Interview with Dr Jason Johnson, British Heart Foundation Senior Research Fellow, Associate Professor of Cardiovascular Pathology, and leads the Laboratory of Cardiovascular Pathology at Bristol Medical School, University of Bristol.
As a scientist, in general do you find that the 3Rs concept is something that is routinely thought of when discussing experimental plans, or is it more of an afterthought? Has this changed over the last decade or in recent years, and lastly do you anticipate changes in use in the future (better uptake etc.)?
Jason Johnson: Attitudes are definitely changing and here in the UK the NC3Rs provide many conferences and meetings highlighting the 3Rs concept alongside exemplars of best practice. Equally, within our University the 3Rs are front and centre, again with annual meetings demonstrating how the 3Rs are implemented University-wide. I still feel there is work to be done as I regularly see abstracts presented at meetings and receive manuscripts/grants to review where the 3Rs do not even appear to have been considered. However, I am also aware more that an increasing number of scientific journals are requesting authors to confirm that 3Rs approaches and the ARRIVE guidelines have been applied, upon submission. Such initiatives should ensure that the 3Rs are at the front of researchers’ minds during the development of experimental plans, rather than an afterthought, and ensure uptake is moving in the correct direction.
What do you think may be some barriers to the uptake and use of alternative approaches to animal testing? (i.e. why may scientists be less prepared to use more novel/alternative methods?)
Jason Johnson: As scientists, our currency and value are determined by grant and publication success, both of which rely on novelty and impact. Invariably, in vivo models are well-characterised, well-cited, and therefore deemed essential to ensure your in vivo studies are deemed of higher novelty/impact. As such, there needs to be a change in attitudes from reviewers and journals towards studies that are developing and/or deploying novel alternative approaches to animal testing. If a scientist has confidence that an ex vivo model for example, will be seen as comparable by reviewers and editors as a mouse model, this should aid the removal of such barriers.
Could you please describe your ex vivo human model of aneurysm formation and progression?
Jason Johnson: A large number of mice are used yearly for scientific studies aiming to understand why aneurysms develop and to test novel therapies that may have the potential to limit such a debilitating disease. As a scientist fully aware of the 3Rs concept which seeks to refine, reduce and replace the use of animal testing, we set out to determine if we could develop a model using surplus human tissue with the ambition of reducing and perhaps replacing current mouse models of aneurysms. I was mindful that when babies are born the umbilical cord is discarded and this could serve as a source of suitable blood vessels (arteries) which could be utilised to model aneurysms within a laboratory setting, using a machine called a bio-reactor which would closely mimic how an artery works in the body, alongside introduction of an aneurysm-inducing agent (angiotensin II) which is used in mice to cause aneurysms. We were fortunate to receive funding from the National Centre for the Replacement Refinement & Reduction of Animals in Research (NC3Rs) and the British Heart Foundation (BHF) to develop our laboratory-based (ex vivo) model of human aneurysm formation.
The model involves dissecting the arteries (20–25 cm in length) out from within the umbilical cord and transplanting them into a bio-reactor with an aneurysm inducing agent, which results in the formation of an aneurysm after three days. We have subsequently validated our model of aneurysm formation by demonstrating that three different treatments that are effective in mouse models of aneurysm are similarly beneficial within our human laboratory model. We have also assessed the arteries which form aneurysm under a microscope and observe similar changes associated with aneurysm formation within mouse models, and importantly, human aneurysms. Additionally, we are able to maintain the arteries within the bio-reactor for a week which allows us to test potential medicines on existing aneurysms, to mimic the situation in patients, and shown that an effective treatment in mice is also replicated in our novel human laboratory-based model.
Collectively, our findings support the use of this model for future aneurysm studies and provides an alternative for ethically challenging animal experiments, reducing the number of mice used in such studies.
At the EU level, do you feel the EU institutions could do more to encourage uptake of alternative approaches to animal testing?
Jason Johnson: Alternative approaches to animal testing should be encouraged by EU institutions and checks put in place to ensure the 3Rs concept is adopted during the funding application process. Such a strategy would ensure that the 3Rs are taken into consideration during experimental design and also highlighted to reviewers. In addition, increased funding streams and initiatives should be supported to aid the development of reproducible and robust alternatives to animal testing.