The PRNP gene: One reason not all of us make good cannibals

original-fore-tribe-papua-kuruThe story starts in the eastern highlands of New Guinea, back in the 1940s-1950s. A fatal disease called kuru blazed through many villages, and women and children were especially affected. It started with a few months of head and body aches. This was followed by trouble standing and walking. Eventually tremors began, and sufferers lost the ability to get around entirely. Finally, euphoria set in (kuru is sometimes called the “laughing death”). By the late 1950s, more than 200 new cases a year were being reported, and, all told, over 3,000 deaths resulted (in a population that numbered only about 12,000). In some places, few young women were left.

Figuring out what was responsible for kuru was not an easy task. According to the Fore, the group hardest hit by the disease, it had first appeared in the 1920s and spread rapidly.  Researchers noticed that often multiple people in a family were affected, so they started building kuru pedigrees. Complicated genetic causes were proposed. But eventually the strange distribution of the disease (it primarily affected women and young children) shed light on the true culprit: cannibalism. When someone died (say, of kuru) the women and children in the family would prepare their body for the funeral. Part of this preparation involved eating their loved one’s body, in a feast that signified respect for the deceased. The brain, which was the most infectious body part, was eaten by women and children. And the infectious entity wasn’t a bacterium or virus. Instead, it was something entirely different: a prion, or a protein folded in a strange way. Once prions enter the body, they cause other proteins to misfold, until there are enough faulty proteins to cause real problems. The gene that encodes the prion protein is called PRNP, and changes in this gene have since been linked to other prion diseases like variant Creutzfeldt-Jakob disease (aka mad cow disease), fatal familial insomnia, and Gerstmann-Sträussler-Scheinker disease. Kuru and similar diseases are called transmissible sponge encephalopathies, because of the sponge-like effect they have on the brain (shown in the picture below).

BrainSectionsWhile nobody knows for sure how the epidemic started, the current theory is that someone among the Fore happened to develop variant Creutzfeldt-Jakob disease early in the 20th century. When his or her loved ones performed the mortuary feast, they ingested the prion and developed kuru. When they died, the chain continued, and the disease spread across the Eastern highlands. In the 1950s, the Australian government instituted strict, new laws that outlawed cannibalism. After this, the disease started to lose steam. A trickle of new cases continued to appear, however, well into the 2000s. Although the average time from participation in a fateful mortuary feast to the onset of kuru is 12 years, it turns out that the incubation time for kuru can be anywhere from 4 years to over 50! What accounts for that variation? And why did some people who participated in mortuary feasts get kuru, while others did not?

It turns out that the story is not so simple! Those early attempts to link kuru to genes were not so far off after all. At the 129th amino acid residue in the PRNP protein, people either have a methionine (M) or a valine (V). Since we all have two versions of the PRNP protein (one from mom, and one from dad), a person can either be an MM, an MV, or a VV. It turns out that being an MM makes you especially susceptible to kuru. MVs and VVs are both less likely to develop kuru AND if they do develop it, the incubation time is longer. But being an MV is the absolute best. After the kuru epidemic ended, there was a deficiency of MM individuals among the Fore, because so many of them had died of kuru. And it turns out that the finding that MM individuals are susceptible to kuru is relevant beyond New Guinea. Patients who develop variant Creutzfeldt-Jakob disease have also invariably turned out to be MMs!

In 2003, an attention-grabbing paper on the PRNP gene came out in Science. Scientists had already established that, among the Fore, MVs were the most likely to survive the kuru epidemic. When the best genotype to have is one that combines two different types of alleles, it is called balancing selection. Natural selection will often end up keeping both types of alleles in a population; the success of individuals with both versions will result in a “balance” being struck between the two. In the Science paper, a group of researchers said they had also found evidence of balancing selection in the PRNP gene worldwide. What could this mean? The authors speculated that maybe a long history of exposure to prion diseases spread from animals (like mad cow disease) could account for selection that favored MVs. Or MAYBE it was a long history of human cannibalism! This study has been a controversial one. Not everyone agrees with the way the analysis was performed, for example. But it’s pretty interesting.

