(This article appeared in the May, 1998 issue of
Wyoming Wildlife Magazine)
The biologists first recognized it in 1967. Some of the captive deer at the Colorado Division of Wildlife's research facilities in Fort Collins began to lose weight on a diet that sustained other deer. After several months, they had wasted away to skin and bones. They drank incessantly, urinated often, and spent much of their time standing listlessly in their corrals, heads down, ears drooping, saliva dripping from their mouths.
The biologists knew they had a unique syndrome on their hands, but what was it? Blood samples showed nothing unusual; liver and kidneys were normal. The disease was like nothing they had ever seenâ€” at least, in deer.
Over a ten-year period, the illness showed up in Colorado research pens and in the Wyoming Game and Fish Department's Sybille research unit near Wheatland. Because the Colorado and Wyoming facilities regularly traded deer and elk, the appearance of the disease in Wyoming came as no great surprise.
At first, researchers monitoring the affected animals suspected that they were suffering from a nutritional deficiency or an unfortunate reaction to captivity, but as the years went by, more and more facts interfered with that diagnosis. Mule deer were living in captivity all over the West; if the stress of captivity or dietary deficiency were causing the illness, why was it confined to deer in these Colorado and Wyoming research pens? And why was this disease so virulent? Between 1974 and 1979, sixty-six mule deer and one black-tailed deer were held captive in Colorado and Wyoming research corrals, mainly as subjects in long-term studies of deer food habits and nutrition. Of these sixty-seven long-term residents, fifty-seven contracted the strange disease. None survived.
A search for several likely viruses and bacteria turned up nothing. Since the illness in these deer was unlike any other disease reported in deer, the biologists christened it "chronic wasting disease" in recognition of the long, irreversible weight loss that eventually killed the victim.
As the death toll mounted, wildlife vets began a painstaking analysis of tissues, looking for a cause. In 1978, Beth Williams, now with the Wyoming State Veterinary Laboratory, found the first evidence in the brains of the victims. Under high magnification, she could see tiny holes in the contents of the nerve cells, so many holes that the tissue looked like a sponge.
The damage appeared in many parts of the brain and upper spinal cord. In addition to the holes, there were patches of protein build-up between some brain cells and degeneration of others, but in spite of this fatal destruction of brain tissue, there was no sign of inflammation or response of the animal's immune system.
The condition of the tissue samples and symptoms of the illness itself reminded pathologists of a sheep disease called scrapie. Like deer with chronic wasting disease, sheep with scrapie tend to lose weight. But scrapie-infected sheep show different symptoms, too; they seem to be itchy and will scratch themselves until they wear off their fleece and break the skin (hence, the common name for the disease). They often lose control of their muscles, staggering and showing tremor in the muscles around their heads.
Scrapie seems to be the oldest of a small group of related diseases called spongiform encephalopathies. First reported in the mid-1700s, scrapie has affected sheep and goats in Great Britain, Europe, and North America for centuries. In all that time, it has never been reported in other animals, including generations of shepherds who have lived in close association with their flocks.
The apparent similarity between chronic wasting disease and scrapie raised more questions than it answered. In the 1970s, no one was sure what caused scrapie. Since the disease took several months to run its course, some researchers assumed that it was a genetic illness. Others thought there must be a "slow virus" too small to be detected by existing techniques. This stealth germ was thought to be the cause of all the transmissible spongiform encephalopathies from scrapie and chronic wasting disease to rare human diseases like Creutzfeldt-Jakob disease.
While the discussion over the cause of chronic wasting disease continued, biologists in the field reported more unsettling news. The disease had turned up in wild deer. Vets with the Colorado Division of Wildlife and the Wyoming Game and Fish Department and pathologists with the Wyoming and Colorado veterinary diagnostic laboratories routinely examine animals that have been collected because they were sick. In March 1981, biologists in northcentral Colorado brought in a sick elk that turned out to be suffering from chronic wasting disease.
Over the next fourteen years, lab work turned up sixty cases of chronic wasting disease; forty-four in mule deer, six in white-tailed deer, and ten in elk. In 1986, a Wyoming elk was diagnosed with the disease, the first case reported in a free-ranging Wyoming big game animal. All of the sick animals were found in northeastern and northcentral Colorado and in southeastern Wyoming.
It was certainly no raging disease outbreak, and it didn't seem to be gaining momentum as time went on. Still, vets and biologists had cause for concern. They were pretty sure that chronic wasting disease was 100 percent fatal to deer once they become ill, and they still didn't know what caused the disease or how it spread.
Their concern deepened as they experimented with ways to sanitize the holding pens in Fort Collins and Sybille. All the deer and elk in the contaminated pens at Sybille were killed, and the pens were left empty for six months to a year. When deer and elk were reintroduced to the pens, they were animals that weren't known to have had direct contact with infected deer and elk. In spite of these efforts, elk in the pens came down with chronic wasting disease within five years after the attempt at sterilizing the facility.
In Fort Collins, the effort was even more intense. All the deer and elk in the facility were killed and buried. Then personnel plowed up the soil in the pens in an effort to bury possible disease organisms and sprayed structures and pastures repeatedly with a strong disinfectant. A year later, they took twelve elk calves from the wild and released them in the sanitized holding areas. In the next five years, two of these elk died from chronic wasting disease.
If the disease were caused by a "slow virus," it was an exceptionally tough organism.
In 1972, a neurologist serving his residency at the University of California's School of Medicine lost a patient to Creutzfeldt-Jakob disease, an exceedingly rare and brutal brain disorder. During his struggle to arrest the disease, he was struck with the lack of information on the cause. Two years later, he established a laboratory at the University of California-San Francisco and decided to look into the notion of an undetectable "slow virus."
His name was Stanley Prusiner and his investigation of the group of pathogens responsible for scrapie, Creutzfeldt-Jakob disease, and other transmissible spongiform encephalopathies won him the Nobel Prize in Medicine in 1997.
Prusiner and a few other pioneers recognized that, whatever caused scrapie, it was hard to defuse. Sterilization techniques that killed known germs (viruses, bacteria, fungi, and protozoans) didn't affect the scrapie pathogen. The only procedures that seemed to short-circuit the scrapie bug were those that actually broke down proteins. He knew that killing normal germs is usually a matter of destroying the delicate DNA and/or RNA that makes up their nuclei. He knew that tissue infected with scrapie showed no foreign DNA or RNA. With all this information, he guessed that the scrapie agent lacked DNA, that it was naked protein.
The notion was near-blasphemy in biological circles. Modern biological theory is based on the notion that all proteins are built from a blueprint provided by DNA or RNA. Without the blueprint, the reasoning goes, it's impossible to reproduce an accurate copy of any protein. Prusiner was saying that a protein could transform other proteins into its own image, and more than two decades of research are proving him right. He called this group of pathogens proteinaceous infectious particles' prions, for short.
If one of these prions causes scrapie, the thinking went, then other prions are probably responsible for the other spongiform encephalopathies. In a few cases, the blueprints for these prions may even be inherited, which would explain why exceedingly rare human spongiform encephalopathies like fatal familial insomnia, Gerstmann-Stussler-Scheinker disease, and some cases of Creutzfeldt-Jakob disease are found only in a tiny number of extremely unlucky families.
Typically, human spongiform encephalopathies aren't passed from one individual to another. There's only one known exception to this rule, an odd prion disease passed from one tribal member to another among the Fore Highlanders of New Guinea. It was custom among the Fores to honor the dead members of the tribe through ritual cannibalism, including eating the brains of the departed relative. This spread a fatal illness called kuru or the laughing death. When western missionaries convinced the Fores to find other ways to honor their deceased comrades, the disease died out. Other prion-caused diseases seem to find less direct ways to jump from one victim to another, but scientists aren't sure how. And there is a possibility that the prions aren't transmitted but arise from a spontaneous change in a protein molecule.
Since proteins differ from one species to another, prions are less likely to prosper in a new species than in the one in which they began. This "species barrier" is hardest to breach when proteins in the two species are most different. Species with closely related proteins may be able to exchange prion-caused diseases, but even in such circumstances, the prions probably won't jump the species barrier unless there is massive exposure or the prions find an unusual way to get straight into a new victim's brain. Researchers working with lab mice have found that the most efficient way to do this is to inject prion-infected tissue directly into the brain. Injecting prions from another species under the skin is thousands of times less effective in inducing the disease, and feeding infected food to the mice is less efficient still.
