Animal experiments for medical purposes will end, expert tells Nation.Cymru

Martin Shipton

A leading scientific expert on medical research methods says he is optimistic that human cell-based techniques will displace animal experiments because they are more reliable and less wasteful.

Dr Andre Menache, originally from South Africa and now living in France, spoke to Nation.Cymru in support of a petition to the Senedd aimed at stopping the Welsh Government funding research that involves experimenting on animals.

He told us: “I want to congratulate Wales Against Animal Experiments for being so pro-active, and I’m very optimistic that they will reach the 10,000 mark and that there will be some form of debate in the Welsh Parliament on the subject of animal experimentations.

“I lived in the UK for about 11 years and was quite involved in the movement there. I’ve also lived in about eight other countries, so I have a fairly broad outlook on things. The situation in the UK is pretty much the same as in Europe, because when the UK was part of the EU it was using the same directive. And the UK’s Scientific Procedures Act pretty much resembles the equivalent EU directives. The UK is among the three biggest users of animals in Europe. We’re talking about the UK, Germany and France. So they are the three worst culprits, if you like.”

Resistance

Asked why there was resistance to the arguments of people like himself, Dr Menache told Nation,Cymru: “There are two main reasons. The first is that it’s very difficult to get a drug or a chemical onto the market without going through animal testing. You’ve got to go back a little in history. At the end of the Second World War, at the Nuremberg Trials [of Nazi war criminals] in Germany, it was decided when the Nazi doctors were put on trial for experimenting on humans that human experimentation, now called clinicall trials because that sounds much better, should put measures in place to protect human subjects used in experimentation, hopefully with fully informed consent.

“But we’re going back to 1946, 1947, and at the time it seemed OK, it seemed logical to say that before we touch a person, before we do anything to anybody, we are going to first test it on animals. A system was put in place that involved testing a new drug on at least two animal species: a rodent, usually the rat, and a non-rodent species because rats don’t really look like people, so let’s test it on something that looks a little bigger. So it’s the dog or the monkey. The dog is pretty much used for heart medicines, you name it, but when it comes to something like vaccines and biological products, then you use the monkey as the second species rather than the dog.

“That was pretty much set in stone at the end of the Second World War, and the legislation has not changed since. The pharmaceutical industry, if it wanted to, could say, you know what, we know that these animal tests don’t work. As a vet, I say to people I will not test a drug intended for horses on parrots. And people laugh – they get that straightaway. So I say to them the next question is why test a drug intended for people on rats. We are not 70 kilogram rats. And then people start to think.

“So the first problem in answer to the question why things aren’t moving is that we need to change the regulations – that’s number one. The second point is that the whole research community still believes in the paradigm of animal experimentation. For example – and I’ve sat on several ethics committees by the way, so I know the tricks of the trade – it’s much, much easier to get funding if you say I want to test something on 100 mice or 100 rats than if you say I want to test something on human cells or human surgical waste. There’s a lot more paper work, believe it or not. You’ve got to go through ethical hoops, bioethics committees etc. It’s much more difficult to obtain human surgical waste that’s going to be incinerated anyway than to get 100 mice.

“So we’ve still got this paradigm that before you test anything, if you’ve got a brilliant idea you must go and test it on an animal before you do anything else. And the sad part about it is that I’ve debated brilliant students – PhD students – and I hate to say this but they’ve lost their critical thinking ability. In other words, they have been launched into a career of animal research and they are in a bubble. We’re talking about brilliant 19, 20 year olds, but to them, their professor is God, and if their professor says ‘yes, of course you can use a mouse or a rat or a dog to test your hypothesis’, that’s what they will believe.

“So we have a problem in the curriculum. We have to change the curriculum to include more courses on things like critical thinking. You don’t have to be a genius to realise that if you test something on a mouse, with a view to testing it on a human, mice and men are separated by 90 million years of evolution. So you can’t tell me that the mouse is going to be predictive for humans. One human is not even predictive for another human. Some people will get adverse drug reactions to an antibiotic and other people won’t. So it’s already tricky, just using one person as a predictive model for another person. Across the species it’s just absolute madness.”

‘Dont have a clue’

Dr Menache said most people don’t have a clue about animal experimentation, even GPs. He said: “Ask your GP whether chimpanzees are immune from HIV AIDS. Ask your GP do chimpanzees get different cancers to people. They don’t have a clue. So imagine the man or woman in the street – they don’t know what’s going on. So when researchers say to them, ‘this is important, give us funding, this is fundamental research, this is important’, people first of all don’t have a clue what fundamental research means. It just sounds important.

