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Nobel Prize to Prusiner!
Full text of the Award
Nobel Prize winner sits on FDA panel
Lancet on Nobel prize to Prusiner
Science: Prusiner Recognized for Once-Heretical Prion Theory
Neurologist Says Nobel Prize vindicates work
Nobel winner could have prevented ``mad cow''
Tiny prion may hold key to deadly brain diseases
Backgrounder on Stanley B. Prusiner, M.D
Swiss scientists appalled by Nobel omission
Collected works of SB Prusiner: 298 publications in 20 years
Curriculum vitae
Off-Site: Karolinska Institutet award page ....
... featuring a third-rate 2.7 meg shockwave animation

Nobel Prize to Prusiner!

STOCKHOLM, Sweden (Reuter) - Stanley Prusiner, a U.S. biochemist whose discovery provided key insights into dementia-related diseases, won the 1997 Nobel Medicine Prize, Sweden's Karolinska Institute said on Monday. The institute said Prusiner's work helped the world to understand more about Alzheimer's and Mad Cow disease through his discovery of the prion, a disease-causing agent like bacteria or viruses.

The prion protein can manifest itself as two proteins, one an innocent ``Dr. Jekyll'' character, while the other, dangerous ``Mr Hyde'' protein causes disease and death. The institute said Prusiner solved the riddle of the prion's properties. Prusiner, 55, is professor of biochemistry at the University of California in San Francisco (UCSF).

``Prusiner's discovery provides important insights that may furnish the basis to understand the biological mechanisms underlying other types of dementia-related diseases, for example Alzheimer's disease, and establishes a foundation for drug development and new types of medical treatment strategies,'' it added.
Prusiner began his work in 1972 after one of his patients died of dementia resulting from Creutzfeldt-Jakob disease (CJD). Ten years later he and his team produced a preparation derived from diseased hamsters' brains that contained a single agent he called a ``Prion.''
``Prions exist normally as innocuous cellular proteins. However prions possess an innate capacity to convert their structures...that ultimately result in the formation of harmful particles, the causative agents of several deadly brain diseases of the dementia type in humans and animals,'' the instutute said.
His work, following up on evidence that CJD can be transmitted through diseased brains, was greeted with scepticism at first but is now linked with understanding Mad Cow disease -- Bovine Spongiform Encephalopathy (BSE) -- and other dementia-related illnesses.
``An unwavering Prusiner continued the arduous task to define the precise nature of this novel infectious agent,'' the institute said.

Karolinska Institutet

Press Release October 6, 1997
The Nobel Assembly at the Karolinska Institute has today decided to award

the Nobel Prize in Physiology or Medicine for 1997


Stanley B. Prusiner

for his discovery of

Prions - a new biological principle of infection


The 1997 Nobel Prize in Physiology or Medicine is awarded to the American Stanley Prusiner for his pioneering discovery of an entirely new genre of disease-causing agents and the elucidation of the underlying priciples of their mode of action. Stanley Prusiner has added prions to the list of well known infectious agents including bacteria, viruses, fungi and parasites. Prions exist normally as innocuous cellular proteins, however, prions possess an innate capacity to convert their structures into highly stabile conformations that ultimately result in the formation of harmful particles, the causative agents of several deadly brain diseases of the dementia type in humans and animals. Prion diseases may be inherited, laterally transmitted, or occur spontaneously. Regions within diseased brains have a characteristic porous and spongy appearance, evidence of extensive nerve cell death, and affected individuals exhibit neurological symptoms including impaired muscle control, loss of mental acuity, memory loss and insomnia. Stanley Prusiner's discovery provides important insights that may furnish the basis to understand the biological mechanisms underlying other types of dementia-related diseases, for example Alzheimer's disease, and establishes a foundation for drug development and new types of medical treatment strategies.

The prize winning research was initiated 25 years ago

In 1972 Stanley Prusiner began his work after one of his patients died of dementia resulting from Creutzfeldt-Jakob disease (CJD). It had previously been shown that CJD, kuru, and scrapie, a similar disease affecting sheep, could be transmitted through extracts of diseased brains. There were many theories regarding the nature of the infectious agent, including one that postulated that the infectious agent lacked nucleic acid, a sensational hypothesis since at the time all known infectious agents contained the hereditary material DNA or RNA. Prusiner took up the challenge to precisely identify the infectious agent and ten years later in 1982 he and his colleagues successfully produced a preparation derived from diseased hamster brains that contained a single infectious agent. All experimental evidence indicated that the infectious agent was comprised of a single protein, and Prusiner named this protein a prion, an acronym derived from "proteinaceous infectious particle." It should be noted that the scientific community greeted this discovery with great skepticism, however, an unwavering Prusiner continued the arduous task to define the precise nature of this novel infectious agent.

The infectious prion particle forms within the body

Where was the gene encoding the prion, the piece of DNA that determined the sequence of the amino acids comprising the prion protein? Perhaps the gene was closely associated with the protein itself as in a small virus? The answers to these questions came in 1984 when Prusiner and colleagues isolated a gene probe and subsequently showed that the prion gene was found in all animals tested, including man. This startling finding raised even more questions. Could prions really be the causative agent of several dementia-type brain diseases when the gene was endogenous to all mammals? Prusiner must have made a mistake! The solution to this problem became evident with the sensational discovery that the prion protein, designated PrP, could fold into two distinct conformations, one that resulted in disease (scrapie PrP = PrPSc) and the other normal (PrP = PrPc). It was subsequently shown that the disease-causing prion protein had infectious properties and could initiate a chain reaction so that normal PrPc protein is converted into the more stabile PrPSc form. The PrPSc prion protein is extremely stabile and is resistant to proteolysis, organic solvents and high temperatures (even greater than 100o C). With time, non-symptomatic incubation periods vary from months to years, the disease-causing PrPSc can accumulate to levels that result in brain tissue damage. In analogy to a well known literary work, the normal PrPc can be compared to the friendly Dr. Jekyll and the disease causing PrPSc to the dangerous Mr. Hyde, the same entity but in two different manifestations.

Mutations in the prion gene cause hereditary brain diseases

The long incubation time for prion based disease hampered the initial efforts to purify the prion protein. In order to assess purification schemes Prusiner was forced to use scores of mice and in each experiment wait patiently for approximately 200 days for the appearance of disease symptoms. The purification efforts accelerated when it was demonstrated that scrapie could be transferred to hamsters, animals that exhibited markedly shortened incubation times. Together with other scientists, Prusiner cloned the prion gene and demonstrated that the normal prion protein was an ordinary component of white blood cells (lymphocytes) and was found in many other tissues as well. Normal prion proteins are particularly abundant on the surface of nerve cells in the brain. Prusiner found that the hereditary forms of prion diseases, CJD and GSS (see the last section), were due to mutations in the prion gene. Proof that these mutations caused disease was obtained when the mutant genes were introduced into the germline of mice. These transgenic mice came down with a scrapie-like disease. In 1992 prion researchers obtained conclusive evidence for the role of the prion protein in the pathogenesis of brain disease when they managed to abolish the gene encoding the prion protein in mice, creating so called prion knock-out mice. These prion knock-out mice were found to be completely resistant to infection when exposed to disease-causing prion protein preparations. Importantly, when the prion gene was reintroduced into these knock-out mice, they once again became susceptible to infection. Strangely enough, mice lacking the prion gene are apparently healthy, suggesting that the normal prion protein is not an essential protein in mice, its role in the nervous system remains a mystery.

Structural variant disease-causing prions accumulate in different regions of the brain

Specific mutations within the prion gene give rise to structurally variant disease-causing prion proteins. These structural prion variants accumulate in different regions of the brain. Dependent upon the region of the brain that becomes infected, different symptoms, typical for the particular type of disease are evident. When the cerebellum is infected the ability to coordinate body movements declines. Memory and mental acuity are affected if the cerebral cortex is infected. Thalamus specific prions disturb sleep leading to insomnia, and prions infecting the brain stem primarily affect body movement.

Other dementias may have a similar background

Prusiner's pioneering work has opened new avenues for understanding the pathogenesis of more common dementia-type illnesses. For example, there are indications that Alzheimer's disease is caused when certain, non-prion, proteins undergo a conformational change that leads to the formation of harmful deposits or plaques in the brain. Prusiner's work has also established a theoretical basis for the treatment of prion diseases. It may be possible to develop pharmacological agents that prevent the conversion of harmless normal prion proteins to the disease-causing prion conformation.

Intrinsic defense mechanisms do not exist against prions

Prions are much smaller than viruses. The immune response does not react to prions since they are present as natural proteins from birth. They are not poisonous, but rather become deleterious only by converting into a structure that enables disease causing prion proteins to interact with one another forming thread-like structures and aggregates that ultimately destroy nerve cells. The mechanistic basis underlying prion protein aggregation and their cummulative destructive mechanism is still not well understood. In contrast to other infectious agents, prion particles are proteins and lack nucleic acid. The ability to transmit a prion infection from one species to another varies considerably and is dependent upon what is known as a species barrier. This barrier reflects how structurally related the prions of different species are.

Prion diseases in animals and man

Without exception, all known prion diseases lead to the death of those affected. There are, however, great variations in pre-symptomatic incubation times and how aggressively the disease progresses.

Scrapie, a prion disease of sheep, was first documented in Iceland during the 18th century. Scrapie was transferred to Scotland in the 1940s. Similar prion diseases are known to affect other animals, e.g., mink, cats, deer and moose.

Bovine Spongiform Encephalopathy (BSE) - Mad cow disease is a prion disease that has recently received a great deal of publicity. In England BSE was transmitted to cows through feedstuff supplemented with offals from scrapie-infected sheep. The BSE epidemic first became evident in 1985. Due to the long incubation time the epidemic did not peak until 1992. In this year alone roughly 37,000 animals were affected.

Kuru among the Fore-people in New Guinea was studied by Carleton Gajdusek (recipient of the the 1976 Nobel Prize in Physiology or Medicine). Kuru was shown to be transmitted in connection with certain cannibalistic rituals and was thought to be due to an unidentified "slow virus". The infectious agent has now been identified as a prion. Duration of illness from first symptoms to death: 3 to 12 months.

Gertsmann-Sträussler-Scheinker (GSS) disease is a hereditary dementia resulting from a mutation in the gene encoding the human prion protein. Approximately 50 families with GSS mutations have been identified. Duration of illness from evidence of first symptoms to death: 2 to 6 years.

Fatal Familial Insomnia (FFI) is due to another mutation in the gene encoding the human prion protein. Nine families have been found that carry the FFI mutation. Duration of illness from evidence of first symptoms to death: roughly one year.

Creutzfeldt-Jakob Disease (CJD) affects about one in a million people. In 85-90% of the cases it has been shown that CJD occurs spontaneously. Ten to fifteen per cent of the CJD cases are caused by mutations in the prion protein gene. In rare instances CJD is the consequence of infection. Previously infections were transmitted through growth hormone preparations prepared from the pituitary gland of infected individuals, or brain membrane transplants. About 100 families are known carriers of CJD mutations. Duration of illness from evidence of first symptoms to death: roughly one year.

A new variant of CJD that may have arisen through BSE-transmission. Since 1995 about 20 patients have been identified that exhibit CJD-like symptoms. Psychological symptoms with depression have dominated, but involuntary muscle contractions and difficulties to walk are also common.

