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Another challenge to the mouse model

Many thanks to Monika Merkes PhD, Honorary Associate, Australian Institute for Primary Care & Ageing, La Trobe University for the following update on the  issue of animal research.

Dr Merkes writes:

A team of medical researchers has recently issued another challenge to the still widely held view that animal research benefits humans. Dr Junhee Seok, together with 38 other medical scientists from across the US and Canada, published a study with the title “Genomic responses in mouse models poorly mimic human inflammatory diseases”  in the Proceedings of the National Academy of Sciences of the United States of America (open access).

The authors report on a systematic comparison of the genomic response between human inflammatory diseases and murine (rat and mouse) models. They looked at burns, trauma and sepsis (infection in the blood).

The mouse model

Mice are one of the most commonly used species in the laboratory. Because they share genes with humans, it is widely assumed that they provide useful models to research human diseases such as cancer, cardiovascular diseases and diabetes.

Compared to other animals, mice are small, relatively inexpensive, and easy to breed and keep. The use of genetically engineered mice who can mimic diseases has become quite common.

While the mouse is considered a good model by many biomedical researchers, others have questioned how well mouse models reflect the complex physiology of human disease.

What did the researchers find?

The researchers of the recently published study found that the genomic responses to different acute inflammatory stresses are highly similar in humans, but these responses are not mirrored in the current mouse models. The mouse immune system and the human immune system do not respond in the same way to stress. The researchers could not find more than a random association between the murine models and the human conditions.

Consequently, drugs that are beneficial to mice and rats may or may not work for the same conditions in humans. They may even be harmful.

The authors of the study conclude that their “study supports higher priority for transitional medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases” .

Animal models are not useful to study human diseases

I have argued elsewhere that animal models are not predictive of human health. This is also the opinion of many experts in the field (see examples 1,2,3,4,and 5 )

Dr Andrew Knight, a European Veterinary Specialist in Welfare Science, Ethics and Law and Fellow, Oxford Centre for Animal Ethics, has recently published a book titled “The costs and benefits of animal experiments”  in which he reviewed over 500 scientific publications about the contributions of animal experimentation to human healthcare and the extent to which laboratory animals suffer. He concluded that actual human benefit is rarely – if ever – sufficient to justify the costs.

This new study about mouse models and inflammatory diseases provides further evidence for the problematic use of animals in biomedical research. But will it stop funding bodies to continue financial support for research that is so fundamentally flawed? Will it encourage researchers to change their long-held beliefs in the usefulness of animal models? Will it propel the general public to question the myth of animal experimentation leading to cures for common diseases?

There are alternatives to animal research. Initiatives such as the Innovative Methods and Alternatives to Animal Research Unit  at the John Curtin School of Medical Research, Australian National University, provide support to the research community in finding alternatives to using animals in biomedical research.

Dr Seok and his colleagues had tried to publish their findings in several journals. While the reviewers did not find fault with the paper, one of the authors reported that “the most common response was, ‘It has to be wrong. I don’t know why it is wrong, but it has to be wrong.’ . Long-held assumptions are difficult to let go.

A paradigm shift towards non-animal alternatives

We are seeing a paradigm shift  in biomedical research from using animals to using non-animal alternatives. Anomalies are appearing in the animal research paradigm with increasing frequency. Seok and his team have added to the body of evidence that highlights the anomalies. There is denial and disbelief from those working within the paradigm, as the above quoted response from the reviewers shows. It will be some time before the paradigm collapses and animal research will be a practice of the past. Until then, we must keep exposing its inadequacies.

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