n e w s of t h e w e e k so McLachlan decided to withdraw the research in this highly visible manner. In the original research, McLachlan tested the estrogenic activities of the pesticides endosulfan, dieldrin, toxaphene, and chlordane individually and then in combination on yeast cells engineered with the gene for the human estrogen receptor. The substances were tested for their ability to bind to and turn on the estrogen receptor in this system. Over the past six months, McLachlan writes, "we have conducted experiments to elucidate the mechanisms to explain the phenomenon of synergy between estrogenic chemicals." Experiments were conducted on the roles that estrogen receptor levels, monomer and dimer configurations of the estrogen receptor, and chemical transport across cell membranes might play in the synergistic action of weak estrogens. None of the experiments provided a mechanism to explain the earlier findings. "Taken together, it seems evident that there must have been a flaw in the design of our original experiment," he writes. "McLachlan did the right thing," says George W. Lucier, director of the Environmental Toxicology Program at the National Institute of Environmental Health Sciences, Research Triangle Park, N.C. "His retraction moves the discussion away from synergy in his yeast system." However, his retraction does not mean that estrogenic chemicals do not have a synergistic effect, Lucier adds, pointing out that synergy in the estrogenic activities of polychlorinated biphenyls has been found in many studies that did not employ yeast cells. Only one or two of the papers that appear in Science each year are retracted, according to staff at the journal. Bette Hileman
Germany tops Chemistry Olympiad On the basis of gold medals won, Germany took first place at the 29th International Chemistry Olympiad, held July 1322 in Montreal. The country earned three gold medals and one bronze medal. The top of the lineup was crowded with "ties." Hungary and Taiwan tied for second place, each pocketing two gold medals, one silver medal, and one bronze medal. South Korea and Poland tied for third, each earning two gold medals and two bronze medals, and Iran and Turkey shared fourth place, with one gold medal 10 JULY 28, 1997 C&EN
needs to be careful not to wash too much. But I think that's what most of the kids did. When they tried to recrystallize their material, they lost it. A good yield would be 100 mg, but 95% of the | kids got nothing." I The U.S. team did well I enough to be rememS bered, said Brennan, de•û spite opening ceremonies •§ that unintentionally ne°- glected to recognize the participation of the U.S. Three of the four team members will enter college this fall and collectively study chemistry, biochemistry, computer science, and physics, while the fourth will complete high school (C&EN, July 7, page 38). Going to Harvard are gold medalist Chen, from Claremont High School, 1997 U.S. chemistry Claremont, Calif., and silver olympiad medalists medalist Andrew Hecker(clockwise from bottom ling (51st place),fromNiles left) Chen, Heckerling, West High School, Skokie, Krall, and Baker 111. Silver medalist Jordan Krall (38th place), from and three silver medals apiece. Russia, Sin- Harvard-Westlake School, North Hollygapore, Ukraine, and the U.S. tied for fifth wood, Calif., will attend Amherst College, place, each winning one gold medal, two Amherst, Mass., while bronze medalist Ian silver medals, and one bronze medal. Baker (112th place), returns to McCallie China, with four silver medals, fell to School, Chattanooga, where he will be a seventh place this year. Last year, China senior. slid to third place, unseated from the top The U.S. team was sponsored by the spot it had held since it began participat- American Chemical Society, principally ing in the olympiad in 1987. Iran took through the ACS Othmer Olympiad Ensecond place last year, and Russia, which dowment. Additional support was prohosted that competition, earned first. vided by the U.S. Air Force Academy, All together, 184 contestants from 47 IBM Research, Merck Publishing Group, countries competed in Montreal, and and Texas Instruments. representatives from seven countries obΜαίήη Brennan served the competition. The 21 highest scoring students were awarded gold medals. The next 36 won silver, and the next 58, bronze. Salih Ozcubukcu of Turkey, Jason Chen of the U.S., and Babak Javidi Dasht Bayazi of Iran earned the top three individual scores. Great Lakes Chemical, West Lafayette, Contestants completed afive-hourthe- Ind., intends to spin off its highly profit oretical exam and a five-hour laboratory able Octel Associates lead fuel additives exam, which this year included a mi- operations to shareholders by April 1998. croscale organic multistep synthesis. "That The shift, say some observers, could leave was really a disaster," says Christine B. both Great Lakes and U.K. manufacturer Brennan, coordinator of the U.S. national Octel open to a takeover. Although the transaction, which is chemistry olympiad program and a senior staff associate for the American Chemical pending government approvals, would allow Great Lakes to focus on its special Society's Education Division. "A multistep synthesis with microscale ty chemicals businesses such as flame re equipment is tricky," she explains. "One tardants, water treatment, and fine chemCÛ
Great Lakes plans to get the lead out
