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Lichens vs. the Almighty Prion

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And in this corner . . . the challenger, Lobaria pulmonaria. Given the common name "lungwort" thanks to its lung-like appearance, medieval herbalists invoked the Doctrine of Signatures to deduce it must be good for treating lung complaints. That is dubious, but it does seem to be good at something much more amazing. Creative Commons Jason Hollinger. Click image for original and license.
If you had to choose the world’s most indestructible biological entity, it would be hard to do better than the prion. It’s the Rasputin of biology: cook them, freeze them, disinfect them, pressurize them, irradiate them, douse them with formalin or subject them to protein-cleaving proteases, and yet they live.

Well, not literally live. After all, they’re only proteins.

Prions — infectious misfolded proteins –  have survived the pressure-cooker innards of autoclaves, the stout metal sterilizers that are the backbone of laboratory, hospital, and surgical sterilization. And they have survived for years in the punishing conditions of the outdoors — wind, cold, rain, snow, ice, heat, and ultraviolet radiation.

These two points should strike fear in the hearts of mammals everywhere, for prions cause incurable fatal neurodegenerative wasting diseases and dementias of the worst imaginable sort — the kind that swiftly strike down the hale and healthy in their prime.

If you are unfamiliar with prion diseases, that is only because you did not know they were caused by prions. In mammals: scrapie, chronic wasting disease, bovine spongiform encephalopathy, also known as mad cow disease. In humans: kuru, Creutzfeldt-Jakob Disease, and variant Creutzfeldt-Jakob Disease, a tidier name for, well, mad-cow disease.

Once symptoms appear in humans, tremors, convulsions, personality changes, hallucinations, and uncontrollable fits of laughter can precede death, usually within six months or so. Deer and elk slowly emaciate and glaze over mentally under the effects of the chronic wasting disease prion. Sheep with scrapie scrape the fleece from their presumably itchy backsides, and cattle with mad cow stumble around aggressively before succumbing.

Some of these diseases, in addition to their horrific manifestations, also have lurid origin stories. Kuru, for instance, plagued the Fore Tribe of Eastern Papua New Guinea thanks to their habit of consuming deceased members in order to return their life force to the tribe. Women and children were many times more likely to get kuru since the men appropriated the choice cuts, leaving them to eat less desireable bits like brain where prion particles congregate. Eventually authorities intervened to stop the practice.

Mad Cow, as you’ll recall, was the result of farmers feeding their cattle ground-up dead cow(called “meat and bone meal”– recall that cattle are herbivores), in which the prions causing bovine spongiform encephalopathy lurked. These, in turn, may have come from cross-contamination in slaughterhouses that also processed sheep with scrapie. When people in turn ate contaminated dead cow bits, to their horror, they too contracted the fatal wasting disease, and in Britain, at least 165 people died.

There was considerable controversy when the hypothesis that infectious proteins could cause disease was put forth, as the Central Dogma of Biology states that DNA is the unit of heredity and replication, and its bidding is done via RNA and then protein. That aberrant proteins could reproduce themselves, transmit disease and stir up trouble on their own without DNA’s help seemed to violate this. When Stanley Pruisner won the Nobel Prize in 1997 for purifying prions, many remained skeptical (though in part because of his sloppiness as an investigator). Even now a few skeptics remain.

Still, the preponderance of the evidence seems to remain with the infectious protein hypothesis. How is it that this could work? Proteins can often change shape. Enzymes — catalytic proteins — and other proteins often undergo shape changes when substrates — the molecules they act upon — or other cofactors bind to them. These interactions are mediated by various bonds and charges, but to you and me, it looks like simple touch.

Usually these changes are reversible. But sometimes proteins can get stuck in misfolded, extremely stable conformations. What seems to have happened was that the normal prion protein at one point mutated in an individual in a way that changed its shape in an extremely unfortunate manner. Then this protein touched another protein of the same type, inducing a permanent shape change in it too and perpetuating the mistake. Like Pandora’s box, once the chain of destruction was initiated, there was no going back.

In infected animals, the more proteins get stuck in the misfolded shape, the more are available to catalyze the reaction. It’s exponential. Eventually, the buildup of malfunctioning proteins in sheets and fibrils called amyloid starts killing brain cells. Though the incubation period for prion diseases can be long, once symptoms emerge, the end usually comes nigher rather than later.

There is some controversy over how this happens — do individual prions simply bump into other individual prions? or do they form long chains or sheets of a substance called amyloid (which you may recall is also a factor in many other neurodegenerative diseases like Alzheimer’s) that break frequently and can catalyze reactions at either end? Regardless, the changes induced are permanent, the diseases incurable.

Recall that prions can persist on surgical equipment even after the sterilization of autoclaving. That’s BAD. Since Creutzfeldt-Jakob disease in humans can occur spontaneously and the incubation period can be long, people may go into surgery not knowing they are a prion carrier. Scalpels, etc. have been contaminated and then autoclaved, only to spread the prions to helpless victims during subsequent surgery. This nightmare, has, in fact, really happened. New sterilization techniques have been decreed by the World Health Organization to prevent this, but it’s a scary thought nonetheless.

In nature, animals have a similar problem. An elk with chronic wasting disease has saliva, urine, and feces full of prions that can linger in soil and contaminate green growth as it bursts forth in spring. When an infected elk dies, these prions are also released into the environment when the animals decay and can similarly hang out in places that elk like to feed. And, as mentioned above, they don’t go away. While UV radiation and the extremes of heat and cold can peel paint and crumble newspaper, prions seem to shrug it off. Sheep and deer have indeed been infected after spending time in places contaminated years or decades ago. Since no evidence for a vector like a tick or mosquito exists, the prions seem to be going the same route cold-viruses take on day-care toys and doorknobs: the fomite, or inanimate object vector.

But there is one organism that seems to have found the chink in the prion’s formidable armor: the lowly lichen.

Cladonia rangifera (likely), a reindeer lichen fed upon by their namesake, by Paul J. Morris. Creative Commons; Click image for license.

Not all of them, mind you. But a few seem to produce a molecule — likely a serine protease — or molecules that can take out prions. And they may do it, surprisingly, because fungi seem to get prions too.

Scientists at the U.S. Geological Survey, the University of Wisconsin, Montana State University and the Universidad de Antioquia in Colombia investigated (and published the results in PLoS ONE) what, if any factors could promote prion degredation in the environment by looking at lichens — fungal/algal/bacterial co-ops which are veritable fonts of chemical and molecular diversity. Lichens produce over 600 “secondary” compounds not essential to their metabolism. They make them for a variety of reasons, including defense from UV, microbes, and herbivory, and as water repellants. Many of these chemicals are responsible for their fantastic colors or fluorescence under UV or surprising color changes in reaction to other chemicals. You can spot a lichenologist in the field by the mini-chemistry labs they haul around for identification.

Since lichens are super-abundant in forest environments (despite the fact hardly any humans notice them), the scientists decided to put a few common lichens in the ring with prions and see who won. For reasons that are unclear to me but may include their abundance in deer and elk habitat, they chose Lobaria pulmonaria, the lungwort, a lichen indicative of pristine forest old-growth northern forests, Cladonia rangiferina, a member of a vastly successful genus common across North America, and Parmelia sulcata, likewise successful in the boreal forests of North America.

What they found was nothing short of stunning. Not only could lichen organic and water extracts degrade prions at least hundred-fold (and sometimes to the point of undetectability), simply incubating the prions in water with an intact lichen could destroy them — mighty prions, which laugh off the rigors of autoclave and radiation, and I hardly need add, a slew of proteases we ourselves have thrown at them.

The researchers checked other species in the same genera, but these species lacked similar ability. They checked whether the algae the lichen fungi were partnering with were producing the lethal factor, and that seemed unlikely, at least when the algae were in isolation. They examined the effect of pH on the lichens’ ability to destroy prion, and found that while P. sulcata’s ability to degrade prions was pH sensitive (acidic was better), L. plumonaria’s wasn’t, suggesting they even have two separate ways of getting the job done — suggesting that, if the effect is not just due to chance, lichens have figured out how to do this more than once, and it isn’t even a big deal.

Parmelia sulcata, prion ninja. Creative Commons photo by James Lindsey at Ecology of Commanster. Click image for link and license.

Further testing suggested it was not one of three common lichen secondary compounds that was responsible, but in fact an enzyme called a serine protease, since only serine protease inhibitors were capable of destroying lichen extracts’ prion-fighting powers. Proteins are built of long strings of amino acids, proteases are enzymes that cleave other proteins, and serine proteases have the amino acid serine in their active sites, the seats of catalysis. Why lichen serine proteases can cleave prions where so many other proteases have failed is not known. It’s also unknown, the scientists noted, whether some other lichen chemical or protein may be acting as a co-factor that helps the serine protease do its job.

Could lichens provide the same services in nature? Could prions that land on or near lichens whose chemicals may leach out by rainwater reach their ignoble end at last?

No one yet knows.

It’s also unknown why lichens might possess this unlikely ability. Yeast — fungi that have reverted to a single-celled lifestyle — are known to have prions with amino acid sequences different from the mammalian prions but similar overall sheet-like amyloid structures.They may induce disease sometimes, but in other cases, they may confer an advantage on their hosts by permitting sharing of resources only between individuals that are sufficiently genetically similar.

No one has checked lichens for prions. But since the overall shape of known fungal prions resembles mammalian prions, the researches suggest it’s possible lichen proteases could act against fungal prions and mammalion prions alike. Whether putative lichen prions are as destructive as the mammalian forms — or even if they might be beneficial — remains in question, but the fact lichens have them suggests prions might be something that lichens are happier without.

You may wonder if lichens could be used to help protect humans from our own prion diseases. This is probably not feasible in surgical environments, both because lichens seem not to achieve complete degradation of prions reliably and because a nuclear option exists: Bleach or sodium hydroxide. Lots of bleach or sodium hydroxide (followed by autoclaving). Bleaching the forest is less feasible. Lichens, however, may be a built-in distributed defense system we didn’t even know we had.

Johnson CJ, Bennett JP, Biro SM, Duque-Velasquez JC, Rodriguez CM, Bessen RA, & Rocke TE (2011). Degradation of the disease-associated prion protein by a serine protease from lichens. PloS one, 6 (5) PMID: 21589935

Jennifer Frazer About the Author: Jennifer Frazer is a AAAS Science Journalism Award-winning science writer. She has degrees in biology, plant pathology/mycology, and science writing, and has spent many happy hours studying life in situ. Follow on Twitter @JenniferFrazer.

The views expressed are those of the author and are not necessarily those of Scientific American.

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  1. 1. skiphuffman 3:43 pm 07/25/2011

    I think you have a typo in this sentence:

    “Recall, as I mentioned earlier that prions can persist on surgical equivalent even after the sterilization of autoclaving.”

    You probably mean “surgical equipment”

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  2. 2. Jennifer Frazer in reply to Jennifer Frazer 3:46 pm 07/25/2011

    Yup! Thanks — it’s fixed now.

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  3. 3. 4:34 pm 07/25/2011

    Wow! Crazy. The lowly lichen packs a punch against prions!? I knew I liked lichens.

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  4. 4. comfort 5:28 pm 07/25/2011

    Nice piece, cool story. One quibble: You state, “Central Dogma of Biology states that DNA is the unit of heredity and replication, and its bidding is done via RNA and then protein.” That’s not quite true. So first, DNA being the unit of heredity and replication is premise of the Central Dogma, not a conclusion. And second, prions didn’t overturn the Central Dogma. The Central Dogma was overturned in the late ’60s, by reverse transcriptase, discovered by Baltimore and Temin. Small point, but it’s worth getting right. Anyway, thanks for the interesting post.

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  5. 5. Torbjörn Larsson, OM 10:11 pm 07/25/2011

    Wouldn’t the real achievement be to know of organic compounds that can indeed destroy prions? I assume prion diseased are so rare that they don’t warrant human medicines. But what about our animal vectors?

    “So first, DNA being the unit of heredity and replication is premise of the Central Dogma, not a conclusion. And second, prions didn’t overturn the Central Dogma. The Central Dogma was overturned in the late ’60s, by reverse transcriptase, discovered by Baltimore and Temin.”

    Still not right. Simply googling would tell you thatthe Central Dogma describes sequential information expression and its irreversibility, not DNA inheritance:

    “The central dogma … states that information cannot be transferred back from protein to either protein or nucleic acid.” [Crick 1958, 1970].

    Many other potential pathways for sequence information are allowed and indeed all of them found, see the first figure. Reverse transcriptase uses one of those, not the crucial one the dogma concerns.

    Ironically, the prion could be considered a protein-to-protein information transfer. But it still doesn’t break Crick’s dogma. (Not sequence information.)

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  6. 6. Torbjörn Larsson, OM 10:17 pm 07/25/2011

    Oops. Thinking about it, Crick’s dogma excludes three pathways (protein-protein, protein-RNA, protein-DNA), while the DNA-protein pathway is allowed but not observed. I guess the nice symmetry of the illustration got the better of me. (Or the prions are exponentially multiplying … dun, dun, duunnhh [/scary background music].)

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  7. 7. Torbjörn Larsson, OM 10:30 pm 07/25/2011

    To connect the popular folk version of the dogma with the biological version, perhaps one could consider that it is “into protein”, not “out of DNA”.

    People insist in revering the wrong end of the stick, because the grip (heritable DNA) is gold plated. But it is the point (functional protein) that is the sharp tool!

