The Tryptophan Tragedy, 1989-1990 (reviewed in 2003)

In 1988, I began my research in a chemical laboratory on plant chemicals. My focus was on the alkaloids and certain substances that were found in over the counter remedies.

The over the counter nutritional supplement business world has essentially the same issues it had more then three centuries ago. In Msr. Pierre Pomet’s History of Drugges, is this section detailing the problems with adulteration, counterfeit and substitutions, in which the most expensive plant medicines and related products were in such high demand that substitutes were produced mimicking the original medicines in looks or appearances. Some of these more effective forgeries still exist to this day and are even considered to have similar medical effects by some, such as the Pau d’Arco, for which an adulterant may now be sold even more than its original species.

Due to their scarcity, certain resins were worth their weight in gold. Some of the hardest to produce substances collected from nature were such substances as spermaceti, isinglass, Baltic amber, damar, true frankincense, the one and only sal glauber, all of these as a result had substitutes out there sold with the same label. In North America, the same sort of history existed for precious remedies like Unicorn Horn, Unicorn Root, Sarsaparilla, and Cochineal, an elusive little greenish-blue bug that grew only on certain cacti in New Spain. As these habits of adulteration versus finding the best and most real medicines continued into the 20th century, over-the-counter drugs were diluted down by the addition of look alikes or counterfeits. a practice that seemed easy for some plants.

Similars are plants with a similar look, and that often became accepted substitutes for some medicinal plants like Solomon’s Seal (Polygonatum sp.), for which the American False Solomon’s Seal (Smilacina sp.) was found to exist, or Western Coltsfoot (Petasites), considered a substitute for the European Coltsfoot (Tussilago) that naturalized in the Eastern states. During the early 1900s, these attempts to adulterate or modify over the counters and prescribed products was reduced somewhat by the passage of the Food and Drug Act of 1906, and the Food, Drug and Cosmetic Act of 1915. These legal maneuvers stated the requirements for the proper labeling of these products and greatly reduced the numbers of medicines that contained the various opiates that were now illegal, and quite incredibly even such ingredients added to over the counter store shelf medicines as cannabis and heroin, a newly discovered derivative of the opium latex.

Still, regardless of these anti-quackery laws, there were several laws that had to be developed during the twentieth century to lessen the misbranding or mislabeling going on and the misclassification of ingredients placed into certain formulas. Misidentification of products through the wrong interpretation of label names was not unusual at the time. A plant had its Latin name to identify it with, but this was rarely included on any label list of ingredients for a product. For foreign products, it was possible for these different names to allow a substance to pass inspection due to lack of appropriate identification. Other times we simply trusted the labeler to be accurate in the name given. In one case of Oriental medicine dispensing in California, a medicine had mistakenly been replaced with a highly toxic similar, due to the accidental misreading of a raw product label with the name written in traditional Chinese; this mistake resulted in a couple of severe poisoning events on the west coast of the US.

Another very important change in the nutritional supplement and drug manufacturing industry occurred during the latter half of the 1980s that impacted the safety of OTC herbal medicine and nutritional supplement products. The first successful attempts at producing food and medicine-related products came about through bioengineering and biotechnology. The very first highly successful industrial attempts to produce chemicals for food and drug use involved the production of amino acids from bacterial cell cultures. Tryptophan was one of these amino acids, which due to its unique cyclic nature was hard to produce through regular non-enzymatic chemical synthesis reactions in traditional vats or chemical synthesis chambers. There was a unique series of enzymes needed to make this amino acid, considered import to the neurochemical pathways in the brain. They were transferred into a standard basic bacterial cell culture consisting of Agrobacterium spp., which in turn could use these enzymatic steps contained in its genome to synthesize this substance at a fairly rapid speed.

This was one of the first such syntheses carried out for a product designed for human consumption, and so familiarity with what could happen due to this new technology was still not well documented. One unexpected consequence of this bioengineering manufacturing process was the production of other substances very similar to the desired product tryptophan, and since no adequate testing had yet been developed for differentiating these very similar compounds from each other, not such screening process for contamination by a similar was ever developed. It ended up, that one similar to tryptophan, since it bore chemical side chain similarity, had the ability to interact with other cell surfaces and enzymatic processes, which in the case of the bioengineered tryptophan OTC users became a medical tragedy since this new, unknown end product of biosynthesis had serious hematic and neuromuscular toxicity effects.

In Winter of 1989/1990 I was sent a sample from a physician in southern Oregon who had just seen one of the first patients experiencing this intoxication by an over the counter. The suspicion of the professor in charge of my lab and myself was that this could be a heavy metal poisoning case due to the symptomatology, in particular the neuromuscular toxic effects. We speculated that this could be due to the way in which the tablets containing TRP were shipped from Japan to the US, in containers with an inner surface coated with a product rich in Vanadium. It ended up this was not the case. Tablets were mailed to me and heavy metal was ruled out due to the lack of evidence and a later review of the product manufacturing process indicated this contact with the inner surface of the containers seemed very unlikely. A couple of months later, the true cause for these intoxications was uncovered, and the focus of work in my lab went in several other directions.

These papers are part of a review I did of this OTC adulteration case I was largely responsible for from about October 1, 1989 to June 30, 1990. It was submitted as a term paper and final presentation for my mass media course.

The 1989 to 1990 Tryptophan Recall

Tryptophan References

Newspaper and Television Mass Media Review and Critique

TRP Use for 5 Major Categories of Disease Type (notes; handout)

Brian Altonen, MPH, MS