h2g2 The Hitchhiker's Guide to the Galaxy: Earth Edition

Our local Bavarian TV had two reports about this topic, and I made a terrible mistake: please substitute 'Mn' for 'Mg', and Manganese is the correct word.

I found some references, using google and "BSE manganese" as keywords. You may also search for "Mark Purdy" who is one researcher supporting this theory. Another place is Bossel's External Link Page (hehe, they said we could have links within entries, didn't they!) at http://www.bbc.co.uk/h2g2/guide/A519383.

I find it hard to believe that manganese can be attributed as a major causal factor for prion formation. Its probably the single most common metal ion found in proteins - ie. its a pretty majorly essential. If it is a major cause then there aint gonna be much we cann do about it I wouldn't think as nearly all our proteins/enzymes contain bound manganese somewhere.

Sorry about the delay in my reply Bossel. Had to find the time to go and read those articles. I have to agree with Orcus about the idea that manganese could be an actual *cause* of prion disease. I found the articles very unconvincing on that matter.

I've heard various rumours about organophosphates playing some role and perhaps its true but again, I found the articles far from convincing. I would agree that, if there's a possibility that organophosphates have anything to do with these diseases, they need to be studied carefully. It's hard to know what to believe reading the Fintan Dunne article. It sounded like something from the X Files. I got the impression that they were looking for explanations to loosely fit the facts rather than actually discovering causes. I'd go into all the things I found unconvincing but that would mean sitting here (which hurts my back) and doing a long message that the mods might then come along and remove or "hide" - as has happened for no very good reason, to other post. If you want a more lengthy discussion of why I'm unconvinced, name your location and we can discuss it there. I've got a prion thread on ezboard's goooverflow if you want to exercise your right to free speech there.

Sal

Well, I've got only limited understanding of chemistry and biology and sure wouldn't stand long in any deeper discussion. My point was to make you aware of recent findings (or would-be findings) on the topic. As far as I got it, manganese /is/ essential (somewhere in the copper and zinc balance), and too much of it --or perhaps Mn contained in the wrong substances like organophosphates-- might create or foster prions. I can imagine that some articles and ideas have been produced out of some publish-or-perish thinking, but on the other hand: Galileo's ideas were unconventinal too!

I don't disagree with you Bossel and until and unless the science is carefully carried out and the results published, we can only speculate. It's the actual articles that leave me unconvinced.

I was in some doubt about how recent these "finding" were. The first or second paragraph in the Purdy hypothesis article states that "The current theory" on TSEs is that it is transmitted via micro quantities of a yet to be identified "slow viral" agent found in animal feeds. Well, that theory was knocked on the head years ago.

The trouble is, you can find all sorts of stuff on the internet that might or might not be trustworthy and it's so difficult to tell which is which. Just because someone has a conspiracy theory, doesn't mean they're completely unhinged - but then again, unhinged people are apt to cook up conspiracy theories. It would be nice to have some sort of litmus test of their veracity. All those people having nasty accidents and getting shot ... it makes you wonder - but you can't just accept things like that on trust.

Sal

Well, you're perfectly right there. What made me believe that there was some truth in it is that [Bavarian BBC Competitor, err, Non-Competitor] featured two reports within a week, and usually, a topic which has been researched by them /has been/ researched.

I know what you mean. There are some programmes I tend to take far more seriously than other. If Jeremy Paxman had presented the story on Newsnight with some convincing evidence, I'd be less sceptical.

It wouldn't surprise me ever so much to hear that organophosphates could be involved in some way in some cases. It's conceivable that high levels of manganese might show up as a symptom of disease but it just seems so unlikely that it could be a cause.

In any case, you can be sure that if I do hear anything more, I'll be listening very carefully.

Sal

Hi Sal,
Nice article - informative too. I would certainly recommend it to anyone!
'nette
P.S. Isn't it true though that the viruses you refer to are some of the very few that can't be transmitted through MS Outlook!

Oh, I would be very careful with that statement. Who on earth knows what's going on in the bowels of [that well-known software item]?

Hiya 'netta. Great to hear from you. When d'you get back? Did you have a good time in Wales? Did you notice h2g2 blinked out and blinked back on again after about 6 or 7 weeks?

Thank you very much for your kind comments. I appreciate them.

As Bossel says, who knows? We can only hope that MS has some barrier against this or that virus. Hope yes. Faith no.

Sal

Orcus, Bossel: prick up yer ears. On BBC2 this evening (25/3/01) at 7.20 "Correspondent" - Mad Cows and an Englishman: is the metal manganese at the root of BSE? Organic farmer Mark Purdey believes it's possible, but his views haven't made him popular. I plan to watch that.

Sal

Oops. 9.45 now, just read your message

Verdict?

It was a bit vague. Mark Purdey seemed an excellent chap. He's an organic farmer and MAFF tried to force him to treat his cattle with organophosphate to guard against warble fly, back in the early 1980s. He refused and had to take them to court to get them off his back and convince them that they didn't have the right to enforce the use of (I think) Phosmet. He had a strong feeling that it would be very harmful. A year or 2 later the BSE cases started appearing with some regularity and he decided that it must be organophosphates causing it. He started his own crusade to prove it, including learning chemistry. He'd just had a basic education up to that time. He got the help of a scientist called David Brown at Cambridge uni. The tests he carried out indicated that organophosphates might play some role in prion disease but it wasn't obvious what that role was. It seemed to cause an increase in prions on the surface of cells, but only normal prions - not the misfolded infectious ones.

