Interviewer: I'm talking with Dr. Chris Gibson, co-founder and CEO of Recursion Pharmaceuticals. They've developed a fascinating model for identifying new ways to treat rare genetic diseases.
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Interviewer: Dr. Gibson, First of all, is there a need for a new drug discovery model?
Dr. Gibson: If you look at the amount of money that pharmaceutical companies have been spending on trying to bring new drugs to market, we see that they're increasing the amount they spend or at least keeping it flat every year, but the number of drugs that are getting the market is going down. What that essentially means is that the old way of doing things is not working very well. Right now, it's somewhere in the range of two to four billion dollars to get each drug to market, and we think that there's probably ways to do it much more efficiently.
Interviewer: So the name of your company, Recursion, actually has to do with the new way of looking for drugs to treat rare diseases. First of all, not everyone may know, what does recursion mean and what does it have to do with your model?
Dr. Gibson: Yeah, recursion essentially means a simple way of doing something in a very repetitive fashion that can give you a sort of complex or a pretty exciting output. So rather than spending 10 years or several years trying to develop the perfect assay for one specific disease, we're trying to spend several years developing an assay that will work for the vast majority of a huge set of diseases.
Interviewer: So describe that process for me.
Dr. Gibson: So we take human cells, we model a genetic disease in those human cells, and by model I mean that we try to replicate some genetic defect associated with a disease. And then we take pictures of the cells and we look at just basic things like what is the shape of the cell, what is the size of the cell, did the center of the cell, the nucleus, did it move? And by looking at these simple things we actually get a very broad sort of idea of a way that a cell is changing that could be specific to a disease. We don't really know why it's happening, and actually we don't really care. We just want to know that the cell is changing in a way that is disease specific, and then we look for drugs that will rescue those changes back to normal.
Interviewer: So maybe if you can give a specific example that will help people to understand how this works.
Dr. Gibson: This company got its start as a research project in the lab of the University of Utah. We were studying a genetic disease called cerebral cavernous malformation, which I'll just call CCM. And we studied that disease because it is a genetic model of vascular instability. So blood vessels basically get leaky and people get these leaky blood vessels in their brain, and they have hemorrhagic stroke and, obviously, that's a very serious outcome.
When we looked at the cells under a microscope, it was very clear that they looked different when we modeled the genetic perturbation that is associated with the disease. We said, "Hey, let's actually take this and use it as the basis of the screen. So we'll take this change and see if there are any drugs that make it better."
So, we actually ended up using computers to automate the entire process. The computer identified two drugs that we thought would be really useful and we put them into an animal modeled CCM and they both worked really well. So now one of those drugs is being evaluated at the Mayo Clinic in conjunction with the University of Utah.
The first clinical trial is a bio-marker clinical trial. So it turned out this drug happened to be vitamin D3, something that we all get every day. So we're evaluating with our collaborator, Kelly Fleming, at the Mayo Clinic, whether or not patient levels of vitamin D3 have some predictive value for their symptomology. That would be sort of our first step and then the second step could be a treatment trial for it.
Interviewer: When you saw vitamin D3 fixing problems in the CCM cells, this was like sort of proving that your model worked?
Dr. Gibson: Very early on, when we first saw this vitamin D coming out of our early screens, there's this bias against natural products in science. And we thought there's no way that can work. My wife is a neurologist and I mentioned it to her and she said, "That is a drug that's really useful or potentially really useful in the treatment of MS. And vitamin D has been shown to be a really important bio-marker in terms of your vitamin D levels, when you're young are potentially really important for whether or not you get MS when you're older."
And that sort of helped shift our thinking into, "Wow, maybe this is something. Maybe we shouldn't just throw this out because it's a vitamin." There's a back lash against these natural products in many cases and I think it's not always deserved. Sometimes, but not always.
Interviewer: That you found vitamin D3 as being something that helps these cells, and hopefully these people in the future, brings up another aspect of this work, which is that you're not making new drugs. What are you doing instead?
Dr. Gibson: Yeah, we're doing what's called drug repurposing or drug repositioning. So we take drugs that people have already spent a lot of time building, and they're known to be bio-active in some way and we're sort of agnostic to what that way is. We just want drugs that are safe and they do something to some pathway in the cells. Because we're really looking for those unexpected interactions between a drug and a disease.
So, if you go to a lot of the pharmaceutical companies, they have dozens and even, in some cases hundreds of drugs that they've spent years working on. In many cases, spent a lot of money taking these drugs through early clinical trials, and they know that the drug is safe, they're confident that it has some specific effect on a specific pathway in the cell or in humans. But for some reason it just didn't pan out for a business reason or because it wasn't efficacious for the disease they though it would be useful for.
And we see an opportunity to take drugs like that, to take drugs that are already on the market, to take old drugs, things like vitamin D, and to look for new, unexpected ways to utilize them. Because it sort of cuts down on this... Typically people think it takes 10 to 15 years to go from start to finish with developing a drug and that's a really long time when you have millions of patients who have these diseases. So if we can cut off five or 10 years of that by sort of using all of the work that thousands of people and hundreds of companies and universities have already done, then that seems to us to be a really effective way to go.
Interviewer: Well, right. I mean, I think I've seen a quote that you anticipate discovering 100 drugs in 10 years.
Dr. Gibson: Yeah, and I expect that we will get a lot of backlash for that. But we believe that's possible. And it wouldn't be possible if we weren't planning to work with many partners. So, we're not expecting to start from scratch, identify 100 brand new chemicals for 100 different diseases. We're expecting to find some more Vitamin Ds.
We're expecting to find a few drugs with a large pharma partner, and a couple of drugs with a small pharma partner, and maybe some drugs with some academic partners. And I think using this recursive approach where we've developed a core, very powerful platform that we can apply to thousands of diseases, we actually don't think it's impossible that we'll achieve that and that's what we're going to shoot for.
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