The CaMV Scare
The latest anti-biotechnology
scare has to do with the harmful affects of the Cauliflower
Mosaic (CaMV) plant virus. Is it really a problem? Three
leading British virologists step up to say it's complete nonsense.
This page concludes with comments from Professor C.S. Prakash and
a sample "scare letter" being sent out by anti-biotech groups.
SUBJECT: Cauliflower Mosaic Virus (CaMV) -- The Next Scare Topic
Date: Thu, 18 Nov 1999 01:25:07 +0100
From: Klaus Ammann
Source: Debate 991117
a: S35 Promoter, rebuttal of Prof. Chris Leaver et al.
Introduction
Thanks to Prof. Chris Leaver (chris.leaver@plant-sciences.oxford.ac.uk)
for a swift response, it might be very useful to read, BEFORE the
press will ask questions.
It is strange enough that the press release is announced as "NEW RESEARCH"
and finding out that this is nothing else than a review paper with a biased
opinion. Anybody who wants one of the basic papers: I can provide thanks
to Mark Tepfer (mark@versailles.inra.fr) a pdf-file. BEWARE, it's 0.6
Megabites.
Kohli, Ajay, Simon Griffiths, Natalia Palacios, Richard M. Twyman,
Philippe Vain, David A. Laurie and Paul Christou
MOLECULAR CHARACTERIZATION OF TRANSFORMING PLASMID REARRANGEMENTS OF
TRANSGENIC RICE REVEALS A RECOMBINATION HOTSPOT IN THE CaMV 35S PROMOTER
AND CONFIRMS THE PREDOMINANCE OF MICROHOMOLOGY MEDIATED RECOMBINATION
Plant Journal (1999) 17 (6), 591 - 601.
CONTENTS:
1) Press release
2) Response of Prof. Chris Leaver and colleagues
3) Summary of scientific reasons
4) General summary
5) Information about the journal where the article Ho et al. is published.
Professor C. J. Leaver FRS, FRSE
Department of Plant Sciences
University of Oxford
South Parks Road
Oxford
OX1 3RB
Tel +44 (0)1865 275 143
Fax +44 (0)1865 275 144
http://www.plants.ox.ac.uk/
In response to requests from the media concerning the following scare
story I have at short notice collated the response from three of the
UKs leading Plant Virologists
Chris Leaver
1) PRESS RELEASE
Subject: Press Release: Dormant viruses can be reactivated with
genetically modified organisms - new research
see also www.scup.no/mehd/ho
New Research Results on Genetically Modified Organisms
The use of the Cauliflower Mosaic Viral promotor (CaMV) has the
potential to reactivate dormant viruses or create new viruses in all
species to which it is transferred. CaMV is known to be found in
practically all current transgenic crops released commercially or
undergoing field trials.
This transgenic instability increases the possibility of promotion of an
inappropriate over-expression of genes to the transferred species. The
development of cancer may be one consequence of such inappropriate
over-expression of genes.
The scientists behind the research "strongly recommend that
all transgenic crops containing CaMV 35S or similar promoters
which are recombinogenic should be immediately withdrawn
from commercial production or open field trials. All products
derived from such crops containing transgenic DNA should also
be immediately withdrawn from sale and from use for human
consumption or animal feed".
These research results will be published in an article by scientists
Mae-Wan Ho, Angela Ryan, and Joe Cummins, researchers at The Open
University in England and University of Western Ontorio, Canada.
The article, "Cauliflower Mosaic Viral Promotor - A recipe for
Disaster?", will appear in the December issue of the international
scientific journal Microbial Ecology in Health and Disease (No. 4, 1999).
See www.scup.no/mehd/ho for pre-publication full text.
This article confirms the growing concern over the safety aspects of the
use of viral promoters in the production of genetically manipulated food
products, hence the recommended precautionary measure of withdrawing all
such products. This uncertainty around the use of viral promoters should
add fuel to the arguments of the anti-genetically modified organism
lobby groups.
The Editor-in-Chief of the journal, Professor Tore Midvedt, who is head
of Medical Microbiology and Ecology at the Karolinska Institute in
Stockholm, is willing to discuss the serious implications of this
article with journalists who wish to obtain further information.
