A Disturbing History of the Discovery of the Prion Diseases
by Ignatius Vincent Trochlear
March 31, 2011
“I’m having a friend for dinner.”
-Hannibal Lector
In the Eastern highlands of New Guinea not more than 50 years ago the most common cause of death among the Fore tribe was a mysterious disease called Kuru. Like a photographer chasing the Loch Ness monster in the murky fog of northern Scotland, an adventurous biologist named Carleton Gajdusek visited obscure corners of the planet tracking down mysterious diseases. In addition to fulfilling his own perverse desires, finding a novel disease was an obsession for Gajdusek. He worked in India, South America, Malaysia and the Middle East in his search. While in Australia studying genetics in aboriginal children he received a tip about what appeared to be a strange neurological disease just north in New Guinea. When he reached the Fore people, besides discovering a new disease, he noticed something else about them – they celebrated a person's life after they died....by consuming their brain (Simmons 2002). They practiced ritualistic cannibalism. I suppose they didn’t enjoy it – the meal occurred at the person’s funeral (Glasse 1968). Unless they disliked the person so much they derived macabre pleasure from munching on them. But even then I think it would take a lot of garlic and black pepper to enjoy it. I don’t know if you’ve ever had venison or moose but human has to be gamier than that.
They weren’t insatiable cannibals like Leatherface and his maniacal family in The Texas Chainsaw Massacre. But I doubt these were your happy hobbits of middle earth. They only used stone tools then. Now I’m sure the have TV and the Internet. They probably watch Lost. But in the 1950s they were in the middle of an epidemic. After the onset of Kuru, loss of muscular control and coordination occurred, followed by dementia, and in a year or two, death (Gadjusek 1957, 1959).
Gajdusek eventually won the Nobel Prize in medicine in 1976 for his discovery of this mystery disease. Kuru was completely different from other infectious diseases. When an infectious disease spreads, it is normally through bacteria, virus, parasite, fungi or some other organism. The body’s immune system acts up when invaded by these foreign bodies and the infection results in inflammation or fever. However, people with Kuru showed no inflammation or fever (Beck et al. 1964). This led to the speculation it wasn’t an infectious disease at all. But Gajdusek and colleagues probably looked at the facts. Not to be too presumptuous, but I imagine his thoughts were something along the lines of - What are these people doing differently which may result in an infection? Oh shit, that’s right, they eat each other!
In actuality, upon encountering the disease, Gajdusek was completely convinced it was hereditary. But the infectious nature of the disease was realized when the ritual of cannibalism was banned in 1959. No people born after that year developed the disease (Gajdusek 1977). I suppose Gajdusek was disgusted by it and helped to ban it on moral grounds. Ironic, considering he was convicted in 1997 of pedophilia.
Apparently Gajdusek didn’t visit obscure corners of the planet only to discover diseases, but also to find exotic boys. Gajdusek never married and adopted numerous boys from New Guinea and Micronesia, turning his Baltimore Manor into a stately Neverland ranch. Eventually the FBI taped a conversation between him and one of his adopted children (as an adult) in which Gajdusek admitted to having a sexual relationship with his adoptee when the man was a teenager. When he was released from prison he promptly moved to France (Simmons 2002).
The other mystery was what the brains of those infected with Kuru looked like. After death, instead of eating the brain, researchers examined it microscopically and noticed the brain had holes all over it, like Swiss cheese or a sponge (Klatzo et al. 1959; Hadlow 1959). The medical term for these diseases was “spongiform encephalopathy.” “Spongiform” meaning resembling a sponge, “encephalus” meaning brain, and the suffix “-pathy” meaning something aberrant with the brain.
In 1966, in a twisted inversion of Spielberg and Lucas’s monkey brain eating scene in The Temple of Doom, Gajdusek and fellow researchers were able to transmit Kuru to chimpanzees by injecting them with the brain matter of kuru patients (Gajdusek et al. 1966). It took two years for the chimps to develop symptoms. This was one of the first experimental models of spongiform encephalopathy. However, even after Gajdusek won the Nobel Prize, no one knew what infectious agent was being transmitted. The loss of coordination and motor control followed by dementia and quick death were symptoms of another rare disease called Creutzfeldt-Jakob disease (Creutzfeldt 1920). The brains of patients with Creutzfeldt-Jakob disease exhibited the similar spongy brain type as Kuru. Years of heroin use can cause a similar effect to the brain matter in humans but Creutzfeldt-Jakob disease was the only non-environmental disease. Creutzfeld-Jakob disease was discovered in the 1920s and named after two men who characterized it in a German hospital (Creutzfeldt 1920; Jakob 1921).
