Notebook

Putting the Freeze on Menopause In Defense of Pesticides Pushing Drug Discovery Race and Health Tumor Stopper Jewel of a Specimen Birth of a Journal Conservation Wins GOLDEN EGG: Michael Tucker caused a media stir when he facilitated the birth of twins using frozen eggs. The birth of twins rarely makes national headlines. But this pair, whose birth was announced on the front page of the New York Times on October 17, sparked a flurry of media attention. A team of researchers at Reproductive Biology Associates (RBA), a private practice in Atlanta, report that a woman suffering from early menopause gave birth to the twins from thawed and artificially inseminated eggs. The new technique has generated excitement among fertility researchers and doctors, as it could effectively shut off a woman's biological clock by allowing women to harvest and store their eggs for later use, according to Michael Tucker, an embryologist and the team's lead investigator. While sperm and embryos easily freeze and thaw, doctors could not use frozen eggs in the past because the thawing process rendered the external membrane impregnable by sperm. Tucker's team overcame this by using a new insemination technique whereby the sperm is injected directly into the egg. By carefully monitoring both the freezing and thawing processes, they avoided another major pitfall in using frozen eggs- chromosomal damage to the egg. Furthermore, by using frozen eggs, doctors can avoid the growing ethical concern of what to do with excess frozen embryos. Current fertilization techniques produce from 18 to 20 unused embryos, according to Tucker. "Embryos are not the kind of thing you really just throw away," he says. "With our technique, the ethical question of disposal is avoided along with the high cost of indefinitely storing them." A report on the technique was recently submitted to Fertility and Sterility for peer review, according to Graham Wright, an embryologist at RBA. IN PRAISE OF PESTICIDES: Bruce Ames argues that eliminating man-made chemicals from food and the environment does little to prevent cancer. Two University of California, Berkeley, researchers have called for a sweeping reexamination of strategies in disease prevention that name pesticides and other synthetic chemicals as causes of cancer. Bruce M. Ames, a professor of biochemistry and molecular biology, and Lois Swirsky Gold, director of the Carcinogenic Potency Project at the National Institute of Environmental Health Studies at UC-Berkeley, argue that the $140 billion spent annually to keep synthetic chemicals out of food is unnecessary if the prevention of cancer is the goal (B.N. Ames, L.S. Gold, FASEB Journal, 11 :1041-51, 1997). They write that human cancer risks from chemicals cannot be assessed by high-dose rodent tests and that most pesticides, natural or synthetic, are potential carcinogens at such high doses. Ames and Gold argue that there is no evidence supporting the view that synthetic chemicals are a major cause of cancer. "If you attempt to eliminate pesticides, you will increase cancer rates by driving up the cost and reducing the consumption of fruits and vegetables," Ames says. "Cancer-prevention efforts are best aimed at known strategies like eliminating smoking and increasing the consumption of fruits and vegetables." In-house research organizations of the top 20 revenue-producing pharmaceutical companies in the United States did not bring a single new product to market from 1990 to 1994, according to a new industry study from Chicago-based Andersen Consulting. In the period examined, each company on average brought 0.45 new product to the market, says Pradip Banerjee, a partner at Andersen who orchestrated the report, entitled "Reinventing Drug Discovery: The Quest for Innovation and Productivity." (Executive briefings on the report can be obtained by contacting Joanne L. Beardslee at Andersen Consulting; E-mail address: joanne.l.beardslee@ac.com.) Banerjee argues that pharmaceutical companies must adopt new strategies and bring more drugs to market to remain competitive into the 21st century. "Most new pharmaceutical products have been developed in small, independent laboratories and at educational institutions only to be licensed to the major pharmaceutical firms," Banerjee explains. "There is no correlation between the size of the research organization and their productivity. Productivity seems to be determined by the organization of the research division, especially how well they use new technology and information systems." Companies like Glaxo Wellcome Inc., based in Research Triangle Park, N.C., already have reexamined their research strategies. As part of its Redesigning Drug Discovery Program, the company increasingly is using robotics for drug screening, bioinformatics databases for discovering new correlations, and multidisciplinary teams for developing research strategies for disease groups. A highly cited Glaxo Wellcome discovery providing possible molecular evidence linking obesity, diabetes, and heart disease was a product of this new research approach, according to Jürgen Lehmann, a member of the research team (Hot Papers, The Scientist, Oct. 27, 1997, page 12). A comprehensive look at health differences among racial and ethnic groups suggests no single factor but does strengthen the argument that race is not a biological definition. The report, Racial and Ethnic Differences in the Health of Older Americans (Washington, D.C., National Academy Press, 1997), emerged from a workshop hosted by the National Research Council (NRC) and funded by the National Institute on Aging (NIA). Factors like socioeconomic status and access to health care have more to do with health than race, maintains the report's coeditor, Linda Martin, vice president for research development at RAND, a nonprofit public policy research institute in Santa Monica, Calif. In models controlling for both race and class, "race pretty much disappears," says Martin. Differences the studies found included death rates for young blacks that were twice as high as for young whites. That gap between races closes and eventually disappears as the groups age. The study also indicated that blacks have poorer access to health care, a factor that could contribute to their illnesses later in life. Getting more explanations for health differences among these groups could prove difficult because of gaps in nationally representative data, a lack of full measures to compare life histories, and legal limits to linking survey data to genetic information. Martin also notes that intermarriage between different races blurs boundaries and makes it difficult to pinpoint people as belonging to one group