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A Virus Sleuth Called Dna


Science & Technology

A VIRUS SLEUTH CALLED DNA

When they diagnose infectious disease, doctors often do tests to confirm their suspicions. If a test can't I.D. the pathogen directly, it may find indirect evidence, such as highly specific antibodies the immune system makes to fight infection. Such tests have drawbacks, however: They can't measure the amount of virus in the patient; antibodies often remain after an invader is gone; and sometimes, antibodies don't appear until long after the patient becomes infected--and infectious.

Chiron Corp. has developed a product--its "branched DNA probe" test--that could cure these weaknesses. The test, which directly measures the concentration of a pathogen, is now used only for research on hepatitis B, hepatitis C (HCV), and HIV. But Chiron expects Japanese approval soon to sell the HCV test to doctors who want to track a patient's "viral load" so they can better plan when to give drugs. The test may also help drug developers evaluate new treatments. By the end of the year, Chiron plans to request U.S. approval for the technology, which Chairman William J. Rutter thinks will spark new interest in curing infectious diseases.

ZIPPER BIND. Since the early 1980s, scientists have used DNA probes--short strips of DNA that exactly match pieces of the genetic sequence of a target organism's DNA. Probes work because identical DNA sequences, when mixed together, bind the way a zipper zips and give off a signal, such as a flash of light. The first probes weren't sensitive enough to flag mi-

nute amounts of an organism in diagnostic tests, however, so some companies gave up. Others developed better tests by amplifying genetic material to make it easier to see. Hoffman-LaRoche Inc.'s PCR (polymerase chain reaction) technology is one of those.

Chiron's branched DNA probes are a new twist on the old idea. By chemically attaching branches to the probes and treating them with luminescent chemicals, Chiron can amplify the binding signal thousands of times. The test still isn't as sensitive as PCR. But scientists such as HIV expert John Mellors of the University of Pittsburgh say it's easier to use and may be more precise. That's important: Studies show that the amount of virus in an HIV patient, for example, can help predict how soon and severely AIDS will develop. Other studies suggest that interferon treatment for hepatitis C patients works only for those with fairly low amounts of virus.

CONFUSED. Analysts, many of whom overestimated the early potential of probes, are split on the technology today. Some believe revenues from Chiron's test could reach $200 million annually by decade's end. But PaineWebber Inc.'s Linda I. Miller says the required patient monitoring could make it too expensive. Japan may be a good test of that: The Japanese spend $2 billion a year on interferon to treat hepatitis but get good results less than half the time. Chiron's test may help limit treatment only to patients who will benefit.

Even if it doesn't win a huge market for monitoring, the test could be a key tool in drug development. "There are no new drugs for HIV before the FDA today because people are so confused as to how to measure endpoints," contends Mickey Urdea, a Chiron vice-president. He says evidence that a drug is lowering virus in a patient could become an indicator of progress. That's why DNA probes amplify hope for sufferers of dread diseases.Joan O'C. Hamilton in Emeryville, Calif.


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