Dr. Neal Nathanson



Dr. Neal Nathanson

TORGHELE: It's May 18, 2016, and I am here in Philadelphia with Dr. Neal Nathanson. My name is Karen Torghele, and I'll be talking with Dr. Nathanson for the Global Health Chronicles Polio Oral History project. The David J. Sencer CDC [Centers for Disease Control and Prevention] Museum is partnering with the Emory Vaccine Center to gather these oral histories to document the history of the Centers for Disease Control and Prevention, including the era that covered polio, from that time in the early days in the '50s to present. So what I want to say in way of introduction to Dr. Nathanson is that I've been interviewing some other polio people, and on many questions what they said to me is, "Oh, ask Neal Nathanson that, because he'll know." So that's what we're here to do today.

To begin, I want to say welcome to Dr. Nathanson, and thank you for 00:01:00participating in this project. Your name comes up over and over again in the history of polio, and with all of the things that you did to contribute to the research and development of the polio program. What I would like to start with is for you to tell me a little bit about your background, and how you came to be interested in medicine and in CDC and public health specifically.

NATHANSON: Right, so after I graduated from medical school, I was at the University of Chicago doing a residency. This was in the early spring of 1955, and my local draft board in Cambridge, Massachusetts, sent me a notice that, under the then-existing doctor draft, within a month or so I was going to be 00:02:00drafted into the military to do my doctor draft obligation. Furthermore, they threatened that they might induct me as a buck private, in spite of the fact that it was supposed to be a doctor draft. At that point I was in a panic, because I didn't know what to do, and I had no time and I was very busy as a resident and I had no contacts.

So I went to one person I knew who was the chief resident in medicine, a fellow named [Dr. J. Thomas] Tom Grayston, who subsequently became the dean of the School of Public Health at the University of Washington, and I asked him, I explained the situation and asked him for advice. It happened, by just 00:03:00happenstance, that he had just completed a two-year tour of duty in Atlanta as an Epidemic Intelligence Service officer, so he knew Dr. Alexander [D.] Langmuir at CDC [Center for Disease Control], who was the head of the epidemiology program at CDC and who had invented the Epidemic Intelligence Service. And he called Dr. Langmuir and explained that I was desperately looking for a position, and it so happened, for reasons I never did understand, that there was one open slot in the program that had never been filled in the previous recruiting season. And Tom Grayston persuaded Alex Langmuir to offer me this slot, sight unseen.

So in March of 1955, early spring, I ended up in Atlanta and was assigned a desk 00:04:00in the epidemiology, it was the floor that the epidemiology department had. And I didn't have any assignment. Langmuir was waiting for someplace to assign me. And then on, I think it was April 11, 1955, the result of the Francis Field Trial, which is a trial of Salk vaccine, was announced, and the vaccine was shown to be both safe and quite effective. At that point there was a rapid effort to deploy some vaccine.

It was interesting, Basil O'Connor, who was the director of the NFIP [National Foundation for Infantile Paralysis], the National Foundation for Infantile Paralysis, who had subsidized this trial, different than nowadays, when the NIH [National Institutes of Health] or a drug company subsidizes. So the NFIP had subsidized the Francis Field trial. But Basil O'Connor, in his wisdom, had looked ahead and said, if the trial is successful there will be a demand for vaccine. So he had personally commissioned and paid five or six manufacturers to manufacture some prototype lots of Salk vaccine.

And in those days things were done rather informally, and so in Ann Arbor, Michigan, in the aftermath, the day or two following the successful trial, and 00:06:00informal, like, I wasn't there, I don't know the details. The decision was made, on the part of the public health service, I guess, to license Salk vaccine based on the trial, and also to license these lots of vaccine which had been produced on spec, commissioned by the National Foundation for Infantile Paralysis. So immediately they started distributing and injecting children. As I remember, the priority was given to the five- to nine-year-olds, because it was a limited amount of vaccine, and the vaccine was supposed to do the most good in these kids who have the highest-rate risk for polio. I can go on from there, but maybe 00:07:00I should stop for a minute and see if you had questions at this point.

TORGHELE: As I understand it, Tom Grayston was in the first EIS [Epidemic Intelligence Service] class in 1951. Is that right?

NATHANSON: Apparently, in my memory, but I may have this wrong, was that he had just returned, and that wouldn't quite make sense, but maybe he had returned a few years earlier. I know he was the chief resident, and some of the facts I never did know. We're talking about a long time ago, so I may have forgotten some of the detail.

TORGHELE: It sounds like it was sort of serendipitous that you knew him.

NATHANSON: Well, he was the chief resident. I never heard of the Epidemic Intelligence Service or Alex Langmuir or CDC. I just went to him for advice, you know, what should I do? One thing I didn't particularly want to do was spend two 00:08:00years, as my brother did, in Iceland as a general practitioner for the Air Force base that the English had in Iceland. So that was the kind of thing I wasn't particularly interested in doing.

TORGHELE: So you hadn't heard of the Communicable Disease Center before, or EIS?

NATHANSON: No, no. I knew nothing. All I knew was, I wanted to do something I thought would be a little more interesting than being a general practitioner at a military base somewhere.

TORGHELE: When you arrived at CDC, you didn't have an assignment, but did you have training?

NATHANSON: No. So I had been through medical school, and I was a reasonably competent clinical person in general medicine at that point, but I had no background in epidemiology, virology, vaccines, I knew nothing about any of that.

TORGHELE: You, of course, had heard about the polio vaccine, the Salk vaccine.

NATHANSON: Yes, I mean, but vaguely. I wasn't into public health or anything like that, so I knew about it vaguely, but remember, I was totally preoccupied with totally other things. Going through medical school, they didn't talk about that, particularly. They weren't into preventive medicine, and as a resident I was taking care of acutely sick patients in the hospital: heart attacks, diabetes, problems like that. And I wasn't into pediatrics, which is where vaccines were focused, and polio, remember, was mainly a pediatric problem. So, no, I was a totally blank slate on all the relevant information.

TORGHELE: How did it happen that you began to specialize in polio?

NATHANSON: Well, what happened, very simply, was, toward the end of April, 1955, there came reports that some of the kids, I think the first one was a baby or toddler from Chicago, was reported to have developed acute paralytic polio at a time when natural polio was at its very low incidence. I should mention in this connection that before the vaccines, polio in the United States was extremely seasonal, and the high point was in late August, early September. The low point was in March, something like February, March, April, and the low point, there was almost no polio occurring in the United States, paralytic polio or infections. A few cases in children or adults at that time of year were very 00:11:00notable, whereas in the middle of the summer nobody would've paid much attention. And then it turned out that these were individuals who had just received, a few weeks before, the newly distributed Salk vaccine.

So at that point Alex Langmuir decided to create a unit, and I'll explain what this unit was, called the Polio Surveillance Unit, and that was simply a single office in which sat the secretary, a woman named Maryann Lyle, myself, and I'll get back to that in a moment, and a statistician, who eventually became a fellow named [Dr. William Jackson] Jack Hall, who was also an EIS officer, because EIS 00:12:00had taken a few people who were statisticians as well as mainly medically trained people. But I was assigned to head this, well, first of all, Alex called this the Polio Surveillance Unit. He created that name and as far as being the head of it, he just designated me as the head of this newly created unit, just these three people.

And we were just down the hall from him, so he basically instructed us on a daily basis what we should be doing, and the job superficially was very simple. We should collect all the cases of polio that were occurring in the United States, and the first thing we had to do was create a standard form that had information about these cases, and particularly with respect to whether or not 00:13:00they had gotten polio vaccine, and then put this information together in an orderly fashion and distribute it back to the people it was coming from. And the people that it was coming from were, in every state there was a state health officer and a state department of public health, and there was also a state epidemiologist. That was an existing structure, and it was the responsibility of the state epidemiologist to investigate, collect information.

Remember, there were only very few cases of polio, or any cases of polio, occurring in their state on a daily basis, and to complete these forms which we distributed, of course, everything in those days, there was no Internet, there 00:14:00was no email, the telephone, was very cumbersome. And there was the regular mail system, and all the information that we put together was typed out by Maryann Lyle every day on a mimeograph machine, and then that mimeograph was copied a hundred times over, and there was a mailing list, and every day a report was sent to all the five hundred people, including the state epidemiologist. Of course, the state epidemiologist could reach out, in each county, or many counties, under the state there were public health officers, and then Alex Langmuir assigned some of the EIS officers on an emergency basis to help investigate these cases and complete this form.

And our job sitting in Atlanta was to take all this information in and actually 00:15:00create what we called a line listing. For each case there was a listing, the initials of the individual, their age, if they got the vaccine, when they got it, and when they developed polio, et cetera, et cetera, some very basic information. And we put this line listing together and every day it went out on five hundred copies that were mimeographed by Maryann Lyle.

TORGHELE: Quite a different communication system, wasn't it?

NATHANSON: Very primitive. Remember, I knew nothing about how to do any of this, and Alex had to sort of show me how to put together, once a week we would do a summary, how to put together even simple tables that were child's play, but nobody ever instructed me how to put together even a simple table that showed 00:16:00for each state how many cases, et cetera, et cetera.

TORGHELE: So you had no training in epidemiology.

NATHANSON: No, no. In fact, I was the only EIS officer in history who had never taken the EIS course, because the way the program worked. It was a two-year program and the first month of the program was an intensive course in the basic methods of epidemiology. But I never took that course, because I arrived in the middle of the year and all the other EIS officers had taken the course. So I didn't even have that background of basic instruction.

TORGHELE: What was Alex Langmuir like to work with?

NATHANSON: Well, at this point I was totally untutored and he was an 00:17:00accomplished field epidemiologist and so he was very, very helpful. And remember, at this point in terms of public health emergencies and epidemics, this was the number one issue in the whole of the United States. What I'm trying to say in another way is this outbreak of cases was on the front page of the New York Times every day for two months. That is almost unheard of, even Zika doesn't make the front page of the New York Times every day for two months.

So this was the number one hot issue, so I would say that everything we did, remember Alex was only a hundred feet down the hall. He was watching over us very, very closely, so in a sense everything I did was under his immediate 00:18:00direction. Obviously, certain routine things, we learned pretty quickly what was expected of us, and so he didn't have to repeat the instructions about those things. We were working fourteen-hour days also, because each day we had to get out a report before the end of the day.

I remember I went home and fell into bed and slept like a log and got up the next morning and went to work. That was all there was in my day, so it was a very intensive kind of thing, and what we were doing in retrospect was quite simple. And then what immediately came out of all this data collection was, as I mentioned, it was the manufacturer situation. One thing that became very 00:19:00apparent very early was, there was an unusual concentration of these cases occurring in children who had gotten polio vaccine, and that concentration was in two states: Idaho and California. Now, it turned out that when the vaccine that the NFIP had ordered was distributed, it didn't just go randomly from the six manufacturers all over the country. It turned out that the vaccine that was made by one manufacturer went mainly to California and Idaho, and that was the Cutter Laboratories in Berkeley, California.

Immediately, it became clear that many of these cases, the great, great bulk of 00:20:00them, were in kids who got the vaccine manufactured by one of the five or six manufacturers, and that was the Cutter Laboratories. So even early on, before we did any formal analysis, at a glance, almost, it was apparent that there was something peculiar. There was a clear association between the vaccine made by one manufacturer and the great bulk of these cases, and that, of course, led to what subsequently was called the Cutter incident, and again, Alex Langmuir was the person who gave it that particular name. So maybe I'll stop there for a moment and get your next question.

TORGHELE: How many other pharmaceutical companies were there involved in vaccines?

NATHANSON: Well, I'd have to check the originals. My memory is there were a total of five or six, I don't remember, but there were Park Davis and Lily and I've forgotten the names. I should mention also, by the way, that the other manufacturers were better-known, more established companies than the Cutter Laboratories. I don't think they had made any vaccines. This was the first vaccine they made, whereas the other manufacturers had made other kinds of vaccines for other infectious diseases.

TORGHELE: Did they all have the same protocol to follow?

NATHANSON: Yes. The protocol to produce the vaccine was one made by [Dr.] Jonas Salk, and when I say that the vaccine was licensed, it was licensed, part of the licensing, although I can't describe the detail because I wasn't involved in 00:22:00that, included a protocol about how to make the vaccine following Salk's recipe. And basically, just a moment to describe it in general, basically, there were three types of polio virus; one, two and three, they were called. Each one was grown in a standard tissue culture in large carboys, and the cultures were then infected with the polio virus, and after a certain point of time those cells were killed and the virus was released. And that fluid, which consisted of dead cells and a lot of virus, was then subjected to formaldehyde treatment at 37 00:23:00degrees for a couple of weeks, they were cooked, and that was to render the live, infectious virus theoretically inactive.

What Salk had shown was that this inactivated virus was, first of all, non-infectious, and, secondly, was immunogenic. In other words, it could induce an immune response in humans that would protect them against polio.

TORGHELE: Was there, then, a way to test the vaccine before they went out, before the vials went out?

NATHANSON: Yes. Yes. Every lot of vaccine, and again, this was not what I was involved with, others were, and would be more knowledgeable, in my best memory, every lot of vaccine, part of the protocol was testing each lot for both safety 00:24:00and effectiveness, or at least certainly for safety. The way that was done was to take samples of the vaccine and inject it, as I remember, inject it into both monkeys and maybe tissue cultures to see, to prove that there was no live virus, residual live virus.

In fact, in retrospect, it turned out that Cutter, the Cutter Laboratories, had a lot of trouble inactivating the vaccine during the inactivation process. That is, apparently many of the batches they made failed to pass their own internal safety tests. And however, because this was not part of the protocol, they 00:25:00apparently just poured those down the drain and never reported their problems to, I've forgotten what it was called, it was the predecessor of the FDA [Food and Drug Administration], the Laboratory of Biologics, as I remember, it was called, at any rate, so that in fact the central certifying U.S. government entity in Washington was unaware of the problems they had been having.

The lots of Cutter vaccine which were released had passed their safety tests, at least appeared to have passed their safety tests, but it was clear that, in retrospect, they were questionable, because of the failure to consistently pass 00:26:00safety tests. So yes, there was a clear indication that they were having inactivation problems. That was never reported to the Laboratory of Biologics at NIH, as I understand it.

TORGHELE: Were the people at Cutter concerned? Did they consult anyone, knowing that they had problems?

NATHANSON: Well, I can't tell you that, but my impression is no, that in fact they concealed their problems. They were in denial, which of course in retrospect was a terrible mistake. I think what they probably knew was, if they had reported these problems, they would have been told to cease and desist making vaccine.

TORGHELE: That would have set them back?

NATHANSON: Well, they would have abandoned that program. Again, they were not 00:27:00officially breaking any of the rules. In retrospect, the rules were changed so that no vaccine could be released if it wasn't part of at least a run of five consecutive batches that passed safety tests. But that was not in the original protocol.

TORGHELE: It sounds like they were responsible for doing their own safety testing and then making the decision about it.

NATHANSON: Yes. It was not written into the protocol. There was not good oversight, and in retrospect that was changed. The protocols were changed after the Cutter incident to require much better federal oversight of manufacturing and safety testing. Also, since you are on the subject, I should mention: it became fairly clear what the problem was with the Cutter vaccine, and that is 00:28:00because the batches of vaccine were prepared from these cell cultures with all these dead cells floating around. There was a filtration step where the fluid was put through a filter that would hold back the residual cells and parts of cells, but would let the virus, which is much smaller, go through.

However, that filtration step did not completely remove all the particulate matter, and in fact, apparently, if you looked at these carboys which are being inactivated, at the bottom you could see a dusting of particulate matter. It turned out that all you had to do was add a couple of additional filtration steps and you could get rid of that particulate matter. So apparently what 00:29:00happened was that aggregates of the virus were being created during the inactivation. Those aggregates would protect some particles from ever being inactivated, and if you filtered those aggregates out, what came through would be totally safe. So that was also part of the change in protocol, adding some filtration steps.

TORGHELE: That gets us up to the point where the immunization program had begun all over the country with five different pharmaceutical companies, including Cutter, and you said how long afterwards were the cases being noticed?

NATHANSON: What happened was that, and I've forgotten exactly the timing here, 00:30:00it's all in the records, within a couple of weeks a decision was made, not at CDC, but in consultation with Alex, was made by the Laboratory of Biologics, the Public Health Service, to terminate the vaccine program, or suspend it, is a better word. So no further vaccine was being used at that point. The idea was that they wanted to wait until there was a clear idea of what was going wrong.

Within, I think it was by the first of June approximately, 1955, because the whole focus was on Cutter, clearly no Cutter vaccine was going to be further released. But the other four or five manufacturers, their vaccine, with one 00:31:00possible exception that we may come to, was apparently okay in terms of being safe in use. Each of the manufacturers was visited by an expert group. I wasn't part of that. These were mainly virologists and production people, and they reviewed the production protocols at each manufacturer, and over the next month or so they relicensed the vaccine being produced by those manufacturers. The program was then recommenced, but not much vaccine, as I remember, was being given until maybe the following fall or maybe even the spring of 1956, because of all the national concern.

You have to remember also another comment: I mentioned that this was on the 00:32:00front page of the New York Times every day for two months. What was at stake was not only the credibility of Salk vaccine, but all vaccines. In other words, there was an outcry that we should abandon all vaccine for every disease in the whole country because none of these vaccines were safe. There was a lot more at stake than just polio vaccine, which was a big enough deal in itself. The relicensing was done partly to reassure the public that, in fact, polio vaccine could be safely produced, or polio vaccine could be produced that was safe to use and would be effective.

Meanwhile, we were collecting these cases, but most of the cases, in other words, had been immunized and had received Cutter vaccine or other vaccines from 00:33:00the period, well, maybe mid-April to mid-May, when the program was terminated or suspended. It was about a one-month period of time when vaccine was being used, including the Cutter vaccine. After that, there was a period when no vaccine was used, and then the program was started up, but with manufactured vaccines that were safe.

We continued to collect information in detail and analyze it, but it was all based on immunizations given in that one-month period: approximately from mid-April to mid-May in 1955.

TORGHELE: How was it that CDC was the agency that was chosen to do that surveillance?

NATHANSON: CDC, although it's not really called that, is the Federal Public 00:34:00Health Service. They are, and I can't really give you a clear explanation, but basically, there's also the U.S. Public Health Service, but they really were the National Public Health Service and still are. I mean, it's called the Centers for Disease Control and Prevention now, but they are equivalent. There is no other U.S. federal public health service, and the so-called "public health service" was really just a group of professional public health service officers who were incorporated into the CDC or had other assignments, but they were not an administrative entity like a national department. That was always CDC that 00:35:00eventually became part of HEW [Department of Health, Education, and Welfare] and so forth.

TORGHELE: Was the National Institutes of Health [NIH] involved?

NATHANSON: Well, not really. The Laboratory of Biologics, and still is the Center for Biologic Control, happens to occupy a building on the NIH campus, but no, that's a separate entity. The NIH was a research organization, and eventually this became incorporated into the Food and Drug Administration, which is a separate entity responsible for vaccines, food, drugs and so forth. It's a totally separate operation really dealing with licensing and quality control, and they do research, but only research in support of that mission.

TORGHELE: So CDC became known more after the Cutter incident?

NATHANSON: Well, again, I'm not the one to really comment about that. I mean, 00:36:00these things evolved in sort of a happenstance way. Remember, the NIH was really created, more or less, after the Second World War, although there had been a laboratory of hygiene for decades or maybe a hundred years before. We didn't really have a system of federally funded biomedical research or grant-giving or anything. People have sort of forgotten, but none of this really existed in a meaningful way until after the Second World War. We really didn't have a full-blown federal public health service in the same way until, I think, after the Second World War.

Actually, the CDC was in Atlanta because it was originally started as a malaria control program and then evolved into infectious diseases. Originally, the CDC 00:37:00stood for Communicable Disease Control or Center, Communicable Disease Center. Then it evolved into Centers for Disease Control and Eradication. So, all of this has gradually evolved, but you'd have to talk to other people who can tell the history of all of that much better than I can.

TORGHELE: During this time, what was the reaction at the Salk lab?

NATHANSON: Now this has been published, so I can say it. The truth is that Jonas Salk was partly culpable here. And of course he's dead, so he can't respond, and I'm sure he would deny it.

But a guy named [Dr.] Julius Youngner, the story which has been now written up and published, so it's not the first time, a senior postdoctoral associate in Dr. Salk's laboratory was a guy named Julius Youngner. I think he may still be 00:38:00alive. He was at the University of Pittsburgh along with Salk. And apparently, at least as Julius Youngner told me the story, he had a meeting and happened to be in San Francisco, and Salk asked him while he was there, this was not in connection or direct connection with the Salk vaccine, to go across the bay to Berkeley and look at what was going on at the Cutter laboratories. This is before the Francis Field Trial was announced, but meanwhile, of course, Salk knew that Cutter, among these other manufacturers, making vaccine.

And Youngner did, I'm not sure if it was a formal, but an informal review look-see, and he was very disturbed by what he found. And he told me he went 00:39:00back to Pittsburgh and told Salk, because of course Youngner knew all about the Salk protocols, that he felt that Cutter, the Cutter vaccine, should not be trusted, and should never be used. I may be misquoting him, but this is what he told me some years ago face-to-face in a private verbal.

He told Salk that he should do something. Salk said, yes, I'll do something, and he buried it because he was afraid that if he cast any question, the whole vaccine program would be called into question. Whatever, I don't know his motivation, but apparently nothing ever transpired. And Youngner was very upset, and he carried that upset and anger with Salk for the next forty years, that 00:40:00Salk had betrayed him and the program by not reporting that there was a problem with Cutter vaccine and that it should not be used before it was ever distributed.

Now, Salk isn't here to defend himself. Julius Youngner has certainly told the story to other people. Julius Youngner was a very respectable virologist. He eventually became, as I remember, the chair of the biochemistry department at the University of Pittsburgh, I think in the medical school, so he's a very reputable guy who mainly did his career working on influenza virus. But at any rate, that's a bit of the story.

Alex Langmuir taught me certain things. He said, not in this connection, but in general, he said, "Don't get up too close to your heroes because you'll find 00:41:00they all have feet of clay." That's a direct quote from Alex, and that could apply to many situations. Apparently, that would also apply to Jonas Salk, at least if this story is correct.

TORGHELE: What about Dr. Sabin, Albert Sabin?

NATHANSON: Remember, Sabin was not in the picture. The Sabin vaccine came along later. Sabin was supported by the NFIP to do research, but his vaccine, which was a live attenuated virus and also had its limitations in terms of safety, but he wasn't involved in this, other than bad-mouthing Salk, because he called the Salk vaccine "kitchen chemistry," sort of like a Donald Trump put-down.

What can I say? Sabin and Salk were not natural enemies, but they were very 00:42:00fierce champions of their own product, so they wrangled. Of course, it turned out that both were correct, and that each of the two vaccines had its strengths and weaknesses. And the United States, as you know, went from Salk vaccine to Sabin vaccine and now back to Salk vaccine. So, pointing out that both of these vaccines had their role, and, as in many scientific controversies, it turns out that both sides have some right and maybe some wrong as well.

TORGHELE: The clinical trials were finished after the Rivers,

NATHANSON: Right. That was, by the way, a special trial. I don't know if it was the only, but one of the very largest trials that was ever conducted. It was written up in a vast book of data with hundreds of thousands of participants, 00:43:00something that would be impossible to replicate nowadays, probably.

TORGHELE: No informed consent.

NATHANSON: Well I don't really know about that. I wasn't involved in the Francis Field Trial, and there's a short version and a large book, a long version. I'm not sure about consent, frankly. There may have been. I really don't know.

TORGHELE: Now, when you were at CDC, who else was involved from your [EIS] class? Were there others?

NATHANSON: Well, basically, no. I mean, all the time I was there, as I remember, originally the statistician in the EIS Unit, in the polio surveillance unit, excuse me, was a guy named [Dr.] Earl Diamond. But he was involved in the Francis Field Trial, and so he went back to the University of Michigan, to Ann 00:44:00Arbor, to finish writing up the Francis Field Trial, because [Dr. Thomas] Tony Francis wanted him there to help. It was a whole big team involved. I mean, the report of this trial was like three hundred pages of data. It was a vast effort. Alex, as I remember, was annoyed at Earl Diamond, but at any rate, shortly after the unit was created, I don't remember exactly when, Diamond left.

