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ISIS Report 12/04/10
SmartStax Maize a Medley of Transgenes with Problems
No case for releasing a poorly characterized GM crop with a
medley of transgenes for which detrimental effects have been indicated in the
limited cases where feeding trials have been carried out Prof. Joe Cummins
This report has been submitted to US Environment Protection Agency
on behalf of ISIS. Please circulate widely and forward to your representatives
with all links intact
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SmartStax is a genetically modified (GM) maize that has eight GM
traits combined or ‘stacked’ together, six for insect resistance (Bt) and two
for herbicide tolerance. Current stacked GM trait crops on the market only have
up to three traits each. SmartStax was created through collaboration
between Monsanto and Dow AgroSciences  SmartStax
Corn: Corporate War on Bees, SiS 46), allowing
the two corporations to share GM traits. The traits are combined together using
crosses between existing transgenic corn lines rather than using genetic
transformation of a single maize strain. USDA/APHIS (United States Department
of Agriculture/Animal and Plant Health Inspection Service) the usual regulator
of GM crops approved the crops without an approval process, because the
transgenic traits had been granted unregulated status previously, and those
traits were combined using conventional breeding. Nevertheless, USEPA (United
States Environment Protection Agency) were obligated to regulate the stacked
crop varieties containing plant-incorporated protectants (PIPS). EPA invited
public comment prior to registration of stacked varieties of corn but they
approved SmartStax corn without allowing public comment prior to its registration.
Senior Regulatory Specialist of EPA Mike Mendelsohn commented :
“Section 3(c)(4) of the Federal Insecticide, Fungicide, and Rodenticide Act
requires publication in the Federal Register of pesticide applications
containing new active ingredients and/or changed use patterns. SmartStax is a
new product, but it contains already registered active ingredients and is for
use on current use sites, therefore we did not publish a notice of receipt in
the Federal Register.”
As insane as it may appear, EPA regards the health
effects of transgenes stacked together and their impact on the environment as
equivalent to a mixture of chemicals pesticides sprayed on a plant. They
presume that there is no need for environmental assessment or toxicological evaluation
of the mixed genes and their products within the crop plant, where many
unintended effects in gene expression and metabolic profile can occur. The
corporations appear to have been given carte blanche to load our food and feed
with untested mixtures of old transgenes, with utter disregard of the
interactions among the transgenes and gene products in food, feed and the
An armoury of transgenes
SmartStax has been created by crossing four transgene varieties: MON89034
x 1507 x MON88017 x 59122 , which together provide eight traits. The
eight traits are accompanied by an array of regulatory sequences derived from bacteria,
plant viruses and other plants, are as follows, as far as one can tell, as
SmartStax is very poorly characterised, and is in all probability a hybrid corn
DAS-59122-7 and TC1507), phosphinothricin N-acetyltransferase (from S.viridochromogenes)
for glufosinate herbicide tolerance driven by CaMV 35S promoter, with CaMV
35S 3' polyadenylation signal as a transcription terminator; two copies of the pat
gene and its promoter and terminator are present, one in each of the events
DAS-59122-7 and TC1507.
CP4 epsps (event
NK603), 5-enolpyruvylshikimate-3-phosphate synthase (Agrobacterium
tumefaciens CP4) for glyphosate herbicide tolerance , driven by rice
actin I promoter, with intron sequences, chloroplast transit peptide from A.
thaliana and A. tumefaciens nopaline synthase (nos) 3'-untranslated
region terminator The genome has one copy of the NK603 event containing 4 transgenes
in one locus.
MON 89034), achimeric Cry1 delta endotoxin (Bacillus thuringiensis)
for insect (Lepidopteron, moth) resistance, driven by CaMV 35S promoter, with 5'untranslated
leader from wheat chlorophylla/b-binding protein, 3' untranslated region of
wheat heat shock protein 17.3 as a transcription terminator. The genome has one
copy of the event MON89034 containing 4 transgenes in one locus.
MON 89034), Cry2Ab delta endotoxin (Bacillus thuringiensis) for Lepidopteron
(moth) resistance, driven by FMV35S promoter from figwort mosaic virus, with
Hsp70 intron from maize heat shock protein gene, and .A. tumefaciens
nopaline synthase (nos) 3'-untranslated region The genome has one copy of event
89034 containing 4 transgenes in the same locus.
