will not be answered by what we consider direct attack, for it is the habit of nature to respond to our interrogations with apparent indirectness. The real indirectness of course lies in the way we put our questions and not in Nature's response. We plan an experiment and await a result which shall be firmly yes or no; the answer is neither of these but something that throws no light on the original inquiry. Blessed is the man who sees in this incomprehensible reply the starting point of a new line of inquiry which may take him far afield from the goal he had first in mind. We scientists are like rag-pickers, some fumble through masses of rubbish looking for a certain coin, while the true investigator takes up each object that is turned over and asks himself what use he can make of it.

Let me illustrate the stages in the evolution of modern medical science from medical art by an outline of the development of our useful knowledge in respect to a single disease, namely, typhoid fever.

Typhoid fever has been, and still remains, one of the significant causes of death and disability. So far as can be shown from the necessarily incomplete statistics of the Public Health Service, there were over 17,000 deaths from this disease in the United States in 1913, which means there were over 170,000 cases, since the mortality averages ten per cent. It is a malady particularly prevalent in crowded groups of men, such as armies and asylums. Sixty per cent of all the deaths in the Franco-Prussian War were due to typhoid, and in the Spanish-American War one-fifth of all the enlisted men contracted the disease, and there were seven times as many deaths from it as from implements of war. And typhoid fever is important not only as a cause of death, but particularly owing to its economic waste; for an acute disease it has a particularly lengthened course and is followed by frequent sequels. It has recently been estimated that the economic loss in this country from typhoid is $50,000,000 annually. The disease ranks in this respect second only to tuberculosis.

Our interest in typhoid fever is heightened by the fact that it is not only an important disease, but one which can and will eventually be obliterated. Recent reports from the Surgeon General of the United States Public Health Service show that the incidence of this disease is probably not more than half what it was thirty years ago, owing in large part, to improved sanitation alone.

Perhaps the one most significant line of advance in medicine has been the gradual recognition of disease entities. On the recognition of separate diseases depends all measures of quarantine, prevention, and rational therapy. Diagnosis, the recognition of a disease entity, depends on the patient's symptoms and these symptoms are of two classes; subjective, or those the patient himself experiences as pain, chilliness, and the like; and objective symptoms which the physician can detect. Among the latter may be mentioned rapidity of the heart beat, fever, eruptions, changes in blood pressure; changes in the blood and urine, and the like. Medical progress has been dependent on the methods of recognizing such constant variations from the normal as are found characteristic of a given type of disease. Such variations were detected at first by the unaided powers of observation, and later by the employment of instruments and methods of precision introduced in the evolution of the medical sciences.

One of the most important symptoms of the parasitic or infectious diseases is a rise in bodily temperature, or fever. A fever is a disease characterized by such a rise in temperature and some fevers continue over a period of days or weeks. The disease we now recognize as typhoid or enteric fever is one of these continued fevers and although probably seen by Hippocrates, was for centuries confused with other lasting fevers of somewhat similar appearance. Recurrent fever, septic infectious, and typhus fever in particular, present pictures which even today in their beginnings and in their purely clinical aspects may be confused with typhoid.

We owe our first full description of what was probably typhoid fever to an English physician, Thomas Willis, who in 1643 described an epidemic of the disease that occurred among the parliamentary troops. Early in the eighteenth century Strother, another Englishman, described ulcerations in the intestine and enlargement of the spleen in that slow nervous fever which we now recognize as typhoid. The effect of this disease in producing a cloudiness or aberration of the mind is what has given it its name, which is derived from the Greek rûpos or cloud. Its particular nervous or mental effect was further observed by Huxham, who in 1737, on a purely symptomatic basis, separated cases of "putrid malignant fever" (or typhus) from the "slow nervous fever. The final separation of these two confused diseases did not come, however, until a century later and was dependent not only on the recognized differences in the contagiousness and course of the two diseases, but on the recognition of the characteristic and almost inevitable lesions or anatomical changes which are found in fatal cases of typhoid but never in typhus fever. These lesions, ulceration of the intestine and swelling of the spleen, liver, and lymph nodes, mentioned by Strother, were described by Riedel in Germany (1748), Baillie in England (1761) and in particular by Roerer and Wagler (1762). We owe further descriptions of the clinical characteristics of typhoid fever to Bretonneau (1826) who called it "dothienenteritis," or abscess of the small intestine, a name which it frequently bears in French literature, and to Louis (1829) who gave the name "fievre typhoide" to the malady.

