Merck hypertension drug nears approval The Food & Drug Administration's Cardiorenal Advisory Committee has unanimously recommended approval of the angiotensin-converting enzyme (ACE) inhibitor enalapril, developed by Merck Sharp & Dohme, to treat high blood pressure. FDA could give approval in less than a year. ACE inhibitors are an important new class of drugs for hypertension. Captopril, the first drug in this class to get FDA approval, has been marketed by Squibb since the mid1970s. ACE catalyzes conversion of angiotensin I to active hormone angiotensin II. Angiotensin II both constricts blood vessels and stimulates the adrenal glands to produce aldosterone, which in turn stimulates sodium retention, all as a part of normal blood pressure control. Early studies suggested that captopril caused such side effects as impaired kidney function, lower counts of infection-fighting white blood cells, abnormally low blood pressure, and loss of taste. As a result, FDA approved captopril only for use with other drugs in cases
where patients did not respond to other drugs or other drugs caused unacceptable side effects. The early studies were done at high doses on patients with very high blood pressure, some of whom had impaired kidney function or had been given immunosuppressive drugs. Later studies at lower doses showed a relative lack of side effects. Thus FDA may lift labeling restrictions on captopril at the same time it gives broad approval to enalapril. This pair of regulatory moves could lead many doctors to use ACE inhibitors as drugs of first choice for hypertension. Believing that the mercapto group of captopril contributed to adverse reactions, Merck chemists designed enalapril to avoid this group. Captopril is N-/3-mercaptoisobutyrylproline. Enalapril has an ethyl 7-phenylbutyrate moiety attached at its a-carbon to the end amino group of alanylproline. Newer studies that find captopril and enalapril comparable in side-effect profiles may mean that the mercapto group of captopril has less importance than once thought. •
Forum urges increased automation m industry U.S. manufacturers must increase their use of advanced automation systems as a matter of economic survival. At the same time, all sectors of society must begin immediately to take steps to mitigate the potential impact of the industrial transformation on U.S. workers. So urges the Business-Higher Education Forum in a new report, "The New Manufacturing: America's Race to Automate." The forum, a group affiliated with the American Council on Education, Washington, D.C., is composed of chairmen, presidents, and chief executive officers of major U.S. corporations, and presidents and chancellors of major U.S. colleges and universities. Currently there are 40 corporate members and 39 academic ones. "Due to the new realities of global competition," the report says, "American manufacturers will have three alternatives in the future: to
automate; to go out of business; or to risk a continuing loss of market share to domestic and foreign competitors." A successful transition to automated manufacturing, the report points out, will cause widespread changes in the workplace, often because of an alteration in the nature of work. In response, the forum urges the start of an immediate "national dialogue" on the subject as a way of coping with the human issues raised by the transformation— which, it notes, will affect not only factory workers displaced by machines, but managers, who will be required to organize and oversee production differently. The report analyzes some of the implications of the transformation for workers, management, and market structure. The report's focus is more on the manufacturing industries than on the process industries. Nevertheless,
many of the implications of increasing automation can apply to the chemical industry as well. Although the chemical industry is among the most highly automated now, that automation is primarily at the process level. The chemical industry, too, seems destined to experience major alterations, as the growing application of distributed digital control and microcomputers broadens process control concepts to include supervisory and management levels (C&EN, May 21, page 7). Copies of the forum report are available prepaid for $12 each from Business-Higher Education Forum, 1 Dupont Circle, Suite 800, Washington, D.C.20036. •
EPA official touts agency's achievements Alvin L. Aim, deputy administrator of the Environmental Protection Agency, spoke to members of the forest products industry last week, and he may have disappointed his audience. They had come hoping to hear about EPA's decision on a pending regulation to control the use of a dioxin-containing wood preservative. Instead, members of the American Paper Institute and the American Forest Products Association listened patiently to a resume of activities of the 13-month-old Ruckelshaus-Alm regime at EPA. Saying that his was no report on "Indiana Ruckelshaus and the Temple of Gloom"—a bad pun on a new movie—Aim pointed with pride to renewed confidence in the agency. "EPA has a firmer and more coherent view of the future and of its own w o r t h , " he says. This was achieved by Aim and Administrator William D. Ruckelshaus making decisions "in the fishbowl," and involving the public in the decisionmaking process. "We believe that the public, whom we are sworn to serve, has a right to know how and why we make decisions affecting their health and safety, and their pocketbooks," Aim says. Renewed confidence in the agency also was achieved by filling in the "areas in which very large policy gaps had been allowed to develJune 25, 1984 C&EN
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Aim: more coherent view of future o p " under the former EPA administrator, Aim says. This was accomplished in part by setting up 10 task forces one year ago to deal with internal organizational problems as well as "substantive issues like acid rain, toxics, compliance and enforcement, and groundwater," he explains.
