REPORT TO THE ROYAL SOCIETY
Risks to Health From The Consumption Of Genetically Modified Foods

Web version of a Report issued in April 2001 by Dr Eva Novotny for SGR

1. INTRODUCTION

Most of the evidence presented below refers to the effects of genetically modified food on animals, rather than on human beings. However, since animals are often used in experiments as models for human responses, it seems appropriate to include these items.

Most of this evidence is available elsewhere. However, sections 3 and 4 contain new analyses by Scientists for Global Responsibility of data on experiments on rats and chickens. The original analyses and conclusions had been accepted in support of an application for placing a GM maize on the National Seed List. Our review, however, leads to different conclusions.

2. THE L-TRYPTOPHAN INCIDENT

‘In 1989 there was an outbreak of a new disease in the US, contracted by over 5,000 people and traced back to a batch of L-tryptophan food supplement produced with GM-bacteria. Even though it contained less than 0.1 per cent of a highly toxic compound, 37 people died and 1,500 were left with permanent disabilities.’ (Quotation from Dr Michael Antoniou, gene therapist, Guy’s Hospital, London, as printed in GM-Free, vol. 1., no. 1, April 1999, p. 3 and again on p. 10.) The article on page 3 continues, without attribution to Dr Antoniou: ‘More may have died, but the American Centre for Disease Control stopped counting in 1991.

‘The US government declared that it was not GM that was at fault but a failure in the purification process. However, the company concerned, Showa Denko, admitted that the low-level purification process had been used without ill effect in non-GM batches. Scientists at Showa Denko blame the GM process for producing traces of a potent new toxin. This new toxin had never been found in non-GM versions of the product.’ (ibid., p. 3)

3. EXPERIMENT ON FEEDING OF GLUFOSINATE-RESISTANT MAIZE TO CHICKENS

3.1 The experiment

The study is entitled ‘The Effect of Glufosinate Resistant Corn on the Growth of Male Broiler Chickens’. Like the study in section 4 on rats, this was submitted by Aventis (and accepted) in support of its application for a National Seed Listing. The purpose was apparently ‘to detect differences in nutrient quality of corn samples’ (p. 1 of the study). The duration of the experiment was 42 days.

In this study, 280 young broiler chickens of a commercial strain were used, divided into two groups. One group ate AgrEvo’s glufosinate-resistant maize, the other ate University of Guelph maize, a non-GM variety. Both diets were a conventional maize-soya type of diet; and both were adjusted on the same days, as appropriate for different stages of growth. The GM maize and the non-GM maize appear to be different varieties, and so the study is flawed in this respect.

All chickens were allowed to eat at will.

3.2 The stated conclusions of the study

The stated results and conclusion are:

‘Results of live bird traits … show that source of corn … had no effect on body weight, feed intake, … or percent mortality over the experimental period …’

‘Glufosinate tolerant corn from the U.S.A. is comparable in feeding value, for 0-42 day broilers, relative to the commercially available corn hybrid. Therefore, the nutritive value of glufosinate tolerant corn hybrid is equivalent to a commercially available corn hybrid.’

The mortality rate was judged to be normal.

3.3 Re-examination of body weights

Fig. 1a shows the body weights of the chickens in the two groups as a function of time. By the end of the study, the chickens on the genetically modified diet (represented by the black curve) have, on average, weights only 1 % below the average weight in the control group (red curve), which is insignificant. However, the error bars, shown by dotted lines for both groups, are very much greater for the chickens on the glufosinate-resistant maize. (The study does not state what is measured by the error bars, another flaw of the study.) Initially the weights and the errors bars are nearly identical, but the percentage error grows much faster for the glufosinate-fed group, as is evident from Figs. 1a and 1b, the latter being a larger-scale plot of the last 11 days of the experiment. Numerical values are given in Table 1 of the study. In spite of the fact that the body weights themselves never differ by as much as 1%, the errors quoted, which are initially the same, grow much more rapidly for the test group. On day 32 the errors are nearly twice as great for the test group; and on day 42 they are 2.5 times greater. Data for individual chickens have not been supplied, and the meanings of the error bars are not clear in terms of how extreme the individual weights of the birds might have been.

3.4 Re-examination of food consumption

Fig. 2 gives total food consumption during the intervals between measurements.

Again, the error bars are much greater for the test group: over the first interval they are only 1.3 times greater, but this ratio grows to 2.6 for the second interval and to 3.4 for the third and last interval.

