Transcript Sujet d`ordre général

Genomics: Philosophy, bioethics, and
culture
Centro de Ciencias Genómicas, UNAM Cuernavaca,
18 Sept 2006
Alex Mauron
Institut d’éthique biomédicale
Outline
1.
2.
3.
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A bit of (mostly recent) history
“Genomic metaphysics”: where does it
come from?
Ethical and cultural consequences:
Bioethical debates on embryo research,
cloning…
Controversies on behavioural genetics
Self-engineering of mankind
1953: A nice understatement
« It has not escaped our notice… »
Watson J & Crick F.
Nature 171, 737-738 (1953).
The genomic turn
 Late
eighties -> today
Expansion of genomics, the studies of whole
genomes (including the human genome)
over and beyond the study of individual
genes or gene families.
The genome comes to the fore as an explicit
object of investigation and representation.
2003: A postcard from the party
[22 April 2003]
Celebrations for DNA and its sequence
in humans.
The International Genome Sequencing
Consortium celebrated the "essentially
complete" human genome early last week in Bethesda,
Maryland, although the sequence itself is due to be formally
unveiled in May. Festivities for the finished sequence were designed to
coincide, more or less, with the 50th anniversary of the elucidation of the
structure of the DNA molecule, and the double-birthday bash became a
backslapping Who's Who of the past half-century in molecular
genetics…………….
Andrea Vesalius : De
humani corporis fabrica
libri septem (Basle 1543)
The genome as
“neo-Vesalian
human anatomy”
(V. McKusick)
The “neo-Vesalian” model

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
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Andreas Vesalius (1514-1564): human macroscopic anatomy becomes a
“universe” open to exploration.
It soon appears that this universe is finite. As a project, there has to be
a point at which the project is essentially complete.
The scientific exploration of human nature moves on to different
“universes” that are themselves finite. For instance the genome.
2003: the end of the road (more or less)
The transcriptome: cell-specificity and alternative splicing both
contribute to making the transcriptome much “bigger” than the genome:
But still finite.
One is reminded of Peter Sloterdijk’s “spheres”: levels of exploration of
human reality, controlled humanized environments…
And now, on to the « omes »
 From
the genome…
…to the transcriptome, proteome, metabolome…
 The
« omes » have become the new
(re)incarnations of the body. The suffix « ome » is basically an ontological operator.
 The
vesalian metaphor carries on.
Know thy genome…

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The Human Genome Project is a cultural artefact too
(and postgenomics will have its share of cultural
influence as well).
Genetic knowledge has become a highly visible form of
self-knowledge.
Knowledge of the genome has fueled speculation
about the self-transformation of humanity by genetic
manipulation.
Knowledge of the genome is challenging received
notions of health, disease and normality.
Another bit of history:
 Why
the genome troubles
the postmodern mind...

“The Sloterdijk affair”:
In 1999, the German philosopher Peter Sloterdijk becomes the centre of
a public controversy: in a lecture on Heidegger at Elmau (Bavaria) he
supposedly advocated a program of genetic revision of the human
species by genetic engineering.
This was a fairly crude misreading of his statements but nevertheless, it
caused much uproar in German intellectual circles.

In reality, Sloterdijk’s thesis (leaning on Heidegger and Nietzsche) is
quite different: he claims that traditional humanistic education is already
a form of “human domestication”, perhaps not so different in principle
from future biological interventions into human nature.
He calls for a new ethical code for “anthropotechniques” in general.
An unnamed opponent
 The
famous German philosopher Habermas
indirectly criticizes Sloterdijk in his 2001 book (Engl.
Ed: The future of human nature, 2003). He
attempts to maintain the major tenets of
conservative bioethics (bases on the « givenness »
of human biological nature), while rejecting the
traditional metaphysical foundation for these views.
Outline
1.
2.
3.
-
-
A bit of (mostly recent) history
“Genomic metaphysics”: where does it
come from?
Ethical and cultural consequences:
Bioethical debates on embryo research,
cloning…
Controversies on behavioral genetics
Self-engineering of mankind
The nature of human nature:
Why is the genome so special?
 «Genomic
metaphysics» : the belief that the
genome constitutes the ontological hard
core of an organism, determining both its
individuality and its species identity.
Mauron A. Is the Genome the Secular Equivalent of the Soul?
Science 291;831-832:2001.
Where does genomic metaphysics
come from ?
 Genomic
essentialism in contemporary culture, as
expressed for instance in the popular reception of
the controversies about behavioural genetics.
 Genomic concept of individuality, for instance as
used in ethical debates on the human embryo.
 Persistence of the typological (pre-Darwinian)
species concept.
Conceptual couples
as « intuition pumps »
1.1 genotype - phenotype
1.2 genes - environment
1.3 germinal - somatic
...these couple seem to reflect a basic pattern:
2.1 inner - outer
2.2 core - surface
...and then there are other more or less similar “philosophical”
couples:
3.1 essential - accidental
3.2 hidden - manifest
3.3 potential - actual
3.4. subject - object
Outline
1.
2.
3.
-
-
A bit of (mostly recent) history
“Genomic metaphysics”: where does it
come from?
Ethical and cultural consequences:
Bioethical debates on embryo research,
cloning…
Controversies on behavioral genetics
Self-engineering of mankind
Aristotle’s Nobel Prize
«(..) form is not appearance, quite the contrary: form
defines essence. But mediaeval biology is no longer
valid today and we know that human «form» gives
structure to human «matter» as soon as the
genetic information (in-forma-tion) required to
define a particular genetic patrimony is put
together».
J.-F. Malherbe
History of the problem

