[Dennis McKenna]: Born and raised in New York City, Jeffrey Gerst has been a professor of biology for over three decades, first in the Department of Cell Biology and Anatomy at the Mount Sinai School of Medicine in New York from 1991 to 1995 and ever since in the Department of Molecular Genetics at the Wiseman Institute of Science in Israel where he is the incumbent of the Beeson Brenda Chair of Microbiology and Parasitology. Professor Gerst investigates key questions regarding how proteins localize within cells and more specifically how trafficking of the blueprints for a given protein, namely messenger RNA, trafficking ultimately controls protein localization and why that’s so important for normal cellular function and the prevention of disease pathologies. Among his many discoveries, his recent work shows that mammalian cells can actually transfer mRNAs from one cell to another. This novel means of intracellular communication allows for cells to genetically sample their neighbors and exchange critical information. Importantly, his lab is now leveraging this phenomenon as a new means of gene therapy to treat rare monogenic single gene disorders in humans to help cure diseases like Zellweger’s, Goucher’s, Batten’s disease, Tay-Sachs, cystic Fibrosis and others. His lab aims to engineer the patient immune system to act as highly specific mRNA delivery vehicles to distribute mRNAs to cells within the body that lack them, thus correcting the disease state. He is also engaged in advocacy for sourcing the psychedelic medicines using genetic engineering instead of harvesting from the wild or by chemical synthesis in order to produce them in an eco-friendly, sustainable, scalable and ethical manner. He has recently published this work in a book entitled Bioengineering Enlightenment, the Revolutionary Science Behind Sustainable Psychedelic Medicine, available on Amazon and he’s lectured at it at the recent Psychedelic Science 2025 conference in Denver, Colorado, where it was my pleasure to meet Dr. Gerst for the first time and it’s now my pleasure to invite you to the Brain Forest Cafe. Welcome, Dr. Gerst. 

[Jeffrey Gerst]: Thank you very much, Dennis. It’s a real pleasure and an honor to be here to speak with you. 

[Dennis McKenna]: Well, it’s an absolute honor and pleasure to have you. We have a lot to discuss. Your book has brought up so many questions for me. I mean, it’s a fantastic book. It’s very well written. My virtual background doesn’t let me show it properly, but I urge people it’s very well written. You do not have to be a molecular biologist to understand it. I’m certainly a layman in that area, but I am trained in science, but you don’t have to be a scientist to understand this and the main concept. To start out, one of the easier questions possibly I have for you is you referred to your work with mRNA and trafficking in mRNA and inducing different cells to acquire characteristics or make proteins by engineering their mRNA. Let me ask you what might be a naive question, but try to bring this back to my own limited sphere of understanding. Does that amount to horizontal gene transfer? 

[Jeffrey Gerst]: Yes, in a way it is. It’s horizontal genetic transfer. You’re not transferring gene in terms of the DNA, but you are transferring it in terms of the RNA, and you’re getting everything that RNA can offer. So RNA, as you know, is basically the blueprints for a protein. DNA is the hard copy, RNA is the blueprints which you copy, and then you send it to the cell within the cell to be translated into protein by ribosome. What RNA trafficking does is it allows the cell to move RNAs within the cell. There’s a good reason for that. If you look at basic biology books, the RNA, again the blueprints for protein, is basically floating around within the cell until it meets a very complex protein machinery called the ribosome, which now can read those blueprints and turn it into protein. Again, protein is doing all the work mostly. It turns out, if you look at these old basic biology textbooks, the RNA is floating around within the cell until it meets a ribosome. This is completely untrue. It turns out the RNA is actually being trafficked, actively trafficked, to specific places within the cell where the protein needs to be once it’s created. It’s not just individual RNAs that are trafficked. You can have whole sets of RNAs being trafficked to specific organelles within the cell, like the mitochondria or the endoplasmic reticulum, places where these proteins need to go. So if your protein is going to be secreted, like alive molecules are secreted, that RNA is likely to be found on the endoplasmic reticulum. If the RNA is meant for encoding a mitochondrial protein, then the RNA is going to be found there as well, for the most part. So there’s a tremendous amount of order. Now, figure the human genome has got 20,000 different genes. Roughly half are being expressed in any cell in a given time. You’re ordering 10,000 different species of RNA within the cell simultaneously, and you have multiple copies of these RNAs, maybe in the hundreds, if not thousands of copies. In this tiny little cell, you have this very complex array of trafficking RNA and protein as well within the cell, so it gets to the right place in the right time in order to carry out its functions. If it’s mis localized, like in certain human diseases, like Alzheimer’s, for example, or frontal temporal dementia, then the RNA doesn’t get to the right place. The protein it’s made, it’s made it all, doesn’t get to the right place, and therefore you have these diseases which specifically affect neurons, for the most part, particular brain neurons, which are most sensitive to RNA trafficking. So there’s a strong connection there between RNA trafficking within the cell, but also in terms of cognitive function and neural pathological disorders are all connected to RNA trafficking. 

