A shot of polio-infected rat brain please, barman!

In this blog our Senior Research Fellow, Professor Ken Donaldson, explores the history of the polio vaccine.

This blog describes the history of the development of the polio vaccine. It was developed in the middle of the 20th century at a stage when our knowledge of the immune response and how viruses behaved in the body were very incomplete and there was a much poorer understanding of how vaccines worked. Yet scientists in public health were courageous in pressing on, their eyes on the prize of vaccines that would protect the public from dreadful diseases like poliomyelitis. Ultimately their efforts made vaccination one of the greatest triumphs of public health.

Hilary Koprowski around the time he developed his attenuated vaccine, CC BY 4.0 via Wikimedia Commons

Imagine the scene – two scientists have developed a vaccine against poliomyelitis after attenuating it, that is weakening it so that it does not cause paralysis, by growing it in rat brain. It’s safe in monkeys, they have tested it and found it does not cause paralysis in the monkeys yet confers protection against polio infection; now they need to know if it’s safe in humans. They meet in the lab, bringing two glasses, and collect some fresh vaccine by blending the brains of rats infected with the polio virus into a grey oily mush. They divide the oily liquid into two and with a cursory chink of their glasses, they each drink down the draft. The year was 1948 and the two men were the brilliant Polish virologist Hilary Koprowski (1916-2013) and his assistant Thomas Norton (dates unknown); Koprowski later said the vaccine tasted like cod-liver oil!

Polio

Five poliomyelitis virus particles at high magnification. Image via Wikimedia Commons

By the mid-20th century polio (full name poliomyelitis) was one of the most feared diseases known to man. Particularly infecting children, UK annual polio cases in the mid-20th century reached 10,000 with almost 1000 deaths. As an enterovirus, poliovirus initially infected the gut, causing fever, a sore throat, headache, achiness and nausea which generally resolved.  However, in a small percent of those infected, the virus entered the central nervous system causing muscle paralysis and even death. The muscles that controlled breathing were often affected, causing children to be confined to an Iron lung that, by changing the external pressure around the chest regularly, artificially moved the chest in and out effectively ‘breathing for them’. This cruel aftermath of the infection, a life confined to an iron tube, caused it to be especially dreaded; in practice infection caused by their immobility in the iron lung almost always ended the children’s life prematurely.

Patient in an Iron Lung Photo Credit: Content Providers(s): CDC, Public domain, via Wikimedia Commons

Developing vaccines against polio

Koprowski had emigrated to the USA from Poland, via Brazil, at the start of WW2 and was in the Lederle Laboratories near New York when he started developing a polio vaccine. The other two American scientists leading the race to a polio vaccine were Jonas Salk (1914-1995) and Albert Sabin (1906-1993).  In their beginnings, vaccines were either killed versions of the virus or attenuated versions.  Salk was working on a killed vaccine and Sabin, along with Koprowski, was working on an attenuated vaccine. The aim of vaccination is for the immune system to experience the microbe in a dead or attenuated form and develop a protective immune response to it, without putting the individual at risk from actual infection with a dangerous virus. Then, if they do encounter the actual harmful virus, they have an immune response that is ‘oven-ready‘ to fight the virus. The killed virus vaccine is just that, a sample of virus killed in a way that conserves the molecular structures that the immune system recognises.  An attenuated virus is a live form of the virus that can infect the individual and pass around the body invoking an immune response against itself, but it has lost the ability to cause severe harm of the type seen with the virulent, non-attenuated form. In the case of the polio virus the attenuated form has lost the ability to enter the central nervous system and cause paralysis.

Koprowski’s attenuated vaccine

Having found his attenuated vaccine to be safe in himself and his assistant by drinking the rat brain concoction, Koprowski had to find a population in which they could fully test a vaccine based on their attenuated virus. In 1956 he teamed up with a Glaswegian pathologist/ virologist George Williamson Auchinvole Dick (1914-1997), who had graduated from Edinburgh University Medical School and who was by then Professor of Microbiology in the University of Belfast. In a preliminary study that would be frowned on by ethical committees today, Dick recruited his friends and colleagues and their children into a study in which they took Koprowski’s oral vaccine. In this small group the aim was to look for adverse effects and to monitor the virulence of the virus in the subject’s faeces after it had passed through their gut, since Dick had recognised the real possibility that in transit through the gut the attenuated virus might mutate back to a virulent form capable of causing paralysis.  To Koprowski’s disappointment, by 1958 Dick had evidence that the attenuated virus did exactly that, undergoing mutation in the bowel of some of the recipients of the vaccine such that the recovered virus was able to cause paralysis in monkeys.  Dick reported his findings warning on the potential dangers of attenuated virus, precipitating a major dispute between himself and Koprowski and effectively putting a stop to Koprowski’s plans for roll-out of his attenuated vaccine: Koprowski never forgave him.

Successful polio vaccination

Attenuated viruses now had a bad reputation, being viewed as risky.  Another factor contributing to the move away from the idea of attenuated vaccine was the success of the Salk, killed vaccine. This was now considered much safer and had also been found to be efficacious in immunising against paralytic polio infection in large scale trials in 1955. The Salk vaccine had a huge impact in protecting against polio but was eventually replaced by an attenuated virus produced by Albert Sabin. Sabin’s attenuated form did not revert to virulence in the gut and was more easily delivered on a sugar cube than the Salk vaccine, which had to be injected, and it also gave greater protection. Between them, first the Salk and then the Sabin vaccines, eliminated polio from most countries in the world.  

Graph showing the impact of Salk vaccine then the Sabin vaccine in complete and sustained elimination of polio in the USA (Figure courtesy of the Centres for Disease Control.) 

Hilary Koprowski went on to a glittering career, eventually developing the virus against rabies that is still used today. George Dick continued working on vaccines in Belfast, developing the virus reference laboratory there before moving to the famous Bland Sutton Medical Research Institute as Professor and doing important work on neurological viruses there. Jonas Salk became one of the most famous biologists in America with his work on the Salk killed vaccine, saving millions of lives and preventing many more from being disabled by polio. Albert Sabin developed the oral attenuated polio virus which replaced the Salk as the vaccine of choice and finally lead to the eradication of polio in the USA and in most countries in the world. Albert Sabin refused to patent his vaccine so allowing it to be more cheaply made and available throughout the world; he did not make a penny from his remarkable efforts in eradicating the dread disease of polio.

Albert Sabin Public domain, via Wikimedia Commons

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