James L. Franklin
Chicago, Illinois, United States

In the midst of the 2020 Covid–19 pandemic, when international scientific cooperation seems to be the order of the day, it is heartening to recall that during the height of Cold War tensions between the USSR and the United States, collaboration between an American virologist and his Russian counterparts resulted in a “vaccine diplomacy” leading to the near worldwide elimination of polio. In January 1956 Albert B. Sabin received a call from the Public Health Service that a group of Russian scientists was traveling to the United States to study the preparation of the Salk vaccine. The laboratory of Jonas Salk in Pittsburgh was their primary destination, but they hoped to meet with other polio researchers including Sabin at the University of Cincinnati. Sabin welcomed the visit and promised a program of conferences and demonstrations. The visit to the US came at a pivotal moment in the fight against polio for the Soviet scientists. For Albert Bruce Sabin, it was a way forward.

Polio was slow to come to Russia. In the latter part of the nineteenth century, small sporadic outbreaks of polio were registered in Latvia, Estonia, and St. Petersburg. In 1929 the USSR had the lowest incidence of disease in Europe: 0.54 per 100,000 compared with rates of 1.7 in Germany, 6.3 in Denmark, and 15.4 in Sweden. Shortly after World War II, epidemics began to occur in the republics of the Soviet Union. The rates were highest in the central and northwest portions of the country, particularly in the Baltic Republics. In 1955 and 1957 the incidence had risen to 8.7 and 9.4 per 100,000 respectively. The Soviet Union responded to these epidemics by establishing the Poliomyelitis Research Institute in Moscow headed by Mikhail Petervoich Chumakov (1909–1993), a forty-six-year-old scientist already distinguished in the field of virology research.

The Russian scientists’ visit to the United States came at a critical juncture in Albert Sabin’s quest for an effective, live-attenuated vaccine. In the winter of 1954–1955, Sabin had tested his attenuated vaccine on thirty adult volunteers at the federal prison in Chillicothe, Ohio. The test had been successful. All the prisoners developed antibodies to the three virus strains tested and experienced no side effects. The National Foundation for Infantile Paralysis, which had sponsored the development and field testing of the Salk vaccine, also contributed significantly to Sabin’s research program. The disaster of the Cutter vaccine incident that resulted in some 200 cases of paralytic polio had dampened the Foundation’s interest in sponsoring another mass trial of Sabin’s oral polio vaccine. With millions of children already vaccinated with the Salk vaccine, it would be difficult for Sabin to find suitable volunteers.

Albert Bruce Sabin (1906–1993) was born Abraham Saperstein in Bialystok, Russia (restored to Poland after 1918). In 1921 he emigrated with his family to the United States and became a naturalized citizen in 1930. He changed his name to Sabin and assumed the middle name Bruce. Graduating from New York University Medical School in 1931, he trained in internal medicine and pathology at Bellevue Hospital. During the 1930s, he pursued a career in research at the Lister Institute for Preventive Medicine in England and the Rockefeller Institute for Medical Research in the US. During World War II he helped develop a vaccine against Japanese encephalitis. After the war he was appointed to head pediatric research at the University of Cincinnati.

The path leading to the development of an effective polio vaccine was the product of work by scientists around the world that spanned the first six decades of the twentieth century. Real progress began in Vienna in 1908 when Karl Landsteiner (1868–1943) and Erwin Popper (1899–1968) established that polio was a viral disease by demonstrating that the infective agent could pass through bacterial filters. It would not be until 1949 when David Bodian (1910–1992) and Isabel Morgan (1911–1996) at John Hopkins University School of Medicine identified the existence of three strains of polio virus. Further work from the laboratory of Jonas Salk (1914–1995) verified that there were only three naturally occurring strains of the virus. This work was crucial, as a successful vaccine would have to produce immunity to all three strains.

