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McNeil, Brennan Mitchell CM 3313 6 December 2013 Lathyrism and the Downfall of Supertramp In August of 1992, hitchhiker and

wanderer Christopher Alexander Supertramp McCandless passed away deep in the Alaskan wilderness. Upon the discovery of his remains, Alexs story was spread across America and eventually the world. Over the following years, Alexs writings and journey slowly became the subject of much interest and debate and have since been the source of the national bestselling book Into the Wild as well as a major motion picture. The circumstances of Alexs death are still surrounded by great controversy. Originally, it was believed that Alex misidentified a common potato seed Hedysarum Alpinum as Hedysarum Mackenzii, a potentially deadly cousin thought to be toxic. However, further research suggests that Alexs demise came not from consuming the wrong seed, but rather, from eating the right one. In order to understand McCandless fatal mistake we must first look in the history books. During World War II, the German army ran a prison camp located in a region of the Ukraine called Transnistria. This camp, known as Vapniarca, consisted primarily of Jews. The overseer of Vapniarca, one Colonel Ion Murgescu, ordered that re-appropriated stores of cow and horse fodder taken from the Russian army be fed to the detainees within the camp. The Colonel, knowing these plants to be potentially toxic to humans, considered the inmates consumption of the poisonous grass pea to be an experiment in mass extermination. Before long, many of the camps inhabitants, especially the young men, began to exhibit weakness and paralysis often leading to death.

The Jewish prisoners, led by Dr. Arthur Kessler, quickly realized the grass peas in the fodder they were eating was causing the illness and eventually staged the first and only food strike within the entire wartime period. Many of these captives, now crippled and disabled, were liberated from the camp at the conclusion of the war thanks to a prominent Nazi commander and eventually settled in the newly formed nation of Israel. Among these refugees was Dr. Arthur Kessler who, having watched the health of many of his comrades in the camp deteriorate, suspected the cause to be the grass pea within the food supply. The plant in question, scientifically named Lathyrus Sativus, was first described around 400 B.C. and has been recognized by countless civilizations since. In fact, Hippocrates observed in relation to Lathyrus Sativus that all men and women of Aions who ate peas continuously became impotent in the legs and that state persisted. The consumption of the grass pea has been banned in numerous countries over the course of history and its effects observed by many historical figures. The high yield and aggressive growth of Lathyrus Sativus have made it a desirable crop to cultivate but always a dangerous one to consume. This species of plant continues to cause problems in developing countries as it has nutritional value despite its toxicity. Seeing the effects of the consumption of Lathyrus Sativus in Vapniarca, Dr. Kessler resolved to open a clinic in order to help scientists and physicians understand the effects of Lathyrus Sativus and help treat Lathyrism, the disease caused by its consumption. Through their research, Dr. Kessler and his associates finally isolated the toxin responsible for Lathyrism in 1962 and helped work out its mechanism of action. The grass pea contains a neurotoxin dubbed ODAP (Figure 1), an abbreviation of beta-N-oxalyl-L-alpha-beta-diaminoproprionic

acid. This toxin, similar to many other poisons and toxins created by plants and animals for defense against predation, is a protein. Once consumed, the protein ODAP enters the blood stream and makes its way to the brain. There, it crosses the blood/brain barrier and reaches the synaptic
Figure 1: The Chemical Structure of ODAP

cleft between nerve cells. These cells send signals to neighboring cells using neurotransmitters. One of the

most commonly used neurotransmitters is the amino acid Glutamic Acid or Glutamate. When Glutamate is released into the synaptic cleft it binds to AMPA receptors which trigger a cascade of events causing an electrical impulse to travel through the associated nerve. When ODAP reaches these areas, it causes overstimulation of AMPA receptors. This overstimulation renders the receptors overly sensitive and causes them to fire with more intensity and at a faster rate than normal. This constant firing does not permit the receptor time to recover from each synaptic event. Eventually, the overstimulation by the ODAP protein causes the degradation and irreversible malfunction of the receptor. Continued receptor destruction on a large scale not only affects signal transduction but is accompanied by the death of neurons and eventually leads to a partial failure of the entire system. For unknown reasons, this neuronal death and decreased signal transduction is the strongest in the part of the brain that controls movement of the lower extremity. One may hypothesize that the structure of the ODAP protein is causing it to be transported to the part of the motor cortex responsible for control of the lower extremity. Another theory is that the area controlling the lower extremity uses a larger percentage of glutamic acid and AMPA receptors than other parts of the brain and is therefore more affected by ODAP.

