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Introduction

The quotes in this paper are extracted from a series of interviews with a number of experts on the use of animals in science. They have been grouped by theme.

Interviewees were asked the following 7 questions:

1. What would you identify as the critical issues for the use of animals in science in the future?

2. Being optimistic but realistic, talk about what you see as a desirable outcome for the use of animals in science in the future.

3. If things were to go wrong, what factors would you worry about most?

4. Looking at your organisations internal systems (or other key organisations), how might these need to be changed to help bring about the desired outcome?

5. Looking back, what would you identify as the significant events which have had an impact on the use of animals in science?

6. Looking forward, what do you see as priority actions which should be carried out soon to reach the desired outcome?

7. If you had absolute authority and could set the direction of the use of animals in science, is there anything else you would do?

We have sought to work with experts with a balance of views on this subject.

The issues paper aims to:

• set out the main ideas and issues surrounding the policy area that were identified in the interview programme.
• identify the emerging themes that need to be tackled.
• highlight conflicting views of the future and expectations of the policy
• highlight the potential trade-offs and choices that policy design will need to address

Welfare

鈥淚 want reassurances that our animal welfare monitoring wasn鈥檛 going to decline because of remote monitoring of animals.鈥�

鈥淥ne thing, this goes back to the link with animal research networks, I think we still don鈥檛 fully understand the use of animal communication in the lab, especially with rodents and how that ties into animal welfare.鈥�

鈥淸A critical issue for the use of animals in science in the future in] [t]he integration of everything to do with ethical monitoring and the ethical wellbeing into some kind of scientific practice.鈥�

鈥淸I think a priority action which should be carried out soon to reach the desired outcome is] [s]etting up of an animal welfare commissioner so that animal welfare is given more priority within the government. And to ensure that there is consistency across government departments.鈥�

Ethics

鈥溾��To try and think about the E than the W of AWERBS. So think more about the ethics. I think it鈥檚 fantastic that the E is in there, but there鈥檚 less understanding in the scientific community about what ethics is compared to welfare.鈥�

鈥淎 key issue is to make sure that there鈥檚 no separation between the considerations about ethics of animal research and the quality of animal research. These issues are completely interdependent and to me they need to be seen as so.鈥�

鈥淲hat happens to experimental design if we put the capacity and needs of animals at the centre鈥�What if we pushed it the other way to design experiments to benefit animals - what would that do to the way we do things. Some more blue skies issues around changing the way we think about experiment design.鈥�

鈥淓thical review to be done before funding applications. It鈥檚 a real problem for AWERBs who are trying to implement local perspective and value and the researchers just sit there and say 鈥榃elcome trust has given me 2m to do this so I don鈥檛 see why I should change this鈥�. Ethical review should be done first because funders don鈥檛 do ethical reviews.鈥�

鈥淎t the moment a lot of people think they are doing ethical review, but what they are actually doing is using the 3Rs. A wider review does use the 3Rs but also a harm benefit analysis and involves a proper scrutiny of benefits and joint up thinking between clinical and preclinical researchers and thinking about if experiments are able to solve problems which need solving.鈥�

Severity

鈥淚 think it鈥檚 time for the project evaluations to take much more account of the level of animal suffering that鈥檚 involved in animal use, and to reject applications that are in the severe category. If the experiment is too severe and the harms to animals are as severe as the severest category, I鈥檇 question how any benefit can be seen as justification.鈥�

鈥溾��I think looking at the types of procedures that are classified as severe and really looking at how those procedures are regulated and justifiable I think would be important to do and particularly therefore being confident about the chances of benefits accruing from those sorts of studies.鈥�

Ending the use of animals in science

鈥淚 would end the use of animals in research in order prevent animals suffering. Clearly that鈥檚 not going to happen overnight, but we believe it could be done in a considered and realistic way that will involve ending the use of animals by the end of 2040 at the latest.鈥�

鈥溾��We would like to see an end to the use of animals in science and the way that we would see that being achieved is being more in step with the public opinion on the use of animals and using these new approach methodologies more.鈥�

鈥淭he desirable outcome is for us full replacement. And the EU directive recital 10 talks about the ultimate goal being full replacement. The UK directive doesn鈥檛 properly reflect that goal.鈥�

Non-animal methods and new approach methodologies

鈥淚 would put replacement front and centre. I would not ban all animal use because I don鈥檛 believe that that would be in the best interests of society as a whole or that society would accept that either.鈥�

鈥淚鈥檇 like to see the reduction and replacement becoming a much more integral part of what we do. I think we need shifts where the process of validating testing and developing replacements runs alongside every experiment we ever do. A key issue for replacement of new techniques is always validation. In my ideal world that validation would be built in and that would help us build the evidence base much faster. But this comes with cost and challenges, but that鈥檚 what I鈥檇 like to see in the future.鈥�

鈥淚n the short term there is some technology available and what is needed is better access to that technology and the associated support to really make that happen, so people can feel confident moving away from these models and looking at other techniques.鈥�

鈥淭rying to really refine. We can have tissues and organoids and mathematical software鈥檚, but for many many things you still need to have the whole animals. Investing money to prove that alternatives are really good and can be validated.鈥�

鈥淩ather than have the concept that we won鈥檛 need to use animals because of computer modelling and cell culture - I think that鈥檚 unrealistic. It鈥檚 more realistic to think we鈥檒l get further with early work using non-animal systems to screen and look for novel mechanisms of action and then move into experiments using animals at a later stage, and that鈥檚 where having really good information on what is the most appropriate model to use in particular circumstances and making sure that previous negative data are all available - if we could make efforts to that, it would help with model selection. I鈥檇 like to see this in the next 25 years.鈥�

鈥淚f I鈥檓 optimistic I鈥檇 scale it back and replace it with more sophisticated, easier to use in vitro models and that has multiple benefits potentially linking back to the first model - it removes animal welfare issues, public perception would be more in favour and it might give more reliable results. It is very important that the public has confidence in computer and in vitro models - otherwise you end up with the same problems with animal testing/GM crops - the public might reject products made using that technology.鈥�

鈥淪cientific journals and their referees should update their policies and recommendations so that when they are considering papers about the use and development of new methodologies, they will not require validation in animals. What we see at the moment is that work that doesn鈥檛 bear any relation to animal research is required to be validated in animals.鈥�

鈥淚 think there鈥檚 going to be more of a trend for replacement models in the future in general, but my own concern about some of the replacement models is how translatable they are. There鈥檚 some fantastic technology out there, but it鈥檚 getting them verified.鈥�

鈥淲hat we would more realistically like to see is a robust and sincere and properly resourced global commitment to replacing animals and non-animal technologies. That would include just not doing an experiment if it fails to pass a harm/benefit analysis. Not doing an experiment if it causes more harm than can be justified or it just isn鈥檛 that important.鈥�

鈥淚f I had absolute authority I would be looking to build consensus and build the evaluation of the alternatives. So not pushing one or the other but looking to say 鈥渨ell we have this existing animal model. Can we develop something else, and how does that alternative spec up?鈥�. That鈥檚 something that is really difficult to fund and support and because nobody thinks it鈥檚 their responsibility to do that evaluation. It doesn鈥檛 get research funding because it鈥檚 not interesting blue sky research. Industry say they don鈥檛 have the money to do it and the companies that are developing the new technology don鈥檛 have the resource to validate and test everything, and if they do they then have to pay for that somehow, which then makes the tech very expensive, which then puts a block to it being rolled out.鈥�

鈥淸If things were to go wrong, I worry about] [f]ailure to innovate in new approach methodologies so the UK falls behind other counties in Europe or the US.鈥�

Funding on non-animal methods and new approach methodologies

鈥淪ome part of your work should be about looking in refinement of alternatives. Some public institutions do this, but for the private, they don鈥檛 do that because it needs money and time and people, so the priority for me would be to encourage and push for looking for alternatives and refinement.鈥�

鈥淚nvestment. Fund the right alternatives and invest in proper validation for those alternatives so no one can say 鈥業 don鈥檛 think this is a real alternative because it鈥檚 not going to work the same鈥欌��.

