GM Protein for Ice Cream Not Ready for Commercial Use

The advisory committee has made considerable effort towards assuring the safety of a genetically modified ice-structuring protein intended for use in edible ices, but large gaps still remain. Prof. Joe Cummins and Dr. Mae-Wan Ho

This report has been submitted to the Food Standards Agency on behalf of the Institute of Science in Society

The Advisory committee on Novel Foods and Processes (ACNFP) of UK’s  Food Standards Agency prepared a draft opinion on an ice-structuring preparation (ice structuring protein Type III HPLC 12) derived from fermented genetically modified baker’s yeast as a food ingredient [1] following the 2006 application from Unilever Corporation for the preparation to be used in edible ices [2].

The ice-structuring protein was derived from a polar fish, ocean pout, and is intended for making ice cream smoother and creamier. The GM protein, produced in transgenic bakers’ yeast prevents large ice crystals forming in ice cream and other frozen foods.

The initial application was put out for public comment, and the Independent Science Panel submitted a report recommending rejection of the application until comprehensive, long term studies have been carried out  [3] (GM Protein in Ice Cream, SiS 31).

Unilever responded to the comments with information from a new study published in 2007 [4], which has been incorporated into ACNFP’s draft opinion. The study found no immune or allergic response in human volunteers given an oral dose of the ice structuring preparation. However, the single-blind placebo-controlled trial left a lot to be desired, and a number of important questions remain unanswered.

• The trial involved only a small number of healthy human volunteers, 23 in the test group, and nine in the control group.
• The preparation used was not purified ISP, but a crude isolate containing an unknown assemblage of yeast proteins and sugars, which would be expected to complicate the immune response, particularly as seven in the test group and four in the control group had predisposition to allergy.
• A low dose of the ice-structuring preparation, equivalent to 16.3 mg of ice structuring protein (ISP) was given daily for five days a week over a short period of just eight weeks, which may well not be sufficient to fully expose the immunogenic potential of the ISP.
• The preparation was given orally in a “flavoured drink” instead of in ice cream, where the use of ISP was intended. This was a serious oversight, as the complex of ISP and microscopic ice crystals was known to elicit immune response distinct from the ISP; antibodies to the complex, but not the protein was found in the ISP’s natural host species, the ocean pout, as well as the Atlantic herring [5].

Despite these serious shortcomings, ACNFP’s Draft Opinion [1] indicated that there was no need for a fuller study in an animal model.

There are other considerations that need to be taken into account.

Even if the study had been properly conducted, and no immune response could be demonstrated as the result of oral ingestion, that would not rule out an immune response from other routes of exposure. Children tend to ‘wear’ ice cream by spilling it on themselves. Open sores, bruises, or cuts provide one avenue of exposure; and dried ice cream on skin or clothing can be inhaled into the respiratory tract as ice cream dust. These other routes of exposure are realistic, but there no published reports on the injection of ISP into experimental animals. The Unilever report [4] and the 2006 report on ISP by Food Standards Australia & New Zealand [6] both describe experiments using monoclonal antibodies to ISP as analytical tools, indicating that the protein itself is indeed immunogenic.

A full investigation should be carried out on the immune response to ISP following exposure by injection, topical application and inhalation. The inflammatory potential of the commercial ISP preparation was dismissed [1] even though no routes of exposure to the ISP other than the oral were studied. The ACNFP further concluded that using cod allergic individuals in assessing the allergic potential of the ISP preparation is representative of the fish allergic population. That conclusion is irrational and unscientific. Cod allergy is caused by parvalbumin; ISP is unrelated to parvalbumin and has no similarity to the protein. Study of ISP allergy in individuals with cod allergy makes no sense at all. Assurances from such meaningless experiments are simply misleading the public.

Similarly, long-term studies should be done on the immunogenicity of the ice-structuring preparation in micro ice-crystal complex.

The commercial ISP preparation appears to be made up of 60 percent un-glycosylated ISP and 40 percent gkycosylated ISP. Only the un-glycosylated form is active in forming micro ice crystal complex, while the glycosylated form is non-functional [1]. Purification of the un-glycosylated away from the glycosylated form and other contaminants should be a priority.

The committee’s recommendation that products containing the ISP preparation should be labelled as having been derived from yeast [1] is not sufficient; it should be labelled as having been derived from genetically modified yeast.

Nevertheless, the Draft Opinion [1] has gone a considerable way towards assuring the safety of ISP and we hope that such efforts will continue.

Article first published 16/04/07

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References

1. Lidner  N. DRAFT OPINION ON AN APPLICATION UNDER THE NOVEL FOODS REGULATION FOR ICE STRUCTURING PREPARATION DERIVED FROM FERMENTED GENETICALLY MODIFIED BAKER’S YEAST Saccharomyces cerevisiae AS A FOOD INGREDIENT Draft issued for public comment, 2April 2007 ADVISORY COMMITTEE FOR NOVEL FOODS AND PROCESSES, http://www.food.gov.uk/multimedia/pdfs/icedraft.pdf
2. Lewis S. Application for the Approval of Ice Structuring Protein Type III HPLC preparation for use in Edible Ices. Safety and Environmental Assurances Centre Unilever Colworth 2006, http://www.food.gov.uk/multimedia/pdfs/ispapplication1.pdf
3. Cummins. J, Ho MW and Hooper M. GM protein in ice cream Science in Society 31 , 9,  2006.
4. Crevel RW, Cooper KJ, Poulsen LK, Hummelshoj L, Bindslev‐Jensen C, Burks AW and Sampson HA. Lack of immunogenicity of ice structuring protein type III HPLC12 preparation administered by the oral route to human volunteers. Food Chem Toxicol. 2007, 45(1),:79-87.
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. Food Standards Australia New Zealand A Safety Assessment Report Ice Structuring Protein as a processing aid for ice cream and edible ices, 2006, http://www.foodstandards.govt.nz/_srcfiles/NO%2042%20Ice%20structuring%20protein%20Technical% 0Report%20_3_.pdf