Dr. Mark Pallansch

TORGHELE: It is March 24, 2017 and I'm here at the Centers for Disease Control with Dr. Mark [A.] Pallansch who is the Director of the Division of Viral Diseases at the Centers for Disease Control and Prevention [CDC] in Atlanta, Georgia. My name is Karen Torghele and I'll be interviewing Dr. Pallansch for the Global Health Chronicle's Oral History of CDC and Polio Project. Welcome, Dr. Pallansch.

PALLANSCH: Thank you.

TORGHELE: So, to start with would you tell us a little bit about your background before you came to CDC and how you came to work here?

PALLANSCH: So I was trained in a fairly typical academic track, so I grew up in northern Virginia and went to Virginia Tech [Virginia Polytechnic Institute and State University] as an undergraduate in biochemistry, ended up in graduate school at the University of Wisconsin Madison, also biochemistry, but that's where I started my studies on viruses. I did a postdoc at Rockefeller University and then came from there to CDC in 1984.

TORGHELE: How did you find out about CDC or how did that come about?

PALLANSCH: So my good colleague from now 40 year ago, [Dr.] Olen [M.] Kew, we had met in Wisconsin and he came to CDC directly from Wisconsin, so he had been here 5 years and called me up one day and said there's a job opening, are you interested? And he described the job and I said no, and then a couple of months later came back and said, well, we have a different concept for the job. And then I said, well, I'll come down and look at it. So that's how I was introduced to CDC in a more direct way. But ever since Olen had come down here, I was aware more of CDC than the general public.

TORGHELE: What did you know about CDC before you came?

PALLANSCH: Probably a lot of my awareness had to do with common messages that came from CDC about health, and I didn't pay a lot of attention to general public health messages at the time; much more interested in the type of research that went on at NIH [National Institutes of Health]. I was aware, of course, of the government. My father worked for the government, so I knew the different ways that the government was organized, so I knew it was a sister agency to NIH, but really didn't understand what the work was done here at the time.

TORGHELE: When you came, did you have to do any additional training to do the job you ended up doing?

PALLANSCH: I think coming to CDC gives you an opportunity to continue to learn all the time. So training is probably not the appropriate word but if you take advantage of working here, you learn about all of the ways that CDC contributes 00:03:00to public health. It's a multidisciplinary approach. So you can easily stay focused on laboratory but when I arrived, we were in the middle of the major scale up for HIV [human immunodeficiency virus] work and so it was a very opportune time to learn about many aspects of public health as it is applied here at CDC.

TORGHELE: When you first came, what types of projects did you have?

PALLANSCH: So I started here at CDC actually to work on the non-polio enteroviruses, so it's a big family of viruses and Olen was already here working on polio so we sort of divided the rest of the viruses and he would work on polio and I would work on all the rest. So, it was a very simple division, we 00:04:00thought at the time and so I started trying to apply the molecular techniques that I had brought in my previous training to the work on these other viruses which had really only been studied by more classic traditional techniques. So, it was introducing new methods here at CDC. It was also then adapting some developing new reagents for these other viruses. So, in a way, it was complementary to work that was being done on polio both here and in other places but focused on these other viruses which were not as well characterized. So those are some of the places I started and the inevitable happened which the distinction between polio and non-polio enteroviruses just started to erode and, of course, the attraction of the polio eradication meant that more and more of 00:05:00my activities were directed toward polio. But in the end, of course, the types of work were all overlapping with what Olen had started in years previous, so the work became much more directly complementary over time.

TORGHELE: When you say you did research on these types of viruses, does that mean characterizing them, and what do you do to do that? How do you differentiate them and what are the things you look for when you do research?

PALLANSCH: So, I mean traditionally, these viruses were discovered over a period of time when other scientists in the past had been looking for viruses that may be causing poliomyelitis, so these studies go back into the '40s and '50s and 00:06:00were part of characterization of viruses antigenically. So, they were looking at the differences among these viruses antigenically starting in the '80s both in terms of work Olen was doing on polio and I was doing on non-polio became the start of genetic characterization. So, we did a lot of sequencing of the viruses to try to characterize them. This led to an understanding of the relationship between the viruses, some of the walls between polio and the other enteroviruses basically fell when it became evident that polio was just another enterovirus that had a specific disease property. So characterizing polio at that time led to an understanding about its relationship to these other human viruses and at 00:07:00the same time the complementary work that I and others were doing led to a better characterization of all these cousins, and of course, the new methods for detecting these viruses led to then discovering many more of these cousins and again that work continues to this day where new viruses in this family are being discovered all the time.

TORGHELE: When you look back at when you first came in 1984, what was the lab like? What were the working conditions like and how is it different now?

