Document 3eJZybNknMkeLvKov7DDmOdMx

Cancer and Environment: Higgmson Speaks Out IARC director says his views on the role of the environment have been misinterpreted, life-style is more important than chemicals John Higginson. (banding director of thr World Haiti) Orgamzadoa's International Agency for Research on Cancer (IARO, is the formuiator of a rather complex Idea which has led many Americans to beiiere that ranerr-raaring agents lark in everything we eat. drink, and breathe. That perapdoa is wrong, he says, and is a misinterpretation of the hypothesis ha first expressed nearly 30 years ago. la a long conversation with Science recently; Hlgginson tried to explain how his ideas have became distorted and argned forcefully against the adoption of too simplistic a view of the cancer process. Higginsoa, 57, was born and educated in Ireland and has been director of (ARC since 1X6 Thomas H. Maugh II In the I9!0`t, you compared the in cidence of certain types of tumors among blacks in Africa and America and concluded that about two-thirds of all cancers had an environmental cause and were therefore theoretically preventable. Thu is a reasonable summary. Once Oettie and I obtained good statistics from African Mack populations, we wen able to calculate a theoretical concept of what the low incidence of cancer could be. and any increased incidence could then be considered due to an environ* mental component. Actually, the idea that geographical differences in. cancer inci dence are due to the environment goes back many years before that. David Liv ingstone. 1 think, said cancer is a disease of civilization, and therefore the-idea that the differences were environmental has a long history. Mv contribution, if I may say so. was limited merely to giving a more concrete estimate of the impact of environmental factors, and to show that most cancers were not due to genetic factors and thus that prevention was not impossible. I ought to make that clear because people are giving me credit where it is not due. But when I used the term environment in those days. I was considering the total environment, cultural as weil as chem ical. By cultural. I meant mode of life. When we ran that study of blacks in 1952. we started looking at their diets, how they lived, the number of children they had. the-age of menopause, the age of menarche--all that was included ia the term environment. I've checked it in every dictionary and every dictionary gives the same: Environment is what surrounds people and impinges on them. The air you breathe, the culture you live in. the agricultural habits of your com munity. the social cultural habits, the so cial pressures, the physical chemtcais wuh which you come in contact, the diet, and so oa. A lot of confusion has arisen in later days because most people have not gone back to the early litera ture. but have used the word environ ment purely to mean chemicals. So. in effect, your conclusions have been misinterpreted all along? They have been misinterpreted, ftinirily enough, not among the majority of the scientists with whom I have contact, but by the chemical carcinogen people and especially by the occupational peo ple. You've done a lot more research since the 1950's. Has something come up to change your original hypothesis? [ have found everything to buttress it. I have found nothing to disprove it. Nor do 1 know any other person who has pro duced data that are acceptable and pub lished that contradicts ic. Then how do you explain the misinter pretation? 1 think this has been due to a combina tion of reasons. One. many people have failed- to distinguish between the envi ronmental origin of cancers with clearly denned etiology--for example, smoking, alcohol, and occupation--and the large group of digestive and endocrine-depen dent tumors whose environmental cause can be inferred oniy circumstantially. The idea of life-style was woolly and illdenned and not expressaMe in biochemi cal terms with the technology available. Most scientists, myself included, don't like something woolly. Two. there was considerable interest in explaining hu man cancer in terms of virology, so (hat chemical carcinogenesis became unfash ionable. The textbooks of the 1950's thus largely discussed occupational cancers which could be confirmed by nice, dis tinct. and easy animal models. Rachel Carson s book was a watershed, as sud denly we became aware of the vast quan tities of new chemicals, pollutants, pesti cides. fibers, and so forth in the environ ment- Naturally, such factors suggested themselves as an obvious explanation of many human cancers. During the 1930's. 1940 s. and I950's. industry had shown a great deal of in sensitivity to potential dangers in the workshop, and ia unwillingness to at tack cancer hazards, associated with the changing political climate among scien tists and politicians and environmental pressure groups, made it easy to place the responsibility for all environmental cancers on industry. The environment thus became identified only with indus trial chemicals. Even tobacco was ne glected. This interaction of scientific and social hypotheses prevented wider rec ognition of the fact that many cancers could not be explained so simply. There's one other thing i should say that has led to the association of the term environment with chemical carcinogens. The ecological movement. I suspect, found the extreme view convenient be cause of the fear of cancer. If they could possibly make people believe that cancer SCIENCE. VOl_ I0S. IS SEPTEMBER IV79 0O3A-SO75/^O9:3-l.'65S00.:?O Capvnyiu S 1V7V AAAS : PLAINTIFF'S EXHIBIT AL-1073 f TMKCa retacca/HcoMt S ] SuaMfRC OcenoatiM / -<S Raaiatiaa `o if A I^- atroftnie Ultstyt* m m 2 I ContMitat UMa Flj. |. John Hiousoti's best estimates for the proportion of cancers attributable to various nnaes. The relative importance of diet CD) and behavioral or cultural patterns (O in lifestyle an only very rough rsrimanrt was going to result from pollution, this would enable them to facilitate the clean up of water, of the air. or whatever it was. Now I'm all for cleaning up the air. and all for cleaning up trout streams, and all for preventing Love Canals, but I don't think we should use the wrong ar gument for doing it. To make cancer the whipping boy for every environmental evil may prevent effective action when it does matter, as with cigarettes. I think that many people had a gut feeling that pollution ought to cause cancer. You asked me. were people dishonest? 1 don't think that some- people- were in tentionally dishonest, but rather that they found it hard to accept that general air pollution, smoking factory chimneys, and the-|ika;are not the major causes of cancer. I mean, people would love to be able to prove chat cancer is due to pollu tion or the general environment. It would be so easy to be able to say "let us regu late everything to zero exposure and we have no more cancer." The concept is so beautiful that it will overwhelm a mass of facts to the contrary. You tneaff there is no relationship whatever between pollution anti cancer? No. The dangers of point-source pollu tion are weilrecogoized. But you cannot explain much of existing cancer patterns only in terms of simple general pollution by industrial chemicals in low doses. You can't-explain why Geneva, a non industrial city, has more cancer than Bir mingham irr the polluted central valleys of Encland.-Jn the United States, reports are coming^-om that there are few dif ferences in^apeer patterns between the so-called diijv and clean cities. In fact, the only thing you can say is that air pol lution may. and 1 emphasize MAY. in crease lung cancer in cigarette smokers. lisa These and other epidemiological dis street, we are exposed to sunlight, which crepancies simply cannot be explained is a weil-recognized carcinogen, but we by variations in general pollution. Some may only develop one skin cancer in a can. however, be explained by differ lifetime, or even none .... despite the ences in life-style. In other words. I believe thousands or millions or billions of ceils that overemphasis on chemical carcino (hat have been exposed to sunlight. Only gens has distorted our approach to the a very rare ceil goes oo to a cancer. So it environmental theory for many cancers. may be that zero exposure is out. From I'm not saying one shouldn't dean up : an epidemiological viewpoint. I believe the environment: of course you should- that attempts to prevent most tumors ; people shouldn't be exposed unnecessar through control only of mutagens and i ily. [But the simplistic approach) has carcinogens will prove to be a disap- prevented possible acceptance of the pointing approach, as will concentration 3 idea that there- may be doses oil carcino only on the initiation phase of cardno* ; gens which, for practical purposes, are genesis. Research should be directed to unimportant. If you consider smoking other possible factors. That's the mes plus asbestos or smoking plus uranium, sage which I feel is the adequate sum- , those combinations lead to more lung mary of the data of the last 20 years. cancer as everybody knows. But the cor Beyond smoking and tobacco, what do ollary. then, that small bita of 20 dif you consider the most important com- ferent carcinogens add up to produce a ponents of life-style? cancer--(here are simply no experimen Two. diet and behavior. tal or