Monthly Archives: September 2016

What’s new in the new guidelines for primate research?

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Baboons. Source: Flickr/  Derek Keats

Scientific purposes: all activities conducted with the aim of acquiring, developing or demonstrating knowledge or techniques in all areas of science, including teaching, field trials, environmental studies, research (including the creation and breeding of a new animal line where the impact on animal wellbeing is unknown or uncertain), diagnosis, product testing and the production of biological products.

Under the Australian federal system, responsibility for animal welfare rests with the states, and all states and territories have incorporated the Code – not always to its full extent – under their animal welfare or animal research laws. This is acknowledged in the new “Principles and guidelines for the care and use of non-human primates for scientific purposes”:

On some issues, this document represents an aspirational standard which may not currently be supported by state and territory legislation and in which case the state and territory legislation takes precedence.

Positive changes (compared to the previous 2003 policy)

Let’s start with the positives in the new principles and guidelines. By that I mean specifications or requirements that are positive from an animal welfare perspective and that were not included in the previous policy.

Great apes (gorillas, orang-utans, chimpanzees and bonobos) are now afforded greater protection. The document notes that no great apes are held in Australia for scientific purposes.

The only great apes held in Australia are in zoological collections for conservation breeding purposes.

And for entertainment purposes, I would like to add.

Now, the use of great apes for scientific purposes in Australia is permitted only when their use:

i) will not have any appreciable negative impact on the animals involved, e.g. observational studies, activities already being undertaken for management or veterinary purposes

ii) will potentially benefit the individual animal and/or their species.

There hasn’t been any research using great apes for decades in Australia. While this is a positive step, it will not impact any current research. For other primates, hardly anything has changed since the previous policy.

But back to the positives:

Non-human primates that are imported from overseas must be captive bred and must be accompanied by documentation to certify their captive-bred status.

It’s prohibited to tear primates from their wild habitats. Still, young animals are torn from their mothers, and import from breeding facilities overseas involves stress during transport.

Further, the new guidelines specify that retirement at conclusion of the research must be considered. The previous policy noted that the existing breeding facilities “will not generally accept animals that have been used for scientific purposes. In most cases, euthanasia will be the only option.” Does this mean that Australian primate breeding facilities accept now animals after they have been used in research?

Provisions for non-human primates at the conclusion of their use must take into account their long-term welfare. Retirement must be considered as an option if suitable in terms of the health and temperament of the animal, and space and resources are available at a facility that can meet their species-specific physical, social and behavioural needs.

But does the NHMRC anything to ensure rehoming options are available? To my knowledge, the answer is “no”.

According to the new guidelines, breeding facilities are not supposed to breed more animals than are needed for research (Australia has breeding colonies for macaques, marmosets and baboons):

Procedures must be in place at all non-human primate breeding facilities to ensure that the breeding programs are matched to the demand for animals, and to avoid or minimise the production of excess animals. Investigators must discuss their requirements for non-human primates with the management of the supply facility early in the planning stages for the project to assist with management of breeding programs.

The previous policy noted that investigators performing experiments overseas under the auspices of an Australian institution obtain approval from an Australian animal ethics committee, and that this may include the delegation of authority to inspect sites and monitor projects at remote sites. The new guidelines state explicitly that undertaking the experiments overseas must not be a way to bypass the Code:

If a project involving the use of non-human primates is to be conducted in another country, Clauses 2.6.9- 2.6.14 of the Code must be upheld. The conduct of a project in another country should not be used as a mechanism for avoiding compliance with Code.

The new guidelines include a section on reward-based training. It is proposed that using positive reinforcement techniques should be considered part of experimental designs for three reasons:

i) assisting in captive management, by seeking the animal’s compliance with routine husbandry and behavioural training

ii) improving the animal’s welfare, by training to facilitate the conduct of routine procedures without the need for chemical restraint

iii) ensuring the quality of the scientific data collected.

The new requirement for “training methods … not be based on approaches that involve punishment such as pain or psychologically distressing stimuli” appears to be primarily motivated by the intent to improve compliance of the captive animal.

Positive changes (compared to the draft guidelines)

The draft guidelines had proposed that the requirement of notifying the NHMRC’s Animal Welfare Committee (AWC) of primate imports be dropped because importing animals is subject to Commonwealth regulation. However, this proposed change did not go ahead:

The institution should ensure that the AWC of NHMRC is notified of the importation of non-human primates after approval from the institutional AEC has been obtained. For NHMRC funded activities, this requirement is mandatory.

In the section concerned with transport of animals, the following sentence was added:

Transport conditions must be designed to minimise stress (see Clauses 3.2.5–3.2.8 of the Code).

But shouldn’t all conditions – in regard to housing, transport and experiments – be designed to minimise stress?

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Macaques. Source: Flickr/ Franx’

Serious problems remain

While non-human primates are our closest relatives and genetically the most similar to us humans, does experimenting on these animals really benefit humans? Aren’t there better, more human-relevant research methods? And more importantly, is it morally defensible to subject these highly sentient and cognitive animals to the stress, pain and often death after experimentation?

