Albert Bruce Sabin developed a polio vaccine consisting of weakened strains of live polio virus, which, when ingested, caused a harmless infection in the gut and stimulated long-lasting immunity to poliomyelitis without causing the paralytic disease.
Almost a century ago, the first major poliomyelitis (polio) epidemic was recorded. Thereafter, epidemics of increasing frequency and severity struck the industrialized world. By the 1950’s, as many as sixteen thousand individuals, most of them children, were being paralyzed by the disease each year.
Within twenty years of the first epidemic, scientists had shown that polio was caused by a virus and had discovered that deliberate injection of this virus into monkeys caused them to develop paralytic polio. This important discovery raised hopes that a vaccine would be developed quickly to control the disease. Unfortunately, although a means was now available to test the safety and effectiveness of potential vaccines in animals prior to use in humans, the choice of the monkey species was unfortunate because it fostered the mistaken belief that the virus infected humans as it did monkeys, namely, by inhalation through the nose.
It is now known that, in humans, poliovirus enters the body through ingestion by the mouth. It replicates in the throat and the intestines and establishes an infection that normally is harmless. From there, the virus can enter the bloodstream. Only in rare individuals does it make its way to the nervous system, where it attacks and destroys nerve cells crucial for muscle movement. The presence of antibodies in the bloodstream will prevent the virus from reaching the nervous system and causing paralysis. Thus, the goal of vaccination is to administer poliovirus that has been altered so that it cannot cause disease, but nevertheless will stimulate the production of antibodies. There are three types of poliovirus; a vaccine must stimulate antibodies against all three types in order to protect against disease.
Albert Bruce Sabin received his medical degree from New York University College of Medicine in 1931. Polio was epidemic in 1931, and Sabin’s experience with the disease stimulated a lifelong interest in polio research. No other man, according to eminent virologist John R. Paul, “contributed so much effective information—and so continuously over so many years—to so many aspects of poliomyelitis, as Sabin.”
While working at the Rockefeller Institute, Sabin studied methods to grow the virus that did not depend on experimentally infected monkeys. In 1936, he and Peter Olinsky
In 1949, Thomas H. Weller
Tissue culture proved to be an excellent source of virus. Jonas Salk
Sabin, however, was not convinced that an inactivated virus vaccine was adequate. He believed that such an inactive vaccine would provide only temporary protection and that individuals would have to be vaccinated repeatedly in order to maintain protective levels of antibodies. Knowing that natural infection with poliovirus induced lifelong immunity, Sabin believed that a vaccine consisting of a living virus was necessary to produce long-lasting immunity. Also, unlike the inactive vaccine, which is injected, a living virus (weakened so that it would not cause disease) could be taken orally and would invade the body and replicate of its own accord. It would, therefore, more closely mimic natural infection and naturally induced immunity without causing disease.
Sabin was not alone in his beliefs. Hilary Koprowski
Sabin’s approach was based on the principle that, as viruses acquire the ability to replicate in a foreign species or tissue (for example, in mice), they become less able to replicate in humans and thereby to cause disease. Sabin used Enders’s tissue culture technique to isolate those polioviruses that grew most rapidly in monkey kidney cells. He then employed a technique developed by Renato Dulbecco that allowed him to propagate and study the progeny of individual virus particles. The recovered virus then was injected directly into the brain or spinal cord of monkeys to identify those that did not damage the nervous system.
These meticulously performed experiments, which involved approximately nine thousand monkeys and more than one hundred chimpanzees, finally enabled Sabin to isolate rare mutant polioviruses that would replicate in the intestinal tract but not in the nervous system of chimpanzees, or, it was hoped, of humans. In addition, the weakened virus strains were shown to stimulate antibodies when they were fed to chimpanzees; this was a critical attribute for a vaccine strain.
By 1957, Sabin had identified three strains of attenuated viruses that were ready for small experimental trials in humans. A small group of volunteers, including Sabin’s own wife and children, were fed the vaccine with promising results. Sabin then gave his vaccine to virologists in the Soviet Union, Eastern Europe, Mexico, and Holland for further testing. Combined with smaller studies in the United States, these trials established the effectiveness and safety of his oral vaccine.
During this period, the strains developed by Cox and by Koprowski were being tested also in millions of persons in field trials around the world. In 1958, two laboratories independently compared the vaccine strains and concluded that the Sabin strains were superior. Nevertheless, amid Cold War tensions, doubts were voiced about the reliability of the Soviet studies and the effectiveness of Sabin’s “communist vaccine.” In 1959, an American microbiologist who was sent to the Soviet Union to evaluate the program returned with a favorable report. In 1962, after four years of deliberation by the United States Public Health Service, all three of Sabin’s vaccine strains were licensed for general use.