In short, MMs don’t make good cannibals–or maybe even meat eaters, since they are also more susceptible to mad cow disease. As it happens, you can figure out your genotype using 23andme! If you’ve been genotyped, you can go to the browse raw data page and enter rs1799990It will tell you your DNA sequence at the relevant part of the gene: An “A” corresponds to the M version of the protein, and a “G” corresponds to the V version. I found out I have two As, which means I’m an MM. I’m not cut out to be a cannibal, and maybe I should consider becoming a vegetarian too! That’s the breaks, I guess.

Human sacrifice: how did becoming part of the Inca empire change things?

HUACA CHOTUNA 005AI was looking through the May issue of American Journal of Physical Anthropology, when I came across an intriguing title: The variable roads to sacrifice: Isotopic investigations of human remains from Chotuna-Huaca de los Sacrificios, Lambayeque, Peru. Even better, when I glanced at who wrote it, I learned that it was a former lab-mate of mine, Beth Turner!

Human sacrifice was practiced in some pre-Columbian cultures in the Andes. But the nature of human sacrifice varied based on time and place.  Early on, in the Moche culture of Northern Peru, the victim was typically dispatched by throat-slitting, and later on chest mutilation (evidently to remove the heart) became important too. Usually, the victims were youngish-to-middle aged adult males who were probably warriors. Whether they were foreign or local is a matter of some debate. On the one hand, some researchers believe that features of their teeth suggest that they were from some other location. This, paired with the fact that a lot of them had what appeared to be battle injuries, led them to believe that they could be war captives. On the other hand, analyses of things like mtDNA, archaeological context, and stable oxygen isotope values indicated that the victims WERE local, and the Moche were sacrificing one another.

Whether the Moche victims were local or not, it’s clear that the Inca culture, which rose to power later in the South Central highlands, did things differently. They focused on juveniles and young adult female victims. They also drew their victims from other locations–apparently, being especially beautiful could make you a prime target, and having someone chosen from your community could be viewed as a sort of honor by subject groups. Once selected, victims were celebrated at ceremonial rituals and feasts in Cusco before being sent to the sacrifice. By measuring stable isotopes in their remains, researchers can actually detect a shift from a commoners’ diet (prior to being selected as a victim) to an elite diet. And this change in diet sometimes started as much as a year before death. Even if it was viewed as an honor, it doesn’t seem like the awareness that you are being fattened up–like Hansel in the fairy tale, only for much longer–could have been very pleasant.

Turner and colleagues got the opportunity to study human sacrifice at Lambayeque, an important political/religious site in northern coastal Peru. This site is particularly interesting, because during the period they studied, different cultures were meeting there. The Inca had recently gained control. The remains of 33 sacrificial victims were unearthed from this period (they’re shown in the picture above, taken by Miguel Mejia), and they were unusual for this area in that they were primarily young and female. This emphasis seemed Inca-like. Other features of their sacrifice seemed Moche-like, though. They exhibited a variety of traumatic injuries that included throat slitting and chest opening. And evidence of flies around the remains of the victims suggested that their bodies were allowed to decompose/dessicate for about a month prior to being interred (also normal for Northern Peru). So what was going on here? Did the emphasis on young and female victims indicate that the Inca takeover changed the way that sacrifice was performed? If so, did that mean that Lambayeque began to draw its victims from other places, preparing them ahead of time for the sacrifice?

In order to answer these questions, Turner took rib samples and, where possible, hair samples from the remains and used them to perform stable isotope analysis. Their results suggested that the individuals had eaten a varied but typical coastal diet. Unlike the typical Inca victims, there was no evidence that their diet changed significantly prior to the time of death. There was also no indication that the Lambayeque victims came from anywhere but in the region. Given the stable isotope data, Turner and colleagues hypothesized that even though the site was under Inca rule, many local sacrificial customs may have remained in place. The individuals selected for sacrifice may have reflected Inca ideas about ideal victims, but the method of killing (throat slitting and chest opening), as well as the way that the bodies were treated after death, had deep roots in the area. And, in Lambayeque, it doesn’t appear that the victims were chosen from a distant locale and prepared for sacrifice a year ahead of time, Inca-style.

