PROBLEMS IN BIOCLIMATOLOGY
BY RENP J. DUBOS
THE ROCKEFELLER INSTITUTE
Ideally, the bioclimatologist should have the characteristics of both the classical and the romantic type of scientist. For he must deal quantitatively with the measurable effects that the known forces of the physical environment exert on biological processes. And he must also cultivate an awareness of the fact that other undefined cosmic factors influence in obscure but profound ways the growth, behavior, and fate of all living things. I must acknowledge immediately that I have never worked in any aspect of bioclimatology, nor have I made a systematic survey of the relevant literature. But as a student of the etiology of disease, both in individuals and in complex populations, I have come to realize, like many others, that bioclimatological mechanisms often condition both the etiology and the manifestations of pathological processes. While this type of experience constitutes no justification for dogmatic statements on bioclimatological problems, it has led to more general questions regarding the effects that environmental forces exert on living things and particularly on man. These questions I shall now try to formulate.
As every one knows, most biological phenomena exhibit rhythms which are linked to those of the physical world. There are many well documented examples of biological cycles characterized by daily, seasonal, annual, or longer periodicities, and some of them have been studied in the laboratory with exquisite precision. For example, the phototactic response of Euglena exhibits a rhythm with a 24 hour period which is independent of temperature, at least between 16'C and 330C. The fact that this endogenous rhythm is exhibited by a unicellular organism demonstrates that "biological clocks"* do not require the complexities of nervous organization.1 Other phenomena like the emergence of insects into activity act as landmarks for the season of the year and may be more complex in their determinism. 2 Our colleague, Dr. Frank L. Horsfall, has told me that he shelters under his Long Island home a colony of termites which regularly emerge between March 15 and March 25 every year, independently of any climatic factor of which he is aware. Clearly, these rhythms are the manifestations of built-in biological clocks and for this reason they appear at first sight to have no bearing on our symposium. After all, as pointed out by Dr. Konrad J. K. Buettner,3 nearly all biological and meteorological factors have a yearly and a daily period and, therefore, any correlation between the two groups is but an expression of the fact that weather and life take place on a revolving and rotating earth. Nevertheless, the problem of cycles is one pertinent to our discussion because the biological clocks are not as immutably set as appears; instead, they rapidly change their timing in accordance with changes in the physical environment. Let me illustrate this statement with a specific example taken from a very recent publication.
In man, the urinary excretion of 17 hydroxycorticosteroids exhibits a well-defined and fairly stable daily rhythm. Thus, measurements of these adrenal hormones made at very frequent intervals during a thirty-hour shift by air travel from Continental United States (Central Standard Time) to Japan and Korea, revealed that the urinary excretion remained synchronized with C.S.T. even after arrival in Asia.4 Progressively, however, the timing of excretion changed and after 9 days it had become synchronized with Asian time.
The rhythm of excretion of sodium and potassium exhibited a similar pattern. Likewise, other physiological phenomena have cyclical patterns which are under the influence of the environment. Thus, the diurnal temperature rhythm in man was observed to change following airplane flight from Ontario to England. In this case, it took three to four days for the Canadian temperature rhythm to fall in step with the European rhythm.- The problem of biological cycles certainly lends itself to experimental analysis since changes in rhythm can be produced at will in laboratory animals. For instance, it has been possible by inverting the light schedule of mice for two weeks to produce shifts in daily rhythm with regard to blood eosinophils, mitoses in pinnal epidermis of liver, he patic nucleic acid metabolism, and blood levels of corticosterone.6
As is well known, the Hippocratic writings repeatedly and forcefully emphasized that the occurrence of many types of disease has a marked seasonal character. In our communities, every one is aware of the winter incidence of acute respiratory disease and the summer incidence of poliomyelitis among human beings. And our colleague, Dr. Richard Shope, never tires of discussing the striking autumn incidence of hog influenza and hog cholera among the swine herds in the Middle West. Less well known, but almost as pronounced, are the seasonal ebbs and flows in the clinical manifestation of metabolic disorders, for example diabetes and circulatory diseases.7 8
A number of well known facts immediately come to mind to suggest mechanisms through which climatological factors could indirectly affect the incidence or severity of disease. Crowding, physical activity, availability of certain types of food, prevalence of parasites and their vectors, etc. etc., are all factors in the causation of disease which are profoundly conditioned by the physical environment. But in addition to these obvious determinants there are others less well recognized, which are probably more significant. This belief is based on the fact that the internal environment of man-as well as of animals-is more variable than was believed a generation ago.9
There is no doubt of course that the essential characteristics of the internal environment must remain within certain limits to be compatible with the maintenance of life. On the other hand, it is also true that some of the biochemical activities of tissues can undergo profound quantitative variations and that some of these changes exhibit a marked seasonal pattern. A striking illustration of these biochemical cycles was discovered by C. and G. Cori some 30 years ago. 10 In the course of their studies on sugar metabolism, the Coris became aware of a marked seasonal variation in the ketonuria of rats kept without food for 48 hours. During the summer months (from May to October) the excretion of acetone bodies brought about by fasting proved consistently to be three times greater than during the winter months. The fact that the excretion of acetone bodies did not rise during the winter when the rats were placed in a room at a temperature comparable to that of the summer provides evidence that factors other than heat were responsible for the greatest fasting ketosis observed during the summer.
These findings have been confirmed and extended in England by Burn and Ling,l who found indeed that the difference in fasting ketonuria between the spring-summer season and the fall-winter season was even much greater than that observed by the Coris. With the strain of rats used in England, the difference was of the order of ten-fold. Furthermore, the amount of glycogen in the liver of rats after 24 hours' fat diet also proved to vary according to a seasonal pattern, being much higher in the winter than in the summer.
There have been suggestions that this seasonal change has an evolutionary basis, namely that animal tissues have developed mechanisms which enable them to withstand successfully long periods of starvation in the winter. According to this view, energy requirements during the winter would be more likely to be met by combustion of the fat stores whereas this metabolic mechanism would not play as essential a role during the summer.9' 11, 12
While the intimate biochemical processes involved in the shift from summer to winter metabolism need not be discussed here, it is of interest to point out that the summer ketosis was associated with a reduced capacity of the tissues to oxidize glucose, and was probably due to a reduced functional activity of the pancreas. It appears, in other words, that the seasonal patterns of physiological behavior can have their basis in seasonal variations of hormonal activity. There are, of course, many other examples of cycles involving hormonal activity-for example, those associated with menstruation or those resulting in the diurnal variation in output of adrenal corticosteroids mentioned above. What must be emphasized anew at this time is that these built-in cycles are influenced by variable climatologic factors. It has long been known that the size of the thyroid and of the adrenals is normally greater in the winter than in the summer in laboratory animals, and can be altered at will by changing the environmental temperature (for a recent example, see reference 13). We have seen also that the rhythm in secretion of adrenal corticosteroids progressivelyvarieswhen thegeographical environment is changed. In fact, the study of these effects constitutes a rapidly expanding field of animal physiology. Suffice it to mention here as examples the studies of human performance in high mountains4' 1 and of the nutritional aspects of climatic stress.'6 Professor Alexander von Muralt has kindly provided me for this occasion with a ij of papers dealing with the pathological effects of weather on man. From these studies it appears that objective tests are available for quantitative observations as shown by the fact that warm fronts are associated with a decrease, and cold fronts with an increase, in capillary resistance.'7 It can hardly be doubted therefore that disease states which in final analysis are always the expression of physiological disturbances can be affected by the complex of physical forces which make up the climatological environment. Moreover, this statement applies not only to metabolic disorders, but just as well to diseases caused by microbial agents.