Last month the National Health and Medical Research Council (NHMRC) released “Best practice methodology in the use of animals for scientific purposes 2017”The document makes for an interesting read and it is available here.
The introduction reads:
“Reports in the international literature and in the general and scientific media have outlined the growing concern that published studies in many scientific disciplines — including studies involving the use of animals — are not reproducible. This issue does not challenge the validity or legitimacy of the scientific method.”
Scientific literature does indeed raise many questions about the reliability and predictive value of animal testing in research for humans.[1],[2]Systematic reviews continue to show that animal experiments are not sufficiently predictive of human outcomes and can be dangerously misleading.[3] Whether the NHMRC chooses to acknowledge it or not, there is no doubt there is plenty of ‘international literature and in the general and scientific media’ that does challenge both the validity and legitimacy of the scientific method -ie animal experiments.
“Irreproducibility can happen for many legitimate reasons — for example, natural variability in biological systems or small changes in conditions. Consequently, there is acceptance in the scientific community that some irreproducibility will occur. However, it is the current scale and the implications of irreproducible research that are of concern”
The term “natural variability in biological systems” translates to “species differences” – the main reason that animals are not appropriate models on which to study human medicine. While it is commendable that the NHMRC is concerned about the scale of this problem it would have been prudent to address the core issue rather than continuing to sidestep it.
Section 1 (Framework for best practice methodology) states:
“It aims to ensure that the use of animals is necessary and not wasteful, contributes to scientific progress, fosters translation of outcomes into practical and clinical application, and provides value for research investment.”
The section from which this statement came (as well as Section 2 – Consequences) provides an excellent argument against the use of any animals at all.
According to FDA (U.S. Food and Drug Administration), in spite of huge research efforts and associated expenses, development of new treatments has slowed, as preclinical success has not followed through into clinical trials. Latest figures have revealed a 95% failure rate of clinical trials following ‘successful’ animal trials.[5] This indicates that medical research advances, not because of the use of animals in testing, but in spite of the use of animals in testing.
In a discussion paper addressing health and medical research, the Victorian government recognised the challenges of “PhD students and scientists confronted by issues related to career progression, security and remuneration.” Page 19 of the discussion paper 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…”.[6] Consider Australia’s ranking of fourth highest (in absolute numbers - not by population)[7] user of animals in research behind only China, Japan and the United States and our lack of resources and incentives to develop alternatives. It’s no wonder we are falling behind in clinical translation - due primarily in HRA’s view to the continued fixation on using animals.
The report also states: “Effective and transparent reporting of animal-based studies is essential to inform future scientific studies and policy.”
Considering the Australian public are funding much of this research then it should also be transparent to us. A 2013 opinion poll commissioned by Humane Research Australia, found 57% of respondents were not even aware animals are used in experimental research in Australia.
As the significant proportion of these experiments are funded by Australian taxpayers, don't we have a right to know what our precious resources are being spent (or wasted) on?
The third section of the report “outlines the most commonly reported flaws in animal-based studies.” Ironically, it does not point out that the use of animals is itself a major flaw.
Flaws quoted include:
- “Failure to use the most appropriate animal model — for example, species, strain, methodology”
- “Lack of consideration and control of variables. Examples include variables related to: – the animal’s biological characteristics, including morphology, physiology, behaviour, genetic makeup, temperament and behavioural conditioning, microbiological and nutritional status, microbiome, and general state of health – the animal’s living conditions including physical, environmental and social conditions”
- “Failure to consider the use of both sexes in the study”
These examples clearly acknowledge that differences in results can occur even through different strains of the same species, different housing conditions and different sexes of the same animal, yet it’s assumed that it’s okay to extrapolate from an entirely different species to a human.
These concerns are further referenced in the following two examples which leads to the logical question of why use animals at all:
- “Failure to consider that findings may not translate to the target species because of inherent species differences.”
- “Lack of consistency in protocols between animal and human studies intending to relate findings from an animal model to humans.”
The final section (Practical strategies) unfortunately puts the onus on institutions, investigators and animal ethics committees to address strategies to improve research methodology – meaning there will continue to be inevitable inconsistencies across the board. HRA has previously suggested to the NHMRC that a central reporting system is necessary. Their response was “NHMRC does not have the remit to establish a national database of all animal research, nor the resources to undertake this role.“[8]
So, it seems from this new publication that the NHMRC is finally acknowledging the shortcomings of animal research and warning about them, but doing little to nothing about enforcing practices to resolve these issues.
The very existence of (or need for) this current release by the NHMRC suggests without doubt that researchers are currently not using best practice, and are wasting precious resources on flawed “research” that is unlikely to result in positive clinical translation – as has been indicated by Australia’s high usage of animals and its extremely poor rate of clinical translation
The release does not sufficiently address the inappropriateness of using animals as models for human research, but does perhaps provide better guidance to avoid duplication (defined as ‘The repetition of scientific work that provides no advances in knowledge.’)
Much of the research uncovered by HRA through its analysis of real life case studies does indeed fall under the category of duplication so we are hopeful that adherence to this document might at least lead to some reduction in animals used. It remains questionable however as to whether the document will serve to actually reduce the exorbitant number of animals used in Australian research every year, or whether it will simply reinforce their use by portraying the notions that the industry follows strict guidelines and animals are used only when absolutely necessary. Unfortunately for the animals themselves and the progress of medical advancement in this country these perceptions are sadly not the case.
For further information about animal experiments: Please visit www.HumaneResearch.org.au
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[1]Bailey J et al. (2014) An Analysis of the Use of Animal Models in Predicting Human Toxicology and Drug Safety. ATLA 42, 181-199.
[2]Hartung T. (2013) Look Back in Anger – What Clinical Studies Tell Us About Preclinical Work. ALTEX 30, 275-291
[3]Greek R, Menache A (2013) Systematic Reviews of Animal Models: Methodology versus Epistemology. Int. J. Med. Sci. Vol. 10: 206-221.
[4] Accelerating the Delivery of New Medical Treatments to Patients, FDA U.S. Food and Drug Administration. (http://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/ucm228207.htm accessed 29/11/16)
[5] Arrowsmith, J. (2012). A decade of change. Nat Rev Drug Discov 11, 17-18
[6]Victorian health and medical research strategy 2016-2020.
[7] Taylor K et al. (2008) Estimates for worldwide laboratory animal use in 2005. Altern Lab Anim 36:327-42.
[8]Personal correspondence from Prof Anne Keogh, CEO, NHMRC 2/8/16.
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