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Bioethics

Launch of James Martin Institute, Oxford University (2006, March)

Oxford forumOxford forum    1 Wednesday    2 Tom Kirkwood    2 Rally curing aging: the other sociological obstacle    4 Aubry DNJ de Grey    4 Jay Olshansky    5 How would you assess current aging research, and the prospects for significant breakthroughs in any of its major branches    5 Extending Life Span: Scientific prospects and political obstacles    7 Richard Miller    7 Discussant    9 Paul Hodge    9 Sarah Harper and Kenneth Howse    11 Is more life always a good thing?    11 Stronger?    14 Ellen Heber-Katz    15 Stem cell research and its ethical considerations in china    16 Pei Xuetao, Beijing institute of transfusion medicine, stem cell research center    16 Thursday    19 Cognitive Enhancement    19 Nick    19 Happier    21 Susan Greenfield    21 Professor Lord Richard Layard    23 nick baylis    23 Donald bruce    23 Fairer?    25 Enhancement and Fairness,    25 Julian Savulescu    25 When /if Longer, faster strong, smarter life is happier: reflectins on slower, sustainable and more inclusive life experiences    28 Anil Gupta    28 Gregor Wolbring    29 Enhancement, Justice and rights: immortality    29 John Harris    29 Utility pets    31 Elio caccavale    31 Governable?    31 Baroness Sally Greengross    31 Suzi Leather    32 Creativity and Governance    32 Christopher Newfield    32

Wednesday

845-1030

Tom Kirkwood Oeppen and Vaupel, Science, 2002 – shows continuing  increasee in life expectancy

Idea that ageing is genetically programmed is fundamentally wrong -    illustrated in 1950-s – david lack – zoology in oxford: wild animals never show any intrinsic sign of ageing, because they die young – do not have a chance to become old

thus, no potential…

peter medawa and george Williams

selection shadow – animals die young because environment is dangerous – don’t need to grow old

disposable soma theory – Kirkwood, nature 1977 -    animals invest only what they see to be necessary to remain competitive

how much should animals bother in maintaining and repair

shouldn’t talk about natural selection in these terms

geens make choices

dawkins – imperative on genes

regardless of thesis, realities exist

how much invest in reproducing or repairing

there is no genetic programme for ageing. We age because in evol past…

ageing process model

age related frailty, disability, and disease – accumulation of cellular defects, caused by random molecular damage

build bridges between biomedical and social sciences -    because we know influ of environment

we know that healthy lifestyle and food can affect this

malleiability of the ageing process -    by decreasing exposure to damage (nutrition, lifestyle, environment) -    enhance natural mechanisms for protection and repairt ( nutrition, novel drugs, stem cell)

traditional view of ageing -    is biololgically determined with inbuilt limit -    progressive, irreversible capacity -    ageing distinct phase of life style -    disases of ageing distinct from intrinsic underlying processes of healthy ageing

dismiss the first -    we are programmed for survival not death -    ageing intrinsically malleable -    youth and age are continuum -    intrinsic ageing and many age related diseases share common underlying

successes and limitations – managing expectations -    current success o    good ustdg, but more to learn o    beginnings of ustdg of underlying mechanisms of ageing and age relationship disease o    can modify longevity in some animal models – fruit fly, etc – but in nearly every case is uncertain -    Current limitations o    V little evidence for effecicaly of drug/nutraceutical effects o    Cannot yet perform successful gene therapy for well-defined targets such as cystic fibrosis o    Cannot yet perform successful stem cell therapy for well defined targets o    Potential future discussions largely speculative and unacceptable in other biomedical spheres

Meeting

Education and public engagement- education and professional training -    expand research capacity in ageing science -    inc professions and industry

Public engagement- government

Public engagement – Citizens -    challenge and change negative atts to ageing

Ageing: scientific Aspects – select committee publication from last year

Rally curing aging: the other sociological obstacle Aubry DNJ de Grey

Strategies for engineered Negligle Senescene (SENS)

Jbs haldane, 1963

Four stages of acceptance i)    worthless nonsense…

Arthur c Clarke

New ideas pas through three periods Tom Kirkwood

The rejuvenation dividend: the precepts -    stretching frailty is v hard, luckilty -    the faster we delay frailty without stretching it, the fewer people wil be frail o    rate, not extent, of progress is key -    partial repair gives more delay than partial prevention o    how achieve? – eg. Someone aged a lot, only so much we can do – concept of reserve: amount of additional damage your body can afford to accumulate before things go wrong.  How help: start sooner – be healthy earlier; -    when a plausible rate of medical progress is presumed o    even better repair is possible!

Promising progress or arrogant nonsense

Embo reports 2005 nov 6,(11) 1006-=1008 -    None of us believes tht plans to ‘engineer’ the body to prevent ageing indefinitely or to turn old people young again have the remotest chance to success’

Reasons given for dismissing SENS -    is unscientific: ‘ easily recognized as a pretence by those -    ‘nnoneof pthe sens] -    T

Technology and science differe in how they best evaluate evidence -    goal: powered flight. Solutions? o    Engineer vs scientist

Scientists way of analyzing evidence is misapplied in context of technological goal

‘if an expet cant explain something in his field to an educated laymen…’

the sens challenge with MIT Technology review – www.technologyreview.com -    offered $20,000 to discredit de Grey – open to any molecular -    editor of technology review thought high profile panel -    panel is: craig venter, rod brooks, Nathan myrvhold, vikram kumar, anita goel -    two entries submitted, another threatened

sens is following Gandhi -    firs tthey ignore you -    then they laugh ay ou -    then they oopose you -    then they say they were with you all along

de grey, adnj, embro Reports 2005; 6(11): 1000 -    offer no apology for using media interest in llife extn to make the biologiyt of ageing an exception to planck’s observation that science advances funeral by funaeral, lives lots of them, are at stake

life extension not just science, a biomedical prob too

causes considerable suffering

spoke

himsworht and goldacre, 1999, bmj, 319: 1138-1339 -    the older you are, the healthier you’ve been (Perls)

Jay Olshansky How would you assess current aging research, and the prospects for significant breakthroughs in any of its major branches

(background in sociology, but leading biodemographers) now at Uni of Illinois

was at US President’s council in 2002 on ageing

in answer to that, prefer question

can we justify theattempts to slow ageing and how?

answerL yes:

March ‘The Scientist’ -    co author with Daniel perry, Richard a miller, Robert n. butler

if can extend healthy life, it would pay longevity dividends, far in excess of anything we could imagine, for indivs and nations

ME: how nations?

Brendon Mayer – editor support for scientist publication

Rationale for pursuing the ‘longevity dividend’ is already in place -    current medical model will not work in long run

current medical model -    biological limit to life

pharmaceutical industry

surgical procedures

early detection of disease

already commited ourselves emotionally, financially to extending lifelonglearning

the value of life at every age -    we value it at every age

by  slowing aging we willl do what no drug, surgical procedure, or behaviour modification can ever do – extend your years of youthful vigor and simiulatenously postpone all t costly, disably, and legal conditions expressed at later ages

‘in pursuit of the longeviry dividend’ – TITLe

operative word is: DELAY

not searching for fountain of youth

not proposing transformation of older people to younger

not stopping or reversing aging process

the words, ‘stopping’ and ‘reversing’ should not be in vocabulary

not dramatic extension of duration of lifelonglearning

‘pursuing health extension’ -    improvement in public health -    extension of period of youthful health and vigor -    reductions in frailyy and disability at all ages

if we succeed in delaying aging, bonuses will likely be extn of life and dramatic….

Target -    7 year delay in boil process of ageing

why 7? -    it tooko 100 yrs for the total mortality risk of a 74… -    Olshanksy, carnes and grahn, 1998 – confronting t boundaries… -    Brody, 1983, prospects for an ageing population, nature -    The7 is associated with great impact to reduce everything associatd with ageing by half

Longevity dividend -    calling on congres to invest 3 biillion dollars annually o    dividends •    compression of mortality and morbidity •    reduction in age-specific risk of all diseases •    reduction health care costs •    inc indiv and national wealth •    benefits will occur for lifespan and across generations •    health and economic benefits will exceed elimination of cancer or hearth disease

if we don’t do this?

For those pushing immortality – this is how you would start doing it

Don’t want people making it too old age extremely frail

Extending Life Span: Scientific prospects and political obstacles Richard Miller

ME: first says should not talk about radical etension,

Traditional approach to medical research – one disease at a time

But conquering one cancer, for eg, would have limited yield

Antiaging interventions. Solid facts -    seer caloric restriction increases mean and maximal life span in mice -    with ex they get old later

now 10 gene mutations that can accomplish same effect

other mutants with lover igf-1 levels also live longer than controls -    dogs too: low igf-1 and long life span

treat later life diseases as a group

ageing can be delayed by two diets and by each of > 9 genes, in laboratory animals that repsont o many of the same drugs and hormones that we do

ME: comments that those making biggest claims about extension get headlines

Longevity projectopn: the reality Based ™ approach -    calorific rstriction: 30-40% -    small dogs: 40% -    methionine..

thesis: the obstacles to finding a ‘cure’ for aging are 85% political and 15% scientific

research on the ageing process -    for every $100 us congress spends on medical, 6cents goes to ageing

why haven’t we cured aging yet? (ie learned how to slow) -    most ‘public’ gerontologist are crackpots and who wants to hang out with that sort of person?

We don’t want to be associated – gi

Eg. Deepak Chopra DHEA Growth Hormne Mealtonin Miracle

This is clearly a scheme for making money

Why haven’t we cured ageing yet?- -= is viewed (incoorectly) as incurable

voters relatives died of some diseas, os diseassa have lobbies, so congress spends money on diseases

aging research lobby v small

drugs that actually slow aging cannot be tested in time to show a profit within the ceo’s lifetime

drugs purported to slow aging are highly profitable even though they don’t work

a poiticaian who wants to conquer cancer or conquer aids is a hero

a politician who wants to slow aging is a nut case

people don’t unstd that quickest way to help diseas

socioo of science

scientists follow money

young scientist follow high tech and need papers NOW, alas key biogerontology expts are often low tech and take a few years

to be honest, it’s not that easy to cure..

gerontologiphobia n: a syndrome charac by a fea of what antiaging might do to soc

‘how far could we go. Too far is one possible answer…like drunks with drink, enough is…

the ‘lynch’ position -    ‘stop research on aging because we don’t want t world to fill up with old people’ -    ethical

if presented to people 200 yrs ago – would people say we don’t want insulin, etc

ethically when:

a)    me only b)    well ok, you too c)    but not them. We don’t want the world to fill up with old people, now do we.

Discussant Paul Hodge

Thanks peter healey

Baby boomers Nothing done after this

2005 whitehouse conference dec 14, was asked to testify on policy issues and mentioned baby boomers, but first point was longevity

Questions and Answers

Question from Scot: key issues is delay, but if can do repair, that is better. Why isn’t repair possible?

Jaye: similar concept to Aubrey

Aubrey: difference are to do with feasibility of approaches.

Alex Kalasha from WHO: was at whitehouse conf and disappointing that such advanced nation presented such a poor public debate around science. How optimistic are you with the $3billion?

Jaye: agree with Bob Butler’s conclusion that we need to be ambitious. Buit relative to amount of money on medicaare - $300billion, going ater one disease at a time, is miniscule. This is just the beginning of full court press to go after aging in a much more aggressive way thant we have gone after diseases previously

Tom: must be more connectivity between science and political/social agenda. I don’t think we are saying same thing. I think Aubrey is trying to generate enthusiasm that sidesteps practical problems facing problem. We all want the science to come through, but it doesn’t serve any usefl purpose to extrapolate beyond immediate. No great exptn about extn but might change profile of health.trying to find better way to age, and if that leads to life extension, that’s great.

Jay: aging research should appeal to people. Same goes for why should talk about delay rather than sudden immortaility

Aubrey: cross agency cooperation. In my own work, many exptl scientists not gerontologisty, many working on repair and regeneration technology. Not simply lines on graphs but collaborations. On political side, emphasise that actually it’s perfectly ok to have signif life extn as side benefit to addressing frailty and decline.

Chaotics, Philidelphiaa.: historical  fallacy, several speakers say we are in a special age. Food, etc. no reason to believe we are in any special time or place. In time of Copernicus, Einstein, etc, every time is special. Advances occurring no diff. Aubrey pointed out max planck’s progress thesis, but he might have chosen Voltaire: I have only made but one prayer…please render my enemies ridiculous, and

Donald Bruce: some speakers mentioned the ‘sales pitch’. What is real in this debate? Question of Shakespeare 7 ages of sans…. All the idea of whatever it is you will do, must have so many things right all at once. Getting one or two bits right not enough. Seems a matter of belief rather than evidence.

Tom: how do you know you wont mke things worse? The rate of progress on research on aging is quite slow. Need to know aims and objectives and priorities. You might say it’s a terrible thing to die of heart disease, but it is quick and if solve, then will leave vulnerable to other degenerative diseases, such as alzheimers etc. it is an imp q.

XX: imp but not answerable in rational way 20 years ago, but middle part of talk was about that. What is evidence. By delaying, one does create animals which postpone, together, these diseases.tf, hypothetical worries about creating people that might have other probs is imp, but are ways that we can begin this.

Jay: what happens if we don’t intervene.

11-1200

Lecture Theatre 5 Sarah Harper and Kenneth Howse Is more life always a good thing?

Sarah: I am an anthropologist by training, interested in demographic and social. Kenneth has a philosophy background.

Discuss both extending max life span, but also extending normal active healthy life span for everyone in world.

IT is better for everyone to live slightly longer than a few much longer.

Now have 4 or 5 generations alive at same time.

Kenneth

2 scenarios -    on one side, Jay, Richard and Tom: best prospect of reducing burden of ill health is to go straight for biology of aging -    everyone endorsed that and concerned to get across to you that this was a good thing, otherwise stick with what current medicine can offer, which is not so useful. -    They suggested that nobody would argue against this -    Next to this, is Aubrey’s ideas:

Must consider continuities and discontinuities of these 2 projects.

Not just a feasibility debate. Must confront gerontophobia

I will lay out the case on behalf of gerontophobia

The question Richard miller flagged up is one that a lot of people have taken very seriously

For eg. Jay mentioned US President’s Council Beyond Therapy, they said ‘let’s suppose we can double life expectancy’ would it be a good thing? General conclusions of that report were mainly sceptical. Commissions report did not come down on one side.

ME: should it have? I don’t think this was its remit. Would we have wanted it to? Public debate. Ethical engagement.

Does Jay’s commitment lead to Aubrey’s vision.

ME: we continually refer to Aubrey’s view in a same way to how we refer to Huxley’s

David Sarfadi, Chaotics: husband of working scientist, when they go into lab, don’t have goal to double lifespan of mouse, for instance. You are altering genes that have effects. Don’t choose which route, it’s what the science renders. If scientist thought was bad idea, would have to kill mouse and tell nobody. Never happens, usually scientist runs to NYT. Society will deal with those choices. Always be confronted with maximal of possibility.

Kenneth: but policy makers decide how much we pay.

David: capital will demonstrate: private funders will begin.

Kenneth: in Europe, worry of inequalities

Bill Baingridge, national science foundation: certainly rtrue that long term goals do shape funding. Rhetoric is that start up companies is on short term goals rather than longer term ones.

XX: do not find 2 approaches mutually exclusive. They will feed each other.

Evelyne Bull, ox student.

Kenneth: if I say yes to Jay, am I committed to Aubrey?

Sarah: public privte us Europe divide.

Raphael Ramirez, oxford: advising on patenting. If life becomes a bnusiness, acceptability of that differes. Nobel prize winner in ox who said whoever igns TRIPS agreement, signed death warrant of tens of thousands of Africans. Human rights vs property rights. Even today can patent mouse in USA. Who owns the findingsa. Is it a good thing? What criteria and ‘for whom’. Who frames this? Not good for some poor somalian.

Kenneth: choice as indiv and collectively.

Rachel Hurst, disability and human rights: assumnption that health is absence of disease and disability. I don’t agree. Whichever side we go down, we need to recog that is humans that we are talking about and are they going to be contained. Whatever way you choose, does it matter, if retaining ethical premise that are dealing with human beings.

Sue (Oxford): assumption that longer means happier.

Anil Gupter: is strongter, etc a better life. Health not absense of sickness, it is well-being.  What is a good thing? When communities.  Society not appreciated handicaps of those who do not see those of others.

ME: allocation of resources as assertion about what is happiness.

Robin Hanson, Economist: often float into abstractions. Prospect of doubling. We have already doubled our lifespan.

ME: is is thte same kind of doubling. Is doubling the issue?

Question: disting ‘whether’ from ‘what if’. Policy has tendency to react to convergent of diff hells. What are hells and heavens in traking this forward.

Donald Bruce: anthropology: what is our ustdg of the human.  Premise is based on functional part of us.  Diminished view of human. I was once on a sci fi programme – ‘what would it be like to live forever’ what do you do after 2000 years. Ok, stupid scenario. Fact that prince charles not king at his age, phenomenon exponential in this situation.

Sarah: finality, goals, - must keep that within human condition. Mustn’t negate that side.

ME: a ritual death?

Question: reproductive span should go to 80-90 yrs old.

Wolfgang Luca: don’t think will hit 9billion level of population, because birthrate decline. Glad that reproduction has been added to reproduction. Why gerontophobia is with diffciculty of imagining.  If assume 3-4 yrs inc per decade, then in west Europe, third of entire population above 80. Prob for legal pension. V little poss for change. Life expectancy goes beyond state increase in retirement age.

Jerry Rav, JMI: is there a culture where is accepted for people to dcide when to go. People in good health.

Gupter: in border of west Bengal and Bangladesh, is custom that go to forest and death by tiger eating you is most devine death.

Sarah: aboriginal – indivs do decide that burden they place on society means they should die. But these are problematic discussions.

James (JMI): by what criteria do we measure a good life. Having discussion about people as indivs planning to life extend as long as poss. Not sure psychologically a good idea. People make choices that involve a whole range of issues. One of obvious techniques of life extension is constrained calorifgic intake – opposite side of prob with obesity. Raises prob. People make choices in that context – taking too much, which makes you live less. These are issues of preventative medicine and public health. People don’t choose to make choices. Am I reasding this issue of calorific intake right. Biggest medical issue at moment is absolute opposite of that.  Food and life choices and risk taking in a social context.

Kenneth: fair amount of disagreement

James: healthcare funding so stilted towards treatement rather than preventionl

??: if we’re right about fertility decline in developing countries, major prob not aging but reproduction.

Srah: various myths about aging. By 2050 2 billion people in developing nations over 50.. not just a developed world problem.

Bill SharpE:  continuity/discontinuity thesis.  Systemic prob. Community in formation here. Contention over goals. None of them know degree of continuity between 2 goals. They are self admitting that we cant tell. Is it worth it? Clearly yes. I have had pleasure watching parents move into 90s. every year has been worth it for them. Only issue is when problems become insurmountable. Tigers as good as some alternatives. Living and learning has indefinite pleasure and learning. Gandhi: live as if you die tomorrow and learn as if you will live forever.

Kahn, oxford:  main issue arising for devle countries. What would be the healthy life expectancy, not expectancy at all.

Michael Morrison, Uni of Nottingham: medical and social ideas of health. Strong strteam of technological determinism.

1300-1500

Stronger? Chair: Zhanfeng Cui

Ellen Heber-Katz

Regrowth of tissue

Tissue remodelling during regeneration

DL Stocum

Transfer cells across scar tissue

If can identify cell might be able tccccccccccccccccc

Kevin Warwick

I, Robot with Will Smith

Last implant was chip into nervous system. 100 electrodes fired into medial nerve in left arm – 10,000 nerve fibres, receive sensory signals.

Not as reported in guardian that fits into top pocket, but it was fired into nervous system. Each pin is 1.5mm long. Nerve fibres are 3.5-4mm in diameter.

What could we do with it.

Link with computer

Human senses 5% of world around them – stats from CERN.

ME: how is this different from extra sensory experience through drug use?

Ultra sonic and infrared

What is difference between tv having it and you having it, ethically?

