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SAFER CANCER GENE THERAPY A twist on a well-studied gene therapy may more safely melt tumors. In clinical trials, a herpes simplex gene encoding the enzyme thymidine kinase (TK) is delivered, via a retrovirus vector, to dividing brain cancer (glioma) cells. The infected cells produce TK, which kills them when the patient takes the anti-herpes drug ganciclovir. But viral vectors are risky--they can enter the nucleus during cell division and disrupt genes. Thomas Wagner, a distinguished professor of molecular and cellular biology at Ohio University in Athens, with researchers at Progenitor Inc. of Menlo Park, Calif., added the TK gene to a plasmid (a ring of DNA) called T7 (X. Chen et al., Human Gene Therapy, 9 :729-36, 1998). The T7 vector never enters the nucleus, and it continuously produces the enzyme. "Expression is transient, just long enough to do what you want it to and it's gone. So it is safer than a viral vector," says Wagner. The researchers injected T7 into human bone tumors growing in 10 nude mice. Tumors shrank in three mice and vanished in three others. Wagner thinks the approach could be used one day to treat breast cancer. "A doctor would image the tumor, then inject [the vector] into multiple places under local anesthesia, then give the patient ganciclovir for two weeks," he explains. Although the vector does not specifically target dividing cells, this may be the key to its success--it can also kill cells at a tumor's core that do not divide often because they lack nutrients. These cells, Wagner hypothesizes, cause tumor recurrences. ELSI COMES TO TOWN Perhaps because of the area's long winters in the days before El Niño, Vermont has a tradition of town meetings and library-held book clubs. A new endeavor funded by the Human Genome Project's Ethical, Legal and Social Implications (ELSI) program is about to hit the state's town-meeting circuit. "Most ELSI programs before this had geneticists speaking to geneticists, ethicists speaking to ethicists, or--in a really radical setup--geneticists speaking to ethicists. The larger public hasn't really been involved in discussions of Human Genome Project issues that have a large social context," explains Alan Guttmacher, principal investigator of the program in Vermont and director of the Vermont human genetics initiative at the University of Vermont College of Medicine in Burlington. The ELSI program will have three components. Beginning next month, two-day retreats will be held for specific groups, such as clergy, educators, lawyers, politicians, and business leaders. "The retreats will include lectures on science and ethics, small-group discussions on readings, and talking about how to use what the participants learn in their work," says Guttmacher. In the second phase of the program, retreat attendees will return to their communities and lead discussions with support from 20 participating scientists. The third component will be larger town meetings held at 10 sites around the state. Concludes Guttmacher, "The object is not to get Vermonters to formulate answers, but to get people thinking about the questions." BRCA1 IN GENERAL Two separate studies conclude that BRCA1 mutations in women with breast cancer are less prevalent than previously thought, meaning general population screenings for the gene mutation may be unnecessary. One study--by Kathleen E. Malone, a professor of public health at the Fred Hutchinson Cancer Research Center in Seattle, and colleagues--found the mutation in 12 (6.2 percent) of 193 subjects under age 35 who had breast cancer (K.E. Malone et al., JAMA--Journal of the American Medical Association, 279 :922-37, 1998). "Women with a family history of breast cancer have less cause for worry about their chance of carrying a mutation," Malone states. She notes that earlier studies of BRCA1 populations, which show mutations in as many as 60 percent of the population, may be skewed, since they were drawn from pools of high-risk families with multiple early-onset cases of breast cancer. Finding solid breast cancer predictors may be more elusive than pinpointing one or two genes. A study with a different population yielded the same conclusion. In that study, only three of the 211 breast cancer patients had the BRCA1 mutation (B. Newman et al., JAMA, 279 :915-21, 1998). "The whole idea of testing is being oversold," investigator Beth Newman, a professor of epidemiology at the University of North Carolina, tells The Scientist. More testing may lead to more instances of women undergoing mastectomies to prevent a disease that may never have materialized. Newman maintains the real issue may be fear: "Women are afraid of breast cancer. It is a common disease. It is a life-threatening disease. It is a scary disease.'" The two studies may not offer any reassurance, since they indicate that multiple factors beyond BRCA1 lead to breast cancer. "Really, all we can do is live with uncertainty," Newman concludes. FOUR-EYED FOWL: Prism-lensed glasses separate owls' auditory and visual neural maps. SHADES OF MEMORY Owls wearing prism-lensed glasses have given science a new look into the plasticity of the brain. The glasses alter the memory maps, drawn from sights and sounds, that help owls navigate. The prisms in the goggles separate normally overlapping neuronal signals, resulting in an out-of-register mental photograph, with visual traces separated from auditory ones. In a series of experiments, younger owls, which had worn the glasses six months earlier in their life, once again adapted by shifting the neural locations of their vision to match the auditory signals. Owls that had never worn the glasses had difficulty adjusting; the two maps remained separated (E.I. Knudsen, Science, 279 :1531-3, 1998). Eric I. Knudsen, a professor of neurobiology at Stanford University School of Medicine, explains that he was surprised that the owls that had worn the glasses when they were younger quickly adjusted, since six months is a long time in the life of an owl. "The most remarkable aspect of this study for me was how long these patterns of mapping persisted," Knudsen remarks. "The general rule is, whatever you don't use, you lose." Knudsen suspects that the owls with prior prism experience had grown extra neuronal connections when they first adapted to the goggles at a younger age: "Something is there that allows the brain to relearn." He plans to conduct another set of experiments this spring to test his hunch that the owl's ability to relearn has an anatomical origin. A POUND OF CURE: NCI's Demetrius Albanes and an international team of researchers found that male smokers who took daily doses of vitamin E were significantly less likely to develop prostate cancer. 