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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.

Wednesday, Feb 9 2000
Dr. Stefanie Jeffrey must remove the tumor growing inside Jean Christ's left breast before it metastasizes, spreading cancerous cells through her bloodstream.

The lump Christ first felt with her fingers measures barely 2 centimeters on a mammogram. The X-ray shows only a tiny white dot sitting close to her nipple, but Christ will sacrifice her entire breast in order to rid her body of the potentially lethal mass. She has chosen to have a radical mastectomy. Though she could have had a less invasive surgery, which would have removed only the tumor -- a procedure known as a lumpectomy -- she would have had to follow this up with a series of highly toxic treatments to kill any stray cells left behind that could cause the cancer to return.

At 78, Christ still likes to dance with her husband. She's afraid getting sick from the side effects of chemotherapy or radiation will jeopardize her active lifestyle and the enjoyment of her remaining years. So she has decided she can do without her breast if that's what it takes to have peace of mind.

Jeffrey, Christ's surgeon, wishes her patients didn't have to make these all-or-nothing choices. And soon, she hopes, they won't. Jeffrey is the chief of breast surgery at Stanford Medical Center, where she is attempting to find better ways to combat breast tumors by researching what makes them work. Why do some spread, and not others? Are there more reliable ways than chemotherapy to stop migrating tumors?

The results of Jeffrey's research, which may end up saving women's lives, are dependent on a new invention called the gene chip. At the moment, Jeffrey makes her own gene chips using a cost-effective homemade robot. But a legal battle over rights to the gene chip could ultimately place her and other medical researchers in the position of having to purchase expensive equipment and services from private companies. A patent dispute among several of these companies -- most notably Silicon Valley biotechnology leaders Affymetrix and Incyte -- is the most recent example of the way private corporations are seeking to control the technology used to study today's hottest medical research subject: human DNA.

If Jeffrey can compare tumors that spread with those that don't, she will be able to see patterns that could determine whether patients like Christ need chemotherapy or not. As it is, all tumors are treated as metastasizing suspects because it is impossible to tell which are which. Jeffrey hopes to change that -- by reading genes. Until now, gene reading has been an arduous, labor-intensive process. Though there are an estimated 80,000 or more genes in the human genome, the most powerful scientific instruments could look at only a few at a time. And every person, and tumor, is unique. Sheer numbers have kept what is sure to be life-saving genetic research out of reach.

But the gene chip has changed that.

The chip allows researchers to read tens -- even hundreds -- of thousands of genes simultaneously, catapulting the study of genetics from the equivalent of the horse and buggy era to the space age in an instant. And obviously, with cures for cancer and other lethal diseases potentially on the line, anyone who can claim rights to the chip stands to make a lot of money. But exactly who thought up the gene chip, who made it work, and who made it better -- and when -- is disputed. The confusion has resulted in a long list of unresolved court battles among the Silicon Valley biotech companies that want to market and sell the chip.

Jeffrey is ignoring the lawsuits. Using the gene chip, she figures it will take her less than five years of gene reading to begin learning which breast tumors are prone to spread, and less than 10 years to develop more effective drug therapies. Within a generation, it may even become possible to predict whether a woman will get breast cancer at all. She believes the research is too vital to be sidelined by a prolonged patent dispute.

Fortunately for Jeffrey and for her patients, so does the group of scientists showing academic researchers how to build homemade gene chips at a fraction of what it would cost to buy them commercially. These Bay Area biochemists were early pioneers of the same gene chip technology now being fought over in the patent courts. For researchers like Jeffrey, the gene chip system widely known as "home brew" has become a welcome and effective way to move scientific progress beyond the control of lawyers and profiteers.

Still in the surgical scrubs she wore during Jean Christ's mastectomy, Dr. Jeffrey walks through the Stanford Medical Center complex to the school's genetics department in her trademark bright pink shoes. She special-ordered her surgical clogs in the color that represents breast cancer awareness. "But I didn't know they would be fluorescent," she says. At the gene lab, Jeffrey checks on the progress of her breast cancer study. There, Stanford scientists are using the home brew gene chips to analyze her growing stock of tumors.

Jeffrey holds up a 1-by-3-inch glass slide to the light. She can see, when squinting, that there are thousands of dots arranged in tiny rows. Twenty-four thousand dots to be exact. Each dot is an individual gene, and together they make a gene chip. "A microarray," Jeffrey corrects. "Gene chip" is the sexy term marketers like to use. The chip itself is not unique, apart from the idea and technology behind it. It simply holds 24,000 known genes in one convenient place. All gene chips are the same, standard boilerplates on which to do comparison experiments with the unknown genes of a tumor.

Like test tubes or litmus paper, it's easy to go through a lot of gene chips while doing an experiment. But unlike test tubes, gene chips are incredibly expensive -- as much as $2,000 for a single commercially manufactured slide. "If I want to look at only 100 tumors, we're talking hundreds of thousands of dollars," Jeffrey says. "That's costly enough to prohibit research." After all, the typical annual budget of an academic researcher may be only $100,000.

About The Author

Joel P. Engardio


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