Genes Without Frontiers

The so-called gene chip could revolutionize the way we treat cancer patients. That is, if biotech firms don't keep it out of doctors' hands.

Patrick Brown, though, has helped many scientists circumvent the problems inherent in depending on commercial technology. With "blast ahead" as his motto, Brown has been instrumental in spreading the home brew technology that Jeffrey and countless other researchers now use.

Brown created a successful microarray system in the early 1990s with the help of two graduate students -- one from Stanford's engineering department and the other from his biochemistry lab. Brown and Dari Shalon, the engineer, are credited with inventing the technology. Joe DeRisi, a student working in Brown's lab, did a lot to help make it work.

Interested in mapping genes, Brown was frustrated that there was no practical way to read them. He had a simple design in mind, so he set out to find someone on campus who could help him build it. Most of the engineers at Stanford scoffed when Brown explained his concept: a robot with "fountain pens" that would dot DNA onto a glass slide. "This is an academic institution and you don't get ahead here doing something so rudimentary," Brown says. "Everyone wanted to do something incredibly complicated and expensive."

Space Age Medical Research: The chip's dots each represent a human gene.
Space Age Medical Research: The chip's dots each represent a human gene.
Brew Your Own: Instructions to build a microarray robot are posted at
Anthony Pidgeon
Brew Your Own: Instructions to build a microarray robot are posted at

But Shalon was eager enough to try Brown's idea that he left the engineering department, joined Brown's lab, and began pursuing a Ph.D. in biotechnology engineering. "Right away he asked me if this was something he could start a company with," Brown says. "I knew it was something with a lot of commercial potential, which is how I was able to persuade Dari to take it on. But it never occurred to me just how big it would become. Dari has a very good quality that is underappreciated here -- pragmatism."

Indeed, as soon as the technology was viable, Shalon left the project and founded his own company, Synteni. There, he spent a few years perfecting the gene chip system on his own before selling Synteni to Incyte -- one of Silicon Valley's largest biotech firms -- for $90 million. Now, at 34, Shalon is back in academia as the new director of Harvard's Center for Genomics Research.

But when Shalon sold his company to Incyte in December 1997, the transaction sparked a patent dispute that pitted the biotech industry's biggest players against each other. Santa Clara-based biotech powerhouse Affymetrix, which had been collaborating with Palo Alto's Incyte on aspects of gene chip technology, immediately sued Incyte when the latter acquired Shalon's company. Affymetrix was developing its own, much more advanced, version of the gene chip. But Brown and Shalon's spotting system remained more popular among scientists, who claimed it was more versatile -- and certainly cheaper -- than Affymetrix's photolithographic method. "Many scientists say the Affymetrix technology is not well-suited for them," says Alex Ward, a Silicon Valley biotech analyst. "They agree Affymetrix can make very dense chips, but it's not good for everything. You don't need a Ferrari to commute down Highway 101."

Incyte's system had its drawbacks, too. Instead of selling gene chips, Incyte acted as a job shop: Scientists would drop off their gene expression experiments and pick up the processed results later. While some customers enjoyed the convenience of not having to buy a microarray system, others preferred to have control over their work. "It's like taking your film to be developed at Walgreens, except you don't get to take the pictures," Ward says. "A lot of scientists don't like that. They want to be hands-on with their own experiments."

Still, Incyte's foray into the business threatened Affymetrix's share of the market. In suing Incyte, Affymetrix claimed infringement by asserting that its patents covered all gene chips of a certain density -- no matter how they were made.

Incyte cried foul. "Affymetrix claims it owns the field," says Incyte lawyer Teresa Corbin. "They're trying to shut out everyone else for things they didn't think of in the first place."

In fact, Stanford's Brown says the intellectual his- tory of microarrays goes back years before he or Affymetrix began doing anything in the field. The idea of reading lots of genes at once is not new, he says, and there are plenty of ways in which it can be done. "There are many subtle as well as obvious differences between the technologies Affymetrix and my lab developed, and in the visions we had for their applications," Brown says. "So the question of what's patentable is really a difficult one."

Affymetrix is already widely known as the undisputed industry leader in gene chips. And the aggressiveness with which Affymetrix has pursued patent litigation -- not only against Incyte, but against companies like Hyseq and Oxford Gene Technology -- demonstrates its determination to continue dominating the market, says Los Angeles-based biotech analyst Alan Auerbach. "Affymetrix is going for the full monty. They're trying to patent anything they can because they want everything," he says. "They have a real crack legal staff that's going after any and all competitors. If the people at Incyte are smart, they will be figuring out ways other than the microarray to make money."

Incyte, too, has been on the offensive, countersuing Affymetrix, as well as getting into its own patent disputes with other smaller biotech companies like Gene Logic. However, Incyte was dealt a blow when the U.S. Patent and Trademark Office ruled in favor of Affymetrix last September, in a broad interpretation that took many patent experts by surprise. "A lot of people feel the normal patent standards that should have been applied in this case may not have been applied to Affymetrix," says Peter Dehlinger, a Palo Alto patent lawyer who served the biotech industry for 20 years.

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