And Jack Hall became a good friend of mine, and is still alive, I believe, as a retired professor of biostatistics at the University of Rochester, Jack Hall was a PhD statistician, but he was an EIS officer who was brought into the unit. So it was Maryann Lyle, the secretary, Jack Hall, and myself, and we basically were it.

There were a vast number of people involved in data collection, and if you look at the 1963 publication, there are three contiguous articles in the American Journal of Hygiene 1963 where all the people who are involved are credited. In terms of data collection, we were just putting it together, but all the shoe-leather stuff was done by dozens and dozens of dozens of people.

TORGHELE: I have a list of the people who were involved in the Cutter investigation, but I think they're mostly state people.

NATHANSON: Well, every state, there were people involved. And so, as I say, it's in the paper. So as far as I know, that's a complete list. And yours may be also. I don't know.

TORGHELE: I got it from your paper.

NATHANSON: Oh, well, it's the same thing. Right. On the front line there were 00:46:00the state epidemiologists. Then below there were the county people and then there were some EIS officers. So basically the idea was that these cases would be often hospitalized or almost invariably, at any rate, they would go to the hospital, look at the record and fill out the standard form based on what was in the hospital record. We would often get forms that were incomplete. There were blanks that hadn't been filled in, and we would then keep pestering people to fill in the rest of the blanks. As I say, it could be anybody. The information wasn't that complicated, but our job was to nag people to fill in all of the blanks: the names, the ages, the whatever. However they wanted to collect information.

And it was from all over the country, so there were many, many people involved. They were really the unacknowledged heroes in the trenches, because all we were doing was just putting together, collating all this information, and then doing some really quite simple-minded analysis of the data.

TORGHELE: What kind of tools did you have to analyze the data?

These are all very simple. You didn't need anything but a pencil and paper, and you could use an adding machine if you wanted, but you know there were no calculators at that time. There were these Monroe mechanical calculators, but you could just use longhand. These analyses were very, very simple. There were a few times when Jack Hall would maybe do some tests of significance and so forth, but basically it was all very simple-minded stuff. I don't mean to say it wasn't 00:48:00relevant or pertinent or didn't deliver the goods, but it wasn't complicated.

TORGHELE: You were at CDC for two years?

NATHANSON: Yes. The tour of duty was two years, and because I started more than partway through the year, I stayed for two-plus years. I was there from March of 1955 to July of 1957. So I guess it was a bit more than two years, because I was 00:49:00the class of '55. In those days, or, I guess, still, EIS classes are based on the year you started, not the year you graduated.

TORGHELE: From there you went,

NATHANSON: I went to Johns Hopkins then. So what happened at that point, Alex Langmuir had been at Hopkins as an associate professor in the epi [epidemiology] department, and he was friendly with some of the Hopkins people. And one of the people he was friendly with was a guy named [Dr.] David Bodian, who is really a basic science researcher. Dave Bodian was still at Hopkins, and his contribution was doing experiments using monkeys, but with live polio virus, to understand 00:50:00how the virus caused polio, otherwise called the pathogenesis of polio. Remember, this was such a hot topic, Alex Langmuir had Dave Bodian come down to Atlanta when all of this was going on, I think twice, I don't remember exactly, but give a couple of lectures about his background information.

This is like Ebola was a little while ago and Zika is now, but even much hotter to talk about what he and other people knew about the pathogenesis of polio. I heard these talks and I was sort of entranced by this kind of research. So when my time to complete EIS came to an end, I wrote David Bodian, with Alex's 00:51:00knowledge and maybe support, and said I was really fascinated by what he was doing, and could I come and do a postdoc with him? Remember, I didn't have a research background. I had an MD, but that wasn't research. In those days, rather than get combined degrees, which weren't available, MD/PhD, people who are interested in research would go through medical school and then do a postdoc, where they would do research training usually for two to four years, and then they would move on to become independent researchers.

At any rate, Bodian wrote back and said he was funded by the NFIP. And he wrote and said he had asked them if they would add to his grant a slot for a 00:52:00postdoctoral researcher for training, and they said yes. And so he said, I've created a slot, and wrote me, you can come to Baltimore. So that's where I ended up, in the anatomy department, oddly enough, but that's another story.

TORGHELE: And you worked with Dr. Bodian?

NATHANSON: With Dr. Bodian, yes. So I ended up as a postdoctoral fellow in Bodian's lab. He had been in the epi department at Hopkins, although he was doing basic science stuff, but it was in support of polio vaccine. Just before I came to Hopkins, Bodian moved from the school of public health across the street to the medical school to be the head of the anatomy department, and so I ended 00:53:00up in the anatomy department. Not that I had any interest in anatomy, but that's where he was, so that's where I was.

TORGHELE: What was he like to work with?

NATHANSON: Oh, he was great. He was great. Dave Bodian was a true scientist. He wasn't like Sabin and Salk, who were advocates. In fact, he refused to get involved in all those controversies. He was much more dispassionate about, what does the science say, and so he recognized that there were advantages and disadvantages of both vaccines and so forth. So his interest was in asking, what are the pertinent scientific questions? And what experiments can we do to try to answer them? He was a great mentor. I stayed there from 1957 to 1964 and then I 00:54:00moved to the epi department in the school of public health.

TORGHELE: That would have been what year?

NATHANSON: 1964 I moved over to the epidemiology department, and I was there and from 1964 to 1979.

TORGHELE: So in the 1960s is when the Sabin vaccine started to be used?

NATHANSON: Yes, right. I was not involved in that, but yes. Well, Sabin vaccine was introduced in 1960, '61, something like that. But nobody could do a proper trial of Sabin vaccine in the U.S. First of all, the kids have received Salk vaccine, and you needed a set of kids who hadn't been immunized. So most of the 00:55:00trials were done in Russia and elsewhere and were never done properly. Nobody did proper trials in those countries in Eastern Europe, Russia and other Eastern European countries. So what never came out clearly was that Sabin vaccine caused some cases of polio, and Albert Sabin certainly wasn't eager to publicize that. At any rate, it did turn out, and the Russians didn't give a damn about safety as long as there wasn't a big problem. In other words, if one kid got paralyzed and a hundred kids were protected against paralysis, that was a reasonable tradeoff for them, but not in the West. They basically massively immunized in Russia and markedly reduced paralytic polio.

