Polio vaccine (Sabin)

The invention: Albert Bruce Sabin’s vaccine was the first to stimulate

long-lasting immunity against polio without the risk of causing

paralytic disease.

The people behind the invention:

Albert Bruce Sabin (1906-1993), a Russian-born American

virologist

Jonas Edward Salk (1914-1995), an American physician,

immunologist, and virologist

Renato Dulbecco (1914- ), an Italian-born American

virologist who shared the 1975 Nobel Prize in Physiology or

Medicine

The Search for a Living Vaccine

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.

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. In some individuals it makes 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 to fight the disease.

Albert Bruce Sabin received his medical degree from New York

University College of Medicine in 1931. Polio was epidemic in 1931,

and for Sabin polio research became a lifelong interest. In 1936,

while working at the Rockefeller Institute, Sabin and Peter Olinsky

successfully grew poliovirus using tissues cultured in vitro. Tissue

culture proved to be an excellent source of virus. Jonas Edward Salk

soon developed an inactive polio vaccine consisting of virus grown

from tissue culture that had been inactivated (killed) by chemical

treatment. This vaccine became available for general use in 1955, almost

fifty years after poliovirus had first been identified.

Sabin, however, was not convinced that an inactivated virus vaccine

was adequate. He believed that it 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.

Sabin was not alone in his beliefs. Hilary Koprowski and Harold

Cox also favored a living virus vaccine and had, in fact, begun

searching for weakened strains of poliovirus as early as 1946 by repeatedly

growing the virus in rodents. When Sabin began his search

for weakened virus strains in 1953, a fiercely competitive contest ensued

to achieve an acceptable live virus vaccine.

Rare, Mutant Polioviruses

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 thus

less able to cause disease. Sabin used tissue culture techniques 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 recover individual virus particles. The recovered

viruses were injected directly into the brains or spinal cords of

monkeys in order to identify those viruses 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 systems 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. Asmall 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. In 1962, after four years of deliberation by the U.S. Public

Health Service, all three of Sabin’s vaccine strains were licensed for

general use.Consequences

The development of polio vaccines ranks as one of the triumphs of

modern medicine. In the early 1950’s, paralytic polio struck 13,500

out of every 100 million Americans. The 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 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.

The oral vaccine is not without problems. Occasionally, the living

virus mutates to a disease-causing (virulent) form as it multiplies in

the vaccinated person. When this occurs, the person may develop

paralytic poliomyelitis. The inactive vaccine, in contrast, cannot

mutate to a virulent form. Ironically, nearly every incidence of polio

in the United States is caused by the vaccine itself.

In the developing countries of the world, the issue of vaccination is

more pressing. Millions receive neither form of polio vaccine; as a result,

at least 250,000 individuals are paralyzed or die each year. The World

Health Organization and other health providers continue to work toward

the very practical goal of completely eradicating this disease.