Rivals in the Race to Decode Human DNA Agree to Cooperate

URL: http://www.nytimes.com/library/national/science/062200sci-human-genome.html

Date accessed: 15 July 2000

June 22, 2000

By NICHOLAS WADE

               After months of fitful negotiation that

               seemed to flame out in a final angry

          exchange in February, the two sides racing

          to decode the human DNA have contrived

          a last-minute truce.

          The first element of the resurrected pact is

          likely to be a joint announcement next week

          of the effective completion of the genome.

          Although it is too late for a pooling of DNA sequencing efforts, the truce

          will include agreement for the competitors to publish their genome

          findings in the same issue of a journal.

          It may also provide for a joint annotation of the genome, the critical

          process of identifying the location and role of the genes on the genome.

          Should the two sides cooperate in such an interpretation of their data, a

          step that has at least been under discussion, the truce could develop into

          a broader pact.

          The truce also implies a cessation of public criticisms between the two

          parties, the Celera Corporation of Rockville, Md., and an international

          consortium of academic centers supported largely by the National

          Institutes of Health and the Wellcome Trust, a London philanthropy.

          Although the institutes and the trust decline to discuss the deal, the trust

          has said it will hold a news conference on the human genome next

          Monday, and sources close to Celera say a joint news conference will be

          held at the White House at which the two sides will announce the

          progress of their respective efforts on sequencing the genome.

          Sequencing means determining the order of the three billion chemical

          units in the DNA of the human chromosomes. The genome sequence is

          expected in time to revolutionize knowledge of the human body and the

          practice of medicine.

          The rival teams appear to have been driven together by a calculus that

          cooperation outweighed the attractions of laying claim to one of science's

          greatest prizes independently, especially now that each has achieved

          successes that vindicate its own approach.

          Celera has established the validity of its high risk genome sequencing

          strategy, which the consortium's two senior scientists had predicted

          would be "woefully inadequate." The consortium has generated a draft

          genome sequence that can be searched for human genes, a principal

          objective of the human genome project.

          Celera was set to declare victory in achieving an effectively complete

          genome assembly many months before the consortium could do so. But

          Celera's business plan is to sell genome data and genomic analysis tools

          to the community of university scientists from which the consortium is

          drawn. Claiming victory might have alienated potential customers.

          The consortium could have attacked Celera's genome as not being the

          real thing -- it still has many small gaps and makes use of the consortium's

          data -- while going on to declare its own independent victory, though

          perhaps as late as 2003. The alternative, which it seems now to have

          embraced, was to accept Celera's proposal of declaring joint victory on

          Celera's timetable.

          "Celera doesn't want the N.I.H. to lose," said Dr. Norton Zinder, a

          microbiologist at Rockefeller University who is a member of Celera's

          scientific board.

          Dr. Zinder and Dr. Richard Roberts, the research director of New

          England BioLabs and chairman of Celera's scientific board, have for

          many months pushed for the two sides to collaborate and, when that idea

          foundered, at least to cooperate by coordinating publication.

          Both said they did not wish the institutes, the federal patron of most

          biomedical research, to seem to have suffered defeat at Celera's hands,

          and that the human genome was too precious a scientific achievement to

          be marred by priority disputes.

          "The discovery and presentation of the human genome, one of the most

          important attributes of man, should be a time of great joy and happiness,"

          Dr. Zinder. "For there to be all this vitriol and hatred just doesn't seem

          right." Dr. Roberts, a Nobel laureate, said that the announcement of

          sequencing the human genome "should be a great celebration of

          humankind, not a race with a clear winner or loser."

          Dr. Zinder said talks began last October when Dr. Eric Lander of the

          Whitehead Institute, one of the five largest centers in the consortium,

          approached Dr. Roberts.

          A meeting took place on Dec. 29 that included Dr. J. Craig Venter,

          president of Celera, and Dr. Francis Collins, head of the N.I.H.'s

          National Human Genome Research Institute.

          The meeting went badly and quickly bogged down in issues like Celera's

          rights to distribute a combined set of human genome data.

          "The problem was there was no referee at the meeting who could have

          taken these guys by the scruff of the neck," Dr. Roberts said.

          The talks finally broke off in February in a fault-finding exchange of

          letters. It took a long time for bridges to be rebuilt.

          Dr. Zinder approached the institutes' new acting director, Dr. Ruth

          Kirschstein, and tried to arrange a second meeting that would exclude

          Dr. Collins, whom he felt had been in part responsible for the December

          failure. In any case, Dr. Venter refused to meet again with Dr. Collins.

          A second negotiation was arranged for March and at the last minute both

          Dr. Venter and Dr. Collins attended. "Ruth insisted Francis had to come

          and wouldn't say a word; Francis swore he would be like a monk at that

          meeting, but he spoke up," and that meeting broke down too, Dr. Zinder

          said, adding that Dr. Venter "put the same deal on the table as is there

          now."

          Dr. Kirschstein said through a spokeswoman, Anne Thomas, that she

          had no recollection of promising Dr. Collins's silence and that the deal

          now being offered by Celera was not what was on the table then.

          Dr. Collins declined through his press secretary, Cathy Yarbrough, to

          comment on the negotiations with Celera. But he has always affirmed the

          policy of completely free and open access to the human genome.

          Because Celera has demanded protection against its data being resold by

          its commercial rivals, data access policy has been a regular stumbling

          block to agreement.

          Following a cooling-off period after the failed March meeting, talks were

          held between Dr. Venter, Dr. Collins and Dr. Ari Patrinos, director of

          the Energy Department's part of the human genome project.

          From the post-March talks, an agreement eventually emerged.

          "The facts haven't changed much but the relationships have become more

          cordial," said Dr. Donald Kennedy, who as editor of Science has been

          involved in discussions about publication of the two sides' reports,

          probably some time in the fall.

          An important element that has been under discussion is to hold a joint

          annotation jamboree, Dr. Zinder said.

          Annotation is the important first step in figuring out the genome's meaning.

          It consists first of finding the genes -- no easy task since their sequences

          occupy a mere 3 percent of the DNA in the genome -- and then of

          assigning functions to the genes.

          Celera and the consortium would probably hold a meeting of genetic

          experts to discuss the two sides' genomic data. Such an event could go

          far toward cementing the partnership and producing a product for which

          both could take credit.

          Other aspects of the deal seem more implicit.

          "It's understood that Craig won't say 'I won,"' Dr. Zinder said.

          The deal has been tightly held and consortium members do not seem

          aware of its details.

          A spokesman for the Wellcome Trust said "We haven't seen any terms of

          a truce" and could not comment on them.

          The scientific community's verdict on who won is still pending because

          Dr. Venter has yet to release his data. Though Celera's version of the

          human genome is further advanced, it has relied on the consortium's data

          to an extent that may turn out to have been essential.

          The best way to sequence genomes may, in fact, be by a combination of

          Celera's whole genome shotgun strategy, which speedily yields the main

          structure, and the consortium's clone-by-clone strategy, which helps fill in

          the many remaining gaps.

          If so, the way would indeed be open for the two sides to agree on an

          honorable draw.