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Old 26-04-2003, 12:23 PM
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Default Recent Evidence Confirms Risks of Horizontal Gene Transfer

ISIS submitted written questions to the upcoming ‘Open Meeting' of the
Advisory Committee for Novel Food Products (ACNFP) in which horizontal
gene transfer is to be discussed. Dr. Mae-Wan Ho, Director of ISIS, who
has written substantially on the subject, and made frequent
representations to the government, asked to be given time to present her
case at the meeting, but her request was refused. She has accordingly
submitted a written version of the case she would have presented
(reproduced below), and asked for a "fulsome" response to it from the
ACNFP at the ‘Open Meeting'.

Please circulate this as widely as possible as part of our contribution
to the ‘National Debate' on GM.

Recent Evidence Confirms Risks of Horizontal Gene Transfer

ISIS Contribution to ACNFP/Food Standards Agency Open Meeting 13 November

Dr. Mae-Wan Ho, Institute of Science in Society
PO Box 32097
London NW1 0XR

Tel: 202-7272-5636

Horizontal gene transfer is one of the most serious, if not the most
serious hazard of transgenic technology. I have been drawing our
regulators' attention to it at least since 1996 [1], when there was
already sufficient evidence to suggest that transgenic DNA in GM crops
and products can spread by being taken up directly by viruses and
bacteria as well as plant and animals cells.

The oft-repeated refrain that "transgenic DNA is just like ordinary DNA"
is false. Transgenic DNA is in many respects optimised for horizontal
gene transfer. It is designed to cross species barriers and to jump into
genomes, and it has homologies to the DNA of many species and their
genetic parasites (plasmids, transposons and viruses), thereby enhancing
recombination with all of them [2]. Transgenic constructs contain new
combinations of genes that have never existed, and they also amplify
gene products that have never been part of our food chain [3].

The health risks of horizontal gene transfer include:

1.Antibiotic resistance genes spreading to pathogenic bacteria.
2.Disease-associated genes spreading and recombining to create new
viruses and bacteria that cause diseases.
3.Transgenic DNA inserting into human cells, triggering cancer.

The risk of cancer is highlighted by the recent report that gene therapy
- genetic modification of human cells - claimed its first cancer victim
[4]. The procedure, in which bone marrow cells are genetically modified
outside the body and re-implanted, was previously thought to avoid
creating infectious viruses and causing cancer, both recognized major
hazards of gene therapy.

The transgenic constructs used in genetic modification are basically the
same whether it is of human cells or of other animals and plants. An
aggressive promoter from a virus is often used to boost the expression
of the transgene, in animal and human cells, from the cytomegalovirus
that infects mammalian cells, and in plants, the 35S promoter from the
cauliflower mosaic virus (CaMV) that infects Cruciferae plants.

Unfortunately, although the CaMV virus is specific for plants, its 35S
promoter is active in species across the living world, human cells
included, as we discovered in the scientific literature dating back to
1989. Plant geneticists who have incorporated the promoter into
practically all GM crops now grown commercially are apparently unaware
of this crucial information [5].

In 1999, another problem with the CaMV 35S promoter was identified: it
has a ‘recombination hotspot' where it tends to break and join up with
other DNA [6]. Since then, we have continued to warn our regulators that
the CaMV 35S promoter will be extra prone to spread by horizontal gene
transfer and recombination [7-9]. The recent controversy over the
transgenic contamination of the Mexican landraces [10] hinges on
observations suggesting that the transgenic DNA with the CaMV 35S
promoter is "fragmenting and promiscuously scattering throughout the
genome" of the landraces, observations that would be consistent with our
expectations [11].

Similarly, I was not surprised by the research results released earlier
this year by the Food Standards Agency [12], indicating that transgenic
DNA from GM soya flour, eaten in a single hamburger and milk shake meal,
was found transferred to the bacteria in the gut contents from the
colostomy bags of human volunteers.

What I found unacceptable was the way the Agency dismissed the findings
and downplayed the risks. The comments, "it is extremely unlikely that
genes from genetically modified (GM) food can end up in bacteria in the
gut of people who eat them", and "the findings had been assessed by
several Government experts who had ruled that humans were not at risk",
are seriously misleading.

