also covers the suspension polymeriza tion of vinyl chloride and vinyl acetate to give copolymer resins. The Wulff process, too, could play a big role in vinyl chloride production. Carbide voices optimism for the proc ess's future despite scaleup and startup problems (C&EN, April 1, page 13). Paul Boliek, Carbide's manager of the process, says that one of the reasons for this confidence is that the poten tial for improvement is still very large. Carbide is directing much of its development effort toward reducing the ratio of investment to furnace productivity. The productivity of a standard furnace pair, or Wulff unit, has increased from 35 million pounds per year of acetylene and ethylene to almost 70 million pounds per year of combined olefin capacity since Car bide began its development effort. As this evolution continues, the Wulff process will become competitive in the U.S. with tube furnaces for the pro duction of ethylene, Carbide says. Carbide has operated a Wulff plant at Institute, W.Va., since 1961. It is now bringing on stream a large Wulff plant at Taft, La., but will not dis close capacity of the plant or its custo mer for acetylene, although Hooker's trichloroethylene and perchloroethylene units at Taft are a prospect.
Dow quiet on cumene source for new phenol plant Where Dow can get the cumene for its new phenol unit to be built at its Oyster Creek Division near Freeport, Tex., seems a question equal to that of where the large quantity of phenol will be used. Dow has said that the initial phenol capacity will be 400 mil lion pounds per year. This capacity will require about 650 million pounds of cumene (isopropyl benzene). Other than that construction is to start early next year and that comple tion will be in 1970, Dow is not saying much about the new Oyster Creek unit. Dow has vinyl chloride mon omer and caustic-chlorine plants un der construction at the same site, which is close to Dow's two massive Texas Division plants near Freeport. Dow currently makes phenol in Mid land, Mich., and Kalama, Wash. The Midland phenol process is based on chlorination of benzene; that in Ka lama is based on oxidation of toluene. The Kalama plant phenol capacity is quite small, probably not more than 50 million pounds per year; the Mid land capacity is more than 200 million pounds per year. Dow officials decline to disclose whether they will buy or make cumene for the Oyster Creek phenol plant.
Dow's Texas division plant near Freeport Possible source of materials for making phenol at new Oyster Creek unit If Dow should make cumene, it will be a change from what has been stand ard procedure in the industry—chemi cal companies buy cumene and oxidize it to phenol (and coproduct acetone), while oil companies make cumene and sell it to chemical companies. Should Dow choose to be a pur chaser, it shouldn't have any supply problem, since plenty of cumene should be available by 1970. Expan sion of cumene capacity is under way with companies such as Gulf Oil add ing large units (C&EN, July 10, 1967, page 2 2 ) . Gulfs new unit will be at Port Arthur, Tex., with a capacity of 300 million pounds per year of cu mene. Sunray DX also has a new cumene plant on the Gulf Coast. Other companies have added new cu mene capacity or debottlenecked ex isting units. Dow's added phenol production, though almost two years off, will come at about the same time other compa nies such as U.S. Steel will add new phenol capacity. Other sizable capac ity, such as the 150 million pounds from Union Carbide, went on stream during 1967. U.S. capacity for syn thetic phenol is now about 1.6 billion pounds annually. However, production of synthetic phenol fell off a bit during 1967 to under 1.19 billion pounds from 1.29 billion pounds in 1966, according to preliminary figures from the U.S. Tar iff Commission. Until last year, phe nol production had been growing steadily since 1961. Consumption of phenolic resins (production of which uses about half of all phenol pro duced), other polymers made from bisphenol-A, caprolactam, and adipic acid showed growth during the first quarter of 1968.
Response of leukemia cells to L-asparaginase explained Why some leukemia cells in man are resistant to injections of the enzyme L-asparaginase while other leukemia cells are destroyed by this promising chemotherapeutic agent has been ex plained by a New York City group of biochemists and physicians. The group explains the phenomenon in terms of a certain "defect" in the al ready errant metabolism of the can cerous blood cells. Speaking at the 59th annual meet ing of the American Association for Cancer Research in Atlantic City, N.J., biochemist Bernard Horowitz summed up the research results from his work at Cornell University Medical College with Dr. Alton Meister, Dr. Bertha Madras, and Sloan-Kettering Institute's Dr. Lloyd Old and Dr. Edward Boyse. The group finds that L-asparaginase treatment is ineffective against those leukemia cells which contain L-asparagine synthetase—another enzyme oc curring in normal cells. But such treat ment is remarkably effective against those leukemia cells which are defi cient in L-asparagine synthetase, they note. Occurring as it does in some leu kemia cells and in all normal cells, the synthetase enzyme catalyzes the bio synthesis of the simple amino acid L-asparagine. This compound—a βamide of aspartic acid—is essential to the metabolism of normal cells. It is also essential to the metabolism of the metabolically defective leukemia cells, graduate student Horowitz points out. Those leukemia cells capable of synthesizing their own L-asparagine APRIL 22, 1968 C&EN
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are not dependent, as other leukemia cells are, on acquiring this amino acid from extracellular fluids. The effect of L-asparaginase treatment is to destroy such extracellular L-asparagine by hydrolyzing it to L-aspartic acid. This hydrolysis terminates the availability of L-asparagine to leukemia cells that depend on a supply of this amino acid. To establish the activity of the synthetase enzyme, the workers first prepared a mixture of ingredients needed in the synthesis of L-asparagine. These compounds include L-asparagine synthetase, aspartic acid, adenosine triphosphate, glutamine, and magnesium ions. The reaction of these compounds yields L-asparagine, adenosine monophosphate, pyrophosphate, and glutamic acid, the New York City group notes. After preparing this assay system for measuring the enzyme activity of L-asparagine synthetase, Dr. Meister continues, a tumor preparation is treated with the solution. Following a 10- to 60-minute reaction with the tumor at 37.6° C. (body temperature), the workers remove the synthetase enzyme from the solution with a protein precipitant. They then analyze the supernatant solution by paper electrophoresis to show that Lasparagine is indeed formed as a result of the synthetase activity. They find, too, a reduction in the concentration of aspartic acid which is proportional to the amounts that are aminated to L-asparagine. "We now understand at the enzyme level an important biochemical difference between normal cells and cancer cells, Dr. Meister tells C&EN. "We're really encouraged with these findings inasmuch as they allow us to therapeutically exploit the metabolic defects of cancer cells."
