versity, 1934-50; chief, medical division, Gallagher Municipal Hospital, 1940-50; professor and head of Department of Preventive Medicine, 1950 to 1951; and professor and head of the department of medicine at the University of Illinois from 1951 to date. We are honored to have you back with us, Dr. Dowling, and, also, it is a great honor to have your lovely mother with us today. She lives here in Washington still, is that correct? Dr. DOWLING. That is correct. STATEMENT OF DR. HARRY F. DOWLING, PROFESSOR AND HEAD OF THE DEPARTMENT OF MEDICINE, UNIVERSITY OF ILLINOIS My name is Harry F. Dowling. I have been a physician for 30 years. I have carried on research in the field of infectious diseases and have tested a number of new drugs in this field, particularly sulfa drugs and antibiotics. I am professor and head of the department of medicine at the University of Illinois College of Medicine. However, the opinions that I shall present will be my own. Senator HRUSKA. Mr. Chairman, may I ask Dr. Dowling a question or two here? You are a member, I believe, of the Physicians' Council, are you not? Dr. DOWLING. Yes, I am. Senator HRUSKA. How many members does that council have? Dr. DOWLING. Well, Senator, I have just recently joined about a month ago. I think about 12 to 20 members. It is a small group. Senator HRUSKA. And the president is Dr. Richmond, who appeared here recently? Dr. DOWLING. That is correct. Senator HRUSKA. There also appeared here as members of the Physicians' Council in connection with the hearings on S. 1552 and in recent days Dr. Butler, Dr. Goodman, Dr. May, and Dr. Modell, all members of the Physicians' Council. My question is this, Dr. Dowling: Is the sponsorship of this bill a project of the Physicians' Council, some special, favored project of the Physicians' Council, that would account for the almost half of the membership, or certainly a third of it, appearing here in support of it? Dr. DOWLING. Senator, I cannot say because I have not, as yet, attended a meeting of the physicians' council, but I can say that my own interest in the bill stems from the fact that I have been interested in this field for some time. I wrote, originally wrote, articles in connection with these matters before I was a member of the Council on Drugs of the American Medical Association or before I was a member of the physicians' council, so that I am appearing as an individual entirely. Senator KEFAUVER. Perhaps I can answer that question, Senator Hruska. This is not a project of the physicians' council, although I am happy that so many members of the physicians' council do approve wholly or in part the bill. I might say that I and members of the staff, in helping to draft the bill, talked with many members of the Food and Drug Administration, with Commissioner Larrick, and with others in the Health, Education, and Welfare Department, with a great many physicians, some of whom are members of the physicians' council and some of whom are members of the AMA's council on drugs and with other physicians who are interested in the bill, with people who are interested in lowering the cost of drugs, and we got information anywhere we could. Of course, the previous testimony we have had has also been helpful in arriving at some of the provisions of the bill. You are a member of the council on drugs of the American Medical Association, are you not? Dr. DOWLING. Yes, I am. Senator KEFAUVER. How long have you been a member of the council on drugs? Dr. DOWLING. About 2 years, I think. The record will show for sure. Senator HRUSKA. It just occurred to me, Mr. Chairman, we have had 2 witnesses from the American Medical Association, 6 witnesses from the physicians' council, which has a membership of 21, and, of course, they were officially represented here. But, so far, no witnesses from any organizations like American College of Surgeons, the American College of Physicians, the American Academy of General Practice, the American Society for Clinical Investigation, American Hospital Association, and so on. I was wondering if witnesses will be called to represent officially those associations which would be of value. I fully agree with the chairman's idea that we should get truth wherever we can find it and enlightenment as much as we can, but I just wondered if it was just coincidence that 6 out of 21 members of the physicians' council would have appeared here for S. 1552 and officially represented to the exclusion of many of these other organizations. Senator KEFAUVER. Let us say that we contacted any physician who expressed an interest in this legislation. Most of the ones who have appeared here have expressed an interest in our work either directly or in their writings. If we find any others who express interest or who have a point of view, they certainly will be invited. I think it should be noted, however, that about the same proportion of members of the council on drugs of the AMA have appeared here as the members of the physicians' council. I think five or six of our witnesses have been members of the council on drugs. Dr. Dowling, you were also appointed by President Eisenhower, upon