New Revolutionary Findings from Pesticide Toxicology Studies - Lessons Have Got To be Applied for Biorisk Assessments Throughout the Biotech Sector

A call to appreciate and apply the insights by Gilles-Eric Seralini

Earlier this year, Professor Gilles-Eric Seralini published a notable paper in Toxics. As part of the Special Issue Pesticides in Formulations: Toxicological and Regulatory Assessments, New Developments, the paper motivates this special issue and reveals some revolutionary findings.

Seralini and collaborators have long exposed serious gaps in toxicity studies and evaluations and have also exposed serious forms of scientific and regulatory misconduct and fraud. A hero for his successful court cases against Monsanto and others, he has been standing up for truth for many years but has been vehemently attacked and defamed. See, for example, the USRTK section on the Monsanto Papers (search for Seralini) and the ENSSER statement on the Retraction of the Séralini et al. 2012 Study:

“Journal’s retraction of rat feeding paper is a travesty of science and looks like a bow to industry

“29.11.2013 – Elsevier’s journal Food and Chemical Toxicology has retracted the paper by Prof. Gilles-Eric Séralini’s group which found severe toxic effects (including liver congestions and necrosis and kidney nephropathies), increased tumor rates and higher mortality in rats fed Monsanto’s genetically modified NK603 maize and/or the associated herbicide Roundup[1]. The arguments of the journal’s editor for the retraction, however, violate not only the criteria for retraction to which the journal itself subscribes, but any standards of good science. Worse, the names of the reviewers who came to the conclusion that the paper should be retracted, have not been published. Since the retraction is a wish of many people with links to the GM industry, the suspicion arises that it is a bow of science to industry. ENSSER points out, therefore, that this retraction is a severe blow to the credibility and independence of science, indeed a travesty of science....”

His recent paper “Pesticides in Formulations: New Revolutionary Findings” is loaded with incredible revelations. Thanks to Seralini’s heroic acts and those of his colleagues, we know of the grave adverse effects of pesticides in an unparalleled manner.

I posit that many of the key insights could be extended to the analysis of other safety/security concerns throughout the biotechnology sector, i.e., of how to evaluate real risk rather than pretend to do so.

More generally, for various biotech applications, because of the additional “gap” afforded by modeling, computerization, and online services and physical/biological/chemical reality, the problems have further been escalating without being adequately recognized. And AI is just adding another layer to this dangerous mess!

The article harbors numerous insights that immediately lend themselves to generalization to other disciplines that are concerned with “risk-benefit” analyses, e.g., “vaccines,” (other) gene therapies, synthetic drugs, and more generally, to the numerous applications of modern biotechnology such as synthetic fertilizers/feed/food and the many other products with broad application and environmental impact. Specifically, many of the important points made should also be applied to risk assessment in synthetic biology (e.g., “gain-of-function” research and other types of dangerous lab experiments).

Even though for the different biotech disciplines, risk analysis requires unique considerations, many of the underlying weak spots are the same. For instance, for lab security, the compounds causing toxic or otherwise adverse effects are not industrial chemicals but may be (unaccounted) genetic material, including viruses, fungi, or engineered nucleotides. In this sense, it should be clear how to replace the key players and compounds depicted by Seralini with relevant entities such as drugs, enzymes, life forms, carriers, etc.

Here are a few important bullets and findings of the Seralini paper with cross-disciplinary relevance - emphasis and suggested generalizations (in square brackets) mine.

• Pesticides [and many biotechnology products] have unintended side effects on species that are often not targeted or considered.

• The products are not single chemical products [or, analogously, those resulting across the synthetic biology pipeline]. Rather, they are mixtures containing other adjuvants [and others].

• The nature of adjuvants [analogously, of other biotechnological additions] is usually not fully detailed.

• Mixtures [of various synbio products] have negative unintended effects on the whole ecosystem. Thereby, “species are not only exposed to the entirety of a single commercial formulation in nature but also to mixtures of a wide range of residual pollutants [….]”

• Pollutants [contaminants] include “plasticizers of different sizes, such as nanoparticles… as well as various heavy metals or metalloids, additives, preservatives, petroleum molecules, etc.”

• These chemicals [many synbio] compounds are very stable and are “all present and have considerably increased to reach any form of life in a chronic way”

• Chemical [many biotech] ingredients are used for different purposes. Including their pollutants [contaminants], their “real long-term effect is not only the additive theoretical effect”

• Non-additive characteristics [of many biotech products] “could explain numerous chronic human or animal diseases in various kingdoms or even in plants or microbes where there is also a loss of biodiversity.”

• Concerning commercially proposed pesticide formulations [and mixtures of biotech commercial products]: “It is then a scientific surprise for the profession of toxicology to observe that toxicity cannot be deduced by industries and authorities using declared purified ingredient toxicity studies, given known classical admissible daily intake (ADI) values plus some theoretical, scientifically unclear considerations of the adjuvants [contaminants or byproducts] in model formulations. Obviously, underestimation occurs.”