Future of research

With wife, did direct telegraphic nervous system link – brain to brain

Remaining humans will be sub-set.

Stem cell research and its ethical considerations in china Pei Xuetao, Beijing institute of transfusion medicine, stem cell research center

Selfrenewal (Extensive or unlimited) Clonal Multilineage differentation Plasticity Engraftment and repopulation

Stem cells can undergo self-renewal

Stem cells – foundation of regenerative medicine

Big problem with aging in china

Number of stem cell and regen med research projects funded by NSFC annually from 199-2005

Two projects for stem cell research and another two projects for tissue engi neering supported by t Chinese national key project of basic research

Ethical considerations of human embryonic stem cells big issue now

Basic principles of life ethics -    respect, non-mal, beneficience, justice

use of stem cell technology -    replaceable tissues/organs -    repair defective cell types -    gene therapy -    chemotherapy -    drug discover -    tumour therapy

ethical debate – i: derivation of ESCs -    harvesting es cells destroys t blastocyst -    ‘this is murder’ -    how to think about embryo, t dispute tht if embryo is a living life has become focus question on each side of dispute

human life, hnumanbeing or human person

definition of personhood - conscio0usly performing personal acts elmi

worldwide cloning research legislation

illegal in china

ethical debate III -    any kinds of

etihical debate in chona -    gov: against reprod cloning, support therapeutic -    scientist: balance sci freedom with erthical constraint public: hESC should not be banned Confucian: human embryo not a person Buddhistic: reincarnation occurs at birth

Ethical Guidelines and regulations for Human ES cell research in china Promiulagated by the ministroy of sc I and technology

Principled stance of china gov -    support biotech -    acknowl and observe international basic principle -    banning human clopning

image of person standing by wal with shadow projecting. At top of wall is apple. Person is reaching for it.

Human Assistance/Function Augmentation/Capability Enahncement by Robotic Advanced Technologies Nagoya University Toshio FUKUDA

Safety, security health -    environment, daily life, war and terrorism, product, health, ITS, communication, plant

Transition of work area -    manufacturing industry -    sensing, recognition, adaptation, learning, security -    service industry o    medical robot o    care robot o    transfer system o    security o    competition (RoboCup, Sport)

Humanoid Robot Vs

Rehabilitation Robot

Society in 21st century

Comfortable space using Robot Technology and Information Technology - in home or

human support technology 1.    physical support, sensory/actuation augmentation 2.    skill support; dexterity/experience, language 3.    intelligence support, information, communication, knowledge, augmentation, enhancement, decision making

human machine symbiosis 1.    cell level 2.    human and unit level (arm leg) 3.    multi human and indiv level (multirobot) 4.    organic device level (stomach, heart) 5.    human and indiv level (one to one) 6.    network level (multi robot and multihuman through network)

Robots: WE4, SAYA, KISMET, CRF1

CRF3 -    quiz, Questions and Answers -    email retrieval -    reaction of touch sensor

communication with CRF multi-scale bio-operations

engineering, bio, medical

Summary: stronger? -    human friendly robnotic technology to be advanced ofr aged society -    physical/skill/intelligence supports realizable in near future -    domains for applications: experts in medical and others. Daily life support for disabled and aged -    usage: depends on human decision back to society

natika XXX: amazement and alarm; only available to only those who can afford it

Donald bruce:

Norton, uni of dankstedt: interested in japan and robotics. What do you think about Kevin warwick. You want to make robots work for us, he wants to be one. Who is better off?

Response:

The Nature of Human Natures?

Chair: James Tansey James Hughes, James J.

Lee Silver

Thursday

845-1030

Smarter?

Cognitive Enhancement Nick

Forms of enhancing intelligence

Stimulants (Lee and Ma, 1995) Nutrients and hormones (Martinez and Kesner 1991) Cholinergic agonists (McGaugh and Petrinoc 1995, Levin 1992, Buccafusco, et al 1995) Piracetam famly Ampakines Consolidation enhancers

Learning enhancement for unlearning phobias and addictions (Pittman 2002; hall 2003)

Animal models

Genetic enhancement of memory

Pre- and perinatal enhancement -    giving choline supp to pregnant rats improves performance of pups (Meck, Smith and Williams 1987; Mellott et al 2004)

external software and hardware enhancements

multielectrode recordings from more than 300 electrodes (Nicolelis et al 2003, Carmena et al 2003, Shenoy et al 2003) Kennedy and Makay 1998 Alteheld et al 2004, von Wild et al 2002

Uploading Neuromorphic engineering Classical AI

Psychopharmacology of cognitive enhancement Dr Danielle Turner, Uni of Cambridge

An espresso at three in the morning is just so last year, article form Stephen Phillips (THES, last week)

Most people engage with some form of enhancement almost every day

Effective cognitive enhancement for patients -    quality of life -    benefits to patient, family, society

drugs as tools to investigate how the normal brain works

to improve cognitio0n in healthy indivs for eg -    military

one-touch tower of London planning task

modafinil

Questions and Answers

Daniel Reynolds

Jennifer Swift

Lucy Kimble, SAID: will robots be smart enough to bring up children

James Tansey – ‘dyfunctional’ people often are most high performing Joel: why would an athlete want to use modafinil?

Danielle: when Kelly white took, was not a specifically banned substance. Not sure if would enhance. Perhaps makes less impulsive.

Question

Danielle: first time take Ritalin, performance improves. Only helps in novel situation. When familiar, it drops.

Chris, nanotech, Santa Barbera: cognitive effects of hockey stick (graph curve)

David Wood (Scottish, mobile phone industry)

Alfred nordmann – nordmann@phil.tu-darmstadt.de

Happier

Susan Greenfield

Healthier and longer lives Increased leisure Expectation of happiness

The thin line…between therapy and lifestyle

Drugs work by -    increasing chemical messewnger (speed) -    slow down removal (cocaine) -    empty stores (ecstacy) -    block it acting (trancquiliers) -    act as imposter (heroin) -    making trarget more /less sensitive (addiction)

cure for life experiences -    flu -    feeling blue -    about to pig-out -    moody -    shy -    need energy? -    Too much energy -    Stupid

Taking a drug might not make you better

Efficacy of smart drug determined by baseline – ie more XX your attention more effective they willl be

So called transhumanist idea probc

Difference between well-being and happiness

Depression -    if medicate, not making them ecstatically happy -    outside world remote -    colourless -    emptionally numb -    little movement -    anhedonia

opposite of this ‘active happiness’

screen induced as well as drug induced – plays some computer game footage.

Are we going to live in this cyberworld which will not giove us the kind of happiness that we really want

Total abandonment

Susan Greenfield – Tomorrow’s People

Alleviation of suffering Active abandonment Fulfilment

Options -    Techno-ism: no indiv, no fulfilment -    Fundamentalism: fulfilment, no individual -    Consumerism: indiv, no fulfilment -    ..or we could use to development new technology o    eureka moment! Basis for happiness.

Professor Lord Richard Layard LSE, Economics, Centre for Economic Performance – Programme on Well-being Welfare to work; chaired UN Universities Economic ; Happiness: lessons from  - published march now translated into 11 languages

Happiness is simpler. A single dimension of various emotions.

David Nutt

Already there? -    happy pills o    pejorative term by both right and left wing media with antipathy to t drug treatment of depression o    refer usually to antidep especially new ones, aprtic SSRIs (Prozac, Seroxat, Lustral) o    previously benzodiazepines (Valium, Ativan) o    but none of these make people happy

potential routes for inc happi -    decrease stress o    amines – 5HT (noradrenaline) etc o    peptides – especially hpa axis -    active ‘happiness’ circuits o    opiates, alcohol-like, ecstacy-like, drugs o    intracranial stimulation (deep brain stimulation)

nick baylis

not happiness, but improvement – in life. Invest in healthy relationships

Donald bruce

Broken shower story

Nuclear energy industry

Computers

What can go wrong….

Athletics -    would have known that he cheated if he had used a pill to beat dave Bedford

would we see drug induced athlete as epitome of human ability or something else.

Are there rules about human race? If we step outside, are we less human?

1530

Stem Cell research

Current Policy in Europe

China, loose standards of ethical review.

Problems.

Human genome project progress through huge global collaboration

Not poss with stem cell because some countries ban it

One of probs is

English researchers want to collab with china or India, but heldback because funding bodies concerned about how the research is carried out in development world -    woo sung wong controversty (korea) – were supposed to come to the conference

Jerry Shatens

Flexible regulation with respect to research

Australia initially rejected cloning research and is now revisiting that

Has had a lot of attention in the media

‘funding bodies must take adequate steps to satisfy themselves that those they fund intend to carry out their research ethically and in accordance with relevant national regulations and appropriate international guidance as it emerges’.

Questions and Answers

Question: if woman consented to organ donation, would it be ethical to remove her eggs.

Julian: healthy young eggs better for research than older eggs. Science would like eggs from young healthy women, but many people’s intuition. Risks of donation eggs, small but real. Superobviation drugs associated with rare but lethal conditions

What risks can healthy individuals undergo for research? I say ‘quite significant’, but others say much less.

John harris and savulescu: like a horse race. What matters is which horse crosses the lline first, but cannot and should not back just one horse – must be collaborative.

1630

Fairer? Enhancement and Fairness, Julian Savulescu

George Annas ‘improved, posthumans would inevitably come to view the ‘naturals’ as inferor, as  subspecies….

Francis Fukuyama -    ‘the first victim of transhumanism might be equality…underlying this idea…

Bill McKibben -    these would be mere consumer decisions – but aht also means that they would benefit the rich far more than the poor’

nothing new about enhancement -    rich buy better o    education o    health care o    technology

these can alter biology direct biological intervention raises no new ethical issues -    just a question of which theory of justice goven socity

4 concepts - 1. Fairness or justice 2. enhancement 3. natural distribution of capabilities and disabilities 4. 1. fairness/justice - util egal: strict equality; rawls maximnl prioritarian

john Mackie ‘rights, utility, and universalisation’ -    right to fair go

maximising version of giving peoplpe a ‘fair go’ -    give as many people as poss a decent (reasonable) chance of decent (good) life

enhancement- -    makes our lives better -    increases t chance of us having a good life – instrumental goods (health, wealth)

biological – mor beautiful, stronger psychology – better person social, incliuding socially determined environment – cleaner air, better osiac secuiorty controversial – biological or internal technological enhacenemtns – focus on these

enhamcement, disability, and capability

well-being: how well a life goes (goodness); difficult to distribute well-being capability: state of person that inc probab of achieving a good life disability: state of person…

what is a disability?

Typically, deafness etc

But is context dependent

Atopic tendency -    asthma in developed world -    potection against worm infestation in devl world

need to fix or predict social or other environment circums

biology/psychology as capability/disability -    biological or psychology state can be predicted as ether -    biologica contributes to health but how well life goes -    we are all disabled

eg self control -    in 1960s Walter Mischel conducted impulse control, 4 year old children with marshmellow, request resist, but if not give two. Followed up and the ‘delay gratification’ more likely to succeed – impulse control

other categories capacity to work hard or be lazy – gene therapy in monkeys

Buchanan, Brock, Daniels and Wikler (‘all purpose goods’ -    intelligence, memory, self-discipline, foresight….

Autonomy enhancing traits Social Moral character

Genes, not men, may hold the key to femal pleasure’- genes accounted for 31% of the chance of having an orgasm during intercourse and 51% during masturbation

3. distribution of capabilities and disabilities

not distrib equally

eg. Intelligence. – normal distribution

example performance enhancement in sport: EPO -    natural hormone produced by kidney which stim red blood celss prod -    Eero Maentyranta: 3 medals, had 40-50% more red blood cells

Correcting natural inequality -    increase red blood cell level o    natural

capability we could efficiently set red blood cell level -    safety -    performance

sport -    test of natural biology? -    We want to reward naturally best

In sport, only one winner

No reason why there has to be a person who comes last in life

If unit not red cells, but units of the good life -    is it really just that there is a natural distrib in how well life goes

social not biological enhancement -    good reasons to prefer social rather than biological o    if safer, more likely to be successful, if justice requires it, etc o    but vice versa – sometimes cheaper, easier, and fairere to alter biology

responses to bioconservatives -    nature alots advantage and disadv with no mind to fairness -    enhancement improves peoples lives -    how well t lives of those who are disav go depends on

conclusion -    fairness requires enhancement -    failing to enahcnce may result in signif injustice (supervaccine) -    conservatives guilty of social detemrinism

When /if Longer, faster strong, smarter life is happier: reflectins on slower, sustainable and more inclusive life experiences Anil Gupta anilg@sristi.org

disabled or differently abled?

When live longer do we exp more?

What is purpose of more meaningful lifelonglearning -    accommodates community happiness -    sensitivey towards children

what is human capital? -    depth of social networks fo which one is a aprt -    how do we enhance this depth -    are we afraid of being in company of other normal impulsive, intuitive and inspirational people

ways of knowing -    knowing, feeling and doing

who is smarter, stronger and stable? -    smartness lies in sharing opps

Towards a Fairer Distribution of Technology… Zhao Yangdong

Inequality and immunisatin

Gregor Wolbring

Enhancement would be doping

Link enhancement products to health

2 chjoices

WHO definition – complete social well-being not just absence of disease -    social well-being still part of health

more common now is well-being above and health is a determinant of it

for today, health is seen as just medical health

transhjumanist model of health -    no matter how conventionally medically healthy, body is defined as limited and in need of modification

‘everyone is impaired’ -    Rachel also said this, but with diff connotation

Amatyra sen

David nutt -    pharma not going into happier drugs – cannot sell in medical framework so too many probs

transhumanisation of medicalisation

1830

Enhancement, Justice and rights: immortality John Harris

Art Panel

Teresa.dilon@polarproduce.org

Theatre/psychology

Polar produce, mixed media experiences Ma, music within therapeutic context

What kinds of knowledge do art/design practitioners have?

Why – it’s I the mix, baby’ Interdisciplinarity Slippage Languages and knowledges Lens and frames Fun

Difference between artist and scientist

Approach, language, tools, privileging certain types of knowledge, methods, outcomes, reception, interpretations

Comparisons -    cyclic creative processes, question finding, depth and explorationh, knowledge generation, outputs/outcomes, transformations

ME: artists believe they are the only ones who are marginal

Blurring the traditional ‘audience-spectator’ relationships – where the audience becomes part of the performance – and the performer becomes a member of the audience

Tina Gonsalves UCL Cognitive Sci, AHRC, ACE fellowship

She had read some pieces

Mobile phone project with University of Toronto

Rama gheerawo Research fellow and programme leader Designing the future through working with users The Helen hamlyn research centre Royal College of Art]

Inclusive design Disability discrimination act 2004

Video ethnography

Utility pets Elio caccavale

GM pets that do not give you the allergy

Translator for dog

Cloning pets

Genetic saving and clone, inc

Transgenic, ornamental fish, taikong corp

Utility pet memento form -    request part of animal to be preserved

www.eliocaccavale.com

social fiction scenario

1100-1230

Governable?

Baroness Sally Greengross

Can we make it fair What is role of state (government bodies) Poss to do it without them?

Wolfgang Lutz Vienna Institute of Demography Austrian Academy of Sciences

Suzi Leather

Spain, compensation of €900 for egg donation – how consistent with altruism?

Last year, euro parliament raised profile on Romanian clinic – led to government intervention

Concern about people trafficking

If we could only enhance one charac or trait, which one would we choose if we wanted to enhance the greatest benefit for humanity as a whole?

Creativity and Governance Christopher Newfield

Uni of California, santa barbera Cultural theorist and anti-dualist Centre for nanotechnolo

Disjunction between economic thought and cultural thought

The Innovator’s Dilemma -    clayton m christenen

open science model

minimum proprietary, peer review, open pub: 1.    tell the people 2.    listen to the people

better model

governance is governmentality, not just regulation (Foucault) -    care for all t elements of a system in their relations

flourishing -    Coleridge: intventions are ‘proofs of original genius only as far as they are modified by a predominant passion, or…when a human and intellectual life is transffered to them from the poet’s own spirit’

The creative process -    mihaly csikszentmihalyi (+CN) o    preparation o    incubation o    insight o    evaluation o    elaboration

governance (governmentality) must support this for community members

governing collaborations -    Simonton, rhotgen, 2003, seibold, henwfield

Maximising innovation is to set up a social system

Better model 1.    governance is governmentality, not just regulation 2.    better modelled as collaborative creativity than as markets, regulation or top-down management (but includes these) 3.    collaborative creativity works much better with equality in relations , in labs (valued ‘bridges’) 4.    analogy among nations: innovation cannot be separated from justice 5.    governance via global institutions promoting egalitarian communication among the diverse knowledge of all stakeholders

better model -    from ‘the lexus or the olive tree’

to innovation via justice

Questions and Answers

Question: egg donation is uncomfortable and not without risk, if no compensation, why would a woman do this?

Suzi: sheer altruism is one, but v few people. All donors extensively counselled. Physical and emotional risks. In uk, we do allow egg sharing – in exchnge for reduce cost. Ie woman using ivf to give away some of eggs to 1 or 2 other women and recompensed in kind with reduced cost for treatment. If open system of donation, poss that fewer people will come through, but might deal with by targeting donor. Earlier, sperm donation was 18-24, now are 35-40 yr olds.

James Hughes:

Suzi: challenge your view that regulation restricts. In uk, not true. Clear benefit. What does restrict is that this is not available on NHS and this is by far most imp issue. Most generous country is Israel. – all about state funding. Perhaps with ageing popultion this will improve elsewhere.

Anders: if free innovation is needed in governmentality, if have more bridges, prob is that transdisciplinarity, but gov structure wil have prob getting solutions, restfucture government? Complementary institutions?

Chris Newfield: practical construction  effort

Donald Bruce: is there distinction between enhancement and medical? HFEA has embodied that on sex selection for family balancing. Council of Europe has embodied on convention on human rights and biomedicine – sex selection only for serious gender related genetic disease. What is rationale for the distinction? It is one I support, but is it valid as result of distinction?

Suzi: evidence is that public does think can draw clear distinction between selection for family balancing and disease, for instance. Do I think this will hold? No I don’t. I thjink it will be increasingly difficult to do that. One of the reasons is because any kind of disadvantage that can be conceived of as a disability, parents will say ‘I must have this’. I must be able to have a child that doesn’t suffer from x, y or z.

Shefield institute for biotech:

Dave Wood: which charac should we enhance? If spread too far, get nowhere. becom

World Anti-Doping Agency Gene Doping Symposium (2005)

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

Welcome

improve people's health. misuse of medical tes

Richard Pound

banbury conference

wada

OM contributions shared by NOCs - but..

gene doping research $3m

gene doping panel in WADA, help with detection

new results - WADC, mar 2003 -

ME: who are stakeholders of gene doping?

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

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

gov actions - now wider gov support

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

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

gene doping inevitable

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

New Trends in Anti-Doping Arne Ljungqvist

need to be ahead of the game first time in history

purpose - describe recent developments

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

arne was olympian in1952 and nothing then,

doping code explanation

doping is definedas...

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

prohibited list - wada publish each year

criteria - enhance, health risk, spirit of sport

(two of three)

doping need not be cheating to be banned

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

need common sense

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

prohib method enhancement of oxygene trtansfer

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

TUE

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

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

ioc never took this responsibility

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

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

need to improve intell

ME: how?

recent negative envts

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

The maked Machine false urine

REcent positive evens

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

two major technical advances

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

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

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

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

gene transfer trials by year crash in 2000

ME: why? at the time of HGP completion

photo of jesse gellsinger

gene directly injected into liver

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

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

visible depression in Society of Gene Therapy

yet, heard of a diff technique

Paris study, Fischer, Great Ormond St LondonX- SCID

photo of Bubble Boy syndrome child - protect from inections

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

ex vivo study

introduiced to bone marrow cells

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

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

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

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

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

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

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

legitmately therapy not just gene transfer

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

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

intra-tumoral...

CNS prophylaxis, new chemo agents

additional info into genome, which maintains mutant gene

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

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

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

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

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

ME: why is informed vol consent unlikely?

sport or bioengineering? is it still sport?