Prusiner Recognized for Once-Heretical Prion Theory

Science  Volume 278, Number 5336 Issue of 10 October 1997, p 214
Gretchen Vogel
The Nobel committee often honors scientists who spent years working against strong opposition on controversial ideas, but usually the prize arrives long after the dust has settled. Not so this year for the prize in physiology or medicine. Stockholm's Karolinska Institute announced Monday that it had chosen to honor Stanley Prusiner "for his discovery of prions--a new biological principle of infection." The University of California, San Francisco, professor of neurology, virology, and biochemistry has championed the idea that infectious proteins can cause a range of degenerative brain diseases by misfolding and causing other proteins to do likewise. The committee also departed from tradition by awarding the prize to a single researcher--the first time it has done so since 1987, and only the 10th time in the last 50 years. While many of Prusiner's colleagues have come to accept the once-heretical prion theory, most say it still faces some crucial unanswered questions. Many argue, for example, that definitive proof that prions can cause disease by themselves is still lacking and that a cofactor such as a virus cannot be ruled out. Nevertheless, they say, Prusiner's work so far in making his case is worthy of the prize. "The distance he has brought [the field] is unbelievable," says Peter Lansbury, a biochemist at Brigham and Women's Hospital in Boston who studies the possible role of prion-type processes in Alzheimer's disease. In a statement, Charles Weissmann of the University of Zurich--who some have argued should have shared the prize--called Prusiner "a true pioneer and iconoclast" who "has waged a scientific battle for over 2 decades to convince his colleagues and the world that the infectious agent responsible for diseases such as scrapie, "mad cow disease," and Creutzfeldt-Jakob disease [CJD] is an abnormal form of a protein ... and has accumulated the evidence which has convinced the vast majority of scientists of the correctness of his view." This year's prize is the second awarded for work with such degenerative brain diseases. D. Carleton Gajdusek won in 1976 for his work a decade earlier demonstrating that kuru--a brain disease that affected highlanders in New Guinea who practiced ritualized cannibalism--was infectious. At the time, Gajdusek's work led many to blame the malady on a slow-acting virus, but it is now widely considered to be a prion disease. Prusiner coined the term in 1982 to describe the "proteinaceous infectious particles" he blamed for causing scrapie in sheep and hamsters. He suggested that scrapie and a collection of other wasting brain diseases, some inherited, some infectious, and some sporadic, were all due to a common process: a misfolded protein that propagates and kills brain cells. In doing so, he was picking up on an idea proposed in the 1960s, when radiation biologist Tikvah Alper, of Hammersmith Hospital in London, and physicist J. S. Griffith of Bedford College, London, suggested that an infectious agent that lacked nucleic acid could cause disease. Alper, studying scrapie in sheep, found that brain tissue remained infectious even after she subjected it to radiation that would destroy any DNA or RNA. Griffith suggested in a separate paper that perhaps a protein, which would usually prefer one folding pattern, could somehow misfold and then catalyze other proteins to do so. Such an idea seemed to threaten the very foundations of molecular biology, which held that nucleic acids were the only way to transmit information from one generation to the next. Inspired by a patient who died of the wasting brain condition CJD in 1972, Prusiner set out to determine the causative agent behind the disease, which resembles both kuru and scrapie. He and his colleagues reported in Science in 1982 that they had found an unusual protein in the brains of scrapie-infected hamsters that did not seem to be present in healthy animals. A year later, they identified the protein and called it PrP for prion protein. In the next decade, a series of experiments, many led by Prusiner, demonstrated that PrP actually is present in healthy animals, but in a different form from the one found in diseased brains. The studies also showed that mice lacking PrP are resistant to prion diseases. Taken together, the results have convinced many scientists that the protein is indeed the agent behind CJD, scrapie, mad cow disease, and others. Key questions remain, however. "The most important bit of information has yet to come forward: What triggers the normal cell protein to transform into the [disease-causing] isotype of the protein?" says Clarence Gibbs, a virologist at the National Institute of Neurological Disorders and Stroke and a longtime colleague of Gajdusek. (Prusiner addresses part of that question on page 245, where he suggests that a possible missing element, dubbed protein X, might help chaperone the PrP protein into its infectious shape.) And no one has been able to inject a prion protein synthesized in the test tube--and therefore free of any possible contaminating virus or other nucleic acid--into a healthy animal and make it sick. "I think it's speculation that the protein itself is infectious," says Laura Manuelidis, a neuropathologist at Yale University who has argued that a virus or other particle is involved. Prusiner acknowledges that there are still many uncertainties. "There are all these other experiments that should be done," he says. "I want to know more about all these details." Although Prusiner had been mentioned frequently as a Nobel candidate, many expected the award would wait for some of those uncertainties to be resolved. Byron Caughey, of the National Institutes of Health's Rocky Mountain Laboratories in Hamilton, Montana, said in a statement that the award is "somewhat surprising in view of the incomplete resolution of these questions." Ralf Pettersson, deputy chair of the Nobel Committee at the Karolinska Institute, says the panel was not bothered by the unanswered questions. The prize was awarded, he says, for the discovery of the prion and its role in the disease process. "The committee is well aware of where the field stands," he says. "The details have to be solved in the future. But no one can object to the essential role of the prion protein" in these brain diseases. Lansbury adds that Prusiner "is really a trailblazer. ... He's captured the imagination of a huge segment of the scientific population." And those imaginations should in no way be limited by this week's prize, Gibbs advises: "There's another Nobel Prize somewhere in this field."

Nobel Prize winner sits on FDA panel

UPn (UPI US & World) Mon, Oct 6, 1997 By SUSAN MILIUS
BETHESDA, Md., Oct. 6 (UPI) -- On the day University of California's Dr. Stanley Prusiner learned he was the 1997 Nobel Prize winner in medicine, he is sitting on an advisory panel of the Food and Drug Administration in Bethesda, Md. He is taking part in a two-day meeting that is examining public health issues linked to the novel infectious agent that are central to his Nobel Prize-winning research. He discovered a brain-killing protein that infects and replicates without any apparent use of genes. He corned the word prions ("PREE-ons") for the naturally occurring proteins that can mutate, and induce neighboring proteins to mutate.

They have been implicated as the cause of mad cow disease and a new variant of Creutsfeld-Jakob ("CROYTS-feld" YAH-cub") disease. The confirmed death toll of these diseases is at least 20 people, and hundreds of thousands of cattle, mostly in the United Kingdom and none in the United States. The award has brought drama and confusion to the suburban Washington, D.C., Holiday Inn, where the FDA often quietly holds its advisory panel meetings. FDA staff on site outside the meeting greet arriving press with a half-teasing, half exhausted, "I bet I know what you want. Reporters get a startled double take from the staff if they ask a question about the substance of the meeting itself.

But tracking Prusiner is easy. Just watch for the lightening storm of photo flashing that starts as soon as he emerges into a public hallway. Photographers jog backward in front of him and besides him, shooting every detail of a Nobel laureate punching an elevator button. Blinking in the glare he says, "You must have a lot of film." Responding to photographers' questions about when he was going to speak publicly about , he says, "No, no, I've got to get into the meeting."

Neurologist Says Nobel Prize Supports Work

Reuters Online Service  Mon, Oct 6, 1997  By Alicia Ault
BETHESDA, Md. (Reuters) - American neurologist Stanley Prusiner, awarded the Nobel Prize for Medicine on Monday, said the prize added great weight to his theory that tiny proteins cause mad cow disease and its human equivalent. Prusiner discovered and named the prion, the usually benign brain protein that mutates into a new form blamed for causing the brain-wasting illness Creutzfeldt-Jakob disease (CJD) and its cousin, bovine spongiform encephalopathy (BSE or mad cow disease).
"This prize is ample support for what I'm saying," Prusiner said.
Prusiner's work transformed research into such brain diseases and provided an explanation for the epidemic of mad cow disease that decimated British herds in the 1980s and is still affecting them today. It also helped explain how BSE could lead to human CJD -- an always fatal brain illness that usually affects only one in a million people.

Prusiner, a 55-year-old professor of neurology at the University of California in San Francisco, was in Bethesda for a U.S. Food and Drug Administration committee meeting on prion disease when he learned the news. He said he got the call at 5:05 a.m. EDT (0905 GMT). "I was delighted," he said, adding that his wife received the call first in San Francisco and knew before he did. He joked that he would use the $1 million prize money to pay his tax bill, telling reporters:

"I am going to use it to pay my taxes." He later grumbled: "This must be the only country in the world that taxes prize money."
Prusiner began his work in 1972, when he was a resident or junior doctor at a San Francisco hospital. One of his patients, a 60-year-old woman, died of CJD. His work with prions took on new importance with the outbreak of BSE in Britain. There is now a global ban on British beef products but experts fear people may have developed a new strain of CJD after eating infected beef products in the 1980s.

Twenty-one people have died from the new strain in Britain, and scientists have clearly linked it to BSE. They say it is too early to tell if an epidemic in humans will mirror the BSE epidemic. Many scientists were slow to accept the idea of prions and argued that some sort of virus must be responsible for the diseases, which are extremely rare in humans and which also are sometimes linked with a genetic mutation. Prusiner said it was right that science was not quick to accept controversial new ideas.

"Most new radical ideas turn out to be incorrect," he told reporters. "I think science is a process." He said it was the data that were important. "There is an amount of data now that has been accumulating over the years that argues very persuasively that BSE and CJD are caused by these pathogens that we call prions," he said. But, he added: "There are a group of people who will never be convinced."
The next step was to work on drugs to treat CJD. "What we'd like to do is develop an effective therapy for these diseases," he said. Prusiner said the next five to 10 years would see a drug that would stop progression of CJD as soon as it was detected. Scientists are working now on a test that will show if someone has CJD -- now it can only be diagnosed with a brain biopsy, usually performed after death. Prusiner, clearly eager to get back into the FDA meeting, spoke only briefly with reporters. "This meeting's important," he said as he left.

Nobel winner could have prevented ``mad cow''

Reuters World Report Mon, Oct 6, 1997 By Belinda Goldsmith
STOCKHOLM, Oct 6 (Reuter) - An American neurologist, whose discovery of a disease-causing agent could have helped prevent the outbreak of "mad cow" disease but for a sceptical scientific community, was on Monday awarded the 1997 Nobel Medicine Prize.

Stanley Prusiner discovered the prion, or proteinaceous infectious particle, an innocent cellular protein present in all humans and animals which can transform into a deadly particle, causing several fatal brain diseases. He found prion diseases such as Creutzfeldt-Jakob Disease (CJD) and scrapie could be inherited, transmitted or occur spontaneously -- a discovery that could have major implications for Alzheimer's Disease.

Although his find dates back to the early 1980s, it took several years for the medical world to accept his discovery -- too late to stop the outbreak of mad cow disease in Britain. The condition is caused by feeding cows offal from sheep infected with scrapie, a disease which attacks the central nervous system.

"During the whole of the 1980s, prion was very controversial," Ralf Pettersson, vice-chairman of the Medical Nobel Assembly at Sweden's Karolinska Institute, told Reuters. "Acceptance took a while. This could have delayed moves. It was more a political decision (in Britain) about when to take action, and by then it was too late."
Mad cow disease -- or Bovine Spongiform Encephalopathy (BSE) -- first surfaced in the mid-1980s but it was several years before Britain banned the use of cattle feed containing offal. Since BSE was identified, about 165,000 cattle have died and one million have been culled as a preventative measure. As of September, 1997, there had been 24 known human victims, suffering a new form of CJD that may have arisen through BSE transmission.

