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BARKING UP THE SAME TREE Ralston Purina announced Jan. 12 an initiative to unite efforts to map the dog genome, consolidating data and planning for more. Most markers accumulated so far hail from the Baker Institute at Cornell University. The linkage map, currently consisting of about 400 markers, provides signposts along the 78 chromosomes to direct sequencing efforts. At the heart of the project are blood samples from 16 multigenerational canine families. The dog genome hardly reflects natural evolution--today's 129 breeds have been artificially selected over the past 250 years from a few ancient types. The 16 families are purebreds, but the individuals studied have the most variable markers. The St. Louis-based company is developing a Web site for breeders to predict transmission of undesirable traits, as well as for geneticists to use in basic research. Ralston Purina, as the world's largest manufacturer of dry dog food, has its eye on applications. Says senior scientist Steven Hannah, "The genome map will also lead to understanding how a gene is expressed. How can we predict modifications in expression from the environment, such as nutrition? By knowing what a dog is genetically, we may be able to provide the environment that will minimize risk of disease and lead to optimal longevity." STEM CELL SHUFFLE After a recent U.S. Department of Health and Human Services ruling that a federal ban on human embryo research does not apply to embryonic stem cells, the National Bioethics Advisory Commission has shifted its debate. The movement has been from discussing whether the government should fund stem cell research to analyzing what stem cell sources and uses may be appropriate, NBAC member R. Alta Charo, professor of law and medical ethics at the University of Wisconsin, Madison, notes. The commission will present their recommendations to President Bill Clinton by June, but it remains unclear whether the National Institutes of Health (NIH) will begin funding stem cell research sooner. NIH Director Harold Varmus asked for earlier guidelines at the Jan. 19 meeting. "But [Varmus] didn't say whether or not he would wait for it," Charo comments. NBAC member Thomas H. Murray, director of Case Western Reserve University's Center for Biomedical Ethics, agrees that NIH may move quickly on funding stem cell research--especially since privately funded research has forged ahead. Geron Corp. of Menlo Park, Calif., funded two studies that successfully cultured the pluripotent cells (P. Smaglik, "Stem Cell Scientists Caution: Clinical Applications Remain Years Away," The Scientist, 12 [23]:1, Nov. 23, 1998). Charo and Murray note that even opponents of most embryonic research, including Richard M. Doerflinger, associate director for policy development at the Secretariat for Pro-Life Activities, National Conference of Catholic Bishops, find some stem cell sources acceptable. At an earlier hearing, Doerflinger opposed funding sources such as tissue from aborted fetuses or from extra embryos derived for in vitro fertilization--sources the Geron- supported researchers used (E. Russo, "Hearing Sets Stage for Stem Cell Funding Debate," The Scientist, 13 [1]:3, Jan. 4, 1999). However, Geron, too, is searching for more socially acceptable stem cell sources. OPIATES KILL CELLS New insights into the way opioids trigger cell death may translate into the development of better painkillers and a better understanding of how the nervous and immune systems interact. Researchers from the Jerome H. Holland Laboratory for Biomedical Sciences, American Red Cross in Rockville, Md., unexpectedly found that opioids induce apoptosis by triggering the expression of a receptor on the surface of cells called Fas (also known as CD95 or APO-1), and then binding to the Fas ligand (FasL) (D. Yin et al., "Fas-mediated cell death promoted by opioids," Nature, 397 :218, Jan. 21, 1999). Scientists have known for some time that large doses of opioids, whether produced endogenously from severe exercise or placed into the body for recreational or medicinal purposes, suppress the immune system. "Many studies have speculated that opioids may interfere with the signal transduction process from T-cell and B-cell receptors," says Holland Laboratory scientist and senior author Yufang Shi. "But what we actually found is that opioids make cells die." In their pilot experiment, Shi's lab treated human blood lymphocyte cell lines with the opioid morphine in vitro. Two hours after treatment, Fas expression increased, but did not cause cell death. Guessing that the Fas ligand (FasL) was necessary, researchers incubated morphine treated cells that expressed FasL and subsequently observed cell death. In follow-up in vivo experiments, however, investigators found that morphine alone triggered apoptosis in mice. They concluded that cells in the body such as macrophages, which are known to express FasL, naturally provide the ligand and help trigger cell death. Shi hopes future work will determine exactly how Fas-induced apoptosis is mediated and whether Fas expression is, in fact, sufficient to cause cell death; it may also be possible, says Shi, that the opioid actually makes the cell more sensitive to the death signal delivered by Fas. Such studies could lead to better opioid painkillers with fewer side effects. DOUBLING TROUBLE? Like last year, President Bill Clinton neglected to mention impeachment during the State of the Union Address. But unlike last year, the president failed to specifically back federal funding for biomedical research. Despite the lack of such explicit support by the chief executive, William R. Brinkley, Federation of American Societies for Experimental Biology (FASEB) president, remains confident that FASEB's fiscal year (FY) 2000 recommendations--unveiled during a press conference the day after Clinton's historic speech--will be met. The recommendations include an additional 15 percent for both the National Science Foundation and the National Institutes of Health (NIH). A 15 percent increase for NIH would continue the general goal of doubling biomedical R&D in five years, a trend started in FY 1999 with a 15 percent hike in the NIH budget. Signs from the White House aren't promising, though. In a telephone interview, one White House science official, who spoke on the condition of anonymity, called FASEB's recommendations "overly optimistic." However, Brinkley remains undaunted by hints that the White House will soon unveil R&D figures below FASEB's wishes. He noted that last year, Clinton recommended an 8 percent increase for NIH, but eventually agreed to the 15 percent hike Congress included in its "omnibus" budget bill. Heavy lobbying on Capitol Hill could accomplish the same goal this year. "It was not a fluke that it happened last year," Brinkley commented, noting that several prominent Democrats and Republicans support the goal. The president is scheduled to present his FY 2000 budget figures early this month. EPILEPSY PROVES COSTLY Epilepsy costs the nation $12.5 billion annually, according to preliminary findings in a new report issued by the nonprofit Epilepsy Foundation of America (EFA). The figure is extrapolated from an EFA-sponsored study of direct and indirect costs that uses data from actual cases (S. Bunk, "Epilepsy Innovations Mount, But Key Mysteries Remain," The Scientist 13 [2]:1, Jan. 18, 1999). The report, the first national one on epilepsy since 1978, bases its cost estimates on figures available up to 1995. About 14 percent of the total annual cost, or $1.7 billion, is direct medical expenditures. The remainder is indirect costs, primarily related to such employment factors as lost wages from people who have withdrawn from the labor market, reduction in earnings, and home production losses. The report estimates that one-fourth of the 2.3 million Americans who have epilepsy, or almost 600,000 patients, have seizures that do not respond to available therapies. "I think epilepsy suffers from being seen as a niche disorder," charges EFA president Jeanne Carpenter. The federal government allocated $76 million to epilepsy research this year, up from $46 million in 1992, but she would like to see that figure rise. "More funding for epilepsy research on a national basis would go a long way to reducing some of these costs," she says. "Epilepsy needs real breakthrough research, and that's expensive." Carpenter, a Washington, D.C.-based lawyer who herself suffers from epilepsy, believes that genetic studies in particular need a financial boost. "It's been a virgin area in epilepsy research." Paul Greengard ALZHEIMER'S AWARD Paul Greengard, head of the laboratory of molecular and cellular neuroscience at Rockefeller University in New York, received this year's prestigious Metropolitan Life Foundation Award for Medical Research in Alzheimer's Disease (AD)-- a $200,000 grant for his institution and a $50,000 personal award--at a luncheon in Washington, D.C., on Jan. 25. Greengard's career of almost 50 years has included numerous major discoveries in Alzheimer's research. He and his colleagues were the first to elucidate protein phosphorylation, one mechanism by which proteins are coaxed into forming harmful, Alzheimer's-related beta amyloid proteins in the brain; the first to find synapsins, synapse-forming compounds that may lead to AD treatments that mimic synapsin behavior; and the first to uncover the molecular mechanism whereby estrogen, which had previously been associated with a reduced risk of AD onset, reduces the amount of beta amyloid produced. They've also investigated how antipsychotic drugs, commonly used to treat the hallucinations and agitation associated with AD, affect intermolecular pathways and block dopamine-findings that they hope will lead to better AD drugs with fewer side effects. "These programs evolved scientifically from earlier programs," notes Greengard. "But [there's] one common theme: I'm particularly interested in the basic science of the brain as it applies to various diseases of the brain .... If the research is showing new leads [that] go this way or that, I always tend to go the way that has more clinical relevance." Having received more than 50 previous awards and honors, including the 1991 National Academy of Science Award in the Neurosciences and the 1997 Charles A. Dana Award for Pioneering Achievements in Health, Greengard was gratified but not surprised that his lab had once again been recognized. MetLife also awarded $100,000 institution grants to two "promising" Alzheimer's investigators: Iva Greenwald, a molecular geneticist from Columbia University College of Physicians and Surgeons, and Karen Hsiao, a molecular biologist and neurologist from University of Minnesota Medical School.

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