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

germ cell -therapy or enhance?

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

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

risks tolerable in light of disease ,but for healthypeople?

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

in US, not entertaining proposals for enhancement

discussion

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

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

change position but

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

holy grail is sequence correction

goldspink:

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

Ted: it hasnt in

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

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

Olivier: side effects?

Ted: dont see them until you see effect.

Olivier: procedure itself not harmful?

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

Q: state for muscular.

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

Ted: but not activitation, but disruption

Q: 3rd case special since dif

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

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

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

Coffee

Effects on organ systems/tissues

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

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

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

Adipose tissue -    reduced amount

Connective tissue/bone cartilage -    inc amount/strengthened

efects on organs systs

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

skin

imune systt

lungs

nervous system/brain -    inc capillaries more utilised

what factors influe performance

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

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

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

ReF: fluck et al 2005,

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

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

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

what prdicts for improved cycle performance following 6 weeks training?

What genes regulate -    better oxy deliv

Timmons et al FASEB K, 2005

Gene ontology analysis

PGC-1 inc by training in following hours

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

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

receptors of VEGF go up – inc to manipulate receptor side

5wks of training, VEGF goes up

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

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

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

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

Questions and Answers

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

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

Question: how do trained, elite athletes differ?

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

Question: can distinguish

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

Question: important?

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

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

A: what would you expect?

REsponse:

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

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

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

Olivier: what level should we detect?

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

Olivier: cells that grown and reinjected

A: yes, like cell

Andren Sandberg is rapporteur

Lunch

Session 2

Chair: Odile Cohen-Hagenauer

Vectors and Delivery Methods C. I Edvard Smith, Karolinska

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

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

concept oif a gene

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

Problem with going from outside of cell to nucleus

Local and systemic gene therapy

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

drawbacks to viruses

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

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

Virus as a vector for therapeutic genes, eg hiv

How use a virus?

Concept: the packaging cell line

IMAGE

Empty particles – allow introduction

Packing cell line 2nd generation

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

Concept: RNAi – how does it work?

IMAGE

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

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

Regulates gene expression

Can achieve stable expression – deliver shRNA

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

Questions and Answers

A: when expresss siRNA, is v short.

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

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

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

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

www.rug.nl/farmacie/tgm

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

adenovirus

shedding data, gene therapy stdies

shedding

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

environmnent – next of kin

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

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

Gene doping detection

IMAGE OF TABLE

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

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

clearance of free dna IMAGE OF GRAPHS

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

dna detection?

Baterial is immunogenic

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

detection?

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

use effect as most promising

specific detection?

IMAGE

Isoelectric patterns of epo

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

detection?

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

Genetic interventions IMAGE

Serum Protein Pattern diagnostics IMAGE

DETECT MAJOR CHANGE

Proteomics IMAGE

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

Detection by proteomics

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

Post translation modifs

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

Gene expression profiles

IMAGE

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

Gene Array

IMAGE OF CHIP

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

Questions and Answers

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

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

A review of current gene transfger models relevant to athletic performance

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

Launched European Society of Gene Therapy

Mainly deal with EPO

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

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

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

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

state of art of vector stys

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

IMAGES

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

regulatable expressoin (3)

companies now investing into this sector

Questions and Answers

Coffee

Gene doping and the regulation of skeletal muscle hypertrophy Lee Sweeney

Skeletal muscle

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

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

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

So, enhancement?....

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

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

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

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

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

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

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

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

IGF-1

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

20% or more depending

prevented fibrosis due to severe injury

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

IMAGES

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

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

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

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

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

gene doping could be detected by screening

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

belgian bull

young child -    parents, mother is competitive athlete

conclusion -    gene transfer could be used for skel musc

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

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

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

acknowledgement -    elizaeth barton, linda morris, rosenthal, farrar

Questions and Answers

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

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

Geoff Goldspink

Animal gene transfer model Interested in musc regulation

Looking at XXX, derived from IGF-1

IMAGES

Biol actions of gh/igf1

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

Igf1 also involved, but later in process

Damage

Real outcome is muscle force

With knockout myostatin not strong – lacking in functionality

35% inc in mujscle strength within 3 weeks

already company on internet creating mgf – Phoenix pharmaceuticals

ME: how did you find this?

Splicing can be induced by siRNA

Prediction

IMAGE

Put

Detection -    rapid screen mas spec

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

Questions and Answers

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

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

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

Odile: but mujst increase other body parts

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

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

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

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

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

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

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

african

expressed through oocyte

males do not contribute

life = structure + energy

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

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

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

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

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

changing of coupling efficiency

excess calories burned as heat

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

can radically change performance

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

Questions and Answers

Question: what is importance of mt ….?

A:

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

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

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

revving up metabolism -    synthetic ligand GW1516

created marathon mouse (ppar)

transgenic mouse -    now expresses ppar-delta

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

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

A – better B – worse C – same

?

treadmill challenge

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

Under study – does GW1516 enhance performance in mice?

Future – magic pill?

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

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

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

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

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

Inflammation/arthiritis – phase I

And repair of: Bone Cartilage Ligament and tendon

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

Gene tansfer to the synovial fluid of joint

ex vivo and in vivo

Some success with ex-vivo

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

use retrovirus

phase 1 study in knuckle joint w rhumatoid arthiritis

put into joints that were due for removal

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

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

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

Targetted genetics company in seattle study.

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

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

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

Absent from horse who recent therapy

Now bone

Direct injection of adenovirus – BMP-2

V responsive to gene transfer

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

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

after 8 weeks,good healing

Wolf’s law – how bone responds to load

After pins removed normal mineral content returns

Effectively repairing bone that would otherwise not occur

Concluding that we can do this

Cartilage

No intrinsic ability to heal

If partial injury to articular cartilage will not repair

If goes through to bone bone marrow defect

Trying to take adv of fact

Use with rabbit

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

see if enhance healing

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

Presnet status

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

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

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

Questions and Answers

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

Monday

Chair: Friedmann Standard in medical doping involves looking for assays

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

Look for local effects Systemic Homeostatic

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

WADA Perspectives on Gene Doping in Sport Olivier Rabin

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

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

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

Fundamental concept

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

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

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

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

some gene regulations not fully understood

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

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

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

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

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

Use of microarrays applied to DHEA (hormone mutant)

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

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

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

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

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

HFL Jane Roberts

Difficulties, always new pharma drugs

Current methods cannot detect gene therapy

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

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

alternative testing strategy -    surrogate marker approach (biomarker)

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

biomarkers -    transcripts -    proteins -    metabolites

transcriptomics vs proteomics

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

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

Surrogate marker approach

Screening approaches

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

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

1.    pattern recog

sample prep is key- proteins in serum

Questions and Answers

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

A: at proof of principle stage. Relies on probability

Proteomics J Yates, The Scripps Research Institute

Used for biol discovery

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

Achieve total protein charcaterisation

Driven by mass spec

Single protein vs shotgun proteomics

Quantification

Global method: Would not stand up in court of law

Questions and Answers

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

A: 20-30 is within sample.

Question: what preventive measures to keep stable.

Question; had possible to look at disease or treatment?

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

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

A: at peptide level are problems

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

How can embryonic SCs be used for …

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

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

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

coffee

Research Report on studies Geoff Goldspink

Exercise -    knee extensor weightlifting exercise -    3 sessions per week

using muscle biopsy

with elderley people

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

relationship between MGF and muscle

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

repeated with trained athletes -    blood levs went up considerably

been taking muscle cells in culture and putting serum on them

use muscle cells in culture

IGF-1 gene transfer

3 Different types of IGF-1 in muscle tissue

actually 6 types (2 classes of 3)

with placebo, inc in class 2 with Gh wen down

with MGF of Class 2,

can now purchase human muscle cells

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

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

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

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

concern that they might be disqualified from sport

Currently collab

1.    mice receiveing hgh delivered using a mini osmotic pump

mass spec can distinguish

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

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

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

Transcriptional and proteomic effects of IGF-1 Ted Friedmann

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

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

Exptl design – short term

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

candidate of genes that can be used to detct

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

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

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

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

microarray procedure

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

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

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

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

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

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

Gene doping makes this problem harder

Peptide hormones

Indirect markers -    physiological effects -    popn studies: probability

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

indirect dtection of GH

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

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

gene expression of gh isoforms

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

A long way to go before detection

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

Outline -    background -    imaging -    potential -    points for consideratoin

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

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

imaging that maybe immediately applicable to gene doping

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

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

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

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

Imaging tc-99m-ad-luciferase

Particle goes to liver

Shows light ommision from liver of mouse

Questions and Answers

Lunch

Session 4

Tom murray

Screening a worry

Matt

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

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

Equal opportunities -    not part of culture of sport

cannot complain that

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

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

limits of accessibility on fair innings argument

need sufficient number of competitors to make it worthwhile

natural variation –s mostly self-regulation

people w extreme gene mutations not become elite athletes

limits of genetic screening

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

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

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

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

snowballing inflation -

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

fairness as equal opp not part of sport

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

as fair play – intrinsic

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

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

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

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

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

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

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

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

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

Need to answer some important concepts

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

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

do not design humans for sport

ME: but we do

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

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

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

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

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

Principle at stake

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

repair is unprobc

incidental improvement -    Tommy John elbow injjury – generalyl accepted

Surgery in absense of defect is enhancement

But Tiger Woods – laser eye

Laser correction public use now

Not like cheating in way that steroid use is

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

Things that are acceptable elsewhere, not aceptable elsewhere

What do with grey zones? -    arbitrary, but

with strict liability

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

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

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

genetic modification and improving humans -    enhancement

sport conflronst problems

if sport faces problems

who decides?

Sport is leading by saying we will regulate

Ethics, enhancement and sport Tom Murray

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

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

Aristotle – eudamonia -    full good natual ilfe

there are unvirtuous ways of getting these

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

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

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

response -    hypothetical

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

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

athletic virtues – fast.

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

But this would not have any of the characteristics of bball

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

would not have a game of bball

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

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

ME: he is now switching to regulative rules

ME: breaking some rules is not bad in intelf

there are silly rules – prohibition in us

So must have a public consensus in support of rules

In sport, if ban certain things but do not enfocre

Argument from Individual Liberty

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

doping control done well provides level playing field

argument from liberty fails to

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

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

No longer throw people to lions

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

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

imagine drug with no side effect

imagine drug diminishes hand tremour and neurosurgeons see benefit

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

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

you would choose one w best results

first surgeon missed practice of surgery

point of sport is natural excellence

point of surgery is to make well

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

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

because of goals and values of practice

challenge of genetic enhancement in sport

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

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

what makes a talent natural?

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

child who has been engineered prenatally, natural?

ME: ecosyst argument – just a complexity argument?

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

ME

Final session

Jacque Rogge

Test to check for drugs for neurosurgeon

Need clear rules for world of sport

Fairness – but is life fair?

Sport is arbitrary in some ways

Can this be accepted?

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

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

Look at high-jumpers

Achilles tendon most fragile for fosbury

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

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

Basis of beliefs

850million people practcising sport, 750million recreational

every recreational is competing with self

only 150million in sports contest

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

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

respct sport, respect society

sport integrates

sport brings health

sport shapes identity

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

we believe that protect health, even if paternalism

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

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

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

doping rules are imperect

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

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

enhancement not be allowed

where draw line must be done with ethicists and scientists

Stockholm Declaration Arne Ljungqvist

Composed of olivier, ted, and arne

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

Challenge?

Change serveal to  ‘a few’

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

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

Comment: these are more general reseacrh

Tom: human beings?

Lee: clinical trials

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

Matt: follows nuremberg, etc

Tom: these are minimal conditions, we can elaborate

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

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

Gary: who will develop?

Comment: since no legal, ma

Maybe unethical or illicit

Illegal implies court of law

Unethical and/or illegal

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

Be developed

Comment: this implies it exists

Olivier: can argue this in animal models

Odiele: reservations, since education can be spreading

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

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

Delete ‘near’?

Lee: must emphasise need for research

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

Comment: ‘should be supported’ at end remove support

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

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

Gary:  government?

Academic, government and private research

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

Rogge: contradiction with screening

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

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

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

Lee: must specify athletic traits, not genetic

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

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

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

Add to ‘select’ or discriminate

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

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

Promote knowledge on medical and physical dangers associated with gene doping

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

Olivier: dangers alone?

Odiele: why not ‘misuse of gene transfer’

Olivier: risks or dangers?

How about potential risks?

Olivier Rabin

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

Mitochondrial Disease Research: Social and Ethical Considerations (2005)

Mitochondrial Disease Research:Social and Ethical Considerations

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

Friday 28th October 2005

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

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

Eumitocombat

Rationale treatment strats combating mito oxidative phosphorylation (OXPHOROS) disorders

www.eumitocombat.org

obj

charac genes and proeins involves in formation and reg

SEAC

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

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

First Session:  Chair:  Carlos Alonso Bedate,  Madrid

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

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

What are Mito

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

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

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

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

how do mito make atop?

- 2 stages

Protoon motive force -    drive atp synthesis

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

2.4 – dinitrophenol (DNP)

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

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

Sean Zhang, 24, of Bloomington

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

Division of mitochondria (assembly)

(mito are scaled down bacteria)

mitochondrial dna looks v much like bacterial dna

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

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

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

Muscle mito from mitol disease patient

Question&A

Question: neurological dysfunction?

Turnbull: not clear.

Blue: but the debilitating effects are precursor to psych cond

Mark: does it spread

Turnbull:  some segregation;

Donald: function of energy production main or only function?

Peter: main, but not only critical function

Donald: diotriphenol, where originate?

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

Donald: not naturally occurring product in body

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

Donald: these are nuclear?

Doug: yes, and protein specific

Donald: mito performance radically affected by hings going on around

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

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

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

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

Clinical features and reproductive options for mitochondrial dna disease

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

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

nuclear mutations might affect mito dna or can affect nuceucide metab

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

nucleus dominates mito

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

NOT TALK ABOUT NUCLEAR

Focus on mito disorder

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

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

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

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

Mito genetics different nucl gen

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

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

influ of mt dna

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

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

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

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

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

Acute medicine - seizures and stroke - increasing coma

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

Gastroen - smooth muscle of gut affected

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

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

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

important to know when advising on reproductive options….

Patients with high levels of mutations have most disease

Mt DNA disorders

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

Newcastle - not much movement of popn within Newcastle)

Looked at all patients that have been referred to us

Common for a genetic disease

Reproductive options fro women w mtDNA mutations

How do we treat patients with mtDNA mut?

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

Patrick Chinery

V little drug trial info - part due to clinical heterogeneity

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

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

women were requesting info on reprod options

MtDNA disease

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

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

Egs

Homoplasmic mutations C1624T in mt-trnavl

Genome sequencing Mt tRNAVal

All children of Sharon have same mt mutation

Why Sharon is unaffected, we do not know.

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

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

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

13513 G>A ND5

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

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

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

Stages of oocyte maturation

No of mt genomes – 1milion

No effective mt replication during embryogenesis

Becoming diluted from 1million

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

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

Not much point in PGD for Sharon (homoplasmic)

So what else could we do?

Prevent transmission of t disease

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

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

there are ethical issues perhaps, but no legal

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

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

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

transfer pronuclei

will it carry any mt?

yes, about 16%

when mice developed had between 10-37% in tissue

threshold for diease is over 50%

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

Lawrence Smith – taken to 20 generations and no defect

Potentially valuable technique to stop transmission

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

Press coverage Ethics of tabloid news!?

MTDNA

Applying for research license

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

Tripronucleate zygotes

Take abnormally fertilised

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

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

Look at proportion of embryos developing to blastocyst

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

One of reasions for difficulty in obtaining license MT dna disorders

MTDNA

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

prob

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

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

Question&A

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

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

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

Donald: making a value judgement.

Doug: we can transfer less mt

4.00 p.m.  Tea/Coffee

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

Disagree with doug that nuclear mutation is going to be common

Clinician Started in field in 1986

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

why study germline segregation?

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

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

NOW NORMAL 3 YEAR OLD.

Refined genetic risk by samplinyg oocytes

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

A3252G - Rory

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

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

nightmare to do CVS and having no idea about likelihood

PGD then CVS

Offered oocyte sampling, pgd, then cvs

Couple chose no intervention

Have we helped or hindered this family?

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

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

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

Question&A

Jo: batteries? Well, cytoplasm contains more

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

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

Jo: mt dna must interact with…

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

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

Donald: not many.

?: can we freeze them?

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

?: big demand on these embryos

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

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

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

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

state of the art of these different contexts

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

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

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

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

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

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

Animal Research

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

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

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

Doug: animal models would be helpful.

Kevin: other animals

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

Clinical Trials

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

Special ethical trials?

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

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

Dog: Exercise might change mt genotype

Ruth: how?

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

How high a proportion of

ME: does this alter on trained or untrained?

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

Jo: stem cell therapy overhyped.

Doug: more sensible to use exogenous stem cells.

Mark: similarity between mt dna

?: patient organisation

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

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

Doug: if you go on internet to find mt disease

Doug: considerable under diagnosis

ME: does this radically transform the estimated

Ubiquinone

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

ME: are some batteries better than others?

Genetically influencing by using third source?

Influencing disease likelihood

7.30 p.m. Dinner in Lancaster House Hotel.

Saturday 29th October 2005

Second Session: Chair: Doug Turnbull, Newcastle

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

What does it mean to be complex?

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

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

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

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

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

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

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

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

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

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

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

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

Jonathan Res

The assumptions of tradl molecular medicine summarised as follows

Assumption has been a paradtim in

- medical genetics - molecular boil - development boil

Brenner and Wilkins, the uniqueness assumption of genetic determ

Unique genes – unique effects

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

1. more than one gene may specify any given function

2. single gene may specify more than one function

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

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

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

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

Disease

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

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

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

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

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

Importance for clnical assays

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

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

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

what we thought was homogenous popn was NOT

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

medicine research has grown as never before:

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

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

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

-    BUT THIS IS A LOW estimate

My proposal

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

All proposals raise ethical issues

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

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

Adequate and fair human subjects selection

Prior decisions

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

Questions and Answers

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

Donald: not looking at specific effect

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

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

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

Celia: what is environment?

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

Peter: need individualised medicine, ie for privileged?

Carlos: perhaps not. Perhaps common elements.

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

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

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

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

Doug: political side needs considerable financial input

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

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

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

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

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

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

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

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

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

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

Generic issues -    consent -    benefit sharing -    resources

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

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

ME: what theory of normal underpins this classif?

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

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

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

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

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

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

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

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

Summary

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

Questions and Answers

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

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

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

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

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

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

Doug: but is it different?

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

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

Celia:

Peter: mt might not be an exception

Celia: might make men feel different

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

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

Celia: guilt is produced by chance.

Doug: but making diagnosis produces the guilt.

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

Ruth: informed consent functions in different ways.

Doug: what interest of animal has

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

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

Carlos: but maybe Huntington will be mt.

Glasses: how move towards harmonisation?

10.45 a.m.  Tea/Coffee

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

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

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

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

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

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

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

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

ME: do confused perceptions warrant prohibition?

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

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

Not as big an issues

-    identity more than genes, but where draw line?

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

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

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

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

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

Questions and Answers

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

Kevin: any position on the ethics of mt?

Donald: not yet. Question of identity

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

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

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

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

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

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

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

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

Doug: some techniques are being developed in other countries.

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

Promised scoping paper on social and ethical issues.

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

www.eumitocombat.org

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

Develop cesagen project linked to European project and other interested parties

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

Mark: can mt dysfunction be desirable

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

Workshop will prove to have been useful.

European project

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

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

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

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

Beard: but cannot assume that is such a big deal

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

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

Ruth: for mt disease?

Mark: question of regulation and transfer.

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

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

GlasseS: will there be a European wide regulatory body

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

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

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

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

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

Bert: orphan disease and justice.

