Mad cow disease – How can something so delicious can be so deadly?

Thomas is off somewhere, I don’t know where, he did tell me but I stopped listening halfway through our conversation and started playing with a slinky. Anyways I’m having to post for him and he decided he wanted to rehash this old article he wrote for On Dit many years ago. Despite the fact I have already written about Mad Cow Disease, Thomas thought his article made some different and interesting points. I just think he’s lazy. Enjoy 🙂

Sexy, sexy proteins

In year 11, my biology teacher (Hi Mr. Everett!) told the class the answer was always proteins; it was what you wrote in exams when you didn’t know the answer. This was because proteins rock because proteins do practically everything in any organism anywhere.

These dogs are composed of and powered by proteins (Rosita Andoreika Baxter Biddophilius Ignatius Theadora a.k.a. Rosie and (Hono)Lulu, Picture taken by Thomas Tu)

A quick rehash on where proteins come from and what they do: DNA codes for RNA, which in turn codes for proteins. Proteins can and do do everything in the body: they are signals to cells, they sense the signal and translate it into something the cell can understand, they can be structural supports, but most importantly, they make chemical reactions run more efficiently (i.e. they act as catalysts). This last function is so important that proteins that do it are given a special name; enzymes.

Catalysing a reaction is starting a chemical reaction go with less start up energy (which is usually supplied by surrounding heat). For example,  say there’s a pile of newspaper and you want to set fire to it. You can either wait for the entire room to get so hot that the newspaper spontaneously cobusts , or you can strike a bit of flint and light up the newspaper with minimal effort.  This needs to happen in biological systems or there’d be no way for us to get enough energy needed to free up energy bound up in the things we eat.

I’ll get to mad cow disease soon, I swear

OK, now we have the background needed to understand prions. There’s a certain protein called prion protein, the common version (PrPc) that’s naturally present on the surface of all cells of vertebrates, but found predominantly on the cells of the central nervous system (i.e. the brain and spinal cord). The function of the protein is unknown, but must be important; as it shows very little change between mammals. Things that are vital for an animal tend not to show much variation because that’d change their function => dead animal => not passing on that gene: natural selection weeds the change out.

PrPC, like many proteins, is rather fragile. UV, heat, acid, and dryness can all break it down. Also like other proteins, it can spontaneously fold up into different 3d shapes by chance. Most of these are useless and subsequently broken down by the cell, but one of such conformations form an extremely stable version, commonly called PrPSc. This cannot be easily broken down by the previously mentioned factors. However, what makes this an infectious agent is the fact that PrPSc has enzymatic activity that catalyses the folding of normal cellular PrPC into PrPSc. The produced PrPSc can then go on to produce more of itself in the body. The simplicity of proteins producing themselves and being such an acute example of evolution by just existing is, in my opinion, one of the most beautiful things in the world (on re-reading this last sentence, I seem a bit nerdy; I should have just said it was sexy).

The section that actually mentions mad cow disease

Since there’s no way for the body to break down PrPSc molecules and they keep producing themselves, they build up in the body, especially near the nerve cells of the brain and spinal cord. Too much of anything in the body is not good and this is no exception. As a result, the neurons get holes in them so that under a microscope the brain looks like a sponge (see picture below). This gives this type of prion disease the technical umbrella name of Transmissible Spongiform Encephalopathy (TSE), which basically means you can catch it and it turns your brain into a literal sponge. The exact mechanism of how this happens is not understood yet, so I guess I still have a job when I get out of Uni.

This brain damage causes a whole lot of symptoms that vary within species and may depend on the route of infection. In humans, common symptoms are dementia, muscle spasms, tremors, behavioural abnormalities, strange skin sensations (such as stickiness) and, in later stages, inability to control breathing muscles and then death. Incubation periods for this disease are extremely long, but once symptoms are observed, the patient soon dies within 8 months to 8 years, depending on the type. No treatments or vaccines exist for TSEs; the patient will die with it.

