Taking aim at the 3Rs

In this blog post, Dr Mark Prescott, NC3Rs Director of Policy and Outreach, explains why this could jeopardise the progress already being made.

As awareness and understanding of the 3Rs has grown in the past decade, so too has their implementation, including by ethics committees reviewing proposals for animal research. Animal Welfare and Ethical Review Bodies (AWERBs) and Institutional Animal Care and Use Committees (IACUCs) now place greater emphasis on scrutinising how the 3Rs have and will be applied in the design and conduct of the research, and investigators are providing ever more detailed information on their 3Rs efforts. This increased attention and activity on the 3Rs is welcome, and benefits both animals and the science, but is it sufficient in terms of ethical review? Of course not. Even where the 3Rs have been fully applied, it does not mean it is morally right to proceed with individual animal research projects. We must also consider the potential societal benefit from the research and whether this justifies the harm caused to the animals involved.

In a book published earlier this year, Tom Beauchamp and David DeGrazia, bioethicists based at two universities in the USA, call for a more comprehensive framework of principles for animal research ethics, going beyond the 3Rs. They suggest this will bridge the gap between the concerns of both the biomedical and animal protection communities. The framework was summarised in an ILAR Journal article late last year and is garnering attention, particularly in North America. An editorial in Science last week took a provocative line, suggesting it might be time to replace the 3Rs in favour of this ‘new’ ethical framework. Across this side of the pond, it’s hard to understand what all the fuss is about.

The framework sets out six principles the authors claim are each a necessary condition of morally justified animal research. Three fall under the category Social Benefit (no alternative method; expected net benefit; sufficient value to justify harm) and three under Animal Welfare (no unnecessary harm; basic needs; upper limits to harm). No alternative method and no unnecessary suffering fit squarely with the replacement, reduction and refinement principles of the 3Rs, so there seems to me to be no conflict there; rather it’s a question of whether the 3Rs are being applied to the fullest extent.

For those of us working in the UK and EU under the Animals (Scientific Procedures) Act 1986 (ASPA) and Directive 2010/63/EU, weighing the harms caused to all sentient beings involved in proposed research, and considering whether the anticipated net benefit is sufficiently valuable or large to justify the harms, are fundamental components of our ethical review processes. That’s not to say performing harm-benefit analysis is easy, but researchers, regulators and/or ethics committees are required to do it already. In my experience and that of my NC3Rs colleagues who also sit on AWERBs, committee members try their best to perform robust harm-benefit assessments, utilising excellent resources available from the RSPCA and others. Is the issue that IACUCs aren’t performing this function, or not well enough?

Beauchamp and DeGrazia’s framework requires the basic needs of research animals to be met (e.g. in terms of appropriate food and water, housing and enrichment) and for upper limits to be set on the harm imposed on them. Whilst it is true that the 3Rs set no limit on permissible harm to animal subjects, the ASPA and Directive do so and they also require fulfilment of basic animal needs (e.g. see Article 33 and Annex III). In this way, EU legislation is a hybrid of utilitarianism and deontological or rights-based ethics and, where fully implemented, goes a long way to fulfilling the requirements of the framework.

Whilst I am in agreement with most of what the authors call for, they do take an old-fashioned standpoint towards the 3Rs, referring back to Russell & Burch’s 1959 book. However, contemporary definitions and viewpoints recognise, for example, that refinement encompasses the lifetime experience of animals not just the scientific procedures performed upon them; and that the 3Rs play a multifactorial role in helping to maximise the benefits as well as minimise the harms from animal research. Applying the 3Rs involves using human-relevant models, proper powering of studies for reliable findings, comprehensive reporting to maximise reproducibility and translation, and avoiding the confounding effects of pain and stress on experimental data. I could go on…

Knocking the 3Rs is a convenient way to grab headlines given the widespread support they receive from the majority of stakeholders. However, this seems to me to do a disservice to the contribution of Beauchamp and DeGrazia and risks jeopardising the excellent and real progress that has been made by the scientific community in advancing and applying the 3Rs. Let’s not throw the baby out with the bath water!