or another. The report is available on the Internet at http://www.nap.edu/readingroom. Targeting the gene mitogen-activated protein kinase kinase 4 (MKK4) may prevent tumors from forming (see Hot Papers, page 12). Researchers suggest that the gene acts as a tumor suppressor by signaling damaged cells to commit suicide. During in vitro tests of human cell lines, damaged MKK4 genes did not tell bad cells to undergo apoptosis (D. Teng et al., Cancer Research, 57 :4177-82, October 1997). "By preventing apoptosis in an injured cell, you may be allowing an injured cell to live," says David H.F. Teng, a researcher at Myriad Genetics Inc. in Salt Lake City. Injured cells that lack the brakes MKK4 provides through apoptosis not only live but also prosper, dividing out of control, ultimately resulting in cancerous tumors. The gene's role in cell regulation makes it a good target for developing therapeutic anti-tumor development agents, says Teng. "If a damaged MKK4 gene's function could be restored through gene replacement or augmentation, one primary step leading to cancer might be eliminated." One key may be gaining a better understanding of the signaling mechanisms. MKK4's signaling mechanism appears to be a linear reaction, but there may also be some crosstalk between other signaling pathways, which could complicate development of a therapeutic agent. The gene is known to be involved in colon, breast, pancreatic, and testicular cancer. RESEARCH GEMS: Ben and Kathy Stout display their jewelry made from the pupa cases of caddisflies. At the National Association of Biology Teachers annual convention in October in Minneapolis, visitors flocked to a small booth offering unusual jewelry. The colorful, elongated shapes incorporated into bracelets, necklaces, and earrings are the pupa cases of caddisflies. Kathy and Ben Stout run Wildscape Inc., from their Wheeling, W.Va., home, nurturing caddisflies in a "simulated stream ecosystem" -pools of water in their garage. Ben, an associate professor of biology at Wheeling Jesuit University, had worked with caddisflies for 15 years. The insects, residents of Appalachian mountain streams, engage in a behavior called casebuilding, in which they deposit silk around small stones to fashion cocoons. Kathy had thought of turning the cocoons into earrings-and then got the idea to recruit the bugs to help her by supplying gemstones as raw materials. "The first experiment, in 1995, used multicolored aquarium gravel. When I realized that the little guys would use this material, I started buying little pieces of rock, like picture jasper, tiger eye, and malachite, and cutting them up," she says. The caddisflies use the gemstones to make cocoons, which the Stouts and their student helpers convert into jewelry. A rewarding aspect of nurturing the caddisflies is expanding awareness of ecology. Says Ben, "I have been able to teach more people about the importance of these organisms through the jewelry than I have through all of my research and teaching." For more information, see www.wildscape.com or send E-mail to kathy@wildscape.com. LOFTY GOALS: The law and business sectors of biotech have a new journal that aspires to New England Journal of Medicine editorial standards. The fast-changing field of biotechnology has a new, peer- reviewed journal that will focus on law and business issues. Aptly titled The Journal of BioLaw & Business, the quarterly is published by New York-based Aspen Law & Business. The first issue appeared in October. "Basically, the whole premise is to create a biotechnology law and business journal that does for those sectors what the New England Journal of Medicine does for the medical sector," says Michael Malinowski, manager of government affairs for the Massachusetts Biotechnology Council Inc. He coestablished and coedits the journal with Robin Blatt, who holds R.N. and MPH degrees and writes and lectures on public health genetics. Malinowski promises articles every issue on business and investment opportunities, legal and ethical questions, and plenty of case histories. Among the topics in the 104-page first issue are the social implications of investing and developing biotechnology products, "socially responsible" investment options, and the latest genetic modification regulations in Europe. The journal's editorial advisory board includes members from the United States, Europe, and Australia with expertise in law and policy, business, editorial work, and the life sciences. They hail from such diverse institutions as the University of Paris; Cambridge, Mass.-based Genzyme Corp.; New York-based Pfizer Inc.; and the High Court of Australia. Contributors include biotechnology company CEOs, attorneys, and government agency directors. Malinowski says European circulation will be emphasized because "biotechnology is newer in Europe, and they're looking for guidance." For subscription information, call (800) 638-8437. In 1963, a young American biologist named Daniel Hunt Janzen was doing field research in Mexico when he learned of a National Science Foundation-funded course on tropical biology to be taught in Costa Rica. He took the course, and his conservation biology research in the tiny country since then has now been recognized by the $430,000 Kyoto Prize, scheduled to be presented on November 10 by Japan's Inamori Foundation. Janzen, the Thomas G. and Louise E. DiMaura Term Professor of Conservation Biology at the University of Pennsylvania, acquired 250,000 acres of low-grade coastal ranch and farmland in Costa Rica in 1985 and began replanting the tropical dry forest destroyed there centuries ago. The Costa Rican government set aside the area as a national park, where Janzen still spends eight months annually. He established a comprehensive biodiversity inventory and wildlands management system, a key project of which is "carbon fixation," using trees to absorb pollutants from burning of fossil fuels for energy. "I view my work as a pilot project, something to generate interest and action from large companies in the big countries," he says, "but it's not going to happen until the U.S. government steps up to the plate and begins to contribute, because we are the largest carbon-producing nation in the world." Other 1997 Kyoto Prize laureates are French composer Iannis Xenakis and the joint developers of the world's first microprocessor, Federico Faggin of Italy, Marcian Edward Hoff, Jr., and Stanley Mazor of the United States, and Masatoshi Shima of Japan. Janzen plans to use his cash award to set up an endowment for the conservation area.

Notebook

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November 1997

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