Some of the task forces have produced tangible results. For example, one has developed a comprehensive groundwater strategy that is now in the hands of 500 reviewers. Another has developed six risk assessment guidelines, plans to conduct risk audit assessment, and set up an internal body to establish a risk assessment policy. Still another produced compliance strategies, which, combined with enhanced resources, has beefed up the agency's enforcement effort. "The total number of enforcement personnel has never been higher than it is now," Aim says. Agency management systems also have been improved, he proclaims. Priorities are clearly established and publicly known. "We are the only federal agency to lay out its priorities for the world to see." Among the top goals are activities to control hazardous waste, reissue water permits, implement the groundwater strategy, and work with the states on so-called nonpoint source control measures. •
Revised laws called for to clean up environment In its just-issued second biennial report on the state of the environment, the Conservation Foundation concludes, not surprisingly, that the U.S. has made and continues to make significant progress in many areas, such as the quality of air, water, and land, where laws and institutions have been designed explicitly to address specific problems. But this very specification means that existing environmental laws and institutions are unable to cope, the Conservation Foundation contends, with the new environmental problems facing the U.S. These problems are characterized by uncertainty about cause and effect, large costs of action or inaction, and inadequacy of laws and institutions. Toxic substances are one prime example of the new environmental problems. As the report points out, "Scientific findings are increasingly revealing that major water pollution problems are due to air pollution being deposited in water; at the same time, studies in Philadelphia and elsewhere are revealing 6
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that municipal plants to treat water pollution are major sources of air pollution from volatile organic chemicals." It says that instead of reducing human and environmental exposure to toxics, much of the existing control effort simply may be shifting pollutants from one part of the environment to another. But even though problems such as these require changes in the basic environmental laws, these laws have expired, and there has been little or no progress in revising or reauthorizing them. This lack of progress is symptomatic of underlying political stalemate, according to the foundation. Neither of the two major contending forces, industrial and environmental interest groups, has enough political strength to pass legislation. However, each has sufficient power to block new legislation. Thus, the report concludes, "environmental policy at mid-decade is suspended between progress and retrogression, between cooperation and polarization." Copies of the report, "State of the
Environment: An Assessment at Mid-Decade," are available from Lydia Anderson, Public Relations Department-KK, Conservation Foundation, 1717 Massachusetts Ave., N.W., Washington, D.C. 20036. The price is $16. •
Gene splicing applied to cheese production Large-scale cheese trials using rennin produced by recombinant DNA techniques recently were completed •and termed a success, according to Genencor, South San Francisco, and Chr. Hansen's Laboratory Inc., Milwaukee. Rennin is the enzyme used in cheese production that causes coagulation of milk solids into curds, which are then separated from the whey. Currently, rennin used in cheese production is obtained from calves' stomachs. The tests were conducted by food scientist Claire L. Hicks and coworkers at the University of Kentucky, Lexington, using rennin produced by Genencor. According to a spokesman for Chr. Hansen's, the cheddar cheese prepared using the genetically engineered rennin possessed flavor and texture equal to cheese p r e p a r e d from commercial calf rennin. The companies believe that recombinant DNA rennin will be competitive with rennin from calves' stomachs and will help to stabilize the market in calves' stomachs. Details of the research are scheduled to be presented this week at the American Dairy Science Association meeting in College Station, Tex. It is the first time rennin has been prepared in large quantities using recombinant DNA techniques. Genencor produced the rennin in Escherichia coli. In other cheese-related developments, Genencor and Chr. Hansen's Laboratory announced the development of a lipase /protease blend that significantly accelerates the aging process in cheese. Use of the blend can cut the aging time of cheddar cheese in half, which promises the cheese industry savings on the cost of storage during the aging process. •