PALLANSCH: So, I came from working in an old building in New York that was historically important dating from before 1910 so I was sort of used to old buildings. But here on campus the buildings were all dating from the early '60s 00:08:00and even then, these were buildings that clearly had never really been intended to do modern research. In fact, it's not clear they were intended to have people in them. There were no windows, there were poor construction of ventilation that was necessary for conducting safe laboratory work. So, it was a bit challenging to establish modern research standard laboratory conditions in this environment. I mean it's remarkable that it occurred just through sheer vision of what was needed to do modern virology and its application here at CDC, and the molecular biology part required a lot more equipment; so simple things like making sure that circuit breakers didn't go off because of electrical load were part of the 00:09:00new discovery. So of course, now today there's almost nothing left on this campus from when I started. All the new buildings that have come in the intervening years and what was sort of the first new building back in the late 1980's is now of course the old building on campus.

TORGHELE: Can you remember anything that came that really maximized the work that you did? Any invention or new equipment that you were all excited about?

PALLANSCH: So yeah. I mean I think that it's probably each of the increments of technology as they've of course were developed outside of the CDC would eventually become commercially available and then the question was always when 00:10:00can we get that here? So, getting the new equipment was always a struggle when resources were tight because you were always competing with a big dollar piece of equipment compared to, but we can hire two people for that same money. So, the investment, the strategic investments were a key part of the early years of developing these technologies here, and it was really the vision of some of the key players at the time including [Dr. Walter R.] Walt Dowdle who made sure that as possible those investments happened. So, to this day we still have this struggle of the right balance between what is necessary for CDC to remain relevant on the laboratory side with the competing priorities, of course, in 00:11:00public health which are quite broad and extensive.

TORGHELE: Your specialty is lab work, pretty much of polio but I know that you know something about the history of public health and polio. So, do you want to talk about that a little bit how it started?

PALLANSCH: So, the work on polio actually began with the U.S. Public Health Service long before there was a CDC. There was surveillance for polio in the United States starting with the outbreaks that occurred early in the 20th century and standardized reporting was created in the public health service and those reports are still sitting in the library and are available and have been electronically summarized in tables now. So, there have been projects looking at 00:12:00this data over a century during the course of the outbreaks of the 20th century right through the introduction of vaccines and then the post-vaccine era with the vaccine-associated paralytic polio, the VAPP [vaccine-associated-paralytic-polio], so these kind of data have always been part of the U.S. Public Health Service even prior to CDC. So, when I started, I inherited some of these surveillance reports so that when CDC was created, they took over the surveillance for polio around the time that of course the vaccine was having an impact on disease. And I still remember a shelf of these old reports that were quite dusty reflecting some of that surveillance work that was done documenting the disappearance of polio, and then what happened was related 00:13:00central nervous system disease surveillance was added on to this system so that indeed it expanded its scope. And this is also something that continues to this day where systems that are established for surveillance can then be used and evolve over time for other diseases. So, a lot of my non-polio enteroviruses that I was fond of were reflected in some of the surveillance reports after polio was gone because there was still disease like aseptic meningitis which polio also caused that indeed were still picked up by these surveillance systems. So, there's a long history at CDC of working on polio aspects and even when Olen arrived, this history both had the surveillance component but also 00:14:00laboratory work being done to identify viruses and characterize them and, of course, the changing technology is part of the rest of that story.

TORGHELE: Since you brought up changing technology, I know there's an evolution of how that happened and the different techniques that are used. So, could you talk a little bit about that?

