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Sounds of Science is a monthly podcast about beginnings: how a molecule becomes a drug, how a rodent elucidates a disease pathway, how a horseshoe crab morphs into an infection fighter. The podcast is produced by Eureka, the scientific blog of Charles River, a contract research organization for drug discovery and development. Tune in and begin the journey.
I'm Mary Parker, and welcome to this episode of Eureka's Sounds of Science in every country, politics affects science sometimes for the better and sometimes for the worse when it comes to the safety of patients. However, most governments have taken a conservative approach to innovation favoring known safety standards until new methods are thoroughly proven. What then are we to make of recent pushes from several regulatory bodies towards animal model alternatives? Here to break down some recent announcements, what they really mean and what we might expect going forward in the industry are two experts. The first is Chris McGee, head of Policy and Media for the UK Advocacy Group Understanding Animal Research. Our other guest is Naomi Hara Lobas, director of Science Policy and Communications at the US-based advocacy group, Americans for Medical Progress. Welcome Chris and Naomi.
Hi.
Hi. Thanks for having me.
Thank you both for coming on and I appreciate you being here even though both of your advocacy group names are very long. And speaking of which I would love some background on you and your organizations. So Chris, can you tell me about understanding animal research and how you got involved?
Well, we are essentially very old organization. We had some protests in the UK in the early 19 hundreds, and it was decided by medical men's scientists that there was so much disinformation out there. In fact, we had, there was a famous incident called the Brando Affair where some activists made up some fictitious things that had happened to a brown dog. None of it was true. It was disproven in court, but the idea ran amuck. The idea of a dog being abused was all it took for people to believe that it was true. There was a statute put up for commemorating the dog and it got thrown in the Thames quite a lot by medical students. It suspected had 24 hour police guard, this is crazy, we need someone to speak for sanity. Why are we doing this? And that mission kind of started. Then later on there was another group called the Coalition for Medical Progress, and that did more of the media side of things, similar thing, just trying to explain what was going on.
And they merged in 2008 to become understanding animal research. And so we carry on that sort of dual thing, engaging with regulators, very closely politicians, but also media facing and that kind of thing. So in some ways we're a very old organization in other ways, the conversation hasn't moved on a great deal in about 150 years, which was the first time that we regulated animal research in 1876. My background was actually in think tanks, first of all before moving into policy. So I worked on a large number of similarly controversial things at the time. So that's what I've done today for now 13 years I think in post.
I remember hearing about that brown dog story, but I'd forgotten all about it until you mentioned it, so thank you. I also really like the term think tank. It makes me think of just a bunch of smart people in a metal room sitting like Rodan the Thinker.
That's certainly how we saw ourselves. I'm not sure if anybody else would see that.
How about you, Naomi? Can you tell us about your organization and how you got involved?
Yeah, yeah. So we haven't been around quite as long as understanding animal research. Americans from Milk Clorox we're based in the us. We were founded in the early nineties, 1991. We are a nonprofit that's really dedicated similar to UAR, to making sure the public hears the facts that we're not the distortions or the things that are often spread by the anti animal research groups and really explain why animal studies are still needed and vital to medical and veterinary progress. We highlight the scientifics necessity, the standards of care that animals are given, and we try to give scientists, institutions and policymakers the tools to understand what's going on and to even advocacy opportunities to push back against a lot of the misleading claims. And so I've worked with a MP for my whole professional career as of now, although I've been officially at the organization for about a year now, but I was a graduate student, so I do have a doctorate in neuroscience and I did work with animals and very quickly saw how a lot of people, if you're not in the science world, a lot of people actually aren't okay with animal research.
And that was astounding to me as a scientist. So I noticed that gap between what scientists know, what policy makers know what the public knows, and I became very interested in policy and advocacy and I was grateful to have a mentor that really pushed me in that direction. So after graduating, I did pursue the policy career route and I've been here ever since.
Excellent. Well, it sounds you have similar backgrounds, which is still useful because you come from obviously different countries. So we can speak to kind of multiple locations, which is great. But to start us off, Naomi, can you summarize some of the more recent announcements from the US Food and Drug Administration regarding animal model use?
Yeah, so back in April, the FDA released their roadmap on reducing animal testing in preclinical safety studies. And it's a fairly lengthy and very dense document that we don't have time to get in the weeds about. But overall, it's essentially just a blueprint, a roadmap with goals and strategies that the agency plans to implement to better develop, validate, and use NAMS in preclinical research. But the messaging in this citations that are included in this document is pretty concerning. So for example, about halfway through the document, it states that the FDA's long-term goal, long-term being three to five years FDA will aim to make animal studies the exception, not the norm for preclinical safety studies. And while that's an aspirational goal and goals are great, it's not realistic from a scientific standpoint, from a practical standpoint. So because in so areas of work still heavily rely on animals, especially in the drug development process, and we don't have the alternatives there. And there's that dearth of robust validated alternatives. That's why this roadmap is praised by those opposed to animal research. But the scientific community has some skepticism about its implementation.
