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Manuel Varela: Jonas Salk and Polio

Jul 9, 2017 by

An Interview with Manuel Varela: Jonas Salk and Polio

Michael F. Shaughnessy –

1) I daresay that most schools and most science curriculums mention the name of Jonas Salk somewhere along the line. First, when and where was he born and where did he get his training?

I believe you have quite accurately described the widespread and current interest in teaching this topic in all levels of schools. Hence, you have indicated the universal importance of Dr. Jonas Salk, discoverer of the polio vaccine, which played a critical role in altering the course of infectious disease history.

Jonas Edward Salk was born on the 28th of the month of October, in the year 1914 in East Harlem in New York City, NY, to Jewish parents, Daniel Salk, his father and a struggling businessman, and his mother, Dora Press, a Russian immigrant, who handled the family’s finances. Jonas was the eldest of three siblings. The young child Jonas had witnessed the devastating effects of the Great Influenza pandemic, just prior to 1920, and of the many children his age with leg braces, the latter presumably from the effects of the potentially debilitating disease poliomyelitis.

The child Salk attended public school number 44, located in the Bronx, New York. His early brilliance was already noticed by his teachers, who arranged for Salk to skip into higher grades. He was a deeply curious child, an avid reader, and greatly enjoyed learning. In 1926, when young Salk was 12 years of age, he was moved to a special and competitive public high school, called Townsend Harris, for talented and gifted children. Salk was reported to have been a serious student while at Townsend Harris, which had a pre-college preparatory curriculum for students.

Earning a competitive college scholarship at the age of 15, Salk was admitted to City College of New York (CCNY) and started attendance in 1929, planning to enter law school and, thus, enrolling in pre-law courses.  Salk was the first member of his immediate family to have gone to college. Surprisingly, Salk’s first semester did not end well, earning poor grades in several courses. His mother was reported to have said that Salk would not have made a good attorney, anyhow.

Although he had earned a relatively poor grade in his freshman Chemistry course, he became interested in the topic. During his sophomore year of college Salk switched his major to chemistry with a pre-medicine tract, and his grades improved but only slightly. Inspired by the reading of a biography of the great Louis Pasteur, undoubtedly one of the greatest scientists of all time, Salk made the decision to conduct medical research for a career, rather than practice medicine. Salk graduated from CCNY with his Bachelor of Science degree in the area of Chemistry, in 1934.

Planning to combine basic science with medicine, Salk was admitted to Bellevue Hospital Medical College, which was later named the New York University College of Medicine, and started medical school in 1934. This is the same school that the famous Walter Reed had attended during the late 1860s. During Salk’s tenure the curriculum consisted of 2 years of medical science courses, such as bacteriology, human anatomy, pathology, pharmacology, and physiology, followed by 2 years of clinical experience in the hospital. Excelling in many of his courses, Salk’s acumen was noticed by one of his teachers, Dr. Keith Canaan, a prominent biochemistry professor, who offered Salk a fellowship to perform research in Canaan’s laboratory.

Thus, Salk took a year off from medical school to conduct research.  He studied egg albumin protein denaturation, which was a protein biochemistry project; next, Salk studied antibody production in rabbits in response to the bacterium Streptococcus pyogenes, the causative agent of scarlet fever and other diseases. In this latter project, Salk discovered a new way to harvest the bacteria from large broth volumes, which turned out to be a new development worthy of publication. Thus, Salk published his very first paper for this work in a scientific journal, at the age of 22.

In 1936, Salk returned to medical school to continue his studies. Presumably while in his immunology course, Salk became perplexed with two seemingly contradictory concepts.  On the one hand, he was taught that effective immunization to the bacterial diseases tetanus and diphtheria could be accomplished by first denaturing their respective bacterial toxins beforehand and then injecting them into individuals.  On the other hand, he was also taught that in order for immunization against viruses to work properly, one had to actually be infected with a live virus and that dead viruses did not properly achieve immunization. At the time, this notion was certainly true with the then known vaccines directed against small pox, developed by Edward Jenner, rabies, developed by Louis Pasteur, and yellow fever, developed by Max Theiler.

Salk’s curiosity about bacteria, viruses, and vaccines led directly to his entry into another research laboratory, this time that of the newly appointed chair and professor of bacteriology, Dr. Thomas Francis, Jr., a virologist and discoverer of a new influenza virus strain. Back in the laboratory of Dr. Francis during his last year of medical school, Salk provided experimental evidence supporting the hypothesis that killed influenza virus provided immunity in mice by measuring antibody production. This was a turning point for Salk.

