practically, though extremely important and interesting. It was only when dogs and, more especially, our still nearer relatives, the apes, were drawn into the experimental field, that we really began to find out what was going on in our own brains. I may add that the observation of the diseased human brain, both at the bedside and post mortem, has always been extremely fragmentary and unsatisfactory.

As with the brain, so with the nerves: most of our knowledge is derived from experiments on the lower animals. It has been the fashion among the antivivisectionists to reserve especially vehement abuse for the great Magendie, who laid the very foundations of our present, still somewhat incomplete, knowledge of nerve-functions, nervetracts, and nerve-regeneration. It is true that Magendie's work involved the infliction of a great deal of pain, but we should, in simple justice, remember that anæsthesia was unknown in Magendie's day, and one of the many results obtained in this field of work is the demonstration that the sensations of man are far keener than those of the lower animals. As sensation, including that of pain, is purely a brain-function, which may be entirely abolished by stupefying the cells of the gray matter with an anæsthetic, it is evident that acuteness of sensation is apt to increase with the complexity of the brain-structure. This is unquestionably highest in man, and higher in the upper than in the lower races; thus the inferior races plainly show that they feel pain less than do the pampered products of civilization. On the average, the endurance of pain will vary in inverse proportion to its severity; if we eliminate the influence of self-control, that deference to convention and public opinion called stoicism, the demeanor of the victim of a pain is a fair guide as to its intensity.

III

It is scarcely necessary for me to remind the reader of the indebtedness of modern medicine to the science of bacteriology, that branch of natural history which treats of the minute germs known as bacteria. The difficulties encountered in studying bacteria will be appreciated, when we consider that millions of the larger germs can live and flourish in a single drop of milk, whereas the smallest, under the most powerful microscope, appear like grains of fine dust.

Some of the ancient writers had suspected that certain infectious diseases might be caused by minute living organisms, but not until 1683, when Leeuwenhook had invented the microscope, could the bacteria even be seen. It was not until the middle of the nineteenth century, when Pasteur found ways of cultivating these germs, that the science of bacteriology may be said to have originated; it was only after 1880, when Koch showed how to cultivate them on solid media, that the science began to make rapid progress, and to revolutionize medicine. The reason for this lies in the fact that, to study bacteria, it is necessary to isolate them; they always occur mixed in their natural state, and of course remain mixed, if they grow in a fluid; it is easy to understand how the different species may be separated, if we cultivate them, like ordinary plants, on a solid surface.

Presently, the supposed germs of numerous infectious diseases were announced, and, as it had become comparatively easy to cultivate bacteria, isolate them, and study their peculiarities, it only remained to prove their responsibility for the diseases attributed to them. Let us remember that, in sick as well as in healthy persons, the harmless bacteria far outnumber those that are dangerous; of thousands

of species, only a few dozen belong to the class called pathogenic, or diseaseproducing. At this stage of the science, Koch, most opportunely, laid down the three clauses of the following law:

1. All cases of the disease must furnish the germ held responsible for it.

2. The germ must be cultivated so as to free it from mixture with other germs; that is to say, it must be obtained in pure culture.

3. Inoculation of germs, from the pure culture, must reproduce the identical disease.

Koch's law has stood the test of thirty years. Whenever one of the three links in the chain is missing, we admit at once that the responsibility of the germ under investigation is uncertain, unless corroborated by strong circumstantial evidence; if two links are missing, the germ has only a questionable scientific standing, in any event. When all three clauses are satisfied, the case is complete, as has been proven repeatedly in other ways into which I cannot enter here; I mention the production of artificial immunity as one of them.

Koch's third requirement presents the greatest difficulties to the bacteriologist. For example, when the tubercle bacillus had satisfied the first two, it was still manifestly undesirable to inoculate a human being with the pure culture, to see what would happen. Even the most scornful skeptic of Koch and his methods would have declined more or less politely to offer himself for this test.

Nothing therefore remained but to inoculate animals, many of which were known to suffer at times from tuberculosis. These experiments were completely successful: the animals became affected with unquestionable tuberculosis, and the germs, taken from them and cultivated, again reproduced the same disease in another series of ani

mals. No one who has taken the trouble to inform himself on the subject now has the faintest doubt that this germ, and no other, is the cause of tuberculosis. Moreover, since the earlier experiments, further proofs have been supplied, also through investigations conducted on the lower animals.

