Clinical impact of high-profile animal-based research reported in the UK
						national pressClinical impact of high-profile animal-based research reported
						in the UK national press

Self Cite

The poor translation of animal research to human biology and clinical benefit is more widely acknowledged than ever before. Much of my work over the past 17 years has made a scientific case for the replacement of animal experimentation with human-specific methods for this reason, also arguing that such a paradigm shift has a human ethical basis, as well as being based on animal welfare. Over this time, the debate has grown from being largely argued by animal rights groups, to a movement that now involves stakeholders from every area of science, including academia, industry and regulators. Initiatives and roadmaps to expedite replacement specifically -not just the Three Rs generally -are ongoing, gathering momentum and finding success (for example [1][2][3][4][5][6][7][8] ). Furthermore, acknowledgements of poor translation/human relevance of animal-based approaches are stated frequently in papers in mainstream journals in a huge variety of specialist fields, as researchers increasingly look to new approach methodologies (NAMs) to find a better way forward. This is all very welcome, naturally. However, it may be a serious mistake to assume that this paradigm shift, when it happens, will be enough for biomedical research to reach its full potential. There are long-established and growing concerns among some academics around how biomedical research is conducted, over and above the methods and approaches it adopts. These concerns deserve much more attention than they currently receive. I recall many and regular conversations with my scientist colleagues during my time in academic research, lamenting certain aspects of how academia operated, how science was funded, the unfortunate weight of the 'publish or perish' mantra, and how research and researchers were assessed and assigned relative value. While this all took place almost 20 years ago, it is perhaps even more relevant today. No matter how good the very best, most human-relevant NAMs may be, if the drivers of research and the modus operandi of biomedical investigation are not optimal, then biomedical research itself will remain, at best, sub-par -and this has serious human ethical consequences. There must be a significant change in this respect, too, which would potentiate, enhance and maximise the capabilities of NAMs and human-specific research, ensuring significant increases in clinical translation and benefit. This limitation of research potential and translation to human benefit is a critical point. Notably, it is distinct from other calls for change in how research is conducted, calls for intellectual/academic freedom, complaints surrounding unnecessary 'regulatory burden' and so on. These concerns are not borne of frustration with the job and career, but of the purpose, goals, and main raison d'être of biomedical research: i.e. clinical impact and human benefit.

mentioning

confidence: 99%

Biomedical Research Must Change — But a Shift Toward Human-specific Research Methods Is Only Part of What Is Needed

Bailey¹

2021

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“…For example, in my own work, I have authored and co-authored over 60 studies and reviews on this topic, all citing numerous supporting references to the work of scientists around the world. These include:— two recent papers that examined the translatability of findings from diverse fields of animal research to humans and found it to be extremely poor; 23,24 — analyses of the contribution of chimpanzee research to the benefit of human health (including in fields such as HIV/AIDS and hepatitis C research), which helped to realise an end to federally funded chimpanzee research in the USA; 25–28 — critical reviews of NHP research in multiple areas and its translational failure, particularly in neuroscience; 29–32 — the need for a shift to human-focused research in the field of Parkinson’s disease research; 33 — how animal testing of potential new human drugs is insufficiently predictive of human safety and toxicity 34–37 (including developmental toxicology 38 );— why a shift away from animal use in science and to a complete focus on human biology is essential, due to inter-species genetic differences 39,40 compounded by the adverse and unavoidable physiological effects of stress for animals in laboratories. 41,42 There are also myriad works by others that augment the evidence base, including various published papers 43–52 and a number of substantial books.…”

Section: An Overview Of the Three Rs And The Case For Changementioning

confidence: 99%

“…— two recent papers that examined the translatability of findings from diverse fields of animal research to humans and found it to be extremely poor; 23,24…”

Section: An Overview Of the Three Rs And The Case For Changementioning

confidence: 99%

“…For further informed and detailed background and discussion on various similar arguments, the publications of Professor Michael Balls, former Head of the European Centre for the Validation of Alternative Methods (ECVAM), Life President of the UK’s Fund for the Replacement of Animals in Medical Experiments (FRAME), and expert in the Three Rs and the work of Russell and Burch, who has published extensively on the subject over many years, should be consulted (see, for example). 7,17,24,68–72…”

Section: An Overview Of the Three Rs And The Case For Changementioning

confidence: 99%

See 1 more Smart Citation

It’s Time to Review the Three Rs, to Make them More Fit for Purpose in the 21st Century

Bailey

2024

The Three Rs have become widely accepted and pursued, and are now the go-to framework that encourages the humane use of animals in science, where no other option is believed to exist. However, many people, including scientists, harbour varying degrees of concern about the value and impact of the Three Rs. This ranges from a continued adherence to the Three Rs principles in the belief that they have performed well, through a belief that there should be more emphasis (or indeed a sole focus) on replacement, to a view that the principles have hindered, rather than helped, a critical approach to animal research that should have resulted in replacement to a much greater extent. This critical review asks questions of the Three Rs and their implementation, and provides an overview of the current situation surrounding animal use in biomedical science (chiefly in research). It makes a case that it is time to move away from the Three Rs and that, while this happens, the principles need to be made more robust and enforced more efficiently. To expedite a shift from animal use in science, toward a much greater and quicker adoption of human-specific New Approach Methodologies (NAMs), some argue for a straightforward focus on the best available science.

“…Of course, the problems of translatability are not limited to the areas explored in this paper — there are issues with other disease areas as well. 3 We realise that oncology is one of the fields in which translatability problems are greater and the failure of traditional models is recognised. 4–10 However, we were not able to include ‘cancer’ among the diseases explored because, with over 200 diseases classified as ‘cancer’, 11 this would be a huge undertaking that would, in itself, require a dedicated paper on the topic.…”

Section: Introductionmentioning

confidence: 99%

Poor Translatability of Biomedical Research Using Animals — A Narrative Review

Marshall

Bailey

Cassotta³

et al. 2023

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The failure rate for the translation of drugs from animal testing to human treatments remains at over 92%, where it has been for the past few decades. The majority of these failures are due to unexpected toxicity — that is, safety issues revealed in human trials that were not apparent in animal tests — or lack of efficacy. However, the use of more innovative tools, such as organs-on-chips, in the preclinical pipeline for drug testing, has revealed that these tools are more able to predict unexpected safety events prior to clinical trials and so can be used for this, as well as for efficacy testing. Here, we review several disease areas, and consider how the use of animal models has failed to offer effective new treatments. We also make some suggestions as to how the more human-relevant new approach methodologies might be applied to address this.