Researchers Create an Artificial Prion (Mad Cow, deer and elk Chronic Wasting Disease, ALERT)

Scientists are reporting that, for the first time, they have made an artificial prion, or misfolded protein, that can, by itself, produce a deadly infectious disease in mice and may help explain the roots of mad cow disease.

The findings, being reported on Friday in the journal Science, are strong evidence for the so-called "protein only hypothesis," the controversial idea that a protein, acting alone without the help of DNA or RNA, can cause certain kinds of infectious diseases.

The concept was introduced in 1982 by Dr. Stanley Prusiner, a neurology professor at the University of California in San Francisco, and is still unsettling to many scientists who have been taught that only bacteria and viruses containing genetic information can spread infectious diseases.

Over the years, the idea that a misfolded protein, because of its shape alone, could trigger an infectious disease, has been gaining acceptance but it has never been conclusively proven.

In this study, Dr. Prusiner said researchers had successfully created a man-made prion and injected it into a mouse brain and produced disease. Then, they took tissue from the diseased mouse and injected it in another mouse, which also got the same disease.

Dr. Prusiner said in a telephone interview that he was "flabbergasted" that it had taken 22 years to prove the hypothesis but that his lab was able to overcome earlier technical difficulties with a new set of experiments. "We have compelling evidence," he said. "We've done it all."

"I am thrilled" by this new study, said Dr. Peter T. Lansbury, an associate professor of neurology at Harvard Medical School and an expert on protein folding. "You can never really prove a hypothesis but only try to disprove it," he said. But with these findings, "we are about as close as you can ever get to proving it."

Dr. Bruce Chesebro, chief of the Laboratory of Persistent Viral Diseases at the Rocky Mountain Laboratory, said that the experiment shows that the prion produced something in the mice. But he said that it remains unclear whether the prion is causing the infection or somehow just exposing an underlying infectious process.

Dr. Laura Maneulidis, a neuropathologist at the Yale University Medical School, one of Dr. Prusiner's most vocal critics, said the prion strain that turned up in the experiment looks like a mouse prion frequently used in Dr. Prusiner's laboratory.

"Basically I think the data look like contamination," she said, possibly stemming from "inadequately washed instruments."

Dr. Prusiner, who won the 1997 Nobel Prize in Medicine and Physiology for his prion research, said some of his critics will never be satisfied. "They'll say we need to do 10 more years of experiments, using controls we didn't do," he said. "It's just silly."

Dr. Prusiner predicted that the newly gleaned information will lead to more effective ways to diagnose and treat a family of deadly diseases called transmissible spongiform encephalopathies, or TSEs, believed to be caused by aberrant proteins.

The stakes are enormous. Last week, a British citizen who died from other causes was found to have been infected by a human form of TSE from a routine blood transfusion. The human form, called variant Creutzfedlt Jakob disease, is contracted from eating cattle infected with mad cow disease. At least two people who died from the variant disease gave blood before falling ill, which means many more Britons could be infected.

American agriculture officials are testing thousands of cattle in an effort to determine if mad cow disease is a problem in this country, but the tests are notoriously imperfect. A deeper understanding of protein diseases should lead to tests that can diagnose the disease even in cattle that show no symptoms.

The biology of protein diseases is new and often difficult to grasp, Dr. Prusiner said. He said he believed that many proteins cause disease when they adopt an abnormal shape and form toxic fibrils that create havoc in the brain or body. Alzheimer's disease, Parkinson's disease, type two diabetes and at least two dozen other human disorders may be caused by misshapen proteins, according to Dr. Pruisner.

But as far as scientists have been able to determine only one protein, the prion, leads to infectious diseases. That is, infectious prions can be passed between and among species through the eating of nervous tissue, exchange of bodily fluids and by direct injection into the brain.

When Dr. Prusiner introduced the protein-only hypothesis, he was greeted with skepticism. The test should be simple: create a prion in a laboratory dish or in a bacterial system far removed from animal cells that might harbor DNA. Then add chemicals or heat to fold the artificial prion into different shapes, including many sheet-like structures seen in virtually all TSEs. Inject the misfolded man-made prion into healthy animals. If such prions cause disease in and of themselves, the animals should get sick.

The hallmark of a TSE is spongy holes and inflammation in the brain. Some of the diseases also feature clumps of fibrils called amyloid.

Laboratories around the world have tried countless variations of this experiment for years, Dr. Prusiner said. They never worked. The mice never got sick. But this time, Dr. Prusiner says, the mice did get sick.

In hindsight, the reasons are now clear, Dr. Prusiner said. In tinkering with artificial prions, researchers never knew what part of the full length protein was responsible for passing on the disease. They reasoned that an infectious core was the culprit. When that core — a fragment of misfolded protein — comes into contact with a similar fragment in a healthy prion, the healthy prion is fatally converted into the disease form. But what fragment? What shapes cause the conversion? If that core could be isolated, the experiments might work.

Nature offered a solution, Dr. Prusiner said. A few TSEs produce huge amounts of amyloid composed of core prion fragments which are easy to see. Researchers synthesized healthy protein fragments similar to the amyloid. They subjected the fragments to agents such as urea and vinegar that alter protein shape and shook the solutions for 40 hours. Amyloids appeared. The man-made proteins were cleansed and injected into the brains of transgenic mice bred with prions that would recognize the fragments.

"We waited," Dr. Prusiner said. "And waited. At 300 days, none of the animals got sick. We thought the experiment had not worked."

But over the next 200 days, every animal developed spongiform degeneration, the scientist said. A brain extract from a sick animal was injected into normal mice with different prion structure. They too got sick.

Oh thats great. Can't wait till they publish how they did it for every madman in the world to read.

I can't remember where I found it but I saved it (2 pages) on my Bro-in-law's web site! :>)
http://www.gohotsprings.com/ranchman/mad_cow1.htm

I still agree with this theory for now:

As an organic farmer, Mark Purdey resisted the order to spray his cattle with organophosphates for warble fly and went to court for a judicial review; he won and was exempted from using the spray. No cows born in his herd developed BSE (mad cow disease). He has contributed numerous articles on the subject of BSE to scientific journals. He farms in Somerset, UK. This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly magazine of the Weston A. Price Foundation, Spring 2000

So that's why these demonrats have been so angry all year long. They must have been among the those rats that got infected with this Artificial Prion. Of course in humans, it affects the brain in an insidious manner and hard to detect. The most notable symptom is that you have this maddening desire to go to the left all the time all the while claiming you are going down the center.

Then, they took tissue from the diseased mouse and injected it in another mouse, which also got the same disease.

Hmmm . . . Wouldn't it have been more sound to inject the second mouse with the prion instead of tissue from the first mouse? Just asking.

Hmmm . . . Wouldn't it have been more sound to inject the second mouse with the prion instead of tissue from the first mouse? Just asking.

Isolating misshapen proteins might be tricky business. Normal proteins fall into two main types, fibrous and globular. The former are typically structural proteins, and the latter are usually enzymes. The usual techniques for purifying proteins may be inadequate.

That is why we purchase our meats from like farms where the animals are grass-fed, raised for us without all of the injectibles. The farmer makes a better living and we get meat "the way it used to be".

See "grass-fed" on the web for more information.
See also http://www.smithsonianmag.si.edu/smithsonian/issues00/jul00/farm.html

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