THE COMMON THREAD

THIS IS THE STORY OF AN EXTRAORDINARY ENTERPRISE, ONE OF THE notable achievements of late twentieth-century science: the sequencing of the human genome. It is a story that has been told and retold in the pages of the popular press, often accompanied by breathless headlines and bold claims about the end of disease. And as if it were not exciting enough already, the story gained even greater appeal when a challenger entered the lists and turned a scientific quest into a “race.”

So why tell this story again? It seemed to us that only an insider’s view could do justice to the dramatic developments of the past decade and more, which have been far too complex to reduce to the convenient but misleading metaphor of a “race” for the genome. And, as the head of the largest genome sequencing center outside the United States, John was in a unique position to comment on the politics of a scientific advance equally critical to corporate wealth and human health.

The sequencing of the human genome is the latest step in a process that began during the 1980s, when two separate lines of research began to converge. One was human genetics, the study of patterns of inheritance that can reveal genetic causes of disease; the other was molecular biology, which studies the stuff of which

genes are made: DNA, the molecule that makes life possible. Using a simple alphabet of only four letters, DNA encodes the instructions to make every living thing as sequences of those letters—the genes.

In 1990 an international, publicly funded effort, the Human Genome Project, was launched to map and sequence human DNA and make the information freely available to the scientific community. Confusingly, people often talk about ‘mapping’ the genome when they mean ‘sequencing’. The difference is on one level a question of scale—you can make a useful map that helps you to find genes without knowing the full sequence of letters (3 billion in the case of the human genome). But although the sequence is in one sense the ultimate map, it is also much more than that: it is also the biological information itself. When we finish collecting the sequence we will have the hieroglyph of biology in our hands, even if we don’t at first understand it all.

Deciphering the information will take a long time, and will need every available mind on the job. And so it is essential that the sequence is available to the whole biological community. No single individual or group can credibly claim that they have the expertise to deal with it. When the commercial company that became Celera Genomics was launched in May 1998 with the stated aim of becoming “the definitive source of genomic and associated medical information,” the whole future of biology came under threat. For one company was bidding for monopoly control of access to the most fundamental information about humanity, information that is—or should be—our common heritage.

To their great credit, the public bodies that were funding the Human Genome Project quickly decided not to leave the field to Celera, but to make the sequence available to everyone even faster, though initially at a lower standard of accuracy and completeness, than they had originally intended. Thus the world celebrated a “working draft” of the sequence with much fanfare in June 2000; and, though it will be some years more before the sequencing centers finish the job, today any scientist anywhere can access the sequence

freely at no cost and use the information to make his or her own further discoveries. We wrote this book so that people might understand how close the world came to losing that freedom.

Insidiously, over the past few decades, the prevailing ethos in the world of science has shifted. What was once a collective enterprise, in which discoverers were acknowledged but their results freely shared, is now frequently constrained by the demands of commercial competition. Motivated by financial gain, hamstrung by sponsorship deals, or simply out of self-defense, many researchers trade their discoveries with the rest of the community only under the protection of patent law or commercial secrecy. On the other hand, there are still many who cling to the older ideals of science and have raised their voices in protest at the way things are going. The Human Genome Project provides a unique illustration of the choices faced by individual scientists and by society as a whole. We hope that this story conveys the sheer thrill of scientific discovery, but also that it provokes reflection on the awesome responsibility borne by those who hold the secret of humanity in their hands.

A word about the “voice” in which the book is written: We wrote it together, as far as possible in an equal partnership. But we agreed from the start that as we were telling John’s story, it should be written in the first person, in his voice. The principal source has been John’s memory, backed up by his email files that constitute a day-by-day record of the project. In addition we have interviewed many of the other protagonists, whose perspectives have been invaluable in rounding out the story and corroborating or contradicting John’s memories. The result is, to the best of our ability, an accurate and unvarnished account of what really happened.

We should like to record our thanks to the following, with all of whom it was a pleasure to talk to or correspond: Bart Barrell, David Bentley, Martin Bobrow, Sydney Brenner, Murray Cairns, Francis Collins, Alan Coulson, Mike Dexter, Diana Dunstan, Richard Durbin, Eric Green, Phil Green, Mark Guyer, Bob Horvitz, Tim

Hubbard, Jon Karn, Judith Kimble, Aaron Klug, Eric Lander, Peter Little, Michael Morgan, Bridget Ogilvie, Maynard Olson, Paul Pavlidis, Colin Reese, Dai Rees, Jane Rogers, Gerry Rubin, Mike Stratton, Adrian Sulston, Ingrid Sulston, Bob Waterston, James Watson, John White, and Rick Wilson. David Bentley, Murray Cairns, Alan Coulson, Richard Durbin, Madeleine Harvey, Tim Hubbard, Aaron Klug, Paul Pavlidis, Don Powell, Jane Rogers, Daphne Sulston, Ingrid Sulston, and Bob Waterston read versions of the manuscript in draft form, and their comments were invaluable. Any deficiencies that remain are ours alone.

We thank the funding agencies who financed the U.K.’s share of the research described here: the Medical Research Council (who also provided access to material in their archives) and the Wellcome Trust. Both helped us with pictures, as did the National Human Genome Research Institute; our thanks to Richard Summers, Anne-Marie Margetson, Jenny Whiting, Sonya Brown, Annette Faux, Kris Wetterstrand, and Maggie Bartlett.

We are sorry that, in order to keep the book within manageable limits, we had to omit many individuals whom we would have liked to include by name (for without them there would be no story to tell). We especially want to thank the members of the Sanger Centre and its partners in the International Human Genome Sequencing Consortium for tolerating John and making all this come about.

The book would not have happened were it not for three people in particular. Alan Coulson has partnered John from the early days of genomics. The collaboration with Bob Waterston sequenced the worm, founded two genomics centers, and drove the concept of free release; Bob shared in the gestation of the book and worked on its contents with us. This is his story as well. Daphne Sulston, amazed by these events, was determined to see a true account of them written down, and prompted our collaboration to do so.

John Sulston and Georgina Ferry

August 2002