Notebook

POSITIVE SIDE EFFECT Proposed legislation designed to ban genetic discrimination may boost participation in clinical trials, says Kathy L. Hudson, assistant director for policy coordination at the National Human Genome Research Institute. Vice President Al Gore issued guidelines for genetic discrimination legislation in a report entitled "Genetic Information and the Workplace"

February 16, 1998

POSITIVE SIDE EFFECT Proposed legislation designed to ban genetic discrimination may boost participation in clinical trials, says Kathy L. Hudson, assistant director for policy coordination at the National Human Genome Research Institute. Vice President Al Gore issued guidelines for genetic discrimination legislation in a report entitled "Genetic Information and the Workplace" January 20 at the National Academy of Sciences. The legislation, if enacted, would bar employers from using genetic makeup in hiring or promotion decisions. Candidates for clinical trials who decline to participate cite the misuse of genetic information as a major reason for their refusal, Hudson explains. The legislation would also allow more people to get tested for diseases without jeopardizing their employment-especially significant as genetic tests for more diseases become available. "There's now a handful of genes we can test for disease," Hudson reports. "That handful will grow to a boatful." Hudson says cases of employees losing their jobs because of positive tests for Huntington's disease already exist. Until the legislation is enacted, "there's going to be more and more cases," she predicts. Several similar bills have been proposed in both the House and the Senate. The report, by the Department of Labor, the Department of Health and Human Services, the Equal Employment Opportunity Commission, and the Department of Justice, is available on the Internet at: http://www.nhgri.nih.gov/HGP/Reports/genetics_workplace.html.



IMMORTAL CELLS? ß-galactosidase staining of cells without introduced telomerase, top, and with introduced telomerase, bottom. The cells on the bottom, which have been transfected with the telomerase reverse transcriptase gene, are youthful (smaller) and do not stain blue for ß-galactosidase.
Jerry Shay
MAKING HEADLINES: Texas researcher Jerry Shay garnered much attention for introducing telomerase genes into retinal pigmented epithelium cells and fibroblasts.
YOUTHFUL CELLS When Jerry Shay and Woodring Wright, professors of cell biology and neuroscience at the University of Texas Southwest Medical Center in Dallas, and their colleagues there and at Geron Corp. in Menlo Park, Calif., announced that they had reset the cell division clock in culture, they knew they would make headlines. Using electroporation, they had introduced telomerase genes into retinal pigmented epithelium cells and fibroblasts (A.G. Bodnar et al., Science, 279:349-52, 1998). Telomerase is an enzyme that tacks DNA repeats onto chromosome tips. Normal cells turn off telomerase production and cease dividing at about 50 divisions. Cancer cells continually make telomerase and ignore the internal clock. In the experimental cells, "we've seen more than 120 doublings," says Shay. "These are perfectly normal cells-they divide at a reasonable rate and have a 'youthful' appearance. We don't see any increased risk of developing cancer." Although he cautions that no one is planning to immortalize people with telomerase injections, Shay does envision some intriguing applications. Telomerase-boosted fibroblasts, for example, might keep producing collagen, delaying skin wrinkling. To boost falling T cell counts in people with AIDS, "one could take patients' own pluripotent stem cells and elongate their telomeres ex vivo, and when they develop a low T cell count, give them back their own stem cells," he suggests. His group has just begun teaming telomere extension with gene therapy to treat Duchenne muscular dystrophy, an inherited muscle degeneration caused by lack of dystrophin, a protein that maintains muscle integrity. The target would be "satellite" cells that, if given longer lives and normal dystrophin genes, could replace affected muscle cells. "This would be a new route to gene therapy-but it is still way in the future," Shay says.


ROLLING OFF DNA COPIES Viruses with circular genomes replicate their genetic material essentially by peeling off copies made on the circle, a little like old-fashioned mimeograph machines used before the age of copiers. A professor of chemistry at the University of Rochester, Eric Kool, has borrowed from this viral strategy to churn out copies of short nucleic acid sequences. The rolling circle approach requires short lab-synthesized DNA circles, free nucleotides, and polymerase, the enzyme that knits a new strand that is complementary in sequence to the circle. "The circle itself is not necessarily a bunch of tandem repeats. But the product is, since the polymerase runs around the circular template many times," Kool says. In one experiment, Kool used a 26-base circle to run off 460 DNA repeats. The rolling circles can also be used to generate RNA. Kool and his coworkers synthesized a 7,500-nucleotide-long catalytic RNA from an 83-nucleotide rolling circle. The RNA cut itself into 83-base-long units (S.L. Daubendiek, E.T. Kool, Nature Biotechnology, 15:273-7, 1997). By adding fluorescently labeled bases, the technique produces labeled copies, useful as DNA probes. Kool also is developing the circles as a new type of gene therapy vector. Rolling circle DNA amplification is easier than the polymerase chain reaction because it doesn't require temperature shifts to separate double-stranded DNA, or continually adding primers. Says Kool, "It's now feasible to make bucketfuls of DNA, an amount we can't even begin to approach with other amplification techniques."


IVF ANOMALY Scottish researchers have described a boy whose hermaphroditism may have arisen from in vitro fertilization (IVF). The newborn had a normal penis and right testis, and an undescended left testis. Fifteen months later, the left scrotal sac was found to house female organs, which were removed. The boy is also a chimera, having both XX and XY cells. "The true frequency of XX/XY chimeras is unknown, but the sparse literature suggests it is rare" in natural pregnancies, says David Bonthron, a senior lecturer in human genetics at Western General Hospital in Edinburgh. Bonthron and colleagues used DNA markers to reconstruct the origin of the chimerism (L. Strain et al., New England Journal of Medicine, 338:166-9, 1998). By distinguishing the maternal and paternal chromosomes in the two cell lines, they ruled out the possibility of two sperm having fertilized an ovum and a polar body, the smaller cell formed as the chromosome number is halved. Instead, two of three four-celled embryos implanted into the mother fused. IVF ups the odds of multiple births, and so far, problems have been attributed to those that occur in any multiple birth. The case of this child, however, suggests that IVF may introduce anomalies. "The frequency of nonidentical twins is approximately 25 percent after IVF, but only approximately 1 in 150 naturally. So the risk of chimerism must be at least 35-fold increased after IVF," says Bonthron.


OLESTRA AT THE MOVIES What if someone offered to treat you to a movie on the condition that you eat as many potato chips and drink as much soda as you like? It's not an offer many would refuse. Now what if you were told that those chips might cause some unpleasant gastrointestinal (GI) problems? Still game? More than 1,000 individuals chose to take their chances in a recent study on the potential harmful effects of the fat substitute olestra (L.J. Cheskin et al., JAMA-Journal of the American Medical Association, 279:150-2, 1998). A research team led by Lawrence J. Cheskin, an associate professor of medicine at the Johns Hopkins University School of Medicine, director of the Johns Hopkins Weight Management Center, and consultant to olestra manufacturer Procter and Gamble Co. of Cincinnati, carried out the study in response to earlier findings that indicated an increased incidence of olestra induced GI problems after subjects had consumed the chips regularly for 56 consecutive days (T.G. Schlagheck et al., Journal of Nutrition, 127:1646S-1665S, 1997). This study focused on the more immediate effects of olestra. Participants were given a free 32-oz. soda of their choice, an unlabeled bag of potato chips, and a free movie pass for one of several movies. Half of the subjects received regular Frito-Lay Ruffles, and half Frito-Lay MAX Ruffles made with olestra. Researchers monitored the subjects during the movie and then via telephone interviews for the next 10 days. Cheskin's team found no significant difference between the two groups; 17.6 percent of the normal group reported GI problems vs. 15.8 percent for the olestra group. "I think you may see some difference [in the results] when you push the envelope and have [olestra for] breakfast, lunch, and dinner," he suggests.


PRESSING SCIENCE: Veteran NBC journalist Jim Hartz, left, and NASA physicist Richard Chappell argue that scientists and journalists need to join together to ensure public support for research.
MEDIATING SCIENCE Unless scientists and journalists learn to communicate more effectively, funding for research will be harder to come by, according to a report by veteran NBC journalist Jim Hartz and NASA physicist Richard Chappell. In Worlds Apart: How the Distance Between Science and Journalism Threatens America's Future (Nashville, Tenn., First Amendment Center, 1997) Hartz and Chappell, associate director for science at NASA's Marshall Space Flight Center in Huntsville, Ala., warn that declining media coverage of science could result in a loss of public interest and federal funding. They attribute this decline to increasing alienation between scientists and journalists; while many journalists complain that tedious jargon and endless qualifications make it all but impossible to report findings from research, the majority of scientists say news stories rarely get the details correct. In their survey of more than 1,400 scientists and journalists about their attitudes on media coverage, Hartz and Chappell found in both groups low confidence in the ability of the media to understand and interpret the significance of new research. Among other recommendations, Hartz and Chappell urge journal publishers to require investigators to include summaries of research in plain English. They also say the scientific community should train people educated in science to be spokespeople. One such program will begin this fall at Vanderbilt University in Nashville, Tenn., under the direction of Chappell. "It is critical for scientists to reach out to the public and work with the media in increasing coverage of science," Chappell concludes.


JUST ASK How do you find out if Russia is conducting biological warfare research? Maybe just go there and ask around. Raymond Zilinskas, an associate professor of international relations at the University of Maryland Biotechnology Institute, claims that will be a main method for his two-year, $268,400 research project titled, "The Former Soviet Union's Biological and Toxin Warfare Program: Assessing Its Proliferation Potential." Zilinskas says he and his coprincipal investigator, senior fellow Milton Leitenberg of the Center for International and Security Studies at the University of Maryland, expect to make at least two trips apiece to Russia beginning this summer. The project's consultant, senior research fellow Anthony Rimmington at the Centre for Russian and East European Studies at the University of Birmingham in the United Kingdom, may spend longer periods in Russia. Although the former Soviet Union's biological warfare program was supposed to have been dissolved under the terms of the 1972 Biological and Toxic Weapons Convention, Zilinskas says the United States government has concerns that it might be continuing in Russia. The researchers hope to rely, in part, on personnel records kept by Russian governmental and private organizations. Zilinskas says they have no idea how they will be received, and if stonewalled, they will seek out key émigrés, especially in the U.S., the U.K., and Israel. He says American agencies seem supportive of the unclassified research, although "I don't think we're even a blip on Clinton or Gore's horizon." The project is privately funded by the Westport, Conn.-based Smith Richardson Foundation.


A GLUT OF SPONSORS Now that the acquisition of Pittsburgh-based Westinghouse Electric Corp. by media giant, CBS Corp., is complete, one might expect trouble for the Science Talent Search. No such thing. Since its inception in 1957, the nationwide competition for high school seniors has been sponsored by the former Westinghouse, which announced it would end that relationship after 1999. But Science Service Inc., a Washington, D.C.-based nonprofit corporation that owns the event, is already knee-deep in potential new sponsors. "This is a once-in-a-lifetime opportunity for us," enthuses Kathy Orando, Science Service's director of development and public relations. "We've had several Fortune 400 companies call us, and several science associations." The new sponsor will have to shell out $1.1 million annually to run the competition, which carries total scholarship prizes of $205,000. Science Service isn't sure yet whether a corporate or society sponsor will be more appropriate to its needs. "We're looking at the total package, how we can grow the program," Orando says, explaining that the Talent Search has stagnated in recent years. Although more than 100 of the world's most coveted science and math honors, including five Nobel Prizes, have been won by alumni of the contest, entries were down this year, and 15 states did not participate. "What are we not doing right that we can improve to get those states involved?" The competition's 1997 winners will be named on March 8, and a new sponsor will be announced on March 24. In 1999, CBS funds will not be required.

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