Chapter XVI: Epilogue: 351 (10)

For example the increase in the incidence of deaths from Cancer has often been emphasized. But Cancer is a disease of advancing life. The age distribution of the death-rate from many forms of Cancer is closely parallel to that of certain other forms of senile disease (Figs. 136 and 137). Now the age constitution of the population of most civilized countries is altering in the sense that the proportion of the elderly and aged is constantly increasing (Fig. 134), so that some increase in the Cancer incidence must be expected. Moreover the appearance of some increase in the incidence of Cancer is due to improved diagnosis. How far there is a real increase, when these factors have been taken into account, is still somewhat doubtful. It must always be borne in mind that a relative decrease in the proportion of deaths from _any_ cause must automatically increase the proportion of deaths from other causes.

Again, there is no doubt of the fall in the death-rate in England and Wales from ‘Phthisis,’ or pulmonary tuberculosis, during the last fifty or sixty years. There is also no doubt of the effect both of bad housing and of urban conditions in inducing a susceptibility to chest disease in general and to pulmonary tuberculosis in particular. Further, there is no doubt that the rural population suffers less from pulmonary tuberculosis than the town population. These matters of common medical knowledge have naturally led to the conclusion that the rise of the great towns has led to a great increase of pulmonary tuberculosis, and that this increase has been remedied by the improved housing and sanitary conditions of the last generation. A study of the statistical evidence, however, negatives this view. The rise in the proportion of deaths from pulmonary tuberculosis took place before the Industrial Revolution. Moreover, the proportion began to fall long before the campaign against tuberculosis could affect the issue. The history of pulmonary tuberculosis may, in fact, be regarded as that of an ‘epidemic’ outbreak, extending over about 100 years, of a disease which has always been endemic and remains so now that the epidemic is past.

FIG. 138. CURVE SHOWING PERCENTAGE OF DEATHS FROM PHTHISIS to total deaths from all causes in London over a period of 200 years. It will be seen that the percentage begins to rise definitely about 1730 and to fall definitely about 1830. This state of affairs may be pictured as an epidemic lasting about 100 years. ]

These points are well brought out in the accompanying diagram (Fig. 138). The fall in the proportion of deaths from Phthisis expressed there gives rise to further considerations. It might seem that the statement that the proportion of those who died from phthisis was diminishing left in itself no doubt that the disease was less prevalent than formerly. This, however, is not the case. Phthisis is more liable to affect those under forty-five years of age than those who are older. Now the proportion of the population that is under forty-five is steadily diminishing (Fig. 134). This is one of the results of the steadily diminishing general death-rate (Fig. 96, p. 196). Therefore the proportion of the more susceptible to the less susceptible is diminishing. It might have been the case (though it is not) that the ratio (more susceptibles)/(less susceptibles) was not only decreasing but was actually decreasing more rapidly than the ratio (total deaths)/(deaths from phthisis). Had this been so, the conclusion would have been justifiable that the fall in the proportion of deaths from the disease did not correspond to any decrease in its infectivity. In fact, however, the prolonged high mortality from phthisis and its later rate of fall do suggest the former prevalence of a more virulent type of the disease over a long period, in other words something of the nature of a prolonged epidemic.

This conclusion leads us to the conception of the nature of an epidemic. To gain some conception of the ideas involved in that word, we must glance back in history.

From the time of Hippocrates onward the subject of Epidemic outbursts of disease has drawn the attention of physicians. A writer in the _Hippocratic Collection_ thought he could perceive an association of symptom-complexes with each other and with the weather. In the great work _Epidemics_, to which the name of the Father of Medicine is attached, such a view, known as that of ‘Epidemic Constitutions,’ is set forth. The view was revived by Sydenham in the seventeenth century and has given rise to a vast literature extending to our own time. In the eighteenth and nineteenth centuries the attempts of the investigators of vital statistics to place the leading events of life in a form capable of exact analysis (pp. 166-68) focused attention on the search for a mathematical expression for the rise and fall of epidemic diseases.