Professor Midvedt is heavily involved in the sensitive issues around
genetically modified organisms. He aims to take a neutral standpoint and
is actively encouraging both sides of the debate to use the journal as
a forum for discussion. He believes that we need an open debate, with
strict guidelines to control the potential dangers of genetically
modified organisms.
Background material for this new research can be found in an excellent
article co-authored by Mae-Wan Ho, "Gene technology and Gene Ecology
of Infectious Diseases". The article can be read in the same journal at
www.scup.no/mehd/ Table of contents /Volume 10/ no. 1.
2) THE FOLLOWING IS A RESPONSE TO THE FOLLOWING MESSAGE AND
ARTICLE BY THREE OF THE UKs LEADING PLANT VIROLOGISTs:
"Cauliflower Mosaic Viral Promotor - A recipe for Disaster?", This is a
review rather than a presentation of new scientific data.
Discussed:
"Gene technology and Gene Ecology of Infectious Diseases" by Mae-Wan Ho,
My assessment is that these are the major points that need answering:
Claim 1. The 35S promoter can recombine with endogenous viruses causing
their re-activation.
The basic yardstick I guess one should apply in assessing the probability
of this is whether it is more likely than would otherwise occur in
non-transgenic situations in wild plants or during conventional plant
breeding. First of all, I know of no examples in the literature of
reported activation of endogenous viruses resulting from transformation
with constructs containing the 35S promoter.
To answer the question that escape of the 35S promoter might lead to
activation of such viruses in wild plants or in crop plants, it is
appropriate to compare this situation with the activity of viruses and
transposons in non-transgenic contexts. The 35S promoter is found much
more widely in the natural environment than in transgenic plants. CaMV
and its viral relatives produce common plant infections around the
world. There is good evidence that these normal virus infections lead
to some degree of integration of viral DNA into the host genome
providing much scope for potential activation of endogenous genes and
viruses, but again I know of no reports showing that this results in activation of endogenous viruses or genes. In fact, plants have
mechanisms (gene silencing) whose role is probably to monitor and
prevent such fortuitous activations.
Moreover, retrotransposons are extremely common in plants (they can
constitute upwards of half the plant genome). Retrotransposons can move
about the plant genome; they have promoters like the 35S promoter (recall
that retrotransposons are distantly related to CaMV), and would be more
likely to activate endogenous viruses or genes than the isolated 35S
promoter in a transgene. To put this into more perspective, the 35S
promoter in a transgenic plant is present as one or a few copies per cell. A cell infected with CaMV (very common) has thousands or millions of copies of the 35S promoter per cell, and retrotransposons will have at least as
many copies of equivalent promoters.
Claim 2. The 35S promoter could activate endogenous plant genes
producing harmful effects. The same arguments apply as in 1.
Claim 3. The 35S promoter could recombine with HIV or other mammalian
viruses in the gut or could activate human oncogenes. Again there is no
evidence for this. Plant promoters like the 35S promoter are not adapted
to animal situations and I find it hard to see how the 35S promoter
could add to the pathogenicity of animal viruses which are specifically
adapted to the animal world, let alone create new viruses. It should be
remembered that we consume vastly more copies of the 35S promoter by
eating our greens which are commonly infected with CaMV, and plants
contain many highly active promoters of their own which seem to pass
through the gut with no ill effect.
Claim 4. The 35S promoter has a recombination hot-spot that promotes the
above. My understanding of the work of Ajay Kohli and colleagues is that
this hot-spot leads to deletion of part of the 35S promoter prior to
transformation resulting in its de-activation.
In conclusion, if the recombinogenic properties of the 35S promoter were
likely te lead to problems, we would probably have seen them already in
natural infections. Most of the recombinogenic properties of the 35S
promoter are manifest only in the presence of the rest of the virus,
which of course is not part of transgene constructs.
I hope this rather rushed reply is some help.
Chris,
3) SUMMARY OF SCIENTIFIC REASONS
But I guess you want some scientific reasons
(i) there is no new data in the paper, no experimental results, it is
simply a view point of someone who is highly against GMOs.
(ii) The first risk which is suggested is that the recombination of
transgenic CamV35S promoter with dorminant viruses may create new
viruses. REPLY: there is no evidence of any integrated dormant viruses, therefore, this risk is impossible. CaMV35S has
now been used in many different plants, and to-date there have
been NO reports of any new or unusual plant viruses.
(iii) The next point suggested is that because CaMV35S occasionally
recombines with other sequences during integration, it has the
potential to allow transfer of the CaMV promoter from plants to
green algae, yeasts and E.coli. (ight now a REPLY CaMV virus has
infected plants naturally for MUCH longer than any transgenics.
In each naturally infected cell there are hundreds, thousands,
millions of copies of the CaMV35S promoter, all of which in the
history of man, could have recombined with green algae, yeasts
and E.coli. Funnily enough, this has never been seen !! The
answer being that such contact can never exist or take place.
(iv) The next point takes us into pure fiction, and lies, the authors
suggest that because CaMV and hepatitis B are sort of related, that
they might recombine. REPLY: Plant viruses infect plants, and
animal viruses infect animals, the two never replicate in the same
cells, therefore this is impossible. If the authors wished to
continue their fiction by suggesting that when we eat transgenic
plants containing CaMV 35S promoter, that the DNA might mix with
hepB in the gut (or somewhere else) and recombine, well this has
been happening naturally for ages and ages. Nothing, and I repeat
nothing, has happened so far.
(v) Then the authors suggest that movement of CaMV promoter in other
species via such recombination may cause cancer. REPLY: Tell the
authors to get a life, wake up and return to the real world, or
more importantly go back to University and get a degree. Over
activation of genes can cause cancer, this is true, but it will
never happen via the route described by the authors. It has never
happened in the past, and it will not happen in the future, it is
IMPOSSIBLE.
4) GENERAL SUMMARY
Summary
-------
The paper contains no new data or experiments, it is only a platform
for the authors somewhat biased views. (It is certainly not news.)
A CaMV 35S promoter has been our diets naturally for years and years.
There are no additional risks from transgenics, in fact there are
probably less, Transgenics typically contain 1 copy of the promoter
per cell, naturally infected cells contain hundreds, thousands, millions.
If CaMV35S promoter could jump around species in nature we would have
seen it by now. It has not...because...it cannot.
Dear Chris,
I have looked at the Ho, Ryan and Cummins script and have the
following comments:
1. One of Ho's scenarios involves the pre-existence in plants of
assemblages of virus-like genes suitable to comprise a viral genome.
The only known example of this is the DNA of banana streak
badnavirus integrated into host banana DNA. However, this viral
sequence already has its own promoter in the appropriate position.
There is no evidence of viruses-in -waiting in other plants.
2. For the 35S promoter to be taken up from plant material and to be
integrated into the DNA of gut or mucosal cells of man or animals in
such a way that endogenous integrated viral sequences in the cells are
activated to generate a new virus involves several steps of
increasingly remote probability. Equally probable might be natural
recombination of integrated viral sequences with endogenous strong
promoters but there is no evidence of such events known to me. Ho et
al. seem to have no experimental evidence for their assertions.
3. We have for years been eating plant material containing the 35S
promoter (CLMV-infected plants) but no ill effects have been noted.
5) Information about the Journal (thanks to Tom Nickson)
Microbial Ecology in Health and Disease
Microbial Ecology in Health and Disease is the official journal of the
Society of Microbial Ecology in Health and Disease (SOMED) and is also
recognised by the Oral Microbiology and Immunology Group (OMIG) of the
British Society for Dental Research (BSDR).
The aim of this international journal is to draw together research on
different human microbial eco-systems, and to increase our understanding
of their role in health and disease. This research has received new
impetus in recent years as it has become clearer what part is played by
the normal, stable, microbial flora in preventing infection, especially
opportunist infection, and related to this, the potentially deleterious
effects of the use of antibiotics. The journal will consider manuscripts
primarily on the human microbial flora, but also that of other animals,
and its development and interactions. Topics covered include: The
microbial populations of the mouth and skin, and in the respiratory,
gastro-intestinal and genito-urinary tracts * investigative methods *
animal and in vitro models * the effect of antibiotics or diet on the
commensal flora or its development * alterations in the host environment
(e.g. the effect of foreign bodies or change in organs and tissues * the
role of immunological and other mechanisms that help maintain a stable
flora * the clinical application of commensal flora in treatment and
prevention of disease. Manuscripts based on gnotobiotic research are
particularly welcome.
* The material published includes Original Papers, Short Communications,
Review Articles, Case Reports, and Letters to the Editor.
Readership
Researchers, Clinicians, Industrialists interested in modern ecology
Current Contents/Life Sciences; BIOSIS; CAB abstracts; Cambridge
Scientific Abstracts; Current Awareness in Biological Sciences; Research
Alert; Science Citation Index; SciSearch; VINITI-USSR Academy of Science;
Editor-in-Chief
Tore Midtvedt, Stockholm, Sweden.
(tried to get his email address at the Karolinska Institute,
but no trace)
Co-Editor
S. P. Borriello,
Central Public Health Lab., London, England.
Editor/Oral Microbiology
Ingar Olsen,
University of Oslo, Oslo, Norway.
Editorial Board
Patricia Conway, Sydney, Australia.
Zinghua Guo, Beijing, China.
J. M. Hardie, London, England.
M. J. Hudson, Salisbury, England.
Tiimo Nevalainen, Kuopio, Finland.
Michel Fons, Jouy-en-Josas, France.
Joseph Beuth, Cologne, Germany.
P. Mastrantonio, Rome, Italy.
T. Mitsuoka, Tokyo, Japan.
Ian Rowland, Coleraine, Northern Ireland.
Elisabeth Norin, Stockholm, Sweden.
G. W. Welling, Groningen, The Netherlands.
R. J. Carman, Blacksburg, USA.
C. Wells, Minneapolis, USA.
Editorial Office
Scandinavian University Press, att: Lena Wistrand, 3255, SE-103 65 ,
Stockholm, Sweden.
Tel: +46 8 440 80 41
Fax: +46 8 440 80 50
E-mail: lwi@scup.se
Publication Information
Volume in 1999: 11
Issues per year: 4
Approx. pages per volume: 256-320
Language: English
ISSN: 0891-060X
(Supplements 1403-4174)
Klaus Ammann
Botanical Garden, University of Bern
Altenbergrain 21
CH - 3013 Bern, Switzerland
Tel. +41 31 631 49 37
Fax +41 31 631 49 93
klaus.ammann@sgi.unibe.ch
http://www.botanischergarten.ch/start.htm
Response from Professor C.S. Prakash on
the CaMV Threat from Biotech Foods
---------------------------------------
This is a typical scare tactic and using high sounding science stuff to
incite fears. When you consume a virus infected soybean (which we always
do), you also consume billions of particles of viruses. In fact, an
infected cell may have often up to one hundred thousand virus particles!
When we take a promoter from cauliflower mosaic virus (a very common
virus), we are using a small DNA sequence from this virus to drive the gene
of interest. I will forward you a couple of articles from scientists
saying how ridiculous the arguments are. There is no plant virus that can
even remotely infect animals or humans. One of the authorities in this
area is Nam-Hai Chua at Rockefeller
University, a highly respected scientist who was responsible for
isolating and studying this promoter from CaMV. You should ask these
nuts to talk to him.
I really sympathise with you as you to have to put up with such nonsense.
See below an article from the respected journal Nature Biotechnology
which exposes the scam in that scare. I am also forwarding another
rebuttal from Chris Leaver of England. Hope it helps.
Yours,
Prakash
Dear Friends,
Here the 35S Promoter arguments put together.
Thanks, John Hodgson (j.hodgson@biotechnology.com), for bringing the
Debate contributions into Nature Biotechnology in a nicely condensed and commented form, well done.
Klaus
Business and Regulatory News
January 2000 Volume 18 Number 1 p 13
SCIENTISTS AVERT NEW GMO CRISIS
John Hodgson
The crop biotechnology community has started to act preemptively in an
effort to temper the overexuberance with which the lay press has seized on
recent papers against genetic modification. Following an announcement in
mid-November that a paper entitled "Cauliflower mosaic viral promoter—a
recipe for disaster" was to be published in the next issue of Microbial
Ecology in Health and Disease, prominent plant scientists circulated their
comments and criticisms rapidly on e-mail networks. The plant researchers
uniformly damned the paper. Their individual responses varied from detailed
scientific critique to rebukes directed at the journal's editors, to
ridicule of the paper itself. The episode demonstrates that researchers in
this field are primed to damp down undeserved adverse publicity concerning
GM plants.
