21
Sat, Dec
3 New Articles

Out of the Blue: The Protein Connection

Commentary
Typography
  • Smaller Small Medium Big Bigger
  • Default Helvetica Segoe Georgia Times

The mountain tribes of New Guinea knew it as Kuru. It was believed to be sorcery, and once the evil entered a person’s 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 Kuru’s transmitting agent. It didn’t appear to be the result of infection or toxicity or heredity. But the disease seemed to favor women and children, and it wasn’t until one researcher asked what women and children did that men didn’t 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 customary—and there is no delicate way to say this—to 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 didn’t 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. It’s September of 1999, and IBM has announced a five-year, $100 million commitment to build the world’s 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? It’s one of the most common biological functions, which occurs spontaneously in but a fraction of a second.

Well, according to scientists at IBM’s Computational Biology Center, it will take Blue Gene about one year of continuous processing to simulate a single protein. That’s 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 Vickie’s 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, it’s 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 Rimmer’s 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 England’s 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 Kuru’s 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 Alzheimer’s. 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.


BLOG COMMENTS POWERED BY DISQUS

LATEST COMMENTS

Support MC Press Online

$

Book Reviews

Resource Center

  • SB Profound WC 5536 Have you been wondering about Node.js? Our free Node.js Webinar Series takes you from total beginner to creating a fully-functional IBM i Node.js business application. You can find Part 1 here. In Part 2 of our free Node.js Webinar Series, Brian May teaches you the different tooling options available for writing code, debugging, and using Git for version control. Brian will briefly discuss the different tools available, and demonstrate his preferred setup for Node development on IBM i or any platform. Attend this webinar to learn:

  • SB Profound WP 5539More than ever, there is a demand for IT to deliver innovation. Your IBM i has been an essential part of your business operations for years. However, your organization may struggle to maintain the current system and implement new projects. The thousands of customers we've worked with and surveyed state that expectations regarding the digital footprint and vision of the company are not aligned with the current IT environment.

  • SB HelpSystems ROBOT Generic IBM announced the E1080 servers using the latest Power10 processor in September 2021. The most powerful processor from IBM to date, Power10 is designed to handle the demands of doing business in today’s high-tech atmosphere, including running cloud applications, supporting big data, and managing AI workloads. But what does Power10 mean for your data center? In this recorded webinar, IBMers Dan Sundt and Dylan Boday join IBM Power Champion Tom Huntington for a discussion on why Power10 technology is the right strategic investment if you run IBM i, AIX, or Linux. In this action-packed hour, Tom will share trends from the IBM i and AIX user communities while Dan and Dylan dive into the tech specs for key hardware, including:

  • Magic MarkTRY the one package that solves all your document design and printing challenges on all your platforms. Produce bar code labels, electronic forms, ad hoc reports, and RFID tags – without programming! MarkMagic is the only document design and print solution that combines report writing, WYSIWYG label and forms design, and conditional printing in one integrated product. Make sure your data survives when catastrophe hits. Request your trial now!  Request Now.

  • SB HelpSystems ROBOT GenericForms of ransomware has been around for over 30 years, and with more and more organizations suffering attacks each year, it continues to endure. What has made ransomware such a durable threat and what is the best way to combat it? In order to prevent ransomware, organizations must first understand how it works.

  • SB HelpSystems ROBOT GenericIT security is a top priority for businesses around the world, but most IBM i pros don’t know where to begin—and most cybersecurity experts don’t know IBM i. In this session, Robin Tatam explores the business impact of lax IBM i security, the top vulnerabilities putting IBM i at risk, and the steps you can take to protect your organization. If you’re looking to avoid unexpected downtime or corrupted data, you don’t want to miss this session.

  • SB HelpSystems ROBOT GenericCan you trust all of your users all of the time? A typical end user receives 16 malicious emails each month, but only 17 percent of these phishing campaigns are reported to IT. Once an attack is underway, most organizations won’t discover the breach until six months later. A staggering amount of damage can occur in that time. Despite these risks, 93 percent of organizations are leaving their IBM i systems vulnerable to cybercrime. In this on-demand webinar, IBM i security experts Robin Tatam and Sandi Moore will reveal:

  • FORTRA Disaster protection is vital to every business. Yet, it often consists of patched together procedures that are prone to error. From automatic backups to data encryption to media management, Robot automates the routine (yet often complex) tasks of iSeries backup and recovery, saving you time and money and making the process safer and more reliable. Automate your backups with the Robot Backup and Recovery Solution. Key features include:

  • FORTRAManaging messages on your IBM i can be more than a full-time job if you have to do it manually. Messages need a response and resources must be monitored—often over multiple systems and across platforms. How can you be sure you won’t miss important system events? Automate your message center with the Robot Message Management Solution. Key features include:

  • FORTRAThe thought of printing, distributing, and storing iSeries reports manually may reduce you to tears. Paper and labor costs associated with report generation can spiral out of control. Mountains of paper threaten to swamp your files. Robot automates report bursting, distribution, bundling, and archiving, and offers secure, selective online report viewing. Manage your reports with the Robot Report Management Solution. Key features include:

  • FORTRAFor over 30 years, Robot has been a leader in systems management for IBM i. With batch job creation and scheduling at its core, the Robot Job Scheduling Solution reduces the opportunity for human error and helps you maintain service levels, automating even the biggest, most complex runbooks. Manage your job schedule with the Robot Job Scheduling Solution. Key features include:

  • LANSA Business users want new applications now. Market and regulatory pressures require faster application updates and delivery into production. Your IBM i developers may be approaching retirement, and you see no sure way to fill their positions with experienced developers. In addition, you may be caught between maintaining your existing applications and the uncertainty of moving to something new.

  • LANSAWhen it comes to creating your business applications, there are hundreds of coding platforms and programming languages to choose from. These options range from very complex traditional programming languages to Low-Code platforms where sometimes no traditional coding experience is needed. Download our whitepaper, The Power of Writing Code in a Low-Code Solution, and:

  • LANSASupply Chain is becoming increasingly complex and unpredictable. From raw materials for manufacturing to food supply chains, the journey from source to production to delivery to consumers is marred with inefficiencies, manual processes, shortages, recalls, counterfeits, and scandals. In this webinar, we discuss how:

  • The MC Resource Centers bring you the widest selection of white papers, trial software, and on-demand webcasts for you to choose from. >> Review the list of White Papers, Trial Software or On-Demand Webcast at the MC Press Resource Center. >> Add the items to yru Cart and complet he checkout process and submit

  • Profound Logic Have you been wondering about Node.js? Our free Node.js Webinar Series takes you from total beginner to creating a fully-functional IBM i Node.js business application.

  • SB Profound WC 5536Join us for this hour-long webcast that will explore:

  • Fortra IT managers hoping to find new IBM i talent are discovering that the pool of experienced RPG programmers and operators or administrators with intimate knowledge of the operating system and the applications that run on it is small. This begs the question: How will you manage the platform that supports such a big part of your business? This guide offers strategies and software suggestions to help you plan IT staffing and resources and smooth the transition after your AS/400 talent retires. Read on to learn: