Canada Says Prion Disease Unstoppable

Editor’s Note: As we have suggested before on this blog, prion disease is impossible to stop. As a cluster of prion disease appeared last week in the human population near Vancouver, Canadian official’s today have announced that eradicating prion disease (chronic wasting disease or CWD) from the deer population will be impossible. Now, the goal is to control the spread in the wild deer, elk and moose populations. If only they would make such admissions on prion disease in people and livestock. (Known as Creutzfeldt-Jakobs and Alzheimer’s disease in people and Mad Cow disease and scrapie in livestock. All are caused by the same contagion–prions).

chronic wasting disease caused by prions

Unfortunately, deadly prions are deadly prions regardless of the species victimized. Therefore, making different assumptions about the characteristics of prion disease in different host species is flawed. Claiming that there is not a common denominator in prion disease between species is reckless. In other words, if prion disease is unstoppable and incurable in wildlife, we can and should make the same assumptions regarding prion disease in people and livestock. The stakes are too high in this life-and-death race with a contagion that migrates, mutates and multiplies. 

Hunters should take note that it is not safe to even touch an animal that has Chronic Wasting disease. Deadly prions are known to be in blood, saliva, feces, urine and tissue of infected mammals. Your knife and saw will become infected and permanently contagious. Same goes for the butcher shop that processes one. If your game processor has ever processed a contaminated animal, the facility is exposing every carcass that follows it down the production line. Despite what officials say, it is impossible to sterilize these facilities.

land application sewage sludge

CWD A Lost Battle

Experts say it may not be possible to eliminate chronic wasting disease (a deadly and contagious prion disease) in deer and elk in Canada. The fatal infectious disease is so well established in Saskatchewan and Alberta that the federal government and some provinces are rethinking how to deal with what is commonly known as CWD.

In 2005, Ottawa announced a national strategy to control chronic wasting disease in the hope of finding ways to eradicate it. Now the emphasis is shifting to preventing CWD from spreading, especially in the wild.

“We have to realize that we may not be able to eradicate this disease currently from Canada, given that we don’t have any effective tools, so we may be looking at switching from eradication to control,” said Penny Greenwood, national manager of domestic disease control for the Canadian Food Inspection Agency.

biosolids management land application

The agency says it is working with the provinces and the game-ranching industry to come up with a better plan, perhaps by next spring.

“We feel that the current program that we have had in place for chronic wasting disease … is not effective in achieving its goals,” Greenwood said.

CWD is caused by abnormal proteins called prions and is similar to mad cow disease. There is no vaccine against it. Symptoms can take months or years to develop. They include weight loss, tremors, lack of coordination, paralysis and, ultimately, death.

Some scientists believe infected animals can pass the disease to other animals through saliva, blood, urine or droppings, or indirectly through prions in the environment. The prions can remain active in dirt for years. There is no evidence that the disease can affect people (there is no evidence that it can’t), but the food inspection agency recommends against eating meat from infected animals.

chronic wasting disease and moose

Prion Disease In Wildlife

The latest report from the CFIA shows the disease is active in herds of deer on Saskatchewan game farms. Scientists say the more pressing challenge is the growing number of infected wild deer and elk in Saskatchewan and Alberta. The disease has also been found in a moose. Researchers believe that in one area of Saskatchewan, up to 50 per cent of the deer have chronic wasting disease.

“This is a disease that is now established in wildlife, and when you have a disease that is established in a wildlife reservoir, it is always extremely difficult to eliminate it,” Greenwood said.

mad cow disease and prions

British Columbia and Manitoba have had no confirmed cases, but have put up billboards on highways warning hunters not to bring in deer or elk that have been shot in other jurisdictions. The caption on the signs that B.C. put up this spring in the Peace and Kootenay regions near the Alberta boundary read: “Stop Chronic Wasting Disease. Do Not Import Intact Deer Carcasses. Keep B.C. Wildlife Healthy.”

Scientists say a big challenge in tracking the spread of CWD is a lack of research into the disease and surveillance programs to track its spread. The federal government ended a program on March 31 that was established in 2005 called PrioNet Canada that was conducting research into CWD and mad cow disease.

Surveillance in the wild is difficult because there is no way to test live animals for the disease. Provincial governments rely on testing the heads of animals turned in by hunters. But in Saskatchewan and Alberta, the provinces where the disease is well-established, it is not mandatory for hunters to do that.

sewage treatment plant and disease

More needs to be done, said Trent Bollinger, a CWD expert with the Canadian Co-operative Wildlife Health Centre at the University of Saskatchewan.

“It is a long-term commitment to both research and management to see how to best approach this and those are difficult things for governments to buy into,” Bollinger said from Saskatoon.

Last year, the Manitoba government ordered conservation officers to kill as many as nine elk that escaped from a Saskatchewan game farm into the province. Bollinger predicted that with infected wild deer close to the provincial boundary, it is only a matter of time before wild animals with CWD wander into Manitoba.

Alberta is funding research into the disease through the Alberta Prion Research Institute.

Debbie McKenzie, a University of Alberta biologist, said there is concern that CWD could eventually infect other species, including caribou. She said researchers hope to develop a vaccine to stop the spread of the disease, but coming up with an effective way of vaccinating animals in the wild will pose another challenge.

“It is one thing for a farmer to vaccinate his cows. It is another thing to come up with cost-effective ways of vaccinating all of the deer and elk in an area.”


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Crossbow Communications specializes in issue management and public affairs. Alzheimer’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and the prion disease epidemic is an area of special expertise. Please contact Gary Chandler to join our coalition for reform

Chronic Wasting Disease Ravaging Wisconsin Deer

Prion Disease Threatens Wisconsin Livestock

Editors Note: A deadly prion is a deadly prion. Hiding behind ignorance and special interests is doing no one any good. Prion disease is always fatal. There is not a cure. Prions migrate, mutate and multiply. Sick animals (including livestock and people) that have prion disease contaminate their environment with prions that are discharged via blood, urine, feces, saliva, and milk. These prions enter the soil and are carried into groundwater, surface water, streams, rivers, ponds and lakes. 

When people have prion disease, their bodily discharges contaminate entire sewer systems–forever. When biosolids and reclaimed sewage water are discharged from the sewage plant, that sludge is then applied to cropland across Wisconsin and the nation. In fact, few counties in Wisconsin have not been subjected to sewage disposal on cropland. Are prions in sewage sludge infecting the deer? If so, what’s to keep the prions from migrating and infecting Wisconsin’s multi-billion dollar dairy herd? The species barrier is a myth. Prion disease is prion disease and a deadly prion is a deadly prion. Don’t buy the spin about “no evidence of” or “species barrier will protect you.” That is pure BS to sell you a bill of goods that covers a lot of asses. 

land application sewage sludge

Further more, asking hunters to kill sick deer, dress it and process it without fear is reckless. As the following article illustrates, hunters are dressing and processing thousands of carcasses riddled with prions every year. In those cases, infected blood and tissue will permanently contaminate the hunter’s knives and saws and clothes and processing plants and beyond. If I dare cut through the spinal chord to remove the head for testing, my chances of prion exposure escalate. If the test comes back positive, I will throw out the remaining packs of deer burger. I should throw out my knife and burn my clothes. Unfortunately, those items have already been in my home and garage. Why isn’t the Fish & Game and Divisions of Wildlife giving hunters better safeguards? With mismanagement like this, eradicating deadly prion disease from deer herds and entire ecosystems is a pipe dream–or make that a nightmare. If you live in Wisconsin or any state impacted by chronic wasting disease, challenge them to hire me as a consultant on this life-and-death issue.

CWD A Lost Battle

The rate of chronic wasting disease (CWD) is on the rise among deer in Iowa County, Wisconsin and elsewhere across the state. CWD is a fatal, transmissible spongiform encephalopathy (TSE) similar to what is commonly known as mad cow disease that is caused by twisted proteins, or prions. For hunters, writes outdoors reporter Patrick Durkin, this means the disease might be affecting the herd now. For anyone who eats venison, this means greater chances that the disease could conceivably make the species jump and infect humans, according to Dave Clausen, a veterinarian whose term on Wisconsin’s Natural Resources Board expired in May.

chronic wasting disease caused by prions

About one out of every three male deer aged 2.5 years and older carries CWD in north-central Iowa County, as does one out of every six yearling male deer (1.5 years old), according to the Wisconsin State Journal, and the rates are climbing at about ten percent a year. As several experts told Durkin, the increasing rates are “unprecedented,” “frightening,” and “disturbing.”

Over 633,000 hunters purchased licenses to hunt white-tailed deer in Wisconsin in 2012, according to the Department of Natural Resources (DNR). The primary deer hunting season (for guns) runs for nine days in late November. An exact number of Wisconsinites who eat hunted venison is not known, although media reports indicate it is large. But testing of these deer for CWD is on the decline, even as infection rates rise. In 2002, over 40,000 deer were tested in Wisconsin, and .51 percent tested positive. In 2012, 6,611 deer were tested, and 5.13 percent tested positive.

As then-Natural Resources Board member Clausen wrote in a white paper on CWD and human health in 2012, the “ever-increasing number of CWD infected deer on the landscape . . . and the accompanying exponential increase of environmental contamination with CWD prion will result in increased inter-species, including human, exposure to the CWD prion. Under our current management strategy, human exposure will increase.”

prion disease epidemic

Less Testing, More People Eating Infected Venison In Wisconsin

One of the reasons why it is possible for CWD to make the species jump to humans is because of insufficient warnings to hunters by the DNR, Clausen says. The DNR website says there is “no strong evidence” that CWD can be passed to humans, but warns hunters to “minimize contact with the brain, spinal cord, spleen and lymph nodes” when processing deer.

But in 2010, the World Health Organization (WHO) changed its definition of infective tissue to include skeletal muscles from CWD-infected deer and elk. And a 2012 Centers for Disease Control and Prevention (CDC) study notes, “CWD prions are present nearly ubiquitously throughout diseased hosts, including in muscle, fat, various glands and organs, antler velvet, and peripheral and CNS [central nervous system] tissue.” It concludes that the potential for human exposure to CWD from handling or eating material from infected deer “is substantial and increases with increased disease prevalence.” Both the WHO and the CDC recommend that people avoid eating meat from CWD-infected deer or elk.

Unlike the WHO and CDC, Clausen said the Wisconsin Department of Health and Safety (DHS) will not publicly recommend against eating infected venison until there is hard evidence that someone has gotten Creutzfeldt-Jakob Disease (CJD, the human TSE) from eating infected venison. But he believes that the government should be operating on the precautionary principle — that “if something is plausible, that we should be erring on the side of caution unless we have absolute hard evidence that it’s not possible.”

chronic wasting disease and moose

But, Clausen adds, the “precautionary principle is bad for business.” If people become so concerned about contracting CWD that they stop hunting, it means a potential decrease in DNR revenue; and the federal government has stopped funding CWD testing and research in the last year or two. UW-Madison Professor Michael Samuel has seen federal research funds for studying “disturbing” new trends in CWD dry up. “There’s little interest in CWD these days, Wisconsin and nationwide,” he told Durkin.

With testing on the decline, the DNR “has tracked hundreds of cases” in which people have eaten infected venison and “knows that there are many more,” according to the Wisconsin Center for Investigative Journalism. As the rates of the disease rise — as the CDC notes — “the potential for human exposure to CWD by handling and consumption of infectious cervid material increases.”


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Crossbow Communications specializes in issue management and public affairs. Alzheimer’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and the prion disease epidemic is an area of special expertise. Please contact Gary Chandler to join our coalition for reform

Recycling Sewage Recycles Brain Disease

Sewage Sludge Spreading Deadly Diseases

I wish that I could support wastewater reclamation and the application of sewage sludge (biosolids). Unfortunately, I have reversed course on my position over the past decade and now I only see unacceptable risks. The reason for my reversal is a microscopic protein particle called a prion.

The problem is that prion diseases are on the rise around the world in people and animals. Since prions cause a deadly, incurable disease in people, wildlife and livestock, it seems to be prudent to question prion pathways and policies. Prion diseases kill everything in their path. There is no cure. They are always fatal. Since prions are unstoppable, they are a threat to food and water supplies around the world. Carelessly spreading prions via any pathway is reckless and criminal. Since the safety of biosolids cannot be proven, the practice must be stopped based on common sense.

We know these prion diseases (transmissible spongiform encephalopathies–TSEs) as:

mad cow disease and prions

Mad Cow (BSE) in cattle. Mad cow disease has emerged significantly around the globe over the past 30 years. Few countries have been immune.

Creutzfeldt-Jakob disease (CJD) and Alzheimer’s disease in humans. At least 10-20 percent of Alzheimer’s disease cases are actually Creutzfeldt-Jakob Disease. Since both are prion diseases, the difference is likely due to genetic and chemistry variations in the host or due to a prion mutation prior to exposure.

Chronic Wasting Disease (CWD) deer, elk and moose. Meanwhile, prion disease is on the rise among wildlife. Deer, elk, moose and other mammals have been dying from chronic wasting disease for more than 30 years, but the impacted regions continue to spread. The deadly disease has been found from Utah to Pennsylvania and from Canada south to Texas.

chronic wasting disease caused by prions

Scrapie in sheep. Farmers in Europe have reported sick and incurable sheep for about 300 years or more. Some speculate that this is one of the origins of the outbreak because they over-bred sheep for specific genetic traits and weakened the herds. Then some of the sick animals became feed for other livestock.

While the death rate for many major diseases, including heart disease and many forms of cancer, are declining, the death rate from Alzheimer’s disease and Creutzfeldt-Jakobs disease are on the rise among many populations (in some regions more than others). If Alzheimer’s and CJD were truly random diseases without environmental influence, the death rate from these diseases would be fairly consistent around the world. Unfortunately, that’s not the case. People who live in Washington State, for example, are lmost twice as likely to die from Alzheimer’s disease as people elsewhere in the nation. Women are almost twice as likely as men to die of Alzheimer’s disease. Why?

People and animals are exposed to prions in multiple ways. Many cattle got the disease from feed that was made from ground up cattle carcasses–a cheap source of protein and an elimination of disposal costs. Some animals have been infected by touching noses with infected animals or licking or ingesting material that sick animals touched. Since infected animals have the deadly prions in their blood, urine, feces, saliva and tissue, they basically contaminate their entire environment–even after death. Animals or carcasses that come along behind them are at risk of exposure and infection. Cattle also are exposed to prions in sewage sludge.

land application sewage sludge

The same risks are present for people. A person with prion disease will permanently infect cups, utensils, dental instruments and surgical instruments. In fact, most coroners refuse to conduct an autopsy on people who are suspected of having prion disease. Call your favorite coroner and ask.

Furthermore, people with prion disease also contaminate their toilets with their bodily fluids and excretions, which contaminate the sewage treatment plant. Just one person with a prion disease will contaminate every sewage system used–forever. Most cities have had more than one resident or visitor with prion disease, which means that prions are incubating and spreading within the pipes and the treatment plants of most sewage plants around the world. Additional prions arrive frequently thanks to the growing population of people with Alzheimer’s disease or CJD.

The prion problem grows thanks to sewage recycling efforts–prions are spread on golf courses, parks and crops as reclaimed water and as biosolid applications. Entire watersheds are at risk as rain, snow and irrigation can rinse the deadly prions into creeks, rivers, ponds, lakes, oceans and groundwater. Some states, such as Wisconsin, have applied biosolids in almost every county of the state. Wisconsin also has one of the worst epidemics of chronic wasting disease in the nation. Unfortunately, the sick deer contribute to the the contamination as they expose other animals, hunters, soil, and water.

The prion problem escalates when you realize that we are dumping millions of gallons of sewage into our rivers and oceans every day. I wonder how many dolphins and whales that beach themselves or just wash ashore are victims of prion disease?

Does it all sound too much like a sci-fi thriller? The plot thickens.

prion disease epidemic

Dr. Stanley Prusiner earned a Nobel Prize in 1997 for identifying, naming and studying deadly prions. President Obama awarded Prusiner the National Medal of Science in 2010 to recognize the growing significance of his discovery. (In June 2012, Prusiner confirmed that Alzheimer’s disease is a prion disease like CJD and mad cow.)

In fact, prions now are such a formidable threat that the United States government enacted the Bioterrorism Preparedness and Response Act of 2002 to halt research on infectious prions in the United States in all but two laboratories. Now, infectious prions are classified as select agents that require special security clearance for lab research. The intent is to keep prions and other dangerous biological materials away from terrorists who might use them to contaminate, food, water, blood, equipment, and entire facilities.

If prions must be tightly regulated in a laboratory environment today, the outdoor environment should be managed accordingly. If we can’t sterilize surgical equipment used on people who have prion disease, why are we kidding ourselves that we can neutralize prions in sewage? Dilution is not a solution to prion contamination. They don’t have a half-life like radiation. They multiply, which means even one will become many. They can’t be stopped.

biosolids land application and disease

Recycling water and waste is a good idea, except when it concentrates and recycles deadly diseases and pathogens that migrate, mutate and multiply. Prions are worse than radiation. That’s why the Department of Homeland Security has classified them as a “special agent” that must be controlled in only two labs in the entire country. Therefore, we should not make our lands and waters an outdoor chemistry experiment that can blow up in our face–and our children’s.

Any place that recycles sewage water and sewage sludge (biosolids) is spreading pathogens and misinformation–if not outright lies. These lands could someday be condemned as Superfund sites and our diminishing water supplies could be further lost to permanent contamination.

For more information on this topic please visit you will see that the EPA and others are mismanaging these prion risks. I hope that you don’t make the same mistake. I would be happy to discuss this matter and consult with your agency to manage this issue.

Alzheimer's disease epidemic

Fact Sheet

Alzheimer’s disease patients shed infectious prions in their blood, saliva, mucus, urine
and feces. The infectious prions bind to the sewage sludge, including sludge biosolids compost, being applied on home gardens, US cropland, grazing fields and dairy pastures,
putting humans, family pets, wildlife and livestock at risk.

Other prion contaminated wastes discharged to sewers include rendering plants (which process remains of 2 million potentially BSE infected downer cows each year), slaughterhouses, embalmers and morticians, biocremation, taxidermists, butcher shops, veterinary and necropsy labs, hospitals, landfill leachates (where CWD infected and other carcasses are disposed), etc.

The US EPA lists prions as a contaminant of concern in sewage sludge and water
eight times. The EPA issued what it calls the “Sludge Rule,” which basically disclaims any responsibility for its premature and questionable risk assessments as it relates to all toxins and pathogens found in biosolids. It reserves the right to adjust the risk assessments as the test of time may disprove its pseudo-science.

Renown prion researcher, Dr. Joel Pedersen, University of Wisconsin, found that prions become 680 times more infective in certain soils. Dr. Pedersen’s research also proved sewage treatment does not inactivate prions.

sewage treatment plant and disease

“Our results suggest that if prions were to enter municipal waste water treatment systems, most of the agent would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids. Land application of biosolids containing prions could represent a route for their unintentional introduction into the environment. Our results argue for excluding inputs of prions to municipal waste water treatment,” said Pedersen.

“Prions could end up in waste water treatment plants via slaughterhouse drains, hunted game cleaned in a sink, or humans with vCJD shedding prions in their urine or feces,” Pedersen says. “The disposal of sewage sludge was considered to represent the greatest risk of spreading (prion) infectivity to other premises.” It is well known that sewage sludge pathogens, pharmaceutical residue and chemical pollutants are taken up by plants and vegetables. 

The Canadian Food Inspection Agency recently warned that plants can uptake infectious prions: “. . . there is a potential risk to humans via direct ingestion of the compost or of compost particles adhered to skin or plant material (e.g. carrots). Another potential route of exposure is by ingestion of prions that have been taken up by plants.”

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Gary Chandler is a public affairs, public relations and issue management strategist with Crossbow Communications, based in Denver and Phoenix. Please contact Gary Chandler to join our coalition for reform

Chronic Wasting Disease Fueled By Sewage Sludge

Biosolids Spreading Brain Disease

By Patrick Durkin

Those who think Wisconsin should just “learn to live” with chronic wasting disease are seeing their surrender take shape as “nature takes its course” on our deer herd.

