Dr. Lawrence Schonberger



Dr. Lawrence Schonberger

TORGHELE: It's August 23, 2016, and I'm at the Centers for Disease Control and Prevention with Dr. Lawrence Schonberger. My name is Karen Torghele, and I'll be talking with Dr. Schonberger for the Global Health Chronicles Polio Oral History Project.

Dr. Schonberger is the assistant director for public health and chief of the Prion and Public Health Office in the Division of High Consequence Pathogens and Pathology at the National Center for Emerging and Zoonotic Infectious Diseases. Dr. Schonberger, welcome to the oral history project.

SCHONBERGER: Thank you.

TORGHELE: Thank you for participating. What I would like to do, just to start out, is to find out a little bit about your background and how you came to be interested in infectious diseases, public health, and CDC [Centers for Disease Control and Prevention].

SCHONBERGER: Okay. In the way of introduction, I'm a 73-year-old medical epidemiologist, and I began working at CDC as an Epidemic Intelligence Service officer, class of 1971. Now, 45 years later, I still feel privileged and lucky 00:01:00to be working here at CDC full-time and continuing an extremely gratifying career. My current title, as you pointed out, is assistant director for public health and chief of the Prion and Public Health Office in the Division of High Consequence Pathogens and Pathology. Although CDC has been reorganized several times since 1971, an important constant for me has been the many talented and friendly colleagues that I have always found here who are truly committed to CDC's public health mission to control and prevent disease.

Since 1968 I've been married to my fantastic wife, Dr. Rachel Schonberger, who is the mother of my two sons, the grandmother of my three grandchildren, and for the past ten years a retired internist and an emeritus faculty member at Emory 00:02:00University. In May, Rachel and I celebrated our forty-eighth wedding anniversary.

TORGHELE: Congratulations!

SCHONBERGER: Thanks! I was raised in a socially conscious, politically progressive family. My parents were professional social workers who emphasized to my two brothers and to me as youngsters the importance of education and of our learning a profession. I was a good student, particularly in math and science, and with my parents' financial help, plus support from scholarship monies, I was able to graduate Oberlin College in Oberlin, Ohio, as a combined biology/chemistry major in 1965, and then graduated Case Western Reserve University Medical School in 1969. Dr. Jack Caughey, the dean who accepted me to the class of 1969, generally liked Oberlin College graduates, and there are many 00:03:00of us who remain very grateful to him. As I will point out later, my having attended Case Western Reserve Medical School played an important role in my ultimately coming to CDC.

In the summer of 1966, as a first-year medical school student, I applied and was accepted to an NIH [National Institutes of Health], supported epidemiology training program that was located in Berkeley, California. It was led by the late Dr. Robert Dyer, who was a prominent public health epidemiologist from the California State Department of Health. Because of our focus today on poliomyelitis, let me point out that Dr. Dyer, I now understand, had played a very important role, along with several other health officials in California, in recognizing and initially reporting to the U.S. Surgeon General in 1955 the 00:04:00initial cases of paralytic poliomyelitis associated with the Cutter laboratory that produced Salk poliomyelitis vaccine, a tragic occurrence of vaccine-caused poliomyelitis that became known as the Cutter incident.

Dr. Dyer's summer epidemiology training program in 1966 provided hands-on experience in epidemiology for selected medical students. He particularly was interested in training people who were interested in a public health career, which I was at that time. This program was important to me specifically in two major ways. It helped to cement my interest in epidemiology and in a public health career, and it led to my meeting my future wife, Rachel, who had joined the summer program as a student from Temple Medical School in Philadelphia.

Now, how did I get to CDC specifically? In the late 1960s, while still a student 00:05:00at Case Western Reserve, I recall having lunch with colleagues at the Metropolitan General Hospital, where I was getting clinical training. We were discussing possible post-medical school alternatives to getting drafted for military service in the Vietnam War. During that lunch, I learned that Dr. Charles H. Rammelkamp, a prominent epidemiologist who had done pioneering research on streptococcal disease and the prevention of rheumatic heart disease and who'd helped develop the medical school's clinical program at Case Western Reserve, had established at the Metropolitan General Hospital a CDC slot for an Epidemic Intelligence Service, EIS officer. I also learned that a medical school graduate could become an EIS officer through the government's commissioned officer residency deferment program, a program that, if I could join, would 00:06:00enable me to continue my medical training for a couple years and then begin work at CDC in a position that would fulfill my selective service obligation.

Accordingly, not long thereafter, I submitted to Dr. Rammelkamp a copy of my medical school research project thesis and asked his help to get into the EIS program. The topic of my thesis was assessing a possible field test for protein malnutrition by measuring the protein-to-DNA ratio of buccal mucosal epithelial cells. I collected the cells by scraping the inside of a person's cheek. When Dr. Rammelkamp returned my thesis, much to my surprise, he had written a note on it that said, "Good luck in the EIS program," as if I had already been accepted. Indeed, I subsequently was formally accepted into the EIS and residency deferment programs, completed two years of internal medicine training at Michael 00:07:00Reese Hospital in Chicago between 1969 and 1971, and then joined CDC's EIS class of 1971.

TORGHELE: What was your initial position as an EIS officer at CDC? Did it influence your interest and involvement in poliomyelitis?

SCHONBERGER: My initial position at CDC was in the Neurotropic Viral Diseases Unit of the Division of Viral Diseases, Bureau of Epidemiology. My obtaining this position was really quite serendipitous. The supervisor of that position, neurologist Fred Hochberg, EIS class of 1970, did not, as far as I could tell, do much recruiting to fill his position during the April 1971 EIS conference period, when position assignments for my EIS class were determined. I had been very positively impressed during the April 1971 conference with the late Dr. 00:08:00Carl Tyler and his group, who were very actively recruiting for their vacant EIS officer positions in the Family Planning Evaluation Division. Dr. Tyler, however, wanted me to take his new position in New York City concerning abortion surveillance. But Rachel and I had pre-decided that among our highest priorities would be for our family to stay in Atlanta. We had just spent a cold winter with our 1.5 year old son in Chicago.

As it turned out, I soon discovered that in addition to being in Atlanta, the Neurotropic Viral Diseases Unit position was a hidden jewel that provided a major positive turning point in my career. Among the unit's key responsibilities was national poliomyelitis surveillance. In addition, EIS officers assigned to this unit provided guidance to state health departments, physicians, and the 00:09:00public on poliomyelitis issues, including vaccinations and the work-up of suspected poliomyelitis cases. The unit also had responsibilities for common and rare virus-related neurological syndromes, including encephalitis, aseptic meningitis, and a relatively newly recognized serious neurological illness of children called Reye syndrome.

When I started work at CDC in the summer of 1971, I was pulled out of the introductory EIS course for an urgent assignment, not for a poliomyelitis issue, but to help investigate the Venezuelan Equine Encephalitis [VEE] outbreak that was coming up from Mexico into Texas. I really enjoyed and learned a great deal from getting immersed so quickly in CDC's emergency response to the VEE public 00:10:00health threat. In addition to working on the VEE investigation and learning about Reye syndrome, as CDC's new EIS officer responsible for poliomyelitis surveillance, I also needed to learn as much as I could about poliomyelitis.

There were several ways I set out to do this. One important way was that I took advantage of all the boxes of polio materials that I had access to at CDC, including many poliomyelitis surveillance reports that had been written since as far back as the Cutter incident in 1955. I began going through these boxes of materials, reviewing original documents and compiling all the available data that I could find on vaccine-associated paralytic poliomyelitis. As I recall, Dr. John McGowan, EIS class of 1969, who had been Dr. Hochberg's supervisor in 00:11:00the Neurotropic Viral Diseases Unit, had initiated a review project on vaccine-associated poliomyelitis before leaving CDC, just as I had arrived there. I soon decided to make completing this project one of my long-term goals.

This project grew in importance and interest to me because in 1971, I ended up receiving reports of nine new vaccine-associated paralytic poliomyelitis cases, including eight among contacts of recent vaccinees, the highest number of such contact cases that had ever been previously reported. It was not until 1977, I believe, when this annual total of such contact cases was exceeded. I brought the 1971 annual US poliomyelitis surveillance summary with me today. I understand that it may be made available online via the Global Health Chronicles website.

In addition to reviewing CDC's polio materials, I also reviewed the polio scientific literature and tried to learn as much as I could from Dr. Milford [Pete] Hatch, who ran CDC's poliomyelitis laboratory. Dr. Hatch was an important mentor. He was very experienced and knowledgeable about polio, a recognized polio expert. In January 1972, seven months after I became an EIS officer, Dr. Hatch and I became temporary consultants together to the Pan American Health Organization to assist the government of Trinidad to investigate and control an ongoing epidemic of paralytic poliomyelitis. My epidemiological skills and 00:13:00knowledge of polio at that time enabled me to be very helpful to the government of Trinidad. At the same time, this experience in Trinidad considerably enhanced my own understanding of the disease and increased my expertise in its control.

TORGHELE: Before going into more detail about your experience in Trinidad, would you describe the domestic situation with polio when you joined CDC?

SCHONBERGER: At the time I became involved in polio, there was a sense that the public health issues related to its control were pretty much settled. After all, the control of poliomyelitis in the United States at that time was, and still is, recognized as a major public health success. Remember that in the early 1950s, there had been an annual average of around sixteen thousand paralytic poliomyelitis cases reported in the United States, with a peak in 1952 of over 00:14:00twenty-thousand paralytic cases. Then in April 1955, immediately after the favorable results of a large, complex, nationwide field trial known as the Thomas Francis Field Trials were announced, the Salk inactivated poliomyelitis vaccine, IPV [inactivated poliomyelitis vaccine] was introduced. The results demonstrated that the vaccine was both safe and effective against the disease. With the widespread use of the IPV in our country, the incidence of paralytic poliomyelitis dropped sharply, and continued to drop at a similarly dramatic rate beginning in 1961, when the first oral poliomyelitis vaccine [OPV] was licensed for use in the United States.

