All About Prions and Food

[docsconz]

But, I don't support genetic tests before being allowed to purchase beef.  The simple fact is, we all got a life sentence when we were conceived.  Whenever I see a patient now as a medic in the Army, or later as a medical student, or even later as a physician, I am always going to remind them to make the most of it, because the last laugh will always be on them.  And my last laugh will be on me.  It's a simple fact.

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This is the way I try to approach life. Way back before my current aged sig line, I had "Life is too short to drink bad wine". There are too many things that can step in the way to screw things up. Burns' line "the best laid plans of mice and men oft go aglay" or something very much like that couldn't be more true. That does not mean that i am not leaving anything for a potential retirement. I just don't want to be derailed along the way without having lived a life that I am happy with. That being said, there are risks worth taking and others less so. Each individual should decide what those are for him or herself. That is why I choose to eat raw milk cheeses amongst other things.

[annecros]

Oh wow. You guys are really coming close to home now. The whole predisposition, then trigger, and you have to have both, have been done to death in my home. Same for any other home that is hosting a member of the rheumatological victims of this years mystery disease, and injectibles are just the ticket. Sucks. Sucks as bad as being diabetic, but probably not as bad as being a cancer patient who goes and gets poison delivered introvenously on a regular basis.

I have scleroderma. My father had ankylosing spondilitis. My grandmother, two aunts, and two uncles died of stroke in their fourth decade of life. Grandma on the other side lived to be 97. Who the freak knows? Not me. I have accepted the whole silly fact that I am human and mortal. It was hard, buy hey, the truth hurts sometimes.

Yep, the HLA B27 marker runs rampant in the family. Yep, it really sucked when I had always been told that females almost never have the type of arthritis that my father's life changing arthritis was, but however, one in five children carry the gene.

Yep, the ONLY girl on that side won the lottery.

Who cares? Honestly. Somebody had to get it. It will no more stop me than it stopped my father.

You can live your life feeling sorry for yourself and expect others to fetch and carry and be all nice and lovey dovey.

Or, you can live.

I choose to live.

Just try and stop me.

(shaking my fist and screaming "KAAAAHHHNN" or some such)

Dad always said I was pure hell.

Annie

Edit to add: END RANT. and I mean it.

Edited February 3, 2006 by annecros (log)

[jsolomon]

After screaming "Khaaann!" It is apropos to follow it up with, "you bastard!!!!!"

Also, the Japanese had it right. There is no dishonor in death. That is a western construct.

[annecros]

After screaming "Khaaann!" It is apropos to follow it up with, "you bastard!!!!!"

Also, the Japanese had it right.  There is no dishonor in death.  That is a western construct.

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Teehee.

Allright.

"KAAAHNNN!!!! You BASTARD."

Doubly ended rant. If you can do that.

I feel much better now.

Thanks for your patience.

[docsconz]

After screaming "Khaaann!" It is apropos to follow it up with, "you bastard!!!!!"

Also, the Japanese had it right.  There is no dishonor in death.  That is a western construct.

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No, but I'm not in a hurry to get there, either

[annecros]

After screaming "Khaaann!" It is apropos to follow it up with, "you bastard!!!!!"

Also, the Japanese had it right.  There is no dishonor in death.  That is a western construct.

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No, but I'm not in a hurry to get there, either

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No rush here.

[jsolomon]

Just serve me some Ortelin like Miterand and sing to me like Painless in M*A*S*H.

Oh, and while you're at it, pass the venison.

[Pan]

Well, you can still color me skeptical.

No, I would not knowingly eat a sick animal. That's just common sense, isn't it?

But, on the other hand, this all smacks of the Avian Flu hype and such.[...]

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Thousands and thousands of people die of "normal" flu every year, there has at least once been a flu epidemic that killed some 40 million people, flu virus is highly susceptible to mutation and can be highly contagious, a significant number of scientists are very concerned that avian flu could turn into a form that could cause a pandemic, and avian flu has killed some 53% of the human beings who have had it, including young, previously healthy individuals. As I posted previously in another thread, I don't think that's a reason to panic, but I surely think that's a reason to watch the disease very closely and take steps to control its spread among both the bird and human populations. So if you think this is similar...

