Research in biology is slow. It is one thing to assemble a bunch of jigsaw pieces into a jigsaw -- even if a lot of pieces are missing, and when some pieces have their tabs broken off, or when some of the colors have faded or been distorted because the picture was processed differently than the one on the piece right next to it. It is another to try to discover each of those pieces through grueling work over time. Eventually, a picture emerges. In the last year, some very interesting pictures have emerged about CWD that are worth sharing.

First, some background. CWD is short for Chronic Wasting Disease. It was discovered at the Fort Collins Agricultural Research Station in Colorado. It bears some strong resemblance to scrapie, another disease that affects sheep. Around the time it was discovered, research was being done to try to understand how a class of diseases, including scrapie, worked. This group included Creutzfeld-Jacob Disease (CJD -- pronounced croitzfelt-yacob) and bovine spongiform encephalopathy (BSE) -- also called mad cow disease. As a group, these diseases are called Transmissible Spongiform Encephalopathies (TSEs). They also affect squirrels, mink, and other animals.

Up until the '70s and into the '80s, it was recognized that CJD was very strange in a few ways. First, there did not seem to be a virus or bacterial agent. There was no fever or immunological response. It occurs spontaneously in the population at a rate of a few per million. The rate of transmission of mad cow was only a few times larger -- but it affected young people, which never happened among the spontaneous CJD population. It could also be transmitted by ingestion. A tribe of New Guinea natives called the Fore (pronounced "foray"), had a funerary ritual where women and children would participate in eating their dead relatives, including the brain. The disease showed up primarily in women -- never the men. The men never participated in the funerary ritual. The loss of neurological control produced involuntary spasms that sounded like "laughing," which in the Fore tongue was called "kuru." It can be transmitted by direct transmission of affected tissues -- which occurred accidentally through the use of instruments during brain surgery. At the same time, it was discovered that normal sterilization procedures, as in an autoclave, were not sufficient to eliminate the active agent. Since onset of BSE transmission into humans produced different symptomatic effects, onset rate was different, it was occurring at a drastically younger age than in the spontaneous population, etc, it was concluded that these things seemed to have different "strains." This led to a controversy over whether genetic information was a part of the agency in the transmission of this disease, or not. In the end, Pruissner got a Nobel Prize for the hypothesis that no genetic agent was involved in the transmission, but rather, that it was caused by misfolded proteins, called prions (pronounced "pree-ons"), that induced other normally configured proteins to misfold too.

Similar to the difficulty sterilizing surgical implements, efforts to clean up pens that had held affected animals proved very difficult as well. Even after burning and sterilization, animals placed in the pens contracted the disease. After leaving a carcass in a pen for two years, the carcass was still capable of transmitting the disease. Even if the pen only had urine and manure in it for two years, the material was still infectious. For this reason, when I asked the DEC medical folks why they didn't require hunters to remove the gut-pile from the woods in the special CWD management areas, they said they figured the load was already so high just from the excretions that it wasn't worth worrying about. However, it has become very important to consider when we consider using lures, that the deer farms where the urine and glandular excretions have been collected are disease free. New regulations are being instituted to require this.

Since this doesn't involve bacteria or viruses, there is no traditional possibility of vaccine, though some research suggests some novel techniques might help. Nor will it be possible to make antibiotics. Proteins are strange things -- they are comprised of one or more linear chains of elements called peptides (amino acids). These polypeptide chains act like they are covered with Velcro, that likes to stick each to its opposite (fuzzy stuff to plastic hooky stuff). In practice, those attachments are "hydrogen bonds." Even with all those sticky points of contact, the proteins fold up in regular ways rather than just any Velcro to any Velcro. If they didn't, they would not behave chemically they way they need to sustain our lives. The linear sequence of peptides is called primary structure. The most regular geometric shapes that fold are called secondary structure. These are comprised of two basic types: alpha helices and beta sheets. There are also turns and loops and such, as well. The way all of those elements pack into a final shape, including the detailed 3D coordinates of each atom, is called tertiary structure.

