In 1952 the United States recorded about 58,000 cases of polio. Over 21,000 people were left paralysed and more than 3,000 died, most of them children.
Parents kept children away from swimming pools and cinemas in summer and watched for a stiff neck. The iron lung ward was a real place with real rows of beds. Within a decade the disease was essentially gone from the industrialised world, and it was removed by two vaccines developed by two men who could barely be in the same room.
The Discovery That Made Both Vaccines Possible
Before either of them could work, somebody had to solve the problem of growing the virus.
Poliovirus had been cultivated only in nervous tissue, which is useless for vaccine production: material from brain or spinal cord carries a serious risk of provoking an immune attack on the recipient’s own nerves. In 1949 John Enders, Thomas Weller and Frederick Robbins at Boston showed that poliovirus would grow in cultures of ordinary human tissue that was not nervous tissue at all.
That is the decisive step, and it is the one that won the Nobel Prize, in 1954. Neither Salk nor Sabin ever received one.
Salk: Kill It First
Jonas Salk, at the University of Pittsburgh, took the conservative route. Grow the virus, kill it with formaldehyde, inject the dead virus. The immune system learns to recognise it, and there is nothing alive in the vial to cause disease.
The hard part is the killing. Too little formaldehyde and live virus survives. Too much and the protein coat is so degraded that the immune system no longer recognises the real thing. Salk had to find the window, and there are three serotypes of poliovirus, so he had to do it three times and combine them.
The trial was extraordinary in scale. In 1954 the National Foundation for Infantile Paralysis, funded by the March of Dimes, ran a field trial involving 1.8 million children, who were called Polio Pioneers. It remains one of the largest medical trials ever conducted, and a substantial part of it was properly placebo controlled and blinded.
The results were announced on 12 April 1955. Church bells were rung. Salk was on the front page of every newspaper in the country, and when Edward R. Murrow asked him who owned the patent, he said that the people did, that there was no patent, and asked whether you could patent the sun.
That answer is usually presented as pure altruism. The lawyers had in fact concluded that the vaccine was probably not patentable given the prior art, but Salk’s position was sincere, and he had never sought to profit from it.
The Cutter Disaster
Within weeks the celebration went badly wrong.
Cutter Laboratories in California, one of the licensed manufacturers, released batches in which the inactivation had failed. Children were injected with live poliovirus. About 40,000 developed some form of the disease, 51 were paralysed and 5 died.
The vaccine was not at fault, the manufacturing was, and the distinction was no comfort to anybody involved. The programme was suspended, and the episode led directly to the modern American system of federal regulation and batch release testing for biological products. It also handed Salk’s critics a weapon they used for years.
Sabin: Keep It Alive
Albert Sabin, in Cincinnati, thought the entire killed virus approach was wrong in principle, and he was not quiet about it. He described Salk’s work in terms bordering on contempt, dismissing it as kitchen chemistry, and he had a substantial scientific case.
His argument ran like this. Polio is transmitted through the gut. An injected killed vaccine produces antibodies in the blood, which protects the individual from paralysis, because it stops the virus reaching the nervous system. It does much less to stop the virus growing in the intestine and being shed, so a vaccinated child can still pass polio to an unvaccinated one, and the virus keeps circulating.
A live but weakened virus, swallowed, does something different. It replicates in the gut exactly as the wild virus would, producing local intestinal immunity as well as antibodies in the blood, and it blocks transmission rather than only paralysis. It also confers longer lasting immunity and it is far cheaper, needs no needle and no trained injector, and can be given on a sugar cube or as two drops in the mouth.
The attenuation was the difficult part: passage the virus repeatedly through cultures until it has lost the ability to attack nerve tissue, but not so far that it no longer provokes immunity.
By the time Sabin was ready, the Salk vaccine was licensed and in mass use across the United States, and there was no ethical way to run a large placebo controlled trial there.
The Trial Held in the Soviet Union
So Sabin went east, in the middle of the Cold War.
He worked with the Soviet virologist Mikhail Chumakov, who had the authority and the infrastructure to run something enormous, and in 1959 the oral vaccine was given to around ten million children in the USSR. It worked.
This is one of the odder facts of twentieth century science: in the years between Sputnik and the Cuban missile crisis, an American vaccine was validated by the Soviet health system, and American regulators then licensed it partly on Soviet data. The United States authorised the oral vaccine in 1961 and 1962 and switched to it almost entirely, because it was cheaper, easier to give and better at stopping outbreaks.
Salk regarded this as a mistake and said so for the rest of his life.
Who Was Right
Both, and each in the situation the other was thinking about.
The oral vaccine is what eradicated polio from most of the planet. It stops transmission, costs almost nothing, and can be given by volunteers, which is why the global campaign is built on it. Cases worldwide have fallen from an estimated 350,000 a year in 1988 to double figures. Wild type 2 and type 3 are gone. Only type 1 survives, in a small number of districts in Afghanistan and Pakistan.
But the live vaccine has a cost that the killed vaccine does not. In very rare cases, roughly one in a few million doses, the attenuated virus causes paralysis in the recipient. And in populations with low immunisation coverage, the weakened virus can circulate from person to person long enough to mutate back towards virulence, producing outbreaks of vaccine derived poliovirus.
That is why the United States switched back to Salk’s injected vaccine in 2000. Once wild polio was gone, every remaining American case was caused by the vaccine, and at that point the safer, more expensive option is obviously correct.
The current global strategy uses both: the oral vaccine to interrupt transmission where the virus still circulates, the injected one to protect individuals where it does not, and a newer, genetically stabilised oral vaccine designed to be less prone to reverting.
The choice between them was never a matter of which man was cleverer. It depends on whether you are trying to protect a child or to eliminate a virus, and those two goals point at different vaccines.
Why They Could Not Share It
The personal animosity was real and lasted until the end. Sabin thought Salk had taken credit for work that was routine and had been rewarded for publicity rather than science. Salk thought Sabin had risked children’s lives and had spent years attacking a vaccine that was already saving them.
Both were operating in a system that made the fight worse. The March of Dimes had raised money from the public by promising a cure, the press wanted a single hero, and the structure of scientific prestige rewards priority rather than contribution. This is the same pattern that had produced the Franco German competition of Koch and Pasteur seventy years earlier, and it produced the same result: two rival methods, both of which turned out to be necessary, and two men who could not say so.
Jenner’s cowpox inoculation in 1796 had established the principle that a milder relative of a disease can protect against it. Fleming’s mould had shown that infections already under way could be treated. Polio is where the two twentieth century strategies for a single disease, prevent it with a dead pathogen or with a tame living one, were tested against each other on a continental scale in the space of six years.
The disease is now closer to extinction than any other human infection except smallpox. It has taken thirty eight years longer than anybody expected in 1988, and the remaining obstacles are almost entirely to do with conflict, distrust and access rather than with biology.
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