[Dennis McKenna]: I see, at least. I think I see. So the reason I asked that question initially is because from your biography, a lot of your work is associated with this, and you are undoubtedly aware that the genes for psilocybin synthesis have been transferred to many different species by horizontal gene transfer, whatever that may be. And I guess the horizontal gene transfer that takes place for this, what you might call the psilocybin synthetase or the psilocybin synthesis gene cluster, did that process, did they acquire those genes in this horizontal gene transfer process by a similar mechanism that you’re working with or something?
 

[Jeffrey Gerst]: That’s a wonderful question. I guess we’d have to go back a few million years to be able to answer specifically how it happened. But as you know, there’s four genes that are involved in the production of psilocybin from tryptophan, which is again this basic very simple amino acid, which the cells can then use to create psilocybin. And so you have this gene cluster that means all these four genes are arrayed on the same chromosome using different promoters to express them, but they’re arrayed on the same chromosome, and they can be removed basically or amplified and transferred to other organisms. Now we do that by using polymerase chain reaction, which is again PCR, and you’re probably all familiar with that. It’s given the corona crisis, which has allowed us to be able to talk about not only PCR, but also RNA. And most people have an understanding with RNAs at this point. And it turns out probably that we’re never going to be sure exactly how it happens. There’s multiple pathways of which genes could transfer horizontally between organisms. One is viral mediated. In other words, the viruses can actually copy genes and actually carry bits of them with them from one organism to another. This is one way it could happen. Probably not the way it did happen. But then you do have, of course, interaction between cells in species, one with the other. And if it was beneficial for another mushroom species, similar to psilocybin, but not identical to psilocybin, and it was in close contact, and yet they were competing with different predators within the system, whether it’s insects or other competing fungi within the niche wherever the psilocybin and fungi are growing or the related fungi are growing. And it’s quite possible that you had direct cell-cell connections. For example, nanotubes, which are something that mammalian cells use to transfer RNAs one to the other. Bacteria can transfer RNAs and genes from one to the other, again, through pili. And so it turns out that cells have a very strong propensity to pick up DNA from their environment, whichever the means it might be, whether it’s directly actively driven by a transfer process or perhaps a viral integration of the genes, or one gene at a time, or perhaps all the genes. And then you have the selection over the millennia to, of course, reinforce the expression of these genes in order to create, again, the, in this case, the psychedelic material. And so there’s also examples now of convergent evolution, where an example that was recently shown that the production of psilocybin can be created from a non- Psilocybe related fungus, which basically develop the genes on its own. And this is a nice example of how two different strategies of evolution can lead to the same pathway.

[Dennis McKenna]: Parallel evolution. 

[Jeffrey Gerst]: Exactly. 

[Dennis McKenna]: Has parallel evolution of psilocybin synthesis been found, or is it all due to this horizontal gene transfer process? 

[Jeffrey Gerst]: No, there was an example recently published, and I don’t remember the article, but I’ll send it to you, was showing that it evolved independently. So if you look back at doing the phylogenetic analysis, it’s basically looking back through the timeline of the gene ancestors chart and looking to see who evolved from what, you can see that these genes evolved independently of one another. And yet they still give the same overall functions in terms of generating the psychedelics. So there’s one example of this, and I will find a paper for you. It’s basically a recent paper, and I think that’s very interesting. And again, this is not so uncommon in evolution that you can, again, by convergent evolution, create some more processes through proteins, which are interspace enzymes, which are structurally dissimilar, to a large extent, but functioning similar. So it is possible, yes. 

[Dennis McKenna]: Right. So it seems that from the ecological perspective, psilocybin and its congeners, this is extremely important for the mushrooms in terms of effectively their repellents for insects. And they give the mushroom an adaptive advantage as far as colonizing the same substrates that insects would like to colonize, like dung and wood and that sort of thing. And you see the horizontal gene transfer occurrence in those species that are competing with other organisms, mainly insects that would be consuming it, possibly also other fungi. But this is sort of a— 

[Jeffrey Gerst]: Interest in a chemical arms race a lot of the time. This is called the red-winged dynamics, where you’re constantly running to stand still because you’re going to have a competitor barking at your door or knocking at your door, so you better have some defensive mechanisms ready or evolve them in a way in order to be able to maintain a balance within the population.
 

[Dennis McKenna]: Right. Well, this is in some ways a bit of a detour from what we want to talk about, but you’re talking about using genetic techniques to basically harvest the genes from, for example, something like psilocybin and transfer it into other organisms such as yeast or bacteria. Is the technical term for that other vectors? Is that the correct term to use?

[Jeffrey Gerst]: I guess you could call it that, yes. 

[Dennis McKenna]: Yeah. So this has been done with psilocybin, and you very clearly lay out how it could be done with other psychedelics. But this is where we get to a nexus, Jeffrey, I think, of where ethics and technology and our capabilities kind of come together. And this raises, to my mind, some very sticky sort of ethical questions about whether this technology should be used and how it should be used. I am a scientist. I’m not as great a scientist as you are, but I’ve been in science, so I sort of understand it. And I admire what science does. Science has given us many blessings over the years in curing diseases and this sort of thing. But I often talk about how any technology is morally neutral. It can be used for harm. It can be used for benefit. It can be used beneficially or harmfully. We are, as a species, we’re very clever that we’ve developed techniques to do this kind of thing. And in our deployments of technology, we can be very clever. We’re often not very wise. And it’s an important distinction. When I read about this, what you’re proposing to do, I waver between several polls. I waver between astonishment and admiration that this is possible. And the other hand, it looks to me like it’s ethically very dubious to rip the genes out of one plant or fungus and put them into another plant or fungus where they would never show up in the course of evolution. Purely, it’s a human artifact. I’m not sure I want psilocybin in my tomatoes, Jeffrey. It comes down to that in a certain way. 