MON 8801), Cry3Bb1 delta endotoxin (Bacillus thuringiensis
subsp.kumamotoensis strain EG4691) for Coleopteran (corn rootworm) resistance,
driven by the CaMV 35S promoter with duplicated enhancer region, 5' UTR from
wheat chlorophyll a/b-binding protein, and rice actin gene first intron; transcription
is terminated by 3' UTR from wheat heat shock protein (tahsp17 3'). There is one
copy of of event MON8801 in the genome, containing 6 transgenes.
TC1507), Cry1F delta endotoxin (Bacillus thuringiensis var.aizawai) for Lepidopteron
(moth) resistance, driven by the ubiquitin (ubi) ZM (Zea mays) promoter and the
first exon and intron; transcription is terminated by the 3' polyadenylation
signal from ORF25 (Agrobacterium tumefaciens). There is one functional
copy of the event containing 6 complete transgenes, and 2 partial copies of the
event elsewhere in the genome.
DAS-59122-7), Cry35Ab1 delta endotoxin (Bacillus thuringiensis strain PS149B1) Insect Coleopteran
(corn rootworm) Resistance The toxin gene is driven by the Triticum aestivum peroxidase gene root-preferred promoter. The transcription is
terminated by the Solanum tuberosum proteinase inhibitor II (PINII)
terminator. There is one copy of the cry35Ab1 transgene
in the genome.
DAS-59122-7), Cry34Ab1 delta endotoxin (Bacillus thuringiensis strain
PS149B1) for Coleopteran (corn rootworm) resistance, driven by the Zea mays
ubiquitin gene promoter, intron and 5'UTR; transcription is terminated by the Solanum
tuberosum proteinase inhibitor II (PINII) terminator. There is one copy of cry34Ab1
transgene in the genome (note cry34Ab1 and cry 35Ab1 are combined in a
single event DAS-59122-7).
The eight main traits in SmartStax corn include
at least 34 transgenes. For the most part, the transgenes were developed and
patented during the mid 1980s through to the mid 1990s. These old events were
combined using traditional plant breeding techniques. The environmental and
human safety of the transgenes have never been rigorously established while the
regulatory agencies justify the safety of those many transgenes on the basis of
the long time in which the transgenes have been used in GM food and feed in the
Americas. However, the modified foods were never labelled in the market, making
epidemiological studies impossible.
Event DAS-59122-7, for example, was claimed substantially
equivalent to non-transgenic corn based on measurements of a relatively few
organic and inorganic nutrients . A sub-chronic feeding
study with stacked Lepidopteran and Coleopteran resistant traits (DAS-Ø15Ø7-1 x
DAS-59122-7) maize grain in rats claimed to find no
differences in pathology between rats fed the stacked corn and those fed an
isogenic corn. Yet, statistically
significant differences were observed in female rats: mean serum sodium
concentration and mean serum chloride concentration were both lower (p <
0.05) in those consuming the transgenic corn diet compared with those consuming
the control diet. A higher incidence of periductal brown pigment was observed
in the pancreas of male rats consuming the transgenic diet (4/12) compared with
animals consuming the control, but was not considered to be treatment-related
. In that way, all statistically significant
differences were explained away, and the government regulators accepted that
without question. Earlier studies with DAS-59122 showed similar significant
differences in nutrients between transgenic and non-transgenic lines that were
Another sub-chronic feeding study of rats with
59122 grain compared with grain from a near-isogenic line for 90 days was carried
out For the most part, the differences between 59122 and unmodified maize
fed animals were not significantly different. However, levels of mean
corpuscular haemoglobin, haemoglobin
concentration, red cell width, reticulocyte count, and platelet count showed
significant differences but these were not deemed significant enough for
regulatory action  GM Maize 59122 Not Safe,
Chickens fed grain from 59122 or from a near-isogenic
maize were assessed after 42 days. The carcass and organ sizes were not
significantly different, but the livers of female chickens fed transgenic maize
were significantly enlarged, and again, not considered biologically significant
by the company researchers.