In fact, folks near Spring Green are living the realities of such clichés. One farmer in the Wyoming valley of north-central Iowa County has shot 21 CWD-positive deer from his family’s 700 acres since 2008, with 11 falling since April 2012.

Those are just a few of the sick deer in a 144-square mile area where CWD (prion disease) is rising at “unprecedented” rates. That one-word assessment came from Bryan Richards, CWD project leader at the U.S. Geological Survey’s National Wildlife Health Center in Madison, after reviewing the latest CWD reports from Robert Rolley, a Department of Natural Resources researcher in the wildlife science bureau.

chronic wasting disease caused by prions

Rolley, Richards and about 50 other citizens, biologists and agency staff were at UW-Stevens Point on April 6 to help implement 62 recommendations from the “Deer Trustee Report,” Dr. James Kroll’s guide to revamping Wisconsin deer management.

Rolley, too, used one word — “frightening” — to assess CWD’s increase in the 12- by-12-mile area around the Wyoming valley. The eastern border of this diseased block abuts CWD’s core area (northeastern Iowa and northwestern Dane counties), where the disease was first discovered 11 years ago.

What constitutes “unprecedented” and “frightening?” First, realize the infection rate in the core area is increasing about 10 percent annually. That resembles annual infection rates of mule deer in southeastern Wyoming’s Converse area, where 40 to 50 percent of the herd is infected with CWD.

prion disease epidemic

Now consider north-central Iowa County:

• CWD’s annual growth rate for all deer (both sexes combined) 2½ years and older is 27 percent.

• Annual disease rates for adult bucks (18 months and older) are doubling every two to three years.

• Roughly every third buck 2½ years and older is infected, as is one in every six yearling bucks (18 months old). Infected deer live two years or less.

• Although the number of diseased females is lower, the infection rate for does 2½ years and older is growing 38 percent annually, faster than for males.

I’m not aware of data anywhere showing wild, free-range deer with similar infection rates,” Richards said. “The only thing worse was the Stan Hall farm (Buckhorn Flats, near Almond), whose penned herd of 76 deer went from one sick deer to 60 in five years.”

That might sound like mere statistics to some, but not to Matt Limmex, 49, an Iowa County dairy farmer who has spent his life on the family’s property. Of the 11 sick deer killed on Limmex’s lands the past year, six fell during 2012 gun seasons.

land application sewage sludge

The other five? Limmex shot them at the DNR’s request after noticing the “droolers and shakers” near his farmyard. In three cases, they were so sick they couldn’t flee when Limmex approached. The DNR retrieved the carcasses for testing and disposal.

“I hate to see this,” Limmex said. “It’s disheartening. I just want to get sick deer off the landscape.”

Limmex said his family deploys about 14 hunters each year during gun season. They’ve also used agricultural shooting permits since 1991 to control the herd. Even so, this is the first time he senses deer numbers decreasing.

“It seems like the disease might be affecting the herd now,” he said.

biosolids land application and disease

So, what’s causing CWD rates in the Wyoming valley to exceed those in the original disease zone? And will it shrink local herds, as experts have long predicted? No one knows, and our state and federal governments aren’t inclined to find out.

The only current DNR-funded deer research by the University of Wisconsin is studying whether predators are affecting North Woods whitetails. Meanwhile, Professor Michael Samuel at the University of Wisconsin is using federal funds to study if deer leave CWD-causing prions in feces, breeding scrapes and mineral licks. But that’s ending soon.

“We’re puzzled by what’s going on in the Wyoming valley,” Samuel said. “It’s very disturbing, but CWD research is on the way out. We could generate hypotheses and proposals to study what’s behind the increases, but I doubt we’d get the funding. There’s little interest in CWD these days, Wisconsin and nationwide.”

Imagine that. The world’s most “disturbing,” “frightening” and “unprecedented” CWD case is growing next door to our capital and flagship university, and our government won’t crack a window to sniff it.

Meanwhile, no group or coalition of hunters, doctors, veterinarians or environmentalists is holding politicians accountable, or funding the research themselves. There’ll be no shortage of shame as this stench spreads.

CWD News Via

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Crossbow Communications specializes in issue management and public affairs. Alzheimer’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and the prion disease epidemic is an area of special expertise. Please contact Gary Chandler to join our coalition for reform

Transmissibility Of Prion Disease In Soil

Sewage Sludge Expands Prion Pathways

Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions.

land application sewage sludge

We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral.

We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent.

chronic wasting disease caused by prions

Transmissible spongiform encephalopathies (TSEs) are a group of incurable neurological diseases likely caused by a misfolded form of the prion protein. TSEs include scrapie in sheep, bovine spongiform encephalopathy (“mad cow” disease) in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob disease in humans. Scrapie and chronic wasting disease are unique among TSEs because they can be transmitted between animals, and the disease agents appear to persist in environments previously inhabited by infected animals.

Soil has been hypothesized to act as a reservoir of infectivity and to bind the infectious agent. In the current study, we orally dosed experimental animals with a common clay mineral, montmorillonite, or whole soils laden with infectious prions, and compared the transmissibility to unbound agent. We found that prions bound to montmorillonite and whole soils remained orally infectious, and, in most cases, increased the oral transmission of disease compared to the unbound agent. The results presented in this study suggest that soil may contribute to environmental spread of TSEs by increasing the transmissibility of small amounts of infectious agent in the environment.

biosolids land application LASS

Citation: Johnson CJ, Pedersen JA, Chappell RJ, McKenzie D, Aiken JM (2007) Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles. PLoS Pathog 3(7): e93. doi:10.1371/journal.ppat.0030093


Bovine spongiform encephalopathy, human Creutzfeldt-Jakob disease and kuru, sheep scrapie, and chronic wasting disease of deer, elk, and moose belong to the class of fatal, infectious neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs) or prion diseases. The precise nature of the etiological agent of these diseases remains controversial, but most evidence points to a misfolded isoform of the prion protein (PrPTSE) as the major, if not sole, component of the pathogen.

Sheep scrapie and cervid (deer, elk, and moose) chronic wasting disease are distinct among TSEs because epizootics can be maintained by horizontal transmission from infected to naïve animals, and transmission is mediated, at least in part, by an environmental reservoir of infectivity. The presence of an environmental TSE reservoir impacts several epidemiological factors including contact rate (the frequency animals come in contact with the disease agent), duration of exposure (time period over which animals come in contact with the pathogen), and the efficiency of transmission (the probability that an exposed individual contracts the disease).

The oral route of exposure appears responsible for environmental transmission of chronic wasting disease and scrapie; the propagation of bovine spongiform encephalopathy epizootics (feeding TSE-infected meat and bonemeal to cattle); the appearance of variant Creutzfeldt-Jacob disease in humans and feline spongiform encephalopathy in cats (presumably by consumption of bovine spongiform encephalopathy–infected beef); the spread of kuru among the Fore of Papua New Guinea (ritualistic endocannibalism); and outbreaks of transmissible mink encephalopathy (TME) in farm-reared mink. Following consumption, TSE agent is sampled by gut-associated lymphoid tissue, such as Peyer’s patches or isolated lymphoid follicles, and accumulates in lymphatic tissues before entering the central nervous system via the enteric nervous system. While ingestion is a biologically relevant TSE exposure route, oral dosing is a factor of ~105 less efficient than intracerebral inoculation in inducing disease in rodent models. The amounts of TSE agent shed into the environment are presumably small. The assumed low levels of TSE agent in the environment and the inefficiency of oral transmission have led to uncertainty about the contribution of environmental reservoirs of infectivity to prion disease transmission.

prion disease epidemic

We and others have hypothesized that soil may serve as a reservoir of TSE infectivity. Deliberate and incidental ingestion of soil by ruminants can amount to hundreds of grams daily. Prions enter soil environments via decomposition of infected carcasses, alimentary shedding, deliberate burial of diseased carcasses/material and possibly, urinary excretion. TSE agent persists for years when buried in soil. The disease-associated prion protein sorbs to soil particles, and the interaction of PrPTSE with the common aluminosilicate clay mineral montmorillonite (Mte) is remarkably avid. Despite this strong binding, PrPTSE–Mte complexes are infectious when inoculated into brains of recipient animals.

For TSEs to be transmitted via ingestion of prion-contaminated soil, prions bound to soil components must remain infectious by the oral route of exposure. We therefore investigated the oral infectivity of Mte- and soil-bound prions. We examined the effects of prion source (viz. infected brain homogenate [BH] and purified PrPTSE) and dose on disease penetrance (proportion of animals eventually exhibiting clinical TSE symptoms) and incubation period (time to onset of clinical symptoms) in experiments with Mte. We investigated the oral infectivity of soil particle–bound prions to Syrian hamsters using four dosing regimes: (1) infected BH mixed with Mte (BH–Mte mixtures), (2) isolated complexes of purified PrPTSE bound to Mte (PrPTSE–Mte complexes), (3) purified PrPTSE mixed with Mte (PrPTSE–Mte mixtures), and (4) PrPTSE mixed with each of three whole soils (PrPTSE–soil mixtures). The rationale for each dosing regime is described below. Survival analysis was used to assess risk of clinical disease manifestation and quantify differences in effective titer. Application of survival analysis to oral bioassays of TSE transmissibility is discussed in Figure S1 and Text S1.

biosolids land application and disease

Oral Infectivity of BH–Mte Mixtures

To examine the effect of Mte on the oral transmissibility of prions in BH, we incubated infected BH with clay particles for 2 h to allow sorption of the agent; controls lacking Mte were treated identically [22]. Three doses of 10% BH (30, 3, and 0.3 μL) were assayed. Diminished gastrointestinal bioavailability was expected to be evidenced by significant lengthening of incubation period, reduced disease penetrance, or both. Binding of either 30 or 3 μL of brain material to Mte yielded disease penetrance and incubation periods similar to BH alone (Figure 1A and 1B), a finding consistent with our previous report that a substantial fraction of PrPTSE in clarified BH binds to Mte and that Mte-bound prions remain infectious [22].

No Loss of Oral TSE Transmissibility Following Sorption of Prions from Infected BH to Mte (BH–Mte Mixtures)

The oral transmissibility of prions in 30 (A) and 3 (B) μL was not diminished by dosing with Mte. Indicates non-TSE intercurrent death. Animals dosed with Mte alone remained healthy throughout the course of the experiment (unpublished data).

Surprisingly, at the lowest BH dose (0.3 μL, Figure 2), sorption of TSE agent to Mte enhanced transmission, increasing disease penetrance and shortening incubation period. Adjusted for the amount of BH administered and combined across doses, Mte significantly enhanced oral transmissibility (p < 0.0001). Survival analysis indicated the risk of clinical disease manifestation relative to Mte-free controls was 3.03 (95% confidence interval [CI]: 1.68, 5.45), signifying an increase in the effective titer of TSE agent. While the influence of Mte was significant when tested across all BH doses, the effect was most readily observed at 0.3 μL. The dose-dependent difference in the influence of Mte on transmissibility may be attributable to competition between macromolecules in BH (e.g., lipids, other proteins, nucleic acids) with PrPTSE for sorption sites on the clay surface. Such competition was evidenced by detection of unbound PrPTSE and other proteins in incubations of Mte with 30 and 3 μL BH (unpublished data).

Ingestion of Mte mixed with a lower dose of TSE-infected BH (0.3 μL) markedly shortens incubation period and increases disease penetrance relative to an equal amount of unbound BH. * indicates non-TSE intercurrent death. Animals dosed with Mte alone remained healthy throughout the course of the experiment (unpublished data).

Oral Infectivity of PrPTSE–Mte Complexes

To examine the influence of Mte on oral transmissibility without the interference of other macromolecules from brain homogenate, we purified PrPTSE and inoculated hamsters using two different dosing regimes. The first dosing regime (PrPTSE–Mte complexes) was designed to directly assay the infectivity of PrPTSE sorbed to Mte surfaces (i.e., the amount of unbound PrPTSE was minimized in treatments containing Mte). Purified PrPTSE was clarified to remove large aggregates, and after 2-h incubation with Mte, PrPTSE–Mte complexes were separated from unbound protein by centrifugation through a sucrose cushion [22]. Hamsters were orally challenged with the isolated PrPTSE–Mte complexes [22] or an amount of unbound clarified PrPTSE (200 or 20 ng) equivalent to that introduced into the clay suspension (Table 1). Immunoblot analysis of the inocula (Figure S2A) demonstrated that the amount of PrP in the unbound samples was not less than that in PrPTSE–Mte complexes.

Prions Adsorbed to Mte Clay Are Infectious Perorally

Sorption of PrPTSE to Mte dramatically enhanced prion disease transmission (Table 1). Approximately 38% of animals receiving 200 ng of unbound clarified PrPTSE exhibited clinical symptoms with an incubation period for infected animals of 203 ± 33 (mean ± standard deviation) days post inoculation (dpi). In contrast, all animals orally dosed with an equivalent amount of Mte-bound PrPTSE manifested disease symptoms (incubation period = 195 ± 37 dpi), an enhancement of transmission comparable to that observed for the lowest BH dose (Figure 2). Animals inoculated with Mte alone or 10-fold less unbound clarified PrPTSE (20 ng) remained asymptomatic throughout the course of the experiment (>365 dpi), whereas 20 ng of clarified PrPTSE adsorbed to Mte produced TSE infection in 17% of animals. These data establish not only that the Mte-bound prions remain infectious via the oral route of exposure, but that agent binding to Mte increases disease penetrance, enhancing the efficiency of oral transmission.

Oral Infectivity of PrPTSE–Mte Mixtures

The second oral dosing regime using purified PrPTSE (PrPTSE–Mte mixtures) was designed to ensure that treatments with and without Mte contained equivalent PrPTSE doses. These experiments differed from those above in two important aspects. First, PrPTSE–Mte complexes were not separated from suspension prior to inoculation so that comparable amounts of infectious agent were administered to both treatment groups. In the first dosing regime, some PrPTSE may have been lost during sedimentation of PrPTSE–Mte complexes (Figure S2A). Second, the purified prion preparation was not clarified and therefore contained a range of PrPTSE aggregate sizes. The sizes of PrPTSE aggregates attached to Mte particles were expected to be more heterogeneous than those in the first dosing regime.

Compared to Mte-free controls, administration of purified PrPTSE mixed with Mte increased disease penetrance at all doses and shorted incubation times in the 1-μg PrPTSE treatment (Figure 3A). At the two lower doses (0.1 and 0.01 μg PrPTSE), binding of the agent to Mte dramatically increased disease penetrance (31%) at PrPTSE doses failing to yield clinical infection in 31 of 32 animals in the absence of the clay mineral (Figure 3B and 3C). Comparison of the survival curves in Figure 3A and 3C indicates that the 0.01-μg PrPTSE–Mte mixture was at least as infectious as 1-μg PrPTSE Mte-free samples, suggesting that sorption of purified PrPTSE to Mte enhanced transmission by a factor of ≥100.

Figure 3. Concurrent Peroral Administration of Mte and PrPTSE Dramatically Increases Disease Penetrance at Agent Doses That Typically Fail to Produce Clinical Symptoms (PrPTSE–Mte Mixture)

Mte increases disease penetrance and shortens incubation periods associated with ingestion of 1 μg of purified PrPTSE. Concurrent peroral dosage of lower, typically subclinical doses of purified PrPTSE (0.1 or 0.01 μg, [B and C]) with Mte increases disease incidence. Animals dosed with Mte alone remained healthy throughout the course of the experiment (unpublished data).

To quantify the contributions to changes in relative risk of prion dose and agent sorption to Mte, we constructed a multivariate Cox proportional hazards model with two covariates: log10 PrPTSE dose and Mte presence (Table 2). Each log10 increase in PrPTSE dose multiplies the relative risk by a factor of ~2 (i.e., a 10-fold increase in dose approximately doubles the risk of infection). Notably, sorption of purified PrPTSE to Mte multiplies the relative risk by a factor of ~8. These values allowed computation of a multiplicative equivalence factor between PrPTSE dose and Mte presence in the inoculum. Expressed in terms of PrPTSE dose, addition of Mte to the inoculum is equivalent to multiplying the PrPTSE dose by a factor of 680 (95% CI 16, ∞); that is, inclusion of Mte increases the effective titer of a given PrPTSE dose by 680-fold. Estimates of effective titer span a wide range (95% CI 16, ∞), and the present data do not allow us to place an upper bound on the increased risk associated with the presence of Mte in a sample. At a minimum, effective titer increased by 1.2 orders of magnitude, but the effect could be substantially larger. The best estimate of the Cox analysis represents a 2.8 order-of-magnitude increase in effective titer.

Estimated Hazard Ratios due to Prion Dose and Mte Addition

Strain PropertiesOral administration of Mte-bound PrPTSE did not appear to alter strain properties. Following limited proteinase K (PK) digestion, many PrPTSE strains can be discriminated by the size and glycoform pattern of PK-resistant core of PrPTSE (PrP-res) [3336]. Strain differences are also manifested in specific clinical symptoms. At the conclusion of the oral transmission experiments described above, the brains of clinically infected animals were assayed for PrP-res by immunoblotting (Figure S3). Differences in the molecular mass and glycoform distribution of PrP-res were not apparent between the treatment groups. Furthermore, clinical presentation of disease (symptoms or length of clinically positive period) did not differ between treatments.

The experiments described above were conducted using the Hyper (HY) strain of hamster-adapted TME agent (PrPHY). To further examine the strain stability of Mte-bound PrPTSE, we employed the Drowsy (DY) strain of hamster-passaged TME agent (PrPDY) to investigate the molecular mass of PrP desorbed from Mte and the effect of this clay mineral on oral transmissibility [35,36]. We previously reported the N-terminal cleavage of PrPHY extracted from Mte yielding a product similar in size to PK-digested PrPHY [22]. PK digestion of PrPHY and PrPDY results in products of characteristically different molecular masses [35,36]: the length of the PrPHY digestion product exceeds that of PrPDY by at least ten amino acids [35,36]. We found that extraction of bound PrPDY from Mte resulted in a product similar in molecular mass to PrPDY cleaved by PK (Figure 4). These data are consistent with the idea that strain properties are preserved when PrPTSE binds to Mte. DY agent is not orally transmissible [37], and we find that sorption of DY to Mte does not facilitate oral transmission (Text S1).

BH from hamsters clinically affected with either HY or DY agents were incubated with Mte to allow binding. Desorbed proteins were analyzed by SDS-PAGE and immunoblotting. Cleavage patterns of PrPHY and PrPDY extracted from Mte parallel PK cleavage patterns for the respective proteins: cleaved PrPDY migrates further (corresponding to a 1- to 2-kDa molecular mass difference) than cleaved PrPHY. Immunoblot used the PrP-specific antibody 3F4.

Natural soils are composed of a complex mixture of inorganic and organic components of various particle sizes. Smectitic clays such as Mte are important constituents of many natural soils and contribute significantly to their surface reactivity [38]. In natural soils, metal oxide and organic matter often coat smectite surfaces and may alter their propensity to bind PrPTSE. Furthermore, additional sorbent phases may be important in the binding of TSE agents to whole soils. We previously demonstrated that PrPTSE binds to whole soils of varying texture, mineralogy, and organic carbon content [22]. To examine the impact of agent binding to whole soil on oral TSE transmission, we incubated 1 μg of purified PrPTSE with each of three whole soil samples (Elliot, Dodge, and Bluestem soils) to allow sorption, and then orally dosed hamsters with the PrPTSE–soil mixtures. Soil-bound TSE agent remained infectious perorally, and two of the soils significantly enhanced oral disease transmission (Figure 5). Hazard ratios between Elliot (4.76 [95% CI: 1.38–16.4], p = 0.019) and Bluestem (6.04 [95% CI: 1.59–22.9], p = 0.013) soils and unbound PrPTSE indicate a significant increase in transmissibility, but no difference for the Dodge soil (1.66 [95% CI: 0.52–1.66], p = 0.578). The hazard ratios for the Elliot and Bluestem soils did not differ from one another (0.79 [95% CI: 0.19–3.25], p = 0.543) indicating statistical equivalence in transmissibility. The limited numbers of animals in the treatment groups precluded derivation of a multiplicative equivalence factor to equate the presence of Elliot or Bluestem soil with dose of infectious agent; however, substantially more animals in the Elliot and Bluestem treatment groups (14 of 16 animals, 87.5% penetrance) displayed clinical symptoms compared to the unbound PrPTSE treatment group (two of eight animals, 25% penetrance).