To explain transmission between and within species, I have used an example of my horrible picture-making skillz:

Picture made by Thomas Tu and the help of Microsoft's wonderful and not at all cliche`d clip art

As you can see, mad cow disease (technically known as bovine spongiform encephalopathy) is just a middle man for the prion. The earliest prion-based disease we know of was first discovered in sheep. We really don’t know how the first sheep got it; perhaps PrPSc folded spontaneously, perhaps it was infected by another species before that. Infection with PrPSc caused infected sheep to scrape against the cages holding them, either because of their crap motor skills or to scratch imaginary itches, both resulting from the brain damage. This earned the affliction the name “scrapie”. It also caused the sheep to have involuntary spasms, to be agitated, paralysed and, eventually, to die.

As described in earlier articles, creating vaccines sometimes involves extracting the serum of an infected animal and putting it into those with the disease (passive immunisation, for those playing at home). Scrapie was shown to be transmissible when, in 1943, sheep injected with a batch of vaccine for an unrelated virus all died of scrapie. Turns out the vaccine was made from the serum of a scrapie-infected sheep and helped its transmission between sheep. Also, since sheep food was made from sheep carcasses, if any PrPSc from dead sheep got into it, the eaters could be infected. Transmission was made easier by the fact that scrapie caused sheep to die, therefore more would be found in the feed. TSE not only spread between sheep, but it’s believed that this is how it hopped the specie gap to cows, since some battery cows are fed with meal derived from sheep and cow meat/bones. Further this also explains the spread of mad cow disease spread among cows.

Of course, once people ate the flesh of infected cows, they got PrPSc in their systems as well. Over 100 cases of this have reached humans in this fashion (given the name new variant Creutzfeldt-Jakob disease, or nvCJD). Around 25 new cases are reported each year since 2000 in the UK (the epicentre of the whole mad cow incident). This number may increase dramatically in the future as the only way of detecting prion-based diseases is to see if people have the right brain damage once symptoms start. However, this mode of transmission is among the least significant ways of getting prion-based disease. Similar cases have been reported in deer and elk hunters who eat the animals they’ve killed, but these are even rarer.

Most human cases of TSE come in the form of Creutzfeldt-Jakob disease (CJD), which comes about when a rogue PrPC molecule is spontaneously (i.e. just by pure chance) misfolded into PrPSc. This occurs in about 1 in a million people, which means, by my calculations, about 6 500 people have it right now (at the moment of the typing of this article (23:05, 12th February 2006) the world population is 6 497 249 631, according to census.gov). Feel free to forget this fact if you’re a hypochondriac.

There is also another mode of infection: having a mutation in the PrP gene. Any mutations that increase the chance that PrPC is misfolded into PrPSc may contribute to familial CJD. Due to their extremely long incubation times, the disease starts to show symptoms at around 45 – 49 years. Because most people have their children by this time, there is also a mechanism of transmission by inheritance.

Transmission between unrelated humans is completely due to human behaviour. Iatrogenic (arising from medical treatment) CJD comes about due to corneal or nerve membrane transplants from CJD-infected people. This is because these parts contain especially high concentrations of PrPSc.

A much more interesting case of human transmission, and the first prion-based disease to be discovered, is Kuru. The Fore tribe in New Guinea used to eat their dead relatives as some kind of tradition. Both eaters and the children of those who didn’t wash their hands afterwards contracted the disease after eating an infected member. This spread the disease throughout the tribe. Ever since the cannibalism has ceased in this tribe, the disease has subsided.

There is plenty of more interesting stuff about prions (the whole prion/virion debate, Stanley Prusiner winning the 1998 Nobel Prize for medicine for studies in the matter, other potential prion based diseases) but if the article gets any longer, the editors are going to cut off my writing fingers. Which would be all of them.

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2 Comments

Filed under Thomas' Corner

2 responses to “Mad cow disease – How can something so delicious can be so deadly?

  1. Pingback: De verborum notatio morbi – On the etymology of diseases « Disease of the Week!

  2. Pingback: Kuru – Brain-eating, Nobel-winning and kiddy-fiddling | Disease of the Week!

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