Notebook

MORE WORK NEEDED: Scientists have discovered a Parkinson's disease gene, but aren’t certain how many cases are caused by its mutation. The end of June brought with it a pair of studies with potentially valuable information on neurological disorders. In one (M. Polymeropoulos et al., Science, 276:2045-7, 1997), researchers from the National Human Genome Research Institute (NHGRI) and from Robert Wood Johnson Medical School in Piscataway, N.J., reported the first-ever discovery of a gene whose mutation can lead to Parkinson's disease. The gene plays a role in the function of nerve cells by coding for a protein called alpha synuclein. The team speculates that the mutation causes an excess of alpha synuclein to gather in brain cells; this excess then attracts other proteins to form deposits that damage the cells. Senior author Robert Nussbaum, chief of NHGRI's Laboratory of Genetic Disease Research, says researchers don't yet know how many cases of Parkinson's can be attributed to the mutation. "We don't think it's an overwhelming cause of Parkinson's disease in general," he allows. Determining this prevalence is "something that needs to be done through a research protocol. I know other Parkinson's researchers around the country are looking now actively." In the other study, a team at the University of Pennsylvania Medical Center announced the finding of a new pathology to join the neurofibrillary tangles and amyloid plaques that are characteristic of Alzheimer's disease (M.L. Schmidt et al., American Journal of Pathology, 151:69-80, 1997). According to the Penn researchers, the new trait is a plaquelike lesion involving a previously unidentified protein. The lesion is believed to make up as much as a quarter to a third of the volume of affected brain tissue in Alzheimer's patients, and it is rare or nonexistent in other neurodegenerative diseases. SPLICED: TIGR's Craig Venter, left, and HGS CEO William Haseltine have mutually agreed to follow their own paths TIGR's Craig Venter, left, and HGS CEO William Haseltine have mutually agreed to follow their own paths In a not-too-surprising announcement, the Institute for Genomic Research (TIGR) and Human Genome Sciences Inc. (HGS), both of Rockville, Md., revealed on June 23 that they were dissolving their occasionally rocky five-year relationship. HGS, a biotechnology firm, will stop future payments to TIGR, a nonprofit research center, in exchange for giving up rights to the institute's future work. For the last five years, HGS supported some of TIGR's research in return for the exclusive right to preview the institute's genomic data at least six months before they were made public. That arrangement was beginning to lead to cracks in the relationship, however. "We were feeling more and more constrained by all our rights going to this one biotech company," says J. Craig Venter, TIGR's president and director. "It also inhibited our ability to publish data as quickly as we wanted to." The mutually agreed-upon, early end of the agreement means that HGS is no longer obligated to fund some of TIGR's projects; the total was to exceed $38 million over the next 51/2 years. "It certainly affects projects that we're supporting internally, but most of our projects are grant-supported right now," notes Venter. That includes $12 million in government and private-foundation grants to support TIGR's genomic research for this year alone, he observes. In fact, the day after the announcement of the HGS-TIGR split, the institute posted DNA sequence data on the genomes of 11 organisms on its Web site (http://www.tigr.org). At the start of the TIGR-HGS relationship, states William A. Haseltine, the biotech firm's CEO, "TIGR provided us crucial genomic information." However, with the institute's increasing interest in microbial genomes, he tells The Scientist, TIGR's research decreased in value to the company. HGS still maintains intellectual property rights to the sequence data just released because the work was completed prior to the June agreement. CANCER KILLER: Duke’s Kim Lyerly has high hopes for a vaccine now being tested. Researchers at Duke University Medical Center have been given the go-ahead to continue their clinical trials of a novel cancer remedy that one investigator calls a potential "Superman vaccine." For the first time, scientists are using RNA-which is produced by DNA and instructs cells to produce proteins-to try to knock out existing cancers and prevent new ones from forming. The Food and Drug Administration approved the test in February, and the National Institutes of Health's Recombinant DNA Committee (RAC) okayed it on June 12. RAC's status had been up in the air after NIH director Harold Varmus called for its discontinuation last year; after much protest, he relented and allowed a modified version of the panel to continue. In the Duke study, 18 cancer-afflicted patients are undergoing Phase I clinical trials now, with Phase II testing to begin later this year. The vaccine is a mix of dendritic immune cells common to everyone and an RNA sequence that encodes for the production of the carcinoembryonic antigen (CEA), which alerts the immune system to the presence of invading cancers. The researchers hope the RNA will induce the dendritic cells to produce CEAs that will signal the body's immune system to attack the cancers. The technique previously was shown to work well in mice with lung cancer (D. Boczkowski et al., Journal of Experimental Medicine, 184:465-72, 1996). "This may be the tool we've all been seeking, a 'Superman vaccine' that many people can use for the predominant killer cancers," remarks H. Kim Lyerly, clinical director of Duke's Gene and Cellular Therapeutics Center. NO CHARGE: The National Library of Medicine’s Medline database is now free. Maybe some things in life are free. The National Library of Medicine (NLM) announced on June 26 that the public now has free access to the popular medical library database MEDLINE via the World Wide Web at http://www.ncbi.nlm.nih.gov/PubMed/. NLM's MEDLINE service previously required registration and a charge of $1.50 to $2.00 per search with the use of the recently released Grateful Med software (Notebook, The Scientist, April 29, 1996, page 30). It added up to approximately $20 per hour. Why the sudden change? NLM officials say that in the