Interested in reading more?

POWER EXCHANGE: Molecular biologist James Battey has become the second person to head NIDCD. SECOND GENERATION AT NIDCD Molecular biologist James F. Battey, 45, has been named the new director of the National Institute on Deafness and Other Communication Disorders (NIDCD) of the National Institutes of Health. Battey, who had been serving as acting director of NIDCD, succeeds the recently retired James B. Snow, Jr. Snow, a former University of Pennsylvania professor of otorhinolaryngology and human communications, became the first director of the institute in 1990. As scientific director of NIDCD, a position he has held since March 1995, Battey has overseen the development of research programs in molecular genetics and its connection to human communication disorders; he expects to see those efforts intensify in the years to come. "Recent advances in our fundamental understanding of the human genome gives us unprecedented opportunity to better understand and identify the genes involved in communication disorders," Battey says. "Without a doubt, this is one of the most promising areas of research, and we want to aggressively pursue it." He also says research using neural imaging devices could provide valuable insight into the pathogenesis of communication disorders. "The long-term hope of this research, of course, is to find new approaches to treating and preventing the onset of many communication disorders and diseases." UNITED DISEASE DATA A study involving 26 Alzheimer's disease centers across the United States has provided the impetus for a planned $3 million database to be established at the National Institute on Aging (NIA). The study results, published in February, establish that testing for an Alzheimer's-related gene called ape-4 following examination of patients can reduce false positive diagnoses of the disease by 30 percent (R. Mete et al., New England Journal of Medicine, 338:506-11, 1998). The study reviewed clinical diagnoses and diagnoses obtained at autopsy of 2,188 patients referred to the participating centers for evaluation of dementia. Creighton Phelps, director of the Alzheimer's disease centers program at NIA, acknowledges that the study's finding is an "incremental" diagnostic tool. "There are plenty of people that have ape-4 that don't get Alzheimer's disease. It's not predictive," he notes. But the compilation of information from the various centers about such patient factors as education, geographical distribution, age, and siblings is unprecedented, he believes, for research on neurodegenerative diseases. "What this information will help to sort out is, are there any patterns emerging when you match up these factors?" An interim Alzheimer's disease database is being set up now at NIA, Phelps adds, and he hopes to have funding in place for the permanent center in fiscal year 1999. HEALING STRAIN: A strain of mice bred to study multiple sclerosis and autoimmune diseases, right, at the Wistar Instate in Philadelphia healed faster than a control strain, left, suggesting a relationship between the immune system and regeneration. MOUSE TALES An experiment designed to study autoimmune diseases like multiple sclerosis and lupus instead led to insights into how mammalian tissue could regenerate. Scientists punched holes in the ears of mice to separate treated from control animals and were surprised that the holes closed within weeks, according to Ellen Heber-Katz, an immunologist with the Wistar Institute in Philadelphia. "It seems clear that the immune response is involved," Heber-Katz says. She speculates that a component of the mammalian immune system blocks regeneration. Amphibians may not reject tumors well, but their body parts can regenerate. While mammals have a more highly developed immune system, they lack the ability to regenerate limbs. Heber-Katz and colleagues also snipped a centimeter of tail from the autoimmune-prone mice and noted that 75 percent of the tail returned after a month. By breeding healer mice with nonhealers, Heber-Katz and colleagues have identified seven chromosomal regions that differ between healers and nonhealers. Heber-Katz anticipates that her findings may help researchers find ways to heal chronic wounds and tissue damage in humans, including spinal cord injuries. The genetic details of her findings are either in press or submitted for publication. KITTY CONTRACEPTION By deleting disease-causing genes from Salmonella and adding a gene encoding a protein normally on the layer surrounding a pig's egg, researchers at Virginia Tech in Blacksburg, Va., have fashioned a contraceptive vaccine for felines. Microbiology professor Stephen Boyle and veterinary student Michelle Meister-Weisbarth performed the genetic swap last summer and are now preparing to test it. "We will feed the vaccine to cats and see if they have an immune response relative to controls," explains Boyle. "We will be looking for antibodies in washings from the vaginal tract" that would bind to eggs and prevent them from being fertilized, explains Boyle. He got the idea from work on elephants and mice. "I had been talking to people in Africa who developed a contraceptive vaccine for elephants three years ago," Boyle relates. And a similar Salmonella-based vaccine "produced a 70 percent decrease in conception rate with one dose" in mice, he adds. The first target: the 30 million to 60 million stray cats in the United States. A contraceptive vaccine would be easier to administer, cheaper, and more humane than current population-control measures. "Eight [million] to 10 million stray cats are put to sleep each year, and we can't get to all the others to surgically remove the reproductive tracts," Boyle states. Domestic cats could eventually benefit, too, with their owners giving oral vaccines. But two problems remain to be solved-determining the optimal dose for long-term contraception and finding a bait that only cats will eat. MUTANT WORM: A male mab-3 mutant worm that is expressing yolk (green) in the intesting. Yolk normally is expressed only in hermaphrodites. SEX-DETERMINING GENE Homology can be humbling. David Zarkower, an assistant professor in the Institute of Human Genetics at the University of Minnesota Medical School in Minneapolis, and coworkers have identified a shared DNA-binding region in a sex-determining gene in the nematode Caenorhabditis elegans, the fruitfly Drosophila melanogaster, and maybe humans (C.S. Raymond et al., Nature, 391:691-5, 1998). This is surprising, because sex determination