At the height of the polio epidemic in 1953, the National Foundation for Infantile Paralysis decided to organise mass trials using Salk’s killed vaccine. A pattern had been established, however, and as expected Sabin and his supporters were horrified and publicly challenged the approach. The situation Salk found himself in worsened as criticism of the proposed trials reached a peak in early April 1954. Scare tactics were aimed at parents. Fantastic rumours were spread that the National Foundation had a stock of little white coffins for the children who would die as a result of their involvement in the trial and a well-known radio personality, Walter Winchell, who had spoken to one of Salk’s opponents, broadcast that the vaccine could be a killer.[28]
Predictably, problems then arose over who should have control of the largescale vaccine trials. Jonas Salk’s mentor, Thomas Francis, with whom Salk had developed the influenza vaccine, was chosen as the director. Laboratories were adapted in order to produce the huge quantities of the vaccine needed. Five pharmaceutical firms manufactured the Salk vaccine: Parke Davis & Co. in Detroit, Pitman-Moore and Eli Lilly & Co. in Indianapolis, Wyeth Inc. in Philadelphia and the Cutter Laboratories in Berkeley in California.
In April 1954 the national field trials began. It was the largest controlled, double-blind study that had ever been conducted, involving nearly 2 million school children aged between six and nine, this age group having become a primary susceptible group to polio. Without knowing which they received, 440,000 children were vaccinated and 210,000 received a placebo. A massive 1,180,000 served as unvaccinated controls.[29] And the results? A staggering 60 to 70 per cent of the vaccinated children were immune to polio.
On 12 April 1955 the world was informed that a vaccine existed which could put an end to polio’s tortures. This monumental news story took on a life of its own. It was the 1950s—the beginning of the media age. Speaking directly to an audience of 500 scientists and physicians, Thomas Francis presented the results in a carefully scripted but detailed one hour and 40 minute talk. Sixteen television and newsreel cameras were recording the event and, in a press room three floors above, over 150 newspaper, television and radio reporters were sending out their stories.
The vaccine was a godsend and Salk came close to achieving the status of a deity. Americans breathed a collective sigh of relief. The Salk vaccine was declared 90 per cent effective against Types II and III poliovirus and 60 to 70 per cent effective against Type I. Within two hours, Salk’s inactivated polio vaccine (IPV) was licensed for use.[30] Because of guarantees from the March of Dimes, as the National Foundation for Infantile Paralysis had commonly become known, industrial production facilities were already built and ready to operate. The goal was to have 5 million US children vaccinated by July 1955.
Then, suddenly and unexpectedly, thirteen days after the announcement, on 25 April, an incident was uncovered which was reminiscent of the tragic Lübeck disaster (in which children died as a result of contaminated diphtheria serum in 1930). Some 200 cases of polio were attributed to Salk’s vaccine. There were eleven deaths and 150 cases of paralysis. Tremendous publicity was given to these cases and once again optimism was shattered. An investigation revealed that the disease-causing vaccine all came from one poorly made batch at a specific drug company. The incident became known as the Cutter Laboratory disaster. On 27 April the surgeon-general recalled all of the Cutter Laboratory vaccines and on 8 May the entire US vaccination program was cancelled. The Lancet, published on 11 June, stated in a leading article that ‘the most likely explanation is that some of the vaccine contained live poliomyelitis virus which had not been completely inactivated by the formaldehyde treatment’.[31]
Higher production standards were immediately adopted and, after confidence in the vaccine was restored, the vaccination program was resumed. By August 1955 over 5 million doses of the Salk inactivated polio vaccine had been administered in the United States. The impact was dramatic. In 1955 there were 28,985 cases of polio; in 1956 the number had halved to 14,647; and in 1957 only 5894 cases were reported.[32] Across the Atlantic, some European countries imported the Salk vaccine from the United States whereas others, including Denmark, began vaccine production in their own government facilities. In Denmark it was proposed that everyone up to the age of eighteen should be vaccinated as a matter of course.
