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Plants: Controversies and knowledge gaps

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Last week the Netherlands Plant Research Institute published a report
commissioned by Greenpeace Nl about the controversies and knowledge gaps
concerning genetically modified crops. I think it is an interesting overview
for anyone who is interested in the scientific backgrounds. Below, you'll
find a summary nd a table of contents. If you are interested in receiving a
copy in Word format, please send me a note and I'll provide it to you (by
email only).

This study has identified several areas of controversial, fragmentary or
missing knowledge concerning the design, functioning and use of genetically
modified (GM) crop plants, from a standpoint of the natural sciences. These
areas concern the biological and agronomical sciences which are discussed
here, while philosophical, ethical, social-economical and legal scientific
areas are indicated to stress their relevance for the public debate on GM
(food) crops. Controversies and knowledge gaps appear to be present at all
levels of biological organization ranging from the levels of DNA and
cellular metabolism to organism and ecosystem levels.

Controversial issues, generally involving knowledge gaps, are: 	section
*	Precision of genetic modification (GM) and predictability of its
effects	3.2.2, 3.3.2
*	Differences between classical breeding en GM	3.2.3
*	Effects of GM crops on (agro)biodiversity	3.4.2
*	Interactions between neighbouring GM and GM-free agro-ecosystems
*	Consequences of the use of GM crops for the environment	3.4.4,
*	'Genetic pollution' of ecosystems	3.4.6
*	Ecological effects of large-scale application of herbicide resistant
GM crops	3.4.9
*	Sustainability of agriculture.	3.4.12
*	'Substantial equivalence' as a guideline in GM food safety
evaluation	3.5.2
*	Long-term effects of GM crops on human and animal health
*	Consequences of the occurrence of horizontal gene transfer in the
field	3.5.4
*	Food safety tests	3.5.6

In addition, knowledge gaps identified concern: 
*	Effects of breaching species barriers (xeno-transformation)
*	 'Junk DNA' functions	3.2.1, 3.2.5
*	Reliability of annotations in genome databases and quality control
*	Regulation of gene expression: transgenes in their 'xeno-genomic'
environment	3.2.6, 3.3.5
*	Use of GM in stress tolerance breeding (metabolic side effects)
3.3.2, 3.3.3
*	Pest-resistance management	3.3.5
*	Irrevocable and unprecedented effects on natural ecosystems
*	Multi-trophic and long-term ecological interactions of
pest-resistant GM crops	3.4.7, 3.4.8
*	Gene stacking 	3.4.11
*	Prediction and testing of allergenic properties of (transgenic)
proteins.	3.5.1
*	Separation and isolation of GM and GM-free food chains 	3.5.5

These findings demonstrate the fragmentary nature of current knowledge of
genome structure and function and regulation of gene expression in general,
and the limited understanding of several physiological, ecological,
agronomical and toxicological aspects relevant to present-day and planned
genetic modifications of crops. Whether and in which case this limited
understanding can be judged as relevant to the public debate on GM and as
sufficient for adequate risk assessment are questions requiring further
interdisciplinary study.

Table of contents


Summary	1
Samenvatting	3
1. 	Introduction	5
	1.1	Background	5
	1.2	Aim, starting-point and scope	6
	1.3	Subjects outside the scope of this report	6
	1.4	Outline	7
	1.5	Terminology	8
2. 	Methodology	9
	2.1	General	9
	2.2	Technical	9
	2.3	Approach	10
	2.4	Criteria for classification of (scientific) issues	11
3. 	Results: Account of present controversies and knowledge gaps	13
	3.1	Design of DNA constructs and GM crop varieties	14
	3.2	Unknown Mechanisms of genetic modification (GM)  and
breeding	14
		3.2.1	Does the interspecific (or xeno-) transformation in
GM differ from the 
		classical transformation that occurs naturally between
closely related species?	15
		3.2.2	Are there predictable, unintended effects of random
insertion of DNA 
		constructs on gene expression and genome functioning and
stability?	16
		3.2.3	Are there differences in mechanisms between
classical, or conventional, 
		breeding (CB) and genetic modification (GM)?	19
		3.2.4	How reliable are present-day genome databases and
annotations?  Is there an adequate proofreading system operative?	23
		3.2.5	What is known about DNA & chromosome structure and
function?	23
		3.2.6	Do we understand the mechanisms of regulation of
(trans)gene expression in higher plants?	24
	3.3	Genetic and physiological performance of GM crops	25
		3.3.1	Are present GM techniques, in combination with
conventional breeding (CB), more successful than CB alone in exploiting
genetic variation?	26
		3.3.2	Can physiological characteristics of transgenic
plants be predicted for relevant environmental conditions?	27
		3.3.3	Are pleitropy and polygenic characteristics a
barrier towards designing and predicting traits of GM crops like pest and
stress tolerance, productivity 
		and food quality?	28
		3.3.4	Are Genetic modifications in crop plants stable
during several generations?	29
		3.3.5	Are pyramidal (trans)gene systems feasible, such as
proposed in future stress tolerance and pest resistance management?	29


