Inside the race of the century

March 29, 2002

Public science was key in decoding the genome, says Ian Wilmut.

The events described in The Common Thread will be of profound importance to everyone. Knowledge of the sequence of the human genome will permeate the whole of biology and medicine in this century. There will be unpredictable effects on our understanding of human health and sickness and enormous social implications that are only just being recognised. The extent to which benefits will be available to all depends on the regulation of the patenting of new knowledge.

As a leading participant in the Human Genome Project and in the dissemination of its information, John Sulston is well placed to relate recent events and to consider their implications. In this book with Georgina Ferry, he gives a fascinating history of the project and describes many elements that played a part, including the new techniques developed, the people involved and the tussle between publicly and privately funded groups.

Genetic information is transmitted from one generation to another in chains of molecules arranged in long thin threads (hence the book's title). It is surprising to recall that little more than 20 years have passed since a method was developed to sequence DNA. For this innovation, Fred Sanger was awarded his second Nobel prize in 1980. It is appropriate that much of the genome project was conducted in what is now known as the Sanger Centre.

Earlier in his research, Sulston investigated how a nematode worm developed. C. elegans was selected for study by Sidney Brenner, director of the Medical Research Council Laboratory of Molecular Biology in Cambridge, because it was small, translucent and easy to keep. Ultimately, it was possible to map the fate of every single cell in the worm. The task required hours of continuous observation on a microscope - exactly the same commitment and dedication was required of Sulston in his leadership of the Human Genome Project.

Sulston describes vividly how he first launched into large-scale sequencing at a meeting to discuss the nematode held at Cold Spring Harbor on Long Island, New York, in 1989 - and his excited realisation that you can only go forward in science.

When sequencing the human genome was first contemplated seriously, early in the 1990s, the largest known sequence was the 240,000 bases of human cytomegalovirus. The fact that the full human genome of 3 billion bases will finally be sequenced during 2003 is testimony to the dedication of a few hundred people. They introduced technical innovations and developed strategies to identify the regions of the chromosomes from which a small fragment was obtained.

The project required huge financial support, which came initially from several governments. But in 1998, Celera was established using venture capital funds with the aim of becoming "the definitive source of genomic and associated medical information". The other groups working on the genome were committed to immediate publication of new sequences, but Celera was not. An unequal relationship developed in which Celera could exploit public information but did not contribute to it. Celera proved to be a master of publicity and was soon portrayed by the media as leader of the field - even raising the possibility that public funding of the Human Genome Project might be unnecessary. Only when the available sequence was published in 2001 was it possible to assess the real contribution made by Celera and see how completely dependent it was on the public sequence.

Throughout the project, Sulston and many others have campaigned hard to ensure public availability of the sequence information because they regarded it as too important to be controlled by one group or company. In contrast, companies have submitted patents for gene sequences as quickly as possible, even if they had relied on the public sequence to identify the genes.

Sulston makes it plain that there is still much to fight for if we are to ensure the rapid development of new medicines and their availability to rich and poor alike. The issue of patents ought to have been resolved long ago. Soon we will all face difficult and important choices about the use of knowledge about our genes. Will we wish to know if our genes make us vulnerable to particular diseases? Should potential employers have this information? We are dependent on books such as this to raise these issues.

A reluctant publicist, Sulston clearly did not relish the hue and cry of the sensational media world. It is probably no coincidence that the two journalists whom he criticises are two of the three with whom we at the Roslin Institute have had disagreements over stories about cloning. It is to the detriment of us all that so much of modern journalism has to be sensational so as to attract a large audience or readership.

I recommend this book unreservedly to those interested in the accurate inside story of the project. For the non-specialist, The Common Thread is an easy and interesting read. In a few places, non-biologists may find specialist terms difficult to follow, such as when "chromosome walking" is used without explanation. But the reader should press on because such technical details are not central to the story. The book should be compulsory reading for politicians who, by defining the scope of patents, will determine the future development and availability of large areas of new medicine.

Ian Wilmut is head of the department of gene expression and development, Roslin Institute, Midlothian.

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