C’était en 1963, dans la banlieue de Philadelphie. Une petite fille de cinq ans, appelée Jeryl Lynn, se réveille malade au milieu de la nuit et court hors de sa chambre pour appeler son papa. “Oh my God, she had a swollen neck like this,” her father, Maurice Hilleman, recalls decades later, mimicking a swelling at the angle of the jaw. “I said, ‘Damn, you have the mumps.’” Now in his eighties, with his white hair, defeated look, and glasses perched on his nose, he remembers with a laugh: “I told her, ‘Go back to bed.’ It was around one in the morning. I went to the lab to get the equipment to take throat swabs, which I brought back to the lab and froze.”
In terms of speed, the development of the mumps vaccine would set his record – a record that no one would beat – until the whole world devoted all its scientific and financial resources to developing a vaccine against COVID-19.
This kind of reaction is not common among parents, but it probably didn’t shock Jeryl, who grew up in an environment where interferons, poly(I:C), and internal politics at the Bureau of Biologics – precursor to the FDA – were common topics of conversation around the table.
Hilleman headed the Vaccine and Virus Research Division of the pharmaceutical company Merck, but he didn’t abandon his scientist hat when he came home. Visits to the cemetery with his daughters, to the grave of his first wife Thelma, who died of breast cancer a few months before Jeryl Lynn’s mumps, turned into expeditions to capture insects in formaldehyde, as remembered by Kirsten, Jeryl’s younger sister. “He wanted everyone to learn and love science,” Jeryl explains.
Born in the rural state of Montana in 1919, in the midst of the deadliest influenza pandemic ever recorded, Hilleman grew up on a farm, which didn’t really predispose him to spend his life behind a microscope. But he discovered Darwin, which opened the doors to another world, more rational than his family’s Lutheran cosmology, and later allowed him to receive a scholarship from the state of Montana to study chemistry and microbiology.
He was talented and worked hard – the harsh life of a farmer was, he said, a very fertile learning ground, because “it turns you into a workhorse – you had to be, to survive” – and he graduated first in his class. He then earned his doctorate at the University of Chicago on a groundbreaking topic, chlamydias, after which the academic world opened its doors to him. But Hilleman was in a hurry and wanted to do practical things, so he entered the industry and started developing vaccines.
When little Jeryl woke him up to tell him her throat hurt, Hilleman was 43 years old and had already achieved a great deal of scientific success. He had developed a vaccine against Japanese encephalitis B, discovered that influenza viruses “underwent gradual and progressive minor antigenic changes punctuated by rare major changes,” which would become the basis for future influenza vaccination strategies; he discovered adenoviruses and produced a flu vaccine to counteract an emerging pandemic.
And he had no intention of resting on his laurels. “My goal was to defeat childhood diseases,” Maurice Hilleman admitted. Considered by his colleagues as a gruff, unemotional man, and, quite amusingly, irredeemably rude, Hilleman loved children and was, according to his daughter Kirsten, “a very kind dad.” Roy Vagelos, who became director of Merck laboratories in 1975, said of Hilleman: “Of all the great scientists I’ve met, he was the most determined to eradicate diseases that affect humanity.” According to Vagelos, his list of targets to fight included “virtually every known disease.” At his death in 2005, he had developed about forty vaccines, including nine among the essential vaccines for children.
In terms of speed, the development of the mumps vaccine would set his record – a record that no one would beat – until the whole world devoted all its scientific and financial resources to developing a vaccine against COVID-19.
Only three years after that famous night when his father had to travel nearly 25 km to deposit Jeryl’s virus in the Merck laboratories freezer, one-year-old Kirsten Hilleman was vaccinated with the candidate vaccine her father had made. In 1967, the vaccine was marketed in a blue and white box with the inscription: “Mumps Vaccine, Jeryl Lynch strain”: “He thought it sounded good,” Jeryl later said, laughing about the product’s name.
Mumps were very common at that time and generally benign, but they could, in a minority of cases, cause encephalitis or deafness. In men who contracted it after puberty, mumps often led to orchitis, a painful inflammation of the testicles, which can make them sterile. In pregnant women, mumps can affect the fetus or even cause its death. But natural infection also conferred lasting immunity – an encouraging sign for the development of a live vaccine.
An attenuated live vaccine is actually a weakened virus, whose ability to cause disease in infected subjects has been reduced, without impairing its ability to stimulate the immune system. That said, it is not so simple to weaken a pathogen. Hilleman’s approach was to exploit the natural process of evolution by culturing the virus in cell cultures from another species, to reduce or eliminate its ability to replicate in humans, which is not always easy.
“After isolating the virus, we attenuated it,” Maurice Hilleman remembers. “But damn, this time it happened like this.” He introduced the virus from Jeryl’s throat swab into a fertilized chicken egg. The virus developed in the egg, and then he transmitted it to another egg, and then another. Then he took a 12-day-old chicken embryo, cut off its head with a pair of scissors, and chopped up the embryo’s body. He treated the resulting slurry with an enzyme to break it down into individual chicken cells, which multiplied until they covered the base of a laboratory flask. It was in this flask that he inoculated the virus. With each passage – from one egg to another, from an egg to chicken cells – the virus adapted and specialized: it changed in a way that allowed it to attack chicken cells better and human cells less.
By the time, in the attenuation process, the virus appeared sufficiently weakened – but still strong enough – to serve as a vaccine, Hilleman’s medical colleagues began testing it on children. In what Hilleman himself, both smug and optimistic, would later describe as “a big ethical problem,” the first subjects to receive the candidate vaccine were mentally disabled children placed in state institutions. It was a common practice at the time, which is rightfully considered abominable today. Speaking to his biographer, Hilleman focused on the practical results: “My vaccine protected these children from the harmful effects of this disease.”
The trial was expanded to thousands of willing families – including Hilleman’s own – who gave their consent by signing 7.6 x 12.7 cm cards. The results, obtained quickly, were unambiguous: antibodies were detected in 95% of vaccinated subjects. There were no…
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2023-10-23 14:35:21
