Stret Trading Regulations continue (infringement, duration, where, enforcement officers, role of trading standards and police) / Ticket Touting – 2006 Act creates crime of selling an Olympic Ticket in course of business) / London Olympics Association Right – prevent unauthorized association with London Games or Para, any ‘representation’ a word, image, sound, etcc – may suggest and association with the Games BUT a court make take particular account use of ‘listed expressions’ / uses eg from 2005 brochure / limits of the law – cannot stop: editorial use, honest statements of fact, use which is not in course of trade, pre-1995 use of the Word Olympic (eg. Little Chef Olympic Breakfast, Olympic Removals, association with London 2012 made prior to 2006. / Beijing, now all eyes on London – ME: don’t forget Vancouver /  farisha.constable@london2012.com / ME: can Ed Uni set up Centre for Olympic Studies – A: we don’t try to stop educational studies, but if too commercial, then might be a problem.

13.50        Commercialisation : the individual & the image

Jamie McDonald, Golf Lawyer, IMG

Mark McCormack – started IMG 50 years ago and invented athlete as brand / IMG Golf  / How does IMG commercialize its clients? – Colin Montgomerie Sponsors – feature sponsors on websites – various products: sky, yonex, starwood, telegraph, EA sports, Gavin Green – Standard Endorsement Deal: grant of image rights (exclusive, non-exclusive, territory), grant of services/appearances, use of equipment, patches, fee, bonus, royalties, extension of endorsements (computer games), licensing / requirement that athlete must use the specified clubs by the agreemnt in place, cannot choose e.g use of 14 clubs, must use all 14 / logos on athlete – different part of body has different values / exceptional players will move from endorsement to bring their own brand – Beckham: still predominantly attached to other brands, not just his own /  Protecting the Image: trade marks of names (Beckham, Greg Norman, Tiger Woods) / Seve Ballesteros image of him from St Andrews now his logo, also tattoed on his arm  – John McEnroe  has trademarked ‘you cannot be serious’ / often try a ‘cease and desist letter – without much foundtion, but to see if it works, and it does /

Gillian Black University of Edinburgh,

Gulf between commercial practice and reality / athlete as property has no legal foundation / images and logos – individuals, rather than brand makes it different / 2 aspects: authorized exploitation (pro-active), unauthorized exploitation (reactive) / authorized: contracts/license, registered trade mark protection / Contracts: potential problems – 1) lack of certainty – enforceability issues, 2) privity of contract doctrine – cannot impact on 3rd parties unconnected to contract, so Telegraph relationship might limit that use, but others could / Zeta Jones an Michael Douglas – decided Ok! Did have legal inerest, but unlikely to be followed – eg. Hello knew what was going on / do sportsmen/women provide ‘goods or services’? – are they trading in them – not like Coca Cola trading goods, what is the athlete trading? – is the mark beng used ‘in the course of trade’ – is the name distincxtive, territories / Unauthorized Exploitation: 3 options – 1) Privacy, 2) Passing Off 3) registered trade mark / PRIVACY: was there a confidential relationship? – eg. Tiger Woods using a medication, if drug company advertised his use of it, would be a breach and could seek an interdict to stop – if not, was there a ‘reasonable expectation of privacy’ -  nature of activity, location, others in vicinity / PASSING OFF – 3 elements: 1) good will or reputation in the client’s ‘goods or services’ 2) misrepresentation by defender leading to public confusion 3) show damaged suffered by client – that law will recognize as damage  ie. Recognized interest, eg. loss of license or commercial exploitation, or damage to reputation / REG TRADEMARK – has client registered trademark, if so, does it cover use, cannot stop person from using one name – cannot stop people using one name , unless bad faith / Hypothetical problem: highland spring run a UK wide ad campaign using paaparazzzi shot of Andy Murray outside Wimbledon drinking highland spring – use image without Murray’s consent – what can he do? A: no privacy expectation, no misrepresentation, nor endorsement,  no reg trademark in Andy Murray, but not use in course of trade anyway, at least not in relationship to mineral water, miht be a breach in license ,but also prevents to third parties – Highland Spring could not enforce. So What legal basis can his advisers white a cease and desist letter?

14.10        Commercialisation : the team & the brand
Seona Burnett, Partner McGrigors & David Marshall CEO Tennis Scotland

14.30        Creative Use of Brands
Gerry Farrell, Leith Agency “Taking ‘Scotland’ to the last Football World Cup”, Abbe Brown “Supporting your Team? The Arsenal Saga”

Online is major prob of all brnd owners right now
Ebay’s rights owners’ programme – to remove rights violation
Register with You Tube -

14.50         Refreshments

15.20        Private Persons in Sporting Life
Professor Hector MacQueen SCRIPT, University of Edinburgh
Doug Gillon, Athletics Correspondent The Herald

Sex generally reasonable expectation of privacy, but many cases of sports stars have been present

Reasonable expectation of privacy at wedding, even if like Douglas and Zeta Jones!

Doug Gillon
Athletics Correspondent, The Herald

Around major events, media interest intensifies

15.40        Sharing in televised sporting events
Helen Arnot, Head of Legal Department STV SMG plc, Roisin Higgins, Advocate, Rachael Craufurd Smith, SCRIPT, University of Edinburgh

Beijing was about how and when/ Athens 2004 – embedded video 2.4m videos/ Beijing 30m videos viewed

2004 – Nobody knew of You Tube
Independent research suggests that change of behaviour in pay tv

Rachel Craufurd
13hrs uploaded to You Tube every minute

ME: Nobody mentioned Google

Creates signif loss of organizations / Class action against You Tube – direct infringement – also accounting for profits and injunction – indivduals / To what extent can You Tube hide behind safe harbours/ Copyright Act / Individuals access to content / To what extent should they be liable / If needed to check every upload, would stall the service / music right,s, this came up via Napster / because You Tube modifies and indexes the file, it is liable / service provider must not interfere / veoh was effective at removing copyrighted material, but You Tube has not been / whether You Tube can control /  You Tube ref to other sites

Rosin Higgins
Cheaper options to subscribe to tv rather than Sky TV

16.00        Sporting Brands and reputations: current themes
Led by Abbe Brown

16.20        ”Sporting experiences”
Gregor Townsend MBE (Scotland and British Lions, rugby union) Julia Bracewell OBE(Olympic fencer) and Heather Lockhart (Scotland, rugby, tennis, hockey)

Followed by open panel discussion
17.00        Close

ME: Google Owns You Tube, BBC You Tube Channel, Olympics now licensing through You Tube

Gene Doping Conference (2008, Oct, Florence)

Gene Doping Conference
Florence, Italy
2008.10.25

15:30            Welcome

Maria Luisa Giovannucci Uzielli

MODERATORS: Angela Schneider and Mauro Giacca

Arne Ljungqvist
1989 following Seoul 1988

Florence was first anti-doping conference in 1988

HM&R committee
-    list: 11
-    lab: 8
-    tue: 6
-    gene: 5

Gene Doping Panel
-    Ted
-    Odile Cohen-Haguenauer, France
-    Lee
-    Doug Wallace, California
-    Kurt Zinn, Alabama

$7m annual budget (1999)

ME: Today?

Torino 2006 – Austrian skiers  – IOC had info from WADA on the team – training site found haematological lab – found no athletes – WADA sent message to IOC – Austrias already in Italy – IOC informed Italian authorities of suspicion – engineer was known to be around athletes – if IOC had not acted, would have been blamed – IOC indicated that it would make a surprise test on team in 48hrs – Italian authorities came back in 24hrs indicating coordinated action – troops were guided to find the skiers – Austrian team panicked and jumped, some escaped, some found – Italian authority were investigating – all tests were negative – but Italians found material (illegal in italy) – would not had been discoeverd had their not been a law in place – based on this, IOC could ban number of Austrian athletes and officials – Austrian Olympic Committee fined $1m to IOC – Italian law prosecuting now

China – did have similar law in place to allow Chinese to do the case –

Gene Doping
-    transfer of cells or genetic elements or the use of cells, genetic elements or pharmacological elements to modulating expression of endogenous genes t having the capacity to enhance athletic performance, is prohibited

can add something to list if makes 2 out of 3, but can

for gene doping is required that is performance enhancing – exceptional case, other elements do not have this stipulation

use of medical treatment without medical indication

PPARdelta agonists
PPARdelta-AMP-activated protein  kinase (AMPK)
Axis aonists (eg. AICAR)

Unacceptable for medical and ethical reasons

St Petersburg 2008
Particular concern about internet distribution
Boundary between therapy and enhancement

ME: what is your best guess on the schedule for how close

Applications and Grants
-    27% of WADA budget goes to detection research

genomics, proteomics, microarray, imaging/detection, markers, bioinformatics

The Future
-    WADA is certainly the lead agency – in fact the only one that I know of – in the application of modern molecular genetics and DNA technology to t devel of improved methods for detection in doping and in averting the use of gene therapy approaches to doping’’ (Ted, friedmann in WADA Play True, 2007).

In certain circumstances we are ahead of cheaters – no evidence of use in sport yet, but have prmade progress

Francois XXX – here at conference – testing Tour de France –

We are ahead of those who might try to do this

Ted Friedmann
Gene Modification in Sport: Doping and Detection

First meeting of this topic outside of WADA’s organization

Certainly possible that gene therapy has been successful and has cured people, but few are willing to say this in public, since many cases have shown disease symptoms later on (SCID-II)

Successes SCID

Progress in treatment of childhood blindness by gene therapy (Leber’s amaurosis in children)
-    little doubt that has been effective.

Gene therapy as an immature technology is reserved for serious disease – “for the moment”

Springsteen – repoxygen

Bhasker and Friedmann (2008) Insulin-like growth factor-1 coordinately induces the expression of fatty acid and cholesterol biosynthetic genes in murine C2C12 myoblasts
BMC GENOMICS, in press

WADA informatics  digital data processing platform

Policy and Ethical Problems caused by anti-doping regulation

WADA Code 2009 –

17:30–18:00

Pietro Mennea,  1980 Olympic Champion (gold medal 100m), expert of Law
“Doping in Sports Between National and EC Regulations”

can you win without drugs? Yes.

I never had any major injury, no muscle tear -  I was regarded as the hardest worker in the world of athletics –

So, I still believe you can win without drugs

I was introduced to Cassius Clay – and he was told that he was the fastest man in the world – Clay said ‘You’re white’ and I said ‘yes, I’m black in side, blacker than you are’ – regardless of genetics it’s possible

Even if not predestined

Comparison between Bolt and myself – win less in Europe? No. today, Afro-Americans are winning today. Jamaicans.

What have we done for anti-doping?
Before WADA was in hands of sports agencies
Previously handled by IOC
Purpose was to control laws

Matter of public health cannot be left to sports – state must be involved.

WADA cannot succeed in battle by themselves

We have to believe in this.

2003 WADA Code in Copenhagen – convention against doping -

BALCO –  THG – Marion Jones not positive, failed to be truthful in court of law

We need a criminal law – marketing now more than it was 20 years ago, in the hands of organized crime – mafia, Italian-American, Chinese, Russian – in sale of substances

Sale in gymnasia, spas, brings in money for criminal activity

Only if the state is involve through law
Community Criminal Law – now 27 nations agree – uniform the control of crime
Law did not pass
-    up to now, nobody has put forth this kind of request. Nobody asked for passing of criminal law.

Countries with laws
1999 Denmark (recently amended)
2000 Italy
2006 France
2006 Spain – effective 2007 – spain one of the last due to Operacion Puerto
2007 Austria

doping will never be defeated because BALCO  for eg – there will always be people like that – problem of making money

people in sport surrounded by businesses

effects

18:00-18:15

Federico Bussolin,
1st at Eurojunior Championship 2008 (200m Butterfly)
2nd at World Championship 2008 (200m Butterfly)
“Testimonies by a Young Athlet”

1999 WADA established
I was an MEP and witnessed creation of WADA, which is doing an enormous amount of work against doping.

18:15-18.30
Voula Kozompoli, silver medal at Athens 2004 Olympic Game (Women Waterpolo), Captain of Olympic Greek Waterpolo Team at Beijing Olympic Game
“Testimonies by an Olympic Athlet”

18:30-19:15

Andy Miah
“Genetic Enhancement via Genetic Selection: Bioethical and Biolegal Boundaries”

19:15-19:40  “This is Florence” A short video-presentation

19:40-20:30  Buffet

20:30           Guided visit to the Palazzo Vecchio

Sunday 26 October 2008, Florence Convention Center, Piazza Adua 1

7.30               Registration  – Poster Exhibition Open

MODERATORS: Theodore Friedmann and Philippe Moullier

8.30 – 9.00      H. Lee Sweeney
“Gene doping: How could it be done and when  might it happen?”

9.05 – 9:35

Hidde Haisma
“Gene Doping- Fact or Fiction”

any students in biology can do this.

9.40 – 10.10   Judith Hall
“Surprises and Secrets of the Human Genome- Things to keep in Mind When Looking
for Gene Doping”

In the long run, gene therapy will be untraceable

Systems biology
-    control of gene expreion

2003 Human Genome project completed, despite 2001 publication

20,000 genes (200,000 proteins)

only 4% of human genome are genes -

protein expression is key

15% of Asians who metabolise testosterone differently

huge variation within normal functioning

10 years from now, could have your genome sequenced for $1,000

pharmacogenomics – drug response
- 5% of people have no response
- 5% over respond
- Must be related to metabolizing pathway

Ethical requirements for human drug research

Athleticogenomics – what factors are important – what research is needed

Genes, Metabolism and systems of interest
Muscle, vaculature, nerves, bain, lung, growth factors, repair mechanisms, sources of energy (mitochondrial variation)
-    in some places they uncouple ther mitochondrial to make heat, but an athlete would not want to do this

Systems Biology
-    affecting one area affects another
-    nothing is in isolation

possible to enhance one pathway

we are a long way from understanding secondary effects

in development of life, you use different genes – eg. embryo uses different set of genes from adolescent, etc
-    haemoglobin different between foetus and adult
-    going back to foetal pathways could be important

gene control
-    expressing genes

Chromatin Structure – DNA

Micro RNA – control a whole set of proteins – not traceable

Other considerations
-    diet, transgenerational effects

Diet
-    north American diet deficient in folic acid
-    don’t know enough about diet
Agouti mice
-    mutation, gene involved is an imprinted gene (only maternal inheritance), if you give mum a lot of folic acid, then can benefit the offspring
-    folic acid metolates intruder by turning it off

Gl flora – by-products shift metabolism and ould be used to enhance performance

What gets inherited is not a deterministic genotype,but rather a genotype that encode a potential range of phenotypes (Gilbert 2000)

Drug effects or gene therapy may be passed on to the next generation

Your grandmother

Grandmother – mother – child
-    the genes of ‘child’ were being developed in the mother’s womb, during gestation in the grandmother

chimera

mosaicism
-    arises brand new
Microchimerism
-    find babycells in mother’s blood
-    can find baby cells in mother blood, but also cells from every pregnancy.
-    The cells stay there for a life time
-    Stem cells

FetoMaternal cell trafficking (Bianchi XXX)

Fetal Maternal Microchimerism – cells can play a role in repair / Future: Easy to identify people with genetic potential for sports, Need huge amount of research to examine effects / Likely to do DNA profiles / Likely to need more tisues / Ormal human variation is enormous and mosaicism and natural microchimerismare unversal / Gene therapy today has signature but in the future my be imposible to test / Unethical to use such therapies without extensive research / Undoubtedly there will be individual variation in response

ME: scenario –

Questions & Answers

Is

In an adult, 1 in 10,000 cells is a stem-cell

Lee nelson

Diane Bianchi

One athlete claimed on ‘vanishing twin cells’

P. Mullier: As soon as we showed results, we had athletes come to the lab asking about it

Lee: real threat is from scientists who want to make money off athletes. India and China – many people who will charge, even though no benefit.