If the laws of Germany had forbidden the inoculation of animals with germs that would make them sicken and die, Koch would have been compelled to pursue his ever-memorable researches in some other country, and that country would have received all the credit. If the whole world had been controlled by the anti-vivisectionists, consumptives to-day would not know how they became ill, nor how to guard the members of their families from becoming likewise infected; furthermore, the doctors, in many cases, would not even be able to make the diagnosis.

It may reassure tender-hearted readers to know that the injection of tuberculous material is no more painful than the familiar hypodermic, and that an animal sick from tuberculosis suffers less physical pain than the thousands of hapless human sufferers from this lingering disease, while of course it is free from the still more acute agony of the mind.

Tuberculosis also furnishes one of the most convincing arguments against one of the favorite stands of the antivivisectionists, namely, that it should be made unlawful to repeat experiments intended merely to corroborate an already established fact. Fifteen years ago most of us took for granted that the tuberculosis of man was identical with that of cattle; this view prevailed only because the investigators had not made a sufficient number of experiments on animals. More frequent inoculations of human tuberculosis on cattle, and a more careful investigation of bovine tuberculosis, would long before have

This

revealed what Theobald Smith showed in 1895, namely, that cattle tuberculosis is caused by a slightly different and far less dangerous germ. leaves open the question whether the one form of germ may, under certain conditions, be transformed into the other; and, what is most important for us to know, whether the chief danger to man lies in the milk of infected cows or in the expectoration of infected persons. If Theobald Smith's contention is established, we shall have to restrict the careless habits of consumptives with more firmness than ever, and relegate the supervision of cattle to a secondary, though still important position. In any case, all the work of studying the relation between human and bovine tuberculosis will have to be gone over again, and this research will have to be made, almost entirely, on animals.

It is curious, but true, that there is more confusion on this subject in England than anywhere else, and that England is the country where animal experimentation is most seriously hampered by law. Most unbiased observers feel that if the English physicians had depended less exclusively on the study of their patients and had given more attention to tuberculosis in animals, they would not have arrived at their present state of uncertainty.

Even more remarkable are the results of animal experimentation in diphtheria. The diphtheria bacillus was discovered by Loeffler in 1879, but its status was doubtful for some years: first, because of the number of other germs found in inflamed throats; secondly, because some harmless germs resemble it closely. But for Koch's third law the whole matter would have remained doubtful. The guinea-pig, however, is remarkably susceptible to diphtheria, so much so that it is employed as a test for doubtful cases. Pure cultures from guinea-pigs that

have died of diphtheria will in turn infect other guinea-pigs, and so on ad infinitum.

It was soon found that the diphtheria germ itself was not the most dangerous element in diphtheritic infection; it does not grow indefinitely, and usually remains exclusively at the site of infection, say the throat, rarely wandering through the body. It acts chiefly through the intense poison that it produces as a part of its tissue-change. The treatment of diphtheria at first made little progress because the only method that could be considered was disinfection of the throat. Unfortunately the throat is one of the most difficult parts of the body to disinfect; indeed, it is practically impossible to disinfect it thoroughly.

A new chapter in medicine was opened when a Spanish physician, Ferrán, in 1890, announced that he had succeeded in immunizing animals against diphtheria. His results were soon corroborated by other investigators. It has been learned that, in the case of certain infectious diseases, probably in the majority, an animal that survives the attack has formed the antidote to the poison of the disease within its own body; this is indeed the reason why it recovers. It has also been learned that if we infect a guinea-pig with diphtheria germs, we can combat the infection by injecting into the same animal the blood-serum of a guinea-pig that has recently recovered. The poison is called the toxin, the antidote the antitoxin, and it has been shown that the latter, in proper dosage, exactly neutralizes the former.

The younger members of the present generation cannot realize what a thrill of horror went through a household when the family physician made the diagnosis of diphtheria. Formerly, we stood almost helpless at the bedside of our diphtheria patients, and expected

a fatal result in about half of the severe cases. To-day the death-rate of cases that are treated promptly is about one per cent. The only reason why there are still many deaths from diphtheria is that some persons alas, some doctors also have a prejudice against antitoxin, because they do not know what it is.

I doubt if there are enough guineapigs in the world to supply all our sick children with antitoxin. Fortunately, it has been found that horses give an ample supply, if we infect them with diphtheria germs. As a horse can give us about a thousand times as much blood as a guinea-pig, this wonderful remedy is not even very expensive. Nor does the horse suffer much from the occasional withdrawal of a moderate amount of blood; as a matter of fact, he is handled and fed very carefully, and has a decidedly easy life of it between tappings. It is a question whether he would object if he knew what was being done, and how many lives he was saving; his fellows in front of coalwagons surely find it harder to earn a living.