The paper in question was not original research but an unrefereed opinion
piece written by Mae-Wan Ho and Angela Ryan of the Open University (Milton
Keynes, UK) and Joe Cummins of the University of Western Ontario (Canada).
The authors discuss the safety implications of recent research on the
cauliflower mosaic virus (CaMV) 35S promoter, pointing out (perfectly
correctly) that the promoter is in practically all transgenic crops
currently released commercially or undergoing field trials.
After arguing that it is "highly likely" that the CaMV 35S promoter will
take part in horizontal gene transfer and recombination and "cause
large-scale genomic rearrangements in the process," the authors go on to
imply that the promiscuity of the CaMV promoter could enable it to trigger
cancer. The promoter, they say, "has the possibility of promoting
inappropriate over-expression of genes in all species to which it happens
to be transferred. One consequence of such inappropriate over-expression
of genes may be cancer." Unsurprisingly, given this conclusion, the
authors strongly recommend that "as a precautionary measure ... all
transgenic crops containing CaMV 35S or similar promoters that are
recombinogenic should be immediately withdrawn from commercial production
or open field trials." They also suggest that products from such crops
should also be immediately withdrawn from sale and use."
The paper, which was available in electronic form (www.scup.no/mehd/ho),
was attacked on many fronts by scientists. Virologist Barbara Hohn from
the Friedrich Miescher Institute (Basel, Switzerland) admitted to being
"terribly irritated" by it. She says the authors inaccurately cite her
work, attributing characteristics to the CaMV 35S promoter based on work
Hohn and colleagues had performed on the CaMV 19S promoter.
Perhaps the main criticism, however, was that the ubiquity of the CaMV 35S
promoter and related sequences means that its presence in GM plants is
simply irrelevant. Roger Hull, an emeritus research fellow at the John
Ines Institute (Norwich, UK) and one of the discoverers of the CaMV 35S
promoter, for instance, had estimated that about 10% of cauliflowers and
cabbages at his local market were infected with CaMV. That data were not
new, having been gathered in the late 1980s as part of the approval
process for the release of the first recombinant plant pathogen in the
UK. Furthermore, a typical infected cell contained around 100,000 copies
of the virus and its genome. Transgenesis would add but one to five
copies of the 35S promoter. In addition, says Hull, plants are "loaded"
with potentially mobile DNA such elements making up close to 50% of the
genome in some cereals. Historically, therefore, humans have been
consuming CaMV and its 35S promoter at levels that are over 10,000 times
greater than those in uninfected transgenic plants. Jim Astwood of
Monsanto (St. Louis, MO) points out that it was precisely this line of
argument that led the US Department of Agriculture (Washington, DC) to
determine early in its regulation of recombinant plants that 35S
promoter-containing plants represent a negligible risk of producing
new viruses or causing environmental damage.
Having consulted a number of the UK's leading plant virologists, Chris
Leaver from the University of Oxford rejected the suggestion made by Ho
et al. that CaMV 35S could be transferred from plants to green algae,
yeast, and Escherichia coli on similar grounds. He noted that such a
transfer had not occurred even though, throughout history, humans had consumed huge quantities of the CaMV 35S promoter by "eating our greens."
He also rejected as "pure fiction, and lies" the suggestion that CaMV
might reactivate dormant hepatitis B virus or create new viruses
because there was a phylogenetic relationship between CaMV and human
hepadnaviruses (such as hepatitis B). Leaver points out the obvious
defect in this argument: the two viruses never replicate in the same
cells; CaMV replicates in plants and hepatitis B in animals.
With considerable irony, several critics of the paper suggested that Ho
et al. had not gone far enough in calling for a ban on transgenic crops
containing the 35S promoter. "Let's stop eating plants and animals
altogether," said Barbara Hohn. "It's a shame we did not have this
information millions of years ago. It would have been so easy to avoid
the perils of life."