Prions Bound to Whole Soils Remain Orally Infectious and Some Soils Increase Transmission

Three soils (Dodge, Elliot, and Bluestem) were incubated in the presence of purified PrPTSE. The samples were orally dosed into hamsters and found to remain orally infectious. Agent association with Elliot and Bluestem soils increases disease incidence, whereas Dodge soil does not influence disease transmission. Animals dosed with soil alone remained healthy throughout the course of the experiment (unpublished data).

These experiments address the critical question of whether soil particle–bound prions are infectious by an environmentally relevant exposure route, namely, oral ingestion. Oral infectivity of soil particle–bound prions is a conditio sine qua non for soil to serve as an environmental reservoir for TSE agent. The maintenance of infectivity and enhanced transmissibility when TSE agent is bound to the common soil mineral Mte is remarkable given the avidity of the PrPTSE–Mte interaction [22]. One might expect the avid interaction of PrPTSE with Mte to result in the mineral serving as a sink, rather than a reservoir, for TSE infectivity. Our results demonstrate this may not be the case. Furthermore, sorption of prions to complex whole soils did not diminish bioavailability, and in two of three cases promoted disease transmission by the oral route of exposure. While extrapolation of these results to environmental conditions must be made with care, prion sorption to soil particles clearly has the potential to increase disease transmission via the oral route and contribute to the maintenance of TSE epizootics.

Two of three tested soils potentiated oral prion disease transmission. The reason for increased oral transmissibility associated with some, but not all, of the soils remains to be elucidated. One possibility is that components responsible for enhancing oral transmissibility were present at higher levels in the Elliot and Bluestem soils than in the Dodge soil. The major difference between the Dodge soil and the other two soils was the extremely high natural organic matter content of the former (34%, [22]). The Dodge and Elliot soils contained similar levels of mixed-layer illite/smectite, although the contribution of smectite layers was higher in the Dodge soil (14%–16%, [22]). The organic matter present in the Dodge soil may have obstructed access of PrPTSE to sorption sites on smectite (or other mineral) surfaces.

The mechanism by which Mte or other soil components enhances the oral transmissibility of particle-bound prions remains to be clarified. Aluminosilicate minerals such as Mte do not provoke inflammation of the intestinal lining [39]. Although such an effect is conceivable for whole soils, soil ingestion is common in ruminants and other mammals [25]. Prion binding to Mte or other soil components may partially protect PrPTSE from denaturation or proteolysis in the digestive tract [22,40] allowing more disease agent to be taken up from the gut than would otherwise be the case. Adsorption of PrPTSE to soil or soil minerals may alter the aggregation state of the protein, shifting the size distribution toward more infectious prion protein particles, thereby increasing the specific titer (i.e., infectious units per mass of protein) [41]. In the intestine, PrPTSE complexed with soil particles may be more readily sampled, endocytosed (e.g., at Peyer’s patches), or persorbed than unbound prions. Aluminosilicate (as well as titanium dioxide, starch, and silica) microparticles, similar in size to the Mte used in our experiments, readily undergo endocytotic and persorptive uptake in the small intestine [4244]. Enhanced translocation of the infectious agent from the gut lumen into the body may be responsible for the observed increase in transmission efficiency.

Survival analysis indicated that when bound to Mte, prions from both BH and purified PrPTSE preparations were more orally infectious than unbound agent. Mte addition influenced the effective titer of infected BH to a lesser extent than purified PrPTSE. Several nonmutually exclusive factors may explain this result: (1) other macromolecules present in BH (e.g., lipids, nucleic acids, other proteins) compete with PrPTSE for Mte binding sites; (2) prion protein is more aggregated in the purified PrPTSE preparation than in BH [45], and sorption to Mte reduces PrPTSE aggregate size, increasing specific titer [41]; and (3) sorption of macromolecules present in BH to Mte influences mineral particle uptake in the gut by altering surface charge or size, whereas the approximately 1,000-fold lower total protein concentration in purified PrPTSE preparations did not produce this effect.

We previously showed that other inorganic microparticles (kaolinite and silicon dioxide) also bind PrPTSE [22]. All three types of microparticles are widely used food additives and are typically listed as bentonite (Mte), kaolin (kaolinite), and silica (silicon dioxide). Microparticles are increasingly included in Western diets. Dietary microparticles are typically inert and considered safe for consumption by themselves, do not cause inflammatory responses or other pathologies, even with chronic consumption, and are often sampled in the gut and transferred from the intestinal lumen to lymphoid tissue [39,46,47]. Our data suggest that the binding of PrPTSE to dietary microparticles has the potential to enhance oral prion disease transmission and warrants further investigation.

In conclusion, our results provide compelling support for the hypothesis that soil serves as a biologically relevant reservoir of TSE infectivity. Our data are intriguing in light of reports that naïve animals can contract TSEs following exposure to presumably low doses of agent in the environment [5,79]. We find that Mte enhances the likelihood of TSE manifestation in cases that would otherwise remain subclinical (Figure 3B and 3C), and that prions bound to soil are orally infectious (Figure 5). Our results demonstrate that adsorption of TSE agent to inorganic microparticles and certain soils alter transmission efficiency via the oral route of exposure.

TSE agent source.

Syrian hamsters (cared for according to all institutional protocols) were experimentally infected with the HY or DY strain of hamster-adapted TME agent [48]. Brain homogenate, 10% w/v, was prepared in 10 mM NaCl. PrPTSE was purified to a P4 pellet from brains of hamsters infected with the HY strain using a modification of the procedure described by Bolton et al. [49,50]. The P4 pellet prepared from four brains was resuspended in 1 mL of 10 mM Tris (pH 7.4) with 130 mM NaCl. In the subset of experiments using PrPTSE–Mte complexes, larger prion aggregates were removed from the preparation by collecting supernatants from two sequential 5-min centrifugations at 800 g (clarification). Protein concentrations were determined using the Bio-Rad ( DC protein assay as directed by the manufacturer’s instructions.

Preparation of inocula and oral dosing.Four types of Mte- or soil-containing inocula were prepared: BH–Mte mixtures, PrPTSE–Mte mixtures, PrPTSE–soil mixtures, and PrPTSE–Mte complexes (see below). To prepare mixtures of BH or PrPTSE with Mte, the indicated amount of 10% brain homogenate (Figures 1 and 2) or PrPTSE (Figure 3) was added to 500 μL of 10 mM NaCl in the presence or absence of 500 μg of Na+-saturated Mte (particle hydrodynamic diameter = 0.5–2 μm) (prepared per [51]). Mixtures of PrPTSE and whole soils (Figure 5) were prepared by adding 1 μg of PrPTSE to 500 μL of 5 mM CaCl2 in the presence or absence of 1 mg of each soil type. Samples were rotated at ambient temperature for 2 h, like samples were pooled, and the equivalent of 500 μg of Mte or 1 mg of whole soil was orally inoculated into each hamster. We previously showed that absorption of purified PrPTSE to Mte was complete within 2 h [22].

Isolated PrPTSE–Mte complexes were prepared as previously described [22]. Briefly, the indicated amount of clarified PrPTSE (200 or 20 ng, Table 1) was added to 500 μg of Mte in 10 mM NaCl (500 μL final volume) per sample. Mixtures were rotated at ambient temperature for 2 h. Each PrPTSE–Mte suspension was placed over a 750-mM sucrose cushion prepared in 10 mM NaCl and centrifuged at 800 g for 7 min to sediment mineral particles and adsorbed PrPTSE. PrPTSE–Mte complexes were resuspended in 500 μL of 10 mM NaCl and pooled. The equivalent of 500 μg of Mte was orally inoculated into each hamster. To control for potential sedimentation of unbound PrPTSE, “mock” samples lacking Mte were processed identically, and any sedimented material was inoculated into hamsters. As a positive control, unbound PrPTSE (200 or 20 ng) was orally administered to hamsters. All oral inoculations were via pipette and voluntary consumption. Following oral dosing, hamsters were observed twice weekly for the onset of clinical symptoms [48] for at least 300 d, a period of time found sufficient to observe most or all clinical cases.

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Crossbow Communications specializes in issue management and public affairs. Alzheimer’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and the prion disease epidemic is an area of special expertise. Please contact Gary Chandler to join our coalition for reform

CJD Kills North Carolina Boy

Creutzfeldt-Jakob Disease Taking Younger Victims

By Andrew Kenney

It wasn’t bacteria or a virus that plagued young Michael Mendy’s body and mind. He did not inherit his symptoms from his mother or father. Nothing toxic was in his blood. An autopsy reveals that he died of prion disease. And while he was sick, Michael’s parents had no explanation.

“I had to figure it out. I had to find an answer. I had to find a doctor that could help him,” said Michael’s mother, Kathleen Mendy, who lives in western Cary. “You don’t think you’re going to come across something that nobody’s ever seen.”

Michael Mendy dies of CJD

But they had. Dozens of specialists and three years of suffering brought no diagnosis. Michael died a year ago, at age 16. And only then did the explanation and the terrible significance of his case emerge.

Doctors estimate that fewer than one in 100 million young people will share Michael’s journey. The sports nut and East Cary Middle School student was killed by a disease that mostly afflicts the elderly. Michael was a heart-wrenching outlier, apparently among the youngest ever to suffer a spontaneous ravaging of the brain.

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Kathleen Mendy thinks it started on Michael’s 13th birthday in 2009. On that January day, another boy knocked Michael’s head to the court during a basketball game. He was playing again a minute later, his mother watching with a tinge of worry.

The symptoms of a years-long illness crept in that weekend, during a mother-son Super Bowl trip to Florida. That’s where she first saw Michael’s confusion, his unsure movements and his inexplicable crying.

It seemed at first like the troubling wake of the teen’s second concussion in three months, but that theory would erode and change. Across the next three years, in a nightmare that kept unfolding, the brawny teenager would drop almost half his body weight, spend months in the hospital, lose his speech and lay debilitated by simple infections.

The printed record of Michael’s hospital visits and test appointments is three and a half pages long. It documents an increasingly desperate search, listing 140 days in the hospital, 91 visits with doctors and 426 therapy appointments from 2009 to 2012.

“I always thought he would get better,” Kathleen Mendy said. “I used to always tell him, ‘Michael, one day you’re just going to run out of your bedroom, and you’re going to come running downstairs, and you’re going to be all better.’ ”

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While his friends went on to high school, Michael was confined to a wheelchair and fed through a tube. His care grew so intense that his mother brought on a full-time medical aide. His father, divorced from his mother, drove in from Florida each time he entered the hospital, and Kathleen Mendy’s family often visited from New York. Each treatment was more esoteric than the last. By the end of 2011, the Mendys had seen more than 30 doctors, medical specialists, faith healers and alternative practitioners.

“I tried chiropractors, reflexology, myofacial therapy,” Kathleen Mendy said. “I tried everything.”

The realization came to Kathleen Mendy on the last night of January 2012, the 22nd day that Michael spent in a UNC hospital bed. He’d been kept alive in an intensive-care unit by a breathing machine while an infection took hold of his lungs. The mysterious disorder had left his body unable to respond. The memory shakes Kathleen Mendy to tears. The scene sticks in her mind.

“Not until the night before he died, is when, honestly, it hit me,” she recalled.

The doctors laid a choice before his parents that night. Michael could go home with a tracheotomy and a ventilator, but they believed he’d live just a few months longer. Or doctors could remove him from life support. Michael’s parents didn’t want him to suffer anymore. He died on Feb. 1, 2012.

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Only months later would Michael’s family learn the reason for his degradation and death. An autopsy showed that the teenager died of sporadic fatal insomnia, a subtype of Creutzfeldt-Jakob Disease.

“I’m so glad I didn’t know what it was” before Michael died, Kathleen Mendy said. “Because then I wouldn’t have had hope.”

“This disease is a descent into hell,” said Florence Kranitz, president of The Creutzfeldt-Jakob Disease Foundation in New York City.

She saw her own husband die in 2001 of an ailment similar to Michael’s. Since then she has heard the stories of many of the 300 CJD victims her organization identifies each year, including cases of fatal insomnia.

“We get this phone call, and tragically it’s the same phone call over and over again,” Kranitz said. “They’ve never heard of this disease.”

The story she heard from Kathleen Mendy fit the profile, with one beguiling exception. Almost everyone afflicted by CJD subtypes are older than 45, except those who contract a variant of the disease genetically or through contaminated beef, which Michael had not.

biosolids land application and disease

Michael’s case quickly drew the attention of national experts, including Pierluigi Gambetti, director of the National Prion Disease Pathology Surveillance Center in Ohio. Gambetti, a pioneering researcher, examined Michael’s brain and in April identified his disease as sporadic fatal insomnia.

He’d later take hours to talk with Kathleen Mendy about her son’s death. Sporadic fatal insomnia and CJD, he explained, are part of the still-mysterious field of neurodegenerative diseases, including Alzheimer’s and Parkinson’s.

Some of these ravages of the brain, such as so-called mad cow disease (another form of prion disease), begin with an infection of prions, or pathogenic proteins, from the outside. CJD in the young also can be caused by prions, often transmitted during surgery.

Prions and Prusiner win Nobel Prize

Like a virus, a prion can essentially “breed.” The virus hijacks human cells, and the prion reshapes other proteins into its own mutated form. And when a prion or virus propagates enough, it can destroy its host.

But there’s a crucial difference: The prion also can come from within. Gambetti believes that Michael’s disease began when the boy’s brain misfolded a protein, creating a prion instead. The defect may then have multiplied out of control and ruined the delicate balance of the body.

It’s not uncommon for the body to make mistakes. Neurons and other cells normally catch and eliminate prions before they replicate. These defensive systems may grow weaker with age; some people may also inherit weaker defenses.

But Michael was a teenager, with no apparent family history of neurodegenerative diseases. Gambetti put the odds of such a case at one in 100 million in the general population; another doctor said it was one in 600 million. In fact, Michael may be among the youngest ever to be affected by a neurodegenerative disease without an inherited or outside cause.

“We just haven’t seen this disease affect someone this young,” said John Trojanowski, a professor of geriatric medicine at the University of Pennsylvania.

Gambetti, who played a key role in the discovery of fatal insomnia, theorizes that Michael’s illness was random, despite the odds. It may be that, by chance or some unknown factor, Michael’s brain perfectly bred its own pathogen.

“The bodies of all animals are a marvel of things, in positive and negative,” Gambetti said. “They can do things striking for the good, but also for the bad.”

Nearly a year after Michael’s death, Kathleen Mendy finds love and support from family, friends and Compassionate Friends, a local group. But the extreme rarity of Michael’s case is isolating.

When she attended a CJD conference last summer with her twin sister, they met the families of people who had mostly died in middle and old age.

Some nights she goes up to her only child’s room. It’s lined with dozens of sports team caps and trophies. Athletes’ names are still painted on the blades of his ceiling fan, and the UNC comforter is still on his bed. All that’s new is the shrine on the desk, where Michael’s photo stands near a glazed statue of praying hands.

“Sometimes I think I’m OK, and other times it’s like it just happened last night. It’s like a rollercoaster,” Kathleen Mendy said.

She may have as many logical answers now as she’ll ever get – a medical, if not a spiritual description of why Michael died.

She still doesn’t know what it was that made her son vulnerable. She believes Michael’s concussions triggered his illness, but his doctors haven’t confirmed the idea.

“I’m a little bit resolved that I’ll never hear the answer,” she said. “It would be nice to know, but if I don’t know it, it’s not what matters now.”

She finds hope instead in the idea that she could help others; she’s thinking of writing a book and becoming a public advocate for those who suffer with CJD.

Meanwhile, as Michael’s birthday and the first anniversary of his death approach, Gambetti and one of Michael’s former doctors are preparing to present his case to their respective medical communities. As painful as the case is, “its rarity may contribute to expand the knowledge on this terrible disease,” according to Gambetti.

He hopes his research will one day allow much earlier diagnosis and treatment of fatal insomnia. Such a breakthrough could key medical progress across the spectrum of prion-related diseases, which are fatal in practically all cases.

Gambetti’s research into Michael’s case will soon yield a more immediate result too: He’ll be able to tell caregivers that sporadic fatal insomnia can strike not just the mature, but perhaps people who are just beginning their lives.

And with Michael’s story spreading, the next stricken family may at least know the harrowing path ahead.

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Chronic Wasting Disease Reaches Pennsylvania

Sewage Sludge Recycles Brain Disease

Forget about the latest outbreak of EHD, which has now run its course here in Western Pennsylvania; there was even worse news last week regarding the state’s deer herd. The Pennsylvania Department of Agriculture has confirmed the first positive case of Chronic Wasting Disease in the state on a deer farm in Adams County.

chronic wasting disease cause

The fact CWD was found at a deer farm in New Oxford is a little better than finding it in the general deer population – since the state can now quarantine that farm – but it is troubling nonetheless.

CWD is fatal in deer, elk and moose, but there is no evidence CWD can be transmitted to humans, according to the Centers for Disease Control and Prevention and the World Health Organization.

“Pennsylvania has an aggressive Chronic Wasting Disease surveillance program and a strong response plan,” said Agriculture Secretary George Greig. “Steps are being taken to prevent further spread of this disease to the state’s captive and wild deer populations.”

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In addition to the Adams County location, a quarantine has been set up on two farms directly associated with the positive deer, one in Williamsport, the other in York County.

“To date, CWD has not been found in Pennsylvania’s wild deer population,” said Pennsylvania Game Commission Executive Director Carl G. Roe. “Concerns over CWD should not prevent anyone from enjoying deer hunting and consuming meat from healthy animals.”

In order to understand the threat, one must understand the dynamics of this neurological disease. Alzheimer’s disease, for example, is a member of an aggressive family of neurodegenerative diseases known as Transmissible Spongiform Encephalopathy (TSE). The operative word is “transmissible.”

TSEs are caused by a deadly protein called a prion (PREE-on). As such, TSEs also are referred to as prion disease. The critical factor is that prions are unstoppable. The pathogen spreads through the bodily fluids and cell tissue of its victims. All tissue is infectious just because of the contact with the contaminated blood.

TSEs also include Creutzfeldt-Jakob disease, Parkinson’s, Huntington’s, mad cow disease and chronic wasting disease in the deer family. Few, if any, mammals are immune. There is no cure.

prion disease epidemic

Dr. Stanley Prusiner, an American neuroscientist from the University of California at San Francisco, earned a Nobel Prize in 1997 for discovering and characterizing deadly prions and prion disease. President Obama awarded Prusiner the National Medal of Science in 2010 to recognize the importance of his research. According to Prusiner, TSEs all are on the same disease spectrum, which is more accurately described as prion disease. He claims that all TSEs are caused by prions.

Prions are unstoppable. Prions shed from humans are the most deadly mutation. They demand more respect than radiation. Infected surgical instruments, for example, are impossible to sterilize and hospitals throw them away. Prions are in the blood, saliva, urine, feces, mucus, and bodily tissue of its victims. Many factors are contributing to the epidemic. Prions are now the X factor. Industry and government are not accounting for them or regulating them. They are ignoring the threat completely, which violates the Bioterrorism Preparedness and Response Act of 2002 in the United States. Other nations also are ignoring laws developed to protect food, air and water.

“There is now real evidence of the potential transmissibility of Alzheimer’s disease,” says Thomas Wiesniewski M.D. a prion and Alzheimer’s researcher at New York University School of Medicine. “In fact, this ability to transmit an abnormal conformation is probably a universal property of amyloid-forming proteins (prions).”