1.00 p.m. to 2.00 p.m.  Lunch

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

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

Life Extension Session

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

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

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

maximum life expectancy has not advanced at all

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

Public Opinion

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

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

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

Questions

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

Method

Structured indiv interviews

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

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

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

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

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

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

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

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

Qual of Life -    health is paramount

looks not a high priority -

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

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

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

Distinctions

Chronological ageing – calendar time Biological ageing – process of decline

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

Args so far

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

observations

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

this paper: coherent alternative viewpoint – 3 args against

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

1.    the time dimensions

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

but time is not an object

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

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

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

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

ME: who needs to many os?

Spiritual

Decentrered self

Meaaningufl life as eternal

Decentred = no interest

2.    the social nature of human

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

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

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

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

quality v quantity

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

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

3.    ethical dimension: global justice

expectancy

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

What moral obligations follow from justice?

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

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

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

life expectancy as a moral challenge

discussion

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

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

Living LongeR: Ethical aspects of age retardation

Elisabreth Hildt

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

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

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

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

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

Grant from NIH on implics of anti-ageing interventions

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

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

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

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

American Academicy of Anti-Ageing Medicine (A4M) -    provides board certif. for practitioners of longevity med -    13000 members -    70 international and national conferences -    2million hits per month on website -    net asserts from $65k to $3.5m

RRonald M Klatz ‘Ten Weks to a Younger You’

Biogerontologists -    40% extn In av life expect and mx life in dietary caloric restrictuions (CR) expts -    development of CR mimetics -    genetic interventions

scientific legitimacy of biogerontologists is shakey -    little better than charlatans -    gerovital, anna aslant and nikita kruschev -    in US, National Instititue on Ageing (NIA) in mid-1970s path to legitimacy, but still fragile

War by gerontologists on Anti-Aging Medicine -‘No truth to the fountain of youth’ - published online (CHECK!) - SILVER FLEECE AWARDS TO A4M – for misleading public - continuing publications and media appearances - boundary work to disting themselves from t illegitimate antiaging med movement ‘Those who have legitimate…. R. Miller’

Similarly A4M seeks legit -    denigrates ‘gerontologist estab’ -    files lawsuits against specific …

Ideal models of aging seniors

Imagery beyond boundary work -    the politics of presentation has important social implics -    3 rhetorial strates for defining aims of anti-aging prods, etc o    1. Med tratement o    2. Enhancement o    3. Prevention

1.    med treatment

eg. A4m: reating maldadeies of aging -    moral authority and prof autonomy of med prof

renews debate over whether aging pathological or risk factor

2.    enhancements

‘stay young’ restore mental and phys capacities that decline w age politically, this rhetoric takes enterprise out of biomed realm -    outside of med prof and gov reg

provokes criticism from bioethicists’not natural’ and tf unethical

beyond therapy (2004)

3.    prevention

forestall chronic health probs, associated w aging for as long as possible strategy avoids criticisms of unethical enahcnement skirts debate over whether aging is a disease

embraced by gerontologists

want to be seen as ‘the good buys who favor…..R.Miller essential for maintaining and enhancing funding for further research

internecine warfare against propoent of enhamcenent – Aubrey de Grey, ‘virtual immortality’ is achievable – claims possible to only die from apoptosis - European Journal of ‘Resistance to debate on how to postpone ageing’

‘We are gradually, much too gradually ….’

The Politics of Presentation: Issues for Empirical Research

Tretment -    will treatment rhetoric by anti-aging entrepreneur and clinicians lead to control by org med? -    Or, will org med engage in boundary work, as t biogeront

Enhancement -    will enhance rhetoric lead to political movement to curtail interventions?

Prevention - does prev rhet succeed in strengthening scientific status of bioger

Friday 26 Aug

Therapy & Enhancement Ruth Chadwick

Disagree with Bayliss definition of enhancement, must disting between improvement

Inevitability thesis is incomplete

Moral argument fails to account for context

Instead, improvement should be focus, but wheth enhancement is improvement depends on context

Eugenics revisited

Negative v positive

Enhancement just eugenics repackaged

Disting between germline and non

Eubionics: the pursuit of bodily perfection – negative and positive -    McNally

Negative eubionics – elimination of body Positivev – pursuit of bodily perfections

Case by case?

Beyond therapy US Pres council -    argue for case by case

enhancements 4 approaches -    beyond therapy -    additionality view -    improvement view o    if qualitative, but if enhance to such an extent that X (human) no longer exists as a category -    umbrella view – enhancement just convenient label for number of interventions

limitations of enhancement/therapy distinct -    enhancements likely to arise from therapeutic med -    this will be difficult o    ME: why?  Drug regulation

Beyond therapy probc definition -    Therapeutic intentions? -    Therapeutic effects -    Evidence based therapy -    Proper scope of medicine -    Indiv vs species issue

Norman Daniels: eliminating shyness relies on understanding cause, which is complex

Why should we be more concerned w cause of condition than suffering

Enhnancement and the self

Baylis and Robert -    ‘the resulting alterations may be conservative (ie used to normalise the self), liberal (i.e used to liberate the self) or radical (used to fashion a self that effectively challenges others’ conception of oneself)’

what would count as a preventive therapeutic intervention? -    preventive mastectomy for woman with strong family history -    since we don’t know whether it would arise, can argument is therapeutic, but also as reassurance -    main aim is to reduce risk status -    counterintuitive to speak of mastectomy as enhancement -    need more to concept of enhancement that just beyond therapy

Norman Daniels, Species typical functionign

While enhancement is always characteristic specific, whether something is improved or not requires a judgement -    good eg. Is height -    depends on what we are trying to achieve – context

improvement should not be included in any definition of enhancement

the inevitability thesis

baylis and roberts -    contemporary Western democracies have no experience with permanently halting the development and use of any enhancement technology on ethical grounds.

What doesit mean that it is inevitable -    if simply that someone will try it, not interesting -    ‘despite the likely failure of particular genetic enhancements, there are some among us who will inevitably attempt to engineer the human genome8 for the purpose of improving Homo sapiens.’ Bayliss and Robert

rape and murder doesn’t stop but doesn’t mean not worth trying

they distance themselves from empirical slippery slope argument -    not clear that views will become more liberal

Ithe future is ours for the shaping, tf genetic enhancement inevitable -    an ‘avant garde’ portayal of human nature o    ME: what not merely health improvement?

Perfectibility different from enhancement

Moral Arguments -    boutique model (individual) -    species approach (collective)

boutique model -    Abdul Adah

Central question is whether medicine resources should be used here

Spectrum of positions -    wrong in itself -    injustice arises -    not a priority -    morally required

Habermasian concern not mentioned

My view is that enhancement permissible in certain conditions

From an impartial position, if can improve, we should make it -    but judgement about what is improvement not easy

no gains without compensating losses

consider context

sport

Aristotle -    if ten pounds are too much for a particular person to eat and two too little, it does not ffollow that t trainer will order six pounds; for this is perhaps too much for the person who is to take it, or too little too little – too little for Milo, too much for the beginner in athletic exercises

whether improvement first depends on context of sport, then internal good of sport

with human ‘improvement’ overall

3 areas in need of consideation

1.    enhancements which undermine t possible of moral agency are not morally permissible

but does either the fact of design or the nature of a given enhancement have this effect?

2.    wht si the relationship between moral permissibility and improvement

is improvement a necessary and/or sufficient condition -    if enhancement did not improve, but did not worsen, might also be permissible -    not sufficient, since issues about distrib

3.    priority should be given to enhancements which reduce existing inequalities

morally required?

Important issue not disting between therapy and enhancement, but whether is improvement -    depends on context and purposes

does thinking about whether it is an improvement overall contradict the context specific position?

There has been a huge trend towards public engagement about ethics -    ME: what does she mean by this?

Nordenfelt, L Honorary Session

Nordenfelt

Health goal as medicine

Edmund Pellegrino and David Thomasma in their book Philosophy as t basis of medicine 14, p.26 -    medicine is an activity whose essence lies in t clinical event, which demands that scientific and other knowl be particularised in t lived reality of a particular human for t purpose of attaining health or curing illness through the direct manipulation of t body and in a value-laden decision matrix

other goals exist – saving lives and QoL, health is central goal

task of interpreting health remains

contemporary philosophy of health determ from scientific point of view -    some argue they are value free and descriptive

Christopher Boorse and Thomas Schramme

BST -    ‘a disease is a type of internal state which is eitheran impairment of normal functional ability, eie a reduction of one or more functional abilities below typical efficiency, or a limitation on functional ability caused by environmental agents’ Health is identical w t absense of disease (Boorse, 1997). -    Ill if probability of survival lowered, or…..

‘health is a state in which we neither suffer from any evil nor are prevented from t functions of daily life’ (galen Ars Medica 193AD)

main rivals – in positive tersms

boorse health bst -    A is completely health, iff , all organs of A function normally, ie if they, given a statistically normal enviro, make at least their statistically normal conttrb to t surviaal of a -    A has a disese, iff, there is at least one organ o As which fns subnormally, given a statistically normal enviro

Holistic theory -    A is completely health, iff, a has t ability given standard cicrcums, to reach all his or her vital goals -    Notion of a vital goal is crucial -    Standard circumstance = different from statistical o    related to a cultural norm -    ‘A has a disease, iff, A has at least one organ which is involved in such a state or process as tends to reduce t health of A. t disease is identical w t state or process itself.’ -    Tends to reduce t health of A – sleected since not all diseases compromise health in relationship to vital goals -    Some maladies can be aborted before they have influenced the bearer

How reconcile these defns?

2 stories

genuses of probable health by considering illness and disting between illness and disease -    percevived problem

in the beginning…

illness recognitionand illness communication the illness language illness experts – doctors did not rely on stories from people who were ill, but looked for causes doctors found regular connections between states and symptoms and fourmed hypotheses designates causes as diseases

disease recognition

a quasi-historical sketch

concept of illness primary to disease

problem to be solved

causes assumed to exist within b or m

illness need not entail threat to reproduction

often concerns pain, suffering or disability subject often believes internal cause thus, human disease relationship to suffering and disability, not inc probability of death

3.    standard medical encounter today

john, pain stomach, sees doctor, presumes illness, pain  indicates this, and observes he is prevented from working

doctor examines, when convinced of nature, will find cause in organic function – organic disease, but not for own seek, not any old malady, needs cause of problem, then treats it in relationship to contemporary art, when successful john is healthy – no longer feels pain and can work as usual

thus: health concept used is variant of holistic – -    estab of fact that he is ill does not rely on diagnosis, john can establish through his own exp of illness -    ME: is he not doing what the doctor does? -    In favour of hgh

Endorse idea of reverse theory of disease XXXX - Josh Congilen? 1943 – Wilford 1989

illness recognition essential, but to avoid misunderstanding, illness need not have occurred in individual case, but disease not discovered unless someone in history who had similar case

Disease (holistic) = bod or ment process which is such rthat it tends to cause an illness (understood as a state of suffering or disability expd by the subject)

ME: presumes sincerity on behalf of subject

Gaylin and Resnik – illness caused by suffering or disability

Ability/disability relevant concepts than well-being/suffering -    pluralist notion of health? -    Do not deny relevance of well-being or suffering, but philosophical technique requires that Ockham’s razor (simple and as universal as possible), ability and disability most potent

Differences

In bst, health is entirely internal In holistic (hth) – goals and other abilities (not just intentional), but ability to perceive, feel, etc

In bst

In hth – extr

In bst – health identical w absence of disease, hth health is compatiable w t presence of disease. T concept of disease is, however, logically related to t concept of ill health (or illness) and also according to t hth. A malady is defined as a state or process which tends to reduce its bearer’s health

Hth – whether person as whole, whether can achieve goals -    goals differ: survival, QoL,

Thomas Schamme

2 theories of health of importance to philosophy of medicine, nordenfelt and boorse

defence of naturalist is critical discussion of nordenfelt

nordenfelt includes too many phenomena in definition of ill health

conclusion: analytical framework of naturalistic view should obtain conceptual priority

nordenfelt focus on concept of health, instead of its contraries – illness, etc

starts with health, which is unusual since typically easier to agree on disease, whereas health more contested

Fullfort focuses on illness, Nordenfelt on health

Cannot identify illnesss unless have view of positive health (nordenfelt)

Critique of N, say something of conceptual priority, but Fulford’s argument is non-starter

Fact that we usually observe illness before seeking explanation has no bearing, merely epistemological effect, -    priority in this case not about temporarlityu

dubious to ground medicine on particular goal (individual health) without idea bout what that signifies

must disting between fullfulling positive health

we might mean positive or direct definition of health – not a lack of something

eg. Boorse says absence of disease, but also positive definition of health

or give more than minimum

other examples, such as freedom – different between positive or negative -    state an ideal, not just minimum -    or ideal/true freedom

if apply this to health, WHO definition states both positive definition and positive conception

nothing depends on wherther we give a positive definition of term -    eg. WHO definition as negative, does not lose positive ideal definition o    ie. Health is merely t absence of disease and infirmity, disease and infirmity are states when complete phys and mental .. is lacking’

common mistake to want to talk about positive health, but then people talk about ideal health, which is different

is N ideal or positive?

N might open way to positive, because includes criterion of individual goals, but he adds a restriction by clarification – ‘vital goals whose aspiriation for minimum happiness…so to count as healthy…good health does not imply ability to become completely happy’ – is less extensive than WHO

But still too wide since coveres disabilities that are not ill health

Paradigmatic eg. – -    Lily, an athlete who struggles to becom accomplished high jumper, but does not succced, wants to jump over 2m, not to succeed means not minimally happy, but even sad, though N says minimal happiness not sufficient, but disability is crucial. Lily is unable to realise at least one vital goal. Still, we would not call her unhealthy or in state of ill health, since not a disease, which would be indep of ambitions.

3 possible responses from N - 2 ambitious goals are ruled out by theory. If goal is unreasonable, cannot count as necessary. N opts for objective accounts, but discusess counter productive and trivial goals. - ME: doesit change if Lily wants to be a doctor? - 2. Must lack a second order ability,ie. We could help her by training or education. - 3. Let’s accept she is not unhealthy. But must not discuss as counter intuitive, because is a welfare theory. Nothing left to argue about. Nothing wrong with this definition, but state reluctance to accept. Welfare theory not approp since health is a medical term – end up with medicalisation of all problems

cannot refer to all people who are unhappy just because cannot fulfil goals as ill

must rely on medical normality

we need distinc between 2 interprets of health 1.    taking account medical science (boorse) 2.    grasping eval of medical conditions (normativism)

since normative is logically prior for N, cannot understand why healthXX

from perspective of medicine science people w same condition are both unhealthy

N proposes ideal which leads to medicalisation

We need scientific perspective to restrict

Defence of naturalism qualified by restriction of particular perspective of science -    naturalism must be supplemented by normative, but cannot be removed

G Khushf

Situate health concepts debate in slightly different state

Beginw observation of the debate which is puzzling -    urge to return to Boorse -    Boorse’s work seems to be situated in theoretical biology, but in theoretical biology, nobody cites boorse -    Why does Boorse play such a role in this debate

Need to see how health concepts have been a lens for models in medicine science

Use debate as a lens and look at background context, to suggest that we have real traction.

It is now moving forward

N has made t contribution that enables us to go forward

Rather than argue with Boorse, argue w N.

Science depends on social conditions, but these conds remain implicit

Division of labour between administrators and practitioners of science

Sustain myth of fact/value divide -    colour all features of scientific landscape

medicine not immune to this divide -    in hyperform

consider division between clinical practitoeners and adminitstrators of health care

inc role of administrators

implied that scientifically based practitioners determine what is medically indicated, then negotiate treatment in accord w patients values – this is essential

contrast, admin provide economic circums – estab the conditions

but they are not supposed to influence

these are manifest in ethical deliberations

eg. How are patient’s views Integrated in medical decision making

patient autonomy does not mean equality with physician’s view

physicians are masters of means

eg. Medical futility – approp and inapprop domains of patient autonomy

thus, fact value divide in 2 features of modern medicine -    admin (value)/physician (fact) -    patient autonomy (value)/clinical interaction (fact)

health and disease

appreciate importance of boorse

examine core features of boorse account -    value free and scientific -    broad social and individual patient values are second strand influencing treatment -    socio-economic factors should not play rolein determining disease o    historically problematic: eg masturbation, etc

if focus on these rubricks, we find his position compelling

Nordenfelt -    appreciated predicament fasced by critics of Boorse -    shows why disease canot be value free, but understand sympathy for Boorsian project -    not coincidental that Boorse has taken the BST term from N and uses it to characterise his own theory

focus on deep resonance between Boorse and N and suggest they are much closer

N view of medical science - health concepts tied to human ends, not survival and reproduction - both he and boorse share fundamental assumptions - both think we can tease out the factual and evaluative and applied science involves reasoning and guard against values - N argues health conceptsa re PARTLY evaluative so must speific where they end - onec we do this, can use as basis for empirical eval - does not question purely empirical investigation what marks of end of the domain -    once end is given can apply to realise that end

can understand why health concept is primary -    allows clarification of the end, which is necessary tyo estabg proper role of medicine

health concepts functional analogue of medicine -    mark of legit from illegit

N’s wants based notion of happiness -    focus on: ends integral to medicine are individually relative -    approp values are thus this or that patient, not patients in general -    ends of clinical encounter specified by patient/physician interaction – allows specification approp treatment -    health concept specifies role of…. -    N upholds core features of Boorse, but sustain value ladenness of Health and disease

Nordenfelt should be seen as biomedical ideal

1.    contrast classes for situating the debate

in one of Boorses early aarticles, presents naturalist, weak naturalist, and strong normativist (pure constructivists) -    these are linked to Boorses health concept -    wanted to disting legit (weak) from illegit (storng

but this clouds the debate hard to find anyone that does not have no descriptive -    everyone is a weak normativist

core difference between N and B

new definition of weak and strong -    weak: can disting between fact and eval components (medical v non-medical), while see values as integral, share w naturalist role of descriptive -    strong: not possible to disentangle fact and value in this way. Seek to show how diverse values configure health concepts

Conclusion: new context

In current context, see shift in whatmakes debate important Until now, has been disconnected from trends in medical practice Health concepts incl’y important

Changes in medicine

Eg. Manage care and total quality review

Now being incorporated into standards of care Overlap between admin and pract

Some see as distortion of medicine – economic

Challenge to classical jurisfictions of medical practitioners

Debate also reframed -    is it possible to disting sociopoliticaland economic from microethic of clinical encounter?

Strong normativist is best? (ME: did he say this?)

Cannot sustain neat fact/value distinc in classical form

How to appropriately address in management strategies?

Nordenfelt Reply

Reply to Schramme -    priority of health -    S says order is solely epistemological not logical priority, so fact that we observe before diagnosis says little. Hwr, purpose was not about logical priority, it is health that is logically prior. The observation temporal priority that Bill fulford has argued, not just epistemology, also bearing on conceptual substance. In doctor patient case, we have paradigm case of HC. Tells us what is at stake in the encounter  - patient’s disaibity and suffering. Fact that we label that as disease, tells us something about concept of disease. -    2 arguments: o    1. Ought to be able to explain why someone canbe medically abnormal, without being badly off •    answer: do not claim that all diseases produce suffering. Consider various stages of disease. But for it to be called a disease in the first place, must in some if not most, result in some suffering. o    2. Must be able ot explain why someone is ill and not simply sufferinf from other impairments, such as loneliness, etc. idfs that we include too much. Someone hwo is sad or unhappy will be labelled ill. EG. Lily the athlete, who cannot jump 2ms. She is obviously healthy, says Schramme, so theory inadequate •    answer: talks about health and illness in contradictory, but also in complete. He also says it is a dimension. So when lily does not achieve and when this is a vital goal, it is not automatically that she is ill. It is merely that her complete health is reduced. She can realise her basic vital goals.  Though S would not admit that her health is somewhat reduced, he would maintain that she is completely healthy. Her is an unrealistic goal. If she should be helped, cure is not to turn to orthopaedics, but in ‘goal care’. We should try to convince lilly about the unrealistic nature of her goal. She can set a utopian goal, but be emotionally prepared for its failure. She has a hidh degree of health. Do not enter into people’s lives when they do not call for it. Unrealistic goal setting.

S accuses of including too much, I say he includes too little

Response to George

Constructivist strong normativism

Present concrete eg to test

Need there be a profound shift in concept of health or that we will constantly reconstruction

Distinc between reconstruction and operationalisation

Eg. If clinic accepts ground of someone as unhealthy because cannot go to work – this is operational

What could be reconstructions of health concept

Eg. Measuring health and divising instruments for such measurements. E. sickness impact profile, euroqual, Nottingham health profile -    all contain critieria for measuring health -    they indicate concepts of health -    perhaps the instrument makers construct different concepts of health -    these are postmodern measures of health -    we might have 1000 withiin a decade -    a good state of affairs? I doubt it, descriptively and normatively -    descriptive: o    instrument makers might claim they are merely trying to describe an aspect of health, eg. Mental or dental, or to measure technologies, so not all aspects are accounted for – practical purpose. o    Evaluative: doubt hey would be happy that theya re constructing new concepts of health. They want to measure ordinary understanding – just a partic way of measuring o    May be 150 defns, but from this does not follow that there are 150 good or adequate concepts. Few have derived from careful conceptual analysis o    Thus, maqy find dubious claims within them. Eg Nottingham health profile ‘I lie awake for most of the night’ – explanation? Not just ill health o    We have some intuitive understanding of health and make good judgements. But this does not mean we or they are constructing new concepts of health o    But is there only one concept of health? •    No. like all abstract concepts, health vague. Borders fuzzy. From conceptual analysis only, cannot define sharply.  Must stipulate minimal. But is, at least, a conceptual torso that is given in conceptual language which tells us what dimensions are relevant to health. •    Cconsider Aristotle or gaylen.

Debate

ME: If I cannot work, I am ill. If I cannot be the best worker, I am not ill.

4.2 Future of Medicine

The moral significance of future ‘persons’ G. Papagounous

Question: role of personhood in ethics in relationship to specific entities, namely human beings

In ethics, should not evaluate natural phenomena -    eg. Earthquake, tsunami are neither good nor bad, but consequences can be described in such terms

what is the different between a pilot and a volcano?

Person

Personhood delimintes 2 things

1.    limits of the act. 2.    Allocatrion of the possibility of an act

Warnock – personhood – consciousness, reasoning, self-motivated, communication, self-awareness

Not complete -    if replace ‘raven’ with 2 yr old child, stil theft of ring? – fits personhood as Warnock

must modify personhood

ME: not harm to future persons – they are not harmed. Rather, environmental actions are worsening the conditions within which future persons will exist

Is transferred parental responsibility legitimately enforceable. Matti Hayry matti.hayry@manchester.ac.uk

Premises -    You have (or want to have ) children -    I do not -    You have not been coerced into having (or wanting to have) children by force, threats, deception, or lack or competence or info -    Your children can have children of their own, and so can your possible grandchildren, and so on

Questions

Are you responsible forr t wellbeing of your progeny, including t future generations in your direct family line Are you resposnib for t ewellbeing of other members of t future gen Ami i Are you entitled to coerce me into securing t wellbeing of t future gens?

Are you respon sible for your own? -    box of surprises o    inherited sealed box, cannot open, may contain valuable material or explosive, but smaller chance for latter. Choice: never open box, or give to stranger as give. If give it away, can open it, but no knowledge of contents. Should you give box to stranger

are you responsible for your own?

Conditions for giving t box -    if ou can you can ask t potential recipient. Free informed consent might provide justif -    if not, consider her current sitn. Abject povery might be a factor -    you should be prepared to assume responsib for t conseqs if they are adverse.

Are you responsible for your own? -    the gift of life o    when consider having children, you consider creating indivdwho does not exist yet and giving her a box of surprises o    you  have metaphorically inheretned t gift of life as an heirloom, and you are thinking of

received cannot but open box life might be good or bad

are you responsib for your own conditions for passing on gift -    cannot seek consent of receiver, can only assume -    cannot argue for t situation of t receiver – can only assume life’s value -    must recog your responsib for wellbeing of the (non-voluntary) receiptients -    you must try to guarantee that t lives of your children etc are as good as they can be

are oyu responsib for your own -    answer to first question o    you are responsib for wellbeing of progency, because commitment to this responsib is moralc ond of having kids

are you responsib for others?

How t parental contract comessa bout -    as a prarent you must ask yourself: o    ‘who will take care of my children and my children’s children if I cannot? o    And the natural answer is o    ‘parents of other children. We make a deal. They take care of my progeny if I cannot and I take control of theirs -    how t parental contract is binding o    because by reproducing you have taken on duty to guarantee wellbeing of offspring o    your mutuial contract is not morally binding to anyone else (nonparents) -    answer to this question: o    ou are responsib to other members o t future generations beasides yourown

am I responsib for your children? -    why would I be? o    Because I have made a parental commitment? NO o    Parental contract? No o    Because a need exists, and I should respond to it? •    3 layers •    immediate need in an emergency sitn: your existing child drawoning in a pond? Only I can help. Should i?-yes •    longer term, non-emergency needs: your children need an education, should I contribuite? – probably (prudential), but you first: ME: WHY? SO, REJECT A NATIONAL EDUCATION SYSTEM? •    the needs of your non-existing progeny: why would I sacrifice my worthwhile goals to promote your reproductive aspirations? •    INVOLUNTARY PRODUCED OFFPSRING: should I respond to needs of future children whose existence is due to force, devception or lack or competence or info, of course, but you should join me in preventing such reproduction •    Saving resources to future generations: 5 generations down t line you have burdened t natural enviro 5 units against my one. Could I have double portions, please? •    ME: is he setting up an us and them that is false? •    Answer to 3rd question o    I am not responsib for wellbeing of your distant progeny, or for t wellbeing of other voluntarily produced members of the future gens because I am in no way responsible for their existence

Can you justifiably coerce me? -    possible grounds o    do I have moral duty that you re entitled to make me dispense by coercion or force? No o    have I made a commitment that you are entitle to hold b to by coercion orfoce? No o    have I entered a contract that you are entitled ot make me honour, by coercion or force? No

possible grounds for coercion? -    doyou represent a dominant protective agency which is entitled to coerce me? NO -    if everyone acted like me humanitiy would cease to exist. NO CHANCE. (and voluntarily, what’s the problem) -    if many peoplea cted like me there would be too few tax payers (MOST UNLIKELY) (revise immigration policies)

answer? -    not entitled to coerce me because no valid moral, social or political grounds for such an entitlememnt (I may chip in from time to time voluntarily)

Soren response -    everyone might trace their roots to involuntary creation -    contractarianism: why no contract between procreator and non-procreator to take care of latter

reply -    yes, some involuntariness, but my first duty as non-reproducer is to change world where every reprod choice is voluntary -    wider contract issue with society? Yes, perhaps, but I acknowledged that immediate needs will be met.

Question: the discourse is liberal, but narrow concept of responsibility -    alternative: necessity of action in face of evil.thus responsible for future generations, because the evil exists. Eveil is beginning of responsibility

Question: if you don’t want responsibility, you don’t have responsib for others and if you have your own, you have sole responsibility. But this is not true. Even if you

ME: parental responsibility does not convey, in its entirety, responsiibilty towards children. Parents do not have sole responsibility over their children.

Responsibility for future generations F. Turoldo (Italy) university of Venice.

Why is t term responsibility not t common term in ancient and modern philosophy? -    why contemporary?

Rotation of meaning of responsibility

Initially a juridicial concept – a consequent way – I am responsible for an action and its consequences

2 conditions 1. individuality (I am responsible) 2. consequent (towards past actions)

respondre – to answer for

moral concept of responsibility -    inner judge

T problem of allocating health care resources considering future generations M Igoumenidis

Is it fair to spend mony on moon trips and cloning sheep when could use money to save present people’s lives?

6

The Future of Our Memories (2005, Royal Institution of Great Britain)

The Future of Our MemoriesRoyal Institution of Great Britain 23 June, 2005

Wendy -    Bruce Almighty, God digitised? ‘file cabinet’ of memorie -    Share v private

Various Jim Carey movies

Neil

Hartley et al 2003 -    VR – ask neil -    Functional magnetic resonance imaging

Graham et al 2003 -    memory related dementia -    Alzeimers -    Factual memory (Semantic dementia)

Vanneber Bush, 1945 – see Bergire (d-Lib), may) -    www.memoriesforlife.org

AR/VR -    mixed reality lab, Singapore

Alan Nevell (dunde, social memory)

Miniature recording device

48 hrs of video – reality tv – dull – audience

Rugge et al

Hans Berger 1929

Quroga et al 2005 – face recog

Kriema et al 2000

|

Sport Medicine Ethics (2005, Stockholm)

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

Christian Munthe Sport, Med and HC

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

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

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

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

Conested procedures – 4 args (doping, etc)

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

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

Claudio Tamburini

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

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

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

Anders Sandberg

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

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

Question&A

JS: by allowing enhancement, implies coercion

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

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

Susan Sherwin

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

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

Sarah Teeztsel

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

Nick Bostrom

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

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

Mike McNamee Slippery Slope

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

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

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

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

NB: Asian disease prob –

600 will die without intervention

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

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

A and C are same

B and D are same People overweigh losses in decision making

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

Jim Parry –

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

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

should not pressure people finto taking big risks

sociall construction of rules – and arbitrariness of rules

MMc: autotelicity – have own rules

Human Enhancement Technology (2005, Harvard Law School)

Dan Brock Positional / competitive enhancements Relative enhancement or intrinsic

Many enhancements Ritalin ‘Enhancement v treatment’ v ‘enhancement v achievement’ surgeon  using drug to steady hand – enhancement? But a good thing! Special diet? – training, tf natural -    distiction – conventiona

natural means, effort, etc -    basis for merit

but use other things – natural talent natural – not what we can take credit for

natural – brings out potential enhancement – changes potential

but flawed! No such thing as a fixed potential

Olivier

Rules for technology -    icu – rules on bikes

press on doping often biased – in what way? -    media over simplify -    sometimes good that not public

record number of positive cases in Athens -    more than history of Games

Misuse of medicine

They are fighting ‘mafia’ of sport – illegal market of drugs -    ME: what is incentive pf pharma to work with WADA?

Protect ‘ future health’ of athletes -    ME: mmm, future health, what does it mean to protect this? – if gene profiling shows I will die at 30, then?

More public exposure than ever before

Anti-doping comes from the Athletes, who do not want to jeopardise future -    athletes want to be natural

standardised v personalised technology

Q&A

Power patches used by athletes – lifewave technology Acupuncture?

Different kinds of technology

polevault -    accessibility

Is there any incentive for Pharma to work with WADA?

If all enhanced, sport no more interesting -    al athletes running 100m at 8seconds, no more interesting than 9secs

not all risks are acceptable, if come with harms that

Olivier: we are in a ‘risk reduction’ society. -    ME: mmm, not that sure! Risk calculating perhaps.

Next generation of EPO -    company who develop panicked, since worried about its use in sport

genetic technology as therapy and enhancement, then is it ok?

Justice, Healthcare and the Trend Towards Predictive Medicine (2004, Brussels)

Conference NotesJustice, Healthcare and the Trend Towards Predictive Medicine 22 & 23 November, 2004.

Intro

M-J Simoen Background on Foundation.

Cecille…. Brocher foundation aim to provide place for research, linked to medical and scientific: socio-political implications of progress. Mr and Mrs Brocher interested in links between science and law.

Is medical care a service like any other?

Alex Mauron Scientific and social aspects focus Access to health care should not just be for determining individual predisposition, but social solidarity – linked to justice.

Importance of Europe. Genomic and medical progress – impc placed on difc between individuals and risk profiles and tendency people have to be affected by certain medical conditions – pharmacogenetics.

First analyse from philosophical perspective (first session) – regulatory concepts.

Bernard Baertschi, Uni of Geneva – philosopher of bioethics One of most signif authors in francophone world

Bernard Baertschi Norman Daniels was student of John Rawls

Sustaining a right to health care Norman Daniels, ndaniels@hsph.harvard.edu Harvard School of Public Health

Can (should) t tradl Euro view of health care as a basic, universal right be sustained in t face of t challenges posed by advances in predictive medicine and t emergence of a more diverse Euro Union and Market

I focus on ‘should’ more than ‘can’, though should presupposes can, so cannot escape feasibility

Small Irony

You should sustain right to health care 45million people uninsured in US –  they get care, but get too little too late

mentions Bush prob

Promise from more competition: more efficiency -    US as model – expts in comp at various levels: hospitals, insurer, managed comp o    Early Rand study evidence: cited as main evidence, but negative effects on patient health not given much attention o    Prob with export of US strategies for health care – led to following bad models o    Era of managed comp – 1990s ‘backlash’ o    ‘consumer driven’ health plans in US – newest phase -    Economists: failures to lower unit costs, to lower rates of cost increase are evidence that ideal market conditions not approximated, try harder

RAND HIE: 1974 (CLOSE READING IN AN AGE OF EVANGELICIALISM – LATER) -    RANDOM CONTROLLED EXPT REGARDING FREE CARE V DIFFERENT LEVS

Appeal to markets: empirical not principled issue -    not in principe against using market forces – if it could be shown that comp worked to make system yield more value per euro and could be channelled to do so equitably through proper reg, I would embrace integrating marketing mechs -    BUT: US unit prices highest in world, despite more market mechs, no evidence of greater value per doller – indeed contrary evidence, and worst outcomes (return to this later) -    Caution

Promise of Predictive Medicine -    early, low cost predictive profile of health risks – through extensive genetic testing o    assumes low cost, good predictive value for more than straightforward genetic diseases eg. Applicability to high prevalence, chronic conditions o    assume privacy issues addressd -    Promise from (hype from?) genomics, proteonomics,- specifically tailored drugs for safe, effective treatment of indiv depending on genotype -    This technology is a mismatch with existing economic incentives for medicine -    Every drug will become orphan drug – only treat a few people, so why develop o    Many economic and oscila probs before

Predictive Med: two paths -    make syst work better, sustain equity o    idf those at risk o    respond better to identified needs •    indiv medicines? But more orphan drugs o    allocate fairly across competing needs -    divid and conquer: undermine equity o    stratify risk pools •    us v them ideology o    shift costs to those at greater risk (poss to identify those at risk and better respond to needs)

overview of argument -    special moral impc of health o    opp range, capabilities •    connected to Rawls’ theory •    from several philosophical perspectives, if one could devel claim that funl right to protect opp range of indivs (Raels ‘equality of opp’), then argument that way to think about healthcare is protection of opp range… -    obligations of justice to protect health o    obligation to promote fair equality of opp -    use predictive medicine to better protect health, not shift costs or deny coverage -    beware temptations of market – evidence, not ideology -    intergenerational equity/justice and sustainability of transfer schemes o    shrinking working age population makes more difficult to finance health care syst in Europe

FEO Account of moral impc of HC -    disease and disability are epartures from normal function

Justice as Fairness -    hypothetical contract (Orignial posn) -    simplifying assumption o    normal functioning over lifespan -    index of primary social goods -    three principles o    equal basic liberties, fair value of political liberties o    fair equality of opp o    difference principle (restricting range of inequalities permissible in soc)

Extending JAF to healthcare -    JAF simplied to case when there is no disease, disabilityt or premature death -    Open to criticism: - arrow sen, others

Whitehalll study (Marmot and Shipley, 1996) -    all-casue mortality by grade of employment – whitemall men 25 year followup -    socio-economic gradient of health -    not explained by health risk factors we usually talk about (such as lifestyle choices) -    hypothesis

(Justice as fairness) JAF flattens gradient

Compliance with 3 Principles of Rawls -    flatter than

theory extends in surprising way as to why justice is good for health

Accountability fo reasonableness -    four conditions of fair process o    publicity: reasons or rationales for imp decisions and indirect limit-setting structures publicly available o    Relevance: fair minded people (relevant stakeholders) agree rationales are aimed at pursuing appropriate patient care under resource constraint o    Revisability/appeals: fair appeals procedure o    Enforcement/regulation

-    REF: Daniels, Sabin Setting Limits Fairly, OUP 2002 o    Moral disagreements surround many decision, don’t have agreement on moral principles that resolve these disputes, so must fall back on account of fair process that minimises choices that are made

Shifting costs to ill or high risk -    argument for Actuarial Fairness – purchase health security at actuarially fair cost o    US substitute insurance concept for moral concept o    People should buy security that reflects real risks o    It should not apply in health setting -    Actuarial fairness is not fair – if protecting health is social obligation -    Burdens according to ability to pay, not need: principle violated

RAND HIE: SOME NEGATIVES DAVIS, J. HSR 2004, 29: 1219:33. -    Adverse effects on low income and high risk indivs (Rassell, 1995, NEJM) -    Lowincome high BP: better control with free care:; lower risk of death for high risk

Risk Stratification: other costs -    culture is created by institutions, instits can encourage or discourage and reduce mutual support – what’s in it for me, rather than us’ spreads like cancer -    stratifying insurance schemes not only shifts costs to ill but undermines more gen concerns for social justice -    not only will access and burden be modified, but content and quality of benefits will stratify

In Europe, 50 yrs of sharing and caring, in US has promoted division and self-interest. Contributory factor to recent US election as well as others. In US until now, one of good thiungs has been universal health care provision for elderly – not sure whether will continue

Use predictive power to improve health for all – other parth -    respects social obligation, equity -    estab priorities using accountability for reasonableness -    improved preditctive power may have efficiency gains -    evidence based improvements, compatible with market

Challenge to sustainability -    societal aging, changing worker to elderly ratios o    China most rapidly aging popn in world o    Dramatic societal aging in Several Euro countries – shrinking workforce in Italy, elsewhere threat to pay as you go financing of universal health care -    Technological cost drivers – medicine is not what it used to be, costs more everywhere

Challenge not from predictive medicine, but promoted as challenge, by rise of aging popn and reduction of ratio.

Jean-Francois Mattel University of Nice

Devel of health care since mediaeval system intended to take careof needy – workers -    was a social issue, now political

hospitals previously funded by charity -    now funded through solidarity

why is there a philosophical issue? -    defn of man, solidarity -    moral prob on defining human and fair sharing in terms of human dignity -    different to compare health care systems around world o    instruments used o    current used indicators are infant mortality and life expectancy – which relies more on social conditions -    health care system o    defn: range of techniques/practices intended to produce health in same way as we produce wealth o    metaphysical/ontological: what is health? •    Material asset or something different

Can health be seen as industrial product – something that can be traded

Syst wich distribs health – hc systm –more different to control, since has many parts and increasingly economic, indl, and financial components -    which is wher political comes into play

central Q: equality of access for patients and legality of assumption of HC costs

perhaps 3 main axes: liberal (US egaltarian / Euro), inegalitarian

tendency in Europe to think syst is preferable to US, since has concept of solidarity that underpins it -    link to historical idea of charity

society has moved HC into social space, rather than religious space -    social spaces collective, whereas religious spaces are individual

Durkheim – collective concept of solidarity

How can justify solidarity and influ in HC?

Imp in HC since calls into q, social prof and human dimension, but also biological and physical concept of human.

For first time in history, biology become social concept in terms of how society assumes costs of HC

Can bring demands of health into HC and move beyond idea of HC as idea of solely doctor to patient. Horison of perfect health – Utopian society – everyone perfectly attended to. – to allow maximum of solidarity

Increased medical component of science and way that HC incly based on technology, gives new way of analysing human and providing HC.

Belief in indiv dimnison that is absolute – human dignity

Need some distance – philosophical q

Requirement for human dignity and solidarity is devel of human beings over 300 hrs.

Anthrop sense – modernity – (not go into postmod) – converging processes -    new kind of socialised human being -    First charact: progressive secularisation of religious concepts o    eg. Religion based on Judaism or Greece, man only perceived of own existence through religion. No right to health care. -    Second charca: de Toqueville – inc socialisation of man, led to tensions between social and moral requirements. Political arena where they are reconciled -    Third charc: social reqs of today, express on individual needs, rel between individual and social sphere – social demand as collective -    Fourth charac: technical development leading society. We ask sci and tech to solve social and medical problems

Change to modern sense of man

Second of these claims is that concept of man incly reduced – focus on body reduced – what the body requires

Think philosophically, but also consider human dignity and relationship to body

Does a dead body have dignity or is there a higher concept in play here?