Michael Turner: vast majority of products not by elite athletes, but by people in gym – cosmetic result. Stem cell treatment widely used in horse racing in repair of tendons – we focus too much on winner of gold medal.

10.15 – 10.35  Discussion

10:40 – 11.10  Coffee break

11:15 – 11:45  Alun Williams
“Human Genetic Variation and its association with physical performance phenotypes”

23 genes – 1 in 7milion chance of existence of 1 in UK
-    but expect many others influence

ME: the individual who has 23 of the genes is more likely to be a good endurance athlete, but is it also likely to be more capable than an individual with 10 or 1? – is there cumulative effectiveness?

Questions & Answers

Jim: low probability of having ultimate athletic genotype, probability

Q: association studies – today, concensus that only way to do it is whole gene snip analysis – has anyone started such an approach?

11:50 – 12.20  Mauro Giacca
“AAV vectors as highly effective tools for IGF-1 gene doping”

12:25-12:55    Giuseppe Lippi
“Gene doping, hypoxia and enhanced erythropoiesis”

gene therapy for lng-term expression of erythropoietin in rats
Proc Nat Acad Sci, USA
1995, vol92, pp 8055-68

13:00- 13:20   Anna Baoutina (scheduled scientific contribution)
“Evaluetion of an approach to directly detect gene doping using EPO as a model
system”

13:20-13.40    Maria Minunni (scheduled scientific contribution)
“Bioanalytical approach based on affinity sensing as promising tool for gene
doping detection”

13:45 – 14:30  Lunch

MODERATORS: Arne Ljungqvist, H. Lee Sweeney

14:30-15:15     Posters Presentation (eight minute each, with slides)

HFL Sport Science
LC/MS/MS and quantitative proteomics
Pamela Brown

Protein in serum/plasma

15.15 – 15:45   Philippe Moullier
“Genetic Doping with erythropoietin cDNA in primate muscle is detectable – Part I”

15:45 – 16:15   Françoise Lasne
“Is EPO Genetic Doping possible b direct approach?

16.20 – 16:45  Tea break

16:50 – 18:50   Round Table:
“Gene Doping: what is possible and what is not”
Theodore Friedmann, Françoise Lasne, Arne Ljungqvist, Judith Hall, Alun, Williams, H. Lee Sweeney, Hidde Haisma”

19:00 – 20:00   Buffet

20:00              Guided Visit to the National Museum of Florence, “Bargello”, especially
open for the Symposium Participants

Monday 27 October 2008,
Florence Convention Center, Piazza Adua 1

7:30              Registration  – Poster Exhibition Open

MODERATORS: Judith Hall, Alun Williams
9:15 – 9:45     Angela Schneider
“Gene Doping: Ethics and Privacy Rights”

athletes not deprived of rights if demed ineligible

must still respect human rights

David Suzuki – challenged research on racial profiling in public sphere

10.00-10.40 POSTER PRESENTATIONS
Jim Rupert
Indirect SAGE analysis – epo
Blood based test
Aim to see if we can distinguish between epo and altitude chamber
Epo expression in absence of hypoxia response is the main interest.

Q: if athlete goes to altitude and uses epo, can you discover?
A: Assumption is that if go to altitude, you don’t need epo

Valeria Mastellone
Vincenzo

Relationship between ACTN3 and ACE I/D

ACTN3 gene directly involved

ACTN3 R577CX polymorphism conists of a converstion of an arginine residue to a premature stop condon at resdue 577

Frequencies of allelic frequences in ialian population compared to elite athletes

ACE

Gayagay (1998), Alvarezz (2000), Nazarov (2001), Scanavini (2002)
-    indicates statistical significance

10:40 – 13:30  Round Table:
“Genetically Modified Athletes: Bioethics,Technology, Legal Implications”
Angela Schneider, Andy Miah, Pier Francesco Mannaioni, Michail Shapiro,, Giuseppe Lippi, Judith Hall, Hidde Haisma, Domenico Giampietro Pellegrini

13:30 – 14:30  Lunch

14:30 – 14:50  Presentation of Posters  (eight minutes each, with slides)

14:50            Conclusions
Theodore Friedmann
Arne Ljungqvist
Andy Miah
Giuseppe Pieraccini
Giorgio Galanti
Massimo Gulisano
Maria Luisa Giovannucci Uzielli

15:50            Symposium closed

World Anti-Doping Agency World Congress

WADA World Congress

Jacque Rogge

Not just about elite sport

‘it is a public health problem
-    ‘high school and university sports programmes’

‘hundreds of thousands of teenagers’

‘general sporting public’ – recreational

EU report doping risen from 5% to more than 20%

Raw Deal

Richard W. Pound

Joining of sport and government

WADC

Minister of Education, Spain

New Spanish law this year

FINANCE

Craig Reedie

Wada history

1998 – festina scandal at tour
1999 – world conference, Lausanne

Foundation under Swiss Law
Foundation board of 38
Executive of 12

Healh, Medical and Research (Ljunqvist)
-    List
-    LAB
-    TUE
-    Gene Doping

ME: where is Ethical Issues Review Panel??

EDUCATION

Presentation

Questons

Lunch

MEDICAL

Arne Ljunqvist

Key outcomes of research programme

Anabolic Steroids
-    disocery of desoxyMethylTestosterone
-    detection of 6 oxo compounds
-    method of detect aromatase inhibitors
-    devel of CRMs for steroids
-    proof of conversion of supplements into nanrolone
-    detection of new long lasting metabolities
-    genetic and ethnic differences in adrogen excretion
-    devel of in vitro syst to identify AS

Blood Doping

Third gene doping symposium in 2008

Food supplements
-    if needed, why? If irregular food intake, should correct.

Even within same bottle, some pills have banned substances and others not.

David Howman

160 tests of Marion Jones – not one adverse finding

Operation Gear Grinder 2005 – mexico

Doping and Public Health (2007, Aug 15-16, Aarhus)

Doping & Public Health
Arhus, Denmark, 15-16 August, 2007.

15 August 2007
10.15 – 10.45
John Bale and Richard Peel (Chairing sections)

Prof. Jens Evald, Chairman of Anti Doping Denmark – Introduction: Anti Doping Denmark’s Action to Protect Public Health

Prof of Legal Philosophy at Arhus.

background
doping and fitness
public health
fitness-doping
anti-doping denmark 3-year project

Background
Anti-doping denmark – independent
Act of Promotion of Doping-Free Sport (2005)
-    ADD is self-governing
-    12 member board
-    7 secretariat
-    ministry of cult = 1/3 of budget

Act 2005
-    doping control
-    info
-    research and development
-    international collaboration on fight against doping
-    provision of advice

Section 9
-    fight against fitness-doping (ie. doping use outside of sport.
-    requires implementation of WADA code in gyms.

Gov argument for fighting doping
-    public health
-    illegal trafficking
-    risk fo drugs spreading to organized sport

Public Health Issue

night-life violence increases by doping

effects of doping:
loss of interest in surroundings
social isolation
suspicion and jealously
new friends with own language
dress code and social code
can’t see anything wrong with own behaviour

big confidence
agrresion
depression
alarm
change in personality
lack of empathy
increase sexual self-orientation

how do users see these changes
- problem is that they do not see the side effects (ME: AS PROBLEMATIC)

ADD a ‘natural born’ protector?
- was never asked to form.
- today, have 70 of 450 centres in system
- working towards new model where commercial centres part of org

ME: is not talking to the political economy of doping (in Denmark). Like the dopers, is unaware of the context of own behaviour.

Is fitness doping a big problem?

Alesandro Donati wrote the WADA report, estimating doping on global scale
- the report mentions 15,000 abusers, the newspaper says 31,000

84% of sold growth hormone is used in sport
ME: but I thought many people believe most athletes are not using hgh, so where is this being used across sport?

also test for doping in prison – the prisoners trust us.

of tests:
0.6% positive in DIF
10% positive in DGI
20% positive in commercial fitness centers

number of positive tests has increased, but could be because of more effective testing.
(testing for steroids/, not social drugs)

some people talk about 60,000 abusers in denmark. we don’t know.

ME: what could improve knowledge. WADA talks about intelligence. it’s interesting for me to hear you throw out the 60,000 figure, given your own estimates. are there formal mechanisms for gathering intelligence and are they different from WADAs? come to think of it, what are WADA’s mechaniss?

Questions:
-    is ADD the right body?
-    Is fitness-doping a real problem to society?
-    which drugs should it test for?
-    can we accept social isolation of doping users?
-    what is lacking the most in fight against doping?

ME: what is worrying about isolationism of dopers? There has got to be at least two more premises to the argument.

ME: the fact that he is asking whether we test for social drugs is v problematic.

Questions and Answers

J: problem is that we cannot register the names of people.

Changes in WADA code allows making separate rules for fitness centres.

10.45 – 11.15

Asst. Prof. Paul Dimeo – The Public Health Origins of Anti-Doping

Key historical moments
- 1948: Dr Christopher Woodward raises concerns about cyclists’ use of drugs
- Late 1940s/early 1950s – returning war verterans and wide availability of amphetamines contribute to rising usage at all levels of American sport
- 1952 – WHO conference
- 1957 – AMAconference
- 1960 – death of Knud Enemark Jensen at Rome Olympics, attributed to amphetamine abuse through later investigations dispute this claim; Avery Brundage raises issue with IOC; British anti-doping expert Arnold Beckett claimed later that IOC knew about t widening use of steroids by 1960
- 1961 – British athlete Gordon Pirie publishers a book ‘Running Wild’ in which he claims some British, many American and many society athletes use doping drugs
- 1963 – CoE meetings
- 1964 – International Congress of Sport Sciences meets during Tokyo Games and prob of doping is raises, also exptl testing conducted on cyclists during Games
- 1967 – British Association of Sports Medicine conf on doping held in London
- 1968 – first testing at Olympics for amphetamines; test for steroids  would arrive in 1076.

(Dimeo, P. 2007. A History of Drug Use in Sport, 1876-1976: Beyond Good and Evil (Routledge))

between 1950s and 1960s, change in anti-doping
postwar period public health movement
questions about how sport played a role in public health
by late 1960s as sports orgs took control, tone of anti-doping changed to defensive of sportin culture and assumption of sport ethics. doping not defined as prob of too much intensity, but as a bleamish on utopia of sport. consequently, for public health officials who were more objective on health, had been lost. chance for moderation had been replaced by fanatic approach to the problem.
beginnings of shift from 1952 Februrary.
IOC had announced in 1933 that it did not like doping, but did nothing until early 1960s.
were not many instances at this time.
1948 Woodward
1949 italian ctyclist died allegedly of amphetamine
in US groupwing prob
first major statements on doping came from health not sport – WHO 1952
- 2 speakers talked: Carl Evan – Norway health – oppressive system – said ‘use of dope….popping up here and there in the amateur sports world….will be a disaster for sports’
- American colleague at the conf: Milton Lomer – Social and occupational health secretary for WHO, didn’t like look of sport – athletes pressured into taking health risks for national prestige. he saw sports in critical terms. he thought sports were to blame.  not clear how these speakers reflected view of WHO. no further action was taken.
June 1957 – AMA initited research studies on the subject. beginning of surveillance process. Herbert Berger narcotics expert – claimed dubious success of 4 minutemilers, but also critical of amphetamine use in college and high school in usa – widespread pattern of drug use ‘shocking and visious’ – saw it asa  public health issue. ‘drug addicts might get their start taking amphetamines in high school and college’. also said users displayed violent and criminal behaviour.

anti-doping among officials at this time
AMA projects on use of amphetamines another was a clinical study about effectiveness of amphetamines for performance.

this affected publich health stratgies of surveillance.
clinical studies were sign of honesty – though sports authorities discourages research on doping in 1960s.

in public health cntext, concept of fairness not visible
if anti-doping had remained focused on public health, then nature of antidoping would have been v different.

early 1960s, in UK Austria,
BASM and itlian counterpart established positions
CoE defined doping as an evil, such a view had become routine
like a religious doctrine
eg. IOC anti-doping Arthur Poierot, also Sec of BASM, in 1965: ‘doping is an evil. it is morally wrong…legally indefensible’. – at this time, no evidence to support any of these points
eg. XXXX immoral act of doping  ‘keep the ideal of sports pure for the welfare fo all mankind’

testing in Olympics by 1968.
guardians disliked modernity in sport – eg. training technology.

no interest to dialogue values
problem in their view was fringe element of sport ‘cancer’ on utopia of sport.
IOC wanted elitism, but with amateur values.
constructed a sense of sport that focused on excellence, but values that ddi not reflect reality of elite sports – inspired by indiv and national glory

how ddi early public health experts compare with later sports colleagues

similarities
both disliked drugs in sport, though for different reasons
both thought monitoring important

differences
if about health , not ethics, then must consider broader public
eg. alcohol – all allowed to drink alcohol and excessive can do, but if drive drunk can be prosecuted since affects others health. other crossovers – approach to alcohol has been realistic pragmatic and yet allowed freedom.

if sports doping had been seen purely as public health, would it  have emerged

ME: hmmm, medical intervention of doping might be a difference?

11.15 – 11.45
Prof. Barrie Houlihan – Doping, public health and the generalisation of interests

how politics is changing and how it might change.

theoretical presentation

theory of policy change

generalizing interests – building alliances with sympathetic policy areas

domestic and international policy making is hotly contested – many polic leaders are under constant pressure to give prominence to their issue and to protect it from others

2 questions:
- how can momentum and commitment to resources at domestic and intenational be maintained?
- to what extent can domestic and international sport interest control discoures….

Anthony Downs – policy ‘life cycle’
-    pre-problem stage
-    alarmed discouvery and euphoric enthusiasm
-    realizing cost of signif progress
-    post-problem stage

much of history of anti-doping follows this pattern

first stage
-    death of Tommie Simpson
-    withdrawal from 1983 Pan-American Games
-    1988 ben Johnson
-    1998 tour
-    2007 tour

each began with enthusiasm which rapidly dissipated

look at discourse that surround doping

3 dominant discourses
- fairness, health of the ATHLETE (not public health), image of sport (role model, etc)

these are generally self-serving, inward looking and politically naïve

WADA Code reflects mixed rationale
-    concern limited to athlete’s community

however, wada needs governmental allies
examine how these other orgs discuss doping – they use broader, social terms
eg. CoE – sport important role in protection of health, moral education, international understanding; EU – competence in area of public health; UNESCO Convention – education, health, development and peace
many govs have publich health emphasis on sport – France, Norway, Sweden, Denmark

Dick Pound – ‘unviversal recognitioj…doping serious threat to public health’

whether it’s being exploited, I’m not sure

but not only discourse

competing discourses:
-    constitutional: sport should be self-governing
-    criminal: doping is big criminal business
-    workers rights: right to eran leaving
-    moral/ethical: fairness:
-    medical: health of athletes, treatement
-    public health: doping spills into non-sport

constitutional, moral medical are most promiinant international, others vary between countries

WADA’s response?
-    is WADA aware that it is competing?

public health not exploited by sport

1998 – watershed
- showed weakness of ‘constitutional discourse’
- French gov intervention (and criminal discourse)

Continued discuss about criminanlization
need for sport to build a defensive ‘generalisation of interest’?

criminalization – ljunqvist – advocates criminalisation of sports related drugs

strategies for generalisation of interests
-    sectional interests (like elite sport) aim to further interest by linking to public good o
o    ‘one has to hrase one’s argument in impartial terms, as if one were arghing for the public good and not fornes own self interest’ (John Elster)

is linking elite doping with public health going to strengthen elite anti-doping?

back to initial 2 questions

discussions
-    what is existing relationship between antidoping and external interests?
o    what evidence is there of alliance building?
o    the evidence suggests that they are not.
-    are we seeking generalisstion of interests by sport to link with supportive external interests or the incorporation of sport by eternal interests.. – rather public health sees sport as valuable to them.

