GM Food & Feed Not Fit for Man or Beast

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7 May 2004 18:09:52 -0000

GM Food & Feed Not Fit for " Man or Beast "

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GM Food & Feed Not Fit for " Man or Beast "

 

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Dr. Mae-Wan Ho and Prof. Joe Cummins review some of the

scientific evidence behind a series of recent scandals

involving the safety of GM food and feed. They expose fatal

flaws in the regulatory process and highlight how Europe is

in danger of approving GM varieties that are genetically

unstable and hence illegal as well as unsafe. They demand a

full enquiry into the abuse of science that has allowed GM

crops not fit for human or animal consumption to enter our

food chain.

 

Based on a paper presented at an ISP Briefing to Parliament,

House of Commons, 29 April 2004.

 

Mae-Wan Ho and Joe Cummins

Institute of Science in Society

www.i-sis.org.uk and Independent Science Panel www.indsp.org

 

Latest incidents to cast doubt on the safety of GM food The

European Food Safety Authority (EFSA) has given Monsanto's

GM maize Mon863, containing the biopesticide Cry3Bb1 against

the corn rootworm, a positive assessment. However, French

newspaper Le Monde [1] has seen secret documents revealing

health impacts of the GM maize, described as " very

disturbing " by scientists of the French commission for

genetic engineering (CBG), including kidney malformations

and increases in white blood cells in male rats and high

blood sugar and reduced immature red blood cells in female

rats.

 

 

Last year, up to 100 villagers in the south of the

Philippines living near GM maize plots suffered debilitating

illnesses when the GM maize came into flower [2]. Prof.

Terje Traavik of the Norwegian Institute of Gene Ecology in

Tromsø found antibodies to Cry1Ab produced by the GM maize

against the corn borer in the blood of 39 villagers [3]. The

maize variety was Dekalb 818 YG, a hybrid between Monsanto's

Mon 810 and a locally adapted variety (Dekalb 818). Report

has come in of the same illnesses recurring this year [4].

 

Bt toxins known to be harmful The Cry proteins, dozens of

them, are also called Bt toxins because they are produced by

different strains of the soil bacterium Bacillus

thuringiensis [5, 6]. Reports in the scientific literature

have documented that bacterial spores of B. thuringiensis,

containing a mixture of different toxins, can cause allergic

reactions in farm workers; that some toxins are immunogenic

in animals, Cry1Ac in particular, has been identified as a

potent immunogen, as potent as cholera toxin; that cells in

the lining of the small intestine in rats have proteins that

bind to the toxins [7], and further, Cry1Ab protein is 92%

indigestible in pigs [8].

 

Regulatory sham over Bt crops The findings on Bt toxins have

been completely ignored in a regulatory process that can

only be described as a sham [5].

 

 

Worse still, Bt genes in crops are synthetic or hybrid

constructions, with important changes from the naturally

occurring bacterial genes. Yet, toxicity tests are routinely

done using the natural toxins, and not the toxin produced in

the GM crop plants, with the result that the Bt toxins in GM

crops are almost completely unknown and untested for

toxicity [5, 6].

 

 

There’s evidence that the natural toxin is not the same as,

or “substantially equivalent” to, the GM toxin. Green

lacewings suffer significantly reduced survival and delayed

development when fed an insect pest (lepidopteran) that has

eaten GM maize containing the Bt toxin Cry1Ab, but not when

fed the same pest treated with much higher levels of the

natural toxin [9, 10]. This is an extremely important effect

passed on through the food chain; and has been documented in

several laboratories. Unfortunately, the researchers

misrepresented the results to mean that Cry1Ab does not harm

beneficial insect predators [11].

 

All GM genes differ from natural genes All foreign genes

inserted into GM organisms are different from their natural

counterparts. The minimum construct consists of a promoter,

a gene-switch that says to the cell, " copy the following

message (the gene or coding sequence) for making a protein " ,

and another signal, the terminator, to say, " stop here, end

of message " . All three parts are often from different

sources. The gene itself could also be a composite of

different DNA, often made artificially in the laboratory

[12].

 

 

It is generally not easy to get the foreign gene to work, so

a very aggressive promoter is needed, literally to force the

cell to make the protein. The cauliflower mosaic virus

(CaMV) 35S promoter is the most popular one used, and is

often accompanied by other 'boosters' from a variety of

sources.

 

 

For example, Mon 863 maize is described on the AGBIOS

Database as follows [13]:

 

 

" The introduced DNA contained the modified cry3Bb1 gene from

B. thuringiensis subsp. kumamotoensis under the control of

the 4-AS1 promoter (CaMV 35S promoter with 4 repeats of an

activating sequence), plus the 5' untranslated leader

sequence of the wheat chlorophyll a/b binding protein (wt

CAB leader) and the rice actin intron. The transcription

termination sequence was provided from the 3' untranslated

region of the wheat 17.3 kD heat shock protein (tahsp17).

The modified cry3Bb1 gene encodes a protein of 653 amino

acids whose amino acid sequence differs from that of the

wild-type protein by the addition of an alanine residue at

position 2 and by seven amino acid changes. "

 

 

There are thus 9 bits of DNA from different sources

including the coding sequence, which has been quite

substantially altered from the natural gene.

 

The GM process is unreliable and uncontrollable That's not

all. The artificial constructs are further spliced into gene

carriers or vectors, and introduced into cells by invasive

methods that result in random integration into the genome,

giving rise to unpredictable, random effects, including

gross abnormalities in animals and further unexpected toxins

and allergens in food crops [14].

 

A transgenic line is essentially regenerated from a single

cell in which specific GM DNA integration occurred. Each

event will give rise to a different line. In other words,

there is no possibility for quality control. This problem is

compounded by the overwhelming instability of transgenic

lines, because the artificial constructs cobbled together

from DNA of different sources tend to have weak joints,

especially if they include elements like the CaMV 35S

promoter, which is known to have a fragmentation or

recombination hotspot (see later).

 

Transgenic lines are overwhelmingly unstable We have

referred to the instability of transgenic lines as the " best

kept open secret " , because everybody has known about it for

years, but agree to say nothing, while regulators turned a

blind eye [15].

 

(Claims of genetic stability based on the failure to depart

from Mendelian ratios have been widely accepted as evidence

of Mendelian inheritance, i.e., a sign of genetic stability.

But such claims are bogus for a number of reasons. First, a

'Mendelian ratio' refers to the proportion of different

classes of offspring predicted from a cross involving

different lines. It depends on assuming that Mendelian

inheritance is true; so in order to depart from a particular

ratio, a sufficiently large number of offspring are needed

to obtain the required level of significance (at 5%).

Consequently, a failure to depart from the predicted

Mendelian ratio does not prove Mendelian inheritance. On the

contrary, the real inheritance may be non-Mendelian (a sign

of genetic instability), but an insufficient number of

offspring has been produced for the statistical test to

reach the required level of significance.

 

More importantly, the precise Mendelian ratio to use in each

case depends on the genotype of the parents, and this needs

to be independently ascertained, but is almost never done.

This makes nonsense of the predicted ratio. Indeed, the

Mendelian ratio used is always the one that most closely

matches the result obtained!

 

One of us had argued this very point at a public hearing on

T25 maize in the UK, and got the representative from the

company Aventis to concede that Mendelian ratios are not

evidence of stability [16].)

 

Instead, we have been pressing, both in international

biosafety conferences and in print, for " event specific "

molecular characterisation of the structure of the insert(s)

and their position(s) in the genome in successive

generations, as the only legitimate proof that the

transgenic line is stable [14, 15]. This requirement was

finally written into the 2001 European Directive

(2001/18/EC) on the deliberate release of GMOs into the

environment.

 

But it was not until last year that French government

scientists checked the transgenic inserts of five transgenic

lines: Monsanto's Mon810 maize, Roundup Ready soya, GA21

maize, Bayer's T25 maize and Syngenta's Bt 176 maize; and in

every case, the transgenic insert(s) had rearranged, not

just from the construct used, but since characterised by the

company [17].

 

The results revealed that,

 

All GM inserts had rearranged from the structure provided by

the company

 

 

Many of the breakpoints for rearrangement involve the CaMV

35S promoter, as can be predicted from its known

recombination hotspot

 

 

Scrambling of the genome occurred at the site of insertion

 

 

GM inserts appear to show a preference for mobile genetic

elements (retrotransposons)

 

 

 

The last feature is particularly important, as

retrotransposons contain strong promoters that could alter

gene expression, and also increase the chances that the

inserts will move again, resulting in further genome

scrambling and horizontal gene transfer.

 

The French scientists presented their results in a poster at

a conference with the title: “Characterisation of commercial

GMO inserts: a source of useful material to study genome

fluidity”. Genome fluidity underlies the paradigm shift in

genetics that makes genetic modification both futile and

hazardous [18].

 

Belgian government scientists carried out another study,

confirming the instability of the transgenic lines analysed

by the French, and found that at least one other transgenic

line, Syngenta’s Bt 11 maize, had also rearranged, and that

it was contaminated with Bt176 [19].

 

In the case of other transgenic lines studied, it was

unclear whether the company has been allowed to submit new

data since its first application for approval, which would

be irregular, to say the least.

 

For Roundup Ready soya GTS 40-3-2, for example, the French

study found clear evidence that the GM insert was unstable

and had undergone rearrangement. The Belgian study merely

referred to the UK’s Advisory Committee for Novel Foods and

Processes (ACNFP) website, where it appears that the ACNFP

had allowed Monsanto to submit new data in 2000, and again

in 2002, presumably to ‘correct’ its ‘error’ in the original

dossier.

 

Transgenic instability is a key safety issue There were

small and large discrepancies between the French and Belgian

studies, which suggest that the transgenic lines were not

only unstable but also non-uniform. Either one of those

should make the transgenic lines illegal for Europe. There

is every sign, however, that the European Commission will

fudge this to lift the de facto moratorium, which will be a

criminal offence in our opinion, as it will subject all

European citizens to serious health risks.

 

Transgenic instability is a key safety issue. A GM variety

that has changed its identity since characterised by the

company, invalidates any safety tests or assessments that

may have been done. It also makes it impossible to identify

the GM variety for post-release monitoring, for implementing

remedial action in case of harm and for assigning liability

 

Event specific characterisation of the GM inserts has only

just begun. It is not clear how many of the GM varieties

currently pending approval in Europe have been analysed (see

Box 1).

 

It is also not legitimate to draw conclusions about the

hybrids from data on parental GM lines. We have pointed out

[20], for example, in the case of NK603xMon810, that both

parental lines have rearranged, but no analyses were carried

out on the hybrid and seeds set by the hybrid, where further

recombinations are expected between the constructs, as they

possess similar sequences that are recombination hotspots

(see later): CaMV 35S promoter with enhancer (e35S) and the

hsp70 intron.

 

There can be no approval of any GM variety or hybrid for

import, either for growing or for food and processing unless

and until event-specific analysis has been carried out and

the GM variety/hybrid proven to be stable.

 

To see the table please go to

www.i-sis.org.uk/ManorBeast.php

 

Major uncertainties over the safety of the GM process Let us

look at the rest of the evidence in brief; apart from the

two incidents mentioned.

 

Between 2001 and 2002, twelve dairy cows died on a farm in

Hesse, Germany, after eating Syngenta’s Bt176 GM maize, and

others in the herd had to be slaughtered on account of

mysterious illnesses [21]. To-date, there has been no

detailed autopsy reports available, even though the company

claims the deaths and illnesses were unrelated to Bt176.

Nevertheless the Spanish Food Safety Authority has just

withdrawn authorisation for Bt176 cultivation in Spain [22]

after it had occupied almost all of the 20 000 hectares of

GM maize grown in Spain since 1998 [23]. The decision was

taken following an EFSA recommendation that GMOs containing

antibiotic resistance marker genes such as that found in Bt

176, be restricted to field trials.

 

 

Arpad Pusztai and colleagues found that GM potatoes with

snowdrop lectin adversely affected every organ system of

young rats, and the stomach and small intestine lining grew

up to twice the thickness of controls [24].

 

 

Scientists in Egypt found similar results in the

gastrointestinal tract of mice fed GM potato with Bt toxin

[25].

 

 

US Food and Drug Administration had data since the early

1990s showing that rats fed GM tomatoes with antisense gene

to delay ripening developed small holes in their stomach

[24].

 

 

Aventis (now Bayer) found 100% increase in deaths of broiler

chickens fed glufosinate-tolerant GM maize T25 compared to

controls [26].

 

 

Numerous anecdotes from farmers and others indicating that

livestock, wildlife and lab animals avoid GM feed, and fail

to thrive or die when forced to eat it [26, 27].

 

 

Different species of GM food or feed with different GM genes

have caused problems in many species of animals. You don't

have to be a scientific genius to suspect that there is

something wrong with the GM process itself or the GM insert.

All of the GM inserts involved contain the CaMV35S promoter

that we have warned against since 1999 [28-31]. This

promoter not only has a fragmentation hotspot making

transgenic lines extra unstable, it substitutes for the

promoter of a wide range of plant and animal viruses, and is

also active in animal cells including human cells.

 

It is high time we ban all environmental releases of GM

crops to make way for non-GM sustainable agriculture [32].

 

The greatest obstacle to a safe and sustainable future is a

corrupt and corrupted science that operates on what can only

be described as the anti-precautionary principle. There must

now be a thorough enquiry into the safety of GM food and

feed, and the systematic abuse of science that has allowed

GM food and feed to be approved, which had all the signs of

being unsafe.

 

References

 

********

 

1. " French experts very disturbed by health effects of

Monsanto GM corn " GMWatch www.gmwatch.org 23 April 2004

 

 

2. " Filipino islanders blame GM crop for mystery sickness.

Monsanto denies scientist's claim that maize may have caused

100 villagers to fall ill " John Aglionby in Kalyong,

southern Philippines, The Guardian, Wednesday 3 March 3,

2004

http://www.guardian.co.uk/gmdebate/Story/0,2763,1160789,00.h

tml

 

 

3. Traavik, T. Lecture to Special Biosafety Genok and TWN

Seminar, 22 February, Kuala Lumpur, and personal

communication.

 

 

4. " Despite ban, agriculturists can't stop farmers from

planting Bt corn " , Allen Estabillo, Minda News 23 April 2004

http://www.mindanews.com/2004/04/23nws-btcorn.html

 

 

5. Cummins J. Regulatory sham over Bt-crops. ISIS report 1

December 2003; also Science in Society 2004, 21, 30.

 

 

6. Cummins J. Bt toxins in genetically modified crops:

regulation by deceit. Science in Society 2004, 22 (in

press).

 

 

7. Vázquez-Padrón RI, Gonzáles-Cabrera J, Garcia-Tovar C,

Neri-Bazan L, Lopéz-Revilla R, Hernández M, Moreno-Fierro L

and de la Riva GA. CrylAc protoxin from Bacillus

thringiensis sp. kurstaki HD73 binds to surface proteins in

the mouse small intestine. Biochem Biophys Res Commun 2000,

271, 54-8; Ho MW. Bt toxin binds to mouse intestine. Science

in Society 2004, 21, 7.

 

 

8. Ho MW. Transgenic DNA & Bt toxin survive digestion.

Science in Society 2004, 21, 11; Chowdhury EH, Kuribara H,

Hino A, Sultana P, Mikami O, Shimada N, Guruge KS, Saito M,

Nakajima Y. Detection of corn intrinsic and recombinant DNA

fragments and CrylAb protein in the gastrointestinal

contents of pigs fed genetically modified corn Bt11. J Anim

Sci 2003, 81, 2546-51.

 

 

9. Dutton A, Klein H, Romeis J and Bigler F. " Uptake of Bt-

toxin by herbivores feeding on transgenic maize and

consequences for the predator Chrysoperia carnea " ,

Ecological Entomology 2002, 27, 441-7.

 

 

10. Romeis J, Dutton A and Bigler F. " Bacillus thuringiensis

toxin (Cry1Ab) has no direct effect on larvae of the green

lacewing Chrysoperla carnea (Stephens) (Neuroptera:

Chrysopidae) " , Journal of Insect Physiology 2004, in press.

