Dr. Stanley Plotkin



Dr. Stanley Plotkin

The following interview was conducted May 19, 2016 at the home of Dr. Stanley A. Plotkin in Narberth, PA. The interviewer is Karen Torghele.

Dr. Plotkin begins by describing his background and path to public health work at the Center for Disease Control.

PLOTKIN: In 1957, I finished my internship in Cleveland and was going to a residency when I was told by a fellow by the name of [Dr. David H.] Dave Carver about EIS [Epidemic Intelligence Service]. So I applied to the Public Health Service. I actually was going into the Air Force at that time, but I applied to the Public Health Service to the EIS and was accepted, and the Air Force gave me up to CDC [Center for Disease Control]. After the training course at CDC, we were offered the list of assignments, and one of them was to the Wistar 00:01:00Institute in Philadelphia, where the CDC had an Anthrax Investigations Unit. I was not particularly interested in anthrax, although it turned out that it was extremely interesting, and I became involved in the outbreak of inhalation anthrax in New Hampshire, which was published and which showed the efficacy of the U.S. Army's anthrax vaccine.

The reason why I was interested in going to Philadelphia at the Wistar Institute was because I had read that [Dr.] Hilary Koprowski was moving from Lederle Laboratories to Wistar. Koprowski was a virologist who was at Lederle working on 00:02:00the first oral polio vaccine. His writings were extremely interesting. He had a great writing style and also was a very charismatic character. At any rate, I arrived at Wistar in the anthrax lab and, as I said, became involved in anthrax, but after a few weeks or so I went to see Koprowski and asked him if I could work in his lab and learn virology, which he readily agreed to. Of course, I had to get some permission from the people in Atlanta, but that was not too difficult.

At the time, as I'm sure you know, [Dr. Alexander D.] Alex Langmuir was the head of EIS, and he was clearly someone who was interested in a variety of things, including polio. At any rate, I spent three years in Koprowski's lab developing oral polio vaccines. Koprowski was testing his vaccines at that point in what was then Belgian Congo, now the Democratic Republic of Congo. I had two 00:04:00involvements. One was, as I said, creating new attenuated poliovirus strains in the laboratory, and the other was to go to Congo and to assess the results of oral polio vaccination, which of course was an interesting experience.

I have to say that Alex Langmuir was not too happy about my involvement, because Koprowski was in competition with [Dr. Albert B.] Sabin and with the folks back at Lederle, and so I guess there was some hesitancy about CDC favoring one or 00:05:00the other of those contestants. Nevertheless, he did come to Philadelphia at a certain point and met with Koprowski and with Sven Gard, a Swedish virologist who was then visiting Wistar. There were some more or less heated discussions about polio vaccines, but ultimately Alex agreed that I could continue to work in the laboratory on polio vaccines. However, my trip to Congo had to be done as a vacation from CDC, which was okay with me because I really wanted to go, and 00:06:00it was a fantastic experience, resulting in papers analyzing the results that showed for the first time that the oral vaccine had limitations in tropical areas. That was not 100% effective, by any means, in those areas. However, it did prevent a great part of the high incidence of polio in Congo.

I had a firsthand or up-close experience of the competition at the time, in the late '50s, between the three developers of oral polio vaccine and, of course, [Dr.] Jonas Salk and the inactivated vaccine. My own participation stopped at 00:07:00the point that Sabin strains were licensed in the U.S. and it was clear those strains would be preferred to the Koprowski strains, and I moved on to other things. I know that you have talked to Neal Nathanson, who preceded me at EIS and who was very much involved in polio, but from another point of view. That really is a summary of my own involvement when I was at CDC. Of course, CDC has been heavily involved in polio eradication later on in history, and I think it's 00:08:00fair to say that without CDC, we would be further from eradication. We are, it appears, close to eradication, but we would certainly not be in that position without the efforts of CDC, because it's CDC personnel, by and large, that have worked and participated and planned the eradication.

