Focus In Sound

FOCUS In Sound #34: Lisa Hara Levin

Welcome to FOCUS In Sound, the podcast series from the FOCUS newsletter published by the Burroughs Wellcome Fund. I’m your host, science writer Ernie Hood.

 

In this edition of FOCUS In Sound, we meet a veterinarian who has become one of the leading voices in the movement to reduce, refine, or replace the use of animals in research and product development testing, also known as the 3Rs. As we will hear, she recently teamed up with Burroughs Wellcome Fund president Dr. Lou Muglia to publish a highly influential paper called Alternative Thinking about Animals in Research.

 

Lisa Hara Levin is a graduate of Cornell University, received her veterinary degree from the Cummings School of Veterinary Medicine at Tufts University, and completed her postdoctoral research training at the Johns Hopkins University School of Medicine. Her professional career has been spent in the animal protection and research environments, notably occupying positions as the Medical Director for New York City’s Animal Care Centers, and now as the Alternatives Director for Coridea, LLC, a premier biotechnology incubator based in New York.

 

Lisa Hara Levin, welcome to FOCUS In Sound!

 

LISA: Thanks, Ernie, I’m happy to be speaking with you.

ERNIE: Lisa, to get us started, tell us how you got interested in the cause of promoting alternatives to animal use in testing…

LISA: Oh that was a long time ago. I was a veterinary student working summers in a research lab at Johns Hopkins, and I was very fortunate to be mentored by a laboratory animal veterinarian having a great interest in animal welfare, so I started making my baby steps in the 3Rs, that’s the refinement, the reduction, the replacement of animals in research, and that’s a style that I carried with me through into my fellowship at Hopkins and later professional roles, where I was in the animal shelter setting, or I was doing research consultancy, and it’s served me very well. But your question did ask specifically about testing, and I want to make it clear that mentally, I place testing, research, and drug development all in the same what I call philosophical basket, so while maybe I started my career in research my field of vision has enlarged to include the other two areas.

ERNIE: Tell us how you and Dr. Muglia connected, and how did the paper come about?

LISA: I wanted to launch a project from a university, and I met him during that funding search. He thought the work I proposed was out of the box, and very happily for me, Burroughs Wellcome funded it. It did launch, set off from a different location, but the content remained the same. It was to have two roundtables with what I call the A-plus team from different groups having interest in the development, the regulatory approval, and the implementation of new approach methods. We also call them non-animal methods, or by the acronym NAMs in research, safety testing, and drug development. In terms of the paper, I’d been thinking a while about writing an article examining the NAMs and animal research question, and after the second roundtable was finished, I was scratching my head and said, you know, these conversations should have some place in the piece. So I spoke with Dr. Muglia, and he agreed to be my co-author.

ERNIE: Tell us a little bit more about the two roundtables that you mentioned…

 

LISA: I wanted to have the roundtables because to me there has been this needless argument between folks on one side who are endorsing animal use, and folks on another side, and it really is that polarizing at times—folks on the other side, who are in favor of NAMS. And in my view, I think this is entirely due to misunderstandings about each of their roles, in the past, the present, and what the predicted future may be for them in advancing science. So I invited members from the eight stakeholder groups that in my view are most closely associated with these areas, the development, again, the regulatory acceptance and the implementation of NAMs, and I wanted to seat them in one place and have some very relevant conversation. So they came, and who I mean by “they” are academics and industry who are working with NAMs, government regulators, government funders, venture capital, philanthropy, venture or otherwise, animal research advocacy, and animal protection. I won’t give you the names of those attending because that’s a confidentiality issue, but I can tell you and will tell you—there was a lot of magic that happened at these roundtables, and it was a beautiful thing to hear and to watch. I was really entirely my privilege to be part of those conversations. Everybody was so smart, so honest, so collegial.

 

ERNIE: What were your objectives for the roundtables?

 