The development of polio vaccines ranks as one of the triumphs of modern medicine. Rarely has a serious disease been controlled so quickly and dramatically as was poliomyelitis in the developed areas of the world. During the high prevaccine rates of the early 1950’s, paralytic polio struck 13,500 out of every 100 million Americans. Use of the Salk vaccine greatly reduced the incidence of polio, but outbreaks of paralytic disease continued to occur: Fifty-seven hundred cases were reported in 1959 and twenty-five hundred cases in 1960. In 1962, the oral Sabin vaccine became the vaccine of choice in the United States. Since its widespread use, the number of paralytic poliomyelitis cases in the United States has dropped precipitously, eventually averaging fewer than ten per year. Worldwide, the oral vaccine prevented an estimated 5 million cases of paralytic poliomyelitis between 1970 and 1990.
There were a number of reasons why the oral vaccine was favored over the inactive vaccine. The oral vaccine is cheaper and is easier to administer; therefore, it is more suitable for mass immunization campaigns. Another advantage is that the live viruses of the oral vaccine multiply in the intestines of the vaccinated individual; some of the vaccine viruses may then be excreted and passed on to nonvaccinated individuals, inducing a protective immunity in them as well. As these viruses multiply, they raise antibodies in the intestines as well as in the bloodsteam. These antibodies subsequently prevent wild (unweakened) viruses from infecting the intestines. Thus, wild viruses cannot spread through a population in which the majority of persons have received the oral vaccine. This form of “herd immunity” helps protect those individuals who have not been vaccinated.
The oral vaccine is not, however, without problems. Occasionally, the live virus mutates to a disease-causing (virulent) form as it multiplies in the vaccinated person. When this occurs, the person may develop paralytic poliomyelitis. Also, the mutated virus may be excreted and picked up by others, and cause disease in them. The inactive vaccine, in contrast, cannot mutate to a virulent form. The use of oral polio vaccine has reduced the incidence of polio in the United States to only a handful of cases each year. Ironically, nearly all of these cases are caused by the vaccine itself.
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Berg, Roland H. The Challenge of Polio: The Crusade Against Infantile Paralysis. New York: Dial Press, 1946. A short book that accurately and impartially describes the history of polio research prior to the major breakthroughs leading to vaccine development. Outstanding for Berg’s remarkable ability to present involved technical problems in simple, nontechnical terms and to convey a sense of the process of medical research. -
Hellman, Hal. “Sabin Versus Salk: The Polio Vaccine.” In Great Feuds in Medicine: Ten of the Liveliest Disputes Ever. New York: Wiley, 2001. Details the controversy over which polio vaccine was the more effective and safest. Bibliographic references and index. -
Klein, Aaron E. Trial by Fury: The Polio Vaccine Controversy. New York: Charles Scribner’s Sons, 1972. Popularized account of the research leading to the licensing of the Salk and Sabin vaccines. Describes the important role of the National Foundation and March of Dimes. Despite reliance on sensationalism, the account conveys how public pressure can affect decisions made by scientific foundations and government. Glossary and chronology are particularly helpful for the layperson; includes photographs, bibliography, and index. -
Paul, John R. A History of Poliomyelitis. New Haven, Conn.: Yale University Press, 1971. A comprehensive, gripping, and thoroughly documented account of the political, scientific, and personal struggles and developments that marked the history of the knowledge about polio. Written by a scholar who was deeply involved in polio research, who served on many key scientific committees, and who knew personally most of the scientists described. Includes numerous portrait photographs of polio researchers, and both subject and name indexes. -
Plotkin, Stanley A., and Edward A. Mortimer, Jr. Vaccines. Philadelphia: W. B. Saunders, 1988. A textbook for advanced students with a good background in virology/immunology. The development, use, effectiveness, and possible side effects for various bacterial and viral vaccines are described by experts. Three chapters are devoted to poliovirus vaccines, focusing on the inactive vaccine, the oral vaccine, and on a brief but detailed history. Well referenced. -
Scott, Andrew. Pirates of the Cell: The Story of Viruses from Molecule to Microbe. New York: Basil Blackwell, 1985. An up-to-date, clearly written, highly recommended introduction to viruses for those with minimal background in biology. Introductory chapters describe key aspects of viruses and virus infections; later chapters deal with more specialized topics including virus vaccines (traditional as well as new approaches), viral therapy, cancer, and AIDS (acquired immune deficiency syndrome). Well illustrated, with references and bibliography. -
Waterson, A. P., and Lise Wilkinson. An Introduction to the History of Virology. London: Cambridge University Press, 1978. An accurate, readable account of the early development of the understanding of viruses as infectious agents of disease, written for those with some background in biology. Illustrated, with brief biographical notes about pioneering scientists who made important contributions to the emerging field of virology.
Waksman Discovers the Antibiotic Streptomycin
Hodgkin Solves the Structure of Penicillin
Duggar Develops the First Tetracycline Antibiotic
Salk Develops a Polio Vaccine
German Measles Vaccine Is Developed