How cannibalism brought a failed entomologist and biophysicist to the Nobel Prize, that even a misunderstanding of the nature of infection can turn into a Stockholm triumph and where the discoverer of prion diseases donated his Nobel honorarium, tells the next issue of the column "How to get the Nobel Prize."
Daniel Carlton Gaidushek (Gaiduzek)
Born: September 9, 1923, Yonkers, Weschester, New York, USA.
Died: December 12, 2008, Tromsø, Norway.
1976 Nobel Prize in Physiology or Medicine (with Baruch Blamberg). The wording of the Nobel Committee: "For discoveries concerning new mechanisms of the origin and spread of infectious diseases."
In fact, the two 1976 "medical" Nobel laureates received awards for very different discoveries. As it turned out later, they even discovered different types of pathogens - our hero dealt with proteins, and his colleague, Baruch Blamberg, with the hepatitis B virus. However, both discoveries were hidden behind vague wording.
Our today's story is dedicated to the American doctor of Slovak-Hungarian origin Daniel Carlton Gaidushek (sometimes they write “Gaiduzek” or “Gaidusek”, but the Slovak surname is spelled that way). He was a pediatrician by training, a virologist by experience, and a genius by nature. But first things first.
Our hero was born into the family of the successful butcher Karl Gaidushek, a Slovak who emigrated to the United States, and Ottilia (Dobrocki) Gaidushek, the daughter of Hungarian immigrants, and was the eldest of the two sons of this couple.
At first, the mother had a huge influence on the children.
“Because of my mother's all-consuming passion for [ancient] literature and folklore, my brother and I were brought up on Homer, Hesiod, Sophocles, Plutarch and Virgil and got to know them long before we learned to read,” Carlton later recalled. However, he proved to be more resilient than his younger brother, who eventually became a poet and literary critic. Natural sciences absorbed our hero - and as a result, he often visited the Boyce Thompson Institute for the Study of Plants in Yonkers, because his aunt, entomologist Irene Dobrotsky, disappeared there.
However, biology also did not capture Gaidushek entirely - after receiving a bachelor's degree in biophysics at Harvard, he began to study medicine, receiving an MD degree in 1946.
However, Gaidushek took the first step to his success 11 years later on another continent, when he had just finished working in the laboratory of Sir McFarland Burnett in Australia. However, the history of the study of diseases that brought glory to Gaidushek began even before the birth of our hero.
Alphonse Maria Jacob
In 1920, the German neurophysiologist Hans Kreuzfeldt described a very unusual disease. It was accompanied by behavioral disorders, impaired coordination of movements and vision, epileptic seizures, and ultimately led to death. A year later, compatriot and colleague of the scientist Alphonse Jacob associated this symptomatology with lesions of the horns of the spinal cord and pyramidal system. So the world learned about spongiform encephalopathy, or Creutzfeldt (Kreuzfeldt) -Jakob disease. Or mad cow disease.
He was only 34 years old, and a vain nature sought to realize his ambitions. He just heard from his colleague that on the islands of Papua New Guinea, more precisely, on one of the high mountain slopes where the Fore tribe lived, a fierce epidemic broke out, which by that time had already killed 15,000 people, of which the overwhelming majority women and young children. For a relatively small tribe, this was a real disaster, putting it in danger of extinction.
Hand of the Fore tribe in the late stage of the Kuru
Since 1953, Vincent Zigas, an expatriate from the Baltic States, who became a district Australian doctor (then Papua New Guinea was part of Australia), already worked among them. It was he who was sent to help him and sent an adventure-thirsty young children's infectious disease specialist, whose main task was to treat syphilis and dysentery. But he wanted more - to understand what kind of mysterious disease lies under what the Aborigines of the Fore tribe called the strange word "kuru". "Kuru" translates as "shaking, shivering" or "spoilage." Another name for the disease - "laughing death" - is entirely on the conscience of the newspapermen. Of course, sometimes it is accompanied by a twitching of the head and a strange "sardonic" smile, but still the main symptom is trembling, and then death - in a year at most.
