28 October 2009

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
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
The Search for a Living Vaccine
Almost a century ago, the first major poliomyelitis (polio) epidemic
was recorded. Thereafter, epidemics of increasing
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.


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