~~~ What the Heck is "Mad Cow" Disease? ~~~

First Great Britain, then regions of Europe, then Canada and now, the United States. In December, 2003, the first case of bovine spongioform encephalopathy (BSE) was diagnosed in a dairy cow in Washington state. The disease is thought to be transmitted to cattle through the feeding of cattle with parts of other animals. The feeding of cattle with rendered meat and bone from other animals has been banned in the United States since 1997. There is a reported 99 percent compliance with this ban; however, it is now clear that 99 percent is not 100 percent - someone didn't get the message.

As of 2003, the spread of mad cow disease in Europe - including, Great Britain, Ireland, The Netherlands, France, Spain, Germany, Belgium, Denmark and Portugal and the appearance of the variant form of Creutzfeldt-Jakob disease (vCJD) in humans in many of these nations, is continuing to cause great concern among officials in Europe, Canada and the United States. A few years ago the United States, in order to protect the nation's blood supply, banned blood obtained from any donor who lived in Great Britain or Ireland for six months between 1980 and 1996. These individuals are not allowed to be blood donors to the United States blood supply, for life. The issue has become even more of a concern as the spread of this disease occurs in Europe. As a consequence, the United States is considering extending the ban of donation of blood from individals who may have lived for a time in other European countries.

Reports of diseased cattle in the British Isles, in many nations of Europe, Canada (one case) and the United States (one case so far) has again raised concern about the possible transmission between species of a yet-to-be clearly identified agent- but thoought to be a prion (a modified protein that can cause the normal form of this protein to become folded incorrectly and over time, cause damage to the brain - please see below). The syndrome presently affecting many of the cattle in the British Isles, "Mad Cow" disease, is a normally extremely rare neurological disorder that affects the central nervous system of the animal. The brain of the animal is slowly, progressively, severely damaged. It is a kind of disease that falls into the category of disease known as spongiform encephalopathy. In this particular case the disease would be known as bovine spongiform encephalopathy (BSE). An encephalopathic condition means that the brain is pathologically damaged, and spongiform means that if one examines the diseased brain tissue, the diseased tissue is spongy - porous - no longer intact.

The first reports of bovine spongiform encephalopathy (BSE) surfaced in Great Britain in 1986, and were thought to be linked to the practice of supplementing cattle food with bone meal prepared from slaughtered sheep. The reason for the linkage is that the disease the cattle were diagnosed as having appeared strikingly similar to that of the disease in sheep known as scrapie. Sheep with scrapie rub their bodies against walls and fences until the skin is completely raw. Eventually, the animal succumbs to the degeneration of the brain. Similarly, cattle become more and more unmanageable and eventually must be destroyed. When the brains of these cattle were examined, there was clear evidence of spongiform encephalopathy.

While cattle had not before been observed with this disorder - at least to the extent of such numbers within a herd which would lead to such investigation or reporting of symptoms - sheep had long been known to somehow acquire this disease - even though the disease is extremely rare among sheep. Consequently, as a precaution the health authorities began to operate under the supposition that this disease might have been passed from one species to another by some unidentified infectious agent. Subsequently, at least as far as I am aware, the supplementing of cattle food with sheep bone meal was halted in an attempt to stop whatever might be occurring. I am not aware of a reported case of "Mad Cow" disease occurring in the British Isles prior to 1986.

Unfortunately, there are several human diseases that fall into this category of spongiform encephalopathies, and include: kuru, Creutzfeldt-Jakob (pronounced: Kroytzfelt- Yakobe) disease, and Gerstmann-Sträussler-Scheinker syndrome of humans. All of these diseases result in eventual spongiform encephalopathy, and like scrapie, and now "Mad Cow" disease, are possibly transmitted by a relatively new kind of suspected infectious agent called a prion - the term prion is an acronym coined several years ago by the scientist, Stanley Prusiner. The acronym stands for: proteinaceous infectious particle - Prusiner just changed the letters around a bit. Prusiner studied the best-documented spongiform encephalopathy, sheep scrapie, and determined that the only identifiable thing which could transmit this disease from animal to animal was unlike any other infectious agent before identified - the disease appeared to be transmitted by pure protein, alone. In October, 1997, Stanley Prusner was awarded the Nobel Prize in Medicine for his identification and characterization of the Prion and the association of this protein with neurological disorders.

