Experiments on mice without benefit

Mouse trials almost without significance

02/13/2013

In many cases, the medical significance of animal studies has been questioned in the past. Now, a team of Canadian and American scientists around Shaw Warren of Boston's Massachusetts General Hospital has featured in the journal „Proceedings of the National Academy of Sciences“ (PNAS) has published a study that concludes that experiments on inflammatory processes and their treatment in mice do not allow any conclusions about humans. Animal rights activists and other opponents of the animal experiments are confirmed in their previous criticism.

Most drugs today are tested on animals long before human use. In addition, countless animal experiments are carried out in the name of basic research. However, not only on the part of the animal rights activists there are considerable doubts about the resilience of the results, which are obtained in the context of such animal experiments. The US researchers took this opportunity for a comprehensive analysis of the effects of inflammatory processes on gene expression in humans and mice.

The observed deviations show that studies on mice have little significance for inflammatory processes in humans. The human organism reacts to the processes of inflammation in gene expression fundamentally different than the rodent's organism, reports the research consortium, in which institutions such as Harvard Medical School, Massachusetts General Hospital and the University of Toronto were involved, in the journal „PNAS“.

Studies in mice without medical benefit?
Model experiments on mice „have been extensively used in recent decades to identify and test drug candidates for later human studies“, but few of these studies have been successful in human studies, Warren and colleagues report. Particularly low is the success rate of studies in the field of inflammation. Inflammatory processes play an important role in many human diseases. According to the researchers, the number of existing studies is correspondingly high. Alone to drug candidates to block the inflammatory response in acute diseases, 150 clinical studies have been carried out, of which „every attempt failed“ is, the US scientists write. Here, the question of the fundamental validity of the studies in mice on inflammatory processes in humans has come up.

Changes in gene expression in humans and mice compared
As inflammatory processes usually cause changes in gene activity, ie gene expression, researchers in the study of Shaw Warren have compared the effects of inflammatory responses to RNA (ribonucleic acid) in white blood cells in humans and three different mouse strains. The effects of inflammation due to burns, intoxications and violent injuries (blunt trauma) on gene activity in humans and rodents were investigated.

The scientists took blood samples from 167 patients 28 days after one „severe blunt trauma, from 244 patients to one year after burn and four healthy people 24 hours after administration of low-dose bacterial endotoxin.“ They examined the changes in gene expression by RNA in the white blood cells and performed a similar experiment on mice. Then followed „systematic comparison of the genomic reaction between human inflammation and the mouse model“, Write Warren and colleagues.

No match in changes in gene activity
Human gene activity has been significantly altered by inflammatory processes in more than 5,500 genes, with mice possessing comparable genes for approximately 4,900 of these genes. These so-called orthologues would actually show a similar change in the course of the inflammatory processes in mice and humans in order to confirm the informative value 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. Also, the changes in gene activity differed significantly in their duration. While humans often showed altered gene expression over months due to the inflammatory processes, the changes in mice usually lasted only a few days.

In addition, the differences in gene activity were relatively identical regardless of the respective causes of inflammation in humans, while in the mice between the individual strains, significant differences were found even with the same type of injury. View of the „worldwide use of mice as a model for human inflammation“,The results are extremely sobering, Warren and colleagues say. The current study argues that medical research should be more geared to the more complex human conditions, „rather than studying mouse models for human inflammatory diseases“. (Fp)

Picture: Remi Loy