Dr. Olen Kew

Olen Kew

TORGHELE: It is May 17, 2016, and I am at the Centers for Disease Control and Prevention with Dr. Olen Kew. My name is Karen Torghele, and I'll be talking with Dr. Kew 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. Dr. Kew provided much of the inspiration and leadership for the development of modern molecular tools for polio eradication. So I am going to start with getting you, Dr. Kew, to tell me a little bit about your background before you came to CDC and how you came to work here.

KEW: Well, thank you, Karen, for the opportunity to come here and to be a participant in this project. My background was in physical biochemistry, genetics and virology, and before I had come to CDC I first did graduate work in 00:01:00yeast genetics at the University of Washington in Seattle. And then Professor Roland [R] Rueckert at the University of Wisconsin--Madison took a chance on a geneticist who wanted to retool to become a virologist. And so he gave me four and a half years of intensive training in virology.

And while I was working in his lab--which is the basic research lab of biophysics at the University of Wisconsin--I was listening to NPR [National Public Radio] and there were many stories coming out of NPR about CDC investigations. Swine flu was one, and Legionnaire's was another. And as I was listening in the afternoons doing some work--I could actually listen to the radio while I was doing the work--I said, this place would really be interesting. CDC would be the kind of place a virologist would really want to come to. So I contacted [Dr. Walter] Walt Dowdle and asked him, would there be a place for a molecular virologist to come to CDC? That was late 1978.

TORGHELE: And the rest is history. And what role did you understand CDC to have when you first came to work here?

KEW: Well, I knew it as the premier epidemiologic center for the United States--and, indeed, the world. The laboratory side--we had some superstars in the lab. We had {Dr. Walter] Walt Dowdle, we had [Dr. Frederick A.] Fred Murphy, we had [Dr. John F.] Jack Obijeski--who became my boss--and [Dr.] Don [J.] Brenner and a number of others who were doing outstanding work. But when I first visited CDC, I was really surprised at the state of the laboratory facilities, and it was for me a hard decision whether I wanted to take a chance with facilities, which really had become outdated--some of them designed in the 1930s. And it actually took six months before the lab that I was given had the electrical power capacity to do any kind of modern molecular work. It turned out that when I came, I noticed the facilities the first week, and then I heard 00:03:00about all the exciting things that were going on and the potential for working with epidemiologists on real human problems. I never noticed the facilities again--until we had visitors. Then, you know, we said, oh, yeah, well, that's a bit of a problem. But that's been solved now.

TORGHELE: Interesting. Did you have any additional training, or did you need any when you got here?

KEW: Well, I did, because Jack Obijeski was a very good nucleic acids chemist. And my training was in protein chemistry and genetics. So I got my training in the lab. I didn't get any other kind of formal training. In fact, most of us had to go to the library at CDC and find out what was going on in the rest of the virologic world, and see whether we could build up to that standard.

TORGHELE: When you began, did you first start out working with polio, or did that come later?

KEW: No. I started working with polio first as a postdoc, and then immediately came in the midst of the polio outbreak among the Amish in 1979. And [Dr. 00:04:00Milford H] Pete Hatch, who was the head of the polio lab at CDC at that time, very generously shared some isolates from that outbreak with me while I was working at the University of Wisconsin. And it was kind of a novelty, because there we were in a basic research facility, everybody was working with what were called laboratory strains, and I'm the first one that actually worked with material coming from human patients. So that was very interesting and exciting for us in the academic world, and I really was grateful to have the chance to come down and actually do this as my career at CDC. So I started working in polio even before I came to CDC, and working on the outbreak even before I came to CDC.

TORGHELE: And did you work with Dr. Hatch when you got here, too?

KEW: I did. My immediate supervisor was Jack Obijeski, who was a molecular biologist. He was interested in other viruses, not particularly interested in polio. But Pete Hatch was interested in polio. And [Dr. James H.] Jim Nakano was 00:05:00very interested in polio, because he was actually in many ways my predecessor in working in a global program--setting the stage first for polio, then moving on to smallpox eradication, where he was the head of, essentially, the global reference center for smallpox and the laboratory reference for smallpox eradication.

So I learned from Jim not only his polio stories, which are many and wonderful, and he guided me in the right direction of where to go and how to use the tools that I had to investigate problems. He'd say, I could bring this question this far with the tools that I have, but you have a different toolbox, maybe you can find some additional things with your tools that I couldn't find. He was very, very generous in that way, and so he mentored me in the way of how to use public health science to address questions that had been longstanding. And I'll come back to some of those later. And then Jack Obijeski gave me training on how to become a nucleic acid chemist, because my area of expertise was in protein chemistry.

TORGHELE: Do you want to talk about some of the early pioneers at this point, since you mentioned Jim Nakano?

KEW: Yeah. I'm of the age or generation that I had the opportunity to know a number of the early pioneers. I knew [Dr.] Jonas Salk, I knew [Dr.] Albert Sabin, I know [Dr.] Julius Youngner. I also know [Dr.] Neal Nathanson, who's still active as an epidemiologist. I had spoken with [Dr.] C.P. Li, who played a key role in developing the type 1 attenuated oral poliovirus vaccine. It's called LSc 2ab. L is for Li, S is for Schaeffer--[Dr.] Morris Schaeffer--and then 2ab are for plaque 2, plaque a, plaque b. Then they sent the virus to Albert Sabin's lab. But the work was done in 1954--early 1950s--in C.P. Li's 00:07:00lab, and that really led to the best of our three oral polio vaccine strains.

OPV [oral polio vaccine] type 1 is most genetically stable--the one that has been effective against the serotype or type of polio which is associated with most of the cases in the world, about 90 percent. And it's the one which we are still dealing with now in Pakistan and Afghanistan [and Nigeria], to finish off polio at long last. We have now about as many cases this year so far as we would have had in about twenty minutes when we started. So Morris Schaeffer had polio. C.P. Li, who was born in China, came to the United States, and fortunately for CDC--then CDC Montgomery--was interested in developing a live attenuated strain of polio vaccine.

TORGHELE: Interesting. When they were working on these things in the early days, 00:08:00do you know anything about the politics at the time that led to the way the polio vaccine was introduced, and about the clinical trials?

KEW: Well, yes. The first polio vaccine--the inactivated polio vaccine--was introduced in 1955 in the wake of very large outbreaks, up to fifty thousand cases in the early 1950s affecting my generation. Children in my community got polio. A little boy in my wife's neighborhood died of polio. So this was something that was very real for us. And there's a very well-known photograph from Rancho Los Amigos, California, about 1952 or '53, where a gymnasium in the school was filled with iron lungs. And the kids in the iron lungs were kids of 00:09:00my generation, and that place was only about thirty miles north of where I grew up--this iconic photograph of children with polio. So there was enormous pressure to develop a vaccine. And the research scientists tended to favor the attenuated vaccine over the inactivated vaccine, but the inactivated vaccine became available sooner. It became available in 1955 and saved a lot of lives--perhaps even myself, my brother and sisters.

In 1961 the oral vaccine was licensed, and it was licensed by serotype: first type 1, then type 2, and finally type 3. Type 3 was licensed a little later because there were some difficulties with it, which we still live with today. And the inactivated vaccine required mass campaigns, as did the oral vaccine. 00:10:00And many people don't remember that, but there were actually long lines of people lining up to get the polio vaccine, and I remember that from my own experience. As you'll read in books--and I lived it, and you may have remembered it, too--church bells rang with the announcement on April 12, 1955, that the vaccine was available. It was, in fact, safe and effective.

But the roots of the polio vaccine go back to the very earliest part of the twentieth century. Soon after the discovery of poliovirus by [Karl] Landsteiner and [Erwin] Popper, there were efforts in the United States and elsewhere to make an attenuated vaccine and a killed vaccine. And they tried formalin inactivation for the killed vaccine, but they had no cell culture. They had no way of growing the virus in sufficient quantities to make a vaccine. They were growing it in monkey spinal cords in those days. So the desire to make a vaccine 00:11:00goes back to the earliest discoveries--about 1908 and 1909--of the viral etiology of poliomyelitis. But the tools weren't there, and at that time they didn't even know that there was more than one serotype--that came later. [Sir Frank] MacFarlane Burnet and [Dame Annie] Jean Macnamara demonstrated there was more than one serotype, and then finally in the late '40s [Dr.] David Bodian and others demonstrated there were only three serotypes. And that really did set the stage for the three vaccine strains for the Salk-Youngner series and the Sabin series.

TORGHELE: So just for clarity, would you describe the difference between the killed vaccine and the attenuated?

KEW: Okay. There's two basic ways of making a vaccine. One is to take the virus and kill it and make it so it's completely noninfectious, and then inject 00:12:00it--usually into the muscle or just under the skin of the recipient--and they make protective antibody to the vaccine virus. With today's modern molecular methods, you can actually use artificially generated antigens, that don't necessarily require killed virus anymore, but something produced in the lab that still has a virus-like surface--what we call determinants--that the antibody recognizes, that will then confer protective immunity. The other strategy is to weaken the virus genetically, and that's called attenuation. And attenuation traditionally had been done by growing the virus in alternative cells and tissues until, by repeated testing, it's shown to be genetically stable and safe 00:13:00and immunogenic. That is, it can, when given to vaccinees, generate antibody that would be protective.

Now, there's been many years of debate about the relative merits of the inactivated poliovirus vaccine and the oral poliovirus vaccine--IPV [inactivated polio vaccine] and OPV--and they have complementary strengths. But the argument in favor of the oral vaccine was that it would mimic a natural infection, and that the tissues that would normally be infected by the wild virus--the virus that's actually out circulating in the community--would also be infected by the vaccine, and you'd get a local immune response there for the attenuated oral vaccine. And that was the argument that Albert Sabin carried forward and pressed very hard in the late 1950s for his attenuated vaccine. And in fact that was the preference, I think, of the scientific community, because it was actually a little more scientifically sophisticated to develop an attenuated vaccine than 00:14:00develop a killed virus vaccine, so that's attractive to scientists already.

But the inactivated vaccine also required a great deal of development, especially to mass-produce it in a very large scale and to make sure that it was safe--not only effective, but safe--and that was the work of Julius Youngner and his colleagues under the leadership of Jonas Salk. We owe a lot to Juli Youngner and Jonas Salk for what they've done, because we really couldn't wait, in the wake of all those cases in the mid-fifties, for an attenuated vaccine to become licensed, which occurred six years later. The clock really was ticking on the children of America and the other parts of the world in the 1950s.

TORGHELE: So that's why the decision was made [to use IPV]?

KEW: IPV was available. There was some early work, done by Hilary Koprowski in the early 1950s, that showed promise for an attenuated vaccine, but in the end 00:15:00it was the Albert Sabin vaccine which was licensed. It had some advantages, in terms of genetic stability, over the others, and I think genetic stability turned out to be one of the most important criteria for selection of the Sabin vaccines. So between 1955 and 1961 a lot of children were spared, and we actually had 90% or more reduction in the incidence of polio after introduction of the inactivated vaccine.

