Welcome back. Let's talk about Prion Diseases. The disease was called scrapie because the animals would compulsively scrape themselves against fence posts. Scrapie was the first neurodegenerative disease to be described, and it is now recognized to be a prion disease. The signs of the disease would appear about 2-5 years after the animal became infected, and once they became infected and showed signs of disease, the animals would live for about six months after the disease onset. There was no evidence that this disease could spread to humans after farm contact or after milk or meat consumption. Another prion disease, Creutzfeldt-Jakob Disease was identified in people by Dr. Alfons Jakob and Dr. Hans Creutzfeldt, both of them were German neurologists. They described a number of patients with progressive spasticity and dementia that resulted ultimately a neurodegeneration and death. They are both credited for discovering this rare syndrome. In the Fore language, Kuru means trembling, and the disease would manifest as severe muscle spasms or trembling of the body. It was transmitted by cannibalism. Family members would cook and eat their relatives as a way to free the spirits of the dead, but only the women and children ate the brains of the deceased relatives, and so as a result, they were the ones who mostly came down with the disease. When cannibalism was ended in the 1960s, the epidemic die down. The last Kuru victim died in the late 2000s. Dr. Carleton Gajdusek traveled to New Guinea and lived among the Fore people to study Kuru as Dr. Gajdusek, pictured here. He concluded that the disease was spread by cannibalism and wanted to prove its transmissibility. He took a small sample of a victim's brain and injected it into chimpanzee's brains. The chimps developed the disease as a result. He recognized the similarities between Kuru and Creutzfeldt-Jakob disease, and he hypothesized that they were both due to a novel agent. For his discovery, he was awarded the Nobel Prize in 1976. Dr. Stanley Prusiner was the one to prove that prions were the cause of these diseases. In 1972, one of his patients died from Creutzfeldt-Jakob disease, and at that time, it wasn't known what it was due to, was hypothesized to be due to a slow virus, but it did not have DNA or RNA as genetic material. After 10 years of research, he identified that it was a misfolded protein, and he called it a prion for proteinaceous infectious particle. His discovery was met with considerable skepticism by other scientists, but nevertheless, he was awarded the Nobel Prize in 1997. Everybody possesses prion genes. Animals, humans, the prion gene will encode for the prion protein, but it's when it gets misfolded that it becomes a problem. Prion diseases appear in a number of different animals against scrapie in sheep and goats. Chronic wasting disease in deer, elk, and moose. There's even feline spongiform encephalopathy seen in cats and transmissible mink and encephalopathy seen in mink. There's also bovine spongiform encephalopathy seen in cattle, goats, cats, and a number of different animals. Let's talk about the bovine spongiform encephalopathy outbreak in Great Britain in the 1980s. BSE is also known as mad cow disease. In December of 1984, account started exhibiting poor coordination on a farm in Sussex, and it subsequently died after two months. Over the next two years more cows started exhibiting signs of the disease. Pathologic examinations, where they took thin slices of the brain and looked at them under the microscope, showed spongiform encephalopathy similar to those seen in scrapie. Here's an example of the pathologic changes seen in the brain tissue. This is normal brain tissue, this is brain tissue that's infected with bovine spongiform encephalopathy, where you get a lot of holes that appear in the brain reminiscent of a sponge. Again, more comparisons of spongiform encephalopathies, normal brain tissue, classic Creutzfeldt-Jakob disease with large holes in the brain. Kuru similarly large holes in the brain, and scrapie large holes in the brain. They all have sponge-like appearances, that's why they're called spongiform encephalopathies. For over 250 years, scrapie in sheep did not infect humans, but this novel spongiform encephalopathy in cattle was spreading. The British Ministry of Agriculture, Fisheries, and Food, also known as MAFF, and the feed industry had to decide what to do about the sick cows. They decided to keep this issue confidential. A note from the head of the central veterinary laboratory to the director of the Central veterinary laboratory revealed concerns about food safety, food export, international trade, and human health. In the note, it said, quote, "If the disease turned out to be bovines scrapie, it would have severe repercussions to the export trade and possibly also for humans. It is for these reasons that I've classified this document as confidential." But political concerns soon developed. The Chief Veterinary Officer of the ministry of agriculture, fisheries, and food, sent a note to the Parliamentary Secretary. Irresponsible or ill-informed publicity is likely to be unhelpful since it might lead to hysterical demands for immediate draconian government measures and could lead to other countries to reject British exports of live cattle and bovine embryos and semen. The political implications of this development could be quite serious, particularly if not handled correctly. MAFF published a short factual report in the British veterinary record, which is a publication of the British Veterinary Association, and this was subsequently followed by a longer report. The Sunday Telegraph, which was a national British newspaper, got hold of this report and issued the first public media report of an incurable disease wiping out Britain's cattle. In response, the British government decided to assemble an advisory committee to investigate this disease. So in May 1988, the British government assembled the Southwood