Of Flies, Mice, and Men by François Jacob

Published by Harvard University Press

It is thanks to François Jacob that I began to understand what evolution meant at the molecular level, when I read his wonderful book Le jeu des possibles (The possible and the actual), more than ten years ago. And “Evolution is tinkering”, Jacob’s catchphrase, is with me ever since. 

Jacob, now 92 years old, began his scientific career after fighting in World War II, and studied lysogenic phages in bacteria at the Pasteur Institute in Paris. There he met Jacques Monod, starting one of the most fruitful collaboration of the 20^th century. Their work on genetic regulation in E. coli culminated in a Nobel Prize in 1965. In addition to their revolutionary contribution to molecular biology, Jacob and Monod also wrote books of great importance and large outreach, notably Chance and necessity (Monod) and The logic of life (Jacob).  

Of flies, mice, and men¹ (1998) is his last book to date, a personal journey across biology that spans several decades. The different chapters feel a little bit disconnected, because apparently they were first written as lectures for different occasions, but the book is very enjoyable. Jacob is one of these great scientific figures with a real literary culture, one who can invoke Dino Buzzatti and ancient greek myths, the poets Paul Valéry and John Keats, or Tolstoy. 

In the first chapter, The importance of the unpredictable, Jacob offers a plea in favor of fundamental research, and he tells a striking anecdote about the importance of emerging sciences: When Charles De Gaulle—the leader of French opposition during WWII, and the first French president after the end of the war—came back to public office in 1958, he met with a group of scientists to decide what fields would primarily be funded. A representative of each scientific discipline was given five minutes to make their case. One proposed the newborn and promising discipline of molecular biology. Jacob quotes the words of De Gaulle at the end of this reunion (p.15):

“You might think that a general would be particularly appreciative of spectacular projects whose descriptions he understands, whose perspective he shares, and whose developments, consequences, and repercussions he readily anticipates. Examples among those I’ve just heard would be renewable energy resources, the conquest of space, and the exploitation of the oceans. But deep down, I wonder whether this mysterious molecular biology, of which I know nothing and will certainly never understand anything, isn’t the most promising of the mid-term developments—unpredictable, rich, capable of doing much to advance our understanding of the basic phenomena of life and its disorders. Perhaps it will be the basis for a new medicine that we cannot even imagine today. It might even be the medicine of the twenty-first century.”

What a foresight! What a lesson!

Jacob had been extremely successful with the study of bacteria, and he could have gone on with it for the rest of his career, but in the mid-sixties he felt that he needed a change. What interested him was embryonic development, and to study it he must abandon bacteria and select a new model organism. This is not an easy move at all! Personally, I do not know any scientist who made such a move in her career. Why is it so? As Jacob put it (p.53), “over time you become a sort of captive of what you have done and what you know. Equipment and other paraphernalia—mutants, enzymes, purified products, all of great value—pile up“. But Jacob decided to make this sacrifice, and to pick up a new organism. It could have been the fruit fly Drosophila, or the worm Caenorhabditis elegans, but finally it would be the mouse. And he kept working on until now.

In addition to guiding us through the history of modern biology, Jacob has many interesting things to say about the philosophy of science. Here’s what he writes about our discipline (p.75):

“Biology admits of a great many generalizations, but very few theories [As opposed to physics]. The most important among these is the theory of evolution, because it unites, from a variety of domains, a mass of observations that would otherwise remain isolated; because it links within these domains all the disciplines that concern living beings; because it brings order to the extraordinary variety of organisms—in short, because it supplies a causal explanation of the living world and its heterogeneity. It’s curious that the theories of physics such as relativity or quantum theory, which are not understood by the public, are neither debated nor contested. With the theory of evolution, it’s the reverse. Everyone thinks they understand it. This theory is controversial, though challenges to it are often based on reasons that are irrelevant.”

Jacob also goes after some of the myths about scientists and the scientific method. He thus distinguishes between “day” and “night” science (p.126):

“Conscious of its progress, proud of its past, sure of its future, day science advances in light and glory.

“By contrast, night science wanders blind. It hesitates, stumbles, recoils, sweats, wakes with a start. […] There is no way to predict whether night science will ever become day science; whether the prisoner will emerge from the darkness.”

Day science is, of course, what we like to present to the public. But the public would better understand the unpredictability of research if it could grasp the reality of night science. As Jacob points out, when we present scientific results (for instance in scientific articles), we get rid of all the hesitation and stumbling, this for good reasons. The truth is that scientific discovery is not a straightforward process at all! Jacob writes, p.130:

“It is popularly believed that to do scientific work, one need only observe and accumulate experimental results until a theory emerges from them. Nothing of the sort. One can contemplate an object form every angle for years, and never produce any observation of the least scientific interest.”

Observations are important in science, but science is by no means a mere collection of observations. You need to instill some ideas in there. This is what Max Planck called the ‘metaphysical’ component of science, in the sense that you need something beyond facts and observations to do science: hypotheses, theories, etc. 

Let’s give the final word to Jacob, who is such a wonderful writer (p.139):

“As in literature or in painting, there is style in science. Not only a way at looking at the world, but also a way of questioning it.”

Notes

1. Lasouris, la Mouche et l’Homme. Editions Odile Jacob, 1997.

References

• Jacob F. 1998. Of Flies, Mice, and Men. Translated by Giselle Weiss. Harvard University Press, Cambridge, 158 pages.