Early in 1955 the Pasteur Institute in France put out a statement that an anti-poliomyelitis vaccine, developed by Professor Pierre Lepine, would soon be produced in large quantities. According to The Lancet published on 7 May 1955, the Swedish government planned to manufacture a vaccine derived from a virus grown in human tissue in the hope that it would be free from the side-effects that might result from the use of monkey tissue; but in the interim the Swedes ordered 100,000 doses of the American Salk vaccine. By 1959, 90 other countries were using Salk’s vaccine.[33]
The first country to be chosen by President Eisenhower to receive the formula of the Salk vaccine was India and the presentation was made on 5 May 1955 to the Indian Health Minister by the US Ambassador. This was in recognition of the contribution made by India in developing the vaccine. A polio research centre in Bombay, financed by the Indian Council of Medical Research, had been working on the problem for several years and was said to have produced valuable data. Also, thousands of rhesus monkeys had been imported into America from India for initial experimentation.
Even though the Indian Health Ministry planned to immediately start manufacturing the vaccine they were still willing to continue exporting monkeys as long as they were transported under humane conditions and would only be used for poliomyelitis research. According to David R. Preston, Director of Scientific Information at the National Foundation for Infantile Paralysis at that time, one monkey’s kidneys could provide enough vaccine for 6000 injections, enough for 2000 children if a course of three injections was needed for each child.[34] At that time, when so much vaccine was needed, the demand for monkeys exceeded the supply. When addressing an international conference in Rome on the subject of poliomyelitis in 1954, Jonas Salk said that he had already at that time made use of 15,000 monkeys. The rhesus monkeys, each of which weighs around 2 to 4 kilograms, were trapped in northern India, carried in bamboo cages on shoulder poles to the nearest railway station to be transported to Delhi where they underwent health screening. The monkeys were flown 4000 miles (6400 kilometres) to London and then a further 3000 miles (4800 kilometres) to New York’s Idlewild Airport from where they were trucked to Okatie Farms in South Carolina. Monkeys were also transported from the Philippines. An average of 5000 monkeys a month passed through Okatie Farms before being dispersed to four laboratories in Toronto, Pittsburgh, Detroit, and Berkeley.[35] At the laboratories the monkeys were anaesthetised, their kidneys were removed and then they were euthanased. Their kidneys were sliced up, placed in a viable solution and rocked gently in an incubator for about six days to promote kidney cell growth.[36]
***
The success of the vaccine won Jonas Salk unsought fame. The March of Dimes, hoping to boost publicity and donations to fund the vaccination programs, pushed Salk into the limelight, which succeeded in offending his opponents even more, if that was possible. He was attacked again for ‘stealing’ his success. Salk had, in fact, applied the findings of others in order to discover a successful preventative vaccine for polio. But those ‘others’ could have done the same.
Another accusation levelled against Salk was that he took credit for himself only, and this would haunt him for many years. Labelled as selfish, he was accused of possessing an egotism that grew parasitically with his sudden rise to fame. It was said that in his press conference in 1955 he had not acknowledged his colleagues. In Salk’s defence, it depends on what one is asked in interviews as to what emerges. Salk did in fact mention the work of the Enders team in interviews and this acknowledgement appears in the New York Times’ five-page coverage of the 1955 press conference. Other researchers were acknowledged in the print media for their contributions as wel
l.[37] That credit was shared cannot be denied.
Conversely, the timing of Salk’s successful vaccine at the peak of polio’s devastation in the mid 1950s rendered the public deaf to criticism and Salk was felt to embody all that was good about science. He had refused to patent the vaccine, having no desire to profit from the discovery but wanting merely to see the vaccine disseminated as widely as possible. There is no doubt that he lamented becoming a public figure; his time was no longer his own and he had to struggle to continue with his work. Salk described losing his anonymity as akin to being in the eye of a hurricane.[38]
While the Salk circus was in full swing, Albert Sabin did not give up his quest and continued his work at the University of Cincinnati on an oral vaccine. His view, still shared by others in the field, was that Salk’s killed virus vaccine was not strong enough and that during the time in which immunity lasted, the body would not have a chance to build up antibodies from natural exposure. In the long run Salk’s vaccine would be a disaster waiting to happen. Only a live vaccine, they continued to argue, had sufficient immunogenicity to provide protection. In contrast, an inactivated vaccine would have to be re-administered regularly and, as time would prove, Salk’s vaccine did in fact require booster shots. Although it took Sabin longer to produce his oral, attenuated vaccine, the tortoise would eventually win a victory of sorts.
***
Undeterred by Salk’s popular success, other researchers were engaged in developing attenuated vaccines. At the Lederle Laboratories in New York, a commercial interest that had received some of the millions of dollars of funding the US government had invested in polio research, Herald R. Cox, the director of the laboratory, and Polish-born virologist and immunologist Hilary Koprowski continued working on live attenuated virus preparations. Koprowski had been employed by Cox and they were co-researchers until their professional relationship broke down in 1952 and they became competitors instead. Like Sabin and Salk, each developed a polio vaccine the merits of which they vigorously defended and debated. Apart from the good an effective polio vaccine could do for humankind, success could bring with it untold benefits to a scientist.
The in-fighting remained bitter. Koprowski later claimed that he created the first successful polio vaccine in 1950 but his live attenuated oral vaccine was not ready for use until five years after Jonas Salk’s injected vaccine reached the market. He also had issues with Albert Sabin, claiming that Sabin used samples of attenuated virus given to him by Koprowski to develop his oral vaccine. Although their relationship had already been strained, one day when Sabin had visited Koprowski at the Lederle laboratory they had agreed to exchange samples; but according to Koprowski, Sabin welshed on the deal. This gave Koprowski grounds for later asserting that the polio vaccine he discovered had become wrongly known as the Sabin vaccine. Everyone wanted the glory.
In his research, it had been Sabin’s aim to mimic the real-life infection of polio as much as possible by using a weakened form of the live virus. By 1956 Sabin had administered his vaccine to approximately 9000 monkeys and 150 chimpanzees and before he experimented on 133 young adults, volunteers from an Ohio prison, he and his associates swallowed avirulent live viruses themselves.[39] The results were a significant rise in antibodies and no signs of polio infection. Sabin was fortunate to have the support of the pharmaceutical company Merck, Sharp and Dohme. The company provided approximately 25 million doses of each selected strain of poliovirus. The stakes were as high for drug companies as they were for individual scientists.
Sabin’s oral vaccine then underwent two major trials between 1958 and 1960 in the Belgian Congo and in the Soviet Union and Eastern Europe. Relations between the United States and the Soviets were strained but the Russians were prepared to trial Sabin’s vaccine because their plight was so serious. At the same time, 1957 to 1960, Koprowski was testing his vaccine in Ireland and in various areas in Africa. It was necessary to trial outside the United States because widespread immunisation with the Salk vaccine meant that most US children had antibody levels that were too high to enable an evaluation of a second vaccine.
Sabin now had new rivals and in an attack similar to that previously aimed at Jonas Salk, Sabin’s vaccine was dubbed the ‘communist vaccine’.[40] He was at last getting some of his own medicine. Regardless of what the vaccine may have been called this did not detract from its staggering success. By July 1960 more than 15 million Soviet citizens were said to have received Sabin’s oral vaccine while Koprowski’s had failed. Kropowski accused Sabin of being unfairly supported by the scientific establishment while he was sidelined as an outsider from private industry.[41]
The rivalry continued. Herald Cox from the Lederle Laboratories, who eschewed the Enders technique of growing the polio virus on monkey tissue because of the danger of contamination with monkey viruses, had reported in October 1952 that he had grown the Lansing strain in fertile hens’ eggs.[42] He too was developing a vaccine. However, it was not ready until 1961. By the time Cox tested his vaccine in Latin America, Sabin’s vaccine was already well on the way to being accepted. This did not stop Maurice Hilleman, a major figure in vaccine research in America and director of the Merck Institute for Therapeutic Research, referring to Sabin as a self-pronounced genius who had taken over Cox’s and Koprowski’s ideas.[43] The sniping seemed endless.
The tide, however, was turning rapidly in Sabin’s favour. His attenuated oral vaccine was deemed to have advantages over Salk’s vaccine. It was found to confer longer-lasting immunity, so that repeated boosters were not necessary, and it acted quickly, immunity being achieved in a matter of days. Taken orally, on a sugar cube or in a drink, the vaccine was much easier to administer than the injected Salk vaccine. Also the Sabin vaccine offered the prospect of passive vaccination because it caused an active infection of the bowel resulting in the excretion of live attenuated virus. This could help to protect people who had not been vaccinated through exposure to faecal matter and sewage.
