(Excerpt from: Assessing the safety and nutritional quality of genetically engineered foods by John Fagan)

Some of the potential biological characteristics of genetically engineered proteins or their metabolites can be assessed by simple in vitro tests. However others cannot, and by the very diversity of possible effects and the complexity of the physiology, it is impossible to carry out laboratory experiments that will exhaustively, thoroughly, and conclusively establish that a genetically engineered food is free of such toxins, and therefore safe. In all cases, a finite probability will remain that some toxin or other biologically active molecule has been generated in the recombinant food for which no adequate test is available. Therefore, it is crucial that each transgenic food be tested for toxicity in human volunteers. Without these experiments, there will always be an appreciable probability that the toxic properties of some genetically engineered foods will not become apparent until that food is placed on the market and the health of consumers is damaged.

An example of this has already come to light, although there is controversy regarding details. The company Showa Denko genetically engineered a microorganism to produce L-tryptophan at high levels. The enzymes expressed in this bacterium through genetic manipulations were not present in massive amounts, but they altered the cellular metabolism substantially, leading to greatly increased production of tryptophan. This organism was immediately used in commercial production of L-tryptophan, and the product placed on the market in the USA. Within two months, 37 people died and 1500 were permanently disabled from using this product. This was, evidently, due to the presence of traces of a toxic contaminant. This contaminant was extremely powerful, since the preparation was at least 98.5% tryptophan.

This contaminant was later identified as a dimerization product of L-tryptophan. Based on fundamental chemical and biochemical principles, scientists have deduced that this compound was generated within the bacteria when internal tryptophan concentrations reached such high levels that tryptophan or its precursors began to undergo side reactions that led to dimerization. Thus, it appears that genetic manipulations led to increased tryptophan biosynthesis, which led to increased internal tryptophan levels. At these high levels, side-reactions occurred, which generated a deadly toxin. Being highly similar to tryptophan, itself, this toxin co-purified with tryptophan, contaminating the final commercial product at levels that were highly toxic to consumers.

Some ambiguity remains regarding this story, since the company destroyed all samples of the recombinant organism as soon as the problem was recognized, and since the company acknowledges cutting corners on the purification procedure used in preparing the batches of tryptophan that turned out to be toxic. Since the recombinant bacterium is no longer available, the definitive experiments cannot be done to resolve which variable-recombinant manipulations or purification procedure-was primarily responsible for the presence of the toxin in commercial batches of L-tryptophan. However, in addition to the biochemical rational presented above, two additional arguments point to recombinant manipulations at the culprit: (1) No evidence exists indicating that the parental bacterium produces this toxin. Thus the ability to produce it must have been conferred by genetic modifications. (2) The tryptophan produced by other manufacturers, who used natural bacteria, was not toxic, even though it is likely that they were als o cutting corners in their purification procedures from time to time. We conclude that it is likely that genetic engineering was the determinate factor in generating this toxin.