Interview Topics:
Interviewers: Ronald T. Ottes
(RO) and Fred L. Lofsvold (FL)
Date: 15 October 1986
Place: Rockville, Maryland
FL: The court did uphold the peanut butter standard.
WG: Yes, it did, in spite of the fact that both the market leaders did not comply, as they were then formulated. But it was easy for all of them to reformulate and come into the market. They're all in the market now; they're all very fine products; peanut butter is a better product as a result of that standard and has never been downgraded as a result of steps that were in the offing at the time the standard was adopted.
Well, going from there, I think the next thing we ought to do is pick up the sequence of events in terms of the commissioners who were here, because in history, that seems to be the most logical way to do this. We have talked earlier about Mr. Campbell, who was the long-time chief of the Food and Drug Administration, from the '20s up till the end of the war, about '45. And then P. B. D., P. B. Dunbar was put in as Commissioner. P. B. D. had been here since Wiley. He was one of the first employees of Wiley and worked with Wiley in the lab. P. B. D. was a chemist by training, and he had been pretty much out of the lab for quite some time, but he was a very fine administrator. He supplemented Campbell quite well in handling the budget and all those things. Campbell was kind of a philosopher king, and P. B. D. was the man who made the railroad run.
That same relationship arose between Charlie and Dr. Dunbar. That is, Charlie Crawford was, I think, probably our best thinker of the ones I knew best, in terms of looking forward to what was down the road. Charlie, of course, as I said earlier, was concerned with the food standards at first. He became interested in the issue of chemicals in foods in the late '40s. Really, after World War II there was an introduction into the bread supply of a new emulsifier which had been discovered by R. K. Vanderbilt Company, but produced by Atlas Powder Company. It was a polyoxyethylene monostearate, that type of product, called spans and tweens, and it was introduced into the bread supply to make the bread stay fresh longer. Those who were not involved in World War II and the economics of that probably have no recollection of stale bread and the habit of people squeezing bread to see whether it was fresh. Everybody that went into the store in those days would squeeze the bread to see how many days it had been there. So it was important in the business to have a bread softener, one that would make it softer to the touch.
Well, mono and diglycerides had been allowed in bread and part of the shortening for a long time and were popular items in the shortenings available to bakers. Swift made them, Proctor and Gamble made them, other companies made them. Indeed, during the bread hearing, back earlier than that, the issue of emulsifiers had been involved through lecithin. The American Lecithin Company was wanting to get lecithin in practically everything you can think of; they considered it both a health godsend and an emulsifier godsend. But anyway, they were basically interested in getting it as an ingredient in a widely used food like bread.
But to get back to where we were, when this new emulsifier was introduced, it was viewed with alarm by the competitors. The competitors then went to the American Institute of Baking, and to the American Medical Association, with concerns about the product both from a functional standpoint and from a biological standpoint. This was not a chemical substitute in the ordinary sense; it was a reaction product made from reacting alcohol with a fat. It had peculiar properties in that it really did make the bread feel softer to the touch.
So the bread standard took up after the war, and one of the major controversies about that was whether or not these new emulsifiers should be allowed. You'd think of standards in terms of promoting honesty and fair dealing in the interest of consumers. That's an economic concern. But the whole issue turned on the safety of the product. That is, the people concerned, both the American Medical Association and the Institute of Baking, of course urged on by Swift and Proctor and Gamble and others, were raising issues about the safety of the thing. So when the hearing got underway, it went on for weeks and weeks and months and a couple of years, all dealing with the safety of this product, whether or not it was safe to put this thing in there.
Again, like in the peanut butter case, these companies were very well represented. As a matter of fact, Potter Stewart, who later was on the Supreme Court of the United States, was the lawyer for Proctor and Gamble and the Institute of Shortening. And Swift had their general counsel down here. And Atlas had their people here. So the hearing went on and on. What made it more protracted than ever was Atlas's proposal to admit not just one ingredient, Myrj-45, but a whole series of spans and tweens which varied by how far the reaction was carried with these various items. They wanted all of them introduced. So the evidence on any one of them was fairly thin.
That hearing went on and on, and ultimately the Myrj-45 was not allowed on the ground that its safety was in question, and that it offered the possibility of deception of a practice called "bread-rolling," in which bread would be picked up at one outlet and turned over to the next customer there as fresh bread, even though it was several days old. Now, whether or not you could tell any difference was a debatable fight. But that controversy was the first one really focusing on Food and Drug's ability to deal with a new food additive of unknown safety.
[Interruption]
WG: When the '38 Act was passed, Congress did undertake to deal with substances that they described as poisonous and deleterious substances. Under the 1906 Act, a food was adulterated if it bore any added poisonous or deleterious substance which may render the food injurious to health. And the old Lexington Mill and Elevator case had held that if by any possibility an additive of a particular food would make that particular food possibly injurious to health, then it was adulterated. But each food had to be considered on its own.
So one of the great flaws that FDA saw in the 1906 Act was the inability to cope with a variety of additives that may individually be poisonous but had come together in the total food supply, but none of which individually would be up to a level that would permit the proof that they would be injurious to health. And even though the Coca Cola case had held that all substances and ingredients in foods were added, that strength of the law there simply didn't get to the issue of poisonous and deleterious substances across the board.
Well, in '38, Congress undertook to deal with what I characterized earlier as the per se rule, which provided simply that if any added poisonous or deleterious substance was in food, it was per se illegal, and thus there was a tolerance for it. And then there was a tolerance authorized for those additives that were required in production or unavoidable in good manufacturing practices. That was to accommodate pesticide residues on growing crops and other unavoidable, environment hazards, is what the legislative history indicates.
But that was the state of the law dealing with those substances, and here we had in the Atlas case an entirely new issue: that is, here's a substance that is greatly suspect, but no one knows enough about it to classify it as an added poisonous or deleterious substance. Whether it was poisonous or not, you really didn't know. They had always had trouble from the very beginning of dealing with a poisonous substance, because you'd have to rely on animal studies and you'd get in court and the guy says, "We don't sell this to rats, and therefore this is all irrelevant." It did involve an extrapolation of the judge or the jury from animal studies over into the human experience. So that was another problem with the early law.
Crawford saw this and his interest was greatly promoted by what he was seeing in the bread softener things. So he became interested in getting either the agency, but he thought primarily getting the Congress, to concern itself with this issue, looking way down the line, as he did, to some kind of law that would cope with these new items. He didn't really fully understand the difference between a poisonous and deleterious substance and one of unknown or uncertain toxicity. In his thinking, he talked about chemicals in foods and added and poisonous and deleterious substances.
He was able to talk with Frank Keefe, who was then a congressman from Milwaukee, I believe, somewhere in Wisconsin--maybe from Madison. Congressman Keefe, in the Eightieth Congress, had created the special committee to investigate the safety of chemicals in foods. That started in about '48 or thereabouts.
