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Mouse experiments with almost no informative value
In the past, the medical significance of animal studies has been questioned in the past. Now a team of Canadian and American scientists led by Shaw Warren from Massachusetts General Hospital in Boston have published a study in the journal "Proceedings of the National Academy of Sciences" (PNAS), which concludes that experiments on inflammatory processes and their treatment do not allow conclusions to be drawn about humans in mice. Animal rights activists and other opponents of animal experiments have been confirmed in their previous criticism.
Most drugs today are tested on animals long before they are used in humans. In addition, countless animal experiments are carried out in the name of basic research. However, it is not only on the part of animal rights activists that there are considerable doubts about the reliability of the results obtained in the context of such animal experiments. The US researchers took this as the basis for a comprehensive analysis of the effects of inflammatory processes on gene expression in humans and mice.
The deviations found show that studies in mice have little meaning for inflammatory processes in humans. The human organism reacts fundamentally differently to the inflammatory processes in gene expression than the rodent organism, reports the research consortium, in which institutions such as Harvard Medical School, the Massachusetts General Hospital and the University of Toronto were involved, in the specialist magazine " PNAS ”.
Studies in mice without medical benefit? Model tests on mice "have been used extensively in recent decades to identify and test drug candidates for later human studies", but only a few of these studies have been successful in human studies, Warren and colleagues report. The success rate of the studies in the area of inflammation is particularly low. Inflammatory processes play an essential role in numerous human diseases. According to the researchers, the number of available studies is correspondingly high here. The US scientists write that 150 clinical studies have been carried out on drug candidates alone, which are supposed to block inflammatory reactions in acute diseases, of which “every attempt has failed”. Here the question arose about the fundamental significance of the studies in mice on inflammatory processes in humans.
Changes in gene expression in humans and mice compared Because inflammatory processes usually cause changes in gene activity, i.e. gene expression, the Shaw Warren researchers contributed to the effects of inflammatory reactions on RNA (ribonucleic acid) in white blood cells in their current study Humans and three different mouse strains compared. The effect of inflammation from burns, poisoning and violent injuries (blunt trauma) on gene activity in humans and rodents was examined.
The scientists took blood samples from 167 patients 28 days after a "severe blunt trauma, from 244 patients up to a year after a burn and from four healthy people 24 hours after the administration of low-dose bacterial endotoxin." They checked the changes in gene expression using of RNA in the white blood cells and carried out a comparable experiment in mice. This was followed by a “systematic comparison of the genomic response between human inflammation and the mouse model,” write Warren and colleagues.
Inconsistency in changes in gene activity The gene activity of humans was significantly changed by the inflammatory processes in more than 5,500 genes, whereby mice have comparable genes for approximately 4,900 of these genes. These so-called orthologs should actually show a similar change in the course of the inflammatory processes in mice and humans in order to confirm the meaningfulness of the animal experiments and thus justify their implementation. But that was not the case. The researchers found no significant correlation between gene expression in humans and mice. The changes in gene activity also differed significantly in their duration. While people often showed changes in gene expression for months as a result of the inflammatory processes, the changes in mice usually only lasted a few days.
In addition, the differences in gene activity were relatively identical regardless of the respective causes of inflammation in humans, while in mice between the individual strains, considerable differences were found even with the same type of injury. Given the "worldwide use of mice as a model for human inflammation", the results are extremely sobering, said Warren and colleagues. The current study argues that medical research should be oriented more towards the more complex human conditions "instead of studying mouse models for human inflammatory diseases". (fp)
Image: Remi Loy / pixelio.de