It was portrayed as the scientific rivalry to end all scientific rivalries. But after two years of often acrimonious competition, the principal players in the Human Genome Project (HGP) came together on Monday this week with Craig Venter, president of Celera Genomics of Rockville, Maryland, to praise one another's achievements — and to bask in the adulation of their political leaders.
Those achievements — the compilation of a ‘working draft’ of the human genome by the HGP and Celera's ‘first assembly’ of a complete genome sequence — may in reality represent arbitrary milestones on the way to the goal of fully deciphering the human genetic code. But for those scientists who have devoted their careers to genomics since the launch of the HGP more than a decade ago, a public celebration is welcome.
In Washington, President Bill Clinton hosted an event at the White House with Venter and Francis Collins, director of the National Human Genome Research Institute in Bethesda, Maryland — joined by video link from London by Prime Minister Tony Blair. In Paris, Tokyo and Bonn, other members of the international HGP consortium made their own announcements. The Wellcome Trust, the main backer of the Sanger Centre near Cambridge, responsible for one third of the HGP sequence, hosted its own press conference in London.
Turning to James Watson, discoverer with Francis Crick of the structure of DNA and head of the HGP until 1992, Clinton described the 1953 Nature paper, which noted the structure's “novel features, which are of considerable biological interest” as “one of the great understatements of all time”. This time, understatement was in short supply. “With this profound new knowledge, humankind is on the verge of gaining immense, new power,” said Clinton.
Mike Dexter, director of the Wellcome Trust, went so far as to describe the project's significance as surpassing the invention of the wheel. “I can see technology making the wheel obsolete,” he said. “But this code will be useful and used as long as humans exist.”
For some scientists, this may seem like hyperbole — particularly as the value of both the HGP and Celera drafts, in their current form, remains unclear. The sequences are difficult to compare, because of the two groups’ different approaches. Celera's ‘whole-genome shotgun” strategy relied on shattering the entire genome into tiny pieces, sequencing these en masse, and then using sophisticated computer algorithms to put the pieces back together. The HGP cloned larger overlapping fragments of the genome into some 24,000 bacterial artificial chromosomes, and sequenced these one by one.
The HGP claims to have cloned 97% of the genome, and sequenced 85% of it to draft standard. That falls short of the 90% figure set as a target for the working draft — although this should be achieved within a few weeks. On average, the HGP has sequenced each base seven times over (7X coverage). Celera's assembly gives 4.6X coverage — some way from the 10X it originally promised in 1998, although the company says its sequence covers 99% of the genome. On the basis of the data presented publicly, it is impossible to verify whether Celera's assembly is correctly orientated and ordered throughout the genome. But Celera has also produced a second map by incorporating data from the public project — which will increase its depth of coverage and allow it to check its shotgun assembly.
Despite the preliminary nature of both sets of data, the White House has been encouraging the two projects to bury their differences and declare their drafts complete. US politicians were appalled at the media portrayal of the sequencing project as a battle between Celera and the HGP. Clinton's aides hope that a joint announcement will end the rancour and lead to greater public recognition of the achievements of both projects.
The rapprochement between Collins and Venter was brokered by senior figures including Eric Lander, director of the Whitehead Institute at the Massachusetts Institute of Technology, one of the main sequencing centres for the HGP, and Ari Patrinos, head of biological and environmental research at the Department of Energy, who hosted meetings over beer and pizza at his home in Rockville. The agreement has four parts: Monday's choreographed joint announcement; a pledge to publish the two draft sequences, simultaneously but separately, later in the year; a loosely defined plan to hold a joint meeting of the two research teams after publication; and a promise to keep open lines of communication between the HGP and Celera.
At the White House event, Collins struck a spiritual note: “It is humbling for me and awe-inspiring to realize that we have caught the first glimpse of our own instruction book, previously known only to God.” Venter was philosophical: “The complexities and wonder of how the inanimate chemicals that are our genetic code give rise to the imponderables of the human spirit should keep poets and philosophers inspired for the millenniums.”
For scientists working on the HGP, the main hope is that the task of finishing the genome sequence does not get subordinated to other activities. Parallels drawn with the Apollo lunar programme — which soon fizzled out after the space race was won — provide a warning. “What we most want to avoid is the fate of achieving this heroic goal at such great cost and to the neglect of the long-term goals,” says Maynard Olson, a geneticist at the University of Washington in Seattle.
Additional reporting from David Dickson in London
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The Bermuda Triangle: The Pragmatics, Policies, and Principles for Data Sharing in the History of the Human Genome Project
Journal of the History of Biology (2018)
Science China Life Sciences (2011)