Scientists: Gene chips key to solving brain disorders?

Scientists hope gene chips hold key to solving brain disorders

By MATT APUZZO
Associated Press Writer
August 14, 2005, 12:21 PM EDT

NEW HAVEN, Conn. -- Shrikant Mane holds in his hand a black cartridge about the size of credit card. It's called a gene chip, and Mane believes it will change the way scientists think about depression, epilepsy, even drug addiction.

The chip contains the entire human genome and, thanks to new federal funding, thousands of neuroscientists around the country now have access to it to study the way brain disorders behave at the molecular level.

If Mane and his colleagues are right, that could speed up answers to some of science's nagging questions: Why do identical brain tumors respond differently to the same drug? Why are some people seemingly immune to antidepressants? What's really happening to Alzheimer's patients?

"If you take your car to the mechanic, he has to identify the problem before he can fix it," said Mane, a gene chip researcher at Yale. "This tells you what the problem is."

Yale is home to one of four laboratories that the National Institutes of Health has just tapped to provide neurological gene research for an estimated 10,000 scientists nationwide, many of whom could not otherwise have afforded it.

When researchers completed the human genome project in 2003, some people thought scientists had all the answers about genetic disease. But it's not that simple. Trying to understand the body simply by looking at the human genome is like trying to understand global politics by looking at a world map.

Scientists need to know how genes act and interact, how the healthy body functions and how diseases affect each gene. Unlike simple traits such as hair color or freckles, a complicated disease such as depression may involve more than 1,000 genes, Mane said.

Understanding how these genes behave is paramount to finding a cure, he said. While some scientists caution against overly high expectations, others believe the gene chip, also called a microarray, holds the key to many cures.

Scientists start with two chips, each containing the genetic blueprint for a human. One is injected with healthy genetic material, the other with diseased material. The two chips react differently. Some genes are turned on, others off.

By comparing the chips, scientists hope to see exactly what a disease is doing. Some see this as a step toward individualized medicine, in which doctors might tailor drugs to a patient's DNA.

Microarrays have been available for the past few years but have been prohibitively expensive for most researchers. The government funded neurological research at three labs in recent years but limited access to the technology.

In June, however, NIH announced a $25 million plan to make it available nationwide. Now, scientists with grants from any of 15 federal agencies can send genetic samples to Yale, ULCA, Duke or the Translational Genomics Research Institute in Phoenix for analysis.

The test results are being catalogued and, for the first time, neuroscientists can build on today's research to speed up tomorrow's development.

Already, the phones at TGen are ringing, coordinator Sarah Brautigam said, as researchers realize that a major barrier to neuroscientific research has been lifted.

Yale, which has been conducting privately funded gene chip research in recent years, expects to be flooded with requests following the NIH grant. The school is expanding the lab and buying a new supercomputer to crunch the data.

Cheryl Sisk, a Michigan State neuroscientist, said expanded access to microarrays will create research opportunities. But every microarray breakthrough, she said, will require more research before practical applications are understood.

"It's a big deal," she said. "But the thing about microarrays is they're not a panacea. They're not going to be the answer to everyone's questions."

Early gene chip research has, however, changed the way some scientists think about studying cancer treatments. By comparing healthy gene chips with cancerous ones, scientists noticed something surprising:

"Tumors that we used to call exactly the same thing and group them together and treat them the same way are actually very different," said Stan Nelson, director of the UCLA microarray lab. "That really screws us up."

Because the same cancer can behave differently in each patient, Nelson said, some patients in a drug trial may be genetically predisposed to resisting the medication, skewing the results.

"One of the first dominoes to fall here will basically be subdividing patients in clinical trials," Nelson said.

Not only is the technology becoming more accessible, it's getting more advanced. Each generation of chips contains more of the known landmarks on the body's DNA map. These landmarks, called single-nucleotide polymorphisms, allow scientists to pinpoint genetic changes during their experiments.

It's like calling 911, Mane said, and reporting a highway accident between New Haven and New York. A few years ago, that was as specific as the technology allowed. Now, scientists know which town the accident occurred in. Soon, they'll know specific exits.

With the financial and technological barriers lowered, Nelson said he expects microarray research to speed up in the coming years, opening doors for medical breakthroughs.

"There will be literally hundreds of medical applications that will come out," he said. "We're in an age of discovery."

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