In the latest twist in the recent scientific discussion over whether double stranded RNA from plants in our diet can interfere with genetic expression once they’ve been consumed, a new study in primates has failed to find supporting evidence for the claim, potentially undermining arguments that genetically modified plants that produce these molecules may pose a risk to food safety.
The new research attempted to replicate findings from a key study (Zhang et al 2012) which appeared to have identified plant microRNAs circulating in the blood and tissues of mice fed a rice-based diet. In this follow up study, researchers searched for soy-derived plant microRNAs in macaque monkeys fed a diet of soy smoothies.
After several different approaches failed to find supporting evidence, the authors were forced to conclude that dietary plant sources are unlikely to be significant contributors to this type of gene regulation, and that the original study was most probably flawed.
“It’s disappointing in a sense — it would open up so many therapeutic possibilities if microRNAs from food really could get into our blood and regulate our genes,” says lead author of the study, Dr Kenneth Witwer of Johns Hopkins University School of Medicine (via Science Daily).
For further background on microRNA, dsRNA and RNA interference, see here and here. See also this compelling animation illustrating the process.
The Science Media Centre has rounded up the following commentary on the new study:
Associate Professor Peter K. Dearden, Director of Genetics Otago, Gravida Executive Team, University of Otago comments:
“This new paper on the subject of plant double stranded RNA is a very careful examination of whether such RNA can be picked up by primates from their diet, potentially regulating genes. This idea was first put forward, with some experimental evidence, in 2012 by Zhang et al and has been raised as a concern for genetically modified plants that express double stranded RNA.
“The new study very carefully assesses if, and how much, plant derived microRNA (miRNA) can be found in serum from primates fed a plant-derived miRNA-rich diet. The authors very clearly show that the amounts of such miRNA found in serum are very very low, if detectable at all. The techniques used are incredibly sensitive, and the work is very carefully presented. The data suggests to me that any such double stranded RNAs are beyond the limit of detection, and thus, because these techniques are very sensitive, unlikely to be present at all.
“The paper is very clear at pointing out the limitations of these experiments, especially as they are carried out with only two non-human primate individuals. It is fair to say that this work will need to be repeated to be confirmed, not because of any issue with the methods used, but just that a small number of individuals are involved.
“Science, especially at the cutting edge, often goes this way. Bold claims are made that are then dialled back as more experiments are performed. The claim that double stranded RNA from plants might regulate human genes is a very interesting one, but as the science advances I think we are getting the picture that this is very rare, if it occurs at all, and that double stranded RNA from diet is unlikely to have a major influence on the regulation of our genes.”
Prof Jack Heinemann, School of Biological Sciences, University of Canterbury, comments:
“This study is a welcome contribution to the field of dietary dsRNAs, but as a ‘pilot study’ should not be over-interpreted.
“These data increase confidence that unintended effects from novel dsRNAs in food may be unlikely or rare. Rare effects, or effects that would be rare because they manifest in a small number of people, nevertheless may be important. The authors also state that their work does not exclude important physiological effects at low concentrations of dietary dsRNA.
“The paper does not specifically address environmental risk assessment for which there is already overwhelming evidence that dsRNAs transmit through food (and other means) to invertebrates.
“Importantly, this is the third paper in just over a year to detect dietary dsRNAs. The concentration of dietary dsRNA was at the detection limit, creating uncertainty about how common they are. Therefore the authors encourage more studies. That should be concerning to regulators who for years just assumed that dsRNAs could not survive digestion. The new work further justifies calls for testing of novel foods to confirm the safety of dsRNA molecules of new sequence composition.
“These authors report poor reproducibility of detection and infer low levels of dsRNAs, and we should expect dietary dsRNAs to be at low levels. The paper does not address relevant risk assessment issues such as: What concentration of dsRNA in blood (or other tissues) matters? What exposure routes (diet, inhalation, contact) matter most? The authors used different animals and food sources than other investigators, the study had only 2 animals, and only a very small number (5) of potential dsRNAs were targeted, so they have not countered earlier work showing physiological effects of dietary dsRNAs.
“Until future work can definitively exclude exposure to dietary dsRNAs, potential unintended effects of novel dsRNA should be the subject of specific biological testing and the results reported to food safety regulators for evaluation. Regulators should consider that evidence on a case-by-case basis until there is a mature body of science establishing the generic safety of dsRNA molecules in our diets.”