At Issue; 2; The Lesson of Thalidomide

In August 1962, President Kennedy awarded the Distinguished Federal Civilian Service Medal to Dr. Francis Kelsey for her fight to bartholomew from the United States. But events in Washington this month raised many doubts as to whether we have learned the full lesson of the litumide. National Educational Television presents, at issue, a commentary on events and people in the news. At issue this week, the lesson of the litumide, Clark Mullin -Hot is in the Washington Bureau of Coals Publications and a winner of the Pulitzer Prize for National Reporting. The litumide was the heroism of Dr. Kelsey, but it was more than that. It was a dramatic lesson in the realities of drug law enforcement. The horror of thousands of deformed babies in Europe made the nation drug conscious. A recent indictment charged a Maryland doctor rigged drug tests and made false reports.

Several grand juries are at work on still more cases of alleged drug frauds. Most people have assumed that some government agency made certain that only safe foods, drugs, and cosmetics were sold. The details hadn't seemed important. The litumide demonstrated that the details were important. One loophole in the law permitted distribution of two and a half million thalidomide tablets in the United States. In theory, it was for experimental purposes. Thousands of persons struck the drug with no knowledge that it had not been approved by the litumide tragedy raised many questions about the policing of drug manufacture and distribution. Was the Food and Drug Administration requiring enough testing before approval was testing being supervised? How reliable were the drug tests? Could these tests be rigged? What steps had the drug industry taken to regulate

and discipline itself? How effective had it been? Were government medical officers given adequate facilities and top -level backing? Had food and drug officials implemented the law with firm regulations? And most vital was it possible for unsafe drugs to be approved and sold in the United States? In perspective, most drugs are safe. Most drug houses have a high regard for public interest. However, thalidomide emphasized that all firms would not discipline themselves. Would there have been a drug reform bill without thalidomide? I asked the question of senators who have sought drug reform legislation for years. Senator Gilbert Humphrey, Senator Thomas Dodd and Senator Phil Hart. I would say that the thalidomide development or incident was the catalytic agent, so to speak. It was

the event, the development that precipitated action on the Keep Offer Harris drug bill. There had been much talk about the importance of strengthening our Food and Drug Act, but much of it had been talked and there had been extended hearings. And then came along this tragic development that was revealed by the use of thalidomide drug and the resultant deforming of babies. This shocked the American people. I think it shocked the medical profession and the pharmaceutical profession and the Congress. So to answer your questions precisely, I think it was the thalidomide incident that precipitated the action. I believe it was decisive. I think that it took that tragedy to wake the Congress up. I do not think we would have had legislative action without it. And this is a sad thing to say,

but it's a fact. My judgment, nevertheless. Thalidomide was the most persuasive witness in support of that bill that turned up and I go further. Absent that thalidomide fright and horror. The bill that would have gone through, I think one would have gone through, would have been pretty much milk toast. Did the Food and Drug Administration do a diligent job of administering and enforcing the law prior to the thalidomide tragedy and since then? Or has there been a laxity, a slowness in enforcing the law and in providing needed regulations? I asked the question of Senator Karl Munt. I also asked it of Senator Dodd and Senator Humphrey. I think there has been somewhat of a breakdown in the administration of the Food and Drug Laws. Certainly our senatorial hearings with the thalidomide case would clearly indicate that, but fortunately we had a South

Dakota lady in the department or the bureau working at that time, Dr. Francis Kelsey, who combined a natural feminine curiosity with a scientific mind and refused to take yes for an answer. Well, I'm of course reluctant to charge anyone with laxity. I would rather put it this way. I hope that from now on the Federal Food and Drug Agency will do a better job. I think there's much to be desired and that's why I say I hope they'll do much better. I believe it would be fair to say that we found evidence at indicated laxity on the part of FDA. Frankly, I've been disturbed over the whole matter of the research and testing processes of these new drugs. Well, the overwhelming amount of research is done well and with high professional standards and the reporting is good. But we have some areas in which there has been shoddy

reporting, laxity of standards, low standards in which there's been actual rigging reports and you cannot condone this and this must be the subject of federal action, I mean, to discipline this kind of negligence. We have a new law, the Keepover Harris drug reform law, but how important is a law? How important is the administration of the law? I ask Senator Humphrey and Senator Hart. The law alone that really protects you. I mean, you can have a rather weak law and effective, diligent, high standard professional administration and enforcement then have a pretty good program. Once you get right down to this area, a law is just about as good in this area as the people that administer it and the scientific professional standards that you apply and what I've tried to do in these hearings is to insist that the Food and Drug Administration be looked upon not as a policing agency but as a scientific agency, as a research agency, as an agency to work with the great medical and pharmaceutical professions of our country to get the highest of standards and I don't think it helps anybody to have less

than high standards when you're dealing with these new drugs. I think our hearings have had a decidedly beneficial effect but may I say in all respect for the hearings. I don't think you ought to have to have hearings to get the job done that ought to be done by administrative procedure. There isn't anything that's written around here that couldn't be improved in the light of experience, hinges on two things. How effectively will the Food and Drug Administration be able to implement the thing? Because if it was written in gold and in magic words, it still wouldn't be any good if the administration of it bogged down. The rapidity or lack of rapidity of which they've moved has not impressed me to the point of sending a lottery though there. Top Food and Drug officials point with pride to the fact that Politamide was not approved for sale. They contend it was symbolic of FDA's fine general performance. Others feel that Dr. Kelsey triumphed over the pressure of the drug firm and the weakness of the FDA system. I asked Senator Humphrey and Senator Munt for their views.

Well, it surely wasn't a triumph of the system because the system was not geared to catch this sort of development. Actually, Dr. Kelsey, who is a devoted and dedicated public servant and Dr. by looking through considerable amounts of research material and reports in this instance from, as I recall, the British medical reports, found certain information almost by accident of the effect of the drug called Politamide upon the unborn child or the child. But the system didn't save us. It was the keen mind and the sense of public duty and even beyond the quality of Dr. Kelsey. I don't think the system was successful at that time because the system was permitting the use of Politamide and that isn't the only drug with this as it occurred, but it was in letting the use of Politamide occur in this country. So that the system had some loopholes which were plugged by her feminine curiosity as a and

her diligence and her talents, which kept her at this job till she found the flaw and the weakness. Politamide was only a starting point for the Humphrey Investigating Subcommittee. Testimony disclosed evidence of many problems within the Food and Drug Agency. Dr. John O 'Nester, one of Dr. Kelsey's colleagues, was sharply critical of FDA. He charged that unsafe and questionable drugs were approved despite warnings by medical office. He criticized the FDA atmosphere and said there was too little regard for safety, too much hurry to give quick approval to new drugs. We had hope to have Dr. Nester here. However, Commissioner Lerick stated he would not authorize Dr. Nester's appearance. He has resented Dr. Nester's criticism of FDA. From the Humphrey Subcommittee, here are the essentials of Dr. Nester's complaints. Several new drugs should not have been marketed. There was not prompt action

to take unsafe drugs off the market. Some clinical researchers had submitted false and fictitious reports to support new drug applications. Other researchers were promoters of drugs rather than objective scientists. One questionable food additive containing vitamin K was kept on the market until the Humphrey Subcommittee heard Dr. Nester. Among the drugs pointed out by Dr. Nester was Mer 29, a cholesterol reducing drug. It was taken by more than 300 ,000 persons before being taken off the market. Dr. Nester states it had harmful side effects, including cataracts, loss of hair, and skin disease. Thousands of lawsuits have been filed as a result of this drug. Senator Humphrey calls Mer 29, quotes a shocking indictment of FDA itself. I ask him his view of Dr. Nester. Dr. Nester has made considerable sacrifice to come into the public service. He

is an eminent doctor, an eminent pediatrician. I believe he has some extra competence in cardiology as well, heart disease. I recall that Dr. John Nester was present at the White House when President Kennedy bestowed a medal of honor upon Dr. Kelsey. So Dr. Nester was working with Dr. Kelsey, and his testimony before our committee. Our subcommittee was a very, very important bit of testimony. We listened to him considerably in a period some months later than the Thalidomide testimony, and he was pointing out to us then that there were still areas that needed improvement. Very definite. Now you may disagree with the emphasis that he placed upon certain matters. And I suppose all of us have our little pet peeves, but I don't think you can dismiss the testimony of Dr. John Nester. Testimony, which to me really was most disturbing

because it revealed a lack of interdiscipline, so to speak, and high standards within the Food and Drug Administration. Dr. Nester did not clear his comments with Commissioner Larry before testifying for the Humphrey Committee. His outspoken criticism was regarded of great value by Chairman Humphrey. There had been difficulty in obtaining frank comments from the agency. A House investigation by L .H. Fountain of North Carolina ran into obstacles when its inquiry turned into questionable new drugs. Well, we had no problems with respect to cooperation from FDA until about May of 1962. If you recall at that time, we began an investigation into FDA's handling of a certain new drug applications for MER -29, Flexin, and a number of other drugs, a drug which had been

withdrawn from the market due to the discovery of dangerous and sometimes fatal side effects. These drugs had previously been cleared by FDA as safe. Initially, the FDA refused the subcommittee access to their files on the basis of a provision in the Food and Drug and Cosmetic Law, which prohibits the disclosure of information which, and I quote, is entitled to protection as a trade secret. The Food and Drug Administration also said that they had an administrative regulation which specified that all information submitted with new drug applications would be treated as confidential. I might say that as an alternative, Commissioner Larek offered to punish us a chronological summary, which was supposed to contain all of the pertinent information concerning the new drug applications for these drugs.

