The Showa Denko Tryptophan disaster reevaluated

New evidence indicates that genetic engineering
was the cause

Published January 6, 2007. Last updated Nov 19, 2014.

Conclusion - genetic engineering was the cause of death to 37 persons

(Link to: Brief summary. Link to Executive summary)
  • The commonly held "filtration hypothesis" - that the accident was caused by insufficient purification of the product - has been definitely disproven.
  • Two abnormal substances "IMT" and "EBT", closely similar to tryptophan, were found in the product.
  • The only tenable scientific explanation for their appearance is a disturbance of tryptophan metabolism caused by the introduction of four foreign genes all designed to influence synthesis of tryptophan.
  • It is of minor importance whether these two substances were the specific cause of the deaths, or not. The important thing is that genetic engineering evidently generated at least two unexpected poisonous substances very difficult to detect.
  • In any case, it is established beyound reasonable doubt that some product from disturbed metabolism due to genetic engineering was the ultimate cause of the deadly disease.
  • The substances were not discovered by the company in spite of using advanced chemical analysis methods. This is because they were there in very small quantities, yet sufficient to cause severe illness.
  • The current GM-food safety assessment procedure based on "Substantial Equivalence" would not have discovered the subtance because it does not require in-depth toxin detection.
  • This is not a unique case. Unexpected or abnormal substances have been found also in other GMO:s and this was already predicted long ago as a potential result of gene manipulation.

This indicates that the present superficial safety assessment procedure for GMO foods is a recipe for disaster. It may be a matter of time only before another unexpected and harmful substance goes undetected, potentially harming millions of people, especially if the effect is not immediate or no labeling of GM-food is done, enabling people to discover the connection.



Brief summary

(Link to: Executive summary)

A poisonous substance in a GM food supplement killed 37 persons and 1500 contracted a chronic severely painful and incapacitating disease. This disaster started in the late 1989 and ceased when the cause was discovered.

At that time, the biotech industry maintained that some change in the production of the supplement caused the accident, but our conclusion, based on recently discovered evidence, is that, with great certainty, a metabolic disturbance, caused by genetic engineering, was the reason for the appearance of the deadly and powerful poison that made the food supplement very harmful, although tests showed it was 99.6% pure.

This disaster demonstrates that genetic engineering may give rise to very dangerous unexpected substances, difficult to detect. Unfortunately, the present safety assessment procedure for genetically engineered (GE) foods is far too insensitive to detect such unexpected dangerous poisons that may appear through genetic engineering.

As all genetically engineered (also called GMO) foods on the market have been approved with this method, all GE foods must be withdrawn to prevent another disaster. The first step should be to immediately label them until withdrawal has been implemented.

ADDITION May 2010: The present campaign by the US government to forbid labelling of GE foods globally may pave the way for a world-wide disaster because the connection with a harmful GE-food will not be discovered in time.



Executive summary

[Definition: GE foods = genetically engineered foods = GMO foods]

In 1989, a disastrous epidemic broke out in the US that caused 37 deaths and disabled 1.500 permanently in a disease called the "Eosinophilia-Myalgia-Syndrome" (EMS). It was caused by a highly poisonous substance in the food supplement tryptophan, which had been produced by genetically engineered bacteria at the Japanese company Showa Denko.

The biotech industry maintained that the disaster was not caused by genetic engineering but by an "impurity" due to reduced filtering of the product. But recently it has been discovered that hundreds of cases contracted EMS before the filtering was decreased.

We have made a careful analysis of the facts to find out if there was any plausible other reason for the appearance of the deadly poison than genetic engineering.

Bacterial fermentation, the method used for producing tryptophan, had an excellent safety record since over 60 years before genetically manipulated bacteria were used. Therefore it is extremely unlikely that the fermentation process produced the poisonous by-product.

On the other hand, molecular biologists predicted decades ago that genetic engineering may cause changes that induce the appearance of unexpected and potentially harmful substances. This prediction has been confirmed in a number of cases. Moreover, not one gene had been inserted into the bacterial DNA, as commonly is the case, but four different genes. The risk for unpredictable consequences increases with the number of inserted genes.