last few years, more people are using the Internet to access MEDLINE, rather than accessing the service directly using Grateful Med. Since NLM does not have to pay any telecommunication charges for Internet access, it is able to offer MEDLINE free of charge to 'net users. NLM hopes soon to offer free MEDLINE to health-care professionals who don't have access to the Internet. Many researchers agree that there is a shortage of adequately trained people in the emerging field of bioinformatics (see Profession, page 13), and universities are just starting to recognize the need for more training programs in the discipline. Last month the University of Pittsburgh announced the establishment of a Center for Biomedical Informatics. The center joins a growing list of academic research and training programs in the United States. "Information technology supporting health care is seen as increasingly important," says Charles P. Friedman, the center's director and a professor of medicine at the university's School of Medicine. "There are many people interested in this field, but they're working independently. The purpose of the center is to promote collegiality, to make the best use of the talent we already have." The center's mission also covers graduate and postdoctoral training, and basic and applied research. Currently the purview of the center is geared more toward medical informatics, says Friedman, but there are plans to expand more fully into the area of computational biology. The center is funded by a five-year, $1.9 million grant from the National Library of Medicine. For more information on the center and its programs, visit its Web site at http://www.cbmi.upmc.edu. Joseph C. Hall is attempting to take the expression "love is blind" literally. The assistant professor of biochemistry at North Carolina State University, Raleigh, has developed a chemical compound he hopes will blind sperm and act as a male contraceptive. Hall's version of "the pill" is a sugary substance that shuts down an essential enzyme, N-acetyl-beta-D-hexosaminidase, that helps sperm recognize eggs. His early tests show about a 90 percent success rate in rats given the oral version; in the test tube, the compound inhibits 98 percent of the enzyme's activity in rat sperm. Still, Hall acknowledges: "What works in rats may not do so in people. We need to find out if it's feasible, and we need to look at it in vitro to see if it inhibits [human sperm enzyme activity] as well." Hall, who wants to patent his idea and his compound, recently formed Innovative Reproductive Technologies Co. in Research Triangle Park, N.C., to continue the research. The biochemistry of the sperm-egg interaction isn't entirely clear, and demand for a male pill is low. Nevertheless, Hall is confident that interest is forthcoming. "With more women entering the work force and delaying childbearing, I think you may see a demand [for a male contraceptive] in 10 or 20 years," he predicts, adding that a cost-effective product may find also find a Third World niche. Hall believes he could deliver a male contraceptive within five to 10 years if he is able to land support from a pharmaceutical company. The James S. McDonnell Foundation is commemorating the 100th anniversary of its founder's birth by establishing the James S. McDonnell Centennial Fellowships. The foundation will award up to 10 fellowships of $1 million to support the work of young scholars doing research in the areas of human genetics, human cognition, astrophysics and cosmology, global and complex systems, and the history and philosophy of science. The fellowships are directed toward scientists in the early stages of their careers; applicants should be under 40 years old or less than 12 years from receiving their Ph.D.'s. "We're looking for that person who's really starting off and has shown great promise, someone who might be thinking about this field in a slightly different tack than the mainstream," says program director Susan Fitzpatrick. Candidates should be both good scientists and good communicators. "We're not looking simply for scholarly or scientific brilliance," comments foundation president John T. Bruer. "We also want to find people who can communicate the importance and excitement of their research to a larger audience." The foundation is also hoping to "send a message to other private foundations and philanthropists about the important role private foundations can play in the support of science and scholarship," Bruer contends. Applications are due by December 15; finalists will be notified by December 1998. Details and application guidelines are available via the World Wide Web at http://www.jsmf.org/centennial. SURPRISING: Duke’s Jonathan Stamler sees hemoglobin as a finely tuned sensor that may actually control blood flow. Hemoglobin, the complex protein molecule that tightly attaches to oxygen in red blood cells and carries it through the bloodstream, may actually be a finely tuned sensor. Jonathan Stamler and his colleagues at Duke University Medical Center reported recently (J.S. Stamler et al., Science, 276:2034-7, 1997) that hemoglobin may be capable of adjusting blood flow to provide just the right amounts of oxygen to tissues and organs. Doctors and scientists have thought that blood flow is controlled solely by hormones and other factors in blood vessel walls, notes Stamler, a professor of medicine at Duke and a Howard Hughes Medical Institute investigator. Hormones such as adrenaline are important, and research by Stamler and others in the past few years has shown that nitric oxide (NO) also plays a role in relaxing and opening vessels. But according to Stamler, hemoglobin really runs the show, changing shape and releasing a slightly different molecule of nitric oxide called s-nitrosothiol (SNO). When oxygen is low, hemoglobin releases SNO to dilate blood vessels, while also sending oxygen to starved tissue. When oxygen is high, it constricts vessels, cutting blood flow. "It's a completely new way to look at how hemoglobin functions," he remarks. "It makes so much sense." The findings may open up a new avenue of treatment for ailments such as heart attack, stroke, and sickle cell disease. They may also help in developing new blood substitutes.

Notebook

The Scientist Staff

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