Creutzfeldt and Jakob assumed they were dealing with something similar to Alzheimer’s or Parkinson’s with extremely different brain type and probably hereditary. Although if someone were to suggest it could be infectious, Jakob would have jumped to the conclusion it was a sexually transmitted disease as he housed one of the largest neurosyphilis wards in Europe (according to wikipedia). To check if the disease was possibly one in the same, Gajdusek and colleges injected brain matter from Creutzfeldt-Jakob disease patients into chimpanzees as well (Gibbs et al. 1968). When the chimps developed the disease, it proved the Kuru and Creutzfeldt-Jakob disease were equally infectious, and likely the same. To infect another animal, it seemed the brain or spinal cord held the majority of the infectious agent (Prusiner 1982). While cannibalizing friends, it’s possible one of the more scrumptious parts to eat is the brain. I was always partial to the foot, but that’s for another chapter.
One of the major events in the history of the United States involving cannibalism was the Donner Party tragedy in 1846. I know because when I was 16 I had to write a report on a major event in American History for my US History class. I thought it would be hilarious to write it on the Donner party, maybe because I played too much Oregon Trail and had lost touch with reality. Oregon trail was like a first person shooter game of the late 80s early 90s, where we felt nothing for the pioneers. I’m not sure what is so humorous about a band of stranded pioneers devouring each other in the Rockies, but I thought it was pretty funny. Soon after writing that report, I went to a movie with a girl from a neighboring town. The girl looked like Winona Ryder and I had a thing for Winona Ryder. Let’s just say I wanted the date to go well. I decided to take her to ‘Alive’ without knowing what it was about. My mother suggested it, probably thinking it was an upbeat tale which would be good for a downtrodden Nirvana listener writing reports on crazed frozen frontier cannibals and dating black haired pasty skin Winona Ryder look alikes. With a title like ‘Alive’ it had to have a good wholesome movie with a happy ending. I knew my mom probably had no clue, so I was hoping it was a one of those crappy thriller zombie movies. She could jump into my arms frightened while I comfort her until we make out like crazy.
But as the movie progressed, we realized we were in the wrong place at the wrong time. I don’t know if any other idiots went to that movie without knowing what it was about, but my mood went from sunshine and balloons to the day my dog died. And then I have to eat it. We never saw the end of the movie that night; my date wasn’t as progressive as I’d imagined and insisted we leave the theater somewhere around the time Ethan Hawke gobbled up a little piece of one of his buddies like he’s munching on a chicken wing. I grew up in Iowa in the middle of nowhere and it was 45 minutes back to her town from the theater. The ride home through the desolate farmland was more than a little frightening for the poor girl. Pulling off in a lane under the stars for a nightcap was out of the question. Needless to say, I’m not even sure I got a kiss at the end of the night. My mouth wasn’t getting anywhere near her body.
Since none of the Donner Party or Uruguayan Rugby team who survived contracted spongiform encephalopathy, either none of the dead had the disease or the survivors refrained from eating brain and spinal cord matter. Some theories believe that Creutzfeldt-Jakob disease, or Kuru, can be contracted by simply eating the brains of another human, infected or not. Another theory is that cannibalism doesn’t lead to contraction of Kuru unless the cannibalized had Kuru.
What is known is that the infectious agent is at much higher concentrations in the brain than other parts of the body and it’s generally believed the amount in other parts of the body are too low to cause the disease (Gajdusek et al. 1966). It’s possible the Kuru epidemic began with someone who had sporadic Creutzfeldt-Jakob disease and when this person died and everyone had a bite of him, they all began to die and then the others ate those people at their funerals and contracted the disease until - like Chlamydia in a freshman dorm – everyone had it.
The Donner Party tragedy occurred over 50 years after scrapie was first described in Iceland. The first known form of spongiform encephalopathy on record, scrapie decimated the sheep in Iceland for centuries until it was accidentally transferred to Scotland in 1935 when parts of scrapie infected sheep were injected in Scottish sheep to vaccinate them from louping ill virus. The injected sheep developed scrapie. This occurred after the parts of the scrapie infected sheep were fixed in formalin for a week (Gordon 1946). Embalming fluid to funeral home workers, formalin and formaldehyde cause protein crosslinks and preserve tissue. It effectively kills any virus or bacteria, etc. So when the infection spread to sheep in Scotland, researchers figured the infectious agent was the most potent one which existed. Or a tricky little virus.
You may be wondering at this point, “What the hell does this have to do with cows?” More likely, you are in one of those bored inattentive dazes where you finish this entire paragraph and realize you have to reread the damn thing. Personally, I’m thinking about getting another Pabst. Either way, we’re at the part about the cows.
Mad Cow’s disease sounds like some wild bovine 28 Days Later scenario, with rabid cows traversing the British countryside as fast as gazelle with fangs dripping with tainted drool ready to kill and feed on anything in their way. By now, after Monty Python, Ricky Gervais and other British imports, most people in the United States are aware that ‘mad’ in Britain denotes ‘crazy’ and not ‘angry’ as Americans understand the word. Oi, wanker, Marmite tastes like Betty Swollocks.
In reality, mad cow’s disease is not a frightening pack of angry cows, nor have the British cattle farms turned into a Far Side cartoon depicting an asylum of crazy cows. It’s been sad. In the 80s someone had the bright idea to recycle dead worthless scrapie infected sheep by feeding their offal {(entrails and bone meal (lips and assholes)} as a protein boost to fatten cattle (Wells et al. 1987; Wilesmith et al. 1988; Hope et al. 1988). Soon cattle all over the British Isles were slowly losing their faculties until they could no longer support their own weight. They were then destroyed, they collapsed, died or were slaughtered and packaged into steaks and ground beef for us to enjoy.
When it was discovered sheep offal was the root of the disease (Hope et al. 1988), the practice of feeding the cows sheep was outlawed in 1988 (Prusiner 1991). However, 184,000 cattle contracted Bovine Spongiform Encephalopathy (BSE) in the 20 years since its discovery in 1986 and tariffs on British meat imports decimated the British cattle industry (Bradley et al. 2006). More frightening was the possibility of transmission of BSE to humans through tainted meat (Collenge et al. 1996; Will et al. 1996; Bruce et al. 1997).
Spongiform encephalopathy has been discovered in elk (Williams and Young 1982), deer (Williams and Young 1980), humans (Creutzfeldt 1920; Jakob 1921; Hadlow 1959), mink (Burger and Hartsough 1965), cats (Leggett et al. 1990), sheep, cows (Wells et al. 1987). And in a paper published in 1994, among animals which in captivity in zoos and wild animal parks in Britain which were fed cattle carcasses unfit for human consumption and developed spongiform encephalopathy – one nyala, four elands, six kudu, a gemsbok, an Arabian oryx, a scimitar horned oryx, a few ostriches, four cheetah and a puma (Kirkwood and Cunningham 1994). A Noah’s ark of animals with swiss cheese for brains. Not to mention the animals humans have transmitted spongiform encephalopathy to - chimpanzees, macaques, squirrel monkeys, mink (poor critters), marmosets, hampsters, rats, guinea pigs and mice. Somewhere some poor kid is probably working on a graduate research project to infect an armadillo.
A research paper in 1996 described humans as young as 18 developing and dying from a disease which clinically resembled Creutzfeldt-Jakob disease (Will et al. 1996). When the brains were examined they had spongiform characteristics. This disease was named ‘variant Creutzfeldt-Jakob disease’ because of the youth of the patients, and researchers claimed it was likely contracted from eating BSE infected beef. However, their research was not conclusive and a species barrier is known to exist with the infection (Bruce et al. 1994; Hill et al. 2000). In fact, it had never been shown conclusively that scrapie can infect humans.
The disease in humans is known to occur through three ways, hereditarily (Hsaio et al. 1991; Hsaio and Prusiner 1990), sporadically and by infection. We all know hereditarily means through your familial line and by infection is by means of another organism, but what does sporadic mean? Sporadic means it arises in someone randomly, either intrinsically or through the environment. So could the cases they examined and dubbed ‘varient Creutzfeldt-Jakob disease’ have been sporadic and not transmitted from cattle? No one is sure, especially when people can develop it 20 to 30 years after being infected (Will et al. 1993; Collinge et al. 2006). Since it has only been 20 years since BSE was discovered, we could all be carrying it and the epidemic might not have happened yet. Maybe next week everyone around the world will progress to an agonizing death – except the vegetarians. It will be the ultimate PETA fantasy. Vegetarians will rule the world.
With the cause still unknown in the early 1980s, scientists (including Gajdusek) had come to the general conclusion that the root of the disease was an uncharacterized type of ‘slow’ virus. Since the infectious agent was able to withstand virus killing agents, Gajdusek and others claimed it was somehow hidden until activation, like the brain had gone into business with Tony Soprano as a silent partner. Eventually Tony becomes dissatisfied and the brain gets wacked.
