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Script of a talk by Dr Brett Cochrane from Animal Free Research at Kettering Vegan Festival 2017

Dr Brett Cochrane of the charity Animal Free Research UK (formerly the Dr Hadwen Trust), gave a talk at the Kettering Vegan Festival this year! He spoke for an hour and then at the end, Animal Justice Project’s Samantha Francis, interviewed him.

It was in April this year that the organisation officially changed from the Dr Hadwen Trust to the working name of Animal Free Research UK. They are currently the UK’s leading medical research charity that exclusively funds and promotes non animal techniques to replace animal experiments. Established in 1970, their first ever research activity was in 1971 at Kings College, London so they have been funding animal replacement, or the human models for human disease type research, for 46 years and they are funded by charitable donations.

“What we aim to do”, explained Dr Brett, “is benefit humans through the development of more relevant and reliable science whilst replacing the use of animals. So we’re worried about human health, we’re worried about the knowledge of human disease that we’ve got currently, and we’re of course worried from an ethical and compassionate aspect about the animals that are being used in the labs.

We’re trying to do both at once, by eliminating animals from being in the lab and also trying to develop better things for human health, to advance human medicine and to eventually get better treatments, safer treatments, more effective treatments. There’s a major problem of animal research not delivering on the promises that is was being given permission to do so in the first place”.

Dr Brett went on to give some startling facts. Four million animals were used in experiments in the UK in 2015. The number of procedures completed was 4.1 million, as the animals are reused to try and keep the numbers as low as possible. The estimates globally are around 110 million a year.

“The reason it’s an estimate is that, for example, in America, mice, rats, birds and fish don’t fall under their animal welfare act. As much as we don’t like animals being used in the UK, we’ve got some of the most stringent regulations, we’ve got multiple levels of licensing and even a single mouse is deserving of a number. I fully appreciate the context that we shouldn’t be using them at all. I am of course not supporting the use of animals. However the Home Office even give us numbers on the genetically modified animals used. They’re often considered in a different way with how other countries report their statistics. So when I say 4 million, it’s covering everything. Is it good we know the number? Yes. Is it good so many are being used? Of course not.

The reason they use genetically modified animals is because lots of animals aren’t answering the scientific questions that they need them to be answering, because animals don’t get a lot of the diseases that humans do. So they need to try and humanise those animals or give them Alzheimer’s and other neurodegenerative disorders, and that’s one of the major problems, they are trying to create the mouse to answer a question that it probably is always going to fail to do.”

Of those 4 million animals, he went on to explain, over 3 million are mice. They breed quickly, they’re small and the genomes are known. Rats are next, then dogs, then non-human primates. Cats are hardly used.

Half of the 4.1 procedures involve the creation and maintenance of genetically modified organisms. Of the 2.08 million experimental procedures, 30% are described as moderate or severe. And this is all completely legal, no licenses are being breached to get these figures.

Over the years the number of experimental procedures remains roughly the same but there is an upward trend of genetically altered animals. “So it’s almost like recognition that the standard mouse isn’t answering the questions that we need to and they’re genetically modifying more and more and more.

“So, why we fund: Animal experimentation raises ethical questions particularly so when the animal derived data has questionable translatable predictive benefit. They might get a successful animal study, it looks like it works, the problem that we’ve got is that too many of these animal studies are a precursor of going into clinical trials. So they might think that they’ve got a promising drug that appears to be safe, they go into the clinical trial which uses people and either the drug isn’t safe or more commonly it just doesn’t work. So as much as it looked promising in the animal study, when it goes to clinic it’s going nowhere. The drug companies effectively stop any further development because the drug is just not doing anything. This is what we’re trying to address.

We do a lot of our work in fundamental biology, so basic research, and this is trying to understand a mechanism of disease progression in humans. This is way earlier in the drug development pipeline before you get to what they call pre-clinical or regulatory toxicology.  So we are right at the early phase because there’s no legal requirement for scientists to use animals in that particular space, so it’s much easier if we’re able to work with scientists to develop the non animal approaches; and it’s all published in really good scientific journals, and the scientific community accepts it, it gets scientific validation. When it’s a legal requirement to do an animal test it’s called a regulatory procedure, or regulatory toxicology, and that’s when we start getting into the legal requirements and for that to change the non animal approach needs to be officially validated and there’s big centres around the world that do this but it’s expensive, it takes a long time. Once it’s been validated through those procedures scientists can’t use animals anymore because there’s a validated alternative.

We’re trying to understand the human disease, so trying to unearth some new targets for drugs, but all based on human cells and tissue etc, so we get that relevance right at the early stage. The problem that everyone has got is even when it gets much further down on the development side of things, at some point in a drug’s development, there is a legal requirement for it to be tested on animals. That’s just how it is. We are trying to do everything that we can to try and demonstrate how we have progressed as far as we possibly can without any animals, so we are replacing animals right now where a group of scientists might have otherwise gone ‘there’s our scientific question, where’s those mice for us to use?’ And because we’ve developed those technologies, they go ‘this is great, this is better. We’ve got human cells, human tissue, we can believe the data that’s coming out of it’,  because mice are different! I know it sounds crazy saying that but we need spell it out!”

It takes anything from 8-15 years to develop a drug, depending on the complexity of what the drug’s trying to do. The latest estimate for how much it costs for each drug to go from development all the way to your GP or pharmacist is about £1.1 billion.

“The reason it’s that expensive is because of all the other failure. If they knew that the one drug was going to get all the way through and without any problems it wouldn’t be that much, it’s because it also features in all of the other failed drugs along the way. That’s why it’s so expensive, and a lot of those drugs are failing because it might have false data from animals or it might fail when it goes to clinical trials.

“We’re on the front lines. We’re not a campaigning organisation, we’re a funder of credible non animal research to develop, apply and validate. So that the scientists don’t have an excuse, they just go straight to not using the animal. We work with the scientists of the future in universities and the current lot as well, not just the young ones coming through.

I’ve spoken to too many scientists in my professional career, you start talking to them about the biological question, they get all excited they go ‘ah! we can answer this by using mice’ and I go, ‘well I know you can’t because first of all I know receptor x in this particular mouse cell doesn’t even exist in humans or vice versa.’ ‘Yeah but we know how to handle the mice and we’ve got lots of experience’ and I go ‘no matter what you do, no matter what experience you’ve got, the data that you get will be relevant to the mouse, sure, but the receptor we’re interested in doesn’t exist in a mouse so it doesn’t translate to a person.’ Then we get down to the discussion of using mouse cells, and I say ‘you haven’t got around the problem. Those mouse cells still don’t have the receptor of the human cells’. ‘Oh right’ and then we start talking about the process we can initiate to develop a program of work to explore what happens with that receptor in human cells.

The law states that suffering is minimised. In complete fairness so much work is going on to try and make sure of that one. We might not agree with it, we might frown at it but a lot of work is going on. They don’t want to stop using the animals, but they are trying to minimise the degree of suffering. Even if you have trouble accepting it from compassionate grounds, the least stressed the animal is, potentially the more reliable the data. All of it is just riddled with problems.

Replacement technologies are to be used when available and only when the use of animals has clear benefit to biomedical research. Too much animal stuff is failing. Animal research for medical purposes in the general public is still acceptable and even supported.”

Dr Brett showed an Ipsos Mori poll carried out on public attitude to animal research last year. It was about how people feel they can accept the use of animals. 71% said they could accept the use of animals in scientific research as long as there’s no unnecessary suffering to the animals and there is no alternative.

“A part of someone getting their license to use animals, they have got to demonstrate that they’ve considered the 3 R’s – refinement, reduction, replacement. The problem is if they go all the way through with lots and lots of paperwork to get their animal study approved they’re effectively saying there is no alternative. So there isn’t a replacement technology, there isn’t a human focused approach that they can use in doing what they want. So it’s almost like a vicious circle.”

65% of the people surveyed said that they were not very well informed or worse about the use of animals in scientific research. But 71% said they accepted the use of animals in research. So they’re giving their views and they’re not very well informed or worse!

7% said they were very well informed on the subject.

“I’ve been in this field a long time, I’ve published in this area in peer reviewed journals and I can probably say that only in the last couple of years have I felt that I’m in that top category; so I’m intrigued about this 7%! That’s pretty high!”

74% of the people surveyed still think more work is needed into the development of alternatives.

“So even though people accept the use of it because it’s now about drugs for their child, for their loved one, their spouse, their family member, it’s easy to go ‘yeah my daughter is way more important than 100 mice’, and it’s an easy justification for them, the problem is those mice are being used but how is it actually helping?

Everything we’re told we should always question. Scientists are told that very early on. Don’t just accept one source of information because it could be absolute nonsense. This isn’t just us, it’s out there. And it’s coming out in almost every single scientific discipline. The scientific community have based everything from a particular set of animal studies and built on that. The problem was, the original animal studies didn’t really work.

The BMJ has published articles about animals in biomedical research and the shaky basis for predicting human benefits. The New Scientist had a headline ‘Lab Mice Are Sending Us On A Wild Goose Chase’. They further wrote that genetically modified animals are used to model all kinds of human diseases but the work doesn’t seem to be helping us to find cures.

“There is some good news – there’s a rapidly increasing uptake of non animal approaches being used. You might say ‘yeah, so what? we want to see an end to animal research’ – us too. But it’s one of those things of time. The Dutch government as you might be aware have got a very ambitious and well considered aim to phase out animal research for safety testing by 2025. They’re pretty much the only government even trying to do something about that. Now it’s not a ban, the media say it is, but it’s not. This is an ambition to. This isn’t like the cosmetic testing that was phased out with the final one in April 2013. It’s not that. This is an ambition to do it, but they’re trying to throw money at the problem, trying to get the mindset of people to move away from animals. Some of the legal stuff doesn’t fall under their 2025 plan, but this is good stuff. We’re all upset that it’s still another ten years because we all want to see the end of animal research but they’re the only government that’s even pushing it forward on this type of political agenda.

“In the UK, with regards to Brexit, I suspect there will be changes for animals in labs. However the government has gone above and beyond some of the minimum requirements for the Animals Scientific Procedures Act 1986 (ASPA). They’ve already taken some of the requirements and made them even more strict. I genuinely can’t think that irrespective of what pans out with Brexit, that will change too much. It’s just my opinion. We’ve asked the Home Office ourselves and it’s difficult to get an answer. Even the government doesn’t know how Brexit is going to unfold.

“How we meet out objectives: we fund the development, validation and promotion of animal replacement technologies. A lot of the basic research is done because people think it’s only a mouse model that we can use. Because a lot of really good non animal research that is actually funded, that when it gets published, if someone wanted to find animal replacement or human approach, it doesn’t immediately come up and there is no universal database for all of this stuff to go in. There’s lots of different resources. And it can take quite considerable effort to find a way to not use the animal. Because, first of all, they think the mouse works, that’s why they keep doing it. And this is going to be an argument between them and all different types of groups forever more. The problem is if they think it works to not use it they need to also use something that does work. And it takes quite a bit of effort to go ‘ok if they’re using mice for this, how could I get better human data by not using the mouse’. When that entire institution might be set up instantly to use mice. They’ve already got their licensing, they’ve already got their welfare people, they’ve already got everything.

So it needs concerted effort to not use the animal. This is why we promote a lot of the replacement technologies. Its not just stuff that we have funded over the years it’s anything from around the world, in order to help the scientific community. Someone might get our science newsletter, and it might have this skin sensitisation, toxicological approach not using animals, and someone in China or US didn’t know this existed, they go and look it up and go ‘ah, we can use this instead’. We’ve just saved some animals right there and then.

So since we were founded in 1970 we’ve funded over 210 different research projects, invested over £4 million over the last 5 years, and as much as that is brilliant and a massive testament to our huge network of supporters and fundraisers, it’s a tiny amount. If you think of how much money is being spent for animal research in this country right now it’s a tiny amount. Even some of the giants, places like the NC3Rs, which are responsible for a lot of the 3 Rs based, refinement, replacement, reduction based research, I think they fund about £10 million a year. And it’s still nowhere near enough.

One of our most successful years was in 2013 where we awarded nearly £900,000 to non animal medical research projects in the UK. We were delighted with that and it’s all testament to our supporters again for raising money for us to be able to do that.

“Last year we also awarded two significant strategic grants. We opened the Animal Replacement Centre of Excellence at the Blizard Institute, Queen Mary University, London. There we have invested £1 million over a 5 year period. To try and develop the non animal approaches but also to inspire the next generation of scientists via education, so they are aware that this research can be done without using animals. The Queen Mary University, London is a very well respected, well regarded university. Their medical school is something like 3rd or 4th in the country at the moment. So they’re embracing these approaches; it is a really good endorsement.

“We invested £350,000 at the University of Dundee. When people leave their bodies to medical science, they need preserving so they can keep using them. At this university they’re doing a lot of medical device testing; so stents and other things that would otherwise need to be tested on large mammalian species, so dogs, sheep, pigs. Not a lot of that goes on in UK, but it’s still about that process of developing the evidence of going ‘we can have much higher confidence that this medical device is safer and works in humans rather than trying it in a dog’. And then we can try and help convince the regulators, stop demanding it’s tested on an animal because we can use human bodies that have been preserved.

“We’re not a hub of arranging leaving your body to medical science, because we can’t, but if someone wanted to leave their body they can contact the University of Dundee directly. Because we don’t know when we die, they can’t guarantee which project it will be used for but they can at least make sure that it’s used at the University of Dundee. And it’s all done with very respectful ethical law as well as just the incredibly compassionate team there. There’s very strict law and regulations regarding this. You can say you want your body to go to the University of Dundee in order for animals not to be used somewhere else. And they do their best to adhere to the persons wishes.

“We also do conferences. It gets all the scientists together, we can talk, lots of different disciplines come, but there’s sometimes nice applicability between different approaches, that if we didn’t bring them all together they might not have seen, so it might be a way of better developing their model based on what someone else has done but in a completely different scientific field.

“Our scientists that we fund are very much expected to publish in peer reviewed journals, and we normally get about 5 to 15 DHT-funded research coming out into the peer reviewed scientific journals every year, and for an organisation of our size we’re very proud of that.

“We also try and form collaborations to get more scientists together for us to try and work together, like-minded scientists trying to work together and being stronger than we are on a separate basis; to try and drive this human relevancy forward, and by doing that it helps impact the animal thing as well, so the scientific community don’t keep going down the animal path.

“So the type of funding we do: the proposed research we might fund must have potential benefits for the advancement of science to be relevant to humans and research must replace the use of living animals in current procedures. They go hand in hand. We don’t do one without the other. It can be very strong science but, even if it’s not using animals, if it’s not helping to replace animals we don’t fund it.

“The sort of research areas that we fund are anything really that’s got a huge health burden for people and if it’s got a huge health burden for people it normally uses loads of animals as well. Cancer, Alzheimer’s, neurodegenerative disorders, diabetes, cardiovascular problems. These have an enormous health impact on people, socio economic implications as well and consequently lots of money is thrown at it from general research and consequently lots of animals are used.

“Our past, recently finished, or current projects, include diabetes and chronic pain. With chronic pain, they’re using stem cells derived from when people have wisdom teeth removed. So it would otherwise be a waste material, but what they’re able to do is extract stem cells from the wisdom tooth and use it to try and differentiate those stem cells into neurons and then you do basic research using human neurons derived from stem cells from wisdom teeth, this is the stuff that we like to fund and it takes this different approach in order to go ‘we can do this, it’s human, it’s human relevant and information that we’re getting out of this has got to be more relevant than doing something to an animal’. But the scientists have to prove that it is. Before using stem cells from human wisdom teeth, they were using quite invasive things using mouse faces. Because some of the research is dental, it’s about pain. Some of the research that goes on often uses mice and it’s cranial, facial type experiments. And that’s one of the really nasty things with the pain research, remember how they are supposed to minimise the suffering as a key component of everything, well if you’re doing pain research, guess what, you’re inflicting it, in order to find out how to treat it. The pain research is a pretty nasty area when it comes to animal research. They test dental implants in dogs. So you’ve got a perfectly healthy dog, beautiful teeth, and they deliberately remove them to test dental plants.

“I’m often asked what are the alternatives, what are the non animal techniques and technologies. The answer is tissue samples, stem cells, computer modelling. The alternative technologies are organs on chips, organotypic models, microdosing, imaging technology, advanced mathematics. Scientists need to interpret the data from these novel approaches so they need interrogate it, collate it and interpret it.

“With reference to organs on chips – a lot of the aspects of some of the toxicologies, they can have different impact on toxic responses based on where the chemical may have been in the body already. And by that I mean has that original compound been metabolised It might be that the metabolic by product of that chemical is actually more toxic to a lung, for example or your skin, or your heart, than it actually was before so there are these sort of aspects. So what they do is they try and develop these relevant physiological conditions in chips where they can almost create a modular virtual human. And this is some of the organs on chip based approaches that’s going on as well.

“How we select our projects – all of our big projects are peer reviewed, and it’s animal replacement and bio medical advancement as well.

“We have some studentships and some fellowships for undergraduates and then for recent graduates, but we also fund post doctoral research, phds, strategic grants, we help them with their conference attendance, publication, so people in the bigger community are aware of what they’re doing.

“We also work with other organisations with common goals. We link and form partnerships, we’ve got a large network of different stake holders as well.

“Our science newsletter alone reaches about 3,000 people around the world. There’s a group in Australia that wait for our science newsletter to come and then they help distribute it from Australia.

“Our social media outlets, Twitter, Facebook, is in excess of 20,000, its building all the time.

“So how do we get there? We need to do more research, we need increased government funding, we need to embrace a phasing out approach, we need more strategic and focused innovation pathways as well, we need better public engagement.

“What can you do? Thank you already for being here. Attend talks like this to be more aware of the problem and how we are trying to deal with it, help us on social media, help us fundraise, have a conversation about us with someone.

