GMW: GM Protein in Ice Cream

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GMW: GM Protein in Ice Cream

" GM WATCH " <info

Tue, 4 Jul 2006 09:18:50 +0100

 

 

 

 

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From Prof Joe Cummins:

 

Below is our brief on the Unilever application for GM ice cream in UK.

 

Unilever has been selling GM ice cream in US with FDA approval. Good

Humor ice cream is a major producer of ice cream bars and other products

mainly targeted to young children. The applications for approval of GM

ice cream have all ignored the impact of GM ice cream on children.

 

In the FDA GRAS application the main focus of safety was the

allergenicity of the ice structuring protein from the pouter fish. The

main test

was to examine effect of the ice structuring protein (ISP) on blood

from 10 people with cod allergy. There was no indication that the blood

contained IgE antibodies (allergic response) to the ISP. This experiment

seems very strange to me because it tests blood that is allergic to cod

but that allergen is a calcium binding protein called parvalbumin which

is unrelated to ice structuring protein. Cod has an ice structuring

protein but that protein is not at all related to the

pouter ISP in the ice cream.

 

What I am saying is that Unilever's main allergy test seems to be a

dummy test that could never produce results relevant to the GM ice cream,

it could only provide results showing no allergy, in other words it

seems rigged to produce favorable results. Unilever provided a GRAS panel

of experts who ignored the fecklessness of the allergy tests.

 

The Unilever approach seems very cold blooded and FDA's response seems

mindless when you consider that the ice cream will target young

children

....

GM Protein in Ice Cream

 

Genetically modified fish antifreeze protein is potentially able to

cause inflammation and

should not be approved without comprehensive tests

 

Prof. Joe Cummins, Dr. Mae-Wan Ho and Prof. Malcolm Hooper

 

This report has been submitted to the Food Standards Agency to oppose

approval of

Unilever's application on behalf of the Independent Science Panel

www.indsp.org.uk

 

Unilever is seeking approval of a genetically modified (GM) (FAQ on

genetic engineering) ice-structuring protein derived from a polar fish,

ocean pout, for use in making ice cream smoother and creamier. The GM

protein is produced in transgenic

bakers' yeast. Ice-structuring, or antifreeze protein protects the

ocean pout in freezing waters by preventing large ice crystals

forming; in

ice cream and other frozen food it would have the same effect.

 

Unilever applied to the Food Standards Agency (FSA) UK for approval,

and its proposal is now open for public comment [1]. Unilever has sent

similar petitions to the United States Food and Drug Administration (FDA)

to obtain the Generally Recognized As Safe (GRAS) status for the food

additive [2] and to Food Standards Australia New Zealand [3]. Both

applications have been approved, which is unfortunate.

 

The transgenic protein produced in yeast was designated ISP Type III

HPLC 12 glyco–ISP. The preparation tested by Unilever contained peptides

from yeast and sugars along with the recombinant protein. Unilever

conducted a subchronic feeding test of the preparation on rats by oral

gavage (force feeding) for 3 weeks, as well as a battery of

genotoxicity tests that proved to be negative. A series of tests that

included those suggested by the World Health Organisation for allergy

were carried out, along with tests for reactivity with serum obtained

from a few people allergic to fish.

 

The report stressed that the recombinant protein was identical to

protein found in edible fish [1], although that kind of statement is

generally untrue as will be discussed below. There is voluminous

literature on

antifreeze glycoproteins, particularly those from polar fish. There are

four main types of glycoproteins each differing significantly from

the others. Type III proteins are around 6500 daltons in size, they

form a beta-sandwich structure and are found only in ocean pout [4].

Although the antifreeze protein itself is not immunogenic for the ocean

pout, there is nevertheless a strong immune response to the micro ice

crystals complex with antifreeze protein circulating in the fish's blood,

indicating that the complex functions as conventional antigens for the

ocean pout [5].

 

The GM protein from transgenic yeast is the product of a synthetic

approximation of the pout antifreeze protein gene. The code sequence was

altered to facilitate production in yeast without altering the amino acid

sequence. Multiple copies of the synthetic gene were inserted into the

yeast chromosomes to boost the synthesis of the protein [1].

 

Production of proteins in yeast destined for human consumption or

therapy is fraught with the problem of secondary modification of the

proteins by glycosylation or other modifications that result in the

human (or

animal) immune system recognizing the yeast modified proteins as

antigens. There has been progress in " humanizing " the glycosylation

patterns

of proteins produced in yeast [6, 7]. However, there has been no effort

to " humanize " the glycosylation pattern of the antifreeze protein

produced in the yeast strain used to produce the protein.1

 

Are the cursory studies on allergenicity carried out by Unilever on the

GM protein to be used in ice cream adequate to rule out allergy and

other immune reactions in the tens of millions of people that will

consume

the ice cream?

 

It is worth pointing out that the transgenic protein is already used in

ice cream in the USA, Australia and New Zealand, and that ice cream has

not been labeled, so any problems resulting from its use may go

unrecognized.

 

We should recall that the transgenic expression of a bean gene in peas

turned it into a strong immunogen, resulting in debilitating even fatal

lung inflammation in mice. That response was related to the

glycosylation pattern of the transgenic protein [8, 9] ( " Transgenic

pea that made

mice ill " , SiS 29).

 

Unilever does not appear to have carried out the inflammation tests

even though there is every indication from the scientific literature that

pouter antifreeze protein is immunologically active. There is also the

question of latency. Some chronic inflammatory diseases emerge

gradually, building up from an initial response that is small and

clinically

variable or insignificant (asymptomatic) [10]. But there is a potential

cascade effect that when triggered, will lead to autoimmune effects that

could affect any organ. Without long term testing, we could be letting

off an immunological time bomb. Tests for inflammatory effects must be

done in both young and older animals with full analysis of inflammatory

cytokines, antibodies and related molecules. Tests in young animals are

particularly important as ice cream is consumed from the earliest age

when there are crucial development processes occurring.

 

In conclusion, contrary to the claims of Unilever, there is no evidence

that the transgenic ice- structuring protein is identical to the

protein produced in pouter fish. The transgenic protein appears to

have the

glycosylation pattern of yeast, making that protein a unique antigen.

Even though allergenicity was studied in a cursory way, there is clear

precedent for studying inflammation comprehensively in the long term in

both young and older animals before exposing the European public to the

transgenic ice cream.

 

References

1. Lewis S. Application for the approval of ice structuring protein typ

III HPLC12 preparation for use in edible ices. Safety and Assurance

Centre 2006 http://www.acnfp.gov.uk/assess/fullapplics/isp

2. US Food and

Drug Administration Agency Response Letter GRAS Notice No. GRN000117

2003, http://www.cfsan.fda.gov/~rdb/opa-g117.html

3. Food Standards

Australia New Zealand Initial Assessment Report Application A544 Ice

Structuring Protein as a Processing Aid for Ice Cream and Edible Ices,

2004,

http://www.foodstandards.gov.au/_srcfiles/A527_Dimethyl_ether_IAR_FINAL.pdf

4.

Harding MM, Anderberg PI and Haymet AD 'Antifreeze' glycoproteins from

polar fish. Eur J Biochem. 2003, 270(7), 1381-92.

5. Verdier JM, Ewart KV, Griffith M and Hew CL. An immune response to

ice crystals in North Atlantic fishes. Eur J Biochem. 1996, 241(3),

740-3.

6. Wildt S and Gerngross TU. The humanization of N-glycosylation

pathways in yeast. Nat Rev Microbiol. 2005, 3(2), 119-28. 2

7. Li H, Sethuraman N, Stadheim TA, Zha D, Prinz B, Ballew N, Bobrowicz

P, Choi BK, Cook WJ, Cukan M, Houston-Cummings NR, Davidson R, Gong B,

Hamilton SR, Hoopes JP, Jiang Y, Kim N, Mansfield R, Nett JH, Rios S,

Strawbridge R, Wildt S and Gerngross TU. Optimization of humanized IgGs

in glycoengineered Pichia pastoris. Nat Biotechnol. 2006, 24(2), 210-5.

8. Prescott VE, Campbell PM, Moore A, Mattes J, Rothenberg ME, Foster

PS, Higgins TJ and Hogan SP. Transgenic expression of bean alpha-amylase

inhibitor in peas results in altered structure and immunogenicity. J

Agric Food Chem. 2005, 53(23), 9023-30.

9. Ho MW. Transgenic pea that made mice ill. Science in Society 2006,

29, 28-29,

http://www.i-sis.org.uk/isisnews.php

10. Arbuckle MR, McClain MT,

Rubertone MV, Scofield RH, Dennis GJ, James JA, Harley JB. Development of

autoantibodies before the clinical onset of systemic lupus erythematosus.

New Eng J Med 2003, 349, 1526-33.3

 

 

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