“We’ve blindly had faith in people with white coats for the last 50 years, and we just give them money because they keep promising us cures around the corner. And we don’t do the maths. We don’t remember how many millions of animals have been sacrificed or killed, and how many billions of pounds have already been spent, with no cure in sight for the most common diseases. So scientists are getting away with things that you and I would go away to jail for if we did these things to animals. Some of the things can only be described as torture: when, for example, you give an animal an electric shock because you want to study depression etc.

“But because the researchers have got a white coat, they can get away with it. An ethics committee has approved it. And the ethics committee, of course, is heavily weighted in favour of the researcher. There are very few public representatives on these ethics committees, and the few that there are cannot challenge – they don’t have the necessary tools to challenge the animal researcher. And even if they did – and I take myself as an example – I’ve campaigned against animal experiments for 45 years, beginning in veterinary school, and I’ve sat on ethics committee – but I cannot sway the researcher, simply because the law – in the case of the UK the Scientific Procedures Act – does not require a researcher to prove his animal model is predictive of human outcome.”

Universities 

Asked whether the fact that much of the experimentation on animals was carried out in universities gave it a veneer of respectability, Dr Menache said: “Very much so. There are two aspects to that. There’s the prestige, but there’s also the funding, because in some universities, when a researcher gets a grant, some of the money goes to the university, it doesn’t all go to the researcher. This is especially so in the United States. You can imagine, a researcher who’s made a career out of studying depression in mice, and has done this for 30 years, is not now going to switch over to human cell culture. They’re not going to stop doing this. Unfortunately we’ve got this older generation who are teaching the younger generation, the brilliant young students, the same paradigm.

“Where is the critical thinking? The ‘tradition’ is being passed from one academic generation to the next, and it’s very rare that you get a student who says ‘I don’t want to do this for ethical reasons’ or ‘I don’t want to do this because I don’t think it works’. Such a student will very quickly find themself studying something else. The few students that really are independent thinkers are rejected by the system. It weeds them out, if you like.”

Explaining the alternative to animal experimentation, Dr Menache said: “Basically you’ve got two types of cells. You’ve got cells that you can get from the operating theatre – in other words, these are living cells, living tissues, for example when people have a tummy tuck or breast reduction, there’s a whole lot of cells there that you can use to experiment on – and hat’s going to get incinerated unless the researchers say can I have some.

“There are human ‘biobanks’ in the UK – I believe there’s one in Leeds. You can basically order any human cell types. There are around 230 different types of cell in the human body. So there’s the fresh cells from surgical waste, and then what’s known as continuous cell lines. They are basically cancer cells that multiply forever. The advantage is that you can keep those cells in the lab for as long as you want. The downside is that they are not normal cells – they are cancerous cells. So they’ve retained some normal properties, but they’ve also got some abnormal properties. Obviously you have to take that into account.

“And then, of course, there are stem cells, which for example you can get from surgical waste from people who have had fat removed from their body. You can program them – you can re-program them to do virtually what you want, and there’s no problem with informed consent, versus embryonic stem cells which are a hotbed of ethical issues. That’s why I personally don’t go down that route. I say we don’t need embryonic stem cells today, we don’t need to get into that debate, because we can use other types of stem cells with the informed consent of the parents. That avoids all of the prickly issues.

“Today with bio-engineering – in other words the marriage of biology and engineering – we’ve got a lot more sophisticated than two-dimensional cell culture. The star of them all is ‘the liver on the chip’. We’re talking about human cells sourced either from donated organs or human surgical waste – so it’s a re-creation of the human liver on what looks like a tiny microchip – it’s about one centimetre square, and it’s also got a blood supply. It’s like a miniaturised version of the human liver, and it’s very close to what the human liver can do. Liver on a chip would come from medical waste, but also from the liver of someone who had died of a disease that affected the liver.

“If you want a whole human liver, say someone’s got HIV AIDS and they put themselves on a transplant list, and they die in a car smash and they’re brain dead – you can’t use that liver and put it in somebody else because the guy’s got HIV, but you can use that liver for human experimentation or for making livers on a chip etc. 100 grams of donated human liver contains one billion cells.”

“This is huge. One liver transplant will cost the NHS £120,000. So we’re talking economy, we’re talking human suffering, and the liver on a chip is way more predictive of detecting and identifying prescription drugs that will cause damage to people’s livers than dogs, rats, monkeys, you name it. Dogs, rats and monkeys are about as predictive as tossing a coin.

