Jonas Salk and Albert Bruce Sabin
In the 1950s Salk and Sabin
developed separate vaccines—one from killed virus and the other from live
virus—to combat the dreaded disease polio.
Source:Science Gistory Institute
nas Salk became a national hero when he allayed the fear of polio with
his vaccine, approved in 1955. Although it was the first polio vaccine, it was
not to be the last; Albert Sabin introduced an oral vaccine in the 1960s that
replaced Salk’s.
Polio Season
In
the first half of the 20th century, summer was a dreaded time for children.
Although they could enjoy the long days of unfettered play, summer was also
known as “polio season.” Children were among the most susceptible to paralytic
poliomyelitis (also known as infantile paralysis), a disease that affects the
central nervous system and can result in paralysis. When exposed to a
poliovirus in the first months of life, infants usually manifested only mild
symptoms because they were protected from paralysis by maternal antibodies
still present in their bodies. However, as hygienic conditions improved and
fewer newborns were exposed to the virus (which is present in human sewage),
paralytic poliomyelitis began to appear in older children and adults who did
not have an infant’s benefit of immunity. President Franklin Delano Roosevelt
is perhaps the most famous victim of the poliovirus. In 1921, at the age of 39,
he contracted the disease, one of the thousands that were afflicted that year.
The Vaccines
In
the early 1950s, 25,000 to 50,000 new cases of polio occurred each year. Jonas
Salk (1914–1995) became a national hero when he allayed the fear of the dreaded
disease with his polio vaccine, approved in 1955. Although it was the first
polio vaccine, it was not to be the last; Albert Bruce Sabin (1906–1993) introduced
an oral vaccine in the United States in the 1960s that replaced Salk’s.
Although the disease was finally brought under control because of these
vaccines, the science behind them fired debate that continues to this day.
Jonas Salk.
Jonas Salk Polio Vaccine Collection, 1953–2005,
UA.90.F89, Archives Service Center, University of Pittsburgh
Salk’s
Education and Work on Influenza
Jonas
Salk was born in New York City, his parents’ eldest son. His mother was a
Russian Jewish immigrant and his father the son of Jewish immigrants. Salk was
encouraged throughout his youth to succeed academically. He graduated from high
school at the age of 15 and then entered the City College of New York. Although
he originally intended to pursue law, he became interested in medicine and
altered his career path, graduating with a degree in science in 1933.
At
19 Salk enrolled in the New York University School of Medicine. His intention
was not to practice medicine, however; he wanted to be a medical researcher.
Toward the end of his medical education he began to work with Thomas Francis
Jr., who was to be his mentor for many years. Salk received his MD in 1939 and,
after completing his internship at Mt. Sinai Hospital, accepted a National
Research Council fellowship to work at the University of Michigan. There he
rejoined Francis (who had since moved to Michigan) and spent six years
researching the influenzavirus and developing a flu vaccine, work largely
supported by the U.S. Army. The vaccine that they ultimately developed in 1943
was a killed-virus vaccine: it contained a formalin-killed strain of the
influenzavirus that could not cause the disease but did induce antibodies able
to ward off future viral attacks. Francis and Salk were among the pioneers of
killed-virus vaccines. Up to that time attenuated (weakened) live viruses were
used to produce vaccines.
The Virus Research Laboratory and
Poliovirus
In
1947 Salk accepted a position at the University of Pittsburgh School of
Medicine to establish a Virus Research Laboratory. He devoted his efforts to
creating a first-class research environment and to publishing scientific papers
on a variety of topics, including poliovirus. His work drew the attention of
the National Foundation for Infantile Paralysis (now the March of Dimes), and
he was invited to participate in a research program sponsored by the
foundation. He agreed and took up his assignment of typing polioviruses.