So there are actually two different kinds of epidemic curves that are presented. One is the preferred Salk-Youngner curve, which will show a linear decline, a 90% decline of polio cases in the United States. The other one is the Albert Sabin curve, which he liked, which is on a log scale, which--then the first 90% reduction is just one interval on that log scale, but the next 90% 00:16:00reduction--or, the next 9% reduction--is the equivalent interval on the log scale. Okay? That debate has been going on since 1955 and 1961.

TORGHELE: So it looks much more dramatic, I guess, on the log scale.

KEW: Well, it looks more dramatic in the linear scale, where 90% of your scale is used up by the drop brought about by the inactivated vaccine, and then the remainder is done by the oral vaccine. The log scale shows, say, 100%, 10%, 1%, in equal intervals. So Albert Sabin liked the log scale, and Jonas Salk and his colleagues preferred the linear scale.

TORGHELE: One of a few differences they may have had.

KEW: There were a few other differences of opinion that they had.

TORGHELE: So, as far as CDC's role in polio, how did that develop? How did CDC--Centers for Disease Control--get involved with polio in the first place?

KEW: The root was the Cutter incident, and Neal Nathanson can tell you a lot more about that because he was there at the time. But the Cutter incident struck home to me very personally because it was centered in the western states. And it became evident there was a problem within the first few weeks of introduction of the inactivated polio vaccine in the western states. My mother had just taken her three children to get immunized. She was one of the earlier adopters of IPV 00:18:00immunization, and as she was driving us home from the physician's--no more than an hour, maybe thirty minutes earlier, we'd just gotten our injections--the news broke in California about problems with children who had received inactivated vaccine and some were getting polio and a few died.

And Neal Nathanson was the epidemiologist based at CDC who investigated that, and I'm sure he'll tell you much more about the details of that story, and he published three landmark papers describing the Cutter incident. That also put CDC's activities on polio on the map, including the lab, because there's an important lab component to that. The main effort was epidemiologic, but there was also a lab component of that, and so both lab and epi [epidemiology] working together had unraveled the Cutter incident.

TORGHELE: And how did that work? How did the lab identify where the tainted 00:19:00vaccine came from?

KEW: Well, first of all, children that had received Cutter vaccine were excreting type 1. It was the type 1 component that was incompletely inactivated. Not quite sure why the type 2 and type 3 were not as much of a problem, but it was type 1 that was the one that was causing the problems. It does have what we call a higher attack rate: the case-to-infection ratio is much higher for type 1. About one in one hundred infections results in a case if someone's not immune, whereas for type 2 it's about one in two thousand; for type 3 it's about one in one thousand. So there's other reasons why the type 1 might've shown up more, but the lab was finding that it was type 1, consistently.

They had some tools which could distinguish--and Jim Nakano developed those tools--the type 1 vaccine virus and type 1 wild virus. But in those days it was the wild virus itself, and it was the Mahoney IPV strain of wild virus. It was essentially indistinguishable by the techniques of the day from the other wild 00:20:00viruses around, but it was the consistent finding of type 1 among vaccinated children. The more powerful data were epidemiologic, and that's what Neal Nathanson did in his investigations. There was a very, very powerful link, temporal link, between exposure to the Cutter vaccine--not the other vaccines, but the Cutter vaccine--and the subsequent appearance of polio cases in some children, and he'll tell you a very rich and detailed story about that.

TORGHELE: So the difference was the pharmaceutical company that manufactured--

KEW: There was enormous interest in scaling up to produce inactivated vaccine in the wake of this public health crisis, and so a number of manufacturers scaled up to produce inactivated polio vaccine. Many were much larger and had much 00:21:00better facilities than the Cutter facility, but Cutter wanted to do its part to help with this outbreak--essentially, these epidemics--and so they adapted their facilities for vaccine production. But they really had a number of deficiencies in their facilities. It turns out that some of the larger facilities also had problems with inactivation. So it wasn't just Cutter, it was a more complex problem than that. But the other ones discarded those lots where they detected the virus, and didn't report it. There was no reporting agency. The FDA [Food and Drug Administration] and CDC were not required to receive reports from vaccine manufacturers. The vaccine manufacturers had the responsibility to produce a vaccine under standardized conditions, and test the lots, and release only safe lots. And so the larger manufacturers, when they had difficulties, would discard that material, autoclave it, destroy the virus, destroy those 00:22:00lots, and only release lots where they could never detect the virus.

Cutter knew ahead of time that they were having some difficulties with their vaccine production, and when Juli Youngner visited the Cutter facilities on April 12, 1955, he saw a number of deficiencies. And he could tell you much more about that, because he was right there on the spot. And it could not be pinpointed to one single problem, and it could not be pinpointed to strictly Cutter alone, because, as I told you, other facilities were having similar problems--but maybe not of the same magnitude, because they had much better facilities for production.

TORGHELE: So there were no regulatory agencies at the time?

KEW: No.

TORGHELE: And did any result after that?

KEW: Yes. It gave the Food and Drug Administration the authority to regulate 00:23:00vaccines. We now have a Center for Biologics Evaluation and Research, which is the offspring of that, the consequence of that. But at the time this was happening we lived in an anti-regulatory mood. This was the Eisenhower administration. The thought among many in that administration was that the private sector will take care of these problems and will regulate itself. There was a change in attitude in the wake of the Cutter incident, and much greater public involvement.

TORGHELE: Getting back to CDC's role, what is your understanding of how CDC got the role of surveillance, and it wasn't, for instance, the National Institutes of Health?

KEW: Originally the surveillance was done in Washington, D.C.--and that's a very 00:24:00good question, where I would have to go back to my records to actually explain precisely which institution it was, but there was a predecessor to, basically, our National Center for Health Statistics, and a man named [Dr. Carl] Dauer, starting in probably the early '40s, was documenting polio cases in the United States, and this major upswing. But he had predecessors, because polio was a notifiable disease in the United States starting in 1915 or so. There was a big outbreak in New York City in 1918, and there was a requirement thereafter. So I 00:25:00say--1915 may be a little bit early, but thereafter there was a requirement for notifying cases of polio. It had been monitored out of Washington, D.C.--various earlier organizations in the federal government reported polio cases--so there's been documentation of polio cases that date back to the early part of the twentieth century.

TORGHELE: And that documentation is one of the things that CDC has taken on and has done well.

KEW: That's right. I wasn't there at the time. I was just a little kid when this was all going on, but I really think that Alexander Langmuir's excellent work, and Neal Nathanson's outstanding work on the epidemiology in the face of the Cutter incident, helped make the decision to shift the emphasis from Washington, 00:26:00D.C., to CDC here in Atlanta.

TORGHELE: Okay. So why don't we move on to immunization itself, and how those programs started? I know that initially they started with a program: they did field trials and they used the inactivated vaccine, and then you said in 1961 they switched to the attenuated vaccine. Then after that, there were some problems that arose with the attenuated vaccine, related to vaccine-associated--

KEW: Yes.

TORGHELE: Do you want to tell us how that was discovered, and what role the lab had in that and your work? You weren't there yet, but--

KEW: I wasn't there when the first epidemiologic reports came out. I was in high 00:27:00school at that time. It was noticed soon after the use of the oral poliovirus vaccine, OPV, that there were some cases that were temporally associated with OPV use--primarily type 3, and to a lesser extent type 2, and rarely type 1, and we know much more about the underlying molecular biology that can explain that today. But [Dr.] D.A. Henderson and his group wrote a seminal paper recognizing the existence of vaccine-associated paralytic polio, or VAPP, and we would have somewhere around six to eight cases a year of vaccine-associated paralytic polio. I'm going to switch to the term VAPP now in the further discussion.

And VAPP was sporadic, and that was in two main categories. It was among those who were recipients of the oral vaccine and among those who were unimmunized household contacts of vaccine recipients. Then there was another group--they were kind of community-acquired VAPP--and then there's a fourth group I can discuss a little bit later, among immune-deficient individuals. But among the healthy individuals, the temporal association among recipients was very clear, that soon after exposure to the vaccine, there were now sporadic and very rare cases of vaccine-associated paralytic polio. Also household contacts of recently immunized children, those may be--caregivers who change the diapers, for example, can get exposed and come down with polio.

VAPP was investigated not only epidemiologically, but also virologically, and 00:29:00the pattern of type 1, type 2, type 3 and the relative importance of the three serotypes was already worked out by Jim Nakano, working from the lab side with [Dr.] D.A. Henderson. And what was unusual about VAPP was that we, again, had a prominence of type 3 and then type 2 and rarely type 1, whereas with the wild virus it was primarily type 1, less type 2, and then type 3. The techniques of the time could not completely distinguish a wild virus from a vaccine virus. The reason was that the vaccine virus would undergo some kind of antigenic evolution--which we now understand in detail, but at the time it was a phenomenon that actually caused some confounding results. Sometimes you get these vaccine virus-related viruses which had wild virus characteristics, and so 00:30:00you had roughly a 10% error rate in what you actually could distinguish by the techniques of the time.

When I came to CDC, I had a molecular toolbox. And Walt Dowdle had already helped set the stage, along with Jack Obijeski, of having everything waiting for me with a new technique called oligonucleotide fingerprinting, which had been developed by [Frederick] Fred Sanger, a Nobel laureate, in England and then refined quite beautifully by Eckard [Albert Friedrich] Wimmer for poliovirus. We learned the technique that Eckard's lab had used--Wimmer, Akio Nomoto, Y.F. Lee had used in their lab for basic research purposes. We applied it to epidemiology, and now we had 99.9% accuracy. We missed a couple of calls, and when we missed those, they turned out to be the basis of some important discoveries later. But we now could identify with absolute precision whether the virus was vaccine-related or wild, and that turned out to be important later, 00:31:00for the eradication initiative to be able to distinguish whether we had VAPP as a residual, versus complete eradication of wild poliovirus.

TORGHELE: So did that change the policy at the time for which vaccine to use? Or was there discussion about that?

KEW: Certainly, there is a level of certainty now about VAPP. Albert Sabin never believed in VAPP, and when I first called him up from CDC and said that we're interested in maybe trying to genetically stabilize the OPV strains to eliminate the problem with VAPP, Albert Sabin said, "Why would anybody want to do that?" There is no such thing as VAPP, and your CDC colleagues are leading you astray.

Okay. So that was his response. And I don't really know whether he really 00:32:00completely believed that, but VAPP would've otherwise been a complication in the discussions about how we go forward with global eradication. And Albert Sabin clearly had global eradication in mind, really, from the earliest days, and I don't think he wanted the stumbling block of VAPP to muddy the waters in the discussion. And frankly, as we got into the program--and we'll talk about the PAHO [Pan American Health Organization] program later--we also wanted to set VAPP aside, because we might've had, at that time, maybe upwards of two hundred to four hundred cases of VAPP in the world. We had four hundred thousand cases of wild poliovirus-associated polio in the world, so VAPP was a minor problem. It was a problem in the United States because when you controlled the wild polioviruses types 1, 2 and 3, polio outbreaks all disappeared. So the only thing we had left was VAPP. So there was a lot of discussion about VAPP in the U.S. But in the developing world, including Mexico, our southern neighbor, they 00:33:00still had polio up until 1990, and so the VAPP discussion became really a distraction from going after the real problem, which is wild poliovirus circulation.

