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But there is now some question over whether the home brew scientists work-ing with Brown's technology will be at risk of being sued by biotech companies once the gene chip patent disputes are settled. In fact, a recent study of the microarray market by Silicon Valley consulting group Frost & Sullivan concluded that besides the ongoing intellectual property battles, competition from home brews will be a key restraint to future profits. "It's a threat for sure, and a concern the companies have," says study author Alex Ward.
While patent lawyers say the home brew scientists could technically be infringing by using a patented method, it is unclear if biotech companies will go after individual scientists. Brown doesn't think so: "There is such a symbiotic relationship between these companies and academic researchers," he says. "They would be shooting themselves in the foot by being so heavy-handed."
Botstein isn't so sure. "I wouldn't say it is impossible. Companies will sue you tomorrow if they think you are trying to profit," he says. "Already, some companies want you to pay royalties not only on the technology, but on what you discover using the technology. I think it's outrageous and I've argued strenuously against it. Bill Gates doesn't expect royalties on the novel you've written using his software."
Still, Botstein isn't worried someone will try to shut down his and Brown's microarray lab. "So far these patent issues have just been a lot of noise and furor," he says. "Unless they come with the marshal and say, 'Don't do that,' why should we care?"
Getting the gene chip into scientists' hands, he believes, may advance medicine in completely new directions. "Since we don't know exactly where we are going, this is research in search of a hypothesis," he says. "We feel like Lewis and Clark, when Jefferson said, 'Go forth and tell us what's out there.'"
Brown, meanwhile, is just happy that in spite of the lawsuits, it's science as usual, with home brew technology ensuring new research won't be stalled.
"I think the answer most real scientists would give to the question of what's really original, and useful, and non-obvious, is sufficiently different from the answer that lawyers would give," he says. "It's almost as if these patent battles take place in some strange parallel universe. I know it's important on some level, but I find it extremely boring."
Last week, Patrick Brown, David Botstein, and others published their first important study proving that a look at global gene expression patterns will be a major help to scientists struggling to understand cancer. Using the microarray to examine B-cell lymphoma, they were able to find that there are two different kinds of tumor, with very different prognoses, which had previously been diagnosed and treated as a single disease. "It validates the concept," Botstein says.
The outcome is good news for Dr. Jeffrey, who's using the gene chip to analyze tumors in her breast cancer study. Now she expects the data she's gathering from Jean Christ's tumor and others will ultimately mean something. And not just for breast cancer: Stanford urologic surgeon Jim Brooks has teamed with Jeffrey to work on a prostate cancer portion of the tumor gene study.
But with the ability to see more than 20,000 genes in each tumor at one time, the amount of data becomes exponentially more difficult to digest. Jeffrey's goal is to study 1,000 tumors, which means she will have to look at and compare more than 20 million genes. "And from that we have to make some sense," she says. "We don't even know what all the genes do yet."
So, as the patent lawsuit between Affymetrix and Incyte moves ponderously toward the courts, Brown and his colleagues have enlisted the help of mathematicians and statisticians to develop computer software that will effectively analyze what the gene chip finds. Botstein predicts it won't be long before the microarrays in the Stanford lab alone will have gathered a terabyte of information. For comparison, he likes to point out, the entire Internet contains 100 terabytes.
And whether or not the eventual winner of the patent dispute decides to start suing researchers, the issue seems completely trivial to the home brew scientists caught up in the excitement of new discoveries. "When I see people like Dr. Jeffrey doing good science, it makes us feel like our goals are being accomplished," DeRisi says. "We could care less what happens to those companies."