“So the nightmare for the pharmaceutical industry is that the MHRA [the UK’s Medicines and Healthcare products Regulatory Agency] says to all drug manufacturers, from now on we want you to use liver on a chip. I’m not saying they’ll stop animal experiments, because that’s going to take a while – it could happen overnight if you wanted it to, but the pharmaceutical industry says no, we want to carry on using animal testing. So before you test your new drug on people, we want you to test it on a human liver on a chip, and be transparent about it – show us the results. Let’s see the results against the animal data.

“That is a nightmare for the pharmaceutical industry. They will lose so many drugs. It will narrow their drug pipeline considerably. Of course it’s going to be great for consumers, because it’s going to mean far less side effects. This is something that needs to be told to the public. Our biggest tool against the power of the pharmaceutical industry and the inertia of the regulatory authorities is public opinion. And it has to be informed public opinion.

“The liver on a chip is something that should have been compulsory 10 years ago. We’re now nearly 2025 and in the United States the Food and Drug Administration (FDA) is now testing liver on a chip to see if it can be included in the regulatory testing programme. But they’re dragging their feet about this.

“Animal experimentation has never been scientifically proven to show that it works for humans. Animals are not predictive of human outcome with respect to drugs and chemicals. So on the one hand the regulatory authority and the government allow the pharmaceutical industry to continue animal testing as the best we’’ve got, while we’ve got things like liver on a chip sitting on a shelf, screaming out to be used. And there are people requiring liver transplants because the MHRA can’t get its act together. That to me is a dereliction of the duty of care of the MHRA. Their mission is to protect the public and patients.”

Waste

Dr Menache argues there is a lot of waste built into a system based on animal experimentation. He said: “There’s an adage in the pharmaceutical industry: fail often, fail early. To get a drug onto the market will cost you about £750m, and it’s going to take about 10 years. The most expensive part in getting a new drug on the market is the clinical trials – that’s when you test it on people. That’s about 80% of the cost. So the pharmaceutical industry hates it when they discover in phase two or phase three that their drug doesn’t work. They’ve poured millions down the drain. So they want to fail early.

“That’s an argument for using the liver on the chip, because it’s then going to show up the adverse drug reactions much earlier, rather than letting this drug loose on the general population, and then a couple of years down the line realising that it’s killing people and causing a lot of side effects, and maybe they should take it off the market.

“The pharmaceutical industry knows full well that animals are not predictive of human outcome. And that’s why they came up with this idea of testing drugs on healthy human volunteers. The public swallowed this idea hook, line and sinker. We think it’s absolutely normal, it’s OK for the pharmaceutical industry to pay young healthy people £2,000 to spend a day in the clinic to receive an experimental drug that’s never been tested on people before, and then at the end of the day if all goes well they go home with £2,000 in their pocket.

“That is outrageous, ethically and scientifically, because of course a healthy person is not going to respond to the drug in the way a sick person would. And the pharmaceutical industry will come back to you and say,’ it’s very safe, there’s never been any problem, it’s very rare for accidents to happen’. Well I take that with a big pinch of salt, because 50% – half – of all clinical trials are not reported to the MHRA, so we don’t know what happened. Something went wrong and they stopped the clinical trial, and that information was not sent to the MHRA. They don’t have to – they can just say, we shut down this clinical trial. It’s very rare, it’s only like the testing of TGN1412, when in 2006 six healthy young men at London’s Northwick Park Hospital became critically ill after taking the drug intended to treat leukaemia and conditions like rheumatoid arthritis, one losing his toes and fingers. When it’s that obvious it hits the headlines, but that is rare.

“I actually know a young lady who used to take part in clinical trials as a healthy human volunteer to make pocket money. Then one day, during a clinical trial, the researcher said to her she could go home. She said, ‘but it’s not finished, we’re only half way through’. But they said ‘yes, but we can see that your liver enzymes are starting to go up. Your liver doesn’t like this drug, so we’re kicking you out from the clinical trial because you are no longer considered to be a healthy volunteer’. So they manipulate the results.

“Most clinical trials can be replaced with liver on a chip. That is the good news. But also the pharmaceutical industry is very clever because when you see adverts in the paper, especially the newspaper that circulates to homeless people, they’re always looking for healthy human volunteers. Healthy human volunteers normally are young, white men between the ages of 25 and 35, average height and weight, non-smokers. And the reason they choose men is that men suffer fewer side effects than women from prescription drugs.