	3.4	Ecological and agronomic interactions of GM crops	31
		3.4.1	Can GM-DNA be contained within experimental field
plots?	31
		3.4.2.	Do GM crops pose a threat to maintaining
biodiversity? (E.g. by outcrossing, running wild, weediness, gene spread,
effects on non-target pests, etc.)	32
		3.4.3	Are there (unintended) interactions between
neighbouring GM- and 
		GM-free agro-ecosystems?	34
		3.4.4	To what extent are the effects on agro-ecosystems of
introduction of 
		GM crops into the field (un)predictable?	34
		3.4.5	Are effects of field introduction of GM crops
irrevocable and unprecedented?	34
		3.4.6	Does introduction of GM crops in the field lead to
'genetic pollution' as the outcome of gene flow, i.e. gene establishment?
		3.4.7	Is there evidence showing that GM-insecticide
production in planta ('Bt crops') differs in its effects on agro-ecosystems
from crop applications of the same insecticide?	35
		3.4.8	Will (pest) insects develop resistance against
Bt-toxins faster in 
		GM-Bt systems than in Bt-application systems?	37
		3.4.9	Does the use of transgenic herbicide-resistant crops
lead to unintended and unavoidable continuation of herbicide use and
accumulation in the 
		environment?	38
		3.4.10	Can GM plants safely be used for the purpose of
fighting pollution, as in 
		phyto-remediation? (e.g. hydrocarbons, heavy metals)?	41
		3.4.11	Are there unintended effects of 'gene stacking' on
(agro-)ecosystems?	42
		3.4.12	Will sustainable agriculture be supported and
promoted by GM?	43
	3.5	Toxicological and allergenic properties of (products of) GM
food crops	44
		3.5.1	Are theoretical models available predicting
successfully the allergenicity of  
		proteins in general and of proteins from GMOs?	45
		3.5.2	Can the concept of 'substantial equivalence' be used
as a reliable and adequate guideline in toxicological studies of GM-crop
products?	45
		3.5.3	Are there specific (long-term) effects of new GM
crops on human and 
		animal health? Is adequate knowledge presently available
concerning the toxicological and allergenic aspects of GM food?	46
		3.5.4	Will horizontal gene transfer (HGT) possible from GM
crops or 
		micro-organisms to (pathogenic) micro-organisms? [Relevant
		hazardous gene spread;  antibiotic resistance of commensal
and pathogenic bacteria; food safety]	47
		3.5.5	Is it possible to separate GM and non-GM food
chains?	48
		3.5.6	In testing for toxicological side-effects, is it
sufficient to test the isolated gene-product rather than the whole plant
part?	49
4. 	General conclusion	50
5. 	Sources	52
	5.1 	References	52
	5.2	Web sites	68
6. 	Explanatory notes	69
	6.1	List of definitions	69
	6.2	Glossary of some relevant acronyms  
	(see for extensive lists, e.g. Kahl 1995; Paula 1999)	70

Huib de Vriend
stichting Consument en Biotechnologie
Postbus 1000
2500 BA Den Haag
The Netherlands
phone: +31 70 44 54 498
fax: +31 70 44 54 592