icals, it effectively strips Great Lakes of a cash cow that provided 53% of 1996 pretax profits of $421 million while ac counting for only 27% of the company's $2.2 billion in sales. But no matter how profitable lead fuel additives are now, their days are num bered. Sales of lead-based engine anti knock compounds have been declining for years. They are already banned in most industrialized countries because of health concerns, and world leaders agreed to phase out lead additives in developing countries at a United Nations General As sembly meeting on the environment in New York City late last month (C&EN, July 14, page 29). Great Lakes' President and Chief Exec utive Officer Robert B. McDonald says the spin-off will allow Octel executives, cur rently led by Managing Director Dennis J. Kerrison, to "maximize the cash flow and earnings from the lead antiknock business and transform Octel into a broad-based pe troleum additives company." Octel will seek a listing on the New York Stock Ex change (NYSE). After the spin-off, Great Lakes will be able to "better focus on its markets and pursue its individual strate gies more effectively," says McDonald. The Octel spin-off marks a strategic departure for Great Lakes. Under former Chief Executive Emerson Kampen, Great Lakes used profits from Octel to help fi nance the acquisition of businesses such as its 1994 purchase of EniChem's poly mer additive business and the Purex Pool Products business. Those days are about to vanish. However, Octel will provide Great Lakes with one last cash infusion before the spin-off. Octel will borrow $450 mil lion and will pay a special distribution of $300 million to Great Lakes. The $150 mil lion balance will redeem a 10.7% interest in Octel now held by Chevron Chemical and finance associated taxes and transac tion costs. Great Lakes purchased a control ling interest in Octel in 1989 from an oil consortium consisting of Chevron, Shell, British Petroleum, Texaco, and Mobil. Investors were apparently unhappy with Great Lakes' planned spin-off of Oc tel. The company's stock dropped $55/s to close at $48 on NYSE on July 17, the day the spin-off was announced. Special ty chemical analyst Jaine L. Mehring with New York City investment banking con cern Smith Barney notes that Great Lakes has lost a lot of investor goodwill. Earn ings have been "disappointing" over the past several years, she points out. Weak earnings combined with "fairly modest
debt" could expose Great Lakes to a take over by another company. Octel could be a takeover target, too. But as Mehring points out, fewer inves tors would be willing to buy and assume the liability of operating a business with about 80% of its sales in tetraethyl lead than would buy and operate a specialty chemicals business. Marc Reisch
Insulin leftover has protective effect A new study confirms what some people had suspected, a peptide remnant of in sulin biosynthesis can alleviate some of the damaging effects of diabetes. And it does so in a surprising way, through nonδ
Ί Ο
chiral interactions rather than specific binding to receptors. The remnant is called C-peptide. It links the two segments of insulin in the precursor called proinsulin, but splits off when insulin is formed. It is cosecreted with insulin in response to glucose stim ulation. No other role has been found for C-peptide, although clinical studies have suggested it has beneficial effects for diabetics. Now, Joseph R. Williamson, a profes sor of pathology at Washington Universi ty School of Medicine, St. Louis, and co workers there and at Lilly Research Labo ratories, Indianapolis, demonstrate that
human C-peptide can prevent and even repair the damage to nerve cells and blood vessels caused by diabetes in rats [Science, 277, 563(1997)]. The beneficial effects are observed only when the peptide is injected at dos es exceeding the levels in normal rats, says Williamson. That may explain why the activity was not unambiguously dem onstrated sooner. Earlier work with dia betic humans involved use of only enough C-peptide to match levels in nor mal people. John Wahren, a professor of clinical physiology at Karolinska Institute, Stock holm, says he's "delighted" with the new study. He and colleagues have observed in clinical studies that C-peptide im proves kidney function and ameliorates nerve damage in patients with insulin-de pendent diabetes, who lack both insulin and C-peptide. "We treat these patients by replacing only the insulin they don't have," he says. "Perhaps treatment can be improved if we also provide C-pep tide." He adds that the new findings "confirm and extend our clinical studies and provide a possible mechanism of ac tion for C-peptide." Remarkably, C-peptide's biological ef fect is unaffected by peptide chirality. This was unexpected, says Williamson, because most hormonal peptides exert their effects through stereospecific rec ognition of receptors on the cell surface. Instead, the researchers find that the D-enantiomer and the reverse-sequence isomer of C-peptide work as well as the native L-enantiomer. This finding is "real ly extremely novel," comments Donald F. Steiner, a professor of biochemistry and molecular biology at the University of Chicago and a senior investigator at Howard Hughes Medical Institute. The researchers say this result implies that C-peptide interacts with cell mem branes not by receptor-ligand interac tion, but by a different mechanism. They suggest the peptide may act by forming pores in cell membranes, similar to the way some antibiotic peptides work. The idea is supported by "very preliminary in vitro studies that strongly suggest C-peptides form pores in lipid bilayers," says Williamson. The researchers also have determined that the activity depends on a glycinerich, turnlike structure comprising resi dues at positions 13 through 19. Because this midportion is relatively nonpolar, it could be the region that interacts with lipid layers. Maureen Rouhi JULY 28, 1997 C&EN 11
