The previous post mentioned an Austrian study of mice fed GM maize in which variations in rodent reproductive rates were noted.
The full study is here:
The author's summary is:
Biological effects of transgenic maize NK603xMON810 fed in long term reproduction studies in mice
Dr. A. Velimirov, Dr. C. Binter , Univ. Prof. Dr. J. Zentek
The aim of the study was to examine effects of the stacked GM crop NK603 x MON810 in different models of long term feeding studies. So far no negative effects of GM corn varieties have been reported in peer-reviewed publications. But the hypothesis, that effects after long term exposure might become evident in multi-generation studies has rarely been investigated.
In this study three designs were used, including a multi-generation study (MGS), a reproductive assessment by continuous breeding (RACB) and a life-term feeding study (LTS), all performed with laboratory mice (strain OF1). The test diets differed only as to the inclusion of 33% NK603 x MON810 corn (GM) versus non-GM corn of a near isogenic line (ISO), both grown under identical conditions in Canada. The MGS also included one group with a non GM corn cultivated in Austria (A REF). All corn varieties used in the MGS and LTS were harvested in 2005, the transgenic and isogenic corn for the RACB were harvested in Canada in 2007. No Austrian corn was used in this case. In the MGS microscopic and ultrastructural investigations were performed to detect changes at the organ and cell level. Gene expression patterns were compared by micro array expression profiles of the intestine as feed-animal interface and by real time PCR.
The results of the MGS showed no statistically significant differences concerning parental body mass. The number of females without litters decreased with time in the GM and ISO group, especially in the 4th generation. In the group fed with A REF corn fewer females were without litters, and accordingly more pups were weaned. The production parameters average litter size and weight as well as number of weaned pups were in favour of the ISO group. These differences were also seen in the RACB design and were statistically significant in the 3rd and 4th litters. In addition, the inter-individual variability was higher in the GM group as compared to the other groups. The LTS showed no statistically significant differences in the survival of 3 groups of mice fed the different maize varieties.
In the MGS the continuative investigations revealed differences between the GM and ISO groups. The comparison of organ weights did not indicate directed dietary effects, except for kidneys. The electron histological investigation of the cell nuclei revealed differences as to fibrillar centres, dense fibrillar components and the pore density in hepatocytes, and cells from spleen and pancreas. This could point to an effect of the GM crop on metabolic parameters. Immunohistochemistry revealed no systematic differences in CD3, CD20 positive cells and macrophages in gut tissue. The microarrays showed differences between the feeding groups. When the data of both non-GM feeding groups from MGS were combined and compared to the GM feeding group, the discrimination became more evident. Analyses of metabolic pathways indicated, that the groups differed regarding some important pathways, including interleukin signalling pathway, cholesterol biosynthesis and protein metabolism.
Summarizing the findings of this study it can be concluded, that multi-generation studies, especially based on the RACB design are well suited to reveal differences between feeds. The RACB trial showed time related negative reproductive effects of the GM maize under the given experimental conditions. The RACB trial with its specific design with the repeated use of the parental generation is a demanding biological factor for the maternal organism. Compared to the findings in the RACB trials it can be assumed that the physiological stress was considerably lower in the MGS trial. The trial design of using “new” parental generations instead of continuous breeding with the same generation has to be considered as being obviously less demanding. This might have masked the impact of dietary factors on reproductive performance. However, this part of the experiment is valuable as such because it underlines the need for different experimental designs for the assessment of dietary effects that have an unknown impact on animals. The outcome of this study suggests that future studies on the safety of GM feed and food should include reproduction studies. Physiological and genomic traits and depending on the nature of the genetic modification proteomic and metabolomic methods might be taken into consideration as additional tools to the tests performed in this study.
The full Austrian report does not provide a full and transparent description of analysis of variance. Readers are advised to consider statistical caveats associated with multiple statistical comparisons, for instance as indicated in a later Pundit post here.
Nov 20, 2008
The Monsanto company has issued a technical response to the Austrian press releases.
It picks up on several significant errors in the Austrian report.
Nov 23, 2008
The Pundit comments on the curious incident of silence about mistreated mice
Dec 4, 2008 EFSA responds
Request from the European Commission related to the safeguard clause invoked by Austria on maize MON810 and T25 according to Article 23 of Directive 2001/18/EC Question number: EFSA-Q-2008-314
Adopted date: 4 December 2008
On 10 June 1999 and on 8 May 2000, Austria invoked Article 16 of Directive 90/220/EEC (safeguard clause) to provisionally prohibit the placing on the market of the authorised genetically modified (GM) maize events MON810 and T25 on its territory. In February 2004 and November 2007, Austria provided additional information to support the national safeguard measure to be considered under Article 23 of Directive 2001/18/EC. To define whether the information submitted by Austria comprises new information that would affect the environmental risk assessment for the uses laid down in the corresponding consent, the European Commission requested in a letter, dated 18 April 2008, a scientific opinion from the European Food Safety Authority (EFSA).Following investigation of the evidence presented in the Austrian submission, the Scientific Panel on Genetically Modified Organisms (GMO Panel) of EFSA concludes that there is no new scientific evidence that would invalidate the previous risk assessments of maize MON810 and T25. Therefore, no specific scientific evidence, in terms of risk to human and animal health and the environment, was provided that would justify the invocation of a safeguard clause under Article 23 of Directive 2001/18/EC for the marketing of maize MON810 and T25, for its intended uses, in Austria.
Details of critical comments by EFSA
Adopted part of the minutes1 of the 46th plenary meeting of the Scientific Panel on Genetically Modified Organisms held on 3-4 December 2008
GMO Panel deliberations on the Austrian report "Biological effects of transgenic maize NK603
x MON 810 fed in long term reproduction studies in mice" as adopted at the plenary meeting of
3-4 December 2008.
On 11 November 2008 the Austrian Federal Ministry of Health, Family and Youth released a research report on studies in mice, which were conducted to assess the impact of genetically modified (GM) maize NK603 x MON 810 on reproduction (Biological effects of transgenic maize NK603 x MON 810 fed in long term reproduction studies in mice, Dr. Alberta Velimirov, Dr. Claudia Binter, Univ. Prof. Dr. Jürgen Zentek).
The report includes three studies, a life-time study, a multigeneration study (MGS), and a reproductive assessment by continuous breeding study (RACB). According to the authors the life-time study showed no statistically significant differences in survival between mice fed with kernels of maize NK603 x MON 810 and the controls. They also reported that, in the MGS study, no significant differences in reproductive traits were found between mice fed with kernels of maize NK603 x MON 810 and the controls. In the RACB study, the authors used a modified protocol of the original RACB study developed at the U.S. National Toxicology Program (NTP) for the testing of chemicals. Male and female mice were housed as breeding pairs for approximately 20 weeks and allowed to produce litters continuously throughout the cohabitation period. The authors identified differences in reproductive parameters between mice fed with the GM maize and the controls. They reported that there were statistically significantly fewer pups born in the GM group in the 3rd and 4th delivery and fewer pups weaned in the 4th litter compared with the control group.
The GMO Panel considered this report and came to the following conclusions.
Regarding the RACB study, the summary Table 59 contains calculation errors and inconsistencies in the treatment of the data regarding the 3rd and 4th litters. In addition, it seems that the authors have calculated the number of pups at birth per pair and not per delivering pair, which is standard practice.
Also, there appears to be methodological deficiencies in the statistical analysis that seriously
compromise the interpretation of the data. For the reasons stated above, individual data are required for a proper assessment. In addition, more detailed information regarding the breeding scheme is needed. In particular, it should be clarified whether in the 3rd and 4th pairing the same or different pairs failed to reproduce.
Information regarding the normal variation of the parameters examined in this study for the mouse strain used (historical control data) is required before any conclusion may be drawn on possible alterations in reproductive performance. In addition, further information on the estrous cycle and histopathological parameters including spermatogenesis, follicle and oocyte counts is essential for assessing the claims of reduced fertility.
The GMO Panel also notes that information on the genetic identity and characteristics of the tested materials is not sufficient.
On the basis of the data presented the GMO Panel is of the opinion that no conclusions can be drawn from the report.
1 Published at http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211902199319.htm. The complete minutes
will be adopted at the 47th plenary meeting (28-29 January 2009) and will be published shortly afterwards.