Most importantly, the poison considered most important in the tryptophan was closely similar to tryptophan (a dimer), but is never found in natural bacteria. This indicates that disturbed tryptophan metabolism generated the poison. Moreover, the inserted genes were designed for altering the metabolism (so as to increase tryptophan production).

Our conclusion is that the only plausible explanation for the appearance of this poison is disturbances of the natural metabolic processes due to genetic engineering.

This deadly supplement would have passed as a safe product if the established procedure for approval of GE foods had been used. It is based on a safety assessment method that is is not designed to reveal unexpected poisons, but leaks as a sieve.

For this reason all genetically engineered foods on the market are unsafe, Therefore all GE foods must be withdrawn. As a first preventive step until withdraval is implemented they should all be labeled.

If not withdrawn, it is no doubt a matter of time only before another GE food disaster occurs.

Showa Denko was the Harrisburg of gene technology. Must we have a Chernobyl before the use of GM foods is stopped?

ADDITION May 2010: The present campaign by the US government to forbid labelling of GE foods globally may pave the way for a world-wide "Chernobyl" because, without labeling and with the insufficient pre-release safety assessment, the connection between the harmful GE food and disease symptoms will not be discovered in time.




The disaster

37 persons died and 1.500 were permanently disabled within a few years from 1989 on in a disease called Eosinophilia-Myalgia-syndrome (EMS) caused by some extremely poisonous substance present in a tryptophan food supplement, which was produced by genetically engineered bacteria at the Japanese firm Showa Denko (1). This lethal epdimic subsided when the tryptophan supplement was withdrawn from the market.

The effects of the poison

The poison (or poisons - it has not been possible to find out if one or a combination of poisons caused the disease) was very aggressive, damaging several organ systems including, among others, heart, lungs, muscles, joints, liver, skin and the nervous system. It caused death from severe muscle damage, severe nerve damage (polyneuropathy) heart damage or lung damage. It caused chronic suffering from severe muscular and joint pain, muscle cramps, severe fatigue and troublesome skin and neurological disorders in survivors. No cure for the chronic sufferers has been found although 25 years (as of 2014) have passed since the disaster.

The incidence of EMS in the United States diminished abruptly following the withdrawal of L-tryptophan containing products from Showa Denko.


New evidence

The disorder has been blamed by biotech advocates on impurities appearing due to reduced filtration of the product. However, this explanation is no more tenable.

The American attorney William Crist has made a very thorough investigation discovering new evidence that has helped bring increased clarity to the question whether genetic engineering was the cause of the appearance of this deadly toxin (2). He found that hundreds of patients had fallen ill before the producer decreased filtration. The report of William Crist was published in the book "Seeds of Deception" by Jeremy Smith (2).


Our analysis, based on the new evidence

Part 1. Was the poison created by the bacteria?

  • The insufficient filtration hypothesis disproven

    The biotech corporations maintained that EMS appeared after Showa Denko reduced the effectiveness of a carbon filter (reduced carbon content) in december 1988. They maintained that this probably had reduced the protection against chemical impurities appearing in the production process (without any explanation from where they came). The filter story was distributed to the press worldwide (with the obvious purpose of eliminating the suspicion that genetic engineering was the cause).

    This argument is untenable, because as explained above, hundreds of cases of EMS occurred before reduced filtration was introduced. This means that the poisonous substance that caused EMS was able to pass the filters even when the filtration was at the standard level used in industrial fermentation (that is, before filtration was reduced by Showa Denko).



  • Tryptophan fermentation using normal bacteria never created any poison

    Tryptophan has been produced in very large quantities for many years by a several other producers through the same bacterial fermentation method as Showa Denko, using bacteria that are not genetically engineered. No similar complication has occurred in any case. Bacterial fermentation is the standard method for this kind of production.


