Brewing Psilocybin with Dr. J Andrew Jones

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Brewing Psilocybin with Dr. J Andrew Jones

 

On the Mushroom Revival Podcast, lead researcher of the E. coli psilocybin project, J. Andrew Jones, PhD., discusses the idea of producing psilocybin and other mushroom compounds in a bioreactor to use for clinical trials, affordably on a commercial scale. 

Listen to Jones in conversation with Mushroom Revival founder Alex Dorr on our podcast to learn more about how Jones' research enabled the first example of psilocybin production from a bacterium.

Show notes:

Interest in psychedelic “magic” mushrooms has seen a renaissance in the last few years—after having lain relatively dormant under the weight of heavy drug regulations for decades. This wave of interest has, in part, been fueled by the therapeutic potential of psilocybin and other compounds found in magic

mushrooms as options for psychedelic-assisted psychotherapy Psilocybin is one of the most well-known psychedelic compounds produced by several species of
mushrooms. There are suggestions that it could help people with depression, addiction, and other debilitating mental health disorders. The issue is that psilocybin is illegal in most states, and effectively researching it is a regulatory challenge. One of the researchers grappling with the potential of psilocybin is John Andrew Jones, Ph.D.—an assistant professor at Miami University. He joins Alex Dorr on the Mushroom Revival Podcast to talk about his work synthesizing psilocybin and the regulatory hurdles.

Key Topics Discussed

  • Dr. Andrew Jones’ inspiration behind psilocybin research.
  • What does metabolic engineering look like? – Biosynthesizing psilocybin using E. Coli
  • Navigating psilocybin laws and regulation
  • What are the legal and health implications of synthetic psilocybin?
  • The cocktail of compounds in magic mushrooms (psilocybin, psilocin, norbaeocystin, baeocystin, norpsilocin, and aeruginascin).
  • The challenges of working with psilocybin.
  •  “If you had no legal, labor, or regulatory restrictions, what research do you feel would be the most important in this industry?”
  • AI drug discovery
  • What advice would you give people interested in pursuing a similar career path?

 

Connect with Dr. Andrew Jones

  • Website: https://www.jajoneslab.com/
  • Email: jones@miamioh.edu
TRANSCRIPT
0:19 Well, welcome, welcome. You're listening to the mushroom revival podcast. This is your host, Alex Dora. And we love to geek out about the wonderful world of mushrooms and fungi. We bring on guests from all over the world to geek out with us and an amazing time. I am currently at an Airbnb in Utah right now. And so I'm using a pretty crappy travel mic. And so the audio might be a little lesser quality than you're used to. But we're gonna roll with it and have an amazing conversation with our friend Andrew Jones. How're you doing, Andrew? Doing? Well, cool, you want to give a brief bio on who you are what you're doing? Absolutely. I'm an assistant professor in the Department of Chemical paper and biomedical engineering at Miami University. I work in a field called metabolic engineering, where fundamentally I try to take synthetic pathways from pretty much any living organism and try to get them to function in a well understood organism we use Ecoli for most of the work that we do. And hopefully the pathways we're pulling can make metabolites that are a particular interest. And the reason we're talking today is because a few years ago, I started to work towards tryptamines. And psilocybin was my kind of first molecule that I targeted, and I was able to create a strain that makes a lot of psilocybin. Now that's having some pretty interesting implications in providing drugs for clinical study. So that's something about kind of what I do quit my own intro. I do have a PhD from Rensselaer Polytechnic Institute in upstate New York, that was in chemical engineering. And then I got a master's degree previous to that in environmental engineering in a school called Mercer University in South Georgia, and a Bachelor's degree in Biomedical Engineering, also from Mercer. So I have a breadth of experiences abroad, that background, I really got into this kind of metabolic engineering space during my PhD. That's the place where I am really enjoying the types of problems I like to solve and think about. How did you originally get into engineering E. coli to produce massive amounts of psilocybin? How did that even come across your plate? I get this question rather frequently, actually, because it's not something anybody else has done, right. So I guess in grad school, like I said, I fell in love with this kind of idea of genetic engineering and enabling Ecoli to make these compounds it's never seen before. And I during grad school, I made a lot of different compounds. nutraceuticals, like anthocyanins and flavonoids that are found in fruits and vegetables that can be used as food supplements, done some pretty cool synthetic biology work making natural purple dice, right? If you could use the dye blue jeans, or made a lot of kind of tool development in synthetic biology, changing genetic elements to be able to fine tune the expression of different compounds. I've even engineered bacteria that can consume methanol and produce high value compounds, right. So I've done a lot of different things. But none of those really had, I didn't feel like I made a lot of impact outside of kind of the academic circle that I kind of worked in. And so when I started my job at Miami, I