First, the experimental design stacked the odds heavily against finding
a positive result. For example, the probe for transgenic DNA covered
only a tiny fraction of the entire construct. So, only a correspondingly
tiny fraction of the actual transfers would ever be detected, especially
given the well-known tendency of transgenic constructs to fragment and rearrange.

Second, the scope of the investigation was intentionally restricted.
There was no attempt to check for transgenic DNA in the blood and blood
cells, even though scientific reports dating back to the early 1990s had
already indicated transgenic DNA could pass through the intestine and
the placenta, and become incorporated into the blood cells, liver and
spleen cells and cells of the foetus and newborn [13].

The observation in the FSA report [12] that no transgenic DNA was found
in the faeces of the ‘healthy volunteers', far from being reassuring,
raises the worrying possibility that the transgenic DNA has all been
taken up into the intestinal cells and/or passed into the bloodstream.

Third, no attempt was made to address the limitations of the detection
method and the scope of the investigation, which grossly underestimated
the extent and frequency of horizontal gene transfer, and hence failed
completely in assessing the real risks. On the contrary, false
assurances were made that "humans were not at risk".

Another research project on horizontal gene transfer commissioned by the
Ministry of Agriculture, Fisheries and Food (MAFF), the predecessor to
the Food Standards Agency, concerns Agrobacterium tumefaciens, the soil
bacterium that causes crown gall disease, which has been developed as a
major gene transfer vector for making transgenic plants. Foreign genes
are typically spliced into T-DNA - part of a plasmid called Ti
(tumour-inducing) – that's integrated into plant genome.

It turns out that Agrobacterium injects T-DNA into plant cells in a
process that strongly resembles conjugation, ie, mating between
bacterial cells; and all the necessary signals and genes involved are
interchangeable with those for conjugation [14].

That means transgenic plants created by T-DNA vector system have a ready
route for horizontal gene escape, via Agrobacterium, helped by the
ordinary conjugative mechanisms of many other bacteria that cause
diseases [15].

A report submitted to MAFF in 1997 had indeed raised the possibility
that Agrobacterium tumefaciens could be a vector for gene escape [16,

The researchers found that it was extremely difficult to get rid of the
Agrobacterium used in the vector system after transformation.

High rates of gene transfer are known to be associated with the plant
root system and the germinating seed [18]. There, Agrobacterium could
multiply and transfer transgenic DNA to other bacteria, as well as to
the next crop plant.

Agrobacterium was also found to transfer genes into several types of
human cells [19], and in a manner similar to that which it uses to
transform plant cells.

We have submitted two relevant ISIS reports together with some specific
questions to the ACNFP for consideration at the November 13 Open Meeting [20].

All the risks of horizontal gene transfer described above are real, and
far outweigh any potential benefits that GM crops can offer. There is no
case for allowing any commercial release of GM crops and food products.

The following experiments and tests should be done to address the risks
of horizontal gene transfer.

1.Feeding experiments similar to those carried out by Dr. Arpad
Pusztai's team should be done, using well-characterized transgenic soya
and/or maize meal feed, with full, adequate, monitoring for transgenic
DNA in the faeces, blood and blood cells, and post-mortem histological
examinations that include tracking transfer of transgenic DNA into the
genome of cells. As an added control, nontransgenic DNA from the same GM
feed sample should also be monitored.
2.Feeding trials on human volunteers should be carried out using
well-characterized transgenic soya and/or maize meal feed, with full,
adequate monitoring for transgenic DNA in the faeces, blood and blood
cells. Also as an added control, nontransgenic DNA from the same GM feed
sample should also be monitored.
3.The stability of transgenic plants in successive generations should be
systematically investigated, especially for those containing CaMV 35S
promoter, using adequate quantitative molecular techniques.
4.Full molecular characterisation of all transgenic lines must be
carried out to establish uniformity and genetic stability of the
5.All transgenic plants created by the Agrobacterium T-DNA vector system
should be tested for the persistence of the bacteria and vectors. The
soil in which they have been grown should also be monitored for gene
escape to soil bacteria. And the potential for horizontal gene transfer
to the next crop via the germinating seed and root system should be
carefully monitored.

