How much do you have in common with a mouse? The question isn’t as fatuous as it sounds – mice are the most commonly used animal for laboratory tests to find new treatments.
Chances are that whenever you take a pill, dab on ointment or have a vaccine, it will have been tested on a humble mouse.
The perceived wisdom has always been that what’s good for the mouse will probably be good for us humans – and better that initial and potentially risky tests on new treatments are done on a laboratory animal than a human.
And there is no doubt that using animals has furthered medical science.
It was thanks to work in dogs, for example, that in 1921 the hormone insulin was first identified – a huge breakthrough for those with diabetes and one which has saved millions of lives.
Work on mice and monkeys led to the development of polio vaccines, which has helped prevent an estimated 20 million cases of paralysis among children since 1988 alone.
Animals have also been key to tests on semaglutide (the active ingredient in weight-loss jabs Wegovy and Ozempic), with experiments on rodents confirming its weight-loss potential.
And much of our understanding of cancer and how it is treated has been underpinned by animal research.
‘Without it we wouldn’t have found out that cancer is not one disease but that there are over 200 different types, and out of 300 cancer drugs about 250 came as a result of animal research,’ says Chris Magee, head of policy at Understanding Animal Research, an organisation that aims to explain why animals are used in research.
According to Home Office figures, there were 2.68 million ‘scientific procedures’ involving live animals in 2023 in Great Britain.
While mice, fish, birds or rats were used in 95 per cent of these, cats, dogs, horses and ‘non-human primates’ (i.e. monkeys) were used in 1.2 per cent.
Most procedures involved ‘basic research’ into the nervous system, the immune system and cancer – but 45 per cent involved breeding genetically altered animals for research.
The perceived wisdom has always been that what’s good for the mouse will probably be good for us humans (file image)
Animal lovers may understandably wince and the question is, does it really help the progress of medical science?
In fact some argue animal testing sometimes holds up the development of new treatments. That’s because potential therapies that fail safety tests on animals could still work in humans.
According to one study, a mouse’s immune system, for example, has only 10 per cent in common with ours.
‘And our lifespan is much longer and our tissue repair mechanisms are very different, as we need to survive for longer,’ says Andrew Knight, a veterinary professor of animal welfare at the Murdoch University in Australia.
‘Most animal research simply does not predict outcomes in humans with sufficient reliability to be of use for human illness.’
Chris Magee, head of policy at Understanding Animal Research, an organisation that aims to explain why animals are used in testing
Recent research by the University of Zurich found only 5 per cent of treatments that show early promise are approved for use in humans. The researchers sifted through data from 367 potential treatments for 54 human diseases and found although half made it to human testing, most then failed.
One reason, they said, was tests on ‘young, healthy animals…may not directly apply to the more complex scenarios of elderly patients with multiple health conditions’. Another was the ‘poor quality’ of animal studies.
While most scientists believe animal testing remains a valuable tool, it remains controversial.
To develop a new drug, thousands of compounds are initially run though computer programmes 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 even to this stage’.
It’s after this that other animals come in. Zebrafish are increasingly used because they are cheap, short-lived and – importantly – transparent, says Magee. ‘So you can see what’s going on inside while they are alive.’
Mice account for about 60 per cent of animal research. ‘A major benefit is that their average life span is two years, which is useful if you want to see any long-term effect,’ says Magee.
And around 90 per cent of human genes are the same as a mouse’s and we have the same organs in similar places.
If something passes safety checks on the kidneys in mice, there is a 96 per cent chance it will also pass in humans. In the cardiovascular system, it’s a 75 per cent chance and for the gastrointestinal tract it’s 69 per cent. But there are major differences, too. Mice lack tonsils, their heart beats faster, their cholesterol levels are significantly lower and they break down fat differently.
That means wild mice don’t develop heart disease.
And using mice brings challenges for conditions such as Alzheimer’s as they don’t naturally develop the condition.
So they have to be genetically modified to have an inherited form of the disease, says Dr Kamar Ameen-Ali, a senior lecturer in biomedical science and a dementia researcher at Teesside University.
The problem is that ‘less than 1 per cent of people have this form of Alzheimer’s’, she says, and mouse testing doesn’t ‘truly reflect the complexity of the disease as we see it in most people’.
Before a new drug is tested on a human, it will be tested on another animal too, such as dog or rabbit.
This step was introduced after the thalidomide scandal in the 1960s, when a drug taken by women for morning sickness caused limb deformities in their children. It didn’t cause limb deformities in the offspring of mice – but it did in subsequent tests on rabbits.
Yet even that isn’t fail-safe. In 2006, six men almost died after being injected with a potential new drug for leukaemia and autoimmune conditions at Northwick Park Hospital in Harrow. It had passed safety tests on multiple animals, including monkeys.
Soon after receiving the drug, TGN1412, all the young, healthy volunteers were in intensive care fighting for their lives.
It’s thought the drug led to an overreaction by the human immune system – but differences in the way genes activate immune cells meant this did not occur in animals.
‘An argument in support of animal testing is that we share many genes with mice, for example, but that doesn’t prove anything – we also have genes in common with bananas,’ says Dr Pandora Pound, research director of the Safer Medicines Trust, a charity pushing for more human based drug development.
‘It’s not having genes in common that matters, it’s how genes function – and there are big differences between us, mice and primates in this respect. And one tiny difference can be significant when it comes to testing a drug.’
The other issue is failings in the way animal studies are designed.
Professor Knight says: ‘Often a problem with primate studies is they include just two or three animals, but that won’t give a result that can be applied to a population.’
On top of that, he says, mice are nocturnal and the noisy daytime laboratory environment increases their stress levels – which can alter results.
‘Temporarily, things such as immunity and digestion are depressed,’ says Professor Knight. ‘That works when stress is short term, but when it’s prolonged – as occurs in these laboratories – the immune system is depressed for a long period of time, he explains. ‘So you are taking an animal that doesn’t predict human responses very well and further distorting that animal’s immune competence.’
What’s more, the body clock difference means drugs tested on mice during the day when they’re biologically ready for sleep may have a different impact on humans when given at the same time, who will be naturally more alert.
In one study, reported in 2020 in Nature, researchers at Massachusetts General Hospital found that three drugs used to treat stroke in mice reduced brain tissue death if given during the day (when the mouse was ready biologically prepared for sleep), but failed when given at night.
‘There is a risk we are throwing away safe and effective new drugs on account of poorly designed research,’ says Dr Anthony Holmes, director of science and technology at the National Centre for the Replacement, Refinement and Reduction of Animals in Research, set up by the Government in 2004.
But do we even need real animals in a digital age?
Dr Holmes says an international project is under way to develop a virtual dog – a computer model based on existing findings from dogs – that could be used to check 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 lab for testing and research.
And there is artificial intelligence – where a computer could ‘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 continued to be used.’
Stress boosts sperm function, was the surprising conclusion of study in the US.
When researchers analysed sperm samples from men over several months, as well as their perceived stress levels, they found sperm respiration (energy production) and motility (movement) improved in the months after a stressful event, reports the journal Nature Communications.
It’s thought to be down to the effects of stress hormones on tissue that produces sperm – further studies to understand this mechanism could help advance fertility treatments.