TORGHELE: Interesting. So, this being the United States, were there legal issues related to VAPP?

KEW: Oh, yes. We originally had seven vaccine manufacturers. Six of the seven dropped out because of the burden of litigation, and the only one who remained was Lederle. And Lederle labs had a particular interest in a live, attenuated polio vaccine, because they were one of the three groups. Herald [Rea] Cox led that group that worked on making attenuated polio vaccine strains. There were 00:34:00other groups, like [Dr.] C.P. Li and so on, also doing this work, but there were three groups who were trying to make a complete package of type 1, type 2, and type 3 vaccine strains. There was Albert Sabin, which everybody knows, there was Hilary Koprowski, and there was Herald Cox at Lederle. So Lederle honored that deep commitment that they had, dating back to the early 1950s, by being the last man standing for making polio vaccine--OPV--in the U.S. But they carried a heavy litigation burden with that. So the cost of litigation exceeded the cost of the vaccine production and packaging and distribution, and some of the judgments against the manufacturers were in the millions of dollars. And it was really very unfortunate, because it drove vaccine manufacturers away from producing vaccines, and still is driving drug companies away from producing vaccines.

Now the precedent-setting case is Reyes v. Wyeth, and we had occasion to reinvestigate that because Jim Nakano told me that he believed that the virus that caused the paralysis of a little child--I'll tell you a little bit more about the child in a moment, a little girl, Anita Reyes--was a wild virus. And the uncertainty in the techniques at the time allowed the judge to instruct the jury to disregard the virologic data and look at the other factors, including the impact of this infection on this poor little girl from a poor family, and how they will now have to bear the burden of taking care of this child with no kind of compensation at all. And the jury could see the human side, and ruled in 00:36:00favor of the plaintiffs, the family. That was a precedent-setting case.

When we reinvestigated this, we saw that the virus was the outbreak virus and the outbreak occurred on both sides of the border. The little girl lived just on the U.S.-Mexico border. The outbreaks frequently spanned the border, and the virus was prevailing wild type 1 outbreak virus. We showed that first with oligonucleotide fingerprinting, and then we showed it again unequivocally with nucleotide sequencing, another technique that was developed a little bit later on. But that didn't affect the subsequent legal cases, because the precedent had already been set that the vaccine manufacturers were liable for production of something which was imperfect.

And, frankly, it's extremely difficult to make a live virus--especially an RNA 00:37:00[ribonucleic acid] virus attenuated vaccine strain--that is completely genetically stable. And that was what was being asked of our domestic manufacturers and all international manufacturers--to make an oral polio virus vaccine that's completely genetically stable. And with all the tools in molecular biology now, we have a much better chance of making something like that. We have things in our freezers that are much, much more stable. With the technology of the day it was essentially trial and error, trial and error. And very, very careful work was done, and the rate of reversion is extremely low--one out of--about one in a million. And we were able to save millions of children from polio using the oral polio vaccine, even though it was not perfect. It was very, very, very good, but not perfect. But the message that I would make to attorneys who would call me and ask me if we can do something in 00:38:00the lab to help make their cases: No. And second of all, if they persist and we no longer have vaccines, then there's going to be a five thousand fold increase in polio cases in the United States, and we don't want to go there.

TORGHELE: Now, do you think that VAPP played a role in the development of the injury compensation that later developed into the National Vaccine Injury Compensation program?

KEW: Definitely did. I'm not the best one to actually tell you about that, but the answer is definitely yes. The lab played a role in proving unequivocally that it was the vaccine viruses causing VAPP--but Jim Nakano had 90% of the answer already, and I just had to close that small gap.

TORGHELE: And also just for clarification, when you say "fingerprinting" of a virus, what does that mean?

KEW: Okay. That's a good question. We did not have sequencing. When I first came to CDC, there were no complete poliovirus sequences yet published--in fact, yet available--and the methods used to develop the poliovirus sequencing at that time were beyond our capacity at CDC--in our infrastructure at that time--to do. And there were a number of impediments for us to do the work. And so other academic labs, actually--the pioneering labs, anyway--had done the poliovirus sequencing in 1981. What we had before that was something called an oligonucleotide fingerprint, and it was essentially a two-dimensional array of fragments of the RNA genome, the genetic material of the virus, that spread out in a pattern in two dimensions in what we call a polyacrylamide gel. It's just basically a molecular sieve, and the constellation of how these spots arranged 00:40:00themselves could tell us the origin of the virus.

And the problem with the technique was, first of all, it required the use of radioisotope P32, and we used fifty millicuries [a unit of radioactivity] of P32 per week in the lab. That was more than half of all the CDC's radioisotope usage then. Second thing was that it was a very laborious technique, and although very precise, it wasn't suitable for a global program. We could process maybe six, at best twelve isolates per week. My technician, Baldev [K] Nottay, produced beautiful fingerprints, but we could not scale this up. And if we were to scale it up, that would be maybe one hundred millicuries or two hundred millicuries of a very hazardous radioisotope they'd be working with. So we had these spots, which we could then say, this is a vaccine virus. We could definitely deal with 00:41:00all the VAPP cases in the United States, but we were not poised to extend that to the global program, which I'll tell you more about in a moment.

But fingerprinting looked something like a fingerprint. It's sort of a constellation of spots, and the arrangement of those spots could tell us a lot about the origin of the virus.

TORGHELE: So later, as techniques became more modern, what equipment did you get that made a difference in modernizing the lab?

KEW: That's a really good question, because when I first came to CDC, our equipment budget was somewhere around a thousand dollars a year. So we would go out, and we would talk to people who had plastic warehouses and glass facilities and explain why we wanted these oddly shaped pieces of plastic and glass. And I 00:42:00can remember going to one warehouse in Atlanta, and I explained to them what we were trying to do. We're trying to track viruses, and we're using these molecular techniques, and we needed these specialized plastics. And he said, Well, I don't like to work with the government, and all the overhead and paperwork we had to do working with the government is just, you know, beyond what I'm prepared to do. But then he said, But you're CDC, you're really not like the government, and you want to do things to help people. So here, you can have it for free. I said, "We can't take it for free". He said, "Well, it'll cost me more for the paperwork for what you need, so here, you can have it for free". And we used that stuff for years.

We built our own equipment. We had a very good shop, outstanding craftsmen. So even though our budget was modest, often what we had to buy from the outside was maybe the platinum wire for some of our equipment, which we used for our electrodes or some more equipment. Everything else was built in-house by our 00:43:00craftsmen, or by merchants who could make things to specifications at a rather modest price. So we were able to muddle through, even on our modest budgets, because we had this facility of outstanding craftsmen who also were engaged. We told them what we were trying to do and why, and they gladly made it for us--beautiful, beautiful stuff.

So now, of course, we have automated equipment, as our techniques evolved and we had to change our techniques to meet the demands of a global program. First of all, we had to get rid of the radioisotope. Second, we had to make it so it could be suitable for mass scale. We first started, again, with some homemade stuff, and then went to commercially available stuff as our budgets increased, and now we have lots of robotic equipment that can do essentially a whole person's career worth of work in a span of maybe a month. But, you know, in the 00:44:00old days everything had to be done by hand.

TORGHELE: And no computers.

KEW: No computers. When I first came to CDC, I came from a heavily computerized lab, but it was a mainframe and what we called mini computers. Not like microcomputers, which is what we call PCs today. And so I visited our mainframe computer facility and I explained what I wanted to do for scientific computing. They said, No problem, we'll just take that part of the core that has your personnel records and your payroll records, and you can use that for your science. So it was a bit of a tough sell in early days to get computerized.

TORGHELE: Seems incredible now.

KEW: Yeah, it's incredible, but that was the response I got. It turns out that 00:45:00that was not the attitude of CDC management, so things changed.

TORGHELE: So the laboratories were pretty much involved with polio work from the very beginning?

KEW: Yes.

TORGHELE: What about vaccine development? Were the labs involved in helping with analyzing the vaccines and their efficacy, or--

KEW: Yes.

TORGHELE: What did they do, and how?

KEW: For the inactivated vaccine, I don't think CDC's role was quite as intense as it was for the live attenuated oral vaccine, OPV. But for the OPV, first of all, I think I already told you C.P. Li developed the type 1 OPV strain, and its name is LSc. Li and Schaeffer and that actually had three lines--a, b, and c--and the c line became the parent to the Sabin one, which he called LSc 2ab, 00:46:00quite properly. There was an enormous amount of work done by CDC for testing the efficacy and safety of OPV, and our freezers had--until recently, until we had to implement containment for type 2--was filled with old strains collected from various field trials in the United States, a number of them in Atlanta. So Jim Nakano and his colleagues were heavily involved in testing the safety and efficacy of OPV and monitoring its impact. There was some earlier work of monitoring the impact of IPV, but most of CDC's epidemiologic work afterward on a routine basis--unlike the Cutter incident, which was a real emergency, but on a routine basis--was with the OPV after 1961.

TORGHELE: How did the labs and the epidemiologists work? Did you collaborate on some of these things, and how did that go?

KEW: It's interesting, because initially when I first came to CDC there was a Bureau of Labs, a Bureau of Epidemiology, and not a lot of regular communication between the two. There was almost a barrier. The labs were the labs and epidemiologists were epidemiologists. And we had a visit from Larry Schonberger about 1979 to see what we had with this fingerprinting and how we could use it. And he was very interested in this because of the Amish outbreak, and we could show him how we could track the virus from the Netherlands to Canada to Pennsylvania, and from Pennsylvania to other states in the midst of this outbreak, and then in Canada going from Ontario out to British Columbia and Alberta. And so it was a visit. It wasn't like a day-to-day working 00:48:00relationship. Of course, we built that with our epidemiologist colleagues over the years. But initially, I think, organizationally we were separate. And that was, I think, a mistake.

[Dr. William H.] Bill Foege, Walt Dowdle, and others had a different vision of unifying programs, having lab and epi working side-by-side, solving problems together. And that was the idea of a National Center for Infectious Diseases, and we had several of these centers. We still had some separation, because we had--what became Global Immunization Division was at one time the National Immunization Program, a separate program. Before that it was in Epidemiology for State Services and just organizationally separate. But already the trend for 00:49:00unification of effort was started--really in the early 1980s, by Bill Foege and Walt Dowdle--to bring the epidemiologists and the laboratory scientists together. And I think that was very important for polio eradication.

TORGHELE: So, speaking of polio eradication, tell me about how that began at CDC and how it evolved.

