Tiny Worms- Experiments Fast

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Elizabeth Frank: Good day everybody and welcome to New Matter, the SLAS podcast where we interview life science luminaries. Today we’re joined by David Weinkove. He’s the CEO of Magnitude Biosciences, they are an Innovation AveNEW company and are going to be joining us at SLAS2022 in Boston in February. We are very excited. Welcome David. 

David Weinkove: Hi, Nice to meet you.

Elizabeth Frank: Nice to meet you too. 

Elizabeth Frank: So I'm going to start you off with the SLAS challenge of describing what Magnitude does in 10 words or less.

David Weinkove: Well, this is what I've come up with. We use tiny worms to test compounds for health. 

Elizabeth Frank: I love that. I'm so glad that you started off with the worms thing David because when I was reading through your website, I got really excited by them because my last podcast interview that I did with Randy Blakely, he’s at the Florida Atlantic University Brain Institute and he's the one that introduced me to the concept of worms, like using worms for this type of science. And I got excited when I looked at your website and saw the very neat chart explaining exactly why you use worms. Tell me exactly what that means in a little more detail. 

David Weinkove: So we use a very specific worm called Caenorhabditis elegans,  or most people call it C. elegans.  It's a really well used model system. So that means that you can do genetics, biochemistry, cell biology and physiology all in the same model. It's a really powerful in vivo model where you can do experiments fast, you can find things out, there's no restrictions in terms of animal ethics or anything like that so you can do your experiments fast and find out things very quickly. 

And it's been really successful in the academic world to find out a lot of things about biology. There have been three Nobel Prizes awarded to people working with C.elegans. But it hasn’t really made an impact in industrial biotech that's proportional to how powerful it is as an academic model. So really that's what we’re trying to do, is to bring that power to a wide range of industrial customers to allow them to test their compounds, so whatever their challenges are, we’ll try to approach it using worms. So we specifically design a worm based experiment to overcome their particular challenge.

Elizabeth Frank: So you said that it’s really successful in the academic world. It hasn't really hit industrial biotech yet. Originally you have an academic background, from Durham University I think, is that how you ended up getting into this? You were working in this field and you wanted to bring it from academia over into industry?

David Weinkove: Yes so I have been working with C. elegans for over 20-years, my PhD was another organism called Drosophila melanogaster   which is a fruit fly. But I started working with C. elegans during a postdoc in the Netherlands. And ever since I started, I've been thinking that this system could be used industrially. Through the years, I've just seen the power of what it can do, but I've also been interested in what people are doing in biotech and in other areas and I just thought, why is that not being applied? That's why I've been thinking about this for many years. Our company is only just over three years old. 

Elizabeth Frank: That's right I think it was 2018 that you guys got started? 

David Weinkove: That's right. 

Elizabeth Frank: Okay so, Can you go over why C. elegans is so fast, especially as an academic model And how that quickness can translate into industry challenges and how it can be applied there? 

David Weinkove: Well I think you have to think about the speed of different kinds of biological systems. So obviously, as many of your members will be familiar with, in working with cell culture, cell culture is very fast as well, you can do experiments quite quickly. Often the next stage once they want to develop that work from cell culture, they need to go into a whole animal model, and so normally it would go to a mouse model or a rat model. 

Now mice and rats take a lot of work, a lot of time, and there’s obviously ethical restrictions and things to think about when you start to design experiments in those models. As I said before, you've got very powerful genetics and biochemistry and so on that you can combine together. 

Elizabeth Frank: Sounds like it translates very well into the aging industry. I recall seeing you working on that on your website. If that is true, with scale and pac,  could you tell us the difference between lifespan and healthspan, for instance, for longevity and aging, as so many researchers will use those terms interchangeably. 

David Weinkove: That's a very good question. So obviously, lifespan is about how long an animal lives for. People think about that a lot when we look at small animals. And most traditional experiments in C. elegans have been to see how long does that worm live. But actually asking people who are developing drugs to slow aging, what they really want to do, most of the time it’s not so much about making people live longer, it's keeping them healthier for longer. There’s no point living for a long time if you're going to be sick and not well. 

Now, in C. elegans the lifespan is only about 2 or 3 weeks. But the time that the worms are being healthy and here by healthy, we mean moving actively and so forth, that time is only about a week. 

We've got some new technology which we developed originally at Durham University and have been developing ever since in Magnitude Biosciences which allows us to monitor how the worms slow down during that first week of adulthood. That gives us really great data on how they stay healthy and we can look for interventions that shift that curve and so allow them to stay healthier for longer and that's really what we want to do. The other advantage is that it gives us much more data because if you're just looking for how long a worm lives for, it's just that one data point, how long does that worm live, it doesn't tell you anything about it's health or what it's doing at that time. 

