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The long-tailed grey rat lies unconscious on the sterile bench.
Anaesthetised for the surgical procedure, toxins are injected into a small number of specific cells on one side of its brain. The toxins will impair the rat’s waking movements in ways akin to that of a human Parkinson’s patient.
"We need to record brain activity while movements are being performed," Assoc Prof Louise Parr-Brownlie explains.
"Therefore, we must do experiments on whole animals.
"We use a rat model of Parkinson’s disease to identify new brain targets and to test new ways to stimulate the brain.
"Ultimately, our research is focused on finding new treatment strategies for Parkinson’s patients."
Use of the brain stimulation probes will cause no pain; the brain — rat or human — has no pain receptors.
But Prof Parr-Brownlie admits that every time she operates on an animal she feels confronted by what she is doing.
"I have to think through the benefit that can come from it ... At the end, we do have to harvest the brain to know where we’ve been stimulating or recording. So, there is a cost of an animal’s life.
"But I guess I’ve also been reflecting on the cost if we didn’t do research."
From this week these experiments and other research using animals will relocate from the former animal laboratory atop the Hercus Building and various other spots across campus to the Eccles Building, the University of Otago’s new, $50 million, animal research facility.
Three years behind schedule, the purpose-built, five storey, 4000sqm building, in Great King St, opened on Tuesday with a deliberate lack of fanfare.
The $50 million has been spent to ensure the facility is world class.
There are 18 dedicated experimental rooms; an imaging suite with a state of the art bio-imager, a multiphoton microscope and an irradiation machine; plus, multiple dissection and tissue harvest labs — in all, 88 bookable spaces that will be used by health and science researchers from throughout the university.
Care of animals, and protecting the university’s investment in multi-year research, has been foremost in the building’s design. It has been built to withstand a one-in-500-year earthquake. It has its own back-up generator, its own steam supply, four days worth of water and automatic feeding systems, Prof Richard Blaikie, who overseas the university’s research, says.
"I was in Christchurch during the earthquakes ... The animal colonies in some areas could not be safely maintained and you had to make really, really tough ethical decisions," the deputy vice-chancellor says.
Security is gold-standard.
Animal cages can be individually ventilated. Procedure rooms can play piped background music and have lighting with programmable dawn and dusk settings. Humidity, 50%, and temperature, variable but about 21degC, is set for the comfort of the animals, not the humans.
And the university staff who use animals in research are proud of the work they do, the advances in knowledge they are making and the improvements to which they are contributing.
Parkinson’s, cancer, pest control, diabetes, stroke, heart conditions and infertility are among pressing health conditions and environmental issues being tackled.
Prof Greg Anderson and his team are researching how the brain controls fertility. Infertility affects about 20% of human couples but is poorly understood, the neuroendocrinologist says. Studying how the whole body — brain, pituitary gland, testicles or ovaries — interacts as a reproductive system means a whole and live subject is needed. They use mice and rats. The team has discovered the role the brain plays, monitoring the leptin hormone to decide whether the body has enough reserves of energy to support reproduction. They have also uncovered a key group of brain cells that respond to stress by suppressing fertility.
Their work is basic science that in time is likely to lead to new clinical therapies to tackle infertility in humans, create contraceptives with fewer side-effects and suppress fertility in pest species.
"If we could control the fertility of stoats and possums, it would be a much more humane way to achieve our goal of a predator-controlled New Zealand by 2050," Prof Anderson says.
The new research facility has those who will use it in a state of excitement.
One researcher, whose team’s breakthroughs have shown the brain plays a pivotal role in causing (and therefore possibly treating) polycystic ovary syndrome, describes the Eccles Building as "amazing".
"It means the work we do will be as good as it can be for researchers and animals," she says.
Despite the pride and excitement, the building opening was unheralded out of concern about possible reactions to what is done to animals there.
