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Vol. 18, No. 12
Future Chemotherapy’ By A. S. Loevenhart PHARMACOLOGICAL LABORATORY, UNIVERSITYoP WISCONSIN,MADISON,WIS.
E
PIDEMIC and endemic diseases have played an important part in the political and economic changes which have occurred within recorded history, and have deeply affected the philosophic and religious thought of mankind. W. H. S. Jones, in his “Malaria and Greek History,” maintains that the disintegration of Greek civilization from the year 400 B. C. onward was due to endemic malaria throughout a large part of the Greek world. Epidemics of bubonic plague swept the world a t intervals between the second century B. C. and the seventeenth century A. D. The greatest pandemic of any disease occurred in the bubonic plague visitation in the fourteenth century, known as the “Black Death,” during which it has been estimated that 25 million persons died. The outbreak of 1665 was immortalized by Defoe. Similar terrible outbreaks of other diseases-cholera, syphilis, influenza, etc.-have occurred from time to time. Although these pandemics have attracted the greatest attention because of their tragic and spectacular suddenness, there can be no doubt that endemic diseases, such as malaria, syphilis, and hookworm disease, constantly reducing the vitality of nations, produce a greater economic, moral, physical, and political disintegration. We criticize the inhabitants of a given section as being indolent and lazy and having no moral fiber, when these characteristics are often the result of the physical state of the people induced by disease. Before the day of modern medicine, visitations of plague were looked upon as evidence of divine displeasure with mankind, and throughout the ages speculation regarding sickness and death has been intimately connected with philosophical and religious thought. Divine healing at the beginning of our era and a t the present time is sufficient evidence of this fact. Medicine and mystery have been almost synonomous terms. Medicine is merely a branch of applied biological science and for its proper development should have no relation to the mystical and the occult. Disease a World-Wide Problem
However nationalistic one may be in his political ideas, it is a fact that science is international and that truth recognizes no national boundaries. The control and treatment of disease is necessarily a world problem, and the promotion of international health should be one of the prime efforts of civilization. The presence of contagious disease anywhere in the world, in spite of quarantine, is a menace to the health of all. The methods used in the control and treatment of disease in any section are almost certain to be useful elsewhere. To use Herbert Quick’s expression, we are all passengers on board the good ship “Earth” and are most vitally concerned with health conditions in the steerage or in the first cabin. The “Office international d’Hygibne publique” was created under the convention of Rome, signed December 9, 1907. This was the beginning of international concert in the field of public health, but the office lacked financial support and was impotent. Under the Covenant of the League of Nations, Article 23, section f , the members agreed that they “will endeavor to take steps in matters of international concern for the prevention and control of disease,” and again 1 Presented at the Round Tahle Conference on “The Role of Chemistry in the World’sPuture Affairs” at the Sixth Session of the Institute of Politics, WiIliamstown, Mass., August 25, 1926.
