Best Post of January 2016: Assistance Needed for National Prion Surveillance!

The next in our "Best of the Month" series is a guest post by Mark Cohen, MD and Jeff Negrey

An important request from Dr. Mark Cohen and Jeff Negrey on behalf of the National Prion Disease Pathology Surveillance Center (NPDPSC):

The NPDPSC serves the United States as the national testing site and repository for tissue samples from suspected cases of prion disease (CJD and others). We accept any autopsy tissues for free-of-charge prion testing. With proper tissue procurement, we are able to diagnose with certainty whether or not prion disease is present; and if so, exactly which form and subtype of prion disease (sporadic vs. familial vs. variant) the patient has. Tissue samples are then stored indefinitely and shared with qualified researchers and institutions around the globe.

In order to provide accurate surveillance of prion diseases in the United States, the NPDPSC needs to test CNS tissue. Patients often pass away in non-hospital settings, and even for those who die in hospital, there is ever-increasing reluctance among medical institutions to perform post-mortem examination on patients if CJD is even considered a possibility. Therefore, the NPDPSC offers financial and logistical assistance to families with loved ones suffering from suspected prion disease to obtain a brain-only autopsy and subsequent testing for CJD free of charge to the surviving family (including transportation to-and-from a regional autopsy site if needed). These procedures are coordinated with the nearest approved regional site willing to perform these procedures.

NPDPSC Staff

Our national network is a group of public and private autopsy providers located across the country. Sometimes procedures are performed in hospital settings; other times they are performed in mortuary settings prior to final arrangements. We are always looking to add autopsy and mortuary professionals to our network. We encourage all hospitals and medical centers to send us tissue samples from possible prion disease cases as part of our mission to identify and contain potential outbreaks of prion disease. However, we also are willing to reimburse individuals or institutions who accept brain autopsy requests on our behalf. We arrange transport of the patient to a pre-designated autopsy site and provide free-of-charge shipping materials for sending tissue.

If you, or someone you know, would like to join our national network of autopsy providers, please contact Jeff Negrey for further information (phone 216-368-1290 or email jtn8@case.edu).

Guest Post by Mark Cohen and Jeffrey Negrey: Assistance needed for national prion surveillance!

An important request from Dr. Mark Cohen and Jeff Negrey on behalf of the National Prion Disease Pathology Surveillance Center (NPDPSC):

The NPDPSC serves the United States as the national testing site and repository for tissue samples from suspected cases of prion disease (CJD and others). We accept any autopsy tissues for free-of-charge prion testing. With proper tissue procurement, we are able to diagnose with certainty whether or not prion disease is present; and if so, exactly which form and subtype of prion disease (sporadic vs. familial vs. variant) the patient has. Tissue samples are then stored indefinitely and shared with qualified researchers and institutions around the globe.

In order to provide accurate surveillance of prion diseases in the United States, the NPDPSC needs to test CNS tissue. Patients often pass away in non-hospital settings, and even for those who die in hospital, there is ever-increasing reluctance among medical institutions to perform post-mortem examination on patients if CJD is even considered a possibility. Therefore, the NPDPSC offers financial and logistical assistance to families with loved ones suffering from suspected prion disease to obtain a brain-only autopsy and subsequent testing for CJD free of charge to the surviving family (including transportation to-and-from a regional autopsy site if needed). These procedures are coordinated with the nearest approved regional site willing to perform these procedures.

NPDPSC Staff

Our national network is a group of public and private autopsy providers located across the country. Sometimes procedures are performed in hospital settings; other times they are performed in mortuary settings prior to final arrangements. We are always looking to add autopsy and mortuary professionals to our network. We encourage all hospitals and medical centers to send us tissue samples from possible prion disease cases as part of our mission to identify and contain potential outbreaks of prion disease. However, we also are willing to reimburse individuals or institutions who accept brain autopsy requests on our behalf. We arrange transport of the patient to a pre-designated autopsy site and provide free-of-charge shipping materials for sending tissue.

If you, or someone you know, would like to join our national network of autopsy providers, please contact Jeff Negrey for further information (phone 216-368-1290 or email jtn8@case.edu).

Best Post of March 2015: The asinine reason why the name JCD was converted to CJD

The next in our "Best of the Month" series is from March 25, 2015.

Originally referred to as Jakob-Creutzfeldt disease (and believed by many to rightfully be called simply Jakob's disease), we now refer to this prion disease as Creutzfeldt-Jakob disease. Why? It all stems from a Dr. C. Joseph Gibbs, a colleague of D. Carleton Gajdusek's at the National Institutes of Health, who worked on this disease back in the 1960's. Here's the explanation, lifted from Nobel laureate Stanley Prusiner's Madness and Memory: The Discovery of Prions - A New Biological Principle of Disease:

"Alfons Jakob wrote a paper in 1921 describing several cases of progressive dementia with widespread neuronal loss in the brain. A year earlier, Hans Creutzfeldt had described the brain of a woman who died after a prolonged series of seizures. He found widespread vacuolation, but some medical scientists believe that his patient died of a seizure disorder complicated by hypoxic brain damage and doubt that she had what became known as CJD. So why did the named Jakob and Creutzfeldt become flipped in an important report on the disease, regarding the transmission to a chimpanzee? Twenty years passed before I found the answer, in conversation with Gibbs. 'When I was writing my first paper on the transmission of Jakob-Creutzfeldt disease to an ape,' he told me, 'I wanted to rename the disease Gibbs disease. I didn't think this would be acceptable to the scientific and medical communities, so I decided to reverse the names, because my first name is Clarence and my middle name is Joseph and my initials are C.J.' Thus did the diease become known as Creutzfeldt-Jakob disease, or CJD for short - a case of mind-boggling scientific mischief." 

Gibbs (left) and Gajdusek with a New Guinea kuru patient in 1972.

 
A remarkable case ofhubris, although from what I hear about Prusiner, he is not one to point fingers at those who grasp credit for the work of others.Gajdusek, also a Nobel prize winner, once wrote inhis diary the following about Prusiner:


""I never heard a word of original thought from you nor read such ideas in anything you authored for which I did not recognize immediately its source, which you always went out of your way to obscure. You a heretic? You a martyr? You a defender of unacceptable ideas? Bullshit! You shrewdly jumped onto a bandwagon of creative ideas and experimental work and shrewdly got on to the winning cart, proclaiming outrageously in press and media it was yours! I respect you less and less as your despicable game succeeds and you bask in your coveted fame."

But then again, Gajdusek himself, who died in 2008 at age 85, was no paragon of virtue.In the course of his research trips in the South Pacific to study kuru , Gajdusek had brought 56 mostly male children back to live with him in the United States, and provided them with the opportunity to receive high school and college education. He was later accused by one of these, now an adult man, of molesting him as a child. In fact, seven men testified in confidentiality about Gajdusek having had sex with them when they were boys.  Gajdusek was charged with child molestation in April 1996, based on incriminating entries in his personal diary and statements from a victim. He pleaded guilty in 1997 and, under a plea bargain, was sentenced to 12 months in jail. After his release in 1998, he was permitted to serve his five-year unsupervised probation in Europe. He never returned to the United States and ultimately died in Norway.

Best Post of January 2015: Dr. Pierluigi Gambetti steps down as director of national prion surveillance center

The next in our "Best of the Month" series comes from January 5, 2015:

Pierluigi Gambetti, MD

Dr. Pierluigi Gambetti has stepped down as director of the National Prion Disease Pathology Surveillance Center. In a letter to members of the American Association of Neuropathologists, Dr. Gambetti writes:

"I will be resigning as Director of the National Prion Disease Pathology Surveillance Center effective January 1, 2015. I will continue to be associated with the Center in an advisory position and as consultant for special cases. Dr. Jiri Safar, Associate Professor of Pathology and Neurology at Case Western Reserve University, will be the new director."

Dr. Gambetti goes on to state that the NPDPSC "will remain unchanged", continuing to coordinate autopsies on suspected prion disease cases. Dr. Mark Cohen will continue to have primary responsibility for the histologic and immunohistochemical assessment of cases.

The asinine reason why the name JCD was converted to CJD

Originally referred to as Jakob-Creutzfeldt disease (and believed by many to rightfully be called simply Jakob's disease), we now refer to this prion disease as Creutzfeldt-Jakob disease. Why? It all stems from a Dr. C. Joseph Gibbs, a colleague of D. Carleton Gajdusek at the National Institutes of Health, who worked on this disease back in the 1960's. Here's the explanation, lifted from Nobel laureate Stanley Prusiner's Madness and Memory: The Discovery of Prions - A New Biological Principle of Disease:

"Alfons Jakob wrote a paper in 1921 describing several cases of progressive dementia with widespread neuronal loss in the brain. A year earlier, Hans Creutzfeldt had described the brain of a woman who died after a prolonged series of seizures. He found widespread vacuolation, but some medical scientists believe that his patient died of a seizure disorder complicated by hypoxic brain damage and doubt that she had what became known as CJD. So why did the named Jakob and Creutzfeldt become flipped in an important report on the disease, regarding the transmission to a chimpanzee? Twenty years passed before I found the answer, in conversation with Gibbs. 'When I was writing my first paper on the transmission of Jakob-Creutzfeldt disease to an ape,' he told me, 'I wanted to rename the disease Gibbs disease. I didn't think this would be acceptable to the scientific and medical communities, so I decided to reverse the names, because my first name is Clarence and my middle name is Joseph and my initials are C.J.' Thus did the diease become known as Creutzfeldt-Jakob disease, or CJD for short - a case of mind-boggling scientific mischief." 

Gibbs (left) and Gajdusek with a New Guinea kuru patient in 1972.

 
A remarkable case of hubris, although from what I hear about Prusiner, he is not one to point fingers at those who grasp credit for the work of others. Gajdusek, also a Nobel prize winner, once wrote in his diary the following about Prusiner:


""I never heard a word of original thought from you nor read such ideas in anything you authored for which I did not recognize immediately its source, which you always went out of your way to obscure. You a heretic? You a martyr? You a defender of unacceptable ideas? Bullshit! You shrewdly jumped onto a bandwagon of creative ideas and experimental work and shrewdly got on to the winning cart, proclaiming outrageously in press and media it was yours! I respect you less and less as your despicable game succeeds and you bask in your coveted fame."

But then again, Gajdusek himself, who died in 2008 at age 85, was no paragon of virtue.In the course of his research trips in the South Pacific to study kuru , Gajdusek had brought 56 mostly male children back to live with him in the United States, and provided them with the opportunity to receive high school and college education. He was later accused by one of these, now an adult man, of molesting him as a child. In fact, seven men testified in confidentiality about Gajdusek having had sex with them when they were boys.  Gajdusek was charged with child molestation in April 1996, based on incriminating entries in his personal diary and statements from a victim. He pleaded guilty in 1997 and, under a plea bargain, was sentenced to 12 months in jail. After his release in 1998, he was permitted to serve his five-year unsupervised probation in Europe. He never returned to the United States and ultimately died in Norway.

Dr. Pierluigi Gambetti steps down as director of national prion surveillance center

Pierluigi Gambetti, MD

Dr. Pierluigi Gambetti has stepped down as director of the National Prion Disease Pathology Surveillance Center. In a letter to members of the American Association of Neuropathologists, Dr. Gambetti writes:

"I will be resigning as Director of the National Prion Disease Pathology Surveillance Center effective January 1, 2015. I will continue to be associated with the Center in an advisory position and as consultant for special cases. Dr. Jiri Safar, Associate Professor of Pathology and Neurology at Case Western Reserve University, will be the new director."

