a killed-virus vaccine. Mice were injected with the vaccine and t h e n , after an interval, they were given live virus. T h e y were protected. Thus, SloanKettering c a n claim t h e first effective vaccine against a mammalian cancer. Further experiments have shown that this vaccine is entirely specific; i t does not give t h e mice immunity t o any other form of cancer. But n o t only does it protect against the virus, it also protects against t h e leukemic cells themselves. Injection of t h e s e cells regularly causes leukemia in unvaccinated mice; it is without effect in nearly all of those vaccinated. SloanKettering believes this is the first real indication t h a t it may b e possible to prepare a vaccine against other types of animal cancer, a n d perhaps some d a y even against some forms of human cancer. Using fluorescent antibodies, SloanKettering researchers a r e able t o correlate the presence of a cancer-causing agent with the transformation from normal to cancer cells and to observe t h e cellular changes step b y step. By t h e presence of antibodies, they h a v e demonstrated viruses in t w o types of cancer in animals. Their work indicates that cancer-causing viruses exist in t w o stages, one as an antibody-evoking complete virus (nucleic acid p l u s p r o tein), which would b e the form in which it is passed from one host to another, and secondly, as an incomplete virus, a p u r e nucleic acid hidden within the cell. Sloan-Kettering says this brings close together t w o main schools of thought on cancer cause: the o n e believing that cancer is caused by an invading extrinsic agent, and tHe other holding that cancer represents a mutation which involves, of course, a. change in the cell's nucleic acid. If a virus functions as p u r e , intracellular nucleic acid, t h e dividing line is slight indeed, the report states. • Enzyme Diagnosis. Using a concept of "enzyme diagnosis,'* SloanKettering researchers determined t h a t increased levels of glutamic oxalacetic transaminase ( G O - T ) in the blood not only occurred in patients who had suffered h e a r t attacks, b u t also in patients with liver damage—cancer, cirrhosis, and viral hepatitis. Furthermore, liver damage can be distinguished from heart damage b y t h e pattern of enzyme rise. Also using this enzyme technique, they w e r e able to determine tJbat lactic dehydrogenase ( L D ) is present in much greatei amounts in the fluid surrounding cancer cells and is apparently
a by-product of the abnormal growth. They also find t h a t elevated L D levels in the blood occur before other signs of cancer appear in test animals. In humans, when the patient improves under treatment the L D level drops, to rise again if the disease becomes reactivated. This indicates that the enzyme method can b e used both as a diagnostic test and as a guide to treatment. In its work toward cancer prevention, Sloan-Kettering has directed its lung cancer research toward developing a safer cigarette. It has isolated a chemical fraction from cigarette smoke condensate which represents 1.5% of the total tar and contains most of the cancer-causing activity. A t present efforts are under way to identify its several components and eliminate them from cigarette smoke. S-K says it is now possible to produce a commercially acceptable filter which will remove 4 0 % of t h e tar from smoke. It says that if all other factors—type of tobacco, size of cigarette, consumption per person—remain equal, use of this filter should, according to its evidence, significantly reduce the toll of lung cancer, now some 25,000 persons a year in this country. S-K tests also show that virtually no cancer-causing substances are present in the tar of smoke when tobacco is burned at 620° C. (rather than present 880° C ) . A safer cigarette might, therefore be made by adding chemicals or changing the cut of t h e tobacco so that it would burn at a lower temperature. They also show t h a t the waxy outer coating of the tobacco leaf contains much of the substances shown to be the source of cancer-causing agents in the tar of cigarette smoke. Drycleaning the leaf with a solvent apparently removes a substantial part of these waxes. S-K says that lab experiments testing the cancer-causing ability of tar from the treated tobacco are now in progress and appear promising.
Inventions, Anyone? A r m e d forces g o fishing for n e w a p p r o a c h e s to technical problems, many chemical JTERPLEXED
ARMED
FORCES
officials
have enlisted the National Inventors Council to make their needs known to the public—hoping to uncover new leads, techniques, and inventions pos-
COMMENT The aspect of nutrition which. J has aroused the greatest interest in j recent months is the possible role | of dietary lipids in . . . hardening J of the arteries and heart disease. | Obviously, the question arises | whether by proper manipulation of j diets we may be able to lower the j incidence of coronary artery disI ease. Exciting as this prospect | may be, it is well to bear in mind | that fact that the available data I are still fragmentary and in many 1 instances conflicting. j There is now considerable eviI dence that various highly artificial j dietary schedules can successfully j alter serum cholesterol levels in j the blood. It is well established I that certain common fats of animal | origin have a specific cholesterol| raising effect. This effect can be | counteracted by eliminating most | of the fat from the diet or by subj stituting large quantities of certain | polyunsaturated fatty acids. Since | the evidence to date is conflicting, | it must be considered as unproven | that the addition of these unsatu| rated fatty acids to diets already 1 low or moderate in fat, will have a 1 comparable cholesterol-lowering ef| feet. 1 Perhaps more important is the j fact that the exact relationship be| tween serum cholesterol levels and | incidence of coronary artery disJ ease remains unproven, despite the | rather voluminous medical literaj ture on the subject. Is the ele1 vated cholesterol level in a patient 1 with coronary artery disease cause | or effect? 1 If one lowers cholesterol . . . may 1 one not be doing some as yet un| discovered damage of another | type? There is some animal evi| dence that prolonged diets high in 1 polyunsaturated acids may precipi| tate deficiency of certain fat-soluble 1 vitamins. Will this occur in man? 1 At the present time, we in the | Food and Drug Administration are | maintaining an open mind on the | subject. . . . Let us not forget | that with present dietary habits we 1 have attained the greatest average | life expectancy yet achieved in the 1 history of the world. The burden | of proof must rest with those who | wish to change these habits. | 1 1 | I
ALBERT H. H O L L A N D , JR., Director, Bureau of Medicine, Food and Drug Administration, before F o o d L a w Institute Conference DEC.
16,
1957
C&EN
45
RESEARCH
sibly overlooked by military researchers. They list more than 380 vital technical problems that need solving. On the chemistry list are over 90 puzzlers. A typical problem plaguing military chemists is finding a method to float sodium fluorescin dye just below the surface of the water. This would greatly bolster air-sea rescue operations. Now. this dye floats on the surface and disperses in rough water. And dye below the surface sinks because of its density. In another field, government chemists are scratching their heads over lubricating problems. They want an all-weather oil that will work well throughout a temperature range of —65° to 125° F . Also, they'd like to run into a lubricant effective to 1000° C. These arc b u t a few representative examples. Chemical brain-rackers fall under the general headings of adhesives; batteries and electroplating; chemicals and processes; coatings, preservatives; crystals; elastomers; rubber and plastics; fuels, oils, and lubricants; and special materials. In addition, the list includes problems that chemicals or chemical processes might solve. Deicing aircraft and runways, and stabilizing rocket fuels are examples of the latter. NIC emphasizes that it is not looking for firms interested in getting government contracts to work on these problems. Of course, this does not mean that they can't submit ideas for examination. In any case, the armed forces branch furnishing the problem to NIC decides if an idea is acceptable or not. Neither does N I C want to locate products already on the market. Most of these have been, or are being, tested. Manufacturers usually submit these through different channels. NIC says legislation was started at t h e last session of Congress for paying contributors of worthy ideas. But no decision has been reached as yet.
New in Cigarettes N o v e l gas chromatographic method finds new acids in c i g a r e t t e smoke—it m a y find other uses too U SING GAS CHROMATOGRAPHY,
Duke
chemists have isolated 10 new acids from cigarette smoke. This technique may prove useful for analyzing these 46
C&EN
DEC.
16,
1957
and similar acids in other fields. These studies are part of a large scale program to find out what is in tobacco smoke and w h a t effect smoking has on body functions. These acids, all nonvolatile, are lactic, succinic, nialeic, oxalic, furoic, levulinic, glutaric, phthalic, adipic, and malonic, says Louis D. Quin of Duke. The most prominent are lactic and succinic, he adds. Most of them are important in biochemistry and enter into the complex chemistry of various plant and animal processes. Quin told the ACS Southeastern Regional Meeting that five other acids were separated but not identified. Marcus E . Hobbs, Pelham Wilder, Jr., and Quin, collaborating on this experiment, started out by separating the acids from the other smoke constituents. They did this by ion exchange methods. Steam distilling got rid of the simple volatile acids. The big problem was getting nonvolatile acids into a volatile form. This was done by converting t h e m to their methyl esters with diazomethane—a quantitative reaction. They used a Perkin-Elmer Vapor Fractometer to separate the complex ester mixture and identify components. They also g o t a rough quantitative estimate b y this method. But they feel that there is some ester loss during the operation. Quin says that the method may work in other fields, such as biochemistry. For example, some of the acids mentioned play an important role in the Krebs cycle for metabolizing carbohydrates. T h e Duke technique might work out as a suitable method to analyze for these acids in this process. The Duke work, which is sponsored by a grant from the Damon Runyon Fund, will continue.
An Orange a Day Man lacks an important enzyme system. Result? Man and other primates can't synthesize vitamin C. This leaves humans susceptible to scurvy. Missing, says J. J. Burns of National Institutes of Health, is an enzyme system that converts L-gulonolactone, a product of sugar metabolism in the body, to L-ascorbic acid. All other ma/amals can produce this vital vitamin, says Burns. Research shows that L-gulonolactone is a forerunner of vitamin C in the liver of the
rat. Working with this clue, Burns tagged L-gulonolactone with carbon-14 and incubated it with homogenates of guinea pig and rat liver. Rat liver converts more than 100 times more L-gulonolactone to L-ascorbic acid than does guinea pig liver. Experiments using human liver show it is unable to maJke the conversion. T h e biosynthesis of vitamin C stazrts with D-glucose, then goes successively through D-glucuronolactone and L-gulonolactone to L-ascorbic acid. T h e step from D-glncuronolactone to L-gulonolactone probably takes place in all species of mammals. At one time, scurvy was one of man's most dreaded diseases. The 19th century witnessed 104 epidemics of scurvy* and it has figured in all wars. While it can be fatal, few deaths result from scurvy today. Still, much of the -world is on an inadequate diet so the threat of scurvy still exists. Next, says Burns, the enzymes capable of producing ascorbic acid must be identified. This is a tou_gli job, because these enzymes, secreted by the liver, are hard to get at.
Testing Anticancer Vaccine More than 1000 extracts from plants all over the world are being tested at the University of Texas Biochemioal Institute for anticancer activity. R e searchers there arc trying to find a plant juice that will destroy or retard cancerous tissue growth. Using plant extracts supplied by USD A, they inject the material into mouse tumors grown in incubating eggs. After checking results of t h e extracts on cancerous tissue growing beside embryonic chicks, the biochemists will then experiment with their effect on tumors in mice. The head of the project, Alfred Taylor, says, "If we get any worthwhile results with the mice, then the extract will be tried on human cancer."
^ Expansion of health research facilities by at least $120 million is under way as a result of the first two years of a three-year grant program of the Public Health Service. The program is "being financed by federal funds and an equivalent amount, or more, provided by the participating institutions. L-ast month, with approval of 43 new grant awards totaling $3.7 million, the $60