A major caveat in earlier environmental safety
studies was the use of bacterial protein surrogates for the proteins produced
in the transgenic crops, which have genes adjusted in DNA sequence to optimize expression
in plants and the resultant proteins differ substantially from those produced
in bacteria both in amino acid sequences and in processing 
Recently, Giles-Eric Seralini and co-workers of
independent scientists group Crigen in France found signs of hepato-renal
toxicity in rats fed GM maize MON863 on re-analysis of raw data submitted by
industry, and obtained through the courts . Further analysis of data on glyphosate
tolerant maize NK603 and Bt maizes MON810 and MON 863 revealed detrimental
effects in the liver and kidney, as well heart, adrenal gland and hematopoietic
system . MON863 maize was found associated with signs of hormone dependent
Arpad Pusztai was commissioned by the German
government to evaluate the Monsanto’s study on MON863. His report, also deemed
confidential, was released after agreement was reached with all
concerned parties. Pusztai's report stated, “..this imperfectly designed and
executed study revealed a huge list of significant differences between the
various biologically meaningful parameters of rats fed GM maize diets and the
proper controls....the study strongly indicates that feeding rats on diets
containing significant amounts of MON 863 corn can potentially be detrimental
to the health of these animals and may cause major lesions in important organs
(kidneys, liver, etc.), interfere with the function of their immune system
(lymphocyte, WBC, granulocyte counts) and change their metabolism (glucose)…”
Pusztai summarized the differences between GM fed and
control-fed rats, and their potential implications : increased basophil
count, which may indicate allergic reaction; increases in the number of
lymphocytes and white blood cells, usually associated
with infections, cancer, various toxins, and disease states; decreased
reticulocyte count, indicative of anaemia; decreased kidney weight, pointing to blood pressure problems; and elevation in blood
sugar levels, which cannot be dismissed as biologically insignificant, given
the diabetes epidemic. There were also elevated levels of kidney inflammation,
liver necrosis, and other changes. Pusztai added, “It is almost impossible to
imagine that major lesions in important organs (kidneys, liver, etc) or changes
in blood parameters (lymphocytes, granulocytes, glucose, etc.) that occurred in
GM maize-fed rats, is incidental and due to simple biological variability.”
Another hazard that has been underestimated is the
CaMV 35S promoter driving two of the traits, which we have warned against as a
recombination hotspot that increases transgene instability. More seriously, it
is a strong promoter promiscuously active in cells of practically all species
including humans, and recent evidence indicates that it specifically induces
transcription factors required for making CaMV, as well as HIV and other
viruses associated with cancer [14, 15] (New Evidence Links
CaMV 35S Promoter to HIV Transcription, SiS43).
There is no case for the commercialization of
SmartStax, which is itself not assessed for safety, but consists of a medley of
transgenes for which detrimental effects have been indicated in the limited
cases where feeding trials have been carried out.
communication from Mike Mendelsohn Senior Regulatory Specialist Office of
Pesticide Programs/ Biopesticides and Pollution Prevention Division (7511P)
U.S. Environmental Protection Agency 1200 Pennsylvania Avenue NW Washington DC
20460 to Mr. Arthur Tesla
4. SmartStax in Europe, GMWatch, 4 August 2009, http://www.gmwatch.org/latest-listing/1-news-items/11359-smartstax-in-europe
5. Agbios GM
Database MON-89Ø34-3 x DAS- Ø15Ø7-1 x MON-88Ø17-3 x DAS-59122-7 (MON89034 x
TC1507 x MON88017 x DAS-59122-7) SmartStax™ 2010 http://www.agbios.com/dbase.php
6. United States
Environmental Protection Agency Office of pesticides and Toxic substances
Pesticide Fact Sheet Pesticide Name: MON 89034 x TC1507 x MON 88017 x
DAS-59122-7 Date Registered: July 20, 2009 Registration Numbers: 524-581 &
7. Herman RA,
Storer NP, Phillips AM, Prochaska LM, Windels P. Compositional assessment of
event DAS-59122-7 maize using substantial equivalence.Regul Toxicol Pharmacol.
LM, Malley L, Mackenzie SA, Hoban D, Delaney B.Subchronic feeding study with
genetically modified stacked trait lepidopteran and coleopteran resistant
(DAS-Ø15Ø7-1xDAS-59122-7) maize grain in Sprague-Dawley rats. Food Chem
Toxicol. 2009 Jul;47(7):1512-20
10. Séralini GE, Cellier D,
de Vendomois JS. New analysis of a rat feeding study with a genetically
modified maize reveals signs of hepatorenal toxicity. Arch Environ Contam
Toxicol. 2007, 52(4), 596-602.
11. de Vendômois JS,
Roullier F, Cellier D, Séralini GE.A comparison of the effects of three GM corn
varieties on mammalian health. Int J Biol Sci. 2009, 5(7):706-26.