Working Party to investigate the risk that this new disease might pose to people. The Southwood Working Party began its investigation and found that both sick and healthy cattle were slaughtered and we're entering the human food supply. Meat and bone meal, which is pictured here, is ground up livestock, and that had been fed to cattle for decades as a protein source. Meat and bone meal included parts of the animals not typically consumed by humans, including the intestines, spleen, and spinal cord. Some of these parts could have been contaminated with the infectious particles, particularly the spinal cord. So their initial recommendations were that sick cattle should not enter the food chain. Entire carcasses of sick animals should be destroyed. The meat and bone meal ban should be voluntary. But if the feed industry didn't comply, then it should be made mandatory. The meat and bone meal ban did not apply to chickens and pigs. However, because these animals did not appear susceptible to the disease. Exports would continue. The BSE order mandating these changes, was signed into law in June 1988 and went into effect one week later. After the new BSE order went into effect, new findings emerged. They found that mice injected with BSE infected brain, did in fact show signs of disease almost 300 days after inoculation. Epidemiologists studying the disease in animals, discovered that young dairy cattle in southern England, constituted the majority of the cases. An epidemic curve pointed to a common source exposure over an extended period of time. Epidemiologists concluded that the cattle were likely exposed to the agent sometime during winter of 1981, 1982. This is an image of the BSE epidemic curve. The first unverified case occurred in 1984, but it took two years before the disease was actually diagnosed and over ten years passed before the meat and bone meal ban was passed. There were changes in the meat and bone meal production. During the 1980s, the sheep population increased from 22 to 25 million and that led to many more cases of scrapie. Here's examples of sheep brains for sale. So more sheep with scrapie went to the rendering plants to make meat and bone meal. Previously, they would remove the brains, but now they were just shipping the whole head through. In addition to using the whole sheep head with the brain included, lower temperatures and different chemical processes were used in the meat and bone meal production process, and that could have further promoted prion transmission. So what were the Southwood Working Parties final recommendations? They concluded that BSE transmission to humans was unlikely. However, if the disease would appear, it would resemble Creutzfeldt-Jakob disease. They recommended surveillance for unusual cases of Creutzfeldt-Jakob disease. So the government should establish a research advisory committee. They also recommended that baby food should avoid using any ruminant offal. Which included parts of brains and spinal cords, as well as the thymus, but it would be okay to use this food for adults. In other words, let the consumers decide. Now, John MacGregor, who was the Minister of MAFF asked, "Why just baby food?" He reasoned that if BSE was a risk, it should be banned in all foods regardless of the age of the consumer. In June of 1989, he announced a ban of offal from all food. But John Gummer, the subsequent Minister of MAFF, pictured here with his daughter, viewed the issue differently. He decided not to ban the potentially contaminated offal and he forced his young daughter to eat a hamburger in front of the press to prove his point. What were the CJD surveillance results? Well, by December of 2003, a total of a 143 people had been autopsied and confirmed to have died from vCJD. The median age of the victims was 29 in contrast to the age of 65 seen in classic CJD. Death generally occurred 7 to 14 months after the first signs and symptoms of the disease appeared. A public inquiry into the government's handling of bovine spongiform encephalopathy, vCJD, subsequently ensued. From 1987 to 2003, more than 180,000 cows had BSE. This epidemic in cattle peaked in 1992 and then subsequently declined. Let's compare the BSE and vCJD epidemic curves. The BSE epidemic curve, appeared approximately 10 years before the vCJD cases appeared in humans. These are considered extended common source epidemics, meaning an ongoing source of food exposure. Unfortunately, there were a number of vCJD cases outside of the United Kingdom. Exports of British cattle continued through the 1980s and early 1990s, which might have contributed to vCJD in these other countries. France, Italy, Ireland, the Netherlands, Spain, Portugal, had the highest numbers of vCJD outside of the UK. Approximately 230 cases of vCJD were reported in 11 countries. Seventy seven percent of the global cases occurred in the United Kingdom. In an effort to reduce exposure to BSE, many European countries banned bovine offal from the human food supply. Unfortunately, for those who were infected, the ban came too late. This graph shows the number of cases over time of vCJD in Great Britain and in non-Great Britain EU countries. This is the y axis, the number of cases, this is years and along the x-axis. The British cases are in blue and the non-British cases are in red. Most of the cases in the early years occurred in the United Kingdom. In subsequent years, it appears that non UK patients predominated. So the questions for this section include: What is a prion and how does it cause disease? How was kuru spread in Papua New Guinea? What stopped the epidemic? Why did the British government officials hesitate to reveal the new disease? How should government officials make public health policies when scientific data is incomplete? At what point should food safety and health interests supersede economic interests? Finally, when should concerning but preliminary data be made public? With that I'd like to thank you for your time and attention.
