Revisiting the history of kuru

Tanzila Atifali Saiyed
Chernivtsi, Ukraine

 

Three kuru patients at the kuru hospital in Okapa requiring support to stand erect.
The Fore adolescent supporting the patient on the right, himself had incipient kuru
and died within one year. The other two died within six months
Courtesy of late D. Carleton Gajdusek. CC BY 3.0.

An eleven years old girl named Kigea had gradually become unsteady on her feet. She had pain in her arms, joints, and legs, and would cry and scream. She had fits of uncontrollable laughter and shaking. She belonged to the tribe of Fore (pronounced as FOR-AY) of the village called Waisa in the isolated highlands of Papua New Guinea, then officially an Australian territory. Fore had been untouched by the outside world until the 1930s and were unstudied until the 1950s, when patrol officers and anthropologists exploring the region reported noticing many ill women and children.

The symptoms of tremors, uncontrollable laughing, loss of appetite, and incoordination caused them to refer to it as psychosomatic illness. An initial tremor typically progressed to complete incapacity and death within about one year. The Fore believed kuru to be a curse and blamed sorcery for the condition; this lent itself to the name, which translates to trembling. In 1957 Dr. Carlton Gajdusek was introduced to the problem of kuru by Vincent Zigas, a district medical officer in the Fore Tribe region of Papua New Guinea. Dr. Gajdusek published the first medical description of this unique neurological disorder, which was miscast in the popular press as the “laughing sickness” because some patients displayed risus sardonicus as a symptom.

In 1961 a medical student from Adelaide, Michael Alpers, who had come came across a report of this mysterious brain disorder, secured after graduation a post of medical officer in Papua New Guinea. Once there, he teamed up with Dr. Gajdusek to study the disease.

Both Drs. Gajdusek and Alpers observed patients afflicted with kuru, starting from the initial stage until the final agonizing stages of the disease when patients died trapped inside their bodies, unable to move or communicate. Even after extensive investigation, nothing was known about the cause or pathogenesis of kuru, nor why its prevalence was localized to the Fore people. A battery of exhaustive testing had been conducted using every available methodology, but the results had proved unhelpful.

Just when they found themselves baffled by kuru, Dr. Gajdusek and Dr. Alpers learned about a neurodegenerative disease common to sheep that had been observed for over 200 years, referred to as the trembling disease by the French and as scrapie by the English. The similarities between both kuru and scrapie were striking, both in its clinical manifestations and in the microscopic sponge-like appearance, with thousands of tiny holes appearing throughout the brain. Moreover, scrapie had been proven to be transmissible and had a very long incubation period.

Provided with that information, the two researchers decided to conduct an experiment to determine if kuru could be passed on to primates. They planned to perform an autopsy on a person with kuru and incubate the pathogenic material in a chimpanzee. This took place just as Dr. Alpers first encountered Kigea, who was then going through the initial stage of kuru.

Kigea was chosen to be the brain tissue donor for the experiment. She gradually entered into a locked-in state unable to speak but otherwise completely aware. Her deterioration was drawn-out, causing her to linger on in pain and eventually die. With the consent of her family, Dr. Alpers Michael extracted a sample of Kigea’s brain, transported it to the USA, and injected it into a chimpanzee called Daisey.

Meanwhile, through the epidemiological data collected over the years with the help of anthropologist Shirley Lidenbaum, it was found that no one born after 1960 had come down with kuru. Therefore it appeared reasonable to focus on whatever change might have taken place around that time period, which led to striking epidemiological evidence. As the government had enforced a ban on the practice of cannibalism in 1959, the Fore people had stopped eating human flesh. They had engaged in cannibalism in the first place because of a complex belief system which placed importance on transumption. According to this, eating the dead was believed to incorporate their essence into living relatives. It was mostly women and children who were engaged in this practice during mortuary feasts.