And over to Chris, can you give us an example of similar policy changes in the uk? I know that the UK is in general a little bit ahead of the US in terms of wanting to get rid of as many animals as possible. So how has that looked for you?
We have had a different approach from the US simply because we started regulating sooner. We already had things in place, which meant we didn't adopt the same language. And we've had the principles since 1876 that you don't use an animal ethe an alternative, but that also became explicit. It's on the face of the law since 1986. You simply can't use number if there's an alternative. And the three RS has become the thing too, so that we don't miss out on that. So it wasn't just about replacement, it was about refinement and reduction as well. That means that we can very easily phase in new tech as it becomes available. We're not dogmatic about how we get there. We are very, very keen to adopt the new toys, use them alongside animals. Really what our work is to try to change international regulations where we've got harmonization initiatives, which mean you can easily transport things between regions and you're not doing a non-animal method for one country and then having to do the animal method anyway just to export it. So our focus has very much been on the international scene, and that means validating things is actually working for this or that very, very focused application. But I think from a regulatory point of view, we've got very few hurdles that aren't international in nature.
When we were talking earlier, you mentioned something about Charles Darwin having some sort of contribution to the early use of regulations around animals. Could you give us a little elevator history lesson? I love that sort of thing.
Absolutely. Yeah. So he was involved from the first time when there was a petition from the very early anti VI section groups that formed in London. Charles's daughter Henrietta bought him a petition print to sign and he said, oh no, this is going to really be bad for physiology. And then setting up essentially the first rival factions against the anti intersection movement, and it became a massive cause in our country. It split the country right down the middle in terms of who you supported. You had Queen Victoria on one side and the great medical men of the day on the other United the aristocracy and the real working class often against the experiments. But you had a scientific class, a medical class in the middle that was saying, we have no choice. We are losing a loss of people. We are losing a lot of kids in childhood.
You can look at the records from the time and who died in my street in London. It is a lot. And they said, it's absolutely immoral not to do this. And that's why we had to quickly find a way to balance those two rather extreme positions. And then you have of course things like religions. We get involved in one part or another, and the Darwin project has all of his correspondence on vi section. It's a fascinating read. And you can see from the very beginning from his first involvement that it's been the same kind of misinformation and the same kind of exaggeration of the harms of the animal. Usually that's focused upon, and we have royal commissions that looked at is any of this true? And they all found in favor of the medical fraternity. And for good reason, a lot of the criticisms were fabrications exaggerations, partial truths, not the whole truth. And it's really important in this topic to have all of the information, the whole truth, and let people make up their own mind about it,
I think would've been around that time when the island of Dr. Moreau would've come out. So that probably didn't help either. Naomi, how would you speculate that the DA and the NI h's policy changes will affect the industry going forward?
Shortly after the DA released their roadmap to reduce the use of animals and preclinical safety testing, NIH sort of followed suit or working in parallel. These two work closely hand in hand. And they announced in late April that they were establishing a new office of research innovation validation and application or RIB A within the NIH office of the director, meaning it will affect the entire agency. And both of these, this document and this new office both reflect a concerted federal agency approach to push and expand the use of non-animal methods, bolster the infrastructure, enhance the training related to it. And that's all a very good thing when the science is ready. But unfortunately, the anti animal research groups spin these announcements to suggest that victory animal research is obsolete no more, it's not needed anymore. They're finally listening. And that is where you run into some trouble because then the public will see those headlines and we're still lacking that scientific community communication about that's not exactly true, and that's irresponsible to even say that. Then in July, FDA and NIH held a joint workshop that was exclusively focused on reducing animal testing, and we could do a whole podcast episode on that workshop itself, but there were a number of nuggets in there on how the agencies view nams, how they use NAMS, and what's the future of NAMS and the like. But there was also some policy announcements made by NIH that NIH will no longer issue notices of funding opportunities called NOFO S that exclusively support animal models or limit or specify the types of models that must be used.
And at the same time, new nofo S are going to be issued that address human-based nams. So shortly after that came out, it was wildly misconstrued and it caused a great deal of confusion. The anti research groups declared victory, no more funding for animals. Others misinterpreted it to say all grant proposals have to include a non-animal model, both are untrue and inaccurate. And it really just underscores the importance of clear communication from funding agencies, from the scientists that are putting forth these policies and direct how science will move forward. What the actual intent of that announcement and what the sense was is that it clarifies that the change applied only to nofo how they're written. So animal research will continue to be supported. It's just simply going to be written in a way to encourage researchers to consider a full range of methods. So NIH is not going to try and prescribe or restrict certain approaches.