Closely confined, the research deer had the greatest possible chance of transmitting the disease. Elk are fairly close relatives of the mule deer and, confined with infected deer, occasionally developed chronic wasting disease. Whether they actually caught the disease from the deer is open to some question. Pronghorns, bighorn sheep, mouflon, and other more distantly related species didn't come down with the disease, even though they were often exposed to it.
In wild deer where there is much less day-to-day contact than there is among penned research animals, the disease spreads very slowly and affects a small proportion of the herd. What remains is to find the way the disease passes from one animal to another and the best way to destroy the prions.
It about the time Prusiner and his colleagues were discovering prions, prions found their own way into international news. In 1986, British vets reported a new disease in the United Kingdom's cattle herds. It started with changes in behavior; nervousness, frenzied activity, sudden fear of doorways, and heightened response to sound and touch. The affected animals began to lose weight, and in dairy cows, milk yield dropped. Finally, the cows began to lose control of their muscles, showed tremors, and stood with their heads and ears drooping.
The vets called it bovine spongiform encephalopathy (BSE); the press dubbed it "mad cow disease." By backtracking the outbreak, disease specialists were able to determine that the first case in history had probably occurred in 1985. The cause may have been a change in the way cattle feed was processed. The British have long used meat and bone meal from animals in their cattle feed. For most of that time, they used a special solvent to extract fat from the protein when carcasses were rendered. Sometime in 1981, the use of this solvent was reduced, possibly allowing a much higher concentration of prions into the finished protein meal. Another possible cause of contamination was that more sheep byproducts were being included in British dairy feeds' more sheep could have meant more scrapie in the feed as well.
As a result of the contamination, British farmers were confronted with a BSE epidemic. There were twelve cases reported in 1986, 461 in 1987, and nearly 37,000 by 1992. More than half of the United Kingdom's dairy herds were infected. In 1988, officials banned the use of ruminant proteins in cattle feed, and a year later, they prohibited the use of cattle brains, spinal cord, tonsils, thymus, spleens, or intestines in human food.
Thanks to the change in cattle feed, incidence of the disease began to drop in 1992 and continues to decline to this day. At current rates of change, officials hope that BSE in Britain may disappear entirely sometime after the year 2000.However, in 1995, a new variant of Creutzfeldt-Jakob disease appeared in British patients. By March 1996, ten cases had been reported. Analysis eventually convinced health officials that the new version was a human form of BSE. By the end of October 1996, three more cases of the disease had been diagnosed in Britain and one in France.
In the wake of the "mad cow disease" news coverage, officials in the U.S. began wondering about the possible risks of chronic wasting disease. After all, they reasoned, BSE is a prion-caused disease; chronic wasting disease is a prion-caused disease. If BSE could spread to humans, why not chronic wasting disease? Headlines in the Denver Post shouted, "To eat or not to eat is the hunter's question" and "Ill animals spook hunters." And, on another front, some ranchers worried about their free-ranging livestock mixing with deer.
Of course, from the standpoint of sensational press, the story is in the similarities between the two diseases, not the differences, but the differences are worth considering. It took a massive contamination of feed to establish BSE in British cattle and contamination of British beef products to produce twenty-four cases of the new variant of Creutzfeldt-Jakob disease. Right now, the human disease has appeared in a little more than .00004 percent of the British population. Since the disease can take years to develop, it may be a decade before we know how many cases of the variant Creutzfeldt-Jakob disease the British BSE outbreak finally caused but with the cleanup in British cattle feed and strict controls on beef sold for human consumption, the likelihood of new infections in humans is infinitesimal.
In comparison, surveys in northern Colorado during the 1997 hunting season showed that few deer there carry chronic wasting disease. Samples taken in Larimer County show that about six percent of the deer killed there tested positive for the disease. Collection of elk show that less than one percent of the animals taken by hunters test positive.
Wyoming did a similar survey among deer hunters in the southeastern part of the state and reached similar conclusions. Last fall, biologists collected samples of deer and elk brain from cooperating hunters in southeastern Wyoming. They took 137 usable samples of deer brain tissue from hunt areas that were suspected to contain chronic wasting disease; areas 16, 59, 60, 62, 63, and 64. Eight of these animals tested positive; slightly less than six percent of the animals tested. Seven of the cases came from hunt area 64.