[annecros]

Well, you can still color me skeptical.

No, I would not knowingly eat a sick animal. That's just common sense, isn't it?

But, on the other hand, this all smacks of the Avian Flu hype and such.[...]

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Thousands and thousands of people die of "normal" flu every year, there has at least once been a flu epidemic that killed some 40 million people, flu virus is highly susceptible to mutation and can be highly contagious, a significant number of scientists are very concerned that avian flu could turn into a form that could cause a pandemic, and avian flu has killed some 53% of the human beings who have had it, including young, previously healthy individuals. As I posted previously in another thread, I don't think that's a reason to panic, but I surely think that's a reason to watch the disease very closely and take steps to control its spread among both the bird and human populations. So if you think this is similar...

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Please don't get me wrong.

Study, study, study.

Find a cure, the sooner the better.

I am all for science and progress. I just am not all for a bunch of hype that effects only a small fraction of the population at this time.

For goodness sake, more people died of starvation than avian flu this year.

That, to my mind, is a sin.

No one person on this planet need go hungry. I am shamed at times cleaning my own fridge.

[eje]

From a research perspective, part of the reason nvCJD is so interesting is that it is one of the few Prion diseases which can be induced fairly easily in transgenic animals in a laboratory setting.

Some of the hope for studying nvCJD and understanding it better, is that the research will result in cures or strategies for treating other diseases of protein aggregation, like Alzheimers, which do affect people in significant numbers.

[Pan]

[...]For goodness sake, more people died of starvation than avian flu this year.

That, to my mind, is a sin.[...]

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No disagreement there.

[Patrick S]

Likewise, there is some information that there's a genetic predisposition, in that all victims of nvCJD (last time I checked -- it has been a few years since I wrote an article on this) had a certain genetic marker and that nobody without that marker has every gotten the disease.

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I'm not sure of the total fact of that statement, but there is a relation between prions and an open reading frame on Chromosome 20 in humans.

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There is at least one genetic polymorphism that does appear to be associated with increased susceptibility to vCJD. The gene PRNP, which codes for the PrP protein. The PrP protein, of course, is the "prion" protein that is thought to become modified and play the dominant role in transmissable enchephalopathies, so it would make sense that genetic variations in the gene that codes for that protein would be associated with susceptibility.

PrP is 145 amino acids long. Each amino acid on the PrP protein is coded for by a group of 3 DNA bases on the PRNP gene called a codon. Codon 129 of the PRNP gene can code for the amino acids methionine or valine. Since each person has two copies of this gene in their genome, any person can have one M and V (heterozygous), M and M (homozygous), or V and V (homozygous). In the general population, what we find is 50% MV, 40% MM, and 10% VV. However, amongst humans with vCJD, all tested have been MM.

In 2004, however, it was reported in the Lancet that one person who had contracted vCJD was a MV heterozygote (Peden et al, 2004). This person died of something other than vCJD, and did not have any symptoms of neurolgical disease, but had recieved a blood transfusion from another person who later developed vCJD. Upon his death, tests showed the presence of the mishappen PrP protein in his spleen and one lymph node, but none were detected in his brain. So, maybe this means that heterozygotes get vCJD, but that they have a much longer latency. Or it may mean that the abnormal proteins can't get to the brain and cause vCJD. Nevertheless, it is still significant that no clinical case of vCJD has ever been found in the 60% of the population that is MV or VV.

Peden et al, 2004. Preclinical vCJD after blood transfusion in a PNRP Codon 129 heterozygous patient. Lancet 254, pp. 527-529.

[docsconz]

Fascinating information, Patrick. That 40% of the population is potentially susceptible is both reassuring and frightening. It is reassuring that not everyone may be susceptible, but frightening that so many may be.

