Report on meeting of molecular biologists and michael meacher in re; GMOs.

[Guest guest]

Report on a Meeting of Molecular Biologists called by Michael Meacher

on March 31st 1999

Prepared by Angela RyanIn attendance:

The Right Honorable Michael Meacher, Minister for the Environment

 

Paul Burrows, Chemicals and Biotechnology division, DETR

 

Steven Tindale, Sustainable Development, DETR

Scientists

Professor Don Grierson, Plant Molecular Geneticist, Nottingham University

 

Dr Mae-wan Ho, Geneticist and Biophysicist, Open University

 

Angela Ryan, Molecular Biologist and assistant to Dr Mae-wan Ho, Open University

 

Dr Michael Antoniou, Gene Therapist, Guys Hospital, London

 

Dr Mark Bailey, NERC Molecular Ecology Lab, IVEM Oxford

 

Dr Andrew Lilley, NERC Molecular Ecology Lab, IVEM Oxford

 

Dr Ian Garner, PPL Therapuetics, Roslin Institute, Scotland. Member of ACRE

 

Dr Phil Dale, John Innes Center, Norwich. Member of ACRE

 

The scientists were invited to the DETR by the Right Honorable Michael Meacher.

The agenda was set to discuss the special safety concerns raised by the effects

of random insertion of DNA vectors and horizontal gene transfer.

 

Following formal introductions the minister asked the scientists: does GM raise

issues beyond conventional breeding practices?

 

Dr Phil Gale responded first and spoke of how GM was no different from

conventional breeding practices except that it is more precise. In conventional

breeding, seeds are irradiated to cause mutations at points all along the germ

line DNA. Following germination the seedlings undergo analysis and selection

protocols which eventually lead to the isolation of varieties that can be used

in farming. With GM a specific gene can be inserted in a single copy so that a

specific desired trait can be introduced into an organism. The site of insertion

is determined using southern blotting and the chromosomal location is also

determined using fluorescent in situ hybridization (FISH). The expression

pattern of the insert is analysed over many generations to demonstrate that it

is completely stable and has become a constitutive part of that organism. GM is

much more precise and therefore safer than conventional breeding.

 

Dr. Mae-Wan Ho disagreed. GM technology is not at all precise. She identified

four special safety concerns arising from current transgenic technologies.

 

1. The exotic genes and gene products introduced into the transgenic organisms

may be toxic. Antibiotic resistance marker genes are also often left in the

transgenic organisms.

 

2. Unintended, unexpected effects of random gene insertion and interaction

between foreign genes and host genes in the transgenic organisms which could

generate toxins and allergens.

 

3. The gene-constructs inserted into the transgenic organisms are also novel.

Foreign genes are typically introduced as 'gene expression cassettes' each with

a strong viral promoter/enhancer to boost expression to very high levels. The

trangenic organism is, in effect, under permanent metabolic stress. The promoter

most frequently used is from the cauliflower mosaic virus (CaMV), which is

closely related to human hepatitis B virus, and less closely, to retroviruses

such as the AIDS virus. The CaMV promoter can drive the synthesis of related

viruses. It is active in all living systems from bacteria to higher plants. Two

kinds of potential hazards exist: the reactivation of dormant viruses, and

recombination between the CaMV promoter and other viruses, dormant or otherwise,

to generate new, super-infectious viruses or viruses with broadened host-range.

 

4. The spread of transgenes and antibiotic resistance marker genes, not only by

ordinary cross-pollination , but especially by secondary, horizontal gene

transfer to unrelated species. The same mechanisms that enable genes to insert

into the genome can help them jump out again. Integrases, enzymes catalyzing the

integration, which exist in all organisms from viruses to higher plants and

animals, also act as disintegrases, catalyzing the reverse reaction. There is

already evidence suggesting that the foreign genes inserted by vector in a

transgenic plant may be up to 30 times more likely to escape than the same gene

created by mutagenesis. Horizontal gene transfer is well-documented in a special

report commissioned by the Norwegian Government Directorate of Nature Management

from independent virologist and genetic engineer, Terje Traavik, and recently

published in English.

 

Trangenic plants of the current generation are unpredictable, unstable, do not

breed true and do not perform consistently in the field. Molecular analysis must

be done to characterize the insert (s) and demonstrate stability of the

insert(s) at least over five successive generations. Such data is often missing

from applications for approval for field trials or marketing.