A new study published in the journal Nature renews concern about the transmissibility of Alzheimer’s disease between people. A second study by the same scientist in early 2016 adds to the stack of evidence.

Chronic wasting disease can spread via many vectors, but the wastewater treatment process and the disposal of sewage sludge on land is being completely ignored. Sewage sludge is the largest prion pathway in the world.

When the U.S. government enacted the Bioterrorism Preparedness and Response Act of 2002, it classified prions as select agents that pose an extreme risk to food, water and much more. Only two labs in the U.S. were allowed to handle them for research purposes. Unfortunately, the CDC quietly took prions off the list because the regulation criminalized entire industries and several reckless practices.

sewage treatment plant and disease

Wastewater treatment plants, for example, are spreading this infectious waste far and wide because they are incapable of stopping prions. All by-products and discharges from wastewater treatment plants are infectious waste, which are contributing to the global epidemic of neurodegenerative disease among humans, wildlife and livestock. Sewage treatment plants can’t detect or stop prions. Just ask the U.S. EPA and the industry trade organization—the Wastewater Effluent Federation. Sewage sludge (biosolids) and wastewater reclamation are causing widespread contamination.


public relations firm and public affairs firm Denver and Phoenix

Crossbow Communications specializes in issue management and public affairs. Alzheimer’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and the prion disease epidemic is an area special expertise. Please contact Gary Chandler to join our coalition for reform

Pandora’s Lunchbox Filled With Prion Disease

Mad Cow Disease, Chronic Wasting Disease Symptoms Of Bigger Threat To Humans

In my opinion: The recent case of mad cow disease in California once again has people around the world asking questions about food safety. A constructive analysis requires a broader perspective and a refined focus on the causes of all prion diseases.

Contrary to government statements, there is not an isolated case of mad cow disease or any prion disease. Prion disease contributes to deadly forms of environmental contamination that essentially recycle and redistribute the disease. Victims are infectious long before they exhibit clinical symptoms. Chronic wasting disease in various deer species is an explosive example. As prion disease is recycled in the environment and up the food chain, prions mutate and become even more lethal to people and other mammals.

land application sewage sludge

Prion Disease

Mad cow disease, also known as bovine spongiform encephalopathy (BSE), is one of many deadly prion diseases (technically referred to as Transmissible Spongiform Encephalopathy (TSE). TSEs are a spectrum disease, where CJD is the most extreme form. We know prion disease as:

  • Mad-cow disease (in cattle);
  • Creutzfeldt-Jakob disease (CJD, Parkinson’s disease, Huntington’s; disease and Alzheimer’s disease in humans);
  • Chronic wasting disease (CWD in wildlife such as deer, elk, moose and reindeer); and
  • Scrapie (sheep).

The common denominator in all of these diseases is the prion (PREE-on) In addition, according to neuroscientist Laura Manuelidas, about 10-25 percent of Alzheimer’s disease cases are misdiagnosed—they are actually cases of CJD, which is further p the prion spectrum.

Alzheimer's disease epidemic

Furthermore, according to Dr. Claudio Soto at the University of Texas, Alzheimer’s is a prion disease. When you sift through the smokescreen and lump all of these diseases together, it begs the question “do we have a deadly epidemic on our hands and is it being mismanaged.”

Prions are a form of protein that cannot be effectively stopped. They can’t be killed because they are not a virus or bacteria and they don’t contain DNA or RNA. These pathological proteins mutate, migrate, multiply, and intensify. Prion diseases kill everything in their path. In reality, there is no way to contain the disease. There is no cure—prion disease is always fatal. (Studies contend that any prion inactivation procedures must be validated by bioassay against the prion strain for which they are intended to be used.)

Prions are a lethal threat to our food and water supplies. We also risk exposure and infection at hospitals, dental offices, restaurants, and through pet food. The buildup of prions in the environment will get worse with time. Mismanagement is accelerating the process. Various forms of prion disease are already spreading around the world, building up in soil and water, and building up in the bodies of virtually every living creature on the planet. The incubation period and the onset of clinical signs of the disease usually take years, which makes these diseases easier to ignore and more difficult to study.

Prions and Prusiner win Nobel Prize

Prions Earn The Nobel Prize

Dr. Stanley Prusiner, an American neuroscientist from the University of California at San Francisco, earned a Nobel Prize in 1997 for discovering and studying deadly prions. President Obama awarded Prusiner the National Medal of Science in 2010 to recognize the growing significance of his discovery. Although his research is ongoing, we know enough about prions to sound the alarm on many levels.

Prions are such a formidable threat that the U.S. government enacted the Bioterrorism Preparedness and Response Act of 2002, which included a provision to halt research on infectious prions in all but two laboratories. Now, infectious prions are classified as select agents that require special security clearance for lab research.

biosolids land application and disease

Thanks to Dr. Prusiner’s discovery and pioneering research, prion disease has been found in humans, livestock and a variety of wildlife species in several countries, including Austria, Canada, Czech Republic, Finland, Germany, Greece, Israel, Italy, Japan, Poland, Slovakia, Slovenia, Spain, United Kingdom, and the United States.

Not only are prion diseases a symptom of a much bigger problem, they are contributing to the buildup of prions in the environment.  A person or animal with prion disease is contaminating their immediate environment and exposing nearby humans and animals to deadly prions.

chronic wasting disease

The Prion Threat to Public Health

The prion pathogen spreads through urine, feces, saliva, blood, milk, soil, and the tissue of infected animals and humans—including bone and muscle tissue. (Contrary to industry reports and a controversial statement from the World Health Organization, research suggests that milk is a pathway to prion exposure).

Humans with Creutzfeldt-Jakob disease (CJD) also are shedding infectious prions into toilets, public sewers and elsewhere. If a single person with prion disease discharges bodily fluids or feces into a public sewer system, that sewage system is permanently infected and the amount of contamination will multiply and intensify over time. The more infected people use the sewage system, the worse the contamination problem. Everything discharged from that sewage system—reclaimed water or biosolids—is at risk of spreading the contamination even further.

Alzheimer's disease prevention

Between 2 and 25 percent of the 4.5 million cases of Alzheimer’s disease and senile dementia victims in the U.S. alone are actually infected with CJD, creating the reality that many thousands of CJD victims are shedding infectious prions throughout their home and everywhere they visit, (Manuelidis, et al, 1989; Boller, et al, 1989, 1995; Harrison, 1991; Teixeira, 1995; Warren, et al, 2005).

Similar pathways exist from an infected cow, sheep, or deer. When infected animals use fields and feedlots, their urine, feces, saliva, and blood permanently contaminates those areas. That contamination becomes bio-available to every creature that follows the path of the infected animal. Those areas are then subject to rainwater and runoff, which can carry the prions further.

sewage treatment plant and disease

Prions No Longer Regulated

In Canada, out of 55,415 cows tested for BSE in 2006, five head of cattle were identified with BSE. If the U.S. only tests 40,000 head of cattle and detects one animal with BSE out of that small test group, we must assume that hundreds more infected animals are missed out of the millions of cattle that are milked and slaughtered each year. Based on those statistics, without comprehensive testing globally, we must assume that beef and dairy operations are producing hundreds of sick animals each year that are being milked, slaughtered and consumed by humans, pets, fish farms, and even other forms of livestock and poultry.

In addition, the land at the feedlot or dairy is contaminated with manure and urine that often is scraped out and used as compost and fertilizer on farms and gardens, which expands the pathways for deadly prions to reach unsuspecting families. “Prions can survive for years in soil,” (Brown, et al 1991). “Animals can become infected from prions in soil,” (Miller, et al 2004). Naturally occurring BSE prions can be up to 1 million times more difficult to inactivate than the most commonly used hamster prions (engineered for clinical studies).

Furthermore, prions can wash from the soil and migrate through irrigation and surface water runoff and settle in groundwater, streams, ponds, lakes, and oceans—where they proceed to multiply and mutate into even more abundant and lethal forms. Wildlife, livestock and humans (especially children) can ingest prions from soil exposure, water exposure, or food. We can’t afford to take the risk of further contaminating entire watersheds – increasing the pathway to humans, livestock, and wildlife downstream.

With these characteristics, there is not an isolated case of Mad-cow or any prion disease. The California dairy where the recent infected animal lived and produced milk is contaminated (two dairies have been quarantined since the discovery of that case of BSE). If the infected cow provided milk to a processor, that supply chain is now in question and those supply chains should be quarantined. In fact, all exposed milk should have been immediately recalled from that entire supply chain. The pathways of that milk still should be traced and condemned.

If the infected animal was rendered for pet food, that rendering plant is now permanently contaminated and will contaminate everything that is processed from now on—exposing our pets to the deadly disease and creating a new pathway in our homes—food bowls that also are permanently contaminated (in fact, an undisclosed rendering plant has been quarantined).

If cattle with BSE are actually processed at a slaughterhouse, that slaughterhouse also is permanently contaminated and will contaminate every carcass that follows the infected animal down the production line. Compounding the problem is the fact that liquid wastes from slaughterhouses are rinsed down the drainpipe and into the municipal sewage system, where they add to the risks associated with that waste stream.

Prion Pathways

Milk and Meat: As stated earlier, highly infectious risk-material (brain and spine) is not the only pathway to prion exposure. Prions have been found in muscle tissue and milk.

Lessons From The United Kingdom: Initially, UK officials insisted the Mad-cow epidemic was not a risk to humans. After 150 human vCJD deaths, they admitted that they were wrong.

mad cow disease and prions

“Thousands of pages of grisly detail on meat-pie making and animal-feed milling might seem like a hard read. As bureaucrats digest the final report of Britain’s BSE inquiry, handed to ministers on October 2nd, 2000 stomachs at the Ministry of Agriculture, Fisheries and Food (MAFF) and the Department of Health must be churning. Not at the finer points of carcass-rendering, but at what is expected to be a thorough dissection of bureaucratic incompetence. Ministers will be considering the findings until the report is presented to Parliament on October 23rd. Three days later, the public will at last be allowed to read the report into Britain’s biggest public-health scandal for decades.

The independent inquiry was established by the UK government to work out the history of two epidemiological crises, bovine spongiform encephalopathy (Mad-cow disease) and its human relative, new-variant Creutzfeldt-Jakob disease (vCJD). The inquiry’s three-person committee, headed by Lord Phillips, a high-court judge, was also asked to assess whether government and industry responded adequately to the situation as it evolved.

Roughly £27m ($39.4m) and 630 witnesses later, the Phillips report is widely expected to be the definitive word on what went wrong in Britain between the first documented cases of BSE in 1986 and the announcement in Parliament, ten years later, that the strange neurodegenerative condition appearing in a handful of young people, now called vCJD, was probably linked to Mad-cow disease.” – The Economist, October 5, 2000.

The Full report from the UK’s BSE Inquiry is available. Furthermore, almost 4,000 Britons aged between 10 and 30 may be harboring the prion proteins that cause the human form of Mad-cow disease. The new estimate comes from direct analyses of human biopsies (tonsils), and is much higher than epidemiological projections of the likely number of deaths from variant Creutzfeldt-Jakob disease (vCJD).

For years, industry experts and government regulators insisted infectious prions could not be found in blood or muscle except for infected sheep and goats. Prions have since been found in blood and muscle of human vCJD and sCJD victims and in the leg muscle tissue of infected deer.

Even organic supplies are not immune from the prion problem. For example, if an organic farm is downstream from a traditional farm that has an animal with BSE, the water runoff from that farm will expose the organic operation downstream to deadly prions.

Let’s assume that everything that the beef and dairy industries, and the USDA, have said about the latest example of Mad-cow disease is true. The tested animal was sent to a rendering plant and was never destined for the food supply.

  1. How much milk did that dairy cow produce before it exhibited clinical signs of the deadly disease? Where did that milk go? On what date was this sick dairy cow withdrawn from the production line? We know that animals are contagious, and shed prions via bodily fluids, including milk, long before they exhibit clinical signs of the disease.
  2. How many other dairy cows have this fatal and contagious disease, but don’t exhibit the clinical signs, yet? How much milk are these animals producing every day?

Growth Hormones and Blood Transfusions: Most growth hormones are made from the pituitary brain of dead cattle or cloned from the DNA of that pituitary gland (bad idea). One infected gland in the production facility and all future products are permanently contaminated. Dairy and beef producers could be injecting BSE directly into live animals with this practice. Similar practices (taking the pituitary gland from cadavers) have killed people from prion disease, including this very recent case from May 2012.

It’s time to stop using growth hormones in beef and dairy cattle. Even if the hormone itself is free of prion disease, what does a growth hormone do to a prion? Has industry or regulators even conducted studies on this dynamic? People have contracted prion disease from infected hormones, infected blood and infected organ transplants. We must assume that the same risk is present for livestock.

Recent studies of variant Creutzfeldt-Jakob disease (vCJD) indicate that this disease is transmissible by blood. One case of probable transfusion-transmitted vCJD infection has been reported, and one case of subclinical infection has been detected. On February 9, 2006, a third case was announced by the UK Health Protection Agency.

Each of the three patients had received a blood transfusion from a donor who subsequently developed clinical vCJD, which indicates that transfusion caused the infection.

Alzheimer's disease infectious

Surgical and Dental Procedures: We can’t sterilize surgical equipment used on people who have prion disease. Prions are so resistant to sterilization that surgical instruments used on a person with CJD must be disposed because they are permanently contaminated. Hospitals have been sued successfully for exposing subsequent patients to deadly prions. Dental and oral surgery settings have the same challenge, but those industries have ignored those risks for the most part.


Risk of Prion Disease Transmission through Bovine-Derived Bone Substitutes

Despite the causal association between variant Creutzfeldt – Jakob disease and bovine spongiform encephalopathy (BSE), bovine origin graft materials are widely used during dental surgical procedures. The aim of this study was to assess the risk of BSE transmission through bovine bone substitutes. Methods: Electronic database of MEDLINE was searched to identify relevant studies regarding our focused questions, presence of BSE prion infectivity in raw bovine bone, BSE prion inactivation by bone substitute manufacturing process, protein contents in anorganic bovine bone substitutes, and validity of current BSE diagnostic methods. Search terms yielded 1,704 titles. After title/abstract screening and duplicates removal, 36 full-text articles were screened for inclusion. Results: A total of 16 studies were included in the final analysis. No eligible studies were identified regarding the efficacy of BSE prion inactivation by the treatments used for anorganic bovine bone manufacturing. BSE infectivity and PrP(Sc), pathological prion, were detected in bovine bone marrow and serum samples.

Prions were detected in Tutoplast® (bovine), Bio-Oss®, and tibia samples treated at the similar condition for Bio-Oss deproteinization. Inconsistent results of different BSE diagnostic tests were not unusual findings (Iwata et al. 2006; Arnold et al. 2007; Murayama et al. 2010), and a study by Balkema-Buschmann and colleagues showed an apparent discrepancy between BSE infectivity and detection of PrP(27-30), the current surrogate marker for prion disease infectivity. Conclusion: This review indicates that bovine-derived graft biomaterials may carry a risk of prion transmission to patients.

Limited efficacy of steam sterilization to inactivate vCJD infectivity.

The transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt-Jakob Disease (vCJD) raised concerns about potential secondary transmissions due to the resistance of the agents causing transmissible spongiform encephalopathies (TSEs), sometimes known as prions, to commonly used methods of sterilization, notably steam sterilization (or autoclaving). It has been suggested that surgical instruments and other medical devices might retain sufficient infected tissue debris after cleaning and steam sterilization to infect patients on whom they are subsequently used.

As noted previously, TSE strains derived from BSE sources appear to be more resistant to steam sterilization and other forms of heat inactivation than other TSE sources.

Pet Food: How many infected animals are sent to a rendering plant, never tested for BSE, and are churned into food for dogs, cats, poultry, fish, and zoo animals? What is the likelihood that we are feeding deadly food to our pets? If and when contaminated, that food dish is another pathway for the prion pathogen to enter our homes and bodies, not to mention the risk to our pets. How often do you actually touch that pet food or the dish? How often do you wash that bowl in your kitchen sink?

farmed fish and prion disease

Aquaculture: Many fish farms use specified risk material—SRM (brain and spinal cords) from slaughterhouses and rendering plants as protein meal. What is the likelihood that infected material from a slaughterhouse or a rendering plant was sent to a fish farm (either in a large lagoon or in the open ocean) and dumped into the water and consumed by farmed fish (and wild fish and mammals such as dolphins and whales). Since every microscopic prion can’t be consumed, how much water are we contaminating every year to extend this science experiment via new pathways.

This questionable practice puts the health of the fish at risk and those who eat the fish. Secondly, the water that the risk material is dumped becomes contaminated with prions, which threatens groundwater, surface water runoff, streams, rivers, and oceans with deadly prions. This factor could be contributing to the deaths of dolphins and whales and it could be contributing to prion disease in people. Many fish have contracted Whirling disease, which could be a form of prion disease (needs research that this author has not conducted, yet).

Animal Rendering & Anaerobic Digestion Of Carcasses: “It’s necessary to use additional heat at the end of the rendering process to fully inactivate pathogens.  However, even with this, prions are not inactivated,” APHIS/USDA, January 2005.

“While finished compost can be spread on farmland as fertilizer, if prions are present and the compost is used as fertilizer prions can re-enter the food chain through grazing plants, hay and straw obtained from those areas. Thus, composting should not be used to dispose of infected deer, elk, sheep, goats, or cattle. Composting is especially unsuitable for specified risk materials, especially neural tissues (skull and spinal cord) encased in bones. The indiscriminate use of composting and spreading its byproducts on agricultural land is inconsistent with the FDA feed rule, would dilute its integrity and invalidate all existing BSE/TSE risk assessment models. This is similar to what may have transpired with the CWD material, given the WIDNR (Wisconsin Department of Natural Resources) disposal policy was indeed implemented,” National Renderers’ Association response to USDA and APHIS, June 2005.

Lotions & Cosmetics

How safe is collagen material? Our purified collagen material is extremely safe and is being used in the manufacture of finished medical devices currently on the market. All collagen devices manufactured by Collagen Matrix, Inc. have passed biocompatibility testing in accordance with ISO 10993 Biological Evaluation of Medical Devices. Any additional potential concerns such as viruses, BSE, bacteria, and pyrogens have been addressed thoroughly in manufacturing process control which includes a step that is proven to inactivate BSE, quality control testing, validations, and internal risk analyses.

Is Mad Cow Disease or Bovine Spongiform Encephalopathy (BSE) transmission a concern with the use of your collagen?

The risk of transmitting Mad Cow Disease, Bovine Spongiform Encephalopathy (BSE) or viruses through the use of bovine tendon or corium as a raw material source of type I collagen for medical devices is considered negligible. This conclusion is based on a thorough investigation and risk analysis process in which various aspects of the material from animal sourcing and harvesting to finished product testing were evaluated. There has been no such documented case of BSE transmission through a medical device using bovine-derived collagen material.

Cosmetic Ingredients, Risks

From cosmetics, candy and gelatins to drugs for diabetes, hay fever and arthritis, there are beef parts in dozens of products that people use every day. Worries about the safety of British beef spread beyond just steaks and chops Wednesday when the European Community ordered Britain to stop exporting all beef-derived products including ice cream, candy, cosmetics and drugs.

U.S. scientists noted, however, that very few of these products use pieces of the steer’s brain and spinal cord, the only parts of the steer’s body where mad cow disease, or bovine spongiform encepthalopathy, has been found. The most widely used beef product is collagen, the spongy substance derived from beef skin or bones. Collagen is often an ingredient in ice cream, custards, cheeses, candies, sausage casings and cosmetics.

Even if it were found to be a carrier, the vast majority of the collagen in U.S. products comes from domestic beef because it is so plentiful, said Bob Rust, professor emeritus in meat science at Iowa State University.