The “Killed-Virus” Principle
In
1951 the National Foundation typing program confirmed that there were three
types of poliovirus. By that time Salk was convinced that the same
“killed-virus” principle he had used to develop an influenza vaccine would work
for polio. He also believed that it would be less dangerous than a live
vaccine: if the vaccine contained only dead virus, then it could not
accidentally cause polio in those inoculated. One difficulty, however, was that
large quantities of poliovirus were needed to produce a killed-virus vaccine
because a killed virus will not grow in the body after administration the way a
live virus will. In 1949 John Enders, Thomas Weller, and Frederick Robbins had
discovered that poliovirus could be grown in laboratory tissue cultures of
non-nerve tissue (earning them the Nobel Prize in Physiology or Medicine in
1954). The work of Enders and his colleagues paved the way for Salk, for it
provided a method of growing the virus without injecting live monkeys.
Salk
developed methods for growing large quantities of the three types of
polioviruses on cultures of monkey kidney cells. He then killed the viruses
with formaldehyde. When injected into monkeys, the vaccine protected them
against paralytic poliomyelitis. In 1952 Salk began testing the vaccine in
humans, starting with children who had already been infected with the virus. He
measured their antibody levels before vaccination and then was excited to see
that the levels had been raised significantly by the vaccine.
Jonas
Salk and a nurse administering the vaccine.
Jonas
Salk Polio Vaccine Collection, 1953–2005, UA.90.F89, Archives Service Center,
University of Pittsburgh
Field Trials
In
1954 a massive controlled field trial was launched, sponsored by the National
Foundation for Infantile Paralysis. Almost two million U.S. children between
the ages of six and nine participated. In some areas of the country half of
these “Polio Pioneers” received the vaccine, while half received a placebo. In
other areas of the country children who did not receive any vaccine were
carefully observed. On April 12, 1955, Thomas Francis, Salk’s mentor and the
director of the trial, reported that the vaccine was safe, potent, and 90%
effective in protecting against paralytic poliomyelitis.
In
order to conduct these massive trials Salk’s vaccine needed to be produced on a
large scale. Accomplishing this required the assistance of the pharmaceutical
industry, and well-known companies like Eli Lilly and Company, Wyeth
Laboratories, and Parke, Davis and Company agreed to make the new vaccine.
Sabin’s Path to Polio Research
In
the meantime a live-virus vaccine for polio was being developed by Albert
Sabin. Sabin, like many scientists of the time, believed that only a living
virus would be able to guarantee immunity for an extended period.
Sabin
was born in 1906 in Bialystok, Russia (now part of Poland). At the age of 15 he
emigrated with his family to the United States. After Sabin graduated from high
school in Paterson, New Jersey, his uncle agreed to finance his college
education, provided that Sabin studied dentistry. After two years preparing for
dentistry at New York University, Sabin switched to medicine, having developed
an interest in virology. In doing so he lost his financial support, but odd
jobs and scholarships enabled him to continue his education. Sabin received his
BS in 1928 and afterward enrolled in the New York University College of
Medicine.
While
at medical school Sabin spent time researching pneumonia, developing an
accurate and efficient method of determining its cause in individual
cases—either pneumococcus or virus. He received his MD in 1931 and, after
completing his internship, traveled to the Lister Institute of Preventative
Medicine in London to conduct research. A year later he returned to the United
States, having accepted a fellowship at the Rockefeller Institute for Medical
Research. There Sabin developed an interest in poliovirus. In 1936 he and a
colleague were able to grow poliovirus in brain tissue from a human embryo.
During
World War II, Sabin left his polio research to serve in the U.S. Army Medical
Corps. There he investigated other diseases like insect-borne encephalitis and
dengue, working on vaccines for both.
