Title: Mad Cow Disease- The Effect of Prions in Cattle
Author: Margot Wolfer
Date: 5/19/2011


Everyone has heard of Mad Cow Disease, but few people are actually aware of the serious nature of this debilitating disease. Bovine spongiform encephalopathy, more commonly known as Mad Cow Disease, is a fatal neurodegenerative disease affecting cattle. The disease causes spongy deterioration of the brain and spinal cord and leads to extreme behaviors that could otherwise classify the animal as having gone mad. Eventually the corrosion of brain matter leads to the ultimate death of the animal. BSE has been a worldwide disease, although it has affected cattle and livestock primarily in Europe. Preventive measures have done a magnificent job of keeping this disease out of the United States, and keeping the transmission to humans rare.
Figure 2: How different areas in Europe were affected by BSE

BSE is caused by an infectious form of proteins called prions. There are two forms of prions, one that is harmless and one that causes the disease. Bovine Spongiform Encephalopathy originated from cattle being fed sheep meat that was infected with Scrapie, another spongiform disease caused by prions. BSE used to only be detected after the animal dies and the brain can be medically examined, but now there are many methods being investigated and tested that may be able to detect the presence of harmful prions before the animal has the opportunity to spread the disease.


I was interested in the topic of bovine spongiform encephalitis because my mother lived in England during the 1980's, when the outbreak of BSE was a scare for the United Kingdom and eventually all of Europe. She was only there for a year, and she was careful not to consume beef. However, because she lived there during the peak of the outbreak, she is still to this day not allowed to donate blood. I wondered why if the disease only affected cattle, why couldn't she give blood? This made me very curious about how this disease originated, how it is transmissible to humans, and how it is detected.

Mad Cow Disease is not the only disease caused by prions that has had detrimental outcomes. Transmissible spongiform encephalopathies (TSE) is the term used to describe a variety of diseases that all have similar histopathological effects. These include a spongiform degeneration of the brain and erratic behavior by animals infected by the specific disease. Sheep scrapie, chronic wasting disease, kuru, and Creutzfeldt-Jacob disease (CJD) are other transmissible
Sheep infected with scrapie- evident by missing wool
spongiform encephalopathies that effect different mammals (Tortora, Funke, and Case, 2010). Of these TSEs, bovine spongiform encephalopathy is the most common. These diseases can be transferred from one animal to another and some even across different species, although cattle have shown more resistance to scrapie and chronic wasting disease (
Amir N. Hamir, Marcus E. Kehrli, Jr, Robert A. Kunkle, Justin J. Greenlee, Eric M. Nicholson, Jürgen A. Richt, Janice M. Miller, Randall C. Cutlip, 2011). More and more research is being conducted on prions daily, since the discovery of prions was fairly recent. However, although many advancements have been made in detecting prions at an earlier stage, there is still no known drug that can counteract the damage prions have done or to stop them on their path of killing their host (Ryou, Titlow, Mays, Bae, Kim, 2011).

The discovery that prions cause BSE, along with other neurogenerative disorders, was a huge breakthrough in medical microbiology. Although prions are still not well understood enough to destroy, we do know how prions become infectious. There are two different types of protein, the normal cellular protein, PrPc, and the abnormal nonfunctional form, PrPSc. The normal form is the in form of alpha-helical content, while the abnormal form is characterized by beta-pleated sheets. The abnormal form is pathogenic, and recruits normal forms to the abnormal variant (Janka, Malderelli, 2004). This causes a chain reaction of protein misfolding, which results in aggregation of misfolded proteins that are found in brains of diseased animals (Tortora et al 2010). PrPc are commonly found in the brain and spinal cord, although their function is not yet well understood. When these
Normal proteins being transformed into abnormal beta-pleated Prion

abnormal proteins accumulate in the central nervous systems of animals, spongiosus, gliosis, and neuronal cell loss result. "The disease hallmark is the presence of the abnormal, protease-resistant form of PrP" (Janka et al, 2004). In BSE, a characteristic plaque formation forms in the brain, and tissues become spongy in consistency. It has not been proven that these plaques cause neuronal degeneration, but they are helpful in identifying effected brains in postmortem examinations.

The methods of transmission for BSE are under constant debate. It has been proved that prion diseases can be transmitted by direct injection of infected brain matter into an uninfected brain and the disease will result (Bhakdi, Bohl, 2003). Originally, cattle were getting the abnormal prions from being fed sheep infected with scrapie. The proteins were absorbed into their digestive tracts and eventually reached the brain. Bovine spongiform encephalopathy is spread cow to cow by being fed meal bone and meat (MBM) from other infected cattle. This is what started the epidemic scare in Great Britain in 1986 (Hamir et al, 2011). Symptoms of infected animals include changes in temperament, abnormal posture, loss of coordination and motor function, and increased weight loss. Transmission between species does face a structural challenge, and there needs to be a great concentration of the abnormal prion to cross species barriers. That is the primary reason the human form of the disease, CJD, is rare. Humans who eat infected meat are exposed to the infectious prions, but not everyone will develop the disease. Once it became known that consuming infected beef could cause human disease, the econocow_brain.gifmy was severely effected in Europe. Many countries developed bans on imported meat, and beef consumption dropped rapidly. While this had negative effects on the beef industry (3.7 million cattle in the U.K. were destroyed), it was an important factor in ensuring that CJD did not become a killing epidemic of people worldwide (Scott, Stefan, Barbie, 2000). Human prion diseases derived from BSE run in families, which indicates a genetic component (Tortora et al, 2010).