KEW: Okay. It's an interesting story. We had this tool of oligonucleotide fingerprinting. I had already learned about the handling of radioisotope waste in developing countries, because I'd visited the Los Alamos labs in the 1980s, and we were working on using some advanced biophysical techniques to identify 00:50:00infectious agents--so a collaboration of CDC and Los Alamos. While I was at Los Alamos, I switched on the local news, and there was a news alert about a truck carrying I-beams--heavy structural steel--that could not make a U-turn in the narrow roads in the mesas of Los Alamos, and had to ask permission to do a U-turn inside the National Laboratory and swing out again. As they entered and exited, they set off the Geiger counters, and it turned out that the structural steel I-beams were radioactive. And it turned out that because of improper disposal of radioactive materials in Mexico--got melted into the I-beams. And once I heard that, I decided we're not going to use P32 [Phosphorus-32 ] in developing countries.

So we started developing other methods that didn't require the use of 00:51:00radioisotope, and in anticipation that if we're going to share our technology with developing countries, that it would be something that would be safer for them to handle. Another incentive for that was, I really wanted to get back to some more basic research, and so if I could develop a way to take care of all the U.S. VAPP cases in a week or two, then I could spend the rest of the year doing more fundamental research. So that was the idea.

So we developed some other techniques called dot blot hybridization, which was a spot test to identify whether the virus is a vaccine virus or wild virus, and by several different steps could identify which wild virus it was--whether it's a Brazilian one or a Mexican one or some other one from another part of the world. So that idea, we developed that. And that would allow me to do more development work, because we could essentially take care of all of the U.S. domestic cases 00:52:00in a short amount of time, and investigate retrospectively some of the interesting ones that Jim Nakano had led me to before. But then it turns out that PAHO had this dream of eradicating polio, and--

TORGHELE: And PAHO stands for?

KEW: The Pan American Health Organization. And there are two stars who I would mention in that. One would be [Dr.] Ciro de Quadros, and he was a program manager for the Expanded Program Immunization--we called EPI. And standing behind him, in complete support of what he was doing, was Carlyle [Guerra] de Macedo. Both of them are Brazilians, and Carlyle gave Ciro all support to going forward on polio eradication in the Americas. So in 1985 Ciro invited me up to Washington to PAHO headquarters and invited me to go into a meeting room where 00:53:00there was a vote to be taken on whether to go forward in polio eradication. And the chairman of this committee was a person from Cuba, Dr. [Miguel] Galindo, because Cuba was the first country to intentionally eradicate polio in the world--and using OPV, and they achieved it in one year, in 1962. And there is a vote, and they voted unanimously to go for polio eradication in the Americas. And Ciro looked at me and said, "Do you know what they're voting on?" And I said, "Well, I just came out of the lab, you have to tell me, please". He said, "They voted to eradicate polio in the Americas", and he says, "There's some implications for you at CDC in all this".

Well, what the implications were was, we worked with PAHO to build a laboratory network. We tried as much as we could with the help of PAHO staff to unify the 00:54:00lab and epi, to have a unified approach to this. We had very good people supporting this initiative. One was D.A. Henderson, who was the chairman of the Technical Advisory Group to go forward. We had [Dr.] Alan Hinman from CDC, also, on the TAG [Technical Advisory Group]. We had a number of real icons of polio on the Certification Commission, chaired by [Dr. Frederick C.] Fred Robbins, who was a Nobel laureate who contributed to the development of cell culture, which made all this possible. So now our responsibility at CDC was to help PAHO build a laboratory network to essentially provide the evidence that polio had been eradicated.

So their vision was, we build a network, we look for virus, and then when there's no wild virus, we'd be able to provide documented evidence that wild virus was completely gone. The techniques at the time were sufficiently powerful 00:55:00that we could identify wild virus with certainty. What we thought was, maybe we could do a bit more than that. We actually could help them track how the virus is moving, where the reservoirs are that it's coming from, and how we could build a network so that they could do the tracking locally within the countries of Latin America. So that was what we suggested might be possible. And Ciro, along with [Dr.] Francisco Pinheiro who was head of the virology lab programs in PAHO, agreed and supported us. And there was a great deal of enthusiasm on the parts of the lab scientists that they could actually do something helpful for their countries.

So some of them were doing research work, or they're doing a little bit of documentation that yes, this is a wild virus; yes, this is polio type 1; yes, we had this outbreak. But there was a sense of frustration because all they were doing was delivering bad news--yes, we had polio again--and we had many examples 00:56:00of that where there was sometimes a pall of defeat over the health ministries. I'd seen it with my own eyes in the early days, before the program was launched. And the opportunity for the lab people to actually work on something that would help their people in their countries--it was a golden opportunity which they seized, and Ciro really held that banner up high, and that polio eradication could be done, and it was achieved in six years. Made us pretty confident it could be done by the year 2000 globally. It was achieved in six years before there was actually very much money, although the Rotarians had already had their own program of PolioPlus. And Rotarians were backing Ciro and backing us completely, and they were providing lots of their own money to support this, and without them we probably would have never been able to get started.

TORGHELE: Can you talk a little bit more about Rotary International and their relationship with the polio eradication?

KEW: They had their own program called PolioPlus, and it started in the Philippines and other developing countries with a vision that they could help eradicate polio. Now, an important thing you need to know is that Albert Sabin was a Rotarian, and he persuaded his fellow Rotarians to take this on. And they had never before taken on such a large global and challenging enterprise, and there was a lot of discussion about whether they should go forward. But once they made the decision to go forward, they were all in, and they still are, now more than thirty years after the launch of PolioPlus and polio eradication. They're still all in, and they are supporting us to this day. They support us at the global level, they support us at the regional level, they support us at the local level giving vaccine to children.

They did things which we couldn't do. They provided volunteers, which, when we were small, we didn't have--we, meaning our overall program. They listened to 00:58:00the technical advice coming from PAHO, coming from our Technical Advisory Group, which had a strong CDC flavor to it as well. They helped us build labs. The local Rotarians in District 6900 here in the Atlanta area helped build labs which we depended on enormously later for the program; built up a lab in Moscow which needed help in a time when the Soviet Union had collapsed and the Moscow lab had all kinds of talented virologists but not much in the way of resources; built the lab up in Ethiopia; a number of other examples. One in Maiduguri, Nigeria, turned out to be ever so crucial in the last stages of polio eradication. There are Rotary contributions to all of that. A Rotarian gave as his bequest funds to build up the Pakistan lab. You go into the Pakistan lab--now a superstar lab, and one of the ones we depend on so much every day now 00:59:00in the last stages of polio eradication--you go in there, and there's the great Rotary gear right in front of the lab, because they bought the equipment and argued, advocated for them.

So that's the lab side. But for the overall program side, they've been with us from the beginning, cheering us on, encouraging us. Sometimes when you get discouraged, the Rotarians, who were always friendly and positive and forward-looking, would cheer us on. So, yeah, they've been partners right from the very first days. And maybe they would see us as their partners, because they had PolioPlus as a precursor to the polio eradication initiatives, and that was the foundation for Ciro's activities with PolioPlus.

TORGHELE: So, they provided resources for CDC and other organizations?

KEW: They advocated for us in so many ways. Without them going to Congress and 01:00:00talking to both sides of the aisle, and discussing it with members of the administration as well, we might not have gotten the resources we've gotten. We've been very generously supported, far beyond our wildest dreams, I can tell you. We were thinking, in the first initiative we drafted, maybe a hundred thousand dollars. We've gotten well over a hundred million dollars per year. The Rotarians have supported us, advocated on our part, and recognized various key legislators--House of Representative members or senators--as Heroes of Polio Eradication from both sides of the aisle. And so without their engagement, I don't think this global program would be anywhere near as far along.

TORGHELE: That's a great story.

KEW: There's lots of stories. I can tell you great stories about Rotarians. In fact, I will. The District 6900 Rotarians, just as a local vignette, asked how 01:01:00they could help. They said, "Whatever we can do, how can we help?" They came to visit the labs. We showed them the labs. How can we help the labs? I said, "Many of the labs in these developing countries have almost no equipment--have people that want to do the work, but they don't have the facilities. Maybe you could help with that". So, since the Rotarians are often the captains of industry, they would call up other Rotarians and say, "They need computers in this lab". And the high management officials would say, "Well, we can't sell you the computers at a discount price, which is what the Rotarians were asking. But we can give them to you as a gift".

So what happened was that on more than one occasion, the Rotarians would gather all of this equipment. We actually took some of CDC's supplies--like glassware, plasticware, things like that, which were critically needed--and we brought a 01:02:00truckload of those things. I drove the truck from CDC full of all these supplies to get these labs started. Then the Rotarians had a container waiting at Naval Air Station Atlanta to be airlifted by the U.S. Navy, in one case to St. Petersburg, another case to Addis Ababa--airlifted--and then from there the equipment was transferred to the lab. In St. Petersburg it was to the Moscow lab. Then there was a special railway car that had this container going to the lab that was under guard and carried all the way to Moscow, and then delivered to the lab. So that's what Rotarians did. We did a little bit. We made suggestions what the needs were. They took it from there. That's just one vignette out of hundreds, thousands of vignettes.

TORGHELE: Talking about the Rotarians reminds me of Bob Keegan. Do you want to 01:03:00talk about his role in all this?

KEW: Oh, yes. We're almost there, and Bob is with us in spirit, but I wish he were here in body. In many ways this is Bob's legacy. Bob was a Public Health Advisor, and he was really--I think he honors Public Health Advisors by being a prototype of Public Health Advisor, but we lost him a few years ago. He was forty-nine, and before that he had devoted 110% of his energies to polio eradication. And although his area was administration and making sure things happened as a Public Health Advisor, he took on all kinds of technical knowledge 01:04:00and, again, served as a bridge between the lab and the program. Bob and [Dr.] Steve Cochi in particular tried to draw us in-- [Dr.] Mark Pallansch and I--to build an even stronger partnership, and Bob was a very, very strong part of that. He invited us in. He brought us in. We discussed what the needs were, what the problems were together, and Bob understood our language. He'd tease us about it a lot, you know, about our crazy genetic trees and our crazy fingerprints. He'd tease us, but behind that teasing was a real sophisticated understanding of what the role of the lab was, and understanding of what our real goals were, and we shared those goals. I think that was part of what made the partnership so strong.

And Bob shared the same vision that Steve Cochi did and Walt Dowdle did and those of us in the lab did, which was: polio eradication was the first step in 01:05:00building global public health infrastructure. We wanted to eradicate polio to save kids from polio for sure, but we also needed to build an infrastructure up to take on measles, take on rubella, to take on invasive bacterial diseases, to take on Ebola now, more recently, or Zika. So it was going to be the foundation, and the vision was that we were going to build this up together--program, epidemiology, lab. We were going to build this up together, and Bob shared that vision and did everything he could to advance that, and we would meet together regularly and Bob would often be the rapporteur. He would organize the meeting. He'd say, "What are the action points here?" What do you lab people got to do? I see that you've got to do this, this, this, this. What do the epidemiologists have to do, and the program people? You've got to do this, this, this, this, you've got to work together. Here's the junction of your efforts".

So, he was an integrationist. He'd integrate program, epi and lab, and he 01:06:00carried the vision. He was an outstanding communicator. He carried the vision wherever he went, and he went into some really rough places to do that.

TORGHELE: Tell us about the bike ride.

KEW: Oh! Bob had this dream of biking all the way across the country--and he was a fit, tough guy--and I actually shared a similar dream, but we still had some other responsibilities, so I couldn't take the time to ride across the country. But Bob started, I think, in Portland or right along the Pacific coast and ended up in D.C., and he had a recumbent bicycle, and he took sort of the back 01:07:00highways. You couldn't really use the superhighways for most of it, and he succeeded in biking from west to east. Sort of the opposite of Lewis and Clark, who started off from east to west, but started about the same place that Lewis and Clark ended up in, in their exploration of the west. He had his supporters. Many of his colleagues would come and join him in various legs of the ride. And he went all the way across, and he wrote a log about his bike ride across America. It was a heroic thing to do. Then he moved to England and we talked about whether he was up to the job of going east to west, a bike ride across England, okay?

TORGHELE: A little different.

KEW: A little different, yeah. But I think he saw a lot of the country that he would otherwise never see. He went through some of my old neighborhoods over the Cascades, across the great deserts and over the Rockies. I mean, some of that 01:08:00across-the-desert stuff was really a difficult challenge. Not unlike what the pioneers did as they were heading from east to west across some of these vast deserts. Then, once he got on the other side, then he had to deal with the warmer weather, the more humid climate of the east. So it was a real adventure, sort of a modern Lewis and Clark in some ways, going from the opposite direction, going with the winds, of course. But that is a terrific story.

TORGHELE: And the purpose was to raise money for polio eradication?

KEW: That's right.

TORGHELE: Is it true that he stayed with some Rotarians along the way?

KEW: Yes, he did, and Bill Sergeant was a Rotarian who helped him in that. Bill was engaged in the program, another person that we lost far too soon. His life was PolioPlus and polio eradication, and Bob had pictures of Bill on his recumbent bicycle. Oh, yeah! Oh yeah! Talk to Gloria, okay, about that.

So Bill Sergeant's got a big smile in Bob's driveway on Bob's recumbent bike. I think that was before Bob went out west, okay. So it was ahead of the trip, is my recollection, but Gloria can tell you for sure. And Bill arranged for Bob to stay at the Rotarians' various homes along the way.

TORGHELE: It's a great story. So, talking about Bob and collaboration and cooperation, you have to tell us about Mo's Pizza.

KEW: Yes. Well, it turned out that we had first started at P.J. Haley's, to have some meetings at P.J. Haley's, but they shut P.J. Haley's down. That was in Sage Hills. No, I'm not sure. Is that the neighborhood? But it's a nearby shopping center. Okay, so do I need to start over?

Okay, so we first started at P.J. Haley's, but then they shut P.J. Haley's down. A place near Bob's home was Mo's Pizza, where he'd take his family for pizza Friday nights. Well, he was able to bring his family but also bring the rest of the polio family with him to Mo's on Friday nights. We'd have our meetings and then we'd adjourn to go to Mo's, okay? So you couldn't really go too far over time in our discussions about the program because that would be cutting into Mo's time, okay?

So I guess the pioneers of that were--certainly Bob was the first pioneer, then Steve Cochi, Roland Sutter, Mark Pallansch and myself, and that was emblematic of the collaboration that we had. I mean, this really was a group of friends 01:11:00working together toward a common problem, where each of us had various aspects of the problem. We had complementary strengths, and then the strengths spilled over because we shared our insights and approaches. And Bob played a key role in bringing that together, bringing us together in an informal setting. Of course, the other GID [Global Immunization Division] colleagues and lab colleagues were happy because it was a very, very happy environment, very, very happy collaboration. We actually were able to discuss things in that setting which you couldn't discuss, the programmatic things that you couldn't easily discuss at CDC. So a lot of problems got solved at Mo's and still do.

TORGHELE: Great story. What about retreats? What role did they play?

KEW: That's [Dr.] Larry Anderson's fault. Larry saw that there was really even more need for discussion, okay? So he was very supportive of us as the branch 01:12:00chief, and it really wasn't a branch, it was a division called a branch. So, as the branch chief he was hearing what our problems were and suggested that we have retreats, and we would have internal retreats. That is CDC, GID--now GID, NIP [National Immunization Program] before--and Mark Pallansch and myself, the polio lab retreats together. And then it got broadened to WHO [World Health Organization] people, and some of the WHO meetings were first held in Atlanta--major WHO meetings, which later, as WHO took more ownership of the program, which we wanted them to do, it transferred to Geneva. We would still have, essentially, the legacy of the retreats in our regular every-month meetings.

So we would have regular retreats, intensive discussions. Larry would attend and 01:13:00also contribute. He would engage with us as well, and those retreats were very helpful because it--again--solidified and strengthened our collaborations. Later it became like every two weeks. It was just, a monthly retreat or quarterly retreat wasn't enough. It became every two weeks or even more frequently if necessary. Now we go to the GID divisional meetings when there are things we can contribute. We have Friday afternoon--about every two weeks, Friday afternoon brainstorming meetings. And a lot of that, I think, we had to lay at the feet of Larry Anderson as kind of pushing in the direction we really wanted to go in the first place.

TORGHELE: And were the retreats all work?

KEW: No. No, we worked together, we played together. We also had that at the division level. We had retreats which were not all work, and we had retreats 01:14:00where we went up to Chattooga Lake and Doug Klaucke and his wife, Louise Martin, hosted us at their home, and we had our sleeping bags, and we had a retreat there right along the lakeshore. Then we would go canoeing, and Doug had a couple of canoes, probably so he could race Louise to see who could paddle the fastest. So they were not all work at all. It was enjoyable at many different levels.

TORGHELE: So when you mention the World Health Organization participating in the retreats, can you think of key people that you worked with? There was a Bruce--

KEW: There was [Dr.] Bruce Aylward, and he has been the program manager until 01:15:00recently. He's been the program manager probably since the late '90s, and he was a dynamo and was extremely energetic, and got on top of things and actually was personally engaged in polio eradication. I first met Bruce in the Western Pacific region, which was in those days pushing toward polio eradication--and I'll tell you about [Dr. Jong-Wook] J.W. Lee later, and his key role. Then Bruce transitioned to Geneva, and it became very clear that he was the kind of leader we needed. He was visionary, he was a quick study, he understood complex issues, could deal with complex issues, and really kept our program alive through the tough days of the continued appearance of cases--a number of countries after the 01:16:00year 2000. And each year after the year 2000, as 2000 was our target date, it got tougher--especially when we had spikes of outbreaks in India, big outbreaks in West Africa. Bruce was the one that would try to put everything in perspective. He'd say, Let's look at where we've been, where we've come from, how far we've come. Let's just look at the way forward. And always for Bruce, the glass was half full, and that helped us a lot.

TORGHELE: So what do you think the reason was for some of the outbreaks after 2000?

KEW: Well, we had more than one reason. One of the reasons was just weak program and weak management. We just had to admit that, and WHO will fully admit that. Some of it was, you had to train the people, because we actually started in some 01:17:00of the easier areas first, then moved to the tougher areas last. This is a lesson I think we've taken aboard for future activities. So we thought we had a tough job in Latin America until we started working in other places. When we moved the program--I keep using "we," but it's the program moved--from Latin America to China, we were astounded by the population densities. You know, it was hard to distinguish a rural area from an urban area in China. So we saw the epidemiologic challenge, but the infrastructure, the dedication and the level of sophistication in China meant that they were able to actually come in ahead of schedule. Their target date was 1995, and they had actually finished the job by early 1994. So that actually energized us. We thought, well, maybe we can actually come in on target. We had countdown clocks towards the late 1990s for the year 2000. We thought maybe we might need December 31, year 2000, to finish 01:18:00it, but we'd come in pretty close.

But 2001 was a watershed year, and in 2001 was the 9/11 attacks and the response to the 9/11 attacks and the rise in militancy in a number of the Muslim countries--particularly in Pakistan/Afghanistan, which is an impediment, and northern Nigeria, which is another impediment, and that's still a problem for us today in Pakistan and Afghanistan. Before that, the program--even though it was in its early stages--had little difficulty, say, in Afghanistan, to immunizing children. The vaccinators were welcomed. After that, it became increasingly difficult.

TORGHELE: And why was that?

KEW: Well, that's a very good question. It turns out that the Afghan Taliban were supportive of immunization. There was a kinship between the vaccination teams, the leadership and the people, local people right up to the border of Pakistan. So when the vaccinators came in they'd say, Our Afghan brothers, our 01:19:00Pashtun brothers are coming to give us vaccine, welcome! Come! The same community on the other side had much more difficulty being reached, because Pakistan is several different communities all in the same house, and the people along the border areas did not necessarily identify as closely with the people who were trying to implement immunization in Pakistan. So they say, well, these people are coming into our community to give us something that we don't want, because there may be some other things that we're concerned about. So militancy amplified that, and there were anti-vaccine rumors, and the anti-vaccine rumors were at their most aggressive in the Islamic countries. They actually first came, first appeared, in Christian countries in Central America and later in the 01:20:00Philippines. Then in the Islamic countries, always the underlying driver was really politics rather than public health. Somebody was trying to use immunization as sort of a whipping boy. The Minister of Health, as a representative of the incumbent government, is a whipping person. So we had a great deal of difficulty with militancy in northern Nigeria and in Pakistan/Afghanistan, to the extent that vaccinators were being targeted and killed in Nigeria and in Pakistan. And I met some of the young women who were vaccinators locally in the tribal areas of Pakistan. They said, Well, my friend was killed trying to give vaccine to the children of these communities, in the Pashtun communities, but I'm Pashtun and I must honor her so I'm not going to be 01:21:00afraid, I'm going to deliver vaccine to honor my friend who gave her life to protect the children. And in fact, the militants really didn't get into the hearts and minds of the people. Many of them in Pakistan were foreign elements, and it wasn't their children who were getting polio. So once the Pakistani army moved in and drove the militants out, the people freely accepted the vaccine. There was some resistance, but by and large the people did accept the vaccine.

That's a similar story in Nigeria, although Nigeria's a little bit more complicated because northern Nigeria was once separate from southern Nigeria. At the time in 1960 when the country became independent, those two parts were joined, but they are culturally different, and the infrastructure is much better 01:22:00in the south, and their literacy levels are much higher in the south, and literacy [is] the key indicator of acceptance of immunization and health-seeking behavior. In northern Nigeria they have low literacy, unfortunately, and maternal literacy is especially low, maybe under 10%. So, the rumors could take hold, take root, more easily, and the posters showing the benefits of immunization could not be read by many of the people who were the target population. So to counter the militants who were arguing against vaccine, spreading rumors about the vaccine, they actually had to give in Nigeria little theaters, little skits going from place to place to describe the benefits of immunization. That was an important part of the communications, was to reach the people with these little skits and theaters for a population where the mothers, 01:23:00in particular, couldn't read. And paternal literacy--and they were heads of the household--paternal literacy is only about 20%. So that was a challenge. This was a disease increasingly of the poorest of the poor, where the literacy rates were lowest, and reaching them was more difficult not just because of insecurity, but just because they were not accustomed to seeking immunization or seeking help. And in Nigeria, as one example, other parts of health infrastructure were so poor that there was some suspicion: Why are you coming with this vaccine free of charge when we can't get anything else for our children or for our people? The health infrastructure, particularly in the north, was a shambles, and now you have all this infrastructure for immunization and it's a rather sophisticated argument to say, well, wait, we are working on 01:24:00this, we have a broader vision, stay with us. We're not just here for polio, we are here for many other things. And that was the Rotarian's PolioPlus concept, was polio plus other things. So it was a page right out of the Rotarian's book and a page out of WHO's book about broader health benefits, but we actually had to use those arguments: Stay with us, it's not just for polio, we're going to come back for other things, but we must do this. We can do this, we're almost there.

