Alex Mauron Institut d’éthique biomédicale

Genomics: Philosophy, bioethics, and cultureCentro de Ciencias Genómicas, UNAM Cuernavaca,18 Sept 2006 Alex Mauron Institut d’éthique biomédicale

Outline • 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. Nature171, 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 thefinished 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 • 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… • 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 • 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 couplesas « 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

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 • «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 ».

«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.

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! • 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): post-metaphysical 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 • Why is “homo faber sui ipsius” (man the self-made maker) a controversial proposition? • 2. Why is a genomic understanding of the self the main focus for debating this autopoietic enterprise? • 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 Co-creator. • 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 • Many “transhumanist” utopias and dystopias, but also current or soon-to-be realized biotechnological projects, are brain-based 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 • 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.

Alex Mauron Institut d’éthique biomédicale