Book of the Month: The Common Thread: A Story of Science, Ethics and the Human Genome
Authors: Michael Steel
Journal: Journal of the Royal Society of Medicine (2002)

One senses that writing an autobiography did not come naturally or easily to John Sulston. He is a minimalist when it comes to divulging personal secrets but he has a story to tell and vital issues to raise about the way in which scientific research should be allowed to operate. His experiences as director of the Sanger Centre during the most productive years of the Human Genome Project have honed his views, while his personality—in many ways that of the archetypal researcher—is highly relevant to the argument.

The Common Thread1 is a polemic but it is also an engaging read. Sulston was an enquiring child, of the type that drives many parents to distraction with the breadth of their interests but the lack of obvious career intentions. Fortunately his meandering course was indulged and, though he ‘never meant to do a PhD’, once faced with a scientific problem and a few feet of lab bench, he was in his element. Later, when he joined Sydney Brenner's group at the Cambridge Laboratory of Molecular Biology, he made no long-term plans for himself but happily locked himself away, for days and nights on end, in a darkened microscope cupboard to record the early stages of cell division in C elegans—a hermaphrodite worm much favoured by developmental biologists. As the possibility of adding a molecular dimension to these studies presented itself, he grasped it with enthusiasm and, from that decision, fame (if not fortune) followed. Yet that was never a consideration. In Francis Crick's words, which he quotes with approval, ‘the major motivation was to understand’. Later still he describes himself as a reluctant manager whose staff made remarks about ‘piss-ups and breweries’. The idea of committing himself to a major logistic exercise, with targets and performance measures, was anathema but this was the inevitable consequence of advances in gene mapping. Complete genome sequencing was an obvious and necessary step and Sulston felt he must be part of that because he had the expertise to make a contribution and because he wanted to know the answers. When he agreed to take a lead in sequencing C elegans, he ‘heard the prison door shut’ but found it one of the most exciting moments in his life.

One subtext that runs through The Common Thread is that researchers have a propensity to form warm and lasting friendships among their peers, even with scientific competitors. It happens in other walks of life, of course, but readers who have no first-hand experience of research may be surprised at the evidence that ‘boffins’ enjoy each others' company and know how to have a good time while indulging their shared obsessions. The ‘drivers’ of the Human Genome Project were, in the main, united by personal friendship as well as by common purpose. This underlies one of Sulston's major contentions—namely, that productive research, while benefiting from efficient organization, depends for its success on the overpowering will to understand. Scientists who believe they are making important discoveries will happily work long hours with astonishing intensity and, provided they have access to facilities and materials that maximize their rate of progress, are largely indifferent to the sticks and carrots that are considered to influence productivity in the world of commerce or industry.

Research is undoubtedly a competitive activity and much ‘work in progress’ is conducted in secrecy until it reaches a stage where priority can be claimed. That, of course, conflicts with the natural gregariousness of most scientists and their urge to talk, to anyone who will listen, about their latest experiment. In the course of the human genome project, competition quite rapidly gave way to collaboration, on agreed terms, among the groups who had the necessary expertise. It was explicitly recognized that together they would reach the common goal faster than by working in isolation. It was also agreed from the outset that, as information on the human gene sequence emerged, fragment by fragment, it would be released into the public domain. By Sulston's account, these important decisions were reached with a minimum of fuss and, crucially, were taken and implemented by the working scientists themselves rather than being imposed by governments or anyone else.

The dominant motif of The Common Thread is the contrast between the attitudes and behaviour of those working to produce a publicly accessible draft of the human genome sequence and the rival, commercially funded, enterprise. From Sulston's perspective, it became a classic contest between the good guys and the bad guys, ending as a ‘damned close-run thing’. Ostensibly, there was latterly a degree of cooperation between Celera Genomics (the commercial team) and the international human genome sequencing cooperative, Sulston being one of the latter's principals. However, he believes their agreement was honoured by Celera in the breach rather than the observance. Given the fundamental difference in philosophy (and funding mechanism) between the two approaches—one might almost say the two worlds—collaboration was bound to be hedged about with restrictions. However, it became a political imperative since both the British Prime Minister and the American President were eager to see a scientific ‘breakthrough’, equivalent to the moon landing in public perception, take place during their terms of office. Their advisers argued that pooling of resources would bring forward the great day when the human genome sequence could be declared complete. Sulston was clearly embarrassed by the involvement of government publicity machines but lived in constant fear that his funding might be withdrawn or cut back, as siren voices persuaded the decision-makers that the combination of business efficiency and commercial funding would get the job done faster and at no cost to the public purse. The ‘public’ cooperative took the view that, since commercial funding was ultimately dependent on recouping research costs by exploitation of the findings, and since exploitation depended on patents or other forms of protection of proprietary interests, Celera could never make their data freely available to all who wanted them. The partnership was therefore bound to be unequal, with Celera (and their backers) benefiting from information placed on an open database but releasing very little new information themselves. As Sulston tells it, that is essentially what happened. The undertakings given by Celera were, in his view, amenable to clever legalistic reinterpretations or, at least, to interminable delays. He also believes that the ‘shotgun cloning and sequencing’ techniques adopted by Celera were fundamentally flawed and, without the mass of data provided by Sulston and his international colleagues, would have been virtually useless.

The ‘good guys’ recognized that the most effective way to frustrate the predatory claims of Celera was to pump information into the public database so fast that many applications for gene patents would be disallowed on the grounds of prior disclosure. That, of course, depended on continued adequate funding of the public research effort. An unlikely hero of the story is the Wellcome Trust, perhaps the only independent body with the financial muscle to support an enterprise on this scale. They did so, nailing their colours to the mast of freedom of access to scientific information, and were probably influential in persuading the US National Institutes of Health to do likewise. Had the project been less far advanced when Celera entered the lists, or had the international cooperative failed to maintain their phenomenal rate of data generation, it is possible that political and commercial pressures would have closed down the publicly funded programme.

There is unquestionably much bitterness, as well as satisfaction, in Sulston's recall of the events leading to publication of the first draft of the human genome. He has derived, perhaps from his clergyman father, a keen sense of right and wrong and is passionately concerned to alert politicians and public to the dangers of a Faustian pact between science and big business. He sees ‘private ownership’ of scientific information as the enemy of progress and, for those who may be seduced by the notion that pharmaceutical companies or other commercial concerns will pick up the bill, he argues forcibly that there is no such thing as a free lunch. His own life story and his experience of the Human Genome Project provide an appropriate stage on which to rehearse these wider issues. His co-author, Georgina Ferry, unobtrusively adds a professional writer's flair to a tale that retains its personal flavour and grips the reader without being sensationalized. Whether the issues and their implications are sufficiently clear to a non-scientist (in particular to politicians who will make the relevant decisions) only time will tell. They certainly matter, and the outcome of the battle that Sulston describes here is going to affect all our lives most profoundly. He has done a considerable service in presenting his view of the world of ‘big science’ and big business—a good and thought-provoking read.