By the time I came on board at CDC in 1971, the use of OPV had totally replaced the use of IPV in the United States. In fact, the 1972 Advisory Committee on 00:15:00Immunization Practices [ACIP] recommendations on control of poliomyelitis dealt only with OPV. These 1972 ACIP recommendations are printed at the end of the surveillance summary that I brought with me and that I understand may be posted on the Global Chronicles website. In addition, between 1971 and 1980, the annual totals of reported U.S. paralytic poliomyelitis cases never exceeded twenty-two cases. By the early 1980s, when my major involvement with polio ended, there were only about ten U.S. paralytic poliomyelitis cases reported each year, and all of the endemic cases were attributable to the polioviruses in OPV.

Already, when I came on board at CDC, as we now know in retrospect, the last documented endemic U.S. cases of paralytic poliomyelitis cases due to two of the 00:16:00three wild polioviruses, the wild polioviruses type 2 and 3, had occurred. The last such documented cases were in 1965 and 1968. Wild poliovirus type 1, however, was still a problem and caused occasional cases and two outbreaks in the United States during my watch in the 1970s. As we also now know in retrospect, the last documented endemic U.S. paralytic poliomyelitis case due to wild poliovirus type 1 occurred in 1979.

TORGHELE: You say "now in retrospect" when you mention documenting the last endemic U.S. cases due to wild polioviruses. Why is that?

SCHONBERGER: I say "now in retrospect" because we not only need to know the results of subsequent years of surveillance, but since the time I conducted U.S. 00:17:00surveillance we now have available laboratory tests that can more clearly distinguish between vaccine-derived and wild poliovirus strains. In 1981, for example, the relatively new RNA [ribonucleic acid] fingerprinting test was at that time the state-of-the-art laboratory test used to distinguish vaccine-derived from wild polioviruses. In 1981, this test had indicated that a type 1 poliovirus that had been isolated from a seventeen-year-old immune-deficient boy in Missouri differed markedly from the oral poliovirus vaccine type 1 strain, hence the laboratory classified the virus as a non-vaccine like or wild poliovirus.

Epidemiologically, however, there was no clear source of wild poliovirus, and the patient was immune-deficient. Based on previous experience, these factors 00:18:00were more indicative of the patient having vaccine-associated disease. On the other hand, neither the patient nor his close contacts had a history of recently receiving vaccine. Most importantly, the fingerprinting results, and the fact that the poliovirus isolated from this paralytic case in 1981 was a type 1 virus, rather than either a type 2 or 3 virus, strongly supported a diagnosis of wild poliovirus disease rather than vaccine-associated disease. I reported these results indicating wild poliovirus disease to the Missouri state epidemiologist, who increased polio vaccinations accordingly. I then received a call from Dr. Jonas Salk, who told me, and I paraphrase, Larry, you know the virus causing this case isn't wild, it's from the vaccine. It's the Sabin vaccine virus that 00:19:00caused the case.

I responded, but the laboratory is telling me it's wild. Fortunately, no secondary cases of paralytic poliomyelitis related to this immune-deficient teenager occurred.

Sure enough, about nine years later I get a call from Dr. Olen Kew, who was working in the CDC laboratory on polioviruses. He reported that the CDC lab's original interpretation of the results on the type 1 poliovirus from the Missouri case was wrong. It was not a wild strain. More powerful, subsequently developed genetic sequencing tests showed that the virus was actually vaccine-derived. It was, however, considerably different genetically from the original vaccine virus. The original vaccine virus most likely was from an OPV dose the patient had received about seven years before his paralytic illness. 00:20:00Based on the genetic sequencing data, the original vaccine virus apparently had been replicating in the boy's gastrointestinal [GI] tract for about seven years, until suddenly in 1981 it was able to cause the paralytic disease. The duration of replication could be estimated because it is now known that the RNA sequence of certain areas of the genome in replicating polioviruses change at a reasonably predictable rate, about 1% per year.

As it turns out, based on genetic testing of the available polioviruses at CDC, the last paralytic poliomyelitis case with a documented wild poliovirus type 1 was not the 1981 Missouri case, but a 1979 case-patient from Chicago, Illinois, who had a Spanish name. The poliovirus type 1 presumably had come from Mexico, a 00:21:00known periodic source of wild type 1 polioviruses in the United States during the 1970s.

Given the current worldwide efforts to eradicate poliomyelitis, the 1981 Missouri case, as well as other immune-deficient paralytic poliomyelitis cases, raise concerns about their constituting a major challenge for eradicating pathogenic polioviruses. Could immune-deficient patients be a continuing source of introductions of these viruses into the community? The good news is that this theoretical problem remains theoretical, because, as with the Missouri case, to my knowledge no other immune-deficient paralytic poliomyelitis case has initiated an epidemic of paralytic disease.

Getting back to the domestic poliomyelitis situation when I joined CDC, wild poliovirus type 1 was still periodically being introduced into our country. Mexico appeared to be the main source of these wild type 1 polioviruses. Every two years, 1966, 1968, and 1970, there had been a paralytic poliomyelitis outbreak in Texas, a spillover from Mexico. Indeed, when I was conducting polio surveillance in 1972, another U.S. wild poliovirus type 1 outbreak occurred. Based on genetic sequencing testing, we can now say, in retrospect, that the source of this outbreak too was Mexico. But the outbreak was not in Texas. Its focus was in a Christian Science boarding and day school in Greenwich, Connecticut.

TORGHELE: Did not the important Reyes case arise from one of these outbreaks in Texas that you mentioned?

SCHONBERGER: Yes, it was the 1970 outbreak in Texas. Dr. John McGowan and the 00:23:00state-assigned EIS officer helped investigate that wild poliovirus type 1 outbreak. To control it, an aggressive public health campaign to get children immunized was waged. One of these cases was in an eight-month-old child whose name was Anita Reyes. During that outbreak, she had received a dose of live oral trivalent poliovirus vaccine from a nurse in a county health department clinic. Within fourteen days after receiving the vaccine, she developed severe paralytic poliomyelitis, and a poliovirus type 1 was isolated from her stool. Subsequently, her father sued for damages, maintaining that the oral poliovirus type 1 virus in the vaccine, rather than the circulating wild poliovirus type 1had caused his daughter's disease, and that the nurse who had administered the vaccine had not warned the family about the risk of vaccine-associated paralytic disease.

At the ensuing jury trial, CDC sent one of its best epidemiologists, Dr. Neal Nathanson, to testify. He explained that the odds of the child having been paralyzed by the circulating wild poliovirus, compared to the type 1 virus in the vaccine, was about eight hundred to one. Other expert witnesses, including scientists and medical specialists, agreed with Dr. Nathanson's conclusion that the wild virus, rather than the vaccine virus, caused the child's disease. Nevertheless, a general medical practitioner who cared for the child after she became ill told the parents and testified in court that the vaccine had caused the paralysis. The jury was sympathetic with the paralyzed child and agreed with the child's physician. Given that the family had not been notified by the nurse 00:25:00of the risks of the vaccination, the patient was awarded $200,000. By 1974, the court of appeals upheld the initial decision and held Wyeth, the vaccine manufacture, liable.

As you can imagine, this decision had, and continues to have, a major effect on public immunization programs throughout the country. During the 1970s, CDC made major efforts to develop materials and methods for providing, in as non-disruptive a way as possible, in immunization programs throughout the country, appropriate risk information to the potential vaccinees.

The courts held that the administration of vaccines by nurses in public health clinics was not the same as when the vaccines were administered by nurses in a doctor's office, despite the American Academy of Pediatrics arguing that the 00:26:00situations were not all that different. As I recall, people like Dr. Bruce Dull, who worked in CDC's Office of the Director and who was very capable in dealing with legal issues, spent considerable time helping CDC to respond appropriately to the obligations established by the Reyes decision. Information sheets about the risks and benefits of each vaccine and permission/acknowledgment forms were developed.

TORGHELE: Is this a form of informed consent?

SCHONBERGER: I believe so. As far as I know, before the Reyes v. Wyeth case, CDC was not providing such forms for use in public health immunization clinics. Meanwhile, the Reyes case, along with the increasing proportion of U.S. paralytic poliomyelitis cases that was vaccine-associated, placed increased attention to information about the risks of vaccine-associated paralytic 00:27:00poliomyelitis and on adverse reactions to vaccinations in general.

In mid-1973, after I completed my two year EIS officer assignment, I was very fortunate to be able to participate in CDC's career development program, during which I earned a master's of public health degree at Johns Hopkins School of Public Health. My superb supervisor there was a medical epidemiologist, associate professor Dr. Paul Stolley, who helped me with, and encouraged me to continue putting together, the information I had gathered at CDC on cases of vaccine-associated poliomyelitis. Indeed, in 1976, my review of such U.S. cases reported from 1961 through 1972 was published in the American Journal of Epidemiology.

I described the changes in incidence and epidemiology of vaccine-associated 00:28:00paralytic poliomyelitis that occurred after national vaccination policy changes had been made in 1964, in large measure to help address the live oral poliovirus vaccine-associated disease problem. These policy changes included the general curtailing of routine vaccination of adults after 1964, and shifting the emphasis from mass campaigns and communitywide programs to routine vaccination of infants. Among the main epidemiological changes that I described were increased numbers of reported contact vaccine-associated paralytic cases. In part, this change, I wrote, reflected improved recognition of such cases as the number of wild poliovirus cases declined. A key message of the paper was that the vaccine-associated poliomyelitis disease problem, despite Dr. Albert Sabin's 00:29:00statements to the contrary, was real and had not been fully resolved.

A few additional points worth making about my paper include my having stuck to a standard definition of recipient and contact vaccine-associated disease. I suggested in the paper, however, that likely other categories of OPV-caused disease were occurring. I mentioned not including in the analysis, for example, an immune-deficient recipient that had too long an interval between receipt of OPV and onset of illness to fit the standard definition at that time. I also mentioned not including community contacts with a vaccine-like poliovirus in the stool, but for whom a history could not link them to a specific OPV exposure. 00:30:00Sticking to the standard definition, I reported an average of about seven OPV associated cases occurring per year after 1964.

