Doctors thought they knew what was killing the family. Diagnoses ranged from “nervous gastric fever” to meningitis, presenile dementia, ictus and alcoholic encephalopathy. Yet this was all speculation, a grasping-about in the dark.

The modern era of prion research began on the morning of March 8, 1957, when 33-year-old pediatrician Carleton Gajdusek from Yonkers, N.Y. appeared in the office of the public health director in Port Moresby, New Guinea. Gajdusek had chosen Port Moresby as the entry point for a multinational study of child development, but what he learned from the director changed his life.

In the early 1950s Australian officials had discovered that members of the Fore tribe, in New Guinea’s remote Eastern Highlands, were being stricken with a mysterious ailment. The Fore thought that sufferers of the disease, whose chief symptom was uncontrollable laughter, were under a spell, and they called the sorcery that afflicted these shivering victims kuru (“shaking”).

Gajdusek, who had trained at Harvard Medical School and the California Institute of Technology, took a more scientific approach, investigating everything the Fore ate, drank and touched. He suspected the smoke in their huts and the copper in their water. He sent patients to Port Moresby and brain tissue to a top laboratory in Melbourne, Australia and to the National Institutes of Health (NIH) in Bethesda, Md. for pathology studies.

Melbourne saw nothing wrong with the tissue Gajdusek had sent, but the NIH was more thorough. What they saw was eye-opening: “very spectacular neuronophagia…very intense gliosis…striking changes affecting Purkinje cells…and bizarre deformities of Purkinje-cell dendrites,” in the words of pathologist Igor Klatzo, who studied them. Klatzo also noted that the disease reminded him of one “described by Jakob and Creutzfeldt” in the 1920s that struck a handful of elderly people, leaving holes in their brains.

Gajdusek never did discover how the Fore were getting kuru. In the early 1960s the anthropologist Shirley Glasse and her husband Robert would trace it to mortuary cannibalism. But by that time Gajdusek had left the Fore region for the NIH to continue working on the disease. Gajdusek thought the disease was hereditary, but he was not sure. Then in 1959 he got some important new information.

An American veterinary pathologist working in England named William Hadlow happened to see an exhibit on kuru at the Wellcome Medical Museum in London that included photographs of the victims’ brains. He felt as if he were seeing the same scrapie slides he had in his lab and wrote a note to the Lancet, the British medical journal, about the coincidence. He also sent a copy of his letter to Gajdusek.

Two things were known about scrapie by then: It could be transmitted, and it took a long time for the symptoms to show up. Those findings gave Gajdusek a clue. He threw himself into trying to prove that kuru was infectious, injecting homogenate made from the brains of kuru victims into everything from mice to hamsters to chimpanzees. Finally, in June 1965, Georgette, one of the chimps who had been injected with kuru tissue 21 months before, began to show the signs, “dragging herself around, shaking, looking for all the world like a kuru patient,” in the words of Michael Alpers, the head of the research program. After the chimp died, Gajdusek asked a British pathologist expert in scrapie to examine the chimp’s brain. What the pathologist saw reminded her of what she had seen in kuru victims. The chimp appeared to have died of the disease that killed the Fore. It was a moment of triumph for Gajdusek and his lab. Here was proof that kuru was an infectious disease, though Gajdusek had no idea what the nature of the infection was—bacterium, virus, protozoan or some other infectious agent.

Gajdusek was intrigued by Klatzo’s comparison of kuru to CJD, so he began inoculating healthy chimps with tissue from sufferers of CJD as well. Ultimately, these chimps also grew sick. When the animals died, pathologists examined their brains and saw that the sponginess and the holes resembled those of both kuru and scrapie victims.

One, as the saying goes, was a novelty; two was a coincidence; three—scrapie, kuru, CJD—was a theory. These long-ignored diseases, Gajdusek declared in the late 1960s, shared a cause, some sort of hard-to-destroy, slow-acting virus. The key sticking point was the word virus. Viruses are essentially bits of nucleic acid covered by protein; they insert themselves into cells and trick the cell’s reproductive apparatus into copying them. They generally provoke an immune reaction in their unwilling host, and it is these reactions that usually reveal the strain of the virus. Though they are not technically alive, viruses do contain bits of DNA or RNA, so they can be deactivated by the same techniques that kill living things—everything from washing with soap and water to heating to irradiation. And most viruses, once they are removed from the cell that they are parasitizing, die on their own, often in a few hours.