Exploring the limitations of animal research regulations

Last month, PhD student, Margarita Kalamara joined FRAME for a three-month internship as part of the Professional Internship for PhD Students (PIPS) scheme.

In this informative blog, Margarita shares what she has learnt so far about the laws and processes regulating animal research in the UK. She reflects on her own experiences of non-regulated animal procedures and discusses the case for more transparency and precaution in current regulations.

I have been a researcher, doing my PhD in the field of Molecular Microbiology, for the last three years and it has been great. I love my research area, the collaborative environment, the variability in what my days look like and learning new things every day. I am also someone that cares deeply about the welfare of animals and this is something that has always been a big part of who I am. These two identities, being someone that loves research and someone that loves animals, have at times felt conflicting. My biggest fear before starting an undergraduate course in biological sciences was that I would have to work on animals so I very carefully selected my modules and research topics in a way that would allow me to avoid that. I have found that complete lack of animal use is very hard to achieve in research at the moment.

The world of scientific research is so heavily built on the use of animals that, even as someone working with soil bacteria on a topic that has no direct correlation to the understanding of the human body or human diseases, it has been very hard to avoid using materials (antibodies in my case) that have been extracted from animals, leading to their death. Although in many cases alternatives to such reagents do exist, they are not as widely used as they should be, and animal derived reagents and methods do still tend to be the standard practice. This contradiction between my values and the world I have chosen to work in is what led me to work with FRAME for my internship. I strongly believe that moving away from the use of animals as research models is something that the scientific community needs to prioritise, both for the sake of research and animal welfare.

During my time in a research environment, I have become aware that the use of live animals is very tightly regulated. I have however also seen animal use taking place, directly or indirectly, for purposes that are not regulated. I was curious to explore the boundaries between what is considered animal work and requires tight regulation and what does involve the use of animals without being regulated. This led me to look into the laws and processes surrounding the use of animals in research a bit more. I have summarised what I have learnt in my time so far as a FRAME intern below.

Overview of licensing required for animal research

The UK Home Office publishes statistics on the use of animals in scientific procedures every year. Statistics on the numbers of animals used in scientific research are of great interest to multiple parties and rightly so. Having this information publicly available and released yearly allows people from various fields (academia, industry, public bodies, charities, interested members of the public) to assess whether we are making progress in terms of reduction of the numbers of animals used in experiments, as well as to get detailed information on the severity of pain experienced by animals, the species used and the fields of research that these animals are used for. These reports are part of a very tightly regulated process. Researchers that intend to work on animals need to go through this process to check whether there are alternatives to animal models that can be used for their work, that the minimum numbers of animals possible are used and that the highest levels of welfare possible are provided. But what does this process look like in practice?

Three levels of licensing are required to conduct research using live protected animals. Firstly, the place where the work will be carried out (e.g., a university) must hold an establishment licence.  To hold an establishment licence, the place must have appropriate facilities (as detailed in the Code of Practice) and have trained staff who can provide the animals with the appropriate levels of care 365 days a year. They are also required to have certain “Named People” in place (that are named on the establishment licence).  These are the Named Veterinary Surgeon (NVS), Named Training and Competency Officer (NTCO), Named Animal Care and Welfare Officer (NACWO), Named Information Officer (NIO), and Named Person Responsible for Compliance (NPRC).

Secondly, each project of work needs to be covered by a licence. A project licence holder is usually an experienced researcher who is responsible for the overall project. They must provide a detailed document with the proposed research they plan to carry out and justify why animals need to be used for this work over non-animal alternatives.  They must highlight the numbers of animals they estimate to use, and what the animals likely experience will be as a result of being part of the project (i.e., the predicted extent to which they will suffer).  All of this information is important to enable a “harm-benefit” analysis to be performed to help decide if the use of animals for the project is justifiable.  The project licence applicant also needs to provide evidence of good experimental design and undergo specific accredited training and pass exams to be allowed to apply to the Home Office for a licence. The project proposal is reviewed by the local Animal Welfare Ethical Review Body (AWERB) committee prior to the Home Office. Only if it is approved by both parties can the work involving animals be conducted.

The third level of licensing applies to the person that will be physically carrying out the work and this is called a “personal licence.” For someone to become a personal licence holder, they must complete accredited training on the legislation regulating animal research, ethics, and on the biology and handling of the species they intend to work with. If all of this goes ahead and the researchers are given permission to work on animals by the Home Office, they will need to record all information about the species, numbers and severity of suffering caused to the animals they used. That information is reported back to the Home Office to be included in the annual statistics.