3.5 Re-examination of mortality

In justification of the conclusion of the study that percentage of mortality is unaffected by the feeding of the GM maize, it is stated that ‘we normally see values of 5 to 8 % in male broilers.’ Nevertheless, it may be significant that twice as many deaths occurred amongst the chickens eating the glufosinate-resistant maize (7.14 ± 5.47 % between days 0 and 42) as compared with those fed commercial hybrid corn (3.57 ± 5.47 % between days 0 and 42).

3.6 Conclusions on the chicken study

Average body weights and feed intakes do not vary significantly, as concluded in the study. Nevertheless, the much larger error bars for both these quantities give concern that the weight gains and the feeding patterns were erratic in the treated group, indicating that at least some of the chickens were not thriving on the glufosinate-resistant maize.

There were twice as many deaths amongst chickens fed the GM maize as there were amongst those fed non-GM maize, although the study considered the number of deaths to be normal.

4. EXPERIMENT ON FEEDING OF PAT-PROTEIN TO RATS

4.1 The experiment

This experiment was sponsored by HOECHST SCHERING AgrEvo GmbH (note that AgrEvo is now Aventis) in support of an application in the United Kingdom to have the genetically modified maize Chardon LL added to the National Seed List. The experiment was accepted as evidence of safety of the maize for the feeding of cattle.

The report on this experiment is entitled ‘PAT-PROTEIN – Repeated Dose Oral Toxicity (14-Day Feeding) Study in Rats’. This study on rats, like that on chickens, has little relevance to cattle, as the digestive systems of these animals are very different: cattle are ruminants and have four stomachs. Furthermore, it was not the maize itself, Chardon LL, but the isolated PAT-protein it contains that was tested; and the effects of feeding the isolated protein must be expected to differ from the effects of feeding the whole maize. Also, the very short time during which the experiment was pursued gives no indication of possible long-term effects of feeding over a lifetime, especially when the maize is to be fed to a very different animal species. Only five male rats and five female rats were used in each of the four groups, and the individual rats had substantial differences in weight even at the start of the experiment. While we believe that the experiment was faulty and that no firm conclusions can be drawn from it, we have re-examined the measurements to confirm, or otherwise, the internal consistency of the some of the conclusions drawn in the study.

The original proposal submitted by the laboratory performing the experiment was for a 10-day study; however, this was rejected by the sponsor and it was agreed that a 14-day study would be undertaken. Although it is stated (p. 15, para. 2) that ‘This study should provide a rational basis for toxicological risk assessment in man’, the conclusions are somewhat pre-empted (p.18, middle) by the statement that ‘As PAT-PROTEIN consists of normal amino acids it was not expected to cause any remarkable toxicity. Therefore, a treatment period [i.e., length of experiment] of 14 days was considered to be sufficient.’ . (In fact, measurements of body weight and food consumption spanned only 13 days.) Measurements were made only on Days 0 (pre-test), 1, 3, 7, 9 and 13. ‘Day 0’ actually occurred several days prior to Day 1, which accounts for the discontinuities in slope of some figures. Only body weights and food consumption will be discussed in this report. Presentations at the Chardon LL hearing held in London in October and November 2000¹ considered further aspects of this study, such as biochemical effects: see the statements of Dr Vyvyan Howard, Senior Lecturer and Head of the Foetal and Infant Toxico-pathology Group at the University of Liverpool, on 18 October; of Dr Bob Orskov, Honorary Professor in Animal Nutrition at Aberdeen Universtiy and Director of the International Feed Resource Unit, also on 18 October; and Dr Arpad Pusztai on 24 October. (We are aware that the Society dismissed previous evidence by Dr Pusztai, on the effects of GM potatoes on rats; nevertheless, we include this reference, should the Society wish to consult it.) All these presentations appeared on the MAFF website. [They can now be found by visiting http://www.defra.gov.uk and searching for ‘Chardon’. Transcripts are listed according to ‘year month day’; e.g., ‘001016’ means ‘2000 October 16’.

Although the purpose of the study was to test for toxicity, the data provide evidence that the animals may not be thriving on a diet including the PAT-protein. The evidence for this suggestion, from body weights and food consumption, will be examined below. Firstly, however, it is necessary to describe the experiment.

A total of 40 rats took part. They were delivered to the laboratory at the age of about 4 weeks, and so were very young animals that were growing rapidly. There were two control groups and two test groups, each group containing 5 males and 5 females. Body weights at the beginning of the experiment varied widely between 53 and 82 g for males and between 50 and 74 g for females. The groups were divided as follows:

Group 1: CONTROL group given a diet normal for laboratory rats throughout the experiment. In the 5-day acclimatisation period preceding the experiment, all rats were given this diet, which provided the standard of total protein content of 50’000 ppm [sic] to which the diets of the other three groups were adjusted.

Group 2: TEST group given a low dose of PAT-protein, 5’000 ppm, plus 45’000 ppm of soya protein.

Group 3: TEST group given a high dose of PAT-protein, 50’000 ppm, without soya protein.

Group 4: CONTROL group without PAT-protein but containing 50’000 ppm of soya protein.

In terms of similarity of diet, the test groups should better be compared with Group 4 than with Group 1.

All animals were allowed to eat at will.

Measurements of body weights and of food consumption were made during pre-test and on days 1 (before administering the new diets) and on days 3, 7, 9 and 13, although the last two measurements had been scheduled for days 10 and 14.

4.2 The stated conclusions of the study

The results of the study are summarised on p.34 of the study:

‘Average mean food consumption over treatment was in the same range for treated groups and controls.’

‘Occasionally recorded differences between controls and treated groups were generally small, showed no dose-relationship or consistent trend. They are considered to lie within the normal range of biological variation for rats of this age and strain housed under the conditions described above.’

‘Mean body weights were similar for treated groups and controls. There were no differences which could be attributed to treatment with the test article.’

4.3 Re-examination of body weights

Fig. 3a (p.39 of the study) plots the body weights of male rats, averaged within each group, against time during the experiment. The rats in Group 2 (dotted curve), which received the low dose of PAT-protein, gained weight at nearly the same rate as control Group 1 (solid curve), which received the standard rat diet. On the other hand, the rats in Group 3 (dashed curved), eating the high-dose of PAT-protein, gradually fell below all other groups, although they had been marginally the heaviest at the beginning of the experiment.

Fig. 3b (p. 40 of the study) shows a similar plot for the body weights of female rats. The rats in Groups 2 and 3 (dotted curve and dashed curve, respectively), eating the PAT-protein, gradually fell below the control groups; Group 3 had been the heaviest group at the beginning of the experiment.

Weights of individual rats were not plotted or analysed in the study, but we investigate these below.

Figs. 4a-d and 5a-d plot the individual body weights of males and females, respectively, against time for the four Groups. These figures are included for possible reference when examining the crowded plots in Figs. 6a and 6b, which show individual curves for all males and all females, respectively.

Fig. 6a illustrates the effect of including PAT-protein in the diet of the male rats: Group 2 (green curves) received the small dose and Group 3 (red curves) received the large dose.

Three of the green curves (short-dashed, solid and dotted curves) display a small gradual rise with respect to the control curves (black curve for Group 1 and blue curve for Group 4).that were nearest on Day 1, although the latter two follow a normal slope after Day 9. The other two green curves (dash-dotted and long-dashed), however, show a distinct downward trend with respect to the control curves.

Amongst the red curves, only the solid-line curve maintains pace with the control groups. The uppermost (dotted) curve begins above any other curve on Day 1 but gradually falls to meet the highest of the control curves by Day 13. Similarly, the short-dashed curve drops progressively lower than the control curves that were nearest on Day1. From Day 9, the long-dashed curve declines with respect to the control groups. The dash-dotted curve is the lowest on Day 1 and drifts ever lower with respect to the control curves.

Fig. 6b is a similar set of curves for females. The colour scheme is the same as for Fig.6a.

In the green set, the dotted curve follows a normal pattern. The short-dashed curve rises at first with respect to the control curves, then attains a normal slope from Day 9. The solid curve displays a persistent decline with respect to the control groups, while the long-dashed curve begins its downward progression only at Day 9. The dash-dotted curve, while maintaining a normal slope after Day 9, falls below all the control curves.

In the red set, the short-dashed curve and the solid curve are normal. The long-dashed curve declines with respect to the control curves between Days 3 and 9, before settling to a normal slope. The dash-dotted curve has a downward trend with respect to the control curves after Day 9; and the dotted curve gradually falls below all other curves, although it attains a normal slope on Day 7.

Alternatively, the slopes may be examined in tabular form. Table 1 lists the slopes for individuals and also for averages within groups, between Days 1 and 13. For the males eating a small amount of PAT-protein (Group 2), average weight-gain per day was the same as that of control Group 4, although it was slightly less than that for control Group 1. For females in Group 2, the average was distinctly below that for the two control groups. For both males and females in Group 3, which consumed the large amount of PAT-protein, average weight-gain per day was distinctly lower than for either control group.

TABLE 1. Weight-gain (gm) per day, between Day 1 and Day 13

4.4 Re-examination of food consumption

Figs. 7a and 7b present the average food consumption per day for each of the four groups. Except for one of the line-styles and the introduction of colour, these curves are identical to those on pp. 37 and 38 of the study. Noteworthy in Fig. 7a, for males, is the steep increase in the food intake of Group 4, eating the high dose of PAT-protein, during the last stretch of the experiment. The peak at week 1.0 for this group, although not significant in itself, may become so in the light of Fig. 7b, which also displays an exaggerated peak at this date for females eating the PAT-protein. There, too, a rapid rise in food consumption is evident in the last interval of the study.

Since food consumption will naturally vary with the weight of an animal, the same data have been presented in terms of food consumed per gramme of body weight per day, in Figs. 4c, d on pp. 41, 42 of the study. Those curves produce the same features as were noted in the preceding pair of figures, and so they have not been reproduced here.

Although the table of contents of the study claims to present data on food consumption for individual animals on p.81 and relative food consumption (relative to body weight) on p. 85, these pages contain only repetitions of the data averaged over each group. Attempts have been made to obtain this information from both the Biotechnology Group of the Department of the Environment, Transport and Regions, and from Aventis; but both organisations say they do not have these data. It is possible that the data have never existed, because all the rats in any given group were housed together in one cage and the monitoring of individual feed intakes may not have been attempted.

4.5 Conclusions on the rat study

Detailed examination of the data does not bear out the stated conclusions of the study. No definitive conclusions can be drawn about weight gain or food consumption, because the numbers of individuals in the groups were too small and the study was terminated too soon. Nevertheless, there are indications that some animals may have been affected by the consumption of the PAT protein. The slow rates of gain in weight of several of the animals eating PAT-protein indicate that they are not thriving as well as the rats in the control groups. Unusual patterns in the average food intake of animals consuming PAT-protein also suggests that the diet does not suit them.

5. ANECDOTAL EVIDENCE ON ANIMALS’ RESPONSE TO GENETICALLY MODIFIED FEED

5.1 ‘When the Corn Hits the Fan’

American journalist Steven Sprinkel wrote an article with the above title in an ACRES, USA Special Report dated 19 September, 1999 (reproduced on the Natural Law Party Wessex website). The following excerpt is relevant to this section.

‘After four months of retrieving anecdotes from Kansas to Wisconsin, I think it’s high time to sample the producer community more thoroughly to see how many stories there are out there. About the hogs that wouldn’t eat the ration when the GMO crops were included. About the farmer who said “Well, if you want your cattle to go off their feed, just switch them out to a GMO silage.” About the farmer who said that his cattle broke through an old fence and ate down the non-GMO hybrids but wouldn’t touch the Round-up ready corn, and as a matter of fact “They had to walk through the GMOs to get to the Pioneer 3477 on the other side.” About the cattleman who saw the weight-gain of his cattle fall off when he switched over to GMO sources. About the organic farmer with a terrible deer problem on his soybeans, and when he drives out at night there are forty of them mowing down his tofu beans while across the road there isn’t one doe eating on the Round-up Readies. About the raccoons romping by the dozen in the organic corn, while down the road there isn’t one ear that’s been touched in the Bt fields. Even the mice will move on down the line if given an alternative to these “crops”. What is it that they know instinctively that most of us ignore?’

5.2 Other incidents of cattle refusing to eat Bt maize

Various scientists working actively with the farming community in the United States have reported difficulties with the feeding of GM maize to cattle. In April 2000, one of them (who has asked to remain anonymous) sent the following information.

There have been dozens of such reports over the last two years. Generally, the reports are concerned with Bt maize. Many farmers feed maize to their cattle just as it grows, without mixing in other feedstuffs. Typical reports are that the farmer buys a new shipment of maize, which his cattle either refuse to eat or eat with reduced consumption. Upon making enquiries, he discovers that the maize is a genetically modified variety. When he replaces it with a non-modified maize, the cattle start eating again.

6. CONCLUSIONS OF THIS REPORT

Experiments on chickens and on rats lead to the conclusion that at least some individuals do not gain weight as rapidly as they should when given a diet including genetically modified feed. Furthermore, there appear to be irregularities in the feeding habits of at least some animals given GM feed. In the experiment on chickens, twice as many deaths occurred amongst those fed the GM maize as amongst those fed non-GM maize.

A substantial amount of anecdotal evidence on both farm animals and wild animals indicates that they will not choose to eat genetically modified feed if given a choice; and, if choice is not available, they do not thrive on GM feed.

On the basis of the evidence available, there is therefore reason to be concerned that genetically modified feed may have adverse effects on human beings, as well. The manufacturer of a food supplement that caused the deaths of 37 people and the permanent disability of 1500 more has insisted that genetic modification of the source ingredient was responsible for the toxicity, which had never occurred previously, during the time a non-GM source was used.

Notes