The mountain tribes of New Guinea knew it as Kuru. It was believed to be sorcery, and once the evil entered a persons body, no ritual or medicine could help. Natives became listless and emaciated, subject to tremors and spastic movement. A progressive paralysis followed, until the person became unable to stand or speak. Sometimes they shrieked in mirthless laughter. Death inescapably followed. No one affected survived.
In 1956, neuropathologists at the National Institutes of Health examined the brains of several Kuru casualties and found some startling irregularities. Kuru brains were spongy and pocked with holes where neurons used to be. It was as if something had been eating them.
The findings were highly unusual but not without precedent. An extremely rare ailment called Creutzfeldt-Jakob Disease, or CJD, had produced similar effects in the brains of the elderly. But at the time, only a handful of cases had ever been reported, and it was considered a medical curiosity. There was another disease, however, that had been well known for over 250 years and produced comparable symptoms in sheep. Shepherds simply referred to it as the plague. Its common name was scrapie, and like Kuru, it was both transmissible and fatal.
For a long time, researchers could not find Kurus transmitting agent. It didnt appear to be the result of infection or toxicity or heredity. But the disease seemed to favor women and children, and it wasnt until one researcher asked what women and children did that men didnt do that the answer began to emerge.
Among the tribes less engaging customs was the practice of ritual cannibalism. As women prepared the bodies of relatives for burial, it was customaryand there is no delicate way to say thisto slice off morsels of the deceased and feed them to the bereaved. Although ostensibly done as a sign of mourning and respect for the barely departed, the origin of the practice may have been rooted in hunger. Men hunted, and, therefore, dominated the food supply. Women and children survived on what men didnt eat and on whatever they could scrounge or grow themselves. When men participated in ritual cannibalism, they always took the tastiest parts for themselves and left the organs to the women and children. The infected brain was the transmitting agent.
Now move the clock forward 43 years. Its September of 1999, and IBM has announced a five-year, $100 million commitment to build the worlds fastest supercomputer. The machine will be 500 times faster than anything running today. It will have 32 microprocessors on each chip, 64 chips on each motherboard, and eight motherboards in each of the 64 towers that will comprise the system known as Blue Gene.
Over a million processors will be churning in electronic lockstep designed to unravel a single mystery: the process by which amino acids fold themselves into proteins.
Huh? The announcement was met with rabid excitement from esoteric researchers in the scientific community and yawns from the rest of humanity. After all, protein folding is not a topic of conversation at the average dinner table. For most of us, folding modifies laundry, not proteins. Besides, how tough can it be? Its one of the most common biological functions, which occurs spontaneously in but a fraction of a second.
Well, according to scientists at IBMs Computational Biology Center, it will take Blue Gene about one year of continuous processing to simulate a single protein. Thats relatively quick considering the number of possible three-dimensional shapes for a protein is greater than the number of atoms in the universe. The bad news is, there are about 40,000 proteins waiting to be unraveled.
But why such interest in the pleating habits of amino acids? And what is the link between Blue Gene, cannibalism, and Kuru? The answers stretch back eight years to England. In 1993, something exceedingly rare happened in Wales: A young girl was diagnosed with CJD. Creutzfeldt-Jakob Disease was thought to be a disease of the elderly and was so rare it was only being reported in about one person per million per year. Vickie Rimmer was only 15. Within a span of several months, she became disoriented and fatigued, complained of deteriorating eyesight, and was eventually hospitalized, where she degenerated into a vegetative coma. As doctors struggled to make sense of Vickies illness, reports of CJD were beginning to trickle in from other parts of England.
Creutzfeldt-Jakob Disease is a human manifestation of a class of afflictions called transmissible spongiform encephalopathies, or TSEs. Like scrapie and Kuru, CJD is a fatal dementia that perforates the brain and turns it to mush. In cattle, its called bovine spongiform encephalopathy, or BSE, popularly known as mad cow disease. British officials had known about a BSE outbreak seven years prior to Vickie Rimmers illness. But it was her unfortunate story that led medical authorities to believe mad cow disease had jumped species, and that Rimmer had acquired the illness by eating tainted meat.