Here we talk about dignity of socialised man

Tension between ethical concept of dignity which, to some extent, has metahistorical/metaphysical concept and need for using body, which means that it naturally comes to disappear

Need medical correctness as equal distrib of care to whole of body or to whole of society

Problem: right to medical care nothing more than political right

Rawls: Demand for right is political demand

In 21st century, law is social demand

Mankind today and societies are trying to provide medicality

2 rights: medicality and sociality

people seem to want a perfect health or life

to have this is to put of death entirely

best to have perfect qualities as human being and to have medical care as close to perfection as possible

producing health as producing products

want a body that will never break down

cannot have perfect mental states, but people want perfect physicality – beauty (ME: not easy)

WHO defined health as ideal health -    state of complete well-being physical. -    Can we attain perfect well-being?

Corpus sanum, not necessarily linked to mens sana

Demands of society a great deal.

Body as product

Product of medicine – from birth onwards, medicine acts on body With GM goes beyond that

Locke distinc between ‘property in’ – obligation to respect people and ‘property on’ – material goods

This health is material property in Locke’s terms – not an inalienable right, like freedom, more like commercial article – privileged to have

But cannot say that a body is good or bad in pure ethical terms

Is it better to die as soon as possible after born to avoid suffering, or the contrary

Our societies are no longer tragic societies, but rational

Philosophical question: can we eliminate all tragedy from human life? -    only way out is death

need to avoid tragic dimension to life

we want perfect mental health and bodily health

we want to look death in the face

and look tragedy of life in death

Aristotelian problem: act of living..

Can we have a happy life in which we aim towards living together in a society, moving forward as society?

In third millennium societies, we are trying to make the challenge of taking biological life and giv it good life in Aristotelian terms -    begins with the body and medicalisation of body

socialisation of medicine is medicalisation of the body

man’s body is locus for application of our technologies

economic dimension as healthcare costs

politics makes final decision on this

fact that man becoming instrument, not just medical or social problem, but a moral problem

if man no longer thinks of self as divine create or natural product or man, but part of social mechanism, how is he then to have a body that no longer belongs to natural world?

The body is more and more a technical object. It is something mediated through the technology.  So man becoming something that technology acts upon. Benson: man is constructing himself nowadays and constructing new way of making himself. The body is something we build. Try to give it perfect life/health.

Back to solidarity – guiding threat.

Justice and solidarity: what are they? No longer religious, even if religion is background to all moral thinking. Morality is articulated through society. No greek term for society. Greek words that come close talk about relationship between people. Our modern world needs more solidarity – and more demand.  This means that individuals often unhappy, when they don’t get what they want.

Is our modern societies, whatever decisions, whether will, in allowing soc to determine way medicine acts on body, whether will regulate that or leave it to the market.

Are we going to see market acting in way that Adam Smith described – hand of market – or hand of politics making sure everyone gets health care.

Remarkable that our society is having to deal with this challenge. Not only recognising everyone’s equality before the law – as political, social terms, - but everyone’s equality in medical/bodily terms.

Can our modern societies, where popn aging, can they give healthcare?

Will Genetic Predictive Testing increase inequalities? The Psychl Theresa Marteau Healthy Psych Section, Guy’s Campus, IoP, KCL

How do people respond to predictive genetic testing Must understand something of context where will be introduced We all know that the rich live longer than the poor. This is likely to increase.

Self-efficacy to stop smoking.

Hall and Marteau, in prep – people of lower education, feel less confident to stop smoking

Genetic Predictive Testing for Heart Disease -    websites sell this, but little available from health service

Anticipated that gen test incorporated into HC syst in 5-20 yrs.

Imp to consider now, how people will respond on impact to justice of implementing tests.

Huge expectation that will impact people Gramling et al. 2003 – Exepcted motivational impact of predictive genetic testing for cancers -    asked what they expected to see in their patients, if they underwent testing -    expected that those with risk would be likely to attend screeing, likely to change diet and stop smoking

Will gen pred test inc inequal? -    depends on social patterning of uptake and motivn to change behav o    uptake 1: hypothesis: t difference in uptake between those who are leadst and those who are most deprived is larger for gen predictive test than other pred test (given preexisting socially patenting of expectations and need for informed choice with gen testing) o    hypothesis 2: motivn to change behhav following testing will be lower in those who are most deprived (due to pre-existing socially patterning of fatalism)

role of media in creating hype -    Dobias et al 2001 – womens magazines – mammography messages in women’s magazines aimed at different education levels o    In magazines asso with low education, more likely to be persuasive and less likely to discuss uncertainties

Domenighetti et al 2000 – impact of info on willingness to accept screening -    more we talk about people of uncertainty, less interest they havein attending screening -    when discussing gen screening, emphasis on informed -    those most deprived, less interested

Schwartz et al. 1999 -    mammography ptake in women at high risk for breast cancer (US based study) -    randomly allocated women who were high risk for breast cancer, to receive counselling session or Control o    found that high educated, risk counselling had no impact, but for low level of education, learning in detail mammography rates went down.

Will gen pred test inc inequal? -    hyp1 o    Evidence to support •    Expectations of t benefits of screening higher in those who are more socially deprived -    Hyp 2

Cartoon caption: “Because my genetic programming prevents me from stopping to ask directions – that’s why!”

Perceived controlover causes of illnesses -    Shiloh, Rashuk-Rosenthal and Benyamini, 2002 -    People feel can control, if perceived behavioural and progresses lower to enviro and finally genetic

For chronic gen conditions, gen part only one aspect

Multi-factorial condition emphasse gen component

Senior, Marteau and Peters, 1999 -    parents perceived casues of raised cholestoral in their newborn babies, deterred during screening -    where parents thought was genetic problem, far more fatalistic about the problem -    whereas when not perceived as genetic, felt that was something not of concern

Debate

For Norman Daniels -    2 complexes of ethical principles: Rawls justice and 4 conditions of fair processes -    are they separate?

Answer: -    work of philosophers in 1990s, unsolved problem of rationing, how much to give to specific groups? -    When should we trade best outcomes in the use of a resource, in favour for just outcome? -    Do not have philosophical framework of consensus -    Need to suplemetn gen framing of problem of distributive justice with fair process -    Gen framework of fair process

Question: Alex Mauro -    for Norman Daniels -    in view of B Baertschi, process is to flatten gradient, but process is tricky since, if some screening is efficient and if implemented in context of gradient, then expected to steepen. It is as if good quality screening is especially prone to being egalitarian. How can we bring in a correcting factor in name of flattening gradient?

Answer: -    gen law in HC research that medical technology are taken up in proportion to socio-economic status -    Marteau argued that predictive testing might be even worse than established knowl -    The response: more institutional effort from within and outside HC syst to educate people about false aspects of genetic determinism. – health literacy programmes -    This would be consistent with view of health as social product, not just as medicalisation of body -    Evidence from social epidemiology is that health in distrib of populations is primarly effect of social determinants and public health measures -    Couple of other comments on prof Mattei’s paper

Marteau -    if you don’t formulate something, then you don’t set out to try to find it. Solutions in many places, but what one wants is an inequality of resource, when setting up programmes o    spend more resource on those who are more deprived -    education is umbrella term. We know self-efficacy much lower in these groups, so need more help.

Daniels -    Prof Martau focus on threat of inequalities -    Much as I am interested in reducing health inequalities, especially when produced by many unjust XXX, always complex normative problem as to how much to give to worse-off peoplee. We do not have social agreement on this. Itself calls for fair process. Supplement gen view that inequalities are bad, because always faced with specific problem with how much benefit you give up for some people to reduce benefits for others

Ruth Chadwick -    for Marteau on evidence on fatalism -    statement ‘if I have familiar hyper….’ How can one distinguish within that between those who think that’s just what it means to have that condition and a fatalistic attitude, which could be quite different

Response: Mareau -    yes, might be a lack of understanding. -    Was not my study! Similar criticism I have -    One would want to have more than one measure, interview people and understand how that statement is ustod. Better defn of fatalism and use range of measures. -    Was only study that measured education.

Question: Mattei -    diffc between solidarity and charity -    seemed to imply that religious spaces were individual, but lose out on a lot of judeo-christian trad with God’s relationship with individuals -    misses fundamental idea of church -    interested to hear Prof Daniels response too

Answer: Mattei -    distinction isn’t just a reflection on Christianity, but type of help can give to others. True that Christianity has community dimension – caritas – love for other people. What history has show is that when first establishments set up for needy and sick, did supply solidarity, but based on Christian idea of charity. Did welcome non-christians, but nonetheless something that happened within religious sphere -    social sphere has taken over. In a religious relationship between different groups or person and group, are different relationship to ones they have in impersonal relationship between person and group under solidarity. -    In modern societies, have hundreds or thousands of indivs, different to develop social network. -    Prof. Daniels said that social but also political forces directing what goes on.

Norman Daniels -    Agree that religious traditions have community value. Hebrew for charity ‘sadaca’ – righteousness. But is different. If I don’t give charity to some individual, they don’t necessarily have a claim against me, it is at discretion of charity giver, whereas rights involve reciprocal duties. Domain of justice a little different from charity. -    Framework of rights reveals that where diverse popn, merely as citizens, we owe each other as deserving of basic cares.

Question: -    charity and solidarity – one of imp aspects is that solidarity comes from workers movement. Autonomous action in charity, not in solidarity. -    Moving towards individualist soc and lost some value -    Difference in some charities – Muslim: fundamental value -    Careful of Eurocentric view -    Question for Daniels: mentioned market aspect and solidarity system, question about pharmaceutical market. -    Given that market is maximising profits, down side. Taking an outside regulatory sphere. Not helping to modulate practices for access

Answer: Daniels -    complex problem with pharma -    have hd this issue close on pricingof endoretro viral treatments. -    Pharma made concession by providing generics -    Decided to lower prices. -    What drugs get developed and for who? -    Njeed to be revisited

MATTEI -    would all like to see most egalitarian distribution of justice -    this is something inalienable, cannot talk about justice without fairness. -    Can we have justice really or is it just utopian ideal? -    Is it something we can concretely have? -    Saying that market is selfish, must ask whether is individuals are selfish -    Niave to say we have some magic wand to solve this problem

Question for Marteau -    data suggests that more detail of info, the more it risks to increase t inegality -    to poor people give simple messages, to richer, give sophisticated, which also increases inegality of knowl? How deal with this problem of communication?

Answer -    this is one of tensions in this field -    magazine analysis shows that simplistic messages to lower levels of education -    highlights tension between individual autonomy and realising public health outcomes

Daniels -    what we owe each other, not just what it would be nice to have -    connected to broad and confused defn of WHO on health -    real people in HC don’t worry about that defn, they look at morbidity -    protecting health and not all aspects of human well-being -    I don’t think talking about groups is an abstraction -    Markets are not simply individuals, they are shaped by rules and regulations to ensure they avoid certain failures -    One of problems with pharma is that IP law may be stacked in favour of houw drugs get developed

Access to healthcare, in particular new medical technology

Yvon Englert

Thoas Perneger

Imagine trying to screen for cancer in over 50s, test A = cheap and available to everyone, avoid 1000 deaths; or test B = more sensitive, can only give it to 1 in 2, save 1,100 lives. Which would be preferable? -    thi was asked to doctors in private practice and public and asked how they would choose for test B – eg lottery, or medical orgs, only a minority choosing test B -    Med Decis Making, 2002, 21: 3-8 -    Doctors were prepared to lose 100 lives in order to preserve fairness -    BMJ 2004; 329, 425-8 o    Would you allow XX into intensive care? o    Woman in A&E and feels bad o    Do we do it? o    Might depend on disease o    Only one bed available in intensive care, or only 3 o    Describe personality of patient. o    Whether is anxious or not o    Swiss doctors split down middle o    Asked 200 doctors and 55% said they would send patient to intensive care. If 3 beds available, 59% if 1, 45% o    Somebody who is being brave is twice as likely to be admitted to intensive care as someone who is anxious and depressed

10% of doctors said did not want to answer the question

Telemedicine, virtual reality and robotics, new technologies for an optimised health care. Luc Soler

The First Keyhole surgery course

Is patient clinical case or a person? How teach future surgeons if don’t really have contact with patients? When dealing with patients, you might see inturns who are with head doctor and some consideration not given to patient Reduction of surgical nature of medicine – smaller incisions. Direct contact between surgeon and patient, beginning to diminish Operate using tv screens or robotics New imaging technology – MRI scanner Helps for greater communication with patient Reaching areas where human patient becomes digital data Technological developments -    Virtual Reality for Tumour Analysis -    Take 3d medical image – computer tomography, magnetic resonancing, set up digital clone -    No risk to patient since working on virtual patient -    Prepare surgery on this basis -    Simulation of surgery -    Pre-op phase helps for actual op, since info can be superimposed onto patient. So , through robotics, willl get to point where levels of care will rely on these procedures and can rely on qual of care too Medical Imaging -    from CT-scan or MRI of a patient -    better tools for visual

Using algorithms, can build up representation -    allows 3D model to be visualised -    software name: Cult3D (works with IE)

made poss by advances in video games and computer games -    computers now have 3d imaging cards within them

used for explaining condition to patient WebSurg – www.web-surg.com -    World Electronic book of surgery -    Financed by various people. Only free site -    This software is freeware

ME: v intrereting software. Look into

Capacity to go backwards within a procedure and start again

Being used in Geneva and Zurich for surgery planning

Also exists as network system – can be shared with various experts

Helped for info sharing

Real time force feedback simulation -    probe includes feelings of resistance -    INRIA – link again with computer games – Project EPIDAURE

Intra-operative VR surgery

Interactive Augmented Reality

JAMA November 2004

Superimposes image of surgery procedure so can see that eth is being done correctly

Huge surgical advance

3D image doesn’t move when patient breathes – current limitation being dealt with

fully automated augmented reality

LNCS vol 3150

Robot: Telesurgery -    2 robots, 1 society : intuitive surgical -    Da Vinci and Zeus machines, now merged -    New solutions: Artemis, Hitashi, Sinters… -    Extremely expensive $1m (access issues) -    Surgeon can be decoupled from OS -    Robot controlled by -    Lindbergh Surgery, sept 7, 2001, Nature -    Idea not to replace local surg team, but support -    V expensive, since fibre optic transmission time across atlantic costs a lot, so not really poss at mo

Visual Servoin -    increased automation -    control instrument remotely -    can take into account t breathing of patient -    instrument moves to follows beat of heart -    microrobotics and nanorobotics – Norika3 – swallow a pill that will look at what the body doess -    Toshiba (Japan) 5 cm tube trying to make smaller -    Intelligent Microsystem Center (Korea) - biomimetic

ME: this is a good argument to reject naturalness of human

Future of surgery?

Automated procedure -    mistakes of movement can be re -    Robot for a better control of the surgery -    Under the control of surgeons! -    Cartoon: robot surgeon

Acess to health care: Patients rights as a tool for priority setting in Norway Ole Norheim, Uni of Bergen Part 1: background -    priority setting in practice: experience from Norway -    assessement according to t ideals of deliberative demorcaty o    Norheim OF: Report on Norway in Eds Ham and Robert, Reasonable rationinign, OUP, 2003

Part 2: recent development -    patient rights as a tool for priority setting

A short history of priority setting in Norway -    1987: the Lonning I-commission and waiting list guarantee o    set priorities according to severity of disease -    1990: expert group developing national clinical guidelines for bone marrow transplantion o    practical priority setting o    was emerging new technology, costing a lot o    many patients competing for this scarce resource o    principle of evidence as basis for rationing o    where firm evidence, priority stronger o    received supp from ministry and health council -    The Sandberg case, 1993\ o    System broke down. Said no to a patient, whjo happened to be brother of a TV personality in Norway, led to media storm, decision challenged, and minister for health backed down. Several cases like this in 1990s. -    1993: publication of national guidelines for anti-hypertensive treatment informed by cost-considerations o    arguing that not all prevention of CV disease should be provided – higher threshold, based on cost and personal resources to screen and treat -    1997: controversies encompassing new prescrip drugs o    Aricept for Alzheimers disease o    Forsamax for primary osteoporosis -    1997: The Lonning II-commission o    adjustment of criteria for waiting list guarantee •    severity of disease cannot be main concern •    Rawls difference principle: distribution favour the worse-off – easy to see cannot follow this principle extensively in special cases. Eg. Terminally ill cancer patients should not have high priority. Medical outcomes also considered and balanced against needs. Cost-effectivenesss introduced. o    proposed procedures for defining core services o    based on t principles of Accountability for Reasonableness o    compromise between competing values: severity, cost-effectiveness, medical outcomes. o    Inspired by Norman Daniels work o    Ministry of health did not takeup idea of implementing procedures -    1997:Philosophy Norwgian centre for health technology assessment estab -    1999: Norwegian govl appeal board regarding medical treatement abroad established o    as a result of lobbying minister of health on specific cases -    1999: Patient Rights Act o    specialized care

Evaluation -    what procedures are used to determine whether health technologies should be funded? o    No estab procedures o    Highly specialised interventions centralised o    Diffusion of technologies is the rule

Government isn’t actually regulating things

Fear that new technology is being easily introduced, might replace other important services that our HC syst should provide

What is t role of t different instits in these procedures? -    rationing was almost a non-existing health policy issue -    regulation is centralised, funding is decentralised -    little research from Norway on houw such decrentralised decisions are made -    centre for HTA: evidence based assessment of new technologies -    Norwegian Medicines Control Authority: Reimbursement drugs, evidence from cost-effectiveness studies are required

What knids of evidence do these institutions expec, req, or consider in making funding decisions? -    exptl or investigational treatment vs established treatment -    t evidence hierarchy: evidence from randomised clinical trials, systematic reviews and meta-analyses -    evidence from cost-effectiveness studies seldom cited

What ‘standard of proof’ do t institutions expect to be demonstrated in agreeing funding? -    no govl institutions have explicitly formulated ‘standards of proof’ -    Oncology: two or moroe RCTs before a new treatment modality is regarded as ‘established’ -    This standard was challenged by Matheson case, 1996 o    Woman aged 50, breast cancer with metastasis o    Received high-dose chemo with stem cel support in Sweden o    Evidence: Bezwoda et al 1995 o    Demined reimburesment from National Insurance Adminsitration o    Appealed to Minister of Health, appeal accepted o    But only in this case, not for comparable cases o    Oncologists objected: violation of t principle for equal treatment for equals

What appeals mechs ar avaialbe or reviewing decisions? -    appeals mechs for coverage decisionwihtin con

Eval of pririy setting in Norway –prior to 2003 -    much high level activity – principles well established -    political and admin reluctance to introduced proceduires and institutions with a mandate to make explicit coverage decisions -    Patients Rights Act not really implemented o    Now change in Legal system -    Appeals mech estab -    Technology assessment playing minor role -    Conclusion o    Stronger institutions will inc demand for more and relevant info o    Implementin right to necessary health care, a way forward?