Fast method for detecting, measuring endotoxin developed Using cells taken from the blood of horseshoe crabs, a Johns Hopkins University scientist has developed a quick test-tube method for detecting and measuring the disease-producing micromolecule endotoxin. Dr. Jack Levin's work—the most sensitive in vitro technique yet developed for endotoxin—promises to assist studies of the mechanism by which endotoxin causes a variety of pathological effects in humans and other mammals. He reported his findings in Atlantic City at the 52nd meeting of the Federation of American Societies for Experimental Biology. Endotoxin is a high-molecularweight lipopolysaccharide and a con14 C&EN APRIL 22, 1968
stituent of cell wall of most gram-negative bacteria. In severe gram-negative infections a condition called endotoxemia often develops, displaying itself as shock and fever frequently as a prelude to death. One of its more pathologically relevant effects is to promote clotting within the blood vessels so that the host's normal clotting mechanism becomes exhausted with resulting uncontrolled bleeding after a wound. Competition among molecular pathologists is intense over determining how endotoxin interacts biochemically with the host's metabolic processes. Does it work through a protein or a chemical mediator? Or does it act directly on the various systems it affects? Dr. Levin's technique, a result of a bit of seashore serendipity by Dr. Frederick Bang of Johns Hopkins, gives biochemists, medical research scientists, and pharmacologists a fast assay with a potential sensitivity for the detection of endotoxin in human blood serum of 0.005 microgram per ml. Other in vitro methods are 100 times less sensitive. The method is based on the ability of endotoxin to form a gel when mixed with an extract of amoebacytes, the circulating blood cells of Limulus, the ancient horseshoe crab. The process consists simply of adding endotoxin or solutions containing it to the extract. The extent and rate of gelation are measured by light scattering and can be used to measure endotoxin concentration. Overall, the technique takes about an hour. "So it seems to me that we have a very sensitive and quantitative technique with which to study the physicochemical reactions of endotoxin with protein," Dr. Levin says. "By studying the nature of this reaction with the protein in the Limulus extract, we can obtain insight into the kinetics of the process, and perhaps how endotoxin acts to initiate or accelerate coagulation, and how it affects blood vessels." Dr. Bang's role in the study began about 10 years ago. His collaboration on the problem with Dr. Levin started five years later.
Are pulsars from intelligent sources or from neutron stars? When pulsars were described by Dr. Frank Drake to the American division of the International Scientific Radio Union earlier this month, the possibility that they are being emitted by an intelligent source far out in space could not be entirely dismissed. But Dr. Drake, head of Cornell University's Arecibo Ionospheric Ob-
servatory in Puerto Rico, is an astronomer. On a scientific basis he considers the arguments against pulsars coming from intelligent beings to be persuasive, although not conclusive. He reported to ISRU that three of four pulsars are generating pulses of 38 to 40 thousandths of a second. The intervals between them are from 1.0 second to 1.3 seconds. These observations support a "neutron star" theory put forward by British astronomers to explain the pulsars. The British, using the Mullard Radio Astronomy Observatory at Cambridge University in November 1967, detected a series of remarkably regular signals or pulses. The radiotélescope was operating at a frequency of 81.5 MHz. Each pulse lasted 0.3 second, repeated every 1.337 seconds. The regularity, constant to better than 1 in 10 7 , suggested to the British a man-made origin of the signals. The absence of parallax showed that the source was lying far outside the solar system but still in our galaxy. The Cambridge team leader Anthony Hewish dubbed the source a pulsar. Further work detected three other pulsars with properties similar to the first. The Cambridge team found that duration of emission of the pulses at any frequency never exceeded 0.016 second. The source size thus could not be bigger than 4.8 Χ 10 3 kilo meter. Furthermore, sharpness of the signal, and a lack of parallax greater than two minutes placed the pulsar at a distance of 100 to 300 light years. In astronomical measures, this is a short distance. The British astronomers threw out the idea of pulsars being associated with intelligent life because the fan tastic amount of energy needed to gen erate the signals suggested a natural phenomenon. They worked up two theories, one based on plasma oscilla tion, the other a binary theory of star pairs spinning around each other. Their final idea was that the signals are natural oscillations of dying stars that have shrunk by gravitational contrac tion into neutron stars. A neutron star is an incredibly dense body of atoms which have collapsed to form neutrons tightly packed and spinning at extra ordinary speeds. Existence of such a star had already been postulated but never discovered. While arguments against the pul sars being artificial in origin are not conclusive, the neutron star theory fits some of the observations. Such a star would spin at the rate required to pro duce energy to generate the signals. But theory is theory. Arecibo-based Americans and Cambridge-based Brit ish have a good deal more listening to do. Perhaps the pulsars are listening now to us listening to them.