[Dr.] D.A. Henderson, by the way, was under Langmuir at CDC in EIS at the time. This was before his own personal involvement in polio, but obviously he played a 00:09:00role later on, and that was after smallpox.

TORGHELE: What point of view did Dr. Henderson have? Did he prefer one vaccine over the other?

PLOTKIN: Well, I think it's fair to say that he was not a great partisan of the oral vaccine, and it was probably the influence of [Dr.] Ciro de Quadros that 00:10:00ultimately influenced him. All along, there's been the competition between IPV [inactivated poliovirus vaccine] and OPV [oral poliovirus vaccine], although from my own point of view they're complementary, and I always thought that it was stupid to think about using one exclusively rather than using both. I think probably D.A. was skeptical about the ability of OPV to do what it was supposed to do, but I think you really have to ask him, because I do remember there was 00:11:00one international meeting where he spoke against eradication, and that was fairly late in the game, I mean, eradication with OPV. At any rate, polio has always been a controversial area.

It started with IPV. CDC was not particularly involved in the testing of IPV originally, and by the early '60s, when OPV came along, I think CDC became more 00:12:00involved at that point, and then, as I said, it has been personnel from CDC who have been very instrumental in the strategies around the use of OPV and in collaboration with PAHO [Pan American Health Organization]. After the early '60s, that did not involve me personally.

TORGHELE: Well, if we can go back a little bit more, you mentioned that you were interested in public health for a while before you joined the Epidemic Intelligence Service. How did you get interested in public health?

PLOTKIN: Because of two books that I read when I was fifteen. One was Microbe 00:13:00Hunters by Paul de Kruif and the other was Arrowsmith by Sinclair Lewis. At that point, I decided what I wanted to do in life. As I said, when I finished my internship I still wanted to do what I just said, but I was unsure about a way forward, and there was the issue of military service at that time during the Korean War, so it was a lucky accident that [Dr.] Dave Carver was also at Cleveland Metropolitan. [Dr.] Fred Robbins was the head of pediatrics at 00:14:00Cleveland Metropolitan, which is why I went there and why Dave Carver was there, and where I learned about tissue culture, which was fundamental to both polio vaccines. Maybe it wasn't such a strange coincidence, but hearing about EIS convinced me to get out of military service with the Air Force and join the Yellow Berets, as we called them at CDC.

TORGHELE: What was Fred Robbins like? He had won the Nobel Prize.

PLOTKIN: Yes, with [Dr. John] Enders and [Dr. Thomas] Weller. He was sort of a jolly type, strong personality, frank, and clearly a leader. That's about all I 00:15:00can say about him.

TORGHELE: Was he a good teacher?

PLOTKIN: Oh yes, he was a good teacher. His science after cell culture was, in truth, not much. He got involved in administration et cetera, and never really returned to the laboratory much, as distinct from Weller and Enders.

TORGHELE: When you got to CDC, did you have extra training when you go there? 00:16:00Did you go through the EIS training course?

PLOTKIN: Oh yes, sure.

TORGHELE: Who were your teachers in the course?

PLOTKIN: I can't give you a list, but Alex Langmuir was the predominant person, as I'm sure you've heard, a strong personality, certainly the most important American epidemiologist of the twentieth century, and an inspiring teacher who made an impression on everybody. He's certainly responsible for the success of EIS. He and I had our disagreements, but that doesn't in any way inhibit me from respecting what he was.

TORGHELE: So how long after you joined EIS was it that you went to investigate the anthrax in Philadelphia?

PLOTKIN: I went from the training program. Towards the end of the training program I was called to D.A. Henderson's office and told that there was an anthrax outbreak in Vinita, Oklahoma, and although I was going to leave for Philadelphia, that I should make a detour to Oklahoma to study the outbreak with a veterinarian from CDC. That's what I did. I went there and that gave me a 00:18:00field experience about anthrax.

TORGHELE: Do you remember who the veterinarian was? The only one I can think of was Jim Steele.

PLOTKIN: It wasn't Jim Steele. It was a younger person.

TORGHELE: Another EIS officer?