For nearly a decade, British government officials denied the existence of a problem in a desire to contain the outbreak. But their lack of decisiveness only resulted in more human infection and in the eventual destruction of over 160,000 cows in an attempt to reassure citizens and importing nations that Englands beef was safe. Nonetheless, several European Union nations banned the importation of British beef, and mad cow disease has now spread throughout the European Union.
How transmissible dementias originated is thought to be a result of mutating proteins called prions, and therein lies the Blue Gene connection. A prion consists of a single molecule with about 250 amino acids. Think of amino acids as strands of ribbon that can fold in endless sequences to form proteins. Proteins are the building blocks of life, but prions fold abnormally and have the power to transform healthy proteins into copies of themselves. Fold, in this context, determines function, and prions create chains of malfunctioning proteins that eventually destroy the brain. Blue Gene, it is hoped, will unravel the folding criteria and help researchers prevent or cure a whole range of terrible diseases by creating proteins capable of stopping or reversing broken chains.
The manner in which mad cow disease spread to humans is believed to parallel Kurus spread in New Guinea. Few cattle are naturally afflicted by BSE, so there is small chance of eating infected meat. For the disease to affect humans in any meaningful numbers, there had to be a vector that spread the illness to additional cattle. That vector was cannibalism.
Until recently, the livestock industry in England employed the vile and unnatural practice of feeding dead cows to live ones, thus turning animals that were naturally vegetarians into carnivores and cannibals. Each year, thousands of cows drop dead without preamble. When encountering a downer cow, farmers have a choice. They can call a vet,
who will charge them to drive out and confirm the animal is dead, or they can call a rendering plant, which will come and take the carcass away.
Rendering is the practice of converting animal waste products into marketable commodities, a process one reporter described as combining the unique charms of the slaughterhouse and the sewer. In addition to dead cows, rendering plants collect tons of offal from slaughterhouses and waste meat from supermarkets; roadkill including deer, raccoons, snakes, and possums; cats and dogs from animal shelters; carcasses from local zoos; dead horses; and downer sheep. These bacteria-riddled carcasses infested with microbiological pathogens are ground up and deep-fried in used restaurant grease and blood. Some of this material is converted into protein supplements that are fed back to the livestock from which they came. The problem is that not all these animals dropped dead because of old age; some percentage were obviously sick, and by processing infected animals, the rendering plants were inadvertently recycling mad cow disease. Highly resistant to disinfection procedures, the tissue from one infected cow could thus be blended with the tissue of thousands of other carcasses, then disbursed to hundreds of ranchers as feed.
Of course, this practice was not limited to the United Kingdom. The United States was the leading practitioner of feeding rendered protein to livestock. Officials here, as their counterparts did a decade ago in England, claim there is no danger and that the beef supply is BSE-free. So far, random testing of cattle supports their claim. But starting from a handful of deaths less than 10 years ago, British authorities have steadily revised the number of projected deaths from 20 upward to 250,000. The real numbers, however, are unknown. The incubation period for CJD usually spans decades. Some researchers even believe that CJD is frequently misdiagnosed as Alzheimers. Before a cure is found, deaths may actually number in the millions. No one knows for sure.
Given the unknown extent of infection and the lengthy incubation of TSEs, Blue Gene offers human and animal populations the potential of deliverance from a pandemic if worst-case scenarios are realized.
As we begin to intervene in basic biological processes, we also begin to see the dangers of doing so. Forcing animals to eat things they would never naturally consume has spawned horrific results: The instructions for making complex proteins were garbled; humans and animals malfunctioned and died.
Unraveling the mystery of protein folding will be an undertaking of mind-boggling complexity. It is fitting that the long-running programs that will decode our biological secrets should be described as self-healing. These software systems, not unlike our bodies, will self-correct and keep running in spite of data or hardware errors. If science succeeds, diseases like CJD will be treated at the genetic level, with treatments individually tailored to the genetic makeup of the patient. The correlation is almost too perfect: Blue Gene, an electronic body driven by self-healing software that will someday make it possible for human bodies to heal themselves.