The Protocol of Prion

Good advice from Mrs Mugumbo

I wrote about viruses recently. One controversy which is hotly debated is whether viruses constitute life. I suspect the debate will continue for a while and the issue may never be resolved to the satisfaction of all. Life is never simple or easily classified. There is one thing biologists do have consensus about: proteins are not alive. They are part of life. They are the structural building blocks of cells and as enzymes control the rate of biochemical processes within cells. Consequently, they alone, would not be expected to cause disease unless their structure had changed due to a precursor gene mutation. But in the last 50 years biologists have had to rethink a few central tenets of biology due to proteins called, prions.  

In the 1950's a doctor working amongst a tribe in New Guinea observed a strange and lethal disease in the people. The Fore people called the disease kuru, which roughly translates as 'stumbling and scared'. Victims of the disease lost weight, the ability to walk, talk, and eventually died.  The tribe indulged in a tradition of eating the brains of the dead as a ritual. No accounting for taste, I suppose. And I suspect a fine Chianti was never on the menu. I've digressed. Anyway, it transpires that the tribe folk contracted a disease from eating dead human brains. Who would have thought that eating dead people was bad for you? Astonishing, I know.  But what piqued the interest of the medical world was that there didn't seem to be a disease agent at work. The usual suspects, bacteria and viruses were not involved.

The culprit turned out to be a protein and a self replicating protein at that. This may not seem particularly special to a none biologist, but it has grave implications to a fundamental proposition in biology: 'The Central Dogma Theory'. I am not keen on the word 'dogma' as it implies a stolid closed intellectual door. Dogma should not be part of any scientific proposition, or anything else for that matter. The central dogma theory states: Only nucleic acids (DNA and RNA) replicate and specify information. Proteins shouldn't be able to replicate or transfer information without an intermediary nucleic acid stage. This was the perceived scientific wisdom until prion disease burst onto the medical stage.

Prions are abnormally shaped proteins with an uncanny ability to convert other proteins to their peculiar tortured shape. They act as a template and actively change the shape of other proteins into their own rogue configuration. Once set in motion a cascade effect ensues; good proteins gone bad. When they multiply to extreme the disease process kicks in. The abnormal proteins adhere to each other forming an ever growing lattice structure which deposits in the brain and other tissue. The immune system detects something amiss and directs cells to mop up the 'strange proteins'. However, in the process they also destroy healthy brain cells as well as the diseased. Thus we end up with the typical histology report: 'A brain with holes': a lack of neurones is never good news. The disease process is relentless and ultimately fatal in every case. There is no cure or ameliorating treatment and the eventual conclusion is a lingering unpleasant death.  

Most cases are sporadic without an obvious initiating event. Other cases are acquired from previously infected individuals. Unlike other disease agents, prions are extraordinarily resistant to destruction. Normal sterilisation procedures by heat and chemical treatment leave the protein untouched and consequently, infectious. Luckily, the disease is not easy to catch. Most none-sporadic infections are caused by medical procedures such as transfusions and contaminated surgical instruments. Eating contaminated tissue is also a route for infection.    

There are several diseases in animals and humans associated with prions however, the incidence of prion disease is rare in humans, something in the order of one in a million individuals. You may recall the 'mad cow' disease scare in the UK during the 1980's. Cattle are also prone to prion disease and exhibit a condition called bovine spongiform encephalopathy (BSE), more popularly and quaintly known as 'mad cow disease'. A medical scare occurred in the UK during the 1980's when at least 180,000 cattle became infected. In total, 4,400,000 cattle were slaughtered causing immense economic harm. The cause of the disease was found to be due to meat products being included in the cow's normally herbivorous diet. Meat from sheep infected with a prion disease called 'scrapie' was thought to be the likely culprit. The disease can be transmitted to humans through the ingestion of infected brain, offal and spinal cord. In humans the prion causes new variant Creutzfelds Jacob disease. At the time there was a grave fear that there would be a human epidemic of the disease ultimately killing many thousands. As is now known the problem was overstated and to date only 177 people in UK have died due to the condition even though many thousands of infected cows entered the human food chain before controls came into operation.

The UK situation was extreme and therefore the response, extreme. It is difficult 30 years on to appreciate the hysterical response to the risk of a truly nightmarish disease. Medical authorities were predicting a Zombie apocalypse (get a grip Flaxen). So let us learn from the past and follow these simple, but profound, precepts:

• Stop eating the brains of dead people; always sound advice
• Stop eating offal (faggots excepted)
• Stop eating nasty foreign food- and if you do, make sure you expose it to greater than 600 degree Celsius for at least 10 hours
• Don’t date women of dubious moral standards. Not wholly relevant, I know, but sound advice nonetheless     

Again, not relevant at all. Aaaaaaaaaarse