Dr. Gambetti goes on to state that the NPDPSC "will remain unchanged", continuing to coordinate autopsies on suspected prion disease cases. Dr. Mark Cohen will continue to have primary responsibility for the histologic and immunohistochemical assessment of cases.

Best Post of April 2014: Nobel Laureate Prusiner Tells His Story

The next in our  "Best of the Month" series is from April 8, 2014:

Just published by Yale University Press: Stanley Prusiner's new book, Madness and Memory: The Discovery of Prions - A New Biological Principle of Disease, is now available for purchase. Although I am not personally a big fan of Dr. Oliver Sacks's work, his blurb on Prusiner's book is worth reading: “Stanley Prusiner is a brilliant scientist whose boldness and tenacity enabled him, against all odds and despite near-universal skepticism, to discover and prove the importance of a new class of disease-producing agents—prions—a discovery as fundamental as that of bacteria and viruses. Prions, by subverting the brain’s own proteins, may play a crucial role in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases—and perhaps afford a clue to their prevention. Madness and Memory is the story of one of the most important discoveries in recent medical history, and it is also a vivid and compelling portrait of a life in science." Special thanks to Dr. Mark Cohen for alerting me to the publication of this new account of a seminal discovery in biological science.

The bookish Dr. Mark Cohen

Nobel Laureate Prusiner Tells His Story

Just published by Yale University Press: Stanley Prusiner's new book, Madness and Memory: The Discovery of Prions - A New Biological Principle of Disease, is now available for purchase. Although I am not personally a big fan of Dr. Oliver Sacks's work, his blurb on Prusiner's book is worth reading: “Stanley Prusiner is a brilliant scientist whose boldness and tenacity enabled him, against all odds and despite near-universal skepticism, to discover and prove the importance of a new class of disease-producing agents—prions—a discovery as fundamental as that of bacteria and viruses. Prions, by subverting the brain’s own proteins, may play a crucial role in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases—and perhaps afford a clue to their prevention. Madness and Memory is the story of one of the most important discoveries in recent medical history, and it is also a vivid and compelling portrait of a life in science." Special thanks to Dr. Mark Cohen for alerting me to the publication of this new account of a seminal discovery in biological science.

The bookish Dr. Mark Cohen

Treatable Neurological Disorders Misdiagnosed as Creutzfeldt-Jakob Disease

A case of primary CNS angiitis thought to be sCJD

Dr. Mark Cohen and a team of workers at Case Medical Center in Cleveland, Ohio have published an important article in the Annals of Neurology entitled Treatable Neurological Disorders Misdiagnosed as Creutzfeldt-Jakob Disease (Ann Neurol 2011;70:437–444). Why is this article important? Well, because mistaking a survivable, treatable disorder for a fatal, non-treatable disorder is not optimal. Cohen's team reviewed the pathologic diagnoses of 1,106 patients who were referred for potential prion disease to the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University from 2006 to 2009. About one-third of the cases did not have prion disease, with Alzheimer disease and vascular disease being the most common conditions accounting for dementia. Further, about one-quarter of the non-prion cases had treatable diseases, including immune-mediated disorders, neoplastic disorders such as lymphoma, as well as infectious and metabolic disorders. The immune-mediated disorders included primary angiitis of the CNS, acute disseminated encephalomyelitis, limbic encephalitis, neurosarcoidosis, paraneoplastic cerebellar degeneration, and one case of Wegener granulomatosis. Of note, more than half of patients with a treatable dementia had a positive CSF 14-3-3 protein test, highlighting the danger of relying too heavily on this test in making a diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). It turns out that the most specific test for distinguishing CJD from other diseases was magnetic resonance imaging. Drs. David Perry and Michael Geschwind, in a review of this study in the September 2011 issue of Nature Reviews Neurology, (Perry, D. C. & Geschwind, M. D. Nat. Rev. Neurol. 2011:7, 479–480) write: "The fact that many of the non-prion diagnoses in the present study were potentially treatable RPDs [rapidly progressive dementias] should prompt thorough diagnostic testing in patients who are suspected of having sCJD, in order to rule out mimics. The use of CSF testing, contrast-enhanced MRI, and autoimmune antibody screening is supported by this study."