[Patrick S]

Interestingly, a similar relationship was found for Kuru. Members of the Fore with the MM genotype at Codon 129 of the PRNP gene appear to have had a much shorter latency period, and to have progressed more rapidly to death than those with MV or VV genotypes. Thus, the cases that occurred in children were mostly in people with MM, whereas cases that occurred in older adults were mostly in people with MV or VV. It remains to be seen whether vCJD will fully develop in humans with MV or VV genotypes, but it is, I suppose, sadly possible that it just has a very long latency period in these people, and the first cases will appear in years to come. It's also significant to point out that Kuru killed over 1100 people between 1957 and 1968, according to the Wikipedia article, whereas vCJD has claimed something like 150 lives.

Regarding the state of the debate over vCJD today, I think its fair to say that there is little disagreement as to whether there is some type of infectious agent in cows with BSE that causes vCJD in humans. The debate that has occurred has been mostly about the nature of the infectious agent itself, specifically whether or not it possesses any nucleic acids (e.g. RNA or DNA).

There is plenty of evidence that, taken together, convinces me that TSEs are indeed transmitted by an infectious agent that it protein-only, and does not contain any nucleic acids. For instance, you can take a sample of brain homogenate from a BSE infected cow, expose it to chemicals that normally decompose nucleic acids, yet the homogenate retains infectivity. There have also been a couple of papers over the past couple of years that seem to provide fairly strong support for the protein-only position. Legname et al (2004) induced "BSE" in mice using purified proteins generated by transgenic bacteria that were engineered to produce PrP.

Creating the rogue prions from scratch was no mean feat. The researchers used bacteria to generate healthy-looking prion proteins and purified them. They shook these proteins until they changed their shape and resembled the twisted, unhealthy prions seen in diseased brains. Then the researchers injected the molecules into the brains of mice.

The mice developed BSE-like symptoms one to two years later, the team report in Science1. They became weak and shaky, and post-mortem analysis revealed that their brains were full of holes and rogue prion proteins.

Critically, when the mouse brains were ground up and injected into healthy rodents, they too became ill. This is the acid test for any prion disease, says Legname.

"The data show that infectious prions can be formed de novo from only protein," says prion researcher Surachai Supattapone from Dartmouth Medical School in Hanover, New Hampshire. The result should help to convince the sceptics who demanded proof from a chemical experiment that prions alone were sufficient to trigger the disease.

Link

Legname et al, 2004. Synthetic mammalian prions, Science 305:673-6.

[docsconz]

Interesting studies. Patrick, do you or anyone else know if these synthetic prions have been fed to rather than injected into animals and caused disease?

[russ parsons]

i've gotta say again, this is what i love about e-gullet. no ranting, no raving, no half-baked conspiracy theories, what other food site has members that can intelligently discuss such an exigent topic?

[Mallet]

Patrick, thanks for bringing this to the table. I had no idea that prions could be "made from scratch", without an abnormal protein to convert them.

[Patrick S]

Interesting studies. Patrick, do you or anyone else know if these synthetic prions have been fed to rather than injected into animals and caused disease?

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I don't think so. Legname et al is only study I know of where synthetic prions were administered, and in that study they were injected.

[JohnL]

i've gotta say again, this is what i love about e-gullet. no ranting, no raving, no half-baked conspiracy theories, what other food site has members that can intelligently discuss such an exigent topic?

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I agree!

What usually happens is--someone posts a link or reference to an article or broadcast and the discussion (sometimes debate) begins here at eGullet.

I believe that sites like eGullet are thriving, in large part, because other media are doing a poor job.

ABC, NBC, The NY Times, Washington Post, et al, are often doing little more than passing along information and positions developed by special interest groups.

Sensationalism and ratings grabs are more important than providing factual information, perspective and context on important issues.

We have seen this in the reporting on stories like Food Lion, Teflon, pesticides (alar), Mad Cow, genetically engineered foods, hunger, obesity etc etc etc.