The story of the conquest of lockjaw is similar to that of diphtheria, the chief difference being that the antitoxin must be injected in advance, whenever we see a wound that looks as if it might contain the lockjaw bacillus. The treatment is therefore not quite so uniformly successful, and seems less effective than it really is, because we never know when we have saved a patient from death from this fearful disease: he simply remains as well as he was before, and no one can tell what might have happened if treatment had been omitted.

It is highly important to remember that the bacilli of diphtheria and tetanus are not at all injured by the antitoxin, but remain as malignant as they ever were; the antitoxin merely pro

tects the infected person against their poison. Physicians have been very successful in protecting the nurses and relatives of diphtheria patients against this disease. A small protective injection of antitoxin absolutely guarantees them against this illness, even if their throats, as is apt to happen, become thoroughly infected with diphtheria germs.

As soon as animal experiments are no longer available, we go on from one defeat to another; the most that we can do is to employ prevention. A conspicuous instance is afforded by that blot on American civilization, typhoid fever. No doubt our fearfully long death-list from that filthy disease would diminish if we could infect some animal and obtain an antitoxin; the recently announced susceptibility of monkeys gives us careless Americans a ray of hope. Otherwise, our only recourse is the right kind of sanitation, which consists entirely in keeping human excrements out of our food and water.

IV

There are still many persons, including, I regret to say, some justices on the bench, who define the practice of medicine as the giving of drugs. Most of our patients still think that the most important thing they can get from us is a prescription, and they pay much more attention to the directions on a medicine bottle than to the verbal advice imparted in the doctor's office. A large part of the community thinks that it might as well obtain its drugs at first hand from the druggist, without consulting a physician at all. This delusion has already slain its thousands, and will continue to fill early graves until the public learns better.

The truth is, that the administration of drugs is often the least important part of the aid we give our patients;

we accomplish more through other means of treatment than with medicines. The progress in physiology, of which I have given a few feeble hints, is already so great that we know the human body far better than many of the things we put into it. Some of our best drugs are employed only as auxiliaries to other treatment, such as diet, exercise, baths, and massage, not to mention surgical operations. Only a few drugs are used for combating disease directly, and these are chiefly of the class called internal antiseptics; for instance, quinine.

The testing of drugs on animals is not always trustworthy, for even the highest, dogs and apes, often respond somewhat differently from man; this does not, however, argue for omitting the animal experiment when we wish to learn the properties and action of a new and unknown drug. Any one can imagine that it would be highly reprehensible to give a little-known, perhaps highly poisonous, substance to a man before trying it on the dog. Sometimes a dog will die from an overdose, because the action of a drug is still uncertain; it were better to lose a thousand dogs in this way than one patient.

Such delicate matters as the effect of a new preparation on the blood-pressure, the kidneys, the digestion, and the nervous system, have to be investigated in living animals. Be it remembered that we aim to have our experiments succeed, and are disappointed when they turn out badly. In the latter case, however, we have the satisfaction of knowing that the untoward result has not injured a human being.

There is a group of four related diseases, measles, scarlet fever, chickenpox, and small-pox, which agree in one not very flattering circumstance, namely, that we doctors do not know what causes them; we merely believe that they are caused by germs too small to

be seen with our best microscopes. One fact, however, is worth noting: formerly, all four diseases were common; now, small-pox, the most dreaded of all, has become rare. The reason for this is as follows:

In 1798, Jenner observed that persons who had come in contact with cattle suffering from a disease called cow-pox were thereafter immune to small-pox; we, of to-day, cannot adequately realize the vast significance of Jenner's discovery. In the eighteenth century small-pox was, like measles, chiefly a disease of children; it killed about one tenth of the population, and permanently disfigured most of those who recovered, very few escaping altogether. We may declare with truth that the slow increase of the population of Europe, before the nineteenth century, was chiefly due to the ravages of the infectious diseases, of which smallpox was the worst. We may thus judge what a boon it was to humanity when the inoculation of cow-pox matter was found to protect human beings against small-pox for at least some years, whereas repeated inoculation, at moderate intervals, gave absolute and permanent protection. This form of inoculation is called vaccination; its compulsory introduction into everyday use has resulted in the almost total disappearance of small-pox from the more enlightened countries. In Germany, where vaccination and re-vaccination are strictly enforced, small-pox is almost unknown among the native population; in our southern and western states, where people are careless about vaccination, the disease is still quite common. We can truly measure a nation's civilization to-day by the relative frequency of small-pox.

To supply vaccine lymph, we must keep a continuous series of calves affected with cow-pox. I am willing to admit that these animals would be more