On 24 August 1960 when the surgeon-general recommended licensing Sabin’s vaccine for domestic use, Salk continued to argue that even though it had been successful in the Soviet trial, the vaccine could actually cause cases of polio.[44] He would prove to be correct, but in developing countries the cheaper Sabin oral vaccine had far more appeal and the risk was minimal compared with the difference it made overall to child morbidity and to cases of paralysis. The advantages of the attenuated vaccine were soon recognised even in the developed world.
SALK’S REIGN ENDS, SUSPICION MOUNTS
The Sabin oral polio vaccine (OPV) was licensed in 1962 and gradually supplanted its rival and predecessor. The frightening polio epidemics which marred the first half of the twentieth century were gone. By 1968, Salk’s vaccine was no longer being administered in the United States and US pharmaceutical companies had stopped producing it. By the 1970s the Sabin vaccine replaced the Salk vaccine in many parts of the world. However, some countries including the Netherlands continued to use only Salk’s vaccine even though the advantages of the live attenuated vaccine seemed clear-cut.
And the reason? As early as 1962, it was suspected that in a very small number of cases, mostly adults, the live vaccine could lead to paralytic poliomyelitis. In 1964, an advisory committee established by the US surgeon-general reviewed the incidence of polio between 1955 and 1961, a period when only the Salk vaccine was used, and between 1961 and 1964, when the Sabin vaccine predominated. It was the judgment of the committee that of the 87 cases of paralytic polio reported in the United States after 1961, 57 were compatible with having been caused by the attenuated poliovirus regaining its virulence.[45] It was exactly what Jonas Salk had warned might happen.
By the mid 1960s, health officials in the United States had to weigh the many benefits of Sabin’s OPV against the small but definite risks that were now known to be associated with its use. Polio was rampant in many countries despite the inroads made and the aim was still global eradication. There were other factors to consider. Immun
isation programs with the OPV and manufacturing facilities were already in place. The costs involved in switching back to the Salk vaccine and the risk of affecting public confidence were too great to risk. These anomalies, however, made it difficult for health authorities to establish immunisation standards and for a time a course of injections was given that included both vaccines. The tortoise and the hare were running side by side.
In an overall review of the vaccines, the Centers for Disease Control and Prevention in the United States found that between 1960 and 1983 of a total of 210 cases of polio, 99 may have been caused by the Sabin vaccine. Sabin, however, could not accept this assessment and hypothesised that other diseases which cause paralysis can mimic polio and his vaccine was not the cause. Salk accused Sabin of not believing the scientific evidence.[46] The animosity continued between the two scientists but Sabin’s reputation in the medical world remained untarnished.
***
During the tug-of-war between the Salk and the Sabin vaccines, Jonas Salk had been aggressively marginalised by the medical community and perhaps permanently bruised by the attacks he had suffered. In 1963, when he founded the Salk Institute for Biological Sciences in La Jolla in California, his cynical comment that he could not possibly have become a member of this institute if he had not founded it himself reveals insight into his ostracism and the depth of the hurt.[47] To add insult to injury his own institute did not bring him the professional satisfaction he may have hoped for. Jonas Salk harboured the view that many of the great scientists who were attracted to work there were no different to those who had sneered at his work on polio, dismissing him as a mere technician. Great minds and great egos walk closely together.
When asked about scientists devoting their lives to humanity and the rivalries that often ensue, Salk’s answer was reminiscent of words uttered by Howard Florey. Salk commented that it is not a bent to help humanity that drives scientists: ‘The motivation to do what we do is different in each instance’ and in some instances, he said, one does not understand what that is until ‘you see the effect it has produced’.[48] He said there is a difference between a scientist dealing with nature in the laboratory and dealing with human nature outside it, which includes how colleagues or others will react—often not from altruistic motives. Jonas Salk’s story is certainly proof of that.
Smallpox, Syphilis and Salvation Page 30