 

 

11. Dutton A, Romeis J and Bigler F. " Assessing the risks of

insect resistant transgenic plants on entomophagous

arthropods: Bt-maize expressing Cry1Ab as a case study " ,

BioControl 2003, 48, 611 " 36.

 

 

12. Ho MW. FAQs on genetic engineering. ISIS tutorial www.i-

sis.org.uk

 

 

13. www.Agbios.com

 

 

14. Ho MW. Genetic Engineering Dream or Nightmare? TWN,

Gateway, Gill & Macmillan, Continuum, 1998, 2nd ed. 1999,

re-issued 2003 in cd www.i-sis.org.uk

 

 

15. Ho MW. The best kept secret of GM crops. Science in

Society 2002, 15, 9.

 

 

16. Ho MW. GM maize approve on bad science in the UK.

Science in Society 2002, 15. 10-25.

 

 

17. Collonier C, Berthier G, Boyer F, Duplan M-N, Fernandez

S, Kebdani N, Kobilinsky A, Romanuk M, Bertheau Y.

Characterization of commercial GMO inserts: a source of

useful material to study genome fluidity. Poster presented

at ICPMB: International Congress for Plant Molecular Biology

(n°VII), Barcelona, 23-28th June 2003. Poster courtesy of

Dr. Gilles-Eric Seralini, Président du Conseil Scientifique

du CRII-GEN, www.crii-gen.org; also " Transgenic lines proven

unstable " by Mae-Wan Ho, ISIS Report, 23 October 2003 www.i-

sis.org.uk

 

 

18. Ho MW. Living with the Fluid Genome. TWN & ISIS, 2003.

 

 

19. Ho MW. Unstable transgenic lines illegal. ISIS Report 3

December 2003; also Science in Society 2004, 21, 23.

 

 

20. Ho MW and Cummins J. Comment on Assessment Report C,

submitted to UK ACRE and European Food Safety Authority 6

April 2004 on behalf of ISIS and ISP www.i-sis.org.uk

 

 

21. Ho MW and Burcher S. Cows ate GM maize and died. Science

in Society 2004, 21, 4-6.

 

 

22. El Estado espanol retirara un OGM a instancias de la UE.

El maiz Bt 176 podria provoca resistencias a los

antibioticos, GARA, Spain

http://www.gara.net/orriak/P27042004/art79966.htm

 

23. Ho MW. Syngenta's Spanish Trojan horse. Science in

Society 2004, 21, 8.

 

 

24. Pusztai A, Bardocz S and Ewen SWB. Genetically modified

foods: Potential human health effects. In Food Safety:

Contaminants and Toxins, (J P F D'Mello ed.),

 

25. Scottish Agricultural College, Edinburgh, CAB

International, 2003. Fares NH and El-Sayed AK. Fine

structural changes in the ileum of mice fed on dendotoxin-

treated potatotes and transgenic potatoes. Natural Toxins,

1998, 6, 219-33; also " Bt is toxic " by Joe Cummins and Mae-

Wan Ho, ISIS News 7/8, February 2001, ISSN: 1474-1547

(print), ISSN: 1474-1814 (online) www.i-sis.org.uk

 

 

26. Novotny E. Animals avoid GM food, for good reasons.

Science in Society 2004, 21, 9-11.

 

 

27. Ho MW. Mice prefer non-GM. Science in Society 2002,

13/14, 24.

 

 

28. Ho MW, Ryan A and Cummins J. Cauliflower mosaic viral

promoter - a recipe for Disaster? Microbial Ecology in

Health and Disease 1999 11, 194-7.

 

 

29. Cummins J, Ho MW and Ryan A. Hazardous CaMV promoter?

Nature Biotechnology 2000, 18, 363.

 

 

30. 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.

 

 

31. 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.

 

 

32. Ho MW, Lim LC et al. The Case for a GM-Free Sustainable

World. Independent Science Panel Report, ISIS & TWN, 2003

www.indsp.org

 

 

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