ME: is this because it would diminish the autonom yof WADA

parallel discourses?
-    internaitonl, still focus on athlete’s health, modest concern on public health and broader pro-social discourse on sport
-    domestically: increasing number of countries a crime/law and order discourse (encouraged by WADA?) but in others an increasing concern with public helaht and sport for al not just elite)

evidence of a changing discourse? sport still claiming tis privileges status (overplaying its hand)
sport/elite soprt has lways been linked with other non-sport interest

ME: how does this function with doping technologies that are not clearly linked to public health issues – e.g. blood doping or hypoxic training? Is there a challenge over boundaries – ie. doping more than drugs. difficult to excite public health policy makers about hypoxia?

ME: would a public health approach require the separation of some doping technologies from others? – ie. some have a clearly larger spill over than others.

what will keep doping on the front burner?
rely on continual succession of crises?
criminalization is easier than public health.
links to either run risk of loss of control by WADA and NADOs.
but criminalization makes more difficult harm minimization.

Verner:
don’t know if prob of doping, but we’ll solve it
in 1960s don’t know if was a big prob, but begin to solve
how politicians trying to solve.
problem generated by political ambition.

ME:mobiilisation fo anti-doping is often

Barrie: different to identify public health dimension of some doping technologies, but for others, it is clearly the case

11.45 – 13.00
Lunch
13.00 – 13.30
Prof. Claudio Tamburrini – Postponing motherhood: an unfair advantage?

follow up project on genetic technology and gender

trying to ascertain how genetics impact on gender equity in elite sports

from time to time here that women give birth after menopause.

none of the techniques to assist this are genetic, but is conceivable.

whether athletes who postpone motherhood gain advantage over those who don’t?
is this adv unfair?

when we speak of motherhood, not suggesting htat elite sports are not compatible with motherhood. some argue that it eventually enhances sports participation. (IRSS 2001).

but still the case that natural difference between mean and women still exists – women bear children and men don’t. so possibilitiy to equalise ability will remedy natural disadvantage.

do not take a stance on whether interventions aimed at delaying menopause should be considered treatement or enhancement.

does postmenopausal….

assume that gender equity is desirable, though this is contested by some.

possible that technology could create more gender equity.
-    eg. resistance to ART – reinforces idea that women should become mothers and limits value of fulfilment without children

Laura Purdy

even if decision makers accept homosexual families, better heterosexual since discrim, but this is not a good argument.

develop a ‘happy child’ criteria – but no reason why could not meet standard

reasonable happiness

postmenopausal motherhood discourse shows resistance.

lets assume many women will do this. impact?

change of family. but no harm in that.

assume that once mothers, will shortly die. need to ensure provision within the community.

no reason to oppose postponing motherhood.

perhaps the children might resent older mother.

sport obvious eg where having children is a disadvantage.
-    those who do not can remain productive during  their peak years.

is genetically postponing motherhood unfair in elite sports?

a substance or method will be considered if 2 of 3 conditions.

assume that the technology will become safe.

is it an unfair competitive adv?

if open to all, then how unfair?

perhaps expensive will create greater unfairness?

not suff reason to label it as unfair, according to anti-doping policy.

trying to underline sport governance of such mattes, when the become a scientific reality.

must search somewhere else to discern whether is unfair or not.

might argue that is unfair adv since put colleagues under tpoo heavy burden – renouncing to motherhood for the same of competitiveness

but all sports persons forfeit plans and put pressure on competitors to do the same.

perhaps the too heavier burden objection could substitute the current criteria, combined with some other form of consideration. eg. ethos of sport – rules out improper manipulation of the body.

ME: What sorts of things are able to become proper manipulations of the body?

hypoxic chamber might be risky if stay in too long, are directly enhancing, but unlike trad doping re ot seen as artificial.

prob is how the competitive adv might be seen by sports bodies.

given that men are fertile for longer than women,

ban on gene doping – what is the non-therapeutic use? possible to treat muscle disorders that might improve muscle strength.? gene encoded epo to boost bone marrow, might also increase for sport.

must be more accuratey specify unapproved aplpictions of genetic technologies.

need increased insight on potential conflicts between socially desirable goals and ethos of sport.

need for open and critical debate on how governing bodies should deal with people who are already modified.

the greater the possibility of other genetic technologies to equalise different, more reason to accept

13.30 – 14.00
Prof. John Hoberman – Is testosterone a supplement or a drug?

20 years ago. West German scientists Manfred Donicker said steroids should not become a popular nutritional supplement

2 months ago in Las Vegas – Intenrational Society for Sports Nutrition
- middle aged man on testosterone on prescription.
- he said, any man over 50 who is not on a testosterone product is crazy.
- ie. donicker’s fear hass come true.

we are talking about a contest between testosterone status

what is difference?

supplement

assume fewer regulations, since assume fewer risks

I will argue that, in order to understand this, must look at history of synthetic tesosterone and realise that campaign to market to the masses

ME: big deal.

Time Magazine
sept 23, 1935
“german and swiss chemical laboratories are already prepared said Dr Ruzicka [one nobel later] last week, to manufacture from sheep’s wool all the testosterone t world needs to cure homosexuals, revitalize old men”

our society has imagined testosterone being put to public health use from the beginning

Newsweek Sept 25, 1996? ‘ Super-hormone hterapy’ ‘tesosterone’
(Uses same cover as john’s book)

Time Magazine – tesosterone again in Time Magazine

The Early Androgens Market: How testosterone did not become a ‘tonic’

there is no critical distinction

Androgen Ointment for careful dosing (1939)
- testosterone drugs being tested.

[see presentation from September 2006 in Newcastle]

Testosterone for Women: the new era of sex as a lifstyle entitlement

Hormones as ‘antiageing therapy’: the medicalization of the ageing process.

dopers in uniform.
- police officers on steroids
- brain doping by students
Chronicle of Higher Education ‘the other performance-enhancing drugs’(2004, Dec 17.)

Does a lifestyle transform a drug into a stimulant?

“I sincerely believe he didn’t see steroids as a drug, none of these kids do’

Tesosterone magazine
- if there is one, it’s probably a lifestyle, not a drug

NEJM – Aging and foundation-of-0youth hormones, paul m stewart. (Editorial)

new york times 1851

ME: treatment of syllvester stallone’s steroid episode in Australia a stunt?

ME:P If I told you that the Sylvester Stallone steroid story earlier this year was a publicity stunt to promote his film, would that change the way in which you would use it as part of your analysis?

what is medical treatment for?

‘if it gives real happiness, that is the most tha  any sufegon or medicine can giv e Dr Harold Gillies, poionieering British plastic surgeon specializing in the cosmetic repair of burned an maimed soldiers.

line between therapy and enhancement more blurred, but in sports it remains distinct.

outside of sport, enhanceemtn becoming part of acceptable lifestle goals.

Questions and Answers

Barrie: impc of context of supplement use. parallel with alcohol use – not supplement, but ubiquitous except in certain contexts, eg driving. so maintain distinction by defining context in which is seen. Also, bigger problem of maintaining definition of what a drug is – performance enhancement. athletes will not take supplements unless performance enhancing.

John: alcohol comparison important, but works one way but not another. focuses on volume of social harm that arses from use – anti-doping can make some analogies. compare social impact of steroid abuse with alcohol. but does not work in following way: putting police officer on alcohol improves performance, but if look hard enough can reconstruct dialogue of police officers on steroids – legit doping to assist in overpowering physically violent criminals. other trade ofd. chief of police of Miami said: we really should think about whether approp to put police on steroids. he was not saying it was wrong, but should think about it. now is v politically incorrect thing to say. but he identified a real dilemma. more common as something like modafinil becomes acceptable as a productivity stimulant. how are our feelings and values going to deal with this? popular wisdom in us that caffeine runs some industries.

Rob Beamish: enhancement as part of popular culture; postmodernist remaking of self; now, we remake self as part of regular way of lif. but also saw enhancement as violation of ethics. but in high performance sport, not anone who says high performance sport is a character building practice. so, enhancement not violation of ethics, but only certain types. where decide that enhancement is no longer ethical. at what point will we see steroids as non-ethical?

John: in 1990,k WHO said in Lancet that small doses of anabolic steroid were safe. research still being churned out in endocriminology. one part of the dilemma is that still in process of deciding how dangerous the drugs are. we know what anti-doping says. but, these are not the only opinions of relative risks. this remains undecided.

14.00 – 14.30
Prof. Bengt Kayser – Current anti-doping policy: harm induction or harm reduction?

doping-like behaviour

Randall, Zimmerman And Crook
prohibited from Olympic strat

kikkan randall – also natural epo peak

spirit of sport – mal defined concept

ME: deliberately so, like many ethical concepts.

repression vs potential gain

consequences of being caught
- exclusion for life

consequences of a medal
- fame and money for life

difficult to punish much more

does anti-doping work in the sense of their being less doping?
- not clear.

transport of doping drugs easier than cocaine, etc

2006 Blood, false-positive detection of recombinant human ep in urine following strenuous physical exercise
- criticised by different groups.

ME: Should WADA institute policies to protect vulnerable perspectives on anti-doping?

mike: people who disagree with your prognosis will agree with our diagnosis. disagree with ethical analysis, but agree with analysis.

14.30 – 15.00
Coffee break
15.00 – 15.30
Privat-Dozent Dr. Giselher Spitzer – Body and mind – biographical and health studies about doping victims in East German elite sport

15 years shift – what you see in doping procedures today was ‘state of the art’ before 1989

when did it start with steroids?
- blue pill oral-turinabol was 14-15yrs median
- half of sample doped before, first estimated 10 yeraas up to 14

why taking bills?
- no true answer
- others: vitamins, help traiing,  therapy

important damage and disease in sample
-    negative developments
-    damae of skeleton and muscle make normal jobs impossible (eg. longer standing, sitting, holding things). typical decision to find work was to find freelance.
-    no control group, so used brothers and sisters and offspring of each. most of the conditions are not present in these relations.

change of genotype – genetic damage
-    virilisation of foets or mandartory abortion because of pregnancy while training or a half year after competition
-    premature death while pregnancy or death birth (6 of 46 died from premature death); 3 parents have death birth
-    risk of premature death of children of doped athletes 32 times higher than normal popn; risk of death birth 10 times
-    important when considering that athletes were strong and medically well controlled
-    even control group did not have these figures

side effects on children born to athlete sing drugs
-    most of 69 surviving children also damaged
-    children of mothers who ere drugged, typically handicapped
o    37 children 54% suffer from 2 illneses
o    17 ids multiple damage
-    Dsisease represented more than 2 times:
o    every fourth child has allerges
o    one of 4 has skin illness
o    one of 4 asthmatic
o    one of 10 crippled
o    nearly one of ten metaboligc
o    1 of 7 psychic
o    1 of 17 mental disability

change of phenotype

1.    side effects: skin
a.    skin disease 12%
b.    allergies 12%

Liver
-    disease 17%

organsof body
-    damage to skeleton 92%
-    operations 67%
-    knee shoulder ankle joint 22%

25% of doped athletes have cancer or had cancer
35% sudden inflammations
17% migraine
15% metabolic
stomach 15%
epilepsy 10%
kidney 6%

disturbance of psyche and behav
-    attempts to suicide  38%
-    psychic illness 62%
-    health nutrition 25%
-    social drug
-    addiction to alcohol 13%
-    addiction to drugs 6%

side effects on male
-    testicle-atrophy or loss ability to produce sperm, 4 athletes
-    operation of testicles 3 athletes
-    enlarged prostate and treament 1 athlete
-    gynacomeastia 3 athletes (11%) (pre-cancer)
-    8 andrological diseases (29%)
o    more often than was thought

side effects on women
-    virilisation in general (breast reduction, facial hair, lowering of voice) 42%
-    injectins after maenorrhoea 4 women
-    hypertrophy of clitoris (not asked!) 0 in literature biggest size is 12cm
-    atrophy of uterus and underveloped 2 women
-    changes to ovaries – 3 women
-    generally
o    12 women gynaecological disease (50%)
o    probs with sexualidentification and identity, resulting from virilisation

no case of transexualism

7 secondary side effects as a result of higher dosese (‘overload)
- new type of damage of connecting tissue
- 7 athletes took drugs against feeling of being hungry or pills to lose water
- german masters or Olympic medallists or candidates were anxious because some gram of body mass. they stopped after reaching goal

The Value of the Results
- what we learn
first: give help to victims of mandatory oping as a humanistic need
second: knowledge to prevent re-emergence of simlar systems based on drugs eg china
third: enhancement of future policy

ME: Why do we have no good answers about what is happening in China?

other values
- value of health motor for anti doping
- boy capital is concrete guide for athletes who have to decide if they want to dope
- beyond ethical arguments, must protect own health.

Caston Lundby – rHuEPO treatment in humans: new findings and considerations for anti-doping work in the future

function of rHuEPO on blood

red cell mass ncerase, decrease plasma – total amount remains similliar

function of rHuEPO on performance

invasive studies – 6 catheters

new: epo also works at altitude. if take epo and ex at altitude, have use until 4100m approx.

so epo works for max ex intensively, but since most comps not held at max capacity, wanted to know at more suitable ex level. – how long could cycle of 80% of max to exhaustion
-    VO2max inc, but sub maximal intensities, much greater effect of epo doping.
-    not that using epo will lead to 54% increase, but that, in cycling, if break away from pack, could go for same velocity for 54% more time.

does epo have other functions than increasing oxygen content?
-    we’ve found receptor for epo in skeletal muscle (Lundby et al, AJP.
-    we’ve found no other physiological function with our model.
-    if develop more capabilities, could inc ex capacities.

to determine whether other effects,  gave subjects epo.
-    cycling exercise.
o    removed new blood from epo inducaed athletes. result showed presccie correspondence with pre-induced performance
•    suggests that effects of epo on performance related to arterial oxygen content

conclusion 1
-    rHuEPO increase arterial oxygen content by inc red cel mass decaeasing plasma vol
-    if arterial o2 inc aerobic also increase
-    m

is it dangeros to take rHuEPO.

transgenic mouse – tg6 mouse – born with 80 hematocrit. lives for 12 moths. wild type lives 24 months.
-    dies ofmulti-organ failure.

Mean Arterial Blood Pressure -0 in our substances, increased by 5-6ml of mercury – if you have this throughout your life, it is of course hazardous, but if increase to 50 and inc mercury for a few months per year for a cycling career, my guess is that it’s not so bad.

also investigated heart itself. found no dangers.

detection strategies and other

are the detection methods good?
-    abolish hematocrit level? because easily manipulated (plasma expanded, or blame sauna)
-    so, think about quantifying total haemoglobin mass, since this is constant measure usually

Hb increases with altitude exposure
Hb increases with training
Daily variation in htc
daily variation in plasma epo

so, to know whether is stable, measured in subjects – breath carbon monoxide

not clear that rapid increases in htc is blood doping

wide variation

so, this method is worthless

the on/off model

future (now) ?

epo receptor activating peptides (ERAPs)
-    do job of epo, but are not epo

when not neede, broken down immediately by
-    prolyl hydroxylase inhibitors

group in oxford has made inhibitors (DETECT FOR INHIBITOR?)

