Ravello meeting on Chance and Necessity

I am at the Ravello meeting on Chance and Necessity in biology, on the 40th anniversary of Jacques Monod's seminal book by the same title, and will be posting a few entries while the meeting is going on this week. The gathering is organized by Giorgio Bernardi and sponsored by International Union of Biological Sciences and the Istituto Italiano di Studi Filosofici.

What follows are the raw and somewhat selective notes only, in order of presentation of the various speakers. Hopefully this will provide a feeling for what the meeting is about and generate some discussion. Throughout, parenthetical comments are my own, unless otherwise noted.

Agnes Ullman, In memoriam of Jacques Monod.

Monod was prominent in the critique of Lysenko and his brand of anti-scientific ideology. Shown charming early photos and even family drawings of young Jacques. I Did not know that Monod early on almost turned to a career as orchestra director before concentrating full time on genetics. He was active in the French resistance during WWII as a chief, a dangerous position that had cost three of his predecessors their lives. After WWII Monod immersed himself in the work on bacterial protein regulation that resulted in his Nobel in 1965. The latter was made possible by the intense collaboration with Francois Jacob, who eventually shared the Nobel. Their work led of course to the classic papers on the concept of the operon and of allosteric regulation of enzymes. In the late '60s Monod was politically involved with the student protest movement. In 1969 he gave four lectures at Pomona College, on "modern biology and natural philosophy," which became the core for Chance and Necessity - the book became an unexpected best seller in the early '70s. Monod then became a very effective manager and fund raiser, starting the first French institute of molecular biology, which now carries his name. He remained involved in politics, for instance in defense of abortion rights, until the premature end of his life.

"A beautiful theory may not be right, but an ugly one must be wrong." -JM

Bernardino Fantini, Monod's vision of life and the theoretical structure of contemporary biology.

Monod's philosophical work is largely under appreciated. It is true that he did not have a professional grounding in philosophy, but he was awake to the importance of philosophy in the biological sciences. According to Francis Crick's obituary of Monod in Nature, Chance and Necessity presented a vision of life that is shared by most practicing scientists, and yet feels alien to the majority of the public: life is an accident and Darwinian evolution is the impersonal causal mechanism that shaped it. Monod was interested in the apparent paradox of living organisms functioning in a way that cannot be explained only by the laws of physics and chemistry, which constitute the foundations of our scientific understanding of the world. He saw molecular biology not as a branch of chemistry, but rather as a biological-Darwinian understanding of biochemistry. Emphasis on biological form rather than specific matter constituents ("Plato sometimes is right" -JM). Monod saw evolution not as a law or a principle of life, but rather as an emergent result of complexity and certain environmental conditions. Monod attributed the idea that everything is the result of randomness and necessity to Democritus, though no specific quote to that effect can actually be found in the Greek atomist. For Monod life is bound by the laws of physics, but requires additional causal principles when it comes to the specificity of biological information. Delbruck quasi-seriously suggested to give the Nobel to Aristotle for the discovery of the basic principle of molecular biology, that DNA plays the role of the unmoved mover in biology. Many biologists rejected this idea that structure and function, form and information, can be conceptually separated in a way reminiscent of Aristotle's causes. Monod's ideas here derived naturally from his experimental work separating the control of enzymatic function from the biochemical function itself: allosteric control is entirely independent of the structural details of the functional enzyme.

Massimo Pigliucci, Biology as a historical and experimental science: the epistemic challenges of chance and necessity.

My talk was about situating the concepts of chance and necessity, in their broader sense, within the context of recent and ongoing discussions about the structure of evolutionary theory - from the Modern Synthesis of the 1940s to the newly proposed Extended Synthesis. I discussed the classic debate between Fisher and Wright, then moved to Gould's emphasis on contingency, at the same time that he was trying to establish paleontology on nomothetic grounds. I then used Cleland's distinction between prediction of future events and postdiction of past ones to mediate between experimental and historical aspects of evolutionary biology. I concluded with an overview of the Extended Synthesis as outlined in a MIT Press volume that I recently co-edited with Gerd Muller.

David Haussler, The genome 10k project, what we might learn from sequencing 10,000 vertebrate genomes.

Cost of DNA sequencing going down faster than cost of microprocessor power. Hence the idea of starting on a 10,000 - out of 60,000 known - vertebrate species genome project. Interested scientists and tissue samples sufficient for sequencing are available already for 16,000 species. Work made difficult by the structural / architectural changes in the various genomes over time, which superimpose on sequence-level changes. Still, one can follow both the birth of new genes, via duplication, and their death, via mutation causing a stop codon. The (rather naive?) long term scenario is to map genomic changes to phenotypic ones, thereby mapping the evolution of vertebrate form at the genomic level. An interesting early result is that early on in the phylogenetic history of vertebrate clades we observe an excess of regulatory innovation affecting transcription factors. This excess then tapers off, and regulatory elements become just as likely to mutate as other parts of the genome. On the other hand, changes in receptor binding sites become more important later in evolution, also eventually dropping off. Finally, more recent evolution is marked mostly by changes in intra-cellular signaling. So, early importance of developmental changes, intermediate period targeting intercellular-level changes, and finally intra-cellular changes. (This was an interesting talk on its merits, though it is hard to see what it had to do directly with the theme of the conference. I suspect this will be true for several other talks over the next couple of days.)

Gill Bejerano, Change and constancy in the evolution of the human genome.

Consider the contrast between having 20,000 protein coding genes vs about 1,000,000 genomic switches controlling the expression of those genes. A large number of cis non coding regions seem to have evolved under purifying selection. (Must admit that my eyes glaze over when slide after slide explains the various techniques used to gather the relevant molecular biology data...) (Still asleep, in the last two talks I have not heard the words "Monod," "chance," or "necessity" very much, if at all.)

Daniel Hartl, Chance favors the prepared genome, copy number variation and the origin of new genes.

Whole gene and partial duplications are frequent, though most of them are lost quickly. Chimeric combinations often lead to the evolution of new genes in Drosophila. The estimate is of about 100 duplications peer million years, 10% of which are chimeras. The two types of genes are then lost at the same rate. The rest of the talk focused on a couple of specific examples of the evolution of particular chimeric genes, one of which has been the locus of a recent - 15,000 years ago - selective sweep. The second example presented the case of a large number of structural events - deletions and insertions - which would maintain functionality only if they happened simultaneously. The way this happened was not by intelligent design ;-) but by way of resolving a stalled replication fork, which would have caused cell death at the moment of division. In other words, a number of molecular events that normally would be interpreted as having happened over a large number of generations likely occurred in a single molecular reshuffling inside an individual cell. (Talk about non-gradual evolution...)