A specific example of my experience in Nigeria was that people were not afraid of polio, because it was becoming increasingly rare, but they were terrified of measles. So we had to use that in working with our measles colleagues in a broader vision of what the legacy would be, to engage the people in things that they were much more gravely concerned about than polio, and we had to counter 01:25:00the militants' arguments. What we learned in a number of countries was that once polio incidence was low, then the militants' messages would resonate, but the militants' message didn't resonate about measles because the people would see the children dying of measles. So they discounted the rumors and they would seek immunization. So then it becomes a challenge to have a program that would deliver immunization, not just for polio but for measles and other things--but to meet the truest needs of the people. So another limitation was the strength of the programs.

Another cause, which is a little bit of a technical side, was vaccine-derived poliovirus outbreaks. We had those as well. So after the wild poliovirus was knocked out, sometimes there would be backsliding and population immunity would 01:26:00decline--particularly to type 2--and the type 2 vaccine virus would spread, and that actually caused outbreaks. In Nigeria, the outbreak lasted ten years. Had a number of outbreaks in Pakistan, and a number of other countries as well. First one that we documented was in Hispaniola. Another one which occurred earlier was in Egypt, which lasted ten years.

That actually was a communications problem as well, because on the one hand you're telling the public--the population of people--that the vaccine's safe, it's going to protect your children. But under certain circumstances--low vaccine rates or low vaccine coverage--it would actually rebound, boomerang back on you and cause outbreaks. So that actually was an impediment to acceptance of vaccine. You've got the people saying the vaccine's going to cause problems, and then you had to actually admit to the people, if you don't use it properly, it is going to cause problems. If you use it properly, it will not, and that's the absolute truth. We never had any outbreaks of VDPVs [vaccine-derived poliovirus] in areas of high vaccine coverage--only in Hispaniola in the Americas because of 01:27:00low vaccine coverage, particularly in Haiti, but we didn't have the same thing happening in other countries after the PAHO program was launched. It just didn't happen, and it hasn't happened in other countries. For example, China has these little micro-outbreaks. They jump on it, shut it down, and it's done. But developing countries with poor infrastructure that often would redirect their funds away from polio would pay a price. They are Congo, Pakistan--India had some episodes, Madagascar repeated episodes, Nigeria multiple episodes.

So the messaging became critical about, if you use the vaccine properly, you're not going to have problems, but if you do not, there is a danger. You must use the vaccine because if you don't, then the wild virus will persist forever, and we are almost to eradication now. We have to get rid of the wild virus. Stay 01:28:00with this. Just use it as directed. Just as Albert Sabin said, there will be no problem.

TORGHELE: So now polio is gone from all but two countries?

KEW: That's right. [WPV1 was subsequently detected in northeastern Nigeria] So far this year we've had in Pakistan/Afghanistan about the same number of cases that we'd have in about twenty minutes worldwide when we started, so there's been a little bit of progress. The areas of Pakistan where there are problems are in the areas where the militants have been strongest. It's been largely controlled there, but there is still some areas where there have been poor performance off and on. And then areas in an urban center, Karachi, where there is lots of migration in and out, tremendous migration in and out--has been some 01:29:00difficulty in reaching some of the people in those communities. Then in Afghanistan you have active conflict in Kandahar and Helmand provinces, which have been the last reservoirs of polio there. So it's down to two countries. It's largely down to actually one cultural group--you might even call it linguistic group or tribal group--in the world, and at one time polio was a threat to everyone in the world. Now it's down to one population, and I think sometimes we have to remind the people in that population that, Your children should be saved like everybody else's children should be saved from polio, because you are the last ones, and the whole world is hoping that you'll have no more cases among your children.

TORGHELE: You mentioned the World Health Organization and Rotary International. 01:30:00Are there other organizations that you worked with that are working on the same problem of polio eradication?

KEW: Well, UNICEF [United Nations Children's Fund] is one of the core partners, okay? So they've been engaged with us from the beginning. They are the ones that paid for the vaccine, provided the vaccine. WHO provides most of the technical support for the program but UNICEF also provides key support for communications, for example, logistics, which is very important. So that's another U.N. agency.

Outside the U.N. agency, there's been a number of groups who have been helpful to us. I think most recently most prominently has been the Gates Foundation [Bill & Melinda Gates Foundation], which--Bill Gates has put his personal fortune behind polio eradication and is deeply engaged in this. I'm going to tell a story about his personal involvement, because I happened to be in Nigeria 01:31:00at the time when he was there, and he spent about two hours with the program people and one hour with the lab people, and what he heard in the lab side--he heard about the program, what it needs and the financial requirements. He already kind of had an idea of what the financial requirements were and he also knew some of the societal impediments, and he saw that as a challenge. Then he sat with the lab people and what he heard was Africans, Nigerians and other Africans--Wale [Oyewale] Tomori was present there as the LabNet coordinator for the whole African region. He saw Africans talking about molecular epidemiology, doing work in their own labs, tracking the virus in their own labs, working with us on tracking the virus. Since Bill had done some work on evolutionary genetics when he was at Harvard, he picked up on it right away and asked a whole bunch of 01:32:00questions, and he was hearing from the Africans. That's the part he liked, to see the technology being transferred to them. They embraced this. They were using it. That information is feeding right back into their program.

He said, "This is great, how can I help?" And we made a few suggestions: Well, you could help us get the samples from the lab--samples from the field--back to the lab intact. So then he said, Okay, write a proposal. And we did, and he supported it. Victoria Gammino spearheaded that, and we came up with cold boxes which we--really a collaboration with Georgia Tech and technical experts in Detroit and elsewhere, with Bill Gate's support--came up with cold boxes, not only for the reverse cold chain, which was taking specimens from the field to the lab, but also--more importantly really--from the vaccine storage facilities 01:33:00out into the field. And that's still making progress in the development and deployment. And that's going to be very important in places like Nigeria, where we have even more expensive heat-sensitive vaccines, where the cold chain infrastructure--the freezers, the refrigerator units along the line from the central storage facility out to the countryside--are pretty rudimentary and have many times broken down. So this is one of the ways he could contribute, and a lot of that came from just sitting with the African virologists and having them tell their story about what they are doing to support the eradication of polio in Nigeria.

TORGHELE: So it sounds like there's a network of labs. Are you all interconnected for your lab work?

KEW: Yes.

TORGHELE: And how does that work?

KEW: Well, that was started in PAHO by Francisco Pinheiro and Ciro de Quadros, 01:34:00and they asked if I could help. And I went down with Pete Hatch to visit the labs in Latin America, and saw immediately there's an untapped reservoir of enthusiasm on the parts of the virologists to support this program. So they had the desire to help. What we really needed was the vision to actually make a program. And that's with Ciro and Carlyle and Albert Sabin and the Rotarians had, was this vision to build this program. So the lab people were quite happy to sign on board. Finally, they could do something that could really have an impact on their people. So the reference lab for that in the Americas was CDC, and then there's a subregional reference lab in Rio de Janeiro. Edson da Silva 01:35:00was the head of that lab, and then there were a number of outstanding labs that got stronger as we progressed throughout the region. That was the beginnings of our global laboratory network. And the first Global LabNet manager, Global LabNet virologist, was Barbara Hull, and Barbara was from Trinidad. She was part of our network in the Americas. So there was already a PAHO or Pan-American region stamp on the global program, because Barbara helped build up the global network later.

Mark Pallansch and I--in 1989, the year after the World Health Assembly had declared the year 2000 goal for global eradication of polio--wrote the plan of 01:36:00action for the laboratory network, Global Polio Laboratory Network, and it was based very firmly on the PAHO model. In the PAHO model, we had John Andrus--who's an epidemiologist, a CDC-assigned epidemiologist--working with Ciro as a liaison with the labs. We had Jean-Marc Olivé, who is still active today in Pakistan/Afghanistan as a chairman of the TAG, who is another epidemiologist who worked with Ciro on the epidemiologic side of information coming from the labs. John Andrus was the LabNet coordinator, in many ways, along with Francisco Pinheiro. And John worked to help us, along with others, get the resources to build up the labs in Latin America, because he was the one who was translating a lot of the information to Ciro, in terms of what the program needed at various levels. And so was Jean-Marc Olivé.

So that was really the foundation of the Global Laboratory Network, and there were a number of very strong labs already in existence that we could build on in Europe and in Japan in particular. From there the Mumbai lab in India became what was called a Global Specialist Lab. But the network was a three-tiered system originally, with national laboratories forming the base of the pyramid, the essential base. Then Regional Reference Laboratories, which were laboratories strategically placed within regions that had good capacity not only to do the work, but actually to serve as reference centers and training centers for virologists. Then we had the Specialized Labs, which CDC was first, but then there are others in Europe and in Japan, and in Mumbai, which became critical to this. Now there's been a lot of blurring of the various lines of demarcation 01:38:00because everybody wanted to develop further, and many have. So we've tended now to erase those lines, and there's a lot of what are now Regional Reference Labs that are doing the same kinds of things that we are doing at CDC--for example, Pakistan or in South Africa and elsewhere. So there's been a tremendous upgrade in the laboratory capabilities in this network over the years, concomitant with the support they've been given, because the potential was always there. The people, the determination and desire to do something was always there. It was a matter of getting them the tools. Once they got the tools, they took off.

TORGHELE: Did CDC Foundation get involved?

KEW: We have gotten a lot of help from the CDC Foundation, and they provided us with a way to have funds for our Heroes Fund--Heroes for Polio Eradication, 01:39:00which is a little bit different from the similar Rotarians term in polio eradication. Heroes is for people who gave their lives in working with immunization of children. The CDC Foundation provided support for staff that we couldn't support otherwise, including research work done in the labs, okay? So they've been supportive of us at many, many different levels. Its stated goal is to provide ways of doing things that CDC itself cannot do. So they did that for us, and they did that for both GID and for DVD [Division of Viral Diseases].

And we had staff working on vaccine development that were supported by the CDC Foundation. That vaccine development has become more important as we try to figure out how we can move from an OPV world to a non-OPV world, but if we 01:40:00needed an OPV, do we want to use the one we know has some limitations or can we use something more modern? CDC Foundation has supported us in that. They have supported us at many, many levels for many years, as has the Task Force for Global Health. So we've had two organizations, local organizations, outside of CDC that worked very closely with us and helped us in every way they could.

