Biology and bile

The eminent geneticist Steve Jones considers one of the great thrillers of modern science and places it in its social and scientific context
March 20, 1997

Science, in the public mind, is detached from the people who practise it. Everyone knows about viruses, or the background radiation of the big bang, but almost nobody could name the individuals who discovered them. DNA is different and this book is the reason why. From its first sentence ("I have never seen Francis Crick in a modest mood") it combines the facts of science with the rattling tale of how they were unveiled. To re-read it after nearly 30 years, is to affirm the genius of those who did the job. It is also a reminder of how much science has changed in the decades since Watson and Crick's 1953 paper which began modern genetics.

In that year science in Britain was still, in the worst sense, British. It was a vocation of the upper middle class, largely male, and remained concentrated in the older provincial universities. Since then, and in spite of determined rearguard action, it has become much more open. For genetics, the meeting in 1951 of James Watson (then only 23) and the 35-year-old Francis Crick was the first step. Although its excitement comes from the discovery of the structure of DNA, The Double Helix is as much an account of the sociology of science as of science itself. Sir Lawrence Bragg, a senior figure in the story, describes it in his foreword to the first edition as a drama of the highest order; but in rather a pained tone adds that "those who figure in the book must read it in a very forgiving spirit." One can see what he meant.

It is almost obligatory for great scientists to claim that their genius comes from standing on the shoulders of giants. Watson and Crick preferred to stand on their toes. The Double Helix is full of gleeful humour at the expense of those grander than themselves. Sometimes it goes beyond wit: there are whole paragraphs of bile aimed at targets whose identity was clear to those in the know. Watson's discussion (somewhat redeemed in the postscript) of the role of Rosalind Franklin in the work ("The thought could not be avoided that the best home for a feminist was in another person's lab") is particularly offensive to the modern reader.

It is worth placing DNA into context. Genetics is a science without a past. Before Mendel, less than 150 years ago, there was nothing. Even after his work was rediscovered in 1901 geneticists were, like Mendel himself, interested only in sex. Genes were mapped in a biological way; by making crosses among mice, flies or fungi and looking at the distribution of characters among their offspring. The nature of the inherited material was ignored.

This work inferred the operation of the genetical machine from what it made. Its roots were in theory rather than practice, in physics rather than chemistry. For a time, indeed, genetics was in danger of becoming a branch of mathematics.

The idea that something so straightforward as DNA could be the agent of inheritance had to wait until 1944. Then, it became possible to change the appearance of colonies of a certain bacterium by treating them with DNA extracted from other colonies with a different shape. The change, amazingly, was inherited. Information was being passed from one generation to the next through the medium of DNA. How, nobody understood.

This book tells the story of how the structure of DNA-two matching chains of simple chemicals called "bases," wrapped around each other in a double helix-was discovered. That gave the immediate prospect of inferring how genes replicated themselves and transmitted information from parents to offspring. Not content with having sorted out the molecule's structure, in another intellectual tour de force eight years later Crick (together with Sydney Brenner and others) deciphered the genetic language itself.

By adding DNA bases one by one to short lengths of the chemical from a virus they showed that the message was based on a three unit code read from one end to the other. What made an elephant rather than an eel from a fertilised egg that looked almost identical in each? What, for that matter, gave rise to eels or elephants in the first place? As schemes to list the order of DNA bases forge ahead-complete for some bacteria and yeasts, soon to be so for a certain worm; and well under way for the 3,000m bases of our own genetic material-these old questions are now being asked again.

Biology has been united by the theory of evolution. The new genetics proves Darwin's notion of shared descent. Life, it shows, exists in a hierarchy of kinship. DNA holds some surprising secrets: affinity between, say, men and bananas is far closer that that between two apparently indistinguishable bacteria. Mushrooms are a group as distinct and diverse as are animals and plants, considered as a single entity that includes elephants, eels and elm trees.

Darwin knocked mankind off his pinnacle. DNA grinds his face into the biological mud. Men and chimps share 99 per cent of their genes. Human inherited diseases are found in mice, cats and dogs. Genes controlling the fundamental processes of life, such as the division of cells, are similar even in creatures as distinct as ourselves and yeast.

In spite of their genetic affinity, men and fish-or even men and chimps-look quite different. How the DNA in a virtually formless egg is translated into an adult body remains almost a mystery. Some genes code for proteins that act as switches early in development, pushing an embryo into one path or another. They need not be complicated: that persuading a human embryo to develop as male rather than female is only a couple of hundred bases long. Others with equally dramatic effects (causing a fly to develop an extra pair of wings) are just as simple. The twin Victorian obsessions-with development from egg to organism and evolution from primeval to primate-have returned. They will dominate biology in the 21st century.

Whatever fundamental advances may be made, genetics, like most sciences, is often pursued for simple gain. So rapidly did it progress after 1953 that, for a time, its commercial prospects seemed boundless. There were a few triumphs (persuading bacteria to make the protein used to treat the blood-clotting disease haemophilia; or sheep to secrete human growth hormones), but most companies produced nothing.

Another piece of biological hubris has also been forced to face reality. Once, it seemed that inherited disease would be cured by replacing damaged DNA. That remains more promise than reality. But there is real hope that understanding genetic defects will help treat them. The great killers of the western world-cancer, heart disease, diabetes-have an inherited component. To identify those at risk before symptoms begin is the first step to a cure.

Science does not exist in a social vacuum. Just as geneticists begin to realise how far it is between DNA and organism, their subject is being hijacked. Society is, it seems, little more than the product of genes. Reports of inherited variation in personality, intelligence or aggressiveness have become banal. No doubt such variation exists. With half of all genes active in the brain it is not surprising that there are inherited influences on behaviour. Some claim that those born with genes for low IQ or short temper cannot be helped. They suggest that society must learn to contain (rather than rehabilitate) its weakest members. Oddly enough, these fatalists usually insist on the best environment they can get when it comes to their own children.

This logic has a fatal flaw. It trips up over the meaning of "for," the most dangerous word in genetics. There are no genes for behaviour. No pattern of conduct is immune to DNA. The fact that heart disease is influenced by genes does not stop it from being treated with drugs. Similarly, the best way to improve the nation's IQ-inherited though much of its variability might be-would be to double teachers' pay.

So many inherited predispositions in both body and mind are emerging that those who study them face the situation of The Gondoliers (the Gilbert and Sullivan operetta in which a whole state is promoted to the aristocracy). When everything is seen to be at least in part controlled by genes, genetics may lose its allure: as the aristocrats who clean the boots sing, with some dismay, "when everyone is somebody, then no one's anybody!" In the same way, if all conceivable human attributes have a genetic component (as they probably do), the public will soon learn how little that need mean. Biology can then return to being a science rather than a social elixir.

The amazing advances since the discovery of the double helix emphasise how hard it is for those in the arts to understand the immediacy of science. In biology it is still possible to talk to figures who would be, to a historian, the equivalents of Hitler or Napoleon. Crick and Watson-both still with us-fall (in the nicest possible way, of course) firmly into that category.

Both have pursued distinguished careers in the 40 years since their greatest find. Watson returned to the US, first to CalTech, then to Harvard and the Cold Spring Harbor Laboratory. For several years he headed the Human Genome Project, the programme to work out the complete human DNA sequence. In 1976, Crick moved from Cambridge to the Salk Institute in San Diego and to the study of consciousness, a subject still as resistant to understanding as was inheritance before Mendel. Maurice Wilkins remained at King's College London until his retirement. Rosalind Franklin died in 1958 and Sir Lawrence Bragg in 1971. Many of the other characters described in the book are still around. Most played an important part in the progress of modern biology, but none can claim a discovery as marvellous as that of Watson and Crick.

In the end, though, science is what matters; scientists not a bit. To read this volume is to know what it must have been to participate in what Watson calls, "the most famous event in biology since Darwin's book." It is notoriously hard to identify turning points in science. Often, they are recognised only years after the idea itself. The structure of DNA was not like that: its importance was obvious as soon as the first primitive model of its shape was made. The double helix is the icon of the modern age and the story of its discovery as told here has not been surpassed in this century. Who knows whether it will be in the next?
The double helix

James D Watson

Weidenfeld & Nicolson 1997, ?18.99