USDA deregulates its own transgenic plum despite overwhelming public objection
The United States Department of Agriculture
Animal and Plant Health Inspection Service (USDA/APHIS) has recently granted
non-regulatory status to a transgenic plum resistant to plum poxvirus 
after receiving 1 725 comments from state farm bureaus, organic growers, growers
associations, consumer groups, agriculture support industries, academic professionals
and individuals, with respondents against the petition (1 708) outnumbering
those in favour (17) by a factor of 100 to 1.
APHIS was clearly biased in
favour of the petition in their Environmental Assessment, and attempted to
justify its decision by stating: “The majority of academic researchers, as
well as the state farm bureaus
that submitted comments, support granting non-regulated status to the C5 plum.
The majority of those who submitted comments opposing granting non-regulated
status were submitted by organic grower or consumer groups, organic growers,
those who favour organic agriculture or those who are opposed to genetic engineering
technology in general.”
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Deregulation based on obsolete and irrelevant FDA notice
APHIS maintains that, in general RNA
and DNA have no toxic properties  based primarily on a Food and Drug Administration
(FDA) 1992 GRAS notice on transgenic microbes used to produce animal proteins
under contained conditions, which is irrelevant and highly misleading when
applied to environmental release in the case of the C5 transgenic plum. More
importantly, the FDA notice is obsolete in view of numerous scientific findings
made since, and its recommendations should be rejected forthwith. For example,
the extensive regulatory role of small RNA molecules,
similar to those in the virus resistance of C5 plums, was not mentioned in
the FDA notice, as it had not
yet been discovered; nor indeed, the potentially fatal effects of such RNA
molecules in mammals highlighted in our detailed comment to the USDA  (USDA Proposes to Deregulate
Its Own Transgenic Plum, SiS
Despite the fact that a small RNA molecule
was present in high concentrations in the transgenic plum, APHIS maintains
that: “Nucleic acids (i.e., RNA and DNA) are present in all living organisms
and are not known to have any toxic properties. Nucleic acids are considered
to be “generally recognized as safe” (GRAS) by the U.S. Food and Drug Administration
(FDA) (FDA 1992) and exempt from the requirement of a tolerance under the
Federal Food Drug and Cosmetic Act by the U.S. Environmental.”
APHIS dismissed comments questioning
the safety of the small RNAs responsible for providing resistance in C5 plum,
including one comment from us  pointing to the use of small RNAs in RNA interference (RNAi)
gene therapy and its potential adverse health effects. APHIS insists that, “the safety
of nucleic acids is widely accepted”, as both RNA and DNA are part of all
food products that we consume; further, “given that plant viruses infect a
tremendous amount of the fruits and vegetables that we consume, it is highly
likely that humans have been exposed to the same or similar viral RNA that
may be expressed in a coat-protein expressing plant.” As to the concern about
safety arising from findings in RNAi gene therapy, APHIS states that such
RNAs “would be specifically designed and intended for targeted use in humans,
and they would be significantly different than those found in the C5 plum.”
All of the APHIS statements cited are false
and or misleading, and are contradicted by extensive scientific literature.
Small RNAs are potentially lethal to mammals
It is questionable whether people tend
to eat virus-infected fruits and vegetables; also, potentially toxic small RNA molecules
are produced, not by the virus
but by the transgenic plum as the result of the insertion of viral DNA into
the plum genome. Virus infected non-transgenic plums would not make large
quantities of the small RNA that prevents virus replication.
There is substantial evidence
that the small RNA molecules may be toxic to animal cells (see below), and
produce off target effects in plants. Contrary to the statement made by APHIS
(above) suggesting that specific sequences were designed for gene therapy,
the researchers tested many
different RNA sequences for toxicity to mice. Out of 49 sequences tested,
the majority (36) were severely toxic, 23 were lethal in every case, killing
the animals within two months  (Gene Therapy Nightmare for Mice, SiS
31). The fact is, the small
RNA molecules produced in the transgenic
plum have never been tested for their toxicity in animals and they have
not previously been produced in quantities in non-transgenic plums or any
other crop plants. The potential toxicity of small RNAs is featured in a number
of publications between 2004 and 2006 [4-9], which show that APHIS’ conclusion
that RNA molecules are safe for humans is false
Toxic DNA a fact of life
APHIS further maintains that DNA molecules
are intrinsically non-toxic based on the 1992 FDA GRAS notice . Even though
toxic DNA is not a major issue in the transgenic plum, it is worth pointing
out that the toxicity of certain DNA molecules is well established [10-12]. DNA molecules are recognized by the immune system
as a means of activating defence against pathogenic bacteria and viruses.
