GENTECH archive 8.96-97


Re: more on L-tryptophan

If I read the below message correctly, Roush is assuming that illnesses
reported in October 1989 were from batches manufactured in the preceding
two months, but there is no justification for his belief. It depends on the
shipping and storage and marketing patterns and how long the goods sit in
the store, etc. etc.

Without analyzing the labels (production codes, batch numbers, etc.) on the
night tables of the 1537 victims you can't do the "analysis" he attempts
here. (Another argument in favor of accurate labeling, no?).

Philip L. Bereano
>Dr Suurkula has raised a number of questions about the tryptophan case.
>Most or all of these can be answered with a review of the paper by Mayeno
>and Gleich 1994 (Trends in Biotechnology, also known as TIB TECH, vol 12,
>pp. 346-352, as cited by Fagan).
>        There are three key comparisons in the Mayeno and Gleich paper that
>allow us to test whether genetic engineering was the cause of the 37 deaths
>and even more disabilities.  The compound that has been fingered by Fagan
>is the dimeric tryptophan, which has the short name of EBT.  There were
>actually FOUR modifications to the bacterial strain used by Showa Denko
>during the years preceding the EMS epidemic (the first three apparently
>without causing trouble, even though they also increased the production of
>tryptophan that could dimerize), but let's assume for the sake of assigning
>blame to genetic engineering that it was the last change, strain V,
>introduced in December 1988 (page 348).  If this was the important change,
>one would expect that the marketed tryptophan would generally have a high
>level of EBT throughout the use of strain V.  The first cases of EBT were
>detected in October 1989 (page 346 of the paper), so Showa Denko would have
>had no reason to change strains until after that.  However, contrary to the
>prediction that high EBT should be generally associated with the strain V,
>the EBT levels in August through September 1989 were generally LOWER than
>recorded in December 1987 through November 1988 (see Figure 4, page 351 of
>the paper) BEFORE strain V was introduced.  This is the first inconsistency
>with the genetic engineering explanation.
>        In addition to the introduction of strain V in December 1988, the
>amount of powdered activated carbon was reduced from 20 kg or more per
>batch to only 10 kg for some batches between October 1988 through June 1989
>(page 348).  The highest levels of EBT were recorded between February and
>May 1989 (Figure 4).  The time periods over which both the new strain and
>the carbon changed are closely correlated; however, the best "odds ratio"
>of EMS development is with the drop in charcoal rather than strain V (page
>348), the second inconsistency.
>        In terms of the 6  contaminants found in the suspect tryptophan,
>the contaminant most strongly associated with EMS is "peak AAA",  NOT EBT
>(page 349), the third inconsistency.   In fact there is no statistically
>significant correlation between EBT and EMS (page 349).
>        I have already noted the reference by Mayeno and Gleich to the
>structural similarities between one of the other tryptophan contaminants,
>PAA, and a substance (PAP) associated with a similar syndrome, toxic oil
>syndrome.  Contrary to Dr Suurkula's comment, the structures of PAA and
>tryptophan are very different; they share little more than the (NH2)CHCOOH
>amino acid group shared by all amino acids.  Will everyone who remains
>interested in this, please look at the diagrams in the paper cited.
>        In sum, it looks like a non-tryptophan non-EBT contaminant was the
>cause of the EMS disaster. Where did the contaminants come from?  That is
>probably a multi-million dollar question, but remember this was a
>fermentation process,  not a simple chemical reaction.  You add food for
>the bacteria;  this may be contaminated, or contamination could come from
>biochemical "errors" during processing by the bacteria, or reactions among
>the products made by the bacteria.  It is the "contaminants" in the
>fermentation of grapes that gives wine its complexity.  Whatever was the
>source of the contamination, Showa Denko apparently thought it was
>important to purify their product long before the engineered bacterium was
>used, because 20+ kg  carbon was normally used in purification. That this
>dropped to 10 kg is strongly associated with the illnesses.
>        If you still think that the EMS tragedy was due to genetic
>engineering, look into the papers.  A lot of work was done on this; I count
>29 papers specifically on EMS among those cited by Mayeno and Gleich, and
>they noted that TIBTECH's policy of short reference lists left still more
>work unacknowledged.
>As Mardi Mellon says, "no one has been able to pin the cause of the problem
>on genetic engineering". See below.
>Date: Fri, 16 May 1997 20:21:07 -0400 (EDT)
>I'm not sure what your question is.  The trytophan stuff is true.  The
>preparations did kill people and they were associated with genetically
>engineered bacteria.  But for a variety of reasons, no one has been able to
>pin the cause of the problem on genetic engineering.  In fact, there is still
>considerable uncertainty about what the problem actually was...the novel
>amino acid was just one of several hypotheses.
>There has been lots of litigation.  Showa Denko, the Japanese company that
>made the preparation has paid millions.  But since there was no question
>about who was responsible, there was no need to figure out why the
>preparations went bad so the issue of genetic engineering never came up in
>court.  We have a package of materials on the issues that I could send you if
>you want it.
>The address for any administrative command like unsubscribe,
>subscribe or help is:

Philip L. Bereano
Department of Technical Communication
University of Washington
14 Loew Hall, Box 352195
Seattle, WA 98195-2195

ph: (206) 543-9037
fx: (206) 543-8858