PLOTKIN: Well, I'm not sure whether he was officially an EIS. As I said, he was a veterinarian, so he may not have been.

TORGHELE: I was just curious, it's all right.

PLOTKIN: The name H-u-f-f- [Dr. Robert H. Huffaker, MPH, DVM, EIS 1957] or something like that. It's in my bibliography someplace, I could try to look it up. At any rate, from there I went to Philadelphia, and was only probably about 00:19:00a month after I arrived when I got a call from a pathologist in New Hampshire who had just done an autopsy on someone who had died of inhalation anthrax. So, of course, that sent me off to New Hampshire to investigate the outbreak. In the typical tradition of EIS, I went there knowing I would say little about anthrax. Phil Brachman, the head of the lab, was in Europe on studies assignment, so I just had beginning knowledge of anthrax.

I went up there and realized that it was not just a case, it was an outbreak of 00:20:00the disease. It was important because the Army had developed a vaccine, which had been distributed to workers in plants or factories that made linings for suits. At the time, I'm sure this is no longer true, but at the time those were made from goat hair, and the goat hair was imported from Pakistan and India, and some of the lots were grossly contaminated with anthrax. Many of the workers acquired anthrax, and so the Army was doing a placebo-controlled study of the 00:21:00vaccine. In that context, it was also of course important to show that there was protection against inhalation anthrax.

TORGHELE: That must have been interesting, to be able to use your epidemiology right off the bat.

PLOTKIN: As I said, it was not atypical to have a young person suddenly given a major responsibility.

TORGHELE: How did you figure out that it was the goat hair?

PLOTKIN: That was not difficult because, as I said, it was known that the goat hair coming in was often contaminated with anthrax spores. It so happened that we figured out that there was a particular lot that was grossly contaminated and spores were up in the air. We were able to culture them from the desk of the 00:22:00manager of the factory, as well as, of course, from everywhere else, but it was the people who were working to clean up the goat hair that were at most risk.

TORGHELE: Do you remember what action was taken after that?

PLOTKIN: Of course, ultimately the anthrax vaccine became a standard for people being exposed in the plants, but aside from that, the British had long experience with that sort of thing, and they had set up a facility through which goat hair was treated with formalin before going into the factories, which we 00:23:00did not have in the U.S. I think basically what happened in the U.S. was two things: one was that incoming hair was treated with more respect, with masks and better ventilation, and also of course synthetics replaced goat hair.

TORGHELE: Did you meet with any resistance from people, because you must have been very young, asking a lot of questions? Was that difficult at all?

PLOTKIN: I don't recall that particularly. I think coming from the federal government gives one some cachet. Of course, they were desperate for some help in New Hampshire. When they saw four deaths, as I recall, obviously everybody 00:24:00was pretty scared.

TORGHELE: After that, you began your work with polio with Koprowski. Did you have any other outbreaks during your time at CDC?

PLOTKIN: Anthrax, no. I was called to handle a couple of things. There was a prison outbreak in Pennsylvania, not of anthrax, but we decided ultimately it was somebody putting an emetic [substance that causes vomiting] in the coffee—and also a supposed case of anthrax, also in Pennsylvania, which I went 00:25:00to investigate, and that was nothing. Those are the ones that I remember.

TORGHELE: That must have been interesting. During your time, you came in 1957 and you stayed how many years?

PLOTKIN: Three years.

TORGHELE: So you would have been there after the Cutter incident.

PLOTKIN: Yes.

TORGHELE: Do you remember, was that talked about in your EIS course, for instance, or did it impact the work that you did?

PLOTKIN: It was certainly talked about, yes. I had no personal involvement in that. I think Neal Nathanson had a very deep involvement in that, but no, by that time, by '57, certainly the methods of making the vaccine had been improved 00:26:00to prevent a wild virus from persisting after formalin treatment. By that time, the vaccine was quite safe.

TORGHELE: Did you feel that there was any impact on other vaccines after the Cutter incident, that people were distrustful?

PLOTKIN: Well, I don't know about distrustful, but one of the results was that the FDA [Food and Drug Administration], which was not called the FDA at that time, but the FDA became much more powerful in terms of controlling production. What had happened basically was that each of the companies had carte blanche to 00:27:00make the vaccine as they thought fit, and there was really little in the way of federal oversight. Cutter was unlucky in the sense that there was some evidence that Wyeth also had some problems, but I think there was something like five different companies making the vaccines. It was a bit of a free-for-all, and if there's any positive thing to say about the Cutter incident it is that it increased oversight and federal control of vaccine manufacturing.

TORGHELE: Were there more consistent ways than it sounded like? Each of the five 00:28:00pharmaceutical companies used Salk's basic recipe for making it, but there were some variations.

PLOTKIN: Right, right. Sven Gard, whom I mentioned, who was a virologist, was critical of Salk's methods, feeling that they were not sufficiently controlled, and he went back to Sweden and made his own IPV using better controls, which the Swedes used. It was definitely a learning experience for everybody.

TORGHELE: Did you have any interactions with Dr. Salk?

PLOTKIN: Well, I met him on several occasions. You may have read the recent 00:29:00biography of him by [Charlotte DeCroes] Jacobs, I think her name is. I think it was a reasonably accurate description of Salk. He was not a brilliant scientist in the sense of having novel ideas, but he was a careful worker and I think he was sincere. In a sense, his fame became a negative thing for him in the eyes of other scientists, but later in life he became somewhat of a mystic. Anyway, what 00:30:00rescued IPV was what happened in France and Holland, where the vaccine was improved by growing the virus in cells on beads and by concentrating the virus, and thus making the vaccine more effective. IPV today is virtually 100% effective. It wasn't at the time.

TORGHELE: One thing I was curious about, too, was that Dr. Salk chose the Mahoney strain to develop the vaccine. That was the most virulent.

PLOTKIN: Yes. Gard disagreed with that also. Again, if you inactivate it properly it doesn't matter. I guess Salk's reasoning was that if a strain is virulent then you'll want to immunize against it, which would be all right if you inactivate it properly. Others chose to use different strains.

TORGHELE: Did you have any work that involved the vaccine-associated paralytic polio?

PLOTKIN: Paralytic disease? No, not really. Much later on, when I was working 00:32:00with Sanofi Pasteur in the 1990s, I was certainly involved in assessing VAPP [vaccine-associated paralytic polio] because Sanofi was making oral vaccine as well as IPV.

TORGHELE: Is that when you were working on the rubella vaccine?

PLOTKIN: Rubella was done in the '60s when I came back, actually, from a year in London, where I started work on rubella while doing a pediatrics residency. The 00:33:00rubella vaccine was developed at the Wistar, in was then my own laboratory. Koprowski was still the director, but at that point I was running my own lab.

TORGHELE: One other question I have for you that I'm going to ask for the CDC Museum's sake: do you happen to have copies of any of your Epi-Aids [requests for epidemiological assistance] that you wrote when you were an EIS officer?

PLOTKIN: Oh God, no.

TORGHELE: There are some EIS officers that kept all that. It's pretty interesting.

PLOTKIN: The only things I have for sure are papers that I wrote at the time. In terms of CDC data, I would have to look in my archives, so to speak. Downstairs, 00:34:00the archive room downstairs, I certainly haven't looked at that stuff for an eon, so I don't know. I can have a look, but I don't know whether I have anything that goes back that far.

TORGHELE: If you do look, just know that there would be very happy recipients of anything like that.

PLOTKIN: I will have a look.

TORGHELE: When you were doing your outbreak investigations, did you just do handwritten epi [epidemic] curves?

PLOTKIN: At that time, it was a typewriter and it was a secretary at the anthrax unit in Philadelphia. So we did a lot of things by hand, sure.

TORGHELE: Did you have much to do with the laboratorians at CDC?

