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STATE OF THE ART: Washington University's Marc R. Hammerman turned his wife Nancy's idea into reality when he transplanted developing kidneys into adult rats. ARTFUL SCIENCE The skilled hands of a surgeon can only do so much to assure the success of an organ transplant. Despite great advances in medicine, the body's immune system remains the ultimate judge of whether to accept or reject. But researchers at Washington University (WU) in St. Louis have found a promising method for growing kidneys that are much less likely to be rejected by the body's immune system. Marc R. Hammerman, the Chromalloy professor of renal diseases at WU, and a team of researchers successfully placed metanephroi, or developing kidneys, in adult rats. When carefully placed in rat membranes and tissues supporting abdominal organs, the kidneys grew to a third of the size of an adult kidney. Hammerman and the group of scientists may have conducted the experiments, but real credit for the idea goes to his wife, Nancy Hammerman, who is an art teacher. She suggested transplanting developing kidneys to avoid immune system rejection after hearing a lecture on transplantation by her husband in London. "A couple days later while we were touring in the country, she came up with the idea of transplanting metanephroi," Hammerman recalls. "Of course, my wife is not a scientist, but an art teacher. So I initially thought that this was the kind of idea that would occur only to a nonscientist who isn't familiar with all of the problems of transplantation. But I thought we might as well give it a try and, by God, it worked. The biggest surprise was that there was little, if any, rejection to the transplanted organ." Hammerman says there are a number of obstacles that must be overcome before the process can have clinical utility. For example, metanephroi have only about 1 percent of the functionality of a natural kidney. Once functionality can be increased to about 10 percent to 12 percent, then researchers will be able to keep animal models alive with the transplants. In the next six months, Hammerman expects to try the procedure on pigs, a close animal model to humans. Photo by: Chris Fritsen LIFE ON ICE: Just below this encampment of scientists on Antarctica, life thrives despite cold temperatures and a thick tomb of ice. LIFE SIX FEET UNDER . . . AND HIGH ABOVE? Where you least expect it, life can thrive. That's what a group of U.S. researchers found on a recent expedition to Antarctica, one of the most inhospitable environments on the planet. They discovered bacteria thriving in colonies embedded in about six feet of ice on the frozen lakes of the McMurdo Dry Valleys of Antarctica. Here, less than four inches of precipitation fall each year, and the average temperature hovers at about -68° Fahrenheit. But in this frozen desert, cyanobacteria proliferate from time to time. Solar heat filtered through the ice allows small pools of water to melt around soil particles trapped beneath the ice, and within an hour dormant microbes are reanimated. As one might expect of this polar dweller, cyanobacteria are resilient and self-sufficient. They can survive harsh seasonal thaws and require only a little bit of light, phosphate, nitrate, and other minerals to survive. The discovery of life deep within the ice was almost accidental, according to Chris Fritsen, a postdoctoral student in biology at Montana State University at Bozeman, who will soon assume a faculty post at the University of Nevada at Reno. The lake had been frequented by researchers since the 1960s and recent studies by MSU professor of biology John C. Friscu have focused on gas signatures detected in the lake. Some of these were enhanced signatures, which suggested that life possibly could exist in the lake. "That finding alone was surprising," Fritsen says. "We had known that life existed in sea ice, but this was an entirely different environment. From that point on, we really focused on finding microbial life in the frozen lake." Fritsen says the discovery is significant because it shows how life could possibly develop on heavenly bodies with similar cold environments. "These microbes are proof that life can develop in a hostile climate like those you would find on Mars and Europa," he explains. "But a number of factors are needed for life to develop, and anything I can say is pure speculation." The research team also included James L. Pinckney and Hans Paerl of the University of North Carolina, Stephen J. Giovannoni of Oregon State University, and Christopher P. McKay of NASA's Ames Research Center. THAT FRESH BREAD AROMA Finally, there's a cure for that foul-smelling lab. In a recently published paper (J.D. Stewart et al., Journal of the American Chemical Society, 120 :3541-48, 1998), scientists from the University of Florida and the University of New Brunswick, Canada, describe a newly created designer yeast that not only yields the enzymes chemists need for routine chemical reactions but, in so doing, leaves labs smelling like fresh baked bread. "We were the first to actually design baker's yeast strains to do specific chemical reactions," explains Jon Stewart, an assistant professor of chemistry at UF. Enzymes commonly come from inconvenient sources such as human livers and bacteria. But in this new procedure, Stewart and his colleagues inserted the gene for the useful enzyme Cyclohexanona monooxygenase into ordinary baker's yeast so that the enzyme would be expressed. After a chemical conversion occurs in the recombinant yeast, the cells are centrifuged and the desired product extracted. According to Stewart, the biggest advantage of the system is that it allows for the regeneration of expensive and unstable co-factors, helper molecules that enzymes need in order to catalyze reactions. "From an experimental