Notebook

LAB-PROVEN: With this equipment, Manish M. Shah of the Pacific Northwest National Laboratory has demonstrated that enzymes in spinach can neutralize explosives. POPEYE WOULD BE PROUD Remember how Popeye turns into human dynamite whenever he eats spinach? Well, the new word is that enzymes in spinach may reduce dynamite to a harmless bunch of chemicals. Manish M. Shah, a research scientist at the U.S. Department of Energy's Pacific Northwest National Laboratory in Richland, Wash., is using nitroreductase enzymes to neutralize the nitroaromatic compounds in explosives. Nitroreductase enzymes--which normally are involved in photosynthesis--are ubiquitous, but Shah buys commercial stocks extracted from spinach. He says the pocket of such enzymes is big enough and comparable enough to suit nitroaromatics, and to continue a virtually endless catalysis of their reduction. Currently, unwanted explosives are incinerated. "It's a huge challenge for the Department of Defense to deal with explosive stockpiles. There are 500,000 tons of them around the country," Shah notes. In his Environmentally Benign Digestion Process (EBDP), enzymes are placed with the explosives in vats of neutral pH water at room temperature and atmospheric pressure. The only other additives are a buffer solution and a reductant, to reduce the enzymes. Shah is confident that field tests next year will confirm low toxicity of the resulting effluent. Another aspect of the tests will be to develop a commercially viable product from the process for sale to the polymer industry. The research project has about $1 million in government and corporate funding. "It's only a matter of time for this enzyme technology," he says. "It has all the necessary characteristics--it's cost-efficient, safe, mobile, and it works in water." A VISIONARY MOUSE Transgenic mice can see beyond where normal mice can peer, thanks to harboring the human gene that encodes L-photopigment. The rodent's spectral range is extended into long wavelength, red light. Because mice can normally see into the ultraviolet--unlike many other mammals including humans--the manipulation gives them the greatest visual range of any mammal. To determine whether optically endowed mice could actually see better, investigators did two types of experiments. "We put electrodes in front of the eye to pick up electrical responses to different wavelengths of light. And we found that the eye was sensitive far beyond that of a normal mouse," says Michael Crognale, an assistant professor of psychology at the University of Washington in Seattle. Crognale, professor of medical genetics Samir Deeb at UW, professor of psychology Gerald Jacobs at the University of California at Santa Barbara, and their colleagues presented the findings at the annual meeting of the Association for Research in Vision and Ophthalmology on May 14 in Fort Lauderdale, Fla. In behavioral experiments, the transgenic mice discerned panels lit by wavelengths that other mice missed. The visionary mice will have several uses. "We can figure out how photopigments are expressed, create an animal model to study human cone degeneration, and answer questions about how the rest of the nervous system copes with this new information," Crognale adds. Gerald Fischbach NEUROLOGY INSTITUTE'S NEW DIRECTOR A neuroscientist who last worked for the U.S. government a quarter-century ago has just been appointed the new director of the National Institute of Neurological Disorders and Stroke (NINDS). Gerald Fischbach, chairman of Harvard Medical School's neurobiology department, will assume the position on July 30. At NINDS, he will oversee a staff of 700 and an annual budget of close to $800 million. "The challenge is to go into a government bureaucracy, which is a bit of an unknown, and to be effective and really make changes," Fischbach says. He anticipates "a lot of new hiring in regard to administering and planning the extramural program" and a review of the intramural program, with its 23 laboratories and branches, "to make sure it's all of the very top quality." Fischbach intends to stress research into neurodegenerative diseases, repair of injured neurons, early neuronal development, synaptic plasticity, and chronic pain. "I would also very much like to expand joint programs with other institutes," he says, citing the new Brain Molecular Anatomy Project (with the Institute of Mental Health) and the half-year-old Brain Tumor Genome Anatomy Project (with the National Cancer Institute). Fischbach, 59, got his first taste of research during medical school and, after his internship, studied the neuromuscular junction during a seven-year stint at the National Institutes of Health (G.D. Fischbach, Science, 169:1331-3, 1970). His academic career has been at Harvard Medical School and at Washington University School of Medicine in St. Louis. Fischbach's lab has recently purified and studied ARIA, a trophic factor thought to increase acetylcholine receptor synthesis (A.W. Sandrock et al., Science, 276:599-603, 1997). As head of NINDS, Fischbach will replace Acting Director Audrey Penn, who replaced three-year director Zach Hall, when he returned to the University of California, San Francisco, last December. Steven B. Sample NO MORE THE TERMINAL PH.D. Is the Ph.D. the terminal degree in preparation for a career in research? Over 100 years ago, the American Association of Universities (AAU) was founded in part to answer that very question. Observing tremendous growth in the number of postdoctoral appointments from 1975 to 1995, AAU once again considered the question. What they found is that in many fields of research, postdoctoral work has become the de facto terminal degree. This trend has been most strongly observed in biochemistry, says Steven B. Sample, president of the University of Southern California and chair of the AAU committee on postdoctoral education. From 1975 to 1995, the proportion of Ph.D.s in all fields of science, engineering, and health accepting postdoctoral appointments has grown from 25 percent to 37 percent. In biochemistry, 80 percent of freshly minted Ph.D.s at institutions surveyed have accepted postdoc appointments. "Trends like this call for our attention," Sample says. "There has been concern from many that postdoctoral work has become a holding pattern before you can find steady employment. The postdoc in essence has become a terminal degree." Among the other key findings of the survey, AAU reports that: Although more than 350 institutions in the United States offer doctoral degrees, two-thirds of all doctoral appointments are made at only 50 institutions. Most of the 50 are considered among the top research universities in the nation. Most institutions make little or no effort to control the number or quality of appointments. Few institutions have campuswide compensation policies for postdocs, and few report any attempt to ensure that foreign and domestic postdocs receive equal compensation. Although many institutions claim to classify postdocs as employees entitled to the usual benefits, postdocs tend to list access to benefits as a major concern. Few universities have conflict-of-interest policies for postdoctoral researchers. Sample is hopeful that the study will prompt universities to reevaluate the role of postdoctoral researchers. "Universities and departments need to take a critical look at how they treat postdoctoral scientists and engineers," he says. "Policies for faculty and graduates are well defined. Many postdocs have had an undefined existence somewhere between student and professor." UNWINDING CLOCK When CLOCK, the gene thought responsible for circadian rhythm, was discovered, researchers still did not understand what made the process tick. Now, several teams of genetic watchmakers have begun to discern the chemical gears that, when disrupted, alter sleeping and waking cycles in mice. "The CLOCK gene itself does not show any rhythmic activity," notes Charles J. Weitz, assistant professor of neurobiology at Harvard Medical School. Weitz and colleagues showed that the biological clock is much more complex. CLOCK and BMAL1 together activate mper1, the gene that actually shows rhythmic activity at a transcriptional level (N. Gekakis et al., Science, 250:1564-73, 1998). Scientists have yet to find the "off" switch, which is equally important to understanding the process. "It's the alternation between those two that gives [the gene] rhythmic regularity," Weitz explains. He suspects that the second switch will be discovered within a year, since researchers now know where to look: "We know what has to get shut down." Another recent paper indicates that the circadian mechanisms are highly conserved in both Drosophila and mouse (R. Allada et al., Cell, 93:791-804,1998). "The mammalian and Drosophila clocks are very similar," Weitz concludes. ACTIN ACTIN' UP Defects in the gene for heart muscle actin cause a hereditary form of idiopathic dilated cardiomyopathy (IDC), a team from the University of Utah and Mayo Clinic reports. The condition affects five to eight people per 100,000 and often means heart transplant or death from heart failure (T.M. Olson et al., Science, 280:750-2, 1998). "We have improved our understanding of what causes this disease and opened up prospects for better treatment," says lead author Timothy Olson. Actin is the most abundant protein in many eukaryotic cells, where as long filaments it governs various aspects of cell motility, including muscle contraction. Actin associates with a host of protein partners including myosin, which generates force along the filaments. Other proteins regulate this interaction or control filament organization. In a process as complex as motility, with lots of room for error, it is not surprising that abnormal proteins would cause trouble. Defects in dystrophin, which links actin filaments to the muscle fiber membrane, are responsible for Duchenne muscular dystrophy, while certain myosins are implicated in genetic deafness. Until now no human disease had been traced to actin, perhaps because it is encoded by several similar genes resulting in functional redundancy (humans have at least six actin genes), or because deleterious mutations would be lethal early in development. The research by Olson et al. changes the terrain. Using genetic analyses, PCR, and gene sequencing, the team examined two families with histories of IDC and discovered two separate mutations in the cardiac actin gene. The mutations, which are not in locations that would affect actin's partnership with myosin, probably disrupt interactions responsible for force transmission and coordination of contraction across the muscle. The resulting dysfunction leads to progressive muscle damage and eventual heart failure.

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