Drawing the Map of Life: Inside the Human Genome Project

  • Victor K. McElheny
Basic Books: 2010. 384 pp. $28, £16.99 9780465043330 | ISBN: 978-0-4650-4333-0

In 1985, Robert Sinsheimer, then chancellor of the University of California, Santa Cruz, convened a workshop to discuss sequencing the human genome. It was an audacious proposal: the longest genome that had been sequenced at the time was that of the Epstein-Barr virus, at 172,282 base pairs compared with 3 billion in human DNA. Sinsheimer's initiative failed.

Yet the idea gained momentum when, in 1988, James Watson was appointed associate director of the Office of Genome Research, part of the US National Institutes of Health (NIH). Watson declared 1990 the official start of the publicly funded NIH Human Genome Project (HGP). In 1998, Craig Venter and his company Celera Genomics, then in Rockville, Maryland, joined the race. Ten years ago in June, both projects announced a finish-line draw from President Bill Clinton's White House. February 2011 will mark a decade since the draft sequences were published.

In Drawing the Map of Life, science journalist and author Victor McElheny relates the story of the HGP, from its methods to the people involved. He describes the project's tortuous path to success, and asks whether its medical impacts live up to expectations. Weaving together so many threads is a formidable task. McElheny offers an entertaining narrative, but his book stops short of being a comprehensive history.

Genome-project pioneers: (left to right) Eric Lander, Robert Waterston, James Watson and Francis Collins. Credit: S. JAFFE/AFP/GETTY

He opens in the 1980s, when many of the technologies central to gene sequencing were developed: the polymerase chain reaction that multiplies DNA fragments for analysis; the use of restriction enzymes to sever DNA strands at particular sites; and the use of restriction fragment length polymorphisms as markers in early searches for the genes involved in inherited disorders. The mapping of the genes underlying Huntington's disease, Duchenne muscular dystrophy and cystic fibrosis in the late 1980s had a huge impact on clinical genetics: suddenly the arrangement of the gene itself, rather than secondary markers, could be used to reveal mutations.

McElheny traces the various stages of the HGP and the power struggles it engendered. The project had two phases under different directors. Watson led the NIH effort from 1988 until his resignation in 1992, after questions were raised about his holding of stock in biotechnology companies. McElheny describes the resignation, but not the finding by the US Department of Health and Human Services that Watson had done nothing unethical. Francis Collins then took over directorship of the HGP, and saw it through to the completion of the sequence in 2003.

We are only at the beginning of interpreting the sequence.

The book also describes the fierce competition between various commercial and academic laboratories to isolate and sequence medically relevant genes. The most famous rival to the NIH project is Venter, a pioneer of large-scale sequencing who left the NIH to set up The Institute for Genome Research to sequence small genomes. In 1998 Venter announced the formation of a new company, Celera Genomics, that would target the human genome. The academics rallied to meet Celera's challenge.

In 2000, HGP and Celera jointly announced the draft human genome sequences to great fanfare. But acrimony and infighting continued over data release until the sequences were published in 2001. Celera published in Science but sought special conditions of access to its data for commercial scientists. The HGP opposed any such restrictions and instead published its sequence in Nature, depositing its data in the open-access GenBank database.

The completion of the HGP in 2003 was a great triumph. With draft sequences finished two years earlier than planned, it is transforming research. The pace of sequencing has since rocketed thanks to techniques that the project hastened. Many complex organisms have now been sequenced, and their genomes will be mined for years to come.

Yet the era of genomic medicine has not yet come to pass. McElheny is right to ask when we will see public-health returns on the huge investment in the HGP. He argues that social change will be needed before genomic information can be integrated into current medical practice and interpreted by the public. He asks, for example, how physicians will use genetic data for diagnosis and treatment, and whether individuals will welcome or fear knowledge of what their genomes hold for the future.

Such social change will follow, I believe, when useful applications of genomic information become available. They might tell us how to alter our lifestyles to improve our health, or distinguish which drugs will be of benefit or have serious side effects, or may guide the development of new drugs. But this will take time. We are only at the beginning of interpreting the sequence and understanding what variants mean for the individual.

Drawing the Map of Life is one of many books that have been written about the HGP. The volume does not add much to earlier descriptions of the project's genesis, such as Genome by Jerry Bishop and Michael Waldholz (Simon and Schuster, 1990) and The Gene Wars by Robert Cook-Deegan (W. W. Norton, 1994). In Cracking the Genome (Free Press, 2001), Kevin Davies brought us up to the completion of the draft sequences. More recently, protagonists John Sulston and Venter have told their contrasting personal stories, while James Shreeve has written a detailed study of Venter's contributions.

All of these books are valuable; what is now needed is a scholarly history of the HGP. Drawing the Map of Life is not that book, but it offers an enjoyable account of the project from origin to conclusion and beyond.