“Why do they choose white men? White men, Caucasians, have fewer side effects from prescription drugs than Africans, Chinese, Asiatics. It’s a fact. So already they’re selecting a population that is going to tolerate their drug as best as possible, because they want to go into the next phase, which is phase two. After the healthy human volunteers they go to phase two, clinical trials, which is actual patients. It’s about 100 to 200 patients. If all goes well, they go to phase three, which is 2,000 to 3,000 patients. And if all goes well then it gets released onto the market.

“You should know that for every 10 drugs that successfully pass animal testing, nine out of 10 will fail during clinical trials. It just shows you how unreliable animal testing is – and I do not know of any comparable industry that would tolerate such a failure rate. The pharmaceutical industry is getting away with it, with the blessing of the MHRA. The MHRA says to the pharmaceutical industry, ‘we want you to produce drugs that are safe and effective. How you do that is up to you. We trust you.’ So the pharmaceutical industry says ‘great, we need animal data because that’s what we’ve used for the last 60 to 75 years’. And the regulatory authority says ‘great, we’re familiar with that data.’ If you turn round as a pharmaceutical manufacturer and you say, ‘can I give you liver on a chip or other non-animal methods that are scientifically right’, the MHRA will turn round to you and say ‘prove it. We don’t know this stuff. We’re not familiar with it.’

“Why should you as a pharmaceutical industry go to the bother of validating, spending money proving and convincing the MHRA that your liver on a chip is way better than animal testing, when the MHRA is quite happy carrying on with animal data?

“By the way, the liver on a chip was not invented by the pharmaceutical industry. It was invented by private and public bodies like the Wyss Institute in the US, who put together under the same roof researchers, engineers, scientists, doctors – and they came up with the organ on a chip.

“The pharmaceutical industry will fight tooth and nail to keep animal testing because it allows far more drugs into the pipeline, and cynically far more adverse drug reactions in the general population. Whereas you could actually reduce the risk to the general population by using things like liver on the chip.”

Asked whether the focus of campaigning therefore had to be on changing the minds of legislators and regulators, Dr Menache said: “No – I’ve been down that route, so I’m talking from experience. Regulation is going to take 25, 30 years. Forget it. The industry says it will replace animal testing by 2035. That’s the timespan they bandy about. In actual fact we could do it today. The technology is there – the technology is not what’s missing. What’s missing is the will to drop the animal experiments and replace them with something that’s far more reliable and predictive. The technology is not being applied.

“Why am I optimistic? Because through articles like yours, through debates in Parliament, plus the fact that the FDA has no choice but to look at the liver on the chip seriously, and if it works they’ll have to include it in pre-clinical testing. You can postpone and you can push away the new technology as much as you like, but at some point in time push comes to shove and they have no choice, they have to include it.

“I’ll give you a really encouraging example. Botox. It has cosmetic and medical uses. In the US, in about 2004, the Humane Society of the United States approached the manufacturer of Botox in the US called Allergan, and they managed somehow to get into a shareholders’ meeting and say to the shareholders, ‘listen guys, you can make just as much money by replacing the use of mice for the batch testing of Botox product, which die an agonising death to test all these batches to make sure the potency is just right. We can replace these mice with a completely cell-based test method.

“What do you think?’ And it was a no-brainer: the shareholders said yes, and in 2011 the FDA approved the use of this completely non-animal human cell-based test method for the potency or batch testing of cosmetic Botox products. That just shows you that if you can persuade shareholders, if you can get the information across to shareholders, good decisions can be made. And there we were talking about mice. Can you imagine if we said to them, ‘look what’s being done to beagle dogs to test these drugs – we can replace these beagle dogs tomorrow, today.’ The shareholders would get it, straightaway. But the pharmaceutical industry is now wise to this tactic, and if as an outsider you want to attend a shareholders’ meeting, you’ve got to buy something like £20,000-worth of shares, and get 100 shareholders to support your motion at the annual general meeting. So the pharmaceutical industry made it very difficult to repeat this fantastic success story.

“So there are two options, as I see it, if we want to accelerate the transition from animal testing methods to human based testing methods. One is to inform the shareholders – you get this information to the shareholders and let them do the work. Or you mobilise sufficient public opinion so as to make people aware of what’s going on – make politicians aware of what’s going on, and almost name and shame the pharmaceutical companies, who will say we don’t want our shares to fall – organs on a chip, OK. That’s how I see things happening strategically.”

The petition aimed at stopping Welsh Government money being used to fund medical research involving experimenting on animals can be accessed via this link: