by Bill Schutt
In 1947, an outbreak of what would become known as transmissible mink encephalopathy (TME) in farm-raised mink led investigators to search for links between the ranches where infected animals had been identified. They discovered that it was a common practice for adjacently located ranches to share animal feed. In these instances, when mink from one ranch came down with TME, invariably so did animals from the adjacent ranch. The feed itself was a vile mess composed of cereal, fish, meatpacking plant by-products like sheep entrails and other internal organs, and flesh from downer cattle. By the time another outbreak of TME occurred in 1963, veterinary researchers suspected that something very strange had happened—the disease had been transmitted across species, in this case from sheep to mink.
By September 1963, similarities in kuru-, scrapie-, and TME-infected brain tissue, coupled with the discovery that TME and scrapie could be transmitted within and between species, led Gajdusek and NIH researcher Joe Gibbs to an important experiment. At the Patuxtent, Maryland, lab they inoculated a trio of chimpanzees with liquefied brain tissue from kuru victims. If the chimps came down with the disease, it would prove once and for all that kuru was not a genetic abnormality or a stress-related psychosis, but an infectious or transmissible agent. As the antsy Gajdusek left the U.S. for another field season in New Guinea, he worried about the long, symptom-free incubation period for scrapie, which sometimes extended up to five years post-exposure. What if his experimental animals didn’t get sick for five years or more?
Gajdusek need not have worried. Less than two years after being inoculated, two of the chimps, Georgette and Daisy, began showing the telltale signs of kuru—at first a drooping lower lip in Georgette, and then changes in behavior as both primates became more lethargic. Eventually the apes began to show even more clear symptoms of the disease: occasional unsteadiness and trembling followed by a gradual loss of balance.
When informed of these developments, Gajdusek was excited but cautious, worrying that the chimps might have been accidentally contaminated with scrapie. His coworkers assured him that there had been no contamination. As the researcher alternated between elation and skepticism, back in Maryland the physical deterioration of the chimps continued at a frightening pace. Only four months after the first symptoms appeared, Georgette and Daisy were almost completely paralyzed. With Gajdusek carrying out field work in one of the most isolated regions in the world, his coworkers called in a neuropathologist from London to assist with the post-mortem analysis.
On October 28, 1965, Georgette was anesthetized and sacrificed by the heartbroken researchers. Her entire body was deconstructed, fixed, and preserved, and her brain was sectioned for microscopic analysis. The results were 100 percent conclusive. Slides of Georgette’s cerebellum were indistinguishable from those of human kuru victims.
Carleton Gajdusek and his colleagues had discovered a brand new disease.
Meanwhile, Michael Alpers, who had been studying kuru since 1961 and who had taken time out from his own field work to collaborate with Gajdusek and Gibbs on the NIH primate study, waded through six years of Gajdusek’s epidemiological data on the Fore. After examining hundreds of Fore genealogies, he and Gibbs came up with a remarkable observation: Instances of kuru were beginning to decline in children, starting with the youngest age group. The question immediately became, “Why?” Shortly after conferring with Robert Glasse and his wife, Shirley Lindenbaum, Alpers came up with a hypothesis.
According to information gathered from interviews with the Fore, kuru victims were favored at mortuary feasts because the physical inactivity that characterized the latter stages of the disease left the stricken individuals with a tasty layer of subcutaneous fat. Starting in the 1950s, though, government authorities in New Guinea began cracking down on the practice of ritual cannibalism, and with mortuary feasts now forbidden by law, fewer people were eating infected tissue. As a result, incidents of the disease were decreasing. Additionally, since kuru had a shorter incubation period in children than it did in adults, the reduced occurrence of ritual cannibalism translated swiftly into a decreased incidence of kuru in the youngest sector of the population.
