mardi 11 février 2014

Christopher McCandless and Lathyrism

I ran into an article on Salon a few months ago about Krakauer suggesting that, after all this time, he figured out, thanks to the investiogation of a certain Ronald Hamilton, that McCandless died as an indirect result of lathyrism. I see there are older threads about McCandless but none seem to talk about lathyrism (unless I just missed it).



From http://ift.tt/1lyKkxz


Quote:








By the time he wrote the book, though, Krakauer had amended the story. He speculated that McCandless had indeed eaten the benign wild potato seeds, but that he had somehow been poisoned by them anyway. He believed this, Krakauer writes, because it’s what McCandless believed — he had written in his diary that he was “extremely weak,” and that potato seeds were the cause. Alaskans ridiculed Krakauer for this preposterous theory, he says, and no evidence was ever found to support it.



But thanks to an essay published online by author Ronald Hamilton, there’s now convincing evidence, Krakauer writes, to suggest that McCandless did, in fact, know enough to distinguish between the seeds. The potato seeds he consumed weren’t believed to be poisonous because normally, they aren’t. It’s only in very specific circumstances that they become dangerous — and those most at risk are young, thin, undernourished men. The only other record of something like this happening was in a Nazi concentration camp. There, starving prisoners were left crippled after being fed seeds containing a certain type of acid — the same acid, tests confirmed, that’s found in wild potato seeds.



So Krakauer had this weird idea that McCandless did not misidentify the plant in question and that it contained a mystery alkaloid (Krakauer thought the alkaloid was SwainsonineWP ) hitherto unknown to be a component of this species. The only problem is that when he sent some plant material to some biochemists to be analyzed they found no trace of this.



Years later, an employee of the library of the Indiana University of Pennsylvania who was familiar with the story found descriptions of lathyrism, a type of intoxication from consumption of Lathyrus sativusWP (which goes by the common name of chickling vetch and many other names) causing paralysis, and found similarities with McCandless' diary account of of his condition at the time nearing his death. He hypothesized that the chemical compound responsible for the toxicity of the chickling vetch might also be found in the wild potato, Hedysarum alpinumWP , and asked some chemists at his school to test it. They ran some thin layer chromatographyWP (TLC) plates and they found a spot at a distance roughly corresponding to the toxin responsible for lathyrismWP , not an alkaloid but rather a non standard amino acid known by the acronym ODAPWP .



Lathyrism is a disease of poverty and famine. It is thought that the undernourished are most susceptible to the presence in the diet of this excitotoxin of the chickling vetch, ODAPWP . The other big reason why it is associated with famine is the fact that this hardy legume tends to be a food item impoverished people resort to eating when there's nothing else to eat such as during times of famine. There also exist a history of using this for the purposes of adulterating various pulses in India.



The Spanish Romantic painter, GoyaWP , used it as a theme in the painting from his dark period titled Gracias a La Almorta (Thanks to the Chickling Vetch), which portrays the characteristic paralysis.







Krakauer's actual blog post in the New Yorker is more informative:




Quote:








Fast forward to a couple of months ago, when I stumbled upon Ronald Hamilton’s paper “The Silent Fire: ODAP and the Death of Christopher McCandless,” which Hamilton had posted on a Web site that publishes essays and papers about McCandless. Hamilton’s essay offered persuasive new evidence that the wild-potato plant is highly toxic in and of itself, contrary to the assurances of Thomas Clausen and every other expert who has ever weighed in on the subject. The toxic agent in Hedysarum alpinum turns out not to be an alkaloid but, rather, an amino acid, and according to Hamilton it was the chief cause of McCandless’s death. His theory validates my conviction that McCandless wasn’t as clueless and incompetent as his detractors have made him out to be.



The linked essay is recommended even if it could have greatly benefited both from a regular editor and from a science editor. It can also be found on six web pages starting at http://ift.tt/17udW8J and, in those web pages, it also includes reproduction of the TLC plate spotting.



So, regardless of whether he was on death's door already or whether the paralysis from being poisoned by his food is what put him there (since paralysis makes food gathering a bit more of an issue than it already was for McCandless), I find it fascinating that he might have suffered from lathyrism.



However, while the evidence presented is consistent with lathyrism (and I kind of want it to be lathyrism because it's a cool story), I am, at the point of reading that analysis, skeptical. The identification of ODAP with TLC is, at the very best, extremely weakly presumptive. It's only a start. If Hamilton's paper had been well done it might even have been good for publication just because it has a good story with it (I'm sure there would be some journal which would take it --maybe something related to forensics?).



Instead, one can tell by looking at the scanned images of the plates that the Hedysarium spp. spots all appear to have a higher Rf value than the ODAP & Lathyrus spots. Of course, this could be artifactual. It is, in fact, very possible for all the spots alleged to represent ODAP to actually be ODAP but one simply cannot tell (and even if the spots alleged to represent chemicals having traveled exactly the same distance did represent this, more than one chemical might be able to do this).



But back on the blog post it does suggest that Krakauer was a little bit more careful than that and investigated further by contacting Avomeen Analytical Services where Dr. Craig Larner analyzed some samples:


Quote:








To establish once and for all whether Hedysarum alpinum is toxic, last month I sent a hundred and fifty grams of freshly collected wild-potato seeds to Avomeen Analytical Services, in Ann Arbor, Michigan, for H.P.L.C. analysis. Dr. Craig Larner, the chemist who conducted the test, determined that the seeds contained .394 per cent beta-ODAP by weight, a concentration well within the levels known to cause lathyrism in humans.



However, despite the more expensive equipment, I would still consider HPLC to be presumptive as well. Even getting similar results as with the TLC is not terribly meaningful if the column packing and solvent phases happen to be similar to the stationary phase of the TLC and the solvent used there since the chemicals would be separating according to exactly the same physical processes.



Krakauer, however, seems to be have been aware of this since in his previous paragraph he quotes Wendy Gruber as saying “To be able to say that ODAP is definitely present in the seeds,... we would need to use another dimension of analysis, probably by H.P.L.C.-M.S.”.



So my assumption is that Krakauer simply misreported the testing done by the analytical chemist and that Dr. Larner did, in fact, use LC-MSWP which would make the finding, in my opinion, a very solid finding.



I did try to send a message through Avomeen Analytical Services' website to be forwarded to Dr. Craig Larner to learn of the details of the analysis but I never received a reply. After that, I just forgot about it.





via JREF Forum http://ift.tt/1lyKncJ

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