PLOTKIN: No, not at that point. No. I mean, of course later on I certainly had contact with [Dr.] Olen Kew in the polio lab, and today I work with people in the rubella lab, but at the time, no, I don't recall a lot of contact. Also, at that point, you must remember CDC was not at Emory. It was in downtown Atlanta, 00:36:00and that was where I worked. There were laboratory facilities at Chamblee, but I don't recall ever going there, so I would have had little contact with the laboratory people.

TORGHELE: They were Quonset huts.

PLOTKIN: Well, so I heard. I may have been there once, but certainly not a lot.

TORGHELE: [Dr.] Morris Schaeffer was the head of labs and he had had polio. I know at the time they were two separate areas, epidemiology and lab. I was just 00:37:00curious if you knew of any of them. I know that you've been very active and involved with ACIP [Advisory Committee on Immunization Practices] and I wondered if you had any recollections or thoughts about how CDC's impact on that organization and vice versa, how they interact and how that works?

PLOTKIN: I think ACIP is fundamental to public health in the U.S. ACIP started out as a small committee meeting in a small conference room, but of course has expanded greatly. ACIP could not exist without CDC, in the sense that the information that goes into ACIP decisions pretty much comes from CDC and even 00:38:00the stuff that comes from manufacturers is essentially vetted, criticized by CDC people. So as I just said, ACIP could not function without CDC. There are committees like ACIP all over the world, but there is none that is as effective, because of the support that ACIP gets from CDC. The closest is the British committee, and I have some experience of the French organization, but they don't 00:39:00have nearly the support that CDC provides to ACIP.

TORGHELE: How did that develop? How did that relationship of collaboration develop, because I think it's kind of unusual?

PLOTKIN: Well, it just grew like Topsy. Especially after CDC moved to Emory and had facilities for large meetings and the ACIP, I don't know actually who made that decision, but the ACIP decided that it was a public meeting, so that there was complete transparency. Things just grew. The ACIP meeting today is much 00:40:00larger than it used to be, but that's in general a good thing, although sometimes it's distracting because of not necessarily very useful comments. By and large, everybody has a seat at the table. It's, I think, a strength, and I know that foreign visitors who come to attend ACIP are always struck by the synergy that is evident in the room.

TORGHELE: I wondered if it had to do with the leadership at CDC, or if you can 00:41:00think of people who might have made a conscious decision to have it work that way and facilitate it?

PLOTKIN: The people who come to mind are [Dr.] Larry Pickering and [Dr. Samuel L.] Sam Katz. Those are people who come to mind as promoting the openness and the synergy. I'd have to see a list of the chairpeople over the years. I think Sam was fairly critical in maintaining the openness and getting advice from everybody.

TORGHELE: I wondered, too, if CDC and ACIP are sort of self-selecting for people who tend to want to collaborate anyway.

PLOTKIN: Probably.

TORGHELE: I think we have covered your experience at CDC and with polio pretty much. I wondered, though, if you had thoughts about the polio eradication efforts, the global polio eradication efforts?

PLOTKIN: Yes, of course I do. Again, I'll be frank. I think it was a mistake to 00:43:00begin with, that is to say that the decision to eradicate polio was based on wrong presumptions about the disease and the biology of the infection. In that, I agree with D.A. Henderson's original views on the subject. Not that the eradication of polio isn't, in an absolute sense, a desirable goal. No one would want polio disease to continue, but the amount of effort and the amount of money that's gone into it, I think, could have been put to better use than the eradication of polio, which does not rate very high on the list of third world 00:44:00problems. That being said, after many years we seem to be on the verge of eradication, so I guess if you believed in it, you would argue that, okay, it's taken more time than expected and more money than expected, but the final result is the elimination of a disease. Well, that's true, so at this point it would be, I think, small-minded to severely criticize the effort, but if I were back in 1980 and had been asked whether this was worthwhile, I would have said no, frankly.

I do think that, although it has largely passed unappreciated, I do think that there have been lots and lots of polio cases caused by the oral vaccine, which is regrettable and is considered by the advocates to be, what's the word when the military kills its own people?

