Friday, June 14, 2002

Supporting science

Improving DNA chips is among the cutting-edge research being funded by the Carilion Biomedical Institute in Roanoke.

By JEFF STURGEON
THE ROANOKE TIMES

   In his mind, Ravi Saraf can see the future of medicine: doctors telling patients what inherited diseases they are likely to get and devising procedures to head them off.

    In the basement of the chemical engineering building at Virginia Tech, the associate professor is trying to develop the tools necessary for that to occur. Working toward a fuller integration of medicine and genetics, Saraf hopes to simplify the DNA chip for use in standard hospital laboratories.

    DNA chips, dime-sized pieces of glass infused with a million human DNA fragments, are one of the most promising breakthroughs in modern molecular biology, but they're still in their infancy.

    Today, genetic analysis is a costly, specialized technique in limited use medically. Not only must doctors and hospitals send work out to specialized laboratories, but genetic conditions also are relatively rare and often difficult to do anything about.

    But if Saraf succeeds, hospital pathologists could someday read genes from blood samples as easily as they gauge glucose or cholesterol. The medical implications are vast. With the improved treatments the technology could foster, patients could receive care before they get sick for any disease that they're predisposed to develop.

    "The Holy Grail," Saraf said, "is if I can take 1 cc of blood and perform molecular diagnostics on it to tell what the patient's genetic diseases are and what diseases he or she has currently."

    Saraf's work is one example of potentially high-impact research being paid for by the Carilion Biomedical Institute . The Roanoke-based institute, which received a $20 million gift from Carilion Health System in 1999, is assisting dozens of biomedical researchers and graduate students at Tech and the University of Virginia with money and other support.

    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.

    Santa Clara, Calif.-based Affymetrix sells about 80 percent of commercially available chips. The company prints genes one layer, or molecule, at a time onto glass surfaces until they stand up like microscopic skyscrapers, each about 25 molecules high, using the human genome available free on the Internet as a blueprint.

    Saraf, 41, is trying to adapt conventional DNA chips to be faster, less expensive and more sensitive.

    He divides his time between a small office and a windowless basement laboratory where he and graduate students who assist him manipulate strands of DNA .

    A DNA test relies on bonding habits of the building blocks of genes, which are not unlike the bonding habits of people in certain respects. Suppose 10 couples attend a social function, but the men go off in one room and the women in another. As men and women wander back randomly to the main room, the couples for which both spouses are present reunite and leave together. Assuming everyone's being faithful, when the host sees John slip out with a female companion, the host can trust she's his wife, Sue.

    In the DNA arena, the genetic building block adenine (A) always pairs with thymine (T), while guanine (G) always pairs with cytosine (C). Suppose a scientist wants to check for the existence of a particular gene sequence 40 letters long known to cause a certain disease. He exposes a sample of the patient's blood to a made-up batch of DNA that contains the compl mentary other half of the sequence. If the building blocks mate, the gene is present.

    Because DNA strands are too small to observe even with a microscope, scientists use light technology to spot the pairings. They put luminescent tags on the patent's DNA, and their glow indicates if there's a match or not.

    Saraf, a native of India who has a graduate degree from the University of Massachusetts at Amherst, has focused much of his attention on ridding science of a pesky problem with the tags: Certain DNA strands collect two or even three tags, while others that need to be tagged may not have any. This skews the glow and, if not corrected statistically, compromises results.

    Saraf invented a fluorescent coating for the reaction surface, which is a small wafer of glass or silicon. He doesn't need to use tags, an advancement for which he is seeking a patent.

    His other aim: to raise the sensitivity of the test, minimizing the DNA required and eliminating the need to make copies, a process that introduces errors unacceptable in medicine, Saraf said.

    Saraf is in line for his third round of yearly institute funding, because the institute sees commercial potential. Just how Saraf and the institute will approach the medical marketplace hasn't been disclosed yet.

    Ethicists, and some patients, fear genetic profiling could peg people with bad genes for discrimination by health insurers and employers on the basis they're likely to rack up high bills.

    "We're a long way from doing these sort of massive screening tests to determine your general susceptibility to hundreds of genetic conditions," said Ann Jewell, a genetic counselor with Carilion Health System, who sees the pluses and potential downsides of wider use of genetics in medicine.

    "When and if they start doing it, it's going to require some serious consideration on the part of practitioners, the patients and insurance companies. There's going to have to be some sort of agreement that we're going to use the information in a good, positive way ."

    The Associated Press contributed to this report.

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