What Mad Pursuit

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By Francis Crick

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Candid, provocative, and disarming, this is the widely-praised memoir of the co-discoverer of the double helix of DNA.

Excerpt

What Mad Pursuit




BOOKS IN THE ALFRED P. SLOAN FOUNDATION SERIES

Disturbing the Universe by Freeman Dyson
Advice to a Young Scientist by Peter Medawar
The Youngest Science by Lewis Thomas
Haphazard Reality by Hendrik B. G. Casimir
In Search of Mind by Jerome Bruner
A Slot Machine, a Broken Test Tube by S. E. Luria
Enigmas of Chance by Mark Kac
Rabi: Scientist and Citizen by John Rigden
Alvarez: Adventures of a Physicist by Luis W. Alvarez
Making Weapons, Talking Peace by Herbert F. York
The Statue Within by François Jacob
In Praise of Imperfection by Rita Levi-Montalcini
Memoirs of an Unregulated Economist by George J. Stigler
Astronomer by Chance by Bernard Lovell


THIS BOOK IS PUBLISHED AS PART OF AN ALFRED P. SLOAN FOUNDATION PROGRAM




What Mad Pursuit

A Personal View of Scientific Discovery



FRANCIS CRICK











Experience is the name everyone gives to their mistakes.

—OSCAR WILDE




Preface to the Series

THE ALFRED P. SLOAN FOUNDATION has for many years had an interest in encouraging public understanding of science. Science in this century has become a complex endeavor. Scientific statements may reflect many centuries of experimentation and theory, and are likely to be expressed in the language of advanced mathematics or in highly technical terms. As scientific knowledge expands, the goal of general public understanding of science becomes increasingly difficult to reach.

Yet an understanding of the scientific enterprise, as distinct from data, concepts, and theories, is certainly within the grasp of us all. It is an enterprise conducted by men and women who are stimulated by hopes and purposes that are universal, rewarded by occasional successes, and distressed by setbacks. Science is an enterprise with its own rules and customs, but an understanding of that enterprise is accessible, for it is quintessentially human. And an understanding of the enterprise inevitably brings with it insights into the nature of its products.

The Sloan Foundation expresses great appreciation to the advisory committee. Present members include the chairman, Simon Michael Bessie, Co-Publisher, Cornelia and Michael Bessie Books; Howard Hiatt, Professor, School of Medicine, Harvard University; Eric R. Kandel, University Professor, Columbia University College of Physicians and Surgeons, and Senior Investigator, Howard Hughes Medical Institute; Daniel Kevles, Professor of History, California Institute of Technology; Robert Merton, University Professor Emeritus, Columbia University; Paul Samuelson, Institute Professor of Economics, Massachusetts Institute of Technology; Robert Sinsheimer, Chancellor Emeritus, University of California, Santa Cruz; Steven Weinberg, Professor of Physics, University of Texas at Austin; and Stephen White, former Vice-President of the Alfred P. Sloan Foundation. Previous members of the committee were Daniel McFadden, Professor of Economics, and Philip Morrison, Professor of Physics, both of the Massachusetts Institute of Technology; George Miller, Professor Emeritus of Psychology, Princeton University; Mark Kac (deceased), formerly Professor of Mathematics, University of Southern California; and Frederick E. Terman (deceased), formerly Provost Emeritus, Stanford University. The Sloan Foundation has been represented by Arthur L. Singer, Jr., Stephen White, Eric Wanner, and Sandra Panem. The first publisher of the program, Harper & Row, was represented by Edward L. Burlingame and Sallie Coolidge. This volume is the seventh to be published by Basic Books, represented by Martin Kessler and Richard Liebmann-Smith.