The legislation that regulates the use of animals in scientific experiments is the Animals (Scientific Procedures) Act 1986 or ASPA. This Act lays out the rules for the use of “protected animals” in “regulated procedures” (1). Under these definitions and licensing systems, the Home Office report for 2019, which is the latest one currently available, shows that 3.4 million procedures were conducted on live animals in the UK (2). This figure however is not the whole story as the regulated use of animals is only part of the picture…

What animal research is actually regulated?

As mentioned above, the Act covers the use of “protected animals” used in “regulated procedures.” A “protected animal” is any vertebrate (an animal with a backbone) or a cephalopod (e.g., octopus). The most commonly used animals in research are mice, fish and rats, which account for 93% of animals used in scientific procedures in 2019 (2). Other animals used in research that are subject to even tighter regulations (referred to as “specially protected animals”) include cats, dogs, horses and non-human primates and these account for 1% of live animals used in procedures in 2019 (2). This definition of “protected animals” means that any invertebrate animal other than cephalopods have no protection under UK law when used in scientific procedures (this is discussed further below). Therefore, animals such as flies and worms are used in very high numbers in research without the need for any  , reporting or provision of any level of welfare.

The fact that the Act does not offer protection to all animals is not its only limitation. A “regulated procedure” is defined as “any procedure applied to a protected animal for an experimental or other scientific purpose, or for an educational purpose, that may have the effect of causing an animal pain, suffering, distress or lasting harm equivalent to, or higher than, that caused by the introduction of a needle in accordance with good veterinary practice.” The breeding of animals that are genetically modified is also classed as a regulated procedure, even if the animals themselves are only used for breeding purposes so that their offspring can be used in further scientific experiments (1). Paradoxically, the killing of an animal is not necessarily considered a regulated procedure. This means that for a researcher to use the organs of a protected animal in their experiments, for example, they do not need to have a licence, provided that this animal is not genetically modified and is killed in a specific way that is considered “humane” (what are considered humane ways of killing is covered by Schedule 1 of ASPA) (1).

Protected animals that are not covered by the three-level licensing system and are not recorded in the annual statistics include any “genetically normal wild-type” animals that were bred and either died or were killed without being used in experimental procedures (3). These may be animals that are “surplus” in the supply and demand chain of laboratory animals so they are euthanised, or animals killed to provide tissues for in vitro and ex vivo experiments.

What is the actual total number of animals used for scientific purposes?

The fact is, we don’t know how many animals were killed in the name of science in the last year, because of the limitations of what is covered in the annual statistics and regulated by ASPA. Until recently there was no requirement for these numbers to ever be published. There is however now a new EU requirement that annual numbers of all animals bred and killed for scientific purposes are published every 5 years (3) and the first one in the UK was published in 2017. In that year – on top of the 3.72 million animals that were used in regulated procedures as defined by the Act (some of which were used in more than one procedure, the total number of procedures was 3.79 million) (4) – an additional 1.81 million non-genetically modified animals were bred for scientific purposes but were killed or died without being used in regulated procedures. In total, 5.53 million protected animals were used in science in that year (3). This means that an additional 32.7% of animals were used for science on top of the usual annual statistics we are used to seeing. Estimating the total number of animals, including all invertebrates used in research, is nearly impossible as there is no record of the invertebrates used due to the fact that they are not covered by ASPA.

Regulations on the use of invertebrates

The lack of protection of invertebrates other than cephalopods in scientific procedures is in part due to the assumption that these animals cannot feel pain, i.e. they are not sentient. Whether or not this is true is unclear and difficult to evaluate and so far, little research has been devoted to determining it. Part of the problem is the difficulty in defining pain in animals, especially for those that lack the brain regions that are associated with pain perception in humans (5, 6).