The beta sheets are composed of segments of peptide chains that act like zipper strands with teeth on each side of the strand. They can zip into other strands, like knitting, to form sheets. The strand runs back and forth, with a turn at each end... just like knitting. The disease process for CWD is that one protein, PrP, will present strands from multiple molecules to tie into sheets, forming huge globules. These form a large part of accumulations called plaques. There are molecules whose job it is to disassemble this (and each of a number of molecules) after they've hung around for a while. The problem is, these molecules don't recognize the misfolded blobs, and so these blobs just hang around, accumulating more and more. Similar blob-building involving other molecules has been implicated in other diseases such as Alzheimer's. The inter-species barriers likely has to do with the differences in the structure of PrPs between species, and the relative ease that the beta strands can see each other to knit into amyloid plaques.

Some recent studies have found some agents that will break up the blobs. However, it has also been found that, in the range of blob sizes, some of the smaller blobs are the most infectious. Therefore, if you break up bigger blobs into smaller blobs, you may increase the rate of onset of the disease.

Until recently, the function of PrP was not very well understood. It had been vaguely associated with memory. This year, some research has indicated that neurons are regenerated regularly in the brain. This countered decades of doctrine, assumed to have been proven and settled to the contrary. Further, the advancement of stem cells to mature neurons is mediated by a number of molecules, but one that is quite effective is PrP. This, even considering its lethal characteristic, the general benefit has outweighed its negative side. Therefore, looking at tissues where stem cells live, and where neuron regeneration is known to occur (olfactory senses, etc), it is clear why tissues such as spleens, bone marrow, and some other glands should have been avoided.

That leads to the next issue. Very recent work, done by people from Ft. Collins, the Colorado department of wildlife, UC, other universities stateside, and some international participants, has indicated that PrP's are showing up in muscle tissue as well. If we eat venison from a diseased animal, we will be exposed to the transmitting agent. To this extent, CWD is very much like the sheep-vectored version, scrapie, and different from the BSE (mad-cow) form. Scrapie has also been endemic to the sheep population for years. In both deer and sheep populations, the endemic affliction rate seems to reach about 30%. However, in the several centuries that scrapie has been known to be present in the sheep population, no instances of its transmission to humans have been shown. While the disease seems to have appeared spontaneously first at the Fort Collins Ag Station and spread from there, it has been suggested that it may have come first from scrapie infected sheep. However, so little was known about CWD when it was first observed and characterized, and it happened so long ago, that it will likely never be known how it started. Since then, transmission has been shown to occur between white-tail (odocoileus Virginianus), mule deer (odocoileus Hemionus), elk (cervus Elephus), and moose (alces Alces) (the last being observed in the wild just this year). While no dietary transmission has been demonstrated to primates, direct injection of affected central nervous system (CNS) tissue has induced onset of TSE. Concentration of PrP material in muscle tissue is much lower than in the CNS and stem-cell bearing tissues.

Transmission of BSE in nature is much lower. However, an agricultural practice in England greatly amplified transmission. Disposal of butchering by-products (offal) were recycled back into the food chain. This solved two expensive problems: waste disposal, and getting new protein sources. However, it greatly spread the disease transmission rate. Further, a number of traditional packed-meat products included sausage stuff made from some organ meats that Americans typically did not include -- some of which bore significant concentrations of infected material.

Some trophy deer management practices include food plots and mineral supplements. Early on, mineral supplements could have been one way that material from infected animals was spread. The DEC has increased its prohibition against the use of mineral licks and supplements that we can put out for deer because of this. While the cause of the outbreak in Wisconsin will likely never be determined, it has been conjectured that some of the supplements put out by local clubs practicing intensive management may have introduced the disease to Wisconsin through their mineral supplements.
   

Information about the disease can be found at DEC's CWD Info. DEC's CWD Status Info. Information about hunting regulations involving CWD management can be found at DEC CWD hunting regulations. Information about the CWD containment area can be found at DEC CWD Containment Area hunting regulations.