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Moderated conference on GMOs in the pipeline, hosted by the FAO Biotechnology Forum in 2012

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Mon, 3 Dec 2012 18:47:18 +0100
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This is Wayne Parrott again. For the past few years, we have been looking at some of the issues that Aruna Rodrigues brought up in message 65, as they deserve answers. The latest result should be in the December issue of Plant Physiology, and it addresses the issues of changes in proteins or DNA alterations.



The whole premise behind safety assessment is that if two things are identical, one cannot be said to be safe, and the other unsafe. Thus if there is any safety issue, it must be associated with a difference. Thus, we first look for categorical differences between transgenics and non-transgenics, as such differences are where novel safety issues would be.



1) Differences in identity: 

There is a report (Tenaillon et al., 2001) that compares amino acid (aa) substitution in the same proteins from different types of maize. Genes 300-400 aa long *normally* differ by some 15-20 aa's. The difference is even greater if the same protein is compared across different species. Importantly, none of these proteins has acquired toxic or other hazardous traits because of aa substitutions. The reason is that toxins require greater structural differences than are achieved by aa substitutions (Pariza & Cook, 2010). Thus, we cannot see aa substitution as a risk. 



2) Presence of multiple inserts or vector DNA:  

There are rice varieties where every individual can have 50-60 new transposon insertions per plant per generation, without safety issues (Naito et al. 2006). No two plants have the exact same inserts in the same places. Why would T-DNA be different? There are lots of other examples of DNA that moves around in the plant, and never with a negative consequence (e.g., Lough et al, 2008; Huang et al, 2004; Staginnus & Richert-Poggeler, 2006; Cohen et al, 2008). Thus we cannot see inserts or additional DNA as being hazards per se.



3) Old/outdated construct:   

Should not be interpreted to mean unsafe or ineffective. For those who are still not convinced of the safety of Bt, an older construct does have the advantage of having far more data of its safety in the field and in various crops than "newer" constructs have.



4) Novel RNA:    

I want to point out that Codex standards are not cast in stone. Accordingly, I want to note the difference between "should be" and "must be" provided. Furthermore, Codex (2003) is a *recommended* Guideline for safety testing, not hard and fast rules. Flexibility is needed in safety assessment; after all science moves faster than law, particularly international law. In the case of RNA, I do not see that one more RNA molecule among the many thousand present in a cell can pose a hazard. Has there ever been any risk associated with longer mRNA molecules in a plant? If so, please let us know. [I provided references/links to the outcome of the Codex Alimentarius Commission's work on principles and guidelines for food safety assessment of foods derived from modern biotechnology at the end of Message 65. The Codex Alimentarius Commission, established by FAO and WHO in 1963, develops harmonised international food standards, guidelines and codes of practice to protect the health of the consumers and ensure fair trade practices in the food trade. It also promotes coordination of all food standards work undertaken by international governmental and non-governmental organizations...Moderator].



Granted, there was a report of rice-derived RNA altering liver function in mice. This report has yet to be repeated, but assuming it is repeated, note the mice had to eat 1/3 of their body weight in dry rice each day to get the effect. If humans also suffered from this effect, we would see far greater amounts of high cholesterol across rice-consuming areas of the world than we do.



Even if the new RNA would result in a fusion protein, it turns out that fusion proteins turn out to be rather common in plants as well. It is not possible to say every fusion protein is automatically safe, which is where compositional analysis comes in. If said fusion protein would reach toxic levels, its presence would be inferred by changes in the relative amounts of other compounds.



In the end, proper safety assessment must be both judicious and based on biologically possible hypotheses. A lot of the concerns about GMOs come from the state of knowledge from a few decades ago. The premise from a few decades ago that insertion of DNA could reactivate dormant pathways for toxic compounds simply has not held up to scrutiny. Many of those concerns have been found to be without a biological basis. Today, those concerns without a plausible and testable biological basis simply serve to block technology and raise costs, while not increasing safety at all.



Wayne Parrott

Department of Crop and Soil Sciences,

University of Georgia,

Athens, GA 30602

United States

wparrott (at) uga.edu



References:



- Tenaillon, M.I., M.C. Sawkins, A.D. Long, R.L. Gaut, J.F. Doebley and B.S. Gaut. 2001. Patterns of DNA sequence polymorphism along chromosome 1 of maize (Zea mays ssp. mays L.). Proc. Natl. Acad. Sci. USA, 98 (16) 9161-9166



- Pariza M.W., Cook M. 2010 Determining the safety of enzymes used in animal feed. Reg Toxicol Pharmacol 56: 332–342



- Naito, K., E. Cho, G. Yang, M.A. Campbell, K. Yano, Y. Okumoto, T. Tanisaka and S.R. Wessler. 2006. Eukaryotic Transposable Elements and Genome Evolution Special Feature: Dramatic amplification of a rice transposable element during recent domestication. Proc. Natl. Acad. Sci. USA, 103 (47) 17620-17625.



- Lough AN, Roark LM, Kato A, Ream TS, Lamb JC, et al. 2008. Mitochondrial DNA transfer to the nucleus generates extensive insertion site variation in maize. Genetics 178:47–55 (2008)



- Huang, C.Y., M.A. Ayliffe and J.N. Timmis. 2004. Simple and complex nuclear loci created by newly transferred chloroplast DNA in tobacco. Proc. Natl. Acad. Sci. USA, 101 (26) 9710-9715



- Staginnus, C. and K.R. Richert-Pöggeler. 2006. Endogenous pararetroviruses: two-faced travelers in the plant genome. Trends in Plant Science, 11, Issue 10, pp. 485-491



- Cohen S, Houben A, Segal D. 2008. Extrachromosomal circular DNA derived from tandemly repeated genomic sequences in plants. Plant J, 53(6):1027-34



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