I explained to Commissioner Larek that that would not be satisfactory and that if our subcommittee was to fulfill its responsibility to the people and to the Congress, it would be necessary for us to see the entire file. We had no interest in seeing the trade secrets, but we pointed out that this was the type of information that we were entitled to see. When you're making an investigation, we have to evaluate ourselves and if we are evaluating something somebody else has evaluated, you oftentimes don't get the true picture. There was general approval of the drug reform law in Congress and at the FDA. However, the drug industry has complained that the law will stifle creativity in the production of new drugs. C. Joseph Stetler, executive vice president of the pharmaceutical manufacturers association, gave the industry view. We believe that the statute itself, and more particularly the regulations that have been promigrated since the statute,

will have a long range effect of stifling and curtailing the development of new drugs, which will not only be to the disadvantage of the drug industry, but of course to the public and to the medical profession. Well, from a practical standpoint, how much policing do you think that the drug industry itself can do on this false reporting by doctors in these few instances, and even some over promotion by a few drug companies from time to time where they get overly enthusiastic about their product? Well, I think that definitely is an industry problem and a problem for the pharmaceutical manufacturers association. I would prefer to see us take the role of trying to the extent we can. We're not in the police business, but we can do a job of education and prevention, and I think we have the responsibility. And if we do it well, there'll be less need for government regulations. What have you been able to do relative to the problems that have come up in the past? Say, with the rigging of the instances of rigging, and then some little evidence before the Humphrey Committee that some

doctors were probably too much the in -house doctor for some firm, and we're lacking an objectivity. What have you been able to do in this area? Well, to the extent we have information and we always do not. If we find that a doctor has made false reports, we certainly try to circulate this information to the industry generally. Now, the cases where we do that, or of course the cases where you do not see much publicity, the matter is solved and taken care of internally. Some of these cases get to the point as some that you have in mind where you're in the stage of an indictment or a criminal investigation, and then we pretty much have to keep hands off of the matter. Well, now, have you put out any general warnings to the drug industry to be wary in these areas? Not general warning letters, no. Do you think there would be any advantage in some type of a code or some type of a warning generally about some of the weaknesses that have showed up? I think it's a definitely good idea. Situation we are looking into and

not a bad idea at all. From the drug industry position, we now turn to Commissioner George Lerich. He has been head of the FDA since 1954, and he has been employed by the agency since 1923. Commissioner Lerich disagrees with those who state there have been witnesses in the operations of the agency. He is particularly in disagreement with Dr. Nestor, who charges that medical men are being overruled by non -medical men in the agency. Well, I think the Dr. Kelsey deserves great credit, but I think the system, the laws that we had been provided with certainly couldn't have been actioned by the personnel of the Food and Drug Administration. Dr. Kelsey took the leadership. Well, now, how do you feel about the pressure that this one drug firm brought on Dr.

Kelsey on Thalidomide? They were in day after day trying to hurry her up to approve this. Do you feel this is proper conduct by the industry? I don't worry about pressure. I feel that government people, people in responsible places in government, are going to be put under pressure. Of course, there are people that respond to pressure, but I don't believe that pressure in this situation was particularly bothersome. Well, now, in the Thalidomide case, there were something like I think it's two and a half million Thalidomide tablets that were distributed on what was supposedly an experimental basis to about 1 ,200 doctors in the United States. Do you feel that this was a reasonable step prior to approval? You put me in rather a difficult situation because it's rather common knowledge that all of the facts and connection with this matter and particularly with respect to your question have been referred to a federal grand

jury by us and it is being investigated by that grand jury. And obviously, if we didn't feel that there was some impropriety, we wouldn't have referred it to the grand jury. Well, do you feel it's practical for the drug industry to regulate itself on these matters? I think the drug industry does a great deal of self -regulation, but I do not think that that is enough. The limitations of science make 100 % safety unlikely. Perfection is seldom achieved. The big question, what is reasonable safety? Dr. Nestor says there is too much drug industry influence at the FDA. Dr. Larick says industry pressure and influence have not resulted in wrong decisions. I think that in the progress in drug therapy, that you never can bring about a situation where the full facts about a drug can be learned during the experimental period. You can never get