“We have two charity shops – our first one opened in Hitchin 2 years ago, our second opened in Hove in February this year. They are both vegan themed so if we receive items that are not vegan we hand them to other charity shops.

“I’d like to leave you with the Vacanti mouse from 1997. A lot of people recognise the picture. It was claimed that a human ear had been grown on the back of a mouse. It wasn’t. This mouse is what is called a immunocompromised mouse. What they did was they seeded cow cartilage in a mould so it looked like a human ear. And it was effectively to demonstrate that the mouse didn’t reject what they were doing and that they could form these structures.

“Twenty years down the line, where are we? New technologies have integrated tissue organ printers that can use human cells; using 3D printing to create the structure. And if it’s their own cells, there’s no rejection problems. So if we have got there in 20 years, let’s keep looking to the future, there’s an incredible amount of work to be done, we’re doing what we can”.

ANIMAL JUSTICE PROJECT INTERVIEW

Do all drugs have to be tested on animals by law?

“Yes. A tiny percentage of drugs have managed to be released without being tested on animals because of pre existing data somewhere or it’s a reformulation or a re-marketed drug, but it’s pretty fair to say that all drugs, all legal prescribed medications for whatever human ailment, at some point in their development have had to have animal research at some point.”

Does every country make it law to test on animals?

“Pretty much”.

Do veterinary drugs have to be tested on animals by law?

“A lot of the drugs that I’m aware of for vet care have actually stemmed from developing drugs for people. I have my own rescue dog. If my vet says he needs to take this particular drug, I don’t just say ‘Ok’, as much as I am very respectful of their decision, I go and look up the adverse side effects of that drug based on when dogs were used to develop a drug for humans. Because a lot of that data is available. So a lot of drugs come from that area. If they’re trying to develop a drug for a dog, dogs will be used very early on in the process.”

Could this be a way to show everyone that drugs not tested on animals work, even if it’s on animals?

“The point that  Animal Free Research UK is trying to argue is that mice, rats and dogs are not people. So the research isn’t valid. If you test a drug for a dog on a dog, then the science is valid as the species is correct.”

Is it correct that 90% of animal experiments fail?

“90% of drugs don’t make it to market. There’s an enormous failure rate. Some of it is because of the animals. That failure rate is not all because of failing animal studies but the failing animal studies is a major component. It’s not 100% why but it’s a major, major issue. It’s hard to say what percentage of the 90% that fail is because of the animals, because not everything is public. I can’t give a figure. It’s a big component but it’s not everything.”

Why do you have to explain the rather obvious fact that mouse biology, for example, is completely different to human biology, to what are supposed to be very clever doctors and scientists?

“This is why there’s a continued big problem. And you’re right, we’ve got so many of our most brightest engineers and scientists and all these other people that are just doing what they’ve done. And what we’re trying to do is not to try and tell them off, it’s not to challenge them in a negative way. It’s a bit like a long term committed carnivore, and they’re trying to go vegetarian, then trying to go the full way to vegan; it’s about encouraging and showing them. There’s lots of different issues around that. That is its own two hour discussion!”

Is Animal Free Research UK involved in animal welfare in laboratories?

“No. We fund no animal research, none. However it is the law that these tests go ahead and if an animal is in a lab I am interested in that animal suffering less.”

Does Animal Free Research UK have anything to do with stem cell research on fetuses?

“We don’t. People obviously have their ethical concerns with all of that. Everything we do that’s got a stem cell component is what they call either from waste material, adult human, like biopsies, or induced pluripotent. This isn’t science fiction this is actually happening. We’ve all got skin cells. Now they have differentiated from a stem cell. So you’ve got this entity that could be anything. So depending on the conditions, depending on what genes are switched on or off it can go from a stem cell into a heart cell, a liver cell, a lung cell. Anything like that. So what we often do is fund research that’s called induced pluripotency, so what they do is they take an adult cell and through a complicated process they take it back to an undifferentiated state. So an adult stem cell, where someone, an adult has said ‘yes, you can have some of my cells, no problem’, so ethical consent, they are able to take it back to an undifferentiated state and then differentiate it into a cell that isn’t skin. And that way it is an adult, not embryonic, not foetal. And the technology behind it is accelerating fast. I don’t think it will be too long before there almost isn’t a requirement for there to be foetal embryonic stem cells to be used. There might be exceptions to that, like there always is.”

So how would someone go about donating their cells?

“It’s often universities who recruit students, it’s often an internal thing. There’s a study going on, we need x amount of students between these ages, these genders, healthy or not, sometimes they’re looking for people who have a particular disorder, it might be something that’s relatively common, asthma for example, and that is how you get on these clinical trials”.