Sabin’s Live-Virus Vaccine
After
the war Sabin accepted a position at the University of Cincinnati College of
Medicine as a professor of research pediatrics. He then was able to return to
his polio studies. To learn as much as possible about the disease, he and his
colleagues performed autopsies on everyone within 400 miles of Cincinnati who
had died of polio. These autopsies indicated that poliovirus affected both the
intestinal tract and the central nervous system. From this finding Sabin was
able to prove that polio first attacked the intestinal tract before moving on
to nerve tissue. This discovery suggested that the virus could be grown in
non-nerve tissue, a feat later accomplished in tissue culture by the Nobel
laureates Enders, Weller, and Robbins. Growing poliovirus in non-nerve tissue
culture was more practical than Sabin’s previous achievement of growing it in
brain tissue from embryos.
Around
the same time that Salk began his work on a killed-virus vaccine, Sabin began
work on an attenuated live-virus vaccine. Sabin felt that an oral vaccine would
be superior to an injection, as it would be easier to administer. He began to
grow and test many virus strains in animals and tissue cultures and eventually
found three mutant strains of the virus that appeared to stimulate antibody
production without causing paralysis. Sabin then tested these strains on
humans: his subjects included himself and his family, research associates, and
prisoners from the nearby Chillicothe Penitentiary.
Albert
Sabin demonstrates how the oral vaccine for polio is given to children.
Hauck
Center for the Albert B. Sabin Archives, Henry R. Winkler Center for the
History of the Health Professions, University of Cincinnati
Testing the Live-Virus Vaccine
Because
Salk’s vaccine was being used successfully in the United States, Sabin was not
able to get support for a large-scale, controlled field trial like the trial of
Salk’s vaccine. In 1957 Sabin convinced the Soviet Union’s Health Ministry to
conduct field studies with his vaccine. After the Soviet trial succeeded in
1960, the U.S. Public Health Service approved the vaccine in 1961 for
manufacture in the United States, and the World Health Organization (WHO) began
to use live-virus vaccine produced in the USSR.
Success and Polio Eradication
In
the late 1950s Sabin entered into an agreement with the pharmaceutical company
Pfizer to produce his live-virus vaccine. He presented Pfizer with the master
strains of the virus, and the company began to perfect its production technique
in its British facilities.
Sabin’s
live-virus, oral polio vaccine (administered in drops or on a sugar cube) soon
replaced Salk’s killed-virus, injectable vaccine in many parts of the world. In
1994 the WHO declared that naturally occurring poliovirus had been eradicated
from the Western Hemisphere owing to repeated mass immunization campaigns with
the Sabin vaccine in Central and South America. The only occurrences of
paralytic poliomyelitis in the West after this time were the few cases caused
by the live-virus vaccine itself.
Live-Virus versus Killed-Virus
Controversy
During
his lifetime Sabin staunchly defended his live-virus vaccine, refusing to
believe any evidence that it could cause paralytic poliomyelitis. Salk, for his
part, believed that killed-virus vaccine produced equivalent protection in
individuals and in communities without any risk for causing paralysis. Despite
Sabin’s belief, the risk for paralysis from the live-virus vaccine does exist,
although it is slight. In 1999 a federal advisory panel recommended that the
United States return to Salk’s vaccine because it cannot accidentally cause
polio. On the basis of a decade of additional evidence, this recommendation was
reconfirmed in 2009.
Later Research
Although
he was the first to produce a polio vaccine, Salk did not win the Nobel Prize
or become a member of the National Academy of Sciences. An object of public
adulation because of his pioneering work, he spent his life trying to avoid the
limelight but nevertheless endured the animosity of many of his colleagues who
saw him as a “publicity hound.” In 1962 he founded the Salk Institute for
Biological Studies in La Jolla, California, an enterprise initially funded with
support from the March of Dimes. Salk’s own research continued, most
significantly on multiple sclerosis, cancer, and AIDS. Salk spent the later
years of his life committed to developing a killed-virus vaccine to prevent the
development of AIDS in those infected with human immunodeficiency virus.
Sabin,
too, continued his work and held a series of influential positions at such
organizations as the Weizmann Institute of Science, the U.S. National Cancer
Institute, and the National Institutes of Health.
With
affection,
Ruben