The FDA, prior to approval of any drug with beef products, should require the manufacturer to certify that the beef only come from countries free of the disease. It does not. The variety of drugs derived from cattle parts is diverse and includes:

  • Growth hormones come from the cattle pituitary glands.
  • Adrenalin products for hay fever, asthma and other allergies, from the adrenal gland.
  • Cortizone, for arthritis, asthma, shock, also from the adrenal gland.
  • Insulin, for diabetics, from the pancreas.
  • Tissues used as patches during heart bypass surgery, from the bovine pericardial tissue.
  • Thromboplastin, a blood coagulant used in surgery, from the brain.
  • Drugs for the treatment of stomach ulcers.
  • Gelatine capsules for many drugs are made from cattle tissues.

biosolids land application LASS

Sewage Sludge, Biosolids, Wastewater Reuse

In June 2012, Nobel Laureate Stanley Prusiner, UCSF, confirmed that Alzheimer’s Disease (AD) is a prion disease like CJD and mad cow. AD victims shed infectious prions in their blood, saliva, mucous, urine and feces. The infectious prions bind to the sewage sludge, including sludge/biosolids/compost, being applied on home gardens, US cropland, grazing fields and dairy pastures, putting humans, family pets, wildlife and livestock at risk.

Other prion contaminated wastes discharged to sewers include rendering plants (which process remains of 2 million potentially BSE infected downer cows each year), slaughterhouses, embalmers and morticians, biocremation, taxidermists, butcher shops, veterinary and necropsy labs, hospitals, landfill leachates (where CWD infected and other carcasses are disposed), Drinking water is at risk for prions if it comes from a surface source (river or lake) which receives treated sewage effluent. Chlorination does not inactivate prions.

The US EPA lists prions as a contaminant of concern in sludge and water eight times.

Renown prion researcher, Dr. Joel Pedersen, University of Wisconsin, found that prions become 680 times more infective in certain soils.

Dr. Pedersen’s research also proved sewage treatment does not inactivate prions: “Our results suggest that if prions were to enter municipal wastewater treatment systems, most of the agent would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids. Land application of biosolids containing prions could represent a route for their unintentional introduction into the environment. Our results argue for excluding inputs of prions to municipal wastewater treatment.”

“Prions could end up in wastewater treatment plants via slaughterhouse drains, hunted game cleaned in a sink, or humans with vCJD shedding prions in their urine or feces,” Pedersen says.

In the July 3, 2010 issue of VETERINARY RECORD, Dr. Pedersen stated: “Finally, the disposal of sewage sludge was considered to represent the greatest risk of spreading (prion) infectivity to other premises.”

It is well known that sewage sludge pathogens, pharma and chemical pollutants are taken up by plants and vegetables. The Canadian Food Inspection Agency recently warned that plants can uptake infectious prions: “. . . there is a potential risk to humans via direct ingestion of the compost or of compost particles adhered to skin or plant material (e.g. carrots). Another potential route of exposure is by ingestion of prions that have been taken up by plants.”

Thousands of tons of sewage sludge (biosolids) are spread on farmland, parks, open spaces, and even lawns and gardens every year. In addition, millions of gallons of sewage water are being reclaimed for various uses.  Spreading sewage sludge and reclaimed sewage water on fields and in our watersheds is another foolish and risky practice. People with CJD (and many with Alzheimer’s disease) excrete prions in their urine, feces, saliva and blood and these recycling practices also are recycling, concentrating and expanding pathological pathways back to humans.

“Prions have been found in the blood and urine of CJD victims,” Gabizon, et al, 2001; Reichl, et al 2002. “Undertakers and medical facilities routinely discharge CJD infected blood and body fluids into public sewers,” Yale, UC Davis, Center for Disease Control.

Prions are not neutralized by sewage treatment. Therefore, prions become part of the sewage sludge and create pathways to the disease on fields and water runoff. It’s time to quit spreading lies and pathogens on farmland and pastures where livestock graze and where surface water runs off into streams, rivers, lakes and ponds.

Sewage treatment does not inactivate prions. In fact, it concentrates the infectious prions in the sewage sludge being applied on home gardens, cropland, grazing fields and dairy pastures, putting humans, family pets, wildlife and livestock at risk.

“Prions are extremely resistant to inactivation by ultraviolet light, irradiation, boiling, dry heat, formaline, freezing, drying and changes in pH. Methods for inactivating prions in infected tissues or wastes include incineration at very high temperatures and alkaline hydrolysis,” U.S. EPA.

Oral transmission of prion disease is enhanced by binding to soil particles. Dr. Pedersen and associates found that anaerobic digestion sewage treatment did not inactivate prions in sludge. Persistence of pathogenic prion protein during simulated wastewater treatment processes.

“Given it is unlikely that the sewage treatment or pellet production processes can effectively deactivate prions, adopting measures to prevent the entry of prions into the sewer system is advisable,” Toronto (Canada) Department of Health, Nov. 2004.

“Pathogen free” is clearly not the case when the Class A sludge compost can contain infectious human and animal prions. Not only are livestock and wildlife at risk from ingesting prion infected soil and sludge, but humans, and particularly children, are especially at risk because their hand to mouth behavior results in the ingestion of dirt,
(Robischon, 1971; LaGoy, 1987; Binder, et al 1986; Gerba, et al 2002; CDC, Callahan, 2004).

Given the volumes of research that clearly point to the risks associated with sewage sludge, how many cattle are being exposed to prions by grazing on land where sewage sludge (biosolids) has been applied? This exposure alone could spawn countless cases of Mad-cow disease around the globe every year. In addition, how many humans have ingested prions directly thanks to this foolish practice? How much water has been contaminated thanks to sewage sludge applications in our watersheds and directly injected into our rivers and oceans?

Sludge proponents claim that there aren’t enough prions in sludge to constitute an infectious dose.This statement shows incompetency or a reckless disregard for human and environmental health. Prions are known to multiply, which means that one can become thousands or millions once a facility or property is contaminated with even the smallest particle.

“Critics say that one example of outdated assumptions is the Harvard study’s assumption that a cow would have to eat one gram of infected material to come down with the disease. Most scientists now believe a cow would have to eat only 10 milligrams of infected material, a piece the size of a peppercorn, to catch the disease. That’s 100 times smaller than the assumption in the Harvard study. Recent British studies suggest the infectious dose could be 400 micrograms, which is 25 times smaller than 10 milligrams,” said Dr. Michael Hansen.

*Above Sources on Sewage Risks Compliments of Helane Shields/

Additional Documents & Research of Interest

“BSE has now been transmitted orally to 16 species,” (S. Dealler, 1995). Animals which have suffered fatal prion diseases include sheep, goats, cattle, pigs, bison, elk, mule and white-tailed deer, oxen, moose, domestic house cats, several species of macaques/monkeys, several species of lemurs, farmed mink, cougars, cheetahs, puma, ocelot, tiger, lion, kudu, oryx, eland, nyala, gemsbok and ankole.Rendered sheep fed to cattle are believed to have initiated the Mad-cow epidemic. Intensive inbreeding of sheep for various genetic characteristics is thought to have spawned prion disease in sheep.

 Contaminated meat and MBM feed are linked to zoo animal infections. A 1999 report documented three German zoo ostriches, which developed prion disease after eating feed made from downer cattle. An elephant at the Oakland Zoo died of prion disease.

Under ordinary circumstances, most sCJD cases go undiagnosed. Few autopsies are done on suspected sCJD victims because the families don’t want to incur the expense. What’s the point if their loved one is already dead? And the pathologist/medical examiner is reluctant to do an autopsy because he/she is concerned about their own risk of infection and the fact that expensive medical instruments may have to be discarded if the case is positive.

By binding to a common soil mineral, the misshapen proteins that cause chronic wasting disease in deer can be as much as 700 times more infectious than exposure to the proteins alone, according to researchers at UW-Madison. The finding, by UW-Madison animal health and biomedical science professor Judd Aiken, may help explain why CWD spreads orally among Wisconsin deer even though animals in the wild are exposed to relatively low levels of the infectious proteins, called prions. Herbivores, including deer and sheep, consume a fair amount of dirt each day as they graze. They also are known to consume soil as a source of minerals. Grazing cattle are known to ingest one kilogram of soil per day (2.2 pounds)

Creutzfeldt-Jakob disease contamination

Health Risk Summary

There are many prion pathways that we need to address and this paper has just scratched the surface in an attempt to redirect the conversation about Mad-cow disease to more productive ground. We still have much to learn about prions and we can’t afford to compartmentalize our thinking based on one pathway or the species affected—prion disease is prion disease, regardless of whether it is killing an animal or a human, or whether the deadly prion is being discharged by an animal or a human. The idea of species barriers for the most part is a myth. However, some races and species appear to be more susceptible (ask the Koreans and Japanese about their research, which points to a higher susceptibility in their genetic makeup). These countries are very quick to test beef and ban beef from any countries of origin with unacceptable risks.

If prions must be tightly regulated in a laboratory environment today, the outdoor environment and other pathways should be managed accordingly. If we can’t sterilize surgical equipment used on people who have prion disease, why are we kidding ourselves that we can neutralize prions in sewage? Dilution is not a solution to prion contamination. Prions don’t have a half-life as radiation does. They multiply, which means even one will become many. They can’t be stopped and the diseases always are deadly.

It’s time to develop a comprehensive prion-management strategy that maximizes safeguards for human health, food, water, and wildlife around the globe.  We have to stop the practice of using biosolids and reclaiming sewage water. We need to rethink several other health care and food-safety practices, too.

The stakes are too high for fragmented and misguided prion policies. It’s time to stop spreading pathogens, misinformation and lies.

public relations firm and public affairs firm Denver and Phoenix

Crossbow Communications specializes in issue management and public affairs. Alzheimer’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and the prion disease epidemic is an area special expertise. Please contact Gary Chandler to join our coalition for reform

CSU Developing Test For Chronic Wasting Disease

Deadly Disease Spreading Through Infectious Waste

New research at Colorado State University could yield better testing for chronic wasting disease, which affects wildlife and other animals in several states (and now Norway), say CSU scientists. The CSU study is developing and evaluating a more sensitive test for the disease, including the potential to test for infection in live animals, animal products and the environment. The CSU project is being funded by the Denver-based Morris Animal Foundation.

chronic wasting disease

Chronic wasting disease strikes deer, moose and elk and is related to similar diseases in cattle and sheep. It is a primary concern for hunters and wildlife ranchers and has spread to 19 states, two Canadian provinces and one Asian country, says CSU.

The research is aimed at prions, rogue proteins that cause the family of diseases that include chronic wasting disease – or CWD. The diseases are known as spongiform encephalopathies. While the Morris Animal Foundation-funded study would be the first in several steps to develop and evaluate a potential new test, it will look at a method that shows promise in detecting a wider array of prions at lower levels than are currently detected. The research could allow the detection of CWD prions in live animals, animal products and the environment.

land application sewage sludge

“Developing this test may eventually lead to a more rapid and sensitive test for CWD,” said Ed Hoover, a CSU veterinarian and researcher with 30 years of experience in research infectious diseases of animals. “But, just as significantly, it may lead to a substantial gain in our understanding of how prions spread, survive in natural habitats, and impact animal and public health.”

Currently, CWD can only be identified either by testing brain tissue after an animal is deceased or by surgical sampling and testing lymphatic tissues. While researchers don’t know exactly how CWD is passed from animal to animal, CSU scientists discovered that bodily fluids such as saliva, blood, urine and feces harbor infectious prions. They essentially contaminate the environment until they die and then threaten the life of any creature that consumes them after death.

biosolids land application and disease

Animals can then be exposed by direct contact with an infected animal or by contact with a contaminated environment. CWD is unstoppable.

Once unleashed on the environment, prions remain infectious. They migrate, mutate and multiply as they infect crops, water supplies and more.

Deer, elk, moose and reindeer are now contracting prion disease from humans. To help cloak the epidemic, it’s called chronic wasting disease (CWD). Deer with CWD are proverbial canaries in a coal mine. They are being killed by government sharpshooters to help cover up the problem.

Wastewater treatment plants, for example, are spreading infectious waste (prions) far and wide because they are incapable of stopping prions. All by-products and discharges from wastewater treatment plants are infectious waste, which are contributing to the global epidemic of neurodegenerative disease among humans, wildlife and livestock. Sewage treatment plants can’t detect or stop prions. Just ask the U.S. EPA and the industry trade organization—the Wastewater Effluent Federation. Sewage sludge (biosolids) and wastewater reclamation are causing widespread contamination.

Crops for humans and livestock grown grown in sewage sludge absorb prions and become infectious. We’re all vulnerable to Alzheimer’s and other forms of prion disease right now due to widespread denial and mismanagement. It’s time to stop the land application of sewage sludge (LASS) in all nations.

Read more about CWD

public relations firm and public affairs firm Denver and Phoenix

Crossbow Communications specializes in issue management and public affairs. Alzheimer’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and the prion disease epidemic is an area special expertise. Please contact Gary Chandler to join our coalition for reform

Incinerating Prions A Bad Practice

Prions Can Become Aerosol Agent

By James B. Woodward

February 19, 2004

Mr. Jonathan Akins
Environmental Engineer
Air Pollution Control Division – Stationary Sources Program
Colorado Department of Public Health & Environment
4300 Cherry Creek Drive South
Denver, Colorado 80246-1530

Subject: Draft Permit #03ME0664 issued to Colorado State University (CSU) for a bio-medical waste incinerator for disposal of pathological waste, some of which could potentially be infected with transmissible spongiform encephalopathies (TSEs), located at 425 29 Road, Grand Junction, Mesa County, Colorado.

Dear Mr. Akins:

The following are my comments concerning the air permit for the proposed Grand Junction incinerator.  My comments are primarily concerned with the question of whether this incinerator will effectively destroy the agents thought to cause Transmissible Spongiform Encephalopathies (TSEs). Since I believe there is no assurance infective material will not be released into the environment, I request that the Air Pollution Control Division prohibit the disposal of waste contaminated or potentially contaminated with TSEs in this proposed incineration facility.

chronic wasting disease cause

The proposed incinerator will be used to dispose of deer and elk heads (and perhaps carcasses) infected or potentially infected with Chronic Wasting Disease (CWD).  If the
facility is permitted to burn TSE-infected tissues, the possibility exists that cattle with Bovine Spongiform Encephalopathy (BSE) or the newly discovered Bovine Amyloidotic Spongiform Encephalopathy (BASE)[1], and/or sheep with scrapie may be disposed of in this incinerator as well.

Surprisingly, the Colorado Department of Public Health & Environment has no departmental rules, regulations, policies, guidelines, and/or recommendations regarding the safe and effective disposal of TSE-contaminated animal carcasses and tissues.  Over the past several months I have submitted Colorado Open Records Act requests asking for any such records or documents.  None have been produced.  Given the department’s lack of regulatory guidance on this matter and the scientific uncertainties surrounding cross-species transmission of TSEs, it would appear to be premature and irresponsible to allow burning of TSE-contaminated wastes in this proposed facility.

The draft permit requires an afterburner temperature of 1800° Fahrenheit  (982° Celsius) with a retention time of two seconds.  As you are aware, there is no scientific data suggesting that these time and temperature parameters will successfully eliminate detectable TSE infectivity.  The parameters are drawn from a 1997 risk assessment prepared for the U.K. Environment Agency by the consulting firm Det Norske Veritas Limited (DNV).  The report looked at the risks from disposing of BSE infected cattle in animal carcass incinerators, specifically the Vetspeed incinerator plant in Cambridge.  The Vetspeed incinerator has approximately twice the capacity of the proposed Grand
Junction unit.  In addition, the Vetspeed incinerator uses a water-spray gas scrubbing unit for removal of particulates, which the study explains is one of the main protective
measures against incomplete combustion.[2]  The proposed Grand Junction incinerator would have no such pollution control equipment.

It is curious that the Colorado Department of Public Health & Environment would utilize the parameters from this study since the department apparently does not possess a copy of the actual study.  The department seems to be relying on a brief excerpt of the study contained in a later report by the European Commission’s Scientific Steering Committee
(EC-SSC)[3].  A careful reading of the actual study reveals that the recommended conditions of operation, 850°C for at least two seconds, are not grounded in any direct scientific evidence.  The authors state: “No experimental data are available on the effect of incineration on BSE infectivity as such.”

The typical method of testing for residual TSE infectivity is the bioassay.  Suspect tissue or material is injected into the brains of test animals.  The animals are monitored
for clinical disease symptoms and are later autopsied and tested for evidence of a TSE.  The DNV study did not use the bioassay to test incinerator ash or emissions.  Rather, they used a surrogate measurement: the total protein content remaining in the ash.  The theory is that, since the infective agent is thought to be a protein, the reduction in
infectivity will be in proportion to the reduction in protein content.

In a 2003 report, the EC-SSC looked at this methodology and concluded that data to date suggest the assumption that TSE degradation is proportional to the degradation of other
proteins is not necessarily justified.  The heat resistance of the TSE agent may simply be greater than other proteins.

The department’s reliance on the DNV study for minimum time/temperature parameters for TSE waste incinerators may be misplaced.  The study provides no direct evidence or
experimental data supporting the parameters.  And it is unclear why the department has disregarded the DNV recommendation calling for the use of pollution control equipment to remove potentially infective particulates.

Below is additional information describing the resistance of TSE agents to typical inactivation methods, problems associated with incineration, the alternative disposal
method of alkaline tissue digestion, and cross species transmission of TSEs (particularly CWD).

Prions and Prusiner win Nobel Prize

TSE Inactivation Impossible

Writing in a study on prion transmission, Dr. C. Weissmann of the Medical Research Council Prion Unit of the Institute of Neurology in London stated:

“A striking feature of prions is their extraordinary resistance to conventional sterilization procedures, and their capacity to bind to surfaces of metal and plastic
without losing infectivity.”

The Centers for Disease Control and Prevention reports that “Prions are characterized by extreme resistance to conventional inactivation procedures including irradiation,
boiling, dry heat, and chemicals.”

The World Health Organization (WHO) writes, “TSE agents are unusually resistant to disinfection and sterilization by most of the physical and chemical methods in common use for decontamination of infectious pathogens.”  The WHO goes on to note “infectivity is strongly stabilized by drying” and that “contaminated materials should be kept wet between the time of use and disinfection by immersion in chemical disinfectants.”[9]

In a scientific study on the heat resistance of the scrapie agent, Dr. Paul Brown observed that TSE agents “are notoriously resistant to most physical and chemical methods used for inactivating pathogens, including heat”.[10]  Dr. Brown is a leading authority on prion diseases and prion inactivation.  A 1998 article by Dr. Brown in the Lancet includes the following discussion of prion inactivation:

“The agents that cause TSE have been known almost since their discovery to have awesome resistance to methods that quickly and easily inactivate most other pathogens…TSE agents are very resistant to virtually every imaginable method of inactivation, and those methods found to be most effective may, in one test or another, fail to sterilise. It seems that even when most infectious particles succumb to an inactivating process, there may remain a small subpopulation of particles that exhibit an extraordinary capacity to withstand inactivation, and that, with appropriate testing, will be found to retain the ability to transmit disease.”

Dr. Brown’s discussion of heat resistant subpopulations refers to experiments by Dr. David Taylor, who is perhaps the world’s leading expert on prion inactivation.  Dr.
Taylor published a study in 1998 showing that during heat inactivation, small subpopulations of TSE agents can become rapidly heat-fixed, and that these thermostable
subpopulations may survive to resist further attempts at inactivation.  The resistant subpopulations can be differentiated by their longer incubation periods in test animals.

In a study on the effect of dry heat on the scrapie agent, Dr. Taylor notes that prions “possess a number of properties which differentiate them from conventional microorganisms, including an exceptional resistance to inactivation by chemical and physical methods”.

The most relevant study on heat resistance of TSE agents was done by Dr. Paul Brown et al., published in 2000.  Brown exposed one-gram samples of scrapie-infected hamster brains to various time and temperature parameters.  The resulting samples were injected intracerebrally into healthy hamsters to test for residual infectivity.  Samples exposed to 600°C and 1000°C for 5 minutes resulted in no detectable infectivity.  A sample exposed to 600°C for 15 minutes, however, infected 5 of 18 hamsters.