Prusiner, 55, a professor of biochemistry at the University of California in San Francisco (UCSF), began his work in 1972 after one of his patients died of dementia resulting from CJD. Ten years later he and his team produced a preparation derived from diseased hamsters' brains that contained a single agent he called a prion, which can be added to the list of well known infectious agents like bacteria, viruses and fungi

. A prion is much smaller than a virus and neither humans nor animals have any in-built defence mechanism, as prions are present as natural proteins from birth and not poisonous. It is converted prions that interact with one another, forming a thread-like structure, and ultimately destroy nerve cells in the brain, causing impaired muscle control, memory loss and insomnia in affected individuals. Pettersson said Prusiner's pioneering work had opened new avenues to understand more common dementia-type illnesses, such as Alzheimer's Disease.

"We now have a theoretical basis for designing new drugs to prevent the transformation to a pathological form of protein," Pettersson told a news conference. "It will help in research to understand other dementia in forms like Alzheimer's which have many features in common."
The Nobel Medicine Prize was the first award in the 1997 Nobel season and will be followed by the ... physics and chemistry prizes on October 15.

Tiny prion may hold key to deadly brain diseases

 Reuters North America  Mon, Oct 6, 1997
 By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuter) - It is neither a bacterium nor virus and resembles nothing so far identified as infectious. But the prion is probably behind a fatal and relentless human brain disease and the killing of a million British cattle. Stanley Prusiner won the 1997 Nobel Prize for Medicine Monday for discovering the tiny prion, a normally benign brain protein that sometimes mutates into a form that causes brain disease.

The American neurologist's work was controversial from the start, with scientists questioning how something as normal and widely present as a protein could cause disease. But Prusiner showed the proteins could take on a mutated form and these mutants could cause other proteins to change. They move very slowly but over years in animals and over decades in humans the brain takes on a spongy appearance that gives the diseases, transmissable spongiform encephalopathies, their name. They include bovine spongiform encephalopathy (BSE), known more widely as "mad cow disease," scrapie, reported in sheep for centuries, and the human version -- Creutzfeldt-Jakob disease (CJD).

Cats, deer and mink, along with a range of other animals, can develop similar diseases. British scientists believe cattle first started getting BSE -- which has only been reported in British cattle and in a few European cases -- when rendering methods changed. Cattle in many countries are routinely fed the remains of other farm animals. The theory is that sheep infected with scrapie were included in this protein feed, and when chemical rendering was replaced by high-heat methods, prions survived to infect the cattle. Very high temperature cooking does not destroy prions. They have been found in the brain, the spleen, parts of the intestine and other body products including, possibly, blood.

Britain eventually outlawed the use of such feed and exports of its beef and beef products have been banned. The epidemic is expected to die out within 10 years. But a new fear arose when cases of a mysterious strain of CJD arose. Normally a one-in-a-million disease that strikes the elderly because of its long incubation period, this CJD hit people under 40. So far 21 people have been diagnosed with the new CJD and doctors say it is too early to forecast a human epidemic.

Prusiner, a 55-year-old professor of neurology and biochemistry at the University of California San Francisco, began working with CJD in 1972. He was a resident, or junior doctor, at a San Francisco hospital and watched in dismay as a 60-year-old woman died of CJD. Published work convinced him to study such diseases. No one else had been able to identify the infectious agent. But Prusiner and other experts knew there had to be one -- children given human growth hormone from human brains sometimes suffered from CJD. Then came the BSE outbreak. Mice injected with BSE-infected brain matter get a disease that looks like CJD. Molecular tests have shown that BSE and the new strain of CJD are virtually the same disease.

Many scientists were slow to accept the idea of prions and said some sort of virus must be responsible for the diseases. Prusiner said it was only right science was not quick to accept controversial new ideas.

"Most new radical ideas turn out to be incorrect," he told reporters after learning of the prize. "I think science is a process."

Collected works of SB Prusiner

James TL, 1997
  Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of
  the scrapie isoform.
  Proc Natl Acad Sci U S A 94(19), 10086-10091 (1997)

Kaneko K, 1997
  Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion
  Proc Natl Acad Sci U S A 94(19), 10069-10074 (1997)

Kaneko K, 1997
  Molecular properties of complexes formed between the prion protein and synthetic peptides.
  J Mol Biol 270(4), 574-586 (1997)

Meiner Z, 1997
  Familial Creutzfeldt-Jakob disease. Codon 200 prion disease in Libyan Jews.
  Medicine (Baltimore) 76(4), 227-237 (1997)

Muramoto T, 1997
  Heritable disorder resembling neuronal storage disease in mice expressing prion protein with deletion of an
  Nat Med 3(7), 750-755 (1997)

Lundberg KM, 1997
  Kinetics and mechanism of amyloid formation by the prion protein H1 peptide as determined by
  time-dependent ESR.
  Chem Biol 4(5), 345-355 (1997)

Telling GC, 1997
  N-terminally tagged prion protein supports prion propagation in transgenic mice.
  Protein Sci 6(4), 825-833 (1997)

Zhang H, 1997
  Physical studies of conformational plasticity in a recombinant prion protein.
  Biochemistry 36(12), 3543-3553 (1997)

Kaneko K, 1997
  COOH-terminal sequence of the cellular prion protein directs subcellular trafficking and controls
  conversion into the scrapie isoform.
  Proc Natl Acad Sci U S A 94(6), 2333-2338 (1997)

Carlson GA, 1997
  Failure to transmit disease from gray tremor mutant mice.
  J Virol 71(3), 2342-2345 (1997)

Harrison PM, 1997
  The prion folding problem.
  Curr Opin Struct Biol 7(1), 53-59 (1997)

Schatzl HM, 1997
  Prion protein gene variation among primates.
  J Mol Biol 265(2), 257 (1997) (no abstract available)

Yehiely F, 1997
  Identification of candidate proteins binding to prion protein.
  Neurobiol Dis 3(4), 339-355 (1997)

Muramoto T, 1996
  Recombinant scrapie-like prion protein of 106 amino acids is soluble.
  Proc Natl Acad Sci U S A 93(26), 15457-15462 (1996)

Telling GC, 1996
  Evidence for the conformation of the pathologic isoform of the prion protein enciphering and propagating
  prion diversity
  Science 274(5295), 2079-2082 (1996)

Vey M, 1996
  Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains.
  Proc Natl Acad Sci U S A 93(25), 14945-14949 (1996)

Tatzelt J, 1996
  Chemical chaperones interfere with the formation of scrapie prion protein.
  EMBO J 15(23), 6363-6373 (1996)

Prusiner SB, 1996
  Molecular biology and pathogenesis of prion diseases.
  Trends Biochem Sci 21(12), 482-487 (1996)

Mastrianni JA, 1996
  Mutation of the prion protein gene at codon 208 in familial Creutzfeldt-Jakob disease.
  Neurology 47(5), 1305-1312 (1996)

Prusiner SB, 1996
  Prion biology and diseases--laughing cannibals, mad cows, and scientific heresy.
  Med Res Rev 16(5), 487-505 (1996) (no abstract available)

Wong K, 1996
  Decreased receptor-mediated calcium response in prion-infected cells correlates with decreased membrane
  fluidity and IP3 release.
  Neurology 47(3), 741-750 (1996)

Diez M, 1996
  Aberrant induction of neuropeptide Y mRNA in hippocampal CA3 pyramidal neurones in scrapie-infected
  Neuroreport 7(12), 1887-1892 (1996)

Heller J, 1996
  Solid-state NMR studies of the prion protein H1 fragment.
  Protein Sci 5(8), 1655-1661 (1996)

Tatzelt J, 1996
  Scrapie in mice deficient in apolipoprotein E or glial fibrillary acidic protein.
  Neurology 47(2), 449-453 (1996)

Telling GC, 1996
  Interactions between wild-type and mutant prion proteins modulate neurodegeneration in transgenic mice.
  Genes Dev 10(14), 1736-1750 (1996)

Williamson RA, 1996
  Circumventing tolerance to generate autologous monoclonal antibodies to the prion protein.
  Proc Natl Acad Sci U S A 93(14), 7279-7282 (1996)

Wille H, 1996
  Separation of scrapie prion infectivity from PrP amyloid polymers.
  J Mol Biol 259(4), 608-621 (1996)

Mehlhorn I, 1996
  High-level expression and characterization of a purified 142-residue polypeptide of the prion protein.
  Biochemistry 35(17), 5528-5537 (1996)

Lledo PM, 1996
  Mice deficient for prion protein exhibit normal neuronal excitability and synaptic transmission in the
  Proc Natl Acad Sci U S A 93(6), 2403-2407 (1996)

Riesner D, 1996
  Disruption of prion rods generates 10-nm spherical particles having high alpha-helical content and lacking
  scrapie infectivity.
  J Virol 70(3), 1714-1722 (1996)

DeArmond SJ, 1996
  Abnormal plasma membrane properties and functions in prion-infected cell lines.
  Cold Spring Harb Symp Quant Biol 61, 531-540 (1996)

Bamborough P, 1996
  Prion protein structure and scrapie replication: theoretical, spectroscopic, and genetic investigations.
  Cold Spring Harb Symp Quant Biol 61, 495-509 (1996) (no abstract available)

Prusiner SB, 1996
  Molecular biology and genetics of prion diseases.
  Cold Spring Harb Symp Quant Biol 61, 473-493 (1996) (no abstract available)

Huang Z, 1996
  Scrapie prions: a three-dimensional model of an infectious fragment.
  Fold Des 1(1), 13-19 (1996)

Wille H, 1996
  Prion protein amyloid: separation of scrapie infectivity from PrP polymers.
  Ciba Found Symp 199, 181-199 (1996)

Prusiner SB, 1996
  Transgenetics of prion diseases.
  Curr Top Microbiol Immunol 206, 275-304 (1996) (no abstract available)

Scott MR, 1996
  Transgenetics and gene targeting in studies of prion diseases.
  Curr Top Microbiol Immunol 207, 95-123 (1996) (no abstract available)

Huang Z, 1996
  Structures of prion proteins and conformational models for prion diseases.
  Curr Top Microbiol Immunol 207, 49-67 (1996) (no abstract available)

DeArmond SJ, 1996
  Transgenetics and neuropathology of prion diseases.
  Curr Top Microbiol Immunol 207, 125-146 (1996) (no abstract available)

Prusiner SB, 1996
  Human prion diseases and neurodegeneration.
  Curr Top Microbiol Immunol 207, 1-17 (1996) (no abstract available)

Gabizon R, 1996
  Insoluble wild-type and protease-resistant mutant prion protein in brains of patients with inherited prion
  Nat Med 2(1), 59-64 (1996)

Guan Z, 1996
  Lipid composition in scrapie-infected mouse brain: prion infection increases the levels of dolichyl
  phosphate and ubiquinone.
  J Neurochem 66(1), 277-285 (1996)

Kaneko K, 1995
  Prion protein (PrP) synthetic peptides induce cellular PrP to acquire properties of the scrapie isoform.
  Proc Natl Acad Sci U S A 92(24), 11160-11164 (1995)

