The Mysterious Prions | Feb 2004

FMBR Editorial: Feb, 2004

The Mysterious Prions

William C. Gough

At the heart of the debate about "mad-cow" disease lies the mystery of the "prion." Prions are proteins that have changed their normal shape. Proteins are the building blocks of living cells that are used by our bodies either as structural elements or as signaling molecules that carry information throughout our body. They consist of chains of amino acids folded into complex shapes. When the shape of a protein changes the spectrum of waves it is emitting changes. The prion protein is now transmitting a different informational message into your body. In effect, your body is now tuned to a new radio station and instead of classical music you may be getting hard-rock. When the prion creates a "disease" in the body it is known as a "mutant prion" since it can start a chain reaction and persuade other proteins to follow its example. That process can spread the disease through the cells and eventually to the brain. Just as we have "informational medicine" like homeopathy that can be used to heal us, we now have "informational disease" that can kill us.

Western science, and therefore our approach to the way in which we handle our food supply, has now been confronted with an informational disease -- mad-cow disease. The phenomenon was not a part of classical biochemistry and was only officially recognized in 1997 when Dr. Stanley Prusiner of UCSF won the Nobel Prize in Medicine for "his pioneering discovery of an entirely new genre of disease-causing agents." Dr. Prusiner had discovered that altered versions of proteins, which he dubbed prions, are to blame for a family of human and animal diseases. Prusiner had pursued his specific area of research since 1972 but was met with incredulity, criticism, and controversy. Unlike bacteria, virus, or parasites, an "infectious" prion cannot be destroyed by heat, freezing or radiation. For example, to destroy mutant-prion infected meat the USDA facility at Ames, Iowa uses a tissue digestor, a large stainless steel vat that melts the carcasses in boiling lye under pressure, then dries the liquid into a powder that is incinerated.

Initially, mad-cow disease was a scientist's worst nightmare since no one knew how it was transmitted. Early estimates were that millions of people in the United Kingdom could get the brain-wasting degenerative disease. Even through in the United Kingdom more than 185,000 cattle were found to be infected, only 143 cases of the always-fatal human version of the disease have been diagnosed. The number of new human cases has now leveled off at fewer than 20 a year. Only 10 people outside of the United Kingdom are known to have died from the human form of the disease. One cause for the low death rate could be the body's quality control system for handling misfolded proteins. When a cell detects such prions it sends a signal to the nucleus to activate a program to destroy these mistakes. However, a disturbing note is that Britain, on Dec. 17, 2003, reported the first case of a person dying after a blood transfusion from an infected donor.

Mad-cow disease, officially known as bovine spongiform encephalopathy (BSE) was first diagnosed in 1986 in Britain. Researchers quickly decided that cattle had gotten the disease from eating brains and nerve tissue of sheep infected with scrapie a variant of mad-cow disease. The tissues had been mixed into cattle feed along with the ground-up carcasses of other animals - including other cows. Such "rendered" feed has now been banned for most food animals. Today Japan tests every cow that enters the food supply for BSE, and Europe tests every animal older than 30 months (the age at which the incidence of BSE starts to climb). However, currently in the United States only about 20,000 of the 35 m5 million cattle slaughtered each year are tested for BSE, i.e., an insignificant 0.06% are tested.

If BSE is an "informational" disease than there should be other variations. We know that mad-cow disease can be caused by a mutation of a single gene, a so-called spontaneous case. Similar spongy-brain diseases have also appeared in at least 10 animal species. Included are farmed mink, domestic cats, cougars, bison, and African antelope (kudu & oryx). The so-called chronic wasting disease also strikes mule deer, white-tailed deer, and elk in the wild. Sheep carry a variant of mad-cow disease known as scrapie. Shepherds and pathologists have recognized it since the 18th century. Sheep haven't been known to transmit their brain disease to people despite centuries of opportunity. In fact, potted sheep's brain is a national dish in Scotland. This has raised questions about current theories regarding the scrapie as the trigger of BSE in Britain.

Could there be another underlying cause for these diseases, and the unparalleled large surge of mad-cow disease in the United Kingdom. An organic farmer, Mark Purdey, and a number of researches are putting forth an hypothesis based upon environmental causal factors. They implicate a warble fly eradication program mandated in the early 1980s by the British government. Warble flies lay their eggs in a cow's skin, causing health problems and reducing the value of cow hides. To combat this heavy doses of organophosphate insecticides were used. These were poured along the spinal column of cows to be absorbed into the cow's body. They exert their toxic effect by entering the central nervous system and deforming the molecular shape of various nerve proteins. Organophosphates were developed by Nazi chemists during the course of World War II as a biological weapon. The effects of organophosphates can be made more severe because they remove copper from the body leaving the door open for manganese or similar metals to replace the copper in the prion protein. This creates a condition akin to the occupational disease known as "Manganese Madness." The "informational" disease caused in humans by BSE is called variant Crueutzfeldt-Jakob Disease (vCJD)s. In addition to CJD and vCJD, could other degenerative ailments in humans, such as Alzheimer's, Parkinson's, and Lou Gehrig's disease involve abnormal changes in the shapes of proteins caused by environmental factors that affect us directly or indirectly via our food supply?

William C. Gough, FMBR Chairman of the Board

Prions and Long Term Memory

We know that a mutant prion protein causes the deadly "mad-cow neurodegenerative disease. However, scientists don't even know what the normal form of the protein does in the body. Yet, the protein is so widespread in people and in animals that researchers think it must play an important role. Now prions have been found to have a potentially positive role -- a positive informational role. The research indicates that changes in protein shape may be a key molecular event in the formation of stable memories. This would represent the first truly novel concept about a molecular mechanism for memory in perhaps thirty years. Although still far from proven, the researchers at Columbia University, NYC and the Whitehead Institute in Cambridge, MA have shown that a certain protein in the sea slug Aplysia is required for cementing cellular long-term memories in neurons. The prion form of this protein in yeast appears to the one active in the memory formation.