 

Dr Michael Antonio explained the way in which genes work in genomes. Genes do

not function in isolation, they work in groups and are highly integrated with

one another. They are constantly interacting and are under strict molecular

control where genomic position is important. There are regions of active

transcription where genes are being transcribed and there are silent regions

where no transcription is taking place. A gene vector can land in either region

but in order for it to be actively transcribed it must land in a region of

active transcription. Random insertion can cause insertion mutagenesis and it is

well understood that many viral induced cancers are caused in this way.

Insertion may also disrupt the gene regulation and natural groupings of the

genes that are functional in the region of insertion. The use of strong

promoters and enhancers in the vectors may cause metabolic stress to the

transformants. Both these factors may lead to the emergence of novel toxins or

allergens and there is no way to predict this at present for we are in the early

days of understanding gene function. In convention breeding, the natural order

or groupings of the genes is not disturbed. Point mutations may result in

changes to the amino acid sequence of the gene products but that does not

interfere with the natural groupings of the genes and alleles, which we know to

be vital to gene regulation. There are just too many unknowns at present.

 

The Right Honorable Michael Meacher then made the point that novel toxins and

allergens may occur in organisms being produced via conventional breeding as

well and perhaps further scientific study should have been done on organisms

being produced in this way?

 

Dr Michael Antonio and Dr Mae-wan Ho both agreed that this is a very valid

point.

 

Dr Phil Dale reasserted his view that although the GM constructs are inserted

randomly at first, further analysis via southern blotting and FISH isolates the

precise region in the genome and on which chromosome the insert has integrated.

 

Dr Michael Antonio replied and said that without further gene mapping work it is

impossible to understand how the act of insertion is affecting the recipient

genomes gene expression. The full extent of gene regulation is yet to be

elucidated and the effects of insertion on the recipient genome will be largely

unknown until we have gained a better understanding of gene function. Knowing

where an insert is on a southern blot and which chromosome it is on, does not

constitute knowing where it is in the recipient genome’s gene regulation system.

He then strongly recommends further research in gene mapping in order to

understand this important safety aspect of GM.

 

Dr Ian Garner stated that it has been known for many years, from the work of

Barbara Maclintock, that genomes are fluid and dynamic. GM is doing nothing more

beyond what nature has been doing for millions of years.

 

Dr Andrew Lilly added that the rate of evolution in bacteria is incredibly rapid

and that they are constantly changing their gene expression. His colleague, Dr

Mark Bailey reasserted that GM is merely utilising an already well established

natural system.

 

Dr Mae-wan Ho agreed that bacteria evolved rapidly and drew attention to a paper

by J. de Vries & W. Wackernagel, Mol. Gen.. Genet.. (1998) 257: 606-613

regarding transfer frequency from transgenic plant DNA to soil bacteria. She

pointed out that in transgenic potatoes, as little as 18 ng of potato DNA (2.5 x

10 3 genome equivalents, each with one copy of an the Kanamycin-resistant gene

npt11) was required to produce one kanamycin-resistant bacterial transformant.

She added that GM may greatly accelerate the rate of horizontal gene transfer

and enlarge it’s scope.

 

Dr Mark Bailey said he knew about this paper because he reviewed it and he knows

the authors personally. He warns we must be careful about misinterpreting this

paper. These experiments were conducted under strict laboratory conditions and

the plasmids were designed to have homology with the Kanamycin-resistant gene

within the transgenic plant DNA. This would not occur normally in the wild in

the absence of such specific homology.

 

Angela Ryan questioned this remark and stated that many gene constructs used in

GM do contain, to a greater or lesser degree, plasmid DNA, viral DNA especially

viral promoters e.g. CaMV promoter, long terminal repeats (LTRs) and left and

right borders, all of which are highly conserved and may in theory find sequence

homology in the wider environment.

 

Dr. Phil Dale remarked that just because it happens in the laboratory does not

mean it happens in nature.

 

Dr Mae-Wan Ho asked whether he could guarantee it will never take place in

nature, and added that although these experiments were conducted in the

laboratory the system used was actually adapted to natural transformation and

therefore could take place in the wild. Furthermore, homology is not neccessary

for successful horizontal gene transfer. Many insertions into the genome happen

without sequence homology, especially those involved in making transgenic

organisms.

 

The Right Honorable Michael Meacher then asked just how much evidence will be

needed before we can be sure that GMOs are safe? And how long will it be until

such time, five or maybe ten years?

