Smallpox, Syphilis and Salvation

by Sheryl Persson

  SALK BEGINS HIS RESEARCH

  Jonas Salk, the son of orthodox Jewish immigrants from Russia, was born in New York City on 28 October 1914. Although his parents did not have a formal education they were ambitious for their three sons to succeed and encouraged Jonas, the eldest, in his studies. Jonas’ father was a designer in the garment industry and the children were brought up in a cultured environment. Because of the opportunities available in the United States, Jonas was able to take advantage of free public education and was the first member of his family to go to college.

  After enrolling at the City College of New York with the intention of studying law, Jonas Salk soon became intrigued by medical science. Salk said that he probably made the right choice because his mother never thought he would make a good lawyer, as he could never win an argument with her. Jonas channelled his interest towards biology and chemistry and decided to go into research rather than medical practice. His ambition, as he saw it, was to be of some help to humankind, not so much on a one-to-one basis but in a larger sense.[11]

  In 1938, while attending medical school at New York University, Salk was invited to spend a year studying virology and researching influenza at the University of Michigan. There, Salk worked on an influenza vaccine with the distinguished microbiologist Dr Thomas Francis, a coup for a young researcher, and Francis became Salk’s lifelong mentor. The virus that causes influenza had only recently been discovered, but the principles for developing a vaccine were still the same as those established by Edward Jenner. If the body is exposed to a very weak or small amount of the disease virus, it will produce antibodies which can resist and kill the virus when a full-strength version attacks. Each virus, however, requires a custom-made vaccine. Salk experimented, hoping to deprive the influenza virus of its ability to infect while still giving immunity. This was the basis for the influenza vaccine that Francis and Salk developed, the principles of which Salk later applied to developing his polio vaccine. When World War II began in 1939 public health experts feared a repeat of the influenza epidemic that had killed millions in the wake of World War I. Fortunately, the influenza vaccine was a bonanza for the armed forces and was used to successfully control the spread of flu during and after the war.[12] The feared epidemic did not happen and Jonas Salk, as a student, had already done much to advance medical progress.

  Salk received his medical degree from New York University in 1939, completed his internship and in 1942 was appointed Assistant Professor of Epidemiology at the University of Michigan where he resumed his study of influenza. It was around this time, though, that Salk began to realise a career path might not be easy for him. He applied to some of the more prestigious universities, including Columbia University, and was turned down. In an interview he gave later in his life for the Academy of Achievement in Washington DC he revealed that he believed anti-Semitism played a role. Then in 1947 he accepted an appointment to the University of Pittsburgh Medical School as the head of the Virus Research Laboratory. (Despite the earlier setbacks and rejections, Salk would go on to become that university’s Research Professor of Bacteriology in 1949, Professor of Preventive Medicine and chairman of the department in 1956, and by 1957 he would hold the position of Professor of Experimental Medicine.) In moving to Pittsburg Salk saw an opportunity to continue his work on influenza and begin work on polio.[13] One can only wonder at the part played by Providence in many of the monumental medical breakthroughs. For the next eight years of his life, Jonas Salk devoted himself to the mission to save children from the horrors of polio.

  Within a few months of arriving in Pittsburgh, Salk was visited by Basil O’Connor, the head of the National Foundation for Infantile Paralysis, who asked him if he would be interested in participating in a program on typing polioviruses. (Typing is the process of classifying or distinguishing types and strains within a seemingly homogeneous species of micro-organism.)The push was on to find a cure and a committee had been set up to deal with all aspects of research. Salk accepted and the funding he was given provided laboratory facilities, equipment and staff.[14] According to Wilfrid Sheed, in an article he wrote for Time magazine in 1999, Salk had somehow found time to do some basic research on the poliovirus and Basil O’Connor, who was zealous in his quest for a cure (his daughter having been afflicted and left partially paralysed), was impressed with the theoretical papers Salk had written. As a result O’Connor had decided to ‘shove some dimes in Salk’s direction with instructions to get going’.[15]

  Jonas Salk was one of many researchers who were seeking a cure for polio and some had been involved in the quest for much longer. No doubt the seeds of resentment were sown when the apparent newcomer was given funding and hence freedom for his research. As Jonas Salk began his work to combat a disease that had caused untold tragedy to so many families, one of the bitterest rivalries in medical science was beginning and soon the competition between two scientific camps to develop a polio vaccine would begin.