In traditional scholastic philosophy, the embryo receives a rational soul
specially created once the embryo is sufficiently formed (Aristotle ->
Thomas Aquinas).

Today: «biologisation» of the problem: some feel that a new individual
is formed as soon as a new diploid genome is formed at fertilisation: in
this view, the genome practically becomes the material manifestation of
the soul.

This view needs « bridge-concepts” between genome and soul:
Aristotelian eidos, entelechy of anti-materialist biologists at the turn of
the 20th century (Driesch), attempts to revive hylomorphism.
Yet genomic identity
is not personal identity
For instance:
- The genomic identity of a new person is
established at fertilization.
- But monozygotic twinning can occur.
- A single zygote (i.e. the bearer of a single
distinctive genomic identity) can become two
persons with separate numerical identities.
Mauron A. Genomic metaphysics. J Mol Biol.
2002:319;957-962
The ideological effects
of genomic metaphysics

Bioethical issues connected with identity problems (cloning,
standing of the embryo, etc.)
Metaphysical genomics drives the controversy in the direction of
pseudo-problems linked to faulty understandings of individuality.
Another example: a common argument for the futility of reproductive
cloning is that another human organism with “the same” genome will
not be a similar person because the environment is different. This is
correct, but largely beside the point:

Two cloned individuals will share (mostly) their genomic identity, but
not their numerical identity.
Only the latter actually counts in defining a person.
“Being the same” is not synonymous with “being exactly alike”
Genomes and species
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«How many human genes do you need to introduce into a
pig to make it noticeably human?»
“There are no human genes”
Pre-Darwinian concept of species: in this obsolete view, the
species is the normal type, the species concept is among
the a priori principles structuring the living world.
Present: The extensive commonality between genomes
makes the relationship between genomes and species ever
more problematic.
-> « Respecting the human species » is not identical
with « respecting the human genome ».
The 1% solution
The human genome and the chimpanzee genome are
about 99% identical.
 There are few specifically human genes: there is no
« Kant » gene to turn the monkey into a responsible
person able « to behold the starry sky above and the
moral law within ».

Outline
1.
2.
3.
-
-
A bit of (mostly recent) history
“Genomic metaphysics”: where does it
come from?
Ethical and cultural consequences:
Bioethical debates on embryo research,
cloning…
Controversies on behavioral genetics
Self-engineering of mankind
«if it’s in the genes...»
 «...it
is more stable, it can’t be changed, there is
nothing you can do about it»
 Genes
are popularly associated with stable,
unchanging defining characteristics of an individual
 It is a common social representation that genes are
closer to one’s «true» nature.
-> genetics become highly relevant to ideologically
charged issues about human differences and
human responsibility.
Right votes for genes, Left votes for
environment…
Behavioural genetics: the field is squeezed
between the opposing ideological forces of
- genetic reductionism,
- the “politically correct” agenda to de-emphasise
genes.
These ideological moves are energised by genomic
metaphysics, because against this background, it is
hoped (or feared) that genetics has something
essential to say about human nature.
The ideological effects of genomic
metaphysics
 The
“genomic turn” brings added energy (an
additional confusions) to old debates about human
nature (nature vs. nurture; biological determinism
vs. free will etc.). These debates often pit a
simplistic “geneticism” against an equally simplistic
“environmentalism”.
 The
categories of genes vs. environment need to
be reformed.
Outline
1.
2.
3.
-
-
A bit of (mostly recent) history
“Genomic metaphysics”: where does it
come from?
Ethical and cultural consequences:
Bioethical debates on embryo research,
cloning…
Controversies on behavioral genetics
Self-engineering of mankind
The paradox of self-making