In a February 1966 article in Nature, Gajdusek, Gibbs, and Alpers described the experimental transmission of a “kuru-like syndrome” to their chimpanzees although the identity of the disease-causing agent was still unknown. Gajdusek, who still believed that they were dealing with a slow virus, was also reluctant to attribute the transmission of kuru to the consumption of infected flesh. Instead, he supported the view that during the process of handling and cutting up the dead, the kuru-causing agent was transmitted via cuts or across the thin mucous membranes that line the human mouth, eyes, and nose (a form of exposure known as inoculation).
By 1973, however, Gajdusek had come around to the idea that inoculation and consumption were both viable routes for kuru transmission.
The mechanism of spread of kuru is undoubtedly contamination of the population during their ritual cannibalistic consumption of their dead relatives as a rite of respect and mourning. They did the autopsies bare-handed and did not wash thereafter; they wiped their hands on their bodies and in their hair, picked sores, scratched insect bites, wiped their infants’ eyes, and cleaned their noses, and they ate with their hands.
Other researchers, like Joe Gibbs, stuck to the hypothesis that Fore mortuary practices, rather than the actual consumption of infected flesh, were the primary routes of kuru transmission. In a 2002 interview, the NIH researcher admitted that initial attempts to transmit kuru to chimps via a gastric tube (which modeled the consumption of infected flesh by humans) had failed, and that it was only after injecting the animals with liquefied brain material from kuru victims that they came down with the disease. As for how kuru was transmitted to the Fore, Gibbs explained that the Fore had multiple routes of inoculation, including their eyes and mouths, as well as skin lesions caused by leeches, mosquito bites, and the razor-sharp blades of puni grass.
Today, in regions of West Africa, the Ebola virus is often spread because of ritual practices that involve handling of recently deceased Ebola victims. For example, some Muslims believe that family members should wash the bodies of the dead, a practice that also includes the elimination of certain bodily fluids. When performed under less-than-sanitary conditions, this ritual can place individuals in grave danger if they come into contact with infectious body fluids like blood, vomit, and diarrhea—all of which characterize the advanced- and end-stage symptoms of Ebola.
I asked Shirley Lindenbaum if she thought that Fore mothers had encouraged their children to handle the dead during mortuary ceremonies.
“Mothers handed food to their small children to eat,” she said. “Since people eat with their hands, most children would touch the food given to them by their mothers and other female relatives. Children would not have been involved in the cutting of bodies, though one of my interpreters remembered sitting with others watching his mother being cut [up] and eaten. So, just as with adults, handling the food was one possible one route of infection, but as I recall, this depended on cuts and scrapes that allowed the infectious agent to enter the bloodstream—which the rest of us agree could not explain the dimensions of the epidemic. That would require a lot of cuts and scrapes, an unlikely scenario.”
In October 1976, 53-year-old Daniel Carleton Gajdusek shared the Nobel Prize for Physiology or Medicine.51 Although he was still attributing kuru to an unidentified “slow virus,” other scientists had their doubts. By now, with cases of kuru dwindling to a few per year and confined to a “stone-aged society” few outsiders had ever seen, research on the disease was winding down. Interest in kuru appeared to have run its course, and with it funding for kuru-related research. Fortunately for the researchers (but unfortunately for a lot of sheep herders), scrapie, a disease that mimicked kuru’s destruction of the central nervous system, was beginning to attract significant attention.
Considering the importance of the European sheep industry, it was no
surprise that by the early 1970s many researchers, including Gajdusek, were pressing to understand the mechanism behind scrapie. At the forefront of the mystery was the observation that whatever the scrapie-causing agent was, it could not be killed or inactivated by disinfectants like formalin or carbolic acid. Additionally, extracts from scrapie-infected brains lost none of their lethality after being heated, frozen, or dried. In another set of experiments, South African radiation biologist Tikvah Alper and her colleagues bombarded the mystery agent with an electron beam from a linear accelerator. Although the beam was strong enough to disrupt the molecular structure of any known pathogenic cell or virus, there was no change in the infectivity of the scrapie extract. The researchers also tried mega-doses of ultraviolet light, a proven disruptor of viral DNA and RNA—all to no avail. The extracts retained their lethality.
Alper’s research team soon reached a pair of conclusions regarding the scrapie-causing agent: 1) it was far smaller than any known virus, and 2) it could replicate without nucleic acids—the chemical rungs of the helical ladder that became Watson and Crick’s model for DNA. Shockingly, this last finding appeared to contradict one of the central tenets of biology, the fact that all organisms require nucleic acids to reproduce.
After reading over Alper’s work, English mathematician J. S. Griffith came up with an unusual hypothesis. Perhaps, he suggested, the agent that caused scrapie wasn’t a virus at all but a self-replicating protein. Griffith proposed that this mutant protein could function as a template for the production of additional mutants, each in turn taking on its own role as a template.
Researchers from competing labs scoffed at Griffith’s idea and Tikvah Alper was ridiculed as a female version of virologist/biochemist Wendell Stanley, who had won a Nobel Prize in 1946 for determining that the infectious agent in Tobacco Mosaic Virus was actually a self-propagating protein—a fact that was disproven only after he won the award.
But Stanley Prusiner, a young biochemist out of UC San Francisco, read the papers by Alper, Griffith, and others, saw an opportunity, and jumped into the fray. In the early 1970s, Prusiner moved to Montana where his work with scrapie expert William Hadlow confirmed Alper’s findings about the absence of nucleic acids in the scrapie agent. Prusiner and Hadlow’s results also indicated that, when exposed to substances like enzymes that could destroy or denature proteins, the disease-transmitting ability of the scrapie extract was eliminated.
Prusiner tried to tell Gajdusek and the other NIH researchers about what he had found, but he was rebuffed. Among the kuru mavens, who were now mostly working on other projects, only Michael Alpers was supportive, inviting the American to the Goroka Institute in New Guinea, where Prusiner studied a group of nine kuru sufferers.
In 1982, Prusiner published his lab findings on scrapie in the journal Science. He coined the name “prion” (pronounced “PREE-on”) to describe an aberrant form of protein, which he claimed was responsible for the suite of neurodegenerative disorders known as Transmissible Spongiform Encephalopathies (TSEs). Prusiner claimed that, unlike viruses, prions were not biological entities, but they could be infectious—transmitted orally or through contact with infected material. They could also be inherited or spontaneous in origin.
When asked about why the body’s immune system didn’t appear to mount a defense against them, Prusiner explained that unlike viruses or bacteria, prions weren’t foreign invaders; they were an altered form of one of the body’s own proteins. Because of this, the body never recognized them as a threat. As a result, prions would spread through the body of a TSE victim unchecked.
Prusiner did hedge his bets by stating that current knowledge did not exclude the potential existence of a small core of nucleic acid within the prion—which might explain how they replicated. Nevertheless, he co-opted Griffith’s protein-as-template model, with his misfolded prion proteins (which were too small to see with even the most powerful microscopes) building up into the amyloid plaques that characterized fatal TSEs like kuru, Creutzfeldt-Jakob disease, TME, and scrapie.
For his work on prions, Prusiner won the Nobel Prize for Medicine in 1997. Some have argued that he should have shared the award with other researchers, and they pointed to the fact that several people had been bumped out—or worse—by the self-promoting American. In his book Deadly Feasts, Pulitzer Prize–winning writer Richard Rhodes wrote that Prusiner “invaded and colonized the work of others in his apparent pursuit of a Nobel Prize.” Prusiner’s list of enemies grew even longer after accusations that he had used the peer review process to stonewall publication of another researcher’s results while submitting his own paper on a similar topic.
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50 “Downer cattle” is a trade term for cows that have become too sick to walk, or die before being slaughtered.
51 A category usually shortened to “the Nobel Prize for Medicine.”
19: Acceptable Risk
I have taken advice from the leading scientific and medical experts in this field. I have checked with them again today. They have consistently advised me in the past that there is no scientific justification for not eating British Beef and this continues to be their advice. I therefore have no hesitation in saying that beef can be eaten safely by everyone, both adults and children, including patients in hospital.