Many studies have however shown responses that indicate pain perception in invertebrates. For example, a study in 2015 shows that crustaceans, crabs in specific, showed responses that indicated pain when they were electrically shocked (7). Their responses included changes in behaviour (e.g. avoidance of locations associated with being electrically shocked) and an increase in the production of stress hormones, which is very similar to responses of vertebrates in pain (7). The gaps in our knowledge of invertebrate pain perception are reflected by the differences in the (very limited) protection these animals receive by legislation in different countries. For example, the use of some crustaceans is somewhat regulated in a few countries (Norway, Switzerland, New Zealand, Austria, regions of Germany, Italy) but not in the UK (8). The protection of cephalopods, the only invertebrates protected in the UK, is a relatively recent phenomenon, as it was only introduced in 2013. Prior to this, only one species of cephalopods was protected, and all others could be used with no regulation. The reason for this change was the increased scientific evidence of their ability to experience pain, suffering, distress and lasting harm.

Reflections on the limitations of regulated animal work

Why is it that, instead of acting on the side of caution and protecting the welfare of all animals when the scientific evidence surrounding sentience (the ability to experience feelings) is not solid, we assume their lack of sentience and provide them with no protection? Shouldn’t it be the other way around? One consequence of invertebrates not having protection is that scientists can use them in vast numbers, even if their use is not necessary. For example, in my first two weeks as an undergraduate student in biological sciences, when I had no scientific research or laboratory skills and was not addressing any important scientific question, I was given live crustaceans (brine shrimps) to work on. The experiment was to determine the concentration of ethanol needed to kill half of the animals that were submerged in the solution (a value known as the LC₅₀, used to determine toxicity). While such an experiment can be educational, many of the skills this session intended to provide students with (e.g., concentration calculations, use of pipettes) could have been acquired using many other methods that did not involve the use of animals.

The concept of toxicology testing could have been demonstrated either in theory or could have been done experimentally using in vitro (e.g. (9)) or in silico (e.g. (10)) methods when students were more experienced. In addition to the waste of animal lives, carrying out experiments on “lower” animals in education promotes the idea that using animals is standard practice, and not that it should be the last resort when designing and carrying out scientific experiments. Shouldn’t there be some ethical consideration and justification for using any live animal to ensure they are not used unnecessarily?

Another troubling aspect of the limitations of regulated animal work is that the annual statistics don’t include all protected animals that were used for scientific purposes, as mentioned above. The fact that a protected animal is killed in a way that is considered humane should not mean that its use does not need to be justified and proven necessary to the same extent that regulated uses of animals are.

Not having the complete numbers included in the annual statistics reports is misleading, as these are numbers that many interested parties refer to when examining animal use in research. There is an increasing focus on transparency surrounding the use of animals. Examples of such efforts include organisations such as Understanding Animal Research, which encourages universities and companies that work with animals to report their numbers, and the Animal Study Registry, which urges scientists to pre-register all animal work in databases. The fact that openness is promoted is fantastic and I think that making the annual information on animal use more comprehensive and representative of the total number of animals used in research would greatly contribute to the cause.

References

1. Animals (Scientific Procedures) Act 1986 [Available from: https://www.legislation.gov.uk/ukpga/1986/14/contents.
2. Annual Statistics of Scientific Procedures on Living Animals Great Britain 2019 [Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/901224/annual-statistics-scientific-procedures-living-animals-2019.pdf.
3. Additional statistics on breeding and genotyping of animals for scientific procedures, Great Britain 2017 [Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/754408/breeding-genotyping-animals-scientific-procedures-2017-hosb2718.pdf.
4. Annual Statistics of Scientific Procedures on Living Animals Great Britain 2017: Home Office; [Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/724611/annual-statistics-scientific-procedures-living-animals-2017.pdf.
5. Elwood RW. Pain and Suffering in Invertebrates? Ilar J. 2011;52(2):175-84.
6. Sneddon LU, Elwood RW, Adamo SA, Leach MC. Defining and assessing animal pain. Anim Behav. 2014;97:201-12.
7. Elwood RW, Adams L. Electric shock causes physiological stress responses in shore crabs, consistent with prediction of pain. Biol Letters. 2015;11(11).
8. Rowe A. Should Scientific Research Involving Decapod Crustaceans Require Ethical Review? J Agr Environ Ethic. 2018;31(5):625-34.
9. Liu J, Mansouri K, Judson RS, Martin MT, Hong HX, Chen MJ, et al. Predicting Hepatotoxicity Using ToxCast in Vitro Bioactivity and Chemical Structure. Chem Res Toxicol. 2015;28(4):738-51.
10. Raies AB, Bajic VB. In silico toxicology: computational methods for the prediction of chemical toxicity. Wires Comput Mol Sci. 2016;6(2):147-72.

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