Mastrianni JA, 1995
  Prion disease (PrP-A117V) presenting with ataxia instead of dementia.
  Neurology 45(11), 2042-2050 (1995)

Telling GC, 1995
  Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of
  cellular PrP with another protein.
  Cell 83(1), 79-90 (1995)

Wiese U, 1995
  Scanning for mutations in the human prion protein open reading frame by temporal temperature gradient
  gel electrophoresis.
  Electrophoresis 16(10), 1851-1860 (1995)

Nguyen JT, 1995
  X-ray diffraction of scrapie prion rods and PrP peptides.
  J Mol Biol 252(4), 412-422 (1995)

Spudich S, 1995
  Complete penetrance of Creutzfeldt-Jakob disease in Libyan Jews carrying the E200K mutation in the prion
  protein gene.
  Mol Med 1(6), 607-613 (1995)

Baldwin MA, 1995
  Prion protein isoforms, a convergence of biological and structural investigations.
  J Biol Chem 270(33), 19197-19200 (1995) (no abstract available)

Zhang H, 1995
  Conformational transitions in peptides containing two putative alpha-helices of the prion protein.
  J Mol Biol 250(4), 514-526 (1995)

Prusiner SB, 1995
  Molecular genetics and biophysics of prions.
  Uirusu 45(1), 5-42 (1995) (no abstract available)

Raeber AJ, 1995
  Expression and targeting of Syrian hamster prion protein induced by heat shock in transgenic Drosophila
  Mech Dev 51(2-3), 317-327 (1995)

Nguyen J, 1995
  Prion protein peptides induce alpha-helix to beta-sheet conformational transitions.
  Biochemistry 34(13), 4186-4192 (1995)

DeArmond SJ, 1995
  Etiology and pathogenesis of prion diseases.
  Am J Pathol 146(4), 785-811 (1995) (no abstract available)

Taraboulos A, 1995
  Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit
  formation of the scrapie isoform
  J Cell Biol 129(1), 121-132 (1995)

Westaway D, 1995
  On safari with PrP: prion diseases of animals.
  Trends Microbiol 3(4), 141-147 (1995)

Tatzelt J, 1995
  Scrapie prions selectively modify the stress response in neuroblastoma cells.
  Proc Natl Acad Sci U S A 92(7), 2944-2948 (1995)

Schatzl HM, 1995
  Prion protein gene variation among primates.
  J Mol Biol 245(4), 362-374 (1995)

Huang Z, 1995
  Scrapie prions: a three-dimensional model of an infectious fragment.
  Fold Des 1(1), 13-19 (1995)

Prusiner SB, 1995
  The prion diseases.
  Sci Am 272(1), 48-51 (1995) (no abstract available)

DeArmond SJ, 1995
  Prion protein transgenes and the neuropathology in prion diseases.
  Brain Pathol 5(1), 77-89 (1995)

Jefferys JGR, 1994
  Scrapie infection of transgenic mice leads to network and intrinsic dysfunction of cortical and hippocampal
  Neurobiol Dis 1(1-2), 25-30 (1994)

Jefferys JGR, 1994
  Scrapie infection of transgenic mice leads to network and intrinsic dysfunction of cortical and hippocampal
  Neurobiol Dis 1(1/2), 25-30 (1994)

Telling GC, 1994
  Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric
  human-mouse prion protein.
  Proc Natl Acad Sci U S A 91(21), 9936-9940 (1994)

Hsiao KK, 1994
  Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

  Proc Natl Acad Sci U S A 91(19), 9126-9130 (1994)

Prusiner SB, 1994
  Neurodegeneration in humans caused by prions.
  West J Med 161(3), 264-272 (1994)

Huang Z, 1994
  Proposed three-dimensional structure for the cellular prion protein.
  Proc Natl Acad Sci U S A 91(15), 7139-7143 (1994)

Westaway D, 1994
  Structure and polymorphism of the mouse prion protein gene.
  Proc Natl Acad Sci U S A 91(14), 6418-6422 (1994)

De Fea KA, 1994
  Determinants of carboxyl-terminal domain translocation during prion protein biogenesis.
  J Biol Chem 269(24), 16810-16820 (1994)

Carlson GA, 1994
  Prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and
  transgenic mice.
  Proc Natl Acad Sci U S A 91(12), 5690-5694 (1994)

Prusiner SB, 1994
  Inherited prion diseases.
  Proc Natl Acad Sci U S A 91(11), 4611-4614 (1994) (no abstract available)

Cohen FE, 1994
  Structural clues to prion replication
  Science 264(5158), 530-531 (1994) (no abstract available)

Westaway D, 1994
  Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural
  Genes Dev 8(8), 959-969 (1994)

Prusiner SB, 1994
  Human prion diseases.
  Ann Neurol 35(4), 385-395 (1994)

Prusiner SB, 1994
  Molecular biology and genetics of prion diseases.
  Philos Trans R Soc Lond B Biol Sci 343(1306), 447-463 (1994)

Kellings K, 1994
  Nucleic acids in prion preparations: unspecific background or essential component?
  Philos Trans R Soc Lond B Biol Sci 343(1306), 425-430 (1994)

DeArmond SJ, 1994
  The neuropathological phenotype in transgenic mice expressing different prion protein constructs.
  Philos Trans R Soc Lond B Biol Sci 343(1306), 415-423 (1994)

Gabizon R, 1994
  Mutation in codon 200 and polymorphism in codon 129 of the prion protein gene in Libyan Jews with
  Creutzfeldt-Jakob disease.
  Philos Trans R Soc Lond B Biol Sci 343(1306), 385-390 (1994)

Carlson GA, 1994
  Genetics of prion diseases and prion diversity in mice.
  Philos Trans R Soc Lond B Biol Sci 343(1306), 363-369 (1994)

Taraboulos A, 1994
  Biosynthesis of the prion proteins in scrapie-infected cells in culture.
  Braz J Med Biol Res 27(2), 303-307 (1994)

Gomi H, 1994
  Prion protein (PrP) is not involved in the pathogenesis of spongiform encephalopathy in zitter rats.
  Neurosci Lett 166(2), 171-174 (1994)

Westaway D, 1994
  Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice
  overexpressing wild-type prion proteins.
  Cell 76(1), 117-129 (1994)

Prusiner SB, 1994
  Prion diseases and neurodegeneration.
  Annu Rev Neurosci 17, 311-339 (1994) (no abstract available)

Fink JK, 1994
  Detecting prion protein gene mutations by denaturing gradient gel electrophoresis.
  Hum Mutat 4(1), 42-50 (1994)

Prusiner SB, 1994
  Biology and genetics of prion diseases.
  Annu Rev Microbiol 48, 655-686 (1994)

Prusiner SB, 1994
  A national strategy for development of effective methods for the prevention and treatment of Alzheimer's
  disease and related neurodegenerative disorders.
  Neurobiol Aging 15, S29-S32 (1994) (no abstract available)

Prusiner SB, 1993
  Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP
  Proc Natl Acad Sci U S A 90(22), 10608-10612 (1993)

Kristensson K, 1993
  Scrapie prions alter receptor-mediated calcium responses in cultured cells.
  Neurology 43(11), 2335-2341 (1993)

Prusiner SB, 1993
  Genetic and infectious prion diseases.
  Arch Neurol 50(11), 1129-1153 (1993)

DeArmond SJ, 1993
  The neurochemistry of prion diseases.
  J Neurochem 61(5), 1589-1601 (1993) (no abstract available)

Prusiner SB, 1993
  Transgenetics and cell biology of prion diseases: investigations of PrPSc synthesis and diversity.
  Br Med Bull 49(4), 873-912 (1993)

Gabizon R, 1993
  Mutation and polymorphism of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease (CJD).

  Am J Hum Genet 53(4), 828-835 (1993)

Borchelt DR, 1993
  Release of the cellular prion protein from cultured cells after loss of its glycoinositol phospholipid anchor.
  Glycobiology 3(4), 319-329 (1993)

DeArmond SJ, 1993
  Three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform.
  Proc Natl Acad Sci U S A 90(14), 6449-6453 (1993)

Scott M, 1993
  Propagation of prions with artificial properties in transgenic mice expressing chimeric PrP genes.
  Cell 73(5), 979-988 (1993)

Prusiner SB, 1993
  Biology of prion diseases.
  J Acquir Immune Defic Syndr 6(6), 663-665 (1993) (no abstract available)

Rogers M, 1993
  Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells.
  Proc Natl Acad Sci U S A 90(8), 3182-3186 (1993)

Prusiner SB, 1993
  Attempts to restore scrapie prion infectivity after exposure to protein denaturants.
  Proc Natl Acad Sci U S A 90(7), 2793-2797 (1993)

Carlson GA, 1993
  Delimiting the location of the scrapie prion incubation time gene on chromosome 2 of the mouse.
  Genetics 133(4), 979-988 (1993)

Stahl N, 1993
  Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing.
  Biochemistry 32(8), 1991-2002 (1993)

Prusiner SB, 1993
  Immunologic and molecular biologic studies of prion proteins in bovine spongiform encephalopathy.
  J Infect Dis 167(3), 602-613 (1993)

Prusiner SB, 1993
  Transgenetic investigations of prion diseases of humans and animals.
  Philos Trans R Soc Lond B Biol Sci 339(1288), 239-254 (1993)

Kellings K, 1993
  Analysis of nucleic acids in purified scrapie prion preparations.
  Arch Virol Suppl 7, 215-225 (1993)

Gasset M, 1993
  Perturbation of the secondary structure of the scrapie prion protein under conditions that alter infectivity.
  Proc Natl Acad Sci U S A 90(1), 1-5 (1993)

Prusiner SB, 1993
  Prion encephalopathies of animals and humans.
  Dev Biol Stand 80, 31-44 (1993)

Riesner D, 1993
  Prions and nucleic acids: search for "residual" nucleic acids and screening for mutations in the PrP-gene.
  Dev Biol Stand 80, 173-181 (1993)

Kellings K, 1993
  Analysis of nucleic acids in purified scrapie prion preparations.
  Arch Virol Suppl 7, 215-225 (1993)

Prusiner SB, 1992
  Chemistry and biology of prions.
  Biochemistry 31(49), 12277-12288 (1992) (no abstract available)

Gasset M, 1992
  Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid.
  Proc Natl Acad Sci U S A 89(22), 10940-10944 (1992)

Prusiner SB, 1992
  Natural and experimental prion diseases of humans and animals.
  Curr Opin Neurobiol 2(5), 638-647 (1992)

Gabriel JM, 1992
  Molecular cloning of a candidate chicken prion protein.
  Proc Natl Acad Sci U S A 89(19), 9097-9101 (1992)

Kretzschmar HA, 1992
  Molecular cloning of a mink prion protein gene.
  J Gen Virol 73( Pt 10), 2757-2761 (1992)

Pan KM, 1992
  Purification and properties of the cellular prion protein from Syrian hamster brain.
  Protein Sci 1(10), 1343-1352 (1992)

Giaccone G, 1992
  Prion protein preamyloid and amyloid deposits in Gerstmann-Straussler-Scheinker disease, Indiana
  Proc Natl Acad Sci U S A 89(19), 9349-9353 (1992)

