When Anna Marsh was 20, she was prescribed an antidepressant called Nardil.
Doctors warned the art student that she might put on some weight, but instead she grew thinner and found herself constantly drained of energy.
Her fatigue became so extreme that she would often lie on the worktops at the Royal College of Art during her lunch break because she was too exhausted.
Scared about what was happening to her, Anna eventually saw her GP. ‘She took one look at me and said “the whites of your eyes are yellow, your skin is tinged with yellow”, which is a sign of jaundice,’ she remembers.
Had Anna known her medication would have damaged her liver – leading to hepatitis and causing two years of debilitating fatigue – she says she never would have taken it.
After being told to come off her meds straight away, which induced ‘terrifying nightmares and hallucinations’, Anna then became so sick that she had to go back to her mum’s home in Suffolk and undergo daily blood and liver function tests.
She also had to eat sticky, sugary and high calorie food every four hours and says her urine went ‘dark brown’ and that her faeces was ‘cream coloured’.
‘When I started getting better the doctor said he didn’t think I was going to recover because my liver was so poorly functioning,’ Anna remembers. She also says that although her terrifying experience happened in 1970, she is still scarred by it.
Now 73, Anna refuses to take any pills and won’t drink alcohol out of fear of what might happen to her liver.
After all she went through, she became convinced that animal testing on medicine is not effective as it purports to be – as it wasn’t enough to prevent her ordeal.
Ever since, she has spent her life campaigning for techniques she believes are more relevant to human bodies.
It is clearly a touchy subject, as Anna asked for her name to be changed for safety reasons.
After protesting outside the Huntingdon Life Sciences laboratory in Suffolk in the late 90s, she woke up the following morning to find her front garden had been torn to shreds by saboteurs.
‘People who protest against animal testing have been demonised,’ she says. ‘The other side will say “you care more about animals than people”, but that’s not true, I’m living proof it’s not true – we need better science for everybody.’
It may have been 50 years since Anna’s health scare, but there have been more recent cases of medicines showing promising signs in animals but harming people.
In 2006, human trials for a drug called TGN1412 – designed to fight leukaemia, rheumatoid arthritis and multiple sclerosis – ended in disaster.
Within 16 hours of the drug being administered to eight young health men, they were all rushed to London’s Northwick Park Hospital with multiple organ failure.
The drug had shown good signs in rabbits, dogs and monkeys, and human subjects were given a dose that was 500 times smaller.
In interviews that followed, the men involved described feeling like their ‘eyeballs were going to pop out’ and that their brains ‘were on fire’.
One of the worst affected was Ryan Wilson, then 21, who was in a coma for two-and-a-half weeks after suffering heart, liver and kidney failure.
He spent four months in hospital with pneumonia, septicaemia and dry gangrene, which meant all his toes, part of his foot and several fingertips had to be amputated.
Another participant, Rob Oldfield, told law firm Leigh Day: ‘I struggled to remember everyday things. We were told to stay away from public transport, choose our food carefully, that sort of thing – because our immune systems might not be able to cope.
‘I had thought it was a good thing – being an ambassador for science – but because of trial I feel like I was just equipment within a system, not a human being. It is hard to see that the corporations are interested in anything other than money.’
Campaigners suggest that cases like this show that animals process chemicals differently to people and therefore aren’t the most reliable test subjects.
‘Let’s say chocolate was a drug that was going to cure depression and we did normal animal testing,’ explains Dr Donna MacMillan, a scientist for Humane Society International (HSI), an organisation dedicated to improving animal welfare worldwide.
‘Chocolate is toxic to dogs, so we would throw that out at that stage, even though we know people can eat it.
‘Because they’ve been used for so long and all the time, resources and investment have always been in animal tests up until very recently.
‘If we were able to redirect funding into new technologies and develop more innovative novel approaches then we’d be able to move away from that.’
And many countries do appear to be doing just that – albeit at a slower pace than campaigners might like.
Last month the European Parliament passing a resolution to move away from animal testing – demanding the European Commission set out a plan.
