VaccinatedI just started reading Paul Offit’s book Vaccinated: From Cowpox to mRNA, the Remarkable Story of Vaccines, which is about Maurice Hilleman and how he created nine of the main vaccines in use today.

It’s a great read, and in the third chapter Offit delves into some of the history of vaccines and what Hilleman learned from those who came before him. For example:

FROM LOUIS PASTEUR, A FRENCH CHEMIST, HILLEMAN LEARNED THAT vaccines could be made from dangerous human viruses. (Jenner had used a cow virus.) Pasteur developed humankind’s second vaccine, one that prevented a uniformly fatal disease: rabies.

On July 4, 1885, a rabid dog attacked a nine-year-old boy named Joseph Meister in the town of Meissengott, a small village in the province of Alsace, France. Meister, who was on his way to school, covered his face as the dog knocked him down and bit him fourteen times. A bricklayer walking nearby beat the dog with an iron bar and carried Meister home. The owner later killed the dog and cut open its stomach; out poured straw, hay, and fragments of wood—evidence that the animal had gone mad. (Old stories about infectious diseases often sound as if they had been written by the Brothers Grimm.)

In ancient times, people with rabies were hunted down like wild animals and strangled or suffocated. By the late 1800s, treatments for rabies had advanced to include the feeding of cock’s brains, crayfish eyes, livers from mad dogs, snake skins mixed with wine, and poison from a viper, or the “dipping cure,” which involved holding victims under water until “they have done the kicking.” Techniques that actually worked to prevent rabies included immediately cauterizing a bite with a hot iron or sprinkling gunpowder on the wound and igniting it; these processes killed the virus.

Two days after the attack, Joseph Meister and his mother arrived at the front door of 45 rue d’Ulm in Paris, the home of Pasteur’s laboratory. When Pasteur came to the door, Meister’s mother dropped to her knees and begged him to save her son. Pasteur took the boy by the hand and gently guided him into his home, later describing the wounded child in his notebook, “Severely bitten on the middle finger of his right hand, on the thighs, and on the leg by the same rabid dog that tore his trousers, threw him down and would have devoured him if it had not been for the arrival of a mason armed with two iron bars who beat down the dog.”

For several years preceding Meister’s visit to his laboratory, Pasteur had studied rabies virus. To make an experimental rabies vaccine, he found dogs that had died of rabies, ground up their spinal cords, injected infected spinal cords into rabbits, and watched the rabbits die of rabies. Then he removed the rabbits’ spinal cords, cut them into thin strips, and dried them in airtight jars. Pasteur found that the longer he dried them, the longer it took for the infected spinal cords to cause disease. After fifteen days of drying, they didn’t cause disease at all. Apparently, prolonged drying killed rabies virus. Pasteur then performed his groundbreaking experiment. He injected dogs with rabies-infected spinal cords that had been dried for fifteen days and then, successively, with spinal cords that had been dried for fewer and fewer days. At the end of the experiment, Pasteur injected dogs with spinal cords that contained live, deadly rabies virus. Typically, the dogs would have died of rabies. But all the dogs that received Pasteur’s vaccine survived.

When Joseph Meister came to his laboratory, Pasteur had not yet immunized people, only animals. But at 8:00 p.m. on July 6, 1885, Meister was injected with a rabies-infected rabbit spinal cord that had been dried for fifteen days. Pasteur knew that such a spinal cord didn’t kill dogs or rabbits. He could only hope that it wouldn’t kill Meister. During the next eleven days, Meister was injected twelve more times with rabbit spinal cords that had each been less and less dried out and therefore were more and more likely to cause rabies. The final dose, on July 16, was taken from an infected rabbit spinal cord that had been dried for only one day—an injection that would have easily killed a rabbit. Pasteur knew that those final injections were potentially deadly. Writing to his children, he said, “this will be another bad night for your father. [I] cannot come to terms with the idea of applying a measure of last resort to this child. And yet [I have] to go through with it. The little fellow continues to feel very well.”

By the end of the month, Meister was home in Alsace, healthy. Using killed, partially killed, and live rabies virus, Pasteur had developed the first vaccine that protected people bitten by rabid animals from getting rabies. Parisians, who had to live every day in fear of rabid dogs prowling their streets, hailed Pasteur’s vaccine as one of the greatest medical triumphs of the nineteenth century. But like Jenner’s smallpox vaccine, Pasteur’s rabies vaccine came with a price. As his vaccine was injected into more and more people, Pasteur found something that he hadn’t anticipated: some people—as many as one of every two hundred who used it—became paralyzed and died. At first, Pasteur thought that people were dying of rabies. But they were dying of a reaction to his vaccine.

Today we understand the problem with Louis Pasteur’s rabies vaccine. Cells from the brain and spinal cord contain a substance called myelin basic protein. This protein forms a sheath around nerves, like the rubber insulation that surrounds an electrical wire. Some people inoculated with myelin basic protein occasionally have an immune response against their own nervous systems: autoimmunity. Pasteur’s vaccine, made from rabbit spinal cords that contained myelin basic protein, caused autoimmunity. (This was why Hilleman cut off the heads of chick embryos before using them. He didn’t want to inject children with small amounts of myelin basic protein from the chicks’ brains.)

Joseph Meister, who survived the bite of a rabid animal, lived to be sixty years old. When the Nazis occupying Paris in 1940 wanted to see the tomb of Louis Pasteur, Meister, then a guard at the Pasteur Institute, was the first to meet them. But the humiliation of opening his savior’s tomb to the Nazi invaders was more than he could handle. Later, locking himself in his small apartment, Meister committed suicide.

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