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  8. 8. Jennifer Frazer in reply to Jennifer Frazer 11:38 pm 07/25/2011

    I think I did get a little sloppy in describing the Dogma, so thanks for the comments! Yes, the main point is information flow — DNA, to RNA, to protein. But DNA as the unit of heredity is also a central point. Reverse transcriptase is a violation, but so is protein to protein information exchange. I didn’t say it was the first violation — just that it was one! : )

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  9. 9. Torbjörn Larsson, OM 9:41 am 07/26/2011

    [bangs head in desk] But clearly there is no violation of *Crick’s* dogma.[/raises bruised head]

    Which makes a molecular biology of cell machinery point, not an evolutionary hereditary one. Now you can argue that you can revise the dogma to other forms, but then it should be “the rejected dogma of DNA exclusivity” or something.

    I am not even arguing that Crick was a genius with a keen insight into cell machinery and its relation to evolution, which later scientists and educators may have lacked.

    I am just arguing that there is a Crick’s Central Dogma, that he has “copyright”, and that his version has never been violated. (Nor should one expect it to, in contrast to the others.)

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  10. 10. Torbjörn Larsson, OM 9:51 am 07/26/2011

    Ah, sorry, you did separate out the “DNA as unit of heredity” as a specific point. My bad!

    If we want to go there, it is obvious that the extant cell machinery is inherited from the LUCA (and earlier), since DNA all by itself would not suffice to reproduce or constitute it; it knows only how to replace key components and make it work.

    So there are plenty of violations of the “DNA as unit of heredity” dogma indeed.

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  11. 11. Blog Pick of the Month – July 2011 | EveryONE 5:39 pm 08/12/2011

    [...] PLoS ONE Blog Pick of the Month for July is Jennifer Frazer of The Artful Amoeba for her post on prions, the proteins that are notoriously difficult to kill: If you had to choose the world’s most [...]

    Link to this
  12. 12. Lichens protect against prion plague « Boreal Bites 7:04 pm 11/11/2011

    [...] Frazer over at the blog Artful Amoeba splendidly summarized the unlikely relationship between lichens and [...]

    Link to this
  13. 13. 2011: Rats attracted to cats, prion-killing lichen & mimicry « Science Calling! 12:50 pm 12/30/2011

    [...] If you were at the recent Ignite #8 talk in the Science Gallery, you’ll know how much the prion (infectious protein responsible for BSE / CJD) amazes me. This post reignited my passion for the prions and their amazing properties. It is a brilliant overview of prions and their power against UV radiation and extremes of hot (autoclave) and cold (freezing). I was also shocked by the lichen’s powers against the prion. An example of the how often in science clues can turn up in usual places! [Read post] [...]

    Link to this
  14. 14. Lichens vs. Prions – Scientific American | Chasing Symbiosis 5:55 pm 01/3/2012

    [...] Here’s the link to the blog post: [...]

    Link to this
  15. 15. The super ancestor of everything here on Earth. 11:58 pm 01/28/2013

    [...] slug! Before I actually try to stay on topic, I gotta show ya 2 cool things, a myko and a lichen. Lichens vs. the Almighty Prion | The Artful Amoeba, Scientific American Blog Network Leprosy bug turns adult cells into stem cells : Nature News & Comment Theres certainly some [...]

    Link to this
  16. 16. Episode five: “Infection” | A Science Story 2:22 am 03/8/2014

    [...] To read more about the indestructible prion and how it might have met its match (in lichens), click here. For more information about Tasmanian Devil Facial Tumour Disease and what we are doing about it, [...]

    Link to this
  17. 17. Episode nine: “Religion” | A Science Story 2:28 am 04/5/2014

    [...] To read more about the indestructible prion and how it might have met its match (in lichens), click here. For more information about Tasmanian Devil Facial Tumour Disease and what we are doing about it, [...]

    Link to this
  18. 18. Science online, urban evolution edition | Jeremy Yoder 11:59 am 07/1/2014

    [...] Mad lichen disease? Some lichens can apparently break down prions. [...]

    Link to this
  19. 19. Sonia5 11:32 am 09/26/2014

    This is extremely interesting information, Jennifer. Thank you so much for posting this. When you consider how modern medicine has taken the active components from plants to create pharmaceutical drugs, it makes sense that there are still yet undiscovered treatments out there hidden in the undergrowth of plants we have yet to study more thoroughly.

    Link to this
  20. 20. PRIONS and the Zombie Disease! | Prescription For Murder 7:13 am 01/21/2015

    [...] proteins and may contribute to such diseases as Alzheimer’s, Parkinson’s and Huntington’s. Scientists describe a prion as the smallest infectious disease-causing agent and also the most indestructible [...]

    Link to this

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