There's more to life than DNA

October 19, 2001

It wasn't just science James Watson hotly pursued, says Ian Wilmut.

I am among the thousands of budding scientists who read the first volume of James Watson's autobiography, The Double Helix , to learn how he and Francis Crick became the first to discover the true structure of DNA, one of the most important steps in understanding the molecular basis of inheritance. Indeed, by now there must be millions of people who have read that book; it is still in print more than 30 years after its first publication in 1968, a few years after Crick, Watson and Maurice Wilkins were awarded the Nobel prize in medicine and physiology.

Crick and Watson were working at the Cavendish Laboratory in Cambridge at the time of their discovery. When The Double Helix came out, I was a graduate student at Darwin College, Cambridge, developing methods for the deep-freeze storage of gametes and later embryos. Like every other scientist who read it, I was struck by the way it frankly described the competitiveness of scientists in pursuit of their research objectives while also showing with more colour than previously that scientists are mere mortals vulnerable to the same weaknesses and limitations of human nature as everyone else. However, the book created the impression that scientific progress follows a linear path towards a specific objective. In reality this is seriously misleading because many important discoveries have been entirely unexpected. Scientific advances are typically made as the result of systematic research in what will later be recognised as a critical area, as the result of much, hard work and very often a dash of good fortune. At the time of the experiments it is not possible to know if a new approach will be productive. Moreover, advances are often the result of collaborations between people who have different scientific backgrounds. In my experience, new ideas are more likely to arise during casual conversation or while doing something totally unrelated, rather than while sitting concentratedly at a desk. Frequently they are a result of social interaction: I assume they arise in the subconscious and escape from there into conversation in congenial circumstances.

Watson describes many such relaxed discussions on beaches or on lawns during breaks in meetings, or while visiting another laboratory, in this second volume of his autobiography. Genes, Girls and Gamow records in detail the events of the five years of his life, 1953-58, immediately after the breakthrough with the structure of DNA, and finishes with an epilogue concerned with a few later events. During this period he worked at Caltech (the California Institute of Technology), Harvard University and in Cambridge, as well as travelling extensively. International travel was, of course, much slower than it is today.

During the period described in the book, one important challenge was to discover how the sequence of nucleotides in a chromosome comes to be represented by the protein encoded by a specific gene. One vital step was the recognition of the role of what we now know as transfer RNA. The nature of a protein is determined by the sequence of constituent amino acids, and Watson records how he and others spent a great deal of time trying to imagine how the amino acids could be held against the DNA helix while the protein was assembled. What was known of the likely chemical interactions between such molecules made this seem extremely unlikely. That is until a new thought occurred to Crick while he was driving back into New York, ready to sail home to Cambridge after attending an out-of-town meeting. He reasoned that a small molecule might hold the amino acid while synthesis took place. If there were different molecules for each amino acid, they could be used to define the sequence of amino acids as the protein was assembled. Later laboratory research isolated and characterised these transfer RNA molecules.

Once again, as in The Double Helix , the author is extraordinarily frank in his description of events and his characterisation of fellow players. Inevitably some people will be hurt by the public record of things long forgotten or by his description of them. I do not know if Watson does not understand that some of his descriptions are hurtful or if he feels that in the interests of accuracy nothing (or very little?) should be omitted. In writing a generous foreword, one of those likely to be hurt - Peter Pauling, son of the chemist Linus Pauling - characterises himself as "unappointed leader of the Victims" and hopes that the Victims will be lenient with the author. He also notes that there are some errors of fact because Watson was not present to observe the event being described, and comments: "As a work of reference to what actually happened, this book is unreliable."

While biochemistry occupied his professional time, the search for a wife apparently dominated his private life. Watson records the often very brief relationships with very many young women, until in the final two pages he hurriedly introduces the woman who became his wife and has remained so for more than 30 years. To one of the earlier companions to whom he was socially attrac-ted for a long time, Christa Mayr (daughter of a well-known biologist), he acknowledges a debt: she provided access to the letters he wrote her at frequent intervals during most of the period covered in the book. Apparently these and other letters he received from close acquaintances provide the basis of what is a detailed record of events more than four decades ago. The others include a large number of very distinguished British biologists such as Sir Lawrence Bragg, head of the Cavendish Laboratory; Sydney Brenner, who collaborated extensively with Crick in studies of RNA and would later be head of the Medical Research Council's laboratory of molecular biology in Cambridge; Hugh Huxley, who devised the accepted model of muscle function; and Aaron Klug, who would become president of the Royal Society. He also describes visits to the Scottish home of the author Naomi Mitchison, mother of two distinguished biology professors (and to whom he dedicated The Double Helix ). Regrettably, there is no index to search out this extraordinary cast of players, although there is a "cast of characters".

Above all, this is a story of the international nature of science. The author describes friendships, collaborations or competitions with two Nobel-laureate colleagues at Caltech: Richard Feynman, bongo-playing theoretical physicist, and Linus Pauling, later an enthusiastic advocate of the value of increased vitamin C intake but better known at the time for recognising the helical structure of some proteins; with Alex Rich, later of the National Institutes of Health and presently Massachusetts Institute of Technology; with Wally Gilbert of Harvard, who devised a method for sequencing DNA; and with the physicist George Gamow, known as Geo, pronounced "Joe". Apart from lending his helpfully alliterative name to the title of the book, Geo clearly played a particular role in prompting collaborations among those trying to discover the code by which the sequence of nucleotides in chromosomal DNA directs production of a particular protein. Like many other researchers in this area, including Crick, Gamow was a theoretical physicist by training; before turning to molecular biology, he was an early proponent of the big bang theory of cosmology. Several of the letters he wrote to Watson are reproduced in facsimile, and they reveal an engaging enthusiast.

It was Gamow who suggested that a club be formed from those interested in RNA - the RNA Tie Club. The idea caught on. No doubt there was competition among the molecular biologists in developing and defending their own ideas, but often one gets the impression of excited discussions conducted in informal atmospheres. One difference between the period described in this volume and the present day is our much greater reliance on commercial funding in research. The money for discovering the fundamental knowledge described in this book all came from government agencies or philanthropic organisations. They lacked the capacity for the quick boost in funding possible with commercial support but, on the other hand, they supported an intellectual freedom enjoyed by few laboratories today.

The 1950s in the United States was the high point of the McCarthy-inspired witch-hunt for Communist sympathisers, from the Korean war up to the election of Kennedy as president in 1960. Watson's account of its effects on science is extremely readable. Enormous social changes took place at this time, with consequences that are hard for today's generation to imagine. Robert Oppenheimer, the leader of the project at Los Alamos that produced the atomic bomb, lost his security clearance because of his opposition to the development of the hydrogen bomb. As a former faculty member of Caltech, Oppenheimer still had friends there when Watson worked at Caltech. He describes a pervasive unease at the institute when this event occurred and great concern when other scientists were denied grants because of alleged left-wing tendencies. Such things must seem incredible to young biologists today.

Genes, Girls and Gamow ends before its author becomes director of the Cold Spring Harbor Laboratory. He redirected the focus of this important research centre toward cancer. Later he helped to establish the human genome project that is only now coming to fruition. We can hope that he will record and publish recollections from these later experiences, as he played a central role in the development of this new era of biology. Perhaps we may also learn why he chose to dedicate the two volumes of his autobiography to Naomi Mitchison and Celia Gilbert, respectively.

Ian Wilmut is head of the team at the Roslin Institute, near Edinburgh, which cloned Dolly the sheep in 1996.

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