Raeber AJ, 1992
  Attempts to convert the cellular prion protein into the scrapie isoform in cell-free systems.
  J Virol 66(10), 6155-6163 (1992)

Taraboulos A, 1992
  Regional mapping of prion proteins in brain.
  Proc Natl Acad Sci U S A 89(16), 7620-7624 (1992)

Borchelt DR, 1992
  Evidence for synthesis of scrapie prion proteins in the endocytic pathway.
  J Biol Chem 267(23), 16188-16199 (1992)

Taraboulos A, 1992
  Synthesis and trafficking of prion proteins in cultured cells.
  Mol Biol Cell 3(8), 851-863 (1992)

Scott MR, 1992
  Chimeric prion protein expression in cultured cells and transgenic mice.
  Protein Sci 1(8), 986-997 (1992)

Hecker R, 1992
  Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters.
  Genes Dev 6(7), 1213-1228 (1992)

Meiner Z, 1992
  Presence of prion protein in peripheral tissues of Libyan Jews with Creutzfeldt-Jakob disease
  Neurology 42(7), 1355-1360 (1992)

Stahl N, 1992
  Glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid.
  Biochemistry 31(21), 5043-5053 (1992)

Bueler H, 1992
  Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein
  Nature 356(6370), 577-582 (1992)

Hsiao K, 1992
  Mutant prion proteins in Gerstmann-Straussler-Scheinker disease with neurofibrillary tangles.
  Nat Genet 1(1), 68-71 (1992)

Dlouhy SR, 1992
  Linkage of the Indiana kindred of Gerstmann-Straussler-Scheinker disease to the prion protein gene.
  Nat Genet 1(1), 64-67 (1992)

Kellings K, 1992
  Further analysis of nucleic acids in purified scrapie prion preparations by improved return refocusing gel
  J Gen Virol 73( Pt 4), 1025-1029 (1992)

Kretzschmar HA, 1992
  Prion protein mutation at codon 102 in an Italian family with Gerstmann-Straussler-Scheinker syndrome.
  Neurology 42(4), 809-810 (1992)

Prusiner SB, 1992
  Molecular biology and genetics of neurodegenerative diseases caused by prions.
  Adv Virus Res 41, 241-280 (1992) (no abstract available)

McKinley MP, 1991
  Ultrastructural localization of scrapie prion proteins in cytoplasmic vesicles of infected cultured cells.
  Lab Invest 65(6), 622-630 (1991)

Rogers M, 1991
  Epitope mapping of the Syrian hamster prion protein utilizing chimeric and mutant genes in a vaccinia
  virus expression system.
  J Immunol 147(10), 3568-3574 (1991)

Stahl N, 1991
  Prions and prion proteins.
  FASEB J 5(13), 2799-2807 (1991)

Stahl N, 1991
  Electrospray mass spectrometry of the glycosylinositol phospholipid of the scrapie prion protein.
  Cell Biol Int Rep 15(9), 853-862 (1991) (no abstract available)

Jendroska K, 1991
  Proteinase-resistant prion protein accumulation in Syrian hamster brain correlates with regional
  pathology and scrapie infectivity.
  Neurology 41(9), 1482-1490 (1991)

Prusiner SB, 1991
  Molecular biology and pathology of scrapie and the prion diseases of humans.
  Brain Pathol 1(4), 297-310 (1991)

Prusiner SB, 1991
  Molecular biology of prion diseases.
  Science 252(5012), 1515-1522 (1991)

Prusiner SB, 1991
  Infectious and genetic manifestations of prion diseases.
  Mol Plant Microbe Interact 4(3), 226-233 (1991) (no abstract available)

Hsiao KK, 1991
  A prion protein variant in a family with the telencephalic form of Gerstmann-Straussler-Scheinker
  Neurology 41(5), 681-684 (1991)

Hsiao K, 1991
  Mutation of the prion protein in Libyan Jews with Creutzfeldt-Jakob disease.
  N Engl J Med 324(16), 1091-1097 (1991)

Prusiner SB, 1991
  Molecular biology and genetics of prions--implications for sheep scrapie, "mad cows" and the BSE epidemic.
  Historical background
  Cornell Vet 81(2), 85-101 (1991) (no abstract available)

McKinley MP, 1991
  Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis.
  J Virol 65(3), 1340-1351 (1991)

Tagliavini F, 1991
  Amyloid protein of Gerstmann-Straussler-Scheinker disease (Indiana kindred) is an 11 kd fragment of
  prion protein with an N-terminal glycine at codon 58.
  EMBO J 10(3), 513-519 (1991)

Carlson GA, 1991
  Genetics of prion infections.
  Trends Genet 7(2), 61-65 (1991)

Epstein CJ, 1991
  Acceleration of scrapie in trisomy 16----diploid aggregation chimeras.
  Ann Neurol 29(1), 95-97 (1991)

Meyer N, 1991
  Search for a putative scrapie genome in purified prion fractions reveals a paucity of nucleic acids.
  J Gen Virol 72( Pt 1), 37-49 (1991)

McKinley MP, 1991
  Ultrastructural studies of prions.
  Curr Top Microbiol Immunol 172, 75-91 (1991) (no abstract available)

Prusiner SB, 1991
  Novel properties and biology of scrapie prions.
  Curr Top Microbiol Immunol 172, 233-257 (1991) (no abstract available)

Oesch B, 1991
  Prion protein genes: evolutionary and functional aspects.
  Curr Top Microbiol Immunol 172, 109-124 (1991) (no abstract available)

Prusiner SB, 1991
  Molecular biology of prions causing infectious and genetic encephalopathies of humans as well as scrapie of
  sheep and BSE of cattle.
  Dev Biol Stand 75, 55-74 (1991)

Hsiao K, 1991
  Spontaneous neurodegeneration in transgenic mice with prion protein codon 101 proline----leucine
  Ann N Y Acad Sci 640, 166-170 (1991)

Hsiao K, 1991
  Molecular genetics and transgenic model of Gertsmann-Straussler-Scheinker disease.
  Alzheimer Dis Assoc Disord 5(3), 155-162 (1991)

Prusiner SB, 1991
  Molecular biology and transgenetics of prion diseases.
  Crit Rev Biochem Mol Biol 26(5-6), 397-438 (1991)

Prusiner SB, 1991
  Prion biology and diseases.
  Harvey Lect 87, 85-114 (1991) (no abstract available)

Hsiao KK, 1990
  Spontaneous neurodegeneration in transgenic mice with mutant prion protein
  Science 250(4987), 1587-1590 (1990)

Hsiao K, 1990
  Inherited human prion diseases.
  Neurology 40(12), 1820-1827 (1990) (no abstract available)

Prusiner SB, 1990
  Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication.
  Cell 63(4), 673-686 (1990)

Baldwin MA, 1990
  Permethylation and tandem mass spectrometry of oligosaccharides having free hexosamine: analysis of the
  glycoinositol phospholipid anchor glycan from the scrapie prion protein.
  Anal Biochem 191(1), 174-182 (1990)

Taraboulos A, 1990
  Acquisition of protease resistance by prion proteins in scrapie-infected cells does not require
  asparagine-linked glycosylation.
  Proc Natl Acad Sci U S A 87(21), 8262-8266 (1990)

Snow AD, 1990
  Immunolocalization of heparan sulfate proteoglycans to the prion protein amyloid plaques of
  Gerstmann-Straussler syndrome, Creutzfeldt-Jakob disease and scrapie.
  Lab Invest 63(5), 601-611 (1990)

Prusiner SB, 1990
  Novel structure and genetics of prions causing neurodegeneration in humans and animals.
  Biologicals 18(4), 247-262 (1990) (no abstract available)

Stahl N, 1990
  Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein.
  Biochemistry 29(38), 8879-8884 (1990)

Rogers M, 1990
  Intracellular accumulation of the cellular prion protein after mutagenesis of its Asn-linked glycosylation
  Glycobiology 1(1), 101-109 (1990)

Westaway D, 1990
  Link between scrapie and BSE?
  Nature 346(6280), 113 (1990) (no abstract available)

Oesch B, 1990
  Identification of cellular proteins binding to the scrapie prion protein.
  Biochemistry 29(24), 5848-5855 (1990)

Stahl N, 1990
  Differential release of cellular and scrapie prion proteins from cellular membranes by
  phosphatidylinositol-specific phospholipase C.
  Biochemistry 29(22), 5405-5412 (1990)

Taraboulos A, 1990
  Scrapie prion proteins accumulate in the cytoplasm of persistently infected cultured cells.
  J Cell Biol 110(6), 2117-2132 (1990)

Lopez CD, 1990
  Unusual topogenic sequence directs prion protein biogenesis.
  Science 248(4952), 226-229 (1990)

Lowenstein DH, 1990
  Three hamster species with different scrapie incubation times and neuropathological features encode
  distinct prion proteins.
  Mol Cell Biol 10(3), 1153-1163 (1990)

Borchelt DR, 1990
  Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells.
  J Cell Biol 110(3), 743-752 (1990)

Boylan KB, 1990
  DNA length polymorphism 5' to the myelin basic protein gene is associated with multiple sclerosis.
  Ann Neurol 27(3), 291-297 (1990)

Gabizon R, 1990
  Prion liposomes
  Biochem J 266(1), 1-14 (1990) (no abstract available)

Yost CS, 1990
  Non-hydrophobic extracytoplasmic determinant of stop transfer in the prion protein.
  Nature 343(6259), 669-672 (1990)

Prusiner SB, 1990
  Prion diseases of the central nervous system.
  Monogr Pathol 32, 86-122 (1990)

McKinley MP, 1990
  Nerve growth factor induces gene expression of the prion protein and beta-amyloid protein precursor in the
  developing hamster central nervous system.
  Prog Brain Res 86, 227-238 (1990) (no abstract available)

Serban D, 1990
  Rapid detection of Creutzfeldt-Jakob disease and scrapie prion proteins.
  Neurology 40(1), 110-117 (1990)

Boylan KB, 1990
  Repetitive DNA (TGGA)n 5' to the human myelin basic protein gene: a new form of oligonucleotide repetitive
  sequence showing length polymorphism.
  Genomics 6(1), 16-22 (1990)

Endo T, 1989
  Diversity of oligosaccharide structures linked to asparagines of the scrapie prion protein.
  Biochemistry 28(21), 8380-8388 (1989)

Carlson GA, 1989
  Primary structure of prion protein may modify scrapie isolate properties.
  Proc Natl Acad Sci U S A 86(19), 7475-7479 (1989)

McKinley MP, 1989
  Acceleration of scrapie in neonatal Syrian hamsters.
  Neurology 39(10), 1319-1324 (1989)

Westaway D, 1989
  Unraveling prion diseases through molecular genetics.
  Trends Neurosci 12(6), 221-227 (1989)

Hsiao K, 1989
  Linkage of a prion protein missense variant to Gerstmann-Straussler syndrome.
  Nature 338(6213), 342-345 (1989)

Owen F, 1989
  Insertion in prion protein gene in familial Creutzfeldt-Jakob disease
  Lancet 1(8628), 51-52 (1989) (no abstract available)

De Armond SJ, 1989
  PrPSc in scrapie-infected hamster brain is spatially and temporally related to histopathology and
  infectivity titer.
  Prog Clin Biol Res 317, 601-618 (1989) (no abstract available)

