are rare side reactions which occasionally are dangerous (as there are with aspirin or any other drug). Again, as an aside, I think the number of deaths from aspirin in the United States runs somewhere between 100 and 150 a year, which is certainly not inconsequential, but we don't regard this as a dangerous drug. In fact, it has such a reputation in England that I understand this is a favorite method of trying to commit suicide, by taking lots of aspirin, which is rather rare in this country as an escape. However, if the physician is fully aware of these side effects and on the lookout for their occurrence, medication can almost always be reduced or discontinued in time to prevent fatalities. So that if the physician is well informed and he recognizes the side effects early, he can avoid, in most cases, fatalities. Obviously, medical judgment consists in weighing the advantages to be obtained against the annoyance or danger of the side reactions. This is the so-called calculated risk in medicine. It should be stressed that this exists with almost any medical procedure and is by no means limited to drug usage. If a patient has signs and symptoms of an acute appendicitis the surgeon has to make up his mind as to the probability of his diagnosis being correct and the danger of not operating against the dangers which may result from giving the patient anesthesia for the operation, the possibility of a blood clot postoperatively, the risk of something happening during surgery itself and the inconvenience, the psychological effect, and the expense of a week or so of hospitalization plus the convalescent period. Further, there may also be long-term effects of the operation with development of postoperative adhesions which may not become evident until 1, 2, or 5 years later. There have been those who decried the use of the drugs since we do not know what their long-term effect may be. They have not been in use long enough for anyone to demonstrate that after 20 or 30 years there may not be some resultant change but on the other hand, and of even more importance, is the fact that no one has demonstrated that they do have any harmful effect or prolonged usage or on shorter usage after a period of many years. I have been told that when insulin was first discovered a Dr. Palmer in Boston raised the same question, that is, what are the long-term effects and at his own time and expense went from one medical society to another arguing against the use of insulin since no one knew what effect it would have at the end of 20 years. His unproven apprehensions, thank goodness, did not prevent general usage of the drug and thereby the lives of tens of thousands of diabetics were saved. As far as we know, his apprehensions were baseless. Medical judgment almost always tends to be conservative but not reactionary and the widespread use of the psychopharmaceutical drugs indicates that in the considered judgment of most physicians the advantages in the treatment of the patient far outweigh the possibiilty that there may, or may not, be some long-term effect which has not been discovered. Another very commonly misunderstood item on this score is "addiction" to a drug. In popular speech this is used to cover three separate and quite different reactions. The first of these is habit formation to which we are all subject in varying degrees and to all sorts of things. With many of us it is a habit to have orange juice for breakfast and somehow the day does not seem quite right if we do not start it off in this manner. Somehow this orange juice seems to be the ap propriate thing to drink since it is cool and refreshing and cleans the residual taste of the toothpaste out of our mouth. In a like manner certain individuals will take a sleeping medication or one of the psychopharmaceutical preparations since they have fallen into the habit, not that they have any great need for them, but they have simply fallen into the habit, and it seems to be the thing to do before you go to sleep to take a sleeping medication or pill X three times a day. Distinct from this is "dependence" which also applies to many other areas than drugs. There are a large number of individuals who are "dependent" upon a cup of coffee with which to start their day and who actually are uncivilized until this has been done. If for one or another reason they do not get their coffee they are acutely uncomfortable, have a strong yearning and preoccupation on the subject, and will exert themselves considerably in order to get that essential morning cup of coffee. If for any reason this is unavailable they are irritable and unhappy. This is true also of certain of the psychopharmaceuticals upon which individuals have developed such a dependence. Finally there is true "addiction" which by medical definition means that if the individual does not receive his accustomed medication there are definite physiological and biochemical reactions causing the person acute physical and psychological distress and even at times endangering his life. In this class would belong such drugs as morphine, codeine, and the barbiturates when used in large doses. I might add that some of the evidence presented that some of the other drugs are addicting does violence to what most of us regard as addiction. That is, if you abruptly change a medication of any type, a person may have an immediate reaction to it, whether it is in the form of a convulsion or a sleepless night or two, but within a relatively short period of time, as soon as this initial reaction is over, the person readjusts, and it is not an addiction in the sense that a body has set up a homeostasis that requires that this drug be administered over a long period of time. It is for this reason that this group of drugs are so closely regulated. Sometimes the term "addiction" is used in its lay meaning by physicians in the same manner that "cancer" is used to refer to whole groups of malignancies although actually cancer is only one very specific type of neoplasm. Yesterday, I was at a conference in Chicago, and Dr. Coghill of the National Institute spoke on progress in cancer research. Even though, by medical definition, cancer is a limited type of malignant neoplasm, when a specific kind, the type that develops from ectodermal cell tissue, it never occurred to anyone to question him on the fact that he was really not talking about cancer at all, but talking about malignant neoplasms. So that, in medicine, we also use this same kind of shorthand. It is much easier to say "cancer" than malignant neoplasm. I think this is sometimes deceiving, because a doctor will say "addiction" when he is referring to this whole class of reactions. This leads to misunderstanding. Actually one of the major advantages of the psychopharmaceuticals is that to my knowledge there has not been reported a single case of addiction although habit formation and dependence are as common as might be expected. The fact that the sale of barbiturates has dropped well over 50 percent since the introduction of these drugs constitutes 25489-58- a great advance since these individuals are not tempted to barbiturate addiction as they might have been in the past. In addition, there appear to be at least a significant number of individuals who were "addicted" to alcohol (that is, had habit formation, dependence, etcetera) and who are now able to get along with these newer drugs. In summary then, in contrast to preparations such as morphine and the barbiturates when used in large doses, this newer group of pharmaceuticals possess the distinct advantage that there is no evidence that they are addicting in the true meaning of the word. Before passing on to criticisms it should be definitely pointed out what the contributions of the pharmaceutical industry to psychiatry have been. Firstly, without the pharmaceuticals invented and prepared by the drug houses it would have been impossible to achieve the promising results described in the previous paragraphs. These pharmaceuticals were not achieved by accident. As an instance, the development of reserpine by Ciba Pharmaceuticals from the crude root of Rauwolfia serpentina-I think, Mr. Minshall, that indicates the relationship of the two-at one time occupied 80 percent of the research capacity of that drug house and involved the expenditure of something over $1 million on the chance that the active ingredient could be isolated and made commercially feasible. It is one of the anomalies of our society that if a firm is successful in producing a product on which it can make money (which is in part used for the development of more such products) that these researches are not regarded as being as scientifically pure as work done in universities or other institutions. What is most peculiar about this is that we speak constantly of the advantages of a capitalistic free-enterprise system and when we have overwhelming evidence of its successful functioning we tend to disdain advances produced in this manner. The fact that commercial enterprises are able to produce the high quality research results that they do should instead be a matter of great pride and recognition. The millions of dollars which are invested by drug manufacturing houses in an effort to find newer and more useful products is one of the most important factors which has made it possible for American science to hold such a prominent position in this field. Secondly, once pharmaceuticals are produced there arises the problem of evaluating them and here again the pharmaceutical industry has made a great contribution to psychiatry. At the time we started our own work in Rauwolfia it was almost unheard of for a pharmaceutical house to give any grant support to a State hospital, the line of reasoning running that the institutions were supported by the State, that there was no or almost negative prestige value in making a contribution to research in such backward institutions, and third that the probability of marketable product coming out of such an exploration was virtually nil. In spite of this Squibb, through its medical director and research grant committee, was willing to venture a small grant to assist our own basic research and to possibly explore whether Rauwolfia serpentina had any effect on psychiatric patients. That the experiment proved interesting and valuable is self-evident. Since that time support in various forms has been given by pharmaceutical house after pharmaceutical house to the various State, county and similar mental hospitals of the country which has acted as a great stimulus to not only drug evaluation but also to the treatment and general care of patients. As I pointed out in an article last year: The provision of grants-in-aid "with no strings attached" has provided an amazing transfusion of vitality into many a struggling clinical or laboratory research group in some clinic or State hospital. Financial watering of this apparently arid region has resulted in the appearance of oases which help to nourish the whole surrounding psychiatric neighborhood. The university departments of psychiatry and neurology have similarly benefited and, in turn, contributed to the greatly expedited attack on the problem. Nor has the research supported by the pharmaceutical houses been limited to clinical testing in the area of biochemistry. Physiological, psychological, and even psychoanalytic projects have been supported. More than one company has adopted the philosophy "What is good for the field of mental health is ultimately good for us." Thirdly, contrary to the opinion of some, pharmaceutical houses do not limit