I think we’re all used to reading about how the confluence of cultures has affected daily life in different locations. But I’d never thought about how the logistics of something like human sacrifice would be affected by being absorbed into an empire. This was a gruesome but very interesting read!

The zombies of Haiti: horror story or Hallmark Special?

zombieWoken by fireworks in the middle of the night for the umpteenth time this year, I remembered The Serpent and the Rainbow by Wade Davis. Davis, who studied zombification in Haiti, believed that turning people into zombies served as a sort of release valve for communities. Is there some jerk in the neighborhood making everyone’s life miserable? Get some zombie poison! After being zombified, the troublemaker will find himself on the other side of the island, where he will labor away on a zombie farm. Translated into Manhattan terms, if I turned my fireworks-loving neighbor into a zombie, he might wake up on the Lower East side and find himself slinging lattés at Starbucks for a few years until I released him, hopefully having learned a lesson. It seemed like a good solution. Then I stopped to wonder: what ABOUT all that zombie stuff in the The Serpent and the Rainbow? Could any of it possibly be true?

Here is the back story. Wade Davis is an anthropologist interested in ethnobotany. At Harvard, he studied under Richard Evans Schultes, rain forest explorer and photographer extraordinaire. Davis has spent his career exploring the medicinal plant use of indigenous cultures. Back in the early 1980s, Davis stumbled onto the world’s best dissertation project: go to Haiti and bring back some zombie poison. There had been rumors for years that zombification might have a pharmacological basis, and he wanted to figure out if there was any truth to this claim.

Studying zombification is not easy, especially since it’s against the law in Haiti (Article 246 of the Penal Code). But Wade managed to collect zombie poison from four different voodoo sorcerers on the island, and found a few consistent ingredients. One of them was puffer fish, which contains tetrodotoxins, neurotoxins that can cause a temporary death-like state. So, potentially, an irate neighborhood or unhappy family member could dose someone with zombie poison, and everyone would think they were dead. After the funeral and the burial–in the dead of night–the zombie-maker would dig up the victim, before they woke from their tetrodotoxin-induced sleep. At that point, the poor slob would be drugged with still other concoctions, to keep them in a compliant, zombie-like state.

Of course a claim like this is bound to draw a lot of attention. Other scientists had many questions. Were the biochemical tests done in a way that could distinguish between active and inactive forms of the puffer fish poison? Were the levels of tetrodotoxin sufficient to actually poison someone? Wasn’t it wrong for Wade to help dig up the remains of a recently buried child in order to get the materials for the zombie poison? (That was part of the book.) Words were said. Critics C.Y. Kao and T. Yasumoto, who found only insignificant traces of tetrodotoxin in the samples Wade sent them, said: “We hold firmly that science done without a moral and ethical foundation can never be more than a mockery of science. And that, in our view, is what [Davis] and [his collaborators] really are.” And Davis accused them of “old-fashioned jealousy.”

In 1997, what has got to be the most interesting paper ever to grace the pages of the Lancet appeared: Clinical findings in three cases of zombification. First, the authors estimated that roughly 1,000 cases of zombification are reported in Haiti every year. I am not making this up. Then, they moved on to their findings. They had identified three Haitians whom family members said were zombies–that is, these people had fallen ill and been buried by their families, only to reappear months or years later, wandering around in a zombie-like state. The researchers listened to the families’ stories, interviewed the putative zombies, performed physical exams, and ended by performing DNA tests. The first woman they examined appeared to have catatonic schizophrenia, and her appearance was quite different than that evident in before-death photos. No DNA tests were performed in her case. The second zombie was a young man in his 20s, said to have been turned into a zombie by a jealous uncle (who was sentenced to life imprisonment for this crime). The researchers diagnosed him with cognitive impairment and epilepsy; DNA tests demonstrated that he was not related to the couple who was convinced he was their son. The last case involved a young woman who had died and then disappeared for over ten years before being found. After leading researchers to the area where she said she had been kept as a zombie for all that time, the villagers there recognized her as a local who had gone missing. And DNA tests showed she was not related to the family who had claimed her as their zombie daughter. Like the young man, this woman appeared to have some sort of cognitive impairment, possibly due to fetal alcohol syndrome.

Based on this case series, the authors concluded that what was probably going on was less mysterious and exciting than the widespread creation of zombies with voodoo poison. The zombies they studied appeared to be young people with psychiatric disorders who were adopted by bereaved families. Mistaken identity, rather than voodoo, seemed to be the culprit. These scientists also pointed out that it seems a little incredible that secret zombie farms could go undetected for long in a place as crowded as Haiti.

So, yes, science kind of ruined a great zombie story. But even if zombies aren’t being created using voodoo poison, something fascinating is going on here. The zombie myth persists in Haiti for a reason. The three people studied in the Lancet article (and others who have been identified over the years) acquiesced to living with strangers who considered them zombies. That’s pretty interesting in its own right! And their adopted families chose to overlook the many differences between their new zombie children and their deceased loved ones. The zombies were filling a need. It makes you wonder if something that began as a horror story could actually be a heartwarming (if bizarre) tale about people opening their homes and hearts to some of society’s most vulnerable individuals. It seems like the Lancet research supports a kinder, gentler take on zombies.

Noble Savages: My Life Among Two Dangerous Tribes

imagesI started grad school around the same time that Darkness in El Dorado by Patrick Tierney came out. In this book, Tierney accused a famous anthropologist, Napoleon Chagnon, of doing some terrible things during his fieldwork among the Yanamamo, a group living in the Venezuelan Amazon. My graduate advisor was in the Anthropology department, and the scandal was a big deal in the field. It was impossible not to be fascinated by the whole thing. As a naive 22 year old, the wild accusations that Tierney made somehow seemed reasonable to me–even the ones of genocide. In grad school we all spent a lot of time thinking about the responsibilities of researchers to the people they study, and the accusations Tierney made against Chagnon seemed to fit into a long history of people from high-income places using and abusing people from low-income places. Frankly, I feel pretty guilty about giving this book the time of day.

Chagnon wasn’t the only one Tierney accused of doing terrible things to the Yanomamo in the name of science. James Neel was a famous geneticist with whom Chagnon worked, and Tierney leveled many of the same claims against him. In particular, Tierney accused Chagnon and Neel of setting loose a measles virus among the Yanomamo in order to document its effect in an immunologically naive population. It’s pretty instructive  to compare the way that the genetics community responded to the accusations against Neel and the way that anthropologists responded to the accusations against Chagnon. Both the American Anthropological Association (AAA) and the American Society of Human Genetics (ASHG) launched investigations into Tierney’s claims. By January of 2002, the ASHG had published their findings, which amounted to a spirited defense of Neel. They stated “The ASHG inquiry finds these allegations to be gross mispresentations and basically false. This commentary represents the response of the ASHG to the various charges against a major, widely honored figure…” They also had choice words for anthropologists Terence Turner and Leslie Spondel, who had widely circulated Tierney’s claims as truth even before his book’s publication, as well as the media coverage that ensued: “These two individuals showed a lack of judgment in propagating these allegations without some effort to ascertain their truth. We deplore their lack of objectivity in accepting as fact statements that, on investigation, can be shown to be false, resulting in severe damage to the reputation of a leading and highly respected human geneticist who was unable to defend himself. We also condemn the actions of certain newspapers and magazines, particularly The New Yorker (usually known for meticulous fact checking), The Guardian, and The Guardian Weekly, that repeated these allegations, now shown to be false, and thus ensured their widest circulation.” By contrast, the AAA didn’t exonerate Chagnon until 2005– and only after they had aided in ruining the poor guy’s life. Alice Dreger, a historian, studied the AAA’s handling of the Darkness in El Dorado scandal and concluded: “While the [AAA’s] Peacock and the Task Force Reports contain some critiques of Tierney, both explicitly took Tierney’s book as the roadmap to follow for further inquiries. Both even essentially thanked Tierney on behalf of anthropologists. The Peacock Commission concluded this: “Patrick Tierney’s provocative book, Darkness in El Dorado, has contributed a valuable service to our discipline” (Peacock et al. 2001). The Task Force later concluded this: “Darkness in El Dorado has served anthropology well” (AAA 2002a:9). No other scholarly organization treated Tierney’s house of cards as constituting a valuable service to their discipline.”

