Download - Antiulcer drug receives FDA approval
The Chemical World This Week
COMPUTATION RESOURCE SET IN MOTION Nominations for policy board positions and for director of the National Resource for Computation in Chemistry (NRCC) are starting to come in at Lawrence Berkeley Laboratory, following selection of LBL as the host organization for the new resource (C&EN, July 25, page 14). LBL hopes to pick a tentative policy board within a few weeks.
That move is the first step in the procedures leading to operation of NRCC, which will begin after the new fiscal year starts on Oct. 1. It will be the U.S. chemical community's first major collective effort.
Once nominations are completed, the LBL director will appoint the initial policy board. The board's first order of business will be to choose, along with the director of LBL, a director for NRCC. The board then will work on setting up a users' organization.
NRCC will use LBL's existing computer center. The NRCC staff will be capable of documenting, testing, and improving software; developing new computational methods; and designing specialized hardware and software particularly suited to solving chemical problems. In addition, it will conduct chemical and computational research.
The new facility, says LBL deputy director Earl K. Hyde, "should make possible state-of-the-art computations that were not possible before." Chemists from academic institutions as well as industrial and government laboratories will have access to the resource for basic research in chemical kinetics, crystallography, macro-molecular science, nonnumerical methods, physical organic chemistry, quantum chemistry, statistical mechanics, and energy systems.
NRCC is the culmination of many studies and analyses over recent years. In 1970, a conference on computational support for theoretical chemistry was organized by the National Research Council's Committee on Computers in Chemistry, under the chairmanship of Dr. Peter G. Lykos of Illinois Institute of Technology. That conference recommended establishment of a national computation center for quantum chemistry. In 1974, an NRC study group headed by Dr. Kenneth B. Wiberg of Yale University showed
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that computational needs extended beyond just theoretical chemistry. Its two-year study focused on the feasibility and desirability of a national computing center and recommended its establishment.
The NRCC idea took a big step forward in 1975 with completion of a study by an NRC Planning Committee for a National Resource for Computation in Chemistry, chaired by Dr. Jacob Bigeleisen of the University of Rochester. That report set out details of physical, management, and funding needs for the facility. In 1976, with planning for NRCC under way and site selection in progress, the planning committee held a workshop that resulted in what amounts to a "handbook" of research needs to aid the NRCC director and staff.
NRCC is being funded jointly by the Energy Research & Development Administration and the National
Antiulcer drug receives I Tagamet, a drug for treating duodenal ulcers that was developed by SmithKline Corp., has just received Food & Drug Administration approval for marketing. Stocking of pharmacies is to begin immediately, and the company expects that physicians can begin prescribing the drug within several weeks. Tagamet has been available in the U.K. for nearly a year and is being marketed throughout the world.
The drug belongs to a newly described class of compounds that act as antagonists of type-two histamine receptors. These receptors are found on the acid-secreting cells of the gastrointestinal tract. The cells release acid when they bind histamine molecules, contributing directly to ulcer formation.
Tagamet interferes with this binding, thus blocking acid secretion. The drug, when administered orally or by injection, can heal duodenal ulcers rapidly, sometimes within weeks, according to SmithKline.
Tagamet, known generically as cimetidine and chemically as iV-cyano-N/-methyl-iV//-[2-([(5-methyl-lif-imidazol-4-yl) methyljthio) ethyl] guanidine, is a partial structural analog of histamine. Both contain imidazole rings, though the ring of the
Science Foundation. The t\#o agencies held a competition to select the host institution, and LBL got the nod.
Under the approved plan, NRCC will become a new division of LBL in order to maintain its national character and its independence from other activities at the laboratory. It will have available to it LBL's computer center, which has a Control Data Corp. CDC 7600 computer coupled with two CDC 6000 series computers. Extensive outside user facilities and software are available.
More or less in line with what was envisioned by NRC, the first-year budget for NRCC is $1.3 million, and it is expected to grow to $2.4 million by 1980. Of the $1.3 million, $440,000 is allocated for staff salaries and $400,000 for computing. The remainder is for workshops, equipment, communications, and the like. D
DA approval new drug is methylated. Actually, Tagamet is one of a series of histamine analogs that SmithKline scientists have synthesized.
It succeeds another candidate, metiamide, that was therapeutically effective but produced the unwanted side effect of reducing white blood cell
SmithKline researchers examine histamine reaction products using TLC
production in some patients. Tagamet appears free of such side effects, although at high doses it has produced liver and kidney damage in rats and dogs.
Development of Tagamet culminates a 13-year program, begun in SmithKline's U.K. laboratories, looking into the chemical and biological activities of histamine. Probably better known as the culprit in hay fever and other allergies, histamine is involved in many inflammatory reactions in the body.