He finished his medical studies, earning his M.D. degree in 1939. Immediately after graduation the newly minted Dr. Salk married Donna Lindsay, whom he had met in Woods Hole, MA, where he had been conducting research during the summers between medical school years.

Salk became an intern at the Mount Sinai Hospital providing clinical patient care and conducting surgery. It is during this time that Salk, influenced by Donna, partook in political activities that would come back to haunt him in later years, as his FBI file has documented during their investigations of him and his wife.

In 1942, with Salk’s internship at an end and having trouble securing a permanent position, some of the trouble being ingrained anti-Semitism, Salk had received a post-graduate fellowship from the National Research Council to work with his former mentor, Dr. Francis, who had since moved to the School of Public Health housed at the University of Michigan, studying influenza immunity, as a research associate. Salk travelled to post-war Germany to investigate the efficacy of an influenza vaccine in the American troops stationed there.

In 1946, Salk was promoted to the rank of assistant professor at the University of Michigan, and in 1947, Salk moved to the University of Pittsburgh as an associate professor and director of their Virus Research Laboratory. It was also Salk’s first position in which he had his own research laboratory dedicated to the study of virology.  In 1949, Salk became full professor.

2) Polio used to strike fear into the hearts of many, but as I understand, it is almost non-existent (except for a few cases here and there). When was polio most common, what were the symptoms, and how did we get it under control?

The disease commonly called polio has the technical name of poliomyelitis among clinicians, and historically it has been called infantile paralysis. In the U.S. cases of polio reached a maximum in the early to mid-1950s (peaking at 37 cases per 100,000 in 1952 in the U.S.), and on a world-wide scale polio was in a full pandemic status, peaking sometime during the early 1960s. During these years, children were banned by their parents from playing outdoors during summers because of the pervasive fear of contracting the potentially debilitating polio.

The mode of polio transmission include the so-called oral-fecal route, brought about by poor hygienic practices, including the consumption of food or water that are contaminated with the virus.  The symptomology of polio has varied in severity, depending on the extent and corresponding severity of the viral infection. In people who are not vaccinated, there are four possible outcomes for those who become infected with the poliovirus microbe.

The first outcome is the mildest and is manifested by having no symptoms. This asymptomatic outcome is the most common, occurring in the vast majority (about 90%) of those individuals who are infected. In these cases, the poliovirus is stopped in its tracks in the throat or the gut by components of the person’s immune system.

The second outcome of poliovirus infection is called abortive poliomyelitis. This outcome occurs in about 5% of infected patients and manifests itself as a minor illness, involving symptoms like fever, fatigue, headache, sore throat and vomiting. These symptoms may appear three to four days after making contact with the poliovirus.

The third outcome is called non-paralytic poliomyelitis and sometimes aseptic meningitis, and it happens in about 1 or 2% of patients who are infected with the virus. In these cases, the poliovirus will have progressed onto the central nervous system (CNS) and the membrane lining that covers the CNS, called the meninges, of the patient.  The symptoms include those found in abortive minor illness, plus new symptoms that include muscle pain, often in the back, and muscle spasms.

The fourth and last outcome of poliovirus infection is called the paralytic polio, paralytic poliomyelitis, or major illness. This particular outcome is the most severe and the least common, occurring in roughly 0.1 to 0.2% of infected patients.

The patients will have exhibited the symptomology of the minor illness first, and after it has come and gone, usually about 3 or 4 days, paralysis occurs. The extent of the paralysis is widely variable, ranging from mild and temporary to severe and permanent, depending on the extent of the viral infection in the patient. In these severe cases the virus will have entered the neurons of the spinal cord and brain, involving flaccid paralysis of one or more of the extremities; if recovery occurs it may take anywhere between 6 months to 2 years.

In the severest case of paralytic polio, called bulbar poliomyelitis, additional muscles are affected, including muscles of the throat, voice cords, and lungs; this condition may be fatal if the so-called iron lungs or modern respirators are not used to help patients breathe. The images of children residing in iron lungs during the early part of the 20th century are compelling.

In older patients who have survived a polio infection, occasionally they exhibit a condition known as the post-polio syndrome; here the neurons that were destroyed by the virus now have an effect on the muscles which had been (but are no longer) innervated by the destroyed neurons, causing corresponding muscle deterioration. In these cases, the virus is not in the patient as the immune system has eliminated it long beforehand.

