July 2011

Primate experiments scrutinised

Andrew Knight

SEE ALSO the August 15th Veterinary Times article

In 2010, British scientists conducted scientific procedures on more than 2,600 monkeys, many of whom were used more than once (1). Invasive research on non-human primates (NHPs) is rendered particularly ethically problematic by their advanced cognitive, social and related abilities. It is also particularly expensive. Accordingly, in 2006 a UK working group recommended that the major organisations funding such research should undertake a systematic review of its outcomes.

In July 2011, the subsequent Review of Research Using Non-Human Primates was publicly released (2). It was commissioned by major funders of such NHP research in the UK, namely the Biotechnology and Biological Sciences Research Council, the Medical Research Council and the Wellcome Trust. It examined all such all NHP research funded by these organisations from 1997 to 2006 inclusive.

The Review Panel considered the scientific importance of each research project, the probability of medical and public benefit, and the likelihood of animal suffering. They asserted that in many cases the use of NHPs was justifiable, but were concerned about approximately 9% of research programmes from which no clear scientific, medical or social benefit had emerged. However, for three important reasons the proportion of cases that were ethically justifiable was probably far lower than 91%.

1. Animal welfare impacts
Firstly, the review Panel appears to have systematically underestimated the animal welfare impacts of the research it assessed. Of 31 neuroscience studies examined for example, half were assessed as having imposed a high welfare impact on the animals used. Disturbingly high though this is, unfortunately it appears to have been an underestimate. Studies involving the surgical creation of experimental lesions (that is, tissue or organ damage) were not assessed as having a high welfare impact, unless ‘significant and lasting impairments to the monkeys’ welfare’ resulted. Therefore, surgery causing significant damage that was not long-lasting would probably have received a moderate impact rating, even such procedures may still severely impact animal welfare.

Additionally, studies conducted under terminal anaesthesia received a low welfare impact rating. This may have been technically correct from a strict welfare perspective, if minimal suffering resulted. However, if makes no allowance at all for the serious moral issues raised by killing. Laboratory animals are not simply expendable. Their deaths should not have been so lightly dismissed simply because they were killed under anaesthesia. The intrinsic value of their lives should have been included in the moral calculus.

2. Importance of experimental outcomes
Secondly, the review Panel appears to have considered animal experiments that contribute to scientific advancements in general to be of similar importance to those providing medical benefits. However, nearly all experiments contribute to the advancement of science. Therefore, they would all be ethically justifiable, if they were cost-free. But of course they are not. The very substantial costs incurred by invasive primate experimentation include animal welfare costs, the consumption of considerable financial and scientific resources, and adverse impacts on human patients and consumers affected by any misleading results. Therefore, experiments that simply contribute to the advancement of science, without providing any credible medical benefit — which comprise a substantial proportion of the 91% condoned by the Review Panel — should not have been assessed as ethically justifiable.

The Panel stated that, ‘In most cases… little direct evidence was available of actual medical benefit in the form of changes in clinical practice or new treatments.’ And, ‘This contrasts with the emphatic public statements about the medical benefits of NHP research made by some of the funding bodies and by grant applicants’.

They recommended that: ‘In their public engagement, the funders and researchers should avoid overstating and generalising the medical benefit of NHP research, since this cannot be substantiated in many cases.’ And, ‘It is important that the justifications offered for research projects are soundly based and demonstrable. Health benefits should only be claimed when their potential is real.’

3. Withholding of information
Thirdly, among 72 questionnaires, three researchers did not respond or declined to participate. Five more could not be contacted. Hence, fully 11% were not included in this survey. As the Panel noted, ‘It is reasonable to expect the recipients of public or charitable funding to be held accountable on issues of public interest and therefore this attitude was regarded as unacceptable’. One can only speculate as to why some researchers chose not to provide information about the animal welfare impacts and scientific benefits arising from their work.

While providing important insights into NHP research, this review cannot be considered conclusive. For several reasons noted in their report, this review could not be considered a systematic review in the formal sense. It has also not yet been published in a peer-reviewed scientific journal.

Formal systematic reviews
In The Costs and Benefits of Animal Experiments (3), I reviewed 30 systematic reviews assessing the contributions to human healthcare of animal experiments. All of these have been successfully published in the peer-reviewed scientific literature. The evidence provided by these reviews is remarkably consistent. When considering costs and benefits overall one cannot reasonably conclude that the benefits accruing to human patients or consumers, or to those motivated by scientific curiosity or profit, exceed the costs incurred by animals subjected to scientific procedures. On the contrary, the evidence indicates that actual human benefit is rarely — if ever — sufficient to justify such costs. Those costs are greatest when NHPs are used.

