MAD COW DISEASE
Author: Juan C. MendiblePublished on: Jun 12, 2001
During the last few years you have heard about "mad cow disease," which not only has wreaked havoc in the British economy but also brought fear into the hearts of the European people because man can be infected with it by eating contaminated meat.
This article is about the history of this disease and what causes it. You will see why it is important to make sure that cattle-raising people are not saving money by feeding the livestock with food from unknown and usually cheap sources.
First, it is important to know that mad cow disease belongs to a group of pathologies known as spongiform encephalopathies because the brain of the affected animals--or humans--becomes so full of holes that it resembles a sponge. In general, it takes years or decades for the symptoms to appear.
The most common form of the disease is scrapie, found in sheep and goats. Sick animals lose coordination and eventually they cannot stand. In some cases, they develop an intense itch that leads them to scrape off their wool or hair (hence the name "scrapie"). Other animal prion diseases are transmissible mink encephalopathy, chronic wasting disease of mule deer and elk, feline spongiform encephalopathy and bovine spongiform encephalopathy. The last one, mad cow disease, is the most worrisome and is abbreviated as BSE.
It was first identified in 1986 by G. A. H. Wells and J. W. Wilesmith of the Central Veterinary Laboratory in Weybridge, England .
In humans, Dr. Zigas from Australia and Carleton Gadjdusek from the USA first described a disease in the Fore aborigines from Papua New Guinea that started with loss of coordination (In medical terms, ataxia) and was followed by dementia and death. They called it "the laughing death" and the natives called it Kuru. Even though they did not know the cause of the disease they thought that it was probably due to the practice of the natives' honoring their dead by eating their brains. When such practices stopped Kuru disappeared.
Another similar human disorder is Creutzfeldt-Jakob disease, which is rare, striking one person in a million, typically around age 60. It can be inherited or it can be acquired iatrogenically. "Iatrogenic" means that it is caused by medical intervention, for example, by operating with instruments that have been used on sick patients and have not been properly sterilized.
The two other human diseases, which are usually inherited and in general appear in midlife, are Gerstmann-Sträussler-Scheinker Syndrome, which also curses with ataxia, dementia and damage to the cerebellum, and insomnio fatal, which starts with difficulty sleeping and is followed by dementia.
The initial advances in spongiform diseases started in 1972 when Stanley Prussiner from the University of California at San Francisco realized that scrapie, CJ disease and Kuru had all been shown to be transmissible by injecting extracts of brains of animals that had died of these diseases into the brains of healthy animals. It was thought that a slow-acting virus caused the infections, yet no one had managed to isolate it.
Prussiner was also impressed by a report by the late Tikvah Alper and her colleagues at the Hammersmith Hospital in London, who took extracts of scrapie-infected brains, destroyed all of the nucleic acids, DNA and RNA, and noticed that the extracts still retained ability to transmit the disease, suggesting that the scrapie agent might lack nucleic acid. This finding meant it was not a virus or any other known type of infectious agent, all of which contain genetic material So, what was the cause of the disease?
The answer came about 40 years later when Prussiner proposed that the agent was a protein. You can imagine the resistance Prussiner and his colleagues met, since this was against the belief that all pathogenic inheritable entities required some sort of genetic material, either DNA or RNA, in order to establish an infection in a host.
Prussiner was proved to be right when he managed to isolate a protein from the brains of mice that had died of the disease, injected it into the brains of healthy ones and--viola!!! The injected animals got the disease and died, which strongly suggested that this protein was the pathogenic agent. He called it prion (pronounced "pree-ons"), which stands for "proteinaceous infectious particles."
Later on, his and other laboratories cloned the gene of the protein, now called PrP (for prion protein), which allowed them to study the structure of its 250 amino acids chain.
With the gene isolated, several groups demonstrated that most animals make the Prp protein without getting sick. This told them that Prp was produced in two forms: a disease causing mutant and the normal one. Soon, they found that the difference between them was a single amino acid change. The mutant one has the amino acid proline instead of leucine at position 34 on the chain.
This change is due to a point mutation, that is, a single base change in the protein gene is capable of causing such a deadly disease. It is important to tell you that the function of the normal protein is still unknown and that more than 15 mutations have been discovered that transform the PrP protein into an infections agent.
The proposed mechanism by which the mutant protein leads to the disease is as follows: The mutation in the prion induces a change in its structure (If you are interested it goes from what is called an alpha to a beta configuration), which inhibits its digestion in the brain and leads to its accumulation in the brain. This somehow causes the formation of vacuoles that give the brain the sponge like appearance.
Prussiner´s team was also criticized when they concluded that prions multiply in a way until that moment unheard of. Perversely, the disease-causing prions stick to the normal proteins, inducing them to change to the same shape. This, of course, converts them into pathological ones, thus increasing the size and number of the vacuoles. This process is a very slow one and that is why it takes so long for the disease to appear.
As you can imagine, Prussiner was awarded the Nobel Prize in Medicine for his finding.
The source of the epidemic in England was eventually traced to food contaminated with meat and bone from dead sheep. It seems that the problem started because they changed the processing of the sheep carcasses in such a way that the scrapie was not eliminated. The British government prohibited the use of animal-derived feed supplements in 1988, but the damage was already done.
In Europe almost half-a-million cows have been burned since 1996, and afterwards it was shown that only a few thousands of them were infected. This incredible economic loss could have been avoided if there have been an adequate test for the prions. Now it seems that there are some tests on the market that can detect the prions in hours. As matter of fact, Germany is testing 100 percent of the animals going to the slaughterhouse. Read this article to learn more about tests for BSE.
The problem today is that it is not known if the disease has peaked or not; and, of course, there is no cure in sight for it.
Just in case, it is important for you to read this provocative article by Benjamin and Anthony Parish offering the interesting proposition that BSE is not only not caused by prions but that it is also not transmissible--that is, you cannot get BSE by eating meat from animals that have died from the disease.
I must say that I also have problems with prions' transmissibility. Prions are proteins, and in order for the ones from cows to cause disease they have through go your gastrointestinal tract, your blood stream and cross what is called the to blood-brain barrier, whose function is to stop big molecules from going into the brain.
Now, in the GI are proteases, enzymes that destroy--digest--most of the proteins that you eat. This is one of the reasons it has not been possible to design a way to take insulin orally--it is destroyed in the GI. Insulin is a much smaller protein than prions.
Even if the prions should make it through the GI system and into the blood, they should be destroyed by your immune system; and if they survive all that, they still have to cross the blood-brain barrier, enter the cells, find the normal prions and convert them to pathogenic. Aren´t they stretching it too much?