The Alfred P. Sloan Foundation




Acknowledgments

THIS BOOK was started at the suggestion of the Sloan Foundation, for whose generous support I am most grateful. I was approached in 1978 by Stephen White, who persuaded me to sign the initial memorandum of agreement but I was very dilatory about beginning to write. I might have stayed in this state indefinitely but for Sandra Panem, who took over as book program director in 1986. She liked the idea of the book that was forming in my mind, and stimulated by her enthusiastic encouragement I produced a first draft. This was expanded and improved enormously as the result of her detailed comments, together with those of the Sloan Advisory Committee. I have also been helped by the comments of Martin Kessler, Richard Liebmann-Smith, and Paul Golob of Basic Books and by the copy editor, Debra Manette, who has improved my English in many places. I am also grateful to Ron Cape, Pat Church-land, Michael Crick, Odile Crick, V. S. (Rama) Ramachandran, Leslie Orgel, and Jim Watson, all of whom made helpful comments on one or another of the earlier drafts.

In writing the rest of the book, I have not made a deliberate attempt to acknowledge those who have been very close associates and have also influenced me strongly. While I shall not try to list here all my many friends and colleagues, there are three whom I must single out for special mention. The text does make clear how much I owe to Jim Watson. It does less than justice to my long and very fruitful association with Sydney Brenner. He was my closest associate for almost twenty years, and during much of that time we had long scientific discussions on almost every working day. His clarity, incisiveness, and fertile enthusiasm made him an ideal colleague. My third debt is to Georg Kreisel, the mathematical logician, whom I always address by his last name in spite of our having known each other for about forty-five years. When I met Kreisel I was a very sloppy thinker. His powerful, rigorous mind gently but steadily made my thinking more incisive and occasionally more precise. Quite a number of my mental mannerisms spring from him. Without these three friends my scientific career would have been very different.

My other major debt is to my family. Not only did they encourage me to become a scientist but they helped me financially. My parents made considerable sacrifices to enable me to go away to boarding school, especially during the Depression. My uncle Arthur Crick and his wife not only assisted me financially while I was a graduate student at University College but also gave me the money to buy our first house. My aunt Ethel, in addition to teaching me to read, helped financially when I first went to Cambridge after the war, as did my mother. They both helped also with the education of my son Michael. While I had very little money when I was young, I was secure in the knowledge that, thanks to my relatives, I would have enough to live on.

During most of the period covered by the main sections of this book I was employed in Cambridge by the British Medical Research Council. I am especially grateful to them, and in particular to Sir Harold Himsworth (then Secretary of the MRC) for providing such perfect working conditions there for me and my colleagues.

I should also record my gratitude to my present employer, The Salk Institute for Biological Studies, and in particular its president, Dr. Frederic de Hoffmann, for allowing me to work in such a delightful and stimulating atmosphere.

While writing this book I was mainly occupied in studying the brain. I thank the Kieckhefer Foundation, the System Development Foundation, and the Noble Foundation for their financial support of my efforts.

I thank the Editor of Nature for allowing me to quote at length from my article entitled, “The Double Helix: A Personal View,” published on April 26, 1974; the New York Academy of Sciences for permission to quote extensively from an article of mine, “How to Live with a Golden Helix,” which appeared in The Sciences in September 1979; Richard Dawkins and W. W. Norton and Company for permission to use several passages from his book, The Blind Watchmaker, published in 1986; V. S. (Rama) Ramachandran and Cambridge University Press for allowing me to quote a paragraph from his chapter “Interactions Between Motion, Depth, Color, Form and Texture: The Utilitarian Theory of Perception,” soon to appear in Vision, Coding and Efficacy, edited by Colin Blakemore; and Jamie Simon for doing the drawings.

Finally, my warmest thanks to my secretary, Betty (“Maria”) Lang, who has coped splendidly with the many successive versions and all the tedious chores associated with producing a manuscript.




What Mad Pursuit

FRONTISPIECE
To show the approximate size of various objects, from molecules to man. Note that each step in the scale is a factor of ten.




