Attached is a PDF from the gene-jiggerers' highest-status
journal. This one-page letter is a very handy item to send to
any scientist who hasn't yet worked out what to think about
gene-tampering. It is of first importance, not least for the
briefest true summary of the lethal GM-tryptophan.
status of the journal Nat Biotech in the whole of science is not
actually high, but within the gene-tamperers' sheltered workshop it
has top status.
status of Prof Schubert is genuinely high. He used to lunch with
Schubert Letter is reproduced as txt below for those not equipped with
the free Acrobat Reader to read PDFs.
A different perspective on GM food
Nature Biotechnology vol. 20 p. 969
As a cell biologist, I am very discouraged by the nature of
the ongoing "debate" on the introduction of genetically
modified (GM) plants into the marketplace. This discussion has
usually pitted irrational emotional arguments against the apparently
rational notion that genetic engineering is just like traditional
plant breeding, only more specific. In particular, I believe
that insufficient attention has been paid to three important
issues:first, introduction of the same gene into two different types
of cells can produce two very distinct protein molecules;
second, the introduction of any gene, whether from a different or the
same species, usually significantly changes overall gene
expression and therefore the phenotype of the recipient cell; and
third, enzymatic pathways introduced to synthesize small molecules,
such as vitamins, could interact with endogenous pathways to produce
novel molecules. The potential consequence of all of these
perturbations could be the biosynthesis of molecules that are toxic,
allergenic, or carcinogenic. And there is no a priori way
of predicting the outcome. In what follows I outline these
concerns and argue that GM food is not a safe option, given our
current lack of understanding of the
consequences of recombinant technology.
The biological activity of a protein can be modified by gene
splicing, which alters the primary amino acid sequence, and by the
post-translational attachment of such moieties as phosphate, sulfate,
sugars, or lipids. The nature of these modifications is markedly
dependent upon the cell type in which the protein is expressed.
For example, if the P-amyloid precursor protein, which is involved in
Alzheimer's disease, is expressed in glial cells, it contains
covalently attached chondroitin sulfate; but when it is expressed in
brain nerve cells the protein contains a much simpler sugar
(1). This is because each cell type expresses a unique
repertoire of enzymes capable of modifying protein structure by mRNA
splicing or at the
post-translational level. In the case of the P-amyloid
precursor protein, its adhesive properties are altered by the
attachment of different carbohydrates (2). With our current
state of knowledge, however, there is no way of predicting either the
modifications or their biological effects. Therefore, a
toxin that is harmless to humans when made in bacteria could be
modified by plant cells in many ways, some of which might be
My second concern is the potential for the introduction of a
foreign gene to either evoke the synthesis of toxic, carcinogenic,
teratogenic, or allergenic compounds, or downregulate the synthesis of
a beneficial plant molecule. Introduction of one gene usually
alters the gene expression pattern of the whole cell, and typically
each cell type of the organism will respond differently. One
example involves the transfection of a receptor gene into human
cells. In this case, the protein was a closely related isoform
of an endogenously expressed gene (3). Monitoring the pattern of
gene expression using microarray technology showed that mRNA levels
for 5% of the genes were significantly upregulated or downregulated.
Recent studies in transgenic plants showed that the over-expression of
a gene involved in pectin synthesis had no effect in tobacco, but
caused major structural changes and premature leaf shedding in apple
trees (4). Although these sorts of unpredicted changes in gene
expression and function are frequently
observed, they have received very little attention.
Furthermore, they are not unexpected. The maintenance of a
specific cell phenotype involves a very precise balancing act of gene
regulation, and any perturbation might be expected to change the
overall patterns of gene expression. The problem, as with
secondary modifications, is that there is currently no way to predict
the resultant changes in protein synthesis.
Third, the introduction of genes for all or part of a new
enzymatic pathway into plants could lead to the synthesis of
unexpected or even totally novel products through an interaction with
endogenous pathways. Some of these products could be toxic.