  • Bacterial fermentation of many other substances without any problem

    Large numbers of bacterial fermentation units have been producing huge amounts of various medical substances, including other amino acids, enzymes, nucleotides, vitamins, antibiotics (including very large amounts of penicillin, tetracyclin and erytromycin).

    Such manufacture has been going on at a large scale since more than 60 years without the appearance of any unexpected highly poisonous chemical impurity (fermentation of the first substance produced at a large scale, penicillin, started in 1945).

    This leads to an important conclusion:

    Considering the enormous amounts of medical substances that have been produced through bacterial fermentation since over 60 years, it is extremely unlikely that there is any fundamental weakness in this procedure that could produce very dangerous poisons. If that had been the case, it would most certainly have been discovered decades ago.

Summary and conclusion of part 1

  • It has been established that reduced filtration was not the cause of EMS.
  • Non-GE tryptophan bacteria have never generated any dangerous toxin. This is especially convincing as such production has occurred at several sites since decades and the amounts produced have been large.
  • The method of production, bacterial fermentation has an impeccable safety record having been used for many other organic substances since over six decades at a large scale without any similar complication
  • No plausible explanation has been presented how an extremely toxic substance could appear in the production process except for in the bacteria.

Therefore, as all other elements in the production method have been cleared beyond reasonable doubt, we can conclude with great certainty that the bacteria themselves caused the emergence of the poison and not some fancied other source in the production process as implied by the biotech corporations.



Part 2. What caused the appearance of the poison in the bacteria?

  • A Non-GE cause is extremely unlikely. The excellent completely poisonfree safety record from over six decades of bacterial fermentation at a very large scale, makes it extremely improbable that the bacterial strain spontaneously started to produce an extremely poisonous and unusual substance.
  • In the case of genetic engineering the siutation is diametrically opposite. Unexpected appearance of poisons due to genetic engineering has been predicted by molecular biologists because of the way gene manipulation can disturb cellular functioning.
  • Moreover, this prediction has been experimentally confirmed. That is, unexpected appearance of poisons has occurred in reality due to genetic engineering (3).
  • In the case of the Showa Denko bacteria, they had undergone an unusual extent of genetic manipulation as not one, as usually is the case in GE, but four different foreign genes had been introduced.
  • The risk for unexpected complications is greater, the larger number of genes are inserted because it brings about a greater instability in the genetic control of metabolic processes.
  • The risk was especially great for a disturbance of the metabolic processes involved in generating tryptophan, because all the artificially inserted genes were specifically directed at increasing the production of this substance. This means that the natural metabolic process was interferred with in four different ways, considerably increasing the risk of abnormal metabolism.
  • Abnormal metabolism can generate abnormal molecules. This is well known from genetic diseases of various kinds (caused by a change in a single gene leading to the generation of an abnormal and harmful molecule).
  • "IMT", one of the impurties, is a derivative of tryptophan (11). It has been correlated with EMS symptoms. The presence of this abnormal tryptophan-related molecule confirms that the metabolism was disturbed in the genetically engineered bacteria.
  • "EBT", the most prominent harmful substance was also closely similar to tryptophan (a dimer). This further confirms that the metabolism in the genetically engineered bacteria was disturbed (for more, see footnote "EBT".)
  • "EBT" is able to cause autoimmune reactions of the kind that was a major causative factor in the Eosinophilic Myalgia Syndrome (10).

Conclusion of part 2

Considering the above points, it can be concluded beyond reasonable doubt that the only plausible explanation is that the poisonus impurities that caused EMS were generated inside the bacteria due to abnormal metabolism caused by genetic engineering.


Overall summary

No other scientifically tenable reason for the appearance of the deadly poison has been found, and the probability for a metabolic disturbance to occur due to genetic engineering was considerable, considering that four different genes had been inserted, causing an especially great degree of instability in the cellular regulation of the production of tryptophan resulting in disturbed metabolism which brings about the risk for the generation of abnormal substances.

Most importantly, two of the poisonous substances "IMT" and "EBT" were abnormal substances similar to tryptophan, which strongly indicates that the abnormality was caused by the manipulation of genes involved in the production of tryptophan.