themselves purely to that which is commercially exploitable. Their interest and development of basic research is quite genuine and as occasionally some applied research results this is certainly not to be condemned. Our own recent recognition of iproniazid as a forerunner of a new class of drugs for the treatment of depression developed, not from the pharmaceutical company which manufactures the product, but from one of their competitors. Again and as an aside, we had quite a job trying to convince the pharmaceutical house that made the drug that it was useful. They were very skeptical of it, and it was a reverse sales job. While visiting the laboratories of Warner-Chilcott, I chanced to see an experiment in basic research attempting to determine the mode of action of reserpine. To demonstrate whether a certain theoretical point was or was not true the animals had been treated with iproniazid prior to being given reserpine and it was the chance observation of the extremely acute alert state of these creatures that suggested the use of iproniazid-made by another company, as indicated-for treatment purposes. This is really a rather trivial example of what is being done in the area of basic research by the pharmaceutical houses. Many of these companies literally employ hundreds of full-time researchers whose concern with basic problems of the field is as great as that of any university professor and whose research productivity, not infrequently, is equal. As in other scientific fields interest on the part of one group of workers arouses corresponding interest on the part of others so that the whole area of the possible influencing of human behavior and the relationship of biochemical to psychological and sociological factors has become of increasing importance in the past few years as the result of the stimulation initiated by the pharmaceutical industry. Mr. BLATNIK. Doctor, at this point I apologize for interruptingmay I interrupt? Ďr. KLINE. Surely. Mr. BLATNIK. This is your industry contribution to research in pharmaceuticals in the psycho and chemical therapy. Are any Federal funds involved through the National Institutes of Health, or the Department of Health, Education and Welfare? Dr. KLINE. Yes, the National Institute of Mental Health, with some very strong urging and support from committees chaired by Senator Lister Hill and Congressman Fogarty, has greatly expedited this. I think it is worth pointing out that this is what I meant when I said the people working in one field stimulate those in others. The evidence which originally came from the drugs produced from the pharmaceutical houses stimulated, in turn, the United States Congress to act to further these investigations. This, in turn, has greatly supported the private philanthropies in giving money for research. The attitude of the Government, or for that matter, of the private philanthropies is that there is no sense in investing in an area where we are not going to get very much. The evidence that arose out of the fact that these drugs were successful in this treatment has encouraged a great deal of support, since there now seems to be a way open to approach what previously was an insoluble problem. The Government has done an excellent job in the field, and the National Institute of Mental Health has shown an increasing support for this type of research, in contrast to the relatively minimal place that it held prior to the introduction of the pharmaceuticals. There was most cordial recognition by the congressional committees of the value of this work, and an immediate desire to do what could be done to further it. I appreciate your asking the question since it gives me the chance to publicly state the appreciation which I think all of us in the field of psychiatry feel for this sort of thing. It also serves a salutary purpose since as the Federal funds for research become available, the individual becomes freer to investigate that which he chooses. I will briefly refer later on to the fact that some investigators are self-deceived, since they feel that what the pharmaceutical industry wants is some promotional material for their drug. That is not what they want at all. What most of them are looking for is an honest answer to a question. I don't know if that covers your question. Mr. BLATNIK. Yes; it does. Just a little more to sharpen this up. If I recall correctly, and we'll check on the figures to refresh our memories, I believe that the National Institute of Mental Health was given by Congress $30 million or, possibly $40 million for research in mental health. How would that contribution compare, as a rough measure, with the contribution made by industry? Dr. KLINE. Well, first, let me Mr. BLATNIK. Would it be one-tenth? One-fourth? Dr. KLINE. No. First, let me get out of the way the comparison with other research support in this area. The congressional support far outweighs that of all the foundations put together. That is, the Ford, the Rockefeller, the Commonwealth, and so forth and so on. The contribution of the pharmaceutical industry is rather difficult to evaluate, specifically, in the field of mental health. I don't know accurate figures, but most of the pharmaceutical houses, at least the ones that I have had any dealings with, devote somewhere between 5 and 15 percent of their gross to research. They I had breakfast yesterday with a gentleman from a pharmaceutical house, a rather small one, with a $6-million-a-year volume. devote 9 percent of their gross to research, which is quite appreciable. Now, exactly how much of this goes, specifically, into problems of mental health, I don't think anyone can evaluate, because the basic research might be the same for one field and for another. For instance, one of the men who has made a tremendous contribution to |