The evidence is in. We’ve been doing it all wrong!

Last weekend a paper was published in Drug Discovery Today titled “Towards a 21^st-century roadmap for biomedical research and drug discovery: consensus report and recommendations.”[1]

The paper, authored by internationally renowned experts in the field of non-animal research, analyses “decades of costly failures translating drug candidates from preclinical disease models to human therapeutic use.” It addresses “the failure of animal studies to predict drug efficacy and toxicity in humans”, examines Alzheimer’s disease, autism spectrum disorders, cholastic liver diseases, respiratory diseases and autoimmune diseases as case studies, and presents recommendations to help achieve a transition towards a human pathways-based paradigm shift.

The paper is not exclusive. A groundswell of literature now supports this view and provides compelling arguments favouring human-relevant (and non-animal) methods of research as being far more likely to accelerate translation to clinical practice and commercialisation.

Meanwhile in Australia, two important documents have recently been announced:

• Healthier lives, stronger economy: Victoria’s Health and Medical Research Strategy 2016-2020
• Medical Research Future Fund - Australian Medical Research and Innovation Strategy 2016-2021

The documents spell out the strategies to be employed to progress medical research in Australia.

Of much concern however, is that neither strategy includes any provision or incentives for the development of non-animal alternatives. In light of the new literature, this is rather disturbing.

Australia has made very little progress in replacing animals in research, as illustrated in the vast numbers of animals used each year (Australia is the fourth highest user), and with growing concern within the research community that animal models are not adequate human proxies for research, this is an area that requires urgent attention.

Both the Victorian Health and Medical Research Strategy and the Australian Medical Research and Innovation Strategy could have been opportunities to include a commitment by the Victorian and federal governments to fund research into seeking alternatives to animal use – as is already the case in other countries. In fact, Page 19 of the discussion paper for the Victorian strategy stated that “Australia punches far above its weight by producing 3 per cent of global research publications with only 0.3 per cent of the world’s population. However, compared with international standards, Australia has a poor record of commercial translation…”

Clearly something is amiss. Could it be our ongoing dependence on animal data in pre-clinical research?

Predictability

Scientific literature raises questions about the reliability and predictive value of animal testing in research for humans. Systematic reviews continue to show that animal experiments are not predictive of human outcomes and can be dangerously misleading.

Humans differ from animals anatomically, genetically and metabolically and interspecies variations are a high cause of clinical trial failure of pharmaceutical products. Animals have different metabolic pathways, present broad ranges of physiological defences, and differ in the way their organ systems respond to toxic insults. Not only does this mean that results cannot be extrapolated to humans, but it also means that some possibly successful treatments are being ruled out preclinically due to adverse reactions or responses in animals. Animal use in research and safety studies is therefore misleading.

Research Translation

In spite of huge research effort and expense, development of new treatments has slowed, as preclinical success has not followed through into clinical trials. The U.S. Food and Drug Administration (FDA) recently reported a 92 percent failure rate of clinical trials following successful animal trials.

In a 2014 British Medical Journal article the author stated, “…if research conducted on animals continues to be unable to reasonably predict what can be expected in humans, the public’s continuing endorsement and funding of preclinical animal research seems misplaced.” (Şentürk, 2015).

The use of animals in research is, according to the code, for cases where no alternative exists, but alternatives will never exist without support for the development of non-animal based scientific testing methods. There have been international moves towards supporting alternatives to animals in research. Techniques such as computer modelling, genomics, nanotechnology, microdosing, microfluidic chips and imaging techniques, just to name a few, have been developed with government funding and support to provide a human-relevant model. The process has been slow, as old habits persist and development of new techniques takes time. 

I do hope the aforementioned paper receives the attention it deserves.  It is remiss for both the Victorian Strategy and the MRFF strategy to exclude provision for research to replace animals and waste the opportunity to illustrate their commitment to the 3R’s Principle, which would in turn contribute to more innovative, high-quality and translatable research. 

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