human data that this is the case. What types of behavior? Certainly I used to believe this myself, Can 1 just explain what I mean by be and I spent many years in the laboratory havior in a simple sense. Brian McMa- . looking for suitable experimental models hon and other people showed, for ex- > : to study combinations of chemicals-- ample, that if a woman had her first child ; with little success. Most work has been at an early age. she protected herself carried out at relatively high doses and against breast cancer-, if she had the child models are more often additive rather at a later age. there was a much greater than multiplicative. Furthermore, some chance of cancer. Now we know that carcinogens even inhibit the action of pregnancy leads to changes in (he others. The existence of noneffect doses body .... but we don't know what of carcinogens has been very poorly in those are. and hence the biochemical ex vestigated. and there is practically no re pression of the behavioral pattern is in search on this subject apart from experi complete. On the other hand, the term ments on two-stage carcinogenesis, behavior, as "when i am going to have which is a very different story. And. as my first baby." is a technically accurate Berenbium has pointed out. we are prob ly expressed term which largely depends ably being exposed to so many carcino on the culture in which you live. Another gens all the time that what happens is example is the fact that sexual activity mostly incomplete at the target-cell lev from an early age leads to a lot more can el: the ceils die .ind nothing ever hap cer of the cervix. Why. we don't yet pens. Because you and I walk across the Conttnufil ttn pay* IJ66\ science, vol. :a5 ALCOA05207 (Ctmxmed fntm 0*9* 1364} know. ,'s it the transfer of a vinis, the fact that frequent sexual intercourse modifies an individual's hormonal read* tions. a stimulation of the vaginal epithe lium? We don't know, but again it's a be havioral pattern. And if you take these two factors, you're dealing with a good lump of female cancers, breast and cer vix. which in the United States and most countries account for 50 percent of fe male cancers. That sounds fine and simple, but run ning parallel with that is the fast that we've had changes in dietary pat terns. ... The age of menaiche in the American female, for example, has dropped extensively. We are having chil dren beginning to have their menarche as early as 10 or 11 in portions of the world, compared to Africa where it is often as late as 16. That difference is probably re lated to dietary factors. For years we have talked about an improving diet, tall er people, better people, but this auto matically leads to modifications, for ex ample. uf the pituitary axis. These changes themselves, associated with be havior patterns, may tie in together to modify the susceptibility of an. individ ual. Diet is under environmental control, the behavioral pattern is under environ mental control, so thisfil what I mean by environment. But as you see. it's a high ly complex system, dealing with hu mans. and therefore we don't have good, models. Are there any kinds of analogous be haviors in men/ The men are funny, you see. . . . Thegroup of cancers you would attribute to life-style for males [neglecting alcohol and tobacco I is much smaller. The major sources are stomach, large intestine, and prostate. Now people have gone around trying to prove that sexual activity is re lated to prostatic cancer--frustrated sexuai relationships, and so forth. But. to date, nohodv has come up with a reason able solution. Now let's take prostate cancer in three groups of males. Japa nese. U.S. whites, and U.S. blacks. We II call the Japanese prostatic cancer incidence one. The incidence in U.S. whites would be about 30 and in U.S. blacks. SO. You look at that and there's no way you can possibly explain that on exposure to air pollution, diffuse dietary pollution, or anything like that. It is just ridiculous- to try to do so. If. however, we look for wnal we call latent carcinoma, we find that, in the United States, about 10 percent of ail men of 75 have a latent cancer sitting in their prostates. And it's almost the same. 10 percent, m Japan and Germany. So I we have the first pan of the cancer here, initiated, but quite obviously the factor that is making it invade and kill the indi vidual is operating much more pow erfully in the U-S. black, less powerfully in the U.S. white, and not at all in the Japanese. Now again. I can't think of any behavioral patterns that would ex plain this, so one tends to think of die tary factors. [This is supported by stud ies of Japanese who have moved to the United States.] Now