• “Most researchers base their reasoning, as per usual, on these data, which are found in the literature. The formulations are in fact much more potent with respect to side effects since these are mixtures designed to act on whole organisms, to penetrate plant or insect cuticles first or to enter various [human or animal] membranes, impacting fungi and bacteria, whether symbiotic, such as in gut microbiota, or pathogenic; this cannot occur through a specific uniform mechanism. They act on human cells differently than declared ingredients do[…]”

• Adjuvants [or other declared biotech compounds] themselves “are not only variable and numerous but also contain residual chemicals.”

• As a result, “these make mixtures hundreds to thousands of times more efficient with respect to oxidative stress [or various forms of toxicity] in vivo and in patients…than what is expected from the sole ADI [or any other believed toxicity threshold] of the purified declared ingredient in the long term that serves as basic data.”

• “It is not only a matter of the solubility [degradability, biodistribution, or any other biological activity] of the declared ingredient[…]”

• We are also dealing with “a list of numerous, unknown, known, declared, and undeclared adjuvants [compounds or biological activities].”

• “The adjuvants or formulants [contaminants or byproducts] have their own unassessed toxicities [or other adverse effects] in mixtures or by themselves”

• The declared ingredient [or biological activity] is often not “the main and most active (toxic) one.”

• There are “several uncertainties regarding pesticide [various biotech product] compositions [which are] not all are declared and known by authorities.”

• We are also dealing with “industrial secrets and permanent changes in formulations [various biotech products] and lots in commercialization [or manufacturing].”

• Some adjuvants [contaminants or byproducts] act [various synergistic effects] in combined forms even at low levels.”

• Several usual compounds in pesticide formulants [e.g. synthetic nucleotides, contaminants, and byproducts] have been known for their “pesticidal activity since 1787 and for their toxicity and carcinogenicity since 1953” [inflammatory nature and genotoxicity for decades]: “It is no surprise, then, if they are not declared, and if their real toxic effects are falsified by industry [e.g., BigPharma] […] and/or by national or international authorities [e.g., Public Health leaders].

That the above is not limited to pesticides is evident from recent examples:

• Various contaminants during COVID-19 “vaccine” manufacturing processes that engender chilling safety risks and still largely remain ignored.

• The mRNA genetic injections (COVID-19 and those in the pipeline) where BigPharma and captured regulators merely report the modeled outcome of some isolated compounds and their intended effects.

• Genetic contaminants that may have led to the insertion of the Moderna-patented sequence into a SARS-CoV-2 precursor genome and evoked many novel and nasty features of the spike (see also my extension of this incredibly important observation by Ambati et al. where I specifically stress that the risks from interactions between contaminating or residual synthetic genetic material with live forms are insufficiently known).

The paper by Seralini is certainly very important. I hope the critical insights and lessons will be adopted by other disciplines that aim to conduct safety/security analyses of various kinds throughout the biotechnology field.

Tragically, some of the points made seem radically outside of contemporary biorisk assessment methodologies. Already in 2020, in a paper in Biosafety & Health, I warned of similar problems as clearly detailed by Seralini, such as the many unknowns stemming from a biological context, ambiguities through the types of tests and measurements used, the overall stochasticity and non-additivity of biological processes, that modeling cannot account for the sheer endless interactions, interrelationships and synergistic and processes and influences, serious flaws how to assess cause and effect, and more.  

Seralini offers clear and sound recommendations and considerations that must not be ignored:

• We must have “knowledge of the toxicity of full formulations [the entire biotech product and how it interacts with its environment]” as opposed to “known effects of the declared active ingredients purified alone.”

• “the full formulations of pesticides [biotech products] must be experimentally tested at a toxicological level, especially for long-term or chronic effects. This has never been requested by authorities, even for models of commercial formulations.”

• “Because of major toxicological differences between declared ingredients [and expected biological activities] and commercialized formulated pesticides [biotech products], which are largely underestimated today, and because long-term toxicity is never really studied, tested experimentally in vivo, or requested by regulatory authorities, even once for model formulations, there is a crucial scientific gap at this level.”

• “the toxicity of a pesticide [biotech product] cannot be anticipated or deduced from the known toxicity of the sole declared ingredient.”

• “additional theoretical calculations or the toxicity thresholds [or the compounding and synergistic effects] of unknown or undeclared adjuvants [or other byproducts or unintended biological activities]” obfuscate reality.

• In sum, “these factors are currently ignored by scientists.”

In addition to accidents and other unintended adverse effects, the far greater problem of the types of predicaments detailed by Seralini is that of deliberate exploitation and of “Corruption of Science and Grievous Harm to Public Health” (particularly, see the Monsanto Affair).

Beyond these known chilling insights, I don’t even want to know how all of this could be misused from a regulatory perspective throughout the bioeconomy, especially when it comes to safety checks, auditing of past/current disasters and cover-ups but also when approving and rolling out new drugs and biologics.