I'm not sure exactly of the year, but by the time the Democrats came back in control of Congress, in 1951, that committee was changed over to the chairmanship of Congressman Delaney, and that's where the big drive for the addition of legislation came. Alvin Gottleib, who still works for Food and Drug, Vince Kleinfeld, who was at the Department of Justice, were counsel there, and, of course, they knew quite a lot about this. Charlie provided them with a list of some 700 items that were, in his judgment, suspect, and so forth. They held very extensive hearings in '50-'51.
In 1952, the Atlas case was decided in our favor, in the court of appeals in Philadelphia. I took that case up; I argued the case, and we won on that issue that they had the authority to exclude under a food standard an item of unknown, uncertain toxicity. But the record was real good for me, and it elucidated all that was really wrong then about food investigations, and problems that still arise today.
Most of Atlas's problem arose in proving the safety of the thing out of first, failing to identify specifically what the additive was and what they wanted it in. In terms of overreaching, trying to get a whole class of items in there, they outsmarted themselves. Second, the research done had all kinds of problems with it. For example, they tested it in rats, and Dr. Krantz at Johns Hopkins was their investigator. The Swift and Potter Stewart cross-examination of that stuff made a joke out of it. Some of the rats got out of the cages over the weekend and were not accounted for. They had all problems--you've all seen yourselves in terms of accounting for every one of these rats every day.
And then they did some tests on rabbits, and the rabbits had cannibalism in the thing. Rabbits are normally a vegetarian animal, and these animals ate each other up. Then some doctor, Rene Dubois up in Rockefeller Institute, had raised the issue about whether surfactines in the diet might exacerbate tuberculosis. They had four monkeys, and one of these got tuberculosis and died. So everything went wrong, and that's why the evidence was inconclusive.
When the Atlas case was decided, that gave Food and Drug a strong hand in terms of calling the shots on what might happen. About that same time, the pesticides had really blown up. After World War II and when DDT came along and was followed by aldrin and dieldrin, and there was a regular flood of those things. There were a great many pesticides coming along, and people who were using them in agriculture were asking more and more questions of the manufacturers: "How the hell do I know this stuff is okay?" The manufacturers would have just as soon gone along with saying, "Well, it's registered by USDA," and no question of concern. But that wasn't an acceptable answer, so they began putting some steam on the pesticide manufacturers to come up with an approval.
We had had a hearing in the early '50s over insecticide spray residues. As you can see, under the law as it was then, the hearing had to prove what pesticides were being used on what crops, which ones were necessary in terms of food, and which were only convenient. Of the ones that were necessary, then, what's known about their toxicity and what would be a safe tolerance. Well, that hearing went on for months. People testified from USDA, from the state experiment stations, from Food and Drug--from everybody. The upshot of it was that the record was inconclusive. You couldn't do anything with it; you couldn't make a single judgment there that would fit what the law was requiring you to do.
So by 1954, we had our first movement in terms of congressional control over these additives, and the Pesticide Chemicals Amendment of 1954 was enacted in that year. It was promoted by the pesticide manufacturers. The one that came through wasn't exactly what they had in mind, [Laughter] but they did get enough pressure from the so-called farm groups to interest the Congress in taking this up as an urgent item. We never could have gotten them to do that, but as a result of the pesticide manufacturers going to the farm users and getting the farm groups to support that, the House committee took up the bill.
The bill they proposed was really pretty damn bad, fundamentally because it would have required the agency to establish a tolerance for each one of these pesticides that were in use within a short period of time--sixty days, ninety days, something. That was the concept. So we said we couldn't live with that at all; we'd have to have some way to turn down a tolerance; we'd have to have authority. Well, they wouldn't give us that, but we proposed that a language up there in the legislative thing, that the tolerance may be affixed to zero level, unless a higher level is justified by the evidence. That gave us the control over the things, and in effect, we would have been the same without that in that of the absence of a tolerance was zero. This confirmed that we had that authority. And so the Pesticide Chemical Amendment was passed.
You'll remember that at that time the registration of pesticides was still in USDA, and the fixing of tolerances was in Food and Drug, and the enforcement of tolerances was in Food and Drug. But there were a great many things registered and in use for which there were no tolerances.
The pesticide amendment was a complicated thing; it had all kinds of committees and all kinds of reports from the secretary of Agriculture to the secretary of HEW and so forth, but it did accomplish the goal of moving that thing along. This was 1954. And from 1954 over the next few years, a great many of those tolerances were regularized and were put into place. I'm going to mention how the procedure came to play on aminotriazole in just a few minutes.
Maybe I should go to aminotriazole now and then come back to food additives after that. No, I think I'm going to have to go to food additives first, because that's where the Delaney clause was, and the pesticide chemical didn't have the Delaney clause in it, and because of that, I've almost got to go to food additives.
When Atlas was decided in '52, as I said earlier, the food industry and Food and Drug began taking a harder look at these things. The urgency on the food industry wasn't fully understood by them because they hadn't had any pressure against the use of these new things; nobody knew anything about them being poisonous, and they assumed they were safe. So they were using them. But people began asking Food and Drug, "What do you think about this?" Dr. Lehman set up kind of an informal adjudication procedure in which he would give opinions on this. That procedure was publicized in the AOAC Journal and was followed for quite some long time.
Charlie then drafted this legislation--he and I did--and it was kind of like the new drug approach. None of the people in the food industry liked that worth a damn; they didn't want to have to have a pesticide guy come and show the safety of food. The pesticide guy wasn't making food, they were making food. So it was a question of who had the responsibility. The pesticide guy had the responsibility, but the food manufacturer wanted the assurance that these substances were safe.
Rule making at that time was a relatively new technique--it wasn't a new technique, but it came in a wider use in the administrative process as a means of settling in advance rules for behavior and let the agencies fill in details from legislation that had binding force and effect of law. Before, there was a great dispute always about whether regulations were binding or whether they were just advisory. We, of course, had that same problem we took up into the court in the Abbott Laboratories case on what rules were binding and what were not. Congress, in '38, clearly thought that the ones that were fully binding, that is, the formal rule making, would be fully binding.
We drafted a food additive amendment which provided for the food additive manufacturer to apply for approval and to obtain a rule that would specify the conditions which they would use. Now, in order to get that through, of course, we had to have a grandfather clause, and that was where the famous GRAS list came along. The "generally recognized as safe" came from the new drug approach. Nobody liked it--we didn't like it, Congress didn't like it--but nobody could think of a better thing to do. So we had to deal with products generally recognized as safe, and then we had to deal with products that were generally recognized as safe like salt and pepper which had never been subjected to any formal procedures.
That's where that part of the grandfather clause came from. Substances generally recognized as safe on the basis of either scientific procedures, or if they were in common use prior to 1958, the date of enactment, and were generally recognized on the basis of long-continued common use, would be approved. After much controversy, the Senate passed the bill. Senator Hill was the chairman of that committee at the time. He pressed a bill that did not have the Delaney clause in it. Jim Delaney, of course, was not on the House Interstate and Foreign Commerce Committee. We went to that committee and asked them to adopt the same thing the Senate had done, but without the Delaney clause.
Delaney wanted them to put the Delaney clause in, and they reported it out that way. But it soon became obvious that we weren't going to get the thing through the Rules Committee, on which Mr. Delaney was a member, unless we had something to deal with the Delaney clause. So we first tried writing into the committee report a statement that the law would be the same with or without it; that is, if a food additive caused any serious condition-a cancer or blood disease or anything else--it obviously wouldn't be approved, and therefore the thing was unnecessary. But it turned out it was necessary for us to get the thing through Congress. So we drafted the Delaney clause down in the department. John Harvey, who was then deputy commissioner, and I talked with Delaney and Senator Hill and got them to agree.
So with that, the food additive law was passed. The first thing that was done was to set up the procedures and set up the GRAS list. I don't suppose there's any reason to go into that; the historical records of that GRAS list are good enough, I think, without me talking about it. Quite briefly, what we did was we obtained from Dr. Lehman's group a list of additives that he would regard as generally safe for use in food, and we publicized that and asked for comment from the scientific community. We sent it out to people he had on his mailing list and we published it in the Federal Register and a few objections came back. And we took off some things like carbon black and a few others that were objected to. But in essence, that rule was adopted.
So we started off with that in '58. Not much controversy about it. Putting it into effect was smooth. That is, Lehman had already had some things done and the GRAS list took off a lot of the pressure. We were able to move into that a lot differently than the way it's run now. "Tillie" Checchi, who was Harvey's special assistant, got together the GRAS list; Winton Rankin, who was Larrick's special assistant at that time, worked on the regulations with me. So we got that thing in operation fairly quick, and without any to-do. We thought the food additive law was the same with or without; it didn't make any difference.
Well, that came to a test in 1959, not under the food additive, but under the pesticide law. Our secretary at that time was Arthur Flemming. Arthur Flemming was a man of great public relations skills: he enjoyed meeting with the press; he enjoyed encouraging the press to come and ask him questions; he enjoyed having press conferences. He was a very good publicist and got a lot of mileage for the department and for himself out of that.
But the way the thing came into a real crisis in Thanksgiving of 1959 was over aminotriazole as an additive for cranberries. It was a weed killer that was used on cranberry bogs, and the idea was to apply it in the spring when the weeds were coming up. And in the fall, when the cranberries were harvested, there wouldn't be any there. So you didn't really have any problems with it, and it would be assured of a zero tolerance. Well, according to the way the pesticide amendment worked, if anybody was seeking even a zero tolerance or a minimal tolerance or a freedom from a tolerance, they would have to apply first for registration, and then when the registration was filed, that was publicized. Then, after a certain length of time, that was studied and the tolerance was granted.
In the normal timing of events, the application for this pesticide was filed and publicized in the spring. So the growers there thought that come fall, it would surely be granted, and therefore, they went on and used the thing with the idea that by the time the cranberries were ready to go, there would either be a tolerance or a freedom from a tolerance. Well, it didn't turn out that way. As the registration process moved along, it was discovered that aminotriazole was a tumor producer to the thyroid in animals. So the tolerance was refused. A lot of cranberries had been treated, and they were put in storage for a year's time. I guess all this registration was earlier than that, around '58. Some enterprising photographer took a picture out in Oregon or Seattle, where these cranberries . . .
RO: It was in the state of Washington.
WG: In Washington. Took a picture of one of those beautiful forests and these red berries and this yellow Caterpillar that was burying the berries. It was really a striking picture. So one of the reporters asked Flemming, "What's this all about?" He said, "I don't know; we'll have to look into that." He came back and he then reported that these berries were being buried because there was not any tolerance and they had had some aminotriazole on them. That explanation was okay for the moment, but it raised the other question, "What about all the other cranberry sauce that's around? Has it been used in New Jersey and Massachusetts?" He said, "I don't know." Of course, the upshot of all that was that he wasn't sure which cranberries had the aminotriazole on them and which didn't.
Just before Thanksgiving--all this occurred in early November--the public started rejecting them. Well, their whole sales crop is about Thanksgiving time. So they were understandably alarmed. Ocean Spray, as you know, was at that time--it may still be--a co-op, and there were other co-ops involved in growing and marketing cranberries. So they were alarmed, and a congressman from Massachusetts, Hastings Keith, was on the committee that we were dealing with, that is, the House Interstate and Foreign Commerce Committee. He came down with fire in his eyes. They were going to really get after Secretary Flemming.
Well, Flemming was a master of public affairs, so instead of meeting all of them individually in his office, he held a big hearing down in the auditorium at HEW. He was the defendant and the judge of that. [Laughter] He invited them all to come down and he heard what they had to say. So the hearing was held, and at the end of it, he didn't really say very much of anything. If any of you ever knew L. D. Elliott, who used to be assistant commissioner for Food and Drug, you could talk to L. D. for an hour, and he never would give any inklings whatever that he'd heard you or agreed with you or didn't agree with you or what.
So Flemming held the hearing; he was very cordial to them, but really gave them no hint of what he was going to do. It was obvious to him, though, that he had to do something. So after the hearing was over, we adjourned up to his office and he inquired about what might be done. There were two courses: one was for the USDA to buy up this cranberry sauce and put it in storage until the safety was determined; the other, which we did, was for Food and Drug and the others to establish that crash inspection program, in which, within a very few days, we inspected, and we then inspected laboratories who inspected and certified that this cranberry sauce was free of aminotriazole. And that way, the crisis was avoided for Thanksgiving and the aminotriazole was over.
Now in the course of that, the issue came up, what is all this about? And Flemming said, "Well, aminotriazole is a tumor producer to the livers of these animals." They said, "So what? I brought an expert in liver tumorgenosis from Tufts University who said that thyroid cancer is really not seen in any significant degree in humans, and this is really not any reason for alarm, and in any event, the amount there is so small that it wouldn't make any difference." So that really raised the issue of allowing an animal carcinogen into the food. When Flemming said that's what the basis was, people said to him, "The Delaney clause doesn't apply to pesticides." He said, "Well, the principle does." And that's when the whole rationale for the action was developed. This was in about Thanksgiving of '59. I'm pretty sure of the year of that. That's about a year after the food additive law became effective.
Meanwhile, the color problem had come up for settling, and we had won the case on that problem in the Supreme Court, dealing with the color used in coloring Florida oranges. A new law having to do with color additives along the lines of the food additive law was under consideration.
[Interruption]
WG: Under the '38 Act, colors had to be harmless and suitable for use. We had taken the view that harmless meant absolutely harmless, and that any animal injury from it was justification enough to outlaw these products. We had no authority to establish a tolerance for them. This is what we went to the Supreme Court on and won.
Since we won that case, the color manufacturers had a certain urgency to try to get a new law into effect, as did Food and Drug. That is, Food and Drug was not interested in outlawing all colors, but they were very much interested in doing something about the safety. Here again, Charlie (Crawford) was responsible for this. He had become concerned about colors back in the mid '50s, '56 or thereabouts, and had told Lehman's group and others to begin investigating some of these things. We had a report on Violet No. 1; we had a report on one or two others. They had to be withdrawn. So Charlie told Lehman's group to begin work to do this. They did, and it turned out that the colors, particularly Orange No. 1, Orange No. 2, and Red No. 32 all had significant toxicity when fed in any appreciable amount. That meant that we had to have some sort of a law if we were going to have artificial colors for soda water and all the other things, to say nothing of cosmetics. In many foods, of course, artificial color is a factor in acceptance of . . .
That change in the law had been proposed in the fall of '59. We had won that case about the same time the pesticide thing was coming to a head. We had a bill up before the committee, but the committee took that as a reason to really get Flemming up there and give him the hazing that he'd given them.
We went up to testify about the color additive bill, and of course, they wanted to know what the Delaney clause was all about, and then they had all this squeal about you'd have to eat 90 million pounds of this stuff in order to do any harm and so forth--the same old argument. The committee heard Flemming. Flemming made a stirring defense of the Delaney clause which I helped write, and in effect, that's where he says, "No one knows how much or how little of it causes cancer, and until we know that, we have to be safe." And that was the theme song. We said to them that the rallying point against the Delaney clause was, it took away your scientific judgment. We said, "No, that's not true. There's plenty of judgment in deciding whether or not the item is a carcinogen. Once it's decided that it's a carcinogen, then there's a little room for judgment because nobody knows how to fix the same tolerance."
That was the first time that we really rationalized the Delaney clause in the sense of any size. That rationalization today is what's being used by the public interest groups to stymie all change in the Delaney clause up at the Capitol. Every time, they quote that language that we wrote for Flemming at that hearing in 1960 as the reason why we still don't know. Flemming said that whenever science makes a breakthrough, we'll make the change. The upshot of all that was that the Delaney clause stood and the Food Additive Amendment was passed and it has a provision kind of like the Delaney clause but not exactly like it in the color additive. So that is where that went.
I believe that pretty much summarizes the legislation on these things and the shift from the old per se rule to the rule-making type procedure, which would set up specifications in regulations on conditions of use of first pesticides and food additives, and ultimately color additives. All of them were treated by rule making, but under somewhat different procedures, depending on who all was involved.
For example, in food additive, there wasn't any advisory committee on the cancer thing. In color additives, there was. The food industry didn't want the advisory committee and the color people did, and was put in that. We were willing to have an advisory committee in pesticides which we used several times. Those advisory committees pretty much all came out with where we were, that is, the evidence is inconclusive; you can't make any judgment on that. [Laughter] Heptachlorepoxide was one, aramite was another of those pesticides that went to the advisory committees and came back accepting what we had done. Now, let me see where I go from here.
As I've indicated, Charlie Crawford was the philosopher king that did think of all these things. He became commissioner in 1951 when Dr. Dunbar retired, and he himself retired in 1954. He was actually at the head of the agency a relatively short time. But he was a major influence both on Walter Campbell in the legislative process, and on Paul Dunbar and his operation of the agency. And in terms of legislation and setting the stage for this material that I've just covered, he ordered the investigations of the colors which resulted in the Color Additive Amendment; he pressed for the Delaney-type investigation; and in all was the one who was thinking ahead. Equally important, Charlie was responsible for reorganizing the agency. That, I think, was about 1948. 1 guess he was a deputy at that time. Before that time, the field had been divided into both districts and regions, I guess they called them.
FL: Districts and stations.
WG: Right. The districts were the three districts, East, Central, and West, and headed up by three strong field people: John Harvey in the West, J. 0. Clarke in Chicago, and I forget the name of the one in New York. Charlie decided to abolish all that extra layer of review in those district offices and make each one of what had been stations who were reporting through the district organization report directly to headquarters. He brought to headquarters a lot of the field people: John Harvey, J. O. Clarke, Malcolm Stephens, Ken Milstead, and others. I believe there were about fifty that came in. Bob Roe was also in that group. He started organizing it maybe before, but almost all the people were here by about 1950. So this was another major thing that Charlie did.
Now George Larrick became commissioner in 1954, and he continued to be commissioner for a very long period of time, retiring in 1966, maybe at the end of '65. Larrick came from the inspection part of the agency. He was at one time chief inspector--that's what they called him--he was head of the Bureau of Drugs at one time, and he had spent his life essentially in inspection and in administration involving drugs.
The administration involving foods were L. D. Elliott and Ken Kirk. Kirk was Elliott's associate. But Crawford was the thinker behind that. L. D. Elliott was the enforcement-type person on foods. Larrick came to the commissionership without any real substantial exposure to food problems. As we've seen, his first several years were devoted to the major problems in the food business which had been set up by Crawford to set the stage for the new legislation. And of course, Larrick was involved in handling the aminotriazole and the other episodes which we have talked about, from 1954 up through about 1960--that's with pesticides in '54, food additive in '58, and color additive in 1960.
But during all that time, he still maintained an interest in drugs. The Kefauver investigations had begun in December of 1959. Larrick was a long-time supporter of improving the New Drug law to require proof of effectiveness as well as safety, and he recognized some other problems. But beginning about 1960, Larrick became a victim or a necessary actor in a tremendous number of investigations by congressional groups in terms of how well we were really operating the New Drug procedures, and the answer was, not very well up to that time.
The first thing Larrick did in an important way was to recover our economic health. Crawford just was not a compromiser; he wouldn't make any peace with anybody on a matter of principle. If he felt a matter of principle, he stood on the matter of principle. If it cost him all of his appropriations, so be it. But he would not compromise under any circumstance. Larrick, on the other hand, was a very jovial, well-met person. He was very friendly with the people on the Appropriations Committee, particularly the congressman from Rhode Island, Fogarty. Fogarty introduced Larrick to other people there that could help him.
About that time, the Citizen's Advisory Committee, which Crawford had been instrumental in setting up, came up with their first reports about improving the appropriations, and Larrick, to his credit, did get that done. He got the ball rolling of increasing substantially over a period of two or three years, and he got that done. He also started the rebuilding of the field stations. I don't know how many of them have been built, but that was one of his first and major accomplishments. This was his line of interest: the inspection, the field, and the appropriations he knew and he did well and got along with the Congress. While he was not a tremendous compromiser, he was a pragmatist and would be able to get along with Fogarty and the Bureau of Budget people and others where Crawford did not.
Larrick, having spent the first few years on these pressing problems of food additives and others which were rather foreign to him, really got caught in the ringer by the investigations on drugs. He was a supporter of Henry Welch's, although I'm sure he knew nothing about what Henry was actually doing. Henry was kind of secretive about where he was making money. He told everybody he was selling reprints, but it wasn't clear that people buying them were just storing them away and in effect giving Henry money. So the Kefauver hearings put him really to the first test. We testified up there, Larrick, myself, Rankin, and the others, in terms of what ought to be done. I think we presented a rather good statement. That statement's in the record, so everybody can look at what we did and said when we went up to testify, which was some time in 1960, as I remember. It could have been '61, in terms of how long before they got around to us.
But about that same time, there came more and more questions about various drugs, particularly the tranquilizers. Valium and Librium were widely prescribed and widely used and widely abused. This was an alarming development in drugs, and this led both the House Interstate Committee and the Government Operations Committee in the House, as well as the Humphrey Committee in the Senate, to begin these various investigations. They took a tremendous amount of Larrick's time and effort for a good period of time.
During all this time, he had really no one running the Bureau of New Drugs. Ralph Smith was in and out as a substitute; Arthur Nelson did it for a while. The money to hire new physicians didn't come until after the '50s when the budget started to improve. So they were very short-handed over there. As a result, a lot of those drug problems simply got out of hand. So when the Government Operations Committee began investigating the thing, they would call for the files and they would find in there that some of the employees had made certain recommendations that were not followed up on. In other words, it was a failure of real follow up on problems that were fairly well recognized by the department itself. So he had a lot of that.
He finally got Joe Sadusk as his medical director. I don't know exactly what year that was, but it was before the '62 Amendments were passed. Joe came from George Washington University. He was a very personable man, but very close to the PMA (Pharmaceutical Manufacturer's Association) and responded a lot to the PMA's desires. The role of Sadusk and Larrick in these things really came to a sharp head in connection with the Parnate case. That was a tranquilizer put out by Smith, Kline, and French, and very widely prescribed in the early '60s. All these tranquilizers were widely prescribed. But this one was widely prescribed, and then it turned out to have a very unique hazard to it. If it was taken with cheese and other products of that kind, it caused these reactions, and was a source of causing strokes. So it was a life-threatening kind of thing.
The agency proposed to take the product off the market, and Smith, Kline, and French demurred and came in with a lot of arguments. During the unfolding of that case, Sadusk became our medical director. He, instead of recommending that Parnate be taken off the market, recommended that it be severely restricted in labeling and continued on, which was what was done. That was probably the right thing to do, but it still didn't sit very well with the Congressional people who thought that there just weren't any adequate and well-controlled studies to justify the continued marketing of Parnate.
Then there was a row about the meclazine, cyclazine sort of thing, and there was kind of an uprising in the Bureau of Drugs by Barbara Moulton and John Nestor and others who were bad-mouthing the thing. All these things contributed to the investigation. So Larrick spent a tremendous amount of time with that in his last few years. The major thing that he had to do was Krebiozen, to put the money there and to put the effort there that was necessary to push that case. That took a lot of money and a lot of field effort to do that. Secondly, he had to get the food additive, color and pesticide amendments going, to equip the field to cope with those new kinds of problems in terms of scientific abilities and people. And thirdly, for the agency to grow with this new appropriation money. He did those things.
But with the enactment of the 1962 Amendments, indeed, even before the enactment of the 1962 Amendments, after the exposé in June of 1962, I believe it was, of the Kelsey Krebiozen episode . . .
FL: Krebiozen or thalidomide?
WG: Thalidomide. When the Congress looked at thalidomide, it was obvious that we weren't doing enough on investigational new drugs. So even before the enactment of the thing, we pulled out these regulations that we'd been trying to get the Bureau of Drugs to adopt for a long time and put in the new regulations. We couldn't get any consensus from our medical people on what ought to be done about investigational new drugs. Before '62, all a person had to do was certificate himself as an investigator and sign a statement that he would use the drug for experimental use only and that he would make reports back to the sponsor. Nothing to us, no obligation to report, even to tell us he was an investigator.
So a whole new era came out of the thalidomide episode. That case showed that the companies were spreading these investigational new drugs very widely, that they were using investigations as a pre-marketing opening of a lot of access to a lot of doctors who were really not investigators in any sense of the word, and that they were not keeping close track on either what was happening abroad with the drug or what was happening here with the drug. So all those things merged into the investigational new drug regulations.
Essentially what those regulations require is that there be an orderly and rational investigational plan executed with respect to these drugs. First, you have to identify what the thing is, how it's standardized, what's known about it from pre-clinical studies, and what's known about it in terms of possibility to introduce in demand. Then the investigation for man involved three stages: one, the initial introduction of the drug to see how it's metabolized and handled by man; two, to wider patient population to get kind of a handle on toxicity; and three, the definitive clinical trial. It was recommended to us that we have a phase four, which we rejected. That would have been a more widespread clinical trial. We thought that the requirement for reporting and the ability to withdraw the application if anything came up there was an adequate substitute for phase four, and we didn't want the investigation to be commercialized like that phase would have been. So that wasn't adopted.
Those regulations were proposed in August, I guess, before the October enactment of the Kefauver-Harris Drug Amendments. We got tremendous opposition on the thing. Every organized piece of medicine came here arguing that they were responsible people, that they didn't need any government supervision, and that the record keeping and reporting was onerous and would cut down the development of new drugs. We had a deaf ear to all that. We did provide that an investigator would have some access to inspectors that were scientifically trained. That was one sop that was put in there. But essentially, those regulations were proposed in August and were finalized in October, right about the time of the enactment of the '62 Amendments, and were put into effect with Krebiozen almost immediately, and with a lot of other people along the same time.
The next thing that had to be implemented was deciding what to do about reviewing the drugs that had been introduced through these years without any proof of effectiveness. There was a big argument between us and the industry over the right to do that. They thought that the grandfather clause was absolute; we insisted that it was not absolute, and that we were not going to go along with that, which we did not. We put out this regulation in '62 or '63 on record keeping and reporting to try to make a requirement of every company that had a New Drug Application any time in the past was to do a self-audit and report to us whether the drug was marketed, whether it was still marketed, what changes had been made, what the basis for the changes were, whether they'd been reported to Food and Drug, whether any changes in the labeling had been made, and this was to update the whole thing.
Of course, we got a lawsuit immediately from the drug industry about that, they didn't want to have anything to do with that. That went along for a while until it became pretty much moot after the developments on Panalba and that group of drugs. But that lawsuit did slow down the influx of those reports, but having put those regulations out, it put the drug industry on notice that it was their responsibility to come up with the evidence of effectiveness.
Next was the record-keeping provisions, how to handle an immediate report, how to handle a routine report, how often to report--all that was covered by the record keeping and reporting. And then the business of the clinical trial. As I've indicated, most of these regulations were put out under Larrick's regime. The drug advertising regulations, for example, were put in at that time. All the regulations to implement the '62 Drug Amendments were enacted within a relatively short time, that is, promptly taken care of. But there again, we did not follow through on that, and Larrick got an awful lot of static about what was happening with these various regulations. And the answer was that we had our hands full with litigation with the drug industry about the regulations, and that was what was holding things up.
Larrick retired in 1965, and then for the first time, we had an outside commissioner--the first time in my experience, and my experience goes back almost to the beginning. But this was the first time from the beginning that the agency had had an outside commissioner. This commissioner was Jim Goddard, who was at that time director of the Center for Disease Control, I think they called it, down in Atlanta. He was a public health officer. He was a colorful person. He came in in about February of '66, as I remember. It was while the Krebiozen case was under trial or about to go to trial in Chicago. He came in with a real stir of activity. He had a speech writer named Ted Cron who was a very gung-ho sort of a person, somewhat influenced by the public interest movement and somewhat anti-PMA certainly.
About the first thing that happened when Goddard got in was the retirement of several of the top people: Malcolm Stephens, Ken Milstead, and others who considered that they were not being consulted or brought into the decision making, that Goddard was kind of going his own way with Cron's advice, and was just being his own man, and indeed he was.
FL: Didn't several of those people actually retire before Goddard came? Steve (Stephens) and Allan (Rayfield) and a number of those, recognizing that a commissioner was going to come from outside?
WG: I don't know. I know that Milstead was around for a while. I'm not sure about Malcolm.
FL: Steve said he announced his retirement before the commissioner did.
WG: Did he?
FL: Yes.
WG: Well, in any event, I think the reason Steve did was that he had expected to get to be commissioner, and he'd been told he was not going to get it. As soon as he was told he was not going to get it, he retired. Now the atmosphere there was such that all these investigations had drawn the credibility of the top leadership of the agency into question. That's why it was decided to go to the outside and to put Goddard in there. Goddard was a colorful, public affairs type; he got along well with the newspapers and was prepared to beat on the industry a little bit, which was what the agency wanted done at that time.
FL: Could anyone from within FDA have taken over the job and done what needed to be done at that time?
WG: Oh, yes, I think so. But that wasn't an option. The option was that they were going to go to the outside. They wanted to go to a physician, and they wanted to go to someone who would have a break with the past and would give a new urgency to the program. That's why they brought Goddard in there.
FL: There was some speculation at the time in the Trade Press that a man named Goodrich might be named for it. Was there ever any formal approach to you?
WG: No. I talked with the Secretary, and what he said to me was what I've just said to you: that they wanted a new person, they wanted it to be a medical doctor that they hadn't had before, and they wanted it to be an aggressive person that would really shake the agency up somewhat, and that Goddard had caught their attention through some of the actions at CDC. So that's why they got him.
Soon after he came in, about his first step was to make a bunch of speeches to the various industry groups. They were hard-hitting, mean-spirited speeches. I mean, he in effect called them crooks and in effect said that they were a sick industry and that they needed to heal themselves and a lot of things needed to be done. He went through the whole rigamarole, and that, of course, interested Fountain in holding a series of hearings on what he was going to do in various areas. This made him concentrate his effort, his attention, early on to these rules. He came in here with the idea that he would rewrite all those rules and all that stuff, but he became convinced fairly early on that he couldn't ever improve on that, and that he would have to go along with what was on.
But the first thing he decided he had to do was get on with the effectiveness review, and coming from the PHS, he was able to put a latch on a bunch of PHS physicians, that is, people who had been educated at PHS expense and were serving out their time with PHS to keep from going into the army. So he was able to draw on 100 people to undertake the review. At the same time, he was able to get the National Academy of Sciences to be interested in this, which Larrick had tried and had not been able to. I mean, they just wouldn't have anything to do with it. As a matter of fact, Crawford tried to get them to become interested in this, and they wouldn't do it. But when Goddard came on and got all this publicity and got these doctors around, the National Academy did organize the Efficacy Review Study.
Goddard had the standing and the public attention to this problem to a degree that meant that he could begin moving that along. So that review started in '66, soon after he got here. Again, the call was for the data to be submitted, and that to be turned over to these panels, and the panels then to make a report back on what they found about this.
The panels were independent beings, if I may put it that way; that is, they were volunteer consultants by and large drawn from the Academy and were serving on panels as consultants. I guess they were paid like regular consultants, but there were several panels organized. The young doctors who were on temporary assignment had the responsibility of drawing together from the files what was in the New Drug Application, what the company had submitted, and then the panel would take all that data and then would make a recommendation on what ought to be done. Their procedures were certainly not due-process-like; they were doctor-like. That is, they would meet around a table and one of them would say, "Well, I think this about this drug," or that "so and so is an expert in this drug," and he would give his view of it. That way, the thing got underway.
One of the first ones they reported on was the bioflavonoids, which we'd always considered to be inert substances. But they were on sale, and that was the first sign that we were going to have a big upheaval in the marketplace with this. Rutin and other bioflavonoids were selected. But the thing really came to a splash when the committee made its report in 1968 on the antibiotic-sulfonamides combinations, and from there to the antibiotic combinations. They reported that all those combinations were irrational. We knew that; everybody that knew anything about medicine at all knew that. But the idea that we could roll back that much of common wisdom in the medical profession--it just didn't seem like it was going to take place.
We did put out, though, a statement of policy on combination drugs, which we were able to get the Bureau of Medicine to agree on. The Bureau of Medicine was just like the AMA on this. They didn't think that you could tell doctors that they ought not to use these combinations, that the doctors already knew that, but they were going to use them anyhow. They may do some good, and the kind of harm they would do was not fully documented, and therefore, they would tend to go along with that.
The first of those reports from the panels came back in early '68, and then the problem was, how were we going to implement them? We put out a statement on what we would do: we would send them to the company and ask the company to comment; and then we would classify the drugs in one or the other of these categories. If they were classified ineffective, we would begin the steps to take them off the market; if they were possibly effective, they'd have so much time; if they were probably effective, they would have so much time. The way the mechanism was set up was to relieve the immediate pressure but keep the ultimate pressure on them to come up with a medical justification for the claim.
Several of these very important items were publicized and the time for action came due sometime, as I remember, in about January or February of 1969. About that same time, there was a hearing up on the Hill about, "How are they doing?" and, "Are you damn sure you're going to go ahead with . . ." In other words, the pressure was on us to really hang in there with that. And of course, Goddard and the others testified they were going to hang in there, and "we're going to do the deed."
Herb Ley was brought in as director of the Bureau of Medicine by Goddard, and he was the one that was down in the lines there with the responsibility for seeing the thing through. We publicized that, announced that these drugs were irrational, and that they were to be taken off the market. Of course, that precipitated a whole series of lawsuits, all of which I defended. The first ones that went to court were the sulfonamide-penicillin mixtures up in Delaware. It seems like we had another one there before that one. But anyhow, there was a series of these cases in which they filed suit, alleging that they had been denied opportunity for a hearing and a right to defend these drugs--in any event, that our regulations weren't clear, these panel things had been ex parte, and they'd not been able to have a hearing--all that whole stuff.