However, its involvement in causing ulcers is undoubtedly most devastating. Four million Americans suffer from ulcers, and more than 6000 of them die each year from resulting complications. Medical costs for ulcer sufferers will reach nearly $1.5 billion this year, and less than 10% of that goes for purchasing drugs. Company spokesmen expect Tagamet to have a significant impact on treating gastrointestinal disease. D
Changes in energy tax laws suggested by PEG The petrochemical industry, having won some and lost some when the House passed its omnibus energy bill, took its case to the Senate earlier this month. In testimony before the Senate Finance Committee, which is considering the tax provisions of the energy legislation, the Petrochemical Energy Group said it "frankly doubted the effectiveness of using the tax system to accomplish energy policy objectives."
Instead it advocates deregulation of oil and natural gas prices as the best way to promote conservation and conversion to other energy sources. However, if the tax system will be used to help achieve such goals, as seems most likely, PEG advocates a number of changes in the legislation as proposed by the President and as passed by the House.
Speaking for PEG, 0. Pendleton Thomas, chairman of the board and chief executive officer of B. F. Goodrich, said that adherence to Administration tax proposals would raise U.S. manufacturers' fuel and feedstock costs above prices paid by foreign competitors. This, he says, actually would frustrate energy policy goals by increasing dependence on foreign energy sources. It also would negatively affect the petrochemical industry's up to now positive trade balance and inevitably raise consumer prices.
To avoid such unwanted effects at least in part, Thomas first suggests that consumption taxes on oil and 1
natural gas be imposed only where practical opportunity exists for conversion from or conservation of oil, natural gas, and natural gas liquids. He urges that the Senate go along with the House and exempt feedstock use and nonsubstitutable process use, such as use of natural gas in cracking furnaces to produce ethylene, from energy consumption taxes.
Secondly, a House-passed provision taxing natural gas liquids as part of the crude oil equalization tax
Thomas: tax would raise costs
should be changed to ensure that the tax is measured from each vendor's ceiling price, not from some arbitrary average price, which would not take into account widely varying prices caused by controls. However, Thomas also advocates subjecting natural gas liquids used for boiler fuels to the same consumption tax imposed on oil used for boiler fuels. If this is not done, he explains, a boiler fuel user could find it cheaper to use natural gas liquids than fuel oil, taking the nonsubstitutable liquids from farmers, petrochemicals, and other feedstock and process users. D
Sterility in workers halts fumigant output In the wake of reports of sterility among male plant workers involved in the manufacture of a widely used soil fumigant, l,2-dibromo-3-chloropro-pane, or DBCP, yet another firm has halted production of the substance.
Dow Chemical stated on Aug. 11 that it has stopped production and sale of DBCP at its Magnolia, Ark.,
plant. Sold by Dow under the tradename Fumazone, the compound is used in agriculture to exterminate nematodes, grublike worms that destroy plant roots. Early this month Occidental Petroleum Corp. closed the agricultural chemical unit at its Lathrop, Calif., plant because of sterility among plant workers exposed to DBCP, which the firm sells under the name Oxy-DBCP-12. At the Lathrop plant, nine out of 23 workers exposed to the chemical had no sperm count at all after working in the plant from four to 15 years. Other workers who had worked for shorter periods of time also showed marked reduction in sperm count. Dow also has found reduced sperm counts among workers at its Arkansas plant. California has banned the sale of the soil fumigant.
The National Institute for Occupational Safety & Health is now investigating plants that either make or process DBCP with any regularity. Shell Chemical is the only major producer of the compound other than Dow, and together they produce about 25 million to 30 million lb annually. Shell has stopped making the chemical for this season. Occidental buys the chemical from Dow, although the firm has produced it in the past.
The Occupational Safety & Health Administration has warned some 80 firms that "appropriate action should be taken to protect employees from this potential hazard." The Environmental Protection Agency, which regulates pesticides, also is investigating DBCP, and an EPA spokesperson concedes that canceling its registration is being considered "as an option."
Dr. Channing Meyer, chief of NIOSH's medical hazards program in Cincinnati, explains that although DBCP is the prime suspect in the Occidental plant incidents, other causes can't be ruled out. He notes, for example, that both the Occidental plant in California and the Dow plant in Arkansas produce other bromi-nated chemicals, such as ethylene dibromide, that also could be responsible. Meyer believes, however, that other causes are unlikely, because animal experiments conducted by Dow in the early 1960's showed testicular damage in rats exposed to DBCP.
So far there is no federal workplace standard for exposure to DBCP, although Dow recommends that worker exposure be kept below 1 ppm. But even that may not be low enough. NIOSH's Meyer says that as far as the agency has been able to determine, exposures in the Occidental plant averaged about 0.5 ppm. D
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