The biotech industry has tried to challenge the question whether these two substances were the cause of the disease. However, this is of minor importance. Even if genetic engineerng appears, beyond reasonable doubt, to be the cause of the deadly disease, what is important here is that ,

  • it was established that unexpected dangerous abnormal, poisonous substances were produced by the bacteria
  • with great certainty, the reason was the manipulation of genes involved in tryptophan production..



Usage of GE organisms, recipe for another disaster

  • This disaster indicates that genetic engineering can generate unexpected substances that are so poisonous that even extremely small quantities can kill or cause severe disease.

  • This is not a unique case, as genetic engineering has generated unexpeted poisonous substances also in other organisms, including at least one genetically engineered plant (see footnote 3 and article). For a scientific explanation why hazardous substances can appear, see "The Safety of Genetically Engineered Foods. Reasons to expect hazards and the risk for their appearance."

    Moreover, there are good reasons to suspect that the biotech corporations have "buried" cases where poisons appeared in their GMOs (for more, see Footnote).

  • The established method for safety assessment of GE foods is insufficient. It is based on "substantial equivalence", and is not capable of reliably detecting unexpected hazardous substances. This is especially so in cases where they cause long term damage including genetic disturbances and cancer.

    In the Showa Denko case, the poisons were present in so small amounts that they could not be detected by the analysis methods considered sufficient for determining "substantial equivalence". (Look here for more details).

    Do also read our explanation "Inadequate safety assessment of GE foods" (written for laymen). For a scientific explanation, see the article by professor John Fagan "Testing the Safety of Genetically Engineered Foods".
  • Therefore, PSRAST finds that there are well founded reasons to believe that it is only a matter of time before another unexpected toxin is discovered in some GE food, which in the worst case might harm millions of people before the connection is discovered, especially if, as is the case in the US and Canada, the GE foods are not labeled.

Because none has been tested sufficiently, all GE foods must be withdrawn from the market before another disaster occurs.

If, for some ethically unacceptable reason, this is not immediately done, at least the GE-foods must be immediately labelled so people have a chance to avoid them (unfortunately, Monsanto and other biotech companies have invested many millions in preventing laws requiring labeling). Presently the only way to do so in countries, including the US, where they are not labeled, is to eat only certified organically grown food.

ADDITION May 2010: The present campaign by the US government to make the international body for food policy, Codex Alimentarius, forbid labelling of GE foods globally, if successful, may have very dangerous consequences. If a GE food, containing a harmful substance, undetected by the superficial and highly insufficinet safety assessment procedure is released on the world market, it may pave the way for a world-wide disaster because, barring labelling, it may take months before the connection to the harmful GE food is discovered.


Genetically Engineered foods can never be safe because of the inherently unpredictable nature of gene manipulation

It will take several decades to develop sufficent knowledge about genetic engineering so as to know how it works (see "Incomplete knowledge about DNA"). Already now there exists enough knowledge about the effects of GE to be able to conclude that GE, because of its unpredictable nature, can never become safe enough for developing any kind of food or for any other purposes. Therefore the only reasonable and sound scientific conclusion is that it is a dangerous method, not to be used, if at all, other than under strictly contained laboratory conditions.

It is no doubt a matter of time only before genetic engineering will be forbidden, and mankind will be amazed how governments and international organs, including the FAO, Codex Alimentarius and EFSA (of the European Union), could allow such a potentially disastrous method to be deployed in spite of very incomplete knowledge of DNA and the effects of gene manipulation on the cell as well as its health and environmental consequences.

The commercialization of genetically engineered foods and other GMOs, in spite of insufficient testing, is nothing less than a great scandal made possible by political suppression of serious warning signals and disinformation from corrupt or incompetent scientists, sponsored by irresponsible multinational corporations. Moreover, scientists who have published results indicating harmful effects of GE foods have been persecuted by governmental or international agencies, or colleagues. The most notable cases of persecution are Arpad Pusztai (world authority on Lectins), Irina Ermakova (research, persecution) and Gilles Seralini (former scientific advisor of EU and the French goverment). This persecution frightens scientists critical to genetic engineering from raising their voices, see for example "Dysfunctional Science" and "Corporate Monopoly of Science".

