W. Müller, EFSA

Transcription

1 W. Müller, EFSA European Food SCANDAL Authority

2 Legal Requirements Assessing long- term effects EC Reg. 1829/2003 Assessing delayed effects and indirect effects in conjunction with 178/2002 Article 14 Directive 2001/18/EC Annex II Assessing cumulative long term effects on human health, soil fertiliy, flora fauna Description of uncertainties e.g. assumptions made in the risk assessment, and of the known limits of mitigation measures Directive 2001/18/EC Annex II EC Decision 2002/623

3 Crop approved (2001/18/EC) Ms8 x Rf3 (2005) Bt 11 cult. (2005) 1507 culti. (2005) Mon 863 (2004) GT 73 (2004) NK 603 (2003) Test no toxicol. test no toxicol. test 90 days subchronic 90 days subchronic no toxicol. test 90 days subchronic GMO are approved without any chronic GMO are approved without any chronic toxicol. test = long term = 720 days study

4 Tests on Pesticides vs GMOs Assessing long- term effects chronic tox. study (720 days) Assessing effects on subsequent generations Assessing cumulative toxic effects Description of uncertainties e.g.assumptions made in the risk assessment, and of the known limits of mitigation measures Pesticide yes yes no no GMO no no no no

5 EFSA methods Method Comment Comparative chemical No scientific basis of how to translate analyses of protein, amino results into human toxicity acid content, ash content assessment etc. Sequence Analyses Almost identical sequences can show differences in function monkey/human 28 days study with the DNA protein Short term toxic studies are useless, and must be avoided from terms of animal rights Comparative 90 day study Subchronic study, not able to with rats ( NK603 and extrapolate to chronic effects 5 Mon863 but not in GT73) (cancergogenicity, immuno toxicity)

6 EFSA vocabulary on observed statistically significant differences between GM and control phrases 1. Altered level of linolenic acid is considered as not biologically significant, ifi greater differences between GT73 and Westar but without statistical analyses 1. no consistent differences, 2. no biological significance, 3. artifactual differences of corbuscular haemoglobin values (90 days feeding study) 4. No conclusive differences of chemical constituents source Rape GT 73 (Monsanto) EFSA Journal 2004, 29:1-19 Maize NK 603 (Monsanto) EFSA Journal 2003, 9:1-14 6

7 EFSA Up to now ALL observed differences between GM and Non-GM variety had been tolerated by EFSA. No argumentation to what extent observed differences are generally tolerated is provided. The question remains why these parameters are tested when statistically significant differences are not of biological relevance. 7

8 Wording of Monsanto and EFSA e.g. NK603 Data interpretation of observed differences found in the subchronic 90 days toxicity study safety claims of CP4 EPSPS-Protein Judgement by Monsanto absence of biologically relevant differences the long history of safe consumption of similar proteins Judgement by EFSA The applicant concludes that these findings are of no biological significance. The panel accepts this as a reasonable interpretation of the data. humans have a long history of dietary exposure to the protein. No adverse effects associated with its intake have been identified. 8

9 Is it sound science to say GMOs are safe? No!

10 What do we know what we don t know 10

11 synthetic gene new for humans Maize DNA P-35S Mon810 maize- YieldGard TM (Monsanto) hsp70 intron CryIA(b) T-nos Virus maize Bt-Bacteria a - Soil- truncated Bacteria Synthetic genes are man made genes and do not exist in any natural living species on the planet 11

12 GC content, cryptic splice sites, premature poly(a) sites, AT rich killer sequences, RNA secondary structures, often makes it necessary to adapt and optimize the gene of interest towards the genetic requirements of the host organism. Apparently, e t an optimized sequence does not occur in nature and has to be designed on a rational basis followed by in vitro synthesis. GENEART offers both steps: state-of-the-art gene optimization plus fast and reliable de novo gene synthesis.

