Biotechnology report dismissed pleiotropic effects
I have just read the IFT Expert Panel Report on the safety of human genetically modified (GM) foods, that was published in the September 2000 issue of Food Technology. It takes two to three months for Food Technology to reach Australia.
I am concerned by the apparent dismissal in the article of possible pleiotropic effects, that is, changes to other gene systems by the introduction of exotic genes, or by gene jumping.
Applications were received by the Australian and New Zealand Food Authority (ANZFA), to market, in Australia, seven Monsanto GM foods, three Novartis GM foods, and one from Optimum Quality Grains, which is associated with DuPont. ANZFA recently released for public comment the technical data provided by the applicants.
Monsanto’s insect-protected corn line MON 810, glyphosate-resistant cotton lines 1445 and GA21, and glyphosate-resistant canola line GT 73 all showed statistically significant differences in the amino acid content of the total protein between the GM and the non-GM foods from which they were derived, as did Novartis insect-protected BT 176 and insect-protected, herbicide-tolerant BT 11 corns. These statistically significant differences in amino acids indicate possible pleiotropic effects that could affect the protein efficiency ratios. PERs are best determined by animal feeding studies, which would also show up other effects.
Of great concern are the results of two one-month feeding studies (Naylor, 1994, 1995) using Sprague-Dawley rats fed Monsanto’s ground unroasted GM canola meal and toasted, defatted GM canola meal. Both studies showed a 12–16% increase in the rats’ liver weights. No information was given about how the livers were affected, but a 12–16% increase in one month must be regarded as a pathological change.
Monsanto also reported (Naylor, 1983) that Sprague-Dawley rats fed for one month on GM potatoes showed enlarged lymph glands and adrenals and hydronephrosis, when compared with those fed the “parent” non-GM potatoes, which were not the Lencape variety mentioned in the IFT report. Monsanto said that a further four rat feeding studies had been carried out on GM potatoes, but the results were not released.
Monsanto said that it was also carrying out rat feeding studies on the MON 810 GM corn, which were expected to be completed in late 2000.
Pigs fed soybean meal derived from GM high-oleic-acid soybeans did not perform as well as pigs fed standard check line soybean meal, as measured by the average daily gain and the food/gain ratio.
No animal feeding studies, or in some cases only five-day studies, were reported for the other GM foods.
The 12–16% increase in liver weight for the GM canola meal, and the increased weight of lymph nodes and adrenals and the hydronephrosis in the GM potatoes after only one month of feeding, should be cause for concern. One can only conjecture what the results would have been if the rats had been fed for a longer period.
I wonder whether these results had been given to the FDA, and if so why they have not become public knowledge before now, as some of the work was reported to Monsanto in 1993. It appears that the IFT panel was not aware of these studies, as the IFT Code of Ethics would have required the panel to comment on them.
The precautionary principle should apply. The results indicate pleiotropic effects affecting the foods and show the need for proper long-term feeding studies before GM foods are released for general consumption.
—Frank E. Peters, Curtin, Australia
Task force chair responds
The author of the above letter refers to the “Human Food Safety Evaluation of rDNA Biotechnology-Derived Foods” section of IFT’s Expert Report on Biotechnology and Foods. The report was developed by a panel of experts convened through an initiative led by IFT’s Task Force on Biotechnology. The Chair of that Task Force and IFT 1998–99 President, Bruce R. Stillings, offers the following response.
Regarding statistically significant differences in amino acid content between genetically modified and control crops:
As the author of this letter states, data generated on the levels of specific amino acids and other compositional components in the rDNA biotechnology-derived plants can show at some frequency, as expected, statistically significant differences in the levels of some of these components from the non-rDNA biotechnology-derived control. It is often assumed that the rDNA biotechnology-derived plant and the control lines are genetically identical or “isogenic,” except for the introduced gene(s)/trait. Transformation, selection, and breeding create a genetically modified product for which there is no true “isogenic” control. There are more genetic differences between the genetically modified plant and the parental control than the introduced transgene(s). These other genetic differences can account for statistically significant differences in some of the measured components.
The key challenge is to determine whether any component shown to be statistically different from the control is biologically meaningful. To do this, compositional analyses are conducted on the rDNA biotechnology-derived variety, the most closely matched genetic control (usually the parental variety from which the product was derived) and representative traditional varieties of the crop. This allows the data generated on the rDNA biotechnology-derived variety to be compared to its closest genetic counterpart. These values can also be compared with the range for other varieties of the crop. If there are statistically significant differences between the genetically modified variety and the control, they are compared to the values measured in other commercial varieties to assess whether they are outside the normal range of existing varieties, and hence whether the observed difference is biologically meaningful.
To date, the statistically significant differences observed in compositional studies of products that have not been intentionally modified to have compositional changes have been within the range of values for conventional varieties. Hence, these differences are not biologically significant. This includes the values referred to by the author of the letter.
For most of the examples mentioned, the safety of food and feed products have been reviewed by the Food and Drug Administration in the U.S., Health Canada and Canadian Food Inspection Agency in Canada, the Ministry of Health and Welfare and the Ministry of Agriculture, Forestry and Fisheries in Japan, and the regulatory authorities in the European Union and Argentina. Animal nutritional studies have consistently supported the conclusion that the food/feed products from rDNA biotechnology-derived crops are nutritionally and compositionally equivalent and as safe as the food or feed from the control or conventionally bred varieties.