PALLANSCH: So once polio was identified as the agent and the vaccines were created, the Sabin vaccine was derived from wild polioviruses, and so when the oral vaccine was introduced, literally children were being given the vaccine and then would shed this virus. And it was a challenge from the very early days for 00:15:00any paralyzed child to know whether the wild virus caused the disease or the vaccine, and I think everyone knows that of course Sabin denied that his vaccine was capable of doing this. However, early on work here at CDC was critical in establishing the epidemiologic link between the oral vaccine and this VAPP that I mentioned earlier. But the virologic part of that, the epidemiologic link could be established with the vaccine but was the virus indeed vaccine related or was it caused by wild virus that nobody could see. And since the rest of the world still had a lot of wild virus, that was a key diagnostic question. And the 00:16:00early CDC scientists worked on this question. [Dr. James H.] Jim Nakano had developed some tests or applied some tests that were used here at that time but had a limitation on how reliable they were. So we've always been focused on can we make these tests more reliable to distinguish between the wild viruses and the vaccine-related viruses, and this has been literally a 40-year quest to improve those methods that continues to this day as opposed to when in the early days all of this testing was done at CDC, now in the global program we're also involved in making these tests available globally. So, the evolution here at CDC started when Olen introduced fingerprinting and that was a method that more 00:17:00reliably could show the difference between wild viruses and the vaccine-related viruses. However, there were always certain vaccine-related viruses that were still problematic even with that technique. And then with the introduction of genetic sequencing of the virus in the '80s, it was then possible to not only more reliably tell the difference but also to get a much better handle on the diversity of wild viruses that existed in the world. So, this is where expanding surveillance to a global scale at this molecular level was a key part in establishing a baseline to watch the wild viruses be eliminated through the 00:18:00global program beginning here in the Americas. So still there are some unanswered questions that are not quite precisely known like when was the last virus case, indigenous wild case in the United States? Olen forever was working on trying to get a more definitive answer to that question. And then later there was the issue of the vaccine-related viruses that reverted and started to transmit like-wild virus and these are the vaccine-derived polioviruses, the VDPV's. They were key to having a different understanding of the distinction between wild virus and these vaccine-related viruses because as I said you created the vaccine from wild viruses and so in hindsight it's not too surprising that they could go backwards and return to their wild parentage. As 00:19:00Walt Dowdle referred to them, they were feral viruses in that they were tamed but then went wild again. So, this has been the challenge at the molecular level to understand this ability to readily distinguish between these viruses being an underlying theme of work that has gone on here at CDC for decades.

TORGHELE: When you're talking about Walt Dowdle and Jim Nakano, I'm wondering if there are people who stand out in your mind from those early days that were influential to you or made a difference in the direction your research took.

PALLANSCH: It's a good question. I think that it's really always hard to point to specific events, specific people. Here at CDC I think the community in those 00:20:00early days was so open and the ability to readily talk to people was a very nurturing environment. I can't point to somebody and say, okay, this is the key person. Obviously, I worked a lot with Olen for a good portion, most of my career. It has always been an intellectual exchange even from our early days back in Wisconsin. So, it's not just the science, it's also the ability to work with somebody, talk to them, be able to go off on a complete tangent and know that it's okay. So, Olen was clearly a key part of my early years here. The supportive nature of leadership here at CDC was critical in that first decade when nobody ever had the idea that there would be enough resources at CDC for 00:21:00CDC to actively participate. So, this was always the positive message from Walt Dowdle is you're doing the right thing, keep doing it, eventually we will get there. And we would meet with him routinely and that was always the message because all we saw were the challenges because there were never enough people, money, the bureaucracy was in the way. So, he was always the person who, in terms of polio, keeping people energized to keep moving forward was critical. The day-to-day always the support of the division director, whether it was [Dr. Frederick A.] Fred Murphy or others, and of course the branch chief, [Dr.] Larry [J.] Anderson, these were all part of a support structure and it was so easy to go and talk to them and air issues and feel like you had support. So I think 00:22:00this was why it was very different than what I expected when I came here because I was expecting something I guess more bureaucratic, less open, and was a little fearful of what I would miss from the academic mentoring more formally but it's just different here in a way that can still be very professionally supportive for early career.

TORGHELE: There were other specialists you worked with within your branch.

PALLANSCH: Yes. Well, that's also the attraction. I mean I mentioned coming into the middle of the HIV early days. There's always a variety of things that are going on and remembering in those early days the fact that we were bringing new 00:23:00tools to the table meant that they were being applied to new diseases all the time. It didn't matter what the outbreak was, you always had the ability to have an awareness and then to think about ways that you might be able to contribute to resolving whatever the mysteries at the time were. So even in those early days of molecular and expanding into the other parts of the division, there were always occasions where we would get together ad hoc to be able to discuss what are the challenges in trying to get answers. It didn't matter whether it was Sin Nombre virus in the Four Corners where that was also something which was unknown through to SARS [severe acute respiratory syndrome] and how do you have a quite significant international outbreak rapidly expanding, identify the cause and at 00:24:00the same time doing all of this in parallel with our colleagues in other disciplines whether it was programmatic, epidemiologic, to figure out ways of intervention to stop the outbreak. So a lot of this is opportunity and you can choose to take the opportunity to work in these various other ways with other people in the branch that are outside your specialty, or you can stay very narrowly focused and treat the rest of the thing as noise. But I always liken CDC to the fire station. Every once in a while, somebody's gonna pull the alarm and you can say I'm not a fireman or you jump on and you say let's go. So very opportunistic things can come your way if you just pay attention.

TORGHELE: Sounds like you had a high level of collaboration ensuring the resources and ideas.

