Imma Perfetto
Cosmos science journalist
This article contains subject matter some readers may find distressing. 1800RESPECT is Australia’s national domestic, family, and sexual violence counselling, information and support service. If you or someone you know is experiencing domestic or family violence, you can call 1800RESPECT on 1800 737 732, text 0458 737 732 or visit the website for online chat and video call services.
A US nonprofit advocacy group of 17,000 physicians has called into question the ethics of an Australian study which assessed the impact of combined mild traumatic brain injury and non-fatal strangulation in rats, saying there was “no clinical or scientific need” for the experiments.
The study, led by researchers at Monash University, was published in the journal Brain, Behaviour, and Immunity in January.
Its aim was to provide insights into knowledge gaps around the detection, pathophysiology, and consequences of the combination of mild traumatic brain injury (mTBI) and strangulation as a result of intimate partner violence.
In a March 24 letter to the editors of the journal, The Physicians Committee for Responsible Medicine requested the immediate retraction of the article, claiming that it “violates key ethical principles, including those outlines in the journal’s guidelines on the ethical and acceptable use of animals in research.”
The “knowledge gaps”
According to the Australian Institute of Health and Welfare, 1 in 4 women and 1 in 14 men in Australia have experienced physical and/or sexual violence from an intimate partner.
“Intimate partner violence is a complex, serious and widespread public health issue, resulting in profound and lifelong impacts on a person’s health, wellbeing and livelihood,” a Monash University spokesperson told Cosmos.
“Physical attacks during intimate partner violence often include strangulation resulting in brain injury which can frequently go unreported and therefore untreated.”
Non-fatal strangulation reduces blood and oxygen supply to the brain and can damage tissues and blood vessels, potentially worsening brain injuries. In their study, the Australian researchers claim that, to date, no studies have investigated the blood biomarkers or self-reported symptoms after these combined injuries.
The first part of the study involved a human clinical trial of a small group of intimate partner violence (IPV) patients – 4 women and 2 men – who presented to an emergency department within 72 hours of a mTBI, 40% of whom also experienced strangulation. The study also included control groups of patients who did not have concussion or whose concussion was due to other factors.
Participants completed a post-concussion symptoms questionnaire and provided blood samples to test for levels of absolute glial fibrillary acidic protein (GFAP) and neurofilament light (NFL), established blood biomarkers for brain injury.
The researchers found that post-concussion symptoms were more severe, and blood biomarkers were elevated, in IPV patients. The primary purpose of this trial was to evaluate the feasibility of conducting research in a crisis setting following IPV, and the authors write that it “provides a foundation for larger more comprehensive studies”.
However, the Monash University spokesperson said that “due to the complexity and sensitivity of investigating intimate partner violence in a clinical setting, and the inability to analyse brain tissue in living human patients, researchers created an animal model to identify and validate blood biomarkers that could detect hidden cases of brain injury.”
The first rat model of non-fatal strangulation
The second part of the study involved experiments on 109 juvenile female rats aged 6-7 weeks, chosen because “intimate partner violence exposure often occurs in adolescence and early adulthood in women”.
The rats were divided into 4 experimental groups. The researchers placed 2 groups on a board with their heads positioned against a “helmet-like metal plate”. A 50mg weight was then propelled against the opposite side of the plate, causing a mTBI. The rats were immediately administered anaesthetic and analgesic before regaining consciousness.
Researchers then placed 1 group on a “non-fatal strangulation (NFS) device”, where a silicone band and attached 680g weight hung from and applied pressure to the rat’s neck for 90 seconds. Afterwards, some of the rats had to be resuscitated with oxygen and chest massage when they did not spontaneously breathe within 5 seconds.
Another group of rats underwent strangulation alone, while another underwent sham procedures which did not inflict injury.
All rats were then tested to assess neuromotor functions 10 minutes after injury and were either assigned 2 hours or 1 week of recovery time, before undergoing further behavioural, blood marker, and pathophysiological tests.
At the end of this period, the rats were euthanised and their brains dissected to examine changes in gene expression related to neuroinflammation, hypoxia (low oxygen), and vascular health.
The study concluded that the combination of head trauma and strangulation exacerbated functional deficits and neuropathophysiology in rats. Higher levels of blood biomarkers were also seen, with NFL elevated at 2hrs and 1-week post-injury, and GFAP increased at 2hrs post injury.
Animal-based research in Australia
Annually, its estimated that more than 192 million animals are used in scientific procedures worldwide, though methods such as organoid technologies, computer modelling, and clinical studies are becoming increasingly used as alternatives to animal models.
Institutes in Australia that receive research funding from the National Health and Medical Research Council (NHMRC) must comply with the Australian code for the care and use of animals for scientific purposes, which states that: “the use of animals for scientific purposes must have scientific or educational merit; must aim to benefit humans, animals or the environment; and must be conducted with integrity.
“When animals are used, the number of animals involved must be minimised, the wellbeing of the animals must be supported, and harm, including pain and distress, in those animals must be avoided or minimised,” it states.
“Where the aim(s) of the project involves the animals experiencing pain and distress that will not be alleviated, the planned endpoint of the project must be as early as feasible to avoid or minimise pain and distress in the animals.”
The Code also requires the application of the 3 Rs: the Replacement of animals with other methods; the Reduction in the number of animals used; and the Refinement of techniques used to minimise the adverse impact on animals.
According to the Code, a judgement as to whether a proposed use of animals is ethically acceptable must be based on these principles while also balancing “whether the potential effects on the wellbeing of the animals involved is justified by the potential benefits.”
“Monash University adheres to the rigorous regulations and relevant codes of practice, and ethical considerations in all research involving animals,” said the spokesperson for Monash University.
“The use of any animal is a necessity accompanied by moral and legal obligations for their care. We support our researchers to understand and meet their ethical obligations and legal responsibilities, underpinned by a transparent and efficient ethics review process.”
In the state of Victoria, where this research was undertaken, the use of animals for scientific procedures is permitted and regulated under Part 3 of the Prevention of Cruelty to Animals Act 1986 and Part 5 of the Prevention of Cruelty to Animals Regulations 2019.
Institutions wishing to conduct scientific procedures with animals must apply for a licence through Animal Welfare Victoria (AWV) and nominate an Animal Ethics Committee (AEC) to oversee it.
This project’s animal procedures were reviewed and approved by an Alfred Research Alliance Animal Ethics Committee. The Alfred Research Alliance is a collaborative research partnership of 8 independent organisations, including Monash University.
“To be considered for approval, research designs that involve the use of animals for scientific purposes must comply with the Australian code,” a spokesperson for the Alfred Research Alliance told Cosmos.
“The Alfred Research Alliance Animal Ethics Committees ensure that scientific and educational activity involving animals is underpinned by principles that protect their wellbeing and quality of life, and that it is also ethically acceptable and justifiable.
“The committees balance whether the potential impact on the wellbeing of animals involved is justified by the potential benefits to human health.
“Following a rigorous review process, the relevant animal ethics committee determined that this research application was compliant with the national code and approved it.”
Were these experiments justified?
But The Physicians Committee claims that the development of an animal model for IPV-related brain injury is scientifically unnecessary and ethically problematic.
The research was “unjustifiable,” they wrote, because well-established, evidence-based protocols for diagnosing and managing non-fatal strangulation and traumatic brain injury in humans already exist.
If further research was deemed warranted, they said, it should have been done using human-specific models.
“Subjecting animals to inflicted trauma and hypoxia to mimic intimate partner violence-related injuries does not contribute meaningful insights that cannot already be obtained from clinical research on human patients,” they write.
“The publication by Sun et al. included data from emergency department patients, demonstrating that such research is feasible without animals.
“By publishing and disseminating research that involves inflicting traumatic brain injury and non-fatal strangulation on animals, the journal risks normalising such abusive methodologies and providing what will be taken for approval for similar experiments in the future.
“This not only emboldens the current researchers to continue their harmful studies but also sets a precedent for other investigators to replicate or expand upon these methods under the guise of scientific inquiry.”