Control of polio has been brought about primarily in two ways. The first is improved hygienic conditions which prevent the fecal-oral transmission mode in developed countries. One problem with this effort has been access to clean drinkable uncontaminated water and food in developing countries. The second way is prevention by use of vaccines and a vast vaccination program. Bringing the control of polio about on a worldwide scale has been one of the most successful triumphs in the history of modern biomedical science.

3) I surmise that there is some type of vaccine that prevents polio- or am I wrong?

You are absolutely correct. There are two principal vaccines that have been in use. The first vaccine was developed by Dr. Salk in which he inactivated the polioviruses by chemical treatment with formalin and is called the inactivated poliovirus vaccine (IPV).

The second vaccine was developed by Dr. Albert Sabin in which he attenuated the polioviruses into a non-pathogenic form by multiple passaging of the virus in cell culture from generation to generation. The attenuated poliovirus is live, and the vaccine is taken by mouth. Thus, Sabin’s vaccine is called the oral poliovirus vaccine (OPV).

Both vaccines are directed against all three types of poliovirus strains or serotypes, called Types 1, 2 and 3.

Because of its ease of administration and its lower costs, the OPV had supplanted IPV in the global eradication efforts.

4) Now, to clarify, what is an IPV vaccine, and why is it important?

When Salk developed the IPV he did it by first growing the three strains of poliovirus, called Types 1, 2, and 3, in monkey kidney cells, and later in the more famous HeLa cells, in culture.  Next, the intact whole polioviruses were purified from the cultured cells and then soaked in the same chemical that’s used to preserve corpses, a mixture of water and formaldehyde, called formalin. The formalin-treated polioviruses are then used for inoculations. The IPV inoculations are administered by 4 intra-muscular injections with a needle at 2, 4, and 12-18 months of age and then lastly between 4 to 6 years of age.

The IPV is important because it was the first effective polio vaccine. Furthermore, the IPV was shown to stem the tide in the polio epidemics and was not involved in causing vaccine-related polio cases.  IPV is also currently the routine polio vaccine of choice in regions where the wild-type polioviruses are absent.

5) As I recall from history classes back in grade school, Franklin Delano Roosevelt was often seated and was rarely seen standing. I believe he had polio- and apparently, it impacted him his entire life. What do we know about the course of polio- when does it first appear, and what are the signs and symptoms?

If I may be so bold as to say so, I am convinced, as probably many historians of science are, too, that had Franklin D. Roosevelt not had a case of the paralytic polio, the success we’ve enjoyed in vastly reducing its incidence and prevalence might never have happened in modern times. FDR was a key figure in the efforts that were generated for the purpose of someday eradicating polio from the face of the Earth. FDR put the issue to the forefront of society’s funding and scientific machine to address the polio disease epidemics and ensuing pandemic.

The process for FDR’s involvement began during the month of August in the year 1921, when he started to exhibit the signs and symptoms of polio while on vacation in his family’s summer home at Campobello Island, located in New Brunswick, Canada. Prior to the onset of polio, FDR had been a senator, assistant secretary of the navy, and had just lost the race for vice-president. The outcome for Roosevelt was that he was paralyzed from the waist down in both of his legs and could not walk. Of all of the difficulties that had been plaguing FDR at the time, contracting paralytic polio was an extremely problematic one, as it was potentially a career-ending situation. Being in the public eye it was unheard of for paralyzed individuals to be running for high office, and in particular Roosevelt had his eye on the U.S. presidency.

Perhaps wishing to provide encouragement, his doctors had informed Roosevelt that there was a good chance of recovery and that he might walk again. Consequently, FDR was forever optimistic that recovery was at hand, and he made every effort to improve his chances for recovery, with physical therapy and any other kind of therapy, no matter how futile the putative therapy might be for him. He never gave up hope.

Meanwhile, until Roosevelt could make a full recovery, if one was to be had at all, that is, he also made every effort to hide his paralysis from the public. He banned the taking of photographs with him in a wheelchair, the telltale sign of being an invalid. Any photographs taken were of him always sitting behind a desk, his wheelchair out of view, or of him sitting in his car, saying a few words to the audience and the press. If he were to give a speech, he had colleagues accompany him to the podium as he wobbled his way. Then, once secure at the podium, he could prop himself up with his arms and deliver his speech. He had a good system going for him.

FDR made it possible for funding, research and healthcare for polio to be pushed to the front burner. He established centers for treatment, physical therapy, and research. The March of Dimes program encouraged all children to mail a dime in an envelope to the foundation—this was a highly successful program. This is also where the push for vaccines and sanitation, etc., were all put into motion. Within a few years the Salk vaccine, and later the Sabin vaccine, became available, although too late for president FDR, who died while in office on the 12th of April in 1945, just before the end of World War II.