As a very crude surrogate for risk, since the number of susceptible people who had been exposed was unknown, and I did not have sufficient data on the OPV dose number that had been implicated in the OPV associated cases I described the epidemiological trends in terms of ratios between the amount of vaccine distributed in the United States and the reported number of vaccine-associated cases. For tOPV [trivalent oral polio vaccine] after 1964, this ratio was 1 case to about 4.3 million doses distributed, a ratio that was only slightly better than that observed in the earlier period. For mOPV [Monovalent oral polio vaccine], the ratio was considerably worse in the recent period, but tOPV had 00:31:00become the routinely used form of the oral poliovirus vaccines.

TORGHELE: Wasn't vaccine-associated paralytic poliomyelitis identified with the Salk vaccine, too, when it was introduced?

SCHONBERGER: Yes, the first vaccine-associated polio problem arose with the Salk vaccine and is known as the Cutter incident. However, the key difference between the vaccine-associated poliomyelitis disease problem with the Salk and Sabin vaccines is that the problem with the Salk inactivated poliomyelitis vaccines was correctable with changes in production and testing. The problem with the Sabin live oral poliovirus vaccines, on the other hand, has not been correctable, it has been inherent in the properly produced live vaccine viruses themselves.

TORGHELE: Did the Cutter incident involve tainted inactivated poliomyelitis vaccine?

SCHONBERGER: Dr. Neal Nathanson is the CDC person to contact about the Cutter 00:32:00incident. You can get a firsthand account from him. My knowledge of it comes primarily from reading his publications. In April 1955, immediately after the inactivated poliomyelitis vaccine was licensed, multiple companies provided vaccine. In a couple weeks in April, about four hundred thousand vaccinations using vaccine produced by the Cutter laboratories in Berkeley, California, were administered to school-aged children. By late April, six cases of paralytic poliomyelitis in the children who received Cutter vaccine occurred, and just about immediately the Cutter Company was asked to withdraw its vaccine, and it did.

TORGHELE: What's the mechanism for that? Was it through the Food and Drug Administration, or how did that work then?

SCHONBERGER: I think you'd have to ask Neal Nathanson for some of those details, but my understanding is that State of California health officials, including Dr. 00:33:00Robert Dyer, reviewed the initially reported poliomyelitis cases that had occurred in California and reported their concerns to the surgeon general. Probably the surgeon general and the State of California requested Cutter to withdraw their vaccine, and the company voluntarily complied. There was a great deal of confusion at that time as to the extent and cause of the vaccine-associated disease problem, and you can imagine all the concerns that this created. My understanding is that in early May, as more polio cases among recent vaccinees were reported, the national vaccination campaign was temporarily stopped.

What I have in my notes was that there were fifty-nine paralytic cases in vaccinees within two months of the time that Cutter had started the vaccinations in April. There were 101 paralytic cases in family contacts and thirty-two 00:34:00paralyzed cases in community contacts. There were also ten deaths. It became obvious pretty quickly, as the number of poliomyelitis cases increased after the initial cases were identified, that the nation needed some central surveillance group within the United States to monitor the situation. CDC filled that role very well under the leadership of Drs. Neal Nathanson and Alexander Langmuir. In collaboration with the states, CDC gathered information and evaluated poliomyelitis cases and issued regular surveillance reports. When the dust finally settled, the numbers of paralytic cases that I just mentioned were reported as likely causally linked to receipt of specific lots of Cutter vaccine.

TORGHELE: How did CDC determine whether a case was due to the vaccine?

SCHONBERGER: There was no way to say for sure. In fact, the surveillance unit 00:35:00identified some vaccine lots produced by Wyeth laboratory that also appeared to be causing vaccine-associated poliomyelitis, so Wyeth laboratory voluntarily withdrew their suspected products.

The key assessments used at CDC in implicating the Cutter vaccines as causing disease included whether a patient clinically had poliomyelitis. What was the temporal relationship with the vaccination? Was there evidence of wild poliovirus activity in the area when the patients became infected? Was the incidence of cases linked to specific lots of vaccine more than what you would expect? Among the temporally associated cases, was the frequency of the paralysis affecting the arms too high, particularly the inoculated arm, compared to what you would expect for wild virus-related disease? The importance to 00:36:00public health of CDC and its EIS officers conducting national surveillance in collaboration with state health departments was clearly demonstrated during the Cutter incident.

TORGHELE: What were some of the impacts of the Cutter incident on CDC and the polio control program?

SCHONBERGER: In the 1950s, in the health field, I understand that the importance of the National Institutes of Health working with its university constituents was well-established. It was the Cutter incident, I believe, that really helped establish the importance to public health of CDC's role of working with its health department constituents to conduct national surveillance.

As part of the Cutter incident, Dr. Nathanson also showed the importance of assessing the time intervals and the incidence of the disease among vaccine recipients in assessing causality. I used these same factors in my own analyses 00:37:00of OPV-associated paralytic poliomyelitis during the 1970s. These same factors were also key to analyses I performed in late 1976, when I reported that cases of Guillain-Barre Syndrome occurring after a swine flu vaccination in the National Influenza Immunization Program were most likely triggered by the swine flu vaccines.

Concerning the IPV itself, the Cutter incident documented the lack of reliability in the system used in 1955 to inactivate the live polioviruses used to make the vaccine. Under certain circumstances, it was possible for some of these polioviruses to have insufficient contact with the inactivating formaldehyde used in the manufacturing process, so that the viruses remained alive and still able potentially to cause disease.

The Cutter incident led to the Bureau of Biologics setting new standards for manufacturers of IPV in order to increase the vaccine's safety, but unfortunately these changes also led to the decreased immunogenicity of the vaccine. What I understand is that the type 3 component of that vaccine was particularly difficult to deal with, and that the inactivation process tended to weaken the immunogenicity of the type 3 component of the Salk vaccine even more than that of the type 1 and type 2 components. Thus, after the Cutter incident, although the IPV became extremely safe, more of the produced lots had relatively weak potency, particularly against type 3 poliovirus.

So the IPV was not ideal, but the vaccine was still able to do tremendous good. After the Cutter incident, CDC continued conducting national poliomyelitis 00:39:00surveillance and enthusiastically encouraged the widespread use of IPV. Hundreds of millions of doses of IPV were distributed and administered in the United States, and CDC's national surveillance documented sharp declines in poliomyelitis incidence. The surveillance also showed that there was no repeat Cutter-like incident. On the other hand, there were significant problems with some lots of vaccine having weak potency. In 1959 in Massachusetts, for example, a type 3 poliovirus outbreak affecting hundreds of people occurred, and a large proportion of the patients with paralytic disease had received at least three doses of IPV.

Meanwhile, Dr. Albert Sabin was using his oral poliovirus vaccine in Russia and other countries, and it was doing beautifully. Particularly if there was an outbreak, the oral vaccine worked much better than the killed vaccine. Unlike 00:40:00IPV, the live OPV could compete with the epidemic virus for growing in the GI tract. OPV was able to immunize the GI tract, and it could reduce the amount of wild poliovirus excreted by subsequently infected persons. With OPV, the outbreaks could be stopped more quickly.

TORGHELE: The World Health Organization felt that those data were reliable?

SCHONBERGER: There were enough countries reporting success with the Sabin OPV that ultimately the data were accepted as reliable enough for using OPV in the United States, even though OPV didn't undergo the same kind of careful assessment in the United States that the Salk vaccine had undergone with the Frances Field trial.

There was also some evidence of OPV and IPV getting entangled in the political Cold War between the communist Soviet Union and the capitalist countries of the 00:41:00West. The Soviet Union promoted the live virus vaccine as better than the IPV that was being used in the United States and other capitalist countries. I remember reading about Japanese mothers, who were apparently influenced by information from the Soviet Union, marching in protest during a poliomyelitis outbreak because the Japanese government was using IPV without great success. The mothers wanted OPV to be used. I believe the protest was effective, and OPV was used to successfully end the outbreak.

In 1961 we began using OPV in the United States, and the incidence of poliomyelitis continued its sharp decline. The Soviet Union and other places where OPV was being used did not report any problem with OPV-associated poliomyelitis. It was thus quite a surprise that shortly after OPV was 00:42:00introduced in the United States, cases of OPV-associated paralytic disease occurred that very much appeared to be caused by the vaccine. In the early 1960s, such cases occurred primarily in adults, and particularly with poliovirus type 3. Henry Gelfand described the situation in a 1963 publication. He mentioned that the reported OPV-associated cases were intensively studied and discussed at meetings of a Special Advisory Committee to the Surgeon General of the United States Public Health Service. In 1972 this committee concluded that at least some of the vaccine associated cases were caused by the type 3 oral poliovirus vaccines. In 1964, a similar special committee in the United States was created to review all the U.S. OPV-associated paralytic cases reported between 1961 and 1964 and to make recommendations.

It is not totally clear why the OPV-associated problem was not recognized before the vaccine was introduced into the United States. Interestingly, even as late as 1978, more than a decade later, at an international symposium on immunizations that I attended, a participant from the Soviet Union told me that as far as he knew the Soviet Union still had no cases of OPV-associated paralytic poliomyelitis. Apparently, similar to the position that Albert Sabin was continuing to take, the problem of OPV causing poliomyelitis did not exist.

SCHONBERGER: The committee was comprised of many polio experts, including Alexander Langmuir and Albert Sabin, and other recognized polio experts.

TORGHELE: Jonas Salk?

SCHONBERGER: I don't know if Salk was part of that or not. I don't think so.

TORGHELE: Did Salk ever acknowledge that there was a problem with his vaccine?

SCHONBERGER: Oh, yeah. He saw that there was a problem, but he thought it was a correctable problem, which it was.

I found the report of the 1964 review of the Special Advisory Committee on OPV to the Surgeon General of the Public Health Service. Salk was not a member. The names are listed in the article that was published in JAMA [Journal of the American Medical Association] in October 1964. They determined that fifty-seven cases were considered compatible with having been caused by the vaccine: fifteen following type 1, two following type 2, and thirty-six, the majority, following type 3. These compatible cases occurred largely among adults: forty-four were fifteen years of age or older, and eight were over fifty years of age. There was 00:45:00no apparent association of cases with specific lots or manufacturers of vaccines, as there had been during the Cutter incident with the Salk vaccine. The committee recognized that it was not possible to prove that any individual case was caused by the vaccines, and that no laboratory tests available could provide a definitive answer. The committee was very careful about attributing causation, but indicated its belief that at least some of these cases were caused by the vaccine.

Years later, when I spoke to Dr. Alexander Langmuir about the committee's report and its recommendations, he told me that the wording represented a compromise, primarily with Dr. Sabin, to get him to agree to co-author the publication. Nevertheless, Dr. Sabin published his own separate dissenting report that was 00:46:00published in the same issue as the committee's report, and Alex was really upset with Dr. Sabin's doing that.

TORGHELE: Interesting.

SCHONBERGER: That, by the way, was reminiscent of something that happened with Dr. Langmuir during the 1976-'77 Guillain-Barre Syndrome, GBS/swine flu vaccine episode. As I believe you know, I was the person at CDC who discovered and published that cases of GBS [Guillain Barre Syndrome] were being triggered by the swine flu vaccine during the National Influenza Immunization Program in 1976. This had led the U.S. Justice Department to create a review committee on swine flu and GBS that was chaired by Dr. Langmuir. The prominent person this time was Dr. Leonard Kurland, rather than Dr. Albert Sabin, who initially concurred, after agreeing to compromises in wording, to co-author the final report of Dr. Langmuir's committee, and then subsequently announcing that he 00:47:00disagreed with the paper's main conclusion. Dr. Kurland was an internationally renowned neuroepidemiolgist. The publication had concluded that the swine flu vaccine had indeed caused severe cases of GBS reported to CDC. It also indicated, however, that the degree of risk overall for GBS was lower than what I had published as CDC's principle GBS/swine flu vaccine surveillance officer.

After this committee published its report, Dr. Kurland objected to the causality conclusion so strongly and publicly that eventually CDC funded Dr. Kurland's efforts to restudy the association in two states, Dr. Kurland's state of Minnesota, and in the state of Michigan, where Dr. Joel Breman had principally authored a separate paper supporting the swine flu vaccine/GBS causal relationship. Years later, when Dr. Kurland's two-state study was finally 00:48:00completed, it showed, much to Dr. Kurland's great surprise, that the swine flu/GBS linkage, in terms of risk, was essentially identical to the risk that I had originally published. As it turns out, the original study and Dr. Kurland's study, unlike the publication of Dr. Langmuir's review committee, appropriately included, in determining the risk, both severe and less extensively affected GBS cases among those that were being triggered by the swine flu vaccinations.

There are other connections between the vaccine-associated poliomyelitis story and the story about the 1976 swine flu vaccine and GBS. I used similar types of analyses to that used by Dr. Neal Nathanson to indicate causality. In addition, GBS was known by many people, including by Dr. Michael Gregg at CDC, as French 00:49:00polio. Both diseases are characterized by lower motor neuron paralysis, and because of this polio connection, Dr. Gregg had recommended me, the polio surveillance person at the time, to investigate the problem of swine flu vaccine-associated GBS.

There is another important connection or similarity in my experiences with vaccine-associated polio and vaccine-associated GBS that deserves some emphasis. This similarity is one that has made working at CDC very gratifying. It is the attitude of CDC's upper leadership. During my investigations of both polio and influenza vaccine-associated diseases, this leadership made it clear that they wanted good science and to get to the truth, so that their public health policy 00:50:00decisions could be science-based.

Getting back to the 1964 report of the Special Advisory Committee on OPV, this committee concluded that the extent of the assessed risk of OPV-associated paralytic poliomyelitis was sufficiently low that polio vaccination programs with OPV should continue, although with some changes in emphasis. These are the changes I mentioned earlier, that is, instead of having mass campaigns and directly giving OPV to adults, the committee recommended emphasizing routine vaccination of children, particularly infants. Most of the reported cases in vaccine recipients were fifteen years of age or older. The vaccination of individuals over school age, about eighteen years, was generally recommended only in those situations in which unusual exposure to polio might be 00:51:00anticipated, such as epidemics, entry into the military service and travel in other countries.

There were other committee recommendations too in 1964 that were described in its publication and designed to reduce to a minimum the observed problem of OPV-associated paralytic poliomyelitis. The committee addressed, however, the OPV-associated disease problem as if it were a problem only for the vaccine recipients. Contact vaccine-associated disease was not recognized at that time as a significant issue.

TORGHELE: Just to clarify, you're looking at the October 1964 JAMA article?

SCHONBERGER: Yes, it's the Report of Special Advisory Committee on Oral Poliomyelitis Vaccines to the Surgeon General of the Public Health Service. In that same issue was the dissent from Dr. Albert Sabin.

TORGHELE: Did Jonas Salk weigh in on this at some point?

SCHONBERGER: Salk was not a member of this committee. Meanwhile, Dr. Salk was focused on how to improve the IPV. During the 1970s, he let people know that progress was being made. There were better ways being developed to measure the amount of virus-specific antigens in the IPV and to more reliably produce more potent vaccine. In 1977, for example, Dr. Salk coordinated a field trial in Mali using four different potencies of IPV, all prepared by the Rijks Institut, the Dutch National Institute for Health. The antigen potency was measured in D-antigen units, and the purpose of the study was to determine the optimal potency of antigen for each poliovirus type for future field trials. 00:53:00Subsequently, he coordinated a field trial in Upper Volta evaluating IPV of three different potencies and the IPV of three different manufactures: Connaught Laboratories, the Rijks Institut, and the Merieux Institute. Similar studies were conducted in Sweden and Finland. My understanding is that the results of these studies were enabling and showing significant improvements in the formulation and production of reliably potent IPV.

TORGHELE: Later on in the 1970s, you reported on the U.S. cases of OPV-associated poliomyelitis that were continuing to occur after the recommendations of the 1964 Special Advisory Committee. Did these cases get reviewed by a special advisory committee too?

SCHONBERGER: Yes. In 1977, a year after my publication, given the declining 00:54:00risks of wild poliovirus disease in our country and the continuing occurrence of OPV-associated disease, a committee of the Institute of Medicine reviewed the U.S. poliomyelitis vaccination policy. Based on its considerations of the risks and benefits of different vaccination strategies, the committee concluded that no change in U.S. poliomyelitis vaccination policy was indicated. I had produced data on vaccine-associated poliomyelitis for CDC's Dr. Michael Gregg to present to the committee, but during the meeting itself I was essentially an observer. Observing along with me were representatives of several vaccine manufacturers. Some were looking for signals from this committee about whether they should be thinking more about producing/improving inactivated poliomyelitis vaccines. The committee gave no such signal.

Years later, I coauthored another paper on OPV-associated poliomyelitis in the United State that was principally authored by Dr. Benjamin Nkowane. This paper covered the OPV-associated disease situation where my initial paper had left off; that is, it summarized the OPV-associated cases occurring from 1973 through 1984. The paper reported 105 OPV-associated cases, an average of 8.75 cases per year. For this paper, unlike for my earlier paper, we included as vaccine-associated disease immune-deficient cases as well as endemic paralytic polio patients who had vaccine viruses in their stool. Importantly, for this paper, unlike for the earlier paper, we had good data available on the specific dose of OPV implicated in the vaccine-associated cases. Not surprisingly, given 00:56:00the expected differences in the susceptibility of the exposed populations, we found that the ratio of paralytic poliomyelitis cases to doses was one case per every 520,000 first doses, compared to one case per 12.3 million subsequent doses.

In 1988, one year after Dr. Nkowane's paper was published, again an Institute of Medicine committee met to review U.S. polio vaccination policy. Again, based on its assessment of risks and benefits, the IOM [Institute of Medicine] committee decided that it would be premature to switch to an IPV strategy for maintaining control of poliomyelitis in this country. In 1988, however, the IOM committee did signal manufacturers to try to incorporate the killed poliomyelitis antigen 00:57:00in the diphtheria/pertussis/tetanus vaccine, so that switching initial vaccine doses administered to infants from OPV to IPV in the future would not require giving infants an additional injection.

After the 1977 meeting, I recall personally feeling very disappointed that the IOM committee did not give any signal to manufacturers about a near-term future that would include increased use of IPV to try to reduce OPV-associated disease. At the same time, I recognized that the widespread use of oral poliovirus vaccine was important and may have been, and probably was, the reason that we were keeping wild poliovirus disease under such good control in the United States. As a surveillance officer in the 1970s, I knew that I was relying 00:58:00heavily on the routinely maintained general immunity of our population to prevent spread of periodically imported wild polioviruses. This protection included that extra immunity induced by OPV as a result of the vaccine viruses' ability to replicate in the gastrointestinal tract.

Dr. Salk, however, vehemently disagreed about the importance of an incremental increase in immunity induced in the U.S. population by OPV, versus that which could be achieved, he thought, with IPV, especially with the improvements that were being made in IPV. He maintained that we could get the same solid protection with IPV, because in the United States most of the person-to-person transmission would be through oral-to-oral contact, and IPV would provide protection against this route of infection.

OPV advocates pointed out, however, that there were many places in our country, particularly in lower socioeconomic areas of big cities, where fecal-oral spread could be a significant problem. There were also individuals, as well as groups of people, in our country who refuse vaccinations or for other reasons are not immune to polio. These groups and individuals, OPV advocates argued, would potentially be at greater risk of infection with wild polioviruses if the general population were using solely IPV rather than OPV.