Evidence of how the disease was spread came two years later when Daisey, the inoculated chimpanzee, did in fact contract kuru (as did Georgette, another inoculated chimpanzee). This discovery proved that this neurodegenerative brain disease was both infectious and transmissible, with the inherent potential to cross barriers of species as well as having a remarkably long incubation period.

It was now clear how cannibalism was responsible for the spread of the epidemic, predominantly affecting women due to their primary participation role. A crucial part of the mystery remained unsolved however: The mechanism, as the cause of the long duration of the disease was still unknown. According to oral testimony by Fore, kuru had begun to appear in their midst beginning in the 1910s. In 1970 Dr. Alpers proposed that the disease had initially spread from a single spontaneous case of Creuzfeldt-Jakob disease (CJD) – a rare but well-documented occurrence in any human population. As CJD bears strong similarities to kuru, it was reasonable for a new inoculation experiment to be conducted – and this led to the conclusion that CJD was also transmissible.

This infective agent was the first new pathogen to be discovered in over a century. It was named “unconventional virus” by Dr. Gajdusek, who received a Nobel Prize in Physiology or Medicine in 1976 for his work. He postulated that viral infection was the cause of kuru, scrapie, and Creutzfeldt-Jakob disease. In comparison to normal viruses, unconventional viruses had a long incubation period and did not cause an immune system response in the host.

In the mid 1980’s, Mad Cow Disease began to appear, also known as BSE or bovine spongiform encephalopathy. It was caused by cattle consuming meal derived from recycled cattle offal. Britons feared that eating diseased beef would see BSE spread to humans and, indeed, this was a rational fear made real in 1996 when the infection began presenting in patients as variant Creutzfeldt-Jakob Disease (vCJD). With 177 deaths confirmed in the UK, and another 52 elsewhere, it failed to reach expected epidemic proportions in part because kuru-based similarities were recognized early on.

Unlike kuru, vCJD was not just a disease of the brain and spinal cord but also present in the lymph organs, spleen, gut, and liver, indicating a possible transmission through blood transfusion or organ transplant. Stanley Prusiner won the Nobel Prize in Physiology or Medicine in 1997 for proposing an explanation of BSE and its human equivalent of CJD. He discarded the previously used “unconventional virus” title and instead coined the term prion, formed from the words proteinaceous and infectious, having in 1982 referred to a previously undescribed form of infection due to protein misfolding also known as proteopathy.

An unknown frontier surrounds prion diseases, and there is currently no cure for kuru or any prion-based disease for that matter. The effects are devastating and coupled with long incubation periods, some extending well beyond a human lifespan, helps to explain the last cases of kuru in 2003, 2005, and 2009. A hope remains, however, that cures will eventually be developed through additional findings as well as broad-spectrum experimentation.

 

Further reading

  1. Alpers, Michael P.  The epidemiology of kuru: monitoring the epidemic from its peak to its end. Philos Trans R Soc Lond B Biol Sci. 2008; 363(1510): 3707–3713.
  2. Lindenbaum, Shirley “Kuru, Prions, and Human Affairs: Thinking About Epidemics”. Annual Review of Anthropology.  2001; 30 (1): 363–385
  3. Shirley Lindenbaum (14 Apr 2015). “An annotated history of kuru”. Medicine Anthropology Theory.
  4. Whitfield, Jerome T.; Pako, Wandagi H.; Collinge, John; Alpers, Michael P. “Mortuary rites of the South Fore and kuru”. Philos Trans Royal Society B Biol Sci. 2008: 363 (1510): 3721–3724.
  5. “When People Ate People, A Strange Disease Emerged”. NPR.org. Retrieved 2018-04-08.

 


 

TANZILA ATIFALI SAIYED hails from India and is studying medicine in Ukraine. Her research interest lies in understanding the brain in its mechanical and psychological forms. She aspires to be a general surgeon and acquire a PhD in psychology.

 

Spring 2019  |  Hektorama  |  Infectious Disease