The signs and symptoms of polio often appear anywhere between 3 and 6 days after exposure to the poliovirus. Sometimes the minor illness symptoms will disappear, and 3 or 4 days later the classic poliomyelitis symptoms set in. The virus often enters the patient after consuming food or water that’s contaminated with the polio-causing virus. The virus may infect the cells of the throat, causing a sore throat.  The virus may end up in the gastrointestinal tract, causing a GI tract disturbance.  The throat and the gut are most often where the virus is stopped by the patient’s immune system. If the virus progresses past these stages to the nervous system, like the CNS, more severe cases can occur. Paralysis may be observed as soon as a week after exposure to the virus. The virus will be shed from the patient in the stool, and it may be a source of transmission to the next patient.

Interestingly, polio disease made one of its first appearances in recorded history as an ancient Egyptian hieroglyph.   The hieroglyph of the 18th dynasty, dating between 1580 – 1350 B.C. shows an unidentified man with a withered right leg indicating a “drop foot” syndrome, pointing to an asymmetric paralysis typical of polio. The leg has atrophied, most likely due to loss of innervation as the motor neurons may have been damaged or destroyed during poliovirus infection.

Speaking of appearances, I think it is encouraging also to speak of polio’s disappearances. In 1979, all three strains of poliovirus disappeared from the U.S., all due to the vaccinations made possible by Salk and Sabin. In 1999, Type 2 poliovirus officially disappeared from the Earth—we’ve not seen polio cases attributable to this strain ever since. Likewise, poliovirus Type 3 disappeared from the world in 2012. The last poliovirus strain Type 1, the worst one of the three, remains in small pockets, with a few hundred cases per year being recorded during the period between years 2001 and 2015. When that day arrives in which all polio disease will be totally gone from the world remains unknown as of this writing. So far, only smallpox has been eradicated from the planet due to human intervention. Polio is second contagion that’s slated for a similar type of world eradication.

6) What have I neglected to ask and is there a contemporary treatment for those, for whatever reason, are afflicted by this disease?

While there are currently no useful anti-viral medicines that target the poliovirus, per se, medical approaches to polio have primarily focused on prevention, with the use of the Salk and Sabin vaccines and improvements in interrupting the fecal-oral route of polio transmission. There has been little need for the iron lungs for many years because of the massive vaccination programs that were established in the 1950s. If an iron lung were needed modern day respirators which are much less cumbersome would suffice in cases of bulbar polio. According to the Guinness World Records, Ms. June Margaret Middleton holds the world record for time spent living in an iron lung—at least 60 years.

7) What have I neglected to ask?

Sixteen year old Bill Kirkpatrick was the first person ever to have received the Salk vaccine. Salk himself had injected the eager volunteer in June, of 1952. In fact, Salk had injected the first 43 volunteers and then had terrible trouble sleeping afterwards, agonizing over what might happen.

Although Salk demonstrated great acumen in making the vaccine happen on a scientific basis, he was reported to have been severely out of his element during the grand announcement of the success of the vaccine trials, by making a huge blunder. In short, he thanked everyone he could think of, except those individuals in his lab who actually made the vaccine and conducted the vaccine trials. What’s worse is that he repeated his blunder time and time again, never seeming to quite convey the credit to his immediate colleagues.

I briefly mentioned the use of HeLa cell cultures for the polio vaccine development; these cells are now of current and wide interest, after the publishing of a book by Rebecca Skloot about the origin of these very important cells.

Sadly, the cells were taken from Henrietta Lacks without her permission or knowledge after she died of cervical cancer. The HeLa designation comes from the first two letters of her first and last names. The cells were of immense importance for biomedicine because of their capacity for indefinite passaging between generations of cell growth. This greatly facilitated the development not only of polio vaccine but for a great deal of advances in both basic and applied research. Today, if biotechnologists or any other investigators wish to use HeLa cells, they need permission from her family. The first publication with the Lack family having provided permission was the study in which the HeLa genome DNA sequence was determined. A film about the “Immortal Life of Henrietta Lacks” was released in 2017.

Although Salk was widely celebrated in his later years with numerous tributes, awards, and accolades—he even had an entire institute named after him, the Salk Institute in La Jolla, CA, he never received the Nobel Prize, and neither did Sabin, for that matter. Salk died on the 23rd of June in the year 1995.

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