References and Notes

1.Correspondences between myself and Ministry of Agriculture, Fisheries
and Food, and Health and Safety Executive, going back to 1996.
2.See Ho MW. Horizontal Gene Transfer. The Hidden Hazards of Genetic
Engineering, TWN Biotechnology Series, Third World Network, 2001
(available fom the ISIS online store); also Ho MW. Horizontal gene
transfer and genetic engineering, SCOPES website, AAAS, 2000.
3.Ho MW. Briefing to the Rt. Hon. Michael Meacher, Minister for the
Environment on the Special Safety Concerns of Transgenic Agriculture and
Related Issues. April 1999 ; published in Seminario Internacional sobtre
Direcito da Biodiversidade, Revista cej: Centro de estudos Judiciarios
do Conselho da Justica Federal, Brasil, pp.120-6, 1999.
4.Science, News of the Week, 4 October 2002; see also "Predicted hazard
of gene therapy a reality" by Mae-Wan Ho, ISIS Report, October 2002
5."GM maize approved on bad science in the UK" by Mae-Wan Ho, Science in
Society 2002, 15, 10-25.
6.Kohli A.,Griffiths S, Palacios N, Twyman R, Vain P, Laurie D and
Christou P. Molecular characterization of transforming plasmid
rearrangements in transgenic rice reveals a recombination hot spot in
the CaMV 35S promoter and confirms the predominance of microhomology
mediated recombination" Plant.J. 1999, 17,591-601.
7.Ho MW, Ryan A and Cummins J. Cauliflower mosaic viral promoter – a
recipe for Disaster? Microbial Ecology in Health and Disease 1999 11,
8.Ho MW, Ryan A and Cummins J. Hazards of transgenic plants with the
cauliflower mosaic viral promoter. Microbial Ecology in Health and
Disease 2000, 12, 6-11.
9.Ho MW, Ryan A and Cummins J. CaMV35S promoter fragmentation hotspot
confirmed and it is active in animals. Microbial Ecology in Health and
Disease 2000, 12, 189.
10.Quist D and Chapela IH. Transgenic DNA introgressed into traditional
maize landraces in Oaxaca, Mexico. Nature 2001, 414, 541-3, 2001.
11."Astonishing denial of transgenic contamination" by Mae-Wan Ho,
Science in Society 2002, 15, 13-14.
12.Netherwood T, Martin-Orue SM, O'Donnell AG, Gockling S, Gilbert HJ
and Mathers JC. Transgenes in genetically modified Soya survive passage
through the small bowel but are completely degraded in the colon.
Technical report on the Food Standards Agency project G010008
"Evaluating the risks associated with using GMOs in human foods"-
University of Newcastle.
13.Doerfler, W. and Schubbert, R. (1998). Uptake of foreign DNA from the
environment: the gastroinestinal tract and the placenta as portals of
entry, Wien Klin Wochenschr. 110, 40-44.p. 40.
14.Ferguson GC and Heinemann JA. Recent history of trans-kingdom
conjugation. In Horizontal GeneTransfer 2nd ed. (ed. M Syvanen & CI
Kado), pp 3-17, Academic Press, San Diego, 2002.
15.Ho MW. What's unspeakable in horizontal gene transfer? Heredity (in
press); "Averting sense for nonsense" by Mae-Wan Ho, Science in Society
2002, 16, 29-30.
16.McNicole et al (1997) The Possibility of Agrobacterium as a Vehicle
for Gene Escape. MAFF. R&D and Surveillance Report: 395.
17.Barrett et al (1997). A risk assessment study of plant genetic
transformation using Agrobacterium and implications for analysis of
trangenic plants. Plant Cell Tissue and Organ Culture 47: 135-144.
18.Sengelov G, Kristensen KJ, Sorensen AH, Kroer N, and Sorensen SJ.
Effect of genomic location on horizontal transfer of a recombinant gene
cassette between Pseudomonas strains in the rhizosphere and spermosphere
of barley seedlings. Current Microbiology 2001, 42, 160-7.
19. Kunik T, Tzfira T, Kapulnik Y, Gafni Y, Dingwall C, and Citovsky V.
Genetic transformation of HeLa cells by Agrobacterium. PNAS USA, 2001,
98, 1871-87; also, "Common plant vector injects genes into human cells",
ISIS News 2002, 11/12, p. 10
20."Stacking the odds against finding it" and "Averting sense for
nonsense" by Mae-Wan Ho. Science in Society 2002, 16, 28-30.

The questions first submitted to FSA 22 July 2002 were as follows:

1.Why were the transgenic soya samples so poorly characterised in terms
of GM content, structure of transgenic insert(s), states of degradation,
2.Why was only one meal administered and monitored?
3.Why was only one small fragment of the entire insert subject to PCR
amplification, knowing that this would drastically underestimate the
presence of transgenic DNA?
4.Why did the researchers make what they know to be unjustified
assumption that transgenic DNA was absent in negative samples?
5.Why did the researchers not monitor for transgenic DNA in blood and
blood cells, when they are fully aware of previous research in mice
showing that transgenic DNA can indeed get into the blood, and from
there to other cells of the body?
6.Why was such a bad piece of research accepted by the FSA, and worse,
misinterpreted to indicate that GM foods are acceptable, when all the
indications are that the extent of horizontal transfer of transgenic DNA
is most likely to be much more extensive than the data indicate?

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Old 26-04-2003, 12:23 PM
Marcus Williamson
Posts: n/a
Default Recent Evidence Confirms Risks of Horizontal Gene Transfer

serious look for experimental studies that supports her opinions.

Have biotech companies done studies which test for this? If not, why


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Old 26-04-2003, 12:23 PM
Jim Webster
Posts: n/a
Default Recent Evidence Confirms Risks of Horizontal Gene Transfer

Marcus Williamson wrote in message

serious look for experimental studies that supports her opinions.

Have biotech companies done studies which test for this? If not, why

because they intend to poison the entire human population so they can
rob the corpses.
don't worry only you will be spared.

Jim Webster

"The pasture of stupidity is unwholesome to mankind"

'Abd-ar-Rahman b. Muhammad b. Khaldun al-Hadrami'


  #5   Report Post  
Old 26-04-2003, 12:23 PM
Marcus Williamson
Posts: n/a
Default Recent Evidence Confirms Risks of Horizontal Gene Transfer

because they intend to poison the entire human population so they can
rob the corpses.
don't worry only you will be spared.

I look forward to a more serious response.

Why are you so enthusiastic about GM and the "biotech" industry?


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Old 26-04-2003, 12:23 PM
Jim Webster
Posts: n/a
Default Recent Evidence Confirms Risks of Horizontal Gene Transfer

Marcus Williamson wrote in message

because they intend to poison the entire human population so they can
rob the corpses.
don't worry only you will be spared.

I look forward to a more serious response.

when you produce a more reasoned and thoughtful question you will
warrant a more serious response.

Why are you so enthusiastic about GM and the "biotech" industry?

why are you so blatently anti? Do you work for the agric chemical
industry or something

Jim Webster

"The pasture of stupidity is unwholesome to mankind"

'Abd-ar-Rahman b. Muhammad b. Khaldun al-Hadrami'


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Old 26-04-2003, 12:23 PM
Torsten Brinch
Posts: n/a
Default Recent Evidence Confirms Risks of Horizontal Gene Transfer

On Tue, 12 Nov 2002 03:49:02 +0000, Marcus Williamson

serious look for experimental studies that supports her opinions.

Have biotech companies done studies which test for this? If not, why

this article might be of interest:

____Forwarded from genet mailing list _________________

The disappearance of science in public interest
Beatrix Tappeser, Institute for Applied Ecology, Freiburg, Germany
19. 10. 2002, Vilm (D)

Over the last two decades there has been a silent shift in research
policies in biology and agriculture. Biotechnology percieved as one of
the key industrial technologies of the new century is the main field
forinvestment. The focus of research programmes is on those fields
where dominating commercial interests are found.
In addition scientist are more and more dependent on money by big
industrial players. Conflicts of interest are one consequence. Another
consequence is that certain research questions are no more addressed
because these questions are not in the interest of the commercial
partners and they are not willing to give money and material for such
research projects (e.g. biosafety research)

An international analysis of biosafety research, that is, research on
possible ecological and health impacts (Sukopp and Sukopp 1997) came
to the conclusion that less than 1% of the world-wide biotechnology
development budget has been used for research regarding safety
effects. In other words, before the first commercial plantings in
1996, ten years of field testing had been performed without looking in
depth into possible ecological consequences.

A review published 2000 in Science came to the conclusion: "A review
of existing scientific literature reveals that key experiments on both
the environmental risks and benefits are lacking." (Wolfenbarger and
Phifer 2000)

The German government spends about 1o,2 Million Euro or 3 % of the
biotechnology budget each year for biosafety research. That seems
quite a lot at least in comparison with the EU-Budget (About 71 Mill.
Euro in 15 Years or 4,7 Mill. _ per year = less than 1% of the
biotechnology budget) or the US-budget (2,1 mill. US $ in the year
2001) but part of the money is dedicated to the development of sterile
plants, new marker genes or better designed gene constructs. That is a
help to develop biotechnology-products to meet public concern, not a
research design to look into the possible outcome of such products in
the environment.

On the other hand investment in agricultural research with direct
benefit for the farmer and the environment eg in the context of
ecological farming is even less than the investment into biosafety
research. The german minister for research and education does not fund
a single project, even though the ministry is spending about 250 Mill.
_ for biotechnology projects.

The German research community funds 12 projects out of 9267 projects.
Only the agricultural ministry is investing a bit more, 20 projects
out of 4230.
But Renate Künast has installed a new research programme dedicated to
further develop ecological farming. About 9 Mill. _ will be spend in
2002 and 2003.

Science in public interest and a proper evaluation of emerging
technologies has to fight with additional difficulties. There are
quite a number of data indicating that aspects of earlier risk
scenarios based on hypotheses derived from biological and ecological
knowledge may become reality but there appears to be a lot of
considerable disconnection between the emerging data coming from
biosafety research and the handling of these data in the context of
evaluation and decision making. There are strong hints that double
standards are used when evaluating the evidence submitted for
market approvals. To arrive at the following summary I refer both to
a study performed by Les Levidow and Susan Carr commissioned by the
European Commission (Levidow and Carr 2000) and to an own study done
for the German Technology Assessment Bureau (Vogel and Tappeser 2000).
The main outcome of both studies is the following: studies or
statements which underline the benefits of transgenic plants are
readily accepted by regulators in the US and the EU even if those
studies are not peer-reviewed and rely only on laboratory experiments.
Studies indicating risks and possible negative ecological or health
impacts are heavily criticised no matter if they are peer-reviewed and
published in scientific journals. These studies are strongly
criticized when they rely only on laboratory experiments.

A central issue that has figured in the discussion on the cultivation
of transgenic plants since its very beginning is that of outcrossing
of such plants and the introgression of the recombinant genes into
related weed and wild plants. It was more or less agreed at least in
the beginning of the debate that pervasive spread of transgenes should
be avoided as if at all possible, as this may have problematic effects
on species networks and on biodiversity in general. A point now
attracting increasing attention is the implication of resistance
development (herbicide and insect resistence) through outcrossing and
the consequences of that development for agricultural land use
systems. In Europe canola is at the center of interest because several
related species are prevalent there. Allexperience and data gained in
the course of the past years point to a high probability of transgenic
rape populations becoming established outside cultivated areas and the
subsequent possibility of gene flow into non-transgenic populations
and related wild herbs. Nowadays gene flow as such is often judged as
being of no special concern. It is said, gene flow only constitutes a
risk when the outcome, the possible impact in the complex networks can
be described and these impacts are judged as having specific negative
consequences. Otherwise such gene flow is qualified as a "so what"
type of conclusion.

But the demand to describe the impacts of gene flow can only be met
with a broad longterm research programme because of the complexity,
the multiple knowledge gaps and uncertainties that exist. Given the
current level of investments in the field of biosafety and assessment
of ecological impacts, such a research programme would extend into the
next twenty years at least.
Allison Snow, a professor in the department of Evolution, Ecology and
Organismal Biology, Ohio State University describes in a commentary
for "Nature Biotechnology" the importance and the investment in
research dealing with gene flow with the following words: "Most
government agencies that regulate GM plants ask for information about
gene flow and its consequences, but it`s often difficult to find
peer-reviewed publications with relevant data. To some extent, the
problem can be traced back to a lack of funding (and interest) from
government programs that sponsor competitive agricultural research
grants. Š To complicate matters further,few biotechnology companies
are willing to fund independent risk assessment research or provide
precommercial transgenic cultivars for study" (Transgenic crops - Why
gene flow matters, Nature Biotechnology, June 2002,page 542)

Looking into the promised benefits of pesticide reduction the
situation oes not improve. The EU Directorate General for Agriculture
published n nalysis on yields, pesticide use and financial return for
the Americanfarmers. The overall conclusion reads as follows: "The
studies reviewed o ot provide conclusive evidence on the farm-level
profitability of GM-crops." (DIRECTORATE-GENERAL FOR AGRICULTURE 2000,
Executive Summary, page 4).

