Web 2.0 Demo

If Robert Louis Stevenson were alive today, he'd know exactly how to refer to prions -- nature's equivalent of Dr. Jekyll and Mr. Hyde.

Most of the time, these mysterious proteins go about their business, serving some unknown function in a variety of species. But every now and then, prions (pronounced PREE-ons) twist their shapes and become miniature destroyers, infecting other prions in their path by merely coming in contact with them.

If the renegade prions hit the brain, they wreak havoc as their victims -- sheep, cows, people -- literally lose their minds.

In his new book The Family That Couldn't Sleep: A Medical Mystery, science writer D.T. Max explores the strange world of prions and their connections to cannibalism, fatal insomnia and hamburgers.

Max talked about his findings with Wired News.

Wired News: What is a prion?

D.T. Max: Prions are perfectly healthy, ordinary proteins that exist in the body. No one knows what prions do, but they must do something -- all mammals have them and for that matter so do frogs.

What's weird is that if you breed these animals without prions -- by knocking out their prion genes -- they still do fine.

A prion becomes infectious when it misfolds. It's almost the only protein that can do this -- I can only think of one other. This contradicts what we thought we knew about biology because prions have no nucleic acid, no DNA. According to basic biological theory, if you're going to create an infection you need to replicate yourself, and the only way to do that is with nucleic acid. That's the central dogma of the field.

The way prions get around this is by something called conformational influence, which simply means that one misfolded protein comes into contact with another and then, whoosh, that protein misfolds, too. It's like only one kid is wearing sneakers and another kid sees how cool he looks and he gets sneakers and then the other kids see him and pretty soon the whole class has sneakers and the only problem is that no one can walk in them.

WN: What makes prions go bad in the first place?

Max: There are three ways. One is through an infection: If you ingest a misformed prion, it will probably make other prions in the body misform. That's Variant Creutzfeldt-Jakob disease -- mad cow disease in humans.

The second way is through genetic mutation, such as in fatal familial insomnia. There's a mistake in your DNA, and your genes are making misformed proteins all the time. Those proteins are commingling with other healthy prions in your body and causing them to misform.

The third way is sporadically (or randomly), although there are some respectable scientists who don't believe in this.

WN: What do infected prions do in the brain?

Max: They basically drill holes in the brain by killing cells. You can see them with an electron microscope -- just dots where brain cells were and now there's nothing except maybe some dead cell goop.

In some prion diseases, the prions drill holes all over the place in the brain. But in people with fatal familial insomnia, the amount of damage inflicted on the brain is tiny -- it pinpoints a tiny part of the thalamus and just eliminates it.

WN: You write about a family in Italy whose most affected branches have a 50 percent chance of dying of fatal familial insomnia. They live for a few years without being able to sleep normally, then die after suffering from horrible symptoms. Why don't they typically not get sick until middle age?

Max: The process of prion conversion is very slow in the infectious form. You're starting with a single prion that has to get processed through the body and find similar proteins. It's going to exist in the body for a while before finding anything to convert.

WN: It seems that a lot of fatal familial insomnia victims suffered from a stressful event before the symptoms kicked in. Could there be a connection?

Max: There definitely could be. It is the family myth that stress brings it on. (One sufferer) was held at gunpoint during a bank robbery and a cousin was menaced by a turkey -- must have been a big turkey! Interestingly, this myth was corroborated by some German researchers in 1999 who published a paper showing that stress affected both when you got prion disease and how quickly it got bad.

WN: The Italian family, which has suffered from this disease for hundreds of years, was ashamed of the illness until very recently. How do they feel about it now that they understand it?

Max: They're moving forward with a lot of courage, and they've joined forces with one of the best of the Italian protein labs. They aren't biting on the new therapies but preferring to cooperate in basic research, a remarkable choice given the sword of Damocles over their heads. They've even gotten some money from the Italian equivalent of the Jerry Lewis telethon to help fund some research.

WN: The Fore tribe in Papua, New Guinea, developed a prion disorder called kuru that's similar to mad cow disease. What is the connection between prion diseases and cannibalism?

Max: Anthropologists found that they'd been practicing ritual mortuary cannibalism -- the consumption of your dead, relatives or friends, to honor them or make you more powerful. They'd clearly made the mistake of consuming a predecessor who had sporadic (random) Creutzfeldt-Jakob disease.

WN: Your book contends that cannibalism nearly killed off the human race 800,000 years ago. How did that happen?

Max: There's a genetic oddity that suggests that humans in prehistory suffered an attack of a prion plague, and those individuals who had the preferred genome survived in disproportionate numbers.

To this day, (some humans) continue to have that signature in our genes. When mad cow came along, we were fortunate to have it. It helped limit the damage that mad cow disease did.

WN: Some people thought the British mad-cow outbreak would potentially kill hundreds of thousands of people. But only about 150 people have gotten sick. What happened?

Max: Fortunately, the bovine protein was just different enough from the human protein that it isn't a very efficient infector. If we'd been closer to them, nobody would be alive in England except vegetarians.

It's an extraordinary piece of luck from a human experience point of view. Certainly the British government didn't know (the truth) and to some extent it didn't want to know.

WN: What do you make of food safety in the United States when it comes to prion diseases?

Max: The USDA does as poor a job as you could imagine. I've never seen an organization that seems more determined to not find what it's in charge of exploring.

They have a couple things going for them: Humans don't get mad cow disease easily. And just by chance, we have a lot more soy protein in this country than animal feed. (Mad cow disease was spread as cows ate food containing infected parts of dead cows.)

WN: One beef producer wanted to test all its cows for the mad cow disease, and the USDA wouldn't allow it, right?

Max: Right now, Creekstone Farms is suing for the right to test its own cattle. It's not something I'd think you'd have to ask anyone for.

It's basically a market-protecting ploy (by the government) to protect foreign markets and prevent other beef producers from having to follow suit

WN: Are you a vegetarian?

Max: I don't eat cheap hamburger. When I learned it was comprised of hundreds of thousands of body parts and when I learned how it was blown off the bones of the cow and steer, I just decided I didn't quite have the stomach for it anymore.

Cheap hamburger comes from old dairy cows -- that's our thanks to them -- and the older the animal, the more the possibility of prion diseases.

WN: Is there hope for a cure for prion diseases anytime soon?

Max: There are two (existing) drugs that are being tried out. It's really just accidental stuff that's going on, but they've had tremendous results.

WN: You suffer from a non-fatal neuromuscular disease that involves the failure of proteins to form properly. What might future research into prions mean for you personally?

Max: The more we know about proteins and their structures and how they learn to assume these structures, the better off people like me will be -- and people who have Alzheimer's, Parkinson's, Huntington's and Type II diabetes.