Fwd: Bt Toxins in Genetically Modified Crops: Regulation by Deceit

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23 Mar 2004 21:48:07 -0000

Bt Toxins in Genetically Modified Crops: Regulation by Deceit

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Bt Toxins in Genetically Modified Crops: Regulation by Deceit

***********************************************

 

Prof. Joe Cummins reviews the impacts of Bt toxins and Bt

crops and points to a fundamental flaw in their regulatory

assessments - toxicity testing based, not on the toxins in

Bt crops themselves, but on surrogate toxins. There is,

furthermore, evidence that some Bt toxins are toxic to

mammals.

 

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Bacillus thuringiensis (Bt) toxin genes inserted into

genetically modified (GM) crops are, along with herbicide

tolerance, the leading modifications of food crops. Bt crops

were planted on over 62 million hectares worldwide as of

2003 [1].

 

Bt bacteria store multiple toxin proteins as crystals in

spores. The individual toxin genes have been isolated and

cloned; each of the toxin genes and proteins are related,

but differ in the range of insects that each poisons. The

main crystal toxins are designated Cry, then individual

toxins are designated Cry1, Cry2 etc. A particular toxin

such as Cry1 may have alternate forms, designated Cry1A or

Cry1B, which differ significantly in gene sequence. Finally,

small differences in gene sequence may reflect significant

difference in specificity and the final designation is

Cry1Aa, cry1Ab, etc.

 

Each toxin that modifies a crop is normally modified in its

DNA sequence from the natural toxin by the introduction of

regulatory sequences such as introns, polyA signals,

promoters and enhancers. The DNA sequence for the toxin is

altered from the natural gene to make the gene more active

in the crop and in many instances the amino acid sequence of

the toxin is altered to make the toxin more soluble in the

plant cell [2].

 

Each toxin in a GM crop must be evaluated separately from

other toxin genes and proteins, making regulatory

evaluations complex. But, in every case, the Bt crops

released in North America have been evaluated based on the

toxicity to mammals and to the environment of the natural

toxins, not the product of the synthetic altered genes in

the GM crops. Regulators have simply assumed that the toxins

produced using the altered synthetic genes are equivalent to

the natural gene toxin so long as the altered toxins contain

domains for insect toxicity and they had an immunological

relationship to the natural toxin [3].

 

Therefore, the actual toxins in the GM crops have not been

tested. This is because the cost of isolating the toxins

from the GM crops was considered prohibitive.

 

Toxicity to mammals

*******************

The Cry toxins have a common mode of action in insects.

The toxin proteins bind to cell membranes of the cells of the

insect gut. The receptors for the toxins have been identified

as membrane-anchored aminopeptidase enzymes and cadherin-like

proteins. Cry toxins form ion channels that cause an efflux of

potassium ions from the insect gut cells, leading to cell

lysis (the cell breaking open) [4]. The actual

aminopeptidase binding sites for the Cry toxin is

glycosylated (short carbohydrate molecules are added to the

protein) and recognized by a lectin-like protein domain on

the toxin [5-8]. Lectins are a class of proteins that bind

to carbohydrates associated with proteins. They are usually

recovered from plants and many are known to affect mammalian

cell growth while others are toxic to plant predators such

as insects.

 

The toxicity to mammals of relatively few of the numerous

Cry toxins has been reported in the scientific literature.

Senior scientist Dr. Arpad Pusztai has prepared a superior

review of the health risks of GM food, which included a

comprehensive section on Bt toxins. Areas covered in the

review included an earlier report from an Egyptian

laboratory showing the Cry1 toxin, either fed alone or in

transgenic potatoes to mice, led to hypertrophic and other

changes in gut ultrastructure. Pusztai pointed out the need

for fuller and much more extensive animal feeding studies on

GM crops [9].

 

Dr. Mae-Wan Ho has reviewed recent findings on the mammalian

toxicity of Bt toxins. Her reports include observations on

the death of cows fed GM fodder, survival of transgenic DNA

during digestion and binding of Bt toxin to the intestine of

mice [10-12]. Some of the studies in those reports are

mentioned below.

 

Cry1Ac toxin was observed to bind to the cell surface

proteins of the mouse small intestine and caused changes in

the physiological state of the intestine [13]. Vaginal and

intraperitoneal immunization with Cry1Ac toxin elicited

antibody response at several mucosal sites, including the

vagina. At the large intestine, the antibody response

changed during the oestrus cycle, while the vaginal response

did not change throughout the reproductive cycle [14].

Intranasal, rectal and intraperitoneal immunization with

Cry1Ac toxin induced serum, intestinal, vaginal and

pulmonary (lung) immune response in mice [15]. Cry1Ac toxin

was a potent immunogen, more potent than cholera toxin [16,

17].

 

These few studies have made important breakthroughs on the

impact of Bt toxins but are seldom followed up vigorously, a

serious mistake considering the widespread consumption of

unlabeled foods containing Bt toxins. Furthermore, the

adverse findings seem to be seldom mentioned in regulatory

reviews.

 

The behaviour of transgenes and toxins in the mammalian

digestive system is crucial to evaluating their impact on

the animal. Cattle were fed maize silage containing Cry1Ab

toxin. After four weeks, the contents of their digestive

system and faeces were analysed. The low-copy Bt genes could

not be quantified in the digestive system, but the Bt toxin

protein was detected in the digestive system and faeces of

the cattle [18].

 

Pigs fed maize containing Cry1Ab were found to have

quantities of the Cry toxin genes and toxin protein; and

Cry1Ab protein was not totally degraded in the digestive

system [19]. Pigs fed StarLink (Cry9c) maize were found to

have about a quarter of the ingested Cry genes in their

rectal material, showing that the genes were only partly

degraded during digestion [20].

 

It is clear that Cry toxin genes and proteins are not

entirely digested in animals fed GM maize. The impact of the

genes and toxin proteins on the animals deserves much fuller

study. As GM foods are not labelled in North America, it has

not been possible to determine whether or not feeding humans

and animals has had an adverse impact. Clearly, the DNA and

toxin proteins studied in the feeding experiments are the

‘real thing’, not the bacterial proteins used as surrogates

in the toxicity testing approved by regulatory agencies.

 

Toxicity to non-target organisms

********************************

The impact of Bt toxins and the genes determining them on

non-target organisms in the environment has been studied to

some limited extent, but nowhere as much as is needed. The

soil around the GM crop may accumulate toxins, if these are

released to the soil.

 

Bt toxin is found released to the soil by maize plants both

in the laboratory and in the field [21]. The toxin is

released in root exudates from a number of maize hybrids

expressing three different transformation events [22]. Bt

toxin released from exudates is bound to soil particulates

and is active for at least 180 days [23]. Bt toxin is not

taken up from the soil by plants, not even from hydroponic

growth media [24]. It has been reported that Bt maize

exudates had no effect on earthworms, nematodes, protozoa,

bacteria and fungi in soil [23]. However, a recent study

showed that the litter from Bt maize, while not fatal to

earthworms, caused a large weight loss in worms exposed for

over 200 days to the litter containing Bt toxin [25].

 

Some Bt crystal proteins have been reported to target

nematodes while the toxins targeting Lepadoptera or

Coleoptera insects do not appear to target nematodes [26],

but further investigation is needed. Soil nematodes include

both plant pathogenic species and species that eat insect

pests (entomopathogenic). The destruction of the latter by

Bt crops would have disastrous economic consequences.

 

Beneficial predators may be destroyed by Bt crops and their

loss would be costly. The green lacewing is an important

predator of the insect pests of maize. Insect herbivores

feeding on Bt maize were fed to green lacewings. Insect

herbivores that ingested little Bt Cry1Ab toxin did not

affect lacewing survival, while herbivores that ingested a

quantity of Cry1Ab toxin caused low survival in lacewings

and delayed development among survivors [27].

 

To test the concern that consuming herbivore insects may

have produced “indirect toxicity to the lacewing predator”,

the herbivores were treated with high levels of the natural

Cry1Ab toxin in the laboratory, then fed to green lacewing

predators. The lacewings that were fed insects treated with

natural Cry1Ab toxin turned out to be far less severely

affected than the lacewings fed insects feeding on Cry1Ab

transgenic maize [28, 29]. The researchers stated that their

procedure was to “give evidence that Bt-maize poses no

threat to this predator” [29]. But they failed to indicate

that the natural Cry1Ab toxin was not identical to the

Cry1Ab toxin synthesized from a synthetic gene in Bt maize,

and the Bt maize proved to be far more toxic. Whether it is

the Bt toxin in Bt maize that is responsible for the

toxicity, or something in the transgenic process itself is

not known.

 

The negative impact of Bt maize pollen on the survival of

the monarch butterfly has been extensively reviewed and will

not be discussed further here [30].

 

Regulatory shortcomings

***********************

The manner in which mammalian toxicity and environmental

impact of Bt crops is evaluated is spelt out in the United

States Department of Agriculture (USDA) Animal and Plant Health

Inspection Service (APHIS) reports on the deregulation of GM

crops that had been field tested. With both Bt insect

resistant crops and herbicide tolerant crops, approval was

not based on the Bt toxin proteins, nor on the bacterial

enzymes providing herbicide tolerance in the crop, but on Bt

toxin proteins or enzymes isolated from bacterial cultures.

 

The Bt toxins in bacterial cultures were produced using

genes that differed from those used in the GM crops. The

proteins were significantly altered in amino acid sequence

from those in GM crops. The regulatory agencies and their

advisory committees argued that so long as the bacterial

products retained their active domains as toxins or enzymes

and had similar immune profiles to the proteins produced in

GM crops, they were “substantially equivalent” to the

proteins produced in GM crops.

 

For example, Cry1Ab toxin gene in maize was tested using a

toxin produced in E. coli bacteria that differed from the

protein produced in the GM crop [31]. Maize altered with Bt

gene Cry3Bb1 was similarly tested using the bacterial

protein [32]. Maize modified with Cry1F and a gene for

herbicide tolerance was approved based on testing the

bacterial - not the crop - proteins for safety towards

mammals and non-target organisms [33]. Cotton modified with

Bt toxin gene Cry2Ab was approved based on studies of the

surrogate product produced in bacteria [34]. Potato modified

with Bt toxin gene was tested, as in the cases above, using

the bacterial surrogate protein, not the protein in the crop

[35].

 

These examples are representative of all risk assessments

for Bt crops. The practice of testing surrogates for toxins

and enzymes produced in GM crops is unsound in the light of

the millions of people and animals being exposed to the

products. Such careless procedures have been made possible

by the absence of labels on GM food and feed, which makes

tracing impacts of the products difficult, if not

impossible.

 

The second report of the UK’s GM Science Review Panel (2004)

commented, “Many of the genes introduced into GM plants are

based on bacterial gene sequences, but are synthesized de

novo in the laboratory to include more appropriate codon

usages for more efficient expression in plants” [36].

However, the report failed to mention that the evaluations

of mammalian safety and environmental impacts (particularly

the impact on non-target organisms) have been done using a

bacterial surrogate for the proteins produced in GM crops.

Consequently, GM crops produced in the United States, Canada

and other countries are untested and unknown for toxicities,

and the failure to label the GM foods produced from the GM

crops has obscured any impact on humans and animals.

 

Apparently, this makes the approval of the GM crops illegal.

 

 

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