It is not a question whether, but when the next disaster occurs. considering the serious incompleteness of knowledge and the highly insufficient safety assessment metods.

Showa Denko was the "Harrisburg" of Genetic Engineering. We should not need a "Chernobyl" before all GE foods are recalled from the market and no new ones are approved before proper testing (see "Inadequate safety assessment.."). No GE food and no other GE product developed so far provides any such benefit to mankind that it is justified to take any risk at all by using it.

PSRAST



References and footnotes

1. For more about the catastrophe, see "Tryptophan summary"

2. The report of William Crist regarding the Showa Denko catastrophe as presented in the book "Seeds of deception" by Jeffrey Smith. It is an excellent presenation of the GE food issue reveailing the governmental corruption and the deceptive behavior of biotch corporations in the process of establishing commercial approval of GE foods.

3. a)Tobacco plants were genetically engineered to produce the Gamma-linoleic acid, a popular food supplement. In stead the plant unexpectedly mainly produced the toxic octadecatetraenic acid. This substance does not exist in the natural tobacco plant. (Reddy SA, Thomas TL. Nature Biotechnology, vol 14, sid 639-642, May 1996)
b) When a yeast was manipulated for increased fermentation there was an unexpected production of a metabolite (methyl-glyoxal) in toxic and mutagenic concentrations. (Inose, T. Murata, K. Int. J. Food Science Tech. 30: 141-146, 1995).

4. FDA lawsuit

5. Excerpt from our Open Letter: "We, the undersigned scientists and physicians, demand that all genetically engineered (GE) foods be withdrawn from the market unless they have undergone rigorous safety assessment including long term testing on animals and humans." No GE food sold as human food has presently undergone such testing.

6. Inadequate safety assessment of GE foods.

7. An example of fatal substantial equivalence. Applying the Showa Denko case, we demonstrate how useless and insufficient the present safety assessment procedure is.

8. Professor Gilles-Eric Seralini pointed out serious weaknesses in the safety analysis of a GE Maize variety that was approved as harmless on the basis of substantial equivalence. More.

9. Unfortunately, genetic engineering is almost entirely sponsored by commercial interests that earn billions from genetic engineering. Therefore, it is highly probable that, if poisons have been generated and detected in the experimentation with GE, they have been kept strictly secret. Because the technology brings about uncontrollable disturbances of the metabolism, that according to molecular biologists may generate unwanted substances, we find it justified to posit that poisonous substances have appeared in perhaps several GMO cases, buried as "business secrets" in the case they were discovered. However, because of the insensitive test methods used, poisons may also have passed unrevealed in the experiments and possibly ended up in GE food due to insufficient testing.

10. a) Kurihara Nobutaka, a, Yanagisawa Hiroyukia, Jin Zhuyua and Wada Osamua. "Production of polyclonal antibodies against 1,1'-ethyliden bis[l-tryptophan] (EBT), a potential contaminant causing eosinophilia-myalgia syndrome (EMS)". Toxicology Letters 66: 231-236 (1993)
b) William C. Buss; Julie Stepanek; Arthur D. Bankhurst; Arthur N. Mayeno; Andrzej Pastuszyn ;David Peabody. "EBT, A Tryptophan Contaminant Associated with Eosinophilia Myalgia Syndrome, is Incorporated into Proteins during Translation as an Amino Acid Analog " Autoimmunity, Volume 25, Issue 1 September 1996 , pages 33 - 45
c) H Barth, R Klein, P A Berg. L-tryptophan contaminant 'peak E' induces the release of IL-5 and IL-10 by peripheral blood mononuclear cells from patients with functional somatic syndromes. Exp Immunol. 126:187-92 (2001)
d) Richard M. Silver, * Anna Ludwicka, * Marta Hampton,Takashi Ohba, * Sarah A. Bingel,' Timothy Smith, Russell A. Harley, John Maize, Melvyn P. Heyesil."; A Murine Model of the Eosinophilia-Myalgia Syndrome Induced by 1,1 '-Ethylidenebis.." The Journal of Clinical Investigation, Inc. 93: 1473-1480; (1994).

11. B Müller, C Pacholski, T Simat, H Steinhart. "Synthesis and formation of an EMS correlated contaminant in biotechnologically manufactured L-tryptophan. "Adv Exp Med Biol. 467:481-6 (1999)


Footnotes

Harrisburg - another accident whose significance was ignored for fostering dubious technology

As long as politics and corporate interets are allowed to suppress scientific safety concerns, the world is in great danger

The "Harrisburg accident" occurred 1979 in a nuclear reactor in Harrisburg, PA, US, that came close to meltdown (also called the "Three mile Island accident"). It sparked the discussion of the safety of nuclear energy. But not until the Chernobyl catastrophe occured in 1986, the further usage of nuclear energy in the US and other countries was either stopped or plans were made to replace it with other solutions as soon as possible.

Before Harrisburg, experts sponsored by the US and other governments, fervently denied that the technology was unsafe. Still several independent experts had warned that nuclear energy reactors are unsafe. This situation is very similar to the denial today of GE risks by biotech sponsored scientists and the refusal of governements to listen to the well underpinned warnings of impartial experts including PSRAST.

This shows that it is unacceptable and dangerous that governmental bodies interfere with, and override technology assessments made by impartial scientists. They evidently don't have the competence, foresight, intelligence and sense of responsibility to be able to handle complex technological issues. Unfortunately corruption of government officials and politicians has contributed to suppression of truth.

This danger is especially great now that science has reached a level where it is capable of generating very powerful technologies that can destroy the Earth.

We have suggested the establishment of national and international councils of truly independent experts that have the ultimate, unrestricted power to decide for the country, or for the world, in issues regarding responsible and safe application of new technologies, see "A suggested procedure...". History has very clearly shown that there are very strong reasons to create such bodies whose decisions are imperative and cannot be overrun by any political or corporate influence.

EBT - an anomalous substance in the supplement

(This text is based on and partly quoted from professor John Fagans article "Tryptophan summary")

EBT, the most prominent of the poisonous substances in the tryptophan supplement, was identified as a dimerization product of tryptophan (a dimer is a molecule consisting of two identical parts - joined in this case by an ethylidene bridge). It comprised less than 0.1% of the total weight of the product, yet that was enough to kill people (1).

Based on fundamental chemical and biochemical principles, scientists have deduced that this compound was probably generated when the concentration of tryptophan within the bacteria reached such high levels that tryptophan molecules or their precursors began to react with each other (5).

Thus, it appears that genetic manipulations led to increased tryptophan biosynthesis which led to increased cellular levels of tryptophan and precursors. At these high levels, these compounds reacted with themselves, generating a deadly toxin.

Being chemically quite similar to tryptophan, this toxin was not easily separated from tryptophan, and contaminated the final commercial product at levels that were highly toxic to consumers.

The purpose of the genetic manipulation was to increase the tryptophan production in the bacteria, and this apparently was successful, however with disastrous consequences.

References: 1. Mayeno, A.N. and Gleich, G.J., Eosinophilia-myalgia syndrome and tryptophan production: a cautionary tale, TIBTECH, 12, 346-352, 1994. 5. Raphals, P., EMS deaths: Is recombinant DNA technology involved?, The Medical Post, Maclean-Hunter, Toronto, 16, November 6, 1990.

Comment by PSRAST

This accident raises a serious warning flag regarding other cases of genetic engineering where the purpose likewise is to increase the productivity of the GMO.

Especially worrisome is that the products of the disturbed metabolism were very harmful in spite of being present in extremely small amounts, that could easily be overlooked in the same way as they were in the tryptophan case.


Physicians and Scientists for Responsible
Application of Science and Technology
- A Global Network -


"Genetically Engineered Food - Safety Problems"
Published by PSRAST

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