Whereas with our technology, we can see what happens to those worms, how they change their behavior, how their movement is affected during that aging period and we think that many of the healthcare challenges out there are all about chronic diseases that get worse with age. So there is an idea that is very strongly supported that, if you can slow aging you can slow the onset of these diseases and slow the severity of these diseases. So we really think that aging is something that's really interesting to look at, but our technology also allows us to look at outputs of health - that might be disease-related for example. 

Elizabeth Frank: That is really neat. So I recall from your website you're not just working on aging itself but you're applying this technology to a whole bunch of different fields. So I want to get into that a little bit because I'm curious about the agricultural components etc. But one last question on the topic of health. Could you talk about metabolism; so industry biologics can be mass tried or tested within this system. Could you tell us about a time when you helped someone come to that conclusion? 

David Weinkove: For example we have worked with some small start- up companies that have had a compound which they thought slowed aging and they found that it slowed aging in a cell based model of aging, that's senescent cells, and they really wanted to know if it was working in the whole organism and they didn't have the funds, or the time to go into mice. So we first looked at the toxicity of the compound which is something we always do first. We found that it had very low toxicity so that was fantastic. And we could take that on to look at healthspan. We actually found that the compound did extend the healthspan really nicely. So that gave our client some great data to take to their investors to get further investment. 

Other examples include people who have a panel of drugs that they think may affect aging or health, and they want us to test which ones do and which ones don't. We have other clients that are looking at natural products or mixtures of natural products. We have another client who is looking at particular microorganisms and how they affect health. So we're helping a whole variety of clients trying to find interventions that affect health for different reasons.

Elizabeth Frank: So I get how you're working with biotechnology, pharmaceutical companies, health product companies and the link and other companies looking at health. One of the things your website mentioned was you also work with manufacturing, agri, green manufacturing. Can you tell us a little bit about what you do with them? 

David Weinkove: Yeah so for those companies that are concerned about the environmental impact of some of their products, or of breakdown products of their products and so we have a very quick way to see if they produce this sort of toxicity. 

What is really good about C. elegans is that because they grow so fast and the generation time from egg to adult is only 3 days, and then in the next 3 days they lay a whole load of eggs and there's a next generation. This means that you very quickly work out if there's any reproductive or developmental toxicity as well as the standard acute toxicity. Using the same technology that we’d look at whether something affects aging we can see if something has a chronic toxicity that causes problems over the life course rather than just straight away. So we get really quick and good data on a compound's toxicity. 

For example, a manufacturing company may have a process that removes that toxicity so they want to test that that process is really working. We can look at their products after the process and see if that still has toxicity to the worms or if their process has removed that toxicity. So it's that kind of experiment we can do. Or they might be developing a new compound and sometimes their medicinal chemist might come up with 1000s of different derivatives and they want to find out if there are any that are really toxic that we want to avoid. We can screen through those compounds and identify those that are toxic and say that you are better off focusing on the other compounds. 

Elizabeth Frank: That’s really cool okay, so for the manufacturing side of things and the green stuff, the impact of that is how they break down in the environment, so the worms are basically like this is toxic for the environment or this isn’t toxic for the environment. 

David Weinkove: It gives you a really good indication. 

Elizabeth Frank: Okay so still on the manufacturing side, you mentioned a lot of technology. Could you tell us about which systems are using in this company? Which technologies are your main stays? 

David Weinkove: So our mainstay technology is something that we developed ourselves, so my co- founder Chris Saunter is a physicist by background, he's been a physicist in Durham University for 20 years, he's now left Durham University to work full time with Magnitude Biosciences. He comes from a background of instrumentation and analysis, so their department uses this to look at the stars in cosmology and look at images from telescopes. For example using images from telescopes to see if there's something moving. A bit like in that film Don’t Look Up! So this is the kind of technology that spots that. So instead of looking at the stars he's using it to look at our worms. We have a whole array of cameras and each camera looks at a petri dish that has about 30 worms on it and it monitors them all of the time, looking to sense movement and that's how we sense movement 24/7 across many many worms at onces. We have over 100 cameras and we are building 100s more and each one of those cameras is looking at a large number of worms. This allows us to continually assess a large population of animals and allows us to test different interventions and compounds and so on. 

Elizabeth Frank: That is really cool. I want to swing into a few more generalized questions for a moment. Just because I'm always curious about this for our start up companies, especially those that are pretty young. I want to know what the squeeze factor was. Was there a moment in the early years of your start-up when something happened where pretty much everyone in the company was just like yes we did it! Was there some really exciting moment whether it be your first sale or first successful experiment. Can you share that with us?

