Tempest In A Test Tube

A private company that mapped the human genome could not have completed its work without data provided by competing public laboratories, which was not apparent in scientific publication of the work, suggests a study by researchers on the public team.

Two efforts, one by Celera Genomics and one by an international consortium led by the Human Genome Research Institute, competed neck-to-neck to map the human genetic structure. Some called the massive project the biological equivalent of NASA's moon project.

In a historic joint announcement at the White House with President Clinton in 2000, representatives of both efforts were honored and given equal credit.

In a study appearing this week in the Proceedings of the National Academy of Sciences, researchers who were on the government team say that Celera actually depended on Web-published data from the public effort to complete its human genome map.

Officials at Celera denounced the study as flawed and erroneous.

"They have completely misrepresented the work that we did," said Celera vice president Mark Adams. "Their paper has very little basis in reality."

The study was written for the proceedings by three members of the government genome sequencing team - Robert Waterston of Washington University, Eric Lander of Massachusetts Institute of Technology and John Sulston of the Wellcome Trust Sanger Institute in Britain.

Waterston said the authors would not be interviewed for attribution.

Dr. Francis Collins, head of the National Human Genome Research Institute, said that although he did not specifically endorse the study, it was important to discuss the issues as "strictly a matter of science."

Shirley Tilghman, president of Princeton University and a noted researcher, said the new paper gives a valuable analysis of what went on in 2000 during the race to map the human genome.

"The conclusion was that Celera had beaten the public project, that they had found a faster, better, cheaper way ... and had shown up the slow, ponderous public project," said Tilghman. "That is a conclusion that cannot be sustained" based on the new analysis, she said.

In their paper, Waterston and his co-authors claim that Celera, in effect, used Web-published data from the human genome project as a road map for piecing together in the right order the 3 billion chemical base pairs of the human genetic structure.

Waterston and his co-authors argue that their analysis of the human genome paper published by Celera in the journal Science shows that the private company did not, in fact, produce an independent draft of the genome. Instead, the researchers claim, Celera researchers incorporated key sequences already developed by the public effort to complete their map.

The public consortium published its results daily on the World Wide Web, giving Celera and other researchers full access to the government data as it was developed.

Richard Lifton, a Yale University professor of genetics, said the Waterston paper "makes the valid scientific point that the Celera assembly was far more dependent on the public effort than was acknowledged in the Science paper.

"These things are important to the scientific community as to who did what and how," said Lifton.

Celera used a technique called the whole genome shotgun strategy, while the public consortium used a modified version that mapped the genome in a series of small segments. Some saw the contest as a test of which method was better. The Waterston paper contends Celera's work did not provide a final answer to that.

J. Craig Venter, founder of Celera and, until recently, the company's chief scientist, denounced the Waterston paper as "game playing at the worst level in academics" and said it was devoid of "substantive science."

Venter said Waterston and his co-authors recently had an opportunity to air their complaints at a scientific meeting but instead chose to write a paper in a journal.

"This is a sad commentary on science - as the stakes get higher, so does the battle for credit and attention," said Venter in a telephone interview. "This has been a whisper campaign for about a year. Now they are slowly coming out in the open with it."

In 2000, with the two competing groups racing to complete the genome, Venter and Collins frequently sniped at each other. It created a public feud that eventually prompted President Clinton to ask that they make peace for the good of science. A mutual friend of the two played host, over pizza and beer, and Collins and Venter agreed to a joint announcement, with shared credit, when a draft of the genome was completed.

The Celera group published its results in Science, while Collins and his group of international researchers published in Nature, a British scientific journal.

By Paul Recer