duce it. Perhaps, on the analogy of the higher plants, in which some of them also occur, we may attribute to the latter category certain bodies closely resembling vegetable alkaloids; these are called ptomaines, and are extremely poisonous. Besides such bodies, Bacteria undoubtedly generate true ferments and peculiar coloring-matters. But there are in most cases of putrefaction a profusion of other substances, which represent the various stages of the breaking up of the complex proteid molecule, and are often themselves the outcome of subsidiary fermentations.

These results are of great interest from a scientific point of view. But their importance at the present moment in the study of certain kinds of disease can hardly be exaggerated. I have already mentioned Henle as having first found the true clue to animal histology in the structure of plants. As early as 1840, the same observer indicated the grounds for regarding contagious diseases as due to living organisms. I will state his argument in the words of De Bary, whose "Lectures on Bacteria," the last work which we owe to his gifted hand, I can confidently reconmend to you as a luminous but critical discussion of a vast mass of dif ficult and conflicting literature.

It was of course clear that contagion must be due to the communication of infectious particles or contagia. These contagia, although at the time no one had seen them, Henle pointed out, "have the power, possessed, as far as we know, by living creatures only, of growing under favorable conditions, and of multiplying at the expense of some other substance than their own, and therefore of assimilating that substance." Henle enforced his view by comparison with the theory of fermentation, which had then been promulgated by Schwann. But for many years his views found no favor. Botanists however as in so many other cases, struck on the right path, and from about the year 1850 steady progress, in which De Bary himself took a leading part, was made in showing that most of the diseases of plants are due to parasitic infection. The reason of this success was obvious; the structure of plants makes them more accessible to research, and the invading parasites are larger than auimal contagia. On the animal side all real progress dates from about 1860, when Pasteur, having established Schwann's theory of fermentation on an impregnable basis, took up Henle's theory of living contagia.

The only risk now is that we may get on too fast. To put the true theory of any one contagious disease on as firm a basis as that of alcoholic fermentation is no easy matter to accomplish. But I believe that this is (notwithstanding a flood of facile speculation and imperfect research) slowly being done.

There are two tracts in the body which are obviously accessible to such minute organisms as Bacteria, and favorable for their develop ment. These are the alimentary canal and the blood. In the case of the former there is evidence that every one of us possesses quite a little flora of varid forms and species. They seem for the most part, in health, to be comparatively innocuous; indeed it is believed that the

are ancillary to and aid digestion. But it is easy to see that other kinds may be introduced, or those already present may be called into abnormal activity, and fermentative processes may be set up of a very inconvenient kind. These may result in mere digestive disorder, or in the production of some of those poisonous derivatives of proteids of which I have spoken, the effect of which upon the organism may be most disas trous.

The access of Bacteria to the blood is a far more serious matter. They produce phenomena the obvious analogy of which to fermentative processes has led to the resulting diseases being called zymotic. Take for example, the disease known as "relapsing fever." This is contagious. After a period of incubation, violent fever sets in, which lasts for some. thing less than a week, is then followed by a period of absence, to be again followed in succession by one or more similar attacks, which ultimately cease. Now you will observe that the analogy to a fermentative process is very close. The period of incubation is the necessary interval between the introduction of the germ and its vegetative multiplication in sufficient numbers to appreciably affect the total volume of the blood. The rise in temperature and the limited duration of the attack are equally, as we have seen, characteristic of fermentative processes, while the bodily exhaustion which always follows fever is the obvious result of the dissipation by the ferment organisms of nutritive matter destined for the repair of tissue waste. During the presence of this fever there is present in the blood an organism, Spirochete obermeieri, so named after its discoverer. This disappears when the fever subsides. It is found that if other individuals are inoculated with blood taken from patients during the fever attack, the disease is communicated, but that this is not the case if the inoculation is made during the period of freedom. The evidence then seems clear that this disease is due to a definite organism. The interesting point however arises, why does the fever recur, and why eventually cease? The analogy of fermentation leads to the hypothesis that as in the case of yeast the products of its action inhibit after a time the further activity of the Spirochate. The inhibiting substance is no doubt eventually removed partially from the blood by its normal processes of depuration, and the surviving individuals of Spirochete can then continue their activity, as in lactic fermentation. With regard to the final cessation of the disease, there are facts which may lead one to suppose that in this as in other cases sufficient of the inhibiting substance ultimately remains in the organism to protect it against any further outbreak of activity on the part of the Spirochate. Here we have an example of a disease which, though having a wellmarked zymotic character, is comparatively harmless. In anthrax, which is known to be due to Bacillus anthracis, we have one which is, on the contrary, extremely fatal. I need not enter into the details. It is sufficient to say that there is reason to believe that the Bacillus produces, as one of those by-products of protoplasmic destruction to which I have already alluded, a most virulent poison. But the remarkable

thing is that this Bacillus, which can be cultivated externally to the body, if kept at a heightened temperature, can be attenuated in its virulence. It drops in fact the excretion of the poison. It is then found that, if injected into the blood, it does no mischief, and, what is more extraordinary, if the Bacillus in its most lethal form is subsequently introduced, it too has lost its power. The explanation of the immunity in this case is entirely different from that which was suggested by a consideration of the facts of relapsing fever. The researches of Metschnikoff have led to the hypothesis that in the present case the white blood-corpuscles destroy the Bacillus. When they first come into contact with these in their virulent form, they are unable to touch them. But if they have been educated by first having presented to them the attenuated form, they find no difficulty in grappling with the malignant. This is a very remarkable view. I should not have put it before you had there not been solid reasons for regarding the idea of the education of protoplasm with scientific respect. The plasmodia of the Myxomycetes, which consist of naked protoplasm, are known to become habituated to food which they at first reject, and the researches of Beyerinck on the disease known as "gumming" in plants have apparently shown that healthy cells may be taught, as it were, to produce a ferment which otherwise they would not excrete.

If Metschnikoff's theory be true, we have a rational explanation of vaccination and of preventive inoculation generally. It is probably however not the only explanation. And the theory of the inhibitive action upon itself of the products of the ferment-organism's own activity is still being made the basis of experiment. In fact, the most recent results point to the possibility of obtaining protection by injecting into the blood substances artificially obtained entirely independent of the organisms whose development they inhibit.

It is impossible for me to touch on these important matters at any greater length, but I doubt if the theory of fermentation, as applied to the diseases of organisms, has as yet more than opened its first page. It seems to me possible, that besides the rational explanation of zymotic disease, it may throw light on others where owing to abnormal conditions, the organism, as in the case of Bérard's plums, is itself the agent in its own fermentative processes.

And now I must conclude. I have led you, I am afraid, a too lengthy and varied a journey in the field of botanical study. But to sum up my argument: I believe I have shown you that at the bottom of every great branch of biological inquiry it has never been possible to neglect the study of plants; nay more, that the study of plant-life has generally given the key to the true course of investigation. Whether you take the problems of geographical distribution, the most obscure points in the theory of organic evolution, or the innermost secrets of vital phenomena, whether in health or disease,-not to consider plants is still, in the words of Mr. Darwin, "a gigantic oversight, for these would simplify the problem."

ELEMENTARY PROBLEMS IN PHYSIOLOGY.*

By Prof. J. S. BURDON SANDERSON.

The work of investigating the special functions of organs, which during the last two decades has yielded such splendid results, is still proceeding, and every year new ground is being broken and new and fruitful lines of experimental inquiry are being opened up; but the further the physiologist advances in this work of analysis and differentiation, the more frequently does he find his attention arrested by deeper questions relating to the essential endowments of living matter of which even the most highly differentiated functions of the animal or plant organism are the outcome. In our science the order of progress has been hitherto and will continue to be the reverse of the order of nature. Nature begins with the elementary and ends with the complex (first the amoba, then the man). Our mode of investigation has to begin at the end. And this not merely for the historical reason that the first stimulus to physiological inquiry was man's reasonable desire to know himself, but because the differentiation actually involves simplification. Physiology therefore first studies man and the higher animals, and proceeds to the higher plants, then to invertebrates and cryptogams, ending where development begins.

It is not difficult to see whither this method must eventually lead us. For inasmuch as function is more complicated than structure, the result of proceeding, as physiology normally does, from structure to function, must inevitably be to bring us face to face with functional differences which have no structural difference to explain them. Thus, for example, if the physiologist undertakes to explain the function of a highly differentiated organ like the eye, he finds that up to a certain point, provided that he has the requisite knowledge of dioptrics, the method of correlation guides him straight to his point. He can mentally or actually construct an eye which will perform the functions of the real eye, in so far as the formation of a real image of the field of vision on the retina is concerned, and will be able thereby to under stand how the retinal picture is transferred to the organ of concious

*Presidential address before the Biological Section of the British Association, A. S., at Newcastle, September, 1889. (Report of the British Association, Vol. LIX, pp. 604614.)