Eat This. But Not In Remembrance of Me!
Dr. Lester CN Simon
The title of this article is aimed at linking two crucial aspects of the basic science of Mad Cow Disease. Mad Cow Disease is the lay person’s term for Bovine Spongiform Encephalopathy (BSE). BSE is only one of a list of spongiform brain disorders in animals and humans in which the brain is literally reduced to a sponge.
To get a clear grasp of the basic science so that we can apply it to public health, we have to understand a peculiar set of diseases caused by agents called prions.
When we think of the causes of infections, parasites, fungi, bacteria and viruses readily come to mind. The first three agents contain many sophisticated, genetic chemicals including DNA and RNA. These three infectious agents grow, reproduce, make and use proteins once nutrients are available. Viruses, on the other hand, are not as sophisticated. A virus possesses either DNA or RNA, not both. Viruses cannot grow, reproduce and make or use proteins unless they inhabit living cells.
As important as proteins are, it was not considered possible that a protein could cause infection by itself. Infection means that the causative agent sets up shop in the host and multiples therein. Proteins should not be able to do this since they do not have the chemical genetic machinery in the form of DNA or RNA.
Enter the prion. In 1980, Dr. Stanley Prusiner evoked a good deal of scepticism when he proposed that the infectious agents causing spongiform brain diseases in animals and, more rarely, in humans might consist of protein and nothing else. At the time, Dr. Prusiner was considered a heretic. His work was revolutionary. He realised that dogma held that the conveyers of transmissible diseases required genetic material, DNA or RNA, in order to establish an infection in a host. Fifteen year later, Dr. Stanley Prusiner was awarded the Nobel Prize in Medicine for his work on prions.
The name prion (pronounced "pree-ons" by Dr. Prusiner), is an acronym. Actually you may say it is a prionic acronym, as you will see later. It comes from the words: proteinaceous infectious particle, using the first three letters of proteinaceous (pro) and the first two letters of infectious (in). Obviously, this would lead to the name, proin but it was decided to call it prion instead of proin, because prion has a better sound.
But even if prions cause diseases, they are proteins; and all proteins are made by genes (DNA and RNA). So how do the prions reproduce when they cause infections? Do they have a piece of genetic material attached to them? No. The genes that make prions are where all genes are: inside the cell. They make prion proteins (PrP) all the time without necessarily causing any sickness. This suggests that prion proteins exist in two states, a normal, innocent state and an abnormal, corrupted, sinister state.
Good prions are easily degraded by the usual protein-degrading enzymes in all cells. Unfortunately, bad prions resist this degradation. Hence, bad prions will always win and the good ones will lose. The concept of good prions is relatively new. When prions were first discovered, they were thought to be intrinsically bad. Just recently, in December 2003, it was considered that one sort of prion has a vital role to play in how memory can be stored in the brain. Hence the name of this article.
Shape or conformation is very important to proteins. Change the shape and the function can change. The bad prion acts as an infectious agent by somehow causing a change in the shape of the good prion, which then becomes a rebel prion and damages the body. The derivation of the name prion is itself prionic in that the name was changed from proin to prion.
The shape of a protein is only one aspect of its structure. There is a more basic building block comprising a sequence of amino acids. The closer 2 prions are in their basic structures, the easier it is for a bad, rebel prion to corrupt a normal prion by forcing it to alter its shape and become a rebel too. Birds of a feather do all sorts of things together.
This raises the concept of species barrier. Species barrier refers to the difficulty of prions made by one species causing disease in another species. The cause of this difficulty is unknown but it is important in light of Mad Cow Disease in which bad prions from other animals such as sheep and cows were part of the feed for cows.
The close genetic link between sheep and cows allows for the transformation of “Mad Sheep Disease’ to Mad Cow Disease. “Mad Sheep Disease”, known for over 200 years is called scrapie because the sheep have a terrible itch and scratch against a fence until they scrape off their wool.
Kuru is a prion disease that was found in 1957 among the Fore tribal population of Papua New Guinea. Transmission was due to the practice of ritualistic cannibalism. With the cessation of this social custom, Kuru has essentially disappeared. Kuru is the Fore word for shivering, trembling or “laughing death”.
Sheep and cow prions differ at 7 positions. Alternatively, cow and human prions differ at more than 30 positions. Because of this greater variance, Dr. Prusiner thinks that the likelihood of transmission of prions from cows to people is low. But low does not mean impossible because it does occur. Maybe only a small area of similarity is required for corruption of the human prions by the bovine prions. Additionally, other types of proteins called chaperone proteins may assist in the alteration and corruption of the good prions.
In genetic and other terms, are we humans far from the madding cow?