Machines to use?
-    Radiometer OSM3

Conclusion 2
-    difficult ot get htc or hb mass measure
-    machines don’t always tell the truth
-    future (and this is now…) is scary with regard to detecting endogenous epo enhancing agents

15.30 – 17.00
INHDR network meeting

19.00
Dinner in Aarhus
4
International Network of Humanistic Doping Research
www.doping.au.dk
16 August 2007
8.45 – 9.15
Coffee
9.15 – 9.45
Asst. Prof. Rob Beamish – The Policy Implications of the Current Social Construction of Steroids as a “Moral Panic”

I try to never use the word doping, since implicit illegality

Umah Bartov ‘Distorted Mirrors’
- perceptions are fundamentally important
- holocaust portrayed through series of mirrors

march 17, 2005 – committee on government reform

social constructionism
- moral panics
- claims makers
- build moral consensus

eg. house committee is one process of claims making

coubertin’s objectives have become the IOC brand

1972 munich – separate GDR
- east german successes embarrassment to west

Wade 1972 raises concern about steroids

‘the first of male steroids to improve performance is said to have been in world war II when….

1988 – 48 strides under 9.8 seconds

Trevor Graham turns in syringe with THG to USADA
BALCO
2004 State of the Union

San Francisco chronicle links Greg Anderson to BALCO who is linked to

bigorexia – young men trying to bulk up. – associated with Viagra, and other enhancements – ‘cult of the body’ within a context where drug/supplement use is widespread.

comic book masculinity

use of steroids part of postmodern world of changing faces.

Questions and Answers

John H: how long did victor conte serve in prison for balco – 3 months. grotesque disproportion of moral panic vs judicial system.

Rob: game of shadows – clear that there are thousands of BALCOs throughout America.

Paul D: mythmaking vs actual fact? how distinguish?

9.45 – 10.15
Dag Vidar Hanstad (Norwegian School of Sport Sciences) – Where on Earth was Michael Rasmussen? Elite Level Athletes and their Whereabouts
dag.vidar.hanstad@nih.no

www.sportsanalyse.com

aim
-    survey of athletes attitudes on doping
-    292 subjects, 80 responses (or was it 80?)

findings
-    80% said they trusted the online system
-    1 out of 4 felt it reduces the joy of being an elite athlete
-    signif percentage felt that 3 warnings in 18months should lead to sanction
-    many athletes felt part of a ‘big brother’ system?
-    few felt that info collected would be misused.

does tracking whereabouts violate self-determination?
need to regulate can get out of control

everyday surveillance is extensive

10.15 – 10.45
Asst. Prof. Andy Miah – Human Enhancement Technologies and Sport: The New Language of Doping?
10.45 – 11.00
Coffee break
11.00 – 11.30
Prof. Mike McNamee – Ethical issues regarding human enhancement technologies: Therapy, Enhancement and the traditional goals of medicine in sport

against doping
- performance enhancement
- allows more training – coercion
- unnatural
- harmful
- unfair advantage
- cheating

idea of enhancement
- valorization of autonomy
- are athletes generally autonomous. if not, cannot make autonomous choices
- athletes are not autonomous, do not understand sports medicine, are passive.

ME: their reliance on expert knowledge is no different from your own knowledge of medicine.

medicine is essentially therapeutic

ME: but a wide range of therapies are context driven. imagine a 70 year old man who can no longer enjoy a sex life. is the prescription of Viagra therapy or enhancement? Alternatively, an individual who has a known late onset genetic condition for which there is an ongoing treatment – you are likely to get Parkinson’s, we should start treating you now’ your characterisaton of these as peripheral to your concerns is mistaken. they are the business of all medicine.

doesn’t follow that what happens within a hospital is all therapy

night and day, cannot tell you when one begins. – ME: yes you can mike, it’s when you wake up

‘there will be cases which are not therapy/enhancement, I don’t have a problem with that’
- ME: that’s precisely the problem you have

demarcate unacceptable enhancement
use of prosthetics in elite disability sport

how desirable is the fact that the performance is dependent on technology? (Loland)
prob is surrending level of control athlete has over daily life
-    ME: so, an athlete that wants to stay at home with family, cannot afford to take them to mountain, her quality of life is diminished by not using hypobaric

will what is left be recognisably human?

Questions for Mike:
1.    if your claim is that athletes are passive – ie. not autonomous – then I also doubt my own understanding of . there is no legal basis for supporting the claim that athletes lack autonomy. In 1985, the case of Gillick vs West Norfolk established what’s called ‘Gillick Competence’. it indicated conditions where minors could obtain abortion without requiring parental consent. it has become a critical part of how we think legally about autonomy and consent. there is no way imaginable that you could argue legally that athletes are not autonomous to such an extent that you could step in for them to decide on the basis of some ‘substituted judgement’. Over the last year, my doctor has quadrupled my preventative prescription for asthma. I’m not sure I understand the medical science too well. I feel like I might be building an unhealthy resistance, but there is no doubt that I have autonomously acceded to this treatment.
2.    Medicine makes us well ‘for something’ it is never free from the lifestyles we want to lead.

11.30 – 12.00

Director Michele Verroken – Anabolic Steroid Use – what is the size of the problem for sport and society?

reliability of data = credibility of information

test date from 1993-2003

no of samples increased from 89166 to 151210

no of anabolic steroid findings inc from 940 to 1169 (872+297 – includes beta 2 agonists)

question – is an approx 2% problem, a problem?

in 2002-3, Australia reported only .59% positive test.

we don’t know about the problem

survey of athletes 1998

54% believe that up to 30% of competitors in their sport were using performance enhancing drugs

4% said 60% were doing so

3% (none from weightlifting or rugby league) believed sport was clean

(from the Indenendent)

new york times 2003
‘how many athletes in us use steroids’
results do not reflect testing data?

also asked whether it bothered people – 30-40% said no.

realibility of testing, random, missed test scenarios

many athletes say random testing is actually targeted.

positive test over the years not significant percentage.

ME: ou mention Beijing. what do we know?

are we helping ourselves by identifying the size of the problem.

better to miss a test than fail a test.

more than 70 British athletes have missed at least one out of competition drug test. 4 of them have missed 2.

IAAF regs say a missed test is for five years, not just 18 months.]

testosterone reporting

testosterone-epitestosterone ratio
- upto 2004: 6:1
- post 2004:

Autologous blood injections in soft tissues complaint

alice in wonderland
‘I don’t think they play fairly…’

£2000 to treat abscess from steroid injectors – if teach to inject properly, lower the cost.

future social problems?
- France BJSM research – 1/100 of eleven year olds use drugs to enhance performance (could be salbutamol)

we know there are inconsistencies between sport and society use of steroids

to WADA
- tighten up testing – not government targets
- promote health consequences of using steroids and opportunities of needle exchange.

12.00 – 13.00
Lunch
13.00 – 13.30
Prof. Alessandro Donati – Connections between doping and narcotic drugs

Australian anti-doping agency – image vs performance enhancing drugs

Schwarzenegger was paid by mafia directly for his films

combination of doping and training knowl
- day of athlete now is full of training – cannot do other things.
- e.g. many cannot read more than 10 books a year
- rogge now interested in youth – fight obesity and sedentary – so, youth Olympic games
- no connection between doping and obesity/sedentary.
- clear that athletes use undetectable drugs, not the others
- anti-doping tests died.
- dick pound says they’ve improved, which is true, but prob is that anyone can modify and disguise drugs.
- we need anti-doping, but not only.

source of proof
- in sport – only test
- in judicial system – searches, seizure, wire ttapping, expert reports, test biology, documents

what is hidden behind high number of negative tests?
- suffer from asthma, high testosterne or hmb
- hides anomalous levels – pathologies behind results
- interest in lives or appearance – I think only appearance
egs.
- upward trend of cholestorol levels through t years. why?
- unexplained fluctuations of haematocrit and haemoglobin levels (more than 20%)
- critical fluctuations of liver transaminase..also azotemia, bilirubin and several other parameters

negative anti-doping hides emerging disease conditions.

electronic health passport is a good idea.

why do we need state laws against doping?
-    every country should pass criminal laws against doping or update existing laws concenring addictive and pharmaceutical substances that would allow effiecient action to contrast t diffusion of doping among amateur athletes and in gymnasia.

mistake in Italian law is that specifies for elite athletes, it should be everywhere.

ME: if the law should be for everyone where else do you want to police usage? schools, gymnasia,

sport system is scarely efficient as regards acquistion of proof but decisions on sanctions are taken swiftly, but process much longer

dishonest officials stay in the environment, while athlete is out.

the old ioc was a disaster. now we hope wada, but we are late

connections between doping substances and social drugs

common ground – cocaine, stimulants, amphetamines heroin, opiates narcotics cannabis, ghb, alcohol.

sport system

difficult to accept sport system.
athlete positive for cocaine. he never went to disco. when is he going to use cocaine for social?

antidoping lasws in eujrope

legal systems on dupong
- in June 2006, Italian minister for social affairs appointed me fconsultant

doping substances are assimilated to addictive drugs so that the judicial instruments and the anti drugs criminal las…

se of doping substances not criminal offence for common practiconers but only for professional athletes….because doping gives them an illicit advantage and damages their opponents
- create indiv health smart card for all practioners of sport federation.
- not important to disqualify, but to stop
- inverstigations coordinated by special police squad
- contrast traffic of doping substance via the internet

Article 28, item 4, establishes internet acess providers….

Slovenia
- websites in several countries
-

ME:

13.30 – 14.00
Asst. Prof. Ask Vest Christiansen – The use of anabolic-androgenic steroids among non-competitive strength training athletes – cultural, social, and psychological explanations

campaigns against non-competitive strength trainers has failed, why?
portrait of a person who took a lot of steroids and loved it
presentation of types of questions received by Anti-doping denmark

1999 national household survey on drug abuse – estmate 3m users of steroids in US
ADD estimates between 10,000-60,000 in Denmark
inexactness reveals how little we know
4 of 5 steroid users are non-athletes
in Denmark: 9/10 users non-athletes
steroid users larger doses today than previously reported
widespread misconception that trainin for improving appearance can only succeed with combined drugs and training

have tried to change things by imposing fear

a paradigmatic change – not just a medical prob but a cultural phenonmenon

take into account cultural norms and values of drug inflicted subcultures

campaigns have been based on bourgeious values, v different from cultures of body-builders

focus of campaigns have focused on side effects and consequences – impotence, acne, damage to vital organs.

subjective experience of drugs vary
- inc stength, virtality, libido, social status

a Danish bodybuilder
- said how use of drugs gave 2 fantastic years of building, but ultimately spiralled out of control.
- from compettive football, but disillusioned. realised potential for muscle building. was well proportioned. but after progress, muscle development levelled off. decided to continue development with steroids. began with anabolic, to nanobolic – injecting 150-250 mg per week – more effective and no side effect of subcut fat, as pills did. achieved high recognition in his milieu. strict diet. other things mattered less. when met a girl, made clear should not complain about his use. experienced none of the side effects, never violent. but lost control of medicine. intervals between treatments completely disappeared. did not bother him at first, but became ill. 3 weeks before contest, body broke down. hospitalized. in recovery, realized seriousness, before moving depression. he felt something was taken from him. – injustice that had not been able to finish project. now recovered and teaching in small village school.
- what can be learned?
- male status of muscles is crucial to understanding doping of weight training
- promise of transformation.

Alan Klein ‘little big men’ – promise of change, from vulnerable to heroic and opposing.

14.00 – 14.30
Coffee
14.30 – 15.00

Prof. Verner Møller – Is the current anti-doping strategy satisfactory, and can it be improved?

doping is what wada assesses it to be

prob not that you dope, but how you dope

eg. caffeine – taken off list, despite being a stimulant
why not oppose vanity dopng?

tamburrini – what is wrong with doping?

fact that doping rules are arbitrary does not mean they are mistaken.
second claim by tamburrini, is that open access would be discovery of actual risks.
-    other areas suggest restrictive use leads to

in spite of these reasons, threre is support for anti-doping

so what is wrong with doping? nothing if ultra-liberalistic perspective

Questions and Answers

Claudio: is the reason for so few doping injuries evidence of underground doping research?

15.00 – 15.30
Final discussions
15.30 – 16.00
Epilogue
17.15
Visit and buffet at City Hall

International Performance in Sport Conference (2006, Sept, Newcastle)

International Performance in Sport Conference
Newcastle, Sept 2006.

Muscle Responses to Exercise
Prof Dave Jones

how optimised muscle performance before (training) and during competition? (i.e. by warm up)

muscle size and strength almost synonymous

technological advances in sports surgrery
Mr Lennard Funk
shoulder and upper limb surgeon,  Manchester, UK.

improvements in surgical skills and ability to teamwork better has asdvanced capabilities
-    teamwork with coaches, physios and the conditioning coaches

advancements faster than literature

www.shoulderdoc.co.uk
www.sportsmedclinic.com

not clearly evidence based

how allow person to recover faster?

aim = return to previous level of sport

National League Player of the month
-    Paul Rowley, Centurians –

shoulder
1.    anthroscopy
2.    surface replacement
3.    osteochondral lesions
4.    rotator cf repair and patches
5.    suturtres and anchors
6.    hyaluronans
7.    acceearted rehab – cryo, tc

knee, sanjiv jari
1.    chondrocye transplantation
2.    meniscal transplant
3.    double bundle ACL

Anthroscopy
-    ‘ the needle with an eye
-    no sutres, less pain, day case procedures, quicker rehab, lower morbidity
-    conditions treated: impingement, AC joint artisritics
-    overhead athletes shoulder –
o    internal impingement, dynamic assessment (Burkhart et al, Arthroscopy, 2003) – not just baseball pitchers
o    anterior plication
-    contact athletes shoulder
o    labral lesions
o    treat all associated pathology
o    rapid return (Funk et al. Clin J Sports Med, 2006)
-    Rotator cuff repair and reconstruction
o    cuff tears
o    outcomes of RCR
•    time ti surgery; previous steroid injections, quality of tendon tissue; quality of muscle; smoking and NSAIDs
-    Collagen patches
o    reinforcement of repair; provide protection; incr strength of repair replacement; accelerated healing (growth factors)
o    GraftJacket regenerative tissue matrix
-    Genetic Engineering
o    putting stem cells on collagen scaffold
-    Wheelchair athletes shoulder
o    acute rotator cuff tear
-    Osteochondrail lesions of sholder and elbow
-    Sutres and anchors
o    extremely strong, semi-biodegradable, controlled release growth factors
-    Anthroscopic stack
-    anthroscopic theatre – bridgewater hospital, Manchester
-    shoulder replacement in young people
o    surface replacement (bone preserving, minimally invasive, easier revision, long term results (Funk, Copeland and Levy, JBJS 2004)
-    Post-op advances
o    anti-implamm
•    mechanical, biochemical (inhibit phagocystits)
o    viscoseal hyaluronan (less pain, better function)
-    Slings and Cuffs (traditional slings, unnatural and no evidence!)
o    in France: preferred: 15 deg ER Sling – better early ROM
-    Cryocuf (less pain, less analgesics, faster ecover Singh et al 2001)
-    Shoulder rehab advances
o    protect from physiotherapst!
o    effects of immobilisation
o    clinical results
•    old protocol – 20|%s stiff
o    protect and rehab at same time?
o    Tendon loading
•    immobilisation: dec tendon weight, dec stiffness and tensile strength, irregulat collagen fibres, type 3 :> Type 1 collagen; degenerative changes; Exercise: (incr growth factors, tensile strength, incr
•    EXERCISE RATHER THAN IMMOBILISE
-    Accelerated Protocol
o    Day 1-3 weks (0-20% EMG exerciseds; Low activitiy)
o    3-6 Weeks (40% + EMG)
o    6+ (40% + EMG)

Kneee (Sanjiv Jari)
1.    chondrocyye

Autologous Chondrocyye Implanatation (ACI)
-    cartilege cells harvested and multipled
-    isolated defects, stable knee reqs,

MACI
-

Summary
Future:
Biological Implants
Tissue Engineering

Questions and Answers

question: how does it fit with doping

a: don’t know?

a: growth factor unlikely to enhance

Lee:

Ron: doping do not prevent treatment

Lee: grey area is gene therapy – once therapeutic over, still a permanent enhancement

Michelle Verokken:

Ron: where next big advances?