the recommendation of Secretary Hobby, when she was head of the Department of Health, Education, and Welfare, to make a study of the Food and Drug Administration, were you not? Dr. DOWLING. To be a member of a committee which made such a study and made recommendations to the Secretary, yes, sir. Senator KEFAUVER. When was that? Dr. DOWLING. I do not remember these dates very well. Dr. DOWLING. About that time; yes, sir. Senator KEFAUVER. As a member of that committee, you did make a study of the Food and Drug Administration? Dr. DOWLING. Yes. Senator KEFAUVER. All right, sir, will you proceed? Dr. DOWLING. I should like to consider several of the provisions in the proposed Drug Industry Antitrust Act as they apply (1) to phy sicians, (2) to patients, (3) to retail druggists, and (4) to the manufacturers of pharmaceuticals. Let us take first the effect of the proposed act upon the practice of medicine by the physician. Much of the testimony given before the Subcommittee on Antitrust and Monopoly of the Committee on the Judiciary showed that the physician needed more authoritative information about drugs, especially new drugs, and that he needed to have it brought to his attention more promptly and efficiently than at present. In my opinion, several of the provisions in the proposed act would accomplish this. The first and one of the most important of these is the authority given by section 4 of the act to the Secretary of Health, Education, and Welfare to evaluate the efficacy of a new drug. Drugs may be placed in three categories insofar as efficacy is concerned. In the first category are those drugs whose efficacy is obvious as soon as the first few patients have been treated with it. Penicillin is such a drug. When patients with serious infections caused by the staphylococcus were first treated with penicillin every one responded dramatically with a rapid drop in temperature and general improvement, whereas without penicillin they would have taken weeks or months to get well and some would not have recovered at all. When this happened, it was obvious that penicillin was a highly efficacious drug. A drug such as penicillin would be approved for efficacy by the Food and Drug Administration on the basis of a relatively few cases. A second group of drugs is composed of those that are efficacious, although extensive tests are needed to show it. One reason for this is the so-called placebo effect. It is a well-known fact that if the physician gives a patient a drug and tells the patient or otherwise implies to him that this drug is going to make him better, an appreciable percentage of the patients will indeed feel better and will insist that the drug has caused the improvement. This is the placebo effect. Thus, if a new tranquilizer drug were to be tested, a certain number of patients should be given an inert substance which looked exactly like the tranquilizer, and neither they nor the doctors evaluating the drug should know who received the dummy and who received the real drug. Only by this method could the efficacy of such a drug be tested properly. This is an extreme case because the evaluation depends almost entirely upon the subjective impression of the patient, but testing in a large series of patients would be necessary for many drugs even though the evaluation did not depend upon subjective impressions. For instance, a drug introduced in recent years for the purpose of bringing the heartbeat back to a regular rhythm when it has become irregular is called procaine amide. But the heartbeat sometimes returns to its normal rhythm spontaneously, and, on the contrary, procaine amide does not always restore the normal rhythm. It was, therefore, necessary to test procaine amide in a large number of patients with irregular heart rhythm so that physicians could be sure that the heart rate of patients was returning to normal more frequently following the use of procaine amide than it would have in the same number of patients who had not received any drug for this purpose. 73753-61-pt. 1-27 With regard to drugs in this second category, it is important to emphasize that the individual physician does not usually have enough patients with that particular condition in his practice to test the drug adequately himself. There is a simple statistical reason for this. Among 100 patients with pneumococcic pneumonia, 30 patients will die and 70 patients will recover on the average, without the use of specific remedies. If a doctor were to use a drug that had no effect on the recovery rate-let us say aspirin-and his patient recovered, this would mean nothing with regard to the aspirin because in 7 times out of 10 the patient would have recovered anyway. If such patients were treated with sulfadiazine, one of the sulfa drugs, 12 percent of the patients could be expected to die. The doctor would have to treat 50 patients with pneumococcic pneumonia with sulfadiazine and compare them with a similar number of patients who were the same in all respects except that they were not given sulfadiazine in order to determine that the differences in the case fatality rates were due to the sulfadiazine