The fact that 5 of the test animals became infected is remarkable, since it seems likely that exposure to 600°C for 15 minutes would decompose all organic compounds.  This
enigmatic result led Brown and colleagues to propose various explanations.  They note “combustion is a series of pyrolysis and oxidation reactions that proceed rapidly but
incompletely,” and that 600°C is a “comparatively low combustion temperature”.

They theorize that incomplete combustion may have introduced elemental carbon into the combustion residues, and carbon has been reported to partially protect TSE infectivity.  The researchers observed that only at 1000°C did it appear that most of the carbon residue had been oxidized.  The most interesting theory proposed by Dr. Brown is that the heat created an inorganic replica of the prion’s molecular geometry.  This inorganic “fossil template” could mimic the infectivity of the scrapie agent.[15]

Although the study’s authors write that the results suggest that such an inorganic template would have a decomposition point near 600°C, the fact is that this is a guess.
Measurable infectivity was found at 600°C and none was detected at 1000°C.  No samples were exposed to intermediate temperatures.

Incineration Of Deer With CWD

Regarding incineration, the European Commission’s Scientific Steering Committee (EC-SSC) concludes that:

“With respect to TSEs, it is generally assumed that incineration is a completely effective method for destroying TSE-like agents.  However, there is no direct evidence for this.  The dry heat experiments described in the literature may not be completely relevant to incineration because exposure to dry heat does not involve oxidative combustion, as occurs during incineration.”

“The possibility that incineration might not be completely effective is clearly being considered.  For example, after incinerating materials that could be TSE-infected, the USDA soaks the resulting ash in sodium hydroxide for two weeks before disposal.”

The EC-SSC’s “Opinion on the use of small incinerators for BSE risk reduction,” dated January 16-17, 2003 notes the following:

1. Because of variability in incinerator design and performance characteristics, each incinerator facility needs to be the subject of a specific risk assessment.

2. There is no direct data on the TSE levels that may occur in airborne emissions and residual ash from incinerators.

3. Because of this lack of data it is not possible to assess the risks.

4. In the absence of reliable data on the possible residual infectivity of the ash, it should be disposed of in controlled landfills.

5. Unburned material is commonly noted in the ash from small

6. The level of expertise available for the management of small incinerators is highly variable because few such facilities can afford to employ specialists in incineration.

The EC-SSC’s report concludes:

“In view of the uncertainty regarding the risks due to BSE/TSE contamination of the fly and bottom ash and airborne emissions it is recommended that further research is
conducted to identify the residual risks (along with attendant uncertainties) from the burial of ash (without further treatment,) in uncontained sites. It is essential that suitable monitoring methods are developed.”[17]

In a presentation to the Food and Drug Administration’s Transmissible Spongiform Encephalopathies Advisory Committee on July 17, 2003, Captain Edward Rau explained that “ash bed temperatures often may run 100°C lower than the actual air temperature” (in an incinerator’s burn chamber).[18] Captain Rau is an Environmental Health Officer with the National Institutes of Health and a co-researcher with Dr. Brown on the scrapie heat resistance study.

A 6,000 pound capacity incinerator burns nearly 3 million times the mass of the samples tested by Brown and Rau.  Many factors can affect an incinerator’s ability to completely
combust TSE contaminated waste material.  As Captain Rau explains:

“Probability of survival in ash not only depends on a lot of factors, the load density, the turbulence, the type of equipment, other operational factors.”

“Particularly, as things are just inserted into the incinerator, you tend to get a boil off of some of the material, a flash burn.  That can be carried over very quickly into the second chamber.”

“Reported temperatures for incinerators refer to the air. That is what is being monitored, and not the actual temperature in the ash.  Under abnormal conditions, a lot of things can really go wrong, cold start up conditions, overloading, inadequate control of the under fire air flow.” [19]

Overloading, excessive load density, inadequate air turbulence, and insufficient control of under fire airflow can all negatively impact incinerator performance.  Any of these conditions can result in incomplete heat penetration of the ash bed and insufficient residence time in the burn chamber.

Dr. David Taylor discusses this possibility in a paper on disposal issues related to TSE infected animals:

“Although incineration is generally regarded as the optimal method for the destruction of all microorganisms, there have been frequent reports of the discovery of organic material
in the resulting ash.  These findings indicate that the incineration process does not always perform according to the required standards.”[20]

Equipment breakdowns during burn cycles are likely to occur at some point.  These include electrical component failure, short circuits, and failure of fuel or air delivery systems. A common incinerator problem is refractory (firebrick) breakage.  If the burn chamber is not inspected and repaired on a regular basis, a damaged refractory can expose the steel wall of the burn chamber to high temperatures resulting in a “burn-through” and emergency shutdown.

Malfunctions can force a shutdown in mid-cycle.  The result is an unintended release of smoke from the stack since there is no way to effectively contain the combustion gases until the partially combusted waste material has cooled down. When an incinerator is in failure mode there is no way to close or contain the system to prevent release of infectious agents and other pollutants into the environment.

Operator training and supervision is crucial to incinerator performance.  Operators of hazardous waste incinerators are required by law to take classroom training courses and
annual refresher courses.[21]  The American Society of Mechanical Engineers has developed certification programs for hazardous and medical waste incinerator operators.[22] The Colorado Department of Public Health & Environment, however, does not require classroom courses, refresher training, or operator certification.

Incinerator upsets and problems may occur often, even in new facilities.  The Colorado Division of Wildlife (CDOW) operated two new pathological incinerators in the town of
Craig, Colorado during the 2002-2003 hunting season.  In daily logs obtained under the Colorado Open Records Act, the incinerator operator documented numerous problems and malfunctions.  Following are excerpts from the daily logs:

10-25-02  9:00 AM   8 hrs
First burn   Primary Temp. 1500°
Secondary Temp 1800°
57 Elk heads   47 Deer heads   104
Burn duration 8 hrs
9:30 A.M. – 5:30 P.M.   Cool down 2 hrs.
Cool down temp. 600° primary chamber.
was able to clean ashes out at this temp.
Produced about 40 gals of ash.
Stirred heads at 5 hrs. 6 hrs & 7 hrs during burn.
Only five heads were not completely incinerated.
Left them in with second burn.

10-25-02  2nd burn   10 hrs
8:15 P.M.   60 Elk   60 Deer   120
6:15 A.M. shut off
8:00 A.M. Temp was 700°
Load was not stirred during night.
App. 30 heads did not burn completely.
Some didn’t even have the hair cinched [sic].
We have been stacking heads in front of door.
Those don’t incinerate very well in this area,
was still some blood on floor in this area.

10-26-02 3rd Burn   8 hrs
9:00 A.M.   42 elk   68 Deer   112
Started pre-heating secondary chamber when loading primary.
Starting primary chamber when secondary is at 1200°-1300°
Increased primary to 1600°
Opened primary air blower to 8
Stirred heads every ½ hour after five hours of burning.

11-3-02   7th   10 hrs.
10:30 A.M   43 Elk   45 Deer   98 [sic]
#4 burner having trouble staying lit at start up

11-6-02   11th   10 hrs.
10:00 AM – 6:00 PM
66 Elk   40 Deer   106
starting to notice odor of burnt hair

11-7-02   12th   10 hr
9:45 AM – 7:45 PM
69 Elk   49 deer   118
Still odor
Secondary burning unit, paint is peeling & cracking around
large connection ring

Testing secondary chamber length of time to reach 1800° w/
primary chamber off.
12:45 A.M.   start  90°
1:15              1000°
1:45         1133°
1:55 1161°
2:45 1245°
3:30 1295°
4:30 1337°
5:50 1375°
shut off

11-13-02   15th   10 hrs
71 elk   46 Deer   12:15 A.M.   117
notice smoke around secondary burner when it ignited

11-14-02   16th   10 hrs
71 elk   7 Deer   78
9:15 A.M.   7:15 P.M.   Now winter fuel
50% #1 & 50% #2   won’t hold temp. in secondary

Frank Searles. Plant manager returned my calls this A.M.
Is sending a new thermocouple for secondary chamber.
Thinks the smoke might be from fuel being to [sic] cold.
Wants me to heat tape the fuel lines.
Also the area of smoke & paint peeling is not an air tight
seal in that area

11-16-02   18th   10 hrs
Elk 75   Deer 0   75
10:00 AM – 8:00 P.M.
Secondary chamber had to be reset
Did not fire

These records document several problems:

– Unburned heads and blood in burn chamber after 10 hour
– Started burning load before secondary chamber reached 1800
degrees F
– Malfunctioning burner
– Noticeable odor of burnt hair
– Secondary chamber unable to reach 1800 degrees F
– Noticeable smoke
– Possible problem with cold fuel

In a May 2, 2002 report prepared for the Northern Larimer County Alliance, Duane Switzer interviewed Craig residents Ed and Pat Relaford regarding their experience living about 300 feet from the two incinerators.  The Relafords told Mr. Switzer:

– Bad smell.  Day and night when the incinerators are in operation.  Singed hair and burning flesh.

– Wispy smoke, that is to say, not billowing clouds.  In any case, the city attorney had told them there would be no smoke.

– Noise. The roar of the incinerators is constant and loud, to the point she could not sleep.

– The noise and smell are continuous day and night for 6 to 8 weeks straight.

The occupants of another house about 1,000 feet from the incinerators told Mr. Switzer they experienced a “foul smell” from the incinerators.[23]  In a July 15, 2003 article in the Craig Daily Press, Ed Relaford confirmed that the stench of burning flesh permeated his neighborhood.[24]

Alkaline Tissue Digestion and CWD

Alkaline tissue digestion is the only proven technology for prion inactivation that is capable of handling large volumes of animal carcasses.  It is based on the process of alkaline hydrolysis, which is the breaking of chemical bonds by the insertion of water between atoms, catalyzed by alkali metal hydroxides.

The technology for hydrolyzing large quantities of animal carcasses was developed in 1992 by Dr. Gordon Kaye and Dr. Peter Weber, professors at Albany Medical College in New York.  The equipment consists of an insulated, steam-jacketed, stainless steel pressure vessel with a lid. Carcasses (or heads) are loaded into a basket that is placed
inside the vessel.  The load is automatically weighed, and the appropriate amounts of water and alkali are automatically added.[25]

The vessel is sealed and the contents are heated by steam. The alkali solution is continuously recirculated and agitated.  There are no moving parts inside the vessel. The
tissues are dissolved and are hydrolyzed into smaller and smaller molecules.[26]  The recommended digestion cycle time is six hours based on experiments done by Robert Somerville in 2002, funded by the UK Department of the Environment, Food, and Rural Affairs (DEFRA).[27]

The Somerville experiments involved digestion of sheep heads inoculated with mouse-passaged BSE agent.  Different chemical and time parameters were tested.  Samples of the resulting hydrolysate were diluted and injected into mice. Although infectivity remained after 3-hour digestion cycles, no infectivity was detectable after a 6-hour cycle.[28]

Due to constraints specific to the Somerville experiments, the European Commission Scientific Steering Committee (EC-SSC) concluded in its April 2003 opinion that further
studies are needed “before any final assurance could be given regarding the safety of the process with respect to TSE risks”.[29]

It should be noted that the precautionary approach to digestion by the EC-SSC has never been applied to the process of incineration.  This is perhaps because of the widely held, though not scientifically proven, assumption that incineration is an effective means of inactivating TSEs.  Regardless, with respect to TSE inactivation, alkaline tissue digestion has been subjected to far greater scrutiny than incineration.

Responding to an early version of the EC-SSC’s opinion, Dr. David Taylor prepared a risk assessment of alkaline digestion assuming a digester with the capacity to process ten BSE-infected bovine carcasses.  Dr. Taylor concluded that “a human would have to consume at least 126,000 litres (over 33,000 gallons) of effluent from the production
process to have a 50% chance of developing variant CJD.”[30]

Further reinforcing the effectiveness of alkaline hydrolysis are Dr. Taylor’s comments in his 2000 review of prion inactivation methods:

“The only methods that appear to be completely effective under worst-case conditions are strong sodium hypochlorite solutions or hot solutions of sodium hydroxide.”[31]

Apparently convinced that alkaline tissue digestion is effective, the European Commission is in the process of adopting the final language of regulations approving
alkaline hydrolysis for disposal of TSE-infected materials.[32,33]

Compared to incinerators, alkaline digesters are safer particularly in the failure mode because the system is self-contained.  In the event of loss of temperature and pressure, or mechanical breakdown, the contents remain inside the sealed vessel until repairs are completed and the process is restarted.

The effluent from a digester can either be dehydrated and the remaining solids landfilled, or an anaerobic digestion process can be utilized.  Many facilities reduce the pH
level of the effluent and release it into municipal sewer systems with no adverse effects.

Alkaline tissue digesters have already become the waste disposal technology of choice at a variety of installations. Health Canada’s Host Genetics and Prion Diseases Federal
Laboratories in Winnipeg took delivery of a small digester in January 2000.  In April of that year, the US Department of Agriculture’s (USDA) Animal Research Service lab in
Laramie, Wyoming installed a 1,500-pound capacity tissue digester.  In February 2001, the USDA’s Animal and Plant Health Inspection Service in Ames, Iowa purchased a 7,000-pound digester to dispose of 350 sheep exposed to an unidentified prion disease.[34,35]

Colorado State University’s Veterinary Diagnostic Lab (CSU-VDL) in Fort Collins installed a 2,000-pound digester in October 2001.  The facility is a joint venture of CSU,
the Colorado Department of Agriculture, and the USDA. During the 2002-2003 hunting season, the DOW contracted with the CSU-VDL to dispose of 140,189 pounds of deer and elk heads and carcasses, many infected with CWD.[36]

The College of Veterinary Medicine at the University of Pennsylvania purchased a 7,000-pound unit last year specifically for prion destruction.[37]  In a joint venture, the USDA, the Wisconsin Veterinary Diagnostic Laboratory (WVDL), and the Wisconsin Department of Agriculture, Trade and Consumer Protection are deploying a mobile tissue digester to be available for state use in dealing with the CWD “emergency” as well as other animal disease outbreaks. The USDA has provided $1 million for the purchase of the digester as part of a homeland security grant to the state and WVDL.[38]

The Cornell College of Veterinary Medicine (CCVM) in Ithaca, New York is finalizing funding for an alkaline tissue digester to replace its 18-year-old pathological incinerator.  In the Draft Environmental Impact Statement for the project, the CCVM concludes the following significant positive impacts on human health are to be expected:

“The significant reduction in air pollutants and greenhouse gases (e.g., NOx and CO2) would result in a positive impact on human health.”

“Moreover, the Proposed Action would provide more reliable treatment of animal remains infected with prions, the causative agents of Mad Cow Disease and other
Transmissible Spongiform Encephalopathies (TSEs) compared with current treatment (i.e., incineration) based on research published to date, and would protect public health
to the maximum extent in the event that prion-infected wastes were received by the CCVM.”[39]

Compared to incineration, alkaline tissue digestion is a more reliable method of TSE inactivation, has undergone more scientific scrutiny, can be contained in failure mode,
is simpler to operate, is a less complex technology, and costs less to operate per pound of waste.

Alzheimers disease epidemic

Cross-Species Transmission of TSEs

The Raymond et al. 2000 in-vitro study found that the human molecular barrier to CWD is approximately as effective as the human molecular barrier to BSE.[40]  While the
transmission of BSE to humans is inefficient, it has certainly proven to be possible.  U.K Department of Health statistics as of February 2, 2004 indicate that 139 people have died of definite or probable variant Creutzfeldt-Jakob Disease (vCJD).[41]  It is believed that variant CJD is caused by consumption of beef contaminated with BSE.

The study shows that, at the molecular level, humans are no less susceptible to CWD than to BSE.  The study’s authors conclude “since humans have apparently been infected by BSE, it would seem prudent to take reasonable measures to limit exposure of humans (as well as sheep and cattle) to CWD infectivity”.[42]

Many of the 692 cases of sporadic Creutzfeldt-Jakob Disease recorded in the U.K. since 1990 may also be linked to BSE. Sporadic CJD has been thought to occur spontaneously and not as a result of exposure to a pathogen.  This theory was called into question in a 2002 study by Emmanuel Asante, John Collinge, and others showing that BSE could produce a disease indistinguishable from sporadic CJD.  The authors conclude, “some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.” [43]

Any natural or molecular barriers humans may have against CWD may be overcome by the agent’s potential for adaptation. In a study by scientists at the Rocky Mountain Laboratories in Hamilton, Montana, a strain of hamster scrapie gradually adapted to cause illness in mice that were previously not susceptible to the disease.

The research revealed that scrapie prions could persist in asymptomatic mice for years at levels too low for standard lab tests to detect.  When the agent was transferred from
the original group of mice to additional groups, the disease grew stronger making the newly infected mice sick. Researcher Richard Race explained: “The scrapie seemed to have learned how to deal with this new species, and it worked much better.  It replicated faster in additional rounds of mice and even became more lethal to them.”

Race noted the study “confirmed that prion disease can adapt to new species”, and that “the process is slow and difficult to detect”.  Applying his results to CWD, Race said: “If BSE were derived from sheep scrapie, then adaptation during passage in cattle may have increased its pathogenicity for humans.  A similar situation could occur with CWD.  CWD transmission to other cervids or livestock could change its characteristics, including its potential for transmission to people.”[44]

In a similar study conducted in the U.K. on subclinical prion infection, results led the researchers to caution that “current definitions of the species barrier, which have been
based on clinical end-points, need to be fundamentally reassessed”.[45]

Noted CWD researcher Dr. Elizabeth Williams from Laramie, Wyoming had the following to say about the risk to humans:

“I do think it is legitimate to be concerned about the potential for humans being susceptible to CWD.  We don’t have evidence…but we can’t say it could never happen and
we have to be prudent.”

mad cow disease and prions

CWD Transmission To Cattle

Regarding CWD transmission to cattle, the results are mixed. In an ongoing study in Wyoming, cattle fed brain tissue from CWD-infected mule deer have not gotten sick after 6 years. A study in Ames, Iowa has yielded different results.  In 1997, 10 calves were inoculated intracerebrally with the same inoculum used in the Wyoming experiment.  As of mid-2003, 5 calves had developed CWD.

Although the Wyoming study involves a more natural route, ingestion may simply result in a more prolonged incubation period.  Alternatively, based on the work done by Race, et al. on TSE adaptation and species barriers, the test cattle in Wyoming may be asymptomatic carriers harboring a gradually adapting CWD agent.

Complicating matters, a recent study analyzing “glycoform” patterns of abnormal prion protein from CWD-affected deer and elk, scrapie-affected sheep and cattle, and BSE-affected cattle failed to identify patterns capable of reliably distinguishing these TSEs.  Difficulty in identifying the source of a TSE following cross-species transmission adds to
the uncertainty surrounding CWD and possible risks to cattle and humans.  The authors write: “Sheep scrapie has been present in the United States since at least 1947, and in many geographical areas, sheep, deer, and elk share pastures and rangeland.  If scrapie-affected sheep were present in these situations, then cross-species transmission might have occurred.  Sheep scrapie is not thought to cause disease in humans, although passage through cattle appears to have changed this characteristic.  It remains to be determined if the same will be true of CWD.”

The European Commission’s Scientific Steering Committee (EC-SSC) released a lengthy, comprehensive report and opinion on CWD in March 2003.  Cross-species transmissibility experiments and risks are discussed in detail.  The EC-SSC report reviews the successful transmission of CWD by intracerebral inoculation to ferrets, mice, a squirrel monkey, mink, a goat, and a sheep.  The report concludes, “…it remains theoretically possible that the CWD-agent could infect humans.

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Mad Cow, Creutzfeldt-Jakob, Alzheimer’s Disease Spreading With Sewage

Prions Connect Transmissible Spongiform Encephalopathies

The U.S. government’s monitoring system for cases of Creutzfeldt-Jakob disease, a fatal human brain illness, could be missing tens of thousands of victims, scientists and consumer advocates said.