Post-modern capitalist society loves the self-made
man…
-> Being self-reliant, adopting one’s own guidelines of conduct, making one’s life
an autonomous « work »: individualistic autonomy.
-> In modern Western history, there are various understandings of autonomy.
Kantian autonomy still recognized a moral law that was outside of human
control: there is a basic difference between:
- making the moral law one’s own (Kantian autonomy),
- being free to do whatever does not infringe on the liberty of others (J.S.Mill’s
autonomy),
- being free to « invent » one’s norms (post-modern autonomy).
…but it is still uncomfortable about self-made
mankind!
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Traditional philosophy: the natural structure of humans is a given.
Nature (both human and non-human) is an intimate nexus of fact and
value.
Modern « conservative » philosophy (e.g. Habermas, 2002): postmetaphysical stance, but still committed to the «ethisches
Selbstverständnis der Gattung ».
Naturalistic and/or « post-modern » thinkers: thinking through
the theme of homo faber sui ipsius.
Self-engineering of mankind:
3 questions
1.
Why is “homo faber sui ipsius” (man the self-made maker)
a controversial proposition?
2.
2. Why is a genomic understanding of the self the main
focus for debating this autopoietic enterprise?
3.
3. Why not the brain instead?
An uneasy proposition...
Classical creation
myth: Prometheus,
Epimetheus and
Pandora.
 Renaissance:
the human “self” is to some
extent constructed by man (Pico della
Mirandola).
 Modern theology (Karl Rahner): Man as Cocreator.
 Peter Sloterdijk: Mankind creates “spheres”
through which it constructs itself.
A narrow focus for debate


Especially in Europe, the debate about homo faber sui
ipsius is mostly played out on topics that involve the
genome and procreation.
“Eugenics” is increasingly used as a synonym for
“biotechnological modification of man”.
Genitum non factum
 In
contemporary criticism of human
biotechnologies,
“begotten, not made”
is easily translated into:
“begotten by normal sex, not manufactured
by biotechnology”.
A simple question
 Educating,
taming, shaping the minds of human
beings by “traditional” means is OK. Intervening
in the human genome is not OK.
 Why is “neuronal manipulation” ethical and
genomic manipulation unethical?
(Mauron A. The Question of Purpose. In: Stock G, Campbell J, eds.
Engineering the Human Germline : An Exploration of the Science and Ethics
of Altering the Genes We Pass to our Children. New York: Oxford University
Press, 2000)
 Intervening
on the phenotype of humans is
thought of as “superficial”.
 Intervening
on the genotype of humans is
thought of as “essential” and “intimate”
The genome vs the brain
Genomes are inherently replicable.
 In contrast, every brain has a biography of its own.
Therefore, the brain provides a much better material
« home » for the self than the genome does.

The genome vs the brain
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Many “transhumanist” utopias and dystopias, but also current
or soon-to-be realized biotechnological projects, are brainbased and have no special link with eugenics or with genomic
identity.
Prosthetics: increasing fuzziness of the living vs. non-living
distinction.
Mood enhancement : the “enhancement vs. therapy” problem
Uncoupling humans from specific physiological contingencies.
Radical anti-aging medicine
From the 1982 classic « Blade Runner »
“Neuroethics”
Genetic determinism, neuronal determinism…...
 “Qualified determinism” vs. determinism tout court.
 In what sense does scientific progress about “qualified
determinism” advance the philosophical question of
determinism?

« Your Honor… »
“…my genes made me do it”
“…my brain made me do it”
Similarities? Differences?
Genome
Brain
relatively modest complexity
extremely high complexity
inherent metric of complexity through rules
of genetic code
highly multidimensional complexity
complexity comes about through relatively
simple combinatorial rules
presumably many levels of combinatorial
rules
Genomic identity has no direct link with
numerical identity
Some forms of brain-based identity have
relatively direct links with:
numerical identity
Genomic identity has no direct link with
biographical identity
Some forms of brain-based identity have
relatively direct links with:
biographical identity
Deterministic explanations of complex
behavior are structurally incomplete
Deterministic explanations of complex
behaviour can be complete

“The anti-technological hysteria that holds large parts of the western
world in its grip is a product of the decomposition of metaphysics, for it
clings to false classifications of being in order to revolt against processes
in which these classifications are overcome. It is reactionary in the
essential sense of the word, because it expresses the ressentiment of
outdated bivalence as contrasted with a polyvalence that it cannot
understand.”
Peter Sloterdijk