was really interested in coming up with something that would impact the world, right, I was very, I'm very interested and still remain interested in training new scientists, right. So I work a lot with undergraduate students and Master's students, to be able to get them excited about the field that we work in, and have them do some really cool work of the student training is really at the forefront of what my motivation was. And one of the best ways to train students is to get them really excited in what they're doing. So I was searching for some molecules, there's some target thing we could try to make, that would get them excited and be something new and novel. And around this started in 2017, in Miami, and then also like, a few months after I started, a paper came out from a group in Germany where they had kind of identified the biosynthesis pathway for psilocybin in the mushroom. And when I was reading that paper, I was like, I think all these will work in bacteria, and I had to tweak the pathway a little bit. And my second year here at Miami, I was able to enable psilocybin production and bacteria. I like to think of that as the the E. coli is best day they've ever had. So that was a really impactful kind of day in my lab. And since that time, we've really worked to expand not only the amount of psilocybin that we can produce, we call that a tighter or a concentration of the drug. Higher the concentration, the easier it is for purification and downstream applications. We're also kind of diversifying and we're looking at a wide range of different terpenes. Turns out the process that we use to make psilocybin can be used to make lots of other derivative compounds of psilocybin that may also have some interesting bio activity. So we're starting to branch into some of those and seeing kind of, maybe they'll have some interesting clinical abilities to alleviate the 5:00 depression, anxiety, post traumatic stress disorder in many ways, the psilocybin at least preliminary data has shown to work. But we're looking for some compound that maybe doesn't have the hallucinogenic connection, right? The side effects that you do on this six hour voyage to a different planet, it would be great in a clinical sense to not have that connected to the drugs, we're starting to branch towards looking at that we don't know exactly what the solution is, or are searching for. But we're starting to do some kind of drug discovery and recently partnered with a lab in psychology department here in Miami, where we're starting to test some of these compounds in animal models looking for interesting applications. That's kind of a story of where we're going. And I think we'll dive into a few of these parts as we discussion. Yeah. So for people who don't know much about genetic engineering, especially with E. coli, and me included, like, what does this look like? If you're going to give a very, you know, if you're giving this pitch to a bunch of golden retrievers, and five year olds, can you kind of give a how to episode of how it's made, I think, is kind of what you're looking for. So even though I'm in an engineering department, right, my lab really looks like molecular biology. Right. So what that means is that, in the last 10 years, there's been this huge resurgence of synthetic DNA and being able to pull recombinant DNA from different microbes and enable it to be expressed in new hosts, right, the tools have been kind of established. Um, so what we're effectively doing is typically it starts with we synthesize DNA, right, so we'll call up our favorite vendor for DNA synthesis. For me that gene was hopefully they hear this and give me a discount. But I really well synthesize whatever DNA fragment we want that encodes the enzyme that does the biosynthesis process, we then put that into a plasmid vector, right, which is a small piece of DNA that's contained within the bacteria. And it's stably replicated and can express the whatever DNA we put on there, right, that's one way to do it, or other ways, but that's where we generally start, once we express these genes of interest, we'll start testing for their activity, right, which means that will, typically an enzyme can convert substrate a into product, it will oftentimes feed substrate A to the bacteria to see if we can detect product being formed, right. And if we can see a little bit of activity, right, that's where my expertise really comes in. Right? If I can see a little bit, I can tweak it in a way and balance the metabolism of the bacteria to be able to greatly enhance that production. And that's kind of where we were with psilocybin. Is this Protoplast? Fusion? Is this CRISPR? What is this? Yeah, not exactly, it's somewhere in between? Yeah, it's actually something else more straightforward than either. So a protoplasts are things that are often used in kind of plant engineering, which is an unwieldy organism, and very slow to grow and hard, right, frankly, think CRISPR. Certainly, I use CRISPR. For some of my work. CRISPR is a tool that has the ability to bind and cut DNA, right. CRISPR is a very useful tool when you want to bind in cat DNA in vivo, like wow, the organism as a living most of my DNA manipulations and cutting and assembling, you know, happens ex vivo, right, so I purify the DNA, I manipulate it however I want in a test tube, and then I put it back in the bacteria to be read again, there are certain things that need to have that you need to do that while the bacteria is living, if you want to mess with their chromosome, for example, then we use CRISPR for these types of things. But