Science . Vol. 275 . 28 MARCH 1997 pg. 1877
In mid-January, Ramon Parsons received a phone call that is every researcher's worst fear. Just weeks earlier, the molecular biologist, who works at Columbia University's College of Physicians and Surgeons, and his research associate Jing Li had finally nailed the tumor-suppressor they had been hunting for the past year. It was potentially a major prize, but they still had to verify that the gene was indeed a tumor suppressor-one whose loss or inactivation can lead to cancer development-and determine the range of tumors with which it might be involved.
But just as they were anticipating the fruits of success, one of their collaborators, molecular biologist Michael Wigler of Cold Spring Harbor Laboratory on Long Island, called to say that he had just read in a biotechnology newsletter that Myriad Genetics had also found a tumor-suppressor. There was scant information in the press release, but what was there set off alarms. Myriad had linked its gene to malignant brain tumors called gliomas-just as Parsons had. The two genes, he feared, were the same.
What happened over the next few weeks, as both the Parsons and Myriad groups rushed to get papers in press and file patents on the gene, is testimony to how complex life has become for researchers tracking down disease genes. With industrial collaborations on the rise, the competition has grown more intense, and patenting and stock-market worries are having an ever greater influence on how scientists go about their business.
The immediate cause of Parsons's panic was a press release that Myriad put out on 22 January. This release simply highlighted the gene's role in gliomas, without mentioning its chromosomal location, or giving any information about its protein product or other cancers the gene might be involved in. Also missing was any indication that the work had been published, or was at least submitted for publication. "I thought it was bizarre, because they were announcing a discovery without publishing it," Parsons recalls.
Mark Skolnick, Myriad's vice president of research, says the company put out the release to guard against possible charges of insider trading by the U.S. Securities and Exchange Commission. Sean Tavtigian of Myriad notes that the company was about to enter one of the quarterly periods during which employees with stock options are allowed to trade their Myriad stock, and wanted to make sure that the public knew what the employees knew-that it had the glioma gene in hand-during that period. "We have to be uniform in our release of information," says Skolnick. "There's a potential liability if information gets out in an uneven fashion."
But when the release was mentioned in the biotech newsletter Bioworld, it also alerted Parsons to the competition at Myriad. "From reading the press release, [it seemed] we were farther along than they were," says Parsons. Nevertheless, he worried that if the two groups had converged on the same gene, this announcement might jeopardize his chance to get credit for the discovery. "Do you know how hard it is to publish in a small lab if you're second?" Parsons asks.
Li and two graduate students worked around the clock for the next 4 days screening various tumor samples, mostly primary brain tumors, to verify that the gene is indeed missing or aberrant, as would be expected for a tumor suppressor (see main text). But they skipped some of the tests they had planned to show that the gene is aberrant in more kinds of tumors, and also put off filing a patent on the gene until the paper was submitted. "My interest was to get a paper out the door," Parson says. Indeed, on 31 January, as soon as the paper was finished, Li flew to Washington, D.C., to hand deliver it to Science. "It was pretty crazy," he says.
Meanwhile, Myriad's academic collaborator on the project, Peter Steck of the M. D. Anderson Cancer Center in Houston found himself caught up in Myriad's commercial priorities. "The first emphasis was patenting," he explains. In addition, he was racing to meet a renewal deadline for his grant. He didn't get to his paper until later, even though he began hearing through the "industrial grapevine," as Steck calls it, that they had competition. The paper was submitted in late February to Nature Genetics, accepted within a week, and published 3 weeks later, technically 4 days after Parsons's report.
But while Parsons beat Steck and Myriad to publication, albeit by a narrow margin, there's no telling yet which group will wind up with the patent. And perhaps neither will. Both groups' searches led as them to the GenBank computer database of gene sequences, which already turned out to contain several small DNA bits, called expressed sequence tags (ESTs), that fell inside the gene. A computer program had even grouped those ESTs into a tentative gene, which contained a sequence indicating that its protein product is a dephosphorylating enzyme. Myriad's Tavtigian points out that this could mean that a company that has generated many ESTs- Human Genome Sciences in Rockville, Maryland-may have beaten both Steck and Parsons to the Patent Office. That company declined comment on that possibility. -E.P.
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