TORGHELE: Friendly fire.

PLOTKIN: Friendly fire, yes. I can't help thinking that that is not a good 00:46:00thing, but it has somehow not been particularly objected to. Again, in the long run we may well achieve the eradication that was hoped for originally. I think I would have been in favor of certainly more vaccination and more use of both IPV and OPV, if only to prevent a vaccine-associated paralysis.

You know, there are lots of things that can be said, and it's very controversial 00:47:00and people justifiably have different points of view, but when I was at Sanofi, one of the things that came up was that the people in Geneva were arguing that IPV was too expensive. The people at Sanofi, the commercial people at Sanofi, were telling me, well, if WHO [World Health Organization] said, we will buy a hundred million doses over X number of years if you reduce the price to X, then they could have worked with that, to drive the price down for volume, et cetera, but that discussion never took place. Of course now WHO, et cetera, is finding 00:48:00ways to use IPV, to use small doses, to use intradermal vaccination to try to reduce the cost, which I can certainly understand, but I think a better foresight could have facilitated a cheaper vaccine.

TORGHELE: And of course, what you must have come across in Congo was keeping the vaccine from going bad in the heat. What did you do about it there?

PLOTKIN: We had ice buckets. Leopold II was a terrible person in the sense of 00:50:0000:49:00his exploitation of Congo, and terrible things happened in the Congo early in the twentieth century. I have to say, when I got there in the 1950s, the Belgian public health system and health system was really admirable in many ways. They really had a well-thought, well-worked-out system of taking care of people in the hospitals and vaccinating correctly. It was a Belgian named Ghislain 00:51:00Courtois who convinced Koprowski to bring the experimental oral polio vaccine to Congo where good studies were done.

The first study in Congo was, I would say, not well-thought-out. Of course I can say that because I was not involved, but it was sort of ad-lib giving out the vaccine. It was really not terribly helpful. The one that I was involved in was a study in what was then called Leopoldville, and that was a good study, where we could derive efficacy data and safety data, et cetera. Because the first 00:52:00study was done in a rural area, which was very difficult to control, and Leopoldville was a city, it was much easier to collect data.

Anyway, the point I'm making simply is that the Congo was not the chaotic mess that it is today. It is really a tragedy to see a country which could be a rich country, which has lots of resources and which could be a tourist destination, go down the drain because of bad management. If there is anything to criticize the Belgians about, paradoxically, it's that they pulled up stakes and left when they were first pushed to leave, and the people who took over from them were in no way prepared to run the country. It's the other side of the coin of colonialism.

TORGHELE: That's an interesting perspective. Well, I think I picked your brain enough and it's been very helpful. Do you have any final thoughts or anyone else you'd like to mention that you worked with, or any final thoughts?

PLOTKIN: I would just mention, as you know, that the CDC polio laboratory has been crucial in the eradication efforts, just from the scientific point of view. The backup that, that lab has given to the science of polio and eradication, the 00:54:00study of VAPP, VDPV [vaccine-derived polio virus] and all that, that's been absolutely critical. So I think that's definitely something to say. I can't imagine that we'd be in the same position without that CDC support. In general, it's perhaps, in a way, beside the point, but my admiration for CDC in general is very high. There's no organization in the world quite like it, so obviously 00:55:00there are always things to criticize, but the world would be a far poorer place without CDC.

TORGHELE: And you were part of it as one of the elite Epidemic Intelligence Service Officers.

PLOTKIN: It certainly was a very important part of my career.

TORGHELE: Do you get back to any of the meetings they have in the spring?

PLOTKIN: I go to the ACIP pretty regularly, and have been there for consultations now and again.

TORGHELE: I'm sure they really depend on you, too.

PLOTKIN: I'm sure they have lots of resources.

TORGHELE: Well, I want to thank you for all your time and your stories and perspectives because you had a unique time in history with CDC. Congratulations 00:56:00and thank you from all of us who've benefited from your work on vaccines.

PLOTKIN: Thank you.

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