Introduction

THE MAIN PURPOSE of this book is to set out some of my experiences before and during the classical period of molecular biology, which stretched from the discovery of the DNA double helix in 1953 till about 1966 when the genetic code—the dictionary relating the nucleic acid language to the protein language—was finally elucidated. As a preliminary I have put a short prologue that outlines a few details of my upbringing and education, including my early religious education, followed by an account of how I decided (after the Second World War) what branch of science to study, using the “gossip test” to help me. I have also included an epilogue, describing in outline what I have been doing since 1966.

There is an important difference between the scientific work described in the main body of the book and that touched on in the epilogue. In the former case we know with reasonable certainty what the correct answers are (the protein-folding problem is an exception). In the epilogue we do not yet know how things will turn out (the exception here is the double helix). For this reason many of my remarks in the epilogue are a matter of opinion. My comments in the main body of the book have somewhat more authority. One of the striking characteristics of modern science is that it often moves so fast that a research worker can see rather clearly whether his earlier ideas, or those of his contemporaries, were correct or incorrect. In the past, this opportunity did not arise so often. Nor does it today in slowly moving fields.

I have not tried to give an exhaustive account of what I did scientifically during those exciting years, let alone the large amount of work done by others. For example, I have said little or nothing about the ideas Jim Watson and I had about virus structure, nor about my collaboration with Alex Rich on a number of molecular structures. Instead I have included only those episodes that seem to me to have some general interest or to teach some general lesson about how research is done and what mistakes to avoid, especially those mistakes most relevant to biology. To do this I have to dwell somewhat more on errors than on successes.

In 1947, at the age of thirty-one, I went to Cambridge. After about two years working at the Strangeways Laboratory (a tissue-culture lab) I transferred to the Cavendish—the physics laboratory. There I became a graduate student again, trying to learn something about the three-dimensional structure of proteins by studying the X-ray diffraction patterns produced by protein crystals. It was then that I first learned how to go about doing research. It was during this period, while I was still a graduate student, that Jim Watson and I put forward the double-helical structure of DNA.

It has been difficult for me to write anything very new about the events leading up to the discovery of the double helix, since this has already been the subject of several books and movies. Rather than go over such familiar ground once again, I have found it better to comment on various aspects of the discovery and also on the recent BBC television movie Life Story, which deals with the discovery. In the same way I have not spelled out exactly how the genetic code was discovered—this is outlined in almost all modern textbooks. Instead I have dwelt mainly on the ups and downs of the theoretical approach, because I think few people realize exactly what a failure all this theoretical work on the genetic code turned out to be.

Since I am concerned more with ideas than with people, I have not included detailed character sketches of my friends and colleagues, mainly because I am reluctant to write candidly about close personal relationships with people still alive. In spite of this I have scattered through the text a number of small anecdotes, to give at least a few glimpses of what scientists are like, and to make for easier reading. Few people will willingly slog through an uninterrupted intellectual argument that lasts a whole book, unless they are acutely interested in the topic. In short, my main aim has been to put over a few ideas and insights in what I hope is an entertaining manner.

I have written both for my fellow scientists and for the general public, but I believe a layman can easily understand most of what I discuss. Occasionally the arguments become somewhat technical, but even in those cases I think that the general thrust of the idea is fairly easy to appreciate. I have sometimes placed short remarks from a more advanced standpoint in square brackets. To help those without a background in molecular biology, I have also included as a frontispiece a figure showing the approximate sizes of molecules, chromosomes, cells, and so forth, as well as two appendixes, the first sketching in the briefest outline the elements of molecular biology and the second setting out the details of the genetic code. Since most people (except chemists) hate chemical formulas, I have banished almost all of them to the first appendix.

In spite of all my efforts at clarification, a layperson may still find parts of chapters 4, 5, and 12 somewhat hard going at first reading. My advice to the reader, should he or she become stuck in such a passage, is either to persevere or to skip to the next chapter. Most of the book is fairly easy. Don’t give up hope just because a few paragraphs seem a little hard to follow.