50 MG OF PREVENTION A recent study by the National Cancer Institute (NCI) and the National Public Health Institute of Finland shows that vitamin E could significantly reduce the risk of developing prostate cancer (D. Albanes et al., Journal of the National Cancer Institute, 90 :440-6, 1998). Demetrius Albanes, a senior research investigator at NCI's Division of Clinical Sciences, and an international team of researchers found that male smokers who took 50 mg of vitamin E every day for five to eight years were 32 percent less likely to develop prostate cancer and 41 percent less likely to die from it. "You can't help but be excited by these results," Albanes says. "If the study is corroborated by another large trial, then we have found a relatively simple and economical way to fight one of the biggest killers from cancer in the U.S." Prostate cancer is the most common cancer afflicting men and will kill almost 40,000 in 1998, according to projections by the American Cancer Society. But Albanes warns that men should not regard the study as a cue to start taking massive doses of the supplement. "Our data are very promising, but further studies are needed before any such recommendation should be considered," he explains. He says future investigations should include nonsmokers and a broader spectrum of racial and ethnic groups. The vitamin E study evaluated data from more than 29,000 white male smokers in Finland who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Earlier analyses of data from this trial showed that men who took supplemental doses of beta-carotene, a form of vitamin A, had an increased risk of lung cancer (D. Albanes, JNCI, 88:1560-70, 1996). HOMAGE: NFID president Herbert Dupont, right, and vice president Susan Rehm present vaccinologist Maurice R. Hilleman with the Maxwell Finland Award for Scientific Achievement. MORE THAN A NAME The National Foundation for Infectious Diseases (NFID) honored Maurice R. Hilleman, director of the Merck Institute for Therapeutic Research of the Whitehouse Station, N.J.-based Merck and Co. Inc., for a lifetime of victories in the war on disease. At ceremonies in February, Hilleman, who also is an adjunct professor of pediatrics at the University of Pennsylvania, received NFID's Maxwell Finland Award for Scientific Achievement. United States Army General Colin L. Powell also was honored for his work with at-risk youth with NFID's Jimmy and Rosalynn Carter Award for Humanitarian Contributions to the Health of Humankind. Vaccinologist Hilleman's five decades of research led to the development and licensing of more than 40 vaccines, including those for chickenpox, hepatitis A and B, pneumococcal pneumonia, meningococcoal meningitis, and Marek's disease. His vaccine for mumps earned him the most fame. In 1963, his daughter, Jeryl Lynn Hilleman, contracted mumps. Hilleman collected specimens from her throat and used them to develop the mumps vaccine. His daughter was immortalized when Merck named the virus strain used in the vaccine Jeryl Lynn. It has been in use for more than 30 years and has nearly eliminated the threat of mumps through its use in Merck's combination measles-mumps-rubella vaccine. But one effect of the vaccine could not have been predicted by Merck researchers. "After the introduction of the vaccine, we began to see lots of girls named Jeryl Lynn," Hilleman recalls. "My wife and I really invented this name. So this was an unexpected satisfaction for us." IN THE MONEY Science Service Inc., the nonprofit organization that owns the Science Talent Search annual competition for high school seniors, may be based in Washington, D.C., but it's also on Cloud Nine these days. When the former Westinghouse Electric Corp. (now CBS Corp.) of Pittsburgh announced it would end more than a half-century of sponsoring the contest, 76 applications to become the new sponsor arrived, many of them from multinational players in media, finance, and natural resource development. "It was a very difficult choice--the longest board meeting in the history of Science Service," says Ann Korando, the organization's director of development and public relations. On March 26, the nod went to Intel Corp., a Santa Clara, Calif.-based manufacturer of computer chips, boards, systems, and software. Korando says a number of the losing bidders are now meeting with Science Service to develop or improve contests or other science programs for them. Intel's winning package for the Science Talent Search includes a big boost in prize money. Starting next year, a total of $330,000 in scholarships will be awarded to the winner and finalists, compared with $205,000 this year. The 1998 first-place winner, announced on March 8, is 17-year-old Christopher Colin Mihelich of Carmel, Ind. Motivated by questions in theoretical physics, he studied certain properties of polynomials having applications to geometry and combinatorics. The top student in his class, with perfect scores on his SAT exams, he wants to attend Harvard University and eventually work as a number theorist. PLANT ESTROGENS HELP A trio of recently completed studies at Wake Forest University add to mounting evidence that consumption of plant-based phytoestrogens will lower cholesterol and may protect against atherosclerosis. The study results, all of which are being prepared for publication, were announced at the annual meeting of the American Heart Association on March 20 in Santa Fe, N.Mex. One of the studies indicates that the natural compounds in soy called isoflavones can reduce cholesterol counts. In the double-blinded study, 156 patients with moderately elevated cholesterol levels were randomly assigned soy drinks either with or without isoflavones, or a placebo. Those who received isoflavones experienced an average 10 percent reduction in total cholesterol over nine weeks. The other two studies were financed by the National Heart, Lung, and Blood Institute. The results of those two studies, involving cynomolgus monkeys fed a high-cholesterol diet, indicate that soybean estrogens may provide protection from atherosclerosis in both abdominal and cerebral arteries equal to that provided by traditional estrogen replacement therapy. Mary Anthony, a research assistant at the university's Bowman Gray School of Medicine who headed one of the projects, notes that over-the-counter phytoestrogen pills are now available in some specialty food stores. "We're very concerned about that, because we have found that some phytoestrogens extracted out of soy have no clinical value," she says. Her next research project will be to examine the effects of such pills on prostate cancer and cardiovascular disease in male monkeys and humans.

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April 1998

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