•
RESEARCH
Injected cancer cells grow in lab animals and in patients with far advanced cancer b u t are rejected vigorously b y healthy
volunteers, indicating that they h a v e natural resistance to cancer. This resistance increases with subsequent i m p l a n t s
Cancer: Prevention a n d Cure M a j o r steps taken toward control of cancer in past two years, Sloan-Kettering report reveals C H E M O T H E R A P Y . . . IS OUR BEST H O P E
for more effective cancer control in the near future," says Alfred P. Sloan, Jr., in revealing results of cancer research during t h e past two years at Sloan-Kettering Institute. He says this awareness is b a s e d on the ability to cure transplanted cancers in animals and to effect substantial improvement in man of some forms of cancer for periods of weeks to years. Among the highlights of the biennial report are results of tests of resistance to implanted cancer. Sloan-fCettering finds t h a t t h e normal h u m a n body possesses some natural resistance to growth of cancer transplanted from other h u m a n beings. T h e resistance is not possessed to t h e same degree by patients with a d v a n c e d cancer. This resistance to implanted caocer in humans increases with second and third implants, not necessarily of t h e same type of cancer cells used initially. Blood studies on cancer patients and well volunteers indicate that properdin is t h e only factor associated w i t h immunity in which cancer patients are demonstrably deficient as compared 44
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with controls. In animal tests the Sloan-Kettering researchers find that small doses of zymosan, a yeast product, raises properdin levels (large doses lower t h e m ) . Sloan-Kettering feels that these studies indicate t h a t t h e normal b o d y possesses means for defending itself against cancer a n d that these means are wanting in patients with advanced disease. In the immunological search for a specific point of difference between normal and cancer cells, Sloan-Kettering researchers found a strong antigenic material associated with lipids in rat cancer cells. This lipid component was absent from many normal rat tissues tested and present in all of eight different rat cancers, indicating that immunologically measurable difference between cancer and normal cells may exist. Just as S-K's biennial report was being written, a small quantity of the lipid antigen from h u m a n cancer tissue was obtained in p u r e form. SloanKettering now feels t h a t it will b e possible to determine definitely whether or not it h a s found an immunological point of difference b e t w e e n cancer and
normal tissue. If this has been f o u n d , it would provide the starting p o i n t for major investigations in cancer d i a g n o sis and treatment, S-K believes. Using a different m e t h o d involving blood samples, another group at S-K has already found a simple i m m u n o logical test for two relatively rare forms of h u m a n cancer. This group has also been able to prove t h a t antigens a r e present in cancer tissues which c a n n o t be detected in the surrounding n o r m a l tissue of the same organ. • Virus Vaccination. W i t h all t h e mammalian cancer viruses discovered until recently, there was a long l a t e n t period of cancer development. Both the mouse breast cancer virus a n d t h e mouse leukemia virus have been given to newborn animals. T h e virus t h e n literally disappears, and there a r e n o signs of it until cancer appears a year or so later. This has m a d e study slow and difficult. However, about a year ago a Sloan-Kettering investigator discovered a new virus in mouse cancer. It produced leukemia in almost all of the animals inoculated, with first signs of the disease appearing within t w o t o three weeks. Starting with mice t h a t h a d survived injection with this leukemia virus, t h e researchers found that 9 0 % of t h e s e were immune to reinjection of t h e virus. To determine whether this resistance was innate or had been built u p as a r e sult of t h e original injection, they m a d e
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
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