Overall, the new guidelines do not represent compelling progress. A few baby steps may lead toward slightly improved animal welfare, but the guidelines are still steeped in an outdated paradigm. Even within this paradigm, we can decry the lack of transparency in animal research, non-existent or insignificant benefits for humans and animals, and the NHMRC and its funded institutions’ lack of taking responsibility for the fate of non-human primates after completion of research projects. The NHMRC funds primate breeding colonies, and funding a sanctuary for “retired” primates should be its responsibility, too.

So, what’s new in the new guidelines for non-human primates? Hardly anything that reduces pain and suffering and improves the lives of our closest relatives who are used for scientific purposes.

The primates used by medical research are sensitive and intelligent beings. We owe them a decent life, not confinement, suffering and untimely death in the lab.

Disclosure

Together with Sir David Attenborough, Dr Jane Goodall and 19 other scientists, primatologists and animal welfare experts I signed an open letter “Testing on non-human primates in neuroscience research is no longer justifiable”, supporting Cruelty Free International in raising concerns about the controversial use of non-human primates in neuroscience research.

 

Further reading  

National Health and Medical Research Council. (2016). Principles and guidelines for the care and use of non-human primates for scientific purposes. Canberra: National Health and Medical Research Council, Australian Government.

Helen Marston, CEO of Humane Research Australia, has commented on the new guidelines on her blog: “New guidelines for primate research will not protect our closest relatives”.

Jeory, T., & Stone, J. (2016, 8 September). David Attenborough calls for end to ‘cruel’ brain tests on primates by neuroscientists. Exclusive: Sir David joins 21 signatories to an open letter published in The Independent. The Independent.

Lidbury, B. A. (2016). Medical science has moved on: it’s time to end primate testing. Australian Doctor(17 March).

Academic articles:

Bailey, J., & Taylor, K. (2009). The SCHER report on non-human primate research – biased and deeply flawed. Alternatives to laboratory animals : ATLA, 37(4), 427-435.

Bailey, J., & Taylor, K. (2016). Non-human primates in neuroscience research: The case against its scientific necessity. Alternatives to Laboratory Animals – ATLA, 44(1).

Bailey, J., Thew, M., & Balls, M. (2015). Predicting human drug toxicity and safety via animal tests: can any one species predict drug toxicity in any other, and do monkeys help? Alternatives to Laboratory Animals, 43(6), 393-403.

Burm, S. M., Prins, J. B., Langermans, J., & Bajramovic, J. J. (2014). Alternative methods for the use of non-human primates in biomedical research. Altex, 31(4), 520-529.

Chandrasekera, P. C., & Pippin, J. J. (2015). The human subject: an integrative animal model for 21st century heart failure research. American Journal of Translational Research, 7(9), 1636-1647.

Gilbert, S., Kaebnick, G. E., & Murray, T. H. (2012). Animal research ethics. Evolving views and practices: The Hastings Center.

Gordon, N., & Langley, G. (2008). Replacing primates in medical research. An expert report by: Dr Hadwen Trust, FRAME, St Andrew Animal Fund.

Greek, R., Hansen, L. A., & Menache, A. (2011). An analysis of the Bateson Review of research using nonhuman primates. Medicolegal and Bioethics, 1, 3-22.

Taylor, K. (2010). Reporting the implementation of the Three Rs in European primate and mouse research papers: are we making progress? Alternatives to laboratory animals : ATLA, 38(6), 495-517.

Wendler, D. (2014). Should protections for research with humans who cannot consent apply to research with nonhuman primates? Theoretical Medicine and Bioethics, 35(2), 157-173.

 

 

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How severe is too severe?

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Source: Flickr/ Creativ92

In the last post I wrote about the large number of animals used for scientific purposes – just under 7 million animals in Australia in 2014. In this post, I will look at the impact on the animals, or rather what we know about the pain and suffering imposed on animals used in research and teaching.

Australia maintains no national collection of animal use data, but Humane Research Australia (HRA) collects annual statistics from the states and makes them available online. The latest available statistics are from 2014 and only available from four states (Victoria, New South Wales, Tasmania, Western Australia). These statistics tell us about the numbers of animals used by state, by species, by project purpose and by procedure severity.

Most animals are subjected to what researchers describe as observation or minor interventions. But in Australia in 2014 there were nearly 190,000 animals who were subjected to “major physiological challenge”, and 26,397 suffered “death as endpoint” – and these are only the numbers we know from four states. South Australia, Queensland, the Australian Capital Territory and the Northern Territory do not provide animal use data.

Death as an endpoint does not mean any type of death. Here is the definition from the National Health and Medical Research Council’s Australian code for the care and use of animals for scientific purposes. 8th Edition:

Death as an endpoint: when the death of an animal is the deliberate measure used for evaluating biological or chemical processes, responses or effects—that is, the investigator will not intervene to kill the animal humanely before death occurs in the course of a scientific activity. ‘Death as an endpoint’ does not include the death of an animal by natural causes or accidents, or the humane killing of an animal as planned in a project or because of the condition of the animal.