Funk: not sure ewhether tissue engineering will be taken over by synthetically derived growth factors.

Athletic Injury and Gene Therapy
Lee Sweeney

muscle injury in context muscular dystrophy

skeletal muscle

somatic cell gene transfer
-    delivery of DNA into fully developed tissues (eg lung, liver, heart, skeletal muscles)
-    technology developed for gene therapy – correction of genetic mistakes that cause disease
-    hwr same technology for genetic enhancement or improvement of functionality of non-disesase, but injured tissue

Gene delivery into muscle
-    primary target is post-imtoic (no-dividiing) nuclei of t mature muscle fibres
-    gene delivery vectors
o    naked (plasmid) DNA – ineffecitent and transient
o    Viruses (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)

AAV mediated gene transfer
-    readily infects skeletal muscle
-    no drop off of expression over time
-    limb delivery possible, body delivery still limited
-    size limitation – some genes don’t fit (duchenne muscular dystrophy)
-    virus production had been a problem, but new technologies in viral production … amount required to treat will soon not be a problem.
-    immune response problem –

Questions and Answers

Question: a lot of body builders using systemic IGF-1 from China

question: will treatments be relevant for diff fibre types?

a: wouldn’t redistribute muscle mass.

Lee: application to dogs – owners would like dogs to be able to keep going for longer.

lunch

biomechanics and sport
salo

definition

support issues
examples

Conflicts of Interest Panel

mark james, acting head of Salford law school
john o’leary
mike townley, parters of athletes1

mark
Dept of Health recognition of Sport and Exercise medicine as a discrete specialism is releavtn here.

ME: ask question about whether should be charcterised as medicine.

discussions of ‘best practice’ more relevant than legal rules that are tight

ME:  we heard earlier that surgical technological developments does not rely on an established evidence base, so can an athlete expect informed consent?

john

what do we mean by implied consent in sport?

mike

need for radical difference in physician’s role in sport performance

ME: Is the patient-doctor model an adequate reflection of the athlete-doctor relationship?

Question: Max Jones (runs Marathons (not the Max Jones of UK Athletics)  in what way should aptient-doctor relationship change just because the athlete becomes so good at her hobby. WADA don’t trust doctors. after 1999 lausanne conference,faq was ‘should medical doping be permitted’. answer was no, because only the IOC could control long term effects of doping.

Mike: how should the relationship change? it needs to be less suspicious. doctors must become less suspicious of performance team. athletes must become less suspicious of conseqs off communication of an injury status. in funded sports, not clear that communication leads to de-selection. get beyond idea that favouritism is what counts. british athletes not happy with waiving competition.

ME: 2 athletes, both get injured, one athlete tends to do better with recovery psychologically than another. on this basis, the doctor recommends the former athlete, but on no scientific basis.

Mike: diff between weekend warrior and elite athlete. athletes want to go to limit. amazed at how medical community have reacted.

Rob Dawson: comments outrageous. patient-doctor relationship is sacrosanct. if correct doctor selected for team, they willl have the right values.

Mike: but when accepting claim that nothing breaks patient-doctor relationship

Ross: GMC – doctors role to protect indiv.

James:

Steve Olivier: research ethics. I don’t think the comments are outrageous at all. things can change. why should a rational adult be allowed to waive confidentiality?

Rob:

Mike: great hostility to that waiving of confidentiality. met with resistance before it gets to the athlete.

James: how does one define relationship between doctor and athlete? eg. a power relationship – doctor is older usually, more formal education, perhaps greater level of sophistication. compared with athletes who are youngerk, less experienced in t ways of life, and, perhaps, possessing lesser degree of sophistication. standard I use to make sense is – lookinjg at perspecxtive of aptient – it’s the REASONABLE athlete standard. defining reasonableness is difficult. how achieve informed consent from this perspective? not as an event disclosure – eg. signing a form = consent – I think, compared to gen medicine, sports practictionaer already has special relationship that there is an ongoing comm., that athletes and doctors are working together. sports produce injury. tf, athletes and doctors will have the regular contact. som, there is a special relationship – not legal term. then, issue of informed consent is easier, as ‘process’ or ‘educational’ consent. PROCESS MODEL.

Michelle Verokken: would be fine if informed consent and confidentiality if all athletes over 18. one of my concerns is youngsters brought rhough sports system, where they learn to trust various people. not consent, but only alternative you have to achieve public funding in order to compete. no genuine capacity to consent. implies doctor has nobody behind them, but we know they are.if try to achieve informed consent, must take sport system as a whole.

James: difference between Consent and Assent – if assent, then different from consenting.

Michelle: difficulty in sports is that getting to top, few people who fund themselves without trappings. ie. not sure there is a consensual relationship anymore.

James: objectify athlete

Max: the athlete? the antidoping codes don’t apply to athletes, but to Athletes – defined as International andnational athletes.  WADA 2004 best practices code – form at end – ‘I agree and had opp to review IAAF anti-doping code). they don’t need consent.
WADA Code not an Agreemnt – if effected by it must sign.  when Dick Pound said antidiopng rules are rules that athletes consent to, he said if they don’t like rules, tough!

john:  concerned about idea of ‘best interests’ in sport. seems to be a nebulous consent that runs riot.. idea of waiving confidentiality falls in that confidentiality? how does this benefit athlete?

ME: if we are propsing a non-medical model, would this change DoH funding?

john: interests of sport, or interest of athletes.

mE: rights of sport, wrong, but protection of a practice is.

Question: as an athlete, you choose to compete and accept rules. eg. agree that netball is a non-contact sport.

Naomi, UK Sport: project on datsa storing of injury data

Mike: IOC philosophy – ‘exhaulting life…’ that’s not the way it’s viewed.

John: are you talking about implics of practie, sport, or criminal law? probably committin criminal act to defraud – money involved? prize money

Michelle: informed consent from eam doctor’s perspective be suspicious of.

Rob: who owns the records?  if change definition of doctor in sport… when a clinent, not same duty of care.

Bruce Hamilton: if genuine consent athlete won’t do it?

Mike: to get informed consent, are you saying

james: ongoing consent. significant practicality – not enough time.

coffee

visualisation techniques

functional equivalence
-    motor iagery and motor preparation are related to same represn stem
-    some differences
o    outcome
o    dual pre-motor system

a good experience is good when you do not recall how you did it

bad ones often bad because consciously controlling what is wrong
-    can recall in fullest detail

Practice makes Permanent

Wednesday

Medical Complicity in doping
John Hoberman

historical imeline

1893: philippe Tissie performs a doping experiment
1933: a german pharmacologist condemns doping
1941: androgens for the ‘male climacteric’
1957: American medical association studies doping
1957: ‘should athletes take ‘pep drugs’?’ (UK)
1957: AMA Denounces Amphetamine Doping
1960: an American sports physician on doping

1969: drugs: a threat to sport (Sports illustrated
1972: physican claims steroids don’t work 1985: west german sports doc condemns ysteria
1988: The Lancet on Physicians an Doping
2005: A South Carolind Doc upplied steroids and GH
006: inteview with Loptha Heinrich (Jan Ullrich)
2005: doc comments on golof and testosterone

1890s, era of high performance sport begins
crude exptl period of stressing human physiology
cyclists become great subjects for testing human limits
Tissier linked with De Coubertin – concerned about stree on body from sport
ie. physician concern about welfare of athlete goes back far

two aspects of tissier –
-    1890s, naïve and is sending cyclists around track with diff liquids, rum, milk, champagne
-    performing a dopping expt of hisoown

before concept of doping existed, he was interested in wht to do about fatigue

he described athlete as a sick person

athlete as a pathological case

when does idea of doping emerge

1920s

1933, A German Pharmacologist Conmens Athletic Doping
- check Mortal engines for quote

UV rays to boost performance

inter-war period, doping discussion as we know it begins

don’t tell me that steroids spoil everything!

marketing of androgens

1941 – Androgens for the ‘Male Climacteric’
healing of male menopause

testosterone synthesisee in 3 labs in 1935

by 1939 being used wrecklessly by US docs

aphrodisiac property of testosterone
-    irony, was given to women who were in no condition to be sexually active

the focus on athletic doping is imp, btut not enough
need to look at the entire medical landscape

booming anti-ageing market

1957
Four Minute Miles accused of Amphetamine Doping, New York Times, June 6
‘AMA to Study drugs in Sports: Use in Four-Minute Mile Hinted’
[front page story]
-    assumption by phywsician was that humans not capable of this without supplementation

this set off a discussion

1957
The New York Chapter fo the AMA Denouncest Doping as a Threat to Youtyh – JAMA, June 13: 1244)

ME: What is the motivation of these doctors?

we are still at this stage of the discussion

1957
Sir Adolphe Abrahams on Amphetamine Doping, The Sunday Times June 16 ‘should athletes take ‘pep’ drugs’?

he did not succumbe to the moralising syndrome of the previous eg

need to understand how naïve some physiscians have been about doping before

a victorian outrage in response of AMA officials

this is also recognisable to use, as their genuione alarm of illegitimate use of drugs, what we get is something that is conflation of moral/ethical argument against drug use and the medical argument

ethics and health underpinned anti-doping

conflation of moral and medical is effortless

for Abrahams and brother who were publishing commentaries at the time, Abrahamas was an indep type. refused to assume drugs were effective. he also said ‘quite apart from the possibility of physical illconsequences, physician cocenr about amphatem…. was about suppressing self-inhibiting;’’’ concrn that would suppress limit recognition
‘as to anything unsporting’… o’one is forced to face debatable’
-    ie. he did not take automatic moralising position. he insists on thinking about what constitutes doping. this was a sophisticated posn for his day.

imp to understand that this issue was being given attention 50 yrs ago

what constitutes doping was unsettled

groping for a workablre doping definition

why?;

partly because assaled by claims about drug use
and by medical concern

1960
An American Sportw Phyiscian on dopin: Amateur vs Professionals, New York Times, sept 12,
‘use of drugs in sport’
first drug induced Olympic athlete death

letter to NYT where immediate parst president of American Coll of Spots Med says
‘the proesional athlete has a job to do, which may be his sole livelihood’ ‘sounds like prince de merode] so he ‘may use any means to acxhieve’
calculated risk of means are recog part of any professional sport

who could describe subculture of toure de france any better!?

using words likke ‘perversion’

he was saying let them do what they want

1969
Sports Illuswtrated: ‘drugs – a threat to sport’
sports Ill, June 23

HK Duley – physician on US team
-    offered 4 args on behalf of physican involvement in steroid doping
o    1. indespensible in weight sports
o    2. physician had no obligatin to dissuade athletes from using drugs ‘I did not give steroids at Taho, but I did not inquire what the boys were doing on their own. I did not want to be forced into a position where I had to report them’
o    3. drugs did not differe in any essential way to other performance enhancing techniques. if I know something that would improve performance, without any serious health risk, I see no reason not to make available to an athlete.
o    4. medicasl supervsision was safer than no supervision at all ‘lesser harm’ argument. ‘athletes hear about these things arnd are going to get them one way or anyohter’

have to agree with hum on one point
-    in 1960s etc were many physicians who did not know about these drugs.

1972
An American sports physician claims that etoids don’t work: doping is quackery, JAMA, vol221 August 28, 1972
‘Drugs and the Athlete’ (Donald L Cooper), pp.1007
‘normal is the best there is’
‘ drugs are for losers’

this phase cost sports physicians credibility

1985
West German sports doc (Mortal engines, 1992, p.262)
condemns hysteroa about therapeutic anabolic steroid use: Heinz Liesen

1976
most prominent german sports physicans testified that steroids were safe and recommended should be used by national athletes

Heinz Liesen (1985) – testosterone less dangerous than female pill
‘why do we make such a drama out of this?’
-    this question keeps returning
-    if we want to get at deep roots of crisis or, more strongly, freefall, mst see how commercial interests in sport, negotiate performance enhancing treaty with war on drugs

West gErman only place I know that had celebrity sports physicians

Lieson has something interesting to say – substitution therapy

therapy vs enhancement problem

1988
The Lancet on Sports Physicians and Doping, Sept 10: 612
two weeks before ben Johnson
‘Sports Medicnie – is there lack of control?’
-    ‘although evidence of involvement of med practitioners…is lacking..they are connivers…’

a real problem brewing with doctors involvement

2006-2006
‘James Shortt’
-    ‘an alternative medicine and longevity doctor provides doping drugs to professional football players in Southc Carolina’ (
-    he has just been sentenced to prison for prescribing GH
-    he is a ‘rogue sports physician’ n
-    not with an official position
-    from Jan 01 to Jun 04, authorised around 139 GH prescriptions, etc etc,
-    comparative context imp
-    market for anabolic steroids has v little to do with elite athletes! (there is a range of clients).
-    prescribed to athletes, police officers (thisis imp)
-    mesamorphists.com
-    cops, soliders, bouncers, security, fireman, all use them
-    he take recordedhis own incriminating conversations
-    he says ‘for you guys what I’m looking for is a non-detectable performance enhancement’
-    athlete as client – what does a sport physician owe an athlete?
-    My guess is that Dr Shorrt is looking for stress from a functional standpointm, rather than therapeutic
-    treated about 14 NFL to help athletes ‘heal’ from athletes
-    but he just said the opposite!
-    medical authorities did not look at Shortt as he saw himself. they blamed him – no medical justification for prescriptio
-    he then collapses and confesses, saying he wrote prescriptions and he says he knows it was ‘federally wrong’
-    he failed his social obligation to create role models

mE: I’m inteeresrted in the range of characters you present.

Dr Lothar Heinrich
-    ‘anti doping work is not my mission’
-    focused on health

ME: why does heinrich not see antidoping work as health work?

-    when Ullrich and other 57 got wiped out of Tour, tv viewings went down by a third
-    ‘cycling is not a drug-ridden sport’
-    in sport ‘you hope to participate in something of historic significance’

so much for the detacthment of sports physicians

Questions and Answers

Rob: crucial aspect is that is ‘sports entertainment’ industry

ME: comparable to others?

Rob: bottom line is that it is against the rules. and this is the key Partl.l the future?

John: public survey data suggest around 30-40% say they are unconcerned about medically supervised steroid use. we’ve reached a point when have to think about being a conscientious defector from performance culture of sport.  Heinrich doesn’t want to take any social responsibility.