The disease spread in a non-trivial way - through ritual cannibalism. It was customary for this tribe to eat their relatives right in the course of the burial ritual - it was believed that in this way he stays with them forever and transfers his knowledge and his experience. The meat, as a rule, went to men, but women and children were left with the insides and, most importantly, the brain, for "braininess" and the development of the mind. This is how a person ate the brain of an infected or diseased kuru (not specifically choosing, of course) and became infected himself. Hence the specific gender bias.
Gaidushek could not understand what he was dealing with. He watched small emaciated children, who were overwhelmed by tremors to the point that they were exhausted and finally fell to the ground. When they died, he, sometimes getting permission to open them and even take samples of blood, internal organs and brain, carefully collected all the material evidence and sent it to the United States. There he was assisted by Igor Klatzo, a neuropathologist at the US National Institute of Nervous Diseases, who had everything necessary to solve the technical side of the issue.
It was he who was struck by the similarity of the cerebellum of the representative of the handicap, who died from kuru, with the picture of the brain affected by Creutzfeldt-Jakob disease, which he once saw in the collection of his teacher, the German neurologist Oskar Vogt. The histological preparations turned out to be so unusual (who can remain indifferent, contemplating holes in the brain, like holes in a cut of bread baked goods) that Clatzo decided to send them to the annual medical exhibition in London.
Almost immediately after the end of the exhibition, Dr. Clatzo received a message from the English veterinarian Bill Hadlow, who pointed out the similarity of the sheep brain with scrapie and the drugs it sees. To unravel the mystery of kuru, he recommended that researchers try to infect monkeys as the closest mammals to humans, which theoretically could give the necessary reaction to confirm the fact of infection.
No sooner said than done. Gaidushek begged from local residents a portion of the brain of another deceased patient and fed five chimpanzees with gruel, as well as some other animals - mice, guinea pigs, rats and even chickens. He waited two months, six months, a year for the result - Hudlow had warned of a long incubation period - but he never got anything. Not a single hint of shivering and exhaustion. Is this a genetic disease?
However, starting in 1959, the Australian authorities introduced a ban on cannibalism and began to stubbornly eradicate it, severely punishing disobedience, and from that time on, the disease suddenly subsided. Although outbreaks were then observed for another 30 years. In a fit of frankness, the natives admitted that they secretly continued to feast on the brains of the deceased, but since the 60s, cases of eating their own kind have ceased altogether. Just as little children stopped being ill.
All these facts, as well as observations of ritual ceremonies, formed in Gaidushek's head into a single picture - the disease is not the fact of eating the affected brain itself, but the fact that women do not wash their hands, with which they grind this brain and put it in portions. Pathogenic particles from them can get anywhere - in scratches, in the eyes, bites and scratches. The logical chain has closed. Without thinking twice, the researcher again organized an experiment with chimpanzees. Now lethal cerebral gruel was injected into the animals directly under the bones of the skull. It only remained to wait
And expectations were justified - after 21 months (!) One of the monkeys developed the first symptoms, and already its cerebellum served as a deadly elixir for the next generation of experimental animals. A series of successful tests ended only by 1966, but after that no one had any doubts about the infectious nature and, apparently, close to scrapie or Creutzfeldt-Jakob disease (CJD). A work worthy of a publication in Nature.
Gaidushek was able to experimentally establish the infectious nature of the disease, but he himself adhered to the "main line of the party" and believed that kuru, like CJD, the infectious nature of which he also established, was caused by some "slow viruses". After all, he was a virologist. Nevertheless, in 1976 it was for this discovery that he received the Nobel Prize (together with the discoverer of the hepatitis B virus, Baruch Blamberg). By the way, Gaidushek donated the "bonus" to the Fore tribe, but until the end of his life he did not recognize the protein nature of the infectious agent. Even the next "prion" Nobel Prize did not convince him.
In the same 60s, the next and incredibly important step towards understanding the causes of disease was made by the British radiobiologist Tivach Alper and mathematician John Stanley Griffith. They independently prophetically suggested that the mysterious pathogenic agent is too small for viruses - the dose of ionizing radiation required to destroy half of the infectious particles is too high (the smaller the object is, the less likely it is to get a charged particle into it, which means that need more particles). The conclusion suggested itself: if these are not viruses, then … proteins? And this was proved by a completely different laureate, Stanley Pruziner. But we have already talked about this.