The first successful attempt to describe epidemics along these lines was made by William Farr (1807-1883), an official in the office of the Registrar-General in London, and one of the greatest of all epidemiological thinkers. His first publication on the subject was in 1840, and had reference to the recent outbreak of small-pox, in which more than 30,000 had died in England and Wales. It was his merit to observe that the successive decreases in the number of cases in successive equal periods during the decline of the epidemic correspond to the successive increases in the number of cases during successive equal periods of the rise of the epidemic. In other words, he observed that the rise and decline of an epidemic tend to be mathematically symmetrical.

Farr’s suggestion that epidemics are liable to follow the lines of regular mathematical rules drew little attention at the time, but in a later year it led to a most remarkable and striking prophecy. At the end of 1865 Cattle-plague broke out in England. Week by week the number of cases increased. In the fourth week of February 1866 the responsible Minister, in a speech in Parliament, gave a very gloomy account of the state of affairs, expressing the belief that the devastation would be far beyond what had yet been encountered. Farr, however, had been watching the returns, and had been applying his rule to them. He thereupon made a public pronouncement of his belief that at an early date the outbreak would reach its maximum and would then decline. The outbreak did, in fact, very closely follow the course which he had predicted by reasoned calculation. Farr even prophesied the number of cases that would occur week by week. His prophecy was near the truth.

During the years that followed Farr’s prediction his views were applied with success to a variety of epidemic conditions. The regular form of the development of the epidemic was found to apply in certain outbreaks of typhus, measles, and other conditions.

Farr’s law was more exactly expressed by him in 1868. It remained, however, simply a mathematical law, a rule of which the underlying cause was not apparent. It was soon observed that his law applied to many but by no means to all epidemics. Moreover, it was perceived that the actual figures which he gave for his epidemic of 1840 resembled those of certain other epidemics in that they could be fitted with greater or less exactness to a well-known mathematically described curve, known as the ‘normal curve of error’. We need not discuss the mathematical foundation of this curve, which is shown in two variants in Fig. 139. For our immediate purpose it is enough to observe that it rises gradually at first, but then more steeply, that the steepness decreases after a while, and then the curve begins to decline again, as it rose. We note that it is symmetrical.

FIG. 139. THE NORMAL CURVE OF ERROR, shown in two types made with the same formula but with different constants. This curve has been shown to be similar to that representing the incidence of cases in some Epidemics.

Vertical lines are drawn from two pairs of symmetrical points. The continuous lines refer to the higher curve, the broken lines (from the points of intersection of the two curves) refer to the lower curve. The lines will be seen to divide the curves into three parts. This division is of such a character that the sum of the two lateral areas is equal to the central area for each case. ]

FIG. 140. Curve of monthly number of deaths from Small-pox during an epidemic at Warrington, Lancashire, in 1743.

FIG. 141. Curve of weekly number of cases of Scarlet Fever registered during an epidemic at Glasgow in 1892.

Both curves are fitted to the theoretical epidemic curve, and are modified from Brownlee. The curves are in both cases explained on the assumption that the infectivity, having reached a high point at the beginning of the outbreak, decreases thenceforward in geometrical progression. ]

When we are dealing with living beings or are dealing with things that may indefinitely approximate to a mathematical rule, but never entirely fit it. Especially when the living beings are also human beings, with their infinitely complex relationships, various factors are present which interfere with the exact application of mathematical findings. Nevertheless, the theoretical form of the epidemic is an extremely useful framework into which actual epidemics may often be fitted, with greater or less exactness. In the accompanying figures (Figs. 140-141) are adduced cases of greater exactness. There are, however, many cases in which an ‘outbreak’ does not seem to fit the simple theoretical curve at all. Examination of such curves has in some cases suggested that we have not one epidemic or disease but two or more to deal with. In some cases it has been possible to analyze the outbreak on the basis of two or more theoretical curves, suggesting in fact two or more outbreaks of similar but not identical causation (Fig. 142).

FIG. 142. THE CURVES OF SOME EPIDEMICS, which do not follow the theoretical curve, may be analyzed as compounded of two or more epidemics, each of which accords individually to the mathematical rule. Thus ‘Summer Diarrhoea’ is a seasonal disease very fatal to infants in England during the hot months, July and August. The angular curve shows the average daily incidence of deaths from this disease in London during the fifty-three years 1850-1903. It can be analyzed into two of the theoretical epidemic curves.

Each reading of the curve, calculated from the actual cases of ‘Summer Diarrhoea of Infants’, can be divided into two, as indicated in the step-like readings, one dotted and the other continuous. These accord beautifully with two theoretical curves, thus indicating not one but two recurrent epidemics. It thus seems probable that two separate sources of infection are confused as ‘Summer Diarrhoea of Infants’.

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What can be the causative element which constrains the incidence of a disease in a population to follow mathematical rules? An answer was provided by John Brownlee (1868-1927), the late statistician to the Medical Research Council of England. The leading fact about an Epidemic is that it rises to a maximum, falls, and then dies out, and that the curve representing the number of new cases in a series of equal and consecutive periods of time throughout the Epidemic is symmetrical. In practice the decline is usually a little slower than the rise. This is sometimes, at least, due to better observation and record of the later cases. Now why does an Epidemic die out? The possible reasons may be reduced to three. Firstly, the end of an Epidemic may be due to the exhaustion of susceptible persons in the population. That is to say, all the survivors are immune, either being so by nature or having become so by having contracted the disease and recovered. Secondly, it is conceivable that the liability to the disease should be decreased, not by rise in the proportion of immunes, but by externally acting causes, as, for instance, by rise of seasonal temperature, which would provide conditions under which the organism loses its infectivity. Expressed in older language, this is to say that the ‘Epidemic Constitution’ (p. 342) has changed. Thirdly, the infecting organisms may, of their own inner nature, lose their infectivity. The second factor may act in special cases, but may be disregarded except in those cases. We are, therefore, left with the first and third.

Now it is possible to construct curves that would correspond to the exhaustion of the supply of susceptible persons by continuous increase of the proportion of those who become immune either by taking the disease or by dying. These curves, however, have the character that their descent is more rapid (and neither as rapid nor less rapid) than their ascent. It is the merit of Brownlee to have suggested that the actual curve of the Epidemic corresponds to a known though very little understood biological phenomenon, namely change in the infectivity of the invading organisms. The simplest expression of his discovery is that the loss of infectivity of these organisms is approximately in the ratio given by a geometrical progression. That is, if the infectivity of the Epidemic be _m_, and at the end of a unit of time _mg_ (when _g_ is less than unity), at the end of a second unit of time it will be _mg_^2, and at the end of the third _mg_^3, and so on. Assuming this to be a fact, the course of Epidemics would follow the curve of normal error (Fig. 139).

Of late years it has been possible to institute artificial epidemics in a series of animals under control conditions. Such experiments must, in the nature of the case, cover a large number of years, but they bid fair to throw much light on the nature and progress of human epidemics.

These results seem to show, what was believed on other grounds, that in the case of highly infective disease, to which, in any population, there are many highly susceptible, isolation of declared cases has little or no effect on the course of the Epidemic. Such diseases are Scarlet Fever, Measles, Influenza, &c. Moreover, the experimental epidemics seem to confirm the conclusions of Brownlee that in some cases at least the course of the epidemic is determined by biological changes within the parasitic beings that cause it.

Thus in the end our health, our lives, and indeed the continuance of our civilization may well depend upon a factor which is outside ourselves. For reasons which we know not, the pullulating billions of living things which are around us, upon us, within us, take up a virulence which before they had not, and after a time they lose that virulence to become as they were before. The world is devastated by an outbreak of Plague, of Cholera, of Influenza. But how and why the organisms that carry these diseases should acquire a new and more deadly infectivity lies among the secrets yet locked within the living cell. Life--the life of the Cell, of the Bacterium, of Man himself--remains among the _Arcana Naturae_. These are the secret things that in their essence--which is Life--remain and will remain behind the veil. From such cells we came, through such cells we shall return. As to what is the force which starts these processes on their way, we are as ignorant as children, and must remain so, in essence, till we understand the nature of the processes of coming into being and passing away. So Medicine must end where she began, quaking before the Mystery of Life, a Mystery which could only be resolved if we could express Mind in terms simpler than itself. If this could be done the veil that is cast over all flesh would indeed be rent. But the author of this work believes that the hope of this is vain and that we are here in the presence of one of the ultimate things.