in Article 25, “The members agree to encourage and promote the establishment and coopeiation of duly authorized voluntary national Red Cross organizations having as purposes the improvement of health, the prevention of disease and the mitigation of suffering throughout the world.” The United States officially held aloof from the health program of the League of Nations until October, 1923, when our Government agreed that the old “Office international d’Hygi&ne” created under the Convention of Rome, to which United States had been a signatory, was permitted to ratify the health program of the League of Nations. All Americans can take pride in the fact, however, that prominent American sanitarians have sat with the Health Committee of the League of Nations and that the International Health Board, which is a part of the Rockefeller Foundation, has generously contributed financial support for the epidemiologic intelligence service. This service publishes monthly at Geneva vital statistics covering nearly the whole civilized world and gives a summary of the prevalence of communicable and other diseases which is of very great value to sanitarians. The office also concerns itself with questions of quarantine, with standardization of vital statistics, with the standardization of pharmacopeias and the methods of testing certgin important remedies, such as antitoxins, salvarsan, insulin, etc. Steps in Control of a Disease
The conquest of a disease such as yellow fever, malaria, diphtheria, etc., is a matter of accumulation of exact knowledge through the patient labor of many men. The general public in all fields of scientific endeavor hears only of the spectacular advances. The spectacular discovery made by a genius becomes possible only by the general increase in knowledge through the accurate, unsensational investigations of many predecessors. I n all cases we must note the s y m p toms shown in the course of the disease, and we must be able by clinical and laboratory methods to make a diagnosis. We must be able t o visualize in the sick man any changes in his tissues and organs and any alteration in their functioning as the result of the disease. This interpretation of symptoms can only be made after a large number of post mortem examinations have been made on persons who have died of the disease. I n the case of contagious disease we must determine the nature of the organism which causes the disease. We must know the life history of the parasite, whether it passes directly from man to man, or whether an intermediate host is necessary, as is the mosquito in yellow fever and malaria. We must determine the types of substances which can kill the parasite without injuring the man. If animals can be given the disease experimentally, this kind of work becomes absolutely necessary and the problem is greatly simplified. If animals are not susceptible to the disease, then physicians and their co-workers always volunteer for the experimental work. Thus, Drs. Carroll and Lazear allowed themselves to be bitten by mosquitoes infected with the organism causing yellow fever, and thereby finally proved that the mosquito carries the disease. Both of these men died as the result of the experimentation. Applying the proof that the mosquito carries yellow fever and malaria, Dr. Gorgas succeeded in clearing Havana and then Panama of both these diseases and enabled this country to build the Panama Canal.
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INDUSTRIAL A N D ENGINEERING CHEMISTRY
Definition of “Chemotherapy”
In controlling disease we are faced with two different types of problems, prevention and cure. We call the subject dealing with the treatment of disease therapeutics or therapy. The methods used in therapy fall into three main divisions: (1) physiotherapy, (2) surgery, and (3) pharmacal therapy. Physiotherapy deals with the use of physical agents in treatment, such as heat, light, electricity, x-ray, radium, etc. Everyone understands what is implied by the surgical method of treatment. The third method of treatment, by means of chemicals or mixtures of chemicals, includes chemotherapy. Pharmacology deals with the action of chemicals or mixtures of chemicals on living organisms, regardless of whether the effects are beneficial or harmful. The term “Chemotherapy” was first introduced by Ehrlich, who used it to cover only a very particular part or‘ the subject of the use of chemicals in therapeutics. As far as I know, the term has not been satisfactorily defined, nor is it, easy to define. Ehrlich’s views regarding this work were based on the general proposition that certain organic chemicals have a specific affinity for certain living cells, and the term was an outgrowth of Ehrlich’s views regarding the nature of immunity. I would define chemotherapy as that phase of pharmacology which deals with the relation between the chemical constitution of therapeutic agents and their effects on living things. The term as used by Ehrlich was only applicable to studie:, of infectious diseases, but there is no reason why the term should not include all types of substances used in therapeutics. In practice, work in this field has always started with a fortuitous discovery that a given organic chemical has certain specific pharmacological action. Following this lead, various derivatives of this drug are then prepared, more or less closely related t o it in the hope of finding a substance that is less toxic to man and more potent in its particular type of pharmacological activity than the original substance. In the case of substances used in the treatment of infections, where a parasitic organism has invaded the body, chemotherapeutic studies are directed toward the production of a substance highly toxic to the invading organism and of low toxicity to man and the higher animals. This is one of the most promising fields of advance in medicine. It is on the border line between chemistry and medicine and requires the cooperative effort of chemists, pharmacologists, and physicians. The particular phase of chemistry which is concerned is synthetic organic chemistry, and the work of the three classes of men must be closely coordinated in order to be successful. Application to Treatment of Syphilis and Trypanosomiasis
The definition and field of work indicated by the term “chemotherapy” can be best illustrated in the investigations of Ehrlich and his co-workers on syphilis and trypanosomiasis. It had been shown by Thomas and Breinl in 1905 that atoxyl clears the blood of mice infected with Tr. brucei. Atoxyl is an organic substance which was first prepared in 1863 by Bechamp by the action of aniline on arsenic acid. The organism which causes syphilis (Spirocheta pallida) is very similar to the class of organisms known collectively as trypanosomes. The diseases produced by the trypanosomes are known as trypanosomiases and economically are of great significance. These diseases occur in man and animals. The parasitic organisms concerned in syphilis and trypanosomiasis belong to the protozoa and are quite different from the bacteria. I n his first work Ehrlich, following the discovery of Thomas and Breinl. studied the action of atoxyl on trypanosomes in
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the test tube and found that it had no toxic action on these organisms and discarded the drug for a time. Later he decided to study the effect of atoxyl on animals infected with trypanosomes and found the drug to exercise a very beneficial effect in trypanosomiasis in animals. Here, then, was the lead. The substance atoxyl was found to be better than any known substance in the treatment of this type of infections. Ehrlich and his co-workers then began the arduous task of synthesizing upwards of one thousand substances, more or less closely related t o atoxyl, and t o test out these various products on infected animals. This work resulted in the discovery of salvarsan, originally known as “606,” which has been of enormous value in the treatment of syphilitic infection in man. Somewhat later the drug neosalvarsan was discovered in Ehrlich’s laboratory and has largely replaced the original salvarsan. Ehrlich and Bertheim showed that atoxyl has the following structure:
ooH //o
As-OH
“2
It was soon found that, while atoxyl has relatively low toxicity as compared with arsenious acid, it has a very deleterious effect on the optic tract in certain individuals and produces permanent and complete blindness in some cases. With the hope of lessening this deleterious action of atoxyl, which was thought to be connected with the presence of the NH, group, one of these hydrogens was replaced by an acetyl group and the substance known as arsacetin was prepared. It was found, however, that arsacetin also injures the optic tract and that it possesses no distinct advantages over atoxyl. This particular effort to improve the action of atoxyl was therefore a failure. Among the substances prepared by Ehrlich was arsenophenylglycine, 45-
A
li
As
A
0
NHCH~COOH NHCH~COOH
This substance possesses excellent properties in the treatment of syphilitic infection in animals and was used in the treatment of trypanosomiasis in man, but it was discarded by Ehrlich because it seemed inferior to salvarsan. Salvarsan, introduced by Ehrlich, has the following formula : AS=
AS
I n this substance the nitrogen is in a different position in the benzene ring from that which it occupies in atoxyl, and also it contains an hydroxyl group in the position occupied by the nitrogen in atoxyl. The announcement of this discovery by Ehrlich and its efficacy in the treatment of syphilis startled the world. The drug had the great disadvantage that it was difficult to put into solution and required neutralization, and it was troublesome for the doctors to use it. In.order to overcome this difficulty, Ehrlich conceived the idea of introducing a so-called solubilizing group and produced neosalvarsan, which has this formula:
INDUSTRIAL A N D ENGINEERING CHEMISTRY
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-As
-
HzN
NHCHlO. S. ONa OH
OH
This substance goes into solution in water without neutralization and can be used in much smaller bulk, the injection takes a shorter time, and it has almost universally displaced the older salvarsan in consequence of this greater ease of administration. While neosalvarsan proved a great boon in the treatment of ordinary types of syphilis, it was a great disappointment in the treatment of neurosyphilis, especially in the treatment of genera1 paresis. I n seeking for a drug which would be valuable in the treatment of paresis, Dr. W. F. Lorenz and I a t the University of Wisconsin had the opportunity to study the action of tryparsamide, a drug which had been developed at the Rockefeller Institute and which gave great promise of being of value in the treatment of trypanosomiasis, judging from the results of animal experimentation. Tryparsamide has the following formula: 40
As-OH
K
O
v
H
NHCHxCONHq
We found this drug exceedingly valuable in paresis and approximately 40 per cent of the cases of general paresis that had been committed to the state insane hospitals in Wisconsin were restored to sanity and were discharged from the institutions, able to take up their work again. Results from a large number of independent investigators have confirmed the results. I n an attempt to analyze the action of tryparsamide in neurosyphilis, we have sought to vary the compound and make various similar types of substances. Since tryparsamide was found useful in trypanosomiasis, in which the salvarsans are of no use, and since it is also valuable in neurosyphilis, we thought that the usefulness of the drug in neurosyphilis might be judged from its effectiveness in trypanosomiasis. The terminal CONHz group in tryparsamide is such an inert type of grouping that we were inclined to attribute the activity of tryparsamide to the part of the molecule to the left of the dotted line:
/o
AS-OH
It had previously been found by other workers that phenylglycine p-arsonic acid,
//o
AS-OH
iToH v NHCHzCOOH
is entirely inert in the treatment of both syphilis and trypanosomiasis. The very slight difference between tryparsamide and this substance gives an idea of the extreme sensitiveness of biological properties to any alteration in chemical constitution. We found that etharsanol, having the formula
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ooH As-OH //o
NHCHzCHzOH
was exceedingly useful in the treatment of trypanosoma1 infections in animals, and we were therefore hopeful that i t would also be effective in the treatment of neurosyphilis. But this turned out not to be the case; and we were disappointed to find it inert in the treatment of neurosyphilis, I n experimental trypanosomiasis, however, the drug has proved very successful indeed and we are anxious to study the action of the drug clinically. We have been able to cure experimental animals later in the disease than with any other drug with which we have worked. The foregoing illustrations show what is meant by chemotherapy-that having found a substance which is somewhat useful in the treatment of a given condition, we prepare many types of closely related compounds to determine whether we cannot increase the therapeutic value of the substance. It deals with the effects of changes in constitution on the curative value of drugs and the application of this knowledge to the production of remedial agents of increased value. These new derivatives are not produced in a haphazard fashion but in the light of accumulated knowledge regarding the relation of chemical constitution to pharmacological action. Threefold Nature of the Subject
It is obvious that chemotherapy is a tripod, the three legs being organic chemistry, pharmacology, and clinical medicine. The production of new drugs is a chemical study, the investigation of their biological properties is pharmacological research, and the determination of their exact usefulness in man together with the important details as to how they should be employed constitute clinical research. The pharmacologist from his work is able to advise the chemist regarding the probable biological effects of certain changes in structure, in fact the chemist cannot work successfully without his guidance. On the other hand, the clinician must depend on the pharmacologist, since his work shows whether or not there will be any danger connected with the clinical use of a new substance, the kind of danger, the proper dosage to employ, the frequency with which the dose may be repeated, and the type of therapeutic effect which may be expected. The pharmacological work is necessary to safeguard the patients’ interests. The pharmacologist therefore stands midway between the chemist and the clinician and interprets the needs of each to the other since he understands the technical language, the difficulties, the methods, and results of the other two. Geographical Distribution of Diseases Requiring Chemotherapeutic Study
Human trypanosomiasis is practically confined to Africa, where a n area of more than a million square miles is affected. The disease is limited to the tropical portion of the continent and is especially common along the rivers and the shores of Lake Victoria and Lake Tanganyika. The form of the disease here is known as gambiense and it extends into the Bahr et Ghazal and along the upper Nile and its tributaries. It is also found in certain islands off the west coast. The distribution of gambiense corresponds with that of Glossina palpalis, one of the tsetse flies. The other form of the human disease is known as rhodesiense. It is much more rapidly fatal and we have a t present no drug which is very successful in its cure. One of the drugs which we are studying
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INDUSTRIAL A S D ENGINEERING CHEMISTRY