TORGHELE: So I think you've been sort of modest about what your role has been and the techniques you developed that helped with polio sequencing. Can you talk a little bit more about that?

KEW: Well, I learned from a lot of smart people, and so I was able to use the tools they taught me. Then when I came to CDC, I sort of had to learn my own 01:41:00tools in some ways, because we didn't have the infrastructure yet to where you could just talk to the person next door. So I actually had to read the literature about how things are done and what was working, and with a lot of support from Walt Dowdle in particular. We were able to build up our capacity, and even through some really tough times at the CDC, the polio lab was supported--but maybe not at the levels we would have most wanted in the early days. But we were allowed to do our work and do our development work. We're in a rather fortunate position because we got very, very strong support from CDC leadership, and in so doing, I had the freedom to work in the lab with my own hands and develop methods. And I had one or two very good technicians and a very 01:42:00good young postdoc who came in, and they helped develop the methods further.

Now we're a large group, but originally it was just three of us. Originally there were just three of us, and the three of us developed some techniques which became the foundation for what we developed further. So it started off with fingerprinting. Then it went to blot hybridization. This is just kind of a spot test which was transferable and didn't require the use of radioisotope. Then we went to something called PCR, Polymerase Chain Reaction, which is a way that you can amplify the sequences that are hidden in a sample, many millionfold. So you can actually easily detect, by straightforward chemical means, the sequence of the virus, and identify it by another kind of a spot test. Now it's automated. Initially, we did it by hand. But in between there was a technique of 01:43:00sequencing, and the fingerprints told us something about the sequences, but not in great detail. And we would lose the scent on the trail with the fingerprinting, because it didn't take very much genetic change in the virus before the fingerprints would change so much the genetic links would not be easily recognizable. By the time there is about 5% to 10% genetic divergence, the fingerprints look so different you can't make a call anymore about what the identity of the virus is.

The important thing to know about that is that poliovirus changes at the RNA level, at the level of the genome, of about one to two nucleotide substitutions per week, which is about 1% per year. Now, compare that with our genes. It would take our genes about a million years to accumulate the number of genetic changes that the poliovirus genes accumulate in one year. That's a challenge when you're 01:44:00trying to develop a live virus vaccine, but it's a real benefit if you're trying to track the virus, because all you have to do is follow the trail of genetic changes and you can track the virus and track it right back to its genetic origins--as long as you have a laboratory network that can collect the samples, process samples that are being collected by the epidemiologists out in the field.

So you can see that the lab was not a standalone operation. All this work had to be based on the work of many others, including those who are giving the vaccine--so that we actually don't have an enormous number of cases to contend with all the time, but you see a shrinking number of cases where the lab information becomes increasingly important. So the way we approach this is we developed sequencing methods, first using radioisotope and using manual techniques, and we could process quite a few in a week, much faster than the 01:45:00fingerprinting and with much greater precision and much greater reliability. Because at 5% divergence, you could document that by just looking at the bands on what we call the sequencing gel. 10% divergent, no problem. We can document that as well. Once you got above 10% divergence, then you can use specialized techniques and see even deeper into the evolutionary history of the virus, something you couldn't do with any other technique.

The advantage of this, though, was that we weren't so interested in the deep evolutionary history--except for a few specialized cases where the vaccine was causing trouble--and we could date when the dose was delivered that actually caused all the trouble later. What we want to know in real time is how the virus is moving, where is it coming from, if you had an outbreak in this place, was the virus always there in that place or did it come from somewhere else? And we could, with sequencing, determine that. We could determine what were called the reservoirs, as opposed to indicator communities. So you could immunize an 01:46:00indicator community because you needed to, because there was an outbreak in the indicator community. That meant that there was some gap in the population immunity. But even more important was to knock it out in the reservoir community where it was there, continuously present. Knock it out there, and then you protect the indicator communities. So it allowed the program to prioritize efforts to where the worst problems were, where the most difficult communities were.

It often complemented the epidemiologic information very, very clearly and confirmed their suspicions. There are other examples where virus in Nigeria moved all the way across West Africa, not only moved west to Senegal but east to Sudan and from there into Saudi Arabia, and there to Somalia, and there into Yemen, and from there in the Arabian Peninsula all the way into Indonesia. Without that genetic data you'd never know where that virus actually came from. 01:47:00So we could easily distinguish imported virus from indigenous virus not only across countries but within a country, and that was the key. So we developed that technique at CDC based on the techniques developed by others. Again, Fred Sanger developed the sequencing techniques we used, just as he developed the fingerprinting technique we used earlier, and we applied those methods at CDC in an epidemiologic context.

And it turned out to be a very exciting epidemiologic context, because the poliovirus evolution rate is as fast as any virus except for maybe one animal virus. It's as fast as HIV-1 [human immunodeficiency virus], it's as fast as influenza A, and it's as fast as anything we know about. But fortunately, most of the changes are at the level of the RNA, the genetic blueprint for the virus, 01:48:00and does not involve changes very often in the viral proteins or the viral biological products--the biological properties, rather. The virus's properties remain essentially the same. There are some exceptions to that with the vaccine virus, but wild virus--the one that's been out there for thousands of years, we know, really, for 3,500 years or longer, we are sure--that virus has already been optimized for spreading in the human population. So most of the changes that we see with the wild virus do not change the biological properties of the wild virus at all, but it allowed us to track the wild virus with very high precision. And that was key to the molecular epidemiology scheme integrated into the program.

Now, I want to come back a little bit. The original vision for PAHO was that the 01:49:00labs could provide clear documentation that the wild virus is gone. And we agreed with that, but we thought we could do a bit more and help them get to eradication quicker by identifying where the reservoirs are.

TORGHELE: It sounds like you took that information and maximized the use of it.

KEW: Well, it's been embraced by the lab network, so there are sequencing labs all over the world now that are doing polio sequencing. They are now still doing it in Pakistan. They replicated my lab at CDC in Islamabad, and with the Rotarian support and government support, WHO support, they are providing real-time information about the status of the program.

TORGHELE: When you mentioned PAHO, I remember someone you mentioned was Fred Robbins?

KEW: Fred Robbins. Fred Robbins was the chairman of our Certification Commission, the Americas Regional Certification Commission, and he was one of 01:50:00three individuals who received the Nobel Prize. John Enders was the head of the lab. Tom Weller and Fred Robbins were working in the lab and they developed cell culture, and cell culture was an essential step for development of polio vaccines. Juli Youngner needed cell culture to do this massive production of the IPV. Albert Sabin needed cell culture to develop the attenuated strains, along with C.P. Li and others who developed attenuated strains. We needed cell culture. That is, growing human cells or animal cells--mammalian cells--in culture, in plastic dishes or plastic bottles. And Enders, Weller, and Robbins won the Nobel Prize for that critical step, and that opened the door for the vaccine.

Fred Robbins, as the chairman of our Certification Commission, was present at all the meetings and was always encouraging to the lab people, always. So he understood the lab people, and sometimes we had some tough times. We had some technical problems in the labs. We were underfunded initially--not so much CDC, but our colleagues in Latin America were underfunded, and we were actually quite sharply criticized sometimes if we made mistakes. And sometimes the expectation was the lab had to deliver at 100% accuracy, whereas the program was still having its struggles in reaching the populations. Fred Robbins would always speak in our defense, and that had enormous benefits in holding our network together, to have Fred, the Nobel Prize winner, speak in our defense.

TORGHELE: The other thing that I wanted you to talk about: You touched on people 01:52:00who were heroes who had died in the polio eradication effort. Can you talk about some of them, maybe not by name, but how they died? What was their--what happened to them?

KEW: Sometimes they died just of exertion. One that I remember: I was given the opportunity by Bob Keegan--because I was a member of the Pakistan Technical Advisory Group in the late 1990s, and a man who went out into the deserts of Pakistan died of a heart attack from exertions of giving vaccine to the children. And my role was to give a portion of our fund to his surviving family members, and since it was a Muslim country there were two wives. So the challenge for me was to not favor one wife over the other, but to kind of hand 01:53:00off the gift at the same time to the two surviving wives.

Unfortunately, more recently we've lost people to overt attacks. In the past, people would die of accidents. Sometimes they'd run over land mines in insecure areas, they would die in car crashes, okay, but not by intentional acts by others. But in more recent years, the last three or four years, there have been outright attacks on vaccinators. There had been some sporadic events before, but nothing as organized and systematic as what had happened in Nigeria and Pakistan. I think I mentioned that I'd already met some of the survivors of women in Pakistan who were friends of people on their team who were killed by the militants.

TORGHELE: And there are lots of other people to talk about.

KEW: A huge number. I'm only touching on a few.

TORGHELE: We probably need to wind up pretty soon, but I wanted to give you a chance to mention other things that we haven't touched on that you wanted to be sure to include, either people or incidents or things that you think are important to know.

KEW: I could tell you lots of different stories. I mean, I've told you a few stories now, and there are a lot of funny stories, too. We've had a lot of really dedicated people who I haven't named that have done a lot, both CDC people, part of the CDC oral history. So, Steve Cochi, whom I think you'll interview, was actually one of the persons who made sure this program succeeded, because Steve--with his personality and his character, and his obvious integrity and his obvious engagement with the people--could engage health ministers and 01:55:00WHO officials and others as well as in the field, epidemiologists and so on, to stay the course, and we had some tough days. Right now things are looking pretty good. You know, we've got very, very encouraging signs from Pakistan/Afghanistan. Ten years ago things didn't look so good, and the Rotarians stayed with us. Steve had to actually defend the program to some very outspoken and prominent critics. He was, again, one of our defenders from within the program, but he was working in the field tirelessly, not only for polio but for the broader vision of measles eradication and many other things. I mean, his vision was polio eradication is a step forward. Just one step in a long journey we are going to take for many years to come. So that would be one person I would name from CDC.

Of course, Walt Dowdle and Bill Foege. Bill Foege has shared our vision not only about the integration of lab and program--I get it backwards--program, epi, and 01:56:00lab. Program's the lead, epi follows the impact of program, lab works with epi to also monitor impact of the program. It's kind of a cycle that Walt Dowdle would refer to and Bill Foege instinctively knew. So Bill Foege is another one of our heroes for sure. I mean, it's a long list.

Within our program among CDC people, [Dr.] Hamid Jafari has done a tremendous job. He got some of the tough places. He worked very, very effectively in India, then very, very effectively in Geneva in the last stages of the program. I saw him in action in his country of family origin of Pakistan, as well as his country of family origin in India. He's very extremely effective. [Dr.] Elias Durry has gotten some of the tough jobs working in South Sudan, working in Yemen, working in Somalia, very, very difficult places. His reward is he is now 01:57:00working in Pakistan, and it is a reward because this is going to be the last stop for the virus, Pakistan/Afghanistan. Elias is there. So there's some of my heroes from that side.

Of course, Mark Pallansch, my partner in working in building up the lab network, and [Dr.] Cara Burns, who with her personality has been working very, very hard. She works with the Global Polio Laboratory Network people. It's her personality that keeps things going in the communication. I mean, there's many, many people that merit mention. Chris Maher in Geneva, who has injected enormous amounts of energy and personal commitment right to the expense of his health; [Dr.] Rafe Henderson, who was an early leader for EPI, who was working in EPI trying to 01:58:00build the polio program up, another CDC contributor working in Geneva.

I mean, there's so many. There's J.W. Lee, who was able to take the baton, handed to him in the Americas, into the western Pacific region, later became the Director General for WHO and was very much engaged in polio eradication, died on a foreign trip when he was giving advocacy for polio eradication, which was WHO's top program. J.W. Lee was from South Korea, worked in the Western Pacific region to encourage China--which didn't need a whole lot of encouragement, but the other countries in the region which may have needed a little bit more, needed more support--Cambodia, Laos, some of the Philippines. J.W. was right there pushing on them to finish the job--and finish early if at all possible--in that region, to show that there could be another affirmative step made outside 01:59:00the Americas for polio eradication. So he's another one I would mention.

TORGHELE: Peter Patriarca?

KEW: [Dr.] Peter Patriarca was another very good one. Was one of the members of our division, okay, and Peter was one of the early architects from the CDC side of the immunization side. [Dr. Walter A.] Walt Orenstein also played a key role. I'll come back to Peter. I'm jumping a bit, sorry, but Peter was the head of the polio program in NIP, as it was called then, National Immunization Program, and he was very interested in a science-based program and had come from our division. So he had a perspective similar to ours about where the role of science and laboratory science would be in this. So he was part of integration, played a key role in integration of the lab at EPI in the polio program. He 02:00:00predated Steve Cochi in that regard but Steve was still active in many, many ways in the PAHO program. You have some others you might want to suggest?

TORGHELE: Bob Kim-Farley?

KEW: Yeah, [Dr. Robert] Bob Kim-Farley had been an epidemiologist whom I met when I first came to CDC. He'd worked on polio and was active in India, particularly in India, which was a very challenging setting at the time Bob had taken the challenge of India on. So India, I think, for all of us was the great goal--to eradicate polio from India. It was the world's largest reservoir. When we started, it had half the world's cases. If you had four hundred thousand cases worldwide, the Indians claimed, with good justification, that they had half of the world's cases. Bob Kim-Farley continued to help push that program forward.

TORGHELE: [Dr.] Jay Wenger?

KEW: Jay, yeah. Jay actually was with us in some of the tough times in polio in India. Let's see if I can--I want to get my chronology right. Jay succeeded [Dr] Jon Andrus, and Jon Andrus helped set up the program using the PAHO experience--he helped set up the infrastructure. Jay was the successor and had to deal with the very difficult challenges post 2000 when we were stalled in India. It had big outbreaks, and Jay had to encourage the program to stay the course, and even though we had some tough times because it looked like we were playing whack-a-mole for a while--we'd catch it here and it would pop up there, 02:02:00and in fact part of that was for Uttar Pradesh and Bihar, with a combined population of three hundred million, slightly less than that of the United States. But the demographic pyramid is very different, so that every month there would be half a million new kids, new susceptibles, being born into those two states, maybe with those two states more than that.

The environmental conditions were ideal for polio circulation--very, very, high population densities. In some places, very, very, poor sanitation, a long polio season. Polio thrives during the warm months. So they have a prolonged polio season in parts of Bihar, isolation of communities, physical isolation in some regions because of floods, so they actually had to deliver the vaccine by boat. But also social isolation, where initially the Muslim population felt that it 02:03:00was underserved. Although the polio program did not want to in any way favor one group over another, there was this history that one group felt they were less favored than another. So there were difficulties in outreach. Jay had to deal with that. Then we didn't have enough personnel or staff to go around for this three hundred million population, so if you deployed your staff in one state, in the reservoir areas in one state, you'd start to see it in another state. Then you'd redeploy in the other state and you'd start to have again: this ping-pong effect until we actually could get enough commitment from the government of India--which we had enormous commitment--but even more to deploy people everywhere so we could really finish it off. So that was Jay's difficult task that he had to do.

His successor was Hamid Jafari, and Hamid knew the neighborhood in depth. So we 02:04:00are now down to the last really deeply entrenched reservoirs, and Hamid understood those communities and could communicate in ways to those communities that none of the rest of us could. So it really resonated and I think he was--all of them were the right person at the right time, but at the last stages Hamid was absolutely the right person at the right time.

TORGHELE: And [Dr.] Brent Burkholder?

KEW: And Brent played another key role. Brent came before Jay. And Brent also, after Jon Andrus--Brent was Jon Andrus's successor, and Brent, again, worked in India and played a really key role building it up, again, through these dark times. So the difficult times were shared, I think, by all of them, actually, in 02:05:00different ways, but the times where there was a real question about whether it was even doable in India, that question was being asked. After the year 2000, we had some outbreaks in 2005, 2004/2005. There was this question again: Can you eradicate polio from India? And the answer is yes, but Brent had to address that and Jay had to address that and Hamid, now with the wind at his back but the most difficult communities left, had to address that. So there was an evolution of the message with each succeeding CDC seconded. Jon could build on the message that, you've done it in the southern Indian states, you can learn the lessons there; we've done it in the Americas, we can learn the lessons there, and here's the infrastructure we have to build. Then Brent had to implement that, and there 02:06:00was lots of progress under Brent. Then Brent had to deal with the doubters. Jay had to deal with the doubters. Then Jay actually had to deal with--efficacy of the vaccine was just lower than we thought, so our vision of just immunizing kids, immunizing kids, and immunizing kids had to be rethought. So there were a lot of adjustments to the program in this challenging setting. Then Hamid was really there to finally bring this to a conclusion and engage the most underserved, poorest of the poor in a very poor part of India.

TORGHELE: The last name I have is [Dr.] Steve Wassilak.

KEW: Oh, yeah! I'll tell you, he's been a pleasure to work with from the beginning. He worked in Europe and so we didn't work quite so closely with him, except for the Newly Independent States or the former Soviet Union states, and 02:07:00we worked primarily with Galina Lipskya, who was based first in the lab and then based in the Copenhagen office, and Galina and Steve worked together. You know Galina.

TORGHELE: Yeah.

KEW: Galina had a really difficult--I'll come back to Steve, but Galina had a really difficult challenge, because unlike some regions where they were quite keen to take WHO advice, and maybe get some help with their infrastructure, Galina was from the European region which had a large number of independent countries, and in every country and in every lab there were already experts. So why did they have to listen to WHO advice? She had to actually bring them together and to standardize the approach so the data were interpretable, to get them to support the program particularly in countries which didn't have polio, 02:08:00to get them to see themselves as part of a region. When the polio is out in Uzbekistan, why should you worry about it in Paris or London? She worked on that very hard, but I think the great challenge was to not only pay adequate attention to the Eastern European countries, but also have to deal with the Western European countries. And Eastern European countries would include Central Asia and the Caucasus, but the Western European countries where standardization and methods--getting people to get all on the same page--was a special challenge.

Now, Steve Wassilak had the same challenges at the program epidemiologic level, and he had the personality, the friendliness and people skills, to bring people together. He now uses those people skills here. He brings--again--like in very rich tradition joins the program epidemiology and lab together every day. Just 02:09:00yesterday we were exchanging emails. He's now in Copenhagen in his old post, working on containment, which is one of my current activities. So Steve is one of the people we all enjoy working with, among the many within GID.

TORGHELE: Maybe we should end up with what you are doing next and what your thoughts are on the prospects for global eradication.

KEW: Well, I still serve on the Pakistan/Afghanistan TAG, and I hope that I'll be allowed to travel to Islamabad next month. I've been on the TAG since 1998--seen it when there was lots and lots of cases of polio in both countries, and hope to be a very outspoken advocate to finishing the job. Now the chairman of the TAG, Technical Advisory Group, is [Dr.] Jean-Marc Olivé from France, who 02:10:00worked with Ciro de Quadros in PAHO. Jean-Marc is serving as the chairman of the TAG in Pakistan, one of the last two reservoir countries in the world for polio, to honor Ciro de Quadros, his mentor in PAHO. He is a very effective chairman.

My role will be not only to support the lab people who are working day and night, even under very unfavorable conditions--they get threats from the militants that they will be attacked for working on polio. So they actually had to build a wall around the Pakistan lab to protect them from attack. So my role 02:11:00is to help interpret the laboratory information for the program in the context of what they have to do. And I have a reputation now of being pretty outspoken at those meetings, because the clock is ticking on all of us and we just don't have the luxury of time anymore to take any wrong turns. So I hope to take the laboratory data, combine it with the epi data and the program data, and help, as a TAG member, interpret it into what action needs to be done to finish the job. And whatever I say, Jean-Marc will amplify as TAG chairman to essentially bring all the pieces together to finish the job of polio eradication.

The other thing I'm doing is I'm working on containment of poliovirus, and in 02:12:00this case is the containment of type 2, which was eradicated in 1999. We know that because of the lab data, which showed that it had ever diminishing genetic diversity until it just died out altogether in India--narrower, narrower, narrower chains. We saw type 2 disappear first in the Americas--check out by 1965 in the United States, and finally in 1999 in India. We must contain poliovirus in the labs. That's what containment means, in the labs, because the labs will be the last remaining place where you'll be able to find wild poliovirus. It won't be in the community anymore, it will be gone. In fact, apart from the vaccine manufacturers, it will also be the last place you'll find the vaccine virus.

The vaccine virus, as I've told you, isn't entirely safe if there's very low rates of vaccine coverage, and we're still concerned there might be declining rates of vaccine coverage going forward after polio is eradicated. That's 02:13:00happened in a number of countries. Sometimes, like in Syria, because of events that were beyond our control, civil wars and the collapse of public health infrastructure. Same thing happened with Ebola, where the public health infrastructure collapsed and polio vaccine coverage declined. So we must contain the virus. Labs that do not need to work with poliovirus really should stop and either refer their strains, if they are still of historic importance, to another lab which could continue. We want there to be a minimum number of labs. Then if they don't have any real need for those strains, simply destroy them so they cannot present a threat to people anymore.

Now, I know that this is a practical problem. You've heard this smallpox story recently in the last couple years, where they found some smallpox material long 02:14:00after smallpox had been eradicated. When I was at the University in Washington, I went into a common cold room and in the freezer in the cold room there was a rack way up in the far corner. It said, "Poliovirus Material, Do Not Remove, 1948." So I know that containment is a real problem, and we're working on it now. The world has shifted away from a trivalent vaccine to a bivalent type 1 and 3 vaccine, no more type 2 component in there, and that's an oral vaccine. So the immunity conferred by the live attenuated oral vaccine will no longer be available to us. We'll have to use IPV to maintain population immunity. And to best protect the population from an extinct virus, you'll have to contain the 02:15:00type 2 virus--and while you're at it, if you don't need to work with types 1 and 3, finish with that, too.

TORGHELE: That's a great way to end, Olen. Thanks so much.

KEW: Thanks, Karen.

TORGHELE: That was a great interview!

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