On that basis, and I can't tell you about the licensing of the Sabin vaccine, it got licensed in the U.S. Although the Salk advocates, and it wasn't just Jonas Salk, Let me put it this way, between 1955 and, let's say, 1960, using only Salk vaccine, the incidence of polio in the United States dropped by maybe tenfold, from maybe twenty thousand paralytic cases a year to two thousand. It wasn't eradicated, but it was markedly reduced.

There were those who felt that we should just continue with Salk vaccine, but, I can't tell you what the arguments were because I wasn't involved, but a decision was made to shift to Sabin vaccine, I think in part because the hope that this would further reduce polio, which it did. In fact, some countries in Europe 00:57:00never did shift to Sabin vaccine, and they managed to eradicate polio also.

So, it wasn't really quite clear, but one thing that was clearly known was that Salk vaccine did not do a very good job about creating mucosal immunity. Sabin vaccine did, because it infected the gut and produced mucosal immunity. People who had been immunized with Sabin vaccine no longer could act as links in the chain of infection. Salk vaccinees were protected against paralytic paralysis, but could still get infected and pass the virus on, could act as links in the chain of infection. So that was one of the arguments. And Sabin vaccine was cheaper to make and easier to administer, no injections, just virus on a sugar 00:58:00pill was a drop of vaccine.

Sabin vaccine was introduced, and in spite of that, there was still a residual of kids who had never been immunized. I mean no program is 100 percent, and in the United States there was something like ten million kids not immunized. At any one point in time, even after Sabin vaccine was introduced, there were ten million unimmunized individuals. And it was thought that the same ten million would be sufficient to keep the wild polio virus circulating, even though the rest of the population was immune.

Suddenly, without anybody predicting it, and sort of interesting, in the early 1970s, and particularly about 1972, it suddenly became apparent that we had 00:59:00eradicated polio, wild polio, in the US. There was none. That was only recognized in retrospect. That was not predicted by anybody, although some people might, in retrospect, deny that.

Suddenly, the whole idea of eradicating polio came out of that. A guy named Ciro de Quadros, who ran a polio program for the Pan American Health Organization, part of WHO [World Health Organization], located in Washington, decided to push this for South America, and he eradicated polio in South America using Sabin vaccine. Meanwhile, of course, in Cuba, which is only a small island, they had done the same. So suddenly, there was no wild polio in the whole of the western hemisphere, and that led in 1988 to the WHO waking up and saying, let's eradicate polio for the world. If you can do it in the western hemisphere, why 01:00:00not the world? As I say, the rest is history, although it's a rather complicated history.

TORGHELE: So do you think it was linked to, because smallpox had been eradicated shortly before this?

NATHANSON: No, no, no, no. The assumption is, a perfectly reasonable assumption was, if you do the numbers, based either on immunization histories or on serological surveys in a large population, there would be a small percentage, but still a very substantial number of people, at any one point in time, mainly kids, who are not immunized, had never been infected, who had never been vaccinated. It was assumed that they could continue to circulate the virus. In 01:01:00fact, it was a mystery why they didn't. That's the reason it wasn't predicted. It wasn't out of stupidity, it was the assumption, a very plausible assumption.

I think the reason, and we've written papers about this back twenty-odd years ago, the reason was what I mentioned before: the seasonality of polio. What one has to understand is that in the low part of the season, there's almost no polio transmission, and that's in March of each year. The difference between the high and the low is extraordinary. The reason, likely, is that in the low the virus just disappeared entirely in an immunized population, because even though there were a few unimmunized people, there was so little natural transmission that 01:02:00they weren't sufficient to maintain the virus. It just disappeared.

What happened in the period from the mid-'60s to 1972, as we look at it, the number of states with no polio for a whole year gradually increased. Well, in the early 1960s, every state reported polio every year. Gradually, it went from fifty to forty-five to forty to thirty-five, and over a period of years, polio gradually disappeared. Nobody really recognized this, and then suddenly it was gone. Of course there was a lot of live virus around, but there was live Sabin vaccine virus, but there was no wild virus.

Of course, along with this were new methods to be able to easily distinguish the Sabin viruses from wild polio viruses based on genetics.

TORGHELE: Speaking of that, there was a case, Reyes v. Wyeth. Is it true that you were called on to testify in that trial?

NATHANSON: Yeah, I'd forgotten. That's a long time ago.

TORGHELE: It was an 8-month-old Texas girl. She got the Sabin vaccine, and several weeks later she became paralyzed.

NATHANSON: First of all, the CDC started to collect, right from the beginning, collect cases of what's called vaccine-associated paralytic polio, VAPP. It turned out that there was a clear pattern, and what we now know in retrospect 01:04:00is, for every million kids who got their first shot of Sabin vaccine and who are susceptible, these are babies, infants, or toddlers, who are totally susceptible, for every million, there are about two cases of paralytic polio. Some of these occur in immunologically deficient kids and some occurred in perfectly normal kids.

It turned out also that if you collected enough of these cases, there weren't many of them over a period of years, there was a clear pattern. They all had 01:05:00onset within a relatively short period of time after getting the vaccine. But there were all sorts of people who were trying to extract money from the drug manufacturers for cases that occurred that were not related to the vaccine, because they were outside of this epidemiological window, which was a very short window.

As I remember, that was one of those cases, but I'd have to look. I just don't remember the details of that case. But there were certainly a lot of trials, and basically what we testified was, this is the window, and if your case conforms to what we know epidemiologically, then one has to assume its cause and effect. If it's outside that window, then there are other reasons of what's going on: either it isn't polio, or they weren't properly vaccinated and it was wild virus, or whatever. There are a number of reasons why, but when you give all 01:06:00that vaccine, there are going to be by happenstance cases of this and that. But I don't remember the details of the Reyes case, frankly. I'm sure if I looked at it I would, but it's a long time ago.

TORGHELE: Having been the author of the seminal paper on the Cutter incident, you with Alex Langmuir, you must have been called on a lot to be an expert witness for certain things.