LISA: If I look at several years back, and probably more than that, cause I’m an old lady, let’s say decades back, of observations about how stakeholders have problem-solved, they take these very siloed approaches. That’s not helpful, and my work recommends putting ideas and concerns out into the ether so that everyone has a chance to study that, and the roundtables let us do that. It was a nice beginning. We all went agreeably into a deep dive to explore the major pain points that each group had about NAMs, and we also started developing action items that we’ll use to create a very well-reasoned and evidence-based path towards integrating NAMs, whether as partial or full replacements. I want to comment about how brilliant these people were who came. One of, I’d really like to mention his name and he knows who he is if he’s listening to this, and everybody else does, but it was such genius, he said such a smart thing, and he said it more than once to remind us: “Let’s focus on best science, not on the question of using animals or using NAMs.” So it was a great kick start for roundtable purposes, and actually does reflect my efforts, which are focused on harnessing these intellectual giants to collaborations that are beneficial to them and to science and to healthcare and certainly animal welfare. And believe it or not, the environment, because animal husbandry and animal use does have a fair amount of pollution so to speak attached to it, and in fairness, in fairness, there’s a good amount of plastic waste associated with NAMs as well. But the folks I’m speaking with about that are working on it, and I think that’s going to come to a good end. So to get us going, I set four objectives for the roundtables. First was that we would identify support structures, optimal support structures for the development of NAMs, and what were the roadblocks that could prevent that? Second, how do figure out how to push forward these support structures and remove the obstacles? Third, we needed to estimate a realistic timeline, and wow, “timeline” surfaced as a very dirty word, but to estimate a timeline, a realistic one, for the regulatory approval and the implementation of NAMs, either as partial or full replacements. And last, we needed to think about developing a metric system to evaluate progress on what I call an approximated continuum, and I say approximated because it does not necessarily follow that the more knowledge you acquire will let you move forward. Sometimes, and I have embarrassingly experienced this in my life, I learn something more, and oh, well, I guess I was mistaken about that something, and now I need to backtrack. And I think other folks do this as well in their work, and need to rethink that something a bit before moving forward again.

 

ERNIE: One thing we haven’t mentioned, Lisa, is when did these meetings take place?

 

LISA: We had the first roundtable in the middle of March, 2022, and the second one was the beginning of June, 2022, and I am really grateful that everybody found time. These are folks with extraordinarily busy schedules, and to give their time and attention, there has to be a new descriptor for that, they were terrific.

ERNIE: Well Lisa, what would you say were the main takeaways from the roundtables?

LISA: Well, you need more time than the podcast to review all of them, but I will showcase the highlights for you. Both roundtables were historic meetings for seating all of the relevant stakeholders in one place, and also, for the level of engaged and respectful conversation. And that, in my opinion, was the first and most important outcome from these meetings, was that diplomacy works. Rather than these silly siloed efforts that I spoke about before toward problem solving, you really have a good way forward now. This benefits the stakeholders, it benefits science, it benefits healthcare outcomes, it benefits animals, and it benefits the environment. If I had to give you another takeaway, it’s that there is an interest, and I think a commitment from the stakeholder groups, to responsibly, and I underscore that responsibly, get to a place of best science with all that’s going to bring to us.

ERNIE: It sounds like it was a wonderful set of meetings and I’m sure it moved the field forward. Tell us more about the paper that you and Dr. Muglia recently published in the National Academy of Medicine Perspectives…

 

LISA: It’s a good time to be talking about questions, animal research, NAMs, there’s certainly been a lot of dialogue about animal research, because it’s existed since at least the fourth century BCE. On the other hand, NAMs are infants, and it’s important to know where they fit in now and how they might fit in in the future. So our article poses a question in the context of history and the future. The piece also calls for an entity that would focus full-time analysis on the policy issues and let’s say catalytic investments in NAMS.

 

ERNIE: Lisa, please fill our listeners in on some of the technical aspects of the conversation. You’ve already talked about NAMs, but what are MPSs, HOOCs, PDTs, and PBTs?

 

LISA: We’re going to get to some of my favorite NAMs. Alright. MPS is the abbreviation for microphysiological systems. There are some really bright people who create these functional microenvironments to study normal and abnormal physiology. And my favorite NAMs are two that you just mentioned—the human-on-a-chip and the patient digital and biomimetic twins. The first one, the human-on-a-chip, is called an organismoid, rather than organoid, as a lot of people may already recognize the term, an organismoid by a friend and colleague Dr. Marx. And he’s correct, because this isn’t the single organ-on-a-chip or two or three, this is upwards of ten body organ systems. It’s simply amazing, and it really does recreate, I should say aims to recreate, human homeostasis. Wonderful stuff. The developer of the patient digital and biomimetic twins, Dr. Lans Taylor, is also doing great things, because these are both systems generated from electronic data and from individual patient MPS linked to the patient with the idea or interpretation and hopefully prediction of outcomes, healthcare outcomes in a certain disease, and once that one gets figured out, then gee, that can get templated for a whole lot of things. Just super developments. I think you can already tell I’m in their cheering sections. I don’t’ want to let artificial intelligence or AI go. That’s important. Talking about more friends and colleagues, Drs. Isaac Bentwich and Szczepan Baran are leading in this field, and that’s more geared to pharma contributions, but we all know the importance of drug discovery, so that’s a big thing.

ERNIE: So how far along are these technologies?

 

LISA: I think they are farther along than their detractors would say, and not as far along as the developers might want, and that I believe is going to come down to a funding issue, because one of the takeaways from the roundtables was that funding, whether it’s government or from VCs, is much more heavily invested in animal studies than it is in NAMs. That changes the face of things.

ERNIE: How would you envision that these NAMs will contribute to advancing the 3Rs?

LISA: Well, replacements are the pinnacle of the 3Rs, and those are NAMs, and it doesn’t get better than that. I think all of us, every one of the stakeholders, can appreciate a reliable NAM, and I’ve said that more than once.

 

ERNIE: How will these technologies support the rapid development of precision medicine?

 

LISA: Well, there again, that concept of funding comes up. It’s going to depend, in my opinion, on how well NAMs development is funded, and if it’s funded well, then the resources that are used are channeling towards NAMs are going to let them proceed forward more rapidly.

 

ERNIE: What about regulatory acceptance? I know that that’s a very important consideration…

 

LISA: The regulators I’ve spoken with are open to simply things that work, whether that’s an animal test or a NAM. They want something that’s reliable. I personally know a regulator who is pretty pro-active and is very welcoming to folks who want to discuss their alternatives. And I think that’s probably most of them. She’s just a little bit more forward. I like that. Rah rah!

 

ERNIE: Also, Lisa, I wanted to ask you about, are your thoughts about the FDA Modernization Act 2.0, which was signed into law by the president in December 2022, and specifies that the FDA will no longer require animal test data for new drugs to be approved…although it will still allow animal testing should pharma wish to employ it?

 

LISA: Well I think it’s very balanced. It addresses the sensitivities of those for animal use, those for NAMs, and those who can see the utility of both. And most people I think do see the utility of both. Now that the FDA Modernization Act is law, it is a great opening for drug companies particularly to submit their new drugs for approval using NAMs, and also eliminating the testing for biosimilars. That’s a big deal. From my experience as a veterinarian, I know that my colleagues and I will just sigh a heavy sigh, “We’re testing another vaccine that’s the same thing, and why do we need to do this?” But I’m not a regulator, and they are in tough positions. I do not envy them. They never have a good day. They’re blamed for something and not often applauded for doing things. It’s a tough job. But I think this is another tool for allowing best science in, and that’s important.

ERNIE: What do you see as the current major obstacles to widespread adoption of non-animal methods?

LISA: I’m going to sound like a broken record. Numbers one through ten are funding. That’s really it. It is the rate-limiting feature of this. I am not judging the prudence of investing in NAMs or in investing in animal studies. All I can say, or present, is just the logic arguments. Not enough money goes in, not enough it going to come out, and I think it’s very worthwhile investing in these.

 

ERNIE: Do you think that’s a roadblock that will eventually be overcome?

 

LISA: Yes, I think it is, because there are some large companies out there doing wonderful work with single and multiple organs-on-a-chip, and again, with artificial intelligence, they need to be given their chance. Funding will do that. It’s really an equation: funding plus really smart people benefits healthcare outcomes and the other factors that I discussed.

ERNIE: Lisa, do you think we will ever completely replace the use of animals in research and product development?

 

LISA: Ever is a long time. It’s going to take a while to reproduce very complex biological systems to the level where they’ll be accepted by investigators, but I think that will happen well before “ever.” I have been criticized by some as having a very Pollyana-ish view about it, but I have faith in really smart people, the integrity of regulators, and this working out. So I think with increased funder interest, which I also faith in, I think it’s going to work out.

 

ERNIE: By the same token, would you foresee a total ban at some point?

 

LISA: No, I don’t see that unless all the stakeholders, and I expand that beyond the eight stakeholder groups I spoke about and we can talk about patient advocacy groups and clinicians, decide to vote in favor of a ban. I think the more likely scenario is that NAMs will develop as better and best science, and will replace the use of animals, again using that dirty word “timeline.” I don’t know when that’s going to be, and there were stakeholders at the roundtable who had different ideas about the time it would take to get there. But, you know, there are social interests involved in this, and that doesn’t rule out the strength of voters’ voices.

 

ERNIE: Well Lisa, before I let you go, I wanted to be sure to hear about your venture called CARAT—the Center for Animal Research and Alternative Technologies. Where does that project stand at this point?

LISA: That’s the most important thing I can’t speak about with you in great detail, but I’ll tell you what I can. CARAT is designed to function as a full-time policy institute for NAMs issues, and should have its own areas of curated studies to accelerate the regulatory acceptance and implementation of NAMs. I did want to make the reveal after the second roundtable but there were confidentiality issues and I couldn’t do it at that time. And now that CARAT has way outgrown its original dimension and involves other people, more people, I’m even more limited in what I can say. But I don’t know if this is a teaser, and I kind of hope it is—let’s just wait and see what grows in the spring, OK, we will revisit it then. There is no full-time think tank for these issues, and that’s the proposed function for CARAT, and as I say, I hope that’s a nice big tree that grows in the spring.

ERNIE: We will certainly look forward to it. Lisa, it’s been a fascinating conversation, and best of luck in your efforts to eliminate the scourge of animal use in research and product development, and thank you so much for joining us on FOCUS In Sound.

 

LISA: Thanks Ernie, it was a pleasure.

We hope you’ve enjoyed the program, and will join us again next time. This is Ernie Hood. Thanks for listening!