A second breakthrough in the search for a vaccine also came in 1949 in Boston when John Enders, PhD (1897–1985), Thomas Weller, MD (1915–2008), and Frederick Robbins, MD (1916–2003) were able to grow polio virus on non-nervous tissue.¹ This led to the cultivation of polio virus on monkey kidney cells in 1951 at the University of Pittsburgh by Jonas Salk (1914–1995) and his colleagues. This method allowed Salk and his team to produce large quantities of virus for a vaccine. By 1952 Salk was able to test a killed-virus polio vaccine on children at the D.T. Watson Home for Crippled Children and at a state school in Polk, Pennsylvania. His formalin-killed virus vaccine produced antibodies to all three strains with no side effects.

In 1952 a surge in the number of polio cases in the United States to 57,628, with more than 21,000 paralytic cases, focused public attention on the need for a vaccine. At this juncture public pressure began to influence the course of events. Despite concerns in the scientific community about the lack of long-term immunity with a killed-virus vaccine and the danger that lurked in Salk’s choice of a virulent Type I (Mahoney) virus strain, the Vaccine Advisory Committee of the National Foundation for Infantile Paralysis (The March of Dimes) approved and sponsored a field test of the Salk polio vaccine. Over 1.3 million children participated in a randomized double-blind trial with enthusiastic public and parental support.

On April 12, 1955, the tenth anniversary of the death of Franklin Delano Roosevelt, at a media-hyped news conference held at the University of Michigan, Thomas Francis Jr. MD, a scientist with extensive experience in the field of influenza vaccines, announced that the vaccine was 80–90% effective against paralytic polio. On that same day, the US government licensed the Salk vaccine. This bright start was marred by the tragic events of the Cutter incident. Within weeks of the landmark press conference, a physician in Idaho reported a case of paralytic polio in a girl who had recently been vaccinated. Reports of similar cases quickly surfaced and US Surgeon General Leonard Scheele suspended the polio vaccination program in order to investigate the production methods of the six drug companies manufacturing the vaccine. In total, eleven vaccine recipients died and over 200 were paralyzed. The cause, though never proven, resulted from a failure to completely kill the Type 1 (Mahoney) poliovirus and failure to follow Salk’s instructions for vaccine production and protocol. The outbreak was linked to vaccine produced by Cutter Laboratories in Berkley, California. When the vaccine program resumed, there was less enthusiasm and fewer children got their shots. In 1955 the attack rates from paralytic polio were “two to five times greater in unvaccinated children in the same age group.” There were more than 28,000 cases in the United States that year and most could have been avoided, a further fallout from the Cutter incident.

This shifted the focus on what could be done to make the vaccine safer, and brought into the public eye the hitherto anonymous Albert Sabin, a believer in the merits of a live-attenuated vaccine over a killed-viral vaccine. The arguments favoring a live-attenuated vaccine included that it could be given by mouth, thereby not requiring injection, and that it followed the natural route of infection. Further, a single dose could be given, which would produce rapid protection and a durable immunity that would not require booster shots. It was also held that passive vaccination through a carrier state could result in immunization of unvaccinated members of the population, promoting so-called herd immunity.

Against these considerations was the greater difficulty in attenuating a virus versus killing it. There was also the possibility that the virus might emerge from the gastrointestinal tract in a more virulent form. Attenuating the three strains of poliovirus for a vaccine required the passage of each strain through monkey kidney tissue cultures multiple times in succession, and producing a virus that could replicate in the alimentary tract with no viremia and little change in neurovirulence when recovered in the stool. As Sabin observed: it was “no job for someone in a hurry.” By 1956 Sabin had made great progress in the development of his vaccine; he had produced optimum type 2 and type 3 progeny and was in the process of testing two type 1 strains.