Gabizon R, 1989
  Immunoaffinity purification and neutralization of scrapie prions.
  Prog Clin Biol Res 317, 583-600 (1989)

Prusiner SB, 1989
  Scrapie prions.
  Annu Rev Microbiol 43, 345-374 (1989) (no abstract available)

Prusiner SB, 1989
  Creutzfeldt-Jakob disease and scrapie prions.
  Alzheimer Dis Assoc Disord 3(1-2), 52-78 (1989)

Snow AD, 1989
  Sulfated glycosaminoglycans in amyloid plaques of prion diseases.
  Acta Neuropathol (Berl) 77(4), 337-342 (1989)

Carlson GA, 1988
  Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.
  Mol Cell Biol 8(12), 5528-5540 (1988)

Mobley WC, 1988
  Nerve growth factor increases mRNA levels for the prion protein and the beta-amyloid protein precursor in
  developing hamster brain.
  Proc Natl Acad Sci U S A 85(24), 9811-9815 (1988)

Roberts GW, 1988
  CNS amyloid proteins in neurodegenerative diseases.
  Neurology 38(10), 1534-1540 (1988)

Turk E, 1988
  Purification and properties of the cellular and scrapie hamster prion proteins.
  Eur J Biochem 176(1), 21-30 (1988)

Gabizon R, 1988
  Immunoaffinity purification and neutralization of scrapie prion infectivity
  Proc Natl Acad Sci U S A 85(18), 6617-6621 (1988)

Bellinger-Kawahara CG, 1988
  Scrapie prion liposomes and rods exhibit target sizes of 55,000 Da.
  Virology 164(2), 537-541 (1988)

Butler DA, 1988
  Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins.
  J Virol 62(5), 1558-1564 (1988)

Gabizon R, 1988
  Properties of scrapie prion protein liposomes.
  J Biol Chem 263(10), 4950-4955 (1988)

Scott MR, 1988
  Prion protein gene expression in cultured cells.
  Protein Eng 2(1), 69-76 (1988)

Barry RA, 1988
  Characterization of prion proteins with monospecific antisera to synthetic peptides.
  J Immunol 140(4), 1188-1193 (1988)

Oesch B, 1988
  Search for a scrapie-specific nucleic acid: a progress report.
  Ciba Found Symp 135, 209-223 (1988)

Prusiner SB, 1988
  Molecular structure, biology, and genetics of prions.
  Adv Virus Res 35, 83-136 (1988) (no abstract available)

Carlson GA, 1988
  Genetic control of prion incubation period in mice.
  Ciba Found Symp 135, 84-99 (1988)

Prusiner SB, 1988
  Novel mechanisms of degeneration of the central nervous system--prion structure and biology.
  Ciba Found Symp 135, 239-260 (1988)

Gabizon R, 1988
  Properties of scrapie prion proteins in liposomes and amyloid rods.
  Ciba Found Symp 135, 182-196 (1988)

McKinley MP, 1988
  Developmental regulation of prion protein mRNA in brain.
  Ciba Found Symp 135, 101-116 (1988)

Prusiner SB, 1987
  Prions and neurodegenerative diseases.
  N Engl J Med 317(25), 1571-1581 (1987) (no abstract available)

Hay B, 1987
  Evidence for a secretory form of the cellular prion protein.
  Biochemistry 26(25), 8110-8115 (1987)

Braun MJ, 1987
  The burden of proof in linking AIDS to scrapie
  Nature 330(6148), 525-526 (1987) (no abstract available)

Wiley CA, 1987
  Immuno-gold localization of prion filaments in scrapie-infected hamster brains.
  Lab Invest 57(6), 646-656 (1987)

Westaway D, 1987
  Distinct prion proteins in short and long scrapie incubation period mice.
  Cell 51(4), 651-662 (1987)

Stahl N, 1987
  Scrapie prion protein contains a phosphatidylinositol glycolipid.
  Cell 51(2), 229-240 (1987)

Bellinger-Kawahara C, 1987
  Purified scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic acids.
  Virology 160(1), 271-274 (1987)

DeArmond SJ, 1987
  Changes in the localization of brain prion proteins during scrapie infection
  Neurology 37(8), 1271-1280 (1987)

Kitamoto T, 1987
  Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids.
  Lab Invest 57(2), 230-236 (1987)

Hogan RN, 1987
  Scrapie infection diminishes spines and increases varicosities of dendrites in hamsters: a quantitative Golgi
  J Neuropathol Exp Neurol 46(4), 461-473 (1987)

Bockman JM, 1987
  Immunoblotting of Creutzfeldt-Jakob disease prion proteins: host species-specific epitopes.
  Ann Neurol 21(6), 589-595 (1987)

Gabizon R, 1987
  Purified prion proteins and scrapie infectivity copartition into liposomes.
  Proc Natl Acad Sci U S A 84(12), 4017-4021 (1987)

McKinley MP, 1987
  Developmental expression of prion protein gene in brain.
  Dev Biol 121(1), 105-110 (1987)

Boylan KB, 1987
  DNA length polymorphism located 5' to the human myelin basic protein gene.
  Am J Hum Genet 40(5), 387-400 (1987)

Prusiner SB, 1987
  Prion diseases and central nervous system degeneration.
  Clin Res 35(3), 177-191 (1987) (no abstract available)

Prusiner SB, 1987
  Prions causing nervous system degeneration.
  Lab Invest 56(4), 349-363 (1987) (no abstract available)

Fernando Bazan J, 1987
  AIDS virus and scrapie protein genes
  Nature 325(6105), 581 (1987) (no abstract available)

Hay B, 1987
  Biogenesis and transmembrane orientation of the cellular isoform of the scrapie prion protein
  Mol Cell Biol 7(2), 914-920 (1987)

Bazan JF, 1987
  Predicted secondary structure and membrane topology of the scrapie prion protein.
  Protein Eng 1(2), 125-135 (1987)

Prusiner SB, 1987
  Prions causing degenerative neurological diseases.
  Annu Rev Med 38, 381-398 (1987)

Prusiner SB, 1987
  On the biology of prions.
  Acta Neuropathol (Berl) 72(4), 299-314 (1987)

Bellinger-Kawahara C, 1987
  Purified scrapie prions resist inactivation by UV irradiation.
  J Virol 61(1), 159-166 (1987)

Prusiner SB, 1986
  Prions are novel infectious pathogens causing scrapie and Creutzfeldt-Jakob disease.
  Bioessays 5(6), 281-286 (1986) (no abstract available)

Roberts GW, 1986
  Prion-protein immunoreactivity in human transmissible dementias
  N Engl J Med 315(19), 1231-1233 (1986) (no abstract available)

Crook RB, 1986
  Vasoactive intestinal peptide stimulates cyclic AMP metabolism in choroid plexus epithelial cells.
  Brain Res 384(1), 138-144 (1986)

Barry RA, 1986
  Monoclonal antibodies to the cellular and scrapie prion proteins.
  J Infect Dis 154(3), 518-521 (1986) (no abstract available)

Carlson GA, 1986
  Linkage of prion protein and scrapie incubation time genes.
  Cell 46(4), 503-511 (1986)

Kretzschmar HA, 1986
  Molecular cloning of a human prion protein cDNA.
  DNA 5(4), 315-324 (1986)

Kitamoto T, 1986
  Amyloid plaques in Creutzfeldt-Jakob disease stain with prion protein antibodies.
  Ann Neurol 20(2), 204-208 (1986)

Basler K, 1986
  Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene.
  Cell 46(3), 417-428 (1986)

McKinley MP, 1986
  Molecular characteristics of prion rods purified from scrapie-infected hamster brains.
  J Infect Dis 154(1), 110-120 (1986)

Barry RA, 1986
  Scrapie and cellular prion proteins share polypeptide epitopes.
  J Infect Dis 153(5), 848-854 (1986)

Meyer RK, 1986
  Separation and properties of cellular and scrapie prion proteins.
  Proc Natl Acad Sci U S A 83(8), 2310-2314 (1986)

Westaway D, 1986
  Conservation of the cellular gene encoding the scrapie prion protein.
  Nucleic Acids Res 14(5), 2035-2044 (1986)

Crook RB, 1986
  H2 histamine receptors on the epithelial cells of choroid plexus.
  J Neurochem 46(2), 489-493 (1986)

McKinley MP, 1986
  Biology and structure of scrapie prions.
  Int Rev Neurobiol 28, 1-57 (1986) (no abstract available)

Hogan RN, 1986
  Replication of scrapie prions in hamster eyes precedes retinal degeneration.
  Ophthalmic Res 18(4), 230-235 (1986)

Kretzschmar HA, 1986
  Scrapie prion proteins are synthesized in neurons.
  Am J Pathol 122(1), 1-5 (1986)

Prusiner SB, 1985
  Transmission of scrapie in hamsters.
  J Infect Dis 152(5), 971-978 (1985)

Monteiro ML, 1985
  A microangiopathic syndrome of encephalopathy, hearing loss, and retinal arteriolar occlusions.
  Neurology 35(8), 1113-1121 (1985)

Takahashi N, 1985
  Cloning and characterization of the myelin basic protein gene from mouse: one gene can encode both 14 kd
  and 18.5 kd MBPs by alternate use of exons.
  Cell 42(1), 139-148 (1985)

Barry RA, 1985
  Antibodies to the scrapie protein decorate prion rods.
  J Immunol 135(1), 603-613 (1985)

DeArmond SJ, 1985
  Identification of prion amyloid filaments in scrapie-infected brain.
  Cell 41(1), 221-235 (1985)

Bolton DC, 1985
  Scrapie PrP 27-30 is a sialoglycoprotein.
  J Virol 53(2), 596-606 (1985)

Bendheim PE, 1985
  Scrapie and Creutzfeldt-Jakob disease prion proteins share physical properties and antigenic determinants.
  Proc Natl Acad Sci U S A 82(4), 997-1001 (1985)

Bockman JM, 1985
  Creutzfeldt-Jakob disease prion proteins in human brains.
  N Engl J Med 312(2), 73-78 (1985)

Prusiner SB, 1985
  Scrapie and Creutzfeldt-Jakob disease prions.
  Microbiol Sci 2(2), 33-39 (1985)

Prusiner SB, 1985
  Prions--infectious pathogens causing the spongiform encephalopathies.
  CRC Crit Rev Clin Neurobiol 1(3), 181-200 (1985)

Prusiner SB, 1985
  Scrapie prions, brain amyloid, and senile dementia.
  Curr Top Cell Regul 26, 79-95 (1985) (no abstract available)

Bolton DC, 1984
  Molecular characteristics of the major scrapie prion protein.
  Biochemistry 23(25), 5898-5906 (1984)

Prusiner SB, 1984
  Sci Am 251(4), 50-59 (1984) (no abstract available)

Friedland RP, 1984
  Bitemporal hypometabolism in Creutzfeldt-Jakob disease measured by positron emission tomography with
  J Comput Assist Tomogr 8(5), 978-981 (1984)

Bendheim PE, 1984
  Antibodies to a scrapie prion protein.
  Nature 310(5976), 418-421 (1984)

Prusiner SB, 1984
  Purification and structural studies of a major scrapie prion protein.
  Cell 38(1), 127-134 (1984)