  CONTROVERSY AND COMPETITION: SALK AND SABIN

  Jonas Salk and Albert Sabin led two competing schools of vaccine research. Sabin favoured producing immunity by creating a mild infection with a live but attenuated virus and this was his methodology for preparing his vaccine. However, virulent viruses could be made into a ‘killed’, non-infectious vaccine by treatment with a standard disinfectant and preservative such as formaldehyde, as Salk had learnt from his flu-fighting days. The immune system could in fact be triggered without infection—using deactivated, or killed, viruses.[16]

  Salk argued that the immune system could be set to work against polioviruses with an injected vaccine without the need to trigger an actual infection. Before Salk’s work on influenza, the effective vaccines had been made with weakened viruses but they still had the capacity to infect. Sometimes, as in the case of the smallpox virus, immunisation would cause serious reactions and occasionally fatalities. The principle that Salk tried to establish was that it was not necessary to run the risk of infection and so it seemed safer to proceed with a killed vaccine.

  As time was of the essence—every summer the number of children who died or were left paralysed from polio kept rising—a vaccine that could be developed quickly was of critical importance. This made Salk’s vaccine more appealing. Sabin, on the other hand, favoured an oral, attenuated vaccine. By the late 1930s it was known that polio entered the body via the mouth and digestive tract, which led Sabin and other virologists to believe that an oral vaccine would be more expedient than a killed vaccine.[17] Conflict and controversy plagued the polio project from this point on.

  Albert Sabin had sound credentials and had become interested in polio after graduating in medicine from New York University in 1931. Sabin was an immigrant who had been born in Bialystok in Poland on 26 August 1906. He was one of four children born to Jacob Sabin and his wife Tillie. The family immigrated to the United States in 1921 and settled in Paterson, New Jersey. Like Jonas Salk’s father, Albert Sabin’s father was in the clothing industry, manufacturing silk, and the two younger men were in the same industry, virology.

  In 1941 when the United States entered World War II Sabin enlisted and joined the US Army Epidemiological Board’s Virus Committee and took on assignments in various theatres of war—Europe, Africa, the Middle East and the Pacific. Sabin’s contribution was outstanding and he was involved in the development of vaccines for mosquito-borne diseases.[18] Over 65,000 military personnel were successfully vaccinated against the mosquito-borne Japanese encephalitis with his new vaccine and he also worked on preventive vaccines for dengue fever and sand-fly fever.

  Many of the experiments Sabin conducted during his early research on the poliovirus he reported to the National Foundation of Infantile Paralysis. When he and Salk, who came from opposite sides of the vaccine research divide, were appointed to the committee that was established to discuss issues associated with developing a polio vaccine, a clash arose over typing the virus, a necessary first step. Jonas Salk thought the committee was heading in
the wrong direction because they favoured determining a strain’s virulence rather than its antigenicity, i.e. how much antibody results from the introduction of the virus. At one meeting when Salk said that a better way forward might be to test an unknown virus’s capacity to immunise rather than its capacity to infect, Sabin condescendingly dismissed Salk’s suggestion. This clash epitomised their different approaches to developing a vaccine, and led to complex and costly experiments that hampered progress.

  Although work at Johns Hopkins and Yale University had established the number of polio types at three—Type I (Brünhilde), Type II (Lansing) and Type III (Leon)—the committee demanded that the 125 strains of the virus that had been identified by various members of the scientific community had to be sorted into these three types. The process took Salk three years: one to sort the strains and two to confirm his findings that they all belonged to one of the three types. Salk later said that the work had been invaluable for him in working towards his vaccine, which to be effective had to contain all three types of the poliovirus.