In the 1980s and 1990s, as the risk of wild poliovirus introductions into the United States decreased due to widespread use of OPV internationally, the benefit/risk ratio for continued reliance only on OPV also decreased. After the 00:59:00second IOM meeting in 1988, as was the situation since 1979, all the endemic paralytic poliomyelitis cases in our country continued to be vaccine-associated. According to an MMWR [Morbidity and Mortality Weekly Report] article, I read, the last case of paralysis caused by indigenously acquired wild poliovirus in the Americas occurred in 1991, and the Americas were certified free of polio by an independent commission in 1994.

Finally, in 1997, we reintroduced a mixed IPV/OPV policy in the United States that successfully prevented OPV-associated disease as well as wild poliovirus disease. Largely because of the efforts of IPV advocates such as Dr. Salk, the 01:00:00IPV introduced back in the United States in 1997 was more reliably potent compared to the IPV that we had been using during the 1950s. Three years later, in the year 2000, we returned in the United States to an all IPV vaccination policy, a policy that continues today.

Although hindsight is 20/20, my own opinion is that the mixed IPV/OPV policy probably should have been introduced in the United States to eliminate endemic cases of OPV-associated paralytic poliomyelitis much earlier than 1997. It is noteworthy that the change in U.S. policy towards greater reliance on IPV in 1997 has not, to my knowledge, significantly reduced the international 01:01:00acceptance of OPV nor harmed polio eradication efforts. For some U.S. polio experts, the potential for such harm was among the understandable concerns about recommending IPV. Regardless of the issue about whether a mixed IPV/OPV policy could have been safely introduced earlier in our country, however, there is general agreement now about the following: The elimination of both wild poliovirus disease and vaccine-associated poliomyelitis in the United States, and our having almost eliminated wild poliovirus disease from the entire world, constitute major public health achievements about which we should be very proud.

TORGHELE: Yes, outbreaks of polio have almost disappeared worldwide. Tell us about the last U.S. outbreaks.

SCHONBERGER: Well, the last two outbreaks of wild poliovirus disease in the 01:02:00United States occurred in the 1970s, when I was CDC's polio surveillance officer. The first of these occurred in 1972. One might say that outbreak occurred right on time, since the previous three U.S. outbreaks were in 1966, 1968, and 1970 in Texas. Epidemiologically, the source of these previous three U.S. outbreaks was Mexico. The U.S. outbreak in 1972, however, was not in Texas. It occurred in a Christian Science boarding and day school in Greenwich, Connecticut.

TORGHELE: And didn't that one originate in Mexico?

SCHONBERGER: Actually, it did come from Mexico.

TORGHELE: Oh, it did.

SCHONBERGER: It turns out that the virus was from Mexico, but at the time of the investigation, my colleagues from Connecticut and I didn't know from where the virus originated, and epidemiologically we found no direct link to Mexico or to any other country where wild poliovirus was known to be circulating. We 01:03:00interviewed family members of children at the school and found only one family that recently had been out of the country. They had been on the French Martinique Island. We followed up, but Martinique officials reported no evidence of any polio activity. So at the time of the outbreak, we did not identify a source of the outbreak. The way I now know that the virus originated from Mexico is that years later, Dr. Olen Kew reported to me that he determined this origin using molecular techniques that were not available back in 1972.

TORGHELE: Fingerprinting?

SCHONBERGER: Well, it was even more powerful than fingerprinting. Actually, he did RNA sequencing, and he discovered a close molecular relationship between poliovirus strains from Mexico and the 1972 Connecticut outbreak strain.

TORGHELE: How did you first learn about the 1972 outbreak?

SCHONBERGER: Well, as I mentioned, the Connecticut outbreak was in a Christian 01:04:00Science boarding and day school. My understanding is that a medical resident in a Long Island, New York hospital reported the outbreak to local health authorities. He did this after a paralyzed child with transverse myelitis, not the typical clinical poliomyelitis presentation, gave as part of his medical history that classmates at his school also had developed paralysis. The patient indicated that many of his friends on the football team had lost their ability to walk and had been sent home from school. I think the surprised resident either diagnosed the patient as having polio or suspected polio. The director of the local county health department in New York contacted the state epidemiologist of New York, who in turn contacted health officials in Connecticut.

TORGHELE: Had any of the children been vaccinated?

SCHONBERGER: Actually, our investigation found that about one-fifth of the 01:05:00children at the school had been fully vaccinated, but most of the children had never received a polio vaccine.

TORGHELE: But Christian Scientists don't generally consult physicians, is that right?

SCHONBERGER: That is right. It was also not clear until the last minute whether the Christian Scientist school master would permit us to vaccinate the children at the school.

Interestingly, the index case was a child of a mixed marriage. One parent was not a Christian Scientist. When their son seemed not to be getting any better, I understand that the non-Christian Scientist parent convinced the spouse that they should try regular medical care.

After the Connecticut State Health Department heard about the situation at the school, Dr. Dewayne Andrews, the EIS officer assigned to the Connecticut State Health Department, started an epidemiological investigation. After a wild poliovirus type 1 was isolated from one of the students and a vaccination 01:06:00campaign at the school was recommended, the Connecticut state epidemiologist arranged for me to come to Connecticut and assist.

I recall the situation being quite tense when health authorities, including myself, appeared in late October at the school's front gate to begin a school vaccination campaign. Television cameras and reporters, too, were at the gate, and it was not clear whether we would be permitted to conduct an onsite investigation and to vaccinate the children. I heard later that the local leadership at the school, seeing what was going on, called the mother church in Boston, and whoever was in charge made the wise decision to agree to let the health authorities enter the school to vaccinate the children. Vaccinating the children and stopping the outbreak was the main focus. When the children gathered to receive the vaccine, I remember being stopped by the school master 01:07:00from collecting blood from the children. He told me that collection of blood specimens had not been part of the initial agreement to permit the vaccinations.

Ultimately our investigation discovered that 11 of 128 students, or 8.6%, had developed acute paralytic polio, and eight of these eleven had residual paralysis sixty days after onset. I mention the presence of residual paralysis at sixty days after onset because this has been a long established clinical criterion used by CDC for surveillance purposes in an effort to obtain more accurate and comparable annual counts of cases of paralytic poliomyelitis. Of the eleven total cases, nine initially occurred among the 38 boys in the seventh through twelfth grades. The two girls with paralytic polio occurred last. The girls were in the second and twelfth grade. So the outbreak consisted basically 01:08:00of boys in the upper grades, followed by two girls.

Ten of the eleven children with paralytic polio, including all eight who had residual paralysis, had a history of never receiving a polio vaccine. By the time the outbreak was reported, eight students with paralysis had been sent home because of the illness. Three lived in Connecticut, three in New York, and one each in Massachusetts and New Hampshire. All the cases had become ill before health authorities had been informed about the outbreak. The first case had his onset of illness about four weeks before we had the vaccination campaign at the school. Despite the delay in reporting, the polio outbreak did not spread beyond the Christian Science community.

One of my first jobs in the investigation was to gather data and establish surveillance for possible poliomyelitis illnesses, specifically aseptic 01:09:00meningitis and acute paralytic disease, at the major community hospital in the local town. By contacting the neurologist and pediatricians and reviewing available hospital records, I was able to quickly corroborate the impressions of the local county health officer that the polio outbreak at the school had not led to polio illnesses occurring in the community. I also examined emergency room visits at the hospital for viral-like illnesses. I compared the period of concern in 1972 with a comparable period in 1971 and found the data to be very similar.

Meanwhile, the state health departments of New York, Massachusetts, and New Hampshire also reported no spread of the outbreak to their general communities. The hospital personnel where a patient had been hospitalized were vaccinated. They were also encouraged to have their children vaccinated. In each of the states, including Connecticut, people were encouraged to make sure polio 01:10:00vaccinations were up to date, but except for New Hampshire, no special general community vaccination campaigns were instituted. The New Hampshire child that had been sent home had weakness of one arm. He created some concern because he had been walking around in the community and eating at local restaurants shortly after he was sent home. Meanwhile, the school children at the Greenwich, Connecticut, school were asked not to intermingle with people in the outside community, and the boarding students were voluntarily kept on campus.

In retrospect, the outbreak was essentially over by the time we began the investigation. It is possible that if the general population had been vaccinated with IPV rather than OPV, this outbreak might have been equally well contained. Nevertheless, the outbreak underscored for me the importance of maintaining the highest levels of immunity in the general population. It also gave me more 01:11:00confidence in the existing immunity in much of our population to prevent the occurrence of a major outbreak. It also underscored for me the importance of focusing control measures based primarily on the epidemiology that could define where and who was at greatest risk of disease. This was an important lesson that I applied when I was confronted with the last outbreak to occur in the United States, a multi-state outbreak in the Amish population in 1979. Another thing I learned was that people can differ markedly in how they regard poliomyelitis.

TORGHELE: Oh, in what way?

SCHONBERGER: In the course of the polio outbreak, I was sitting writing something down and I overheard a conversation of a woman who lived on the school campus, whose unvaccinated seven-year-old daughter had developed paralytic poliomyelitis. This daughter was the only poliomyelitis patient in the outbreak who was under twelve years of age. And I was thinking that the situation for 01:12:00this paralyzed daughter and her family was tragic and very sad. To my surprise, however, based on the mother's conversation, she was clearly not unhappy, and this was difficult for me to understand. She was explaining to the other person how lucky and honored she was that God had chosen her, like God had chosen Abraham when God had tested his faith by telling him to sacrifice his son, Isaac. You remember the biblical story. Just before Abraham was about to kill Isaac, an angel stopped him and a ram appeared for Abraham to sacrifice at the altar instead. The mother was identifying with that story and thinking that God had chosen her to test her faith. She was not unhappy about it. She knew her faith was strong.

So I was struck by this experience with how some people can look at things so differently.

Another difference in this Christian Science community was that illness, 01:13:00including paralytic poliomyelitis, was regarded as an indicator that a person's relationship with God was not quite right, it was not in harmony. To get well, what you had to do was to get your relationship straightened out with God.

For poliomyelitis, we know that normally a certain proportion of initially paralyzed poliomyelitis patients will recover from their paralysis. And, indeed, many of the football players who had gotten paralyzed in this outbreak recovered. In the Christian Science community, I presume that many people interpreted this recovery as due to the paralyzed person's getting his proper relationship back with God. I was thinking that such a belief might put an unfortunate extra psychological burden on the children that did not recover.

TORGHELE: Were there other things that surprised you as different about this outbreak?

SCHONBERGER: Well, the most unusual and amazing aspects of this poliomyelitis outbreak were, first, that it occurred at all, and second, that there was such a high attack rate among the boys in the upper school. Generally we expect one or fewer paralytic cases for every hundred people who get infected with wild poliovirus. In this outbreak, 24% of the boys in the upper school developed paralysis. That was absolutely amazing. Ultimately, I attributed this primarily to the high dose of infection that they must have received. The fact that they were teenagers rather than infants, and that most of them had no immunity to any of the polioviruses, also contributed to their high attack rate. But the key factor probably was the humongous dose of exposure.

Some people thought it's because they exercised. We know that people who get the 01:15:00virus in their central nervous system, and would otherwise recover if they rested, may end up paralyzed because they exercised. Clinically, the virus in the central nervous system generally manifests itself as a major illness such as aseptic meningitis, fever, severe headache, and stiff neck. But exercise is not believed to cause the virus to get into the central nervous system in the first place, even though exercise might convert a non-paralytic major illness into a paralytic illness.

TORGHELE: Like it seemed to in Franklin Roosevelt?

SCHONBERGER: Probably, yes. When I spoke to Dr. Alexander Langmuir in 1972 about the outbreak, he told me that from what I described, polio was undoubtedly "coming off the walls" in the boys' locker room. What I had described was that there was a requirement for all students at the school to be part of either a 01:16:00soccer or football team. The boys all met in a locker room, and this was the only place where the upper school boys that had such a high attack would come together in the absence of the upper school girls. That locker room had a large cooler with an automatic stirrer. The cooler was filled with lemonade or some other kind of drink. It turned out that the automatic stirrer had broken earlier that academic year. Based on reports from some of the upper school boys, they would often stick their arms into the big container to stir the drink. A couple of them were disciplined for spitting into the container. It was clearly a totally unsanitary mess in that locker room.

Undoubtedly, as I have hypothesized probably occurred, once the epidemic strain 01:17:00of poliovirus got into that locker room and contaminated the drink, you can imagine how the boys, but not the girls might well have been exposed to huge doses of poliovirus. In addition, a couple of the days in late September fell within an expected incubation period for all the affected upper grade boys. In other words, it was possible that all the boys who developed paralytic polio were exposed on the same day in the locker room. On the other hand, the girls presumably were exposed from contact with the boys, hence their later onsets of illness and lower attack rate.

Polio epidemics with unusually high attack rates have been reported in the past. They have been observed, for example, in unvaccinated island populations where residents have gotten to older ages without ever having been exposed to any of the three types of polioviruses. As I had mentioned, at the time of the 01:18:00outbreak, we did not identify any family member who had recently been in Mexico or another known endemic poliomyelitis country. I speculate now that the wild poliovirus responsible for the school outbreak that Dr. Olen Kew tells me originated in Mexico may have gotten into the school from an unvaccinated Christian Science community member who had recently visited New York City or another of its suburbs. Greenwich itself is very close to New York City, and although no 1972 imported wild poliovirus case from Mexico into the New York metropolitan area was reported, it would not be totally unexpected for this metropolitan area to have been the immediate source of the poliovirus infection that caused this outbreak.

TORGHELE: You mentioned that your experience with the 1972 outbreak influenced your response to the last wild poliovirus outbreak in the United States. Tell us 01:19:00about that outbreak.

SCHONBERGER: First let me point out that my 1972 outbreak experience, along with my observation that sporadic poliomyelitis cases in subsequent years had not led to secondary paralytic cases, reinforced the same point about the status of the protection of the general U.S. population against paralytic poliomyelitis. It impressed me that this protection, derived primarily from the U.S. routine vaccination policy with OPV, was substantial. The 1972 outbreak also underscored, however, that groups in the general population who are inadequately vaccinated and who live together or regularly comingle with each other, remained at a significant risk of experiencing an epidemic of paralytic poliomyelitis.

Indeed, the 1979 outbreak occurred in an inadequately vaccinated population who lived together and comingled with each other. This outbreak consisted of fifteen acute cases of paralytic poliomyelitis among Amish residents of both the United 01:20:00States and Canada. Thirteen of the cases lived in four U.S. states, and two in Ontario, Canada. In addition, two non-Amish patients with aseptic meningitis due to poliovirus were also part of this outbreak. They lived in Pennsylvania. One was an unvaccinated man from an Old Order Mennonite community whose members had known contact with Amish. The other was a woman whose husband bought eggs from the Amish and lived in the same county as two of the paralytic cases.

The Amish live in communities that emphasize the importance of remaining separate and distinct from the outside world, so they do not generally accept vaccinations. In 1979, there were about seventy-five thousand Amish who lived in twenty-three states, almost 25% of whom lived in Pennsylvania

The index patient in this outbreak became ill in January. She lived in a small 01:21:00town of Pennsylvania. An investigation by Pennsylvania State Health Department personnel, as I recall, uncovered the fact that in the previous summer an Amish family had moved into the index patient's small town from Ontario, near where poliomyelitis cases in a Dutch religious group had occurred. This Dutch group, like the Amish, generally do not accept routine vaccinations. The Canadian poliomyelitis cases, in turn, were linked to a large poliomyelitis outbreak in the Netherlands in 1978 among members of this same Dutch religious group.

A memorable aspect of the 1979 outbreak for me was the use of the fingerprinting technique on the polioviruses themselves that confirmed the epidemiological relationship of the U.S. outbreak to the poliomyelitis cases in Canada and the 01:22:00Netherlands. I brought with me this afternoon two newspaper articles about the 1979 U.S. outbreak, one written by Dr. Melinda Moore and me that was published in the Amish newspaper called The Budget on June 27, 1979, and the other written by reporter Harold Schmeck in the Science Times of the New York Times on August 28, 1979. The latter article describes the fingerprinting confirmation of the epidemiological relationships. The Times article suggests that the source of the virus for the Netherlands may have been Kuwait, but I understand from Dr. Olen Kew that the molecular sequence data now suggest that the Netherlands virus is more similar to viruses in Turkey and China.

Another memorable aspect of the 1979 outbreak was the tremendously hard work 01:23:00performed by the Pennsylvania State Health Department personnel to try to get the Amish communities in Pennsylvania to accept vaccine. It may have been Dr. Robert Gens himself, the director, Division of Acute Infectious Disease Control in Pennsylvania or a member of his staff that went from Amish community to Amish community in Pennsylvania trying to persuade the leader of each Amish group to give approval for his community to get vaccinated. This effort began in mid-February, but it really was not until the occurrence of additional cases among the Amish in April and May that large numbers of Amish accepted vaccine. The last case of paralytic polio in the outbreak occurred in early June. By the end of that month, it was estimated that over 70% of the Amish population in the 01:24:00United States had received at least one dose of OPV.

In the meantime, I recall earnest discussions back at CDC about whether or not CDC should initiate mass vaccination campaigns in the states that were reporting the presence of wild poliovirus. In addition to Pennsylvania, ultimately Iowa, Wisconsin, and Missouri reported paralytic cases in their Amish communities, and Maryland and Michigan reported wild poliovirus but no paralytic cases.

Dr. Don Millar, who was the director of the Bureau of State Services at that time, was very much surprised by my not going along with the idea of responding to this multistate poliomyelitis outbreak with mass community vaccination campaigns in each of the affected states. I kept pointing to the epidemiology that indicated that Amish communities in distant states were at much greater 01:25:00risk than the general U.S. populations that lived relatively close to the affected Amish communities. Whereas Amish communities from distant states would intermingle for celebrations, particularly weddings, social interactions with outsiders, I argued, were very limited. In addition, and here is where my experiences with the 1972 outbreak and sporadic wild poliovirus disease influenced my position the immunity of the general population, particularly if we simply encouraged people to make sure their vaccinations were up-to-date, should be adequate.

Finally, I observed that vaccinating religious groups that do not routinely accept vaccinations, like the Christian Scientists and the Amish, is not easy. They less likely come for vaccinations in mass campaigns. Vaccinating the Amish target group was taking considerable time and much effort on the part of state 01:26:00and local health authorities. But nevertheless, this, I argued, was the right focus. Vaccinating these communities was what was needed and what we should continue to emphasize.

Finally, as a compromise, we agreed to organize one mass vaccination campaign in Lancaster County, because interactions between Amish and the general community were reported to be relatively higher there than anywhere else in the country.

Melinda Moore, EIS class of 1978, who worked in my group, participated in an Epi-Aid [Epidemiologic Assistance] investigation in Lancaster.

TORGHELE: Did she submit an Epi-Aid on that investigation?

SCHONBERGER: Yes, as part of this Epi-Aid she completed a stool survey among young non-Amish school children, as well as serological studies and interviews of persons participating in the mass vaccination clinics held in the county. 01:27:00Among her findings were the absence of evidence of spread of the wild poliovirus into the general community, and that the vast majority of the people who showed up for vaccination in the clinic were already immune.

TORGHELE: Did you take part in that investigation?

SCHONBERGER: I was Melinda Moore's supervisor at the time. I did not actually go to Lancaster.

Let me mention an interesting link between vaccine-associated poliomyelitis and the Amish outbreak. In 1977 or 1978, there was a vaccine-associated paralytic poliomyelitis case in an Amish child. The investigation of that case included the collection of serum specimens from some members in the Amish community. A striking finding, as I recall, was the high proportion of the unvaccinated Amish community who had detectable antibodies against the type 2 poliovirus, but not 01:28:00against type 1 or type 3 polioviruses.

I mention this vaccine-associated poliomyelitis case because it illustrates that not all Amish were unvaccinated. Some Amish were routinely receiving OPV. In addition, the high prevalence of type 2 antibody in the Amish could well have provided some protection against more of the Amish developing paralysis after infection during the type 1 outbreak in 1979. The source of the high prevalence of type 2 antibody is uncertain, but it probably was from the spread of the type 2 vaccine virus in the OPV used routinely by a small minority of the Amish population. The contacts of such OPV recipients were largely unvaccinated. There is some evidence in the scientific literature-I remember a paper by Dr. Salk, for example, that indicated type 2 antibody provides some protection against developing paralysis during a polio type 1 outbreak. Because of this possible 01:29:00cross-protection between type 2 and the other polioviruses, one of the recommendations in 1964 by the Special Advisory Committee on OPV to reduce the risk of OPV-associated paralytic poliomyelitis had been to administer monovalent type 2 OPV first, that is, before either the type 1 and type 3 monovalent OPVs.

In a paper I wrote in 1984 that included summaries of the last two U.S. wild poliovirus outbreaks, I ended with a point that emphasized the importance of routinely maintaining high vaccination levels. I indicated that the immunization level of the general public, primarily responsible for its protection during each of the last two U.S. outbreaks, was that achieved on a routine basis before the initial cases were reported.

TORGHELE: So you were there for these important findings from those outbreaks, and these were some of the last polio outbreaks in the United States.

SCHONBERGER: Yes, the Amish outbreak in 1979 was the last wild poliovirus outbreak in the United States, and a subsequent paralytic case that same year in a child with a Spanish name in Chicago was the last endemic wild poliovirus case in the United States.

After 1979, what was happening concerning U.S. polio surveillance is that it became primarily surveillance of vaccine-associated disease. In 1981, CDC underwent a major reorganization under the leadership of Drs. Bill Foege and Walter Dowdle. As part of this reorganization, the Bureau of Epidemiology that had included my Division of Viral Diseases and the Bureau of Laboratories were largely combined into a new center, the Center for Infectious Diseases. Within 01:31:00that center, I became the acting assistant director for medical science in a newly created Division of Viral Diseases that was several-fold larger than my previous Division of Viral Diseases and had major new combined epidemiological and laboratory responsibilities. However, the primary responsibility for polio surveillance was combined with the polio immunization program in the Immunization Division located in a different center, the Center for Preventive Services.

Although I was thus no longer primarily responsible for U.S. polio surveillance, for many years thereafter I continued to enjoy working with and coauthoring a few scientific papers with the epidemiologists in the Immunization Division and with the polio laboratory experts in my own division. I also continued to participate in domestic and international polio conferences and consultations. During the 1980s, however, my involvement with polio slowly declined. My major 01:32:00responsibilities became eliminating Reye syndrome, supervising national influenza surveillance, including consulting on possible links between seasonal influenza vaccines and GBS, and addressing special, usually outbreak-related projects, such as transfusion associated AIDS and iatrogenic Creutzfeldt-Jakob disease.

TORGHELE: When endemic wild poliovirus was eliminated from the United States, were people thinking that eliminating it globally would be possible?

SCHONBERGER: Yes. A key question discussed in the 1980s was whether or not we could eradicate wild poliovirus from the world. It was a topic at a 1984 symposium, in which I had presented on the control of paralytic polio in the United States. Michael Gregg at CDC argued yes, and Dr. James Chin from the 01:33:00California State Health Department changed the question to, can paralytic polio be eliminated by the year 2000 or shortly thereafter? And answered no. Both agreed eradication was theoretically possible, but Dr. Chin was skeptical that the world would be able to come together strongly enough to do it, particularly by the year 2000.

TORGHELE: And this was soon after Smallpox had been eradicated?

SCHONBERGER: Exactly, but Dr. Chin pointed out epidemiological and program differences for preventing the two diseases that would make eradicating polio even more difficult.

TORGHELE: What were some of the differences between polio and smallpox that Dr. Chin mentioned?

SCHONBERGER: The fecal-oral route of transmission of polio, and the much higher ratio that you and I talked about earlier, of in apparent or mild illness to paralytic disease. Further, the elimination of polio would require higher levels of sanitation, higher levels of immunization, and more needed doses per 01:34:00individual of a vaccine that requires a better cold chain. These challenges for controlling polio are often readily apparent in areas where poliomyelitis cases continue to occur.

TORGHELE: Tell us about some of your own experiences serving as a consultant on poliomyelitis control in less industrialized countries. Were the problems mentioned by Dr. Chin readily apparent at that time?

SCHONBERGER: Yes. I saw these problems firsthand when I served as a temporary consultant of the Pan American Health Organization to help the Trinidad Ministry of Health investigate and control its 1971-'72 poliomyelitis epidemic. They were also evident in Burma and in Egypt, where in 1979 and 1981 I served as a World Health Organization consultant to address the increased concerns in each of 01:35:00these countries about poliomyelitis. I found in my old files my reports of these consultations, including a DVD that shows my examining 6 of the 205 hospitalized poliomyelitis cases in Trinidad in January, 1972. I understand that ultimately these materials, along with the other polio-related materials I brought with me today, may become available online via the Global Health Chronicles website.

The country of Trinidad and Tobago in 1972 had a population of about nine hundred fifty -thousand, and by the end of the several-month outbreak, we had identified about two hundred paralytic poliomyelitis cases. I initially had learned about this outbreak from a phone call I received in early January, 1972, from Dr. Pierre Ardoin, the director of the Trinidad Regional Virology Laboratory, located in Port-of-Spain. He was very concerned, because his 01:36:00laboratory had isolated poliovirus type 1 from most of almost fifty patients with suspected poliomyelitis in Trinidad. Details are provided in my report of this outbreak that I understand will be made available via the Global Health Chronicles website. Under the auspices of the Pan American Health Organization [PAHO] Dr. Hatch and I arrived in Trinidad January 8 to assist the Trinidad Ministry of Health with this poliomyelitis outbreak. I stayed in Trinidad for about a month.

Maintaining the cold chain and questions about the storage and use of OPV were, as I recall, major issues. The first day Dr. Hatch and I arrived in Trinidad was the same day a major supply of trivalent OPV, or tOPV, arrived, over four hundred thousand doses. Much to our dismay, the just arrived shipment, we discovered, had been left outside in the tropical heat, unrefrigerated, as 01:37:00people left work at the end of the day. As I recall, we ultimately were able to arrange for the vaccine to get stored temporarily in a cold room of a local butcher shop. Very soon thereafter, including during much of the night, the government successfully distributed the vaccine to hundreds of vaccination centers around the country. This shipment played a key role in the success of the first national vaccination campaign that had just begun. We determined that over the next couple days this campaign reached over half the target population, children three months to six years of age. A subsequent wrap up campaign raised this proportion to over 80%.

The Ministry of Health had chosen tOPV, rather than type 1 monovalent OPV, because of the frequent isolation of type 2 poliovirus before the epidemic. I 01:38:00was able to set up an emergency operation center at the Regional Laboratory and conduct both retrospective and prospective case surveillance at the two major hospitals in Trinidad, the only two hospitals that would treat polio patients. As my report details, I was able to document that despite the fact that tOPV was used, instead of the generally recommended type 1 monovalent vaccine for controlling a wild type 1 poliovirus epidemic, the tOPV was remarkably effective in controlling this outbreak. For example, I was able to show that within the second calendar week after the first national campaign, the attack rate among those that had been vaccinated was less than one-third of that among those who had not been vaccinated.

TORGHELE: Were there other unusual aspects of that epidemic besides the use of trivalent instead of monovalent oral polio vaccine?

SCHONBERGER: I did observe that the Christmas holiday had an important negative 01:39:00effect on this epidemic. First, it contributed to the lack of success of the government's first vaccination program that was planned to start just before Christmas. The public was not aroused at that point, and vaccine was in short supply. Second, the major spread of the epidemic occurred during a poliomyelitis incubation period, three to twenty-one days, after Christmas, when people were traveling throughout the island to visit family and friends.

One big decision during the epidemic in January was whether the government should postpone the Carnival, a planned major cultural and tourist event on the island that was scheduled for February. Dr. Hatch and I thought such a postponement would be a prudent thing to do, given the many anticipated visitors to Trinidad for this celebration, including potentially inadequately vaccinated 01:40:00persons from other Caribbean islands. In 1972, the Carnival in Trinidad was postponed from February to May.

Another memory I have of that outbreak was the difficulties created by a sensational newspaper article about a tragic poliomyelitis case in an adult. At our recommendation, the Ministry of Health was trying to maintain the focus of the vaccination campaigns on the most susceptible populations, initially children under six years of age, who ended up with an attack rate over fifty times that of adults. Some adults panicked, however, and at least one satellite clinic was attacked by them in an effort to get vaccinated ahead of the children. Vaccine was offered to adults in local health centers.

I learned that the vaccination strategy of setting up many satellite clinics, a 01:41:00strategy used in South Trinidad, worked better than depending upon a few large, centrally located vaccination clinics, the strategy used in North Trinidad. The South reached a higher proportion of the target population and was more effective in stopping the outbreak.

TORGHELE: Tell us about the video recording from the Trinidad outbreak. What does it show?

SCHONBERGER: The DVD from the Trinidad outbreak, that I understand will become available via the Global Health Chronicles website, was made from a film that was shot at the Port-of-Spain general hospital several days before I left the Island. The DVD shows my examining six paralytic polio cases in children six years of age or younger. It shows the crowding in the hospital, two patients in a bed. It shows flaccid paralysis with absent reflexes, and a child in a tank 01:42:00respirator. It also shows a patient with head lag, stiff back, and the tripod sign of polio, and another patient with diaphragmatic breathing with lack of intercostal muscle assistance. The last patient in the film was very surprising to me, as he was only five weeks old at onset. He had never been vaccinated and was not being breastfed.

TORGHELE: What were some of your most important recommendations for the Ministry of Health and the Pan American Health Organization after the Trinidad epidemic?

