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These Chips Are Good For Health

Steven Potter is attempting to grow kidneys in his laboratory in hopes of someday saving the lives of patients who now die awaiting organ transplants.

He's a long way from achieving his goal. But dime-sized pieces of glass infused with a million human DNA fragments are helping him get there faster than he ever could have imagined.

They're called DNA chips and an increasing number of researchers couldn't do without them in their work developing new drugs and improving on disease diagnosis and prediction.

Even agricultural scientists use them in their research with plants and animals.

"It's been a major technological breakthrough in biology," said Potter, a pediatrics professor at Cincinnati Children's Hospital Medical Center. "I think 'revolutionized' is the proper word."

Potter is attempting to understand how humans develop from a single cell and is studying genes that control how and where organs and other body parts develop.

Until DNA chips came into vogue about five years ago, genetic scientists slogged slowly through their research, often investigating one gene at a time. Now they can analyze thousands of genes simultaneously.

The most popular chip is made by Santa Clara-based Affymetrix, which sells about 80 percent of commercially available chips.

The company uses the human genome available free on the Internet as a blueprint for its chips, which are technically known as microarrays.

Employing semiconductor manufacturing technology, workers "print" genes one layer, or molecule, at a time onto the glass until they stand up like microscopic skyscrapers, each about 25 molecules high.

Researchers then drop fluorescently tagged RNA, which serves as the go-between between DNA blueprints and a cell's protein-making machinery, onto the chips.

The portion of a chip on which genes interact with the RNA will be fluorescent, enabling computers to easily isolate it for scientists.

Scientists believe many diseases are caused by genes "turning on" when they shouldn't. Knowing this, researchers can design drugs to attack suspect genes. This drug discovery is the primary use for the chips today.

The chips are also giving researchers insight into how illnesses such as cancer develop. What researchers are finding is that diseases affect people in different ways.

Researchers are finding increasing proof that cancer is an individualized disease, with many different subtypes, identifiable only by their molecular fingerprints.

This will ultimately lead to more sophisticated treatments for cancer and other diseases, said Dietrich Stephan, an assistant professor of pediatrics at Children's National Medical Center in Washington D.C.

That is expected to foster less reliance on chemotherapy as less harmful, more targeted therapies are developed.

Some envision a day when a doctor, armed with a handheld computer, will be able to make an instant disease diagnosis. But for now, analyzing DNA chips takes at least several hours and hundreds of thousands of dollars worth of computer equipment and software.

DNA chips are daily getting smaller, cheaper and more powerful — as are the machines and software used to decipher them.

Four years ago, chip makers could fit about 5,000 genes onto a chip for a cost about $3,000 each. Today, chips costs about $400 each and accommodate three times the genes.

Affymetrix recently began shipping a two-chip combination that contains the entire human genome. Last year, the company shipped 280,000 chips, and with only one major competitor — Agilent Technologies — analysts expect Affymetrix to ship even more chips this year.

Analysts at Frost & Sullivan predict the market for DNA chips will grow from $874 million last year to $2.6 billion by 2004.

But as the technology gets better and the market for the chips grow, so do ethical questions.

Because the chips can to screen adults for predisposition to certain genetic diseases, such questions loom large.

There are concerns insurance companies and employers might use the information they provide to discriminate against people found to possess certain genetic defects or predilections.

DNA chips also raise the specter of aborting embryos deemed to have unwanted traits by the parents.

The concern is that someday soon parents will be able to test embryos for genetic traits that will appear after birth ranging from proclivities to develop certain diseases to intelligence quotients to eye color — and make birth decisions based on results derived from gene chips.

"This adds fuel to the whole abortion debate," said Erin Williams, executive director of the Foundation for Genetic Medicine, in Manassas, Va., a think tank that deals with ethical issues.

"We're not there yet," Williams said. "But we're getting closer everyday. It's a very powerful tool."

by Paul Elias

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