 

Dr Mae-wan Ho responded and confirmed that there are many unanswered questions

surrounding GMOs and that is imperative that the precautionary principle be

applied. An inverse precautionary principle has been at work regarding GMOs to

date. She recommended an immediate ban on all commercial plantings of GMO crops

and called for a five year moratorium in order to further identify the risks and

conduct the necessary experimental research. A full independent inquiry into the

future of agriculture and food security for all was also needed.

 

Dr Ian Garner and Dr Phil Dale said they did not believe a moratorium was

necessary.

 

Steven Tindale then asks about the CaMV promoter and its affects?

 

Dr Phil Dale said that we eat the CaMV all the time and it is present in many of

the vegetables that make up our staple diet. It does not have any harmful

effects.

 

Dr Mae-wan Ho refuted this remark and said that there is a great difference

between the CaMV we may eat everyday in vegetables and the CaMV promoter used in

GMOs. Viruses are protected in the environment by a protein coat which also

confers species specificity. The CaMV cannot enter mammalian cells because it’s

protein coat is specific to plant cells. The CaMV promoter used in GMOs however,

comes in the form of naked viral DNA and naked DNA of any sort is highly

infectious. The CaMV promoter is also highly conserved and has been shown to

have sequence homology with other viruses. It is closely related to human

Hepatitis B virus and also to retroviruses like HIV. It is a very strong

promoter, it shouts in a recipient genome to be transcribed and that is why it

is so widely used. It may recombine with latent or infecting viruses within the

host or beyond and give rise to new super-viruses. The wide use of the CaMV

promoter alone carries enough risk to impose an immediate moratorium on GMOs.

 

The Right Honorable Michael Meacher then asked the scientists for their views on

Dr Pusztai’s results?

 

Dr Ian Garner stated that we must be very careful not to take too seriously

experimental data that has not been peer reviewed.

 

Dr Mae-wan Ho refuted this remark and explained that Pusztai’s work has been

peer reviewed by 20 scientists who confirmed his results as significant.

 

Dr Phil Dale added that lectins are well-known toxins and therefore the result

is not unusual considering this.

 

Dr Michael Antonio clarified this comment and said that the snowdrop lectin had

been specifically selected because it had no toxicity in mammalian cells, it was

only toxic to insects. He explained that the transgenic potato contained the

snowdrop lectin to confer insect resistance.

 

Angela Ryan then added that Dr Pusztai’s experiments were designed to develop

new methods of testing GM food. He had worked for seven years on this and was

alarmed by the results he found. The symptoms observed in the rats were

consistent with viral infection.

 

Dr Phil Dale and Dr Ian Garner said they did not believe this.

 

Dr Mae-wan Ho confirmed that the rats had reduced weight in vital organs,

impairment of immunological responsiveness and signs suggestive of viral

infection.

 

Steven Tindale then asked if other feeding experiments have been conducted?

 

Dr Phil Dale explained that because GM food is completely digested in the gut,

feeding experiments had been considered unnecessary, although he wasn’t sure

what had happened in America. Nobody had died yet from eating GM food and he

believes it to be perfectly safe.

 

Dr Mae-wan Ho confirmed that Dr Pusztai’s experiments were the first

comprehensive feeding experiments to be conducted. She refuted the claim that GM

food is completely digested in the gut and referred to evidence which

demonstrates that viral and plasmid DNA fed to mice had been found to resist

digestion in the gut. Large fragments passed into the bloodstream and entered

white blood cells, spleen and liver cells. It was found attached to mouse DNA,

suggesting integration, and when fed to pregnant mice it was found in the

nucleus of cells of the foetus and new-born. She warned that if GM foods were

having ill-effects on the public we would not know about them as no one is

monitoring for such effects. She pointed to the catastrophic thalidomide

incident in which 8000 babies with truncated limbs were born before thalidomide

was admitted as the harmful agent. Dr Pusztai’s work should be repeated and not

be dismissed in any way.

 

The Right Honorable Michael Meacher confirmed that the Government was taking Dr

Pusztai’s experiments very seriously and would certainly not dismiss them.

 

At this point the meeting came to and end and Michael Meacher thanked all the

scientists for coming along and giving their time. He said he has come to a

better understanding of the complications regarding GMOs now, and that he would

welcome further help and advise.

 

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