differs substantially among animal groups. In centuries past, whether conception produces a boy or a girl has been attributed to the phase of the moon, the testicle from which the successful sperm comes, or how passionate the sex act. Today we know that specific genes determine sex. Zarkower and colleagues noted similarities between the worm mutant mab-3 and the fly mutant doublesex and found that the two genes share a DNA-binding region called the DM domain. They then found a gene containing the domain that is expressed in human testis cells and mapped it to a band on chromosome 9, calling it DMT1. They found that DMT1 hails from a part of chromosome 9 already known to be absent in some individuals who are XY but appear female. "Patients deleted for that chromosome band had sex reversal to varying degrees. We are now looking at DMT1 in XY females without obvious deletions to find a microdeletion or point mutation," says Zarkower. Finding such a small-scale mutation will show if the DMT1 gene, fished out using counterparts in flies and worms, is one of the genes required in two copies to make a human male. NEW APPROACH FOR LUPUS Scientists at Rockefeller University may have discovered a new therapeutic approach for the treatment of systemic lupus erythematosus, an autoimmune disease that causes chronic inflammation and severe kidney disease. The disease, which primarily affects women between the ages of 20 and 40, develops when the immune system produces autoantibodies, or antibodies directed against its own cells. In a recent paper (R. Clynes et al., Science, 279:1052-4, 1998), Rockefeller researchers describe the role of antibody-binding molecules called Fc receptors in the onset of lupus. They developed a strain of mice lacking the gamma chain of the Fc receptor, the one responsible for activating immune cells by antibody complexes. Eighty-two percent of the mice without the Fc receptor were alive after nine months; less than 20 percent of the mice with intact Fc receptors survived. The anti-inflammatory and immune system-suppressing drugs currently in use cause unwanted side effects and are generally ineffective and nonspecific. According to senior author Jeffrey V. Ravetch, Theresa and Eugene Lang Professor and head of the Leonard Wayner Laboratory of Molecular Genetics and Immunology at Rockefeller, the study shows that preventing the activation of antibody receptors using autoantibodies may be an effective, alternative way to treat autoimmune diseases like lupus. After four years of study, the immune systems in the mice lacking Fc receptors don't seem to be adversely affected. "Based on these studies," says Ravetch, "we are trying to find some pharmaceutical partners that would be interested in developing a model for antibody specificity just for this receptor in humans." PROMISING APPROACH According to the Centers for Disease Control and Prevention (CDC), each year 20,000 people are infected with the pathogenic bacterium Escherichia coli O157, and 250 people die of the infection. E. coli O157, a mutant strain, is responsible for the recent highly publicized tainting of ground beef. It can cause the potentially fatal conditions hemorrhagic colitis (resulting in bloody diarrhea) and hemolytic uremic syndrome (resulting in damage to, and possibly failure of, the kidneys). According to a recently completed Phase I study (E.Y. Konadu et al., Journal of Infectious Diseases, 177:383-7, 1998), a new vaccine developed by scientists at the National Institute of Child Health and Human Development (NICHD) may provide some relief in the relatively near future. NICHD researchers chemically linked, or conjugated, a polysaccharide from the capsule of E. coli O157 to the genetically inactivated toxin from another bacterium, Pseudomonas aeruginosa. Team leader John B. Robbins, chief of NICHD's Laboratory of Development and Molecular Immunity, helped pioneer the technique. Conjugation enables the immune system to make antibodies against the bacterium as if it were a protein. In a clinical trial, 81 percent of the volunteers produced protective levels of antibodies within one week after vaccination, and all of the volunteers did so within four weeks; sufficient levels of antibodies were sustained for six months. Researchers are currently investigating the feasibility of immunizing cattle to effectively eliminate the pathogen at its major source. "We should know within two years whether this approach is going to work," says NICHD director Duane Alexander. "If we can't do that that, then we obviously have to do a human study, which we might do anyway because it would be useful to have a vaccine for outbreak control." ROGUE ER? Infectious proteins called prions are believed to cause degenerative brain disorders such as Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (mad cow disease). According to the Nobel Prize-winning hypothesis of Stanley B. Prusiner, a professor of neurology and biochemistry at the University of California, San Francisco, prions fold abnormally and cause other proteins to do the same. In a recent follow-up paper (R.S. Hegde et al., Science, 279:827-32, 1998), Prusiner and other UC-San Francisco researchers investigated how prions trigger the widespread death of neurons. They focused their efforts on the prion responsible for the noninfectious brain disorder Gerstmann-Straussler-Scheinker (GSS) disease. Unlike the prions implicated in GSS, those responsible for the brain diseases in Prusiner's original study accumulate to huge levels, making an analysis of the pathway leading to neuronal death very difficult. In the recent study, the researchers investigated mice with GSS and discovered that the pathway involves a somewhat unexpected player: the endoplasmic reticulum (ER). A cytoplasmic membrane that functions in the transport of materials within the cell, the ER in GSS cells sticks prions to its membrane rather than secreting them, as is the case with normal cells and proteins. Although it's not clear if the findings represent the discovery of a pathway common to all prion diseases, the study may illustrate a previously unknown mechanism of gene expression. "A number of disorders . . . that people have not understood might be explainable by this kind of process," notes coauthor Vishwanath R. Lingappa, a professor of physiology and medicine at UC-San Francisco. The team is currently trying to clone the gene responsible for this ER function.

Notebook

The Scientist Staff

Mar 15, 1998

Interested in reading more?

Become a Member of