PALLANSCH: I think that was part of the culture and, of course, the size of CDC is also something that has changed over these decades. It used to be while I was the 20th person hired in the branch and this was just a different scope and so there literally were never enough people in any little section to be able to handle all of the questions and so bouncing ideas off of each other was critical because nobody had a critical mass sufficient to tackle all the problems. So, as programs grew like the polio eradication program, it became a very different environment because then it had its own critical mass. So, in a way it can 00:26:00become more isolated if you are not paying attention in that way. So, it's much easier nowadays to focus just because you have so many colleagues that are focused on the same problems.

TORGHELE: Can you think of ways within your branch that that sense of collaboration was enhanced and what you all did that made that such a collegial environment?

PALLANSCH: Well, I think there are many things that add up and the intangibles are always part of it because not everybody gets along with everybody else. But one of the things that happened early on after my arrival was, we started a branch birthday party. So, it's as simple as recognizing people's birthdays. It was a chance to get together. It was sort of this backing away from the professional scientists and saying, no, we're people, we have birthdays, we like 00:27:00to chat, and those are the kinds of things that started the ability to think differently about coming to work. So, team building in its various forms is something that has to be worked on. In the early days of polio eradication here at CDC, there were different groups working on polio both on the laboratory side and the epidemiologist program people, and truthfully we didn't really get along most of the time, but with the focus on polio eradication and the immunization side came a restructuring which brought in [Robert A.] Bob Keegan and [Dr. Stephen L.] Steve Cochi who were gonna head up this new unit and Bob was really instrumental in saying on his list of things to fix for his boss before he started was issues with the laboratory. So, he actually called us up. They were 00:28:00on a different campus so not physically near us and said I'd like to come over and meet you and see how some of these issues we can talk through. And, of course, Olen and I were saying, no, it's no big deal, don't worry, everything's okay. So, we kind of sugarcoat the whole thing because we're inherently not confrontational. But Bob insisted and so he came over and in this old building we were in, they were appropriately numbered going down so there was the first floor, the basement, the sub-basement, sub-sub-basement, and so it's not very attractive sounding, so we only had one meeting room which was a small square cinder block walls, one door, no windows, and that's where we met. Olen and I sat on either side of the door and Bob said, well, I've heard that you have some 00:29:00issues with some of our people. And again, we said, no, no, it's fine. Then he said, no, no, I really want to hear what's the problem. So, then Olen and I went for at least an hour tag-team back and forth, back and forth, just finishing each other's sentences, the whole thing. Finally, we just by coincidence stopped talking at the same time. And at that moment Bob sprang up because he couldn't figure out how to get past us throughout the door, and he said, do you guys drink beer? And since Olen and I had both been at Wisconsin where that's the only beverage available to adults, we looked at each other and said, well, of course. Then Bob immediately set up an appointment to say, okay, I'll meet you at P.J. Haley's on Friday afternoon and we can discuss this some more. And that 00:30:00literally started a tradition back in 1992 where every Friday since then we have met to talk things over, over beer, and that has been the reason that we can establish this cross-agency collaboration on polio. It got us through those early difficult growing pain days and now, of course, it's just a tradition. So, the original five people that were part of that tradition are on a picture that hangs on the wall of Mo's [Pizza]. So, it's still to this day a record of how that all got started.

TORGHELE: What a great idea.

PALLANSCH: But you have to be able to not only work with people but to be very effective you have to understand them and that, I think, was the lesson in this 00:31:00whole process. So, Bob Keegan gets all the credit for that insight.

TORGHELE: He listened to you and then you began to listen to each other.

PALLANSCH: Exactly. So, it goes back and forth and, you know, we complained. So, after a while we stopped complaining about each other and then, of course, we got around to what are we gonna need to do to eradicate polio? So, then we'd complain about a lot of things whether it's the bureaucratic infrastructure at CDC, the lack of U.S. government support, who are the partners here? We spent long times trying to figure out how we could find some other partner other than the World Health Organization [WHO] to work with and were never successful in finding an alternative because they're the institution that has global reach. CDC doesn't, the USAID [United States Agency for International Development] doesn't, all of these other organizations are much more focused on specific 00:32:00countries. But to eradicate polio you had to have global reach and that was still WHO. So that's when you start to discuss all of the pluses and minuses of all the partner organizations, and again, this has developed this partnership over time because it took a lot of frank discussions among the partners to be able to resolve issues and make progress.

TORGHELE: Among the partners there were some others besides WHO and USAID that came along, and I imagine they have different working techniques. For instance, how did Rotary [International] get involved and what was that like and how were they different?

