It is not every decade that humanity makes a discovery so radically different from existing theory that it is rejected as “impossible.” Such a thing happened in 1982 when Stanley Prusiner announced the existence of a disease agent that was NOT a bacteria or virus. That is, a third “thing” could cause diseases, and it was neither DNA or RNA, both of which are found in bacteria and viruses. And, shockingly, Prusiner hypothesized that it was a protein. He named this thing a “prion” and in1997 he got a Noble Prize in Physiology and Medicine for his work.
Talk about thinking outside the box! To even suspect that a protein could be transmitted from organism to organism and cause a disease was a truly radical notion.
The diseases caused by prions (“transmissible spongiform encephalopathies”) all have several factors in common: they are progressive degenerative neurological diseases; they cause deterioration of the brain and other neurological tissue, making it “spongy”; they result in deposits of what are called “amyloid plaques”, a tangle of protein fibers caused by the uniquely-shaped prion; they do not cause an immunological response (so we can probably forget a vaccine cure, though there may be some slight possibility here). They are not transmitted via air, but by bodily fluids. Disease takes a long time to develop, but once the infection starts, its progression is exponential. There is no cure, but prions themselves are generally specific to a particular species, so infectivity may depend on the type of genetics you have. Prions are resistant to eradication by heat (autoclaving) or chemicals. Once formed, prions may persist in the environment forever.
One of the problems associated with the prion hypothesis is that no one knows how it works. That is, how a prion “infection” works. What is known is that a “normal” prion (let’s call it PrN) does not cause any disease. In fact PrN may be necessary for normal brain function. And we all contain a gene that makes PrN. The problem is that PrN can become converted into a new “shape” (let’s call it PrD, with a “D” for “diseased”). What happens is that when PrN is in the presence of PrD, it gets converted into PrD too. That is, PrD causes or catalyzes a normal prion to change shape and become a PrD. This is an EXCEPTION to the central rule of molecular biology, which states that only DNA or RNA can make proteins.
As with most “rules” in biology, or science for that matter, there are usually exceptions to the rules (except for “big” rules, such as: all matter is made of atoms, E=MC2, all living things are made of cells, the surface of earth is made of tectonic plates, and stars cluster in galaxies), and prions are one of them. Whatever is meant by the saying “the exception proves the rule” (and I think this is a nonsense phrase, because exceptions don’t prove anything), in science “exceptions” are highly valued, and really only prove that “there are many ways to do things.” Like all reptiles have 3-chambered hearts, except for crocodiles, which have a 4-chambered heart (as do all mammals). Or all fish have gills, except for lungfish, which have both gills and lungs (though pretty primitive). Or all plants have roots that grow down, except for mangroves, whose roots grow up, etc., etc. (This could be another blog topic. . . .)
As mentioned above, we all make normal prions. Therefore, we have a gene that makes normal prions. Interestingly, this gene can become mutated to make diseased prions, but fortunately this is very very rare. One of these inherited PrD diseases is Fatal Familial Insomnia (FFI), found in about 40 families worldwide. First described in the 1700’s, this is a horrible disorder that causes infected family members to eventually become unable to sleep, resulting in hallucinations, dementia, and then death. Always. And it only takes 7 to 36 months from onset, which generally occurs about age 50. Think about not sleeping for 6 months!
Another fascinating disease is called “kuru” (from a word for “shaking”), which it is found among the Fore tribe in Papua New Guinea. It is a neurological disease that is transmitted via cannibalism. That’s right—when members of this tribe consume the brains (especially) of people that have kuru, they can develop kuru too, after a latency period of 5 to 20 years. And, as you might have deduced, the infective agent is a prion. Interestingly, in 2009 it was reported that these same native peoples had high frequencies of a “normal” prion gene that may confer resistance to kuru. Yet another example of evolution in action.
Kuru is closely related to yet another fatal prion-caused neurological disease called Creutzfeldt-Jakob disease (pronounced Kruts felt Yahcob) or CJD. CJD is a very rare disease, occurring in about one in a million people. However, it has received much publicity because it is either the same as, or is closely related to, “mad cow disease,” or Bovine spongiform encephalopathy (BSE).
I guess it is mad cow disease (MCD) that really brought prions to the public’s attention in the mid 1990’s—when the first human death from MCD was reported in the United Kingdom. MCD in CATTLE had been known in the UK since 1986, and by 1989, between 460,000 and 482,000 BSE-infected animals had entered the human food chain. So, when someone actually died from what was believed to be (and certainly was) consumption of beef contaminated with BSE, much well-deserved paranoia ensued in the UK and other places where BSE-contaminated beef had been widely consumed. Given prion disease’s long latency period (time from infection to manifestation of the disease), combined with no known way of sterilizing contaminated meat or eating utensils (neither boiling water nor autoclaving, for example, will degrade prions), the full extent of MCD in humans is as yet unknown. However, by 2009 only 176 cases of CJD (probably derived from BSE) had been found in Great Britain, 27 in France, and 3 in the United States, with a smattering in other countries. So all we know at present is that “mad cow disease” may or may not be a significant future problem for humans.
Cattle with BSE have been found in the United States, however. As recently as 2012 it was found in a dairy cow in California. And there are other four-legged critters in the United States that have yet ANOTHER prion disease called “chronic wasting disease” (CWD). CWD is found in members of the deer family—white tailed deer, elk, mule deer, and moose. To date CWD has NOT been found to be transmissible to humans.
So this may be good news for humans. But it is bad news for deer, since CWD is spreading geographically, and is increasing in deer herds that have a history of CWD (for example, the incidence of CWD in Wisconsin white tail deer in the most-affected areas has increased from a low of 10% among adult bucks in 2002 to a peak of 23% in 2010). However, for us humans, there has been no increase in human CJD in those parts of the US (Colorado, Wyoming) that have the longest history of CWD in its deer and elk populations (about 40 years). Hopefully this indicates a very low or nonexistent cross-species potential.
Control, or at least management, of transmissible spongiform encephalopathy (TSE, a generic name for these prion diseases) in our cattle and wild animals is variable. The only way to control it in members of the deer family is to kill them. Period. However, due to a ridiculous public outcry in Wisconsin among animal rights groups, the state lost an opportunity in the early 2000’s to greatly limit CWD in the state when they elected not to pursue a policy of eliminating 100% of the deer population in the very small geographic areas where CWD was first found. Since prions may persist in the soil for very long periods (possibly forever), maybe the incidence of CWD would never have been reduced to zero, but it could have been contained. That is now impossible. I guess the animal rights groups thought CWD must be good for wildlife. Kind of like thinking cancer is good for humans, so no surgical removal of cancerous tissue is required, thank you very much. Hopefully other states in which CWD is just emerging, such as Maryland, will adopt non-fuzzy-headed policies at the start of the disease.
Control of TSE in cattle has been somewhat more sensible. First, as you would hope, some attempt is being made to eliminate affected animals from the food supply. However, there are no really good tests for affected animals, and some of the beef suppliers (especially Creekstone Farms Premium Beef, LLC) argue that the USDA is not moving fast enough to implement or even permit suppliers to use the tests that we currently have. Creekstone Farms maintains that testing only costs about $20 per animal, which amounts to a negligible increase in cost to the consumer (around $0.10/pound). Second, since 1997 mammalian byproducts (blood, bone meal) have been prohibited from being fed to ruminants such as cattle and goats. Unfortunately, however, these byproducts can still be fed to pets, poultry, and pigs, and byproducts from poultry and pigs CAN be fed to cattle. So even though TSE is not at present a significant threat to our human food chain, it seems to me that we are not doing all that reasonably could be done, and I wonder about the influence of political groups on these decisions—as was seen with CWD control in Wisconsin deer as well as, apparently, TSE testing in US cattle.
Looking to the future, there is emerging evidence that OTHER diseases may involve prions, such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis. This is very new science, but it is being hypothesized by none other than Stanley Prusiner, the guy who discovered prions in the first place.
So prions are instructive for many reasons—as an example of how science changes, as an example of how central tenets can be overthrown or at least modified, perhaps as an example of a unifying concept for several of our most devastating and puzzling neurological diseases, and as an example of how infinitely variable biology can be.
And amazingly, it took 30 years and millions of dollars of research for the prion concept to be widely “accepted”. Think about that the next time you read about some discovery or new scientific assertion being made (like global warming?). It takes a lot of independent evidence to get the scientific community to agree on anything. But when they do, it is pretty tight. And then you can “believe.” Maybe.
Talk about thinking outside the box! To even suspect that a protein could be transmitted from organism to organism and cause a disease was a truly radical notion.
The diseases caused by prions (“transmissible spongiform encephalopathies”) all have several factors in common: they are progressive degenerative neurological diseases; they cause deterioration of the brain and other neurological tissue, making it “spongy”; they result in deposits of what are called “amyloid plaques”, a tangle of protein fibers caused by the uniquely-shaped prion; they do not cause an immunological response (so we can probably forget a vaccine cure, though there may be some slight possibility here). They are not transmitted via air, but by bodily fluids. Disease takes a long time to develop, but once the infection starts, its progression is exponential. There is no cure, but prions themselves are generally specific to a particular species, so infectivity may depend on the type of genetics you have. Prions are resistant to eradication by heat (autoclaving) or chemicals. Once formed, prions may persist in the environment forever.
One of the problems associated with the prion hypothesis is that no one knows how it works. That is, how a prion “infection” works. What is known is that a “normal” prion (let’s call it PrN) does not cause any disease. In fact PrN may be necessary for normal brain function. And we all contain a gene that makes PrN. The problem is that PrN can become converted into a new “shape” (let’s call it PrD, with a “D” for “diseased”). What happens is that when PrN is in the presence of PrD, it gets converted into PrD too. That is, PrD causes or catalyzes a normal prion to change shape and become a PrD. This is an EXCEPTION to the central rule of molecular biology, which states that only DNA or RNA can make proteins.
As with most “rules” in biology, or science for that matter, there are usually exceptions to the rules (except for “big” rules, such as: all matter is made of atoms, E=MC2, all living things are made of cells, the surface of earth is made of tectonic plates, and stars cluster in galaxies), and prions are one of them. Whatever is meant by the saying “the exception proves the rule” (and I think this is a nonsense phrase, because exceptions don’t prove anything), in science “exceptions” are highly valued, and really only prove that “there are many ways to do things.” Like all reptiles have 3-chambered hearts, except for crocodiles, which have a 4-chambered heart (as do all mammals). Or all fish have gills, except for lungfish, which have both gills and lungs (though pretty primitive). Or all plants have roots that grow down, except for mangroves, whose roots grow up, etc., etc. (This could be another blog topic. . . .)
As mentioned above, we all make normal prions. Therefore, we have a gene that makes normal prions. Interestingly, this gene can become mutated to make diseased prions, but fortunately this is very very rare. One of these inherited PrD diseases is Fatal Familial Insomnia (FFI), found in about 40 families worldwide. First described in the 1700’s, this is a horrible disorder that causes infected family members to eventually become unable to sleep, resulting in hallucinations, dementia, and then death. Always. And it only takes 7 to 36 months from onset, which generally occurs about age 50. Think about not sleeping for 6 months!
Another fascinating disease is called “kuru” (from a word for “shaking”), which it is found among the Fore tribe in Papua New Guinea. It is a neurological disease that is transmitted via cannibalism. That’s right—when members of this tribe consume the brains (especially) of people that have kuru, they can develop kuru too, after a latency period of 5 to 20 years. And, as you might have deduced, the infective agent is a prion. Interestingly, in 2009 it was reported that these same native peoples had high frequencies of a “normal” prion gene that may confer resistance to kuru. Yet another example of evolution in action.
Kuru is closely related to yet another fatal prion-caused neurological disease called Creutzfeldt-Jakob disease (pronounced Kruts felt Yahcob) or CJD. CJD is a very rare disease, occurring in about one in a million people. However, it has received much publicity because it is either the same as, or is closely related to, “mad cow disease,” or Bovine spongiform encephalopathy (BSE).