Example 1: « ethisches Selbstverständnis der Gattung » (Habermas)
cannot be naturalized by continuing to proclaim our genome to be
« unverfügbar ».
Exemple 2: Attempts to make the human brain « unverfügbar » in some
sense would appear even less promising, if only because the human
brain structure is largely constructed in feedback with human activity.
 The
question of what structure or aspect of
the human organism is touched by wilful
interventions in human nature is less and
less decisive in the ethical evaluation of such
interventions.
From the
announcement
of the 2004
Wright
colloquium,
Geneva
Anti-aging medicine
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Many aspects of current medical research
(stem cells, neuroscience, etc.) are currently
united under the label: « regenerative
medicine ».
This fuels legitimate hopes for innovative
treatments of degenerative diseases.
This also fuels futuristic speculations about
massive increases in human life-span or even
the abolition of mortality.
Arguing for death

These speculations have raised many
criticisms, often on ethical grounds.
1. Disturbing the workings of nature (or « Playing
God »)
Example: mortality is needed for the frictionless
motion of evolution to occur.
Answer: who needs evolution? Not we, the current
humans!
Who wants to be superseded by a « new and
improved » species (unless we do the
superseding, of course)!
2. Upsetting the moral confines of the human
condition. Many high-powered conservative
intellectuals want to persuade us that mortality is
part and parcel of what we understand to be
humanity.
Answer: This argument is based on the assumption
that content-full, naturalistic statements about
mortality and disease are morally binding. Difficult
to sustain outside of special ethical or religious
communities.
3. Breaking the “laws of the species” (Habermas)
Answer: The notion of species that operates in these
arguments is far removed from current biological concepts
(Robert, Baylis). Still, there are arguments invoking the
cultural significance of species characteristics that are more
sophisticated than the « playing God » kind.¶ But at the end
of the day, they amount to a kind of philosophical
anthropology that has little normative force by itself.
¶American
Journal of Bioethics. Issue dedicated to “Crossing
Species Boundaries”. 2003, vol 3.
The various organised reactions against high-tech
interventions in human nature, such as:
-
« yuk-reaction » à la Leon Kass (former head of
George Bush’s presidential ethics commission
Culture wars against « scientism »
Religions and/or philosophical wars against « antihumanism »
… are basically « symbolic crusades ».
Traditional moral entrepreneurs…
… Tend to be conservative in outlook, and to instigate
moral panics about « eugenics »,
« dehumanization », « the complete
instrumentalisation of human life ».
This explains for instance the Mitteleuropean skeptical
attitude to futuristic technologies, but also to more
current issues such as:
- preimplantation genetic diagnosis
- embryonic stem cells.
Non-traditional moral entrepreneurs
- Proponents of high-tech intervention into human nature are
also organized in militant, ideologically-charged movements.
example:
 World Transhumanist Association
 Extropianism
- Transhumanism is touted as an all-encompassing philosophy,
medicine, aesthetics, culture, etc.
Life expectancy at birth (WHO, 2002)
Japan
Switzerland
Greece
Cuba
Costa Rica
USA
Brazil
Bhutan
Russia
Uganda
Mali
Zimbabwe
male
78.4
77.7
75.8
75.0
74.8
74.6
65.7
60.2
58.4
47.9
43.9
37.7
female
85.3
83.3
81.1
79.3
79.5
79.8
72,3
62.4
72.1
50.8
45.7
38.0
We are not yet a genetically
engineered species, but do
we still belong to the same
species?
From: Social Determinants of Health: The Solid Facts. WHO 2003
Universal inequality
 Marmot,
Wilkinson, the Whitehall studies:
Inequality in life expectancy is not (just) an “us
vs. them” issue. It cuts across all societies
and all social strata.
The pecking order
 Disease
and premature death are more
prevalent on the lower rungs of the social
ladder
 It is not just a matter of material
circumstances and access to medical care.
 Life entails a series of more or less stressful
transitions and the lower you are on the
social ladder, the harder you are hit at each
of these steps. This is the case even in
affluent societies.

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
Equality is a central value of the
Enlightenment.
But nowadays, equality is unfashionable as
a source of social-ethical guidance.
Since longevity is an important indicator of
global inequality as it is, our culture may
have little moral resources when it comes
to implementing radical anti-ageing
medicine in a way that wouldn’t aggravate
inequalities further.
Equality matters
 Obsolete
metaphysical conceptions will be
powerless to forestall a self-engineering future of
mankind.
 The self-engineering future of mankind will stand or
fall according to a completely different set of ethical
concerns, namely its attention to the problem of
justice.
 If we are to be post-humans, we ought to be equal
post-humans!
Thanks to…
Bernard Baertschi and Samia Hurst for sharing
their hospitable neuronal spaces.