| BUSINESSWEEK ONLINE : APRIL 10, 2000 ISSUE | ||||||||
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| SCIENCE & TECHNOLOGY
First Silicon. Then DNA. And Soon, Protein Chips Faced with the task of analyzing thousands of genes at once, researchers routinely turn to DNA chips--thumbnail-size wafers of glass or plastic with thousands of microscopic bits of DNA arrayed on their surface, made by Affymetrix Inc. (AFFX) and others. The chips are one of the key innovations that have transformed genomics from a cottage industry into a large-scale automated business. Now, as researchers begin work on the complete set of human proteins--the proteome--they are betting that protein chips will be one of the mainstays of research. A future experiment might look something like this: First, generate a million or so antibodies that recognize every protein in the human proteome. Next, put a few drops of spinal fluid from a Parkinson's patient or a normal patient onto the chip. Some of the sample's proteins will mate with antibodies on the chip and latch on to them. Because the proteins have been labeled with a fluorescent dye, they can be seen, with the help of a laser, as little glowing squares of red or green or yellow. The protein pattern that lights up in a Parkinson's patient will differ in a few critical ways from that of a normal person. By going after those discrepancies and finding the proteins that cause them, researchers can rapidly identify the proteins that are present in normal patients and not in Parkinson's sufferers. And that may point directly to the cause of the disease. Sounds simple, doesn't it? It's not. Because proteins are far more complex than strands of DNA, it's not an easy leap from DNA chips to protein chips. That hasn't deterred Stanford University biochemist Patrick O. Brown, who played a critical role in developing simple, cheap DNA chips. He and his graduate student, Brian Haab, recently completed a pilot study to test the feasibility of protein chips. ''We mooched antibodies from other labs, put them on glass chips, and looked to see what stuck to them,'' says Brown. Roughly a third of the 120 off-the-shelf antibodies they have tested bonded specifically to their protein counterparts. Brown is encouraged by the results and plans to scale up the technology and start testing clinical samples within six months. Eventually, he hopes to turn these chips into cheap diagnostics. Instead of sending a urine sample to a lab for a pregnancy test, for example, a physician could put a few drops of the fluid onto a chip and scan for protein changes that might indicate that the woman is expecting. J. Craig Venter, president and chief scientific officer of Celera Genomics (CRA), also believes that these protein chips are one of the keys that will unlock the secrets of the human proteome. ''It's going to be our key reagent,'' he says. Venter plans to use them to uncover the complicated networks of interactions that occur among proteins in a given cell. He believes this technology will totally supplant the need for DNA chips. That won't happen overnight. It's not easy to make specific antibodies to fight every variant of every protein in the human body. It takes months to make just one. Imagine having to repeat that million of times over. Rudolf H. Aebersold, a molecular biologist at the University of Washington in Seattle, believes that ''protein chips have a lot of potential'' but cautions that ''as a research tool, [they] still have a long way to go.'' Aebersold's lab is trying to make a different kind of chip that miniaturizes and automates protein separation. He will have competition from Ciphergen Biosystems Inc., a biotech startup in Palo Alto, Calif., that hopes to become the Affymetrix of the protein-chip world. Just what form protein chips ultimately take is anybody's guess. But sophisticated tools like them are essential if researchers are to solve the riddles buried in the human proteome. By Ellen Licking in New York, with John Carey in Rockville, Md. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ BACK TO TOP |
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