The Hidden Health Benefits of Cannibalism?

Kuru, prion diseases and the genetic imprint of eating people

Nobody will tell you this, but eating people is good for you. Let me clarify, eating people is good for your descendants and great-grandchildren. I suspect you’re sceptical of this proposition, so I shall lay out for you the hidden secrets of cannibalism through its most infamous story, the outbreak of the terrifying disease - kuru - in 1950’s Papua New Guinea. This event was a pivotal moment in the history of medicine, allowing researchers to identify for the first time what is still a baffling and murky biological phenomenon, the destruction of the human brain through a ‘contagious’ misfolded protein - a prion. This naturally took the limelight, but underneath the surface there is another story, only recently teased out, that prions and cannibalism have a special place in evolutionary history. We may soon discover through the power of genetics, that your innate protection against prions depends on your ancestors having eaten people many millennia ago…

Kuru, a History

During the Second World War Papua New Guinea (PNG) found itself being used as a battleground between numerous foreign powers. Japanese forces were painfully slowed down and then pushed back through a combination of local recruits, Australian reservists and American firepower. The Papuan ‘Green Shadow’ infantry slugged it out in the hot, sticky jungles, and it may be the first time in history that Papuans, Japanese Ainu, Torres Islanders and Aboriginal Australians were in all combat together at the same time.

After the war PNG became part of an extended Australian administrative territory, until its independence in 1972. During that time Australian officials and bureaucrats found themselves facing the daunting task of governing a country with hundreds of languages and a landscape so extreme that many valleys had isolated tribes from one another for millennia, if not longer. One such place was the Eastern Highlands, a region of forest inhabited by horticulturalists such as the Auiana, Awa, Usurufa, Kanite, Keiagana, Iate, Kamano and Fore. The Fore live in the Okapa District, and had been sheltered from the outside world until the 1950’s, when Australian officials and missionaries began to appear, looking for people for the census and souls to be saved.

Taken from Kuru Sorcery Disease and Danger in the New Guinea Highlands (2016) Shirley Lindenbaum

The Fore, like many Highlander Papuans, live in patrilineal clans and practice a form of slash-and-burn horticultural farming. Pigs, taro, insects, wild game, fruits, edible plants and sugarcane are all raised, hunted and foraged. They occasionally made war on their neighbours and believed in the animistic power of the forest. They also ate their dead in communal mortuary feasts. For the Fore, a person had many types of soul - one type that needed to be carefully ushered into the next world, another that passed on their qualities to their kin, another that contained the power of the ancestors and so on. A person also had a polluting, corrupting power, especially in death. For this reason a person’s body needed to be cooked and consumed to cordon off the kwela, the damaging aspect of their soul.

Endocannibalism (the eating of relatives) was a component of South Fore mourning rituals, in contrast to exocannibalism (the eating of enemies), which was practiced in the north, the difference having consequences for the transmission of the disease. By the 1950s, cannibalism ceased in the North Fore, but was still practiced surreptitiously in the south, where the South Fore said that they continued to hide and eat deceased kin throughout the 1950s.

When a body was considered for human consumption, none of it was discarded, except the gall bladder, which was considered too bitter. In the deceased person’s old sugarcane garden, maternal kin dismembered the corpse. They first removed the hands and feet, then cut open the arms and legs to strip the muscles. Opening the chest and belly they avoided the gall bladder. They next severed the head, fracturing the skull to remove the brain. Meat, viscera, and brain were all eaten. Marrow was sucked from cracked bones, and sometimes the pulverized bones were cooked and eaten with green vegetables.

-Kuru, the First Human Prion Disease (2019) Paweł P. Liberski et al.

Crucially the division of the body between family members was not random. The woman and children ate the brain, whilst adult males often refused to partake or only ate the muscle meat. This was to have long term consequences. As found in many peoples around the world, Fore women were given the lowest quality protein, whilst the men ate the best of the pigs and wild boar. For this reason, protein shortage drove the consumption of the dead, and Fore men tended to view cannibalism as part of the domestic-reproductive-childish milieu from which a boy is supposed to grow out of and leave behind him.

Since the early 1900’s a strange supernatural-like affliction had been slowly spreading through the valley towards the Fore. It appeared first in the Keiagana Uwami village and then moved across the river into the territory of the northern Fore. From there it branched outwards amongst all Fore-speaking peoples, prompting an epidemic of accusations - sorcerers were attacking people with a new form of evil magic. It manifested first as joint pain, fever, chills and an uncontrollable shaking and trembling. The earliest Fore histories of the disease note that they initially found it funny, nicknaming sufferers ‘negi nagi’ or ‘foolish people’. Since the victims would shiver like a tree frond or cassowary feather, they called it ‘kuria’ - ‘to shake’. The first kuru victims were mostly women, and as they struggled to walk with jerking limbs and spasming legs, men would amuse themselves by sexually assaulting them. But it didn’t take long before the Fore realised this magic only led in one direction, to the grave.