The Russian virologists who visited the US in January 1956 included: Mikhail P. Chumakov and his wife, Marina Voroshilova, a distinguished researcher in her own right, Anatoli Smoridentsev, and Lev Lukin, prominent Soviet virologists. The Soviet visit was conducted under strict State Department supervision and special permission was required to visit Jonas Salk’s laboratories in Pittsburgh as the city was off limits to Russians. Cold War tensions required that the Russians travel by train; they were not allowed to travel more efficiently by air. American observers were convinced that at least one “doctor” in the group was a KGB operative.² The visit to Salk was at the top of their list as his vaccine had already been proven to be effective. When the Soviet delegation reached Cincinnati in early February, Chumakov found in Sabin a friend. Though Sabin had been born in Russia he spoke little Russian and Chumakov spoke little English, however the two men hit it off. Chumakov had been born into a humble family in the Caucuses. His father was an army veterinarian and his mother a peasant. He went to Moscow to study law and medicine before settling on a career in medicine. In 1952 he had been removed from his position at the Ivanovsky Institute for refusing to fire Jewish associates as part of an anti-Semitic campaign known as the Doctor’s Plot. Chumakov and his wife, Marina Voroshlova, actively took part in a movement to free Soviet medicine from its Stalinist past; for example, the genetic theories of Trofim Lysenko that had dominated Soviet science.

The Russians promised Sabin an invitation to Russia and when it was received, he jumped at the chance. After two intensive FBI interrogations, Sabin was able to travel to Leningrad and Moscow in June of 1956. He spent a month in Russia meeting with scientists, giving lectures, and all the time lobbying for his vaccine. On returning to Cincinnati, Sabin wrote to the State Department requesting permission to send some of his viral samples to the Soviets.³ Despite State Department concerns about the possibility that the virus samples could be turned into biological weapons, his request was approved. Chumakov had also invited Jonas Salk to visit the Soviet Union to discuss mass testing but Salk turned him down. During an interview David M. Oshinsky conducted in November 2002, Salk’s son Peter told him that his father regretted his decision, feeling that it might have “changed history.” Salk placed the responsibility for his decision with his wife, who felt that his work had separated him from his family for too long.⁴ Early experiments with the Salk vaccine had shown mixed results: “though polio had been reduced in the Soviet Union, the vaccine was expensive to produce, difficult to administer and erratic in potency.”⁵ Chumakov was convinced to proceed with the oral polio vaccine.

Chumakov initially tested a vaccine made from the seed virus that Sabin had provided. The trial showed that the vaccine was easy to administer and safe. Sabin was invited back to Moscow in the spring of 1959 and observed that the work being conducted “on a scale that would have been impossible in the USA. Chumakov at first could not get permission for a large clinical trial. The Health Ministry opposed the trial on the grounds that they already had the Salk vaccine and did not need another one. As related by Chumakov’s son Konstantin, with a single call using one of the red telephones provided for the most powerful people in the Kremlin, his father called Anastas Mikoyan, the Politburo member responsible for public health—a figure who went back to the revolution—and received permission to proceed with the trial.⁶ In 1959 the vaccine was tested on ten million children, administered by medicine dropper or wrapped in candy. The vast majority received three doses, Type I, II and III spaced a month apart; a small number received a trivalent vaccine as one dose. To quote from Polio: An American Story, the success of the trial was “a tribute to Dr. Chumakov, to good planning and to the coercive powers of the state.” The scene at vaccination centers had the making of a “military campaign.” Vaccination centers were set up at “schools, nurseries, kindergartens, clinics, factories and the like. Parents were told where and when to bring their children. Local officials made sure that everybody showed up. Pediatricians took care of the medical end and meticulous records were kept.” Mikhail Chumakov’s son Pytor, a Doctor of Biologic Sciences, provided his recollection from this period:

In 1960, I was 9 years old. First, the vaccine was tested on us. Chumakov’s children, Smorodintsev’s granddaughters, relative and colleagues. I remember being injected with Salk’s vaccine earlier. It was an intramuscular injection in my forearm. It was normal state of things, since developers always test their developments on themselves and their children. My parents were sure that it was safe. The relatives were all for it, too, as everyone understood the dangers of polio and believed that the vaccine would protect children from the disease.⁷

By the end of 1960, seventy-seven million people under the age of twenty in the Soviet Union had received the vaccine, as well as twenty-three million in Eastern Europe. The Russians did not follow the double-blind model that was used in testing the Salk vaccine in the United States. There were no controls or placebos and no children were denied the vaccine. Chumakov stated that their sole aim was to wipe out polio.

Strongly positive results on the safety and effectiveness of the oral vaccine were reported in June 1959 at the First International Conference on Live Poliovirus Vaccines held in Washington, D.C. Sabin was elated and wrote to Chumakov that at this rate the USSR would be the first country to eradicate polio. However, Cold War tensions still loomed in the background and there was concern that the results would be viewed as Soviet propaganda. Dr. John Paul, a virologist and close friend of Sabin, convinced the World Health Organization to send his Yale colleague, Dorothy M. Horstmann, to Russia to study the vaccine trials.

Doctor Horstman spent six weeks in the Soviet Union in the fall of 1959. Between August 30 and October 11, 1959, she visited Moscow, Leningrad, Tashkent, and Riga. Her report to the World Health Organization concluded that the standards of laboratory work were high, the facilities adequate, and “the marked reduction in cases in 1959 in orally vaccinated Republics suggests that the vaccine may have played a significant role in reducing the incidence of paralytic poliomyelitis.” The report, though widely circulated, was never published. In 1991 Dr. Horstmann summarized the results of her survey in the Yale Journal of Biology and Medicine, pointing out that “the positive assessment led to a rebirth of interest in the oral vaccine and paved the way for large field trial in the United States, leading to licensure of the oral vaccine.”⁸

At the Second International Conference on Live Poliovirus Vaccines in Washington D.C. held in 1960, the Soviet delegation presented an account of the progress made in their country toward the eradication of polio. The Horstmann Report had convinced the researchers of the legitimacy of their claims. After an American scientist, Charles Armstrong, rose to express some doubts, a Russian delegate told the attendees: “I would like to assure [you] of one thing, that we in the Soviet Union love our children and are as concerned for their well being as much as people in the United States, or any other part of the world are for their children.”⁹ The Soviet delegation received a standing ovation at the conference.

In April 1960 the Sabin vaccine was administered to 200,000 people, mostly young children, on “Sabin Oral Sundays” in Cincinnati and surrounding Hamilton County, Ohio. By August 1960, Surgeon General Leroy E. Burney approved the manufacture of the Sabin vaccine in the United States. While the US Public Health Service had stalled on approving the vaccine, the USSR sent millions of doses of the oral vaccine to places in the world still experiencing epidemic outbreaks of polio. The Soviets reaped the propaganda benefit of this humanitarian act and were not transparent about the fact that the vaccine had been developed in the United States.

Events related to the 1956 visit by Russian virologists to the US sheds an interesting light on the scientific community during this period.¹⁰ When Sabin visited Russia in June 1956, he reached an agreement with Victor Zhadanov, the Deputy Minister of Health, that he would send aliquots of his live virus vaccine to Professor Anatoli Smoridentsev, who would test them in children’s homes in Leningrad. Smoridentsev was one of the Soviet scientists who visited Sabin’s laboratories between February 5 and February 7, 1956 and was Chief of the Virus Research Laboratories of the All-Union Institute of Experimental Medicine in Leningrad. Sabin had reservations about Smoridentsev, whom he had met in 1944 at the Rockefeller Foundation Laboratories. On that occasion Smoridentsev had sent samples of a virus he believed to be a new strain of spring-summer encephalitis, but when tested proved to have been misidentified.

It was the sort of thing for which Sabin had a long memory. In spite of these reservations, late in October 1956 when Sabin had selected the optimum strains for the vaccine, he sent several lots to Smoridentsev as promised. Chumakov was not included in the agreement with Zhadanov at this time because he was setting up production of the Salk vaccine in the Soviet Union.

In the spring of 1958, while Chumakov was managing the Salk vaccination programs, he became increasingly skeptical of the usefulness of the vaccine and convinced of the superiority of Sabin’s live virus vaccine. In July he asked Sabin to send him “the greatest amount” of the attenuated strain for a trial program. But in December, he was forced to write Sabin of a complication that had arisen. The Ministry of Health informed him that Smoridentsev had tested his own “Leningrad vaccine” on 1,200 infants and had been given permission to study the effectiveness of his live vaccine on 20,000 children. Chumakov was informed that he would be allowed to perform a comparative study on the effectiveness of the vaccine he had received from Professor Sabin on 20,000 children in Moscow. Chumakov correctly suspected that Prof. Smoridentsev’s strains had initially come from Sabin in 1956. Chumakov closed his letter by encouraging Sabin to again visit him in Moscow in the spring of 1959.