The neuronal death that is the result of ODAP introduction into the brain is irreversible and degenerative in nature. The resulting paralysis never improves. Instead, depending on the dosage, there is an increasing inhibition of motor function until the patient is unable to move his or her lower extremities or is killed by the effects of the neurotoxin. However, not all patients die from the toxin or are greatly affected. It is unclear why, but the most susceptible demographic to lathyrism is men from the ages of fifteen to twenty five. In addition, the effect of Lathyrus Sativus and its neurotoxin ODAP is greater in individuals who are malnourished or starving, who are under physical stress, and whose bodies contain shortages of vitamins and minerals such as Vitamin A, Vitamin C, Zinc, and Copper. Interestingly enough, all of these factors were present in the case of young Christopher McCandless. In the summer 1992, McCandless was living inside an old bus deep within the Alaskan Backcountry. Hunting and gathering his own food, he ingested the seeds of what he believed to be the Hedysarum Alpinum plant. This specific plant is a species of legume related closely to the Hedysarum Mackenzii which is a presumably toxic species. Mccandless death, therefore, was prescribed to a misidentification of the Alpinum and consumption of the toxic Mackenzii. It was decided that an alkaloid existing within this plant were responsible for the death of the Supertramp. this point, Jon Krakauer, author of Into the Wild, theorized that the alkaloid that caused Christophers death was the likely swainsonince, a compound known to inhibit glycoprotein metabolism in animals (figure 2).
Figure 2: The Chemical Structure of Swainsonince

At

Krakauer soon collected both species of legume and sent them to the University of Alaska for testing. The testing of these two species demonstrated that they contained zero toxic alkaloids in their roots, stems, leaves, flowers, or seeds. These experiments were performed by soaking samples in organic solvents to extract the organic compounds from the solid material, which was then discarded. However, it must be noted that the lab at the University of Alaska did not test for other poisonous substances or proteins potentially existing within the two species. For several months the there were no leads in the death of Christopher McCandless. At this point, the cause of death was unknown and any hope of finding it seemed to be growing slim. In an unlikely turn of events, a professor at the University of Indiana and published author R. C. Hamilton discovered the story of Christopher McCandless and began to ponder the circumstances of his death. Considering Alexanders symptoms and his increasing inability to walk, Hamilton was strangely reminded of the events at Vapniarca. In a moment of clarity, he wondered if Alexander had died not from alkaloid poisoning, but instead from the consumption of ODAP. Following his hunch, Hamilton contacted the Chemistry Department of the Indiana University of Pennsylvania and obtained samples of both Hedysarum Alpinum and Hedysarum Mackenzii to be tested. Additionally, they obtained pure samples of ODAP as well as the plant Lathyrus Sativus. In order to test for ODAP, the researchers used silicon test plates to view footprints left behind by amino acids. The specimens were frozen in liquid nitrogen, ground into powered, dissolved into ethanol, refrigerated, and then separated using centrifugation. The remaining liquid, containing amino acids and proteins, was spread across silicon test plates. Capillary action then caused the liquids to move up the test plates and separate based on size and composition. Essentially, different compounds each travel up the plate at their own rate. This fact allows the

compounds to separate from each other as time passes and then to be observed by the scientist. Each plate was then dried and sprayed with ninhydrin to help bring out the color of each marker. Multiple substances were tested for including: ODAP, isoleucine, praline, tryptophan, glycine, valine. For a mode of comparison, legume family members which are known to be nontoxic were tested as well. The study showed that while the roots of the Hedysarum Alpinum and Hedysarum Mackenzii did not indicate the presence of ODAP, the seeds of both species tested strongly positive for ODAP. The concentration of the toxin was so high that it dwarfed the concentration found in the grass pea Lathyrus Sativus. With this data in hand, Hamilton could confidently say that his hypothesis was correct and that McCandless had contracted lathyrism by the consumption of the notably harmless Hedysarum Alpinum. McCandless, vulnerable to the toxin contained within the leaves of the Alpinum due to his age, activity, and diet, had a strong reaction to the ODAP protein. Additionally, he consumed a large amount of the readily available seeds in a short amount of time. The content of these seeds, containing including extremely high levels of ODAP, along with the dosage he ingested, quickly caused overstimulation of McCandless AMPA receptors leading to neuronal death and loss of neurological function. This led to his paralysis and self described having much trouble just to stand up. Unable to walk or leave his small shelter, McCandless met his end as he starved to death. Many have called Christopher Alexander Supertramp McCandless a fool since the publication of his story. They have blamed his death on reckless arrogance when, in fact, he most likely did nothing wrong. Like the men imprisoned at Vapniarca, like tens of thousands in China

and Bangladesh, like an estimated 100,000 people worldwide currently suffering from lathyrism, Alexander Supertramp consumed the deadly neurotoxin ODAP and suffered the consequences.

Figure 3: Results of silicon plate experiment showing different footprints of tested compounds.

Works Cited Krakauer, Jon. Into The Wild. New York: Anchor Books, 1997 Hamilton, R.C. "Christopher McCandless aka Alexander Supertramp." The Silent Fire (2012): 06. Chris McCandless Now I Walk Into The Wild. Dec. 2012. Web. 06 Dec. 2013. Plants Profile for Lathyrus Sativus (white Pea). Rep. USDA, n.d. Web. 06 Dec. 2013. "Hedysarum Alpinum." US Forest Service. N.p., n.d. Web. 06 Dec. 2013. <http://www.fs.fed.us/database/feis/plants/forb/hedalp/all.html>. "Vapniarka." Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 4 Jul. 2013. Web. 6 Dec. 2013. Spencer PS, Roy DN, Ludolph A, Hugon J, Dwivedi MP, Schaumburg HH. Lathyrism: evidence for role of the neuroexcitatory aminoacid BOAA. Lancet. 1986 Nov 8;2(8515):1066-7.