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Animal Testing in Drug Development: An Interview with Dr Pandora Pound

Trigger warnings for this interview include: Mentions of animal testing

With all the years of research, what is holding back drug development for diseases such as Alzheimer’s, for example?

Pandora: It’s a lot to do with using animal models as our primary way of developing drugs. Animals tend to model human diseases when they’re at an advanced stage, once the disease has gotten its claws into us. For example, with a stroke, although it can take years to develop, as people get older and get high blood pressure and so on, when animal models are developed, they tend to model the last part of that process, the moment that the blood vessel gets blocked. To me, it seems like a very crude way of modelling a disease which has taken a long time and has many factors contributing to it in the human population. 

It’s also a problem of species differences. You can learn a lot about animals by doing research on animals, but you may not be able to extrapolate that to humans. In some cases the similarities may be sufficient, but in other cases even very small differences between the species can mean very big differences in outcomes. So we end up having all these drugs that seem to work in animals, but then when they’re tested in humans, there’s a very low success rate.

Animal testing, regardless of efficacy, has all of these ethical debates. So given these problems, why is it persisting? Why is it still a preferred method?

Pandora: It has its roots in the 19th century, when animal models were emerging, because they used the experimental method. Previously, doctors would observe humans at their bedside and try various treatments, but it was based on clinical observation. Optimism about the experimental method developed in the 19th century, and physiologists and doctors at the time felt this was a good way to make their disciplines more professional, like ‘proper science’. Experiments in the lab, using statistics, seemed better than just watching patients. 

Animal use shot up after the World Wars because they were used in experiments to look at chemical warfare and radiation, then with the rise of the pharmaceutical industry. Gradually, industries began supplying animals, animal feed, housing and surgical equipment, so you get a lot of industries that are depending on animal use, and people’s livelihoods begin to be dependent on it. Then it gets embedded in universities – it’s good at churning out PhDs and papers, and brings money into departments. Once the whole department is dependent on the money that animal research brings, you get conferences and journals dedicated to it, so it gets locked into our institutions and our culture. 

Once the whole department is dependent on the money that animal research brings…it gets locked into our institutions and our culture

A lot of the general public feel that it’s a necessary evil because that’s what we’ve been told for decades; it’s locked in and regulations serve to keep it locked in. It’s difficult to break out of that, even if you’ve got evidence to show that animal research doesn’t work in many cases. It’s difficult if you’re an animal researcher and you’ve built your whole career on this to then suddenly switch. Unless you’ve got the funding and support to switch, no one’s going to want to do that voluntarily. (The way) academic departments work doesn’t make it easy to transition.

So if there was a willingness to fund alternatives to animal testing, are there any viable alternatives at the moment, and if so, how effective and safe are they?

Pandora: Well, I don’t like calling them ‘alternatives’ because that sees animal models as the gold standard, which I don’t believe in, so I call them human biology-based approaches. They may use human tissues, they may use data that are then fed into computer models or AI. But they’re based on human data, so there’s no problem of species differences; immediately you’ve got rid of one thing that makes animal experiments unreliable and inconsistent. Of course, there are issues with human biology-based approaches, as there are with any approaches; they’ve got to be reliable and valid. 

Within in vitro approaches, you’ve got things like organs on a chip. They’re tiny, about the size of a memory stick, (with) little microscopic channels that can be lined with cells from human tissue, then you can pump nutrients, air and blood through so it’s like a home from home for the cells. Then you can start adding a drug to see how the cells react, and organs on chips have been used successfully to predict toxicity in drugs that animal models failed to predict. There was an excellent study done [in] 2002, which used 870 liver chips to test 27 drugs that had been judged safe for human use based on animal study evidence, but which had then gone on to cause adverse reactions in humans, including liver failure and death. But the liver chips were able to detect toxicity in almost 7 out of every 8 drugs that were toxic to the human liver, so they far outperformed the animal studies. 

AI and in silico models are also being used in drug development because you can then build these models to look at similar types of drugs and predict how they will react. It’s an emerging way of predicting toxicity for new experimental drugs without using animals – you’re able to get accurate data on how a drug will react in humans. Also, it’s quick – it can take months or years with animal studies, never mind the ethical aspect, but this is far quicker, cheaper, and more accurate. It’s very easy to oversell the benefits of human biology-based approaches and we shouldn’t do that, but there is some really good emerging evidence to show that they compare favourably with animal studies.

It seems that there needs to be a systematic overhaul – do you think that’s possible? Can you see that happening at any point in the near future?

Pandora: There are signs of change already. In the Netherlands, they have a really good transition programme: they’re aiming to transition away from using animals in safety testing [of] chemicals, and they originally had a deadline of 2025 to do that. They faced a lot of opposition from animal researchers, and they’ve dropped that deadline, but they’re still working hard towards this transition. In America, the US Environmental Protection Agency has a similar aim to reduce and eventually eliminate the use of animals in testing, and they had a deadline of 2035, which again has been quietly dropped.

The US Environmental Protection Agency has a similar aim to reduce and eventually eliminate the use of animals in testing

So there is a lot of opposition to change. But at the end of last year in America, the FDA Modernisation Act was passed: this means that scientists in the US are no longer compelled to use animals in drug development and testing. So, it doesn’t specify that animals have to be used – [scientists] can use anything they feel is most appropriate, so that opens the door for people to legally use whatever they feel is the best approach. Already people are beginning to use organs on chips, in-silico, AI, alongside traditional human-based approaches like clinical trials. So it is happening. At a snail’s pace, but it will happen.

It’s interesting what you mentioned about there being a lot of opposition from animal researchers. Many people would assume that scientists are logical and move forward on the basis of evidence, and it seems illogical for people to be digging their heels in. Do you think it’s an example of human nature?

Pandora: It’s clear that evidence alone is not enough to make change. Obviously you need evidence, but you’ve also got to look at the context, so you’ve got to look at society, institutions, [and] the culture, because those will also exert an influence on whether transition can occur. Scientists aren’t the rational creatures that we imagine, who just go on the basis of data. There are all sorts of factors influencing them –  their careers, interests, egos. They are subject to human fallibilities like everyone else.

Our newspaper is read by students in all sorts of disciplines. What, if anything, can the non-scientist do to help move industries and universities away from animal testing? 

Pandora: We’ve got to put pressure on our political representatives, our MPs. The public needs to show that they’re no longer satisfied with relying on animal models when we know that there are better, quicker, cheaper, more ethical ways of doing this. I work for Safer Medicines Trust, a charity concerned with the safety of patients. Animal research doesn’t just harm animals: it harms humans, because it’s not generating treatments for even our most common diseases. We have to get that message across to our MPs, (and) to have conversations about it with our friends. And read my new book: The Rat Trap: The capture of medicine by animal research – and how to break free, about how animal research got entrenched, the obstacles to transitioning to human-based research, and the limitations of animal research.

So if anyone wants to find out more and learn about this topic, then your book is the go-to for information?

Pandora: Oh yes – well, I would say that! But I have tried to make it accessible, because I want the general public to understand these issues. It’s explicitly written to get the scientific evidence out of journals and into the public domain. So please do spread the word, because I would love for students to read this book. Students are our future and it’s up to you to carry this forward!

Dr Pandora Pound’s latest book The Rat Trap: The Capture of Medicine by Animal Testing – and How to Break Free is out now in paperback.

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