The most important theme of the book is natural selection. As I explain, it is this basic mechanism that makes biology different from all the other sciences. Of course anyone can grasp the mechanism itself, though remarkably few people actually do so. Most surprising, however, are the results of such a process, acting over billions of generations. It is the general character of the resulting organisms that is unexpected. Natural selection almost always builds on what went before, so that a basically simple process becomes encumbered with many subsidiary gadgets. As François Jacob has so aptly put it, “Evolution is a tinkerer.” It is the resulting complexity that makes biological organisms so hard to unscramble. Biology is thus very different from physics. The basic laws of physics can usually be expressed in exact mathematical form, and they are probably the same throughout the universe. The “laws” of biology, by contrast, are often only broad generalizations, since they describe rather elaborate chemical mechanisms that natural selection has evolved over billions of years.

Biological replication, so central to the process of natural selection, produces many exact copies of an almost infinite variety of intricate chemical molecules. There is nothing like this in physics or its related disciplines. That is one reason why, to some people, biological organisms appear infinitely improbable.

All this can make it difficult for a physicist to contribute to biological research. Elegance and a deep simplicity, often expressed in a very abstract mathematical form, are useful guides in physics, but in biology such intellectual tools can be very misleading. For this reason a theorist in biology has to receive much more guidance from the experimental evidence (however cloudy and confused) than is usually necessary in physics. These arguments are set out in more detail in chapter 13, “Conclusions.”

I myself knew very little biology, except in a rather general way, till I was over thirty, since my first degree was in physics. It took me a little time to adjust to the rather different way of thinking necessary in biology. It was almost as if one had to be born again. Yet such a transition is not as difficult as all that and is certainly well worth the effort. To discuss how my career developed, I turn first to a brief account of my early years.




1

Prologue:
My Early Years

I WAS BORN IN 1916, in the middle of the First World War. My parents, Harry Crick and Anne Elizabeth Crick (née Wilkins), were a middle-class couple living near the town of Northampton, in the English Midlands. The main industry in Northampton in those days revolved around leather and the manufacture of footwear—so much so that the local soccer team was called the Cobblers. My father, with his eldest brother, Walter, ran a factory, founded by their father, that produced boots and shoes.

I was born at home. I know this because of a curious incident connected with my birth. While my mother was not deeply superstitious, she did like to cultivate certain mildly superstitious practices. Each new year she would try to arrange that the first person who crossed our threshold was dark rather than blond. This practice—I have no idea if it still goes on—is called “first footing” and is supposed to bring good luck in the ensuing year. After I was born she instructed her younger sister, Ethel, to carry me to the top of our house. My mother hoped that this little ceremony would make sure that, in later life, I would “rise to the top.” Most superstitious practices reveal more about their perpetrators than they realize, and this family legend shows rather clearly that my mother, like many another mother, was ambitious for her first born son even before she could have had, any inkling of my character and abilities.

I have little recollection of my very early years. I do not even remember being taught to read by my aunt Ethel, who was a schoolteacher. Photographs make me appear to be a very normal child. My mother was fond of saying that I looked like an archbishop. I’m not sure she had ever seen an archbishop—she was not a Catholic or a member of the Church of England—but she may well have seen a photograph of one in the newspaper. It is hardly likely that at the age of four or five I resembled such a venerable person. What I suspect she meant, but was too restrained to say, was that she thought I looked like an angel—very fair hair, blue eyes, an “angelic” expression of benevolent curiosity—but with perhaps something extra. Odile (my current wife) has a locket, a gift from my mother, from that period. It contains two small round tinted photographs, one of my younger brother, Tony, and one of me. I once commented to her that, from the look of it, I seemed to have been a rather angelic child. “Not really,” she said. “Look at those piercing eyes.” And she spoke with feeling, having often, in our many years together, been subjected to that same critical inquiring gaze.