Well, we worked our way out of that, but the major case that came along was Panalba. That, through a series of events, took root. We decided that instead of going ahead without any hearings whatever, we would try this shortened procedure of really saying, "Now, we'll give you a hearing. You come in and I'll tell you what I think about your presentation, what you've presented. Present your written stuff, then we'll decide whether there's any issue of fact." And when they would present the written stuff, we then decided we would have a hearing in which Herb (Ley) would preside, and he would have a doctor-to-doctor discussion with the Upjohn's doctors. And Stan Timko, their lawyer, and I would be the bystanders. [Laughter]
In preparation for that, we prepared an analysis of their filing, and it was the first time I think that Food and Drug really put its mind to analyzing the documentation for these drugs, what it really consisted of, and how it measured up to the new standard of adequate and well-controlled studies. So we decided in the Panalba case to go ahead and have that hearing, which we did. And then we put out a tentative order explaining our reaction to what their paper presentation was and what their oral presentation was, and in ordering the product be taken off the market by X date. We were pressed in all this, again, by the committee up at the Hill to go ahead and take the action--don't delay--and we didn't.
So that case moved pretty rapidly. The first notice was published in '68, and they had some time to come in, and it went to the hearing in early '69, and the order to withdraw it from the market was in about May of '69. Then it went to the court of appeals, and it was argued in October of '69 and decided in January or February of 1970. So we moved that along pretty fast, and that made it possible to see the end of the tunnel, that is, that we were going to be able to go through this thing without getting involved in a thousand and one hearings which would have kept us forever.
During the consideration of Upjohn's product, it became necessary for us to articulate where we stood on adequate and well-controlled studies. That order on Upjohn did explain that, and the court of appeals sustained it. But then PMA filed suit in Wilmington, Delaware, on the ground that we didn't have any regulation on that and we were trying to proceed without . . . We'd put out a regulation without asking comment, consistent with what we'd done in Upjohn. And the judge, Judge Latchum, took a dim view of this. He was pretty hard on me on that and on the sulfonamide-sulfathiazole, but he never really went over the cliff on it. He looked like he was going to jump out of the traces two or three times, but he didn't.
What he ruled was that we didn't give notice and that, therefore, the thing was not legal. When I decided to withdraw it and have a hearing, he was tickled to death. He was afraid I was going to go on to the court of appeals and reverse him there. He thought we were right on what we were doing, but that we hadn't been through this. But in order to get these new rules out, first of all, we had presented an affidavit in support of the rule we issued without a hearing, explaining how we got there.
Bill Devers, who is a teacher down in Georgetown University and was a part-time consultant for us, and may still be, was working here, and he is quite a student--he's a teacher kind of a fellow, and he's one of the world's leading experts on analgesia. He was on the National Academy of Science's panel on analgesia. Even in those days, he was really a very well controlled expert in working on analgesia. He was really put to the test on how to devise a study and how to make the results be equal. So he gave us an affidavit.
So when we came back down to go through the administrative process again, to put these rules out after notice and opportunity to comment, we filed that affidavit with it and explained this was where we were, and that we wanted people to comment on whether we were right or wrong on that. The comments that came back were, "Well, those are probably right"--of course they were all taken right out of the scientific literature--"but they're too stringent; it should be applied with some rule of reason." Well, we put in that it would have to have an adequate and well-controlled study by those rules or explain why your thing was the equivalent. "What you're telling me is that what I've in effect saved that day." Then we went back to Judge Latchum and he upheld us in the rules. From that stage on, the pattern of reviewing for effectiveness was set. That's the story on that.
On the advertising regulations, this, too, was a matter of considerable interest to Goddard and was a matter of considerable publicity, which he was also interested in. After the '62 Amendments were passed, this was of course our first experience with drug advertising, particularly prescription drug advertising. That had always been the role of Federal Trade Commission; we'd never done anything about it. One of the proposals in the legislation was to hand that over to them, but we held our lines and we acquired jurisdiction over the prescription drug advertising.
Well, the first thing we had to do was to put out the advertising regulations after notice of public hearing, which we did. We put out a proposal. We got ready for a hearing, and in getting ready for the hearing, we used a lot of the stuff that had been put in the testimony of the Kefauver hearings--about what advertising was all about, how it was being carried out, what there was to support it, why it was lacking in support by and large, why it was unbalanced, and why it needed major improvement.
Dr. Dowling was one of the major spokesmen who elucidated that point of view before the Kefauver hearings, and of course, he was a consultant to us. I believe he was teaching in Chicago at that time.
FL: That's Harry Dowling?
WG: Harry Dowling, right. When we had the pre-hearing conference on the prescription drug advertising, the industry was represented by Gary Gesell who is now a district judge here in the District of Columbia. He was with Covington-Burling and was their chief counsel. He was prepared for a hard fight until he began looking at the advertising. As a matter of fact, we put in the record what we had and sent the inspectors out to get additional advertising from the companies. Well, he told them all not to give us anything, so that came to a crunching halt with us. We were going to put that in evidence, that he had refused to allow the collection of the samples, and that therefore we were right.
To make a long story short, he decided fairly soon that he would compromise with us on those regulations rather than go to a hearing where it would give them more and more bad publicity about their advertising. They'd already had plenty of bad publicity from Kefauver, and they didn't want any more bad publicity about this. This was before Goddard's time, but this was a matter that was being followed rather closely by the press; they were very much aware of what Kefauver had done. Morton Mintz was still very active in writing all this stuff. So we were getting a lot of publicity out of it.
The law provided that any prescription drug advertising should contain a brief summary, a statement of effectiveness, side effects, counter indications, warnings, etc.--a brief summary, in accordance with regulations published by the Secretary. So we had the choice of trying to do this class by class, specify just what claims could be made for what drugs, how they'd be made, and what kind of counter indications, warnings, and other things that would have to accompany them. We decided that that would take too long and wouldn't really get us there with the speed that we had in mind. So we adopted an alternative that said that any prescription drug advertising had to have a brief summary that was consistent with, not contrary to, the official brochure. It would have to give in fair balance a statement of effectiveness, side effects, counter indications, and so forth.
Well, the fair balance, of course, really didn't tell them anything in the way they wanted, but it told them one thing: they could not leave out or minimize these various things. And that's what we were explaining at the hearing, that we weren't against graphics, we weren't against photographs, we weren't against any of the advertising techniques that were being used there, unless they misled or put a different slant on this. We thought they could determine what the message was, but we knew damn well we couldn't determine what the message was. Therefore, we were going to hold them to a fair presentation of that official brochure.
We'd already had full disclosure under the 1960 regulations, and that was in effect in the PDR. So the PDR had already begun to improve by '62. I guess '61 was the last time it was really bad. By '62, they'd begun to improve. So they first tried to ridicule the regulations, saying that we wanted them to make all advertising closely-knit and single-spaced that you had to read with a magnifying glass. They brought up some adds that had been in use back in the early days in which that technique was used in the medical journals and so forth. But with the onset of modern advertising, the advertising was an entirely different breed of cat.