The Panel did, however, provide several commendable recommendations, which animal researchers working with all species would do well to comply with. For example, it recommended that ‘where grants were awarded on the promise of human health benefits, the grant-holders should provide evidence of interest in and use by the medical and biopharmaceutical sectors,’ to ensure their claims can be verified.

It also noted the disproportionate failure to published negative results, and asserted that researchers have a moral obligation to publish results — even if negative — in order to prevent work being repeated unnecessarily.

The full report can be found here.

1. Home Office (2011). Statistics of Scientific Procedures on Living Animals: Great Britain 2010. London, UK: The Stationery Office.
2. Bateson P et al. (2011). Review of Research Using Non-Human Primates. Biotechnology and Biological Sciences Research Council, Medical Research Council and Wellcome Trust, London. http://www.bbsrc.ac.uk/web/FILES/Reviews/review-research-using-nhps.pdf, accessed 29 Jul. 2011.
3. Knight A (2011). The Costs and Benefits of Animal Experiments. Basingstoke, England: Palgrave Macmillan.

2010 laboratory animal use statistics for Great Britain: welfare implications

Andrew Knight

In July the 2010 laboratory animal use statistics for Great Britain were released by the Home Office. Just over 3.7 million scientific procedures using animals were commenced in 2010, an increase of 3% (105,000) compared with the previous year. 3.6 million animals were used for the first time in procedures started in 2010, an increase of 3% (101,000). The number of procedures is always slightly higher than animal numbers, due to re-use of some animals.

Laboratory animal numbers have steadily risen over the last decade. There were 1.0 million more procedures than in 2000 (37%), mostly accounted for by the use of an additional 921,000 animals in breeding procedures to produce genetically altered animals. Such animals include those whose genomes have been artificially modified during the initial stages (GM animals), rather than through natural breeding or mutation, as well as animals with harmful genetic mutations. The maintenance and expansion of all genetically altered strains requires further breeding, however. Excluding such breeding procedures, there were still 4% (89,000) more procedures than in 2000.

Consistent with these trends, the 2010 increases when compared to 2009 were largely due to greater use of genetically altered animals. The increase in procedures using GM animals was 6% (88,000), and the increase in procedures using animals with harmful genetic mutations was 4% (17,000). Most of these increases were attributable to an 8% (73,000) increase in the use of GM mice in breeding procedures.

Within the 3.7 million total procedures in 2010, 1.6 million procedures (43%) used GM animals and 400,000 procedures (11%) used animals with harmful genetic mutations. Procedures using such genetically altered animals exceeded those using normal animals for the second year in a row. Genetically normal animals accounted for the remaining 1.7 million procedures (virtually the same level as in 2010), slightly less than half (46%) of the 3.7 million total.

The welfare implications of such heavy reliance on GM animals are disturbing. Particularly in the initial stages, the production of GM strains involves surgical procedures and significant physiological challenges. It is also an inherently inefficient process, frequently resulting in a high proportion of discarded animals, with the welfare of the survivors more likely to be adversely affected than for non-GM strains.

The use of non-human primates rose by 10% (425, to a total of 4,688) when compared to 2009. The advanced emotional, psychological and social capacities of primates markedly increase their risks of suffering within laboratory environments and procedures. They have advanced capacities to understand and remember that certain people, tools or procedures are likely to cause pain and distress, and their ability to anticipate future aversive experiences is likely to compound the distress such events may cause.

Sixty nine per cent of all procedures (2.6 million) did not utilise any form of anaesthesia. This was an increase of 6% (154,000) compared to 2009, and represented the greatest number of procedures conducted without anaesthesia since records commenced in 1988. From 1988 to 2010, the proportion of procedures conducted without anaesthesia fluctuated from approximately 59 to 69%. Analgesic use was not reported.

Whilst anaesthetic and analgesic use undoubtedly alters normal physiology, claims that such alterations are sufficiently important to hypotheses under investigation to warrant their exclusion, require careful scrutiny. Despite increasing recognition that pain relief improves both animal welfare and research quality – via minimisation of pain-related physiological, psychological and behavioural distortions – pain monitoring and analgesic provision remains less than optimal within many research protocols.

The steady increases in the use of GM animals and those with harmful mutations, of non-human primates, and of procedures conducted without any form of anaesthesia, several of which are now at record highs, demonstrate that neither the British government nor its research community are serious about reducing the use of animals, or of procedures that pose the greatest threats to animal welfare.