ISIS Report 11/03/08
MON810 Genome Rearranged Again
Stability of All Transgenic Lines in Doubt
Dr.
Mae-Wan Ho
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The instability of transgenic
lines is not exactly news, but something too seldom reported, being The Best Kept Secret of GM Crops
[1], and even we in ISIS have missed this item hidden in the final paragraphs
of a technical paper published in 2003, which found new signs of instability
in a transgenic maize that has been grown commercially since 1995.
Researchers from
the Institute of Molecular Biology in Barcelona, Spain, analysed
MON810 maize Certified Reference Material (CRM) obtained from the European
Commission’s Institute for Reference Materials and Measurements (IRMM) and
commercialised by Fluka (Buchs, Switzerland); using the most sophisticated
and sensitive polymerase chain reaction (PCR) methods available [2]. They
found that the transgene insert had rearranged and probably moved, yet again,
from its whereabouts reported a year ago, when MON810 maize, along with at
least 5 other lines were found to have rearranged, and no longer matched the
genetic maps provided by the companies [3-5] (Transgenic
Lines Proven Unstable, SiS
20; Unstable Transgenic Lines Illegal,
SiS 21).
These initial
discoveries [3-5] were so serious that on 28 November 2003,
I wrote to Dr. William Moens, Head of the Service of Biosafety and Biotechnology
(SBB), Scientific Institute of Public Health (IPH), which had reported one
of the two different sets of data on transgenic inserts, and I raised two
important issues [6]:
“First, there appears to be both major and minor inconsistencies between the
results reported by your Institute and those reported by the French laboratories.
Could that be due to methodological problems or to different samples of the
same transgenic line being analysed? If the latter is the case, it would suggest
that the transgenic lines are not only unstable (see below) but also non-uniform.
In other words, they do not pass the DUS [Distinct, Uniform and Stable] test,
which I understand, is required by European law [for a commercial variety].
“Second, the
new EU Directive 2001/18/EC specifically requires event-specific molecular
data documenting genetic stability
(Annex IIIB) as a condition for market approval. In view of the finding that
practically every transgenic insert has rearranged from that reported in the
company’s dossier, it would indicate that the transgenic lines have failed
the test of genetic stability, and are no longer the same lines that were
risk assessed, and in some cases, placed on the market.
“For either
or both those reasons, it would seem illegal, under European law,
to grant those transgenic lines commercial approval; and the lines that have
been approved should surely now be withdrawn.”
The reply from Dr. Moens
came two days later. It stated [7]:
“I thank you very much for
your email and related data. The experts of the Belgian Biosafety Council
are just busy to evaluate in a hurry all these elements. Your email and data
have been transmitted for further review.
“No doubt that the outcome
of such analysis will be handled on a transparent way within delays that are
not yet defined. (sic) I can guarantee you that I’ll make you aware about
our conclusions when legally possible.”
I never heard
from Moens or anyone else from SBB again.
In December
2007, I resent my message and Moens’ reply to him, to remind him that I was
still awaiting his answer, but received nothing so far. The reason seems to
be that our regulators have allowed the companies to submit new data, and
probably even new certified reference materials, in order to justify continued
market approval, which is still illegal .
The Spanish
finding highlights how unstable a transgenic line could be. Specifically,
the Spanish team characterized the 3’ region (tail end) of the transgenic
insert, and found it was no longer in the long terminal repeat (LTR) of the
alpha Zein gene cluster of the maize genome, as reported a year ago [3-5].
Furthermore, they failed to get any PCR product from the wild type maize genome
that corresponds to the site at which the transgenic insert had landed. That
is indicative of substantial genome scrambling at the MON810 transgenic insertion
site; and there are other signs that further sequences have been deleted from
the original insert.
Recently, researchers
in the Industrial Toxicology Research Centre in Marg Lucknow,
India, have also analysed the MON810 insert using multiple PCR primers, and
came to the same conclusion [8]: their finding “confirms the structural instability
of MON810 transgene cassettes.” Contrary to Monsanto’s claim that nptII is absent in MON810, they consistently
found the presence of nptII
as well as Tnos in their sample.
This inconsistency has been noted previously [5].
Another research
team at the University of Florence, Italy, has just published their characterization
of the 3’ insertion site of MON810 [9] and identified scrambled sequences
belonging to the maize HECT E3 ubiquitin ligase. They found several new mRNAs
that are fusion proteins of the truncated Cry1Ab and the uibiquitin ligase
sequences, the safety implications of which are totally unknown.
For at least
the past ten years, I have been looking for credible evidence that transgenic
line is stable and found none. That remains true to-date. The transgenic insert
is not the same as a natural piece of DNA. Transgenic DNA has features that
make it behave somewhat like a loose cannon even after it has inserted into
a genome, it can jump elsewhere in the same genome, scrambling the genome
on the way, or it can insert into the genome of another cell [10] (Horizontal Gene Transfer
from GMOs Does Happen, SiS
38) to wreak the same unpredictable havoc, and worse, to activate cancer genes
with its revved up promoter that makes the transgene over-express out of control.
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