For example, retinoic acid (vitamin A) and its derivatives are used in
many signaling events that control mammalian development (5). As
these compounds have effects at ultra-low concentrations, a GM plant
making vitamin A might also produce retinoic add derivatives, which
act as agonists or antagonists in these pathways, resulting in direct
toxicity or abnormal embryonic development. A relevant example
is a genetic manipulation carried out in bacteria during the 1980s to
increase the yield of tryptophan for use as a nutritional supplement.
The resultant product caused a novel illness that was highly
correlated with the aberrant appearance of specific trace contaminants
Given that GM plants will sometimes produce different amounts of
proteins, and perhaps totally new proteins, as compared with the
parental species, what are the possible results? A worst-case
scenario would be that an introduced bacterial toxin is modified to
make it toxic to humans. Prompt toxicity might be rapidly
detected once the product entered the marketplace if it caused a
unique disease, and if the food were labeled for traceability, as were
the GM batches of tryptophan. However, cancer or other
common diseases with delayed onset would take decades to detect,
and might never be traced to their cause. Conversely, plant
flavonoids and related molecules have great health benefits (7), and
there is evidence that these can be depleted in GM crops (8).
If the above concerns are valid, what can be done to address
them? Secondary modifications could be assayed by monitoring of
the introduced gene product by mass spectroscopy; changes in gene
expression could be assayed by DNA chips; and metabolically active
molecules could be measured biochemically.
The problem is, of course, that unless we know exactly what to
look for, we are likely to miss the relevant changes. To me, the
only reasonable solution is to require that all GM plant products
destined for human consumption be tested for long-term toxicity and
carcinogenicity before being brought to
market. These safety criteria must be met for many
chemicals and all drugs, and the magnitude of harm caused by a widely
consumed toxic food could well be much greater than that from any
single drug. However, even extensive animal testing might not
detect the consequences of deficiencies in beneficial plant products.
As GM crops offer potential benefits, it would be in the industry's
best interest to more thoroughly examine these products before
continuing with their introduction into the food supply.
1. Shioi, J. et al. J. Biol. Chem. 270,11839-11844 (1995).
2. Salinero, 0.. Moreno-Flores, M.T. & Wandosell, F. J.
Neurosci. Res. 60,
3. Srivastava, M., Eidelman, 0. & Pollard, H.B. Mol. Med. 5,
4. Atkinson, R.G., Schroder, R., Hallett, I.C., Cohen, D. &
Plant Physiol. 129, 122-133 (2002).
5. Gronemeyer, H. & Miturski. R. Cell Mol. Biol. Lett. 6,
6. Kilbourne, E.M., Philen, R.M., Kamb, M.L. & Falk, H. J.
7. Middleton, E., Kandaswami, C. & Theoharides, T.C.
Pharmacol. Rev. 52,
8. Lappé, M.A., Bailey, E.B., Childress, C. & Setchell, K.D.R.
J. Med. Food
1, 241-245 (1999).
David Schubert is a professor at the Sulk Institute, 10010 N. Torrey
The main response in Nat Biotech to the Schubert Letter was the
'enraged' rave (Nov 2002) by main Monsanto-connected gene-jockeys
Roger Beachy, Wayne Parrott et bulk:-
' The reality is that "unintentional consequences"
are much more likely to occur in nature than in biotechnology because
nature relies on the unintentional consequences of blind random
genetic mutation and rearrangement to produce adaptive phenotypic
results, whereas GM technology employs precise, specific, and
rationally designed genetic modification toward a specific engineering
commend this sentence as a prototypical example of stupid
reductionism, bad science, and the type of blunder depicted in
I claim that this immortal sentence shows how the big lie entailed in
atheism is all to likely to cause drastic degradation of truth &
L. R. B. Mann M.Sc Ph.D
22a Ardern Ave., Stanmore Bay 0932, New Zealand
(9) 424 0808