It is to the great credit of a Philadelphian, William Gerhard, to have given in 1839, a convincing basis of separation between typhus and typhoid fevers. He based this differential diagnosis on accurate descriptions of the greater contagiousness of typhus, the presence of characteristic lesions in typhoid, and on careful comparison of symptomatic differences between the two maladies. His observations, later confirmed in Germany and England, gave us

the first basis on which to regard typhoid fever as a separate and distinct disease entity.

The final chapter in the clinical or purely observational study of typhoid fever is represented by two important observations in reference to its transmissions from one human being to another. The disease as contrasted with typhus fever was regarded, and properly so, as only slightly contagious, that is, directly transmissible from one patient to another. In 1856 Budd pointed out that the danger of transmission in typhoid, the poison of the disease as he expressed it, lies in the patient's excreta, and in 1873 Murchison actually traced an epidemic to a contaminated milk supply, and showed that the stools of typhoid patients are the principal source of danger in spreading the disease.

The brief statement then outlines the significant advances that were made over a period of centuries in the differentiation and recognition of typhoid fever by purely observational methods, confined to the patients themselves and made by practitioners of medicine. In so far as alleviation of the disease is concerned, there is little or nothing to report beyond purely symptomatic and palliative treatment, the most significant point in which was the introduction of hydrotherapy by James Currie in 1770 and its rediscovery by Brand a century later. The recognition of the danger of spreading the disease through contamination with typhoid excreta must be regarded as a great contribution to preventive medicine.

We come now to a period, which may be roughly defined as the year 1880, which ushered in the two most productive of the medical sciences, bacteriology and its twin sister, immunology. Whereas the experimental sciences of chemistry, physiology, and some aspects of experimental pathology, were already established and had made, and continued to make, valuable contributions to human welfare, bacteriology was destined to explain the causation of a series of diseases known as infectious, and immunology to utilize these discoveries in the specific prevention and cure of many of them.

The infectious diseases are not only important in themselves, but are recognized as indirectly the cause of many of the chronic diseases, so called, which are slower in their course, but none the less health destroying and fatal in their outcome. The growth of bacteriology has been coincident with the filling of the ranks of our present army of laboratory workers, many of whom have been primarily concerned in advancing this science. Bacteriology owes its stable beginnings to two men, Louis Pasteur, a chemist, and Robert Koch, for a brief time a country physician and later Professor of Hygiene in Berlin. Immunology, the science which explains natural protection to infectious disease and utilizes this knowledge in creating such conditions artificially, we owe first after Pasteur to Metchnikoff, a Polish biologist with no exact medical training. It is characteristic of these sciences that their problems, although arising in cases of human and animal disease, have been developed, in large part, away from the bedside, under the conditions of greater accuracy and completeness afforded by the experimental reproduction of the disease in animals. Such an experimental disease may be interrupted and attentively studied in its successive stages and its course may often be followed outside the animal body under conditions of greatest clearness.

It was the great service of Pasteur, and particularly of Koch, to show that each one of an increasing number of infectious diseases is caused by a separate and identifiable type of micro-organism. Such a micro-organism is always found in each case of the disease in question, but in no other instance, and will give rise again to the same disease when re-introduced in a healthy animal of the same species. The first instances of infectious diseases studied, anthrax, typhoid, chicken cholera, tuberculosis, and others, were found to be due to minute plants called bacteria. Later observers have described similar infectious diseases due to equally lowly animal parasites, particularly to those known as protozoa.