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Of Flies, Mice, and MenReview - Of Flies, Mice, and Men
by Francois Jacob
Harvard University Press, 1999
Review by James Brody, Ph.D.
Jun 30th 2001 (Volume 5, Issue 26)

Francois Jacob and Jacques Monod shared the Nobel Prize for Medicine in 1965 for their work on the regulator sequences in genes. Jacob argues here that modules, each consisting of 20-30 genes, are an Erector Set for the combinatorial mosaics that characterize each of us. Small changes in regulatory genes make large changes in organisms, perhaps by shifting entire blocks of genes on and off or by changing activation sequences. But, whether flea, fly, or Celine Dion, the materials are the same.

Jacob's text, a collection of 7 lectures, is itself an example of combinatorial mosaics and models the very processes that he describes. He anchors his case with genetic engineering, he polishes it with classical myths and anecdotes about politicians and biologists, and he decorates his creation with observations about human good and even the arts. The book's cover is a deceptive white, beige, and Williamsburg Blue. It suggests both refinement and tradition but Jacob the geneticist gives very few nods to environment. I really like his viewpoint and his richly embroidered prose and will refer to him often. He may, however, upset other people but as Jacob reminds us, if you are going to have science, you have to take all of it and not just the parts that you like.

His modules are:

1) Today's concepts and tools continue to evolve and refine each other, thus, we cannot predict what basic research will teach us tomorrow or what we might say about it.  Likewise for most emergent products: we can explain a snowflake but cannot predict the pattern for any one of them. We explain some aspects of a cell in language that must be consistent with what we know about water but our knowing water would not lead us to predict cells. (A similar theme is presented in Sole & Goodwin, 2000).

2) There is a unity in life's organization. D'Arcy Thompson attempted to infer organizational principles in the structure of organisms but without help from genetic engineering. Geoffroy Saint-Hilaire also recognized a unity in the structural organization of mice and men and flies. More than a century later, we found that Hom genes in flies are strongly similar to Hox genes in mammals. Swap a Hox gene from a mouse into a fly and get a normal fly rather than a gifted one. The "same" gene produces eyes in flies and in mice but it produces a compound eye in the former and a familiar round brown one in the latter. Our sharing our Hox genes with nearly every plant and animal testifies to the continuity of life and persuades us of evolution's truth more eloquently than any shelf of skulls. (See Eldridge, 2000, on the persuasive impact that displays of fossilized human and prehuman skulls have had on fundamentalist doubters.)

3) Jacob argues that molecular biology changed the rest of biology in the '90s. Molecular biology allows us to understand our dog with greater precision than was possible 10 years ago when we might have described Rover as a mass of colloids --- instead, he is the outcome of linear combinatorial processes. Jacob's view implies that traditional biologists must retool their thinking; these newer ideas also give some of us outside of biology a chance to get in the door.

4) The building blocks of life are constant but their combinatorial mosaics have endless surprises. Not a new idea! Saint-Hilaire commented in the early 19th century that "Nature constantly uses the same materials and her only ingenuity is in varying the forms" (cited by Jacob, 1973, p. 107). Given the strong probability that combinations of genes are arranged or rearranged as units, then saltatory effects and spandrels become possible. Gradualism is out for many structures. That is, a mutation and a structure appear, the  organism discovers how to make it work. While needing environmental resources, Rover's form becomes somewhat independent of environment.

5) Genes occur and then seek or shape environments. (It is as if Galatea comes to life and starts to shape Pygmalion.) Genes have an immediate effect on environment whereas environment modifies genes across generations. Each "instructs" the other and each sometimes does so through selection. "... the ambient system could not modify an organism without the organism exerting a corresponding influence. The organism cannot be dissociated from its environment. It is the whole system that is modified and transformed" (Comte, Cours de philosophie positive; Oeuvres. 1838, Vol. III, p. 235; cited by Jacob, 1973, p. 155). Lewontin (1998/2000) is only the most recent advocate for this concept; Leibnitz and Comte spun it past Locke and Darwin to Popper, Turner, Jacob, Lewontin, and others of us. (See especially Turner, 2000, on environments as products of selection by organisms.)

Jacob's anecdotes are wonderful and so are his examples from Greek mythology & French literature. For example, a scorpion once asked a frog for a ride across the river. Halfway across, the scorpion stung the frog. The frog gasped, "Why?" The scorpion apologized, "It's my nature." Jacob also uses Daedelus as an icon for a science without conscience, one that allows politicians and tyrants to act on their hubris. Tiresius has his biographies woven into the text as do Prometheus and Pandora. Other gods, a.k.a. politicians and scientists, also have their tiles in Jacob's mosaic: Charles de Gaulle (led the French government's first investing in molecular biology), Pompidou (who once held up funds --- "politicians have the memory of an elephant and the spitefulness of a rhinoceros"!), Thomas Hunt Morgan, Ernst Hadorn, Louis Pasteur, Francis Galton, and, of course, Jacques Monod who worked with Jacob (great research is done by pairs of scientists who communicate with each other in their own jargon, excluding 3rd parties and in a manner similar to that of identical twins). There are also villains such as Lysenko: "The style of Lysenko's declarations ... bring to mind the ramblings of self-published autodidacts convinced they have found the secret of life or a cure for cancer and furious because 'official science' is ignoring them. (p. 29)" Welcome to the Internet!