These are all serious and important issues that deserve thoughtful reporting so people can make informed choices. It is a shame that ABC does not have a PatrickS to vet science related reporting--fortunately we do!

and on a lighter note--where else can one get good information on prions and a recommendation for a hot dog shack for lunch!?

This is really news we can use!

[Patrick S]

This is indeed disturbing. I am well aquainted with Koch's Postulates and the requirements for application for NIH etc. funding. It is disturbing that prions have not passed Koch's test. It is also disturbing that the scientific community has jumped on board without that test.

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Koch himself realized that Koch's Postulates were far from hard and fast rules for establishing that a particular agent causes a particular disease. And in fact, Koch proposed them for the bacterial illness he was studying, not viruses and certainly not prions. Koch's first two postulates were:

1. The organism must be found in all animals suffering from the disease, but not in healthy animals.

2. The organism must be isolated from a diseased animal and grown in pure culture.

Regarding (1), Koch himself realized that there can be asymptomatic carriers of a pathogen. "Typhoid Mary" demonstrated this a century ago, while Koch was still alive. Today we know this is true of lots of pathogens, like Cholera, Polio, Hepatitis, Herpes, HTLV, and HIV. This is not surprising, since we now know, as Koch could not, that there are myriad genetic differences between individuals that affect susceptibility to virtually all infectious diseases.

Regarding (2), if prions really are protein-only, do not self-replicate, there is no way they can be cultured (i.e. grown in a petri dish on nutrient media). Viruses also can not be cultured.

[eje]

I don't think so. Legname et al is only study I know of where synthetic prions were administered, and in that study they were injected.

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A similar cast of characters also published on a related subject in 2005:

Strain-specified characteristics of mouse synthetic prions.

Legname G, Nguyen HO, Baskakov IV, Cohen FE, Dearmond SJ, Prusiner SB.

Proc Natl Acad Sci U S A 2005, 102: 2168-73

medline link

Somehow, I can just imagine a research assistant somewhere saying, "Here mousy, mousy, come and eat your delicious steak."

[Mallet]

Looking at the original Science article and also the PNAS one, it seems that Legname et al. are using a synthetic/recombinant prion as the infectious agent. I can't seem to find a sentence about the part of Patrick S' quote which I found the most interesting:

The researchers used bacteria to generate healthy-looking prion proteins and purified them. They shook these proteins until they changed their shape and resembled the twisted, unhealthy prions seen in diseased brains. Then the researchers injected the molecules into the brains of mice.

Can anyone point me to the appropriate part of the paper?

[Patrick S]

Looking at the original Science article and also the PNAS one, it seems that Legname et al. are using a synthetic/recombinant prion as the infectious agent. I can't seem to find a sentence about the part of Patrick S' quote which I found the most interesting:

The researchers used bacteria to generate healthy-looking prion proteins and purified them. They shook these proteins until they changed their shape and resembled the twisted, unhealthy prions seen in diseased brains. Then the researchers injected the molecules into the brains of mice.

Can anyone point me to the appropriate part of the paper?

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The technique that Legname et al used to change the conformation of the PrP proteins was described in a previous paper by the same group (Baskakov et al, 2002), which is reference (11) in Legname et al. The procedure involves constantly agitating the proteins in a mildly denaturing, 37C solution with a neutral PH.

Baskakov et al, 2002. Pathway Complexity of Prion Protein Assembly into Amyloid. Journal of Biological Chemistry 277, 21140-21148.

[docsconz]

Regarding (2), if prions really are protein-only, do not self-replicate,  there is no way they can be cultured (i.e. grown in a petri dish on nutrient media). Viruses also can not be cultured.

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Maybe I am missing something, Patrick, but I am very much under the impression that viruses can be and are cultured. Perhaps there is a semantic misunderstanding?

[slkinsey]

Doc, I don't think viruses can be cultured in a nutrient media. Think about it: viruses don't have a metabolism and replicate by using the machinery of a living host cell. If there is no living host cell, the viruses cannot replicate. Since a nutrient medium is not a living host, no replication. Right?