13 Partikel Gun Gene Gun 1 of 1000 sucessful integration Grafik: BioLinX GmbH

14 synthetic genes cause unintended recombinations CHARACTERISATION OF COMMERCIAL GMO INSERTS: A SOURCE OF USEFUL MATERIAL TO STUDY GENOME FLUIDITY. Sequence expected (public data) T25 maize - Libertylink TM (Bayer) Tolerance to herbicide glufosinate, Peg-mediated transformation Construct content : truncated bla gene (bla*), puc cloning vector (puc), synthetic pat gene (pat), CaMV 35S promotor and terminator (P35S, T35S). bla* puc18 P35S pat T35S Sequence observed P35S* puc18 P35S pat T35S puc18 bla* bla* Maize DNA (Presence of cloning vector + the 5 first bp of bla on the 3 end ) DNA rearrangement: presence of a second truncated and rearranged P35S on the 5 end. Insertion site: the 5 and 3 ends of the insert show homologies with Huck retrotransposons. (Collonnier et al. (2003) Eur. Food Res. Tech. (submitted)) Mon810 maize- TM Resistance YieldGard to lepidopteran (Monsanto) insects, Bombardment Construct content : CaMV 35S promotor (P35S), CryIA(b) toxin synthetic gene (CryIA(b)), nos terminator (T-nos). Sequence expected Sequence observed P-35S hsp70 intron CryIA(b) T-nos P-35S hsp70 intron Truncated CryIA(b) Maize DNA Maize DNA DNA rearrangement: dlti deletion of T-nos in the insert (but Tnos dt detected tdin the genome) and dlti deletion of apart of CryIA(b). (Hernandez et al. (2003) Transgenic Res. 12: ; Holck et al. (2002) Eur. Food Res. Tech. 214: ) Insertion site: the 5 end of the insert shows homology with LTR sequences of the Z. mays alpha Zein gene cluster. No homology between LTR sequences and the 3 end: rearrangement of the integration site. 14

15 Gold in the gene-desert (junk DNA) Science (2003) 302:41 Non-coding genes/(rna genes) 15

16 Eric Neumann, vice president of bioinformatics at Beyond Genomics We really have a poor understanding of what a gene actually does and where and when it should do it. You can understand the entire genome and [still] understand less than 1 percent about what is going on in a cell." DODGE J (2003) Data glut. The Boston Globe 16

17 Food-DNA pieces of rubisco gene had been detected in lymphocytes, blood, liver, spleen, kidney, muscles and milk 17

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19 Synthetic DNA IN BLOOD AND TISSUES Mazza R, Soave M, Morlacchini M, Piva G, Marocco A (2005) Assessing the transfer of genetically modified DNA from feed to animal tissues. Transgenic Research 14: Sharma R, Damgaard D, Alexander TW, Dugan ME, Aalhus JL, Stanford K, McAllister TA Detection of transgenic and endogenous plant DNA in digesta and tissues of sheep and pigs fed Roundup Ready canola meal. J Agric Food Chem Mar 8;54(5):

20 Several receptors for foreign DNA/RNA 20

21 Food-DNA pieces interact directly with the immune system The protective effects of probiotics are mediated by their own DNA rather than by their metabolites or ability to colonize the colon Rachmilewitz et al: Gastroenterology 2004 Feb;126(2):

22 transgenic pea causes allergenic reactions

23 PRSCOTT V 2005 T i E i f B A l PRSCOTT V 2005: Transgenic Expression of Bean r-amylase Inhibitor in Peas Results in Altered Structure and Immunogenicity: J. Agric. Food Chem. 2005, 53,

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25 With methods used by EFSA this transgenic pea would have been approved save. So far all GMO applications has been approved save by EFSA.

26 short list of effects of GMO from studies of the biotech industry von Kurzzeit-Studien ignored by EFSA effects90 days study 1. increase counts lymphocytes, differences in kidney cells 2. differences of blood parameters (artifactual differences of corbuscular haemoglobin values) % increased liver weights source Mais Mon 863 (Monsanto), EFSA Journal 2004, 50:1-25 Mais NK 603 (Monsanto), EFSA Journal 2003, 50:1-25 Raps GT 73 (Monsanto), EFSA Journal 2003, 50: changes of liver, kidney and blood parameters Mais 1507 (Bayer) EFSA Journal 2004, 124:1-18

27 While the duty of preventing damage to the environment is based on a known risk, the notion of precaution is based on lack of certainty. (OECD 2001) as a consequence of the lack of long-term tests and major uncertainties in the risk assessement of GMOs the approval of GMOs is not in line with the precautionary principle as outlined in Directive2001/18 and Regulation 1829/

28 Summary We eat synthetic genes We know almost nothing about genes und junk genes Pieces of food-dna are found in various organs Food-DNA interacts t with the immune system Transgenic crops are badly tested

29 Why we are forced to eat GM food? EFSA pushes for GMOs instead of scientific evaluation

30 Solution? Change the approval system don t allow EFSA to play a decisive role in the approval system