Prusiner SB, 1984
  Some speculations about prions, amyloid, and Alzheimer's disease.
  N Engl J Med 310(10), 661-663 (1984) (no abstract available)

Crook RB, 1984
  Hormones and neurotransmitters control cyclic AMP metabolism in choroid plexus epithelial cells.
  J Neurochem 42(2), 340-350 (1984)

Prusiner SB, 1984
  Prions: novel infectious pathogens.
  Adv Virus Res 29, 1-56 (1984) (no abstract available)

Prusiner SB, 1983
  Scrapie prions aggregate to form amyloid-like birefringent rods.
  Cell 35(2), 349-358 (1983)

Hogan RN, 1983
  Retinal degeneration in experimental Creutzfeldt-Jakob disease.
  Lab Invest 49(6), 708-715 (1983)

McKinley MP, 1983
  A protease-resistant protein is a structural component of the scrapie prion.
  Cell 35(1), 57-62 (1983)

Roach A, 1983
  Characterization of cloned cDNA representing rat myelin basic protein: absence of expression in brain of
  shiverer mutant mice.
  Cell 34(3), 799-806 (1983)

Baringer JR, 1983
  Replication of the scrapie agent in hamster brain precedes neuronal vacuolation.
  J Neuropathol Exp Neurol 42(5), 539-547 (1983)

Kingsbury DT, 1983
  Genetic control of scrapie and Creutzfeldt-Jakob disease in mice.
  J Immunol 131(1), 491-496 (1983)

McKinley MP, 1983
  Resistance of the scrapie agent to inactivation by psoralens.
  Photochem Photobiol 37(5), 539-545 (1983) (no abstract available)

Bolton DC, 1982
  Identification of a protein that purifies with the scrapie prion.
  Science 218(4579), 1309-1311 (1982)

Prusiner SB, 1982
  Further purification and characterization of scrapie prions.
  Biochemistry 21(26), 6942-6950 (1982) (no abstract available)

Kasper KC, 1982
  Immunological studies of scrapie infection.
  J Neuroimmunol 3(3), 187-201 (1982) (no abstract available)

Diener TO, 1982
  Viroids and prions.
  Proc Natl Acad Sci U S A 79(17), 5220-5224 (1982)

Prusiner SB, 1982
  Research on scrapie
  Lancet 2(8296), 494-495 (1982) (no abstract available)

Prusiner SB, 1982
  Kuru with incubation periods exceeding two decades.
  Ann Neurol 12(1), 1-9 (1982)

Prusiner SB, 1982
  Novel proteinaceous infectious particles cause scrapie.
  Science 216(4542), 136-144 (1982)

Prusiner SB, 1982
  Measurement of the scrapie agent using an incubation time interval assay.
  Ann Neurol 11(4), 353-358 (1982)

McKinley MP, 1981
  Reversible chemical modification of the scrapie agent.
  Science 214(4526), 1259-1261 (1981)

Prusiner SB, 1981
  Scrapie agent contains a hydrophobic protein.
  Proc Natl Acad Sci U S A 78(11), 6675-6679 (1981)

Prusiner SB, 1981
  Thiocyanate and hydroxyl ions inactivate the scrapie agent.
  Proc Natl Acad Sci U S A 78(7), 4606-4610 (1981)

Baringer JR, 1981
  Scrapie-associated particles in postsynaptic processes. Further ultrastructural studies.
  J Neuropathol Exp Neurol 40(3), 281-288 (1981)

Prusiner SB, 1981
  Determination of scrapie agent titer from incubation period measurements in hamsters.
  Adv Exp Med Biol 134, 385-399 (1981)

Hogan RN, 1981
  Progressive retinal degeneration in scrapie-infected hamsters: a light and electron microscopic analysis.
  Lab Invest 44(1), 34-42 (1981)

Kasper KC, 1981
  Toward development of assays for scrapie-specific antibodies.
  Adv Exp Med Biol 134, 401-413 (1981) (no abstract available)

Hadlow WJ, 1980
  Brain tissue from persons dying of Creutzfeldt-Jakob disease causes scrapie-like encephalopathy in goats.
  Ann Neurol 8(6), 628-632 (1980)

Prusiner SB, 1980
  Gel electrophoresis and glass permeation chromatography of the hamster scrapie agent after enzymatic
  digestion and detergent extraction.
  Biochemistry 19(21), 4892-4898 (1980) (no abstract available)

Prusiner SB, 1980
  Molecular properties, partial purification, and assay by incubation period measurements of the hamster
  scrapie agent.
  Biochemistry 19(21), 4883-4891 (1980)

Prusiner SB, 1980
  Experimental scrapie in the mouse: electrophoretic and sedimentation properties of the partially purified
  J Neurochem 35(3), 574-582 (1980)

Chatigny MA, 1980
  Biohazards of investigations on the transmissible spongiform encephalopathies.
  Rev Infect Dis 2(5), 713-724 (1980)

Prusiner SB, 1980
  Electrophoretic properties of the scrapie agent in agarose gels.
  Proc Natl Acad Sci U S A 77(5), 2984-2988 (1980)

Prusiner SB, 1980
  Slow viruses: molecular properties of the agents causing scrapie in mice and hamsters.
  Prog Clin Biol Res 39, 73-89 (1980) (no abstract available)

Chatigny MA, 1979
  Evaluation of a class III biological safety cabinet for enclosure of an ultracentrifuge.
  Appl Environ Microbiol 38(5), 934-939 (1979)

Prusiner SB, 1979
  Evidence for multiple molecular forms of the scrapie agent. pp. 591-613.
  Persistent viruses , 591-613 (1979) (no abstract available)

Prusiner SB, 1978
  Sedimentation characteristics of the scrapie agent from murine spleen and brain.
  Biochemistry 17(23), 4987-4992 (1978)

Prusiner SB, 1978
  Partial purification and evidence for multiple molecular forms of the scrapie agent.
  Biochemistry 17(23), 4993-4999 (1978)

Baringer JR, 1978
  Experimental scrapie in mice: ultrastructural observations.
  Ann Neurol 4(3), 205-211 (1978)

Garfin DE, 1978
  Mitogen stimulation of splenocytes from mice infected with scrapie agent.
  J Infect Dis 138(3), 396-400 (1978)

Garfin DE, 1978
  Suppression of polyclonal B cell activation in scrapie-infected C3H/HeJ mice.
  J Immunol 120(6), 1986-1990 (1978)

Prusiner SB, 1978
  An approach to the isolation of biological particles using sedimentation analysis.
  J Biol Chem 253(3), 916-921 (1978)

Prusiner SB, 1978
  Evidence for hydrophobic domains on the surface of the scrapie agent.
  Trans Am Neurol Assoc 103, 62-64 (1978) (no abstract available)

Prusiner SB, 1977
  Sedimentation properties of the scrapie agent.
  Proc Natl Acad Sci U S A 74(10), 4656-4660 (1977)

X-Sender: Mime-Version: 1.0 Approved-By: "Robert A. LaBudde" Date: Tue, 7 Oct 1997 17:42:04 -0400 Reply-To: Bovine Spongiform Encephalopathy Sender: Bovine Spongiform Encephalopathy From: "Robert A. LaBudde" Subject: Prusiner & Nobel Prize To: "Dr. Thomas Pringle" Source: FSNET (D. Powell, Univ. Guelph) U.S. SCIENTIST WINS NOBEL PRIZE FOR CONTROVERSIAL WORK October 7, 1997 The New York Times/ San Francisco Examiner/ Washington Post Lotsa coverage this morning of Stanley B. Prusiner winning the Nobel Prize in physiology or medicine yesterday for his work on prions. Dr. Lars Edstrom, a member of the Nobel award committee at the Karolinska Institute in Sweden and the head of its neurology department was quoted as saying, "There are still people who don't believe that a protein can cause these diseases, but we believe it." Prusiner is the first single winner since 1987 and only the sixth in the last 40 years. Prusiner was cited as saying that he did not believe he was necessarily vindicated by the Nobel award, adding that, "Concepts are vindicated by the constant accrual of data and independent verification of data. No prize, not even a Nobel Prize, can make something true that is not true." Prusiner added that skepticism was important in science; it forces researchers to provide convincing evidence, he said, because the overwhelming majority of new concepts turn out to be wrong. Dr. Byron Caughey of the federal Rocky Mountain Laboratories in Hamilton, Mont., was cited as conceding in a statement that Prusiner "tirelessly and charismatically stimulated interest in the field," but added that "there is no direct proof that a protein alone is the infectious agent (or that a virus isn't involved) and considerable uncertainty remains about how these enigmatic infectious agents propagate and cause disease." Dr. Laura Manuelidis, who is head of neuropathology at Yale Medical School and a leading critic of Prusiner's claims, was cited as saying the Nobel committee's endorsement of the prion theory would stifle other avenues of inquiry. Dr. Manuelidis added she suspected that a virus would ultimately be proved the culprit in mad cow disease and other diseases attributed to prions. The story adds that since 1975, the U.S. National Institutes of Health has paid more than $56 million in grants to Prusiner to carry out his research. Robert Rohwer, director of the Molecular Neurovirology Unit at the Veterans Administration Medical Center in Baltimore, was quoted as telling Science that, "The prion hypothesis is really the cold fusion of infectious disease - it's a very radical idea and just like cold fusion it has some very appealing aspects. But because it's so radical, it deserves a very very high level of criticism and scrutiny before it's adopted."

Backgrounder on Stanley B. Prusiner, M.D., UCSF discoverer of the "prion"

 October 6, 1997 (from a press release)
Stanley B. Prusiner, MD, 55, is Professor of Neurology and Biochemistry and Biophysics at the University of California, San Francisco. Prusiner discovered and characterized an entirely new class of proteins called prions, which cause several rare and fatal neurodegenerative diseases.

Prusiner's elegant work and seminal experiments, often conducted and presented in the face of skepticism and controversy, have proved revolutionary in establishing the cause of some of the most baffling diseases of the central nervous system.

The identification of an entirely new class of disease-causing pathogens that appears to replicate without genes is one of the most revolutionary conceptual advances in medicine and has opened a new era of biological research. To set forth what many scientists considered to be the heretical idea that the transmissible agent in several rare neurodegenerative diseases is a protein, and not a slow-acting virus as had been generally thought, required great scientific and personal courage.

Among these diseases are scrapie, an infectious disease of sheep, and "mad cow" disease, an infectious prion disease responsible for an epidemic among cattle in Great Britain fed meat and bone meal contaminated with scrapie prions. The most exotic infectious prion disease of humans is kuru, which was spread among New Guinea aborigines by ritualistic cannibalism.

In 1982, Prusiner proposed that the infectious agent causing scrapie, a neurodegenerative disease of sheep, is a mysterious pathogen which he named the prion, for proteinaceous infectious particle. From the brains of scrapie-infected animals, Prusiner and his colleagues purified the prion (pronounced PREE-on), which appeared to be composed only of protein. When Prusiner looked in the prion for a nucleic acid (DNA or RNA) that could direct the synthesis of progeny prions, he was unable to find one.

This discovery posed a conundrum that seemed to threaten the very foundations of modern biology, as nucleic acids are the building blocks of genes, the basic units of heredity found in all living organisms, including viruses. These genes must be passed on to progeny in each generation. Genes encode proteins which are the action molecules of life, controlling metabolism, movement and growth. Yet prions, apparently lacking genes, multiply nonetheless.