It’s also interesting to delve a little into Tierney’s background. In order for such dramatic accusations to be taken so seriously, this guy must have serious reporting chops, right? An impressive history of investigative reporting? Nope. Prior to Darkness in El Dorado, he’d written a single book, The Highest Altar: Unveiling the Mystery of Human Sacrifice, which is now out of print. And Dreger reports that although Tierney provided copious notes in Darkness in El Dorado, “many of Tierney’s hundreds of citations lead nowhere. Others essentially say the opposite of what is claimed.” The fact that this book was taken seriously by a number of prominent anthropologists, reported on widely in the media, and even named a finalist for the National Book Award is pretty scary.

Now, in Noble Savages: My Life Among Two Dangerous Tribes, Chagnon finally gets the chance to tell his story. And not surprisingly, he is pretty pissed off. The book deals with both his work among the Yanamomo and his trials and tribulations at the hands of his colleagues in Anthropology. There have been a lot of high profile, well written reviews of Noble Savages by Charles Mann, Douglas William Hume, Rachel Newcomb, Greg Laden, and others. And if you missed the fabulous profile piece on Chagnon in the New York Times magazine by Emily Eakin, timed to coincide with the book’s release, check it out. I thought Noble Savages made for really interesting reading. Despite all the hoopla surrounding Darkness in El Dorado, I’d never really learned much about Chagnon’s findings, and this was a great introduction to his work.images-1

The controversy, of course, isn’t over. Marshall Sahlins recently resigned from the National Academy of Sciences in protest over Chagnon’s induction. And the response of many anthropologists to Noble Savages has been far from positive. I was surprised that some critics, like Elizabeth Povinelli, felt the way that he portrayed the Yanomamo was very negative, irresponsibly so. In her opinion, Chagnon  depicted a “hideous society” composed of “deceitful, stubborn and murderous people.”  I finished the book with a completely different assessment. I felt Chagnon’s portrayal of the Yanomamo was nuanced and pretty evenhanded. Some of the people he met in Venezuala were kind, and some were cruel, and that was true of both the Yanomamo and the non-Yanomamo with whom he interacted. Chagnon certainly didn’t sugarcoat things, but he was quick to point out all of the acts of kindness he witnessed. It seems as though some of his detractors in anthropology believe that vulnerable study subjects should only be portrayed in a flattering light. While I can understand that no one wants to write something negative about a group of people that might provide a reason for other groups to treat them badly, sacrificing honesty to avoid writing something that could be construed negatively doesn’t seem very respectful to the people with whom you’re working. No self-respecting reporter covering a story in the United States, for example, would decide to depict his or her subjects in a wholly positive light prior to even beginning their investigation. If we treat the people we study differently than we expect to be treated ourselves, it seems as though we are automatically turning them into “others.” Whether anthropologists are studying workers at the World Bank or people living in some remote region of the Amazon, their research involves the study of other human beings. And humans deserve to be treated as individuals. Portraying whole groups of people as uniformly “good” or uniformly “bad” plays into stereotypes–which isn’t helpful to anyone involved and certainly isn’t scientific.

I guess if anything positive has come out of this decade-long saga, it is that it has thrown into relief some of the schisms inside Anthropology. Perhaps bringing these different approaches to ethnography into the light will lead to some fruitful debates. I haven’t seen much evidence of that so far, though. Chagnon’s book has also led to some interesting considerations of his actual work. After gathering data for decades, he has drawn some fascinating and controversial conclusions about the motivation for violence in human societies, and engaging with his hypotheses in a scientific way is important. I can’t imagine this mess has improved anyone’s perception of Anthropology, though, and I doubt many anthropologists feel they can count on support from the AAA if they find themselves unfairly accused of something. And that’s a shame.