David Weinkove: I think to begin with most of our clients were academics and then we were really excited when we started getting some industrial customers and some biotechs. We signed a biotech customer in Cambridge, UK and it was really exciting to work with them. And then we’ve started to work with several biotechs in the US, which has also been really exciting, doing different things. We've got clients based in the far east as well. It’s been really exciting to do that and also really fantastic when we do find a drug or intervention which makes the worms live healthier. 

We had one really recently which obviously I can reveal but everyone was very excited. To a point where we thought that this was something that could really have an impact on people's health and aging. Obviously it takes a while from our part of the process to actually becoming available to people but it can be really really exciting to think about that. The other thing about this is that we get to work with some really amazing people. Much more so than in academia, but when you’re actually talking to people developing new things there's a real excitement and different way of thinking and I've really enjoyed that. 

Elizabeth Frank: That is awesome, I can see how that would be super exciting, knowing that your work, even its at the base level in the worms knowing that it's something that will eventually be translated into humans. That sounds really fun. One of my next questions would be, that you are going to be exhibiting in Innovation AveNEW in February. Who are you looking forward to networking within SLAS? Is it biotech companies you're trying to get some connections with or is it just a widespread of industry, or academia? 

David Weinkove: SLAS is a new thing for me, and I'm really looking forward to meeting some of the people that attend SLAS on a regular basis. I'm coming in with a really open mind and hoping I can form some new networks and find some partnerships that might be long term. So I don't want to prejudge it and say I want to talk to this type of person. I really want to see what people want to do. What are their problems? Are they problems we can solve with C. elegans? And sometimes the answer is no but sometimes it really is yes we can help with that. It's really great to have those conversations with someone and you really talk about what their issues are, and you start to think hang on a minute, maybe we can use C. elegans here to do this particular thing, and it is something neither of us have ever thought about before and that’s really great. So I'm really hoping that I have those kinds of interactions and I'm really looking forward to it. 

Elizabeth Frank: That is awesome. I can't wait to meet you personally and see the booth at SLAS 2022. I'm going to ask one final question and then open it up to anything that you might want to add that we didn't touch base on. You mentioned early on in the interview that three Nobel Prize winners had used C. elegans in their research - something about using their cells to make the worm grow or die. Can you tell me any really neat fun facts about C. elegans that the general public may not know that we should? I’m quickly becoming obsessed with them honestly! 

David Weinkove: Well it's interesting because they have 300 neurons. For a long time it was thought that they had 302 neurons but two of them got downgraded to non-neuron cells. So that’s their brains, and you might think that's quite simple but someone using electron microscopy has looked at all the connections and their 57,000 interconnections between those neurons, so it's an amazing system and they respond to all the neurotransmitters that we’re familiar with. So like Dopamine, Serotonin, Sarcoline, Gabba, Glutamine, all those kinds of things. Sydney Brenner, who was the original person who set up C. elegans as a model. He always wanted to use C. elegans to understand the nervous system. The first Nobel Prize which was won was for discovering the genes involved in apoptosis cell death which is now used in cancer research. The second one was to do with RNA interference which is now being used as therapies. And the third was to do with GFP which is now used in many many different systems. All of those things were in a way accidental discoveries on the way to understanding how the C. elegans nervous system works, and the funny thing is we still don't really understand how it does work even after 60 years of working on it. We've found an awful lot about C. elegans nervous system but we still don't really know how it works. 

Elizabeth Frank: I liked that fact, it was fun. Okay so I'm going to close this out with just seeing if there's anything I didn't talk about that you want to share about your company, or how to find out more about you. Obviously your website and I'll link it in the notes. Is there anything final you want to say to the audience? 

David Weinkove: I think I would like to say, I’d like people to start to imagine what you could do with an intervention that slowed aging. What would that do to disease, what would that do to the way that people work and is it worth putting that effort into trying to slow aging rather than putting effort into individual diseases. 

Elizabeth Frank: I like that you gave our listeners a homework assignment! 

David Weinkove: Another thing that's worth mentioning is that from this year I’m the chair for the British Society for Research on Aging. So I'm very much tapped into the aging network in the UK and abroad, so I'm often thinking about aging. But what I'm trying to do is think about how aging and thinking then about disease and how those interact with each other. 

Elizabeth Frank: Okay, well I'm going to be very much thinking about it. I'm really excited to see Magnitude Biosciences at SLAS 2022. Thank you for talking to us today and I'm looking forward to seeing you soon! 

David Weinkove: Thank you, I’ve really enjoyed it.