The first step in ridding and preventing BSE is identifying it. This can be extremely hard to do because of levels of prions circulating in the blood are too low to be noticed. In order for a test to be able to detect prions in blood plasma, some scientists conducted experiments to amplify these levels of prions, much in the same way polymerase chain reaction amplifies DNA. The researchers were able to achieve their goal, however this was not the most realistic experiment because it was conducted in hamsters that had been directly inoculated with prion disease (Enserink, 2005). There are a great number of other tests that are now effective in identifying BSE, including Western blotting techniques, fluorescent dyes, and electron microscopic examination of tissues (Janka et al, 2004). In addition to destroying millions of cattle found to be infected with BSE, there have been numerous other efforts to halt this devastating disease. The United States has done a magnificent job at keeping BSE limited in our country, and they do so by enforcing rules prohibiting the consumption of some parts of cattle carcasses and using meat from "downer" animals (cattle who have fallen and cannot easily rise and walk). Not many cattle in the U.S. are tested for BSE anymore because there have been so few cases in comparison to Europe and Japan (Tortora et al, 2010).

Prions are extraordinarily hard to kill. As of the present time, no known procedure or drug can inhibit the action of the prion in changing protein structure or reverse the damage it has already caused once inside a viable host. However, new research has shown that polymers of amino acid lysine (polylysines) are able to block the reproduction of prions by targeting plasminogen. This is a substance that stimulates and encourages the multiplication of prions. A study done on mice showed that infected mice treated with polylysines showed lower levels of prions in their brains than untreated infected mice. This validates plasminogen as a possible therapeutic agent against prion diseases (Chongsuk et al, 2003).

Although there is still a great deal of unknown information to be discovered regarding prions and the diseases they cause, science is constantly changing and uncovering new tests and experiments to be carried out. The progress of research on bovine spongiform encephalopathy and other TSEs has moved remarkably quickly, and one can only assume that this trend will continue until a cure and vaccine have been identified and produced.

Literature Cited:

Bhakdi, S., & Bohl, J. (2003). Prions, mad cow disease, and preventive measures: a critical appraisal. Medical Microbiology Immunology,1(192), Retrieved from http://0-www.springerlink.com.iii.sonoma.edu/content/2cuw87k23t7frajm/fulltext.pdf doi: DOI 10.1007/s00430-003-0184-z

Chongsuk Ryou, William B. Titlow, Charles E. Mays, Younsoo Bae, Sehun Kim. The suppression of prion propagation using poly-l-lysine by targeting plasminogen that stimulates prion protein conversion.Biomaterials, 2011; 32 (11): 3141 DOI:10.1016/j.biomaterials.2011.01.017

Enserink, M. (2005). An Easy Assay for Prions?. Science Now, 2-4. Retrieved from EBSCOhost

Hamir, A.N., Kehrli, M.E., Kunkle, R.A., Greenlee, J.J., & Nicholson, E.M. (2011). Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle.Journal of Veterinary Diagnostic Investigation,23(407), Retrieved from http://vdi.sagepub.com/content/23/3/407 doi: DOI: 10.1177/1040638711403404

Janka, J., & Maldarelli, F. (2004). Prion diseases: update on mad cow disease, variant cruetzfeldt-jacob disease, and the transmissible spongiform encephalopathies. Current Infectious Disease Reports, 1(6), Retrieved from http://0-www.springerlink.com.iii.sonoma.edu/content/fw72620346040316/fulltext.pdf

Johnson, S., Theil, S., & Nadeau, B. (2000). How Safe Is Their Beef?. Newsweek, 136(23), 43. Retrieved from EBSCOhost.

Tortora, Garard. Funke, Berdell. Case, Christine Microbiology. 10th ed. U.S.: Pearson Education, 2010. (203,393,630-632). Print

Figure 1: http://topnews.us/aggregator/sources/32?page=4
Figure 2: http://www.mad-cow.org/00/dec00_more.html
Figure 3: http://coloradodisasterhelp.colostate.edu/prefair/disease/dz/Scrapie.html
Figure 4: http://www.triroc.com/sunnen/topics/prion.htm
Figure 5: http://www.accessexcellence.org/WN/NM/madcow96.php