The relationship between Sabin and Chumakov involved much more than providing samples of the vaccine. They shared information on their ongoing research programs and Sabin shared with the Soviet virologists his laboratory techniques and critical apparatus for conducting the trial and analyzing the results. Chumakov and Sabin were excellent virologists, but as historian Saul Benison notes: “it is doubtful Chumakov had ever run across anyone who checked his work as carefully as or gave such meticulous attention to details as Sabin.”¹¹ The warmth in their relationship can readily be sensed in their correspondence, addressing each other as “My dear Albert” and “My dear Mikhail Petrovich.”

Smoridentsev’s false claim, which he would finally acknowledge in a letter to Sabin, had its origin in envy he felt toward Chumakov, who had received approval to conduct the massive nationwide Russian trial with the Sabin vaccine. Smoridentsev felt that his initial work with the vaccine between 1956 and 1958 had given him exclusive rights to study the vaccine. The tension between the two scientists again surfaced when Chumakov, in an effort to make the vaccine more palatable, incorporated it in a candy base. He was immediately attacked by Smoridentsev, claiming that this would lower the potency of the vaccine. Chumakov was compelled to send samples back to Sabin and Dr. Roderick Murray at the NIH who verified the potency of the vaccine.

Two examples of Soviet propaganda surfaced as a result of these events. In July of 1959 an article appeared in Izvestia by E.D. Arenin claiming that the vaccine had been developed by Smoridentsev, while in the United States they were still using the Salk vaccine to the profit of doctors and the drug industry under the “vulpine laws of capitalism.” The New York Times brought the article to Sabin’s attention and he telegraphed Chumakov asking for an immediate retraction. Within several days, Tass, the official news agency of the Soviet Union, carried Chumakov’s response disavowing the statements published in Izvestia and affirming that the polio trials were a collaboration between Professors Chumakov, Smoridentsev, and Sabin.

During the 1960s, the Soviet Union became the largest producer of the Sabin vaccine. It was sold throughout the world and promoted as “the communist vaccine.” In 1968 Dr. Boris Petrovsky¹² published a “History of Public Health in the USSR,” making the claim that Chumakov and Smoridentsev had developed the polio live-virus vaccine. A Cincinnati physician who had recently visited the Soviet Union and seen an English translation called it to Sabin’s attention. Because Dr. Petrovsky was considered a patriarch of Soviet surgery and a member of the Academy of Sciences and the Academy of Medical Sciences, Sabin felt compelled to lodge a formal protest. Eventually he received a letter from Professor Vladimir Timakov, an eminent bacterial geneticist and President of the Academy of Sciences, regretting the claim and attributing it to an unfortunate mistake in translation of the Russian text to English. Timakov asserted the passage had only credited the Soviet virologists with organizing the massive immunization program. A year later at a World Health Organization meeting in Geneva, Sabin received a formal apology from the Soviet Deputy Minister of Health.

In 1963 Chumakov wrote to Sabin that he was awarded the highest professional award, the Lenin Prize, for his work and use of the oral Sabin polio vaccine. He went on further, “I am sorry that for formal reasons it was impossible to nominate you . . . I consider you to be one of the main heroes of this event . . . Soviet virologists and with them millions of parents [are] eternally grateful to you.”¹³ Sabin refused to patent his vaccine, donating his poliovirus strains to the World Health Organization in 1972. He thereby blocked commercial exploitation by the pharmaceutical industry, keeping the price of the vaccine low so as to make it available throughout the world. As the frequency of new cases of polio dramatically fell, it became apparent that a small number of cases of paralytic polio resulted from the vaccine itself. It was a fact that Sabin refused to accept, but estimates placed the frequency of vaccine-associated paralytic polio at 2–4 out of every one million children vaccinated. In 2000, forty-six years after the successful Salk poliovirus vaccine trials in 1954, concerns about polio developing from the oral polio vaccine led the United States to return to the inactivated poliovirus vaccine (Salk)-only schedule. Today, the Type–2 strain of the polio virus has been eliminated worldwide and is no longer included in the vaccine. Afghanistan, Pakistan, and Nigeria are the only countries still reporting sporadic cases of polio.