PALLANSCH: Rotary signed on very early at the time when it wasn't clear that there was going to be traction for polio eradication and so it is part of 00:33:00visionaries in the organizations that see opportunities or indeed ways that they can have impact. I'm not sure Rotary completely understood the scope of their involvement at the beginning, but it was part of this idea they could have an impact and that is philosophically very aligned with the organization. So, I think there was a natural attraction. It's also attractive because at least at the beginning it was sold as something with a defined goal and a defined timeline. We would have eradication in the Americas by 1990. In '88 they resolved to eradicate globally by 2000. So, a lot of those aspects of defined scope are attractive to organizations looking for projects to support. Then the 00:34:00big push in terms of going out to all the rotary clubs globally to raise funds and they exceeded their targets by wide margins and were instrumental in making the international support a reality. So, CDC didn't have the resources to support a global program. No other agency did. So, they were the ones that financially made the entire program credible and so I think that their early role was instrumental in that kickoff to have the global credibility that this actually could be done. So the demonstration in practice was PAHO [Pan American Health Organization]; the resource mobilization could this be done, Rotary was instrumental in that and then, of course, partners have come in to supporting 00:35:00this activity over the years and there have been a lot that have come and gone, but the core partners and now adding in the Gates Foundation which has been of course critical for the last decade, that has been the continuity that holds the whole program together.

TORGHELE: So Rotary, like the World Health Organization, in its way had international reach as well.

PALLANSCH: Yes.

TORGHELE: And they provided volunteers as well.

PALLANSCH: Yes. So not only did they raise money, but volunteers were part of all of the immunization activities in countries. So, local Rotarians in countries all around the world became part of the process of delivering vaccine to children. So, the role that Rotary had was from global advocacy right through 00:36:00local mobilization and so this was the scope of the organization. We had many Rotarians of course who volunteered in the STOP [Stop Transmission of Polio] program to go out and be part of international missions to improve the quality of surveillance or vaccine delivery. So, they got involved in many different ways. They were actually instrumental when Olen was contacted by a local Rotarian who said how can we help? Then it started a whole discussion about, well, the laboratories in a lot of these countries have no equipment. And it became then, well, can we buy them a piece of equipment and get it delivered there? So that's how the whole Polio Plus program started where what are the 00:37:00other things that are more concrete? So literally local clubs could mobilize their own resources that could be then linked to them and partner to a specific country laboratory, and this became much more a direct engagement for local clubs as well. Of course, Olen and I and others here at CDC have gone and talked to many a Rotary Club to update them on how progress in the global program-- to again, what is the return on their interest and engagement.

TORGHELE: You hear the terms vertical versus horizontal programs. I wondered if you could talk about that as it relates to some of the programs you all had.

PALLANSCH: Yes. It's absolutely a major issue because it is viewed as a 00:38:00competition meaning you can do either one or the other, and I think that's a false comparison. I think that from the very beginning the Polio Eradication program envisioned strengthening routine immunization, which is considered a horizontal program. In practice, I think there were many, many missed opportunities to effectively do that. Now, one can argue that it's because there were insufficient resources to do both and that's probably true at some level. However, I think conceptually there was not a clear vision on how that could be done. So, you have to have ideas on how to implement beyond just either or as the choices. So, I think in practice what we're doing now is realizing all of 00:39:00these investments in a vertical program have an opportunity to be used to strengthen other public health systems. There's a long documentation now of how polio resources have helped in other public health settings whether it was Ebola introduction into Nigeria where the polio infrastructure helped to control that outbreak through to other things including public health catastrophes, so it can be earthquakes or whatever. There are people who have experience working in countries in a structured way where the efficiency of leveraging that means that the impact in those settings can be greater. So, can this be done more systematically? Absolutely and I think a lot of the discussions now about polio 00:40:00transition planning are trying to focus on actually how you do this because this is the challenge we have now is not making this false choice between them; it's how do you really do both because the scope of public health challenges are real. Vertical programs have the advantage of more visible outcomes whereas horizontal programs really are trying to raise the floor for all children globally if you look at immunization as an example.

TORGHELE: Going back more to a basic laboratory questions, a lot of people don't understand how that fits in now with the global eradication program. You've talked about some of the ways that the laboratory methods have evolved so that 00:41:00you can differentiate the types. There's wild virus and there's vaccine-associated and there are types within wild viruses. But what do you do now in the lab when you get samples? Where do they come from and what are they used for and why are they used?