My only other clue as to my early nature comes from Michael, my son by my first wife, Doreen. When he was about the same age, he lived for a time with my mother. I noticed that, more than once, in reply to an explanation by her, he would answer, “But that can’t be right.” My mother, puzzled, would ask, “Why not?” to which Michael would give a simple, logical explanation that was transparently correct. I suspect that I too made such remarks to my mother—which was not difficult because she was not a precise thinker—and she found these both disconcerting and fascinating. In any event, it is clear to me now that my mother thought (as many mothers do) that her elder son had exceptional talents, and coming from a solid, middle-class background, she did everything possible to see that these talents were nurtured.

It must have been to parry my constant questions about the world—for neither of my parents had any scientific background—that they bought for me Arthur Mee’s Children’s Encyclopedia. This was published serially, so that in any one number art, science, history, mythology, and literature were all jumbled together. As far as I can remember, I read it all avidly, but it was the science that appealed to me most. What was the universe like? What were atoms? How did things grow? I absorbed great chunks of explanation, reveling in the unexpectedness of it all, judged by the everyday world I saw around me. How marvelous to have discovered such things! It must have been at such an early age that I decided I would be a scientist. But I foresaw one snag. By the time I grew up—and how far away that seemed!—everything would have been discovered. I confided my fears to my mother, who reassured me. “Don’t worry, Ducky,” she said. “There will be plenty left for you to find out.”

By the time I was ten or twelve, I had graduated to experiments at home—my parents must have bought me a student’s textbook on chemistry. I tried to make artificial silk—a failure. I put an explosive mixture into bottles and blew them up electrically—a spectacular success that, not unnaturally, worried my parents. A compromise was reached. A bottle could be blown up only while it was immersed in a pail of water. I got a prize at school—my first prize ever—for collecting wildflowers. I had gathered far more species than anyone else, but then we lived on the edge of the country whereas all my fellow schoolboys lived in the town. I felt a little guilty about this but accepted the prize—a small book on insect-eating plants—without demur. I wrote and mimeographed a small magazine to entertain my parents and my friends. But in spite of all this, I do not recall being exceptionally precocious or doing anything really outstanding. I was fairly good at mathematics, but I never discovered for myself some important theorem. In short, I was curious about the world, logical, enterprising, and willing to work hard if my enthusiasm was aroused. If I had a fault, it was that if I could grasp something easily, I believed I had already understood it thoroughly.

My family were all tennis players. My father played for many years for Northamptonshire, an English county, and once played at Wimbledon. My mother also played, but with much less skill and only moderate enthusiasm. My younger brother, Tony, was a much keener player, doing well in the Junior County Championship and also playing for his school. I can hardly believe it now, but as a boy I was mad about tennis. I can still remember the day when my mother woke me early and told me (what bliss!) that I could miss school that day as we were going to Wimbledon. My brother and I would sit, sometimes for hours, beside the courts at the local tennis club, waiting for the drizzle to stop and hoping at least one of the courts would become dry enough for us to play on it. I did play other games (soccer, rugby, cricket, etc.) but without any distinction.

My parents were religious in a rather quiet way. We had nothing like family prayers, but they attended church every Sunday morning and when we were old enough my brother and I went with them. The church was a nonconformist Protestant one, a Congregational Church, as it is called in England, with a substantial building on Abington Avenue. As we did not own an automobile we often walked to church, though sometimes we made part of the journey by bus. My mother greatly admired the clergyman because of his upright character. For a time my father was secretary of the church (that is, he did the church’s financial paperwork), but I did not get the feeling that either of them was especially devout. Certainly they were not overly narrow in their outlook on life. My father sometimes played tennis on Sunday afternoons, but my mother warned me not to mention this to other members of the congregation since some almost certainly would not have approved of such sinful conduct.

Genre:

On Sale
Aug 6, 2008
Page Count
208 pages
Publisher
Basic Books
ISBN-13
9780786725847

Francis Crick

About the Author

Francis Crick is the Kieckhefer Professor at the Salk Institute in La Jolla, California. He shared a Nobel Prize with James Watson and Maurice Wilkins in 1962 for the discovery of the structure of DNA, regarded as the greatest biological advance of the twentieth century.

Learn more about this author