The first Australians to come across the disease were patrol officers from the Department of Native Affairs in 1951. Part of their remit was to stamp out these mortuary feasts, but with such a massive territory to cover the Fore simply practiced them in secret. Doctors began to note the symptoms of kuru immediately, with a tentative diagnosis of encephalitis arriving in 1955. But what was initially a curiosity was soon to turn into a medical horror show. Between 1957 and 1977 around 2,500 Fore died of kuru, mostly women. For a population of no more than 20,000 this was not a trivial matter. The sex ratio rapidly began to skew out of control - 1:1.6 women to men, then 1:2, and even 1:3. Male Fore were forced to become women, to take on household tasks, to care for infants. The traditional practices of Big Men taking several wives had to cease, and everybody knew somebody who had died of the disease.

The medical profession was stumped. Kuru acted like a contagious virus, but it didn’t pass from mother to child, it killed far more women than men, and the symptoms were consistent but slowly accumulative. First the patient struggled to walk, then they struggled to sit up, and then they became helpless - a immobile, twitching being whose muscles wasted away and would randomly grasp things or be unable to open their mouths. Most unnervingly many kuru patients would laugh uncontrollably for no reason, as if gripped by a spell or possessed by a demon. The Fore blamed witchcraft, as did their neighbours. The Fore had a reputation for being powerful magicians and sorcerers, and kuru only added to this. Government patrols at the time noted that Fore villages were silent after dark, with households barricading up their doors. Kuru sorcerers were believed to gather material belonging to the victim and put it in a kuru-bag. Fingernails, hair, excrement, old sweet potato skins, anything could be a vector for attack, so everything became locked down as kuru continued to spread.

The Mysterious World of Prions

For Drs Daniel Gajdusek and Vincent Zigas, the world of disease had three agents - bacteria, viruses and genetics. When they began work on the problem of kuru in the 1950’s they faced a major problem, the disease didn’t fit any known pattern. In 1957 the two of them published a report in the Medical Journal of Australia linking kuru to Parkinson’s disease and other slow degenerative disorders, suggesting that they have a genetic origin. Then an unbelievable thing happened:

No new childhood kuru cases were reported for the cohort born after 1957-1960

A disease which appeared amongst only a certain group of language speakers, that primarily targeted women and children, and that disappeared around the same time as cannibalistic mortuary feasts were banned pointed to an infection. In 1959 Gajdusek then received a letter from a Montanan veterinary pathologist, William Hadlow, then at the Rocky Mountain Laboratory. In it Hadlow pointed out to Gajdusek that kuru looked very similar to a condition found in sheep called ‘scrapie’, which also caused a wasting neurological decay in the animal. He urged Gajdusek to try inoculating animals with brain material from kuru victims, which he duly did. Back in the United States, he and his team managed to introduce infectious brain matter from several kuru victims into two chimpanzees. Several years later they were flabbergasted to observe the poor animals starting to shake uncontrollably. Soon hundreds of animals were playing host to whatever killed off the women of the Fore, and one by one spider monkeys and goats and gibbons and baboons in laboratories around the world succumbed to the tremors and twitches of kuru.

Gajdusek won a Nobel Prize for this work, since he had discovered an entirely new kind of disease. Over a decade later the race to identify whatever it was finally arrived on an answer - the culprit was a protein, a protein which acted like an infection - a prion.

Prions defy much of what we understand about biology, and about disease. Proteins are made up of amino acids, the sequence of which is coded for in the DNA, and they fold into a 3D structure to perform their job. Typically a protein is produced for some purpose, lets say an enzyme, and is then broken down by other proteins when it is finished. Prions do not behave like that, instead prions are both resistant to being broken down, and also force other proteins to change their structure and become new self-replicating prions. As these misfolded proteins begin to accumulate they form fibrous bundles outside of the cell, eventually creating plaques which lead to holes in the brain. This happens slowly over many years, accounting for the progressive nature of kuru and other prion diseases. There is no stopping it once the process begins, and there is no cure.

The protein responsible for doing this is called the major prion protein or PrP. This protein is found in every person, where it happily goes about its life, performing whatever unknown function it does without an issue. However, this protein can also misfold into the wrong shape, and when it does it starts replicating this incorrect shape by making other PrP proteins fold incorrectly. Nobody knows exactly how this happens, although several theories exist. The incubation period for prion diseases make understanding the causes difficult, it can take up to 50 years for the disease to show itself. PrP can misfold into a pathogenic prion spontaneously (1 in a million people), a genetic mutation can run in families, it can be introduced accidently by doctors (iatrogenic) or it the protein can be ingested from the environment, usually from infected meat.

Only a handful of prions have been identified, along with their corresponding diseases. Some animals also suffer from prion infections, most famously ‘mad cow disease’ or bovine spongiform encephalopathy. Deer can contract ‘chronic wasting disease’, which is a serious problem in many parts of the world, since the prions seem to be accumulating in the environment:

Since CWD-prions have been shown to persist in the environment it is postulated that a decaying CWD-positive carcass could saturate the environment with PrP(RES) which could then be taken up into plants as growth of new flora occurs. An experimental study contaminated soil with Scrapie adapted hamster brain homogenate and grew Barley plants (Hordeum vulgare) in the contaminated soil and then analyzed various tissues with sPMCA. They found PrP(RES) in the stem and leaves of plants grown in contaminated soil for three-weeks indicating that uptake of PrP(RES) can occur (Pritzkow et al., 2015). Another study also used wheat plants ability to transport both PrPC and PrP(RES) and their reported findings show detection of PrPC and PrP(RES) in the root tissues of the plants.

-The role of plants as an environmental reservoir of chronic wasting disease prions (2016) Aimee Elise Ortega

Human prion diseases include Creutzfeldt–Jakob disease (CJD), fatal familial insomnia and a few others. It is hard to overstate how difficult it is to destroy prion proteins once they misfold. Researchers like Stanley Prusiner struggled to reconcile theory and evidence when looking for the culprit of these diseases. They subjected scrapie infected sheep brain to chloroform, radiation, intensive heat, freezing and degrading chemicals - but nothing worked - prompting him to write:

The idea that scrapie prions were composed of an amyloidogenic protein was truly heretical when it was introduced… One scientific theory, viewed as heretical in that it seems to challenge the role of nucleic acids as the exclusive carriers of genetic information… a deadly variety of a normal protein that has the ability to amplify itself in the brain. The hypothetical protein is called a prion (pronounced PREE-on).

Scientists in Iceland were mystified when they buried infected tissue underground for years, came back and found the prions were still active and dangerous. Preventing the build-up of lethal prions in the deer forests of the world is going to be an enormous challenge.

Health notice in British Columbia regarding Chronic Wasting Disease

Resisting Prions, Prehistoric Feasts

As dark as that sounds, its not all doom and gloom. Even as Australian doctors struggled to make sense of the villages emptied of their young women they also noticed something - not everyone caught the disease. Many years later geneticists and researchers studying the Fore observed a clear pattern - elderly women had a slightly different genetic profile to the men, and both had something unusual going on compared to the rest of the world.

The prion protein is coded for by a gene called PRNP. This gene has been heavily scrutinised for the past 30 years, and good detailed reviews are available for those interested in the details. For our story we are concerned with a particular mutation of the PRNP gene. Mutations in nature are rare and typically deleterious or have little to no effect - the cell has a number of mechanism to proofread and correct mutations, and certain areas of genes are heavily targeted during natural selection. To simplify things down: genes are made up of the four DNA bases, which are laid out in a sequence to code for 22 amino acids. DNA bases are read in groups of three. A number of mutations can occur, including inserting new code, deletions and substitutions.

Types of DNA mutations

The prion protein gene PRNP has a well known sequence known as ‘codon 129’. This little triplet of DNA seems to regularly suffer what is known as polymorphisms, that is to say, mutations that change the resulting amino acid are common at exactly this point in the DNA sequence. An example of this is the shift between two amino acids - methionine and valine. You may think this is splitting hairs or being overly technical, but the difference between these polymorphisms is life and death.

We know that everyone receives two sets of DNA, one from each parent. Hence, any mutations which appear at the same place on one set but not the other is called heterozygous, whereas a person born with two mutations at the same location is homozygous for that mutation. In a few rare instances it can be advantageous to be a heterozygote for certain conditions, most famously sickle cell disease. A person with two sickle cell genes will suffer, a person with one copy of the gene has an advantage under the impact of malaria. And so it was for the Fore of Papua New Guinea - those who possessed one copy of the codon 129 polymorphism were more likely to survive consuming infected brain tissue. Those who were homozygous succumbed to the kuru prion and died.

The practice of endocannibalism underlying the kuru epidemic created a selective pressure on the prion protein genotype. As in CJD, homozygosity at codon 129 (129 Met Met or 129 Val Val) [Met = methionine, Val = valine] is overrepresented in kuru. Furthermore, Mead et al. found that, among Fore women over fifty years of age, there is a remarkable overrepresentation of heterozygosity (129 Met Val) at codon 129, which is consistent with the interpretation that 129 Met Val makes an individual resistant to prions and that such a resistance was selected by cannibalistic rites

--Kuru, the First Human Prion Disease (2019) Paweł P. Liberski et al.