— Sir Donald Acheson, Chief Medical Officer, UK Department of Health, 1990
The kuru/Bovine Spongiform Encephalopathy (BSE) story now jumps to 1988.
Given the degree of bureaucracy inherent in a government such as Great Britain’s, many people would have been surprised that year if the ministry had reacted to epidemiologist John Wilesmith’s news on how BSE was being spread with an immediate ban on meat and bone meal, or even a warning. Instead, because they still believed that they were dealing with a disease that hadn’t been transmitted to humans, the government dragged its feet. Clearly, many officials were far more concerned with preventing a panic that might impact negatively on the rendering and beef industries than they were about the possibility of their citizens consuming prion-contaminated meat pies. The government also knew that closing rendering plants would have placed the burden of eliminating unwanted livestock parts squarely on the shoulders of the beef industry, a significant new expense that would have resulted in higher meat costs and a concurrent decrease in the competitiveness of British beef on the world market. So rather than demanding immediate and industry-wide changes, the politicians did something a bit less dramatic: They quietly called for the formation of a “blue ribbon” panel led by the eminent Oxford zoologist Richard Southwood. The “Southwood Working Party” met for the first time on June 21, 1988, and again in November and December of that year. The problem was that neither Southwood nor his three-member team had any experience dealing with spongiform encephalopathies.
Earlier in June, government officials met with members of the UK Rendering Association. On the strength of the data provided by Wilesmith, the ministry informed the renderers that they would be suspending the sale of ruminant-based protein (i.e., meat and bone meal) as a dietary supplement for cows and sheep. Although the ban went into place the following month, that would become the extent of the good news. Farmers were also asked to voluntarily stop feeding meat and bone meal to their cows. Unfortunately, many of them had already spent thousands of pounds on what had suddenly become an illegal nutritional supplement. But since the government hadn’t offered to buy the protein supplement back from them, and since there were no efforts to enforce the government’s request, there was little incentive for the farmers to stop using it. The results were predictable.
After quietly acknowledging the fact that removing infected cattle from the system was an important step in curtailing BSE, the ministry did decide to compensate cattle owners who turned in their visibly sick animals. But instead of offering to purchase the diseased cattle at market value, they low-balled the herd owners, offering them only 50 percent of market value for their animals. By comparison, the government was already
handing out 75 percent of market value for cows infected with tuberculosis.
Ultimately, it’s impossible to know just how many sick cows were hurried off to the slaughterhouse, but the numbers are thought to have been significant, especially since examples of this sort of practice are not unheard of within the meat industry, even decades later. In August 2014, Federal prosecutors indicted three Northern California slaughterhouse workers. They were charged with cutting off “USDA Condemned” stamps from sick cows and then slaughtering them while inspectors were on their lunch breaks. It is suspected that significant numbers of diseased animals were processed and sold for human consumption.
Until this time, there hadn’t been much publicity about what was going on, and the British government made an effort to keep it that way. Their veil of secrecy might have remained in place far longer if several publications hadn’t broken the BSE story in April 1988. The industry standard, Farming News, ran a front-page headline that read “Spongiform Fear Grows,” while the Sunday Telegraph set the stage for the term “Mad Cow Disease” with a story entitled “Raging Cattle Attacks.” An earlier paper in Nature also demonstrated that scrapie had been experimentally transmitted from sheep to monkeys, supporting Wilesmith’s hypothesis that cows had gotten sick from eating scrapie-infected sheep rendered into meat and bone meal. Note: Most scientists now believe that it is more likely that BSE originated from a spontaneous mutation in cows and did not result from sheep scrapie jumping to a new species.
The Southwood Committee published its official report in February 1989. Their most important finding supported the government’s claim that they were dealing with scrapie, and so they reported that, “the risk of transmission of BSE to humans appears remote.” They also concluded that there was no evidence the disease was related to Creutzfeldt-Jakob disease (CJD), the rare but deadly form of human spongiform encephalopathy.