NATHANSON: Well, actually, yeah. There was a time when I was, and I mainly would look at the cases, as I say, testify in support of a manufacturer when I thought that the case didn't meet the epidemiological criteria. In general, I think the manufacturers, I don't know what they did, negotiated settlements for the cases 01:07:00that clearly fell within the associated parameters. Yes, I was involved, but it's a long time ago. So over a period of maybe ten or fifteen years, I may have testified in a dozen cases. I don't really remember. Somebody has a record of that, but I don't remember exactly.

TORGHELE: It was all because you came in March of 1955 to CDC.

NATHANSON: Well, you could put it that way. It was all happenstance.

TORGHELE: And you were the right person for the job.

NATHANSON: Well, I don't know that I was the right person. Somebody else might have done just as well, to put it bluntly. I was totally unprepared, and in no way would I have been considered the right person for the job, based on my training I mean.

TORGHELE: Just to go back a little bit, do you remember if you worked with the lab at all? Did Epi [Epidemiology Division] and the labs work together?

NATHANSON: Alex had his own feet of clay, and one of the things was, he was totally hostile to laboratory people. He was just crazy about that. Alex made other total crazy mistakes. He predicted, when AIDS [acquired immune deficiency syndrome] first came along, that it was just going to be a passing problem. I don't know if there is a record about that, but yeah. He totally pooh-poohed it as a major problem at its very beginning. But Alex had a peculiarity that he believed in the shoe-leather epidemiology. But he was, for some reason, and I don't know where this came from, totally hostile to laboratory support of epidemiological studies.

At that time, CDC was in its infancy. It was maybe 1 percent of the size it is 01:09:00now. The laboratory, for some reason, was someplace in Montgomery, Alabama, as I remember, and he was totally at odds with the guy. It was [Dr.] Morris Schaeffer who was in charge of the laboratory. They never worked together. It was one of his blind spots. And in fact the laboratory is obviously critical, even if it's just simple-minded tests for immunity of whatever.

Alex never worked well with laboratory people, and that was clearly his limitation. He never paid any attention to what anybody else ever said about that.

TORGHELE: So as a consequence, you didn't work with lab people either?

NATHANSON: Well, no, no. Let me put it this way: I think he would have said we could solve the Cutter incident without any lab people, without needing any lab 01:10:00people, so the hell with them. We don't need them. They're extraneous.

It turned out that in fact they were relevant because, let me mention one instance, because there were vials of all these different vaccines during/after the Cutter incident that various people had in their freezers. And it turned out that when the laboratory retested them, they could isolate wild virus from some of these batches of vaccine from the Cutter. In fact, they could confirm that in fact there was residual live virus. And that's just one example.

Another example, by the way, where the laboratory was really critical was in the 01:11:00basic Francis Field Trial. Because what they did, they had measured the antibody responses of the kids who got the Salk vaccine. They could therefore determine what proportion had titers at each level, and it turned out that the protection correlated with everybody who had a titer of 1:8 or 1:4 or higher, I think it was 1:8. It turned out that what that proved was that if you were going to test a vaccine, all you had to do was show that it had induced a neutralizing antibody titer of 1:8 or greater, and that proportion of individuals would be protected. So that's a really critical example of the epidemiology and lab 01:12:00working together. That was the Francis Field Trial. Alex, he ignored all that. It was a blind side. I was just a protégé. I never argued that with him. But other people did, but they didn't get anywhere.

TORGHELE: Through the years you've stayed involved and interested in polio.

NATHANSON: Well, yeah. When I went to Bodian's lab, I worked on polio for basically half a dozen years in monkeys. And then I moved over to the School of Public Health and I moved on to other viruses, because I was really interested, basically, in how viruses cause disease, and polio was sort or passé at this point. The vaccines were out there. They were working. And so I moved on to other viruses in other animal models, and that's basically what I spent my 01:13:00career on.

TORGHELE: Did you get involved in the discussion about polio eradication?

NATHANSON: Well, only indirectly. I've certainly not been very central to it. I did publish a couple of review pieces: one on the epidemiology, which touched on all that, and there were two versions of that. One around 1980, and the other I think around 2010. And then also around that time I did publish a review about the pathogenesis of polio called, "What We Don't Know About the Pathogenesis of Polio." So mainly it was in terms of review articles and so forth, so I really wasn't working in terms of laboratory. I was working on other viruses.

TORGHELE: What's your thinking about the possibility of polio eradication?

NATHANSON: Polio eradication was going like gangbusters, as everybody knows, and it's estimated that before there was any vaccine, there were, every year, around the globe, in terms of paralytic cases, about three hundred fifty thousand every year. We got to the point where we were down to the level of one to two thousand. That's an enormous, over 99 percent reduction. At that point, it looked like we were going to go to zero. The line was pointing down toward zero very sharply, and we ran into a brick wall.

It turned out, of course, that there were three countries that were the problem: 01:15:00Nigeria, northern Nigeria, India, northern India, and a region in Afghanistan and the tribal areas of Pakistan, one contiguous area. In the last five or six years, Nigeria has been cleaned up. First, India was cleaned up by an enormous effort on the part of the Indian government. Then, Nigeria, on the part of the Nigerian government, all with some extraneous help, but mainly internal. The only one left of the three standouts, holdouts, are these tribal areas of Pakistan and a bit of Afghanistan, and it's all political. These folks who are running things, and of course it's a constant civil war, Taliban and so forth, feel that it's a government program, and they're therefore not going to participate because it's done by the same people who have bombed their leaders 01:16:00with drones and things like that. It's a totally political situation.

This is all hypothetical: if there was a ceasefire for a week and you saturated those areas with Sabin vaccine, we probably could eradicate polio forever, wild polio. Then there's the issue of shifting from wild polio, from a Sabin vaccine to Salk vaccine. That's another issue, but you probably could get rid of wild polio very quickly, as has been done in Cuba and so forth by mass immunization.

It's all political issue, and who knows, I mean, it's been tied up with the politics of, these people are very anti-USA. The vaccine is associated with the USA, so we won't do it. They don't give a damn about their kids all getting paralyzed. These people, by our standards, are willing to sacrifice the welfare 01:17:00of their kids in support of their political views. So, who knows? You'd have to talk to the experts on the politics of that area to find out whether it's ever plausible. I mean, as I say, there are precedents, where there's a civil war, for having a moratorium for a week or two, doing your vaccine, then going back to killing everybody. What can I say?

