By Alma Laney and Alison Bernstein
This article is the sixth and final article in a series on transgenerational inheritance, epigenetics, and glyphosate that addresses questions raised by the publication of the article, Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology.
Do the reported results support the authors’ conclusions?
In the conclusions section of the article, the authors had this to say:
Glyphosate exposure of the F0 and F1 generations had negligible toxicity and pathology, which supports low-risk direct exposure, however, germline-mediated transgenerational inheritance promotes significant pathology and disease.
Unfortunately for the authors, it is difficult to draw these conclusions from the data presented. Experimental design issues may have doomed the experiment before it began. This may be more of a misreporting issue and the experimental design may actually be good – we just can’t tell by looking at this article.
Even if the experimental design is indeed appropriate, the other problems we have described make it very difficult to conclude that the observed pathology is the result of glyphosate-induced transgenerational epigenetic inheritance and not some other effect of confusion independent of glyphosate. As to whether this is relevant to humans and real-world exposures, the dose is clearly too high to have any real relevance to real-world scenarios.
Reports from both “sides” did not accurately explain this study
Quite predictably, reports of this study range from citing this study as positive evidence that glyphosate is dangerous and should be phased out of use altogether, such as recent Moms Across America posts, to knee-jerk reaction from the skeptical community with invalid criticisms of the problems with the study and the complete rejection of the idea of epigenetic inheritance.
The question of how epigenetic changes are inherited from one generation to the next is complicated and very unclear at this point. Even with one of us (Alison) working in developmental neurotoxicity and epigenetics, it took a long time to dig deep into the methods and results to understand what was going on here.
Alma’s experience with this article is instructive and a useful reflection on the importance of recognizing the limits of our expertise.
I myself fell into this trap despite my training including courses in epigenetics, even though it was epigenetics in microbes, which is different from what happens in plants and animals. When I first read the study, I too noted the Venn diagram and how there were no shared epigenetic changes between the three generations and thought I had identified a critical error. Inherited changes should be inherited, right?
While discussing this article with Alison, I quickly realized how little I knew about how epigenetics works in mammals. I then started reading quite a few articles on epigenetic inheritance. I was so out of my area of expertise that I had to spend almost as much time researching definitions and asking Alison questions as I did reading the articles and reviews she suggested. In all of this, I’ve barely scratched the surface to wonder if I’d even be able to address an article like this.
I could see that there were issues with the experiment, but what I was able to identify were issues with statistical analysis and removal of control groups. But these problems were just the tip of the iceberg. Simply put, despite my high level of education, I was not an expert on this subject. Alison, on the other hand, looks into epigenetics and epigenetic inheritance in her research. She is quite qualified as an expert on this subject.
If it were me writing this article alone, you would just have a short article on statistics and control groups rather than the much more in-depth analysis we have presented. Expertise matters. There is no way around this. With studies like the one we’ve covered here, having an expert to break down what it actually means is extremely important. If even scientists in the field may have questions about a study like this, how can we expect journalists and even scientists in other fields to do a better job of reporting the results?
A study like the one we discuss here shows why expertise is so important. Even people with expertise and training in other fields can have difficulty interpreting a study like this, especially when the methods are not clearly stated in the article, as was the case here. If people with extensive training can easily misinterpret this type of study, chances are the report will also misinterpret the study.
Should we think about grandchildren?
This question is important. Are we able to show that there is a concern based on the data presented in this article? Unfortunately, methodological and reporting issues make it nearly impossible to draw conclusions about whether transgenerational inheritance is occurring or whether it is epigenetically mediated. Additionally, the chosen dose is largely unrelated to actual human exposure levels and the method of introducing this dose is not a way people would normally be exposed to glyphosate. This makes it really hard to say that normal levels and routes of exposure would cause harm.
A study with more precise methods and analyzes would be necessary to determine whether the results of this study are realistic or not. But even if we took the results at face value and uncritically accepted the authors’ conclusions, that wouldn’t necessarily mean we should worry about poisoning future generations.
Transgenerational effects are, by nature, reversible and modifiable. So, as an individual living in a world of complex exposures (both protective and risk factors), when considering the entire risk landscape, the behaviors and exposures that mitigate risk will further mitigate the risks of past and future exposures to current and future generations.
See the other parts of our series on transgenerational epigenetic inheritance: