Jon Krakauer responds: What killed Chris McCandless?

Editor's note: The following commentary was written in response to a recent column by Alaska Dispatch's Dermot Cole. Readers interested by this discussion may also find interest in a related column by Dispatch's Craig Medred published on Sept. 13.

I'd like to clear up a few of the misleading statements in Dermot Cole's Sept. 17 commentary on the story I posted last week at The New Yorker about the neurotoxin ODAP and its role in the death of Chris McCandless.

A key source for Cole's screed was a retired University of Alaska Fairbanks professor of chemistry, Thomas Clausen, who explained to Cole that there are two forms of ODAP, "which would likely have vastly different levels of toxicity." According to Clausen:

Even though Krakauer explicitly states the 'L' form is present in the plant, it is very unlikely that the tests to establish this were done. While this error of Krakauer's is understandable for a non-chemist to make, it certainly reinforces the need for Krakauer's claim that ODAP exists in Hedysarum alpinum to be put through a standard review process by technically trained and unbiased individuals.

There are indeed two forms of ODAP, commonly referred to as alpha-ODAP and beta-ODAP. They are nearly identical, except for one important difference. The alpha form (alpha-N-oxalyl-L-alpha,beta-diaminopropionic acid) is non-toxic. The beta form (beta-N-oxalyl-L-alpha,beta-diaminopropionic acid) is highly toxic. But Dr. Clausen is wrong to assume that proper care wasn't taken to ensure that the toxic beta-ODAP was the form actually tested. The ODAP submitted for analysis was positively identified as a pure sample of beta-ODAP produced by Dr. S.L.N. Rao, among the world's foremost authorities on ODAP and lathyrism.

Using Rao's sample as a benchmark, significant levels of toxic beta-ODAP were detected in the seeds of Hedysarum alpinum by means of reverse-phase High Pressure Liquid Chromatography (HPLC). The testing was done by unbiased, experienced chemists at a highly regarded laboratory.

Before my piece was posted on The New Yorker website, its accuracy was independently confirmed by that magazine's famously meticulous fact-checkers, who consulted with organic chemists and lathyrism experts. Next summer, when fresh seed samples can be harvested in Alaska, I will arrange for a peer-reviewed study, as well. But the standard peer-review process, in and of itself, is no guarantee of credibility.

In 2008, Clausen and his protégé, Dr. Edward Treadwell, published a peer-reviewed paper in the journal Ethnobotany Research & Applications, titled, "Is Hedysarum mackenziei (Wild Sweet Pea) Actually Toxic?" In this paper, Clausen and Treadwell announced "No chemical basis for toxicity could be found" in either Hedysarum mackenzii or Hedysarum alpinum. Given that unpublished analysis with Thin Layer Chromatography (TLC) done by Wendy Gruber in 2004 was strongly suggestive of toxic beta-ODAP in both species, and given that the much more definitive HPLC analysis I commissioned last month clearly identified toxic beta-ODAP in Hedysarum alpinum seeds, I hope Clausen and Treadwell reconsider the conclusions they presented in their paper, lest foragers take them at their word and come to grief as a consequence.

Four or five years before Clausen and Treadwell published their paper, having learned from reading "Into the Wild" that Treadwell had tested Hedysarum seeds for poisonous alkaloids, Ronald Hamilton emailed Treadwell out of the blue to ask if a toxic amino acid such as beta-ODAP might have "been a contributing cause" in McCandless' death.

Treadwell replied:

I must admit that the presence of ODAP in the Hedysarum seeds is intriguing. I would have to say that it is a possibility. All of my work was done on extracts of the Hedysarum plants (roots, leaves, stems), where the plant material was soaked in some organic solvent to extract the organic compounds from the solid material, which was then discarded. (Much like making tea – the water seeps into the tea bag and brings out the "tea flavor" from it). Although I do not know this for sure, ODAP probably isn't very soluble in organic solvents and hence might have remained with the rest of the solid material.

Second, the "tests" I used for alkaloids basically consisted of spraying a TLC plate of the extract with reagents that turn colors on a plate when they react with an alkaloid. Once again, ODAP being an amino acid, it might not have behaved like most alkaloids….

All told, I am not sure if this is a very satisfactory response, as I cannot definitively state that Hedysarum alpinum and/or mackenzii contain /do not contain ODAP.

It is possible.

Treadwell thus considered it an "intriguing" possibility that ODAP was present in the seeds of Hedysarum mackenziei and Hedysarum alpinum long before the paper he and Clausen co-authored was published, yet, inexplicably, he and Clausen chose not to test their plant samples specifically for ODAP, as I did. Nor did they rely on sophisticated HPLC analysis, as I did. Instead their data were derived from relatively crude TLC methodology and a "preliminary cytotoxic assay," neither of which yielded results that can be considered definitive as far as the presence of ODAP is concerned. Their paper's conclusion — "no chemical basis for toxicity could be found" in either species of Hedysarum — therefore shouldn't be trusted.

On Aug. 16, before I asked Avomeen Analytical Services to test the seeds of Hedysarum alpinum for beta-ODAP, I emailed Dr. Treadwell to inquire whether he would be willing to perform the HPLC analysis of the seeds, and offered to have an ODAP sample sent to him. He did not respond to my inquiry.

So here's where things stand: HPLC analysis has confirmed that crippling levels of beta-ODAP are found in the seeds of Hedysarum alpinum, the wild potato plant. Taking into account all the available evidence, especially the symptoms McCandless described in his diary and explicitly attributed to the wild potato seeds he ate — "EXTREMELY WEAK. FAULT OF POT[ATO] SEED. MUCH TROUBLE JUST TO STAND UP." — there is ample reason to believe that Chris McCandless was stricken with lathyrism from eating Hedysarum alpinum seeds, became too disabled to hunt effectively or walk out to the road, and died from starvation as a consequence.

May he one day rest in peace.

Jon Krakauer recently started an Instagram feed (http://instagram.com/krakauernotwriting), and is the author of numerous magazine articles and books, including the book "Into the Wild," which explores the life and fatal starvation of Christopher McCandless in Interior Alaska.

The views expressed here are the writer's own and are not necessarily endorsed by Alaska Dispatch, which welcomes a broad range of viewpoints. To submit a piece for consideration, e-mail commentary(at)alaskadispatch.com.