In 1982, Stanley Prusiner published a paper which described a series of experiments he had been conducting with scrapie infected mice and hampsters. Hampsters were chosen because they apparently have no problem with cannibalism. In 1961, the first model of scrapie in mice was developed by injecting them with brain matter from infected sheep (Chandler 1961). This model was perfected with transmission of the scrapie infectious agent to hampsters (Marsh and Kimberlin 1975). When Prusiner isolated the infectious agent from the brains of these rodents, he first confirmed previous research that the particles were resistant to many forms of DNA destruction indicating it was not a virus or other organism (Prusiner 1982). He then applied various agents which destroy proteins and was able to inactivate the infectious particle. Further research completed the story by demonstrating the infectious agent was a misfolded form of a protein which already existed in the brain (Prusiner 1998). When placed in vitro, the misfolded form of the protein caused the natural form to misfold which precipitated the multiplication of misfolded proteins, depositing themselves in the cell membrane and causing cell destruction (Prusiner 1998).
Theoretically, the protein is in a normal state and then either a genetic mutation, an infection or a sporadic change can create a misfolded protein. Prusiner had found the only plausible explanation for the three ways the disease can arise. Like Agent Smith in the Matrix, the creepy misfolded proteins are able to conform each other and multiplicate into a group of killing machines devoted to cyber dominance and utter control over humanity. Or at least to destroy some brain cells.
Prusiner called these proteins ‘Prions’ for ‘PROteinaceous INfectious’ particles. He must not have liked the way ‘proin’ sounded so he reversed the vowels for the hell of it and without explanation.
Prusiner also insisted everyone pronounce ‘prion’ as ‘pree – on’ to keep with the latin pronunciation of the letter 'i'.
Gajdusek firmly believed Prusiner’s research was wrong. Other researchers claimed Prusiner’s prions were crack pot science and thought he was completely insane. They bickered like Anna Nicole Smith and the Marshalls over who gets the inheritance.
Personally I think a ‘prion’ is what an alien would call his manhood. Or maybe a robot would.
When other laboratories slowly began to confirm Prusiner’s research – as slow as Gajdusek’s ‘slow’ virus – everyone realized his science might be true. The mad cow’s outbreak verified much of Prusiner’s work, and the scientific community collectively said, ‘um, we’re sorry for saying you suck for 15 years,’ and gave him the Nobel prize in 1997. Coincidentally, in 1997 I was studying abroad in England. While I was there the scare for mad cow’s disease was prevalent. That year was torture for an Iowan. No foreigners would eat red meat. If you even looked at it other foreigners treated like a leper. Once, in a fit of carnivorous rage, I devoured a frozen burger patty in my dorm freezer at 3 in the morning. As I remembered it, the meat was slightly green, like an old time cartoon character with nausea. Theories spread that it had been there for years and maybe decades. I was pretty drunk and pretty stoned and subsequently pretty hungry, but the next day I regretted eating it. All I remembered was that it was delicious.
My only respite from the agonizing vegetarianism splashed with intermittent dry chicken was my trip back home in December. My dad and I fired up the grill in -20 degree weather for two weeks straight and I swear to God we put down a side a beef that Christmas.
The freak out in England started before I got there and lasted after I left. It had been shown that the misfolded prions can cross into the blood stream after digestion. It can then cross the ever important ‘blood brain barrier’ which our body has designed to stop any junk from our blood invading our precious brain, like parents putting an internet filter on their kids devices (Collinge et al. 1996; Bruce et al. 1997).
Controversy still exists in Britain over whether tainted beef with Mad Cow’s can be transmitted to humans. It has never been proven. Current research has shown that sporadic Creutzfeldt-Jakob disease cannot be transmitted through blood transfusion but the variant form can (Lleweyln et al. 2004). Misfolded prions can also spread to mice bred with human prion protein (Bruce et al. 1997). But researchers have been obsessing over the connection like Russell Crowe in A Beautiful Mind. And based on the transmission from sheep to mice and humans to humans and humans to chimps and sheep to cows and cows to cheetahs, etc., they probably have good reason for their paranoia.
What is known is that prions can survive through formalin fixation (Gordon 1946), extremely high temperatures and acid (Prusiner 1982) and resistance to ionized and ultraviolent light (Alper et al. 1966; Alper et al. 1967; Gibbs et al. 1978). And once the symptoms start you don’t have long.
So enjoy life, proteins can kill you too.
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