when you look at diet, the classi cal thing is to think of diet in terms of carcinogens. We have a vast body of evi dence that goes back to 1940. and which we studied extensively in the Bantu, for example, showing that diet has non specific factors--the amount of fats, the amount of fiber, and so on. We say lack of fiber is a risk factor for colon cancer, well how in the world can you say lack of fiber is a carcinogen? It's a ridiculous ex pression. So one would prefer to use theterm carcinogenic risk factor. It is about the only dietary thing there is that has stood up for 30 years. But Eats, protein, carbohydrate, vegetable inhibitors may also be important--a lot of research is going to be in this area. But the problem is. we are being asked to give an answer now. "How should we deal with diet?" and we just don't have the answers. The only thing I can say is reduce calories and Cat. and possibly add some fiber, but without making any promises as to what will happen. We simply don't know enough at the present time in many areas to advise leg islation or marked changes of life-style. If you take Copenhagan. for example, we have found that colon cancer is four times more common in Copenhagen than in Finland. Yet both populations drive cars and live exceedingly well. But there are significant dietary differences. So you might say, let's tell the Danes to eat the Finnish type of diet. But then you find that the Finns have the highest rate of heart disease in Europe, and probably in the world, so what they're gaining on the swings they're losing on the round abouts. One has to be terribly cautious, in my opinion, of making advocation. Now you take urban and rural Denmark. People have said that breast and colon cancer are related tu fat intake. Well, when we compare urban Copenhagan and rural Denmark, we find that the in cidence of cancer of the breast is higher in the urban area .... but they eat much mure fat in the rural area. 50 per cent more. It's quite contrary to the hy pothesis. There is obviously something in the way they live m the rural area compared to the town that hasn t been solved yet. so let's not rush into a r-n- piistic statement "Let's cut down on your fats" unless we know why. Considering pass failures in getting people to change their smoking and drinking habits, isn't your view ofcancer rather pessimistic? / I'm sorry. I didn't mean to imply that at alL la fact. I think it actually'offers a much more optimistic view in practice. It would appear to me almost impossible to reduce to zero the thousands of potential carcinogens to which one is or will be ex posed. Nor should such action necessari ly be justified in view of the intense com mitments required in terms of national resources, without better supportive data. On the other hand, if cancers of the digestive system or endocrine-dependent systems are eventually related to life style. it should not automatically be.as sumed that control of them will be impossible. Quite obviously. Congress can't legis late an early first pregnancy to protect against breast cancer, but there is a good possibility that we may be able to mimic it with a pill when we know about the biochemical effects. Already there is evi dence that contraceptives may reduce precancerous lesions in the breast. There are also two reports indicating that con traceptives protect against ovarian can cer by inhibiting ovulation. I am optimis tic that once we have a better under standing of the mechanisms involved and the relation to behavior and nutritional patterns, not only may it be possible to intervene with some success but also to identify individuals at high risk. Inter vention of this type is already-tfeifig con sidered and is called chemopreveiition. a comparatively new approach to cancer control. "* However, the real reason ft am opti mistic is that in a wider intellectual cli mate some scientists are no longer think ing in terms of simple carcinogens, muta gens. and initiation, but are developing a new sophisticated approach to study ail complex mechanisms involved in multi stage carcinogenesis. This is' largely thanks to the work of Berenblum. even if in many circles this approach ^remains unfashionable. Lastly, we dodcaow that there are populations with low.frequen cies of these cancers: thus, the Japanese have a very low frequency of bceast can cer and the Finns have only arquarter of the colon cancer incidence in the United States. Once we can explain these differ ences at a more fundamentallel/ei. I am confident that we will be ublecfo take ac tive measures to reduce this large group of cancers due to lifestyle in countries of high incidence. SCIENCE. VOL. :oj ALCOA05208 ALCOA05205 I