So we did try to accommodate that and were able, through that accommodation, to get the thing into effect. In order to get them to agree, they brought in a series of ads that they had, and asked us to react to that in terms of fair balance. Bob McCleary was the head of advertising at that time, and he and I went through each one of those ads for them, saying, give them an idea of what it is we thought was wrong, and how we thought they might comply. Well, having heard that on the record, they decided that they could live with that and that they could do without all the other publicity, so the advertising regulations were placed into effect.
Before Goddard came here, McCleary was already in the process of making some advertising cases; that is, he was picking out ads that were not satisfactory in his way, and he was a very, very intelligent physician who had a background in advertising on Madison Avenue. So he knew how they were developed and he knew what went on about these ads and who was calling the shots, who was doing the layout, the storyboard, and that they fully understood what they were trying to put across there. But McCleary was also a stickler for detail, so he brought in some of his early ad cases, details about the ads that were kind of--he was right, but they were kind of hard to explain to a judge and to a jury. So we didn't have very much luck getting the Department of Justice to file those cases. So that had pretty much disillusioned him.
When Goddard got here, he was quite interested in the advertising. And McCleary presented to him some of these cases. Goddard was a man of direct action. He'd call up the president of the company. He'd say, "I've got this ad. I want you to come down here with your scientific people and I want to go over it with you." And when he got here, he would present to him what McCleary said about it and say, "What have you got to say about it?" Well, of course, many times the company president didn't know anything about that, and he was embarrassed by what he heard, and his medical people were embarrassed because they'd been called on the pan in the presence of the president getting a lecture. So that worked very, very well. We told them that we had taken a sample of the drug and if they wanted to talk with us, we would withhold the seizure until we could talk, but otherwise we were going to file a seizure of the product. So that's how the drug advertising regulations moved ahead.
Well, through a lot of what we said on the record at the hearing, through a lot of experience over the next year or two, it became obvious that we needed to be more specific in the regulations. So we proposed and ultimately adopted a new series of regulations, this time specifying those kinds of claims that were absolutely forbidden, and those kinds of claims that were allowed, and those kinds of claims that had to be qualified. We dealt with such things as use of statistics, use of animal studies, use of all other techniques that we saw that were contributing to an unbalancing of the ad and getting across a bad story.
We got the attention of the companies right away, and we got the attention of the advertising, the creative people. So they invited us up there to New York to speak to the New York Advertising Club. McCleary and I both spoke. I had obtained from Dr. Jean Lockhart, who was then in the Bureau of Drugs, and another doctor who worked with her who is now dead, gave me the ads for the ten drugs introduced within the last year that had become best sellers in their first year in the marketplace, and gave me an analysis of the ads' follow up, and every one of them was misleading. So I took that as the theme. I said, "I want to show you what's going on, how we look at it, and it'll tell you what we think of what you're doing here." That was a blockbuster, too. They had ads for avental, which was a new tranquilizer; they had two for birth control pills--they were very much promoted at that time; they had one for Enovid, one for one of the other competitors; there was one for a combination antibiotic-pediatric formulation; there was one for a very widely prescribed tranquilizer. But to make a long story short, each one of those ads had a gross exaggeration of what it was for.
For example, the one on the combination antibiotic for pediatric use showed a picture of a pediatrician at 9:00, 10:00, 11:00, 12:00, 1:00 with different patients. He was giving them all the same shot. [Laughter] We said, "Now, you've got to understand we're not fools; we can read what you're saying." The avental was a new tranquilizer by Lilly, and they were really embarrassed. They had picked up the old saw that then was used for promoting tranquilizers--sadness, crying--just a bunch of symptoms that are ordinary frustrations of daily living. They equated that with a reason to prescribe avental. Oh, they were adamant that all they were presenting was a galaxy of symptoms that added up to depression and that they were not recommending it for the everyday frustrations of living, but only for serious depression.
But this did get the attention of the advertising people, and the advertising improved substantially. It's still got a long way to go; you're still seeing these same issues, but anytime the agency wants to do anything with that, the rules are out there. It's tempting for the agency to treat that as, "Oh, hell, that's not important. You know, doctors don't really go by advertising." My answer to that was-I got this from Jean-"you can be assured that if the advertisement doesn't sell, it will not continue to run." [Laughter] So I said that to them. "We take the view that if it doesn't sell, if it's not being persuasive, we won't be seeing it again. If it disappears, why, that'll suit us fine. But as long as it continues to run and we've got this to say about it, we think it is doing these things."
The agency was tempted like others to consider advertising as a part really outside of the practice of medicine. It was a necessary part, all right, but it wouldn't really have any health consequences. We became convinced that by selling all these drugs with a lot of advertising, it was a major factor in why people were choosing the drug. It was a competitive selling thing, particularly in the case of the birth control pills, for example, where they were sold against one another as more effective--all were 100% effective, so none of them was more effective; better safety--they were all the same safety. And they all had the same brochure. It was this kind of advertising that was leading doctors to shift their patients from drug to drug and was confusing their understanding of what the drug was all about. And in the case of tranquilizers which were being used very, very widely, they were encouraged to prescribe these things for these minor conditions which led to the over-prescribing that we were seeing with Valium and Librium.
We have talked about the advertising regulations and why I thought that some regulatory action in the heel of prescription drug advertising made a lot more sense than regulatory action in other ways, my reason being that prescription drug advertising is a very high-intensity operation, and it must sell drugs or it wouldn't really be anything under the order of magnitude it is now. I think that because it's giving a direct message to the prescribers, the agency ought to spend a lot more effort in watching that. And particularly one thing I recommended--I don't know what they're doing now--was to watch the advertising of a drug soon after it's approved to make sure it gets off on the right foot. If it does get off on the right foot, then without any exaggeration, the chances are it's going to be all right from there in.
Having talked about the adequate and well-controlled clinical study regulations, I want to be sure I attribute to Herb Ley full credit for that. While it's true I made some suggestions about the Panalba shortened procedure and suggested to the Bureau of Drugs, the Bureau of Medicine, that they study this situation to get the affidavit which we got from Devers, it was Herb Ley who really put that thing through and gave it some scientific stature that it otherwise wouldn't have had. Paradoxically, Herb was doing this, which is one of the greatest things that ever happened to Food and Drug, yet at the same time he was losing his job over cyclamates.
I don't see any real reason to go into that whole cyclamates thing, because the history of that is so well developed in that court case. Every scrap of paper that had to do with cyclamates is in that court case, and as you know, the court of claims first ruled against us and ultimately ruled for us that everything we did in that case was right, and that the other side had no claims for damages. For that reason, I would simply defer the cyclamate discussion to that as a better source of history than anything else. While I testified in the case, I helped the Department of Justice identify the people who were really involved in it, and the history of that is very well laid out there.
[Interview with William W. Goodrich: Part 1 | Part 2 | Part 3 | Part 4 ]
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2002-JUN-04.