Notebook

LEAVING HOWARD HUGHES After serving as the president of the Howard Hughes Medical Institute since 1987, Purnell W. Choppin has announced his resignation. "While my enthusiasm for the position I have been privileged to hold and my dedication to the Institute remain as intense as ever, I believe that it will be time for someone to take up the reins and lead HHMI into the new millennium," Choppin wrote in a letter to the institute's staff. He will remain in the position through 1999. Under Choppin's tenure, the institute's budget grew from $77 million to $556 million. Choppin also oversaw the construction of the Institute's campus headquarters and conference center in Chevy Chase, Md. Choppin came to HHMI in 1985 as vice president and chief scientific officer from Rockefeller University, where he was Leon Hess Professor of Virology, vice president for academic programs, and dean of graduate studies. He headed the laboratory of virology at Rockefeller, which concentrated on viral structure, replication, interaction with cell membranes, and the mechanisms by which influenza, parainfluenza, and measles viruses produce cell injury and disease. IN MOTION : A computer-generated model shows SNARE proteins joining curved, neurotransmitter-filled vesicle (top) with membrane of presynaptic neuron (bottom). SHOOTING SNARES What's it look like right before one neuron spurts neurotransmitter across a synapse to contact another neuron? A team of researchers headed by Axel Brünger, a Howard Hughes Medical Institute (HHMI) a investigator and professor of electro-biophysics and biochemistry at Yale University, recently got a pretty good idea (R.B. Sutton et al., Nature, 395 :347-404, Sept. 24, 1998). Using X-ray crystallography, investigators produced the first high resolution images of a family of proteins called Soluble NSF Attachment protein Receptors (SNAREs), a part of the molecular machinery that helps propel neurotransmitters into synapses. SNAREs form a complex that fuses neurotransmitter-filled vesicles to the cell membrane, thus triggering neurotransmitter release. Images had previously been done only with low-level electron microscopy. Brünger's team, working with researchers from the Max-Planck Institute in Göttingen, Germany, spent several years working out the biochemistry of the system and another year doing the crystallography before successfully capturing the image--a feat that several other teams had attempted and failed. But, aside from having a nice picture, why would scientists want to capture the finest details of SNAREs in action? Bryan Sutton, an HHMI associate researcher and coauthor of the paper, likens the utility of the images to knowing the mechanics of how a car works, compared to simply knowing how to drive. Driving is relatively easy, but once the car, or in this case the neuron machinery, breaks down, scientists need to know the finer details of how it works to get the machine going again. "We're able to tell which actions take place between these proteins, and which, in turn, might be important for their function," maintains Brünger. "It kind of provides the framework ... for future experiments in this area." Brünger, Sutton, and colleagues are now working on imaging higher order vesicle fusion complexes involving SNAREs and other accessory and regulatory proteins. SCIENTISTS ON THE WEB A new National Library of Medicine (NLM) Web site (www.profiles.nlm.nih.gov) promises to provide a comprehensive archive for some of the great scientists of the 20th century. Called "Profiles in Science," the recently unveiled site will post unpublished writings, letters, and lab notes, as well as relevant video clips and photos, of renowned scientists selected by an advisory committee. "The idea is to make the history of science come alive for anyone who's interested, but particularly students and scholars of the history of medicine," says Alexa McCray, leader of the team that developed the site. According to McCray, site developers will initially focus on, and obtain materials directly from, living Nobel laureates. They made an exception, however, for the first featured scientist, the late Oswald Theodore Avery, who in 1944 was the first to prove conclusively that DNA was the genetic material. Although his research provided the basis for all of modern genetics, Avery, who failed to receive a Nobel Prize, has received relatively little recognition. But the site isn't just about the lives of prominent figures in science, says Joshua Lederberg, a Nobel laureate and the former president of Rockefeller University. "It's about the history of DNA, the molecular biology, and how science gets done ..., how people collaborate, how they communicate with each other, how they criticize each other. That's part of the dynamic of competitive science." Lederberg helped compile the materials on Avery and is a consultant for the project. He calls the site, which will be continually updated as new materials become available, "a pioneering effort," but one that will become "mainstream in terms of how historical collections are made available." ENERGY HOT SEAT If the Department of Energy (DOE) doesn't do a better job coordinating its research efforts, another government agency should run its national laboratories, recommended Victor S. Rezendes, director of the General Accounting Office's Energy, Resources, and Science Issues, during a Sept. 23 hearing in Washington. Rezendes told the House Subcommittee on Basic Research, Energy, and the Environment that, for nearly 20 years, the DOE's national laboratories have conducted good research on an individual basis, but have been poorly led on the national level. As a result, the labs as a group have no overarching vision. "There has been some progress achieved," replied Charles V. Shank, director of the Ernest Orlando Lawrence Berkeley Laboratory, noting that signs of progress include outsourcing of jobs such as security, travel, and maintenance. He also pointed to the DOE's contributions to the Human Genome Project. That's not enough, retorted Rezendes, adding that those examples illustrate his point that individual labs may make changes, but collectively, they still lack vision--which is supposed to come from the top of the DOE. "Fundamental change has remained elusive," Rezendes added. Rep. Ken Calvert (R-Calif.), the subcommittee's chair, also expressed frustration over lack of change. "This is not a new problem," Calvert commented. Rep Tim Roemer (D-Ind.) commented that he supports research the labs perform, but wants to know who is responsible for the national laboratories and what broad research agenda the DOE supports. SUPERBUG RESISTS RADIATION Bioremediation pairs microbes with tastes for toxins with a contaminated site in the hope that the organism will metabolize away the problem. But the radionuclides in these dumps often harm the bioremediators. A solution: transfer detox genes to Deinococcus radiodurans, a bacterium so radiation-resistant that it's been found in nuclear reactors. Discovered in 1956 in a can of sterilized spoiled ground meat, D. radiodurans can withstand intense radiation because it has extra genetic material that rapidly repairs itself. So Cleston Lange, Lawrence Wackett, and Kenneth Minton at the center for biodegradation research and informatics at the University of Minnesota, and Michael Daly of the Uniformed Services University of the Health Sciences in Bethesda, Md., gave D. radiodurans the toluene dioxygenase gene from Pseudomonas putida. "It seemed logical to take genes from other organisms and put them into organisms that can survive the radiation and grow," says Daly, an assistant professor of pathology. The superbug withstands continuous radiation and oxidizes toluene, chlorobenzene, 3,4-dichloro-1-butene and indole. Such boosted bioremediators might someday help clean up the 3,000 dump sites that are the Department of Energy's legacy of the cold war. "From 1946 through the late 1960s, thousands of open pits, each the size of an Olympic swimming pool, were dug and lined with concrete. But the concrete has broken down, and solid and liquid organic wastes have leaked. In 50 percent of these pits, the leaks threaten groundwater supplies," Daly says.

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October 1998

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