UNIVERSITY OF CALIFORNIA, BERKELEY A Tribute to Ihe People of California SPACE SCIENCES LABORATORY BERKELEY, CALIFORNIA 94720 January 24, 1969 Professor Joshua Lederberg Stanford University Medical School Department of Genetics Stanford, California 94304 Dear Josh: Out of the mass of complexities surrounding the pesticide problem, | shall try to select the topics that are pertinent to your recent newspaper column. 1. Effect of DDT on reproduction in peregrirefalcons and, by implication, on the survival of this species. (a) Reproduction: obviously no controlled experiments have been done with peregrine falcons. However, certain game birds have been tested. In quail, little or no effect on fertility and hatchability at the very high level of 200 ppm of diet (Note - tolerance in crops is currently 7 ppm). The 200 ppm level is toxic to young birds but did not arrest hatchability. This is very interesting in itself, (see enclosure). (b) Egg Shell formation: no effect noted by H. R. Bird (Professor of Paultry Husbandry, University of Wisconsin) on laying hens. DDT lowered egg production but not hatchability at 310 ppm of diet; hatchability was lowered by 620 ppm but no effect on egg shells was noted (Bird, personal communication, 1968) (Note - During the incubation of the embryonated egg, calcium is withdrawn from the eggshel! to provide for the skeleton of the chick. As a result, the thickness of the eggshell decreases, and it becomes fragile at hatching time. Measurements of the thickness of egg- shells of wild birds have no comparative significance unless this fact is taken into account). My conclusion is that finding DDT and DDE (if, indeed, the test was actually measuring these) may have interfered with reproduction, but the only controlled. experiments shew that birds are extraordinarily resistant to DDT as a substance affecting reproduction. Levels that are toxic to young birds apparently do not reduce reproduction. The effect of PCB on reproduction is unknown. The possibility that it may be deleterious should be examined before blaming everything on DDT. (c) Survival of the species: the peregrine falcon is not extinct in the eastern U.S.A., as the Hawk Mountain Survey shows. Starker Leopold informs me, that it used to nest on ledges of skyscrapers in eastern cities, and feed on pigeons, but it has disappeared from these habitats ‘'as a result of DDT." | cannot help wondering, however, in view of the fact that the peregrine made such a remarkable adaptation, may it not have fallen victim to some unidentified condition of urban life? In other words, it may have been a fatal move, unrelated to DDT, to leave the cliffs in the wilderness and move to the cornices of office buildings. Page 2 Professor Joshua Lederberg January 24, 1969 What factors affect the peregrine population? Undoubtedly gunfire is very prominent. Most hunters and farmers like to kill hawks. Their excuse is that hawks kill game- birds and poultry. Hunters are on the increase. According to Spencer, the peregrine is ''fair game'' (inadequately protected against hunting) in over half the area of U.S.A. and Canada. Incidentally, the British killed off peregrinesin World War II for air defense reasons. The article that you sent me from NATURE stated that "breeding pere- grines persist in apparently normal numbers in British Columbia and in the Arctic." | note that in Table 1, three of the birds were listed as Arctic migrants, and one of these was reported to have the highest content of DDT, which seems very strange, Since peregrines are breeding in Canada and the Arctic, and since the Arctic peregrines seem to contain DDT, there is a deficiency in the thesis of the authors. | cannot verify your statement: ''ln some wild species of birds, DDT has accumulated in body tissues to the point of causing serious disturbances in the metabolism of sex hormones, These are manifested by a serious thinning of the calcium carbonate shells of the birds' eggs and interference in breeding.'' | know of no evidence that would support the non sequitur in these two sentences. | recognize, of course, that species differences among birds may result in different responses to DDT, but so far, the experimental results with DDT and reproduction in birds show the existence of considerable resistance to DDT. Incidentally, despite Riseborough et al, vitamin D is not a steroid, and its metabolism is not known to be mediated by hydroxylases. For causes of soft-shelled eggs, | refer you to textbooks of poultry husbandry. The most common cause in domestic poultry is psychological disturbances, which cause expulsion of the egg from the uterus of the hen before completion of the calcification process ~ ask any poultry farmer what effect he expects from sonic booms and he wil] probably tell you ''soft-shelled eggs.'' | joined the Poultry Science Association in 1930, so | have had some contact with questions of avian biochemistry. 2. The effect of DDT as an inducer of steroid hydroxylase. This has been reported to occur in rats when DDT is fed at 1 ppm of the diet (Science, 161:397, 1968). However, reproduction in rats is unaffected by far higher levels of DDT. Fitzhugh, of the FDA Labs,reported as follows: "Rats fed diets containing 50, 100, and 600 ppm of DDT showed a progressive decline in the percentage of young successfully weaned, as compared with rats fed diets containing 0 or 10 ppm of DDT. However, the mortality of infant rats of mothers fed 50 and 100 ppm, although greater than the mortality of groups exposed to less DDT, was not greater than the mortality of infant rats in many laboratories. No effect on the number of rats born alive was evident in the first generation, but in the second generation rats fed 600 ppm produced very few living young, of which none survived the nursing period." | therefore conclude that the effect on steroid hydroxylase is not necessarily correlated with reproduction. The body has all sorts of contro] mechanisms for regulating enzymes and their effects. 3. Your column does not ask,but provokes, the question: What are the effects of DDT on human beings, especially on reproduction? | shall not attempt to deal with the extensive literature on human volunteers who have consumed enormous quantities of DDT. According to J. M. Barnes (W. H. 0.): "', Unless epidemiological studies on the health of people who have been heavily exposed to DDT for 20 years or more reveal an unsuspected long-term toxic effect, this insecticide will go down in history as one that has killed more insects and Saved more people than any other substance.'' Page 3 Professor Joshua Lederberg January 24, 1969 Extensive reviews of this topic have been written by Hayes (see, for example, Ann. Rev. Entomology, 1962). Rather | draw attention to the effect of DDT on the Indian popula- tion as summarized by Pal (World Review of Pest Control, 1962, vol. 1, p. 6). "Since 1953, about 147,593,270 lb. of DDT have been used, with smal] amounts of BHC and dieldrin. As a result, malaria morbidity has been significantly reduced in the country. The proportional case rate of malaria (per cent of malaria cases to total diseases as clincially diagnosed) in each year of this programme has shown a decline and the figures are presented in Chart |. Estimates of actual morbidity and mortality are difficult but it would appear, from the available data, that malaria in India has been reduced from 75 million cases to less than 5 million.