Brain Power

Doctor solves mystery of ‘silent killers’ linked to mad cow disease

Originally appeared in The Daily.

A staple of kung fu movies is the “silent killer” punch that feels like a tap when delivered but that minutes, hours or years later causes the victim to keel over, stone dead. Biology has many such silent killers, such as cancer and HIV, but none is stealthier or more insidious than the family of diseases uncovered by American neurologist Stanley Prusiner in 1982. And, he found, to deal a death blow, these diseases needed nothing more exotic than a plain old delicious steak.

The history of Prusiner’s discovery, which won him the Nobel Prize in 1998, is one of the great detective tales of modern medicine. The disease family he studied had terrible but mysterious effects. At first, its victims (many between age 40 to 60) began to shudder and shake. Within months they started losing their ability to speak, walk and think. Within a year, they became quivering messes; autopsies showed their brains had been reduced to Swiss cheese, bubbled with pockets of fluid or air.

The diseases, called spongiform encephalopathies because of the spongy texture of the brain, took two forms in humans: Creutzfeldt-Jakob Disease and kuru. Creutzfeldt-Jakob Disease kills about one in a million people worldwide. But only New Guinea’s Fore people became afflicted with kuru — in their language, it means “the shivers.” In the 1950s, when scientists first got serious about tracking the disease, kuru was killing the Fore at a rate of about 200 a year, or one in 100. There, the disease had a particularly ghoulish flourish, causing people to laugh madly and uncontrollably as it robbed them of their senses.

Doctors found no cure. But they did observe unusual trends. Kuru felled women 50 times more often than men and appeared less and less frequently after the 1960s. An Australian doctor, Michael Alpers, hit upon a reason: The Fore had ceased practicing cannibalism.

Previously, to honor deceased relatives, the Fore had eaten their corpses. Missionaries and government officials discouraged and then outlawed the practice in the 1950s, and the disease began to vanish. Moreover, when the Fore ate their dead, the men claimed the choice meats first, stripping off fillets of muscle and leaving the women just organs — specifically the brain. By the 1970s, scientists determined that whatever was causing the disease could be transmitted by eating the brains of the dead.

But the one American out of every million who was dying of Creutzfeldt-Jakob Disease was not dining on Fore brains or anyone else’s. The poor twitchers appeared to be just extremely unlucky, struck down with utter stealth by a killer that left no telltale bacteria or viruses. Most mysterious of all were the few instances where doctors discovered brain-to-brain spreading of Creutzfeldt-Jakob Disease. In 1977, an old woman who died of the disease had electrodes implanted in her brain for a medical procedure.The electrodes were removed and thoroughly sterilized; but when doctors sank the sterilized electrodes into the brains of two young people for an electroencephalogram weeks later, they transmitted the disease, and both died two years later. Whatever this infectious agent was, it could survive a long bath in alcohol and formaldehyde. Any surgery that involved touching brain or spinal tissue risked spreading it.

So when Stanley Prusiner began to research the disease, he knew he was up against some kind of superbug: tiny, hardy and ghastly. His breakthrough was to find the link among cases of Creutzfeldt-Jakob Disease, kuru and animal diseases such as scrapie, which made sheep shake and itch uncontrollably. Prusiner painstakingly purified the infectious element and found that the culprit substance was a protein, as many had suspected, and that the protein contained no nucleic acid. This second point confused scientists because although countless proteins have no nucleic acid, until then, nucleic acids such as DNA and RNA were thought to be the blueprint material for all infectious agents. These strange new proteins, which Prusiner called prions, were like an alien virus.

In the end, Prusiner and his colleagues determined that prions were essentially normal proteins gone haywire. Normally, proteins fold up into particular shapes, dictated by the genes. But certain proteins, it turned out, could be misfolded — and when these misfolded proteins touched other, properly folded ones, the misshapen ones reshaped the proper ones into deadly and infectious configurations. In time, the misfolded proteins multiplied, clumped into deadly plaques, and cored and jellified the brains of those afflicted. When Fore women and children ate brains, they were consuming the most prion-rich parts of the body. Whether they died in just a year or two or long after was probably a matter of genetic resistance; some brains fought off the prions longer than others.

But where were the prions coming from in the human cases not involving cannibalism? It seemed that prions could form spontaneously, subject to certain genetic predispositions.

And people could also get them from eating the wrong animals, such as some of the nearly half a million prion-rich cows in Britain that were slaughtered and fed to humans during the 1980s. This is what happened in mad cow disease. According to reports after the fact, cows had been fed a grainy powder of meat and bone meal, composed of the ground-up parts of their fellow cows and sheep, including some that might have had scrapie or mad cow. The cows were, in essence, re-enacting the Fore ritual on a grand industrial scale, and they suffered the same consequence.

So far, at least 200 people in the West have died from prion-related disease, with sporadic cases still cropping up at a diminished rate. It’s now illegal to use meat and bone meal as cattle feed in most countries, though not in the United States. Recent research suggests that the prions burrow into the system through cracks in the teeth. (Also disproportionately affected are those who eat a Kentuckian squirrel-brain stew called burgoo, which was responsible for several deaths in the late 1990s.)

Six years ago, scientists revisited the Fore people to check whether the end of cannibalism had stopped the disease. It had not: The scientists found 11 more cases of kuru, all from people who had eaten brains before the practice was outlawed. One had sworn off brains for 56 years. This killer is not just silent but very, very patient.


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