a t Madison seems quite promising, judging from the results of treatment of rhodesiense infection in animal. The tsetse fly, known as Glossinz morsitans, seems to be the carrier. Rhodesiense fortunately has a much more limited habitat than gambiense, being confined to Rhodesia, K>asaland, and Portuguese East Africa. I n Belgian, French, and Portuguese Congo, arid in Uganda there have been severe epidemics of African sleeping sickness. Greggio (1917) stated that sleeping sickness firct occurred in the locality of Kisaritu about 1900 and in less than ten years had resulted in the death of two-thirds of the population. Various investigators have found the incidence $of the disease in different localities from 5 to over $0 per cent of the inhabitants. Mr. Ormsby-Gore, undersecretary of state for the colonies, presiding over the League of Nations conference on trypanosomiasis in May, 1925, stated that the disease killed more than three hundred thousand natises in Cgaiida about twenty years ago. Letonturier and his eo-xvorkers point out that trypanosomiasis has been firmly implanted in the Cameroon for many years in the region on Haut-Nyong and la Doum6. I1 has been extremely contagious among the natives living along the Kyong River. They state that it kills as many persons as all other diseases combined and it is mainly due to this disease that the death rate is twice as high as the birth rate It is apparent, then, that if we can successfully cope with African sleeping sickness, it will considerably increase the surface of the earth available for mankind and would be equivalent to the discovery of a new continent. It may well be that the control will be accomplished by preventive measures but these measures ol’er so vast an area will mean that we must be able to keep the workers free of the disease. Curative measures as well as methods of prevention are urgently needed. It should be emphasized that African sleeping sickness is an entirely difyerent disease from encephalitis lethargica, which occurs in this country and is sometimes called sleeping sickness. The African disease of horses, cattle, and other domestic animals known as nagana is due to Trypanosoma brucei and is transmitted by the tsetse fly. Owing to this disease it is impossible to have any dairy cattle or draft animals, and the natives must do all their work without such assistance. Three other diseases of trypanosoma1 origin of great importance affecting domestic animals are mal de caderas, dourine, and surra. Mal de caderas is a disease of horses due to T . equinum and is said to be uniformly fatal. The disease is very extensive in the vast Paraguay valley in South America. Some of the larger ranches lose all of their horses each year, thousands dying annually. The disease is carried by a biting fly. Dourine is also a disease of horses, caused by T . equiperdum. Large numbers of horses have been destroyed in our northwestern states in order to prevent the disease from spreading. At present the only infected district seems to be the Navajo Indian Reservation in Arizona. Surra is a disease of horses, camels, and other live stock. It exists on a large scale in the Philippine Islands. The infecting organism is T . evansi. About 50 per cent of the carabaos and 30 per cent of the cattle in the Philippine Islands are chronic carriers of the disease. I t is a very serious economic problem. These diseases constitute a very important field for chemotherapy since they cause very important economic losses. Endemic malaria is one of the greatest problems. The only therapeutic agent of value is quinine, and there is urgent need of chemotherapeutic studies so that we may not have to depend on a single substance. A certain amount of chemotherapeutic work has been done in the field of tuberculosis, but thus far it has not yielded practical results. Chaulmoogra oil has been found of great value in the treatment of leprosy; and we are now in a position to investigate this disease from
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the chemotherapeutic point of view since important contributions to the chemistry of the active ingredients have been made. The cancer problem cannot be attacked from the chemotherapeutic point of view until a lead is discovered in this field. A great deal of chemotherapeutic work has been done in local anesthetics and exceedingly valuable contributions of the greatest import to mankind have resulted. Similarly in the field of drugs used in the relief of insomnia and also of pain, chemotherapy has yielded most valuable results. More work, however, remains to be done in all of these lines, especially in the commoner diseases-colds, arthritis, and the diseases of infancy, and of old age. Seed for Chemotherapeutic Laboratory
The diagnostic phase of medicine has far outstripped its therapeutic aspect. Medicine is now in position to make an accurate diagnosis in many conditions, in which it has no satisfactory treatment. About thirty-five years ago, Dr. Osler emphasized the futility of many drugs that were in common use in the treatment of disease, and we entered upon an era of therapeutic nihilism which was very worth while because it tended to remove the blind faith that many people had in the efficacy of drugs in the treatment of disease in general. We have now passed through this nihilistic stage and we are no longer satisfied with an accurate diagnosis as an end, although it is obviously necessary before rational treatment can be instituted. We must be able to treat effectively many conditions which cannot be satisfactorily treated a t the present time, and we must realize that diagnosis is only a means to the end that the patient may receive satisfactory treatment, relief of pain and suffering, and prolongation of life. Medicine is still the “healing art” and the “diagnostic art.” Although the avowed purpose of medicine is the treatment of the sick, it is an amazing fact that no adequate laboratory has been established in America devoted to the subject of chemotherapeutics, nor, indeed, to therapeutics in general. Contributions are being made, but they are incidental and do not represent the