Best Post of February 2011 -- Finally, an alternative to 14-3-3 protein in the diagnosis of CJD!

The next in our "Best of the Month" series is from February 2, 2011:

prion protein

Researchers report in an article in Nature Medicine that a new cerebrospinal fluid test, known as real-time quaking-induced conversion (RT-QUIC) assay, appears to be more specific than the problematic 14-3-3 test, which not infrequently gives false-positive results. ('Quaking-induced' refers to in vitro shaking, which helps to accelerate the reaction.) Not only that: it looks as though RT-QUIC may work on serum samples too, opening up the possibility of much earlier diagnosis and more widespread screening of donated blood. This development could truly revolutionize the pre-mortem diagnosis of prion disease! (Thanks to Dr. Doug Shevlin for calling my attention to this article.)

Finally, an alternative to 14-3-3 protein in the diagnosis of CJD!

prion protein

Researchers report in an article in Nature Medicine that a new cerebrospinal fluid test, known as real-time quaking-induced conversion (RT-QUIC) assay, appears to be more specific than the problematic 14-3-3 test, which not infrequently gives false-positive results. ('Quaking-induced' refers to in vitro shaking, which helps to accelerate the reaction.) Not only that: it looks as though RT-QUIC may work on serum samples too, opening up the possibility of much earlier diagnosis and more widespread screening of donated blood. This development could truly revolutionize the pre-mortem diagnosis of prion disease! (Thanks to Dr. Doug Shevlin for calling my attention to this article.)

New Sporadic Prion Protein Disease Identified by Case Western Reserve

A new sporadic prion protein disease has been discovered. Variably protease-sensitive prionopathy (VPSPr), as it has been named, is the second type of complete sporadic disease to be identified since Creutzfeldt-Jakob disease (CJD) was reported in the 1920s. The landmark finding from the National Prion Disease Pathology Surveillance Center at Case Western Reserve University is published in the August issue of Annals of Neurology. 

In 2008, Pierluigi Gambetti, MD (pictured), and Wen-Quan Zou, MD, PhD, with collaborators, reported the discovery of this novel disease, which affected patients who exhibit only one of the three types of the prion protein gene. In this follow-up study, they discovered that all three genetic groups can be affected also by this novel disease which now joins sCJD in displaying this feature. However, VPSPr is associated with an abnormal prion protein that exhibits characteristics very different from those of sCJD, as well as other prion diseases, suggesting that it may be caused by a different mechanism, perhaps more akin to other neurodegenerative diseases, such as Alzheimer’s disease. This finding may exemplify, for the first time, the possibility that the prion protein affects the brain with different mechanisms.

While examining cases received at the National Prion Disease Pathology Surveillance Center where he is the director, Dr. Gambetti observed that a subset of cases had clinical and pathological features quite different from those of all known types of human prion diseases. Further, after being tested for prion proteins via the Western blot – the gold standard of prion disease diagnosis – the cases were negative. Dr. Gambetti then collaborated with Dr. Zou, associate director at the center, to solve the riddle of a disease that exhibited some features of a prion disease in histopathological examination but was negative using the standard Western blot test.

Dr. Zou’s lab performed a full characterization of the disease and discovered that the VPSPr-associated abnormal prion protein formed a ladder-like electrophoretic profile on Western blot. “When I obtained the first Western blot result of these cases with a different antibody against prions, I was surprised that these cases consistently exhibited this particular profile; one that I had never seen in my more than 10 years of work on human prion diseases,” Dr. Zou, assistant professor of pathology at Case Western Reserve School of Medicine, recalls. This ladder-like profile is quite distinctive and very different from the profile of common prion diseases. “Discovery of this unique type of prion provides solid evidence that this novel disease may possess a pathogenesis that is different from that of the major prion diseases currently known,” Dr. Zou adds.

Despite extensive research, a relatively large group of neurodegenerative diseases associated with dementia remain undefined. The discovery of VPSPr is chipping away at that group. In the two years since its discovery, more than 30 cases have been reported.

“If, as the current evidence indicates, the VPSPr mechanism of affecting the brain is different from that of other sporadic prion diseases, such as sCJD, the discovery of VPSPr would also provide the first example that the prion protein may spontaneously damage the brain with different mechanisms,” concludes Dr. Gambetti, professor of pathology at Case Western Reserve School of Medicine. “This might apply to other dementing illnesses as well, and has implications for the strategies that need to be followed to attain a cure.”

Drs. Gambetti and Zou, along with their extensive research team, plan to further characterize the abnormal prion protein associated with VPSPr as well as other important features of the protein, such as the disease’s propensity for transmission upon inoculation and its replication in test tubes. These features in VPSPr will be compared with those of sCJD to obtain a complete picture of how the abnormal prion protein attacks the brain in these two diseases.

This research was supported by funding from the National Institutes of Health, Centers for Disease Control and Prevention, Britton Fund, CJD Foundation, Alliance BioSecure, and University Center on Aging and Health with the support of the McGregor Foundation, and President’s Discretionary Fund (Case Western Reserve University).

Best Post of January '10: Eight states still do not mandate reporting of CJD cases to public health authorities

The next in our series of "Best Posts of the Month" is from January 8, 2010:

Neuropathologists are obligated to keep generally up to date on Creutzfeldt-Jakob disease (CJD) research as they are called upon to perform autopsies on patients whose dementia may have been caused by a prion disease. The most overlooked players in the CJD research arena are patient advocates. Many patient advocates are fiercely motivated, often having been inspired to act by the CJD-related death of a loved one. One such advocate is Theresa Matthews (pictured on a 2006 lobbying visit to Washington with her teenage daughter Mary and Illinois Senator Durbin and then Senator Obama). Patient advocates often raise worthy questions about issues surrounding CJD research. One such question is whether adequate epidemiological data on CJD is being collected in every state. Ms. Matthews informs me that currently there are eight states that do not require physicians to report CJD cases. She testified about this issue at a June 2009 meeting of the FDA's Transmissible Spongiform Encephalopathies Advisory Committee. Here's an excerpt from her testimony:

"Accurate disease reporting is a basic and fundamental step of epidemiology... This cannot possibly be done if you are not even counting the cases. The current state of CJD epidemiology in this country is a joke and it is no laughing matter."

Strong words. But Ms. Matthews makes a good point. Mandated reporting is the first step in reliable epidemiological research. Every state should mandate reporting of CJD cases, whether discovered pre-mortem or only at autopsy. Here are the states that fail to mandate reporting: Washington, Nevada, New Mexico, Iowa, Indiana, Alabama, Kentucky, and West Virginia. If you are a resident of one of these states, contact your governor or state legislator to get this situation corrected!

Sleepless

Neuropathologist Henry Brown, MD, PhD (pictured) recommends the novel Sleepless by Charlie Huston to those in the neuropathology community with an interest in the fatal insomnias. A review on Amazon.com describes the book as a "thriller set in a postapocalyptic Los Angeles, [where] a devastating illness renders the afflicted unable to sleep. In about a year, those with SLP (as the sleepless illness is known) deteriorate and die." Dr. Brown says that the novel may be "a little out there for some of our neuropathologists, perhaps", but a good read nonetheless.