鈥淲e also think the government should provide proper funding and supportive infrastructure for new approach technologies and should work with a wider range of partners with this and not focus solely on NC3Rs and should engage with existing parliamentary groups working to promote new methodologies such at the APPG for human relevant science.鈥�

鈥淭he thing would be to fund the testing of the alternative systems in the short term. In the long term I would look to fund the training of people that could develop these systems, because I can鈥檛 believe that in the long term we鈥檙e still going to be using a mouse model to understand human disease - because we aren鈥檛 mice! That鈥檚 the direction, but we first have to build consensus and put in the money to train the next generation who are going to drive this forward and develop the new models.鈥�

鈥淸We] want to see total replacement and so the funding and resources that are available and the incentives available and drivers for replacement are all going to be critical issues.鈥�

鈥淔unding bodies for example, they would need to look at the way in which they consider animal testing alternatives in their award process.鈥�

Reduction

鈥淭hat we can gather more information from fewer animals. Things like telemetry modelling, automatic monitoring and micro monitoring. Less invasive so you 鈥渃an gather more information with fewer animals鈥�

鈥淭he future is more data on fewer animals.鈥�

鈥淎 desirable outcome in the future would be that the numbers of animals that are used continues to reduce over time as we find alternatives for the early research and that we are really refining the proof of concept use of animals to smaller numbers but to answer really critical questions where we鈥檝e got the stage where it looks like this is going to work based on computer modelling, cell culture type work, organoid work and so on, and then ultimately it鈥檚 a relatively smaller number of animals that are needed in that key proof of concept study that is really well designed to give as much information as possible from the smallest possible number of animals.鈥�

鈥淪econd desired outcome is to improve the science. Caring about treating animals better and reducing the numbers as much as possible is also conducive to better science that is more planned and conducted with more attention.鈥�

Translatable models

鈥淚 also think critical issues surround at the moment the use of the most appropriate animal model. There鈥檚 a lot of groups out there that maybe aren鈥檛 choosing the right models, so they might need some help鈥︹��

鈥淸A critical issue for the use of animals in science is] [t]he lack of ability for animal research to produce results which reliably relate to humans. Only 41% think animal research can be reliably related to human health (a drop from 46% in recent years).鈥�

鈥淚f you鈥檙e using an animal model that doesn鈥檛 predict human behaviour then really we鈥檝e got to move away from that and if it poorly predicts then we鈥檝e got to think very carefully if there are better alternatives, whether that鈥檚 development of better animal models, or whether there are in vitro models or whether it is possible to develop other human models that are not an animal model.鈥�

鈥淎nother critical issue is translatability. There鈥檚 a translatability and reproducibility crisis in life sciences. There鈥檚 a lot of poor-quality science being done that isn鈥檛 translatable because of the drive to get publications. The drive to publish seems to be getting more acute. There are large numbers of journals. Academic work is determined by the number of papers rather than quality.鈥�

鈥淎 proper systematic review of animal models would also be a really important step. There鈥檚 a stroke model which is widely used despite the fact its translation has been regularly brought into question.鈥�

鈥淚f we鈥檙e not careful we work from the basis of an assumption that isn鈥檛 always justified on the relevance of the animal model and the animal data that is generated for the purpose we are trying to do, which is often more linked into human exposures, be it from the point of view of human disease and for the use of animals for efficacy and safety studies where we know from a pharmaceutical point of view the traditional animal species like rodents and dogs are not always the most relevant and are chosen on pragmatic grounds.鈥�

Repeatability

鈥淩epeatability. You try to do the same experiment twice and the results and different. Sometimes you feel like you have wasted animals and you don鈥檛 understand why. There鈥檚 a general feeling from the scientific community even if have been using animals for a long time, because the information seems to be wrong and the results seem to be unpredictable, so I fear we are not doing the right thing.鈥�

Publishing negative results/dsharing data

鈥溾��The scientists tend to publish only the positive outcomes. It would be good to have a list of research with all the negative results, so you can think - I鈥檓 not going to do this again, because it鈥檚 already been done. At the moment we keep repeating and repeating animals.鈥�

