as phosphorus acts upon the formation of bone, but that there are also cell excitants, such as cantharidin, which, without themselves having any effect on the bacteria, can bring about the cure of diseased tissues, so that the nosoparasitic bacilli are destroyed.

But here begins a branch of science which, like the theory of immunity and serum therapy, occupied the end of the nineteenth century, and the waves of discussion still run so high that it is as yet unsuitable for an historical survey. It is sufficient to say that all the investigations of the present as well as of the past century afford us a guarantee that we are following the right road of progress in therapeutics, and assure us that in regard to the healing of disease there lie before us "infinite possibilities," to use the apt phrase which has been already employed in regard to the development of your country by Ludwig Max Goldberger, "Das Land der un-begrenzten Moeglichkeiten."

THE PROBLEMS OF THERAPEUTICS

BY SIR LAUDER BRUNTON

[Sir Lauder Brunton, Physician to St. Bartholomew's Hospital, London. b. 1844. M.D., Sc.D., LL.D. (Edinburgh); LL.D. (Aberdeen); F. R. C. P.; F. R. S. Author of The Bible and Science; Text-Book of Pharmacology; Therapeutics and Materia Medica; Disorders of Digestion; Lectures on Action of Medicines; Disorders of Assimilation; Collected Papers on Circulation and Respiration; and numerous papers in scientific and medical periodicals.]

THE subject of my lecture to-day is "The Problems of Therapeutics." My audience is a select one of persons interested in science and art. But science in these days has branched out so widely that it is impossible for any single person to be acquainted with every department of it, so that the terms used by a zoölogist may be unintelligible to a mathematician, or vice versa. There are some here whose researches have led them far into abstruse departments of science and if they were speaking I should gladly welcome a few introductory words from them on the very rudiments of their science in order to help me to understand a disquisition on the more advanced parts of their subjects.

Judging others by myself, I think they may be glad if I do the same, and I must beg the indulgence of those acquainted with medical science and its branches if this lecture should seem to be unnecessarily rudimentary. By therapeutics we mean the methods of healing. In the great staircase of St. Bartholomew's Hospital in London there is a large picture by William Hogarth representing the Good Samaritan. The poor traveler is seated on the ground, the Good Samaritan is pouring oil and wine into his wounds, while close at hand is a dog busily engaged in licking a cut which he has received in the fray. Both dog and man are engaged in solving, as far as they can, two of the primary problems of therapeutics, viz.: (1) how to relieve pain, and (2) how to restore health. For disease is want of ease, and health is only one form of the word "whole," by which we mean that a thing is entire and neither cut, broken, nor cracked. The closure of wounds is one form of restoring "wholeness" or "health" to the body, but it is by no means the only one, for the vital organs lie below the surface, and it is with disturbances of their functions, even more than with external wounds, that therapeutics, or the science and art of healing, is chiefly occupied. As exemplified in the dog or in the Good Samaritan, therapeutics is simply an art. Certain things are done because they have been found to do good before and so they are repeated again and again, but neither the dog nor the Good Samaritan un

derstands the reason why their procedure is useful. It is only when we learn the reason why that an art becomes converted into a science. Therapeutics in its primitive form is one of the simplest of all the arts and is practiced by animals as well as by man, but as a science it is one of the most complex and most difficult of all because it requires a knowledge of the functions of the body in health, or physiology; of their changes in disease, or pathology; of the action of drugs upon the body, or pharmacology; and of chemistry, physics, and other sciences on which physiology, pathology, and pharmacology are based. Finally it requires the practical power of recognizing from the symptoms (in any individual case) the nature of the pathological changes present and the ability to apply the right methods of treatment in order to counteract these changes and heal the patient. It is evident that such complex knowledge as this must be very difficult of attainment, yet nevertheless the change of therapeutics from an art into a science is progressing with considerable rapidity. In a text-book on the subject which I published eleven years ago, I mentioned the use of quinine in ague as the best example of the art of therapeutics whereby we could cure a disease of which we did not know the nature by a remedy whose curative action we did not understand. Since that time, however, we have learned that ague depends upon the presence of a foreign organism in the body and that the benefits obtained from quinine are due to its poisonous action upon this intruder. This malarial parasite is only one of the many minute organisms which mar or destroy the health of the human body. Minute organisms or microbes are most useful in their proper place and without them the world would be uninhabitable because they are the natural scavengers which produce putrefaction in dead plants and animals and thus bring about their return to dust, fitting them for new life instead of allowing them to incumber the ground. But not content with this function some of them proceed to invade living beings, attacking not only the weak but even the strong, and by growing and multiplying within them weaken or destroy their hosts.

One of the great problems of therapeutics, then, is to defend the body from attacks of microbes. This may be done either (a) by weakening or destroying the microbes themselves or (b) by increasing the power of the organism to resist them.

It is convenient to speak of the body as a whole when we are discussing its invasion by microbes, but we must not forget that the body, like a country, is composed of many parts. The interests of the different parts are by no means identical, and while they generally act together for the common good they may not always do so, and either by their sluggishness and inaction or by their mischievous

activity may do harm instead of good to the body as a whole. What is requisite for health is an harmonious action of all the different parts of the body, or as St. Paul very well puts it, "And thus all the body framed and knit together through that which every joint supplieth, according to the working in due measure of each several part, maketh the increase of the body unto the building up of itself" (Ephes. IV, 16, Revised Version), so "that there should be no schism in the body and that the members should have the same care one for another." No doubt in their long wanderings together Luke the beloved physician discussed physiology largely to Paul, and his expression is so good that I introduce it now.

Just as the people of a country is composed of individuals, so the body is composed of numerous cells. The whole class of microbes consists of isolated cells which are like a nomad population, each individual complete in himself, and all ready to form a swarm for attack and invasion. The cells which compose the body, on the contrary, are mostly fixed, and differ from each other in structure and function, but ought all to act together for the common good, like civilized people. Each cell lives in the fluid which surrounds it, blood or tissue juice, from which it takes what it needs for its own nutriment and pours back the products of its tissue activity which may be partly waste and partly manufactured products of the utmost utility.

In order to have a complete comprehension of therapeutic problems it is necessary that we should know something about the life of the cell, because the life of the whole body depends upon that of the cells which compose it, and the cure of disease and the preservation of life depend on our power to influence cell-life. The processes of life are to a certain extent the same in the human body as a whole, in the cells which compose it, and in the smallest living organisms or microbes as they are termed. They all digest and assimilate food, they all breathe, and they all excrete waste products. A knowledge of the processes of life in man helps us to understand them in low organisms and vice versa. The use of pepsin and pancreatin in indigestion is so common that almost everybody knows that these substances have the power of dissolving meat and that pancreatin converts starch into sugar. Everybody knows that these are got from the stomach and pancreas of animals and that it is by similar substances formed in our own digestive canal that we are able to dissolve the food we eat and render it fit for absorption. It has recently been found that pancreatic juice, as poured out by the gland which secretes it, is very slightly active, but it is made active by another ferment secreted from the intestine which is called enterokinase. The pancreatic juice contains several ferments; that which acts upon meat is called trypsine and in its inactive state it is called trypsogen. The action of the enterokinase on the trypsogen may be compared

to that of a man who opens the blade of a knife and renders an instrument previously inactive very active indeed. If trypsine were absorbed into the blood unchanged it might digest the tissues themselves and it must be rendered again inactive. This seems to be effected by certain substances present in the blood which have a so-called "anti" action upon the ferments and render them again inactive. But though the digestive ferments might do harm if present in the blood in an active form and in large quantity, yet it is probable that all the cells of the body digest the food which is brought to them by the blood and tissue juices and break up this food for their own use by ferments which they contain themselves. Thirty years ago I advanced this view and supported it by the fact that I was able to extract from muscle by glycerine a substance which decomposed sugar. This observation received but very little attention at the time, but recently German literature is full of papers which support my views and confirm my results, although their writers apparently are ignorant of my work. Fifteen years ago, along with Dr. Macfadyen, I showed that bacteria not only excrete ferments by which the soil in which they are growing is digested, but that they are able to modify these ferments in accordance with the soil so as to digest either proteid matter or sugar. Curiously enough, within the last few years the pancreas in animals has been shown by Professor Pawlow to have similar powers.

No individual microbe has received so much attention as the yeast plant and no poison which is formed by any of them has done so much harm as the toxin or poisonous substance produced by yeast, for this toxin is alcohol, whose poisonous action has given rise to the term intoxication. The yeast-plant, when grown in sugar, excretes into it a ferment, invertase, which splits up ordinary cane-sugar or saccharose into two other sugars, dextrose and levulose. The yeast-plant may be separated from the solution of sugar by filtration, but the ferment which is already excreted will remain in the filtrate and may still continue to act on the sugar, just as pepsin may dissolve a piece of meat in a jar although the pig which produced it is dead and gone. But no alcohol will be formed by this excreted ferment. Alcohol is produced by something contained within the body of the yeast itself and its production was formerly supposed to be due to so-called vital action. It has now, I think, been proved that alcohol is produced by the action of a ferment which is contained within the body of the yeast-cell and is not excreted from it, so long as the cell is intact, but only passes out after the cells have been crushed into fragWhilst the cell is alive and intact it absorbs the sugar into its interior, breaks it up there, and forms the alcohol which is afterward excreted.

ments.

To make this clearer I may perhaps be allowed to use a very crude