On Thursday, the Ministry of Primary Industries released the latest figures on the numbers of animals used for research, testing and teaching (RTT) in New Zealand. They show that in 2019 there were 131 organisations, including seven universities, that used a combined total of 315,574 animals for RTT. An additional 136,679 animals were recorded as being bred for RTT but not used and then killed. During 2019, the University of Otago used 35,076 animals for RTT across its Dunedin, Christchurch and Wellington campuses. The lion’s share, 33,064, were used in Dunedin.
That year a further 67,641 University of Otago animals were bred and killed without being used, 65,048 of them in Dunedin.
The university’s own figures reveal that last year the total number of animals bred for use in Dunedin reduced 23% to 76,077 animals. There were 54,509 mice, 11,989 rats, 7855 aquatic species, 1454 reptiles, 234 amphibia, 32 hedgehogs and four rabbits. At the end of their use, 2498 were released to the wild, re-homed or returned to owners, including the 32 hedgehogs and 1279 of the reptiles.
Of those bred for scientific use in Dunedin last year, 54,900, or 72%, were killed without being used — 40,754 mice, 9291 rats, 4851 fish and four amphibia.
Tara Jackson, who is the Christchurch-based director of the New Zealand Anti-Vivisection Society, describes the 2020 Dunedin figures as a "sad indicator" of what she believes is a university that has "no interest in improving their science and embracing new technologies".
"Our researchers are well aware that working with animals is a privilege," he says.
"Every animal under our care, whether they become part of a study or not, is counted.
"We are committed to reducing, refining and replacing the use of animals involved in our research, and it’s very pleasing to see that commitment reflected in the statistics; some 22,000 fewer animals were involved in research in 2020 compared with 2019."
Only rats, mice and xenopus (sub-Saharan frogs) are housed in the Eccles Building.
MPI requires that each animal used in New Zealand for research, testing or teaching is given an individual welfare impact grading. The grades range from no impact or virtually no impact (A) for "manipulations that cause no stress or pain or virtually no stress or pain" to very high impact (E) for "manipulations of high impact and long duration". Killing an animal humanely is considered low impact. Examples of very high impact manipulations include surgery without anaesthetic, causing animals to die by poisoning or repeatedly applying extremely harmful stimuli from which the animal cannot escape.
At Otago last year, the outcomes for 39 research animals (eight reptiles and 31 mice) were graded high impact or very high impact. Of those, 19 mice were graded high impact because of the cumulative effect of manipulations, none of which involved pain. For the other 20, they were upgraded to high impact or very high impact due to unforeseen circumstances, often unrelated to the experiments.
An Otago researcher, who asked to be anonymous after hearing of colleagues in the United Kingdom being threatened, studies how changes in calcium within cells can lead to heart disease and Alzheimer’s.
The work has already led to drugs that are helping prevent arrhythmia, particularly in children with hereditary forms of the disease.
To do this research a beating heart is required. The researcher and his team use mice genetically engineered at Australian National University to develop heart arrhythmia when under stress.
The mice are anaesthetised and placed on a warm mat. Acupuncture needles are inserted under the skin of each limb and the mouse is injected with adrenaline to mimic exercise. Echocardiograph and ECG tests are used to measure heart function and rhythm.
"With all the experiments, once they’ve been anaesthetised, the animal never wakes up, one way or another," he says.
In New Zealand, all research, testing and teaching involving animals has to be in line with the Animal Welfare Act 1999. No animal manipulations can be carried out without prior approval of an animal ethics committee, whose members must include at least three independent members — a vet nominated by the New Zealand Veterinary Association, a nominee of the Royal New Zealand Society for the Prevention of Cruelty to Animals and a representative of a local territorial authority.
Those provisions underline how contentious an area this is.
"Ethical dilemmas arise when there are harms to animals," the University of Otago bioethicist says. "Because, generally speaking, we shouldn’t harm animals."
The researchers themselves certainly do not shy away from it.
"There is a dilemma. There always should be a dilemma. You’re using an animal," one researcher says.
"With humans there can be a consent process ... That’s not the same with animals."
Conundrums inevitably produce debate.
Opposition to the use of animals in research at Otago is long standing. The new facility, despite university researchers saying it will mean better research requiring fewer animals, will do little to change that.
Jackson’s animal rights campaign against the new facility stretches back to 2016 when she fronted a protest by more than 75 people at the building site.
"It is morally wrong to exploit animals," Jackson says.
She argues that due to the many differences between species, animal experiments are not a reliable way to predict human responses to diseases and drugs.
"In 2004, the FDA [United States’ Federal Drug Administration] estimated that 92% of drugs that pass preclinical tests, including ‘pivotal’ animal tests, fail to proceed to the market," she says.
"More recent analysis suggests that this failure rate has increased and is almost 96%. The main reasons for this failure are a lack of efficacy and safety issues, which weren't apparent in animal tests."
Instead of trying to justify existing research, she believes the focus should be on developing non-harmful approaches.
"There are a lot more non-animal-based research and testing methods available for cosmetic testing than there are for medical research and, put simply, that’s because cosmetics are largely driven by consumer pressure whereas the pharmaceutical industry is less controlled by public opinion."
Jackson is not opposed to using existing medicines developed using animal research and rejects any suggestion of hypocrisy.
"I encourage people not to fall into the trap of being guilted into blindly supporting something (animal testing) because they have no other option but to partake in it," she says. "It would be like advocating for the ongoing use of fossil fuels just because you drive a car."
Some people have taken their opposition to animal research and testing to greater extremes. Some of the Otago researchers spoken to by The Weekend Mix have experienced abuse and witnessed bomb threats when working overseas.
Jackson is opposed to the use of intimidating or threatening behaviour.
"We do not condone violence or abuse of any kind, verbal or otherwise, and we advocate respect for all beings, including humans.
"This is something I feel really passionately about as I don’t think fear will create long-term change."
In response to Jackson’s critique of the validity of using animal models for tackling human diseases, Prof Blaikie maintains animal models continue to be essential for understanding underlying causes of human disease or behaviour, but he says the use of humans plays a big part when it comes to clinical trials.
“It is through this combination ... that the international research community helps to develop new medical interventions, such as the current successful Covid-19 vaccines,” Prof Blaikie says.
At one level, Dr King says, the use is ethical, is justified, if attempts have been made to reduce, refine or replace the use of animals but a harmful use is still needed in order to benefit humans.
Sitting behind that answer, however, is a much deeper discussion about whether humans can rightfully claim this preferential treatment.
Dr King says we can. To try to illuminate our privileged position, he gives three examples.
Humans are unique in their ability to think about how they treat others, including animals, and the environment.
"So, we are the decision-makers on whom obligations fall ... We find ourselves in the position of having to make moral choices," Dr King says.
"If we decide not to do animal research any more, that will have all sorts of consequences. It will be a choice that we would be held to account for.
"In that sense, we are at the top of the totem pole."
Secondly, more is lost when a human dies than when, for example, a rat dies because there is more capacity for welfare in a human life.
"The life of a normal adult human can go for 80 to 100 years. If it’s a good life, that can be a lot of years of goodness. Whereas the maximum life of a rat or mouse is many times less than that."
Thirdly, humans have a sense of themselves; they can make plans and have aspirations for their lives that span many years.
"If you get killed before you’ve made good on your plans, you are much worse off when you die because it frustrates all those desires, that good you wanted to achieve.
"If [a rat], is killed, there isn’t the same frustration of future plans and interests.
"In the case of a rat, it does matter, but it just matters less."
The surprise, given how firmly the opposing views are held, is that those against and those justifying the use of animals in research are both looking forward to such similar futures.
"Our work is based on the desire to make the world a better place for both animals and humans," Jackson says.
"We need to advance medical research to prevent and stop the pain and suffering of many humans; we just believe that there is a quicker and kinder way of reaching this goal than using animals."
"A modern, caring society needs to be constantly refining the way it uses animals," Prof Anderson says.
"I am hopeful for a time when animal research is hardly ever needed."