Eur. J. Epidemiol. 0392-2990 July 1992, p. 625-626
Vol. 8, No. 4
LETTER TO THE EDITOR
THE THIRD EPIDEMIOLOGICALREVOLUTION Keywords: Epidemiology - Advances - Studies
In 1976, Milton Terris signalled the extension of epidemiological perspectives with the term "The Second Epidemiological Revolution". He was correct. After 1940, population-based studies of infectious agents of disease were increasingly augmented by investigations of non-infectious causes, ranging from cigarette smoking, asbestos, B napthylamine to vinyl chloride, bischloromethyl ether and radiation. Much valuable data were accumulated, so much so that by 1970 or so there was a change in the general public's and the scientific community's understanding of cancer, from an inevitable accompaniment of aging to a set of diseases associated with exogenous causes, some identified, others still to be found (Doll, 1981). These observations, nonetheless, were incompletely rewarding. They told us something of what might increase one's risk of bladder cancer or mesothelioma or lung cancer or leukemia and when neoplasms were likely to appear. Such identification could help avoid exposure of future generations and so, ultimately, 30, 40, 50 or 60 years from now, reduce the incidence of cancer. They could provide statistical background for efforts of OSHA, NIOSH, EPA and other agencies in planning control efforts. But, by and large, they didn't help much in decreasing the projected risk of cancer among those of us already exposed, apart from benefits from cessation of cigarette smoking. We have been faced with the proposition that sufficient exposure to substances capable of causing human cancer sets in motion an apparently inexorable cascade of events, collectively categorized as "multistage carcinogenesis", which proceeds quietly,
without clinical symptoms or signs, during an incubation period of 20-40 years or more, to suddenly erupt as "cancer". This incubation or "latent" period has largely been a "black box". We know very little of what goes on, although more recently, by measuring adducts in cells, we have had evidence that biochemical alterations can occur after exposures. Yet even with such limited knowledge there has been little doubt that changes were under way in the latent period.
Molecular biology of the latent period There is hope that we can, open the "black box" with another advance in epidemiology. During the years in which discoveries were made about cases of cancer and other non-infectious disease, this was primarily done by observing the experiences of groups of exposed people, those working with benzidine dyes, hexavalent chromium, asbestos, coal tar pitch, in nickel smelting or furniture making. Such studies identified high risk groups. In other words, in a statistical sense (all too often, clinically as well), we came to know who was in the process of developing cancer (i.e., at increased risk), next year, in five years, in 10, 20, 30 or even 40 years. With knowledge of duration of exposure, duration from onset of exposure, intensity of exposure, other concomitant exposures, latency and expected rates, we could often be fairly confident about predictions and risk assessments. (Nicholson, Perkel and Selikoff, 1982). Access to high risk groups offers a new epidemiological perspective and opportunity. The first
Selikoff I.J. a n d L a n d r i g a n P.J.
Eur. J. Epidemiol.
two epidemiological revolutions (epidemiology of infectious and non-infectious disease) will continue and, indeed, themselves be considerably extended by appreciation of "slow epidemics". They will now be joined by consideration of what happens to high risk groups, over the long term. There will be another dimension to this new phase. Just as bacteriology went hand in hand with studies of the effect of infectious agents and analytical chemistry and environmental measurements with studies of non-infectious materials, so will molecular biology be the basic science hallmark of the third epidemiological revolution. We will ask our molecular biology colleagues to use their remarkable new techniques to explore what is occurring in the high risk groups being observed. How do their cells, their proteins, their chromosomes, their DNA, their growth factors, their oncogenes, their protocongenes, their anti-oncogenes differ from those of people not known to be at increased risk, if indeed they do. Which changes occur, when? What approaches might be considered to interrupt these changes, during the latent period? Might we even discover how to alter the molecular phenomena associated with the increased risks. Alteration does seem possible in light of the reversal of risk for lung cancer among smokers who discontinued cigarettes, even among asbestos workers who stopped smoking, (Hammond, Selikoff and Seidman 1979).
Close collaboration between epidemiologists and molecular biologists will mark new third epidemiological revolution. It will be worth it, whatever new languages we will have to learn. But it will be worth it*. I.J. SELIKOFF and P.J. LANDRIGAN1 Department of Community Medicine Mount Sinai School of Medicine of the Oty University of New York. REFERENCES
. Doll R. (1981): Avoidable cancer: attribution of riskS. Afr. Cancer Bull. 25: 125-146. .
Hammond E.C., Selikoff LJ. and Seidman H. (1979):
Asbestos exposure, cigarette smoking and death rates - Ann. N.Y. Acad. Sc. 330: 473-490. .
Nicholson W.J., Perkel G. and Selikoff LJ. (1982):
Occupational exposure to asbestos: population at risk and projected mortality - 1980-2030 - Am. J. Ind. Med. 3: 259-311. .
Terris M. (1976): The epidemiological revolution, national health insurance and the role of health departments - Am. J. Public Health 66: 1155-1164.
i C o r r e s p o n d i n g author. * P r e s e n t e d at t h e m e e t i n g o f t h e C o l l e g i u m R a m a z z i n i in Carpi - Italy - O c t o b e r 20 - 1991.