Introduction 

   General Info 

   Metabolic Role 

   Supplement 

   History 

   References 

Tryptophan was first isolated in 1901, from the milk protein casein, by Sir Frederick Gowland Hopkins. By feeding mice a diet devoid of tryptophan, he was later able to demonstrate that it is essential for animal life. As well, he demonstrated that tryptophan and several other amino acids cannot be manufactured in the body and must be obtained from the diet. He was awarded the Nobel Prize for his discovery of vitamins, produced by amino acids like tryptophan.

Tryptophan was widely available as a nutritional supplement throughout the 1980's. Like other food supplements, it has been produced for many years by fermentative processes, in which large quantities of bacteria are grown in vats, and the supplement is extracted from the bacteria and purified. In the late 1980's Showa Denko K.K. decided to use genetically engineered bacteria in the manufacture of tryptophan to speed up and increase the efficiency of this process.

Tryptophan produced by this process was placed on the market in 1988. As it was considered essentially equivalent to conventionally-produced tryptophan, it required no further testing to be deemed safe. However, in less than a year it had been linked to thousands of cases of eosinophilia myalgia syndrome (EMS) caused by toxins in the supplement. More than 1500 cases of permanent disability and 37 deaths resulted. As the genetically engineered supplement was not labelled to distinguish it from other tryptophan, it took months to establish it as the cause of the disease.

EMS results in eosinophilia (overproduction of blood cells) and myalgia (muscle pain) initially, giving it its name. Over the long term this condition causes symptoms including paralysis and neurological problems, painful swelling and cracking of the skin, heart problems, memory and cognitive deficits, headaches, extreme light sensitivity, fatigue, and heart problems. The disease was later linked to several toxins in the tryptophan supplements, most prominently EBT (1,1'-ethylidene-bis-tryptophan), a dimerization product of tryptophan. It was deduced that at the high concentrations used in production, tryptophan molecules were reacting with each other to produce this deadly toxin.

Click here to view the landmark paper by Smith et al. which identified the deadly toxin, "contaminant 97." We are indebted Dr. Eugene Mazzola, one of the co-authors of this report, for his help in preparing this summary.

Tryptophan supplements were recalled in 1989, and then banned completely in 1990 by the FDA. It is unclear whether the disease was primarily the result of inadequate purification of the tryptophan, or the use of genetically modified bacteria. However, it is clear that only batches of tryptophan produced by one company, by one unique method, were toxic. No tests prior to or since the ban have shown toxins in any other tryptophan supplements.

Owing to this ambiguity, tryptophan is now the topic of numerous debates about food supplements. It is a prime target for those cautious of (or opposed to) the consumption of genetically engineered products, and the inadequate labelling of these products. However, the recall of this product is also subject to criticism relating to the role of politics in drug regulation. Critics point out that tryptophan supplements, aside from those produced by Showa Denko using genetically engineered bacteria, have never been shown to contain toxins.