How much do you have in common with a mouse? The question isn’t as silly as it sounds: mice are the most commonly used animal for laboratory testing to find new treatments.
Chances are that when you take a pill, apply an ointment, or receive a vaccine, it has been tested on a simple mouse.
The perceived wisdom has always been that what is good for the mouse will probably also be good for us humans – and it is better that initial and potentially risky testing for new treatments be conducted on an animal rather than a human.
And there is no doubt that the use of animals has advanced medical science.
For example, it was through work in dogs that the hormone insulin was first identified in 1921 – a huge breakthrough for people with diabetes and one that has saved millions of lives.
Work on mice and monkeys led to the development of polio vaccines, which have helped prevent an estimated 20 million cases of paralysis in children since 1988 alone.
Animals have also been crucial in tests of semaglutide (the active ingredient in slimming shots Wegovy and Ozempic), with rodent experiments confirming its weight loss potential.
And much of our understanding of cancer and how cancer is treated has been supported by animal research.
“Without this research we would not have discovered that cancer is not one disease, but that there are more than 200 different types, and that of the 300 cancer drugs, about 250 are the result of animal research,” says Chris Magee, head of policy at Understanding Animal Research, an organization that wants to explain why animals are used in research.
There were 2.68 million ‘scientific procedures’ involving live animals in Britain in 2023, according to Home Office figures.
While 95 percent of these used mice, fish, birds or rats, 1.2 percent used cats, dogs, horses and ‘non-human primates’ (i.e. monkeys).
Most procedures involved “basic research” into the nervous system, immune system and cancer – but 45 percent involved breeding genetically modified animals for research.
The perceived wisdom has always been that what is good for the mouse will probably also be good for us humans (file image)
Animal lovers may understandably shudder and the question is: does this really contribute to the advancement of medical science?
Some even argue that animal testing sometimes holds back the development of new treatments. That’s because potential therapies that fail safety tests on animals could still work in humans.
For example, according to one study, a mouse’s immune system has only 10 percent in common with ours.
“And our lifespans are much longer and our tissue repair mechanisms are very different, because we have to survive longer,” says Andrew Knight, professor of animal welfare at Murdoch University in Australia.
“Most animal research simply does not predict human outcomes with sufficient reliability to be useful for human disease.”
Chris Magee, head of policy at Understanding Animal Research, an organization that aims to explain why animals are used in testing
Recent research from the University of Zurich found that only 5 percent of treatments that show promise have been approved for use in humans. The researchers sifted through data from 367 potential treatments for 54 human diseases and found that while half passed human trials, most subsequently failed.
One reason, they said, was that testing on “young, healthy animals…may not be directly applicable to the more complex scenarios of older patients with multiple health problems.” Another problem was the ‘poor quality’ of animal studies.
Although most scientists believe that animal testing remains a valuable tool, it remains controversial.
To develop a new drug, thousands of compounds are initially run through computer programs to identify potential candidates for a condition.
“Then you start testing on animal or human cells in the laboratory – and if it still looks hopeful, you move on to fruit flies,” says Magee, “but it takes years to get there.”
Then other animals join in. Zebrafish are increasingly used because they are cheap, short-lived and, most importantly, transparent, says Magee. “This way you can see what’s happening inside while they’re still alive.”
Mice are responsible for about 60 percent of animal research. “A big advantage is that their average lifespan is two years, which is useful if you want to see any long-term effect,” says Magee.
And about 90 percent of human genes are the same as a mouse, and we have the same organs in similar places.
If something passes kidney safety checks in mice, there is a 96 percent chance of it happening in humans. In the cardiovascular system the chance is 75 percent and for the gastrointestinal tract 69 percent. But there are also big differences. Mice have no tonsils, their hearts beat faster, their cholesterol levels are significantly lower and they break down fat differently.
This means that wild mice do not develop heart disease.
And using mice poses challenges for conditions like Alzheimer’s disease, because they don’t develop the condition naturally.
So they need to be genetically modified to get a hereditary form of the disease, says Dr Kamar Ameen-Ali, senior lecturer in biomedical sciences and dementia researcher at Teesside University.
The problem is that “less than 1 percent of people have this form of Alzheimer’s,” she says, and mouse tests “don’t really reflect the complexity of the disease that we see in most people.”
Before a new drug is tested on a human, it will also be tested on another animal, such as a dog or rabbit.
This step was introduced after the thalidomide scandal in the 1960s, when a drug women took for morning sickness caused limb deformities in their children. It did not cause limb deformities in mouse offspring, but it did in subsequent tests on rabbits.
But even that is not flawless. In 2006, six men almost died after being injected with a potential new drug for leukemia and autoimmune diseases at Northwick Park Hospital in Harrow. It had passed safety tests on multiple animals, including monkeys.
Shortly after receiving the drug TGN1412, all the young, healthy volunteers were in intensive care, fighting for their lives.
It is thought the drug led to an overreaction of the human immune system – but differences in the way genes activate immune cells prevented this from happening in animals.
‘One argument in support of animal testing is that we share many genes with, for example, mice, but that proves nothing – we also share genes with bananas,’ says Dr Pandora Pound, research director at the Safer Medicines Trust. , a charity pushing for the development of more human-based medicines.
‘It’s not about whether the genes are shared, it’s about how genes function. In this respect there are major differences between us, mice and primates. And a small difference can make a big difference when it comes to testing a drug.’
The other problem is the flaws in the way animal studies are designed.
Professor Knight says: ‘A problem with primate studies is often that they only include two or three animals, but that doesn’t produce results that can be applied to a population.’
Additionally, he says, mice are nocturnal and the noisy laboratory environment during the day increases their stress levels – which can affect the results.
‘Temporarily, things like immunity and digestion are under pressure,’ says Professor Knight. ‘That works if the stress is short-term, but if the stress is long-term – as happens in these laboratories – the immune system is suppressed for a long time, he explains. “So you take an animal that doesn’t predict human responses very well and further distort that animal’s immune competence.”
Furthermore, the difference in the biological clock means that drugs tested on mice during the day when they are biologically ready to sleep could have a different impact on humans when given at the same time, who will naturally be more alert.
In one study, published in Nature in 2020, researchers at Massachusetts General Hospital found that three drugs used to treat stroke in mice reduced brain tissue death when given during the day (when the mouse was biologically was ready for sleep) but failed when given. at night.
“There is a risk that we are throwing away safe and effective new medicines because of poorly designed research,” said Dr Anthony Holmes, director of science and technology at the National Center for the Replacement, Refinement and Reduction of Animals in Research, founded by the government in 2004 .
But do we even need real animals in a digital age?
Dr. Holmes says an international project is underway to develop a virtual dog – a computer model based on existing findings from dogs – that could be used to monitor the potential toxic effects of new drugs without using live animals.
Other projects include organoids, miniature versions of organs that can be grown in the laboratory for testing and research.
And there is artificial intelligence – where a computer can ‘learn’ to predict what a drug might do.
But for now, animal research – despite its imperfections – is the best we have, says Dr. Holmes.
“I don’t believe any scientist wants to work on animals, but until we have alternatives, they will continue to be used.”