In other words, death as an endpoint means that a study involves some form of experiment where the animal is observed until death occurs, without providing pain relief.

For example, the LD50 test involves groups of animals being exposed to increasing doses of a toxic substance or infection with a disease to determine the dose required to kill 50% of the animals. The animals do not receive any pain relief. In contrast, the term “humane endpoint” means a procedure whose endpoint is death, but the animal’s pain or distress is alleviated.

A “major physiological challenge” might involve

  •   major infection
  •   major phenotypic modification
  •    oncogenesis without pain alleviation
  •    arthritis studies with no pain alleviation
  •    uncontrolled metabolic disease
  •    isolation or environmental deprivation for extended periods
  •    monoclonal antibody raising in mice

(University of New England. You can find examples for other severity categories on this web page as well. Other Australian universities provide similar guidance for categorising the severity of experimental procedures.)

But even some of the procedures categorised as “mild” or “minor” don’t sound mild or minor to me. For example, the European Commission published a report by an Expert working group on severity classification of scientific procedures performed on animals that includes in the “mild” category procedures such as gavage (force-feeding), induction of tumours, intravenous administration of substances and short-term (<24 hours) restraint in metabolic cages. Metabolic cages allow for accurate monitoring of waste production (urine, faeces).

Besides, why would metabolic cages be used if the stress experienced in these cages has been found to compromise research results? A study published in PLOS ONE found that the condition of mice in these cages “cannot be considered representative of a normal physiology”. Further, the authors of the study wrote:

“Similarly elevated HPA axis activity, persisting for as long as three weeks, is rarely encountered in literature; in our laboratory we have not previously encountered a stress response of this magnitude. The overall physiology of these animals must be considered severely affected, making them a poor model for most experimental studies.”

If you want to see how mice are force-fed, this video shows mouse oral gavage training.

 

The production of genetically modified animals is increasing. They are mainly mice and rats who have been genetically manipulated to “model” different types of diseases. Chicken, pigs, sheep, cattle have been genetically altered to increase their production of meat, milk or eggs.

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GFP transgenic mice. Source: Wikimedia Commons/ Ingrid Moen, Charlotte Jevne, Jian Wang, Karl-Henning Kalland, Martha Chekenya, Lars A Akslen, Linda Sleire, Per Ø Enger, Rolf K Reed, Anne M Øyan and Linda EB Stuhr: Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation. In: BMC Cancer. 2012, 12:21.

The production of GM animals involves high numbers of “wastage”. Up to 54 animals die for the creation of a single genetically modified animal. This is how AnimalAid describes the process:

In order to create a new strain of transgenic mice, young females are injected with powerful hormones to make them superovulate. After mating, they are killed to extract the embryos, which are microinjected with the foreign DNA. These altered embryos are then surgically implanted into many surrogate mothers, who have also been hormone-injected to assist implantation and who will later be killed before or after giving birth. Many of the resulting baby mice are malformed and die before or shortly after birth. The surviving babies have to be tested to see if they have the new gene: this can be done by saliva or faecal sampling but is more often conducted by cutting off the tips of their tails or a notch from their ears.

Only 1-10% of the baby mice will have successfully incorporated the new gene. The other 90-99% will be destroyed as ‘failures’. This translates into so much killing that many of the animal technicians responsible for killing all the ‘waste’ animals find it traumatic and are left feeling ‘physically and emotionally exhausted’. While hundreds of animals are sacrificed to produce a new transgenic ‘model’, life for the survivors can be even worse than for the failures.

AnimalAid is an animal rights organisation from whom we might expect a critical view of the genetic engineering of animals. But academics broadly in support of this practice offer words of caution as well. The following is from an article in the Canadian Veterinary Journal:

Although genetic engineering may provide substantial benefits in areas such as biomedical science and food production, the creation and use of genetically engineered animals not only challenge the Three Rs principles, but may also raise ethical issues that go beyond considerations of animal health, animal welfare, and the Three Rs, opening up issues relating to animal integrity and/or dignity. Consequently, even if animal welfare can be satisfactorily safeguarded, intrinsic ethical concerns about the genetic engineering of animals may be cause enough to restrict certain types of genetically engineered animals from reaching their intended commercial application. Given the complexity of views regarding genetic engineering, it is valuable to involve all stakeholders in discussions about the applications of this technology.

Animals in labs suffer not only from experimental procedures, but also from life in the laboratory. They might live in barren cages, be isolated from other animals or live in overcrowded cages, never experience sunshine, or live in bright light contrary to their natural habits. Daily life in the lab – with fear, boredom and confinement – is stressful enough without experimental interventions that bring additional suffering.

The standard housing temperatures for mice in labs, for example, are much lower than is comfortable for the mice. Some researchers have argued that this causes cold stress which has implications for tumour growth and immunity.

Most of the procedures that go beyond observation only would be considered animal cruelty if they were performed outside the lab and without the prospect of improving the health and wellbeing of the animal (for example, surgery in a veterinary clinic). Given that all this is done as part of an ever increasing industry without much, if any, benefit for either human or non-human animals, it is morally wrong and bad science.