Researchers deliberately induce brain injury in baby and adult marmoset monkeys


Teo, L & Bourne, JA 2014. 'A Reproducible and Translatable Model of Focal Ischemia in the Visual Cortex of Infant and Adult Marmoset Monkeys', Brain Pathology, 24: 459-474.


Associated Institutions: The Australian Regenerative Medicine Institute, Monash University


The Experiment

This experiment used 3 neonatal (baby) marmoset monkeys (14 days old), and 5 adult marmosets (>18 months old), in an attempt at developing a pediatric and adult non-human primate "model" of cortical focal ischemia (insufficient blood flow to the brain). All 8 of the marmosets were obtained from the National Nonhuman Primate Breeding and Research Facility (Monash University).

Both the neonatal and adult marmosets had focal ischemic injury induced in the primary visual cortex of the brain.

In order to induce brain injury, the marmosets were first anaesthetised, and had their heads shaved and swabbed with an antibiotic solution. Adults were also administered with antibiotics and dexamethasone (a steroid medication) to prevent cerebral edema (excess accumulation of fluid in the brain). They were then placed in a stereotaxic frame.

 
Figure 1. Example of a marmoset in a stereotaxic frame (source at bottom of page)

A craniotomy was performed using a burr drill. The outermost membrane enveloping the brain (the dura) was then thinned using a diamond knife. A microsyringe was positioned proximal to the calcarine artery. Intracortical injections (within the cortex) were then administered to induce injury to the primary visual cortex, with the needle remaining in place for a further 2 minutes after the injections were given.

Continuous video monitoring of the surface of the cortex was performed to determine the extent of the injury caused.

1-2 hours after the injections, the exposed surface of the cortex was covered with a piece of soluble film, and the dura membrane was replaced over the film. The craniotomy was then replaced and secured with tissue adhesive, and the skin was sutured.

The marmosets underwent post-surgical MRI scans under anesthestia, 1, 7, 14, and 21 days after the brain injury was induced. Some of the marmosets also underwent dextran administration via injection into a vein in the leg, while under anesthesia.

After the nominated "recovery periods" (up to 21 days), all of the marmosets were killed via an overdose of pentobarbitone sodium. Cerebral tissues were dissected and preserved for immunohistochemistry analysis.

Relevance to Humans

There are major anatomical, genetic, dietetic, environmental, toxic, and immune differences between animals - including marmosets - and humans(1), making them inappropriate for use in studying human brain injury and human disease. Many studies and systematic reviews show that there is discordance between animal and human studies, and that animal ‘models’ fail to mimic clinical disease adequately.(2)(3).

In fact, the publication itself notes that "the majority of experimental neuroprotective therapies discovered and trialed in rodents are not translated to clinical use. All too often, promising results from studies undertaken in rodent models are not realised when applied clinically" and that "the large infarct zones observed in most rodent and some NHP MCAO [non-human primate middle cerebral artery occlusion] models are not representative of survivable strokes in humans, raising the issue of translatable clinical relevance" (Teo & Bourne 2014, 459). The publication also concluded that their own non-human primate "model" "may not directly mimic physiological etiologies observed in the clinic" (Teo & Bourne 2014, 472).

Given the research paper itself identifies previous human trials investigating functional visual outcomes of stroke (Teo & Bourne 2014, 472), one must seriously question why the researchers engaged in this study did not utilise a human sample to conduct research in this area, and/or use a battery of advanced human biology-based methods of research, in order for results to be directly relevant to human health outcomes.

Funding

The experiment was funded through National Health and Medical Research Council of Australia (NHMRC) project grants to researcher J Bourne, and a National Stroke Foundation grant and South Melbourne Alliance for Research and Technology scholarship to L Teo. The experiment was also supported via grants from the State Government of Victoria and the Australian Government to the Australian Regenerative Medicine Institute.

What You Can Do

Please use the form below to tell Monash University how disappointed you are with their use of animals in this experiment. You can use the text provided or compose your own (remember polite personalised messages carry more weight).

Your message will be sent via email to the Executive Assistant of the Vice-Chancellor of Monash University.








Message
Use the text below or change it compose your own message.

Dear Professor Gardner,

I am writing with regard to a publication titled 'A Reproducible and Translatable Model of Focal Ischemia in the Visual Cortex of Infant and Adult Marmoset Monkeys', Teo & Bourne (2014), in which researchers at Monash University describe an experiment where both adult and baby marmosets were subjected to surgery, had focal ischemic injury induced in the primary visual cortex of their brains, and were then killed.

I am deeply disappointed that such unethical research, involving very invasive procedures, is being conducted by your university.

It is becoming increasingly acknowledged that animals are poorly predictive of human outcomes and are therefore not good models on which to base scientific research.

There are major anatomical, genetic, dietetic, environmental, toxic, and immune differences between animals - including marmosets - and humans(1), making them inappropriate for use in studying human brain injury and human disease. Many studies and systematic reviews show that there is discordance between animal and human studies, and that animal 'models' fail to mimic clinical disease adequately.(2)(3).

Given the research paper itself identifies previous human trials investigating functional visual outcomes of stroke, one must seriously question why the researchers engaged in this study did not utilise a human sample to conduct research in this area, and/or use a battery of advanced human biology-based methods of research, in order for results to be directly relevant to human health outcomes.

I am therefore concerned that Monash University is allowing such experiments to occur, rather than encouraging the development and use of innovative technologies and human-biology based methods of research, in order to enable direct study of human conditions. I look forward to receiving your comments on this.

I would also be grateful if you could please provide details on how this research was justified by the animal ethics committee which approved it, and what alternatives were considered to the use of these healthy baby and adult marmosets – as is required by the code of practice – and look forward to your reply.

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References:

(1) Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I; on behalf of the Reviewing Animal Trials Systematically Group. 2004. ‘Where is the evidence that animal research benefits humans?’, BMJ, 328, 514-7.

(2) Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P, et al. 2007. ‘Comparison of treatment effects between animal experiments and clinical trials: systemic review’, BMJ, 334:197.

(3) Van der Worp H, Howells DV, Sena ES, Porritt MJ, Rewell S, O''Collins V, et al. 2010. ‘Can animal models of disease reliably inform human studies?’, PLoS Med.


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References

References:

(1) Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I; on behalf of the Reviewing Animal Trials Systematically Group. 2004. ‘Where is the evidence that animal research benefits humans?’, BMJ, 328, 514-7.

(2) Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P, et al. 2007. ‘Comparison of treatment effects between animal experiments and clinical trials: systemic review’, BMJ, 334:197.

(3) Van der Worp H, Howells DV, Sena ES, Porritt MJ, Rewell S, O''Collins V, et al. 2010. ‘Can animal models of disease reliably inform human studies?’, PLoS Med.

Image Sources:

Figure 1 source - Yun, J, Ahn, J & Kang, B 2015, 'Modeling Parkinson’s disease in the common marmoset (Callithrix jacchus): overview of models, methods, and animal care', Lab Anim Res, 31(4): 155-165.

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