November was a rollercoaster month at the National Academy of Sciences (NAS). First, the United States Supreme Court declined to hear NASA's appeal of a lower court ruling subjecting the academy and its committees to the Federal Advisory Committees Act (FACA) of 1972. Animal rights groups argued that under FACA there should have been more public representation on a committee set up to revise the NIH Guide for the Care and Use of Laboratory Animals (R. Finn, The Scientist, July 22, 1996, page 1)

Dec 8, 1997
The Scientist Staff

November was a rollercoaster month at the National Academy of Sciences (NAS). First, the United States Supreme Court declined to hear NASA's appeal of a lower court ruling subjecting the academy and its committees to the Federal Advisory Committees Act (FACA) of 1972. Animal rights groups argued that under FACA there should have been more public representation on a committee set up to revise the NIH Guide for the Care and Use of Laboratory Animals (R. Finn, The Scientist, July 22, 1996, page 1), and that the committee's deliberations should have been open. But Congress immediately took steps to counter NASA's judicial defeat. By mid-month both the House and the Senate had passed identical amendments to FACA requiring NAS committee meetings to be open to the public only when the committee is gathering data or hearing testimony. Meetings in which committees deliberate their recommendations may continue to be closed. At press time the legislation was awaiting action by President Clinton.

National Institutes of Health leaders announced November 21 the abolishment of a grant program that was designed to help young investigators but that actually may have hindered them. Applications for the grants -- known as both R29 and First Independent Research Transition and Support (FIRST) awardsÑwill no longer be accepted after June 1, 1998. New investigators instead will be encouraged to apply for R01 (investigator-initiated) grants. NIH's Working Group on New Investigators determined that recipients of R29 grants had less luck competing for the R01 grants after the first award expired. "We felt that these differences were just not helpful to the new investigators," says Wendy Baldwin, NIH deputy director for extramural research. "Although they might find the initial success rate -- somewhat higher than for R01s -- attractive, later success rates were less favorable, so was this mechanism really helping them?" The R29 grants also had a five-year time limit and a maximum award of $350,000 over five years. The maximum R01 award is $500,000 per year. The smaller R29 awards were limiting to investigators because most of the amount went toward salaries, leaving little extra money for supplies and equipment. This arrangement was especially confining to clinical investigators, who were probably least likely to mount a project within the limits of R29. NIH will design a way to identify first-time applicants and will fund at least as many new investigators as in FY1997. "The key is that we will keep up the number of new investigators even at increased cost," Baldwin says.

TESTING PATIENTS: A national system of named HIV reporting might deter people from being tested, says GLMA's Marj Plumb.
The San Francisco-based Gay and Lesbian Medical Association (GLMA) is worried about a plan recently announced by John Ward, chief of HIV/AIDS surveillance in the Atlanta-based Centers for Disease Control and Prevention (CDC), urging a national surveillance system for HIV infection (S. Bunk, The Scientist, Nov. 10, 1997, page 1). "We are concerned that named HIV reporting will deter people from being tested and therefore from getting into treatment," says Marj Plumb, director of public policy for GLMA, which represents about 2,000 lesbian, gay, bisexual, and transgendered physicians, medical students, and their supporters nationwide and in 12 countries outside the United States. Ward has said he wants all states to begin reporting every case of HIV infection, although he left open an option to allow anonymous testing. Plumb recently met with Ward to urge CDC to further develop alternative surveillance methods such as anonymous testing. More than half the states currently have HIV surveillance, but 10 of them do not offer anonymous testing. California and New York, the two states with the biggest HIV and AIDS problems, have widespread anonymous testing and do not require HIV reporting. "We support fully CDC's effort to have the HIV surveillance system developed," Plumb declares. "We are certainly interested in looking at different aspects of the system that might be workable. But we believe the CDC is attempting to do this in a way that might be rushed." Ward has said he plans to build a consensus with the states and announce a national HIV reporting policy next year.

TAKING NAMES AND NUMBERS: K.K. Marino of the Immune Deficiency Foundation will coordinate a new registry for patients with primary immune deficiency diseases.
The National Institute of Allergy and Infectious Diseases (NIAID) has announced the creation of a clinical registry for residents of the United States suffering from primary immune deficiency diseases (PIDDs). Late in October, NIAID commissioned the Immune Deficiency Foundation (IDF) of Towson, Md., to establish the registry. IDF already has two registries running and expects to complete registries for six other PIDDs in the next year, according to K.K. Marino, the IDF registry coordinator. Unlike acquired immune deficiency diseases, primary immune deficiency diseases are caused by intrinsic defects in cells in the immune system. Increased susceptibility to infection is a common manifestation of PIDD as well as chronic rheumatic, autoimmune, gastrointestinal, and hematologic diseases. Severe combined immunodeficiency, or "boy-in-the-bubble disease," is perhaps one of the best known PIDDs. The registry, which grew out of an NIAID-sponsored pilot project, will improve researchers' access to patients as well provide up-to-date information on clinical trials to patients and physicians, according to Jerry A. Winkelstein, director of IDF and a professor of pediatrics at Johns Hopkins University. "The rarity of PIDDs really forces physicians and researchers to cooperate and pool information if the patient is to get the best care possible," Winkelstein says. For more information on the registry, call (800) 296-4433.