standpoint," says Stewart, "for the person who's doing the organic reaction, there's very little work involved--just put in some yeast cells and let it go." Stewart does acknowledge one disadvantage: "There are a few kinds of substrates we've found that kill the yeast. And if that happens, then you're finished." Although this strain of yeast is available to all interested chemists, Stewart is currently investigating ways to create designer yeasts suitable for industrial-scale chemical reactions. PLOTTING THE PATH OF C Scientists finally may know how plants make vitamin C. L-ascorbic acid is vital for human health, yet human bodies can't produce it (that's why it's called a VITAmin). Thank goodness for plants--up to 10 percent of the soluble carbohydrate in leaves is ascorbate, which protects chloroplasts from the oxidative effects of light. Vitamin C is one of the main reasons humans eat leafy vegetables and fruit. However, nobody has been able to figure out how plants synthesize this relatively simple six-carbon molecule. According to Clanton Black of the University of Georgia, an authority on plant metabolism, ascorbate synthesis is "one of the last big unanswered questions." Pending confirmation, a team from the University of Exeter in England has solved the mystery (G.L. Wheeler et al. Nature, 393 :365-369, 1998). Using barley, peas and Arabidopsis thaliana, the researchers identified several sugars in the biosynthetic pathway, plus a new plant enzyme that converts L-galactose to L-glucono-1,4-lactone, the immediate precursor of ascorbate. Since L-galactose is not abundant, the group backtracked and discovered that it forms from ubiquitous D-glucose-6-phosphate via fructose and mannose intermediates. The switch from D to L configurations requires an epimerase enzyme. Because "ascorbate is probably the major fate of mannose in mature [i.e. nongrowing] plant cells, [the new pathway represents] a significant and previously unrecognized flux of carbon," says Exeter's Nicholas Smirnoff. Interestingly, animals use different sugars to make ascorbate (some species, including humans, lack the last enzyme in the pathway), and invert the carbon skeleton to switch configurations. William Brinkley NEW FASEB PRESIDENT The Federation of American Societies for Experimental Biology (FASEB), a coalition of 17 scientific, biomedical and life science societies, has inaugurated a new president. On July 1, former FASEB vice president William R. Brinkley began his term as president of the 56,000-member federation, a position he will hold for one year. Brinkley, the vice president for graduate sciences and dean of the Graduate School of Biomedical Sciences at Baylor College of Medicine in Houston, Texas, has been a member of several National Institutes of Health advisory panels and currently serves on the Association of American Medical Colleges (AAMC) Advisory Panel on Biomedical Research. As FASEB President, Brinkley will meet frequently with members of Congress, federal administration officials in research agencies, and leaders of other scientific organizations to discuss issues of concern to scientists. Referring to the recent proposal in Congress to double NIH funding in the next five years, Brinkley emphasizes that the major issue facing FASEB members continues to be the availability of research dollars. "I feel optimistic that we're going to be able to continue to get major [funding] increases for health research, and that's my goal," he maintains. Brinkley's first order of business, however, will be to evaluate FASEB's public policy, governance policies, financial affairs policies, and admission and membership policies at a special meeting of the FASEB board this September. He also hopes to "expand FASEB's focus on basic research to the clinical arena." Suggesting, "it's a good time to be coming in as president," Brinkley says his only major concern is a "happy one." He cautions that a continued sharp increase in membership could make FASEB more difficult to govern. DOUBLE TROUBLE FOR TUMORS? Synergy and serendipity may provide another weapon against cancer. Ralph R. Weichselbaum of the University of Chicago was initially conducting experiments in mice to see how tumor necrosis factor (TNF) interacts with radiation, when a colleague suggested he try pairing the anti-angiogenesis agent angiostatin with radiation instead. "Lo and behold, we got a synergistic effect," Weichselbaum comments, adding that the combined approach killed more tumor cells than either radiation therapy or angiostatin administration alone (H.J. Mauceri et al., Nature, 394 :287-91, July 16, 1998). Late last year, a team led by M. Judah Folkman, of Children's Hospital of Boston, demonstrated angiostatin and a similar agent, endostatin, as potent tumor killers in mice (T. Boehm et al., Nature, 390 :404-7, 1997). Angiostatin shrinks tumors by stopping blood vessels from developing, thus denying the tumor nutrition. Weichselbaum hypothesizes that adding radiation to the mix fights different parts of the tumor. "My suspicion is that angiostatin targets the vessels, and the radiation targets the tumor cells." He also suspects that the radiation makes the blood vessels' endothelial cells more susceptible to angiostatin. Weichselbaum notes that the combination doesn't cause any increase in toxicity than either treatment alone, suggesting that it may be viable for humans. The approach echoes other attacks on cancer that use both chemotherapy and radiation. "Nothing works by itself," Weichselbaum concludes. "Even angiostatin by itself isn't curative." Rockville, Md.-based biotechnology company EntreMed Inc. and Bristol-Myers Squibb Co. of New York City are developing both angiostatin and endostatin for clinical trials.

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July 1998

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