 Eugenics and Responsibility: Verschuer & Mengele get special attention but Jacob further remarks, (pp. 119-120) "What matters here is not the role of the physician who performed what he called 'experiments' in the camps. It is that of the scientist who inspired the theory." Scientists have responsibility for what might be done with their discoveries.

This is an old problem and Jacob doesn't resolve it. He first denies the possibility of making predictions in science, especially from basic research (in Chapter 1). He puts great faith (Chapter 6) in some antiseptic consequences from giving full information ("the whole truth and nothing but the truth") to the public and from getting informed consent. Jacob, however, does not address the problems of conflicting sectors within any public or that of prima donna feuds between scientists. (Ed Wilson and Dick Lewontin likely each told their respective publics their respective versions of the whole truth.) Jacob also praises Pasteur for his military mind and "swaggering," "irresistible" style, for being a "little Napoleonic,"(in Chapter 7) and for inoculating dairy herds against anthrax despite strident objections from French farmers (in "Conclusion"). So much for informed consent. (Some of these inconsistencies may be attributable to each chapter's originating as a separate talk over the past several years.)

Jacob's position also resembles that of Thom Huxley and his philosophical great grandchildren who advocate that we ignore our genes and transcend our nature. Humbug. These positions are smoke from elder mutualists and young Puritans who rarely imagine that kindness and cooperation might be our sensed awareness of our genetic heritage. Their very argument is apt to be a physico-genetic emergent, one just as adaptive as copulating or killing (Haig, 1999; Hamilton, 1995, pp. 134-135). (See Ridley, 2000, pp. 286-300, for another interpretation of eugenics and the Holocaust.)

Recognizing Individuality: Darwinian gradualism (although Darwin himself saw the possibility of changes "per saltum") and a growing emphasis on large populations accounted for the origins of species. Neodarwinism sought order and tried to build science  but ignored individual variations while doing so. It also ignored the variations that ran in families of closely related individuals.

Clinical and educational work, however, demands we recognize those variations. As Jacob comments on p. 100, "Until now, confronted with a patient, medicine established a diagnosis from which it drew a prognosis. Now it evaluates the genetic profile right away, from which it predicts the medical destiny of the person. We no longer interrogate the gods to learn about a person's future life or that of his descendants. We interrogate the genes." Thus, clinical applications come from molecular genetics rather than from Darwinian models that idolize uniformity.

An Empirical God?: Finally, Jacob has faith in an unlimited exploratory human nature. I am less optimistic. Other cultures have remained in stasis for centuries while humans reasoned about truth instead of measuring it with their fingertips. Further, he does not mention the fundamental role of technology in shaping our beliefs. Pasteur was not possible without a microscope, genetic engineering depends heavily on polymerase chain reactions and other methods unknown a dozen years ago. However, once a tool is available, it interacts with human nature to refine our understandings. We use science to reshape nature and to build our personal Edens. As Jacob wisely notes, we each find the God that we want.

--------------------

Audiences: Intermediate and advanced students in biology, psychology and philosophy. Also, some of us gray heads with nostalgic memories about the biological and behavioral sciences in the last part of the 20th century. Jacob's style reminds me of Loren Eiseley, The Immense Journey. You might compare: All the Strange Hours (Eiseley's autobiography) and The Statue Within (Jacob's), Darwin's Century (Eiseley) & The Logic of Life: A History of Heredity (Jacob). Of Flies, Mice, and Men complements Genome (Matt Ridley), Heredity: the Logic of Life (Jacob), Triple Helix (Richard Lewontin), Signs of Life (Richard Sole & Brian Goodwin), and Consilience (Ed Wilson).

 References

Eldredge, N. (2000) The Triumph of Evolution and the Failure of Creationism. NY: Freeman.

Haig, D. (1999) Genetic conflicts and the divided self. A talk given at Hunter School of Social Work, May 6, 1999. See also: (1997) The Social Gene. In J. R. Krebs & N. Davies (Eds) Behavioral Ecology: An Evolutionary Approach, pp. 284-306. London: Blackwell Science.

Hamilton, W. (1996) Narrow Roads of Geneland: The Collected Papers of WD Hamilton, Vol 1, Evolution of Social Behavior. NY: Freeman

Jacob, F. (1973) Logic of Life: A History of Heredity. NY: Pantheon.

Lewontin, R. (1998/2000) Triple Helix. Cambridge, MA: Harvard.

Sole, R., & Goodwin, B. (2000) Signs of Life: How Complexity Pervades Biology. NY: Basic.

Ridley, Matt (2000) Genome: The Autobiography of a Species in 23 Chapters. NY: Harper Collins.

Turner, J. S. (2000) The Extended Organism:The physiology of animal-built structures. Cambridge, MA: Harvard University Press.

© 2001 James Brody, Ph.D.

James Brody, Ph.D. is moderator of the Behavior.net web discussion forum on Evolutionary Psychology.


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