and not due to chance alone. When the individual physician treats a patient with pneumonia with sulfadiazine, therefore, he must rely on the results of tests made on large groups of patients by competent investigators and reported in the medical journals to which he has access. The proposed bill would make sure that the proper tests had been done and that a summary of this information was available to him at the same time that the drug was placed on the market. Furthermore, the individual physician usually does not have the facilities needed to make the laboratory investigations that are often necessary in such tests. Accordingly, he must depend upon the tests made by physicians who do have access both to the necessary laboratory facilities and to a sufficient number of patients. All pharmaceutical companies arrange to have some tests of efficacy made; the more responsible companies make extensive tests for efficacy. The proposed act would assure the physician-as well as the public-that every company made a sufficient number of tests before it placed a new drug on the market. Senator HRUSKA. Would you yield, Doctor? What would be considered a sufficient number of tests? Dr. DOWLING. This varies tremendously depending upon the drug which one is testing, Senator, but I have already given an example of one disease and one drug in which it would be absolutely necessary that at least 50 patients be treated with the drug and 50 patients be treated in another way in order to show the efficacy of a drug as compared with another drug which was already on the market and was effective. Senator HRUSKA. Would this be called experimenting on humans? We had testimony last week that some companies did not experiment on animals because it cost too much. They did not want to do this but they experimented on humans instead. Would this be experimenting on humans in that sort of testimony? Dr. DOWLING. Senator, in order to answer your question I have to go a little far afield. Whenever a doctor uses a drug on a patient, he is in some sense experimenting on that patient, because this patient's constitution, this patient's reaction to a drug, is bound to differ from any other patient's. If he then uses a new drug, obviously, he has not used this drug before on any patient himself, and he is not as well acquainted with it as he would be with some other drug and not quite as well acquainted with what to look for. Therefore, this is another step in what one might call experimentation. Now, then, if a doctor uses a new drug which is similar to another drug which is already on the market and would be expected to act in the same way, this is a further step in what one might call experimentation. If he uses a new drug which is completely different from any drug which is on the market, this is still a further step. What I am trying to say is that the use of the word "experimentation" in humans without any qualification would mislead all of us, and that what the doctor is doing is using all of his skill and all of his knowledge in order to determine what does this particular drug do to this particular patient. If he must do this with a new drug, he must use much greater safeguards than he would use with a drug which had been used before, and he must have particular knowledge and he must have particular facilities which every doctor does not have. Shall I proceed, Senator? Senator HRUSKA. Yes. Senator KEFAUVER. Here is a thought in that connection. This is a paragraph from the testimony of Dr. Lasagna, who made the point that is brought out by Senator Hruska. He said: I might add that the present FDA prerogatives do not satisfy me with regard to toxicity either. It is shocking that experimental drugs are subject to no FDA regulations of any sort before the patients receive them. Some drug houses perform extensive animal tests before a drug is first put into man. Others perform almost none. It is reprehensible for man to be the first experimental animal on which toxicity tests are run simply because bypassing toxicity tests in laboratory animals saves time and money. That was the testimony, I think, that Senator Hruska may have referred to. Senator HRUSKA. Yes, and I would like to ask Dr. Dowling if he knows of any instance where a pharmaceutical company, in applying a new drug and developing it, bypassed animal tests in favor of experimenting on human beings just because it costs money to buy animals and do it that way? Do you know of any such instance? Dr. DOWLING. I do not know of any such instance myself, Senator, because when a company brings a drug to me for testing, I look very carefully at the animal tests. If I do not believe that the animal tests are sufficient to warrant the use of the drug in humans, I will not touch this drug. Therefore, I have not had much traffic, one might say, with the kind of company that does not do many animal tests. Senator HRUSKA. Do you know that there is such a company? Senator KEFAUVER. Senator Hruska, they do test drugs on animals. This does not mean they bypass animal tests. As I understand it, what Dr. Lasagna said was that they test them on animals and that |