A strong immune reaction is triggered; even one leading to death in mammals,
as stated in a report published in 2004 :
“The mammalian innate immune system has the ability to recognise and direct
a response against incoming foreign DNA. The primary signal that triggers this
response is unmethylated CpG motifs present in the DNA sequence of various disease-causing
pathogens. These motifs are rare in vertebrate DNA, but abundant in bacterial
and some viral DNAs. Because gene therapy generally involves the delivery of
DNA from either plasmids of bacterial origin or recombinant viruses, an acute
inflammatory response of variable severity inevitably results. The response
is most serious for non-viral gene delivery vectors composed of cationic lipid-DNA
complexes, producing adverse effects at lower doses and lethality at higher
doses of complex.”
APHIS’ conclusion on the lack
of toxicity of DNA is evidently also false and misleading.
We have stated on many occasions
(most recently in GM Food Nightmare
Unfolding in the Regulatory Sham , ISIS scientific publication) that
DNAs, as opposed to non-transgenic DNA, share certain features that make them
Sequence homologies to many species including
pathogenic bacteria and viruses, which enhances horizontal gene transfer
and recombination to create new pathogens
Antibiotic resistance marker genes that could
transfer horizontally to pathogenic bacteria and render infections untreatable
Recombination/fragmentation hotspots such
as the CaMV 35S promoter that further enhance horizontal gene transfer and
Insertion sequences that enable transgenic
DNAs to invade genomes and transfer horizontally
Strong viral promoters that could activate
oncogenes and trigger cancer.
A string of false and invalid claims on safety
APHIS has falsely claimed that RNA and DNA molecules are intrinsically safe
for humans, based solely on an obsolete FDA notice now refuted by numerous
This is the latest in a long string of false and invalid claims on safety from
the USDA. ISIS has submitted at least 34 detailed objections containing safety
warnings against deregulation or field releases of genetically modified organisms
(GMOs) to the USDA and other US regulatory agencies since 2001 , all to
no avail. The same goes for ISIS’ submissions to the European Food Safety Authority
and the UK Food Safety Authority .
Approval of USDA-ARS Request (04-264-01P) Seeking a Determination of Non-regulated
Status for C5 Plum Resistant to Plum Pox Virus, Finding of No Significant
Impact and Decision Notice. Federal Register 72, No. 134 / Friday,
July 13, 2007 / Notices.
Cummins J. and Ho MW. USDA proposes to deregulate its own transgenic plum.
Science in Society 31,
Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P,
Salazar F, Kay MA. Fatality in mice due to oversaturation of cellular microRNA/short
hairpin RNA pathways. Nature 2006, 441(7092), 537-41.
Marsden,P. RNA interference as potential therapy — not so fast. N Engl
J Med 2006, 355, 953-4.
Barik S. RNAi in moderation. Nat Biotechnol. 2006, 24(7), 796-7.
Snove O Jr, Rossi JJ. Toxicity in mice expressing short hairpin RNAs
gives new insight into RNAi. Genome Biol. 2006, 7(8), 231.
Fish RJ, Kruithof EK. Short-term cytotoxic effects and long-term instability
of RNAi delivered using lentiviral vectors. BMC Mol Biol. 2004, 5(9),1-15
Jackson AL, Burchard J, Schelter J, Chau BN, Cleary M, Lim L, Linsley PS.
Widespread siRNA "off-target" transcript silencing mediated by seed
region sequence complementarity. RNA 2006, 12(7), 1179-87.
Luyer MD, Buurman WA, Hadfoune M, Wolfs T, van't Veer C, Jacobs JA, Dejong
CH, Greve JW. Exposure to bacterial DNA before hemorrhagic shock strongly
aggravates systemic inflammation and gut barrier loss via an IFN-gamma-dependent
route. Ann Surg. 2007, 245(5), 795-802.
Obermeier F, Dunger N, Deml L, Herfarth H, Schölmerich J, Falk W. CpG motifs
of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice.
Eur J Immunol. 2002, 32(7), 2084-92
Khazanov E, Simberg D, Barenholz Y. Lipoplexes prepared from cationic liposomes
and mammalian DNA induce CpG-independent, direct cytotoxic effects in cell
cultures and in mice. J Gene Med. 2006, 8(8), 998-1007.
Yew NS and Cheng SH. Reducing the immune stimulatory activity of CpG-containing
plasmid DNA vectors for non-viral gene therapy. Expert Opin Drug Deliv.
2004, 1(1), 115-25.
Ho MW, Cummins J and Saunders PT. GM food nightmare unfolding in the regulatory
sham. Microbial Ecology in Health and Disease 2007, 19(2), 66 – 77.
List of ISIS submissions to USDA and other US regulatory agencies.
Ho MW, Cummins J, Burcher S, Gala R, Lim LC, et al. GM Science Exposed:
Hazards Ignored, Fraud, Regulatory Sham, Violation of Farmers’ Rights,
Compilation from Science in Society archives, 2003-2007, ISIS CD Book, http://www.i-sis.org.uk/includes/frontpage11.htm