Michelle: where is best pase to have debate about medeicl involvement on performance enhancement

lunch

prof. david cowan, UK Sport
kings college London

DTI Foresight
-    ‘analysis of substance that influence performance’
-    he was involved with this.
-
-    landmarks in drug analysis

pharmacogenomics
microchip technology

post 2010
-    inviv in situ analysis
-    electromagnetic scanning
-    direct measurement in complex matrizes
-    isotope signatures

would we have sport where everybody wins? no.

as long as it is the will of sport comptitors to control doping, effective doping control must be continued

bruce

Garnier ‘medscape ortopediat and sports med 2006 ‘in sport with are dealing with  a health even a super-healthy population

Medication Use in Athletes Selectf for Doping Control at t Sydney Olympcis 2000
Caorrigan and Kazlauskas CJSM 2003
‘it is diffi to udst why t med starff has endorsed such under dosing as apriri one a day…

autologous blood injections

blood spinning
-    spin off from autologous blood injections

jim

baseball
need consent of union in order to do doping tests

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 Symposium
4-5 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

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

Sport Medicine Ethics (2005, Stockholm)

Sport Medicine Ethics, Stockholm,
May 2005-05-24

Christian Munthe
Sport, Med and HC

HC goods
-    securing certain lev of health (prevention, restoration, ailment)
-    in a just way

SM goods – secure health conducive to athletic performance
-    beyond HC lev ofhealth and goals, also enhancmenet not approach reqt of justive

dual influences of SM
-    ethos of trad med (life and qual, autonomy, justice)
-    ethos of sports (supreme performance and excellence), autonomy, fairness

Rationing HC
-    HC: need paramount (and prognosis); prov for worse off upto a level; contested ideas about relevance of numbers;l contested ides about relevance of merit/desert
-    SM: unclear about what is paramount; resource not limted by same funds; numbers probc; merit desert can work both ways (sports injuries, self inflicted, heroes benefit soc)

Conested procedures – 4 args (doping, etc)

1.    SM should adapt to ethos of HC (either prob: goals different; or: reason for revising
2.    HC adapt to ethos of Sports (excellence, fairness): either: prob: rules and goals of sport arbitrary from medical view, or: recom for breaking SM out of HC
3.    Sports should adapt to ethos of HC (but: safety or justice arg)
4.    HC should adapt to ethos of SM (safet, justice) Either: probc, due to dit; radical revision of HC

Remarks:
-    what ethos is relevant for ethos of SM?
-    ‘place’ of SM?
-    Basic prob for ethos based ethics – virtue sport philosophy, or communitarian theories of justice
-    Challenge for medical ethics – sm/sport
-    There is no archimedian point
-    Inquiries into concrete, partic issues needed

Claudio Tamburini

No difference view – between med everything and sport med ethics – latter only more specific applic of normative framework in med ethics generally – NOT TRUE – eg. Autonomy/privacy function/meaning in different way in sport – sport med more paternalistic – eg. Training technique – athletes are not protected -, must subit to rules, – testing = privacynot same – no difference view obviously wrong

But should they be different? – yes: athletes are not sick – wrong to giv medicine for sick – Lyjungqvist = doping is medicine – ‘athletes are healthy’ – thus athletes are not patients – not general rights of HC system  – what’s wrong w athletes using med (prov not state funded) – athlete are patients – meaning of patient – suffer from pathology – too narrow – today healthy people give treatment – not clear where to draw t line – healthy people already consume – WHO – well-being – dependence of medical prof for (non(athlete – exposure to effect of medicine makes vulnerable and this vuln indicates patient status , regardless of whether customer – athlete? – are patients – conclusion: recog as patient

ME: ethos of medicine is that absence of proof does not mean absence of reasonable expectation or evidence; cannot refer to WHO for support for an ethical view same for anti doping code

Anders Sandberg

Health consumerism – what are enhancement treatments? – alcohol caffeine, etc – st johns wort – ginseng – positive psych – beta blockers (musicians) – growth hormone – since it is an enhanceent(?) – IGF – improved elasticity – cognitive enhancement – social (prozac -= leadership) – acceptance is complex =- is morphological freedom a right? – functional food yes, GM less, but dfferes in culture – Japan 50%, would consider, 66% would for … therapy – Thaliand, India, yes, if adv – WHO – health as optimal but function relation to ones own cgoals – conclusion: doping and enhancement  – performance artists: how they change their body

ME: only medical intervention reqd
; modafinial, global GM same?

Question&A

JS: by allowing enhancement, implies coercion

MMc: autonomy – inc vulnerability = higher standard
SH: sm goal fro physiocan as not ‘excelelnt’, but goal of employer – make sure team wins
CL: health definition tooo wide – who – boorse – too narrow
Tomas (athlete): paternalism – we let athlete do unhealthy things, so not too paternalistic – wada: not prov risk to health – Is pressure on autonomy so freat for an athlete?
CT: as patient more exposed to med prof – athlete can choose not to expose themselves
JP: beta-blockers not analogous – art and creaft

REF: MIGUEL NICOLELI – NEUROSCIENCE, CHIPS IN ARMS, MAGNETIC

Susan Sherwin

Should we welcome/resign/resist – social polic y or indiv choice? – Francoise Bayliss/ – oppose – to pursue GE = research prog – sports req different kinds of body type – enthusiasm for GE = popular reductionism – avoid enthusiasm welcome – also reject 2nd (resign) – beleief in efficacy will lead to demand (!) – resigned acceptance is self-fulfilling- reject inevitability – opt for resistance – social policy, not indiv choice – indiv choice: autonomy as informed choice – prog grants to challenge rights based – for some implices reduced autonomy – must include right to refuse – but in sport not possible – broader implic for young athletes – most likely to be applied in adolesecenc, this is bad time – cannot claim ‘iformned’ – challenge indiv – reject trad economy defences – reject indiv autonomy and personhood and supplement w relational theory – persns as partially contested by social relations – liberal theorie treat self-hood as indiv, relations -= selfhood as ongoing project – wht are t proceses by which a person holds certain prefers – fem theory – irrationality based on consensus (irrational to resist conformity – become irrational NOT to select enhancement – excellence as GM conveys something to those who are genetically deficitine – new expctation for improvement – entrenches legitimacy of comp (social Darwinism) – precautionaryu princip0le needed – excellence is not GM, but social programes – less sexy perhaps

ME: what else shouldn’t we have done based on this model?

Sarah Teeztsel

Adam Moore – unexamined life..open to inspection – proivacy and tech – gene doping – uise of legl gene theory for sport not acceptable – banning just
-    drug testing in sport (Canada report) – invasion of privacy – acknowleged

Nick Bostrom

(w Toby Ord) – good or bad – double epistemic prob – 1. radical disagreement about conseqs, 2. Eval of consqs: even if we know what would happen, diffi to say whether, on balance, is good orbad – double epistemic chance of only major reform – eg implic of abolishing slavery, rely on stat and subj intuitions judgement – biases – ‘status quo’ bias – doc by exptl economits – defined as inapprop or irrational pref for state, just because it is XX – ‘mug’ experiment – choc bar or nice mug – predict that 50% would get what they wantede, but 90% choose to return item – ‘endowment’ effect – place value on something just because given to us – irrational? – but status quo bias clear explanation in bioethics, definition of judgmeent for this

how elminate bias? – hypothetical enhancement of cognitve (eg. Memory) – conseq: should we think enhancenment would have good/bad oconseqs? – oft doubts about this (fear of unknown) – how adjudicate between opposing views – ask counter intuitive: what if did opposite? – decrease human cognitive capacity – clearer agreement that bad – those who also bad must judge why ‘current’ level is optimal – burden of proof is on those who make these claims – seems implausible that isat peak – reversal test –doesn’t say is wrong, but that burden of proof on ‘status quo’ – cognitive enhancement: arg from ‘evol adaptation’ reg ratio of heart size to body size – w cognitive enhancements, arg doesn’t work, since eg enviro different now than was previously (ie now cognitive society, previously physical soc);  – if human cog cap corresponded w brain size, then might be good – preventing costs to bigger brain – now less – now less – what evol optimises, so inclusive fitness, but human sep side undermine this – eg. Intell – 2. Arg from transition costs: (do not sxXX, kust because implies t difficult – cost to great – - 3. Arg from risk – but this works both ways – riskness doesn’t imply anything specific -  cognitive benefits enormous – 4. Arg from ‘persons affecting’ – consier not likely to effect – 2nd reason of reversal – imagine – double reversal – more powerful heuristic – as takes into account these other args – toxin in water, reduce cog, intro therapy to water – then toxin removes, then cog enahncenemts above optimal (double reversal test) – reverswal and double reversal best comforts to status quo bias – it extent bias – must interpolate  2 versions of status quo – can take into account genesis choices , deontological considerations, and social policy – intuition about ‘natural ‘ prevalent in bioethics – natural = good – intuition about natural more properly about ‘status quo’

Mike McNamee
Slippery Slope

Half-baked HN – witnessin convergence of system – no human or postmodern consition – but convergenet – views of transhumanism not clear – ‘transcend limits’ of HN is wrong – ‘features? Is more approp – reduce vulnerability to human – posthuman? – use to enahncene H choices – no need to shed HN, but augment – in favour: facilitate 2 aims: use technology to improve Hs – transhumanism: ‘ideal blue print’ – personhood: if indep of species, then moral status maintained – arg: 2 types of being|: human and posthuman – Buchanan et al: found on category of H – no longer common H – expand inequalities – genetically deficient – autonomy as RRATIONAL CHOICE THEORY – DEMOcratic technology is naïve and idealistic – surely coomerce will govern – in elite sport prevalent – double blind: poor pay for pleasure of envy – for other transhuman 0 engineer resistance – what is idal type? – criteria of THN – affront to morality – eg. HR, tranhusmanist might be beyond human – why moved by approach of ‘solidarity’ – life span: agening as a creapping evil – woody allen: ‘immortal not by doing great deeds, but by not dying’ – burden of proof should be on transhumanist – transhumanist has no limits and thi is a prob – eg. Bod transplant – burden of proof is on ‘us’ – t human is ‘repugnant (Kass) – proof of transhumanist (HE!) – misuse of drugs for sport enhancement – genetic enhancement – approach to therapy first and subjective normalise these – Kant’s ‘dove’ – preconditions of dyling – should celebrate human vulnerability

For NB : does arg depend on stable conseqs? Different versions of autonomy

Jared Diamond – h not changed much in thouse years, but h can find new ways of re-working hu  limits – intell  (rather acculating of cuilture allows more effective development )

Kate fox book – ‘what do we want, gradual chance, when do we want it, in due course’

NB: Asian disease prob –

600 will die without intervention

A  – 200 saved 75%
B – 1/3 600 saved, 2/3 0 saved 28%

C 400 die 22%
D 1/3 0 die, 2/3 600 die %78%

A and C are same

B and D are same
People overweigh losses in decision making

JS: satuat quo not irrational
-    if neither v good nor v bad, then not irrational
-    - if chose for 150 age, but might me 40 yr, stick w 80
-    in absence of giving people choice to change, giv opp to do that
o    if has rich, then prob not whether conformist – cosmetic surgery entrenches norms

Jim Parry –

Supplements – rusedski – defence – supplement – is suppleenmt controlled
Different between an orange or taking vitamin pill – ME: an orange is more (still don’t really know what foos is) – foods are unknown ssubstances

Soren Holm
-    new drugs – social position  – should not expect sports doctors to prov good advice
-    no reason to beloieve that no ban would lead to open safer doping

should not pressure people finto taking big risks

sociall construction of rules – and arbitrariness of rules

MMc: autotelicity – have own rules

Technology and Sport (2004, San Sebastian)

San Sebastian
Dec, 2004

Basque

Thank you very much -  Milaesker
Hello – Kaixo

Regards – gorantziak

Zer moduz – how are you

Aldor Cobanera

Edurne Pasaban – Alpinista (athlete?) elite,  Mountain Climber
-    only woman on opening panel
-    since 1998, major changes in technology
-    in climbing, far better known thanks to technology
-    materials, but also other technology connected with communication
-    ICT to stay in touch through mobile phone technology
-    Telephoning from summit
-    Breakthrough in medicine and technology
o    Can contact physicians  when injured in mountain
-    Even more important in a minority sport
-    Now when on expedition, now take laptop, mobile phone, web access
-    It is still difficult to peak
-    Technology does not help that much

Victor M. Izquierdo Loyola, Subdirecter General of the Info Soc Enterprises, Ministry of Industry, Tourism and Trade
-    ministry of trade
-    EC paper on IT
o    Talks about how applics and experience should be present from beginning of research design
o    Users must be the consideration of a product development

Noberto Santiago Elustondo, President of GAIA
-

Jaime Lissavetzky Diez,  Sec of State for Sports and President of the Higher Council for Sport
-    subjects have economic and social impact
-    physical activity,  and doping
-    which is most important? – boosting of physical activity, particularly interesting.
-    Enormous amount of consumption

Juaqin Villa, Dept of Innovation and t Knowledge Society
-    need to create social network for innovation
-    innovation broader than technical and corporate
o    also management, services,
o    not just in company enviro
o    society in general
o    innovation as a social phenomenon
o

ME: Nobody yet has actually addressed the social concerns, but they have been intimated.

Kim Blair
Technology and Sports: Developing Consumer Products

2000 Olympics
-    Speedo Fastskin – received tremendous pulblicity, Speedo said, anyone can have one, so was ok.
-    Sydney pool was state of the art – hardly discussed
-    Reason why records broken in Sydney, was because of the pool
o    Though did not have the political resonance

Trek Madone 5.9 Bicycle – I used by Lance Armstrong in Tour de France

Technology and Golf
-    1920s Steel Shafts replace hickory shafts
-    1960s: fiber glass, aluminium titanium shafts – never made it to market

change was an ‘accident’
-    material not caused change, but that titanium springs
-    St Andrews changed spirit of rules – face of club has spring like effect
-    In golf industry, believe that curve will flatten out
-    When technology introduced, see sudden change, then flattens out and comes back to athleticism

Sports Producct Industry

Attitude to risk
-    nuclear, civil engineering and aerospace industry
o    slow to adopt new technologies
o    whether or not technology is viable
o    high regulatory climate
-    sporting goods manufacturer
-
o    Marketing and fashion driven
•    Marketing often head of product development
•    Signif vol of product sold by brandingt
•    Signature products, star endorsement
•    Need to seel your vision and the ‘wow’ factor
o    Time to market is fast
•    Typical small changes on seasonale schedule
•    Continuous product intro
o    Research horizon
•    5 yrs is long
•    less than two years typical
o    Personnel
•    Closed network
o    Highly secretive
•    Technology barriers are low
•    Extremely high lev of secrecy on new products
•    Control ofIP is reqd by sports company

No innovation infrastructure in US
-    nothing llike SPORTIS

Before 2004 Tour de France, Lance Armstrong called sponsors wanting to put together F1 team – Trek Nike Oakley, Giro and HED – to form collab effort between them

USOC
-    relies on product sponsors for nearly all product R&D

Developing Sport Products: Product Attributes
-    need to understand all
-    aesthetic
-    attributes of association
-    perceived attributes
-    emotional attributes
-    style

User-Centred Focus
-    talk with lead users – passionate sports people
o    understand what they like in their product
o    understand why they are passionate about sport
o    understand how sport influences daily lives
o    understand how daily lives influ their sport
-    understand core market
o    development surveys
o    validate t data
o    typically use demographic data
-    understand own business
o    innovation/product needs to send right message about company’s vision

Cost Sensitivity
-    eg. Consider cost of raw materials
o    golf tee about 2x cost of materials
•    change in material has huge impact on cost
o    Golf club about 20x cost of materials
•    Change in material has small impact on final cost
•    Can change to more expensive…

Heart Rate monitors – 20yrs ago, people did not understand it. Now a company come out with a product and lot of effort in training consumers in using that tool.
Plan for and expect slow product adoption

Never underestimate challenge of changing consumer behaviour

Capturing Product Value

Limiting comp
-    retain control of IP
-    retain key assets
o    people, trade secrets, licensing, partnership agreements
-    typically, technical barriers are low – easy to copy something new

Developing Alliances
-
Large multi-nationals
-    have patents in place
-    development clear vision for product from customer’s viewpoint
-    more complete t concept t better

Universitie
-    useful for product testing
-    can be useful for prototype development
-    due diligence required on IP ownership

Venture backed efforts
-    develop venture division of your company
-    solicity ideas from inventors (internal or external)

consultants
-    highly recommended to have ‘insiders’ on team
-    provide industry expertise
-    prodide industry introductions

Rene Eijlens
Innovation for Gold

Beat the heat Clothjing
-    hat used to remove heat from head.