really, I'm using most of the tools that I use are not the kind of newest and novelist, directions, right. But it's kind of the tried and true restriction enzyme digestion, a lot of well plate screening. So in the platform of maybe three inches by four inches, right in a standard well plate, we can screen 48 Different mutants at once, right, and my lab has typically has 10 to 15 of those plates going all the time. Right? So we're screening hundreds of mutants a week looking for enhanced production. And then once we've kind of identified that, right, by feeding that substrate and making that product, we'll start to kind of assemble genes into Pathways, right, where we can feed into three A and then enzyme, one makes intermediate product A and then immediate product B and then our final product. And as we start to assemble these pathways, we start getting into kind of significant kind of chemistry steps that overall that enable our biological process to compete with a traditional synthetic chemist, something that would work better without living organisms helping you along the way. Yeah. And why is E. coli the model organism for genetic engineering? Every time I hear it, it's always E. Coli. But E. coli is pretty dangerous to us if we consume it, so it Yeah, I don't know if there's a simple reason of why it's always used. So E. coli is the most well studied organism on the planet. We know more about E. coli than we do anything else. It's has a long history of both empirical study and basic research but also in kind of bioprocess application. 10:00 shins for use of production, the first recombinant product that was made was done in E. coli, that was kind of the insulin on a peptide. And so it's just something that works really well. It grows quickly and enables us to screen things in short periods of time. And we have lab strains of E. coli that aren't dangerous, right? They're called biosafety level one, right, which means that we don't have to, there's no harm to human health by being in the presence of it. It's not the same E. Coli. So you gotta remember, there's lots of different types of E. coli, lots of different strains, some of which are the ones that give you kind of incredible diarrhea, right? And then some of which are the ones that inhabit your gut all the time, right? You have tons of bacteria, and tons of E. coli growing in you all the time. And that's what's healthy, right? It helps in the digestion of food and your microbiome. We're learning every day, how more interconnected you are with your microbial kind of hosts that really helped with lots of different functions and signaling pathways and variety of other things. So we call it it's not bad, right? And then our lab strains are kind of slowed down and pain, diversity that are well studied and know how they respond to certain stimuli and those types of things. Yeah, I had no idea. I thought they were all harmful for human health. So yeah, that's something new every day 11:17 is the coolest. So obviously, you're you're producing a ton of psilocybin in your lab, and which is federally illegal right now. And what is the process or loopholes that you have to go through or regulations with the DEA? How strict is it for you to do this research? Yeah, absolutely. It certainly is a big hurdle. First off, I want to correct it, I'm not making a ton in case the DNA is taking that literally, we're making grams well within our thresholds that have been established. But yes, there's a lot of paperwork, I have a DEA schedule one license, which enables me to have these compounds in the lab, I have very controlled scenarios, right, it like to get to any of my kind of purified drug, you have to go through these four different locks doors, right with different combos that very few people know have access to right key doors and keypads and swipe cards. And so there's a wide range, and it's a little bit more than what's required. In my case, I'm just because I do work in a university setting, I have a lot of undergraduates that are not far away from the work I'm doing. And I want to make sure that take extra precautions to make sure I can continue to do the research that I'm doing right, and continue to kind of develop these drugs that will hopefully help humans wanting. So there's a lot of restrictions, there's a lot of reporting, a lot of accounting for what I've made and what I haven't made. It's not unrealistic, I found that when I've been working with the DEA, they've been realistic, right when I first came to them and told them like, I have a bacteria that can eat glucose and form psilocybin. Right. And it's not something they'd seen before, right? It's not something that anyone else had really done. And their structures are very set up for kind of preclinical studies, right, where you buy your drug from a supplier and you bought 100 milligrams, right, and you dose this out to milligrams per animal for X number of animals, and you should have X milligrams remaining. Right. That's how they react with the setup. And when I told them like I engineering, this bacterium, the goal of my research and how I'm pushing forward this field is to enable these microbes to make more of this product every time and I can't always predict how well it's going to happen. And that kind of threw for loop for a while. But we worked out a kind of process, most of the drug that I make gets destroyed, because they didn't get it the methods I'm trying to develop into strength. Very little of mine actually goes through a purification pipeline to make final product in the end. So a lot of it gets destroyed, right, soon after it was produced. And they know the the yields that you're getting were way more than you were originally expecting, which I think in the 2019 paper it was 1.16 grams per liter, which was 500 times what was already out there in terms of yields, which is significant. Did you reach a point where you had to set up an agreement with the DEA, like, we're only going to produce x amount of grams, and then you produce 500 times more than you originally thought? And you know how to flush it all down the drain? Yeah, I mean, that's kind of how it works. Right? So when you go through two parts to the answer. The first is, when you start up, you're kind of DEA kind of you submit your proposed work and all of this, right, you estimate what these numbers would be. But those numbers are really the amount of compound that you're keeping on hand. Right? It's not the amount that passes through or gets destroyed. That was part of the kind of agreement and negotiation we had to talk about how to structure because I don't know it's like hard for me to predict how well the microbes will perform. Yeah, are the ones that you keep Have they gone to any clinical trials yet or are they purely for establishing your r&d and your your methods? Yes, so nothing has gone to clinical trials. We have put some 15:00 In with my collaboration in psychology here, we fit some to preclinical work. So mainly rat models, and a few other small things, nothing for clinical trials yet my work has been, I guess, full disclosure, my work has been licensed by Biotherapeutics, which is a public drug company working to develop some of our technologies. So all my stuff is at small scale and not under kind of GMP processes, which is kind of the good manufacturing processes, or their goal is to kind of take what I've developed, take the kind of genetically superior optimized strains, and scale those up under those kind of more stringent conditions, developing products that they can put into future clinical studies. So I can see the end of the pipeline, right, I can see where that could potentially return to me with my process could go into humans, which is absolutely exciting. As an academic, right, like, all I want is I want something that I've done in the lab, something that I dreamed up and with the help of my students, right, we're able to see a product go into human and help someone, right? It's yeah, the number of emails I've gotten in the last few years, and people being like, I really struggled with depression and I, I had thoughts of suicide, and I couldn't function right. And then I started recreationally self dosing with psilocybin mushrooms, and that changed my life, right? And I know it's anecdotal, it's not going to get you an approved drug by listing off all these people that have said to help, like, just seeing that time and time again, has really changed my perception. And like, it's made me that much more driven to make a product and a process that's going to help these people that can't find help with current kind of treatments. And I don't know how much you're following the status in Oregon. But do you feel like they're going to push forward with synthesized psilocybin or psilocybin rather than the full mushroom? And do you feel like for kind of clinical or medical settings, that would be the pathway forward? Because it's more regulated, rather than a full cocktail of mushroom that has all these compounds that we don't even know yet? Yeah, so I don't know the current status of the Oregon legislation. But I can't speak to this question. The idea here is the fact of the matter what, like psilocybin is safe, right, but it does have this stigma that's associated with it. And it has this stigma that it isn't safe, and that it's this illegal drug that's going to cause you to do what? So I think what's very important about this field is that we take a very methodical approach to proving the efficacy, safety and efficacy of this drug through specified clinical routes. And what I'm afraid of right, I do think that a lot of people see benefit from using kind of the natural product, taking mushrooms. And I think there may even be value to mushrooms that are beyond a purified psilocybin or Cillessen compound, because that's some of the work that I'm getting into is looking at some of the other compounds that are present the mushroom and how they interact with psilocybin to maybe change the experience that you're on, right? Many recreational users report, one strain of mushroom gives you a different trips than another. And I'm trying to unravel that scientifically. And what that means. So that's something that's really exciting to me, we have to be very careful, right? We don't want to have a poorly designed clinical study that used an inconsistent natural product, lead to some results that can put the field back even further. Alright, so right now I want to see either chemically synthesized or preferably biosynthesized. With my process, they both make the same drug, same purity, everything's identical. There's just a economics argument that you need to make to figure out which one actually was, but I want to see purified drug be studied first, right? I want to see that be established as a gold standard, right? And then we can start to explore these kind of, what do you want to call it an entourage effect, or whatever it would be with the whole natural product? There's some value there. But that's a hairy problem that has the potential to push the field backwards. If it's not handled correctly. That's the caution that I give. Yeah, I have a couple of follow up questions for that. But let's start with your work with Nora biosystems. And I'm curious if you are working are currently working or plan to work with other tryptamines in philosophy, mushrooms that are of interest? Yeah, absolutely. So we published a paper either late last year earlier this year, where we took our same process for at least a very similar process to what we use for psilocybin. And we produced Norbury system, which is an intermediate product, and it's actually the for psilocybin is a Dimethyltryptamine. So we actually made even more, I think we published about 1.5 grams per liter of orbera system in those studies, showing that our processes applicable to other tryptamines which is exciting. And we also had some preliminary animal studies that show that norba system is not hallucinogenic, or at least didn't elicit a head Twitch response in robots, which is something that I think might be potentially exciting, because there's some discussion 20:00 Should in the field, right? Is the clinical benefit? Or the medicinal benefit linked to the psychedelic experience? Or do they have some type of are those kind of independent apps? I don't know the answer. Yeah, that's kind of outside my field. But I think being able to produce this other compound, which is one of the compounds that's natively in mushrooms, right, which could be an interesting starting to look at it, and its interactions with psilocybin. Those are all incredibly important questions, and it's the start to be able to do that. We're in the process of looking at pretty much every intermediate you would look at in the psilocybin pathway, your bay asst and origination. Right? Those are things that maybe are more familiar to those in the recreational space come, then we're also looking at a ton of non natural versions, right? What happens if you have a, you put a fluoro group on one of those on psilocybin or a, what if you put on nitro group or cyano? Group, right? How does that influence the kinetics in the psychedelic experience and the potential efficacy towards disease treatment? So we're looking at kind of a broad range, right, because drugs fail clinical studies, right, there's a chance that there's going to be something crop up that we can't predict with psilocybin, and we want to have some suitable alternatives that may not have that same kind of issue, but can still give the kind of treatment potential. So I would argue hundreds of different variations at this point, looking for something that initially starting with strain development to make enough where we can purify it and have a stable source for the preclinical work. So I know with cannabis, there was a lot of different alterations to these chemicals. Delta eight is pretty famous right now. And it was just the alteration to CBD. And then spice and Ketu, were really famous back in the day, I don't know, like 10 years ago, and they were trying to get around the loopholes of legality, and they're able to sell basically synthetic weed without it being illegal. And I'm sure, I don't know how legit these health concerns are. But there's a ton of people really concerned about human health effects posts consuming these synthetic alternatives. Obviously, we would need to do human clinical trials and safety tests to find out that these new drugs are are safe for human consumption. But are you worried that somebody in their garage is going to make these synthetic alternatives to bypass the legal ramifications and then really seriously affect someone, there's certainly a possibility. We published a paper not too long ago, six months ago, at this point, titled homebrewed, psilocybin, a little bit of press. And the goal of this paper was not to make a wild how to guide homebrew your psilocybin, right. But it was really to kind of highlight the power of our strain, right? Even not using our $25,000 equipment in the lab, right, just using a rudimentary setup that you could put together in your garage for a few 100 bucks, it's feasible to be if you had access to my strain, you could produce psilocybin. And so in that paper really focused on what are some legal mechanisms to make sure that this is properly controlled, right, and that we don't have access to key things such as our strain repository, that would enable this kind of recreational market because there are lots of unknowns, right from my process, in particular, right, tons of just recombinant E. coli, right? We don't know a genetically modified organism, right, that's producing this compound has never made before. And enzymes that were expressing it are lacking on other metabolites. And there's, there's a lot of purification downstream, that's not really possible in your garage, right? And we don't really want people experimenting there, because there could be some health implications that again, like I mentioned earlier, right, that might derail the direction that we really want this field to go. We want these things to become legalized, right, and prescribe herbal and put into a position where you can help people that are struggling with these little illnesses. Is there anyone doing research? Or has there been any published research on the effects of nor biosystem biosystem nor psilocybin or psilocybin and all these kind of entourage effect chemicals that we're finding out? And I know, you know, we're finding new chemicals every day. And I'm just curious if we're at the point where that we know they exist and have no idea what they're doing or that we have some sort of understanding of what they're doing. Yeah, there are