Throughout the late twentieth century and into the twenty-first, joint US–Russian cooperation on health activities has continued. At the 1959 meeting of the WHO’s World Health Assembly in Minneapolis, Viktor Zhdanov, a Soviet virologist and deputy health minister, proposed a five-year plan for the worldwide elimination of smallpox. Soviet scientists developed a unique process for preserving the smallpox vaccine in harsh environments through the development of a freeze-dried technique and produced hundreds of millions of doses. This was the key to a celebrated campaign led by Donald Ainslie Henderson, an American public health physician and epidemiologist, to eradicate smallpox by 1977. In 2009 a Bilateral Presidential Commission between the US and Russia was established for cooperation in public health issues including infectious diseases and noncommunicable diseases such as alcohol and tobacco consumption.¹⁴

The story of how the Sabin oral polio vaccine came to be tested in Russia in the early 1960s, during a period of intense Cold War tensions, is an exemplar of the benefits accruing from international cooperation. While the 2020 Covid–19 pandemic is still evolving, cautionary tales are already emerging as to what can occur when nations turn inward and refuse to share vital public health information. On the other hand, heartening events are coming to light that demonstrate how nations can come to each other’s aid through the global supply chain and shared expertise.

 

End Notes

1. John F. Enders and his colleagues were awarded the Nobel Prize for Physiology or Medicine for their work on the cultivation of poliomyelitis viruses.
2. William Swanson, Birth of a Cold War Vaccine, Scientific American, April 2012, 66 – 69.
3. From Catherine the Great to the red hippo: History of Vaccination in Russia. In a section, “How Soviet scientists defeated polio,” asserts that the Soviet scientists on returning from their visit to the United States, carried “several thousand doses of vaccine in an ordinary suitcase and made the first vaccination.” https://www.mos.ru/en/news/item/62002073/
4. David M. Oshinsky, Polio: An American Story, Oxford University Press, 2005, p. 251
5. Ibid. David M. Oshinsky, p. 251
6. Ibid., William Swanson, p.69er3
7. From Catherine the Great to the red hippo: history of vaccination in Russia, https://www.mos.ru/en/news/item/62002073/
8. Dorothy M. Horstmann, The Sabin Live Poliovirus Vaccination trials in USSR, 1959, The Yale Journal of Biology and Medicine, 64 (1991), 499-512
9. Ibid., David M Oshinsky, p. 254
10. Saul Benison, International Medical Cooperation: Dr. Albert Sabin, Live Polio Virus Vaccine and the Soviets, Bulletin of the History of Medicine 1962: 56, Pp. 460 – 483. A detailed account of the events detailed in this section can be found in this excellent article
11. Ibid. Saul Benison, International Cooperation, p. 475
12. Boris Vasiljevich Petrovsky was described as a patriarch of Soviet Surgery in an obituary appearing in the British Medical Journal 2004 June 5; 328 (7452) 1381. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC420306/
13. Ibid., David M. Oshinsky, p. 267
14. Peter J. Hotez, Russian – United States vaccine science diplomacy: Preserving the legacy, PLOS/Neglected Tropical Diseases: 2017 May: 11(5)

JAMES L. FRANKLIN, MD, is a gastroenterologist and associate professor emeritus at Rush University Medical Center. He also serves on the editorial board of Hektoen International and as the president of Hektoen’s Society of Medical History & Humanities.

Highlighted in Frontispiece Volume 12, Issue 3 – Summer 2020

Spring 2020  |   Sections  |  Infectious Diseases