Creutzfeldt-Jakob disease or CJD can be caused by prion exposure, including eating beef contaminated with mad cow disease, but the critics assert without a better tracking system it might be impossible to determine whether any CJD cases are due to mad cow disease or obtain an accurate picture of the prevalence of the disorder in the United States.

Alzheimer's disease epidemic

In order to understand the threat, one must understand the dynamics of this neurological disease. Alzheimer’s disease, for example, is a member of an aggressive family of neurodegenerative diseases known as Transmissible Spongiform Encephalopathy (TSE). The operative word is “transmissible.”

TSEs are caused by a deadly protein called a prion (PREE-on). As such, TSEs also are referred to as prion disease. The critical factor is that prions are unstoppable. The pathogen spreads through the bodily fluids and cell tissue of its victims. Blood, saliva, mucus, milk, urine and feces carry deadly prions from victims. All tissue is infectious just because of the contact with the contaminated blood.

TSEs also include Creutzfeldt-Jakob disease, Parkinson’s, Huntington’s, mad cow disease and chronic wasting disease in the deer family. Few, if any, mammals are immune. There is no cure.

Dr. Stanley Prusiner, an American neuroscientist from the University of California at San Francisco, earned a Nobel Prize in 1997 for discovering and characterizing deadly prions and prion disease. President Obama awarded Prusiner the National Medal of Science in 2010 to recognize the importance of his research. According to Prusiner, TSEs all are on the same disease spectrum, which is more accurately described as prion disease. He claims that all TSEs are caused by prions.

prion disease epidemic

Prions are unstoppable and the pathogen spreads through the bodily fluids and cell tissue of its victims. Prions shed from humans are the most deadly mutation. They demand more respect than radiation. Infected surgical instruments, for example, are impossible to sterilize and hospitals throw them away. Prions are in the blood, saliva, urine, feces, mucus, and bodily tissue of its victims. Many factors are contributing to the epidemic. Prions are now the X factor. Industry and government are not accounting for them or regulating them. They are ignoring the threat completely, which violates the Bioterrorism Preparedness and Response Act of 2002 in the United States. Other nations also are ignoring laws developed to protect food, air and water.

“There is now real evidence of the potential transmissibility of Alzheimer’s disease,” says Thomas Wiesniewski M.D. a prion and Alzheimer’s researcher at New York University School of Medicine. “In fact, this ability to transmit an abnormal conformation is probably a universal property of amyloid-forming proteins (prions).”

A new study published in the journal Nature renews concern about the transmissibility of Alzheimer’s disease between people. A second study by the same scientist in early 2016 adds to the stack of evidence.

The first symptoms of CJD typically include memory loss and difficulty keeping balance and walking. As the disease destroys the brain, patients rapidly progress in a matter of months to difficulty with movement, an inability to talk and swallow and, finally, death.

Clusters of CJD have been reported in various areas of the United States — Pennsylvania in 1993, Florida in 1994, Oregon in 1996, New York in 1999-2000 and Texas in 1996. In addition, several people in New Jersey developed CJD in recent years, including a 56-year-old woman who died on May 31, 2003. Although in some instances, a mad cow link was suspected, all of the cases ultimately were classified as sporadic. The common thread is more likely sewage sludge, also known as biosolids, dumped on land.

land application sewage sludge

People who develop CJD from eating prion-contaminated beef have been thought to develop a specific form of the disorder called variant CJD. But new research, released last December, indicates the mad cow pathogen can cause both sporadic CJD and the variant form. A deadly prion is a deadly prion and there are now hundreds, if not thousands, of mutations.

“Now people are beginning to realize that because something looks like sporadic CJD they can’t necessarily conclude that it’s not linked to mad cow disease,” said Laura Manuelidis, section chief of surgery in the neuropathology department at Yale University, who conducted a 1989 study that found 13 percent of Alzheimer’s patients actually had CJD.

Several studies, including the one by Manuelidis, have found autopsies reveal 3-percent-to-13-percent of patients diagnosed with Alzheimer’s or dementia actually suffered from CJD. Those numbers might sound low, but there are 4-million Alzheimer’s cases and hundreds of thousands of dementia cases in the United States. A small percentage of those cases could add up to 120,000 or more CJD victims going undetected and not included in official statistics.

biosolids land application

Experiences in England and Switzerland — two countries that discovered mad cow disease in their cattle — have heightened concerns about the possibility some cases of sporadic CJD are due to consuming mad-cow-tainted beef. Both countries have reported increases in sporadic CJD since mad cow was first detected in British herds in 1986.

Switzerland discovered last year its CJD rate was twice that of any other country in the world. Switzerland had been seeing about eight to 11 cases per year from 1997 to 2000. Then the incidence more than doubled, to 19 cases in 2001 and 18 cases in 2002.

The CDC says the annual rate of CJD in the United States is one case per million people, but the above studies suggest the true prevalence of CJD is not known, Manuelidis told UPI.

Diagnosing CJD or Alzheimer’s disease is difficult because no test exists that can identify either disease in a living patient with certainty. So physicians must rely on the patient’s symptoms to determine which illness might be present. Sometimes, however, the symptoms of one disease can appear similar to the other disorder. The only way to determine the disease conclusively is to perform an autopsy on the brain after death.

Unfortunately, although autopsies once were performed on approximately half of all corpses, the frequency has dropped to 15 percent or less in the United States. The National Center for Health Statistics — a branch of the CDC — stopped collecting autopsy data in 1995.

“If we don’t do autopsies and we don’t look at people’s brains, we have no idea about what is the general prevalence of these kinds of infections and (whether) it is changing,” Manuelidis said.

At the same time autopsies have been declining, the number of deaths attributed to Alzheimer’s disease has increased more than 50-fold since 1979, going from 857 deaths then to nearly 50,000 in 2000. Though it is unlikely the dramatic increase in Alzheimer’s is due entirely to misdiagnosed CJD cases, it “could explain some of the increase we’ve seen,” Manuelidis said.

“Neurodegenerative disease and Alzheimer’s disease have become a wastebasket” for mental illness in the elderly that is difficult to diagnose conclusively, she said. “In other words, what people call Alzheimer’s now is more broad than what people used to call it, and that has the possibility of encompassing more diseases — including CJD.”

The autopsy studies that found undiagnosed CJD cases raise the question of whether the United States “already has an undetected epidemic here,” Jeff Nelson, director of, a vegetarian advocacy Web site, told UPI.

“What’s the source of that?” Nelson asked. “Could it be the same source of encephalopathy we saw in mink?”

Nelson referred to an outbreak of a mad-cow-type disorder in mink in Wisconsin in the 1980s. The origin was traced back to the animals’ diet, which included parts of so-called downer cattle — sick cows that are unable to stand, which often indicates a neurological disease, including mad cow. The mink disease raised concerns about whether U.S. cattle were carrying a mad-cow-like pathogen even prior to the U.K. epidemic that began in 1986.

Andrew Monjan, chief of the neuropsychology of aging program at the National Institute of Aging — part of the National Institutes of Health in Bethesda, Md. — acknowledged there has been an increase in U.S. Alzheimer’s cases. However, he told UPI, this probably is due to the aging of the population — as people grow older, they develop a higher risk of developing Alzheimer’s (bullshit).

“There’s been no change in the number of CJD cases in the country and there has been clearly a tracking of the unusual cases of CJD” that could be due to mad cow disease, Monjan said. However, Terry Singletary, coordinator of CJD Watch — an organization founded to track CJD cases — says efforts to track the disease have been close to nonexistent. For example, only 12 states require such reports. Therefore, many cases might be going undetected, unreported or misdiagnosed.

mad cow disease

If more states made CJD a reportable illness, there would be more clusters detected across the United States, said Singletary, who became involved with CJD advocacy after his mother died from a form of CJD known as Heidenhain variant. In the 18-year period between 1979 and 1996, he noted, the country saw a jump from one case of sporadic CJD in people under the age of 30 — a warning sign for a link to mad cow because nearly all of the U.K. victims were 30 years of age or younger — to five cases in five years between 1997 and 2001. “That represents a substantial blip,” he told UPI.

Singletary also said there have been increases in sporadic CJD in France, Germany and Italy, all of which have detected mad cow disease in their cattle.

So far, the CDC has refused to impose a national requirement that physicians and hospitals report cases of the disease. The agency has not chosen to make CJD a reportable disease because “making it reportable is not necessarily directly helpful in surveillance because in some states where it’s reportable you may not get the physician to report it,” said Dr. Ermias Belay, CDC’s medical epidemiologist working on CJD.

Instead, the agency relies on other methods, including death certificates and urging physicians to send suspicious cases to the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, which is funded by the CDC. However, because autopsies generally are not done, if a CJD case is misdiagnosed as Alzheimer’s or dementia, a correct diagnosis might never be determined and therefore the cause of death listed on a death certificate might be inaccurate.

Belay told UPI he discounted this possibility. It is unlikely to happen, he said, because it is easy to distinguish CJD from Alzheimer’s — the two conditions display different symptoms.

Manuelidis disagreed. It can be quite difficult to determine accurately if a patient has CJD, as evidenced by her study, in which respected and competent neurologists and psychiatrists at Yale originally diagnosed patients with Alzheimer’s, yet were wrong at least 13 percent of the time. Another study conducted at the University of Pennsylvania, which found 6 percent of dementia patients actually were suffering from CJD, supports the difficulty in distinguishing the illnesses correctly.

The U. Penn. researchers concluded: “These results show that in patients with a clinical diagnosis of dementia, the etiology (cause) cannot be accurately predicted during life.”

In addition, the NPDPSC sees less than half of all the CJD cases each year, so the CDC’s investigational system not only is missing many of the misdiagnosed CJD cases, it also is not conducting autopsies on most of the detected cases.

Belay said the CDC follows up on all cases of CJD that occur in people under age 55, as these could be linked to variant — mad-cow-related — CJD. But so far, all have turned out to be sporadic forms of the disease. About 30 cases of the disorder occur each year in the United States in this age group, while the remaining 270 or so are older.

The case of Carrie Mahan — a Philadelphia woman who developed a brain disorder that appeared to be CJD and died from it in 2000 at the age of 29 — illustrates just how difficult it can be to diagnose the disease.

Mahan’s physician, Dr. Peter Crinos of the University of Pennsylvania Medical Center, ruled out other disorders and felt certain the young woman had died of CJD, a concern that raised the possibility of a link to mad cow disease because of her young age. When neuropathologist Nicholas Gonatas, who had seen CJD before, examined Mahan’s brain after her death, he, likewise, was confident he detected the microscopic, sponge-like holes caused by the disease. But when he sent brain samples to the NPDPSC, the results came back negative. Gonatas, convinced the surveillance center’s finding was erroneous, sent off two more samples, only to have them both come back negative.

Subsequent research, however, has shown the test used by the surveillance center cannot rule out CJD, said Crinos, an assistant professor of neurology.

“There’s no question that Carrie had a spongiform encephalopathy,” Crinos said, but added although it appeared to be CJD, it is difficult if not impossible to say if it was due to mad cow disease.

Crinos told UPI until the CDC implements a better tracking system, a lot of questions will remain about CJD and cases like Carrie Mahan’s. One central question: Why are cases of what is presumed to be a rare disease popping up in clusters in certain areas of the country? Crinos said the clustering suggests an environmental or food-borne cause, but so far, “No one knows the answer to that.”

The Second Part Of The Prion Equation

We can split hairs about the diagnoses, misdiagnoses and causes of the prion disease forever, but the problem with prions is that the victims are infectious themselves and serve as prion incubators and distributors. The bodily fluids of victims are loaded with infectious prions. Blood, urine, feces, saliva and mucus transport the disease throughout the victims’ environments. Downstream, wastewater treatment plants, for example, are spreading this infectious waste far and wide because they are incapable of stopping prions. All by-products and discharges from wastewater treatment plants are infectious waste, which are contributing to the global epidemic of neurodegenerative disease among humans, wildlife and livestock. Sewage treatment plants can’t detect or stop prions. Just ask the U.S. EPA and the industry trade organization—the Wastewater Effluent Federation. Sewage sludge (biosolids) and wastewater reclamation are causing widespread contamination.

biosolids land application and disease

Once unleashed on the environment, prions remain infectious. They migrate, mutate and multiply as they infect crops, water supplies and more.

Deer, elk, moose and reindeer are now contracting prion disease from humans. To help cloak the epidemic, it’s called chronic wasting disease (CWD). Deer with CWD are proverbial canaries in a coal mine. They are being killed by government sharpshooters to help cover up the problem. It’s insane.

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Prion Disease Described By Prusiner

Prions Cause Many Neurological Disorders

By Stanley B. Prusiner, Nobel-Prize Laureate, Prion Discovery and Research

Fifteen years ago I evoked a good deal of skepticism when I proposed that the infectious agents causing certain degenerative disorders of the central nervous system in animals and, more rarely, in humans might consist of protein and nothing else. At the time, the notion was heretical. Dogma held that the conveyers of transmissible diseases required genetic material, composed of nucleic acid (DNA or RNA), in order to establish an infection in a host. Even viruses, among the simplest microbes, rely on such material to direct synthesis of the proteins needed for survival and replication.

Prions and Prusiner win Nobel Prize

Later, many scientists were similarly dubious when my colleagues and I suggested that these “proteinaceous infectious particles”–or prions, as I called the disease-causing agents–could underlie inherited, as well as communicable, diseases. Such dual behavior was then unknown to medical science.

And we met resistance again when we concluded that prions (PREE-ons) multiply in an incredible way; they convert normal protein molecules into dangerous ones simply by inducing the benign molecules to change their shape. Today, however, a wealth of experimental and clinical data has made a convincing case that we are correct on all three counts.

Prions are indeed responsible for transmissible and inherited disorders of protein conformation. They can also cause sporadic disease, in which neither transmission between individuals nor inheritance is evident.

Moreover, there are hints that the prions causing the diseases explored thus far may not be the only ones. Prions made of rather different proteins may contribute to other neurodegenerative diseases that are quite prevalent in humans. They might even participate in illnesses that attack muscles.

The known prion diseases, all fatal, are sometimes referred to as spongiform encephalopathies. They are so named because they frequently cause the brain to become riddled with holes. These ills, which can brew for years (or even for decades in humans) are widespread in animals. A common form is scrapie, found in sheep and goats. Afflicted animals lose coordination and eventually become so incapacitated that they cannot stand. They also become irritable and, in some cases, develop an intense itch that leads them to scrape off their wool or hair (hence the name “scrapie”).

chronic wasting disease cause

The other prion diseases of animals go by such names as transmissible mink encephalopathy, chronic wasting disease of mule deer and elk, feline spongiform encephalopathy and bovine spongiform encephalopathy. The last, often called mad cow disease, is the most worrisome. They all are deadly and unstoppable. There might not be any difference between these diseases, except for the resistance of the victim.

mad cow disease and prions

Gerald A. H. Wells and John W. Wilesmith of the Central Veterinary Laboratory in Weybridge, England, identified the condition in 1986, after it began striking cows in Great Britain, causing them to became uncoordinated and unusually apprehensive. The source of the emerging epidemic was soon traced to a food supplement that included meat and bone meal from dead sheep. The methods for processing sheep carcasses had been changed in the late 1970s. Where once they would have eliminated the scrapie agent in the supplement, now they apparently did not. The British government banned the use of animal-derived feed supplements in 1988, and the epidemic has probably peaked. Nevertheless, many people continue to worry that they will eventually fall ill as a result of having consumed tainted meat.

The human prion diseases are more obscure. Kuru has been seen only among the Fore Highlanders of Papua New Guinea. They call it the “laughing death.” Vincent Zigas of the Australian Public Health Service and D. Carleton Gajdusek of the U.S. National Institutes of Health described it in 1957, noting that many highlanders became afflicted with a strange, fatal disease marked by loss of coordination (ataxia) and often later by dementia. The affected individuals probably acquired kuru through ritual cannibalism: the Fore tribe reportedly honored the dead by eating their brains. The practice has since stopped, and kuru has virtually disappeared.

Alzheimer's disease epidemic

Creutzfeldt-Jakob disease, in contrast, occurs worldwide and usually becomes evident as dementia. Most of the time it appears sporadically, striking one person in a million, typically around age 60. About 10 to 15 percent of cases are inherited, and a small number are, sadly, iatrogenic–spread inadvertently by the attempt to treat some other medical problem. Iatrogenic Creutzfeldt-Jakob disease has apparently been transmitted by corneal transplantation, implantation of dura mater or electrodes in the brain, use of contaminated surgical instruments, and injection of growth hormone derived from human pituitaries (before recombinant growth hormone became available).

The two remaining human disorders are Gerstmann-Straussler-Scheinker disease (which is (2) manifest as ataxia and other signs of damage to the cerebellum) and fatal familial insomnia (in which dementia follows difficulty sleeping). Both these conditions are usually inherited and typically appear in midlife. Fatal familial insomnia was discovered only recently, by Elio Lugaresi and Rossella Medori of the University of Bologna and Pierluigi Gambetti of Case Western Reserve University.

I first became intrigued by the prion diseases in 1972, when as a resident in neurology at the University of California School of Medicine at San Francisco, I lost a patient to Creutzfeldt-Jakob disease. As I reviewed the scientific literature on that and related conditions, I learned that scrapie, Creutzfeldt-Jakob disease and kuru had all been shown to be transmissible by injecting extracts of diseased brains into the brains of healthy animals. The infections were thought to be caused by a slow-acting virus, yet no one had managed to isolate the culprit (Prusiner later stated that he believes that Alzheimer’s disease is a prion disease).

In the course of reading, I came across an astonishing report in which Tikvah Alper and her colleagues at the Hammersmith Hospital in London suggested that the scrapie agent might lack nucleic acid, which usually can be degraded by ultraviolet or ionizing radiation. When the nucleic acid in extracts of scrapie-infected brains was presumably destroyed by those treatments, the extracts retained their ability to transmit scrapie. If the organism did lack DNA and RNA, the finding would mean that it was not a virus or any other known type of infectious agent, all of which contain genetic material. What, then, was it?

Investigators had many ideas–including, jokingly, linoleum and kryptonite–but no hard answers. I immediately began trying to solve this mystery when I set up a laboratory at U.C.S.F. in 1974. The first step had to be a mechanical one–purifying the infectious material in scrapie-infected brains so that its composition could be analyzed. The task was daunting; many investigators had tried and failed in the past. But with the optimism of youth, I forged ahead [see “Prions,” by Stanley B. Prusiner; SCIENTIFIC AMERICAN, October 1984].

Alzheimer's disease prevention

Amazing Prion Discovery

All our results pointed toward one startling conclusion: the infectious agent in scrapie (and presumably in the related diseases) did indeed lack nucleic acid and consisted mainly, if not exclusively, of protein. We deduced that DNA and RNA were absent because, like Alper, we saw that procedures known to damage nucleic acid did not reduce infectivity. And we knew protein was an essential component because procedures that denature (unfold) or degrade protein reduced infectivity.

I thus introduced the term “prion” to distinguish this class of disease conveyer from viruses, bacteria, fungi and other known pathogens. Not long afterward, we determined that scrapie prions contained a single protein that we called PrP, for “prion protein.” Now the major question became; Where did the instructions specifying the sequence of amino acids in PrP reside? Were they carried by an undetected piece of DNA that traveled with PrP, or were they, perhaps, contained in a gene housed in the chromosomes of cells?

The key to this riddle was the identification in 1984 of some 15 amino acids at one end of the PrP protein. My group identified this short amino acid sequence in collaboration with Leroy E. Hood and his co-workers at the California Institute of Technology. Knowledge of the sequence allowed us and others to construct molecular probes, or detectors, able to indicate whether mammalian cells carried the PrP gene. With probes produced by Hood’s team, Bruno Oesch, working in the laboratory of Charles Weissmann at the University of Zurich, showed that hamster cells do contain a gene for PrP. At about the same time, Bruce Cheseboro of the NIH Rocky Mountain Laboratories made his own probes and established that mouse cells harbor the gene as well. That work made it possible to isolate the gene and to establish that it resides not in prions but in the chromosomes of hamsters, mice, humans and all other mammals that have been examined. What is more, most of the time, these animals make PrP without getting sick.