Regarding rat feeding studies on genetically modified canola:
Three rat feeding studies (not two, as mentioned by Dr. Peters) were conducted with Roundup Ready® (RR) canola. In all of them, liver and kidney weights were measured as part of the evaluation. In the first study, processed canola meal was fed to male and female rats at dietary levels of 5 and 15% wt/wt in the diet for 4 weeks. There were no differences in liver and kidney weights (either absolute or as percent of body weight) between rats fed canola meal from the two different RR lines and the parent line from which they were derived. Subsequent to completion of the study, it was discovered that the two RR lines had been commingled so that 50/50 mixtures were tested and not the discrete lines.
The study was subsequently repeated, with only one of the RR lines previously tested; the other RR line had been dropped from development. In the repeat study, there was up to a 16% increase in liver to body weight for rats fed the RR meal when compared to rats fed the meal from the parent control line. Since the increase in relative liver weight was at variance with the first study result, a third rat feeding study was conducted to try to resolve these contradictory findings.
The third study was much larger and included in addition to the same RR and parent lines processed meal samples derived from commercial, non-transgenic canola lines grown in various locations across Canada and in Europe. There were a total of five Canadian canola varieties and three European varieties tested, to represent varieties of divergent germplasm and growth in different locations. The intent of these “reference controls” was to establish some background information on the normal range of responses of rats fed different commercial canola varieties. New varieties of canola derived from conventional breeding are not normally fed to rats during commercial development. There were two replicate groups of rats for each canola line tested to examine potential variation that might occur during processing of canola meal. Thus there were twice as many rats fed RR and the parental control canola meal in this study compared to the previous two feeding studies. Processed canola meal was added to diets at 10% wt/wt and fed to rats for 4 weeks. There was no difference in absolute or relative liver or kidney weight between rats fed RR canola and the parental control. Moreover, the liver weights for both RR and the parent group were well within the range of liver weights established for groups fed the different commercial varieties of canola meal. Thus, the most definitive study of the three feeding studies confirmed the results of the first study, namely, that feeding processed meal from RR canola had no effect on liver or kidney weights. There were no apparent gross pathological changes in the livers and kidneys of rats in any of the three feeding studies following examination at necropsy. Thus, the weight of evidence indicates that rats fed RR processed canola responded in a similar manner to rats fed meal from the parent line. Moreover, these responses are well within the range of responses of rats fed different commercial varieties of canola meal.
Regarding rat feeding studies on genetically modified potatoes:
Statements made by the Australia New Zealand Food Authority in its “Final Risk Analysis Report” (ANZFA, 2000) concerning the Naylor (1993) study include:
“Consumption of potatoes (both control and test groups) were slightly reduced for the first three days of the study, however, both groups’ potato consumption increased rapidly and remained high for the rest of the study. Consumption of Rodent Chow was similar for both the test and control group. Cumulative weight gains were normal and equivalent to the control group. No adverse clinical signs were observed. Gross pathology revealed a number of abnormal findings, such as enlarged lymph nodes, hydronephrosis and enlarged adrenals, however, these findings were observed in both the test and control groups and could not be related to the test substance. There were no significant differences in absolute or relative organ weights of the kidney, liver, or testes for the test group when compared to the control.”
These gross findings are not unusual. The fact that they were observed in both control and treated groups is not surprising and supports the conclusion that they were not related to the genetically modified potato.
We appreciate very much Dr. Peters’ comments on this important topic. With regard to Dr. Peters’ concerns, it is clear that the proper feeding studies were conducted. When all the facts are interpreted in the proper context, the data provide clear evidence that the products are safe and substantially equivalent to their non-rDNA biotechnology-derived counterparts.
Article ignored monounsaturated fatty acids and nuts
I always read and enjoy Don Pszczola’s articles in Food Technology, but must admit that I was disappointed in the lack of completeness in his “Putting Fat Back into Foods” article (December 2000, p. 58). Although I realize that the emphasis was fat replacers and new ingredients, I think he was remiss in not making some mention of the growing body of science and knowledge about the positive role of monunsaturated fatty acids in human health. Whether the source is specialty vegetable and nut oil products or ingredients or the foods themselves (as ingredients in formulations), this is an important component of this trend.
Obviously, I’m biased toward almonds and almond products and other treenuts—but the Mono & Health message is what is important, along with the naturally occurring phytosterols, vitamin E as alpha-tocopherol, etc.
—Karen Lapsley, Director of Scientific Affairs, Almond Board of California, Modesto
Associate Editor Pszczola responds:
The Ingredients section is not meant to be a review of all the ingredients under a particular umbrella. Rather, it is an update in which I try to discuss and analyze the newest (usually over an 18-month period) developments in a particular area. Obviously, the material used in an update will be different from that of a review.
Naylor, B.S. 1983. One month feeding study with C.B. (Colorado potato beetle) control potatoes in Sprague-Dawley rats. Study No. 92209, Monsanto Co., St. Louis, Mo.
Naylor, M.W. 1994. One month feeding study with processed and unprocessed glyphosatetolerant canola meal in Sprague-Dawley rats. Monsanto Co., St. Louis, Mo.
Naylor, M.W. 1995. One month feeding study with processed canola (line GT73) in Sprague-Dawley rats. Monsanto Co., St. Louis, Mo.
ANZFA. 2000. Final risk analysis report. Subject: Application A382—Food derived from insect-protected potato lines BT-06, ATBT04-06, ATBT04-31, ATBT04-36, and SPBT02-05. Dec. 20, 11/01. Australia New Zealand Food Authority.