Monday, June 04, 2001

Gene research growing at UC

By Tim Bonfield
The Cincinnati Enquirer

        Tucked away in an unremarkable room in an out-of-the way building at the University of Cincinnati, a team of three casually dressed researchers works in what looks like any other graduate-student science lab. But this isn't any other science lab.

        This 20-by-20-foot room, jammed with hundreds of thousands of dollars worth of equipment and computers, is UC's Genomics and Microarray Laboratory, one of the few “core” facilities in Greater Cincinnati playing a crucial role in boosting biomedical research.

        The lab is part of a broader effort at UC that already involves hundreds of scientists, hundreds of millions of dollars in grants and infinite possibilities for advancements in genetic research.

        Yet some say the work here needs to double in scale, to keep Cincinnati on pace with the exploding research opportunities flowing from the Human Ge nome Project, the massive national research effort that made history last year by defining all 3.1 billion base pairs of DNA making up the human genetic code.

  High-tech grunt work by biomedical researchers is being done to answer an ever-growing list of questions about disease and public health:
  • Why is it that some people who smoke get lung cancer, but others who smoke do not? What are the genetic factors that make some people more likely to suffer heart attacks?
  • Why do some people become obese when others who eat just as much don't? Why do some workers develop cancer from exposure to workplace toxins that cause others no apparent harm?
  • Why do some medications cause serious side effects in some people but not in others? What determines who becomes addicted to alcohol and drugs?
        Cincinnati could become one of the 10 to 12 major centers for biomedical research nationwide, said Dr. Donald Harrison, senior vice president and provost for health affairs at the UC Medical Center.

        “This is the growth industry of the future, for the next two decades, for the entire country,” he said. “Every medical center in the country is trying to expand in these areas.”

        The hope is that expanding genetic research will lead to important medical discoveries, which will inspire companies to form and create a variety of jobs as discoveries move from laboratory concepts to commercial products.

        UC hopes to double its biomedical research funding to about $286 million a year by 2006, while adding hundreds of researchers and support staff, Dr. Harrison said.

        But a large part of this biomedical economic development vision depends on the work going on in the third-floor lab of the Kettering building, home of UC's department of environmental health. The lab, though a little cramped, is packed with powerful equipment.

        The hardware was purchased in November 1999, said Dr. Alvaro Puga, director of the microarray lab. After several months of testing and troubleshooting, the lab started producing real genetic reports in February.

        “The space is what we have,” Dr. Puga said. “It looks small, but a lot is going on.”

        In the back, tucked under a hanging shelf, rests a $25,000 DNA amplifier, which creates samples of genetic material. There, two $80,000 robots process the samples and prepare microwell racks, which can contain the equivalent of up to 384 test tubes.

        In the corner, under a glass box, is a $65,000 microarrayer, which takes a mere 12 hours to “print” up to 10,000 genes at a time onto a single glass microscope slide. Just two years ago, it would take experts days to perform such work on just one gene.

        On a shelf above a large-screen computer terminal rests a featureless blue plastic box, about the size of a cable TV descram bler. This $50,000 chunk of hardware contains a dual set of lasers that scan all those genes so they can appear on the computer as a grid of multicolored dots.

        And those dots — each no bigger than 100 microns across (about 1/250th of an inch) — are everything.

        They show which genes get turned on, and which ones get turned off, when a sample of healthy tissue is exposed to a disease-causing virus, bacteria or toxin.

        The dots also show how diseased tissue responds to a medication under development.

        Once the data are scanned, the microarray lab staff burns a CD of the data and ships it off to the researcher who needs it.

        As scientists gain understanding of the complex genetic circuitry revealed by the dots, entire realms of treatment options emerge, Dr. Puga said.

        This is the kind of work that has allowed researchers nationwide to discover genes linked to many kinds of disease, from breast cancer to Alzheimer's. This is the technology that helped develop the breakthrough leukemia drug, Gleevec, recently approved by the FDA for wide-scale use.

        The newer, faster technology and completed gene maps mean the work is coming faster every year, said Dr. Dan Nebert, professor of environmental genetics at UC.

        Research speed will leap yet again this summer, when a $2.3 million supercomputer gets in stalled at Children's Hospital, Dr. Nebert said. That computer will allow faster interpretation of data from the microarray lab.

        In the 1980s, the average post-doctoral candidate in a university lab could isolate and analyze about 18 genetic base pairs a week, he said. This summer, they'll be able to do 1 million base pairs a week.

        Researchers are using UC's microarray lab to delve into the causes and possible treatments of cystic fibrosis and asthma, better treatments for head and neck cancers, analyses of rare types of hemophilia, genetic links to lung cancer, and a new understanding of how people may be affected by mixes of toxins found in Superfund environmental clean-up sites.

        Dr. Nebert envisions a day when people could have their genetic code scanned like a bar code, so doctors could detect health problems long before serious symptoms appear. Such data could also help doctors know exactly which drugs may best treat health problems and which ones could cause harmful side effects.

        None of this would be possible without the advances in computers and robotic technology at work in the Kettering building, Dr. Nebert said. Yet, as powerful as that equipment may be, it has limitations.

        “These machines speed up work, but they cannot replace good, sound science,” he said. “You still have to interpret the results. You still have to have vision to develop solutions.”


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