Part II

Implementing patients rights as tool for priority setting in Norway Experience from Bergen: largest uni hospital Bottom u

Norwegian Patients Rights act 1999 -    obje: ensure pop equal access -    no sepecifiction on right

Financial sanctions -    since Sep 1, 2004, every patient has right, if not patient free to seek service at other hospital or abroad and regional health authorities wil reimburse t expenses

Implementation -    Wstern health region, -    Consensus based guidance for patients rights -    - based on accepted criteria -    Development by specific group -    Output: rough ‘guidelines’ for all relevant patient groups and interventions with recommended max approp waiting time -    Process:

Aim of project -    strengthen provision of well documented and reasonable cost eeffective health services to all patients with serve conditions

Priority setting model -    core services that should be provided -    elective necessary with right

Results so far -    16 guidelines from different specialistes

-    available for all health professionals on intracnet of hospitals

egs. -    rheumatology

next steps

1. evaluation, adjudtement and comparative analysis

1.    severity of diseas 2.    effectivness of technology 3.    reasonablness

2. Hearing process

3. revision 4.  publication: internet (accessible)

Conclusion: -    rights to core services can be defined through delib open process -    requires consider of who is worst off, clinical outcome,s cost-efectiveness, and qual of evidence -    but leaves room for indivd deiscretion -    openand explicit guidelines prov an opp for starting process toward fair and legit priority -    though not yet evaluated

Genes, food and drugs Ruth Chadwick

Outline -    new technologies have led to revisitng of t individual-collective relation in public health -    and to questions of their impact on health inequalities

related to political will and underlying presuppositions and inconsistencies in policy that can affect whether new technology can inc or dec equality

partic ref to individual choice

Issues -    opp costs: what else could we do with the money? -    access and benefit-sharing Choice? -    upholding of choice coincides with new forms of stratification -    no consistency in argument -    examples: nutrigenetics, obesity, and fnl foods

Two white papers (UK two strategies -    “we will learn more about t genetic featuresof common diseases, such as heart disease and diabetes and t way exeternal factors such as diet and smoking interact with our genes to increase t likelihood of developing a given diease” -    “There will then be t option to test peopole for a predisposition to diesae or a higher than normal risk. Trreatment, lifestyle advice and minotriing aimed at diease prevention could then be tailed appropy to suit each iniv, “Our inhertance, our future” -    Choosing health (2004) o    Sets out stratefy for action based on principles of informed choice….identifies how people can be empowered to make health choices. It sets out how health can be supported and improved in jey environments such as restail outlets local

First white paper, might have thought wil get individual advice in continuing to smoke, more rrecent one is to try to prevent them from smooking

Pulblic engagement -    2003 – traces of deficit model in public understanding o    people don’t understand, but if they had, they would be able to make approp choices -    2004 White paper – shaped by public consultation o    so that individual preferences have influenced development of policy document, but still hang on to view that info will empower people to make healthy choices. Though recog that not simple matter of giving people info and then make healthy choices, because of complecity of people’s lifves Key question -    how do these strategies relate -    impact on health inequalities -    what notions of perosnalised health care and choice are at stake -    2004 white paper talks about false dichotomy ‘nanny state’ – ‘freedom’ can imply neglect

Key example -    food and diet -    nutrigenetics -    food labelling -    obesity, diabetes

Nutrigenetics -    study of individual differences at genetic level (SNPs) influencing response to diet (whole genes or part)

Nutrigenomics -    aplic of genomics in nutrition research enabling assocationbw nutrients and genomic factors

info leading to applic -    understand how nutrition influ metabolic pathways -    understand how this goes way in diet -    understand how individual genotypes are influencing factors

Context -    public perceptions of genetics -    novel foods, eg gm -    prevailing ethical paradigms o    individualism and choice

Public health -    will nutrigenomics have signif public health benefits -    different between nutrigenomics and pharmacogenomics o    the other great promise in the 2003 white paper

pharmacogenomics promises individualised presecribing on basis of genotype -    enable avoidance of adverse reactions -    genetically informed prescribing (type of drug and amount -    greater safety and efficacy -    patient stratification -    signif differences to nutrigenomics o    food stuffs have many different effective ingredients, drugs are much greater characterised, acting on particular pathways o    more diffi to predict effect of specific foods o    promises of nutrigenomics more diffi to establish

testing – empowerment? -    single gene disorders (huntingtons) -    suspectiability testing o    idf recessive genes o    idef genetic makeuip which may increase risk of developing common diseases (heart disease and some cancers) -    pharmacogenetics testing o    medicine response test -    nutrigenetic testing (a form of suscpet test) -    empowerment depends on number of factors (partly due to interpretation, options, and whether people want them or not – right not to know)

Screening -    testing versus screening o    testing: of an individual through referral or self-referral o    screening: ascertaining of prevelance of genes in popn -    criteria for introducting screening o    important condition o    acceptable and reliable test o    scope for action

conditions -    PKU for newborns good example o    Phenylketonuria allows diagnosis to be made and if positive, diet can be adjusted o    However, is single gene disorder and nutrigenetics wont offer that sort of info. -    Diabetes o    Better candidtate -    Obesity o    Genetic Factor A – predisposition to obesity with food X o    Case for screening? o    Importance/scope for action?

Individualism and public health -    personal pills and personalised diets? -    More individualised t promise, t more collective action is required

Acquisition of info -    association studies o    popn groups o    specific disorders -    national dietary surveys o    established for many years, but new twist with genetic element, require setting up large genetic databases -    genetic databases

WHO (on genetic datbaseS) -    ‘..t justification for a database is more likely to be grounded in communal value, and less on individual gain….it leads to t question whether t individual can remain of paramount importance in this context’ -    ‘the achievement of optimal advances in t name of t collective good may require a reconsideration…

Alternative in 2004 whitepaper -    ‘environmental’ approach o    healthy choices (encourage people) o    labelling (Clear) o    restrictions on advertising (of junk food) o    children as a special group -    undelyin principle o    informed choice o    two qualifications •    children •    responsibilities to others (smoking) Inequalities? -    how this approach deal with? -    Increase buren of responsibility for health? -    Whose choice and for what?

Autonomy and choice

Identity – Individual autonomy –    utility – responsibility

White paper operates with notin of ‘responsible choice’ -    if people have info, they will b helped to make those choices -    though antoher notion, which does not arise o    choosing one’s identity: the sort of life one wants to live – which might include not wanting not to know genetic info, or choosing particualrl food style or lifestyle

implics for info -    food, body and self -    what sort of person do I want to be? (eg. Vegetarianism)

Fnl foods -    specific health-promoting or enhancing foods -    regulatory appracoh – highlights importance of freedom to market, subject to safety o    allows rejection in euro, if unsafe, though not whether effective (drugs must prove safety and effectiveness) o    problem: fnl foods targeted at partic audience,s but not like drugs prescribed by professionals, are available in shops; can be bought by anyone who might not benefit -    case by case approach o    tf. No mechanism for looking at… -    potential problem identified with fnl foods – target groups and overdosing -    e.g. cholestoral lowering margarines and yogurts – if same ingredients in many foods, poss to overdose – risk assessed on product alone -    cannotbe solved by labelling alone -    plus or minus nutrigenetics? -    For fnl foods, no drive to protect children as sep group -    Fnal food might be GM

Benefit-sharing -    turn towards sharing benefits of genomics (HUGO 2000, 2002) -    what counts as benefit? -    added value? -    Sharing of burdens? -    Return to issues of class

We are seeing, despite explicit ref to informed choice, return to class divisions

Rights and class -    financial times 20-11-4: ultimately, t worldwide reg push against smoking is being driven by a rev not just in rights but in calss… a class syste is solely being reereced on new bassis, brining with it a new and narrowe understand of rights o    by trying to persuade people to give up smoking, is disproportionately targeted against poort. Same can be said about food styles. – less affluent groups are targeted in strategy. o    By looking at extent to which these policy development will inc/dec inequalities, must look at other strategies, which say certain food choices have to be made. o    Not that people will make more informed choices

It widens genomics divide, but need for joined=up thinking in the two polices

Debate

Question: Norman Daniels -    to all 3 presenters -    first, Norheim, Matteson case, where min of healh backed down, the Bazooda study was later proven to be a fraudulent manipulation of evidence, and was a case that was reviewed in US, Blue Cross, Blue Shield debate – split decision 8 to 7 (scientists voted against it and managers voted for it) – when one capitulates to public, politically manipulated demand, often have signif harms to popn and huge costs. In this case, survival not increased by bone marrow transplant, but decreased -    hype of nutrigenomics might lead to experimentation on popn based on prospect for benefits -    Soler’s presentation was innovative, but problem of distincc between human subject research (requires clinical review and IRBs) and innovative therapies, which do not. o    The 3D tech does not require procedures -    What is case for ethical review for innovative technology

Response

Ruth Chadwick -    agree: fnl foods introduced on case by case basis and nobody is thinking about overall consq of mass consumption -    for nutrigenomics, willl not have enough added value to deliver and wil become fashion accessory for few, real agenda is to get people to make responsible choices -    pharmacogenomics big demand, so bigger issue

Norheim -    medical truth have a half life of five years: be sceptical of medical evidence. -    High standards of evidence a wise approach

Soler -    already performed some evaluation -    ethics: new technology bringing separation of physician and patient -    cannot forget patient is still there, so must see them

Comment rrom Y Englert: Daniels claim v important, current distinc between pharmacology (strict exptn) and expt of therapies -    in Europe, reimbursement for

Question: fro Y Englert: -    poss risk in strategy of prioritising by structure of health care (for Norheim) -    diffi and dangerous for minister to be the one to decide -    also risk that political decision that places framework

Question: for Norheim -    high standard for evidence, reasonable to prefer benefit with high certainty than low, but assumes that research questions are equitably distributed -    research questions are inequitable -    link between framework and research agenda

Response: -    might have problem -    acknowl different criteria in law would be need to be interepreted differently. -    Acknowled different equal disttrib in funding for research -    Framework of accountability – give reasons (scientific) -    Ethical arguments on severity of disease is another argument

Question: -    context in which people make decisions on food important -    food deserts – areas where no food shops and some less than optimal foods -    option for healthy choices has gone down -    changing the context?

Answer: Ruth -    reliance on labelling totally insufficient -    person that eats, not always person who buys -    gov white paper does recog that labelling not suff -    though not clear how help people to make choices -    bear in mind that eveidence of healthy choices is always years out of date – national dietary surveys – produced 5 a day policy – took place in mid-1990s.

Question: Theresa Marteau -    for norheim -    extent to which there is a tension between informed choice and thinking in those providing health care that there is a right choice -    nobody wants to talk about weaknesses in medicine –s ometimes doesn’t work -    people offered pills and potions, but chances are will not benefit -    if there was more of an informed choice, people less interested in choices people made, might be less demand for things

Response: Norheim -    studies on giving info -    BMJ some years ago on managing market -    Prostheic problems -    Prov info about risks/benefits of different interventions, changed demand for the services

Question: Euopean Commission: Health Technology and Informatics -    we are more and more influ by genomics -    interested in projects on popn data -    Question for Chadwick o    Puzzled by dichotomy o    enviro approach sounds like eastern religions. Don’t go into level of atoms, just believe in holistic truth that there are good and bad foods o    other view that analyse to level of gene o    why are we being put in this dilemma o    we have indogenous and exogenous determiniant s(nature/nurture), need to understand from level of cell and synthesise. We have v different worlds with different ontologies, which are sep: molecular biologist, clinicians, and health care people o    each live in their own worlds o    need vertical integration o    seems like policy based evidence, rather than evidence based policy

Response: Chadwick -    need for joined up thinking -    should not look at these things in isolated way -    these 2 policy documents have done that -    not either or, hwr, in case of nutrition, serious question about whether could get suff added value, by going down that research route, over and above generliased dietary advice -    not an argument against genomics approach per se, but in nutrition much more diffi to be clear about cause and effect

Question: Precise philosophical model being discussed on patients -    autonomous informed indivs, but implies info supplied in good faith and checked by publishers -    closer look at accuracy of that info -    problem not having access to it, but having too much info -    in  NEJM article on access to health care, something Clinton admi had raised – access to Hc discrim -    report rewritten twice by next admin in US and new version said something completely different – political interference -     also market interference on report, not pharma industry, which had right not to publish resultst hat didn’t suit them, rather, where info is a merchandise, new info sells best -    eg. New diets being sold to us -    should be talking about autonomous and correctly informed citizen -    Question: how you manage access to info for citzen and make sure is correct?

Response: Chadwick -    serious problem -    diet: one week red wine is good for you, next week it is not -    channels of info need to be examined -    issue about scientific responsib in communicating with public 0 increasingly addressed -    media responsibility -    different for citizen to know where to turn

Question: -    for Ruth -    issue about return of class -    what kind of class is this -    have mentioned various sorts of social stratification -    eg daniels – if genetic diversity is treated only through an actruarial model, might have unwanted genetic stratification. Marteau described social stratification in atts to genetic testing -    so what dimension of class is particuarlly concerned about?

Response: -    different interventions could impact on this in different ways -    social stratify: policy is reinforcing social stratify, since health behavious are those associated with poorer groups of soc -    problem with this is that, if you take this approach, - voting against lifestyle choices – sits uneasily with purported unholding of individual choice assoc with genetic testing, since suggests that indivdiualised medicine approach willl not be to support particular choices -    both strategies wil reinforce social stratify, though one explicitly claims to allow individual choice

Response Norheim -    ban on smoking in restaurants and bars since Jan and argument was about workplace rights -    this might also be a classist debate

Response Ruth -    this argument also used in UK debate, but proposal is that will still be allowed in private clubs, so employees in private clubs not protected

Response Norman Daniels -    availability of info -    Ministerial sumit in Mexico, WHO health systems research -    One of proposals is interenational registryo fo all clinical trials and public assurance of acess to all clinical trials -    Could not have propriety management over info – couldnot manipulate clinical trial info -    Establish a public goods environment for management of these Its.

Response: Englert -    Registry of medicines to provide all data available -    Cannot be some parts left out for negative result -    Transparency issues about study itself and decisions taken over results orientation -    These are difficult to monitor

Question thereas Mareau -    changes in UK trying to improve, where might be divisive -    partly a semantic issue -    choice socially patterned and behaviour socially patterned -    just because people are engaging in behaves doesn’t mean is a choice -    in UK at any one time 70% of smokers would like to stop smoking. While engaging in behaves, perhaps would like to stop.

Response: Ruth -    worth some consideration, but main concern is not reasons why people make certain choices, but view that policy has about what choices people ought to make -    must look at what policy makers mean when they mean choice and upholding choice

Protection of medical and genetic data Heidi Diggelmann Olivier Guillod

Dilemma of Predictive Medicine Y Englert

Medicine evolve to predictive and to collective Move from single gene to multi gene Pre-clinical diagnosing been around for decade or so, since being able to detect for unborn child More complex when trying to deal with diagnosis of illness, which hasn’t yet appeared, but feared by patient or family

If we look at diseases that come later on, more difficult Access to jobs, insurance and social organisation

Pre-clinical screening as starting point, must first consider whether test straightaway and influence of that. Often no symptoms.

Poss of testing raises number of people who want test by 50%. If poss during pregnancy, number raises to 98%. Thus, predictive medicine provides reassurance, rather than distress

For someone with Duchenne syndrome, can avoid no of tragedies

Importance of genetic counselling before test, but not enough – need info for everybody – education programmes. Avoid stigmatisation of people

Not much use for employment purposes

Insurance implications clear

Key issue is data protection

Most sensitive of all data, because of predictive power and shared in specific group of individuals

Goes beyond individualistic approach

Can be used exclusively for identification purposes

INTERNET AVAILABLE GENETIC TESTS

Who owns genetic info?

Council of Europ recommendation 97.5 -

Stefano Rodota

Legit of tests only for health or research Therapeutic model Conference Review: Justice, healthcare and the Trend Towards Predictive Medicine For British Medical Journal

Thus week, Brussels held a symposium on the future of health care, which aimed to bring young and senior scholars to question the ends of current trends in medicine. In particular, the symposium focused on ‘predictive medicine’ and the emerging opportunities for working towards a more just healthcare system. The symposium was supported through the Brocher Foundation, a research foundation interested in questions concerning the socio-political context of science and medicine. It was a relatively small meeting, though the kinds of guests reflected key authors and speakers in bioethics.

The symposium began with a lecture from Norman Daniels, whose work on XXX

Norman Daniels drew attention to the inadequacies of the US model and the worry of exporting its medical models to other countries. His Rawlsian approach to healthcare justice reflected the social obligation to provide socially just …. He also spoke about the challenges faced by the emergence of predictive medicine as a moment of opportunity for requestioning how medicine takes place. Acknowledging that predictive medicine will raise challenging economic realities for the medical industries, Daniels argued that this can be seen as a chance to provide greater justice in healthcare, or it can be used to exacerbate the needs and lack of the most vulnerable people.

Rawlsian ideas were taken up in the subsequent presentation byXX. However, the focus was significantly different, raising questions about the body-as-product both commercially and ideologically. XXX addressed the challenge of Utopian medicine, the prospect of which seems wholly inadequate even in best-case scenarios. The acceptance of tragedy in life is considered indicative of the human condition and the rejection of this circumstance can be seen as socially divisive. It is not that people should not seek to optimise their health, but that the process towards realising that will be to the detriment of those who have the most need.

Neither of the speakers fully addressed the difficulty with limiting individual desires to pursue health at all costs. Indeed, there was lmite

Engaging with synthetic biology (2009 18 Jun, London)

Engaging with synthetic biology 18th June 2009, 9.45am – 12.15pm The Royal Academy of Engineering London

Chair:                           Professor Robert Winston HonFREng FMedSci, Imperial College, London

Speakers:         Professor Richard Kitney OBE FREng, Imperial College London Dr Jane Calvert, University of Edinburgh Dr Suzanne King, People Science & Policy

Panellists:          Professor Robin Gill, University of Kent Professor Paul Freemont, Imperial College London Fiona Fox, Science Media Centre

If you would like to attend, please complete and return the booking form which is available from: http://www.raeng.org.uk/events

Please do forward this invitation to colleagues, who may also be interested in attending

Nanotechnology and Postmodern Culture (2009, Jun 9)

Giving talk at Sheffield Uni on 9 June - Nanotechnology and Postmodern CultureWhat kind of future is nanotechnology creating for us? What will it mean to be human in the twenty-first century?Professor Richard Jones (Physics and Astronomy), Dr Alex Houen (English), and Professor Andy Miah (Media, Language and Music, University of the West of Scotland)

http://www.sheffield.ac.uk/english/arts-science/events.html#June+2009

The Perfect Body (2009, Oct 9-13, Sweden)

- Call for Applications -Closing Date for Applications: 1 July 2009 ESF-LiU Conference The Perfect Body: between Normativity and Consumerism Scandic Linköping Väst, Linköping, Sweden 9-13 October 2009 www.esf.org/conferences/09273

Chaired by: Katrin Grüber - IMEW, DE & Ursula Naue - LSG, AT

ESF Contact: Anne Blondeel-Oman - ablondeel@esf.org

Enhancement as the improvement of desired characteristics (W. French Anderson) means to focus on abilities, capacities and quality of life. These categories can be viewed and defined from different value-driven perspectives which are based upon certain viewpoints on what constitutes “normality”. Furthermore they are framed by the concept of autonomy. The general approach towards the issue of enhancement can be understood in the context of consumerism – the “production” of enhanced persons as an act of individual freedom and choice. But another approach, which will be the main focus of the conference, is based upon the fact that perspectives of disabled persons on enhancement have been neglected so far. This is important as enhancement technologies can have different societal and political implications for disabled and non-disabled persons. The discussion about enhancement focuses on therapy of something in need of treatment. But with regard to disability, this debate about enhancement in contrast to therapy and treatment has to be re-thought and re-contextualised.

Hence, the conference takes as its starting point the view that it is socio-politically as well as ethically necessary and important to look at enhancement technologies from a “disability-perspective”. In the context of historic developments and the intersection of medicine and economy, enhancement technologies will be discussed from several different scientific perspectives. The conference is organised as an interdisciplinary dialogue and aims to provide an open forum for discussion and networking. This approach towards enhancement technologies is necessary, as the field of enhancement is an increasingly important area of intervention into life and the body. The conference will be the first international meeting to bring together Disability Studies, Science, Technology and Society Studies and Ethics. The following are some of the questions that will be discussed:  § To what extent and in what way does consumerism influence the current debate about enhancement technologies? § Which problems arise from this understanding of enhancement technologies for disabled and non-disabled persons and consumers of these technologies? § What are the consequences of enhancement technologies for disabled persons? § Is the “upgrade” an upgrade from old established norms or is a “new normal body” created? § Who is excluded by both starting points of enhancing the human being? § Do enhancement technologies carry a risk of excluding certain groups within society, such as disabled persons? § How can consumerism be embedded in an ethical framework? § What role does normativity play? § What new possible forms of exclusion and inequality on several levels might occur as a result of using enhancement technologies?

Questions such as these make it quite clear that the conference is a necessary and important way of approaching enhancement technologies that already have implications for both human beings and for society.