European Paralympic Committee
-    from therapeutic to elite
-    technology central to this development

LUNCH

Xtema… – golfer

FRIDAY MORNING

Xabeir Azkargorta
-    medico y entrenador de futbol

En busa del futbolista excelente
Luis Fradua
Universidad de Granada

Nestor Lucas
Cairos System: the intelligent football

Radio based tracking system that analyses data of ball and players in real time

Useful for referee, for graphical presentation of replay

Xabier Azkargorta
-    technology is leading to an easier contest and reluctance to train as hard
-

ICSSPE Pre-Olympic Congress (2004, Thessaloniki)

ICSSPE Pre-Olympic Congress,
Thessaloniki, August, 2004-08-07

Bengt Saltin
Energetic limits to performance

Leo Hsu

Concept of the good foul
Bsketball
Soccer

Good foul unethical
-delib interfere
- no equal opp for contest
-    not agreed on

good foul not cheating
-    cheating: intention to deceive and unfair adv
-    good foul: intention to break rules  plus unfair adv

simon ‘strategic foul’
-    intention and action
-    penalty might become adv
cheating\break rules deilib
avoid penalty
inend to deceive
win or gain adv

good foul
breaking written rules delib
expect to accept penality
win and gain adv

a good player…
-good intention
act rightly
keep spirit

concl
good foul
-    not cheating
-    against purpose of sport
-    morally wrong act
-    indicates deficiency of rules
-    violates spirit

Q&A
Scott: opponent stalling – good player wants to play good game, so breaks a rule in order to create a good game. Is this good foul?
-    response: NO

Sigmund:
Good foul morally wrong act, but ethos

Leo: depends on defn of morally right: – if ethos is morally justified, then ok, but if not, then is morally wrong.

Heather

Beauty of Olympic sport typically allow more than one way of playing the game
Not clear whether poss to decide between beautiful and corrupt
-    elitism, sexism, racism

need to estab criteria for changing sports practices

set out Rawls’ method reflective  equilibrium

narrow
-    justif ororig posn, if match
-    choose strongest convictions as fixed points then work backwards

wide
-    demonstrate why justified to apply in  specific contexts, by increasing breath of test

benefits
-    clarification, systematic, democratic

going through process of wide refl equilib help clarify views

can uncover more systematic

democratic: in context of other beliefs. Where conflicts with other values, then indication of problem

disadv with this method
-    uniersal and cross Cultural undemocratic
-    indivs and their interests

diving or shirt pulling in elite soccer, decision could include everyone in debate as to whether is acceptable – these people unlikely to be aware of internal goods of game
-    they’re likely to have limited knowl of game (HMMM)
-    to follow wide refl  equilib

abstraction is undemocratic, since must disconnect from cultural context

democracy not about truth

while wide refl equilib is useful – it is too thin, since too far removed from sports practices to have any normative force
-    could not determine which ethos is most justified.

Tradition practice bound reasoning:
-    Which criteria?
-    Who ought to evaluate?

Liberal interpret of practice community allows spectators, etc
-    only views about goods internal to game count
-    a limited  democracy, providing correct credentials

Gunnar:
-    would work in new sports, with fast developing ethos
-    would rely on imagination of people to a much higher degree

Mike
-    liberalism v communitarianism

Sigmund Loland
Fairness in spor t- critical comments on Olympic competitions

Not Fairness as indiv obligation, but ‘structural’ fairness
-    when is a competition fair,not when is a competitor fair

fairness in sport
-    competitions
-    relevant and non-relevant inequalities
-    fairness ideal
-    implementation of fairness in practice

gen principles of fairness
-    eliminate or compensate for inequals that exert SIGNIF influ on performance
o    indivds cannot control and influt
o    for which cannot be held responsible

-    conseqs for Olympic  sport?

Inequalities
-    ext conditions
-    person-dependent inequalities: INCLUDING GENETIC MAKEUP, BODY SIZE, ETC
-    system inequalities

ext cond
-    direct competition – standardisation
-    indirect comp (outdoor) – seeded groups, drawing of positions

person depdendent
-    sex and age, over-clasficiation (sex classification seems reasonable in some sports – where biological differences are significan, though in others, they are not justified)
o    – ME: interesting analogy for genetics, would we seek to ensure athletes are all the same age? To what degree? Where it seems to have some influence on performance, we should.
-    body weight – under classification

CAN SPORT SUPPORT ADDITIONAL CLASSES AND DISTINCTIONS AND DO YOU THINK IT POSSIBLE TO LOOK TOWARDS PARALYMPIC DISTINCTIONS TO IMAGINE HOW IT MIGHT FUNCTION?
- A QUESTION ABOUT THE SPORTING SPECTACLE AND ITS VALUES

TALENT IDENTIFICATION IN SPORT

What makes a Champion?

Talent
-    natural endowment or superior ability
-    single most imp factor contributing to achievement
-    other factors include

identified
developed
selected
science or art?

Intuition, rolling dice, magic, sport science (multidisciplinary, evidence based)

Nature v nurture

Genetic endowment
-    intrinsic potential 46xy
-    structure, function, behav
-    genetic manipulation
-    next doping frontier?

Environmental influence
-    extrinsicfactors

Suzuki Method
-    all  Japanese children speak Japanese
-    inborn greatness or mediocrity not known
-    advanced ability can be nurtured  in any child

Why does it matter?
-    parental imperative
-    Olympic imperative
-    Financial imperative

Jason Gulbin
-    South Australian Sports Institute
-    AIS
-    National Coordinator of Talent Search
-    Published on athlete profiling, ex induced muscle damage

Thomas Reily
-    Liv John Moores
-    President-elect of Int. Soc Adv. Kinanthropometry

Darlene Kluka
-    Grambling State University
-      Volleyball talent

Jason Gulbin
Paradigm Shifts in Talent Identification
National Talen Search Coordinator, AIS

Concerned about young athlete and talent identification – but much of the work is also on older athlete

Terminology
Talent (identification/detection) – athletes from outside of the sport (non-specialist, quasi scientific approach, to examine predisposition for a specific sport)
Talent Selection (within the sport, watching athletes)
Talent Development (vital to process)

Intentiaonal Search for answers
Ireland (NCTC) 2001
-    factors prpmoting and inhibiint  success of H Performance players and athletes n=207

USOC 2002
Talent id and devel of US Olympians

AIS 2003
How do elite Athlete develop n=681

NZAS 2004
Linking promise to t podium taskforce report

Why such a focus on this area?

Australian
Typical spending patterns ($AUS)

Costs $37m for a gold medal

$8m for any medal

(Hogan and Norton, 2000)

reducing costs isa  huige bonus

US Census Bureau 2000

Population for Oz significantly less than other countries, so identification critical

National Talent Search Program
10 yr programme
www.ais.org.au/talent
in each academy, talent search coordinator
phase 1: ask pe teachers in highschools to collect data for basic phys test
phase 2: submitted to talent search coordinator
phase 3: if athlete good, invited to talent devel programme

program  issues
-    growth and devel conundrum (too much to measure, children of same age too different)
-    labour intensive  (reject around 95% of data from schools)
-    athlete acceptance uncertainty (not all kids want to do selected sport)
-    variable enthusiasm of schools/teachers
-    information privacy concerns (now, they use id numbers, rather than names)
-    inability to respond to immediate needs of coaches in age group (
-    emerging adulthood and retention

paradigm shifts
-    broad – focussed
-    young – older
-    novice – experienced
-    schools – public domain
-    TID

e.g Cycling
-    ad in paper for talented female cyclists for 500m event
-    females 18-26
-    non-cyclists
-    explosive leg power
-    competition history
-    recruitment via the media
-    initial screening n=247 applicants
-    peak power, 30 sec av power, vertical jump test
-    selected 26 girls
-    age 16-29 (played various sports: bball, rock climbing, athletics, rowing, netball)
-    lab performance: peak power: (1300w, av power: 700w; 10+yrs),  these athletes peak power: 1134W, av power: 625W – after 6weeks (gardner et al, 2002)
-    performance in less than two years, 5 athletes when on to win national comps

Paradigm shifts
-    simple – complex models
-    from physical to physiological
-    focused cohort of 32 selected, based on:
o    water ‘feel’
o    school grades
o    parental background
(molecular biological approach will be critical in advancements)

paradigm shift
-    centralised – decentralised
-    generalist – specialist

Regional postgrads
-    offer maters by research (cycling) – fee-free position plus stipend, to assist talent search coordinators and also develops local support

Summary
Consider maximising talent harvest by supplementing traditional TID approaches

KIM SCHIMMEL
Deep Play – political hierarchies  in  new Olympics

Reconstitution of Olympic space
-    nato resources
-    70000 troops
-    greek forces
-    us coast guard
-    us special forces

private security entitites and gov alliances

eyes and ears of the games

cancellation insurance
-    first time in Olympic history
-    $170m coverage/$6.8m premium  usd
-    terrorism, earthquake, landslides (not construction delay)

Olympic Spirit
-    if terrorism threat to Olympics real, then why stage it in  modern world (july 26, 2004, b KI Angelopoulous)

www.anti2004.net

current cost of Athens 2004  6billion euros, 1% of Greece gross product

Beijing 2008

Kristine Toohey
-    (Sporting) Legacy of Sydney (Cashman)
-    economic (direct and indirect)
-    vbuilt environment (nonsport)
-    info and education
-    public life, politics and culture
-    sport
o    elite, mass (FOCUS ON MASS SPORT IN THIS PRESENTATION), financial, built infrastructure
-    symbols memory history

Mass particpation as Olympic legacy (grassroots sport) – theory/intent
-    de Coubertin
-    Olympic Charter
-    IOC invlve with sport for all, since 1983 (samaracnch)
-    IOC Sport for aLL commission
-    IOC WHO 5th World SFA congress 1994
-    SFA congress declarations sponsored by IOC, Seoul, 1996, bcn 1998, quebec 2000
-    IOC Legacy symposium 2002 (Hein Vergruggen) – to remain educational
-    55 papers: mass participation addressed in 3 (2 winter sports)

Ressearch Q
-    given intent, does hosting OG boost mass sport particpation in host communities?

Past Olympics
-    international conf held in late 1980s in seoul, korea
-    reps from 5 previous Olympics
-    agreed that mass participation most imp
-    but little evidence that actually happens
-    2 exceptions
o    LA 1984: AAFLA – runs number of programmes
o    BCN (Truno, 1995)
o    Sport paritipation in BCN
•    1+ per week
•    1983 36%

Sydney 2000
-    in aus $60m dollars per gold medal

Houlihan from ASC

IOC World Congress on Sport Science (2003, Oct, Athens)

IOC World Congress on Sport Science, Oct, 2003

Genes and Performance
Wednesday, 1030am, Chair: Bengt Saltin

Genes and Health
Greg collier, AGT Biosciences, LTD, Deakin Uni, International Diabetes Institute and South West foundation Texas

PARL a  new gene involved in muscle function and type 2 diabetes

Literature is full of candidate gene studies – not worth the paper their written on

Unique DNA collection

AGT Biosceince cetre for Stat Genomics

Outbread Israeli Sand Rat Colony

Ezpress Technology Platform

AGT Biosceinces has access to number of human DNA sample collections

Access to unique DNA collections from worldwide populations

Major Collaborators

Dr. John Blangero, Texas
-    analysis of genetics of many complex diseases
-    devel opf new stat software
-    SOLAR

Native habitat is semi-arid regions of middle east

Israeli sand Rat develops diabetes and obesity in manner similar to humans

PARL – Preseneilins-associated rhomboid-like protein

7 transmembrane protein

predicted was located in mitochondria – regulating basic muscle function

Located at chromosome 3q27

Reduced gene expression in muscle of diabetic P. obesus

PARL gene expression was increased after exercise-training

Human gene expression data
-    Eric Ravussin, Anthony Civitarese (Pennington Biomedical Research Center)

Discovered by microarrary….

REF: McQuibban, Nature 423, 534 (2003)
-    in mitochondria, yeast equivalent….
-    if knock gene out, mitochondria shrink and don’t function correctly

PARL cleaves human equivalent of OPA1…
-    in diabetic muscle, where decreased expression of PARL, this is a problem

Mitochondrial defects in genes occur before diabetes occurs

Dgene expression I skeletial musc asso with

REF: Kissebah, AH PNAS 97, 14478 (2000)

Genotyping 50 individuals, XXX

Association studies

Look at relationship of XXX

Responsible for about 5% of variation in insulin levels

Largest yet genetic variation causing insulin resistance

Discovered in muscle of animals

Leu26Val variant of parl asso with plasma insuli, with a strong genotype-by-age variant

Finding genes like this is not simple

Need to combine human linkage studies with expression

Not a worthwhile task to identify a gene and find an association

Brain health, and voluntary running
Frank Booth

Epidemiological reports indicate that physically active elderly humans have less cognitive dystnfunction

Laurin Arch Neurol. 58:498, 2001
-    women 65 yars or older, evaluated
-    highlevel of phys activ corresponsed to exercise

What is the mechanism?
How phys activ tie into brain disfunction

Brain derived neuro..factor (BDNF)

Lu Learn, Mem. 2003, 10: 83-85

Wifdenfalk Neurosci Res 34 125: 1999
-    animals running more had increase in XXX (i.e.

Located in hippocampus
-    Hippocampus is highly plastic structure normally asso with cog function, rather than motor

Malcangio Trends Pharmacol Sci 24:116, 2003-10-08

Increase in neurogenesis in hippocampus in animals that are running, compared to animals who are not running

Running primes t brain to enhance neuronal health

It is dogma in medicine that health indivs are the control group and t sick patients are treatment group

It is dogma in exercise that healthy indivs are t treatment group and t sicker population is t control group

Nby calling t phyaically active group t treatment, some others outside of exercise believe that being sedentary is health and thus see no reason to further supp exercise research

Carro, J. Neurosci. 21, 5678, 2001
Carro Mol Neurobi9ol 27, 153, 2003-10-08
-    Increased sendetarism, contributes to an increasing incidence of neurological diseases
-    Sedentary life is a risk factor for neurodegenerative disease

What genese are changing in brain that will protect you from neural degeneration

(Saltin: Have identified candidate genes, now how activate?)

Kinetic Consideration of endurance training adaptations
Name?