Eight states still do not mandate reporting of CJD cases to public health authorities

Neuropathologists are obligated to keep generally up to date on Creutzfeldt-Jakob disease (CJD) research as they are called upon to perform autopsies on patients whose dementia may have been caused by a prion disease. The most overlooked players in the CJD research arena are patient advocates. Many patient advocates are fiercely motivated, often having been inspired to act by the CJD-related death of a loved one. One such advocate is Theresa Matthews (pictured on a 2006 lobbying visit to Washington with her teenage daughter Mary and Illinois Senator Durbin and then Senator Obama). Patient advocates often raise worthy questions about issues surrounding CJD research. One such question is whether adequate epidemiological data on CJD is being collected in every state. Ms. Matthews informs me that currently there are eight states that do not require physicians to report CJD cases. She testified about this issue at a June 2009 meeting of the FDA's Transmissible Spongiform Encephalopathies Advisory Committee. Here's an excerpt from her testimony:

"Accurate disease reporting is a basic and fundamental step of epidemiology... This cannot possibly be done if you are not even counting the cases. The current state of CJD epidemiology in this country is a joke and it is no laughing matter."

Strong words. But Ms. Matthews makes a good point. Mandated reporting is the first step in reliable epidemiological research. Every state should mandate reporting of CJD cases, whether discovered pre-mortem or only at autopsy. Here are the states that fail to mandate reporting: Washington, Nevada, New Mexico, Iowa, Indiana, Alabama, Kentucky, and West Virginia. If you are a resident of one of these states, contact your governor or state legislator to get this situation corrected!

Univ of Wisconsin tells 53 patients they are at risk for CJD

The Wisconsin State Journal reports today that the University of Wisconsin Hospital informed 53 patients that they face an “extremely low” risk of having contracting Creutzfeldt-Jakob disease (CJD) from surgical instruments used on a woman who died of CJD on Tuesday. The woman had been operated upon on June 11 to remove a benign brain tumor which was thought to be causing her problems with walking, vision, and memory. In retrospect, these symptoms seem to have been related to CJD. Although the instruments went through normal sterilization procedures between cases, destruction of the prion agent responsible for CJD requires more stringent cleaning procedures. “This is not mad cow disease,” said Dr. Nasia Safdar (pictured), a specialist in infectious diseases who oversees infection control at the hospital. “(People) need not be concerned about that relationship.” Despite her statement, Dr. Safdar admits that conclusive results ruling out "mad cow disease" (variant CJD) have not yet been received from the National Prion Disease Pathology Surveillance Center. To be frank, regardless of what Dr. Safdar says is being done to sterilize the surgical instruments, if I personally were undergoing surgery at the University of Wisconsin I would request that the instruments used on the CJD patient not be used in my procedure.

Best Post of May '09: D.T. Max writes the back story on prion disease

The next in our series of "Best Posts of the Month" is from May 7, 2009.

Most of us accept the party line that there are three basic forms of Creutzfeldt-Jakob disease (CJD): acquired, inherited, and sporadic. The general neurology and neuropathology textbooks do not acknowledge that the very existence of sporadic CJD is controversial. But D.T. Max (picture from nytimes.com), in his book The Family That Couldn't Sleep: A Medical Mystery (2006), does not skirt this controversy. Some patient advocacy groups claim that CJD cases now classified as sporadic are in fact infectious. "A surprising number of mainstream scientists also doubt the existence of sporadic CJD -- among them protein experts, epidemiologists, and neurologists," Max writes. "Their objection is that sporadic CJD is an unnecessary idea. If a disease is known to spread by infection, why assume that some people also get it by chance? Why not find the infectious source in their cases as well? They see theoretical gaps in the idea of sporadic CJD theory too. For one thing, it is strange, if sporadic CJD comes about as a result of the body's declining ability as it ages to manufacture proteins correctly, that the chance of getting sporadic CJD goes down at around seventy years of age." Among the sporadic CJD doubters is none other than D. Carleton Gajdusek, who in 1976 shared a Nobel prize for his work in tracking the cause of kuru (a disease later classified among the prion disorders) as resulting from the practice of funerary cannibalism among the Fore tribes in New Guinea. Of course, in 1976, the word prion had not yet been invented. It took Stanley B. Prusiner, who himself won the Nobel in 1997 for his discovery of prions as a new biologic principle of infection, to come up with that catchy term. But Gajdusek (who died this past December) never took to the term "prion", preferring to call the infectious proteins "nucleating amyloids" -- in large part because of his rabid animosity toward Prusiner. Gajdusek addresses Prusiner in this spicy journal entry made at the time of the announcement of Prusiner's award:

"I never heard a word of original thought from you nor read such ideas in anything you authored for which I did not recognize immediately its source, which you always went out of your way to obscure. You a heretic? You a martyr? You a defender of unacceptable ideas? Bullshit! You shrewdly jumped onto a bandwagon of creative ideas and experimental work and shrewdly got on to the winning cart, proclaiming outrageously in press and media it was yours! I respect you less and less as your despicable game succeeds and you bask in your coveted fame."

There is no doubt that the prejudice, jealousy, and ambition played a large role in both the development and elucidation of the prion diseases. D. T. Max has written a wonderful book about the fascinating history of this strange class of diseases -- including CJD, kuru, fatal familial insomnia, bovine spongiform encephalopathy, and scrapie. As the mysteries surrounding the prion diseases are further unraveled, the secrets behind the more common neurodegenerative diseases (which feature their own kinds of aberrant, aggregating proteins) may also begin to be revealed.

D. T. Max writes the back story on prion disease

Most of us accept the party line that there are three basic forms of Creutzfeldt-Jakob disease (CJD): acquired, inherited, and sporadic. The general neurology and neuropathology textbooks do not acknowledge that the very existence of sporadic CJD is controversial. But D.T. Max (picture from nytimes.com), in his book The Family That Couldn't Sleep: A Medical Mystery (2006), does not skirt this controversy. Some patient advocacy groups claim that CJD cases now classified as sporadic are in fact infectious. "A surprising number of mainstream scientists also doubt the existence of sporadic CJD -- among them protein experts, epidemiologists, and neurologists," Max writes. "Their objection is that sporadic CJD is an unnecessary idea. If a disease is known to spread by infection, why assume that some people also get it by chance? Why not find the infectious source in their cases as well? They see theoretical gaps in the idea of sporadic CJD theory too. For one thing, it is strange, if sporadic CJD comes about as a result of the body's declining ability as it ages to manufacture proteins correctly, that the chance of getting sporadic CJD goes down at around seventy years of age." Among the sporadic CJD doubters is none other than D. Carleton Gajdusek, who in 1976 shared a Nobel prize for his work in tracking the cause of kuru (a disease later classified among the prion disorders) as resulting from the practice of funerary cannibalism among the Fore tribes in New Guinea. Of course, in 1976, the word prion had not yet been invented. It took Stanley B. Prusiner, who himself won the Nobel in 1997 for his discovery of prions as a new biologic principle of infection, to come up with that catchy term. But Gajdusek (who died this past December) never took to the term "prion", preferring to call the infectious proteins "nucleating amyloids" -- in large part because of his rabid animosity toward Prusiner. Gajdusek addresses Prusiner in this spicy journal entry made at the time of the announcement of Prusiner's award:

"I never heard a word of original thought from you nor read such ideas in anything you authored for which I did not recognize immediately its source, which you always went out of your way to obscure. You a heretic? You a martyr? You a defender of unacceptable ideas? Bullshit! You shrewdly jumped onto a bandwagon of creative ideas and experimental work and shrewdly got on to the winning cart, proclaiming outrageously in press and media it was yours! I respect you less and less as your despicable game succeeds and you bask in your coveted fame."

There is no doubt that the prejudice, jealousy, and ambition played a large role in both the development and elucidation of the prion diseases. D. T. Max has written a wonderful book about the fascinating history of this strange class of diseases -- including CJD, kuru, fatal familial insomnia, bovine spongiform encephalopathy, and scrapie. As the mysteries surrounding the prion diseases are further unraveled, the secrets behind the more common neurodegenerative diseases (which feature their own kinds of aberrant, aggregating proteins) may also begin to be revealed.