PALLANSCH: Okay, I think what has changed is actually we get fewer samples now than ever before because part of the work we've done is to build up capacities globally, so instead of just having a big reference laboratory and having everybody ship specimens from the very early days when Olen and I went to Geneva [Switzerland] to write the global plan for the entire global network, philosophically we had a decentralized system. So, the idea was to create this capacity in countries so that they could indeed do their testing for their 00:42:00children and that was the start of the design. Now, accomplishing that was of course far more complicated than just having a few reference labs and having everybody work on shipping. So over the years we have been successful because unlike those early years where we were indeed getting a lot of specimens, we are now at the point where most regions of the world have the capacities to handle their own specimens and get the equivalent results to what they would get if they sent them here, and that was partly be design. So I think when you look at what we do, we have evolved past this role focused on surveillance to incorporate many more activities in the laboratory whether it's related to supporting different clinical trials, trying to come up with better vaccines 00:43:00whether it is new schedules for IPV [inactivated polio vaccine] use or new vaccines derived to replace the oral vaccine. So, we can be involved in a lot of those clinical trials. We do work still on trying to make better ways to do the surveillance activities whether it's new methods that then will be sent around the world or working with other partners to develop environmental surveillance as an alternate or supplementary surveillance activity. And then we, of course, have research in actually developing some of these new vaccine strains. So there are many different activities now in scope than what we did previously, so the idea that we were the reference lab where everybody just spent specimens, or if 00:44:00there was an outbreak we would support an outbreak, has evolved into a much more complex portfolio of laboratory activities that support this much more complicated global program, and trying to address a lot of the questions now on how to finish, how to remove the live vaccine so that it is not causing these VDPV's. These are all questions that have to do with both technically being able to understand virus transmission but at the same time what potential solutions to these problems are and then informing policy choices that have to be made at a global level. So, it's not only informing our colleagues here at CDC what the issues are but being part of those discussions on what options, what are technically feasible are and what are the tradeoff's. So, I think as the program 00:45:00has gotten much more complicated, the role of the laboratory has also had to get more complex in scope to keep up.

TORGHELE: Did you then- people from CDC have to go to different countries to provide training or standard techniques?

PALLANSCH: Oh, yes. So, as part of this, again, grand scheme of the laboratory network a key part was all of these places had to be trained. There were only a handful that really started at the beginning knowing everything they needed to know, so in those early days we had people coming here. For example, we held the first training workshop in PAHO where they came to CDC for that training. Subsequently, it's been found to be much more efficient to go out. I personally have been to more than 60 countries as part of that process, so I think that I'm 00:46:00very familiar with what is needed to be able to conduct this training. Troubleshooting sometimes requires you go to a specific lab, not just go for a workshop because they're having unique situations that are really hard to understand without going there and seeing what the challenges are. Also, sometimes we get to leverage other CDC program investments in those same institutions and this is where also trying to have CDC acting in a more cooperative way in these settings not having again vertical programs showing up and being manifest in these countries where we're trying really to build similar capacities. So, this has been part of the issue, too.

TORGHELE: I'm interested in hearing maybe some specific examples of labs you 00:47:00went to where you were surprised of what was going on and where something unusual happened that you hadn't seen before.

PALLANSCH: I mean some of the earliest trips that I took were actually to places in China so not only was there of course a national lab in Beijing but each of the provinces had a polio laboratory. So getting a chance to go to some of those provinces in the early '90s when China was just opening up more extensively to collaborations with the outside world, it was interesting because showing up its literally the first person from outside of China to visit some of these places and you would find all sorts of interesting situations that they had adapted to 00:48:00be able to do what they were told was supposed to happen. So I had been involved in a workshop in 1990 in Beijing and some of the same people of course went to that workshop and then went home and tried to implement what they were taught, and then following up several years later on how far they had gotten was always instructive because then it helps you to understand when you're not clear. So, things that you think are transparent in how you're explaining and showing people doesn't automatically translate back when they get back in their laboratory. So, some of the things were almost comical. A biological safety cabinet is a standard workspace that was introduced in many of these countries by the polio program. There were many partners who donated these types of 00:49:00things. I mentioned Rotary, JICA, the Japanese International Cooperation Agency also did that for China. So, they would actually buy these for the Chinese provincial labs and have them shipped there. And the problem is, is they couldn't keep up with--they could ship 30 at a time but they couldn't get 30 people to go and help all of these labs set it up. So literally this is a standard biological safety cabinet you sit at. It's this level and they had not known that you had to put the legs on the bottom in order to get it off the floor, so they were trying to work with this on the floor, which was interesting but highlights the fact that not everything is automatic if you've never seen something before. We had another one where there's an alarm for airflow not 00:50:00being appropriate in these cabinets and we came and saw, and they said are you using this? And they said no. And he says, why not? Because it's too noisy. So of course, we thought it was just because the fan, the blower makes some noise; but no, it was because they had not been told they have to lock the sash to keep the alarm from sounding. So, they didn't use it for I don't know how long, for very simple things like that. Other places you go and you're trying to figure out why things are not working and it's the water that comes into the building is so bad they have no way to clean it up. So these are then simple things technically to fix but until you actually walk through in their shoes, you don't 00:51:00actually remotely detect the core problem, and there are many, many examples in different countries that that's what troubleshooting feels good about is you can solve a problem, you fix it, they can then do their job. They want to do their job. They want to do it well, but there are a lot of hurdles that we don't fully appreciate coming from a developed country, the challenges that they face. And over 20 years of doing this it has gotten to the point where the polio labs are performing at a very, very high level. So, we still look at this back to the vertical-horizontal as building capacity because they are now in a position to do something other than polio as well. So, it's there.

TORGHELE: These are great stories. When the Americas had polio gone from them, 00:52:00how was that demonstrated and what was the lab's role in that and how do you do it now? There are just a few places where it's left so how does the lab help to document that?

PALLANSCH: Right, so the lab is of course the critical final piece of information in a surveillance process. So, there are many steps in the surveillance process that reflect quality of surveillance. So, in AFP surveillance, Acute Flaccid Paralysis surveillance, you need to be able to identify those children. If you don't identify the children, your surveillance is no good. The lab is irrelevant. So, you have to have a system that can identify these children. You then have to be notified in a timely way. You have 00:53:00to be able to go and do the investigation which includes collecting specimens. In this case, polio is found in stools so that is our favorite specimen, and those specimens then have to go to a laboratory. All of these steps in that process before it ever gets to the laboratory have quality performance standards that are globally applied and affect how successful the laboratory can be. Once it gets to the laboratory the laboratory has the same types of performance standards that they have to meet in terms of being able to find the virus, characterize the virus and do all of that in a finite period of time. So, it will go from a notification of a child with paralysis to a final genetic sequence in this process that has been established and is operational virtually 00:54:00globally. So, where we are in terms of quality means you have to observe zero for a minimum of three years which is currently the global standard, but this is where the laboratory finding zero, we have to eliminate all of the trivial explanations. Cases are identified late, the specimens don't get to the laboratory, the laboratory isn't really functioning at the level it should be functioning, it has less sensitivity. So, then you have a trivial example of not finding virus because you're not looking well enough, and so trying to assure this quality surveillance globally for a sustained period of time is the only way that we certify. So, in PAHO we got to work out a lot of those conditions 00:55:00for being convinced there was no wild poliovirus in the Americas. So now this same condition has been applied in three more regions around the world and those four regions are certified free of indigenous wild polio and so far, empirically we have not seen that certification be invalidated by discovering something that we missed. So, we're in the right neighborhood of what criteria are needed for certification and so we still have this now for the remaining two regions and even within those regions it's very clear that most countries indeed don't have polio but only regions are certified free. So, we can say that there are just the three countries with active circulation at this moment but that's two regions that have not been certified even though most countries in those regions 00:56:00have not seen indigenous wild polio.

TORGHELE: When a child has acute flaccid paralysis, or a person, where do you get the samples? You sample the child and the family and what else in the community would you sample?

PALLANSCH: So usually if it's a timely investigation, it is just the child that is sampled, and it is two samples collected so that's part of the requirement because polio isn't shed continually. It can be one day yes, the next day no. So at least two samples are collected from each child. If you find out that you are late, meaning more than two weeks after the child became paralyzed, then there are protocols in each of the regions where you do indeed sample contacts of that 00:57:00child, and it's important to do just to make sure that you have not missed an authentic polio case. And again, because there are many other causes of AFP that are not polio, a child could've been paralyzed for a different reason but the only way to know for sure is to make sure you're always looking for polio. So again, when there's a deficiency in one of these steps, there are protocols to then supplement with the additional sampling. Now, when we're getting down to the very end here, there is an enhanced degree of nervousness about are we really done, and this looks really like polio. How are we sure, we're late, and then they could sample even more extensively, particularly in high risk areas of the world that of course are either with conflict, poor accessibility, 00:58:00infrastructure, a variety of reasons that you might have concern about polio transmission.

TORGHELE: Are there cases that have confounded you all?