I guess it is mad cow disease (MCD) that really brought prions to the public’s attention in the mid 1990’s—when the first human death from MCD was reported in the United Kingdom. MCD in CATTLE had been known in the UK since 1986, and by 1989, between 460,000 and 482,000 BSE-infected animals had entered the human food chain. So, when someone actually died from what was believed to be (and certainly was) consumption of beef contaminated with BSE, much well-deserved paranoia ensued in the UK and other places where BSE-contaminated beef had been widely consumed. Given prion disease’s long latency period (time from infection to manifestation of the disease), combined with no known way of sterilizing contaminated meat or eating utensils (neither boiling water nor autoclaving, for example, will degrade prions), the full extent of MCD in humans is as yet unknown. However, by 2009 only 176 cases of CJD (probably derived from BSE) had been found in Great Britain, 27 in France, and 3 in the United States, with a smattering in other countries. So all we know at present is that “mad cow disease” may or may not be a significant future problem for humans.
Cattle with BSE have been found in the United States, however. As recently as 2012 it was found in a dairy cow in California. And there are other four-legged critters in the United States that have yet ANOTHER prion disease called “chronic wasting disease” (CWD). CWD is found in members of the deer family—white tailed deer, elk, mule deer, and moose. To date CWD has NOT been found to be transmissible to humans.
So this may be good news for humans. But it is bad news for deer, since CWD is spreading geographically, and is increasing in deer herds that have a history of CWD (for example, the incidence of CWD in Wisconsin white tail deer in the most-affected areas has increased from a low of 10% among adult bucks in 2002 to a peak of 23% in 2010). However, for us humans, there has been no increase in human CJD in those parts of the US (Colorado, Wyoming) that have the longest history of CWD in its deer and elk populations (about 40 years). Hopefully this indicates a very low or nonexistent cross-species potential.
Control, or at least management, of transmissible spongiform encephalopathy (TSE, a generic name for these prion diseases) in our cattle and wild animals is variable. The only way to control it in members of the deer family is to kill them. Period. However, due to a ridiculous public outcry in Wisconsin among animal rights groups, the state lost an opportunity in the early 2000’s to greatly limit CWD in the state when they elected not to pursue a policy of eliminating 100% of the deer population in the very small geographic areas where CWD was first found. Since prions may persist in the soil for very long periods (possibly forever), maybe the incidence of CWD would never have been reduced to zero, but it could have been contained. That is now impossible. I guess the animal rights groups thought CWD must be good for wildlife. Kind of like thinking cancer is good for humans, so no surgical removal of cancerous tissue is required, thank you very much. Hopefully other states in which CWD is just emerging, such as Maryland, will adopt non-fuzzy-headed policies at the start of the disease.
Control of TSE in cattle has been somewhat more sensible. First, as you would hope, some attempt is being made to eliminate affected animals from the food supply. However, there are no really good tests for affected animals, and some of the beef suppliers (especially Creekstone Farms Premium Beef, LLC) argue that the USDA is not moving fast enough to implement or even permit suppliers to use the tests that we currently have. Creekstone Farms maintains that testing only costs about $20 per animal, which amounts to a negligible increase in cost to the consumer (around $0.10/pound). Second, since 1997 mammalian byproducts (blood, bone meal) have been prohibited from being fed to ruminants such as cattle and goats. Unfortunately, however, these byproducts can still be fed to pets, poultry, and pigs, and byproducts from poultry and pigs CAN be fed to cattle. So even though TSE is not at present a significant threat to our human food chain, it seems to me that we are not doing all that reasonably could be done, and I wonder about the influence of political groups on these decisions—as was seen with CWD control in Wisconsin deer as well as, apparently, TSE testing in US cattle.
Looking to the future, there is emerging evidence that OTHER diseases may involve prions, such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis. This is very new science, but it is being hypothesized by none other than Stanley Prusiner, the guy who discovered prions in the first place.
So prions are instructive for many reasons—as an example of how science changes, as an example of how central tenets can be overthrown or at least modified, perhaps as an example of a unifying concept for several of our most devastating and puzzling neurological diseases, and as an example of how infinitely variable biology can be.
And amazingly, it took 30 years and millions of dollars of research for the prion concept to be widely “accepted”. Think about that the next time you read about some discovery or new scientific assertion being made (like global warming?). It takes a lot of independent evidence to get the scientific community to agree on anything. But when they do, it is pretty tight. And then you can “believe.” Maybe.
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