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Miracle cells

Science | Cutting-edge researchers are making unheralded breakthroughs with stem cells from umbilical cords-but have a hard time breaking through the NIH funding wall.

Issue: "Johnny Carson: In memoriam," Feb. 5, 2005

LAWRENCE, Kan. - At the University of Kansas, Dr. Kathy Mitchell has two small labs that resemble high-school biology classrooms, just with more expensive equipment. In the smallest one, the size of a large supply closet, she pulls up a computer screen showing fluorescent dots in a sea of translucent green. She clicks her mouse, and the dots, which are stem cells, start to repair a gash in the green membrane, which is a layer of kidney cells.

Dr. Mitchell wants to test on animals what she has learned under the microscope about fixing kidney damage. It would bring her one step closer to healing the malfunctioning kidneys of people with leukemia, diabetes, and other disorders. She might someday save the healthcare system millions in dialysis costs, if she could just get a little funding for her research. The National Institutes of Health has shunned her grant applications three times. In one grant review, a fellow scientist commented that her stem cells come from tissue inside umbilical cords, not days-old embryos.

"We already have a good source of stem cells," the grant reviewer wrote. "Why do we need another?"

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But ethical questions surround the practice of extracting stem cells from embryos. While stem cells from embryos can produce all the tissue in the body, recovering them destroys the embryo. Doctors can extract stem cells from an umbilical cord with no negative impact on the infant.

Dr. Mitchell and Harvard researcher Dr. Denise Faustman say they have little to contribute to the ethical debate of using embryonic stem cells but much to contribute to medicine. Those contributions, however, have been ignored and even delayed because of the public fray over embryonic stem cells, they say.

Dr. Faustman also said she believes some research, such as her studies of the role of proteins in diabetes, has had little support or recognition because it goes against the popular belief that embryonic stem-cell research is the answer to curing diseases.

Science has always had its own popular culture, Dr. Faustman said. "It's pretty typical for research to go through phases where one discipline is emphasized over another," she said.

Frequently, the scientists supporting the popular culture are the ones deciding which research projects receive grants from the NIH. The NIH provides the bread and butter for medical research in the United States-more than $19 billion a year in grant funding since 2002. Before a scientist can tap into that money, a panel of peers must review and accept the scientist's research proposal. If a research proposal goes against the flow of popular science, it will have a hard time getting through the peer review process, Dr. Faustman says.

Drs. Mitchell and Faustman have both been frustrated by peer review. The problem, Dr. Faustman says, is that her peer reviewers also compete against her for different grants.

"The review is totally different than every other segment of the economy," she says. "If every time you wanted to open a dry cleaners you had to go to 90 percent of your competitors and get a consensus, what would be the chance you'd be able to open a profitable business?"

She says she would have abandoned her research several years ago had she not received a surge of funding from an unusual source. Lee Iacocca, former chairman of the Chrysler Corporation whose wife died from diabetes, funded a seven-year, $4 million research project for Dr. Faustman, with the promise of an $11 million fundraising campaign. Dr. Faustman used the initial money to test her ideas about diabetes in mice.

For almost 20 years, many scientists have hoped to cure diabetes by putting insulin-producing islet cells into the pancreas, replacing islet cells that were destroyed by white blood cells. Recently, they predicted that embryonic stem cells could be transplanted into the pancreas to produce the needed islet cells.

Dr. Faustman realized that such a treatment would be futile if white blood cells kept attacking the transplanted islets. She instead focused on why the white blood cells attacked the islets in the first place. She discovered a protein-processing defect was the cause and developed an easy way to treat it. The treatment cured the mice of Type 1 diabetes.

Successful experiments on mice are a critical step in getting approval to try a treatment on humans. One reason Dr. Faustman said she has not tried embryonic stem-cell research is because she has not seen research in which a diseased mouse was successfully treated with an embryonic stem cell.

"I was taught something pretty young, and that was: Don't follow the dogma, follow the data," she says. Despite the lack of mouse data, however, the NIH has set aside millions for research on embryonic stem cells.

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