Notebook

Table of Contents More Newsworthy Sheep Grade Strike Earns an F Brain Drain Sexual Chemistry Cheaper Journals Michign Misconduct Matters Lucky 7 Cloning BRCA2 Credit: Graham G. Ramsay ON THE LAMB: Dario Fauza performed fetal surgery on ovine patients. While Dolly the cloned sheep has yet to disappear from the headlines, other ovines have made medical history. Dario Fauza, a fellow at Harvard Medical School and Children's Hospital in Boston, along with Anthony Atala, an assistant professor of surgery and urology, cultured bits of skin and bladder from sheep fetuses with a synthetic scaffold, then implanted the tissue into newborn sheep, to correct defects that resemble congenital anomalies in humans. The work was reported at the 44th Annual International Congress of the British Association of Paediatric Surgeons in Istanbul on July 23. Sheep were ideal candidates, Fauza notes: "Fetal surgery can trigger preterm labor, but the sheep is very tolerant of fetal surgery." Skin was used because "there are a number of congenital defects in babies that affect the body wall, where it isn't possible to cover the lesion. You can't borrow skin from other body parts, and synthetic skins can become infected." Bladder tissue could be used to correct defects in which a developing bladder opens to the outside. The new approach weds tissue engineering with fetal surgery. And while engineered tissues are already in clinical trials, fetal surgery is in its infancy, Fauza notes. Still, clinical trials of fetal engineered tissues could begin in about five years, he projects. The team is currently working on muscle and tracheal tissue. An administrative law judge from the United States National Labor Relations Board (NLRB) has ruled that the withholding of students' grades by graduate teaching assistants (T.A.'s) at Yale University was not a protected activity (R. Finn, The Scientist, April 29, 1996, page 1). Judge Michael O. Miller dismissed a complaint filed by NLRB attorneys that alleged Yale violated the employment rights of the T.A.'s by retaliating against them for participating in the grade strike. Yale was accused of demoting some T.A.'s, threatening to expel others, and putting negative letters of recommendation in strikers' files. Jonathan Kreisberg, a regional attorney at NLRB's Hartford, Conn., office, expresses surprise at the ruling and says his office decided to file the case primarily because "the teaching [that the Yale T.A.'s] get paid for is not required to get their degree. If they are employees, they may engage in a lawful strike." But Miller ruled that the strike was not lawful because strikers must withhold all of their services, not just some of them. Significantly, he issued no ruling on whether the T.A.'s were primarily students, and thus not permitted to strike at all. At press time, the NLRB general counsel's office was deciding whether to appeal Miller's ruling. SHOW TIME: NIA's Pietro Pietrini and team stress-tested the minds of Down's syndrome patients by showing a video. Exercise alters the body's metabolism, so why not that of the brain? That was the reasoning of National Institute on Aging (NIA) researchers when they began a groundbreaking study into dementia, published in August (P. Pietrini et al., American Journal of Psychiatry, 154:1063-9, 1997). Earlier work by team leaders Pietro Pietrini, the NIA Laboratory of Neurosciences' senior staff fellow, and Mark D. Schapiro, chief of the brain aging and dementia section, had revealed no significant differences in the resting brain activity of nondemented, younger and older Down's syndrome patients, despite an increasing risk of dementia with age. Continuing the search for early warning signs, their latest study adapted cardiology's treadmill to the mind: They showed their 16 subjects a movie. "They had to process information," notes Pietrini, "which, if you will, is like the heart pumping more blood when you run." During the video, positron emission tomography detected problems: The increases in glucose metabolism of the older patients were significantly smaller in regions of the brain most affected by Alzheimer's disease. Down's syndrome dementia is indistinguishable from that of Alzheimer's, giving the study importance in developing treatments for early intervention in Alzheimer's. Next, the scientists will pharmacologically probe nondemented subjects who have a family history of Alzheimer's. "The idea is to use a drug that impairs memory function," says Pietrini. "We may be able to show abnormalities that are not noticeable at rest." Meanwhile, NeoTherapeutics Inc. of Irvine, Calif., has announced that a limited trial of AIT-082, a novel small molecule compound designed to cross the blood-brain barrier, showed one dose improved memory function in six of 10 Alzheimer's-afflicted subjects. A paper is being prepared. After years of relatively slow growth in jobs and salaries for chemists, the results of the American Chemical Society's (ACS's)1997 survey are positive (M. Heylin, Chemical and Engineering News, 75:13-9, 1997), but C&E News editor Madeleine Jacobs is disappointed nonetheless. According to the survey, women chemists still earn less than their male counterparts and work part-time far more often. "Personally, I've been following this issue as a journalist and a chemist for 30 years," she says. "It will probably be another 30 years before we see anything approaching gender equality." A random sample of 20,000 ACS members at all degree levels drew 9,800 responses from chemists. Only 2 percent of them were unemployed and seeking jobs, down from 3 percent reported last year. Unemployment for both genders at all degree levels was about the same, but women respondents without full-time jobs outnumbered men, 4.2 percent to 1.6 percent. The overall figure dropped to 6.4 percent from 8.5 percent last year. The median annual salary of respondents rose 5 percent, to $63,000 ($66,900 median for men, $50,100 for women). The salary gap between the genders, while small at the degree level, expands thereafter. Cash-strapped librarians, who have endured consistently rising subscription prices for scientific journals over recent years, will warm to a recent announcement from the Endocrine Society. Effective January 1, the nonprofit organization, based in