TORGHELE: Sounds sort of counterintuitive, doesn't it?

NATHANSON: Well, the world's full of counterintuitive happenings right now.

TORGHELE: I've had you talking for over an hour, so I imagine you're getting tired.

NATHANSON: No, I think we should go ahead and just finish up whatever you want to do.

TORGHELE: So I wondered if there are any other things that you wanted to talk about related to polio or your time at CDC, or other people you worked with during that time that you wanted to mention? Did you happen to work with [Dr.] Phil Brachman?

NATHANSON: Well, I know him, certainly. No, I didn't work with him, but he was certainly a colleague at CDC. Let me comment about one thing. Can I comment about a totally different subject?

TORGHELE: Sure.

NATHANSON: And that's about an ongoing epidemic in the United States, and that's the AIDS epidemic. I'll make two comments about this. One is, as you know, I ran 01:19:00the office of AIDS research for two and a half years. Two comments: one about the vaccine development program for AIDS. We have spent more money without a result on trying to develop an AIDS vaccine than any other vaccine ever invented in the world. In fact, you could probably put together twenty different viral vaccines, the cost of developing them, and it would be less, in the aggregate of twenty, than what has been spent on trying to make an AIDS vaccine. In my opinion, that's because the field is narrowed down much too rapidly on options. I really think that the AIDS vaccine development program, we're talking about investing, at least globally, probably a couple billion dollars a year on research, and it really needs to be re-looked at with a much more open mind, one point.

The other point is this: in AIDS right now, the mantra of the month or maybe the year is curing AIDS in the individual. I think that is a totally misguided goal that it is impossible to reach, and that it totally diverts attention from what we should be talking about, which is curing the population and not the individual. Furthermore, we do not have the tools to cure the individual, but we do have the tools to cure the population. I think it's a national disgrace because we do have the tools, a national disgrace that the incidence of AIDS has 01:21:00not decreased in the last twenty-plus years. And let me just stop there and say the number of new infections for HIV is the most important criteria, and for any epidemic, and what you want, of course, is to get to a situation where each year there are fewer and fewer new infections that eventually go to zero. That's sort of Epi 101.

In the United States, as maybe your listeners all know, the number of new infections in the United States, about fifty thousand a year or so, hasn't dropped for about twenty to twenty-five years. Yet we have the tools to really reduce this, and I think that's a national disgrace that is more of political problem than any other thing. I think we should be, as a country, ashamed of ourselves for having done so badly in the effort to control HIV and AIDS.

Those are maybe my eccentric views, and I think the problem starts at the White 01:22:00House and goes on down. AIDS is a forgotten issue, and people are talking about a world without AIDS but aren't doing a fucking thing about it, to put it bluntly, in terms of really reducing the annual number of new infections. I could go on from there, but since you asked for some further comments about other things, to me that's more important than the polio thing, or very important anyway.

TORGHELE: What would you do for the population?

NATHANSON: Well, as I say, the tools are there. Remember, we have cleaned up the blood supply, at least in the United States and other civilized countries, for all practical purposes. We have eliminated pediatric, that is, newborn, AIDS for all practical purposes, and one thing that we could do is eliminate AIDS in 01:23:00injecting drug users by making freely available clean needles and syringes. So that certainly works where it's been done, so that's one thing we could do. The other thing is that two-thirds of the AIDS that are now occurring is in the gay population.

Now, of course, one of the reasons why AIDS, and again, this is a political statement, has been forgotten is because the primary victims are either the homeless, drug users, or African-American men and the gay population, all of whom are disempowered populations. If this was occurring in white women, we would have done something. Basically, you need to go in with a lot more money and with a very activist program. Between PEP [post-exposure prophylaxis] and 01:24:00PrEP [pre-exposure prophylaxis] and condoms and a whole variety of other things, it is possible to reduce transmission. In spite of the present, very effective therapies, it's much better to live without AIDS than to live with AIDS, even if it's just one pill a day. There are all sorts of other complications living that way, which are becoming more and more apparent.

I think there are a variety of things that could be done, and we probably need to start out with picking a few cities which are hot spots that are interested, and where the Department of Public Health is interested, and really throwing a massive effort in to prove that as a prototype that you really could do something. I think it's doable, and certainly what I do know: we're certainly 01:25:00not making the effort that we should be making in order to really try a whole variety of things. I think some of the people at CDC who are in charge of the AIDS program are very, very good people and, if given the mandate and the resources, could accomplish a lot. But it needs to start with the White House and go all the way down. It has been a lost cause because the people who are impacted are disempowered, and so they have been ignored. I mean, that's a political statement, but I think it is very much a political situation. Enough said, my crotchety views.

TORGHELE: So you would maybe reallocate some of the money used for vaccines?

NATHANSON: I wouldn't reallocate anything. If the public health service has close to a billion dollars to work on AIDS, or half a billion, I would add a couple of billion dollars and a mandate. But I would also insist that the 01:26:00political leadership of the country really get on top of this and really push it. I would go maybe to San Francisco, and the folks there are very, very good, and it's one of the hot spots where you probably could, with sufficient resources, use that as a prototype. I've forgotten her name, but the chief AIDS epidemiologist in San Francisco in the Department of Public Health is really excellent. I think if you gave her a carte blanche and told her, there's no limit on the resources you have, but go do it, I bet we could do it in San Francisco. And then we could build on that for other cities. It's idiotic not to prevent needle exchanges and so forth. So what can I say? Again, it's all 01:27:00political, and if it weren't for the self-righteous folks who think that people who are drug abusers should die of AIDS, we would make needles freely available, harm reduction. What can I say?

TORGHELE: It's a great public health message.

NATHANSON: It is a public health message, yeah. It's true.

TORGHELE: Well, thank you very much. This has been very interesting, and I know now why everyone said to ask Neal Nathanson when I had questions!

NATHANSON: Well, I hope so.

TORGHELE: It's been a pleasure talking to you.

NATHANSON: Yeah, me too, Karen.

TORGHELE: Thanks so much!

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