It was never a marriage made in heaven.
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nytimes.com
March 9, 2000
Genome Decoding Plan Is Derailed by Conflicts
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With the race to decode the human genome nearing completion and the stocks of genome companies soaring, a last-minute merger negotiation between the public and private competitors has foundered in a clash of principles and egos. In an exchange of letters over the last week and a half, each side sought to blame the other for the breakdown and for failing to negotiate in good faith.
Although a long history of disagreement between the principals on each side probably did not help matters, a basic obstacle was an impasse between the public consortium's desire to make the information in the genome freely available to all researchers and the need of the private company, Celera, for enough proprietary safeguards to make a profit.
The decoding of the human genome is expected to mark a new era in medicine in which diseases will be analyzed and treated in terms of the genes that cause or influence them.
Identifying the sequence of the 3 billion chemical units of DNA that make up the human genome has been a 10-year project of a public consortium of university centers, financed largely by the National Institutes of Health and the Wellcome Trust of London.
But in May 1998, the newly formed Celera Corporation of Rockville, Md., leapt into the fray with the surprise announcement that it would sequence the genome from scratch with a novel approach and finish several years ahead of the public consortium's target date. Both Celera and the public consortium have said they will finish decoding the most important parts of the genome sometime this spring, a deadline that for both seems to be slipping into summer.
When Celera's approach seemed to be succeeding, despite predictions from some scientists that it could never work, observers in both camps realized that they were pursuing the same end with complementary means. Celera had a top-down method for sequencing the genome, the public consortium a bottom-up approach. If the two data sets were combined, the genome might be sequenced much sooner.
Most of the DNA sequencing on the public consortium's side has been carried out under Dr. John Sulston at the Sanger Center in Britain and Dr. Robert Waterston at the University of Washington in St. Louis. Both strongly support the idea of placing all human DNA immediately in the public domain, and have reservations about dealing with Celera.
It was another member of the public consortium, Dr. Eric Lander of the Massachusetts Institute of Technology, who approached Dr. J. Craig Venter, the president of Celera, with the idea of a collaboration.
After preliminary talks, a meeting was held between the principals on Dec. 29. On the public consortium's side were Dr. Waterston, Dr. Francis Collins, head of the National Human Genome Research Institute, and Dr. Harold Varmus, then director of the National Institutes of Health. Dr. Venter was joined by Tony White, president of Celera's parent company, the PE Corporation.
But Dr. Lander and other doves were absent, resulting in a meeting of hawks without a mediator. The meeting broke up in mutual feelings of distrust. After two months silence, Dr. Collins and Dr. Varmus wrote on Feb. 28 to Celera that they would assume the idea of cooperation was dead unless they heard from Celera by March 6. The two officials included a proposed statement of shared principles, including that "the current antagonism and excessive competition should be replaced with a more collaborative spirit."
On Tuesday, a day after the institutes' deadline, Dr. Venter replied that Celera was still interested in collaboration and that the institutes' letter had "dramatically misstated" the company's position on its needs for intellectual property protection.
The stark disagreement is in one sense surprising because the two sides recently joined forces in successfully sequencing the genome of the laboratory fruit fly, used by Celera as a critical pilot project for its human genome strategy.
But fruit fly genes are of no direct medical value, and the two sides were able to share credit and make their data public without acrimony.
With the human genome data, there are much higher stakes in terms of intellectual credit for a landmark achievement and the prospect of a huge commercial payoff.
At the Dec. 29 meeting, the institutes' side insisted that the merged data set should be freely used by everyone, including Celera's commercial competitors, like Incyte Pharmaceuticals. Mr. White indicated he could not agree to that.
"The meeting went far astray when Waterston started defending Incyte's right to sell the Celera data," Dr. Venter said.
According to Dr. Collins, Mr. White declared that Celera "wanted to gain a monopoly on the human genome as a database," and that "it would be difficult for a publicly supported enterprise to become complicit in that." As for Celera's wish to prevent competitors from selling its data, "That is taking a whack at the entire sector that seeks to take this sequence and provide it in a usable form," Dr. Collins said.
But in refusing to allow Celera proprietary safeguards, N.I.H. officials may have pushed the company too hard. "I don't think the director of a publicly traded company can afford to give away everything they have," said Dr. Gerald Rubin, the University of California biologist who led the public consortium's side of the fruit fly genome project.
Dr. Rubin said Celera and Dr. Venter had "completely honored the letter and spirit of their agreements." He said he was puzzled at the pressure on Celera to release its data when it had already made public far more than any of its competitors.
Although the human genome is a gold mine in principle, it is unclear exactly where the commercial payoff will come.
The genome itself is just a mystifying string of the same four chemical letters, with no evident punctuation, annotation or chapter headings. Interpreting and making use of it will be the work of decades.
Dr. Norton Zinder of Rockefeller University, a member of Celera's scientific advisory board who had favored collaboration, attributed the breakdown in talks partly to the difficulty of predicting the course of the genome's commercial development.
"There is no paradigm for how you value the information in the human genome sequence in itself," Dr. Zinder said. "When you do other things to the information, it is priceless -- but that value comes afterward and you don't know at what stage of this later work it will be found."
Dr. Venter said he still intended to make Celera's human genome sequence available to academic researchers without restriction on commercial uses they might develop from it.
Disagreements seem certain to continue even if the two sides go their separate ways.
In an asymmetry caused by the public consortium's open access policy, Celera can use its rival's data, which is made public in a computer database known as GenBank. Dr. Venter plans to publish a human genome sequence based on both Celera's and the public consortium's data. But the N.I.H. officials in their letter called this plan "a breach of scientific ethics" because it involved publishing other scientists' primary data.
Dr. Venter termed the position ridiculous because the posting of data in GenBank constituted a publication, he said.
He said the differences with the public consortium began at a May 1998 meeting when Dr. Collins of the N.I.H., under pressure from his English colleagues, first decided against collaborating with Celera. |