major effort of the institution. An immense amount of medical research is being done, but a comparatively small amount of it, even if successful, would be immediately applicable in the treatment of the sick. Innumerable problems are awaiting solution which can be attacked by methods that are well understood. There should be a group of workers whose obligation it would be to attack therapeutic problems. Exceedingly important contributions to therapeutics have recently been made in America, the most notable being the discovery of insulin by Banting and its use in the treatment of diabetes, and the recently introduced serum in the treatment of scarlet fever discovered by the Drs. Dick and Dochez. Both of these lie in the field of biological products and not that of chemotherapy. Many other isolated attempts are being made to improve therapy where a man has an inspiration and can find the financial support for his effort. But the difficulties are great, because if he is in a laboratory branch he may lack clinical facilities to determine the value of his product, and if he is a clinician he will haiTe difficulty in having such chemical and pharmacological work done as to justify a clinical trial. Fern medical schools haye a department of therapeutics. I n most places the subject is handled by a man of a grade less than a full professor, and it represents an ineffecthe and hybrid effort of the departments of pharmacology and internal medicine. I n England this field is more cultivated than in America, but even there it is not dignified to the extent that its importance demands. The literature on diagnosis is so extensive that it is impossible for the average
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clinician to do more than master this field. He does not have opportunity to read the fundamental scientific literature which often contains suggestions of therapeutic application. The physiologist, biochemist, pharmacologist, bacteriologist, and pathologist is each too busy teaching and advancing knowledge in his own particular field to face the difficulties of cooperative research in the therapeutic field. The clinician with his burden of teaching, caring for patients, and research in the fields of clinical pathology and physiology has very meager facilities to advance therapeutics unaided by men with other types of training and interests. Whoever undertakes to direct such an institute must be a man who understands at least the relation of physician to patient and his sacred duty to the individual patient. The work should be done in such a manner and with sufficient controls so that the efficacy of the treatment, when the work is finished, will not be a matter of opinion but of demonstrable fact. The basis of therapeutics a t present has been largely handed down through the ages, and present-day work is, in the main, less well controlled than work in any other branch of science. Fundamental researches in all of the biological sciences are required and many of these will ultimately be of value in the treatment of the sick. Provision has been made for these phases of research, but there should be some endowed laboratory where important questions of immediate therapeutic application a t the bedside may be attacked and answered. It should be realized by the public that any advance in the field of therapeutics does not benefit the physician primarily; it becomes the heritage of mankind. The physician has no more interest in medical advance from a pecuniary standpoint than has any other member of society. The physician will always be called in cases of medical distress regardless of what he may be able to do to alleviate that distress, and he only profits as does every other member of society. It is obvious, however, that his happiness in his profession will be increased with increased power to cope with human distress. The institute, therefore, would be serving mankind, and not any special group. Scope of Proposed Institute
The proposed therapeutic institute should cooperate with the great drug manufacturers and with all medical and chemical agencies in advancing this particular field of knowledge. Chemists have produced literally hundreds of thousands of new compounds, very few of which have ever been studied from the viewpoint of their biological properties. Many substances are known to chemistry which would be of great value in therapeutics if we knew their biological properties. Ether was known for three hundred years before its anesthetic property was discovered and utilized. Chloral was known twenty-five years before its power to induce sleep was discovered. Cocaine was known twenty years before its local anesthetic action was found and twenty-four years before it was used clinically as a local anesthetic. Innumerable other cases could be cited. Chemists everywhere should be invited to send any new and interesting compounds which they produce to the institute for at least a consideration of their pharmacological activity, and perhaps a few preliminary experiments. A few types of problems which such an institute should attack may be cited. Physicians are often in doubt whether morphine should be given after a severe surgical operation. The patient may be exceedingly uncomfortable after coming out from under the anesthetic, or may be suffering acutely, and yet the physician may withhold morphine or other drug which would relieve the suffering, for fear that it may exercise an unfavorable effect on the kidneys or other vital organ.
