Polio vaccine (Salk)

The invention: Jonas Salk’s vaccine was the first that prevented polio,resulting in the virtual eradication of crippling polio epidemics.The people behind the invention:

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

immunologist, and virologist

Thomas Francis, Jr. (1900-1969), an

American microbiologist

Cause for Celebration

Poliomyelitis (polio) is an infectious disease that can adversely

affect the central nervous system, causing paralysis and great muscle

wasting due to the destruction of motor neurons (nerve cells) in

the spinal cord. Epidemiologists believe that polio has existed since

ancient times, and evidence of its presence in Egypt, circa 1400 b.c.e.,

has been presented. Fortunately, the Salk vaccine and the later vaccine

developed by the American virologist Albert Bruce Sabin can

prevent the disease. Consequently, except in underdeveloped nations,

polio is rare. Moreover, although once a person develops polio,

there is still no cure for it, a large number of polio cases end without

paralysis or any observable effect.

Polio is often called “infantile paralysis.” This results from the

fact that it is seen most often in children. It is caused by a virus and

begins with body aches, a stiff neck, and other symptoms that are

very similar to those of a severe case of influenza. In some cases,

within two weeks after its onset, the course of polio begins to lead to

muscle wasting and paralysis.

On April 12, 1955, the world was thrilled with the announcement

that Jonas Edward Salk’s poliomyelitis vaccine could prevent the

disease. It was reported that schools were closed in celebration of

this event. Salk, the son of a New York City garment worker, has

since become one of the most well-known and publicly venerated

medical scientists in the world.

Vaccination is a method of disease prevention by immunization,

whereby a small amount of virus is injected into the body to prevent

a viral disease. The process depends on the production of antibodies

(body proteins that are specifically coded to prevent the disease

spread by the virus) in response to the vaccination. Vaccines are

made of weakened or killed virus preparations.

Electrifying Results

The Salk vaccine was produced in two steps. First, polio viruses

were grown in monkey kidney tissue cultures. These polio viruses

were then killed by treatment with the right amount of formaldehyde

to produce an effective vaccine. The killed-virus polio vaccine

was found to be safe and to cause the production of antibodies

against the disease, a sign that it should prevent polio.

In early 1952, Salk tested a prototype vaccine against Type I polio virus

on children who were afflicted with the disease and were thus

deemed safe from reinfection. This test showed that the vaccination greatly elevated the concentration of polio antibodies in these children.

On July 2, 1952, encouraged by these results, Salk vaccinated fortythree

children who had never had polio with vaccines against each of

the three virus types (Type I, Type II, and Type III). All inoculated children

produced high levels of polio antibodies, and none of them developed

the disease. Consequently, the vaccine appeared to be both safe in

humans and likely to become an effective public health tool.

In 1953, Salk reported these findings in the Journal of the American

Medical Association. In April, 1954, nationwide testing of the Salk

vaccine began, via the mass vaccination of American schoolchildren.

The results of the trial were electrifying. The vaccine was safe,

and it greatly reduced the incidence of the disease. In fact, it was estimated

that Salk’s vaccine gave schoolchildren 60 to 90 percent protection

against polio.

Salk was instantly praised. Then, however, several cases of polio

occurred as a consequence of the vaccine. Its use was immediately

suspended by the U.S. surgeon general, pending a complete examination.

Soon, it was evident that all the cases of vaccine-derived polio

were attributable to faulty batches of vaccine made by one

pharmaceutical company. Salk and his associates were in no way responsible

for the problem. Appropriate steps were taken to ensure

that such an error would not be repeated, and the Salk vaccine was

again released for use by the public.

Consequences

The first reports on the polio epidemic in the United States had

occurred on June 27, 1916, when one hundred residents of Brooklyn,

New York, were afflicted. Soon, the disease had spread. By August,

twenty-seven thousand people had developed polio. Nearly seven

thousand afflicted people died, and many survivors of the epidemic

were permanently paralyzed to varying extents. In New York City

alone, nine thousand people developed polio and two thousand

died. Chaos reigned as large numbers of terrified people attempted

to leave and were turned back by police. Smaller polio epidemics

occurred throughout the nation in the years that followed (for example,

the Catawba County, North Carolina, epidemic of 1944). A

particularly horrible aspect of polio was the fact that more than 70 percent of polio victims were small children. Adults caught it too;

the most famous of these adult polio victims was U.S. President

Franklin D. Roosevelt. There was no cure for the disease. The best

available treatment was physical therapy.

As of August, 1955, more than four million polio vaccines had

been given. The Salk vaccine appeared to work very well. There were

only half as many reported cases of polio in 1956 as there had been in

1955. It appeared that polio was being conquered. By 1957, the number

of cases reported nationwide had fallen below six thousand.

Thus, in two years, its incidence had dropped by about 80 percent.

This was very exciting, and soon other countries clamored for the

vaccine. By 1959, ninety other countries had been supplied with the

Salk vaccine.Worldwide, the disease was being eradicated. The introduction

of an oral polio vaccine by Albert Bruce Sabin supported

this progress.

Salk received many honors, including honorary degrees from

American and foreign universities, the LaskerAward, a Congressional

Medal for Distinguished Civilian Service, and membership in

the French Legion of Honor, yet he received neither the Nobel Prize

nor membership in the American National Academy of Sciences. It

is believed by many that this neglect was a result of the personal antagonism

of some of the members of the scientific community who

strongly disagreed with his theories of viral inactivation.

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.