The editor of Microbial Ecology in Health and Disease, Tore Midtvedt,
a professor at the Karolinska Institute for the past 18 years, was aware
the article would be controversial. "My intention is to stimulate
debate," he says. Part of his editorial strategy when he became
editor-in-chief two years ago, he says, was to make the journal "an
open place where people can come up with ideas." Midtvedt cites the
editorial remark made recently in the Lancet when that journal
published some of the work by Arpad Pusztai on rats fed
lectin-containing transgenic potatoes: "If the paper is not
published, it will be claimed that there is a conspiracy to suppress
information." Midtvedt believes, however, that readers would know that
the paper was not original research and was unrefereed. The non-peer-
reviewed articles are "always commented on previously in the editorial
section," he says.
However, the journal's publisher, the Scandinavian University Press,
does appear to be guilty of misrepresentation of its own content.
Their press release is entitled "New Research Results on Genetically
Modified Organisms" and speaks of Ho and colleagues as "the scientists
behind the research," both statements being difficult to reconcile with
the article's status as an opinion piece. Roger Hull is marshaling
the various comments in order to submit a formal response to Microbial
Ecology in Health and Disease.
A Typical CaMV Scare Letter:
---------------------------
(This letter from sent to the offices of Lumen Foods
sometime in February, 2000. Its contents are similar
to other CaMV-type letters being circulated by the anti-biotech
activitists. It is clearly debunked by the preceeding arguments
from leading virologists, but we reproduce it so that readers
know how the CaMV argument is being presented to subject/targets.)
A risky virus promoter gene--called CaMV--has been spliced into nearly
all of our G.E. food crops.
Did you know about the CaMV being in nearly all our G.E. crops?
Do you know why this CaMV gene is dangerous for human exposure?
I believe that this is a dangerous procedure to put Viral genes
into our food supply and especially when these Viral Genes are highly
interactive with other viruses and bacteria--that means the Viral
Genes are part of a recombinant DNA hotspot--and will interact with
bacteria and viruses in our mouth and our intestinal system.
This is nothing more than basic Virology 101.
But the biotech companies are not telling the public or yourself
about why they had to use the CaMV virus promoter gene in order to
sneak their biotech genes into plant cells and thus to turn them
into G.E. foods.
If food producers and food distributors like yourself don't even know
about this dangerous CaMV viral promoter gene being in the G.E. Foods
and why it's so dangerous to human health, then you have no business purporting to claim that biotechnology-based food production using
such a dangerous virus gene is safe!
Please read the article below by a retired professor of genetics Joe
Cummins who does not earn a living working for the biotechnology
industry like Dennie Avery does.
As a scientist, I think that it's absolutely unethical, unacceptable
and unconscionable to be putting such Viral genes into our food supply.
And this GE food is not labeled!
You have no basis for claiming these G.E. foods are safe except
regurgitating the propaganda of the same companies who are profiteering
from them.
Neil Carman, Ph.D.
Austin, Tx
Friday, September 11, 1998
Virus Promoter (CaMV) Used in the Majority of Genetically Engineered Crops
Prof. Joe Cummins
Professor Emeritus of Genetics
University of Western Ontario
738 Wilkins Street
London, Ontario N6C4Z9 Canada
e-mail: jcummins@julian.uwo.ca
In crop genetic engineering, genes from various sources including
plants, bacteria, or even mammals--including humans--are placed in crop
plants. For those genes to function a regulator gene called a promoter
is essential. The promoter turns the introduced gene on and maintains
its output at a high level. Promoter genes of the crop plant do not
work very well with foreign genes so a powerful promoter that controls
replication of a virus has been used extensively because it functions in
most plant species from corn to pine trees. The Cauliflower Mosaic
Virus (CaMV) promoter has been used in virtually all of the genetically
engineered plants.
The CaMV promoter proved to be a key solution to the problem of
keeping foreign genes active in crop plants. It is not only effective in
gene activation but it is also compact and easy to manipulate, it is
readily available at low cost from gene suppliers. The CaMV promoter
took over most promoter applications in crop biotechnology because it
gives consistent high level expression of foreign genes in crops and no
other promoter whether from virus or plant has been found to supersede
it. However, use of the gene poses threats to the environment and to
human health and discussion of these threats have been ignored, for the
most part, in regulatory reviews and risk analysis.
CaMV is a pararetrovirus, closely related to the human Hepitis B
virus and less closely related to retroviruses including HIV the cause
of AIDS (1). Retroviruses and pararetroviruses share the trait of
alternating their genes between RNA and DNA and reverse transcribing the
RNA to make DNA. The virus promoter is a small gene that acts to start
replication of the DNA into many virus copies. When that gene is
attached to a gene from a bacterium, crop plant or animal then added to
a crop plant chromosome, many copies of the foreign gene are produced
by the plant. The promoter gene is active in all the cells of the crop
plant and little influenced by environmental conditions or the crop
cell's genetic controls. The CaMV promoter is active in most plant
species from simple vascular plants to the giant evergreen trees. It is
also active in yeast and insect cells as well (2,3). The CaMV virus is
transmitted by insects, pollen and by contact between plants. Even
though the virus promoter is active in plants, yeast and insect cells,
the virus is spread through a limited number of plant families, but
these include a number of important crops both crucifers and crops such
as potatoes and beans (4).
The major threat from the CaMV promoter in crops is the process of
recombination. Numerous studies showed that CaMV genes genetically
engineered into crop plants recombine with infecting viruses to create
viruses that are unique and frequently much more infectious than the
infecting virus (5,6,7,8,9). These recombination events are fully
capable of creating viruses that spread in an uncontrolled manner and
cause food shortages and famine worldwide. Such recombination events
have been estimated to take place at one per million cell division (10),
a moderately-sized plant would have over a thousand such recombinats
while a large plant or tree could have a million recombinants.
Furthermore, CaMV promoter has been associated with clones that are DNA
copies of a wide range of viruses, such clones produced infectious virus
(11,12) . Recombination leading to clones that would be carriers of
potent infecting viruses is a real possibility.
The CaMV promoter is a "hot spot" for genetic recombination (13).
That promoter is the starting point for replication of the virus, most
recombination appears to start at the promoter gene. Recombination may
take place when RNA virus is reverse transcribed to make DNA or when the
DNA form of the virus makes RNA, in the latter case the recombinant RNA
is returned to the DNA form by reverse transcription. The normal
replication cycle of the virus is that the virus is spread in its DNA
form. When the virus infects the plant cell it first replicates as RNA,
which is then reverse transcribed to make DNA. Recombination takes place
at both the RNA and the DNA phase of replication. The CaMV promoter gene
in the chromosome and its neighboring genes participate in recombination
to make recombinant virus. As indicated earlier, such recombinant
viruses may be more virulent than the original virus.
The ability of the CaMV promoter to create steady elevated level of
gene product can lead to problems. For example, lectins are natural
plant defense toxins used to defend against browsing from predators and
disease causing pests. Such lectins are present at low level in many
crops but when elevated using CaMV promoter may exceed levels toxic to
the immune system of mammals. Lectins, such as snowdrop lectin
extensively field tested and patented may not be safe at the level
achieved in genetically engineered crops. Wheat germ and barley lectins
are well known to be toxic but are being introduced into a number of
crop plants. Field testing has allowed the spread of such genes in the
environment before the safety of the constructions has been proved.
When lectin modified crops are marketed they are unlikely to be labeled,
in that way jeopardizing sensitive people such as the celiac population
sensitive to wheat gluten and associated lectin. Field tests (14)
and patents(15) for lectin genes in crops have been taking place for
the past seven years while the public have been left unaware of the
hazard.
CaMV promoter has been used to activate a number of mammalian
genes in crop plants, the gene products are mainly vaccines, dietary
proteins or disease treatments. There has been little thought given to
the hazard of recombinant forms of such genes. One interesting
construction involved use of a mammalian interferon gene in crops to
fight crop virus. The genetically engineered tobacco plants resisted
one virus completely but all the plants died immediately when infected
by a different virus, a result completely unexpected (16). Unpredictable
toxicity of genetically engineered crops is a worrisome reality.
CaMV DNA has been used in disturbing experiments with infants and
children in a day care setting. The DNA was used to trace spread of
pathogens in the day care setting (17). Such experiments are unsafe
because the DNA may be taken up through skin lesions or breathed
attached to dust particles. Such DNA may penetrate cells and produce
products that are allergens or toxins.
In conclusion, CaMV genes are used in most of the genetically
engineered crops. The impact of these genes has not been effectively
evaluated. Experiments with infants and children do not contribute
effectively to the safety evaluation of the many genetic constructions
with CaMV. Such experiments should not have been permitted by an
effective ethical review process.
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