PALLANSCH: In the early days, yes, there's no question, and I think I mentioned that this was a driver to always improve the techniques we use to really be sure of everything we were talking about. So that stage was easily achieved with wild polioviruses very early. I mean literally decades ago. There have not been confounding cases per se. We have discovered unexpected viruses that needed to be explained. A trivial example is in the Dakotas we had a report of poliovirus being isolated and it turned out of course it was a laboratory contamination. 00:59:00So, we could characterize the virus readily, but it's not supposed to be in the Dakotas. I can't remember whether it was North or South but anyhow it was one of those things where we'd have clarity on the answer in the laboratory but that doesn't mean we always have automatically an explanation. So, we also had another virus that showed up, I forget which lab in Asia, but it was a Brazilian virus from 1986 and the answer was is that was a virus that we had sent out in the proficiency panel that was, again, a contaminant in the laboratory of clinical samples. So, these are the things where we work backwards and because we had these viruses completely characterized, it was obvious that this had to be the exact same strain. So, then we know its source, CDC. How it got there was 01:00:00we shipped it there. Now, in the laboratory how they mixed them up, that's a different problem. I did another trip to Costa Rica because their laboratory reported a wild type reference strain, and this is highly unlikely because Costa Rica was one of the first countries in the hemisphere to be free of polio. It has a very good immunization program. Why do they have polio there? And then it was like, oh, because it's a reference strain. But they all claim they didn't have it. So, I went there and it was very clear how they contaminated in the laboratory and, again, not to blame a specific student but you could tell the work that was going on in the workflow and, again, limited resources, space, etc., meant everything was shared. So, traced it back to, okay, here's a box in the freezer that they inherited from some professor who retired, and some 01:01:00student decided to do a project. And so, it was very simple. You just say is there anything in this box that you really need? And the answer was no. I said, take this box, put it in the autoclave, and you're done. So, I think in the end it was like I saved a day and a half of my trip, so I got to go visit a volcano. So, these are all the things that are side benefits when you solve problems quickly.

TORGHELE: They must appreciate that so much.

PALLANSCH: It was because it was just, you know, they were scared, really petrified when I show up and it's not that I'm there to shut laboratories down, it's to identify what caused the problem and then provide solutions. They make a choice on what their solutions are and, again, understanding the situation, you 01:02:00don't really know. You get there and you see these students all standing in line basically to use the same equipment and then you understand, okay, you're supposed to decontaminate between working with clinical samples in these projects, and they are in a hurry and this is like, okay, you the supervisor of the laboratory, it's your responsibility that they get trained properly, and this is establishing these global standards for not only how to work but also in this case it does have a safety element as well. So, introducing concepts of biosafety in these laboratories is another product of the work in the polio area.

TORGHELE: I'm sure when they learned those lessons from you, they pass them on to other people.

PALLANSCH: Oh, yes. So, I mean that's part of showing up there. It makes a different impression than trying to remotely diagnose which has a mixed result usually.

TORGHELE: Makes a lot of sense. We're sort of winding up here because I realize we've been talking for a while. I wanted to give you a chance to include anything in your recollections or points that you thought were important to make about your work and about the eradication efforts or anything that came to mind that you would like to include.

PALLANSCH: Polio eradication is interesting in the sense of its scope. There are very few international activities with the comprehensive scope that really is a true global program, meaning reaching every child in every country. And so, I think those represent the challenge of the program but also it is really an 01:04:00opportunity to learn a lot about what is needed to make effective global programs. So, it is not only just the awareness I have from the laboratory side but it's when you get to go places, you get to talk to people that are involved in many, many different aspects of what it takes to be effective in global health, and these are very different challenges than what was faced domestically. So polio in the United States was a different struggle than what we look at globally and I think that just because, you know, I was involved with the domestic program as well but there really are few lessons that you get from that that you automatically think, well, we'll just do this elsewhere. And that, 01:05:00to me, was what I learned when I finally was traveling and resetting your mind frame around how to approach problem solving. That changed completely and I don't think people truly pick up on that because they either started working internationally and never knew the difference from comparison with domestic, or they don't have programs they're working on that really have the scope of issues and disciplines that need to be managed; in addition to, of course, all of the folks who get involved with making global policy which is a whole different group of people and skill sets. So that's where I think I've come to appreciate the fact that you really are looking at an opportunity, just like I think 01:06:00smallpox was an opportunity for a whole generation of epidemiologists to learn key skills. Polio is also that but much broader. Smallpox didn't have a significant lab requirement. It had laboratories but they weren't really required to eradicate. Polio does have a requirement, measles has a requirement. The differences between smallpox, polio and measles all are something that are not fully assimilated in people trying to tackle specific program areas. So, this is, again, back to the contrast when you look at vertical programs. I think you really have so many specific details that are needed to be addressed compared to trying to get children immunized in general and that has a huge 01:07:00logistic lift, but it is building infrastructure, it is building the facilities in countries to deliver that. The vertical program builds things but is much more focused to achieve more immediate impact. So, I think they're complementary and not really understanding this up front, this is where I think there's always opportunities for people to learn about these differences. I think looking forward, this can inform a lot of discussions and, as I say, trying to avoid this either-or false choice that I see.

TORGHELE: That sounds like a great way to end up here. You've given us such a great picture of how CDC works with polio programs around the world and the role the lab has played in all of this and you've played in going and visiting these 01:08:00labs and learning from them and them learning from you. So, thank you so much. It's been great listening to your descriptions and your stories.

PALLANSCH: You're very welcome.

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