Biologists also took ninety-three deer samples from surrounding hunt areas; deer areas 15, 55, 57, and 73. None of these deer had chronic wasting disease. Fifteen elk samples from elk hunt areas 5, 7, 12, 13, 21, 82, and 110 were also free of the disease.
Since chronic wasting disease first turned up in the wild in 1981, about 100 cases have been reported in wild mule deer, white-tailed deer, and elk, and only eleven of those cases were in Wyoming. The number of cases has gone up in recent yearsâ€” no one knows whether that is because we're looking harder for the disease or because more deer are infected now. At this point, chronic wasting disease remains rare in the wild, and it is confined to a few hunt areas in northcentral Colorado and southeastern Wyoming. And in the thirty years we have known about the disease, no human has ever come down with it.
Veterinarians at the U.S. Department of Agriculture's Agriculture Research Service, the University of Wyoming, the Colorado Division of Wildlife, and the Wyoming Game and Fish Department are studying the issue of chronic wasting disease in livestock. They are looking for the answers to three questions. First: Can cattle be infected with chronic wasting disease? The vets have injected infected tissue directly into the brains of calves to find out whether it's even possible for a cow to suffer the illness.
Second: If infection is possible, can a cow pick up the disease in its feed? The vets have given cattle a single dose of contaminated feed to find out whether chronic wasting disease can be orally transmitted.
And third: Can cattle catch this disease by living in pens where it has occurred in the past or by sharing pens with infected deer and elk? Deer and elk may catch chronic wasting disease in this way, but only many years of tests will show whether the same can be said of cattle.
Chronic wasting disease can take several years to claim its victims, and the vets running the studies expect to continue them for as much as a decade. In the meantime, the Wyoming State Veterinary Laboratory will continue to cooperate in the national watch for BSE, and the Game and Fish Department will continue to test for chronic wasting disease to keep tabs on how many animals are affected and where the disease is found.
Chronic wasting disease isn't known to affect people. Scrapie, a disease related to chronic wasting disease, has existed in sheep for at least 300 years, yet there has never been a case of scrapie reported in a human being, even among people who work with sheep and the millions of people who eat lamb and mutton.
There has been concern over Great Britain's experience with "mad cow disease" and a handful of cases of human new-variant Creutzfeldt-Jakob disease. Those twenty-four cases resulted after a population of 50 million people was exposed to a huge outbreak of spongiform encephalopathy in British cattle. With the passing of the disease in British livestock, the likelihood of further cases of the new variant of Cruetzfeldt-Jakob disease will drop rapidly.
Even in the parts of Wyoming and Colorado where chronic wasting disease is found, less than six percent of deer are infected. In these areas and in other places where big game animals may carry different diseases, a few precautions are sensible:
1) Don't shoot an animal that is acting abnormally or looks sick.
2) Wear rubber or latex gloves when you field-dress your animal.
3) In areas where chronic wasting disease has been reported, minimize your contact with a dead deer's brain and spinal cord and wash your hands after contact.
4) Don't eat deer brains or spinal cord.
5) Bone out your deer meat and discard the brain, spinal cord, eyes, spleen, and lymph nodes.
Since our discovery of the chemical basis of genes in the 1950s, our understanding of the chemical working of cells has exploded. But the more we discover, the more we find needs discovering
Even though Stanley Prusiner recently won the Nobel Prize for his work on prions, the concept of a prion as a protein that can transform other proteins still has opponents in the scientific world. However, intense research with genetically engineered mice here in the U.S. and in Great Britain is proving him right
In yeasts, prions may act as a kind of gene, passing valuable traits from one generation to another. In mammals, normal proteins of this general class are found on the membranes of nerve cells. Researchers are still working to define their role. Mice that are genetically engineered to keep from producing prions suffer from changes in the way electrical charges move through the brain. Some scientists believe that an absence of these proteins may interfere with the mouse's ability to learn. Too many of them may lead to muscle diseases
But these problems are insignificant compared to the difficulties these proteins cause when they twist into certain forms that resist the attacks of enzymes. These molecules stick together in microscopic mats called beta sheets. As these uniquely twisted molecules contact normal protein, the normal molecules twist as well, forming a new generation of dangerous prions.
These sheets of molecules collect and eventually kill the nerve cell, leaving microscopic holes in the tissue of the brain.