As our lifetimes get longer and medical science’s diagnoses get more sophisticated, we end up finding new diseases (e.g cancer, Alzheimer’s, diabetes). More often than not, we are unable to treat them because they’re unlike anything we’ve ever encountered. For this reason, I probably won’t become redundant, which is nice. What’s not so nice is that we’ll probably always have the sword of Damocles hanging above our heads, just waiting to be struck down by some intractable lightning bolt. Currently, prion diseases (Bovine Spongiform Encephalopathy, variant Creutzfeldt–Jakob disease, Fatal Familial Insomnia and Kuru) are amongst the scariest.
As we’ve mentioned before, prion diseases are caused by misfolded prion protein. Prion protein is a protein produced naturally by nerve cells with no known function. Certain misfoldings of prion protein change its function: now mutated prion protein can convert normal prion protein into more mutated prion protein. Mutated prion protein builds up in the nerve cells and damages them. Depending on the misfolding, mutated prion protein produces different symptoms, which I’ll explain in the next couple of posts. First off, the incredible story of Kuru.
What really kicked the idea for this post off for me was watching Michael Alpers talk at the RiAus for the opening showing of a documentary on kuru (I highly recommend you watch it on SBSOne – Sunday, December 19 at 8:30PM). Alpers was an Adelaide medical doctor turned researcher when he heard about a “laughing disease” that was affecting the Fore people in the highlands of Papua New Guinea, then an Australian colonial outpost. What was causing this laughing disease? Why was it only the Fore people affected? This piqued his interest so much that he travelled up to PNG and lived amongst the Fore people for more than 40 years to investigate.
What Alpers found were people were men, women and children stumbling around drunkenly. Affected people would begin to uncontrollably tremble, faces locked in risus sardonicus, joints braced in pain. They would succumb to a flaccid paralysis, when their close family would feed them sugar water to desperately extend their painful existence of being locked into an unresponsive body for months. Eventually, the muscles used for breathing or digestion would be paralysed with the rest of the body and they would die from suffocation or starvation. Hundreds each year were being diagnosed with kuru (Fore for “trembling”).
What was happening? Why were these people being struck down to such a heinous state? This was first dismissed as a psychosomatic response to the colonisation and resultant banning of culutral practices, forced labor and adoption of Western customs; a hypothesis that didn’t explain why it was only restricted to the Fore people. The Fore themselves thought it was due to sorcery; a hypothesis unpalatable to science. Still, this did not prevent “retributive” murders of sorcerers by relatives of those affected by kuru. Genetic disease was ruled out because it did not fit any Mendelian pattern.
Alpers noticed that kuru was not found in anyone born after 1959, the year that colonial administration had started in the villages. But with so many changes being forced upon the Fore during this time, which one was responsible for the drop in kuru incidence? A group led by Daniel Carleton Gajdusek, with whom Alpers worked, hypothesised that ritualistic transumption was the key. The Fore believed that a person’s spirit was not freed until their body was eaten by their close relatives. While the documentary focuses in on elders who smile unnervingly while recounting the sweet taste of human flesh, it’s important to know that it was ritualistic and the entire body was eaten (sometimes with great difficulty): the meat, the skin, the bones, the faeces, and the brain.
Supporting the hypothesis that kuru was caused by a infectious agent spread by transumption, brain tissue taken from the deceased affected by kuru resembled that of scrapie-infected sheep (scrapie was an known infectious disease that affected the nerves of sheep). Scrapie had previously been shown to be transmitted by eating contaminated material.
To conclusively prove that the brain tissue indeed harboured the infectious agent, Gajdusek’s group sought to experimentally infect chimps. Alpers had followed a young girl, Kigea, since she had first shown symptoms of kuru. Knowing Kigea and her family well, he asked for permission to take a piece of brain tissue upon her death. The family allowed this. When Kigea finally succumbed, amongst the wailing and lamenting of family members, Alpers hardened his heart and got to work. He efficiently levered open Kigea’s skull, took out some brain samples and sewed her features back together. He paid his respects to the family and left.
Fighting the Nobel War
Armed with potentially infected brain material, Gajdusek and his group got to work. They experimentally infected two chimps, Georgette and Daisy, by injecting Kigea’s brain matter directly into their skulls. Within 2 years, Georgette and Daisy developed kuru-like symptoms. Post-mortem brain biopsies confirmed this. For this work, Gajdusek won the Nobel prize in 1976.
But what was the actual causative agent? Gajdusek remained steadfast that kuru and scrapie were caused by unconventional viruses, a theoretical group of viruses that didn’t cause inflammation, were not affected RNA- and DNA-destroying enyzmes, and had incubation periods of years to decades. Stan Prusiner led the opposition, stating that they were actually caused by proteins. Harsh criticisms of each other’s work (and more often than not, character) followed. Prusiner eventually showed strong evidence for the protein model in his paper “Novel proteinaceous infectious particles cause scrapie”, which eventually won him the Nobel Prize in 1997.
The year was not a good one for Gajdusek; in addition to having his scientific arse kicked convincingly, he also pleaded guilty to child molestation charges. While working in PNG, Gajdusek brought children back to America with him to give them a chance at higher education. He also had sex with some of them. Like his views on the cause of kuru, Gajdusek was stubborn in his actions, citing that man-boy sex was unremarkable in some cultures. Through plea bargaining, he was jailed for only 2 years and served out his probation in Amsterdam, where he died in 2008 from congestive heart failure.
While this was going on, kuru, while less common now, was still affecting the Fore. Elders were unconvinced or ignorant of the Nobel prizes and still believed kuru was caused by sorcery. Amongst their complaints were that if it was a sickness, why couldn’t the Westerners cure it? It was around this time that vCJD (Mad Cow disease) was plaguing Europe. So Alpers managed to bring some representative elders to England to show them the battle scientists were fighting against the ravages of another Kuru-like sickness. Alpers was unsuccessful in showing the elders any patients suffering from vCJD, but managed to gain an interview with the mother of a vCJD patient.
On the whole though, the elders remained unconvinced on their return to the PNG highlands. They returned to their villages where they still helplessly watch over their shivering dead. And despite continual hope, the truth is that Kuru will die out amongst the Fore before any cure is found.
(The documentary and discussion at the RiAus is free to download and watch on the RiAus website HERE)
D. Carleton Gajdusek – Nobel Lecture”. Nobelprize.org. 27 Nov 2010 http://nobelprize.org/nobel_prizes/medicine/laureates/1976/gajdusek-lecture.html
Prusiner, S. (1982). Novel proteinaceous infectious particles cause scrapie Science, 216 (4542), 136-144 DOI: 10.1126/science.6801762