Systematic reviews are currently favored methods of evaluating research in order to reach conclusions regarding medical practice. The need for such reviews is necessitated by the fact that no research is perfect and experts are prone to bias. By combining many studies that fulfill specific criteria, one hopes that the strengths can be multiplied and thus reliable conclusions attained. Potential flaws in this process include the assumptions that underlie the research under examination. If the assumptions, or axioms, upon which the research studies are based, are untenable either scientifically or logically, then the results must be highly suspect regardless of the otherwise high quality of the studies or the systematic reviews. We outline recent criticisms of animal-based research, namely that animal models are failing to predict human responses. It is this failure that is purportedly being corrected via systematic reviews. We then examine the assumption that animal models can predict human outcomes to perturbations such as disease or drugs, even under the best of circumstances. We examine the use of animal models in light of empirical evidence comparing human outcomes to those from animal models, complexity theory, and evolutionary biology. We conclude that even if legitimate criticisms of animal models were addressed, through standardization of protocols and systematic reviews, the animal model would still fail as a predictive modality for human response to drugs and disease. Therefore, systematic reviews and meta-analyses of animal-based research are poor tools for attempting to reach conclusions regarding human interventions.

Many pesticides are used increasingly in combinations during crop protection and their stability ensures the presence of such combinations in foodstuffs. The effects of three fungicides, pyrimethanil, cyprodinil and fludioxonil, were investigated together and separately on U251 and SH-SY5Y cells, which can be representative of human CNS glial and neuronal cells respectively. Over 48h, all three agents showed significant reductions in cellular ATP, at concentrations that were more than tenfold lower than those which significantly impaired cellular viability. The effects on energy metabolism were reflected in their marked toxic effects on mitochondrial membrane potential. In addition, evidence of oxidative stress was seen in terms of a fall in cellular thiols coupled with increases in the expression of enzymes associated with reactive species formation, such as GSH peroxidase and superoxide dismutase. The glial cell line showed significant responsiveness to the toxin challenge in terms of changes in antioxidant gene expression, although the neuronal SH-SY5Y line exhibited greater vulnerability to toxicity, which was reflected in significant increases in caspase-3 expression, which is indicative of the initiation of apoptosis. Cyprodinil was the most toxic agent individually, although oxidative stress-related enzyme gene expression increases appeared to demonstrate some degree of synergy in the presence of the combination of agents. This report suggests that the impact of some pesticides, both individually and in combinations, merits further study in terms of their impact on human cellular health.

Personalized medicine is based on intraspecies differences. It is axiomatic that small differences in genetic make-up can result in dramatic differences in response to drugs or disease. To express this in more general terms: in any given complex system, small changes in initial conditions can result in dramatically different outcomes. Despite human variability and intraspecies variation in other species, nonhuman species are still the primary model for ascertaining data for humans. We call this practice into question and conclude that human-based research should be the primary means for obtaining data about human diseases and responses to drugs.

An analysis of the use of nonhuman primates in biomedical research in the UK, the Review of Research Using Non-Human Primates (the "Bateson Review") was released in 2011. The review was applauded, to varying degrees, by most of the stakeholders in the controversy over using nonhuman primates in biomedical research. However, there has not been a scientific analysis of the review. In this paper, the Bateson Review is examined for both methodology and the science relevant to the use of nonhuman primates in biomedical research. The relevant science includes complexity theory, evolutionary biology, genetics, empirical evidence regarding the reliability of interspecies extrapolation, and the value of basic biomedical research in general in making discoveries that lead to human treatments. The authors of this paper conclude that the Bateson Review does not meet the criteria for a scientific assessment, in part, because it fails to consider the current science that impacts on the practice of using animals, in general, and nonhuman primates, specifically, in biomedical research. This lack of scientific consideration has legal and ethical ramifications. Since the Bateson Review fails as a scientific evaluation, the ethical and legal recommendations that are based on science are also suspect.

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