a few people working in the space. Adam Halberstadt is one researcher, I think he's at UC San Diego, who has published a little bit on a assistant I believe, and started to look at that and it said to which response and roads and a few other things, but we don't know what they're doing. We in my collaborations here, we guess stay tuned would be the best way to put it on. We're studying these we have some pretty exciting data that we're hoping to publish in the next year. I'll certainly keep you in the loop on when those come out. I'm sure they'll make some good press. If you had a gut feeling guess of what they were doing. What would you guess? My gut feeling guess would be that they are bioactive because they've very similar structures and may 25:00 We work to affect how psilocybin acts, it could increase the action of psilocybin or it could decrease it, right and understanding how those interactions work and really, really understanding the pharmacology, right, and the kind of molecular binding and kind of how all these different molecules would present together, how they compete for binding spots and affinities in that space. That's something that a lot of people have looked at last thing people have thought about that are in this space, but it's something that really excites me, one of the really things that's holding this field back is, we have very few researchers actually working in this area because of the legal hurdles that you have to jump to work on these compounds. That's one of the reasons I went to Norbert sistent. Because I have a nice letter from the DEA that says this is not a regulated compound, right? It really makes it where I can do more science that I'm not limited in quantities and I can kind of use that as a stand in for a lot of processes. Because a caveat on that it's not a regulated compound, as long as I don't have plans to put it in humans start putting in humans a whole nother rulebook. Oh, interesting. Yeah. So that enables us to do a little bit more work and allows me to have a little more flexibility in locations where I can do the work and volumes of things I can use and how I can kind of process those. Are you able to ingest it yourself? No, no? What would happen? If you did? I am not that big of a risk taker. Okay, I see. Yeah. Yeah, I'm not a big experimental drug taker in general. Sure. Somebody probably why you're still you're breathing right now. 26:34 Going on several these types of podcasts, I think something oftentimes surprises the guests and audiences that and it's because I believe in the power of the right, I've talked to so many people, and I've seen how it changed people's lives. And I'm really happy with how my brain works right now. And I'm afraid that it might rewire it in a way that I'm less happy with, right. But if it was something that I was struggling with depression or anxiety or something like that, oftentimes I see people that are cripples their lives to work on that and, and mushrooms have changed their life. Yeah, that's really cool that you could say that you're happy with where you're at. That's pretty rare for any human to say, so incredibly happy that I don't have to fight the struggle that many people do. And it took me a while to realize how big a struggle that is for so many people. And now that I'm working in this space, that's where it's really kind of changed my perception, then I become much more emphatic, or like, have much more empathy for people that struggle with that, and I'm starting to understand it. And I realize how big of an issue it is also working with 18 to 22 year olds all day at university, I see how prevalent it is, and that student population in particular, and it's only getting worse with COVID. than that just drives me even harder to find solutions for these. What has been the hardest time in your research? Yeah, I mean, certainly some of the administrative hurdles, right there were certainly at some time in there, where I was unsure if my university or my state or my or the DEA, we're gonna let let me continue doing this work that I saw a lot of promising. So there is administrative hurdles, and certainly fighting some public perception on some of the work. I guess that was a hard time. But I think most of that is in my rearview mirror for now, hopefully, honestly, this has been it's like, science is awesome, right? When it works, it works. And it just like moves in there's, there's really exciting directions. And then when things aren't working, it's like something, you just feel like you lose faith in science. But really, it just hadn't figured out that much. And yet, and this has been one of those projects that just runs and it's been fantastic. The people I've met in the community in the kind of psychedelic space, but the academic researchers and the investors and the recreational users, and it's just been a very welcoming community. And people are just genuinely want to learn more. Right? I think it's a very, very different space than many other research spaces where there's lots of competition, I, the number of people that are kind of positively have a synergy, right. And they want to facilitate that synergy is fantastic. And that's something that I found is pretty exciting. And it's certainly not an answer your question. It's not Yeah, I guess that's maybe the scene how interactive about society people are, I don't get the anti science vibes that I get in some other research fields, right? You go work in biofuels, or like, energy, green energy or something, right. And you get all these people be like, I don't believe your science. I do feel like in the psychonaut community, I guess, maybe not the best word. But people generally want to learn more, right? They want to see and they trust that you're doing good science. And that's something that gives me kind of faith. And I guess this is my plug for scientists and try to drag this kind of mentality into other fields as all because 29:49 science doesn't lie, right? Sometimes our interpretation of it's not correct, but being able to look for people that can critically think about problems and develop solutions in a synergistic synergistic that 30:00 That's the future. That's where we need to go. And if you had unlimited funds and an unlimited team, you know, no regulatory loopholes, you know, or restrictions, getting in your way, what research would you feel like would be the most important to do to push this industry forward? I think a lot of my work right on the production side of things, right, is something that could be solved with more money, if you can get a diverse set of people and build through in much the same way that COVID vaccines case through, right like that was the fastest output of a biotech industry that I think has ever happened, right? We have multiple, highly functioning vaccines. That was amazing, right. And that's what happens when you put money and resources behind a big problem. So we could solve a lot of the production side of things, right? Whether that's the bio side or the synthetic chemistry side, I think that's really just a piece of the pie. But probably the larger piece is trying to understand this clinical side of things, right? Can we figure out how these drugs work? Can we document their safety and efficacy towards different diseases? Can we find clinical studies, right, lobby the DEA to increase the quota limits so that we can actually do these clinical studies. 31:17 There's a lot of moving parts in this space. And I think a lot of it is we're right at that precipice, at least looking at psilocybin, I think some of the other compounds have some discovery left to do. But I think money and resources probably could get us a little bit further towards legal prescribe double psilocybin the east with therapy, approach to solving some of these really big mental disorders. So I know with cannabis, there's you walk into a dispensary. And I don't know if you smoke in this, or I've ever I don't, but I've been in a couple of dispensaries. And I've been blown away of all the just designer strains, and they have all these different names and all these different varying levels of compounds, this many milligrams of THC, this many of CBA, CBD, all these different things, and this is the effects that you're gonna get out of it, or you should. And do you see this happening with psilocybin with both synthetic versions, and then also with just like growing the mushrooms, like, do you see future clinical trials? And in medical settings, do you feel like, you know, once we get the research done, and your bio system and all these different tryptamines? You know, are we going to have, instead of pure A, you know, psilocybin or psilocybin? Are we going to have a cocktail, but it's a very strict cocktail. Exactly. We know exactly how many milligrams are in each thing. And we can reproduce that and replicate it. I can envision a case where if we fully understand how these compounds work, right, realistically, there might be a compounding solution where maybe a psilocybin heavy cocktail is something that is prescribed for depression, right where maybe a bay asst heavy cocktail is an anxiety thing, or in a really nice and nervous system that he cocktails, something that helps with post traumatic stress, right? We're a long way from being able to have the science backing to make that decision. But I could see that in the same way that you might get a a cocktail of antibiotics to fight off bacterial infection or something, right, you could very well get a cocktail of tryptamines that can help with the different kind of mental illnesses that I can see that that's my dream thinks that's the direction I'm pushing my lab to explore right and wrong 90% of the time, so maybe that's not a viable direction. Maybe he's also had been good enough to help with all of them. Right. And, but it's certainly something to explore, because psilocybin is not perfect, right? Like, sure there's some grandmas out there, that wouldn't mind it, right. But like, in general, I couldn't see my grandma doing psilocybin, right. Like, I just don't see the hair, like having the wanting to undergo that side effect and unknowns there. So I think getting rid of that really helped more people. So that's what I'm hoping for, right? Getting away with these cocktails are difficult. What do you feel like is the future of biosynthesis for these compounds? Have you been itching to use a certain machine that you hadn't been able to use before? Like some certain thing that the DEA won't let you do that you you feel like will boost production by you know, X amount? Or is there anything that you haven't done yet that you feel like is the future of the industry? We're going a lot of directions, the current limitation I have is a screening approach. Right? So right now I have to create my strains and I can create them in the millions right? That's easy. Creation stuff is easy design and build is easy when the testing is what takes a lot of time to isolate them individually and test them individually. Is the analysis individually a process to dive in individually? There are some pretty fancy 35:00 have equipment out there that can really speed up that testing stuff. Right? There's also some science that ways to produce these compounds, or screen the production of these compounds, maybe with some type of flow cytometry or kind of rapid analysis, right. There's some interesting like laser based approaches, you can kind of select and screen more quickly. So I think if I had circled back to a previous question, if I had limited money and resources, I do think there's some kind of cool toys that could speed things along. And I think if we were to see these compounds be legalized in a way that enable other people other, let's say, other pharmaceutical companies to work on it, right? Because that's where the money is. That's where you can move these things fast, right? COVID, like the basic research for the COVID vaccine happened in academia. But the real work happened in industry, because they had all the money in backing, because that's what I think if we could lower that risk of fertile the burden, hurdle or industry, they have these tools, they have the money, they have the money to double down and develop some of these a little bit more quickly. In a way that doesn't make sense for academia. Have you heard of API? Does Canada applied pharmaceutical innovation through a AI partnered drug discovery company? Haven't heard of them? But I have talked to several people over the last years doing AI based drug discovery. Yeah. Is that something of interest that you think would help you in this process? It has potential to help. Personally, I'm an experimentalist. And I don't have a lot of faith. I haven't partnered with any of these AI based firms to look at it. But mainly because I haven't seen anything that convinces me. Yeah, they're AI predictions or machine learning, or whatever you want to call it. I haven't seen a computational prediction that I thought I trusted. Yeah, but yeah, I mean, it's given that every day, there's certainly drug companies that are making drugs that are envisioned in the kind of machine learning and AI space, right, and then that's reduces the number of things they have to screen to be able to get. 37:02 I just don't think we have the knowledge, this particular space to be designers. 37:08 So we have listeners from all over the world and many different backgrounds, and I'm sure we have listeners about to go into school or looking for their PhD, and maybe in your field that are looking to pursue it further. What advice would you give those people that are interested in pursuing similar things that you are, I think it is the future, I think that this at least in my field, right, if you wanted to go do a PhD in chemical engineering, or in metabolic engineering, specifically, 37:37 like if you wanted to go after this, and that's what you have a passion for. And that's gonna make you want to put in the hours and undergo the failures that it takes to do research, that's a great direction to go, send me an email, reach out to other people that do these things. And you can start those discussions, I think that the skill set you've learned in that process, right, is a very useful skill set. Learning how to kind of manipulate biology to add it produce, the compound you want is a skill set that could work for psychedelics, but it could also work or biofuels and commodity chemicals, and protein therapeutics and the next antibody, right, these are things that you could take, and you could go any direction you want to with it, right, you're not pigeon holing yourself into, I only know how to do X, really developing a broad skill set that is super valuable. So I think that I believe in the future of this field, right. And I, I don't know that the future is valid metabolic engineering and psychedelics or even small molecules, I think a lot of it is going to push towards more kind of biological compounds, material based things. There's a lot of cool directions to feel this going right now. But I do think that the skill sets are pretty similar across most of those areas, and that it's the right place to be cool. Where can people find you and the work that you're doing? I don't know, if you have a website, or what's the best place? People can follow you? Yep. So my labs website is Jay Jones lab.com. And we'll have this in the show notes as well. I not real active on social media, necessarily. But certainly you can send me an email. It's just Jones pet Miami. Oh, h.edu. I'm happy to answer questions, right. And I get overwhelmed with emails sometimes. So be patient when I'm responding. But I'm happy to talk to somebody wants to get into higher education. They want to start thinking about doing research in this space. There's certainly prerequisites you need to get there. But I believe that having excited people in this field that are smart and learning and wanting to improve, that's the future, right. That's how we push this forward. I can't do it without people. Amazing. Well, thanks for coming on. And I appreciate it. And thank you everyone for tuning in and tuning in for another episode. And thanks for being patient with the sound quality and maybe some noises in the background as I'm traveling. Yeah, check out mushroom revival.com We don't have any 40:00 donations to power this show. This is all a work of love. So if you want to support the show, we have a whole range of products that are on our site from gummies to tinctures, capsules to powders and yeah, it helps to to leave a review, tell your friends and let's keep this mycelial network running. So thank you Transcribed by https://otter.ai
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