SCHONBERGER: We addressed the key problems of the poor vaccination status of the Trinidad population since the last mass campaign five years earlier. Less than 10% of the children since that time had been immunized. We recommended that the Ministry of Health push for at least 75% coverage and, if not reached through routine clinics, that it conduct a couple weekend mass vaccination campaigns 01:43:00each year and, if necessary, even organize some door-to-door immunization campaigns. We also recommended instituting a vaccination requirement for school entry. We also made recommendations on strengthening the cold chain and on the handling, storage, and use of OPV. Another important recommendation was that the Ministry and the Regional Virology Laboratory in Port-of-Spain work more closely together, and that PAHO [Pan American Health Organization] establish a regional storehouse of vaccine at the laboratory in order to avoid delays and lapses in availability of vaccine. These and several other recommendations are listed in the report.

TORGHELE: When you served as a WHO [World Health Organization] consultant in Burma, did you find similar vaccination problems to those you found in Trinidad?

SCHONBERGER: Believe it or not, in 1979-the year, you will remember, of our last endemic U.S. case of wild poliovirus, Burma had yet to even introduce the use of 01:44:00poliomyelitis vaccine. In 1979, Burma had an estimated population of 32.9 million, about thirty-five times the population of Trinidad. Some members of the Ministry of Health had raised concerns about the risk of an imminent major poliomyelitis epidemic, particularly in the capital city, Rangoon. Given that poliomyelitis vaccine was not available in Burma, there was also concern and uncertainty about the extent to which circulating wild poliovirus among young children was causing paralytic disease. In collaboration with several Burmese colleagues, including from the Ministry of Health, my findings in Burma were made public through a 1980 article in the Development of Biological Standardization journal entitled "The epidemiology of poliomyelitis in Burma, 1963-1979." This article is among the materials that I believe will become 01:45:00available through the Global Health Chronicles website.

During my consultancy, I analyzed the results of three serosurveys, reexamined most of the children included in a survey for lame school children of Rangoon that had been conducted in 1978, and reviewed and stimulated hospital-based polio surveillance. Among the key findings were that Burma was paying a steep price in terms of paralytic cases by not using polio vaccine and instead depending for polio protection upon the natural acquisition of immunity at a young age from the circulating wild poliovirus. Presumably, the infections at a young age would be less likely to cause paralysis. However, the annual paralytic poliomyelitis rates were regularly averaging around a quarter to a half of the attack rate observed during the major Trinidad epidemic that I had investigated 01:46:00in 1972.

Because of the good evidence from the serological surveys that a very high proportion of children in Rangoon had antibody against poliovirus type 1 by age three years, I reported that an imminent unusual major outbreak of paralytic polio in Rangoon was unlikely. During my investigation in Burma, however, I did stimulate increased reporting, so I did expect that surveillance data in 1979 would more closely show the true high endemic incidence of paralytic disease that was going on in Burma. For children one year of age and older, my coauthors and I estimated from the Burmese data I had collected that there was approximately one paralytic case for every 140 or 163 immunizing infections to poliovirus type 1, and substantially higher paralytic rates among those who were 01:47:00triple seronegative at the time of this infection.

Just before leaving Burma, I collected in a small nonmetal cup-like container a loose stool specimen from an acutely paralyzed child. I then placed the container in multiple plastic and paper bags. I did not have a cooler during the many hours I spent carrying this specimen back to Atlanta via New Delhi, and Geneva, Switzerland, where I was debriefed by WHO officials. Although the package was often at room temperature on this trip, the excellent CDC laboratory personnel successfully cultured wild poliovirus type 1 from the specimen. This experience reinforced what I had been told about the potentially high stability of polioviruses in a moist stool environment.

Let me also share with you several non-polio memories of Burma in 1979 that help 01:48:00to put the polio situation there in context. In addition to the country not having any poliovirus vaccine, physicians in Burma at that time also did not have access to many drugs and antitoxins to treat their patients. During a visit to the Infectious Disease Hospital in Rangoon, for example, I saw a very sick child whose very knowledgeable attending physician had diagnosed with diphtheria. The physician explained that his patient would likely die, because in Burma he could not obtain the antitoxin needed to save the child's life.

I also remember my host from the Burmese Ministry of Health taking me on a harrowing plane ride to Pagan, the city of temples, and our then travelling to a rural area near the Irrawaddy River. I recall seeing how water was obtained for use at a local village. I saw a young boy balancing himself on a huge, 01:49:00horizontally positioned oil tank on a cart with large wheels. While riding on the oil tank, the boy was whipping an ox that pulled the cart down a moderate slope towards the river. The boy had the oxen pull the cart deep enough into the river so that the tank filled with water when the hole on the upper side of the tank became submerged. Once the tank was full, the boy had the oxen turn and pull the cart back on the shore.

TORGHELE: After Burma, when and why were you asked to consult on polio in Egypt?

SCHONBERGER: In 1981, two years after reviewing the polio epidemiology in Burma, I was asked again to serve as a WHO short-term consultant. This time I was asked to review available polio data in Egypt, recommend ways to facilitate better poliomyelitis control, and answer several specific questions of the minister of 01:50:00health. These questions included why, given Egypt's polio control program, so much polio had occurred in Egypt in 1980. How effective was the currently available OPV in Egypt? Should the minister initiate another mass vaccination campaign? Should IPV play a role in the control of polio in Egypt?

I submitted the report of my findings in Egypt, including the answers to the minister's questions, to WHO's Regional Office for the Eastern Mediterranean in Alexandria. In 1981, the report was then circulated both within and outside of this region. I understand that now it will also be made available through the Global Health Chronicles website.

Interestingly, WHO representatives added to my report their own well-written summary of it. They also modified one of my recommendations related to initiating a study to test whether the recently developed, more potent IPV could 01:51:00facilitate polio control in Egypt. Instead, the WHO representatives encouraged the Ministry of Health to first implement the many important recommendations I had made to optimize the use of tOPV, and only then, if polio remained a problem, to begin a study of a potential role for IPV in controlling the disease.

My report was comprehensive and detailed and included the results of my review and interpretation of a substantial amount of available polio data in Egypt. It also included the results of my interviews of poliomyelitis investigators in Egypt, who had conducted prevalence surveys of paralytic polio in the country. In addition, it included the results of my own small vaccine coverage survey in three areas of Cairo that I completed during the consultancy with the help of 01:52:00several local physicians. The areas I had selected each had either an estimated low, medium, or high incidence rate of paralytic polio.

I found that despite the compulsory routine vaccinations and periodic mass vaccination campaigns, poliomyelitis remained an important public health problem in Egypt. The country was experiencing annual incidence rates between ten and sixteen cases per one hundred thousand population, equivalent to about half to three quarters of the attack rate that I had observed during the major epidemic in Trinidad in 1972. Yet I found consistent evidence, much to my surprise at the time that the routine polio vaccination program with OPV was reaching well over half the children and after the mass campaigns vaccination rates would reach over 70%. Supporting the existence of reasonably good rates of vaccination in 01:53:00Egyptian children overall was the high vaccination rates among the polio patients over eight months of age-as many as 18% to 50% had a history of three or more doses of tOPV. At the same time, the evidence I collected also did not support a conclusion that administration of impotent tOPV in recent years was a major problem.

Concerning the epidemiology, I found a marked inverse correlation of paralytic poliomyelitis attack rates with socioeconomic status, and an unusually young age distribution of paralytic cases. There was also a clear seasonality, with higher incidence rates occurring between June and October.

I reported that the major, most easily correctable problem with the polio control program was its failure to provide for a sufficient number of tOPV doses 01:54:00early enough in life. Egypt was using a routine vaccination schedule appropriate for use in the United States but not in Egypt, where up to a quarter of the annual paralytic cases had onset between three and eight months of age. The passive antibodies from their mothers were not providing the Egyptian children sufficient protection. I recommended a change in the routine vaccination schedule. I indicated that there was a need for more emphasis on earlier and additional routine doses of tOPV. I also provided evidence that the attack rate of paralytic polio in those with three or more doses of tOPV, compared to those with fewer doses, was markedly reduced, but that the doses received beyond the third dose were contributing significantly to this protection.

I also recommended that when mass campaigns were conducted, that they should take place before the summer season of high polio incidence. I indicated that it was more than coincidental that the only summer not preceded in recent years by a mass vaccination campaign in the previous winter or spring was the summer of 1980, when the incidence of polio rose sharply to earlier levels.

In my detailed report, I included a brief description of a 1980 published study of a polio vaccine field trial conducted in three Egyptian villages. The study showed that in Egypt, one dose of the improved IPV was more immunogenic [able to produce an immune response] than one dose of tOPV. Accordingly, among my recommendations, I suggested that WHO help plan a further IPV study to assess 01:56:00the degree to which the improved IPV potentially could facilitate polio control in Egypt. As mentioned earlier, the WHO representatives discouraged studying the potential use of IPV. Today, as we get closer to the goal of eradicating wild poliovirus disease from the world, there is universal acceptance and appreciation for the important role IPV now has in the control of poliomyelitis. It is quite remarkable that since 1997 IPV has been playing such a major role in the control of poliomyelitis in the United States, and since around 2000 has been the only vaccine routinely used in our country. In addition, WHO now recommends that every country using only OPV add at least one dose of IPV to its routine vaccination schedule.

TORGHELE: Dr. Schonberger, you have provided some vivid details to the polio story that we otherwise would have not known. Is there anything else you would like to add before we finish here?

SCHONBERGER: Well, let me just say thanks to you and to the many others who are making this polio history project successful. My late, older brother, Dr. Howard Schonberger, was a history professor at the University of Maine. His devotion and commitment to history have made me more appreciative of its importance and of the value of the type of work that you are currently doing. I very much appreciate your efforts to collect oral histories and historical documents and to make these more publicly accessible. So thanks again.

TORGHELE: Thank you so much for relating your experiences from your amazing career and for your participation in this oral history project for the Global Health Chronicles.

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