2.8—Food Contains Lots of Novel RNAs
Many novel RNA molecules are present in our food and they don’t cause any harm.
Analysis of Peer-Reviewed Research:
RNA is a polymer that is known to be involved in a lot of important cellular processes. Every cell has numerous forms of RNA and they carry out transmission of messages from genes to the protein assembly machinery, together with production of proteins themselves. In recent years understanding of the wide range of biological roles of different types of RNA has expanded dramatically. It is now known that RNA molecules such as dsRNA have important roles in regulating the behavior of many many different genes, both in plants and in humans.
Genetic Roulette sees the possibility of new dsRNA molecules in transgenic plants as a potential hazard, but its attribution of risks to dsRNA are an example of biased risk analysis. Smith discusses potential RNA hazards in transgenic crops without making a comparative risk assessment of similar hazards that are already part of existing diets. He does not consider similar hazards posed by new dsRNA structures coming from radiation induced mutations or from DNA parasite movement, and neglects to mention the large amounts of dsRNA that we currently consume. Such RNA is abundant in soybean, corn, rice and other plants.
Smith cites two papers as evidence of the risks of dsRNA that are in reality good evidence of why dsRNA poses no threat to humans—we have probably evolved so as to not be influenced by the presence of dsRNA in our diets. Finally, Genetic Roulette ignores the reality of modern molecular science. Scientists know how to create dsRNA-encoding inserts when they are needed, and they know how to avoid including them in new genetic constructs when they are undesirable. Once again, Smith fails to get the facts and the basic science right.
1. RNA is regarded as safe to consume; humans eat as much as 1 gm/day. In speculating about the possible hazards of RNA molecules, Jeffrey Smith fails to mention that most forms of RNA are unstable and are relatively easily degraded. Enzymes that destroy RNA are found everywhere in the environment, in our saliva, and in our stomachs. RNA is quickly destroyed by digestive enzymes in the gut (Carver, Walker 1995, Park and others 2006).
2. Plants, and consequently human and animal diets, contain large amounts of dsRNA molecules yet no adverse effect has ever been associated with dsRNA consumption in animals or humans. Nowhere in Genetic Roulette’s discussion of possible hazards of novel RNA molecules does he mention that we are continually exposed to novel forms of RNA in our food. It is estimated more than 10 percent of the RNA we consume is dsRNA—much of it has structure that corresponds exactly to structures of human genes, yet no ill effects have been observed (Carver, and Walker 1995, Ivashuta and others 2008, Lewin 2008).
3. What is true for worms is not necessarily true for mice and men. Smith cites papers that show that when a very primitive worm, C. elegans, is bathed in a solution of dsRNA, or in other cases fed bacteria contain dsRNA, dsRNA spreads through the worm’s simple body. This RNA spreading phenomenon is confined to some insects, worms and plants. The method has been has been repeatedly tried in higher animals and it does not occur. In fact, while there has been great hope for useful uses of dsRNA in medical therapy, the major problem has been that dsRNA does not spread through mammalian tissues, and it has proven essentially impossible to administer (see Wang and Barr 2005 May and Plasterk 2005).
4. Smith cites a paper in which dsRNA is administered to mice inside a pathogenic E. coli bacterium—this paper actually helps prove that dietary dsRNA poses no threat to human health. The experimenters (Xiang and others 2001) were trying to devise a way to deliver dsRNA into mammalian cells in order to overcome the barrier to oral delivery of dsRNA pharmaceuticals. They placed genes that encoded dsRNA molecules into a pathogenic E. coli bacterium. They knew the bacteria would invade gastrointestinal cells of the mice and deliver the dsRNA to those cells. The experiment was a success, but what it shows is that it takes a purposely-constructed pathogenic bacterium that does not occur in the wild to act as a Trojan Horse to deliver dsRNA to mammalian cells. To claim that this paper means dsRNA can get into our body is to have not read the paper, or to be willing to misrepresent it.
5. In bacteria, regulation of genes by RNA occurs differently to how it happens in humans and other higher organisms. This section of Genetic Roulette asserts that “Silencing instigated by dsRNA occurs in organisms of all biological kingdoms”. The context in Genetic Roulette creates the misleading impression that the RNA interference mechanisms used by bacteria are the same as in humans, when they are not. Indeed, one of the references he cites (Tchurikov and others 2000) explicitly says that RNA interference was not found in bacteria. Smith is confused about two distinct types of RNA regulation—antisense RNA in bacteria (eg Altuvia and Wagner 2000) versus RNA interference that is confined to eukaryotic organisms.
6. Genetic Roulette overlooks the fact that researchers can easily avoid using sequences that would create new dsRNA molecules. Smith fails to cite the literature that describes the basic structure of dsRNA and the methods that can be used to insert dsRNAs in cells. Scientists have created dsRNA insertions and using them have turned off specific genes in plants. Our rational understanding of dsRNA-forming structures allows us to not use genes or sequences of DNA that would form unwanted dsRNA molecules. The state of the art is that dsRNAs can be created if wanted or avoided if not wanted in a new GM plant.
Altuvia S and Wagner EGH (2000) Commentary: Switching on and off with RNA. Proceedings of the National Academy of Sciences of the United States of America 97(18):9824–9826
Carver J, and Walker WA (1995). The role of nucleotides in human nutrition. The Journal of Nutritional Biochemistry 6: 58-72. Information on RNA in food and its digestion.
Citizendium. RNA interference encyclopedia article. en.citizendium.org/wiki/RNA_interference accessed Dec 19 2008.
Ivashuta SI and others (2008). Endogenous small RNAs in grain: semi-quantification and sequence homology to human and animal genes. Food and Chemical Toxicology (2008), doi: 10.1016/j.fct.2008.11.025 . This paper is relevant to understanding speculated hazards of RNA molecules being present in foods. Similar RNAs are present both in maize and human cells.
Lewis BP, Burge CB, Bartel DP (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120:15-20.
Lewin B (2008). Genes VIII. Jones and Bartlett. www.ergito.com/
May RC and Plasterk RHA (2005). RNA interference spreading in C. elegans. Methods in Enzymology 392:308-315
Park NJ and others (2006). Characterization of RNA in saliva. Clinical Chemistry the 52:988-994. RNA is degraded in saliva.
Tabara, H., Grishok, A., Mello, C.C., 1998. RNAi in C. elegans: soaking in the genome sequence. Science 282:430-431.
Tchurikov NA (2000) Gene-specific silencing by expression of parallel complimentary RNA in Escherichia coli. Journal of Biological Chemistry 275(34)26523-26529.
Wang F and Barr MM (2005). RNA interference in Caenorhabditis elegans. Methods in Enzymology 392:36-55.
Xiang S and others (2001). Short hairpin RNA–expressing bacteria elicit RNA interference in mammals. Nature Biotechnology 26(6):697-702.
Novel RNA may be harmful to humans and their offspring
1. Small RNA sequences can regulate gene expression, most commonly by silencing genes.
2. RNA is stable, survives digestion and, can impact gene expression in mammals that ingest it.
3. The impact can be passed on to future generations.
4. Genetic modification introduces new DNA combinations and mutations, which increased the likelihood that harmful regulatory RNA will be accidentally produced.
Genetic Roulette speculates that novel double stranded RNA (dsRNA) molecules created by genetic engineering may be harmful.