  Sabin had delays of his own. His conclusion after conducting a series of experiments was that the poliovirus grew only in the nerve cells in the spinal cord and brain and invaded the body via the respiratory system. This view was supported by an eminent group of scientists and for that reason the virus was grown for some years in the nerve tissue of expensive laboratory primates, monkeys, which made it difficult to obtain.[19] One of the hardest things about working with the poliovirus was manufacturing enough to experiment with, let alone making large-scale vaccine production practical.

  At Harvard in 1948, three researchers—John Enders, Thomas Weller and Frederick Robbins—made a breakthrough that facilitated a solution to this problem. They had been working on growing the cold sore virus and mumps virus in a mixture of human embryonic skin and muscle tissue but had not bothered with the poliovirus because of the prevailing view. In the storage cabinet there just happened to be the Lansing strain of poliomyelitis virus so almost on a whim the decision was made to do with it what they had been doing with the other viruses. Utterly surprised, they succeeded in their first attempt.

  Enders, Weller and Robbins immediately realised that given the right conditions the poliovirus could grow in many different sorts of cells. They grew it on scraps of tissue from stillborn human embryos, then chicken embryos and then on other tissue, without needing an intact organism.[20] Bacteria usually contaminated the tissue but Enders and his colleagues, thanks to Howard Florey and the Oxford team, now had access to the new drug penicillin, which prevented the bacterial growth. The Enders team won the 1954 Nobel Prize for Physiology or Medicine ‘for their discovery of the ability of poliomyelitis viruses to grow in cultures of various types of tissue’.[21] This was the only Nobel Prize ever awarded for polio research. There were no laurel wreaths for Salk or his rival Sabin.

  Perhaps this was a case of déjà vu. Without the Oxford team no Enders, Weller and Robbins; and without them, no Jonas Salk or Sabin producing vaccines for poliomyelitis. Salk had a way forward. Enders and his team had shown that viruses like mumps and polio could now be grown in test tubes in large enough quantities for study. Salk made the necessary adjustments to his laboratory and employed the Enders method, incubating the virus using rhesus monkey kidneys and testicles.[22] In a television interview after he had developed his vaccine Jonas Salk said, ‘Enders threw a long forward pass and we happened to be at a place where the ball could be caught.’[23] By examining previous research Salk had also found a way to kill the poliovirus with formaldehyde while it remained intact enough to trigger a response in humans. This enabled him to significantly speed up his research program.

  It was this ability to inform his own research with that of others which later told against Salk and led to one of Sabin’s vitriolic attacks on him. Sabin was quoted in newspapers in the United States as saying that Salk ‘never had an original idea in his life’ and that ‘you could go into the kitchen and do what he did’.[24] John Enders supported Sabin and his approach to developing a vaccine and he is reported to have referred to Jonas Salk’s work as quackery.

  The National Foundation for Infantile Paralysis was aware of the antipathy between the two camps but supported research efforts by both. A sea voyage was to prove fateful in determining what would happen next in the race for the polio vaccine. Basil O’Connor and Jonas Salk were returning from the International Polio Congress in Copenhagen in 1951 on the ocean liner the Queen Mary. The two men spent some time together and once again O’Connor was impressed by Salk’s knowledge. Salk convinced O’Connor that the killed virus vaccine was almost ready for trialling and it was unable to cause the disease, whereas attenuated vaccines could because they were still virulent. O’Connor as head of the March of Dimes gave Salk immediate approval to prepare his vaccine for trial.

  ***

  The year 1952 was a critical one in the United States. That summer 57,628 cases of paralytic polio were recorded.[25] There were 3000 deaths and 21,000 victims were left paralysed, making it the worst year yet. There was a crescendo of hysteria. Children were kept indoors and whole families left the cities en masse, some even escaping to Europe in the hope of finding sanctuary from this destructive disease. Those who stayed were clamouring for a breakthrough. What had been achieved by 1952 was that both vaccines, the killed and the attenuated, caused a rise in blood antibody levels against the virus but no one was sure what level was needed to provide immunity. The real competition was about to begin.