Now, certain extraordinarily small disease-causing infectious agents called viruses have been known for a long, long time - these infectious agents may infect for example, bacteria (known as bacteriophage), plants (plant viruses like tobacco mosaic virus), and animals (poliovirus, HIV, influenza virus, to name only a few). However, without a single exception every virus identified to date has been found to contain a genome (genetic material) comprised of nucleic acid (either RNA or DNA), which contains all of the information (genes) for the formation of virus progeny (offspring). No form of existing life ever identified on the earth - (or semi-life form like a virus which requires a host cell in order to make more virus) which can propagate its own form has ever been found to be devoid of either DNA or RNA. Only viruses have RNA as a possible genome - all other known life forms have only DNA as their central genetic information. Therefore, an infectious agent which consists of protein alone, is extremely difficult to yet comprehend, e.g., how can copies of itself be made? How can a protein cause an on-going, progressive disease and the disease be transmissible?

There is no known mechanism which accounts for protein alone serving as a template for making many copies of the same protein, or for a protein alone to cause infection (an infection is the invasion of a host by a microorganism which results in the presence and growth of the microorganism - an infection may not lead to disease - a disease is any deviation from the normal function of the body that is characterized by a defined set of symptoms - an infectious disease is therefore a disease caused by the establishment and growth of any infectious organism which results in defined dysfunction as a result of the presence of the organism or product of the organism). Although protein toxins are well-known (such as botulism toxin; tetanus toxin) - these proteins are not infectious - the organism which produces the toxin is the infectious agent and the cause of the disease - which may result from release of the toxin from the living organism (like Clostridium botulinum - botulism; or, Clostridium tetanii - tetanus). Yet, Prusiner and by now many other investigators have failed to identify anything but protein in these infectious particles known as prions.

As it turns out, the protein in question (prion) is also present in a normal form in all animals - it is called PrP. As far as I know, the actual function of this protein is not known. The gene that encodes this protein is found on chromosome number 20 in humans (humans have 23 pairs of different chromosomes - for a total of 46 - one of the chromosomes within each numbered pair comes from your mother, and the other from your father). The PrP protein is abnormal (structurally different in sheep with scrapie - is called PrP-sc). It is this altered form of PrP (PrP-sc) which is apparently infectious. If PrP-sc is given to healthy sheep, the normal PrP is either over-produced and somehow altered to PrP-sc; the information from the normal gene (called messenger RNA) is possibly altered in the presence of PrP-sc, or, the injected PrP-sc reproduces. Reproduction may occur in the following way: altered Prp-Sc proteins interact with normal PrP and this interaction causes a change in the folding pattern of the normal protein. This now abnormally folded, and therefore now abnormally shaped protein can then interact with other, normal PrP protein molecules. Consequently, over time there is an exponential increase in the number of dysfunctional PrP proteins within the cell. Thus, one would naturally interpret the appearance of more and more abnormally shaped PrP within a cell as a result of an "infection" - a result of a reproductive event that leads to a continuous increase in the number of abnormal particles inside the cell. Why this alteration of normal PrP protein to an abnormal shape results in brain damage is not yet understood. Too, how the original, altered form (disease form) of PrP enters the bloodstream and eventually enters the cells of teh brain is also unknown. In this regard, a possible receptor in the membrane of cells that line the intestine may have been found that could bind and transport PrP-Sc into the cell that bound it - and therefore eventually allow the protein to enter the bloodstream.