Approx 4 weeks before protein increase, through training

In 1980s, mRNA increase detected after 2 weeks

How do muscle cells adapt to exercise?

Metabolic genes: at transcription or mRNA (transient response)

Measure mRNA increases (transient) 48hrs after exercise – inc in protein concentration

Stress genes
Priority Genes
Metabolic/Mitochondrial Genes

Adaptations from training have to stem from acute stimulus (exercise bout)

Trying to indicate different categories of genes

Example: PDK4

protoocal after 4 weeks of one-legged knee extensor exercise train

24 hrs after exercise bout, mRNA back to basel levels

during exercise, why would muscle want to shut of a gene that produces carbohydrates?
-    hyp: as glucose ….muscle no longer want to use…

Endurance (PGC-1)
David Hood, York University, Toronto

Endurance = high capacity of mitochondrial enzyme activity
Not only applicable to endurane athletes, but also sedentary individuals – no exercise, low mitochondrial content and endurance capacity)

Ageing and low physical activity, bring mitochon down

Changes in energy status and calcium,. XXXX l

Leads to change of nucleus – transcription factors

Stimuli that affect transcription of nuclear genes

Mitochondria has its own genome
-    very limited, only codes for 13 genes (and 100s of genes reqd for mitochondrial function)
-    transcription factor for 13 genes is TFAM

Studied with animal model
-    chronic stimulation

typical marker for mitochondria (cytochrome C)
-    Freyseeenet, et al AJP 277, E26, 1999

Performance change
-    muscle force greater fatigue resistance (40% improvement)

PGC-1alpha
-    popular due to widespread effects in cell biology
-    mediates thyroid
-    influ on muscle fibre type
-    affects mitochondrial biogenesis

co-activator not a transcrioption factor
not binding DNA, but binding transcritpopn factors
-    e.g. NRF-1, thyroid receptors (can enhance)

with chronic stim model, looked at PGC-1 level
-    nothing happened after 3 days, but by 5, 7, 10, increase in PGC-1 protein by 50% (Irrcher et al AJP 2003, 284)

used cells for better control
induce to fuse together
-    immature muscle cell. Can make contract, or treat with drug
-    not physiological, but useful
-    is calcium important in mitochondrial biogenesis

number of transcriptors that could be involved in calcium response
-    2.5x inc in PGC-1

effects of exercise on PGC-1 might be mediated by calcium

stimulation model
-    cells stimulated in disk
-    compared to non stimulated
-    looked at factors
o    PGC-1 coactives NRF-1
o    NRF-1 transcriptionally activates Tfam and Cyto c)
o    Tfam imported to mito and inc mtDNA transcption and copy number
o    P38 MAP kinases phosphorylation stablizes PGC-1 protein
o    Irrcher et al AJP… (as abobe)

Effect of altering AMPKalpha activity with AICAR
-    inc in PGC-1 levels
-    which will ultimately affect mito levels

if understand PGC-1, can understand what affects mitochondrial levels

thyroid hormone is another potent stimulator of metabolism
-    high thyroid, high mito
-    hypo-thyroid is opposite
-    also acts by PGC-1

Conclusion

Contractilve activity-endurance signalling of mito bigenesis involves both calcium signals and changed I  ATP turnove and is mediated by PGC-1alpha

Important role of PGC-1 in mataining normal levels…

How neuronal activity controls muscle fiber type and fiber size
S. Schiuaffino, Padova

Dissecting signalling pathways involved in activity-dependant muscle gene regulation

Fiber types in skeletal muscle
Genetics important, but other factors can modulate fibers
-    motorneuron activity is major factor

motorneuron modulate fibre size and fibre type

mechanical effects also important, and one of less explored areas
-    sports that generate tension in muiscle (e.g. weightlifting) can induce muscle hypertrophy
metabolic changes
-    exercise can inc AMP and can activate…?

Try to identify important transaction pathways (activate and block)
-    How?
o    Pharma not helpful
o    Need a genetic approach
•    Somatic transgenesis
•    Transgenic mice: long procedure
•    Instead make transgenic muscles
o    Inject foreign DNA through plasmid
o    In few days, see effect in muscle phenotype
e.g. Changes in MyHC gene expression inducaed by slow motor neuron…

injected mutant  transducers to see if can block effect of nerve or to induce denervated muscle

Murgia et alNature Cell Biol, 2000
Serrano el al PNAS 2001
Pallafaccihna et al PNAS ,2002

Effects: two fibres (injected with foreign DNA) do not express slow myocin

More recently identify transcription factor
-    NFAT (transcip factor, protein binding DNA
o    Known to translocate
o    This translocation been able to….directly, linkd to GFP (fluorescent protein)

Same approach can be used to study muscle hypertrophy

(Saltin: people are on path to find out how performance is regulated)

An overwall enlargement of skeletal muscles is obtained by training and enhanced by anabolic steroids
Name? (Female, Paris)

What’s important in skeletal muscle is, as muscle grows, inc proteins, mitochondria, and myonuclei and satellite cells are controlling this

What happens to nuclei in muscle that accompanies growth of muscle fibre
As indiv trains (power train), is inc in myonuclear number, and anabolic steroids increase myonuclear number
-    amount of cytoplasm remains constant

if inc in no. of nuclei, means that cells have to be added in and must come from myonuclear component

skeletal muscle has cell, reserve cell

satellite cells can proliferate, to allow muscle to grow
-    also used to repair muscle

sat cells can be isolated from muscle and grow from biopsy

sat cells isol from human muscle fibres, have ltd capacity to cell

from birth can make 60-70 divisions
-    most of these lost during rapid growth

then, muscles stop growing
-    from 20-90yrs, maintain capacity to grow and repair skel muscle

Mitotic Clock
-    this is why there is a limited capacity, limited by Telemere (on each chromosome, is a piece of redundant DNA, each time cell divides, small part of this DNA will be lost, after while, signals to stop cells from further division, protects cells from cancer, but limits no. times can divide)

in athletes, no. of satellite cells increase on muscle fibre
-    to inc muscle mass, to repair muscle

same biopsies – look at telemere length, compared to sedentary
-    in elite pro athletes, is small decrease in Tele DNA, muscle is turning over much more than in sedentary population

Athletes with FAMS (Fatigued Athlete Myopathic Syndrome  – Noakes)
-    suffering from chronic fatigue
-    connective tissue abundant
-    inc internal nuclei
-    abnormal mito nuclei

compared with control group of sports people

in this syndrome, where overtrain and genetic background, where cannot replenish sat cells, is pathologic – comparable to genetic disease

similar decrease in sat cells in weightlifters with large doping history

lose telemetric DNA each time cell divides

in cell culture, when isolated from elite athletes, compared to sedentary, doing small amount of regular activity is beneficial, because amateurXXXXX?
-    what level of activity is beneficial, compared to excessive exercise

Muscle satellite cells activation and skeletal muscle mass recognition
Geoff Goldspink

Muscle mass muss be regulated locally and systemically
-    must be local growth factors

Alterantive Splicing of Human IGF-1 gene
-    now call mechano growth factor (only detected in ?)
o    derived from IGF-1
•    IGF-1 genereal growth factor that makes cells inc in size

Normally think of IGF-1 as produced in liver

But MGF has different sequence and different action to systemic factor
Activated by chemical signals quickly after exercise?

49 base insert
-    ie.  Downstream shifts

put cDNA into different plasmids using same techniqe as earlier paper (inject to muscle of mouse)

made some constructs for in vitro
when pt into mouse, found that a group of fibres that hve been tranZZ have inc in size within 2 weeks (25% larger)
-    potent growth factor)

how was it doing this?
-    looked at cells in culture
-    put interest into C2C12 cells
o    saw effects of systemic IGF-1, increased in mass, but …?

Subjected rat to mechanical damage, put in myotoxin agent
-    to see repair, etc

if look at marker for sat cell activation
-    sat cells inc in numbers quickly after injury
-    what sort is activating?
o    Discovered that shortly after injury MGF is expressed
•    Chief contender as major factor activiating sat cells
Need to replenish pool of cells, but not too much

Muscles respond to mechanical signals – how?
-    not enough sat cells
-    seems that they are not activated
-    all muscles do not respond to exercise as well, since do not prod enough MGF

(Saltin: now health subject)

Muscle Contraction
Febbraio?, Female, Brown hair

Plasma IL-6
-    Ostrowksi et al J. Physiol 1998
-    Ostrowski,

Is IL-6 produced during exercise?
-    yes, by working muscles, when it is released into circulation

role of muscle glycogen?
-    systemic vs. local effects
-    transcription rate inc with exercise, but further enhanced when muscle glycogen is XXX?

What does it mean to feed athletes carbohydrates during exercise?
-    IL-6 is inhibited

Febbraio et al 2003

If IL-6 was being produced to signal to liver to produce glucose?
-    not clear from findings

Febbraio hiscock, fischer, sachetti, Pederson
-    2hrs cycling, at 40% VO2max….etc
-    IL-6 can influence glucose production, but co-factor is required

Does IL-6 induce lipolysis?
-    yes. Van hall, et al J clin endorcinol metab june 2003-10-08

Keller, FASEB, J, December, XXXX?

Nutrition – supplementation and sports performance

Ergogenic aids:food for performance or food for thought

Diet, training and ergogenic aids: t evidence from antiquity
Louis Grivetti

Examples of

Doping Substances in Nutritional Supplements: Results of an IOC study
Hans Geyer

Since 1996, Prohormones available over counter

Prohormones of Testosterone
-    DHEA

Prohormones of Nandrolone

Labelling of preparations does not reflect actual content

Parasrampuria M. et al 1998

Insufficient urveyence of prohormones

Now analyse  non hormonal

Broad based study of international market

634 nutritional supplements
purchased from Oct2000 – Nov 2001

in 13 countries

mainlybourght in shops (91.2%) and internet

289 supplements (49%) from prohorone selling companies

Results:
15% of nutritional supp,ements contained anaboligc androgenic not on label

most of positive nutritional included DHEA andendion

most positive products came from US companies (about 90%!)

do only prohormone companies have positive samples?

10% of products from non pro-hormone also positive

does application of such contamination of substances, lead to positive doping results
-    Yes, especially if prohormone of nandrolone

Many victims of contaminated substance?
-    Christie, ottie, etc

Conclusion

Problem of non-hormonal nutritional supplements containing prohibited anabolic-androgeneic is international problem

Consumption can lead to positive doping

Minimize risk, athletes should only buy nutritional supplements from companies which perform qualiy check for prohormones that guaranteee

In germany have companies that

www.osp-koeln.de
-    low risk suppplments (cannot excp

www.dopinginfo.de

in this study, cases were too low to have a physiological  affect

example from Belgium where athlete has managed to gain compensation from

Muscle Glycogen: train low – compete high

Carbo ingestionduring exercise of longdurationin c performance

High muscle glycogen enhances time to exhaustion

What are infol of CHO ingestion and uiscle glycogen on training??

Training adaptation: what is influ of training at low versus high XXX

Training adaptation
-    what is that?
-    Molecular mechanisms?
o    Accumulation of proteins
o    How accumulate protein in muscle?

Prof. Choulis,

Framing it as a problem.

Number of durugs see

Questions

Randy Welberg, USOC presentations

Goldspink
- china, factor 8 – haemophilia

Start the Week with Andrew Marr

On Monday 15th at 830am GMT, I’ll be appearing on the BBC Radio 4 flagship Radio programme to talk abou thte future of humanity and my new book Human Futures: Art in an Age of Uncertainty.

Tune in, or iTune in (then buy the book – great Xmas present).

Andy Miah @ Human Futures: Symposium and Book Preview

Buy the Human Futures book by clicking here

Human Futures conference programme (2008.10.30, Liverpool)

Find below the full Programme for 30 October, 2008, FACT, Liverpool, UK. Book Tickets

And, via a presentation I gave last week, a sense of the book’s visual content:

10.00-10.15    Why Human Futures? Mike Stubbs

10.15-11.45    Envisioning the Future,

Chair: Steve Fuller

10.15-10.40    An Ethics of the Unknown, Russell Blackford    AUS
10.40-11.05 Notes Towards the History of the Present, Norman M Klein    USA
11.05-11.45    Questions & Answers, Discussion

11.45-12.15 Tea and Coffee

12.15-13.45    Designs on the Future,

Chair: Andy Miah

1215-12.45    Design for Debate, Fiona Raby    UK
12.45-13.00    Enhanced Humans as Super-Organisms, Michael Burton     UK
13.00-13.15    Natural Kingdoms and the Post-Biological World, Revital Cohen    UK
13.15-13.45    Questions & Answers

13.45-14.45 Lunch & ISEA 2009 Meeting

14.45-15.45    Life after death in the 21st century,

Chair: Ernest Edmonds    UK

14.45-15.05    Mission Eternity, etoy.CORPORATION    SWITZ
15.05-15.45    Discussants: Paul Brown, Linda Candy    UK

15.45-16.45    Unsustainable Futures? FACT in 2009 ,

Chair: Nicola Triscott

15.45-15.55    Overiew & Summary, Nicola Triscott    UK

Rapporteurs:
15.55-16.05    Steve Fuller
16.05-16.15    Ernest Edmonds
16.15-16.25    Nigel Cameron
16.25-16.45    Laura Sillars

17.15-18.30    Book Launch Reception, Speeches & Signings

Mike Stubbs – Human Futures: The Programme

Andy Miah   – Human Futures: The Book

Related Events
Also taking place in Liverpool that day is the Long Night of the Biennial, an evening of cultural activities running from 8pm-12am. The following day sees the start of the BBC’s Radio 3 Free Thinking Festival, which is also at FACT. If you’ve not had a chance to get to Liverpool during its year as European Capital of Culture, this could be your time.

Human Futures: Art in an Age of Uncertainty

Human Futures: Art in an Age of Uncertainty

Originally uploaded by andymiah

Human Futures: Art in an Age of Uncertainty

website: http://humanfutures.wordpress.com

30 October 2008
Symposium & Book Launch
10.00-5.00pm

Location: FACT, Liverpool, UK (which is also the location of Picturehouse Cinema Liverpool)

The world around us is changing. What will make the first century of the millennium different to the last? What will we love, how will we live, what will keep us awake at night?

Join artists, scientists, ethicists, futurologists as they explore questions, ideas and propositions that explore our changing environment and the challenges humanity faces in the future.

This conference brings together contributors from FACT’s Human Futures: Art in an Age of Uncertainty edited by Andy Miah which features work by George J Annas, Fiona Raby & Anthony Dunne, Norman M Klein and William Sims Bainbridge and Oron Catts.

An updated schedule of the symposium will be added soon, but for more information contact gabrielle.jenks@fact.co.uk

To order the book contact shop@fact.co.uk

Tickets £25.00/20.00 (members and concessions)

Tickets available from 0871 704 2063 or www.picturehouses.co.uk (Liverpool, FACT)

Paralympics 2.0

Just published a new position piece for the Hastings Center online environment, Bioethics Forum:

Friday, June 6, 2008
Paralympics 2.0
BY ANDY MIAH

Oscar Pistorius was right all along, at least for now. He was right to appeal the ruling from the International Association of Athletics Federations that forbade him from competing alongside Olympians in Beijing for one simple reason: he is an Olympian…

http://www.bioethicsforum.org/Court-of-Arbitration-for-Sport-discrimination.asp

Trying out Slideshare

Sports, Medicine and Immortality (London, 28 March 2008)

[Conference Closes 17:00]NB. Programme is subject to change (this information already superseding that contained in the registration form).