Baby monkeys used in invasive brain lesion experiments


Warner, CE, Kwan, WC, Wright, D, Johnston, LA, Egan, GF & Bourne, JA, 2015. 'Preservation of Vision by the Pulvinar following Early-Life Primary Visual Cortex Lesions', Current Biology, 25: 424-434.

Associated Institutions: Monash University


The Experiment

This experiment used 9 neonatal (baby) marmoset monkeys (average age of 13.1 days old), 5 adult marmosets (1-3 years old), and 8 adult control marmosets (>2 years old), in an attempt to investigate age-dependent effects on the visual system circuitry following a lesion of the primary visual cortex in the brain.

Initially, both the neonatal and adult marmosets had lesions induced in their primary visual cortex. To do so, the marmosets were anaesthetised, administered with antibiotics, and then placed into a stereotaxic frame.

Examples of stereotaxic frames (image sources at bottom of page):

 
 Figure 1. A rhesus macaque monkey positioned in a stereotaxic frame
 
 Figure 2. A marmoset in a stereotaxic frame

After the marmosets were stabilised, an incision was made following the midline of the skull, and a craniotomy was made, exposing the primary visual cortex of the brain. The dura (the tough outermost membrane enveloping the brain) was then surgically removed, and then the operculum of the primary visual cortex was removed using a blunt scalpel. Sterile absorbable gelatin foam was used to stop bleeding.

Once the flow of blood was stopped, a piece of gelatin film was placed over the surface and the dura was repositioned over the lesion region. Bone fragment was then replaced and affixed with tissue adhesive, and the scalp was sutured. In order to prevent cerebral edema (accumulation of excessive fluid in the brain), the marmosets were given glucose saline, analgesic and dexamethasone (a type of steroid medication).

The marmosets were then recovered in humidicribs before returning to their cages. They were subsequently allowed to ‘recover’ for around 12 months.

Four of the baby marmosets, two of the adult marmosets with lesions induced, and two of the control adult marmosets (with no lesions) were anaesthetised and placed in a stereotaxic frame, and, after receiving an injection directly in the right eyeball, they underwent another craniotomy and had tracer injected into their cortex.

After 14 days, the eight marmosets that received injections were dark adapted for 16 hours, then exposed for 45 minutes of ambient light directly over their cage, before being killed by an overdose of pentobarbitone. They were then transcardially perfused, and cerebral tissues were removed. Brain sections were then examined using immunohistochemistry analysis.

Two of the neonatal lesion marmosets, two adult lesion marmosets, and two control marmosets also had their brains examined through MRI analysis.

All marmosets were killed for the experiment and brain section 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).

Given the research paper itself identifies previous human trials investigating functional outcomes of damage to the primary visual cortex at different ages, 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 (APP1002051 and APP1042893) to researcher J Bourne, as well as by 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 'Preservation of Vision by the Pulvinar following Early-Life Primary Visual Cortex Lesions', Warner et al. (2015), in which researchers at Monash University describe an experiment where both adult and baby marmosets were subjected to surgery, induced with brain lesions, had injections made into their eyeballs and 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 outcomes of damage to the primary visual cortex at different ages, 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 - Roopnariane et al 2012, 'Quadrature RF Coil for In Vivo Brain MRI of a Macaque Monkey in a Stereotaxic Head Frame', Concepts Magn Reson Part B Magn Reson Eng, 41B(1): 22–27.

Figure 2 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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