So for example, things that I tell people instead of issuing a notice of funding opportunity calling for applications on mouse models for understanding Alzheimer's disease, they're updated kind of language will just call for applications on biomedical research models for understanding Alzheimer's disease. So it's a lot more broad, a lot more inclusive, and that's a subtle change, but it's very significant because it signals that all methods and all models are going to be eligible for funding. So in a way it makes sense, it's very science forward and very forward thinking, but the implications and the subtle nuances that people are misconstruing is where we run into
Problems. And I think that's a pretty common problem in sort of communication in general. Science is especially prone to it where someone will discover a molecule and then the headlines will be like cancer cured by this miracle drug. And it's like, no, no, no, no, no. Exactly, exactly. Slow your role. We're in the early, yeah, so that's definitely an issue with science communication in general. Obviously a issue that is near and dear to my heart, but what do you both say about the kind of arbitrary timelines that various regulatory agencies have laid out? Have historically these deadlines been met or are they just kind of goalposts that inform people's decisions going forward?
Well, I can certainly say where they've been put in. They're typically not met unless the model has already become redundant.
So in the UK for instance, we kept bringing down the number of animals we used in cosmetics research domestically. I think there still were some tests happening elsewhere. So we knew that this or that compound was probably safe, but it was an import ban as well. But by the time we phased it out in cosmetics testing in 1998, we weren't really using animals anyway. We've actually got a bill in our parliament at the moment to prohibit animals in medical research by 2035. It is largely aspirational. The idea is if they just light a fire under us, then we'll be forced and just financial and commercial pressures will force us to invest in these things and it will just work. But that's just not how science happens. It is great. It is great to have investment. I mean, greater investment will definitely shoo things along, but you've got to be very careful about getting rid of regulations before the alternatives are ready. That isn't going to help animals. That's not great for wild animals. It's not great if we're releasing stuff into the environment. We don't really understand how it works, how it's metabolized. Even drugs for pets, how much of those are excreted? Are people picking up their dogs urine when they go out for a walk? I don't think they are. I think that's entering the environment and therefore you need to have an understanding of how this stuff works.
Naomi, would you agree?
Yeah, completely a hundred percent. And I would say we're seeing similar pushes in the us. It just simply is not work because it's not scientifically realistic, but it's a good tactic. It's a good headline for the activist community to really try and hold the agencies accountable and then garner more support from their supporters. But at a MP, we always like to say that policies and the resources that are given, we want to ensure that they serve the science, not define the science. You can't put the policy before the science. It's just not how that works. And a clear example is EPA in 2019, they made a pledge to eliminate mammalian studies By 2035, we're going to cure cancer by 2050. These declarations that sound really great and might seem like a great win for these activist communities, but in practice are just not practical. So it was celebrated by the anti animal research groups, but it was later scaled back when scientists recognized that's not quite feasible or responsible.
There are certain areas that maybe are farther along than others, toxicology being one of them. But those deadlines great soundbites, but they're repeatedly just proven to be poor guides for sound science and policy. And thinking back to my lab days, if my principal investigator, the boss of my lab told me, you have one year to do all of these studies that quite frankly would take my entire dissertation as it does multiple years, I would be rushed. I would cut corners, then you also risk sloppy science, and that's not what we need. We want good science and we want good animal care, good science, they go hand in hand. So we have to be thoughtful about this, and that's where scientists really need to be driving the policy and be at least at the table providing their perspective.
I was just thinking that behind every regulation there's somebody or something that got harmed, the regulations don't come from nowhere. They're always introduced retrospectively after something went horribly wrong. We've got to make sure that the new methods, whatever they are, can adequately protect against that which we originally ported in for.
That's a really good point. Can we get into an example of how a safety test that has promising animal alternative models like liver on a chip or an example that is something and an example of something that is not even close to having an alternative like reproductive ology. We just want to demonstrate that there is a wide range, and even though there are so many promising alternatives, it doesn't mean that the end is near.
Yeah, I'm happy to start. So for one liver on a chip is great for that example. I like to tell people the best model that's out there actually has, it demonstrates four or has four human liver cell types, but an actual human liver has seven different cell types. So just there in and of itself, which is the best model on the market, and it's making great strides, which is fantastic, but it's still not quite fully replicating what is in our own bodies. But I think skin sensitization is often held up as one of the best examples where non-animal methods has made real progress. Again, the toxicology space. So for decades, animal tests such as the mouse, local lymph node assay was the standard. But today we have validated very safe and effective in vitro assays and computational models that can reliably predict whether a substance is going to cause an allergic reaction on the skin.
On the other hand, if you take pediatric cancer, that's a field where non-animal methods are valuable and they can get you only so far, but they cannot completely capture that full biological reality. So childhood cancer develops in the context of a growing developing immune system, and it's still maturing. Everything is still developing. So those factors can't be fully recreated in a cell culture, in an organoid, in a computer model. So for example, the way tumors interact with a child's immune system, how it responds to maybe systemic drug delivery or how it metastasizes throughout the body, that's going to require a whole organism to better understand what exactly is going on. And we want to ensure the safety before it even enters a child. We have to be extremely sure it is safe and effective. So nams, again, provide those crucial insights at the molecular and cellular level, but they cannot replace the animal studies when it comes to replicating those complex dynamic biology of pediatric cancer and other very complex diseases in a living system,
Which is of course, not to say that NAMS or non-animal models are not useful at all. I think that what it sounds to me like is one of their main uses is weeding things out early on. Exactly. If you test things in those first, it could be pretty obvious from those whether it's going to be viable or not. And that way you have saved an entire run of assays on animals.
Exactly. Exactly. And the thing is, we've been using these non-animal methods for decades already. It's kind of embedded into how the scientific process works. If you're discovering a drug target, how can we screen for what we need to be looking for? You're not going to just look for everything. So it is part of the scientific process and there are these checks and balances to make sure that we're very mindful of how we're using the resources when we're using the resources because these are public investments.
Chris, do you have a favorite example of a non-animal model that works or a place where it doesn't
Maybe have some really good ones there? I think stuff to do with the immune system is a bit of an onion. Every time we think we understand it, we simply peel back another layer of complexity, and that's kind of the problem. I mean, maybe the next one will be the last that's not been experienced thus far. So I think it's the unknown for me. I think that the NAMS are generally very good. Like you say, using 'em early, it's like peering through the mist so you don't build a bridge to nowhere way roughly where you're going to land, which will be a better candidate. And that saves assays of all sorts. I think that reducing animal numbers is only one impact of nams, if you like. It's one that certain people are fixated upon. I'm more interested really in the new directions it might open up. And also you going to screen nice and early, really just a quick dirty tool in some ways, if it's quicker, if it's cheaper, if it's roughly as good. It is all really helpful. I love new tech and I'm very excited to see it applied.
Exactly. I think too, one important thing is that I think a good way that scientists can message this is that non-animal methods, these nams and animals need to be used in tandem. They need to work together to really get at answering all of these scientific questions. And we use them together all the time as we've discussed just now. And I think a great example is just a few months ago in the New York Times, they shared a story about a baby nine months old was the first to be healed using a personalized gene therapy. And if you dig into the supplementary data, like the nerd I am, you can find that their first step was they took a non-animal method. They used liver cells from the child and cultured them in the cell to really study them more and then developed it into a mouse, transgenic, mouse model, humanized mouse model, and then put it into a large animal model to then develop the treatment that saved the baby's life. And without the three step process, that child will not be alive today. So if you prematurely take away access to large animal models, mouse models, whatever that may be, you are going to risk someone's life. So I really like to share that example and really it crystallizes everything, at least in my mind.
That segs perfectly into my last question. For both of you. What advice would you have for scientists who are navigating these new regulations? What should they be looking out for and what can they maybe don't have to panic about?
So first, I think it's really important to know the policy landscape as difficult as it can be, because anti animal research groups are shaping the narrative. And as Chris mentioned earlier, we are a narrative storytelling driven species. So policymakers may be hearing their version of the facts more than the actual science-based facts. So second, try to document and communicate why your area of expertise and the model that you study to study it, whether that involves using an animal, whether it involves using a non-animal model, why is that the right tool for your question? And how can you articulate that in a way that a general lay audience can understand it? And then finally, don't underestimate the power of advocacy and stakeholder engagement. The scientific community needs to be right there fighting the good fight. A lot of us in these advocacy organizations are doing, we represent the scientific community, but we need those individual voices as well. So submitting public comments when opportunities come up, connecting with your lawmakers and sharing who you are, inviting them into the lab to see the work that you're doing and where those public dollars are going. Because if the scientific community isn't providing accurate, nuanced information about this complex environment that we're in, those gaps are going to get filled by the rhetoric of anti activists and activist groups. Instead of the evidence,
Let's say you Chris,
Precisely the same thing in an English accent. If you leave a vacuum, it will be filled by disinformation and it's by people who I think maybe actually believe what they're saying and all that kind of thing, but they need to look deeper into it. And only specialists in science can really, you are the only one who can actually really tell your story as well as possible. Understand that your dedication to science is going to be greater than any lawmaker. So you have to really stand up for science, don't need a vacuum, and get out there and tell your story.
Thank you both for joining me and having this conversation. I think it's really important to get some facts out there and some levelheaded perspective when sometimes the headline seems like they're going off the rails.
For sure. No, happy to be here and thanks so much for doing this. I think it's important to get the information out, and we're happy to help however we can.
Great. Thanks for having us.