BIG BENEFACTOR: After giving $10 million to build a new biomedical research facility at Penn, P. Roy Vagelos and his wife, Diana, gave the university another $10 million for undergraduate scholarships in science.
P. Roy Vagelos, retired chairman and CEO of Merck and Co. in Whitehouse Station, N.J., and his wife, Diana, have promised the University of Pennsylvania $10 million to establish a scholarship for undergraduates in molecular life sciences. The study program, which is slated to begin next fall, will combine intensive research experience with study in mathematics, chemistry, physics, and the life sciences. Vagelos, who graduated from Penn in 1950 and now serves as chairman of the board of trustees there, says the scholarship will help the university produce a new generation of cutting-edge scientists. "The basis for understanding the life sciences now requires a deep understanding of mathematics, chemistry, and physics," Vagelos explains. "The days of descriptive biology are dead. With this interdisciplinary approach, we hope to give undergraduates the proper foundation for research into the 21st century." The scholarship was inspired by Penn's successful interdisciplinary programs in management and technology, and international studies and business. Beginning next fall, 10 undergraduates will be admitted to the program. The program is complemented by Penn's new $52 million interdisciplinary biomedical research facility, which was funded in part by a $10 million donation from Vagelos and his wife. It will house chemistry, chemical engineering, and biomedical engineering laboratories. Penn president Judith Rodin announced the scholarship gift from the Vageloses at the November 10 dedication of the facility.

A leader in antibody research, Marian E. Koshland, a professor of molecular and cellular biology at the University of California, Berkeley, died October 28. One of Koshland's major findings was that antibodies differ in their amino acid diversity. Her most recent work investigated how cytokines regulate gene expression in the cells of the immune system. "I've lost a wonderful wife, and the scientific community has lost a great lady," says husband Daniel E. Koshland, a professor, emeritus, of molecular and cell biology at UC-Berkeley and former editor of Science. He recalls many years he and his wife spent updating each other on their research progress. "We exchanged information all the time, but she was totally independent." She also devoted as much energy to teaching as to research. Since his wife's death, Koshland has received hundreds of letters from her former students. "She really cared a lot about people.

But she was also very forthright." Marian Koshland was a member of the National Academy of Sciences and the past president of the American Association of Immunologists and served as a member of the National Science Board.

TRANSGENIC PIONEER: Penn's Ralph L. Brinster received the John Scott Award for a culture that allows the egg to be modified and manipulated.

TRANSITION ELEMENT: Texas A&M's F.A. Cotton received the John Scott Award for opening the door to thousands of compounds chemistry previously overlooked.
Two scientists received John Scott Awards from the city of Philadelphia on November 21. The award was founded in 1816 by Edinburgh, Scotland, druggist John Scott, who left money to the United States city to honor creators of inventions with practical applications. Ralph L. Brinster, the Richard King Mellon Professor of Reproductive Biology at the University of Pennsylvania School of Veterinary Medicine, received the $10,000 award for developing a technique for producing transgenic mice. Brinster created an egg culture using microdrops of medium under liquid paraffin that allows the egg to be modified and manipulated. The culture, which Brinster developed as a graduate student, remains the most widely used system for culturing mammalian eggs and is used for human eggs during in vitro fertilization. The paper describing the technique (R.L. Brinster, Experimental Cell Research, 32:205-8, 1963) has been designated a Citation Classic by the Philadelphia-based Institute for Scientific Information. Brinster says that, as a graduate student, he had no conception of how widely used his technique would become. His work has allowed scientists to change any gene inside the mouse. The next frontier is developing transgenetic therapies for humans; "It will involve a lot of ethical and moral considerations." Brinster also won the first March of Dimes Prize in Developmental Biology last April along with Beatrice Mintz, a senior member of the Institute for Cancer Research at the Fox Chase Cancer Center. Brinster also garnered the Bower Award from Philadelphia's Franklin Institute earlier this year. Receiving the John Scott Award along with Brinster was F.A. Cotton, Doherty-Welch Distinguished Service Professor of Chemistry at Texas A&M University, College Station, for his work in catalysis and enzyme action. Cotton's work has focused on how metal atoms bond. He discovered a whole class of compounds that had more than one metal atom at their core. Chemists had concidered only chemicals built aroung one atom.

For several years, scientists have known that grapefruit juice can enhance the body's absorption of some medications, but no one could figure out exactly how. A research team at the University of Michigan Medical Center has now identified the grapefruit's active ingredients -- chemical substances called furanocoumarins.

They prevent an enzyme called CYP3A4 from breaking down certain medications in the lining of the small intestine, including drugs prescribed for high blood pressure, heart disease, allergies, AIDS, and organ transplantation. Paul Watkins, director of the university's General Clinical Research Center, says of the enzyme, "Presumably, it's there to protect us from things we shouldn't eat."In earlier work, his team had shown that grapefruit juice rapidly destroys CYP3A4 in the small intestine. The latest research, published in November, isolates two furanocoumarins as the primary active ingredients (P. Schmiedlin-Ren et al., Drug Metabolism and Disposition, 25:1228-33, 1997). One of the two, 6'-7' -dihydroxybergamottin (DHB), appears to be the major constituent. "We know there are over 20 furanocoumarins," says Watkins, "but if the whole is equal to the sum of the parts, then we're pretty confident that DHB is responsible for most of the effect." The researchers also found that different forms of grapefruit juice -- fresh, frozen, squeezed, or grapefruit oil -- and different lots of the same brand all yield varying volumes of furanocoumarins. Watkins sees value in the chemicals as a research tool. For example, the knockout effect of furanocoumarins could be used to test substances without CYP3A4 in the system.