鈥淏eing optimistic, I鈥檇 like to see a requirement for publicly funded research to be published and for this whole positive vs negative studies to be challenged, so that a study that is deemed to be a negative study is deemed as helpful as a positive study. If it鈥檚 published, it means someone else won鈥檛 make the same mistake.鈥�

鈥淚 think sort of making it mandatory to make public the outcomes of research that involves the use of animals under license would be a step that I could support and would address some of the issues over negative results.鈥�

鈥淪haring data from industry is also quite important, so the harms to animals are not repeated to generate the same sort of data.鈥�

鈥淎nother urgent thing is to think more organically about investment in data structures. The UK has already invested a lot, but I don鈥檛 see a systematic approach to animal research as a whole. It鈥檚 divided by domain. It鈥檚 not helping more generally with the question of sharing data more generally to help with animal welfare and reducing animal sacrifice. At the very least there needs to be a signal from government that this is a priority.鈥�

鈥淚 think you should be able to share and have an open agenda for everything that involves a live animal or at least be more accessible than it is鈥�.

鈥淭here鈥檚 a lot of trends towards centralisation鈥�Centralisation can put everything in one place, but can stop people looking outwards. We need to encourage people to exchange ideas between sites and places, both for learning purposes, but also emotional support and resilience.鈥�

Education

鈥淢y main focus internally would be more about better education, making sure that people have access to resources that promote the NC3Rs.鈥�

鈥淚 know the ASC have a successful link with the AWERB, but at the moment, that鈥檚 only open to members that are part of the AWERB. I would make a suggestion to review that to make it a more open resource. Maybe the general public is too much, but sort of animal technicians, early career researchers who might not necessarily be members of AWERB, but there might be some really important researchers in there.鈥�

鈥淲e鈥檙e a world now, not just a country. We can get on an aeroplane and study anywhere. Unless Covid changes it I think we will see a lot more work going overseas.鈥�

鈥溾��More support should be made available to early career researchers who want to focus on human relevant research and focus on an animal free pathway. We think we need to support that next generation of researchers to develop career using non animal methodology.鈥�

鈥淭he key thing here is the availability of the alternatives, both the availability of the alternative models and the expertise to develop those models and to use them and that鈥檚 something which there is a concern that in the UK we鈥檙e not training people with the skillset to be able to drive forward this huge potential growth area.鈥�

鈥淭op of the list is a shift in thinking with respect to animal and non-animal technologies. Greater financial investment and incentives to use these. Greater ability to train people up in changing techniques and researching new techniques. This ties in with the global commitment. The question is largely a matter of will. I think there are large human behaviour factors that come into play here as well. People are locked into current techniques and very resistant to change.鈥�

鈥淭raining for scientists in using and finding and identifying alternative approaches. In my experience of sitting on AWERBS, most scientists just say they searched on the NC3R website when asked if they had looked for alternative.鈥�

鈥淚 would invest very heavily in training and have more imposed training standards. For example if you鈥檙e working on a genetically modified animal, you need to know a bit about genetics. I would make that an obligation.鈥�

Interdisciplinary work

鈥淚 have always been passionate about working closely with other professions - physicists, chemists. We shouldn鈥檛 just be animal professions, we should work with others. It鈥檚 becoming much more multidisciplinary. That鈥檚 possibly a critical issue if you want to go on using animals in choice.鈥�

鈥淪ome investment in cross disciplinary work.鈥�

Public perception

鈥淢y critical issue is the role of public and how they relate to what goes on in animal research and how it鈥檚 regulated.鈥�

鈥淭he public not being listened to. Public opinion is quite nuanced but certainly not in support of a lot of animal testing, and this is not reflected in the amount of animal testing in the UK. People are only moderately in support of animal testing if the animals don鈥檛 suffer and there aren鈥檛 any alternatives.鈥�

鈥溾��There are also issues around public perception of the use of animals and whether the public will be willing to accept products that are associated with animal testing. Obviously it may depend on what it is that you鈥檙e developing - perhaps a sliding scale form developing treatments for cancer - I think the general public would go along with us there as long as they are appropriate and predictive.鈥�

鈥淚 fear in the future that the lobby against eating meat gets rolled into the fact that we鈥檙e using animals in research as an element of the use of animals by society.鈥�

鈥淏attles of public acceptance and increasing societal concern. This couples with the awareness and debate about animal sentience. The level of concern about animal use in research and testing remains pretty high (although not everyone concerned).The concordat doesn鈥檛 seem to have made any difference to the data on animal acceptability.鈥�

鈥淲e need to think about how the public can contribute and take ownership of this issue.鈥�

鈥淭o improve public attention with animal research and to get over the tension in the public landscape between people who are virulently opposed to it and people who practice it.鈥�

COVID-19

鈥淚n terms of deployment of a covid-19 vaccine and the involvement in animals - we have seen a huge increase in people wanting to understand the science. 鈥淭he fact that clinical trials and animals trials were taking place in parallel shows the usual linear process of the past can be disrupted, and with a lot of success.鈥�

鈥淥f course Covid will have an impact but we鈥檙e yet to see what that will be鈥�One of the impacts of Covid I hope will be greater collaboration between different groups working on the same diseases鈥︹��

鈥淎nother critical issue will be demand for animal use created by new epidemics, pandemics, antimicrobial resistance.鈥�

鈥淭he idea of trying to improve public understanding of the role of animal research in the pandemic is urgent. This is the moment in the next year to capitalise on that. This is really important to do now because doing this as soon as possible could have an impact on anti vax and also affiliating better engagement around animal research and better engagement.鈥�

GM animals

鈥淭he other thing is ongoing GM of animal models. I think that鈥檚 a good thing because they can make better scientific models and make them more exact, but I don鈥檛 want them to get too manipulative that that starts alternating their welfare.鈥�

鈥淯se of genetically modified animals. In 2019 the creation and breeding of genetically modified animals accounted for almost half of all procedures on animals.鈥�

鈥淭echniques for the genetic modification of animals have certainly had an impact on the use of animals, I would say in a negative way because interest in GM of animals has led to an increase in the number of animals used. [This outweighs the numbers saved by using alternative measures].鈥�

鈥淭echnology is accelerating faster than we can keep up with鈥�. We don鈥檛 have experience in looking after and how they [the modified animals] are used. This is a big challenge.鈥�

鈥淭he establishment of genome editing which completely changes how we do animal science鈥�

Regulation

鈥淚n terms of regulation, I think there will be greater scientific scrutiny of project applications, partly because it鈥檚 going to be so important to make sure science funding is allocated effectively. There鈥檚 a growing trend of the ASC getting more involved and giving more scientific scrutiny. I鈥檓 not sure why, but I think I have observed it and it will continue.鈥�

鈥淲e鈥檝e got the new electronic licensing system. I think we need investment in regulatory tools, mechanisms, but also prompting the validation of replacement. So building an evidence base for replacements. Replacement should be a much more integral part of what goes forward.鈥�

鈥淎t the risk of creating more work, I鈥檇 like to see licenses be smaller, more focussed and more distributed among individuals. This would give the people running experiments more oversight and improve the communication aspects.鈥�

Government/policy

鈥淒espite the government鈥檚 wish for the UK to become a science superpower, we risk flagging behind other countries if we continue to focus on animal research.鈥�

鈥淭he current approach to the regulation of animal testing is very passive. It is dependent on the development of alternative methods and the desires of researches to test on animals or no test on animals. We would say you are not likely to see a significant reduction in animal testing on that basis. You need more of an active policy driver.鈥�

鈥淚 would stop all use of animals and request then that people started to justify in the current and a forward-looking climate why animal use is essential and why no other way could realise the same information required to make decisions. I would work with a team of future leaders in this space, those who already have a bit of experience - those who have come through PhDs in the range of disciplines and are not wedded to a 鈥榯his is how we do it鈥� and ask them to paint their picture for how they see an animal free research environment in the UK.鈥�

