The Death of a Disease: A History of the Eradication of Poliomyelitis

10. Revolution in the Production of Vaccines

Revolution in the Production of Vaccines 89 89 10 Revolution in the Production of Vaccines Lyon, France, 1955–1990 The production of polio vaccines marked a turning point in the vaccine industry. For the first time ever, huge quantities of a vaccine—tens of millions of doses—were in demand and manufacturers needed to be both imaginative and daring to meet this challenge. The story of the industrial development of any product is rarely a public affair. Such episodes in the history of medicine are rarely written down, perhaps to protect industrial secrets, out of habit, or simply because no one looks into them. We had the good fortune of meeting and interviewing former scientists, technicians, directors, and employees of the Connaught Laboratories in Canada and the Mérieux Institute in France. Today these two companies are both part 90 The Death of a Disease of sanofi-aventis, the world’s largest private manufacturer of oral and injectable polio vaccines. They both played a critical role in the history of the polio vaccine. As was explained in previous chapters, Connaught supplied the viral fluids that made the Francis Field Trial of the Salk vaccine possible, while the Mérieux Institute moved vaccine production to the industrial scale. Shortly before his death on January 19, 2001, we spoke to Dr. Charles Mérieux, who led the Mérieux Institute as it took its first steps into the world of human vaccines. He told us the story of this “extraordinary adventure.” During one of his many journeys across the Atlantic, in 1955 Charles Mérieux met Jonas Salk, Albert Sabin, and Hilary Koprowski. He was struck by the fact that the biologists of the world did not speak a common language. How, then, could they possibly establish international standards to guarantee basic safety for candidate vaccines? “With no common standards to establish and test vaccines and sera,” said Charles Mérieux, “scientists were unable to evaluate or compare them, which meant they could not import or export them. As a result, it was impossible to develop international cooperation or define a coherent policy for worldwide prevention.”1 Dr. Mérieux wanted to organize a congress on biological standards, which he succeeded in doing in 1956, in the Lyon city hall, thanks to the support of Édouard Herriot, the then-prime minister of France and former mayor of the city of Lyon. In the thick of the cold war, the presence of American scientists gave the encounter an international flavor. After the congress, in 1957, Charles Mérieux became interested in an injectable vaccine developed by Pierre Lépine, a scientist at the Pasteur Institute. Lépine had developed a vaccine that, although based on the same inacti- Revolution in the Production of Vaccines 91 vation principle as Salk’s IPV, was not the same vaccine. The virus in the vaccine was inactivated twice. Bernard Montagnon, former head of viral production at the Mérieux Institute, explained: “In addition to formalin, the Lépine vaccine used betapropiolactone, which speeded up the inactivation process. It took just four days to inactivate the Lépine vaccine, compared to twelve for the Salk vaccine. The chemical agent betapropiolactone had another advantage: it killed the viruses that were likely to contaminate the monkey kidney cells.” This was not the case when formalin was used alone. The Merck, Sharp, and Dohme Laboratories were forced to abandon attempts to produce a killed vaccine when, in 1960, they discovered that a simian virus, SV 40, was not destroyed by formalin and contaminated simian cell cultures. In twenty years, Lépine produced several million doses of vaccine for the Pasteur Institute at Marnes-la-Coquette. Convinced that the vaccine was totally safe, Charles Mérieux decided to begin production. The polio vaccine was the first human vaccine to be produced by the Mérieux Institute . The first cell cultures used to make the French IPV vaccine came from dog-faced (cynocephalus) baboons; subsequently patas and vervet monkey cells were used. The type 1 virus was made with a viral strain isolated in the sewage water of Paris. The steps after isolation—inactivation and controls of the vaccine—were very similar to the methods the Mérieux Institute had developed to manufacture a veterinary vaccine to prevent foot-and-mouth disease. Every day at six A.M., the laboratory technicians arrived at the animal facility to remove monkey kidneys. Wearing...