  During his research Jonas Salk had noticed an interesting phenomenon. The pattern of infection and transmission of polio had changed over time. Previously it had struck infants first, hence the name infantile paralysis, but as hygienic conditions improved, the virus spread in the population in a different way. If infants acquired polio in the first six months of life they were protected against paralysis because of maternal antibody. However, after the maternal antibody was lost, if infants were then infected with polio, paralysis would ensue.[26] So as time went on and hygienic conditions improved, many people were contracting the disease later in life. By the early 1950s, about 25 per cent of paralytic cases occurred in those aged 21 and older, which could account for the fact that Franklin Delano Roosevelt became paralysed at the age of 39.27 The age distribution had changed because polio was now spread less by the water supply or by exposure to faecal contamination but more in a family context or amongst playmates through the secretions of the nose and throat. For these reasons polio was on the increase and unpredictable.

  It was against the backdrop of fear and hysteria that on 2 July 1952 Salk tried a refined vaccine for the first time. Children from a crippled children’s home near Pittsburgh, polio victims who had recovered, were vaccinated to see how well the vaccine elevated the antibodies of the strain of the disease that they had suffered from. After the vaccination, their antibodies increased. Then the vaccine was tested on children from the Polk State School who had not had polio. About 5000 children in all were involved in the trial.

  Scientists often have blind faith or perhaps informed faith in their own work. Jonas Salk then tried his killed vaccine on a number of volunteers who had not had polio, including himself, his wife and their three sons, fortunately without detriment. By the end of the year Salk was convinced that antibody response was real in humans because tests showed that the antibodies in both groups of children in the trial had remained high and none of the children had suffered any worrying side-effects.

  News of this early testing leaked into the public domain and there are varying accounts of how this happened. Salk himself said that the leak had occurred via a journalist who had tracked down the story after being present at an advisory committee meeting of the March of Dimes. It had been the intention of the committee to avoid any publicity at this stage but Salk decided to publish his results as soon as possible, hoping to prevent any misconceptions about the trial. He did so the following year in 1953, in the Journal of the American Medi
cal Association.

  The publicity, which had not been sought, brought both accolades and acrimony for Jonas Salk. He was lauded by the public but accused of being a ‘glory hound’ by opponents. Accusations were rife that Salk and perhaps even the National Foundation for Infantile Paralysis had entered into a deal with the pharmaceutical company Parke Davis. Salk had always felt like an outsider as far as his colleagues were concerned and now he was being marginalised even more. It seemed he could not take a trick and although Salk called his vaccine ‘the Pittsburgh vaccine’ after his university, the newspapers called it the ‘Salk vaccine’, a name that stuck in the public mind causing further affront to the medical establishment.

  Amidst this maelstrom, in 1953 Sabin was persevering with attenuated strains of poliovirus and did not have a vaccine ready for trialling while Salk’s vaccine had passed the first test and it seemed safe and effective. Many virologists still agreed with Sabin, however, that an oral attenuated vaccine would in the long term provide greater immunity than a killed vaccine. Salk maintained his objection that, unlike a killed vaccine a weakened vaccine was always potentially dangerous and had to be tested with intense rigour.

  The fundamental, scientific principle that Salk followed was to choose the safe option that could be controlled. He believed in trying to work like nature instead of simply imitating it and as a result his killed vaccine had been ready while Sabin’s still needed fine-tuning. The Salk team had experimented with dose, quantity, duration and the kind of immunity that might be required but did not have to worry about the virulence of the virus. When the leaders of the rival factions presented and defended their positions on polio vaccines at a major medical conference in Rome in September 1953 there was a palpable absence of collegiality.