Gene genies
By Clive Cookson
Published: October 20 2007 01:18 | Last updated: October 20 2007 01:18
A life decoded: My Genome: My Life
By J. Craig Venter
Allen Lane £25, 390 pages
FT bookshop price: £20
Avoid boring people: And Other Lessons from a Life in Science
By James D Watson
Oxford University Press £14.99, 348 pages
FT bookshop price: £11.99
For anyone interested in the recent history of genetics research, this is a wonderful week. James Watson and Craig Venter, the scientists who have done more than anyone to push forward the study of DNA, have brought out autobiographies at the same time. Both men are bold, brash characters and their books brim with entertaining revelations about the feuds, fights and friendships that underlie great research projects.
Simultaneous publication makes it irresistible to compare the two stories, though they do not cover the same ground. A Life Decoded is the first book by Venter, 61, who led the privately funded effort to decode the human genome during the 1990s. He has written a wonderfully original work that captures the whole of his life, from a wild 1950s boyhood in California, through harrowing military service in Vietnam to his current programme to produce the world's first "synthetic organism" from laboratory chemicals.
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Watson, 79, is the author of The Double Helix, which describes how he and Francis Crick won the race to discover the structure of DNA in 1953. This became an instant classic when it appeared in 1968 because it was the first warts-and-all account of a famous discovery written by an insider. Watson's new book, Avoid Boring People, takes his life story back to his Chicago childhood and forward to the mid-1970s. This adds interesting insights and anecdotes about Watson's battles first to build up Harvard's molecular biology department (which he largely failed to do) and later Cold Spring Harbor Laboratory on Long Island (a great success). Apart from a provocative 10-page epilogue lamenting the poor state of science at Harvard today, Avoid Boring People ignores the past 30 years.
Therefore we have only Venter's account of the crucial period from 1988 to 1992 when Watson led the nascent Human Genome Project within the US government's biomedical powerhouse, the National Institutes of Health (NIH) – and frequently crossed swords with Venter. The late 1980s and early 1990s were a critical time in Venter's scientific development. He was then a senior researcher at the NIH, desperate to move into what he knew was going to be the biggest project in the history of biology: reading the three billion chemical "letters" of the human genome or "book of man", as commentators called it.
Venter, a remarkable innovator, had come up with a technical short cut that focused on finding the most interesting parts of the human genome: the 3 per cent of DNA directly involved in making proteins, the molecules that do most of the biochemical work in the body. According to his angry account in A Life Decoded, Venter's approach – based on gene fragments known as "expressed sequence tags" or ESTs – was turned down for funding by Watson's human genome review group on four occasions, although Watson had each time indicated his support in advance.
Indeed Venter portrays Watson as insincere and a poor administrator. "For the past two years [1989-91] the bureaucracy he had helped to create had become a pointless, annoying and frustrating distraction from science," he writes. The priority for Watson and his colleagues was not science but "money and control. I knew I had made a breakthrough that could change genomic science, and I was wasting my time, energy and emotion on battling with a group that seemed to have no serious interest in letting an outsider analyse the human genome."
Worse was to come at a US Senate hearing. Venter writes that Watson ambushed him verbally as he was telling the senators about ESTs and controversial plans by the NIH to patent them. "Virtually any monkey" could use the EST method to discover genes, Watson blurted out. Then, by talking consistently about the "Venter patents", Watson turned him into "the poster boy for commercialisation of research, a scapegoat and a villain, all rolled into one".
By 1992 both Venter and Watson had left the NIH. Watson resigned soon after a blazing row with Bernadine Healy, the NIH director, in which (according to Venter) "he began ranting about gene patents then started to shout at Bernadine. When Watson's tantrum ended, so did the one chance of detente at the NIH and of us all taking on the challenge of the genome as partners, not competitors."
Watson resumed research into cancer genetics at Cold Spring Harbor Laboratory, while Venter – disenchanted with government science – fell into the embrace of the private sector, first with Human Genome Sciences and then Celera Genomics. As it happened, Venter's falling-out with NIH almost certainly speeded up the sequencing of the human genome, because he could move faster with the resources provided by the biotech industry – and his commercially funded competition galvanised the public project to work more efficiently.
(Who really "won the race" to sequence the human genome remains controversial seven years after the transatlantic press conference hosted by Tony Blair at 10 Downing Street and Bill Clinton at the White House to announce the project's completion. The private and public programmes reluctantly agreed to share the credit, although each side felt it deserved most of the plaudits.)
Although Avoid Boring People does not tell Watson's side of the human genome project, it suggests that his management methods were unorthodox. He ends each chapter with a series of "remembered lessons". One is: "Don't be shy about showing displeasure. When someone working for you says something stupid or in other ways makes your blood boil, express your anger immediately. Don't go about silently seething, letting only your spouse know you are upset."
Watson frequently feels slighted and undervalued particularly when it comes to money. In a fascinating chapter about the publication of The Double Helix, he describes how AndreDeutsch, the London publisher, offered an advance of just £250. He asked a publishing contact "to find a British publisher who understood that scientists are not indifferent to money". That led straight to George Weidenfeld, another emigrefrom central Europe, who immediately offered $10,000.
Yet there is no doubt that Watson could be an effective leader, as he demonstrated over two decades transforming Cold Spring Harbor from an impoverished and ramshackle lab into an international powerhouse of molecular biology. While his status as a scientific celebrity helped woo the Long Island elite into making generous donations to the lab, he ensured that the millions were invested well in top-class facilities and staff.
At Harvard, Watson had been less successful. His unconventional and often abrasive approach failed to win over the complacent administration of what he portrays as an academic dinosaur, relying on reputation rather than effective action to attract top scientists. The position has become worse during the 30 years since Watson left the university, according to his epilogue, so that in the life sciences, its neighbour and rival – the Massachusetts Institute of Technology – now "completely outclasses" Harvard.
Watson says Harvard's only hope is to offer salaries "much higher than those of serious competitors" to attract star scientists. "No one goes into scientific research to get rich but one doesn't want to evade the comforts of life," he writes.
Enjoyment of the comforts of life is one thing that the two authors have in common. Both were born into families that counted themselves as middle class but were financially hard-pressed. Both were motivated initially more by the joy of scientific discovery than financial reward but, as they saw opportunities to accumulate wealth, they did not hesitate to seize them. Watson spends serious money on contemporary art, while Venter has indulged himself in an ever more extravagant series of yachts.
The men are less than a generation apart in age. Yet Watson, born in 1928, writes – and acts – in a way that seems quaintly old-fashioned compared with Venter, born in 1946. The difference shows up particularly in their attitude to love, sex and marriage. Watson's pursuit of what he consistently calls "pretty girls" remains largely unsuccessful until the age of 40, when he meets and marries Liz Lewis, a 19-year-old student.
Venter, on the other hand, describes sex with a series of girlfriends from the age of 16 onwards, in a manner that would be unthinkable for Watson. (At 16, Watson's passion was spotting rare birds on the shores of Lake Michigan with his father, a keen amateur ornithologist.) Last year Venter became engaged to Heather Kowalski, his public relations executive, who will be his third wife.
While both men are self-evident egotists, Venter comes across as a more forceful character. There is something almost otherworldly about Watson, as if he does not know what effect he is having on people. It is clear that, in order to "avoid boring people", he must have inadvertently caused considerable offence. And I cannot imagine that his self-confessed habit of reading a newspaper during seminars endeared him to colleagues.
Venter, on the other hand, knows exactly what he is doing, whether he is taking a physical risk for sheer exhilaration, such as deliberately sailing a yacht through a storm, or a scientific risk by spending many millions of dollars on unproven DNA sequencing machines. As a "rebellious and disobedient" schoolboy he jumped on and off the freight cars on trains passing his home south of San Francisco, and he has not hesitated to put himself in physical danger ever since.
Watson and Venter are the first two people to have had their individual genomes sequenced. Watson has revealed his personal DNA on the Cold Spring Harbor website, in the hope that this will encourage the development of "personalized medicine" – identifying and preventing diseases to which we are genetically prone before they appear. The only exception, withheld for reasons of family privacy, is the ApoE gene, variants of which are associated with Alzheimer's and heart disease.
Venter has gone further, interspersing A Life Decoded with relevant revelations about his own genome. For example, he declares that, of the two copies of ApoE inherited from his parents, one is the harmless ApoE3 but the other is ApoE4 – which can predispose carriers to Alzheimer's and heart disease. "By reading my own book of life, I have been given a chance to address these potential conditions, because they involve a biochemical imbalance that can be treated," he writes. "Diet and exercise is one way. I am also taking a statin, a fat-lowering drug, to counteract [the gene's] effects."
Watson won his Nobel prize with Francis Crick 55 years ago. An award to Venter for his pioneering work on DNA sequencing is overdue – the delay may reflect the outdated bad-boy image he retains among some sections of the scientific establishment. Eventually the Nobel committee will have to recognise that Venter, for all his self-promotion, is no longer an isolated "maverick".
Clive Cookson is the FT's science editor.
Copyright The Financial Times Limited 2007
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