Data publisded [sic] are quite diverse and often not comparable. 3 -
13 % less yield, and growing pesticide use since 1998 after a short
period of reduction is the result of the EU analysis concerning Round
Up Ready soy beans. These data are confirmed by Benbrook, an
independent agricultural consultant specialist (BENBROOK, C. (2001) Do
GM crops mean less pesticide use? Pesticide Outlook, Oktober 2001,
p.204-207.). Even a study published by the Economic Research Center of
USDA admits that soy farmers don`t see any financial return (Adoption
of Bioengineered Crops, ARS Report No. 810, May 2002).
Planting of herbizide resistent maize did not allow for herbicide
reduction but led to a 30% higher consumption of herbicides on the
field (Benbrook 2001) Again the use of Bt-maize did not reduce
pesticide use, yields were the same or slightly more according to the
Herbicide resistent canola yielded between 15% less to 15 % more.
There are no clear-cut data on herbicide use, but emerging data on
double and triple resistent canola plants becoming a severe weed.

Only Bt-cotton allowed for pesticide reduction. (BENBROOK 2001)
But resistence development and weed shift can be observed and produce
new problems. Because of emerging resistant weeds in herbicide
resistent cotton Monsanto recommends spraying with additional
herbicides. New herbicide-mixtures are on the market to fight
resistent volunteers and less sensitive weeds. (Farm Press online
15.8. 2002)

According to a study published by the Soil Association not only the
claimed ecological and economic benefits are missing. To the contrary
the adoption of GM soya, maize, and oilseed rape could have cost the
US economy US $ 12 bn since 1999 in farm subsidies, lower crop prices,
loss of major export orders, and product recalls., the report
estimates. The Soil Association based its report on interviews with
academics, advisers, and industry analysts in North America, as well
as organic and conventional farmers in the US. (www.soilassociation.

What rests: We spent billions of Euro and Dollars in favour of 5
global players: Monsanto, Syngenta, Dupont , Dow and Bayer. These are
the winners of a research agenda fitting into an industrial paradigma.
Science inpublic interest has been lost on that way.

Agronomic Research Service (2002) Adoption of Bioengineered
Report No. 810, May 2002
Benbrook, C. (2001) Do GM crops mean less pesticide use? Pesticide
Oktober 2001, p.204-207.
Directorate General for Agriculture (2000) Economic Impacts of
Modified Crops on the Agri-Food Sector, A First Review
Levidow, L., Carr, S. & Wield, D. (1998). Market-stage precaution:
regulatory disharmonies for transgenic crops in Europe. Binas Online:
Biosafety Reviews.
Sukopp H, Sukopp U (1997) Ökologische Begleitforschung und
im Zusammenhang mit Freisetzung und Inverkehrbringen gentechnisch
veränderter Kulturpflanzen. In: Thüringer Ministerium für
NuU(TMLNU) (eds.), Erfurt, Chancen und Risiken der Gentechnik im
Umweltschutz, 43 -51
Snow, A. (2002) Transgenic crops - Why gene flow matters, Nature
Biotechnology, June 2002, p. 542
Vogel B, Tappeser B (2000) Der Einfluss der Sicherheitsforschung und
Risikoabschätzung bei der Genehmigung von Inverkehrbringung und
Sortenzulassung transgener Pflanzen. Öko-Institut e.V.; Study
by the German Technology Assessment Bureau Auftrag, Berlin, available
pdf-file under (only german)
Wolfenbarger L L, Phifer P R (2000) The Ecological Risks and Benefits
Genetically Engineered Plants. Science 290: 2088-2093.

Florianne Koechlin
Blauenstrasse 15
CH 4142 Münchenstein

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