Purdy was determined to find the answers so he travelled the world taking all sorts of samples from areas where there were clusters of BSE, CJD and vCJD. He said he consistently found high levels of manganese and low levels of copper in those areas. When Brown carried out more tests involving not only organophosphate but also manganese, he found that manganese replaced copper in prions and caused the prion to change to the infectious conformation. They examined the brains of people who'd died of vCJD and found that the manganese was 10 times the normal level.

The story is that MAFF and their evil little goblins have tried hard to suppress this investigation from the beginning, using fair means and foul. It seems a bit odd that they should try to do that but, in any case, it looks as though MAFF might now be giving them a grant to continue the study.

It was hard to know what to make of it. He started off with this theory and seems to have devoted the last 15 + years of his life to trying to prove it. He and Brown brushed aside the findings of all the other studies even though they haven't yet actually proved anything any more convincingly than those other studies yet. They didn't deny the widely accepted means of transmission now the diseases are established, but they think it all started with organophosphates in areas with high levels of manganese rather than feeding sheep to cattle.

I don't know. What do you think?

Sal

Hmm. Could be. Organophosphates are notoriously poisonous compounds. That's why they make good insecticides, herbicides and nerve gases.
Still not convinced about the Manganese thing though.
Do manganes ions cause the prion misfolding or does this misfolding just provide a better binding site for manganes than copper? I would have to read David Brown's papers to find out (I'll have a look). Also, his name seems familiar. Do you remember my original posting on your prion article about how all proteins can misfold in this way? I now wonder if it was the very same man who gave the lecture I referred to .
How was it transmitted to humans also? Did beef contain this organophosphate which we ate?

Most importantly, they have largely eliminated the dangerous strain of BSE here by the huge cull they enforced in the early nineties. Has the use of this organophosphate also been stopped? If not, why are there not still lost of cases?

Not convinced as I said, but will always listen. Noone still really knows do they. I certainly find the possibilty of a few organophosphate molecules getting into brain cells and causing the misfolding more plausible than a large aggregated, insoluble protein mass doing so.

Hope you are well Sal. How are your wee doggies? Not too bored with the resticted walks I hope. I'm afraid I haven't visited your goooverflow journal for a while, hope there's not *too* much backlog to get through.

My dogs and I are bored rigid with not being able to go for a walk. Back's playing up so I can't sit very long - probably because I need to walk. I've got behind with the f&m journal but I've been keeping notes. For your information there were 40 new cases yesterday and another 47 today taking the total to 607. The army's digging a dirty great hole in Cumbria ready to take hundreds of thousands of dead animals. They anticipate (worst case scenario) that there could be as many as 4,000 cases by June. To prevent future outbreaks the govt is considering banning the feeding of swill to pigs and will limit the movement of sheep. They reckon the most likely source of this outbreak was swill from a catering establishment fed to pigs.

On the organophosphate/manganese thing. That was what I meant about it being vague. They really didn't go into very much detail and because they just kind of stated this thing and dismissed that thing without giving any detailed explanation of why, it just wasn't sufficiently convincing to really sway me (much).

He checked out Slovakia and found the people living in the area of a CJD cluster (mainly inherited), drank a tea made from pine needles that were high in manganese. It wasn't quite clear why, how, if at all, the pine needle tea influenced the genetic problem.

The suggestion seemed to be that by providing cells with manganese while depriving them of copper, the manganese would occupy the position normally taken by the copper and this would cause the prion to flip. Once that had happened, it could cause other prions to misfold in the usual (accepted) way - the cascade. The point was that they believed organophosphates used on cattle in areas where there was a high level of manganese *started* it. After the thing started, humans got it by eating beef. They seemed satisfied that prion diseases could be transmitted that way. Or at least they didn't mention a problem of organophosphate contaminated meat - just prions.

I remember your original post. It would be interesting if it turned out to be the same man. If you find out, be sure to let me know.

Sal

Hi Sal,
we got back from Wales just before Christmas, then went to Tunisia to warm up, and got back a couple of weeks ago.

Re: manganese, it has been suggested to me that it might just act as a magnet to prions, concentrating them in its area in a similar manner that radon gas is concentrated in some areas. Hope this makes sense.
'nette

Hiya 'netta

Sorry I'm a bit slow in replying. Did you enjoy yourselves in Wales and Tunisia? Hope you did.

I wonder how that would work - the manganese drawing the prions to it. Is radon gas drawn to an area? I thought it came from particular sorts of rocks that are found in some locations. I live near such an area.

I guess it might make sense if we knew more about it.

Sal

Hi Sal, Yes we had a great time

Re: prions and radon - I'm afraid I don't know. A friend who had been studying prions informed me that there seems to be a concentration of prions wherever there is manganese, and compared it to some areas where there is a concentration of radon (although I don't think that the radon was attracted by manganese - it all got (a lot) over my head
'nette

I HAVE RETURNED!!!

Down to business. My professer is having me write a ten (10!) page report on all things prion related. What do you think would be most useful to include? I would be eaternally greatful.

Hiya George. Good to see you back.

On your 10 pager, I can only suggest that I think I put all the major points in my entry but if you go through this thread there's a lot of speculative, unproven stuff that you could mention, being careful not to call anything a fact that's really just a speculation. There's a lot of stuff here, I'm sure there's more than enough to fill 10 pages. If you want more, click on the links in the article. Better do it soon because there's no telling when this entry might get edited and they'll probably strip out those links then.

Sal