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This question should be definitely settled. We regard October 16, 1846, as one of the greatest days in human history because general anesthesia was then first given public demonstration, but relatively little work has been done to determine to what extent we can relieve post-operative pain and thereby avoid the shock and prolonged period of recuperation often required following a serious surgical operation. Again, in many severe and usually fatal types of bacterial infection we are a t a loss for a n effective therapeutic procedure. Relatively little work has been done to determine the nature of the processes by which we develop immunity to disease. With the methods now at our disposal a vast amount of work should be done to see how we can stimulate and intensify natural immunological processes which in many cases of illness seem to lie dormant in the individual. I n the field of local anesthetics we are in need of more effective and less toxic agents, especially in the case of those which must be absorbed and act through the intact mucous membrane. The institute should undertake to read the scientific literature of the world from the therapeutic viewpoint and to verify important observations. It could issue a bulletin periodically dealing with therapeutic advances in every branch of medicine. There already exists the means of reaching almost the entire world with any new therapeutic agent of great value. The International Health Board of the Rockefeller Foundation is doing a piece of work that must command the admiration and respect of every one who is acquainted with its activities. During 1924 the board extended help to ninety states and countries in an effort to improve health conditions. Their work in malaria, yellow fever, and hookwwm is far too extensive to review here. In Siam alone, 276,396 treatments for hookworm alone were given in 1924. I n Ceylon, over 1,000,000 hookworm treatments were given the same year. No provision has been made, however, for the discovery of new and much needed therapeutic agents. Finally, the proposed therapeutic institute should extend its scope to include diseases of the economically important animal which i t could very readily and properly do since the preliminary experimental work is done on animals. Summary
Chemotherapy-the field where organic chemistry and medicine meet-is one of the most promising aspects of science which, if cultivated, will yield results of very great value to mankind. Research in this field must be cooperative. Therapeutics is the most neglected branch of medicine and there is great need of a therapeutic institute in this country to devote itself to problems which when solved will be immediately applicable to the treatment of the sick. The fundamental underlying biological problems having no immediate application should be left to the many laboratories of medical science already established in this country. Such an institute would be of infinite value to mankind and would greatly advance medicine, the most ancient and honorable of professions.
American Rayon Exposition Progress is being made on plans for the American Rayon Exposition, which will be held on the roof garden of the Pennsylvania Hotel, New York City, January 17 to 21, inclusive. The plan is to bring before the producers and users of rayon a composite picture of what the American rayon industry is offering. The exposition has for its purpose the unification of the American rayon industry and the promotion of the rayon i t produces. The exposition is not of interest t o foreign rayon companies, nor to their American representatives. Space will be provided for about sixty exhibits. Exhibitors will include firms making both the raw and the finished product.