Invited Speakers will include:

·         Michael BURY - RHUL London., UK Another look at the body ·         Inez DE BEAUFORT - Erasmus MC, NL tbc ·         Barbara DUDEN - Hannover U., DE Never good enough? The "body" between normativity and consumerism ·         Marcus DÜWELL - Utrecht U., NL Liberal Societies and the Moral Evaluation of Human Capacities: Ethical presuppositions in the Enhancement-debate ·         Jennifer FISHMAN - McGill U. Montreal, CA ·         Joakim ISAKSSON - Umeå U., SE ·         Rosemarie GARLAND-THOMSON - Emory U., US ·         Katrin GRÜBER - IMEW, DE Cochlea implant as a case study for promises and expectations ·         Robin MACKENZIE - Kent U., UK ·         Judit SANDOR - CEU Budapest, HU ·         Silke SCHICKTANZ - UMG Göttingen, DE Morality and Perspectivism in the Therapy-Enhancement-Distinction ·         Frida SIMONSTEIN - Yezreel Valley College, IL Reprogenetics, enhancing and the invisible vessel ·         Jackie Leach SCULLY - Newcastle U., UK This is how I am: Bodies, difference, and identity ·         Bertrand TONDU - Toulouse U., FR Cyborgs and Humanoid Robots: Myth and Reality ·         Simo VEHMAS - Jyväskylä U., SF Dimensions of disability ·         Paul VERSCHURE - U. Pompeu Fabra, ES How to Build a Cyborg ·         Anne WALDSCHMIDT - Cologne U., DE Body, power, difference - reflections about normativity, normality and disability ·         Gregor WOLBRING - Calgary U., CA Ableism, Transhumanism and the transhumanization of Ableism: The Future has started today?

Full conference programme and application form accessible online from www.esf.org/conferences/09273

Some grants are available for young researchers to cover the conference fee and possibly part of the travel costs. Grant requests should be made by ticking appropriate field(s) in the paragraph "Grant application" of the application form.

Kind regards, Corinne Wininger Communications Officer - ESF Conferences

European Science Foundation - Communications Unit 1 quai Lezay-Marnésia, BP 90015 67080 Strasbourg Cedex, France Phone: +33 (0)388 76 21 50 Fax: +33 (0)388 76 71 80 clemoal@esf.org www.esf.org/conferences

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ This conference is organised by the European Science Foundation (ESF), in partnership with Linköping University (LiU).

With support from

Climate for Change (FACT 2009, March 13-31 May)

Here's the press release for FACT's first major exhibition of 2009, curated by Heather Corcoran. Looks like I'll be getting involved for the final event on May 9th, 2009. We'll also bring Heather and some of the residents at FACT from Eyebeam New York for the IMDE event on Social Media and Healthy Environments on March 17th. Get in touch if you'd like to attend.

NEWS RELEASE Climate for Change 13 March - 31 May 2009 (private view 12 March)

For its first new exhibition of 2009, its UNsustainable year, FACT is proud to present Climate for Change, a unique experiment in activism, engagement and networking, examining the multiple crises affecting the planet – ecological, financial, food and housing. From peak oil to peak credit, Climate for Change seizes the moment, and asks how do we respond?

In Gallery 1, a range of groups will take up residence in an environment created from the leftover building materials from 2008's Capital of Culture year. The networked activities of Merseyside and beyond will become a key part of the experiment, as FACT hands over the keys to the door and becomes a hub for meetings, socials, discussions and workshops, supporting grassroots networks to practise and imagine new models of governance and organising - live in the gallery space. Dealing with topics as diverse as the Transition Town movement to underground nightclubs, Climate for Change speculates that distributed networks who share methods of selforganising are the most important tools we have for responding to sustainability. Underpinning this action will be a number of artist-led activities. In Gallery 1, New York’s Eyebeam Art and Technology Centre stages its Sustainability Road Show – a series of hands-on workshops and activities that are both playful and social, highlighting Eyebeam's strong media lab culture built around tinkering, hacking, making and doing.

Artist Stefan Szczelkun presents his Survival Scrapbooks. Originally published in the early 1970s, the Survival Scrapbooks are DIY manuals for autonomous living, covering topics from “bio-diesel-making” to “increasing your chi”. Loosely formatted and intended to be re-edited in a pre-internet information-sharing format, the books will form the basis for workshops and discussion in Gallery 1.

Mute Magazine Contributing Editor Anthony Iles revisits the magazine’s Climate Change issue – Mute Vol 2, no.5 It’s Not Easy Being Green from May 2007 to update it in light of changing perspectives on finance, capital and current affairs. Iles will curate a discussion and screening series that runs throughout the exhibition. Meanwhile, The People Speak and renowned think tank New Economics Foundation will unveil a new facilitation format that creates a dynamic conversation around sustainability and climate change.

In addition, Gallery 1 will house a loose and rotating line-up of artists working in Liverpool and beyond, including British-born Chinese artist Kao-Oi Jay Yung, activist Nina Edge and artist-led environmental group The Gaia Project in partnership with L@tE.

In Gallery 2, FACT presents Melanie Gilligan’s film Crisis in the Credit System. Originally commissioned and produced by Artangel Interaction, the fictional four-part drama explores the bizarre scenarios and disturbing conclusions employees from a major investment bank come up when they are invited to role-play a future-facing strategy for today’s unstable financial climate.

Berlin-based art duo Nik Kosmas and Daniel Keller (AIDS 3D) will unveil Forever, a new installation alluding to a post-apocalyptic future where our machines remain as beautiful relics of our former glory.

Copies of a spoofed New York Times newspaper, created by thousands of volunteers and originally distributed in November 2008 - but dated July 4, 2009 - will get a further outing at FACT.

In the Media Lounge, Copenhagen-based art and architecture collective N55 set up SHOP, a unique exchange area with its own alternative economy, where visitors can swap, borrow or use donated items.

FACT’s Atrium will become the drop off point for The Ghana Think Tank. A collaboration between artists Christopher Robbins, John Ewing and Matey-Odonkor, the project asks visitors to submit their problems which will be given to a network of Think Tanks established in Ghana, Cuba, El Salvador, Mexico, Ethiopia and Serbia to ‘solve’. Afterwards the artists will enact the solutions.

Notes to Editors FACT’s new online arts channel, FACT TV (www.fact.tv) will stream video highlights from Climate for Change and related content throughout the exhibition’s run. Artists involved in Climate for Change: AIDS 3D (USA), Eyebeam Art and Technology Centre (USA), The

Ghana Think Tank (USA/Ghana), Melanie Gilligan (USA), N55 (Denmark), The People Speak (UK), Stefan Szczelkun (UK), The Yes Men (USA), Kao-Oi Jay Yung (UK), Nina Edge (UK), The Gaia Project (UK).

UNsustainable In 2009, Liverpool’s Year of the Environment, FACT responds with UNsustainable - its own theme for the year. FACT asks: is the way we live UNsustainable? Examining sustainability from an artistic perspectivein a series of exhibitions designed to illustrate how humans can be invested in the change needed to protect our civilization. Is society itself becoming unsustainable?

SHOP by N55 is a collaboration between FACT and Radiator Festival, Nottingham. For more information please contact: Lucie Davies, Press & Communications Officer T: 0151 707 4405 or E: lucie.davies@fact.co.uk www.fact.co.uk

Human Enhancement in Brussels (2009, Feb 24)

February 24, 2009Brussels, Belgium

IEET fellow Andy Miah will be speaking at the one day workshop for the European Parliament in Brussels, on Tuesday 24 February 2009

Sponsored by the Rathenau Institute

Human enhancement is the trend to improve the body & mind of human beings by technological means. Examples are the use of “smart pills” to improve concentration or cosmetic surgery. Other examples are selecting embryos that are genetically disease-free to use in an IVF procedure, mood brightening drugs or devices.

These and other technologies promise benefits for the individual using them, but what are the long-term effects? Will human enhancement enlarge social and economic differences? And will the health care remain affordable? Should research into such technologies be stimulated or not? We believe that there are three strategies that the EU could take in response to the challenges human enhancement will pose to the EU. We think that human enhancement raises serious challenges to the EU, and we have identified three strategies that the EU could take to respond to these.

These strategies will be presented by and discussed with experts during the workshop. Some more information on human enhancement, the challenges it poses, the three strategies, and the workshop can be found in the attached information folder.

The workshop is a part of our project on human enhancement. The goal of the project is to provide policy options on human enhancement to the European Parliament. This project is commissioned by the European Parliament and is carried out by ITAS and the Rathenau Institute. We will incorporate the debate during the workshop in the final report.

The workshop will be held on 24 February 2009 in the European Parliament (Rue Wiertz 60, 1047 Brussels). The first part of the workshop will be from 12.45 to 14.15 in room ASP 5F385 and will explore which of the three strategies will be most suitable for the EU. During this part of the workshop, a sandwich lunch will be provided.

The second part of the workshop will be held in room ASP 5G2 from 14.45 to 16.30. In this part, the strategies will be put to the test and will be thoroughly debated – hopefully by you as well!

If you want to attend the workshop, you need to register by sending an e-mail with subject “workshop human enhancement” to info @ rathenau.nl before 16 February 2009. This e-mail should include your name, nationality and date of birth. This information is necessary to ensure your access to the European Parliament and will be treated confidentially.

Please do not hesitate to contact us in case you have any questions about the workshop or our project.

Yours sincerely,

Martijntje Smits and Mirjam Schuijff Rathenau Institute

E-mail: m.smits @ rathenau.nl or m.schuijff @ rathenau.nl Telephone: + 31 70 342 15 42

Yours faithfully,

Mirjam Schuijff, Researcher Technology Assessment Rathenau Institute

Phone: (0031) 70 34 21 524

Address: Anna van Saksenlaan 51 2593 HW The Hague

Postal address: Postbus 95366 2509 CJ THE HAGUE (NL)

The Rathenau Institute focuses on the influence of science and technology on our daily lives and maps its dynamics; through independent research and debate.

New PhD studentships

Deadline for applications is 12 January, 2009: http://www.uws.ac.uk/research/MediaStudentships.asp

Finally, here are the project outlines:

Blogging the Vancouver 2010 Olympics (Ref.PHDMLM003) Director of Studies: Dr Andy Miah Research into the new media dimensions of an Olympic Games has become a focal point for researchers in recent years. Sports governing bodies have also responded to the rise of new media, as a distinct reporting form within the organizational framework of a mega-event. For instance, for the 2008 Beijing Olympics, the television rights contracts were separated from internet broadcast rights for the first time in history. Also, in February 2008, the International Olympic Committee provided extensive blogging guidelines for the first time, which affect all accredited persons at the Games, including athletes. Additionally, a remarkable number of citizen journalists is visible at recent Games and their capacity and entitlement to report on the proceedings is a much more contested set of circumstances. As traditional media outlets rush to converge and consolidate their online presence, questions arise as to the contribution of dominant social networking platforms to the construction of the Games-time narrative. Evidence suggests that organizations are making strategic decisions to affect these conditions. For instance, in March 2007, the BBC purchased a You Tube Channel. Alternatively, in August 2008, the IOC signed agreements to broadcast parts of the Olympic Games on You Tube to countries where no television broadcast license was in place. This PhD studentship will focus on the Olympic Winter Games of Vancouver 2010 to study how a range of new media is infiltrating the Olympic infrastructure. It will seek to contextualize the new media culture of Vancouver 2010 within a series of cultural and political issues that have surrounded the lead-up to its Winter Olympics.

Candidates should have a higher degree and particular expertise in qualitative research methods and social media.

Prospects of immortality: public engagement with Biogerontology and life/health span expansion (Ref.PHDMLM004)

Due to its broad application to a number of other sciences, biogerontology is one of the most relevant fields of inquiry today. It speaks to the convergence of the NBIC sciences and to the redefinition of health care that arises by describing ageing as a disease to be cured, rather than a natural process to accept. Biogerontology engages us with the prospect of extending health or life span to an unknown degree and, as such, it is a controversial discipline. Over the last ten years, work in this area has shifted from scientific impossibility to becoming a core part of scientific endeavour. A range of media coverage, from aspersion to fascination, has accompanied this shift. In the literature on public understanding of science, there is no research yet attending to this distinct, but profound area of scientific inquiry. As such, this PhD studentship aims to explore the following questions:

* How has biogerontology been articulated though the media? * What issues surround the political economy of research into life-extension? * How do different research communities orientate themselves around the various media narratives on life-extension? * How do journalists report research on biogerontology? * What can be learned from this subject area to broadly inform work into science communication?

Candidates should have a higher degree in science communication and qualitative research methods in media sociology.

Director of Studies Andy Miah External Adviser: Aubrey de Grey

The ethics of human enhancement in film (Ref.PHDMLM005)

Studies in the ethics of human enhancement have advanced considerably in the last five years through the emergence of new communities of scholarly inquiry. A number of scientific disciplines have been brought under the spotlight due to their likely use for lifestyle, non-therapeutic purposes. The connections between filmic narratives and bioethics are made manifest in recent cultural studies and can be linked to broader, literary origins. Yet, there is very little research that investigates the range of narratives that emerge on the ethics of human enhancement within film. This absence affects the degree of complexity that is brought to how such debates are played out in the media and in policy. This PhD explores the contribution of film to such imaginations and aims to add complexity to our understanding of how film conveys such alterations. It should also help us understand how film functions as a posthuman device of expressing humanly experiences, such as process of remembering, perceiving and the possible disruption of sensory encounters. It also aims to explore the limitations of cultural reference points within scientific policy making on the ethics of human enhancements, exploring the range of metaphors, analogies and stories that contribute to shaping the public understanding of science.

Candidates should have a higher degree and particular expertise in film theory and technological fiction.

Director of Studies: Andy Miah

The BioCentre Debate on Arts and Technology (2008.10.14, London

My Presentation: [slideshare id=666917&doc=miah3008biocentre-1224321969659504-8&w=425]

On 14th October, I'll give a talk at the Southbank in London and want to play a couple of clips. I hope the Internet works. This first clip is from The Big Donor Show, a reality tv programme from the Netherlands, which purported to have 3 contestants all in need of a new kidney. The winner of the show would receive the life saving transplant. The programme attracted widespread media coverage in advance of its broadcast and in the final few minutes of announcing the winner, revealed the truth:

[youtube=http://uk.youtube.com/watch?v=-lnoVaYj1XI&feature=related]

Trying out Slideshare

[slideshare id=372085&doc=miah200612hastings2-1209129492787872-8&w=425]

Synthetic Times (Exhibition, Beijing, Jun 10 -July 3, 2008)

A BEIJING OLYMPICS CULTURAL PROJECT

namoc2.jpg

National Art Museum of China (NAMOC) No. 1 Wusi Street Dongcheng District Beijing 100010 P.R.ChinaJun 10, 2008 -July 3, 2008

During the 2008 Beijing Olympic Games, the National Art Museum of China will present “SYNTHETIC TIMES – Media Art China 2008” in its current location at the center of Beijing. NAMOC is the only national art museum in China that is dedicated to research, presentation and promotion of modern and contemporary arts. “SYNTHETIC TIMES – Media Art China 2008”, scheduled from June 10th to July 3rd, will be one of the most important cultural events leading up to the Olympic Games in Beijing.

The exhibition will occupy approximately 4500 square meters (48000 square feet) of the museum gallery space and an additional outdoor area of ca. 2000 square meters (22000 square feet). The internationally recognized Dutch architecture firm NOX/Lars Spuybroek will architecturally transform the entire first floor of the museum in response to the nature of the works on display. A full-color catalogue will be co-published by NAMOC and the MIT Press to accompany the opening (with international distribution). An online forum dedicated to the discourse of the respective exhibition themes and beyond will be created prior to the opening of the event. A pre-Exhibition symposium will be held in New York City in collaboration with MoMA (Museum of Modern Art) and other major cultural and educational institutions. The forum and the subsequent symposia will be moderated by a group of distinguished scholars and media arts professionals. Selected discussion essays will be included in the catalogue. Meanwhile, a number of satellite exhibition venues have been planed within the greater Beijing art community, engaging prominent galleries of the booming Beijing art scene. In addition, a number of special evening events during the opening days of the Exhibition are conceived to celebrate countries with significant contribution to the development of media art and culture.

Synthetic Times – Media Art China 2008 will showcase both established and emerging artists from approximately thirty countries, and over fifty media art installation works will be on view along with performances, workshops, presentations and discussion panels. To complement the theme exhibitions, The Museum of Modern Art (MoMA) will contribute a special screening program consisting of seminal video art works. Ars Electronica is set to present the award winning Animation Festival while European Media Art Festival will bring in an edition of International Emerging Video Art. The Exhibition is envisaged as a landmark event in the history of contemporary Chinese art dedicated to embracing the most innovative artistic production and theorization to date, and aspiring to foster and advance new modes of thinking and novel ways of artistic engagement in an increasingly technologically immersed society and global cultural landscape, resonating with the leitmotifs of “Cultural Olympics” and “Hi-Tech Olympics” put forward by the 2008 Beijing Olympic Games.

Supported by the Chinese government, international cultural foundations as well as embassies from the participating countries, renowned museums and media art institutions worldwide will collaborate with NAMOC to produce the Exhibition and its related events.

Philosophy and Human Enhancement (Brussels, 8-10 May, 2008)

I'll be speaking here on the 10th May: Programme provisoire Preliminary program Enhancement – aspects éthiques et philosophiques de la médecine d’amélioration

Jeudi 8 mai

19h30            Accueil des participants 19h45            Conférence inaugurale Cocktail dînatoire

Vendredi 9 mai

Session I : Enhancement et Science-Fiction 9h00-9h50        Jérôme Goffette                Modifier les humains : anthropotechnie (Maître de Conférence, Université Lyon I)    versus médecine 9h50-10h40    Sylvie Allouche                Aspects éthiques et philosophiques de (Lectrice, Collège Eötvös de Budapest)      la médecine d'amélioration dans la science-fiction 10h40-11h        Pause Café

11h00-11h40         Gérard Klein                La Science-Fiction, une littérature                (Edition Robert Laffont)            prothétique

Session II Enhancement and other topics 11h40-12h30    Gilbert    Hottois                        ? (Professeur, Université libre de Bruxelles)

12h30-14h00        Lunch

14h00-14h50        Marie-Geneviève Pinsart                    ? (Chargé de cours, Université libre de Bruxelles) 14h50-15h40        Bernard Baertschi            Devenir un être humain accompli. Idéal (Maître d’enseignement et de recherche,       ou cauchemar ? Université de Genève)

15h40-16h00        Pause Café

16h00-16h40        Kermisch Céline                 Enhancement et perception des risques (Aspirant FNRS, Université libre de Bruxelles) 16h40-17h30        Pascal Nouvel                Un aiguillon philosophique à la conquête (Professeur, Université Montpellier III)     des records : les amphétamines 17h30-18h20        Jean-Yves Goffi                Soigner, augmenter : une frontière floue ? (Professeur, Université Pierre Mendès)

Samedi 10 mai

Session III : Enhancement and sport. Chair : Pierre Daled.

10h-10h50        Alexandre Mauron            Homo faber sui: quelques questions (Professeur à l’Université de Genève)           d'éthique démiurgique 10h50-11h40        Patrick Laure                Ethique des conduites dopantes (Université Paris XI-Orsay) 11h40-12h30        Quéval Isabelle                Le corps rationnel du sport de haut (Maître de Conférence,             niveau: ambivalences du  dépassement de     Université René Descartes-Paris V)    soi

12h30-14h00        Lunch

14h00-14h50         Claudio Tamburrini             What´s wrong with genetic inequality? (Chercheur, Université de Göteborg) 14h50-15h40        Andy Miah                 Human enhancement in performative (Reader, University of the West of Scotland)                    cultures

Human Dignity and Bioethics

I just received my copy of the new publication from the US President's Council on Bioethics. This volume looks like a great addition to the literature. Human dignity featured heavily in my Genetically Modified Athletes and is a concept I am continually drawn back to when thinking about the range of issues arising from discussions about human enhancement.