Bethesda, Md., will decrease library rates by 5 percent for its four highly rated journals. "There's a practical, almost selfish objective here," acknowledges Lenne Miller, the society's director of journal publications. "We felt if we could reduce our rates and make our journals a better value to libraries, we could cut down our nonrenewal rate, and make it more attractive to librarians to subscribe to all four of our journals." After taking over self-publishing in 1992, the society raised its subscription prices for two successive years, ostensibly to compare with those of competitors. Lately, cost savings have come from improved production technology and renegotiation of printing contracts, Miller says. The society publishes Endocrinology, Molecular Endocrinology, the Journal of Clinical Endocrinology and Metabolism, and Endocrine Reviews. Combined circulation is 22,500, of which libraries represent about one-third. The magazines are profitable, although Miller demurs at the term. "The journals do turn an excess of revenue over expense," he says, "but all that is plowed right back into services for members." PAYMENT RECEIVED: The University of Michigan paid Carolyn Phinney $1.671 million, ending a longstanding misconduct case. The Office of Research Integrity (ORI) has found that former University of Michigan graduate student Amitav Hajra committed scientific misconduct by fabricating and falsifying data in five publications, his doctoral dissertation, two review articles, one submitted paper, and an entry submitted to the GenBank database. The case generated attention because Hajra's mentor was Francis Collins, director of the National Human Genome Research Institute, who was at the University of Michigan before 1995 (Notebook, The Scientist, Nov. 11, 1996, page 30). Hajra has accepted ORI's finding and agreed to a voluntary exclusion agreement, which states that for four years beginning July 7, 1997, he will not contract with, subcontract with, or receive grants from the United States government or serve in any advisory capacity with the Public Health Service. Further, Hajra has agreed to cooperate in efforts to retract or correct his reported fictional results. . . . Psychologist Carolyn Phinney received a check for just under $1.7 million from the University of Michigan on July 30, ending a nearly decade-long case. In 1989, Phinney accused Marion Perlmutter, head of a lab at the university's Institute of Gerontology, of stealing ideas pertaining to her research aiming to measure wisdom and institute director Richard Adelman of retaliating against her after she complained. In Washtenaw Circuit Court in Michigan in 1993, a jury agreed with her and awarded $1.5 million in damages; the Michigan Court of Appeals in April 1997 upheld the decision and added interest (F. Hoke, The Scientist, Sept. 4, 1995, page 1; Notebook, The Scientist, April 28, 1997, page 23). Phinney, who intends to form a foundation called Whistleblowers for Integrity in Science and Education (WISE), says the reason she succeeded and other whistleblowers have not is that is that she had "a jury of normal, educated people instead of scientists" deciding the case. "A smart jury is a beautiful thing to behold." University official Lisa Baker told the New York Times (P.J. Hilts, Aug. 10, 1997, page A13) that the school "continues to stand by our personnel in this matter." 7-UP: Eric Green of NHGRI has mapped chromosome 7, which contains 5 percent of the human genetic code. The map of our genetic blueprint recently became a bit more complete. After mapping the X chromosome a few months ago, scientists with the Human Genome Project reached another important milestone in July by mapping chromosome 7 (G.G. Bouffard et al., Genome Research, 7:673, 1997). For the past eight years, a team led by Eric Green, chief of the genome technology branch at the National Human Genome Research Institute, has been developing a physical map of the chromosome. Famous for harboring the genes for cystic fibrosis and obesity (the human homologue of the mouse ob gene), chromosome 7 contains 170 million base pairs, or a whopping 5 percent of the human genetic code. "The goal of the genome project is to map a sequence tag site-one of [the] landmarks that could be detected by a PCR assay-every 100,000 base pairs across the human genome," says Green, who notes that this goal has been accomplished only for the X chromosome and chromosome 7. The mapping of chromosome 7 marks an important transition in the Human Genome Project from the mapping phase to the sequencing phase, according to Green. Because it has a good map associated with it, he hopes that chromosome 7 will be one of the first chromosomes to be completely sequenced. Scientists hope to sequence the entire human genome-approximately 3 billion base pairs-by early next century. Using a recently developed gene isolation and cloning system known as transformation-associated recombination (TAR) in yeast, a team of American and visiting Russian scientists at the National Institute of Environmental Health Sciences (NIEHS) has developed a new method for making quick duplicates of the breast cancer gene BRCA2 (V. Larionov et al., Proceedings of the National Academy of Sciences, 94:7384-7, 1997). The gene can be cloned in about two weeks using the new method, compared with previous approaches that typically took a few months to a year. TAR already has proved successful in isolating and cloning BRCA1, the first gene discovered to be responsible for breast cancer. TAR uses a vector to retrieve the desired gene or region of interest rather than attempting to do so by sorting out randomly cloned DNA. "The old method is based on cloning of random fragments from the genome and then identifying or attempting to identify your fragment of interest, which is a slow, laborious process," says Michael Resnick, a research geneticist and head of the chromosome stability group at NIEHS and a collaborator on the project. "The new method targets a region of special interest using sequence information from that region." Resnick foresees being able to use TAR to access diseased genes directly from humans who have some mutation by cloning that gene directly from the DNA in a small blood sample.

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