12. Séralini GE, de
Vendômois JS, Cellier D, Sultan C, Buiatti M, Gallagher L, Antoniou M,
Dronamraju KR. How subchronic and chronic health effects can be neglected for
GMOs, pesticides or chemicals. Int J Biol Sci. 2009, 5(5), 438-43.
13. Puszta A. Evaluation of
and Final Report on the summary report of the "13-Week Dietary Subchronic
Comparison Study with MON 863 in Rats Preceded by a 1-Week Baseline Food
Consumption Determination with PMI Certified Diet #5002(Report
MSL-18175/Covance Study No. 6103-293)". http://www.twnside.org.sg/title2/service219.htm
14. Ho MW and Cummins J. New evidence
links CaMV 35S promoter to HIV transcription. Microbial Ecology in Health
and Disease 2009, 43, 1-3.
15. Ho MW and Cummins J. New evidence
links CaMV 35S promoter to HIV transcription. Science in Society 43,
Kawai Genovia Comment left 28th April 2010 08:08:16 Hello Professor Joe Cummins of ISIS, my name is Kawai Genovia(its hawaiian) and i am currently working on an writing assignment on how GMO food and products have a wold-wide negative effect and are harmful and dangerous. So in this case i am in dire need for information that is backed by a significant scientific background. I ask for contact info or other sources that you would recommend to garner this information. I would hope to change others views on GMO and help them realize the current dangers that face us now. I view the monopolization of GMO crops as a global issue that should be confronted as soon as possible. The way i view the situation is "we may not have to worry about Global Warming killing us when we will willingly eat our-self to oblivion"
Douglas Hinds Comment left 13th April 2010 08:08:49 Joe, your article sheds light on the nature of GM Crops and makes the issue crystal clear: No one who reads the contents of your article could accept the presence of GM crops in the open environment and the international food supply, or fail to recognize the gross incompetence of those charged with preserving the environment and protecting the health of the USA's citizens.
What does seem insane is the fact that people that useless could have been entrusted with positions of responsibility, which allowed them to put so much at risk.
I quote you:
"As insane as it may appear, EPA regards the health effects of transgenes stacked together and their impact on the environment as equivalent to a mixture of chemicals pesticides sprayed on a plant".
"They presume that there is no need for environmental assessment or toxicological evaluation of the mixed genes and their products within the crop plant, where many
unintended effects in gene expression and metabolic profile can occur".
"The corporations appear to have been given carte blanche to load our food and feed with untested mixtures of old transgenes, with utter disregard of the interactions among the transgenes and gene products in food, feed and the environment".
Nothing could be clearer than that! (And corroborated with data and references)
Good work, Joe.
(We did translate the GM Meltdown article into Spanish, which I'll send along shortly).
David Ryan Comment left 13th April 2010 16:04:46 Has Canada given regulatory approval?
Do you know how many hectares are planned for cultivation in Canada, and where?
Joe Cummins Comment left 14th April 2010 05:05:22 Replying to Douglas Hinds,
Thanks for the useful comments Douglas, Your work in Mexico is highly regarded around the world.
The problems with SmartStax are great and the fact that old trans genes are slapped together after being exposed to pests ( some of which have mutated to resistance) along with their use having allowed invasion by pests that have natural resistance to the toxins.The parent transgenic maize plants will have been exposed to the pests and the invaders for many years Those farmers who pay handsomely for the use of the patented seeds have paid for a corn plant full of old trans genes that may soon succumb to pests and invaders. Of course, the seeds from the hybrid cannot be saved because of the lawyer pests and the fact that the insect and herbicide resistance traits will segregate in the second and later planting generations. Regards , joe
joe cummins Comment left 14th April 2010 05:05:18 Replying to David Ryan;
My understanding is that Canada approved SmartStax maize January this year for a two year trial period. There was no public input into that decree, to my best knowledge. SmartStax seeds should be available this month. The food and feed corn will not be labelled as being SmartStax. The information on sale and planting of the seed s has not been disclosed but the planted fields may bear small SmartStax signs. I expect that the planting in Ontario and Quebec may be quite large. Thanks for the question. sincerely, joe
Dirkjan Comment left 19th August 2013 21:09:52 Thanks for sharing this.
It will probably be admitted in September or October in Germany, according to this article: http://rt.com/news/smartstax-maize-germany-approval-428/
I will share this article on my FB for references to Smartstax, for those caring enough to read.