Remarkably Gajdusek and his colleague had inferred this back in 1965 through simple observation, without knowing anything about prions or PRNP. As they wrote:

In order to explain the combination of high incidence and high lethality, which at first glance might seem to entirely rule out a genetic cause unless there was an immense heterozygote advantage, we postulated that environmental change, of relatively recent origin, has given a lethal expression to a previously benign gene mutation established in the Fore population as a genetic polymorphism.

-Changing pattern of kuru: Epidemiological changes in the period of increasing contact of the Fore people with western civilization (1965) Alpers, M.P.; Gajdusek, D.C.

In layman’s terms we have here a singularly strange phenomenon: eating infected brain tissue made the next generation more resistant to that same infection. By killing off all those with the same two mutations, and allowing those with different mutations to live, the kuru outbreak made it less likely that the Fore people would die from future prion epidemics.

Our results suggest that kuru may have imposed short-term balancing selection pressure on humans, where a fitness advantage for heterozygosity caused an increase in the frequency of heterozygotes in the population during the kuru epidemic. Although genome scans have indicated numerous potential targets of balancing selection, there are only a few examples of balancing selection imposed by a known pathogen in humans, including the major histocompatibility complex/human leucocyte antigen locus, the b-haemoglobin locus and the G6PD locus.

-Epidemiological mechanisms of genetic resistance to kuru (2013) Katherine E. Atkins et al.

A few sharp-eyed researchers have realised, looking at this data, that kuru was not humanity’s first encounter with cannibalistic prion diseases. In fact several papers now have assessed global PRNP mutations and differences, and found some striking patterns. These include very strong signals of 129 Val in both the Eastern Papuan Highlands and in some Native American groups, a cline of 129 Val from Europe to Asia and many interesting mutations found in India, Japan and parts of Africa. The conclusion to be drawn from this is that instances of prehistoric cannibalism almost certainly led to kuru-like scenarios, pushing whole populations towards heterozygosity and introducing many variants of the PRNP gene into the global human genome.

Going one step further, some have even tried to link such an epidemic to the demise of the Neanderthals, who almost certainly practiced cannibalism at some times and places:

Because of this 129^{Met Val} heterozygote advantage, it has been suggested that the heterozygous genotype at codon 129 has been sustained by a widespread ancient practice of human cannibalism [159]. Furthermore, there is a hypothesis that extinction of Neanderthals co-existed with Homo sapiens some 45,000 to 30,000 years ago is connected to the appearance of “Kuru-like” epidemics spread by cannibalism [160,161]. Collinge et al. [120] suggested that the survival advantage of the PRNP 129^{Met Met} heterozygotes provides a basis for a selection pressure not only in Fore but also in those human populations that practiced cannibalism.

-Kuru: A Journey Back in Time from Papua New Guinea to the Neanderthals’ Extinction (2013) P.P. Liberski

Concluding Thoughts

Hopefully I have convinced you dear reader of my opening argument, that cannibalism is good for your offspring. From a group survival standpoint the promotion of protective mutations is beneficial, and our genome likely bears out the scars of those instances where prions may have killed off a significant number from small hunter-gatherer tribes. The story of kuru and its legacy is fascinating, since it opened up an entirely new kind of biology hitherto unknown and unimaginable. Medicine would not be the same today if the Fore people of one of the world’s most remote regions had not eaten their dead, and if WW2 had not brought together western science and Papuan mortuary traditions. Prions continue to be a problem, and degenerative diseases such as Alzheimer’s are ultimately derived from the same biological mechanisms. Our knowledge of kuru has likely sped up the development of cures for these diseases by an unknown degree. Many variants of the PRNP gene are still uncharted territory, and as genetics advances in both modern and ancient populations, we may yet see all kinds of similar kuru stories reaching out to us through the language of DNA. For all we know our future health may depend on whether our Palaeolithic ancestors once ate their relatives in the depths of an ice age winter.

Further Reading:

• Naturally occurring variant of the human prion protein completely prevents prion disease (2015) Asante, E., Smidak, M., Grimshaw, A. et al. Nature 522, 478–481). https://doi.org/10.1038/nature14510

• Genetic susceptibility, evolution and the kuru epidemic (2008) Simon Mead et al. Phil. Trans. R. Soc. B (2008) 363, 3741–3746 doi:10.1098/rstb.2008.0087

• Balancing Selection at the Prion Protein Gene Consistent with Prehistoric Kuru like Epidemics (2003) Simon Mead et al. Science Vol 300, Issue 5619 pp. 640-643

  DOI: 10.1126/science.1083320

• Kuru: Genes, Cannibals and Neuropathology. (2012). Liberski et al. J Neuropathol Exp Neurol

• A history of kuru (2007). Michael Alpers.