beyond trying the drug on several thousand patients. And when you jump from having administered the drug to several thousand people, to administering it to millions, you are going to find in those millions some people that react differently than any in the thousands. And if we're going to make progress in drug evaluation in this country, we will have to take some risk. Our problem is to let progress be made and not to stifle the appearance of new drugs, but to reduce that risk as much as it's humanly possible to do so in the life of current human knowledge. I think that in the case of mirror 29, that if we had known everything at the time the drug was offered to us, that we learned by virtue of it being

administered to thousands more people, we would not have allowed it on the market. There has been testimony before the Humphrey Committee that rigged reports, false reports, and slanted reports have been filed by doctors and clinical researchers, and that these have become a factor and approval of questionable drugs. Is this charged true? I think that in any field of endeavor, you're going to find some people who are crooked, whether it's the ministry, whether it's physicians, or no matter what it is, the integrity that the top flight investigators have is something that you can put there by law. And I think our job is to catch the people that you referred to at the onset as the occasional person who is a downright crook. I think that investigations to determine whether the Food and Drug Administration personnel was lacks.

We not only conducted investigation ourselves, but we ask an outside committee of eminent scientists who were named not by us, but by others to make a fundamental appraisal of the scientific accuracy and validity of the conclusions that were made by the Food and Drug Administration as a result of their total appraisal of the data that was submitted to them. And this committee gave our scientists a very good name. Commissioner Lerick, why was there no action to remove this food additive that included K3 until the Humphrey hearings on March 20, 1963? Very in mind, you're dealing here with matters that can be determined solely on the basis of expert opinion. When it became apparent that there was a difference of opinion inside the Food and Drug Administration about the

proper course of action to follow. In consultation with our experts, we went outside and we selected people with the help of the scientific community to advise us in this matter. And we got the top flight scientists in the country to advise us. On the basis of our best judgment in Food and Drug and with this group outside, we did not see any need to proceed with this action on vitamin K any more rapidly than the rules provided. And I'm still convinced that was the right course of action to follow. Dr. Nestor testified that for months there was good reason for dowing the safety of vitamin K3 in the food additive. It was not taken off the market until last March. Dr. Nestor says that if there was any doubt about the safety of a product, it should be taken off the market immediately. No, I disagree with him on that, but I also should bring to your

attention that the law did not permit the action unless there was an imminent danger to the public health, which there was not. Commissioner Larek, are you generally satisfied with the key fover Harris drug reform law? The key fover Harris bill is a great forward step and it will take care of many problems, but we will learn and as we administer this law, we will learn many things. We will learn there are some areas where we perhaps are too strict. We will learn there are some areas that it doesn't cover adequately. But we have a legislative program that has been sent up on the hill and has been pending up there for some years. What about the Dodds bill? Do you feel the Dodds bill to control perpetuates and the like? Do you feel that this legislation is something that is necessary right now or do you think it's all right for the Congress to carry a bit as it has? I think that the use of habit forming drugs, the barbiturates and the amphetamines for

non -medical purposes is progressively becoming a more and more serious public health problem in this country. I do not think that the laws either at the federal or at the state level in general are adequate to deal with this growing menace. The first pure food and drug laws were passed in 1906, following the publication of the novel The Jungle by Upton Sinclair and a crusade by the great muck -wrecking reporters of that era. The next changes in the law was 1938, the tragic death of more than 100 people resulted from the poisonous drug being distributed. It jared Congress and paved the way for reform. The key fob or Harris drug reform bill was another case of reform being born from tragedy. However, his passage of a reform law and none. Some say still more legislation is needed.

Senator Phil Hart wants laws to control over the counter -non -prescription drugs. Senator Dodd says greater control is needed to the distribution of barbiturates. Representative Lenore Sullivan and Missouri says there are great new polls in the cosmetic law. Also, there are still problems of obtaining competent personnel and having a proper atmosphere for good law enforcement. There has been the indictment of one doctor on charges of submitting false drug tests. Other cases of rigged reporting are being probed. A federal grand jury is studying the distribution of two and a half million to litamide tablets. To maintain high standards, there must be a continued public interest to combat the tendency to relax following a crisis. Each citizen should continue to ask questions. Does FDA have sufficient personnel to handle the new chores under the law? Is there a top -level backing of competent medical personnel? How much self -regulation can the industry do? How much is practical? Conditions are corrected only if the public and congress react at the first evidence of weakness in the law or

laxness in the administration of the law. We have seen some of the evidence. Will it take a scandal or tragedy to bring needed change? Have we learned the real lesson of the litamide? This is NET, National Educational Television.