M. B. Shimkin

The effect of portacaval shunt on 7,12-dimethylbenz( a ) anthracene-produced mammary carcinoma in the rat

Abstract Portacaval shunt significantly reduces the incidence of DMBA-produced mammary carcinoma in the rat. Tumorogenesis is inhibited whether the shunt is done before or as long as 2 weeks after DMBA administration, indicating that tumor inhibition is related to an effect of the shunt on the metabolism of the host rather than to a direct effect on absorption and metabolism of the carcinogen. The reason for tumor inhibition by the shunt is unknown. Major circulatory, metabolic, and hormonal changes evidently occur after portasystemic bypass; further studies are required to explain the relationship of these changes, individually or collectively, to the significantly decreased incidence of tumor production after portacaval shunting.

The effect of distal small bowel bypass and resection on 7,12-dimethylbenz[a]anthracene-produced mammary carcinoma in the rat☆

Abstract Distal ileal bypass or resection performed prior to the intragastric instillation of DMBA in sesame oil to 50–52-day-old female Holtzman rats significantly reduces tumor production. This effect is not present when animals are bypassed after the administration of carcinogen. Tissue levels of DMBA are low in the groups with lowered incidence of tumor and reflect decreased absorption of this agent. Significantly fewer tumors developed with ileal bypass than with ileal resection. The addition of cholic acid reverses this effect. Both serum cholesterol and weight gain are not affected by these procedures.

CARCINOGENESIS: FRONTIERS IN INNER SPACE*

Sackcloth and ashes are as fashionable these days as are miniskirts and Nehru jackets-and perhaps for related reasons. Certainly as we look at the international scene and closer around us, it is difficult to be complaisant. But it is also easy to exaggerate. We in the United States are observing the end of a golden era in biomedical research. For two decades, biomedical scientists and their institutions have enjoyed an ever-increasing flow of funds for our activities. Now we are faced by actual reductions and the resultant stresses. Biomedical research is part of our society and must share in its nausea. For perspective, it is useful to review how we got here in the first place. How were governmental funds for biomedical research expanded from a few millions to over a billion dollars within a decade? The events are hard to reconstruct from official annual reports. We finally do have one “as-it-happened’’ description that is reasonably factual and fun to read. It is a piece by Mrs. Elizabeth Brenner Drew, entitled “The Health Syndicate, Washington’s Noble Conspirators,” which appeared in the December I967 issue of the Atlantic Monthly. I commend it to your attention. The federal developments, however, are but half of the tale. The actual research was taking place in universities. The reactions, problems, and questions that have arisen are well described in a recent compilation of the American Council in Education entitled “Sponsored Research in American Universities and Colleges.” That also should be required reading for us. The fact is that the federal cornucopia for biomedical research was not all for the good. Certainly the endless largesse had some undesirable effects on universities and related institutions. The obesity of the research budgets from outside sources produced lethargy of the institutional role and responsibility. It is during a time of relative adversity that such unpleasantnesses can be pointed out in order that remedial actions are at least considered; in flush times such alarums are considered to be almost facetious. Early in the days of federal support of biomedical research some of our institutions of higher learning were reluctant to touch these tainted dollars. This phase soon passed, and some of the most vociferous champions against federal funds became champion recipients. Then there were the criticisms of research support because it was stated to interfere with teaching, although no institution was ever forced to accept funds, and an increasingly larger proportion of the funds were allocated to training programs and other devices for the subsidy of education. An interesting position regarding federal research funds was successfully de-

SUMMARY OF THE CONFERENCE ON BIOLOGICAL EFFECTS OF PESTICIDES IN MAMMALIAN SYSTEMS

Just five years ago a gracious lady, dying of breast cancer, published a book called Silent Spring. Rachel Carson struck a responsive chord among the public, not only about pesticides, but about man’s place in his world. Should man, reaching for the stars and holding in his hands the tools of his own complete destruction, strive for total victories, or seek balance with nature through compromises and partial controls? The book aroused considerable reaction, especially from agricultural and chemical industries and their spokesmen. Miss Carson was not a toxicologist. Undoubtedly, the case was overdrawn, and errors of fact and interpretation could be identified. Nevertheless, her book does belong in that list of provocative publications that touch man’s conscience, such as Harriet Beecher Stowe’s Uncle Tom’s Cobin of 1852, Upton Sinclair’s The Jungle of 1906, and, more contemporaneously, Ralph Nader’s Unsafe at Any Speed and Morton Mintz’s The Therapeutic Nightmare, both of 196s. This meeting, as d o many others, represents to a great extent the continued wave of reaction to Rachel Carson’s pleas. It is obvious that modern technology in pesticides, especially Muller’s discovery of the antiarthropod activity of DDT, for which he was awarded a Nobel prize in 1948, has provided man with another tremendous power to control his environment. Just as in the case of atomic fission and fusion, this power can be used for purposes to which the human evaluative words of “good” or “evil” are applicable. These attributes are not contained either in atoms or in pesticides; they arise from how man uses them. World War 11, I a m told, was the first major war in which casualties caused by military actions exceeded those attributable to disease. DDT was an important, although certainly not the only, reason for this achievement. I know that we became rather contemptuous of typhus fever as we doused whole populations with D D T powder. I also know how much personal comfort was derived from its use in movie houses in San Francisco, which once used to rank.among the flea centers of the world. The obverse side of the coin, even in only the baldest of human terms, is an estimate by the Public Health Service that the average annual death rate in the United States from pesticides in one per million and that nonfatal poisoning is one per 10,000 population. That totals 200 recognized deaths and 20,000 recognized poisonings per year. Although these figures alone define this as a national health problem, the chronic effects on man are yet to be defined. Add to this the many consequences to other species. Add also the fact that this is but one source of continued, mounling contamination of our air, water, food, and every other environmental feature. The problem then acquires the elements for what may well become a catastrophic situation. Several views, therefore. can be discarded at once as untenable. One is that there i s no problem. Two, that things will straighten out if they are ignored, especially by the government. Three, that we really know nothing about the dangers and need a decade of research to determine whether there is a problem.