One interpretation of such findings was that we had made a terrible mistake: PrP had nothing to do with prion diseases. Another possibility was that PrP could be produced in two forms, one that generated disease and one that did not. We soon showed the latter interpretation to be correct. The critical clue was the fact that the PrP found in infected brains resisted breakdown by cellular enzymes called proteases.

Most proteins in cells are degraded fairly easily. I therefore suspected that if a normal, (3) nonthreatening form of PrP existed, it too would be susceptible to degradation. Ronald A. Barry in my laboratory then identified this hypothetical protease-sensitive form. It thus became clear that scrapie-causing PrP is a variant of a normal protein. We therefore called the normal protein “cellular PrP” and the infectious (protease-resistant) form “scrapie PrP.” The latter term is now used to refer to the protein molecules that constitute the prions causing all scrapie-like diseases of animals and humans.

Alzheimers disease epidemic

Prion Diseases Can Be Inherited

Early on we had hoped to use the PrP gene to generate pure copies of PrP. Next, we would inject the protein molecules into animals, secure in the knowledge that no elusive virus was clinging to them. If the injections caused scrapie in the animals, we would have shown that protein molecules could, as we had proposed, transmit disease. By 1986, however, we knew the plan would not work. For one thing, it proved very difficult to induce the gene to make the high levels of PrP needed for conducting studies. For another thing, the protein that was produced was the normal, cellular form. Fortunately, work on a different problem led us to an alternative approach for demonstrating that prions could transmit scrapie without the help of any accompanying nucleic acid.

In many cases, the scrapie-like illnesses of humans seemed to occur without having been spread from one host to another, and in some families they appeared to be inherited. (Today researchers know that about 10 percent of human prion diseases are familial, felling half of the members of the affected families.) It was this last pattern that drew our attention. Could it be that prions were more unusual than we originally thought? Were they responsible for the appearance of both hereditary and transmissible illnesses? In 1988 Karen Hsiao in my laboratory and I uncovered some of the earliest data showing that human prion diseases can certainly be inherited. We acquired clones of a PrP gene obtained from a man who had Gerstmann-Straussler-Scheinker disease in his family and was dying of it himself. Then we compared his gene with PrP genes obtained from a healthy population and found a tiny abnormality known as a point mutation.

To grasp the nature of this mutation, it helps to know something about the organization of genes. Genes consist of two strands of the DNA building blocks called nucleotides, which differ from one another in the bases they carry. The bases on one strand combine with the bases on the other strand to form base pairs: the “rungs” on the familiar DNA “ladder.” In addition to holding the DNA ladder together, these pairs spell out the sequence of amino acids that must be strung together to make a particular protein. Three base pairs together–a unit called a codon–specify a single amino acid. In our dying patient, just one base pair (out of more than 750) had been exchanged for a different pair. The change, in turn, had altered the information carried by codon 102, causing the amino acid leucine to be substituted for the amino acid proline in the man’s PrP protein.

With the help of Tim J. Crow of Northwick Park Hospital in London and Jurg Ott of Columbia University and their colleagues, we discovered the same mutation in genes from a large number of patients with Gerstmann-Straussler-Scheinker disease, and we showed that the high incidence in the affected families was statistically significant. In other words, we established genetic linkage between the mutation and the disease–a finding that strongly implies the mutation is the cause. Over the past six years work by many investigators has uncovered 18 mutations in families with inherited prion diseases; for five of these mutations, enough cases have now been collected to demonstrate genetic linkage. The discovery of mutations gave us a way to eliminate the possibility that a nucleic acid was traveling with prion proteins and directing their multiplication.

We could now create genetically altered mice carrying a mutated PrP gene. If the presence of the altered gene in these “transgenic” animals led by itself to scrapie, and if the brain tissue of the transgenic animals then caused scrapie in healthy animals, we would have solid evidence that the protein encoded by the mutated gene had been solely responsible for the transfer of disease. Studies I conducted with Hsiao, Darlene Groth in my group and Stephen J. DeArmond, head of a separate laboratory at U.C.S.F., have now shown that scrapie can be generated and transmitted in this way [see BOX at end of this article]. These results in animals resemble those obtained in 1981, when Gajdusek, Colin L. Masters and Clarence J. Gibbs, Jr., all at the National Institutes of Health, transmitted apparently inherited Gerstmann-Straussler-Scheinker disease to monkeys. They also resemble the findings of Jun Tateishi and Tetsuyuki Kitamoto of Kyushu University in Japan, who transmitted inherited Creutzfeldt-Jakob disease to mice.

Together the collected transmission studies persuasively argue that prions do, after all, (4) represent an unprecedented class of infectious agents, composed only of a modified mammalian protein. And the conclusion is strengthened by the fact that assiduous searching for a scrapie-specific nucleic acid (especially by Detlev H. Riesner of Heinrich Heine University in Dusseldorf) has produced no evidence that such genetic material is attached to prions. Scientists who continue to favor the virus theory might say that we still have not proved our case. If the PrP gene coded for a protein that, when mutated, facilitated infection by a ubiquitous virus, the mutation would lead to viral infection of the brain. Then injection of brain extracts from the mutant animal would spread the infection to another host. Yet in the absence of any evidence of a virus, this hypothesis looks to be untenable.

In addition to showing that a protein can multiply and cause disease without help from nucleic acids, we have gained insight into how scrapie PrP propagates in cells. Many details remain to be worked out, but one aspect appears quite clear: the main difference between normal PrP and scrapie PrP is conformational. Evidently, the scrapie protein propagates itself by contacting normal PrP molecules and somehow causing them to unfold and flip from their usual conformation to the scrapie shape. This change initiates a cascade in which newly converted molecules change the shape of other normal PrP molecules, and so on. These events apparently occur on a membrane in the cell interior.

We started to think that the differences between cellular and scrapie forms of PrP must be conformational after other possibilities began to seem unlikely. For instance, it has long been known that the infectious form often has the same amino acid sequence as the normal type. Of course, molecules that start off being identical can later be chemically modified in ways that alter their activity. But intensive investigations by Neil Stahl and Michael A. Baldwin in my laboratory have turned up no differences of this kind.

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The Protein Pathogen

How, exactly, do the structures of normal and scrapie forms of PrP differ? Studies by Keh-Ming Pan in our group indicate that the normal protein consists primarily of alpha helices, regions in which the protein backbone twists into a specific kind of spiral; the scrapie form, however, contains beta strands, regions in which the backbone is fully extended. Collections of these strands form beta sheets. Fred E. Cohen, who directs another laboratory at U.C.S.F., has used molecular modeling to try to predict the structure of the normal protein based on its amino acid sequence. His calculations imply that the protein probably folds into a compact structure having four helices in its core.

Less is known about the structure, or structures, adopted by scrapie PrP. The evidence supporting the proposition that scrapie PrP can induce an alpha-helical PrP molecule to switch to a beta-sheet form comes primarily from two important studies by investigators in my group. Maria Gasset learned that synthetic peptides (short strings of amino acids) corresponding to three of the four putative alpha-helical regions of PrP can fold into beta sheets. And Jack Nguyen has shown that in their beta-sheet conformation, such peptides can impose a beta-sheet structure on helical PrP peptides. More recently Byron W. Caughey of the Rocky Mountain Laboratories and Peter T. Lansbury of the Massachusetts Institute of Technology have reported that cellular PrP can be converted into scrapie PrP in a test tube by mixing the two proteins together.

PrP molecules arising from mutated genes probably do not adopt the scrapie conformation as soon as they are synthesized. Otherwise, people carrying mutant genes would become sick in early childhood. We suspect that mutations in the PrP gene render the resulting proteins susceptible to flipping from an alpha-helical to a beta-sheet shape. Presumably, it takes time until one of the molecules spontaneously flips over and still more time for scrapie PrP to accumulate and damage the brain enough to cause symptoms. Fred Cohen and I think we might be able to explain why the various mutations that have been noted in PrP genes could facilitate folding into the beta-sheet form.

Many of the human mutations give rise to the substitution of one amino acid for another within the four putative helices or at their borders. Insertion of incorrect amino acids at those positions might destabilize a helix, thus increasing the likelihood that the affected helix and its neighbors will refold into a beta-sheet conformation. Conversely, Hermann Schatzel in my laboratory finds that the harmless differences distinguishing the PrP gene of humans from those of apes and monkeys affect amino acids lying outside of the proposed helical domains–where the divergent amino acids probably would not profoundly influence the stability of the helical regions.

No one knows exactly how propagation of scrapie PrP damages cells. In cell cultures, the conversion of normal PrP to the scrapie form occurs inside neurons, after which scrapie PrP accumulates in intracellular vesicles known as lysosomes. In the brain, filled lysosomes could conceivably burst and damage cells. As the diseased cells died, creating holes in the brain, their prions would be released to attack other cells. We do know with certainty that cleavage of scrapie PrP is what produces PrP fragments that accumulate as plaques in the brains of some patients. Those aggregates resemble plaques seen in Alzheimer’s disease, although the Alzheimer’s clumps consist of a different protein. The PrP plaques are a useful sign of prion infection, but they seem not to be a major cause of impairment. In many people and animals with prion disease, the plaques do not arise at all.

Even though we do not yet know much about how PrP scrapie harms brain tissue, we can foresee that an understanding of the three-dimensional structure of the PrP protein will lead to therapies. If, for example, the four-helix-bundle model of PrP is correct, drug developers might be able to design a compound that would bind to a central pocket that could be formed by the four helices. So bound, the drug would stabilize these helices and prevent their conversion into beta sheets.

Another idea for therapy is inspired by research in which Weissmann and his colleagues applied gene-targeting technology to create mice that lacked the PrP gene and so could not make PrP. By knocking out a gene and noting the consequences of its loss, one can often deduce the usual functions of the gene’s protein product. In this case, however, the animals missing PrP displayed no detectable abnormalities. If it turns out that PrP is truly inessential, then physicians might one day consider delivering so-called antisense or antigene therapies to the brains of patients with prion diseases. Such therapies aim to block genes from giving rise to unwanted proteins and could potentially shut down production of cellular PrP [see “The New Genetic Medicines,” by Jack S. Cohen and Michael E. Hogan; SCIENTIFIC AMERICAN, December 1994].

They would thereby block PrP from propagating itself. It is worth noting that the knockout mice provided a welcomed opportunity to challenge the prion hypothesis. If the animals became ill after inoculation with prions, their sickness would have indicated that prions could multiply even in the absence of a preexisting pool of PrP molecules. As I expected, inoculation with prions did not produce scrapie, and no evidence of prion replication could be detected.

The enigma of how scrapie PrP multiplies and causes disease is not the only puzzle starting to be solved. Another long-standing question–the mystery of how prions consisting of a single kind of protein can vary markedly 2n their effects–is beginning to be answered as well. Lain H. Pattison of the Agriculture Research Council in Compton, England, initially called attention to this phenomenon. Years ago he obtained prions from two separate sets of goats. One isolate made inoculated animals drowsy, whereas the second made them hyperactive. Similarly, it is now evident that some prions cause disease quickly, whereas others do so slowly.

Prion Mutations

Alan G. Dickinson, Hugh Fraser and Moira E. Bruce of the Institute for Animal Health in Edinburgh, who have examined the differential effects of varied isolates in mice, are among those who note that only pathogens containing nucleic acids are known to occur in multiple strains. Hence, they and others assert, the existence of prion “strains” indicates the prion hypothesis must be incorrect; viruses must be at the root of scrapie and its relatives. Yet because efforts to find viral nucleic acids have been unrewarding, the explanation for the differences must lie elsewhere. One possibility is that prions can adopt multiple conformations. Folded in one way, a prion might convert normal PrP to the scrapie form highly efficiently, giving rise to short incubation times. Folded another way, it might work less efficiently. Similarly, one “conformer” might be attracted to neuronal populations in one part of the brain, whereas another might be attracted to neurons elsewhere, thus producing different symptoms. Considering that PrP can fold in at least two ways, it would not be surprising to find it can collapse into other structures as well.

Since the mid-1980s we have also sought insight into a phenomenon known as the species barrier. This concept refers to the fact that something makes it difficult for prions made by one species to cause disease in animals of another species. The cause of this difficulty is of considerable interest today because of the epidemic of mad cow disease in Britain. We and others have been trying to find out whether the species barrier is strong (6) enough to prevent the spread of prion disease from cows to humans.


There Is No Species Barrier

The barrier was discovered by Pattison, who in the 1960s found it hard to transmit scrapie between sheep and rodents. To determine the cause of the trouble, my colleague Michael R. Scott and I later generated transgenic mice expressing the PrP gene of the Syrian hamster–that is, making the hamster PrP protein. The mouse gene differs from that of the hamster gene at 16 codons out of 254. Normal mice inoculated with hamster prions rarely acquire scrapie, but the transgenic mice became ill within about two months. We thus concluded that we had broken the species barrier by inserting the hamster genes into the mice. Moreover, on the basis of this and other experiments, we realized that the barrier resides in the amino acid sequence of PrP: the more the sequence of a scrapie PrP molecule resembles the PrP sequence of its host, the more likely it is that the host will acquire prion disease.

In one of those other experiments, for example, we examined transgenic mice carrying the Syrian hamster PrP gene in addition to their own mouse gene. Those mice make normal forms of both hamster and mouse PrP. When we inoculated the animals with mouse prions, they made more mouse prions. When we inoculated them with hamster prions, they made hamster prions. From this behavior, we learned that prions preferentially interact with cellular PrP of homologous, or like, composition. The attraction of scrapie PrP for cellular PrP having the same sequence probably explains why scrapie managed to spread to cows in England from food consisting of sheep tissue: sheep and bovine PrP differ only at seven positions. In contrast, the sequence difference between human and bovine PrP is large: the molecules diverge at more than 30 positions. Because the variance is great, the likelihood of transmission from cows to people would seem to be low.

Consistent with this assessment are epidemiological studies by W. Bryan Matthews, a professor emeritus at the University of Oxford. Matthews found no link between scrapie in sheep and the occurrence of Creutzfeldt-Jakob disease in sheep-farming countries. On the other hand, two farmers who had “mad cows” in their herds have recently died of Creutzfeldt-Jakob disease. Their deaths may have nothing to do with the bovine epidemic, but the situation bears watching. It may turn out that certain parts of the PrP molecule are more important than others for breaking the species barrier.

If that is the case, and if cow PrP closely resembles human PrP in the critical regions, then the likelihood of danger might turn out to be higher than a simple comparison of the complete amino acid sequences would suggest. We began to consider the possibility that some parts of the PrP molecule might be particularly important to the species barrier after a study related to this blockade took an odd turn. My colleague Glenn C. Telling had created transgenic mice carrying a hybrid PrP gene that consisted of human codes flanked on either side by mouse codes; this gene gave rise to a hybrid protein. Then he introduced brain tissue from patients who had died of Creutzfeldt-Jakob disease or Gerstmann-Straussler-Scheinker disease into the transgenic animals.

Oddly enough, the animals became ill much more frequently and faster than did mice carrying a full human PrP gene, which diverges from mouse PrP at 28 positions. This outcome implied that similarity in the central region of the PrP molecule may be more critical than it is in the other segments. The result also lent support to earlier indications–uncovered by Shu-Lian Yang in DeArmond’s laboratory and Albert Taraboulos in my group–that molecules made by the host can influence the behavior of scrapie PrP. We speculate that in the hybrid-gene study, a mouse protein, possibly a “chaperone” normally involved in folding nascent protein chains, recognized one of the two mouse-derived regions of the hybrid PrP protein. This chaperone bound to that region and helped to refold the hybrid molecule into the scrapie conformation. The chaperone did not provide similar help in mice making a totally human PrP protein, presumably because the human protein lacked a binding site for the mouse factor.

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Prion Disease Spreading Through Sewage

An unforeseen story has recently emerged from studies of transgenic mice making unusually high amounts of normal PrP proteins. DeArmond, David Westaway in our group and George A. Carlson of the McLaughlin Laboratory in Great Falls, Mont., became perplexed when they noted that some older transgenic mice developed an illness characterized by rigidity and diminished grooming.

When we pursued the cause, we found that making excessive amounts of PrP can (7) eventually lead to neurodegeneration and, surprisingly, to destruction of both muscles and peripheral nerves. These discoveries widen the spectrum of prion diseases and are prompting a search for human prion diseases that affect the peripheral nervous system and muscles. Investigations of animals that overproduce PrP have yielded another benefit as well.

They offer a clue as to how the sporadic form of Creutzfeldt-Jakob disease might arise. For a time I suspected that sporadic disease might begin when the wear and tear of living led to a mutation of the PrP gene in at least one cell in the body. Eventually, the mutated protein might switch to the scrapie form and gradually propagate itself, until the buildup of scrapie PrP crossed the threshold to overt disease. The mouse studies suggest that at some point in the lives of the one in a million individuals who acquire sporadic Creutzfeldt-Jakob disease, cellular PrP may spontaneously convert to the scrapie form.

The experiments also raise the possibility that people who become afflicted with sporadic Creutzfeldt-Jakob disease overproduce PrP, but we do not yet know if, in fact, they do. All the known prion diseases in humans have now been modeled in mice. With our most recent work we have inadvertently developed an animal model for sporadic prion disease. Mice inoculated with brain extracts from scrapie-infected animals and from humans afflicted with Creutzfeldt-Jakob disease have long provided a model for the infectious forms of prion disorders. And the inherited prion diseases have been modeled in transgenic mice carrying mutant PrP genes.

These murine representations of the human prion afflictions should not only extend understanding of how prions cause brain degeneration, they should also create opportunities to evaluate therapies for these devastating maladies.

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No Difference Between TSEs

Ongoing research may also help determine whether prions consisting of other proteins play a part in more common neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. There are some marked similarities in all these disorders. As is true of the known prion diseases, the more widespread ills mostly occur sporadically but sometimes “run” in families. All are also usually diseases of middle to later life and are marked by similar pathology: neurons degenerate, protein deposits can accumulate as plaques, and glial cells (which support and nourish nerve cells) grow larger in reaction to damage to neurons.

Strikingly, in none of these disorders do white blood cells–those ever present warriors of the immune system–infiltrate the brain. If a virus were involved in these illnesses, white cells would be expected to appear. Recent findings in yeast encourage speculation that prions unrelated in amino acid sequence to the PrP protein could exist. Reed B. Wickner of the NIH reports that a protein called Ure2p might sometimes change its conformation, thereby affecting its activity in the cell. In one shape, the protein is active; in the other, it is silent. The collected studies described here argue persuasively that the prion is an entirely new class of infectious pathogen and that prion diseases result from aberrations of protein conformation. Whether changes in protein shape are responsible for common neurodegenerative diseases, such as Alzheimer’s, remains unknown, but it is a possibility that should not be ignored.

Several studies have shown that prions composed only of PrP are able to convey infection from one animal to another. In one such experiment, the author and his colleagues created mice carrying many copies of a mutant PrP gene; these animals made high levels of mutant PrP, some of which appears to adopt the scrapie conformation. Eventually all the mice displayed symptoms of brain damage and died.

Then the workers injected brain tissue from the diseased animals into genetically altered mice making low levels of the same mutant PrP protein. (Such mice were chosen as recipients because scrapie PrP is most attracted to PrP molecules having the same composition.) Uninoculated mice did not become ill (indicating that making low levels of the aberrant protein was safe), but many of the treated ones did. Moreover, brain tissue transferred from the diseased recipients to their healthy counterparts caused illness once again. If the aberrant protein were unable to transmit infection, none of the inoculated animals would have sickened.


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Crossbow Communications specializes in issue management and public affairs. Alzheimer’s disease, Creutzfeldt-Jakob disease, chronic wasting disease and the prion disease epidemic is an area special expertise. Please contact Gary Chandler to join our coalition for reform