The use of genetically altered non-human primates in research

Today (1 September) is International Primate Day – an event founded by Animal Defenders International that aims to highlight the threats to, and abuses of, apes and monkeys.

To mark the event, FRAME outlines the use of non-human primates (NHPs) in biomedical research, the ethical issues surrounding the use of gene editing and the potential for researchers to apply for a license to use genetically altered, non-human primates in UK research.

Non-human primates in research

NHPs are our closest living relatives, and therefore have historically been used as models to study human physiology and diseases. The majority of NHPs used in biomedical research are either marmosets or rhesus macaques. In 2020, 2393 procedures were carried out on primates in the UK.

Over the past two decades, there has been significant scientific interest in the use of NHPs for human neurological conditions, such as Parkinson’s disease. The genetic similarity of NHPs to humans, and their complex brains, mean that many scientists view them as being the best analogy for humans. Neuroscience is a particularly difficult area for the successful development and implementation of alternative, non-animal research methods, and therefore one of the most intractable to change due to the sheer complexity of the human brain, which we are not currently able to replicate in the lab (in vitro). Given the prevalence of neurological diseases across society, the wave of support for research using NHPs is – sadly – currently unlikely to abate.

In addition, advances in genetic engineering technology – techniques used to modify DNA within a cell or organism – over the past decade has made the development of genetically altered NHPs much more achievable. This includes the development of the CRISPR/Cas system, which has opened the door to generating genetically modified NHP models for basic neuroscience and brain disorders research.

To find out more about the limitations of using genetically altered animals to investigate human conditions, read our blog: The yin and yang of genome editing.

Concerningly, some researchers see a ‘bright and promising future for the generation of transgenic and gene-edited non-human primates,’ despite the limitations of, and suffering induced by, these techniques.

Gene editing: limitations and ethical issues

FRAME strongly believes that the differences between humans and monkeys are significant when it comes to disease models and responses to drugs. Indeed, in 2005, FRAME submitted key evidence to a working group on ‘The use of non-human primates in research’ chaired by Sir David Weatherall, which emphasises that the use of NHPs for fundamental research or for regulatory testing fails to take into account the fact that, although NHPs are anatomically and physiologically similar to humans, they are not necessarily relevant models for studies on human disease or human physiology. FRAME believes we have a duty to ensure that these animals are not used without overwhelming evidence that they are the only suitable and relevant models for use in work of undeniable significance. Not only is this important for research outcomes and human health, but it is also crucial to reduce animal suffering. The high level of sentience and social character possessed by NHPs makes them particularly susceptible to suffering in captivity, particularly in a research environment, meaning they should not be used except under exceptional circumstances, if ever.

A number of serious animal welfare concerns arise from the generation and use of genetically altered NHPs. A key paper recently published in the Journal of Applied Animal Ethics Research groups these concerns into five broad categories – the welfare impacts of the procedures to generate the genetically altered monkeys, the mother-infant separation, the genetic modification itself, the procedures used to study the genetically altered monkeys, and the housing in the laboratory. The paper also highlights the large number of NHPs required to undergo regulated procedures in order to produce a handful of offspring carrying the genetic mutation that can be studied experimentally, as well as the fact NHP species have long, slow life histories, small litters, much slower reproduction rates than mice, and are expensive to purchase, transport and maintain in the laboratory.

At FRAME, we are concerned that the availability of gene editing tools will potentially increase the number of NHPs used in biomedical research. We stand by the view that, despite the apparent similarities between NHPs and humans, there are substantial species differences highlighted by research, meaning that the conditions under investigation will be triggered differently and manifest differently compared to humans. As discussed, not only are there significant ethical concerns, but there are also scientific ones. The time and funding would be much better spent in developing human-based models for study.

The potential for NHP gene editing in the UK

Whilst there has not yet been a license application submitted to the Home Office for work on genetically altered NHPs in the UK, we believe it is only a matter of time until this happens, given the growth of this research in other countries. Significantly, this issue was raised at a recent multi-stakeholder workshop as part of the Animals in Science Committee (ASC) Futures Working Group attended by FRAME. The ASC Futures Working Group was established to identify areas or trends on the horizon which may impact policies on animal use in science and on which the ASC should be advising the Secretary of State.

In the workshop, with representation from the full spectrum of views on the use of animals in science, concerns were raised about the ethical issues associated with an application for such research and that it would require further consideration in terms of the harm-benefit analysis (compared to other types of applications). FRAME agrees with this view, and will continue to be involved in the conversation and speak out against the genetic alteration of NHP species.

Whilst genome editing in primates is now achievable, its use to produce animal models of human disease is a retrograde step. Use of genome editing in human cell and organ models must be the priority for human relevant scientific outcomes. These techniques are already showing promise, with complex neural activity seen in lab-grown organoids derived from human stem cells, in a recent research study. With targeted funding and concerted effort, these models could be developed more quickly.

Find out more about the use of genetically altered animals in the UK in this long-read.