Book Review/Science in the Media A Brief (If Insular) History of the Human Genome Project

Michael J. Morgan*

September 2010 was the 70th anniver- National Center for Human Genome sary of the Battle of Britain. A number of Research at the National Institutes of commentators, historians, and other pun- Health, respectively. When John and dits have debated the significance of the Bob were being solicited by Frederick battle: was it a truly significant turning Bourke to join his private effort to point (or tipping point in present parlance) sequence the human genome, it was not in World War II? Similarly, historians of surprising that Watson alerted the MRC science and others will no doubt be to the danger of losing their star sequencer mulling over the true significance of the and an approach was made to the Well- human genome sequencing project 70 come Trust in the UK to help fund a years hence and thereafter. In Drawing the human genome sequencing programme. Map of Life, veteran science journalist and The Trust responded in 1992 by not author Victor McElheny offers a view only agreeing to join the MRC in ‘‘inside the human genome project’’ that supporting an initiative that would play a covers the origin of the project in the role in mapping, sequencing, and decod- United States, its development and imple- ing the human genome and the genomes mentation, and its impact since its ‘‘com- of other organisms, but also, for the first pletion’’ in 2000. It is a hugely readable time in its history, to establish its own account that gives the reader a sense of the research station, now called the Wellcome excitement and drama that gripped the Trust Sanger Institute at Hinxton, Cam- main protagonists along with a description bridgeshire. This decision was not due to a of the technological advances that made change of strategy by the Wellcome Trust, the project feasible and affordable. It relies but was a pragmatic response to the need heavily on interviews with a number of to get a large sequencing facility up and McElheny VK (2010) Drawing the Map of scientists, mainly from the US, newspaper running as soon as possible. John Sulston Life. New York: Basic Books. 384 p. ISBN articles, and radio and television reports, 978-0465043330 (hardcover). US$28.00. and I visited a number of possible sites, doi:10.1371/journal.pbio.1000601.g001 but pays scant attention to the interna- including a poultry research centre where tional character of the project. It is John thought the chicken sheds would important to reaffirm that one country provide adequate housing for sequencing! state-of-the-art sequencing facility in a did not do it alone; it was an international A number of universities were considered, period of a few months. The first new effort and the many partners are justifiably but it became clear that none were likely occupants moved in during March 1993, proud of their contribution. to be able to provide suitable accommo- and by the end of the year there were over There seems little controversy that it dation in a timely fashion. John identified 80 staff on site and space was tight. In was Robert Sinsheimer, then chancellor of a site at Hinxton, Cambridgeshire, for- October 1993, the facility was formally the University of California at Santa Cruz, merly a Tube Investments plc engineering opened and named by Fred Sanger as the who was the first to call a meeting (in May research station, purchased by Capital and Sanger Centre. 1985) to discuss the feasibility of sequenc- Counties plc, who had ambitious plans for In a chapter called ‘‘Building the ing the human genome. As related by a business park—a venture that never got Toolbox’’, McElheny describes the recom- McElheny, among the dozen or so scien- off the ground. (At the time, there were ill- binant DNA technologies developed by tists at the meeting was John Sulston from founded rumours that Tube Investments Hamilton O. Smith, Fred Sanger, Walter the Laboratory of Molecular Biology had been involved in the UK’s nuclear Gilbert, Kary Mullis, and Lee Hood, (LMB) in Cambridge, United Kingdom, weapons research.) The Trust acquired amongst others, that enabled the manip- who published his own account of the the site in the autumn of 1992 and the ulation of DNA, its amplification and project in 2002, a year before the metallurgy laboratories were re-fitted as a sequencing, and the development of auto- completion of the sequence was declared [1]. John, with Bob Waterston of Wash- ington University, St. Louis, were arguably Citation: Morgan MJ (2011) A Brief (If Insular) History of the Human Genome Project. PLoS Biol 9(3): e1000601. the first to invest heavily in the sequencing doi:10.1371/journal.pbio.1000601 of an animal genome, Caenorhabditis elegans, Published March 8, 2011 funded jointly by the Medical Research Copyright: ß 2011 Michael J. Morgan. This is an open-access article distributed under the terms of the Council (MRC) in the UK and the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. National Institutes of Health in the US. This was a unique partnership champi- Funding: The author received no specific funding for this work. oned by the Secretary of the MRC, Sir Competing Interests: The author has declared that no competing interests exist. Dai Rees, and Jim Watson, Director of the * E-mail: [email protected]

PLoS Biology | www.plosbiology.org 1 March 2011 | Volume 9 | Issue 3 | e1000601 mated sequencers. He then goes on to About the Author describe some of the early efforts to garner public support (and funding) of the project, Dr. Michael Morgan is a consultant for scientific affairs and is involved in the particularly in the US, and the role of Jim Human Genome Archive Project at Cold Spring Harbor. Recently, he was Chief Watson in convincing Congress to fire the Scientific Officer at Genome Canada. As chief executive of The Wellcome Trust starting pistol. Genome Campus, Hinxton, Cambridge, he played a major role in the international John, Bob, and many of their colleagues coordination of the Human Genome Project. As director of Ventures and were determined that the effort should be Partnerships at the Wellcome Trust, he was instrumental in the SNPs Consortium international in scope and involve all (TSC), a partnership with 12 industrial partners; DIAMOND, a new third generation laboratories able to engage in large-scale synchrotron in Oxfordshire, a joint project with the UK Office of Science and sequencing; they were also concerned at Technology; and the Structural Genomics Consortium, a partnership with the apparent lack of cooperation in the Canadian and Swedish public entities and pharmaceutical companies that is human genetics community (in contrast to tasked with determining the structures of human proteins of importance to their experience with the worm commu- human health. All of these partnerships are dedicated to putting their data into the public domain as early as possible and with no restrictions on use. He is nity). To promote international coordina- presently working for INSTRUCT (a European Infrastructure Project) coordinated tion and cooperation, the Wellcome Trust by Oxford University. decided to host a meeting to which all relevant parties would be invited. It was decided to hold the meeting on ‘‘neutral principles have been extended to many Spiegel [3], casts doubts on the (medical) ground’’ in Bermuda, and in February other large-scale collaborative projects in worth of the project. McElheny seems to 1996, the first meeting of representatives biology, such as the SNPs Consortium be on the other side, admitting that many from sequencing centres and funding (TSC) and the Structural Genomics Con- benefits lie in the future, but that some, for agencies around the world met and sortium, and have driven scientific prog- established a coordinated effort, in the example diagnostic tools in treatment of ress and industrial application alike. public domain, to sequence the human some cancers and in the emerging field of genome. Some 50 or so scientists and McElheny covers the ‘‘race’’ between pharmacogenomics, are already part of administrators from the US, UK, France, the public consortium (managed by Fran- good medical practise in America. It is Germany, and Japan (joined a year or so cis Collins of the National Human Ge- comprehensive, but, inevitably, superficial later by China) discussed the scientific nome Research Institute, Ari Patrinos of in its treatment of many of the social and strategy for a distributed sequencing effort the Department of Energy, and myself of political aspects of the project. For exam- and, in particular, agreed on a policy for the Wellcome Trust) and the private ple, the early role of the Human Genome the release of data generated by the company, Celera, headed by Craig Ven- Organisation (HUGO), the grassroots project, the so-called Bermuda Principles ter. It is well documented how Craig broke organisation established by the early [2]. The principles evinced the benefits of ranks and decided to commercialise the pioneers in genomics, does not even get the immediate release of raw data on the sequence and seek patent protection on a a mention. The inevitable stresses and Internet without any privileged ‘‘first sight number of genes. As a result, the ‘‘race’’ to strains that beset the public programme or use’’ and to pledge not to seek patent sequence the human genome began. It is and the behind the scenes negotiations protection. These principles did not re- perhaps salutary to report that eventually that led to the ‘‘Clinton-Blair’’ joint ceive universal acclaim, and caused con- Celera deposited its sequence in GenBank statement in 2000, in which they applaud- sternation among a few groups who were and the human sequence and that of many ed the decision to rapidly release human concerned that their institutions, funding other organisms are freely available to DNA data into the public domain, are yet bodies, or governments might be unwilling anyone with access to the Internet. to be related. This is not, therefore, a to agree to the data release guidelines. McElheny’s account admirably covers definitive history of the human genome However, it was made clear that continued the period from the early days of recom- project, or even a definitive history of the membership in the human genome se- binant DNA (1960s) through to 2010 and American contribution to the project. It is, quence ‘‘club’’ required agreement to the the days of the exploitation of the however, a very entertaining and well- principles. In the end, these misgivings knowledge garnered from the project. written account of the material it covers proved unfounded. These data release There is significant debate in the media, and provides, unusually for a ‘‘popular’’ principles helped assuage the impression no doubt reflecting that 2010 is the 10th treatise, a comprehensive series of notes to that a small cabal of privileged and anniversary of the release of the ‘‘working sources (some 24% of the book!) that will massively funded researchers would be draft’’ of the genome about the worth of lead the keen student into deeper studies. given an unprecedented advantage over the project. One camp, notably espoused the rest of the scientific community. The by Craig Venter in a recent article in Der

References 1. Sulston J, Ferry G (2002) The common thread: a ac.uk/About-us/Policy/Policy-and-position-state nothing from the genome.’ Der Speigel, Avail- story of science, politics, ethics, and the human ments/WTD002751.htm. Accessed 2 February able: http://www.spiegel.de/international/ genome. London: Bantam Press. 2011. world/0,1518,709174,00.html. Accessed 2 Feb- 2. The Wellcome Trust (1997) Statement on genome 3. von Bredow R, Grolle J (29 July 2010) SPIEGEL ruary 2011. data release. Available: http://www.wellcome. interview with Craig Venter. ‘We have learned

PLoS Biology | www.plosbiology.org 2 March 2011 | Volume 9 | Issue 3 | e1000601