Whatever their makeup, prions are clearly infectious: when brain tissue from infected animals is treated to isolate the protein thought to cause scrapie, and the altered form of the protein alone (prion - PrP-sc) is injected into healthy animals, spongiform encephalopathy eventually results. The transmission of disease can be accomplished by injection of prion preparations from diseased sheep into mice - and the subsequent transmission of the disease from mouse to mouse by purification of prions from a diseased mouse and subsequent injection of healthy mice with these prion preparations. I do not know the details of these experiments, since I do not have the publications which adequately describe them - I am operating from memory here - and my memory may be faulty.

In addition to these experimental results, the disease known as kuru (another human spongiform encephalopathy) has long been recognized and was first diagnosed among certain tribes in New Guinea who practiced cannibalistic rituals - the women often smeared the brain tissue of the tribe's member who had died onto their body as a way to receive the life "power" of the victim - and later within this tribe, women who participated in these rituals acquired the disease (possibly through cuts in the skin). As cannibalism has decreased, so too, has kuru. There are other examples of a connection between an infectious agent of some kind and spongiform encephalopathies among humans - one important possible connection which has ominous association with the recent outbreak of "Mad Cow" disease. This connection is to the human spongiform encephalopathy known as Creutzfeldt-Jakob disease (CJD).

This human disease is extremely rare - but - there are cases of acquisition of this disease through organ transplantation (donor later found to have CJD), and receipt of human blood products (donor later found to have CJD). And, these patients have, just as the donor, the altered form of PrP, e.g., PrP-sc, present within their brain tissue. Persons receiving human blood products will be informed if the "batch" of blood product from which their material was supplied is later found to contain donor material from a person who developed CJD after donating the blood product(s) - there is no simple test for this disease. Further, Creutzfeldt-Jakob disease appears to run in families. It is not known, however, whether there is direct transmission of the disease (via an infectious agent) within the family, or whether there is transmission of genetic susceptibility to the disease. The disease CJD, is normally observed in humans of 50 years of age, or older. You may wish to read more about this particular disease - please see:
Creutzfeldt-Jakob Disease.

The association of Creutzfeldt-Jakob disease (CJD) with "Mad Cow" disease has only recently been suspected (1996 or so) - a group of younger-aged people (a cluster) within Great Britain were diagnosed with a variant of Creutzfeldt-Jakob disease - an unheard of circumstance a the time. Since then, numerous cases of vCJD have appeared in Europe and the number of cases is expcected to increase. Indeed, as of January, 2001, there are approximately ninety cases reported. As of 2002, 139 cases of vCJD had been diagnosed (129 in Great Britain). Of the cases in Great Britain, approximately 50 percent were in persons below the age of 30. The disease is invariably, fatal.

The people in Great Britain and elsewhere in Europe who were diagnosed with CJD, are mostly very young - usually in their 20's. The condition CJD has before been observed only in humans older than 50 years of age. And, the lesions in the brains of these recent patients are atypical of the standard CJD symptoms - in that there are what are called "plaques" within the tissue - rather than the predominant spongiform characteristic. These plaques are areas of pathology in the brain tissue which contain a tangled mass of a protein known as amyloid protein - this appearance of "plaques" containing a tangled web of amyloid protein are normally found in patients who suffered from Alzheimer's disease - not CJD. Additionally, the PrP (prion protein) found within the brain tissue of these patients is indeed altered - therefore - the sum of these data is one of the connections which made health authorities suspicious that BSE had perhaps been transmitted to humans.

As said before, this disease is very rare - maybe less than two-hundred out of 270,000,000 people per year in the United States (about one person per million people) - thus, to find a number of individuals with this disease - and in particular to find the disease among the young - and to date, only within Great Britain, caused significant alarm. The first thing one suspects in such circumstances is that an infectious agent is at work - an unidentified - not easily detectable infectious agent. It is my understanding that the only connections apparently among these individuals are: most are in Great Britain; the in-common consumption of beef or beef products; their relative youth; and, their similar symptomology (outward symptomology characteristic of CJD - but - all symptoms of which were atypical CJD symptoms - Alzheimer's disease-like amyloid protein plaques in the brain, prion protein in the brain tissue, all less than 50 years-old; and, rapid onset of brain degeneration once symptoms appeared). There were no apparent associations among any of the patients with potential sources of CJD - none had received any human blood products; none had received human organ transplants; and, there was no history of CJD in any of the families.

Thus, with the known outbreak of bovine spongiform encephalopathy in 1986, and more recently, it is suspected that an infectious agent - if it is an infectious agent - may have been transmitted first from diseased sheep to cattle, and now from cattle to humans. There have been a limited number of investigations since 1986 which have examined the possibility that BSE could be transmitted to humans. In one of these studies, there appears to be a species barrier which prevents such transmission.

Unfortunately, one cannot know whether or not a cow (or a person for that matter) is infected - there are no obvious symptoms of disease until the animal is significantly affected; and presently, there is an absence of methodology which could detect the disease - can't test for an altered form of PrP (PrP-sc) - found only in brain tissue (not in the blood). The symptoms in cattle appear a long time after apparent infection - early symptoms might not even be noticeable. And, there is no absolute evidence yet that this disease can or cannot be transmitted from cattle to humans. Consequently, there is currently significant debate as to the procedure to be used by the health authorities in Great Britain. One sad but possibly necessary thing to do will be to slaughter every single cow in the British Isles - a procedure with obvious devastating effects on those who depend upon the beef industry for their livelihood.

Imagine the devastating effect on the United States, if every member of every cattle herd in the nation had to be killed - as only a precautionary measure! Imagine the lengthy debates which would include testimony from scientist after scientist after scientist - virologists, neurologists, microbiologists, immunologists, biochemists; from others with knowledge of such diseases - veterinarians, physicians, statisticians; epidemiologists; from still others - economists, historians, beef industry representatives, lawyers; governmental organizations - U.S. Department of Agriculture, National Institutes of Health, Centers for Disease Control and Prevention, Congress, the President - every knowledgeable person would be asked to help to decide what to do. For your information, since 1989 all imports of beef, beef products or live cattle from Great Britain into the United States have been banned.

Since 1989 the National Institutes of Health, Centers for Disease Control, and the United States Department of Agriculture have established an on-going coordinated inspection of all cattle herds within the U.S. To date, (December, 2003) one case of BSE has been publicly reported in the United States.

By 2001, BSE (Mad Cow Disease) had appeared in cattle within the following European countries: approx. 200 cases in Switzerland, 100 in the Republic of Ireland, 30 in Portugal and possibly 80 in France and Germany. Cases are also now present in Lichtenstein, Belgium and Spain. There have been several gatherings of scientists from across the world - to aid in investigation of this possible disease transmission from cattle to humans.

These recent events provide powerful examples of how much we do not understand - and the need to support efforts to investigate such things - such as the transmission of disease among species - investigation of the biochemical mechanism of such transfer - investigation of a possible association of infectious agents (no matter what these agents might be) with neurological and other disorders - rare though they may presently be, investigation of the causes of diseases in general - among all living things. We should support genetic work which allows production of life-giving human substances in bacteria (cloning) - would prevent the exposure of humans who need human substances to sustain life, but who must presently obtain such substances from human donors.

In order to perform this work, science needs popular support - which can lead to monetary governmental support of basic research - popular support which can lead to an understanding of what science is about - the search for the truth. Science deserves an understanding by everyone for the necessity to investigate difficult, and what might initially appear to be eclectic things. For such understanding, one needs education. Scientists must make this education possible, available to everyone - no matter the person's science background. To make wise but difficult decisions, one needs education. To avoid the pitfalls of panic and lack of an informed, reasoned attack on any problem - one needs education.

Please see the following link to time-line information provided by a friend of mine, Dr. Eddie Power, Microbiologist, St. Thomas' Hospital, London, England. Dr. Eddie Power.

Book: Don't Touch That Doorknob!

Copyright John C. (Jack) Brown, December, 2003
This Page Last Updated: December 24, 2003

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