Meanwhile US Senators Rand Paul and Corey Booker introduced a bill to end mandatory animal testing.
Just last week MPs in the UK argued passionately on the subject during a Parliamentary debate, following a government petition to ban animal testing signed by more than 235,000 people.
Comedian Ricky Gervais has also started a parliamentary petition of his own calling for lab animals to be included in the Animal Welfare Act – signed by 100,000 people.
Clearly the demand for an end to animal testing is there, but is the technology?
Already scientists are using computational models which can predict whether a chemical is likely to be toxic to humans.
They can improve as they are fed more data – known as machine learning – and can even employ artificial intelligence for better accuracy.
In 2018, researchers from the University of Oxford tested a new cardiac drug on a virtual human for side effects with an accuracy of 89-96%, compared to 75% using rabbits.
Dr MacMillan says computational models can have a good idea of a chemical’s impact, even if it’s new and has been nowhere near a human.
‘If there is a certain part of a molecule that causes toxicity – that’s called a toxophore,’ she explains.
‘It’s relatively easy to identify if you understand the chemistry of people’s bodies, so it often doesn’t matter what the rest of the molecule is, because it’s this little active part that causes issues.
‘If a certain chemical causes cancer because of the way it binds to DNA, then another chemical that has that same bit that binds will probably also cause cancer.’
Dr MacMillan adds this could be a more reliable way of predicting a drug’s effect than using an animal, which she likened to a ‘black box’.
‘If you run the same test in 10 different animals, you only get the same answer seven times out of 10,’ she says.
Another tool already being used by scientists are bio-engineered miniature organs, grown using human skin cells and used to test drugs.
‘A blinking eye has been created, and a breathing lung and a beating heart and a kidney that produces urine,’ says fellow HSI scientist Dr Lindsay Marshall.
They don’t look anything like an organ you’d take from a human, she adds, rather it’s a functional unit of cells that have the same physiological function.
Many scientists argue that while these developments are exciting, they don’t quite capture the complexity of the entire human body.
However in a promising sign in November 2019, a liver-chip developed by bioengineering firm Emulate managed to pick up toxicity caused by a drug called fialuridine that went undetected in animals.
Meanwhile, just last year, researchers at the Harvard Wyss Institute developed a ‘body-on-a-chip’ consisting of up to 10 organ chips, connected to mimic the blood flow between them.
Dr Marshall says advances in stem cell techniques mean scientists can carry out research based on a patient’s organs without having to take it from their body.
‘I can’t really access your brain in any sort of ethical manner, I can’t take a chunk of it away to the lab,’ she says. ‘But I can reprogramme your skin cells to become your brain cells essentially. So in the lab I can have a sample of all your organs.
‘Every human is different, we all respond to diseases slightly differently. So using this, we can start to get a better signature of what that disease looks like in humans.
‘The flipside with animals is “I have a mouse, I know that people with asthma have tight airways and respond to allergens with their airways closing up, so let me see if I can get that mouse’s airways to close”.
‘It’s all backwards because you’re trying to drive a symptom by throwing different things at a mouse rather than taking a person with asthma’s cells and growing them into organ chips.’
Scientists are now also able to take samples from a patient’s tumour, grow it in a lab far quicker than if they were to plant it in a mouse, and then use that sample for drug tests, Dr Marshall explains.
This enables researchers to find out the right drugs and doses for the patient, opening the door to a more tailored form of treatment.
On top of this, there are 3D lab produced tissue models – artificial human skin – which can be used to test the irritability or corrosiveness of a chemical.
Such models have led to a huge decline in the Draize test – which sees chemicals put on rabbits skin or eyes.
By combining results of several techniques and putting it through a strict mathematical model, scientists can assess the hazards of a drug in what is known as a next-generation risk assessment.
In the summer of 2021 the Organisation for Economic Co-operation and Development adopted guidelines for this method to be used to test human skin’s sensitivity to chemicals instead of mice.
Given that many of these alternatives are already used by scientists, the big question is: why is animal testing is still a requirement across the world?
‘The regulators have to be risk averse, they can’t afford to let something out on the general public that they have any concerns about,’ explains Dr Marshall. ‘I don’t think they can see an easy way to replace it so they’re kind of just ticking along with that because it would take a lot for them to revisit their entire processes, everyone would have to be on board.’
However, there is already one organisation in Britain dedicated to doing just that.
The NC3Rs awards millions in funding to a wide range of institutions with this aim of refining animal tests, reducing unnecessary suffering, and hopefully one day, replacing it altogether.
It recently published a paper clarifying that forcing rats or mice to swim for antidepressant trials is not a requirement.
One researcher working in regenerative medicine told Metro.co.uk how he hates working on animals but is nonetheless bound by UK regulations.
He asked not to give his name, given how people in his field have had bombs planted under their cars in the past by animal rights activists.
‘The scientific community are trying to be a bit more public about this – providing more information so the public can understand the topic better,’ he says.
‘But the people telling you that aren’t the ones with targets on their backs.’
He believes computer models could have the best chance of one day replacing animal testing, but thinks we are still a far way off.
‘It’s so difficult to explain to the public how complicated the human body is. A lot of scientists will put a drug into a model and just wouldn’t have thought of everything, so it will be missing things.
‘In order to test that model, you need a control, and the only control you can test it against is a live animal.
‘Whether that’s a human or not is another matter, but you’ve got to test it against something.’
Chris Magee, head of policy and media at Understanding Animal Research, believes animal rights groups often paint a narrative of scientists as being uncaring on this issue. He also warns that an outright ban on tests would mean sending to countries with poorer standards.
‘The best thing is if it’s here,’ he insists. ‘We count absolutely everything – in America they don’t even count rats and mice as animals, which skews their statistics.’
Referring to Anna’s case, Chris says that the UK only properly started regulating animal tests from 1968 and that it was a bit of a ‘wild west’ prior to that. While on the Northwick Park disaster he explains: ‘If you had a system that works 99% of the time then eventually something will go wrong.
‘It was tested on human tissues, it was tested on human blood cells, it wasn’t as if only animals were used.’
Chris insists that animal data ‘correlates very closely’ to damage on human organs, adding: ‘If it’s safe in an animal 90% of the time it’s safe in a human.’
This isn’t to say he wouldn’t like to see an end to animal testing, and he has long called for greater funding for the NC3Rs.
He believes a combination of methods could one day be used to replace it, but for now it is ‘complementary’.
‘It is phenomenally complicated to replicate our systems, it would be like modelling the City of London in Lego. So many working parts,’ adds Chris.
Although some people have been concerned about how quickly the Covid vaccine was developed, there’s been little outcry on what it was tested on – and neither has stopped over 45million people becoming fully vaccinated.
Dr Marshall says this is because ‘animal research as a body does a really good job of promoting itself’.
‘I feel like it’s really been rammed down my throat how important the animals are and how much of a hero the animals were, as if they had any say,’ she adds.
However, Chris says that animal testing for the vaccine was ‘crucial’.
‘I did wonder at the beginning, is this going to make people change their minds about animal research because it happened at a faster pace?’ he admits.
Chris also says the law already states that if there is a viable alternative to animal tests then researchers are required to use it.
‘When the day comes that we don’t use animals, it won’t have anything at all to do with the anti-groups,’ he says adamantly.
‘They undermine the case for further investment by pretending that we’re already there. We’re not, the whole point is we need more.
‘I get it that they’re passionate about it, but they’re also trying to steal the glory of the long march of science and they’re trying to paint people as psychopathic idiots.’
Chris adds that it ‘could well be the case’ that not all animal tests could be completely eliminated, but that some biological systems will be easier to crack than others.
‘I think AI might surprise us,’ he says. ‘Putting a year on it is very difficult. Whatever happens it’ll be really patchy, I’d bet my house on that.
‘What I don’t think we should do is have a set date for it. It’ll be done when it’s done. The sooner we get on with funding it and working towards it, the better.’
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