NEWS OF THE
WEEK
Phosphonates haven't attracted a great deal of attention as drug candidates, notes Norbert Bischofberger, vice president for research at Gilead Sciences and a coauthor of the Science paper. Scientists had assumed these molecules aren't stable and don't get into cells. But what's unique about compounds like PMPA and PMEA, Bischofberger tells C&EN, is that they have a phosphoruscarbon bond. This makes them resistant to hydrolysis in biological systems. "They do get into cells and they are very potently active," he says. According to Tsai, PMPA is more effective than either PMEA or AZT at protecting monkeys exposed to SIV, and it is also less toxic. He views PMPA as a
promising candidate for anti-HIV treatment, either alone or in combination with other antiviral therapies. His group is now gearing up to conduct experiments—already approved— to see if infection can be prevented by administering PMPA to newborn monkeys immediately after they are exposed to SIV. "This study could have important implications for pediatric AIDS," Tsai points out, because about 70 to 80% of neonatal HIV transmission is thought to occur during the birth process. PMPA hasn't yet gotten the green light for clinical trials. But Tsai hopes the results in macaques will accelerate approval of human tests. Ron Dagani
Fertilizer merger weds IMC Global and Vigoro IMC Global has inked a deal to acquire Vigoro Corp. for about $1.2 billion in stock. Merger of the two fertilizer makers in early 1996—assuming shareholder and regulatory approval—will create one of North America's largest fertilizer producers. IMC Global is the lowest cost North American phosphate producer and Vigoro, the lowest cost potash producer worldwide, according to the companies. "The strength derived by the combination of these complementary companies will allow the new company to compete more effectively in the
Vigoro and IMC Global at a glance Sales: $804 million (in 1994) and $1.9 billion (year ended June 30, 1995), respectively Earnings: $53.4 million (in 1994) and $114.7 million (year ended June 30, 1995), respectively Headquarters: Chicago and Northbrook, 111., respectively Employees: 2,100 and 6,800, respectively Major businesses: Vigoro—potash, nitrogen-based fertilizers, specialty and consumer products (including water softeners, and lawn and garden products), and 200 retail stores; IMC Global—potash and (through joint venture IMC-Agrico) phosphate fertilizers and animal feed ingredients
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NOVEMBER 20, 1995 C&EN
global crop nutrient marketplace, with the new IMC as the most efficient producer of potash and concentrated phosphates," says Wendell F. Bueche, IMC Global's chairman and chief executive officer. IMC Global, based in Northbrook, 111., produces potash at two mines in Saskatchewan and one in New Mexico. It makes phosphate-based fertilizers and animal feed ingredients at six facilities in Florida and Louisiana through IMC-Agrico, its joint venture with Freeport-McMoRan Resource Partners. Vigoro, based in Chicago, produces potash at two mines in Saskatchewan and one in Michigan, and it makes nitrogen products at two U.S. plants. Its solution mining technology—used at two of its three potash mines—could help solve IMC Global's problems at its Canadian Esterhazy mine, which has suffered water inflow since 1985. The new company will retain the IMC Global name and be headquartered near Chicago, with Bueche serving as chairman and CEO. Vigoro has 19.9 million common shares outstanding. The merger calls for each Vigoro share to be exchanged for between $49.50 and $64 worth of IMC Global stock, depending on IMC Global share prices. The transaction may be reassessed should IMC Global shares fall below $58.235 or rise above $85.333. IMC Global closed on Nov. 13, the day the merger was announced, at $73, down $l5/s. Vigoro closed at $55, up $93/4, reflecting the deal's premium for Vigoro shareholders.
The merger "furthers an ongoing trend where producers try to broaden their product line to contain each of the three fertilizers—potash, phosphates, and nitrogen—as well as distribution [capability]," says David Silver, a chemical industry analyst at New York Citybased investment banker CS First Boston. Increased potash capacity also will smooth IMC Global's earnings, which have been buffeted by the erratic nature of phosphate exports, he notes. Elisabeth Kirschner
Monsanto offers second $1 million challenge The success of Monsanto's first $1 million contest has led it to issue a new challenge to the research community: Find a practical, cost-effective way to recover high-purity amino acids and both phosphoric and phosphorous acids from wastewater, leaving only a clean sodium chloride stream. The new challenge was announced last week at the American Institute of Chemical Engineers' (AIChE) national meeting in Miami. Monsanto hopes the $1 million prize will lead to an innovative, commercially practical solution to an expensive waste problem, says Earl R. Beaver, the company's director of waste elimination and manager of the challenge program. The deadline for proposals is March 31,1996. The first $1 million challenge, issued in August 1994, sought a process to separate and remove ammonia—the firm's single largest waste component—and at least 99% of the organic pollutants from waste streams. The winner was SRI International of Menlo Park, Calif. Details of the winning process are confidential, but Beaver says it uses an anaerobic bioreactor, an ammonia recovery and separation step, and a sulfur recovery step. SRI's team included Ronald M. Smith, senior consultant in the firm's petrochemicals, polymers, and energy center; Abhoyjit S. Bhown, manager of separation science and technology; and Luke V. Schneider, manager of the bioprocess technology program in the materials and chemical engineering lab. "Monsanto is still looking for more ways to reduce the generation of waste at the source of its operations and to do a better cleanup job with the established
Beaver (Hght) greets SRI winners (from left) Smith, Bhown, and Schneider.
technology/7 Beaver notes. In the first contest, Monsanto received 182 formal proposals and about 200 other submis sions. Independent judges named by the Center for Waste Reduction Technolo gies (CWRT) in Washington, D.C., which is affililated with AIChE, nar rowed the field to 54 finalists. The final ists were reviewed by six experts from government and industry. CWRT mem ber firms have the option of jointly fund ing runner-up proposals and have al
ready decided to fund two projects based on four similar ideas. SRI received an initial $500,000 when the award was announced last spring (C&EN, April 10, page 9) and will get the remaining $500,000 if development work indicates the technology can be ap plied to Monsanto's manufacturing op erations. SRI has a year to demonstrate the process's feasibility on a bench scale with a flow rate of at least 1 lb per hour. Joseph Haggin
FDA panel probes safety of fat substitute Procter & Gamble's (P&G) eight-year effort to win Food & Drug Administra tion approval to market olestra, its noncaloric synthetic fat substitute, en tered a new stage last week. A working group of FDA's Food Advisory Com mittee began hearings on P&G's safety review of olestra use as a fat replace ment in some snacks.
The panel will determine if all criti cal safety issues have been addressed and if there is a "reasonable certainty of no harm" from olestra consump tion. FDA will base its decision, in part, on the panel's work. If FDA gives a green light, olestra could be used to replace 100% of the fat used in snacks such as cheese puffs and pota to chips. However, there is op position to approval of OR olestra. Opponents say it causes, among other things, depletion of im RO OR portant nutrients and a variety of gastrointestinal Triglyceride ROdisturbances. Olestra Olestra is a sucrose polyester. It looks like fat, R= 6-, 7-, or 8-carbon fatty acid group cooks like fat, and gives food the rich taste and Olestra has all the qualities of ordinary triglyceride mouth feel of ordinary fats, but its size and shape make it indigestible. fat. It is heat stable, so it can be used in frying,
cooking, and baking. But it differs from ordinary triglyceride fats because the sucrose polyester molecule is too big for fat-digesting enzymes to attack, thus contributing neither calories nor fat to the diet. For example, a serving of ordinary potato chips contains 10 g of fat and 160 calories. The same serving of chips cooked in olestra contains zero fat and only 70 calories. 'Olestra is the most thoroughly test ed new food ingredient ever consid ered by FDA," says Keith C. Triebwasser, P&G's director of regulatory and clinical development. Over the past 25 years, P&G has conducted more than 100 animal and 98 human studies, and it submitted 150,000 pages of test data to FDA. P&G is reported to have spent about $200 million researching and testing olestra. On the other hand, the Center for Science in the Public Interest (CSPI)—a Washington, D.C.-based health advoca cy group—is urging FDA to deny ap proval to olestra. "Olestra sounds too good to be true, and it is," says CSPI Executive Director Michael F. Jacobson. "Olestra is the first food additive with negative nutritional value." Indeed, Jacobson adds, "In recent weeks, Procter & Gamble has been run ning away from its own best studies." These studies, he says, indicate that olestra significantly depletes serum carotenoids and other fat-soluble nutri ents, which many believe are essential to protect people against heart disease, cancer, and blindness. In fact, P&G in tends to compensate for any potential drop in lipophilic nutrients by adding vitamins A, D, E, and Κ to products made with olestra. But CSPI says that won't work. CSPI also says that P&G data dem onstrate that even small amounts of olestra can cause gastrointestinal symptoms—ranging from loose stools to nausea, cramps, and fecal urgency, to passive anal leakage of olestra. P&G contends that people eating normal amounts of olestra-containing snacks do not experience such problems. But Jacobson cites studies of subjects who experienced gastrointestinal symptoms after eating 8, 20, and 32 g of olestra per day divided over three meals. Those levels would be found in 0.8, 2, and 3 oz of olestra-fried potato chips, respectively, he notes. Linda Ruber NOVEMBER 20,1995 C&EN
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