Research conducted by Prusiner and his colleagues revealed that the protein of the prion was derived from a normal protein that is encoded by a gene found in all animals examined, including humans. Prusiner called this protein "prion protein," or PrP.

In 1986, Prusiner and his colleagues substantially advanced prion research when they found that the tempo of scrapie in animals is controlled by the sequence of nucleic-acid building blocks in the gene encoding PrP. Three years later, they reported that patients dying of Gerstmann-Straussler-Scheinker disease possess a specific nucleic-acid substitution, or mutation, in the PrP gene. Slightly different mutations in the PrP gene were also found in familial Creutzfeldt-Jakob disease (CJD).

Next, Prusiner and his colleagues produced genetically engineered (transgenic) mice harboring PrP genes with the human disease mutation. As a result of this genetic alteration, these animals spontaneously developed brain degeneration similar to that seen in scrapie after inoculation with prions.

The finding from these studies that prion disease can arise as a result of genetic alterations posed yet another riddle for those scientists who believed that scrapie, GSS and CJD are caused by slow-acting viruses, which are not transmitted across generations according to the laws of genetics.

The results of the experiments on genetically engineered animals led Prusiner to conclude that prion disease can be inherited as well as infectious, a truly unprecedented notion.

His ideas explained how prion diseases of humans can (1) arise spontaneously in some people, (2) be inherited by patients who have a family history of prion disease, or (3) be acquired by infection.

In a study that spanned almost a decade, Prusiner and his colleagues searched for the difference between the normal and disease forms of the prion protein. They eventually discovered that the normal form of PrP is folded into a twisted corkscrew or helical shape, whereas the disease-associated form exists as a flattened sheet.

For several decades each protein has been thought to have only a single, natural shape. Therefore, Prusiner, by demonstrating that the normal corkscrew form of the prion protein can change its shape into the disease-associated sheet-like form, again challenged another basic tenet of biology. Shape is vital to a protein, because it determines protein activity.

Studies with genetically engineered mice over the past six years have revealed that the interaction of the normal, or "C" form of PrP, with the diseased, or "S" form, underlies the multiplication of prions. The disease form of PrP seems to act as a template for the refolding of normal PrP into a second diseased PrP.

Prusiner emphasizes that prion replication is a complicated process. In a family with a history of inherited prion disease, two different "C" forms of PrP can exist in the same individual. One "C" form of PrP is the normal, or as geneticists call it, the wild-type form and the other "C" form of PrP is a mutant one. A mutation within the PrP gene programs the brain to produce mutant PrP in which one or more amino acids have been changed. The amino acid substitution seems to destabilize the "C" shape of PrP and render it more susceptible to folding into the "S" form.

Among humans carrying a mutation of the PrP gene, nearly all will develop prion disease; whereas only one in a million with normal PrP become ill. Using transgenic mice carrying artificial PrP genes, Prusiner and his colleagues also have begun to unravel the mysteries of the "species barrier," the obstacle that minimizes transmission of prion disease from one species to another. The UCSF researchers have constructed artificial genes by embedding a segment of the PrP gene from the human or hamster within that of the mouse, and they have found the barrier is due to slight differences among species in the amino acid sequence of the prion gene.

Genetically engineered mice have also been used by Prusiner and his colleagues to investigate some of the processes that cause brain degeneration in humans. The accumulation of the "S" form of PrP, sometimes as large clumps or plaques in the brain, seems to be responsible for the pathologic insults that the brain suffers as it undergoes degeneration. From these and other investigations, Prusiner concludes that prion diseases are disorders of protein shape.

While Prusiner indisputably continues to be a leader in the study of neurodegenerative diseases, he credits the many years of hard work by his many talented colleagues for his success. His own dedication to advancing investigations of all neurodegenerative diseases, including more common disorders such as Alzheimer's disease, Parkinson's disease and ALS (Lou Gehrig's disease), is widely recognized.

Prusiner was born in Des Moines, Iowa and received his undergraduate training and MD degree from the University of Pennsylvania. He is the winner of numerous awards and honors including the Albert Lasker Basic Medical Research Award, the Potamkin Prize, the Wolf Prize, the J. Elliott Royer Award, the Ehrlich-Darmstaedter Award, the Gairdner Foundation Award, the Charles A. Dana Award and the Max-Planck-Forschungspreis.

Swiss scientists surprised by Nobel medicine award

Reuters North America Tue, Oct 7, 1997 By Greg Calhoun
ZURICH, Switzerland (Reuter) - Swiss-based scientists involved in research on the links between mad cow disease and its human variant expressed surprise Tuesday that the Nobel Prize went to a lone American with whom one of them recently worked. It was announced Monday that American neurologist Stanley Prusiner had won the Nobel prize for medicine. He won the prize for his discovery of the prion, a usually benign brain protein that mutates into a new form blamed for causing the brain-wasting illness disease (CJD) and its cousin, bovine spongiform encephalopathy (BSE or mad cow disease).

Adriano Aguzzi, a researcher at Zurich University Hospital, said he was not disappointed by the Nobel committee's decision to award Prusiner the prize. But he was surprised by the fact that the American won the prize alone. Aguzzi said his colleague Charles Weissmann, a scientist at Zurich University's Institute for Molecular Biology, had contributed a similar amount of data to support the prion theory. Aguzzi has worked with Weissmann on prion-related research for the past six years.

Prusiner's interest in prion disease started in 1972, when he was a resident or junior doctor at a San Francisco hospital and one of his patients died of CJD. His work with prions was treated with skepticism at first but took on new importance with the 1980s outbreak of BSE in Britain. There are known genetic mutations that predispose to BSE, as well as to scrapie and CJD. Aguzzi said that in 1993 Weissmann's work showed that the absence of the gene prevented the disease.

"Prusiner himself said this. He said that actually it was unfair that he was the only one to get the Nobel Prize because many people contributed," Aguzzi said in a telephone interview. "Some experiments were conducted in San Francisco and some were done in Zurich," he added.
According to the Swiss daily Tages-Anzeiger, another Swiss scientist involved in prion research, Bruno Oesch, also expressed disappointment that Weissman's work was ignored.
"While there is no doubt that Stan Prusiner has merited the Nobel Prize, I was astonished that he would get it alone, not shared with Charles Weissmann," he was quoted as saying.
" The newspaper article also pointed out that Prusiner and Weissmann together were cited recently by the German foundation, Gertrud Reemtsma Stiftung, for their research work. Weissmann could not be reached for comment. But his office provided a written statement in which the researcher praised the American researcher.
"Prusiner is a true pioneer and iconoclast, and fully deserves the Nobel Prize he has been awarded," Weissmann said in the statement.

Prusiner awarded the Nobel prize for work on prions

Lancet Oct 11, 1997
Dorothy Bonn, Alicia Ault
This year's Nobel prize for physiology or medicine has been awarded to Stanley Prusiner for his discovery of prions and their role in the pathogenesis of fatal dementias associated with spongiform brain changes. Prusiner's work has a special meaning for people in the UK, where 20 out of the 21 confirmed cases of new variant Creutzfeldt-Jakob disease (nvCJD), a prion disease, have occurred.

Prusiner, speaking in Washington, DC, USA, after hearing of the award, said, "I don't think we have any major new threats on the horizon", in the USA, but added, "it's not like what they are facing in Great Britain where a large number of young people may get CJD". Prusiner's fears about the UK situation were echoed by the admission on Oct 7 by the UK government that there may be a risk of nvCJD transmission via blood donations.

When Prusiner, now professor of neurology, virology, and biochemistry at the University of California (San Francisco and Berkeley, CA, USA), began his award-winning work in 1972, classical CJD, like kuru and scrapie, was already known to be transmissible through extracts of diseased brains. Prusiner took 10 years to isolate the "proteinaceous infectious particle" (prion) from scrapie-infected hamster brain. But, since all known infectious agents contained DNA or RNA, Prusiner's "protein only" hypothesis of CJD pathogenesis was met with scepticism.

In 1984, Prusiner and colleagues identified the prion gene and demonstrated its presence in all animals tested, including man. Then came the startling discovery that the prion protein (PrP) could fold into two distinct conformations. One version resulted in disease (PrPSc), the other (PrPC) did not. PrPSc, claimed Prusiner, was infectious and could initiate a chain reaction that resulted in the conversion of PrPC to PrPSc.

Even now, not all researchers are wholly convinced by the prion hypothesis. Moira Bruce (Institute for Animal Health, Edinburgh, UK), for instance, argues that there are potentially too many strains of transmissible spongiform encephalopathy to be accommodated by PrP conformations alone. "The prize", says Bruce, "acknowledges Prusiner's enormous contribution to the field but there are still a lot of questions hanging over the prion hypothesis".

Prusiner is used to criticism of his theory, and said in Washington that "most new radical scientific ideas turn out to be incorrect. What's correct is based on data and independent confirmation of data". A "delighted and honoured" Prusiner went on to tell the Washington audience that he is working with Fred Cohen and other colleagues on a drug therapy for sporadic CJD and hopes to have a product in "5 to 10 years". He also hopes that this will provide a blueprint to develop a drug for Alzheimer's disease and Parkinson's disease, which Prusiner believes are caused by similar protein aberrations.

STANLEY B PRUSINER, born May 28, 1942

Department of Neurology, HSE-781, University of California, School of Medicine, San Francisco, CA 94143-0518, USA

Academic Education:

1964 A.B. (cum laude), University of Pennsylvania, The College
1968 M.D., University of Pennsylvania, School of Medicine, Philadelphia, PA
1968-69 Internship in Medicine, University of California, San Francisco, CA
1972-74 Residency in Neurology, University of California, San Francisco, CA

Appointments and Professional Activities:

1974-80 Assistant Professor of Neurology in Residence, Univ of California, SF
1976-88 Lecturer, Department of Biochemistry and Biophysics, UCSF
1979-83 Assistant Professor of Virology in Residence, UC, Berkeley
1980-81 Associate Professor of Neurology in Residence, UCSF
1981-84 Associate Professor of Neurology, UCSF
1983-84 Associate Professor of Virology in Residence, UC, Berkeley
1984- Professor of Neurology, UCSF
1984- Professor of Virology in Residence, UC, Berkeley
1988- Professor of Biochemistry, UCSF

Major Honors and Awards:

Potamkin Prize for Alzheimer's Disease Research, American Academy of Neurology, 1991
Christopher Columbus Quincentennial Discovery Award in Biomedical Research, NIH, 1992 Metropolitan Life Foundation Award for Medical Research, 1992
Dickson Prize for Distinguished Scientific Accomplishments, University of Pittsburgh, 1992
Charles A. Dana Award for Pioneering Achievements in Health, 1992
Richard Lounsbery Award for Extraordinary Scientific Research, NAS, 1993
Gairdner Foundation Award for Outstanding Achievement in Medical Science, 1993
Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Res., 1994
Albert Lasker Award for Basic Medical Research, Albert and Mary Lasker Foundation, 1994
Paul Ehrlich Prize, Paul Ehrlich Foundation and the Federal Republic of Germany, 1995
Wolf Prize in Medicine, Wolf Foundation and the State of Israel, 1996
Keio International Award for Medical Science, Keio University, Tokyo, Japan, 1996

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