鈥淲e believe the government should develop a road map that commits to phasing out the use of animals in research. We would like there to be clear targets to get to that point to ensure that sufficient progress is being made and a clear date for when the use of animals will end. We think a date of 2040 is realistic for that. We think this is similar to other dates seen in other areas, e.g. commitment to net zero.鈥�

鈥溾��We would like to see the government take up a policy to reduce animal testing that isn鈥檛 solely based on the availability of alternative methods, so it would look at more efficient use of animals, avoiding duplication etc. But in order to inform that policy there will need to be a general review of animal testing where reductions can be made in the short medium and long term.鈥�

鈥溾��It would be really good to see inspectors or ASC thinking about what technologies could be used instead of animal-based research by putting together panels of experts in different disease areas who can properly address the subject of 鈥渋f you didn鈥檛 do it this way, how else would you do it鈥�.

鈥淯KRI should start recording how much of its funding is allocated to human relevant research and conduct proper monitoring of this.鈥�

鈥淚t would also be very helpful to have more joined up thinking between different government departments that regulate and generate animal research.鈥�

鈥溾��The EU ban on cosmetics testing on animals in 2013 had a significant impact on the development of animal free techniques, because it became a business critical issue for the cosmetics industry. That shows that ambitious regulatory action can drive innovation and significant leaps forward in moving away from animals.鈥�

鈥溾��The cosmetic testing ban in the UK and the EU helped focus everyone鈥檚 minds on animal testing and certainly drove the development of alternative methods.鈥�

Transparency

鈥淚鈥檇 like a system where non-technical summaries were made available in a much more timely way and they referred to other ongoing research to avoid duplication. So being optimistic, we need a lot better transparency and better reporting.鈥�

鈥淲e would also like to see ASRU provide greater transparency around how many licenses are approved and rejected each year. We think there should be a more rigorous assessment of each application to determine which non-animal methods could be used instead of animals.鈥�

鈥淥pen access journals. Less conservatism in trying to book publications, so that people who have worked in vitro are not asked to go away and demonstrate the same thing in an animal. So in general, less conservatism.鈥�

鈥淚 think there should be an attempt to understand trends in animal use and funding. So for instance funding allocated in a particular disease area - how much is spent on projects that use animals vs projects that don鈥檛. Transparency around that would be really useful because they would show that reducing animal use is not damaging to the outcomes of the investigation in general.鈥�

鈥淲e would seek a culture change within the Home Office animal scientific procedures unit that would foster a culture of change, and greater transparency. Putting animal protection at the centre of what they do, at the moment it is more steered towards the protection of the rights of researchers.鈥�

Cyber vsecurity

鈥淭hinking about cyber hacks, I鈥檇 be worried about personal security and data breaches, meaning loss of scientific data.鈥�

Generic licences

鈥淢ultiple generic licenses must be addressed to avoid duplication and animal testing that needn鈥檛 happen.鈥�

Veterinary patients

鈥淩esearch on veterinary patients that could inform human medicine and reduce the number of animals used in research and give more appropriate models would be a development that would assist science and reduce the number of experimental animals that are used and the reliance on them without there being too much of a risk of it being abused.鈥�

Ageing population

鈥淎 related concern is (just thinking about wider geopolitical factors) we have an ageing population. Animal models are often used to tackle diseases associated with ageing e.g. dementia, loss of muscle mass.鈥�

Culture

鈥淕lobally, some of these questions are around how we increasingly work collaboratively and that means we鈥檙e working with different guidelines, histories, attitudes - there are some challenging issues on how we set a global standard.鈥�

Brexit

鈥溾��We can now go further than EU legislation, such as the directive on the use of animals in experiments and other pieces of legislation. We can now do better and make improvements for animal welfare.鈥�

鈥淭he idea of tackling animal use field by field and setting realistic targets and milestones and setting out a proper strategy and road map that everyone has to commit to would be a really positive thing to do. Now is the time to do it. The European directorate that regulates use of animals in testing requires it. We don鈥檛 any more because we鈥檙e out of the EU. If the UK could strike out with a credible and properly resourced strategy for ending animal use that would be good.鈥