[Jeffrey Gerst]: Well, at least as long as you know which one has the psilocybin and which one doesn’t, that’s important. But I’m totally sensitive to what you’re saying. I get that point. There is an ethical consideration here and serious ethical considerations. I think the whole idea of this popped into my head where I was inspired to write about this was because the fact we are moving in the direction of legalization of the psychedelics. And we’d like to use them for at a global level to heal trauma, which is happening all over the world, not just in North America, but basically in every continent, wherever people are, there’s trauma, whether it’s micro trauma or macro trauma. So we have to have a way to be able to bring the psychedelics or at least the treatment psychedelic assisted psychotherapy with the psychedelics to people around the world. In other words, there has to be a global supply. And the question is, how do you meet the demands once legalization occurs? And it’s not psilocybin is less of a problem than other psychedelics like ayahuasca or mescaline or, for example, even DMT and 5-Meo DMT. All these psychedelics, and I am going to treat them all together because it’s the same ethical question. Is it okay to take them from their original organism and move them into an organism which is rather more easily grown, maybe simple to grow and can grow everywhere? And the idea then here is that the advantage is that now we have a way to be able to deliver them to people throughout the world in a much easier fashion. Growing mushrooms is relatively easy, but maybe in Somalia it’s not, for example. But for example, if we take the pathways for psilocybin production or mescaline production or 5-Meo DMT and put them into yeast or tomato plants, these can be grown basically anywhere. And the idea is not only that they’re relatively easy to grow, they’re very fast to grow, much faster than it takes to grow mycelium into the fruiting body of a mushroom, for example. And so there’s advantages in terms of scalability that we don’t have with a lot of the psychedelics. And again, mushrooms is not the big problem, but if we’re talking about peyote cacti or San Pedro or Sonoran desert toads, which are the source of 5-Meo DMT, these are very limited. In terms of their availability, they’re very limited. And everywhere in the world where they’re found these days, their populations are being decimated, not just by over-harvesting, but the environmental degradation that’s also involved in the harvesting process. For example, many people use MDMA, which is an empathetic enforcement necessary psychedelic, but it’s very popular. But most people don’t realize that the MDMA that they’re using is chemically synthesized. And it’s synthesized from saffron, which is a precursor coming from sassafras trees and aquatea trees. And it turns out that in Southeast Asia, whether it’s in Cambodia or Myanmar or Laos, they’re cutting down all the sassafras trees in order to utilize root bark in order to the bark to get sassafras, to get saffron. And then they have to burn a number of other trees just to distill the saffron out. And so you’re looking at this rampant deforestation in order to generate saffron, which we’re going to use the term to create MDMA, which we’re going to use to heal trauma in the human population. Meanwhile, we’re creating trauma to the local environments in which these organisms live. And the same is true for caapi vine, for ayahuasca and peyote. These things take many years to grow, five to 10 years. So we need a more rapid means of developing them if we really want to reach people on sort of a worldwide basis. Now, you could argue that synthesis, chemical synthesis might be the way to go as well. But the problem with chemical synthesis is it’s highly polluting. It’s restricted maybe to underground farmer. You’re not really sure the origin of it. And most people have no idea where their psychedelic medicines come from in the first place. And there’s also, again, the pollution that’s involved, the fact that the generation of the psychedelics by chemical synthesis doesn’t generate money for communities. It doesn’t give money to indigenous societies. It basically is money which stays within whoever the producer was. So there’s no fair trade practices with chemical synthesis, basically. So you’re looking at a balance between sourcing from nature or chemical synthesis. And the question is, what do you choose? And I would say that the middle ground, the middle path, is, again, using genetic engineering to create organisms which are, again, easy to grow, scalable, sustainable, and in some ways more ethical because they now give a chance for indigenous populations to use them in order so that they can benefit from the creation of these psychedelics. But there’s something to be said for removing it from the organism.

[Dennis McKenna]: By taking these genes out of their native plants, out of the plants that they’re traditionally used, and mushrooms, because they’re a fungus, that may be a major exception. But it seems to me that from an indigenous perspective, if I didn’t know anything about what you were doing and if I didn’t know a bit from reading your book about your perspective on this, which is benign, benevolent, you’re not a corporate predator, but much of the psychedelic industry these days is run by corporate predators. And it seems to me that from an indigenous perspective, if you came and said, well, I’m going to take the genes out of your most sacred plant and transfer them into yeast, and then we’ll give that to a biotech company to scale up production. I mean, it seems like these plants exist in a biocultural context. These are sacred plants. So this is not meaning to offend, but this looks like the most egregious kind of biopiracy you could imagine. You’re stealing the genes. You’re leaving everything else behind. You’re not acknowledging the cultural context. It seems like ethically, this is a problem to me. And in some cases, it makes sense to do this with something like ibogaine, for example. It’s very difficult to grow, and it takes 17 years or something to reach maturity. And the alkaloids in ibogaine are difficult to synthesize. So the idea that you would apply this genetic engineering technique, gene harvesting and metabolic engineering, get the pathways for ibogaine installed in yeast or something like that, it makes sense because this is an important medicine. There’s a need for it. The plant is endangered, and a more sustainable means of production needs to be found. But it seems that most of these plants, they can be synthesized. One thing, I mean, yes, chemical synthesis produces can be polluting, but I’m not sure that chemical, organic chemistry in general is polluting. So it seems like the psychedelic synthesis wouldn’t be too great. But more importantly, it’s just a disconnect between these genetically engineered organisms and their origin. And you say, well, the industry can support Indigenous communities. They can give a bit of their proceeds, a bit of their properties to support Indigenous communities. I don’t see that happening now. I don’t think that corporations are particularly interested in supporting Indigenous communities. I mean, we’re looking at 500 years of biopiracy. It never bothered them that they stole most of our food and medicinal plants from the New World. I don’t see the corporate hegemony having a big come to Jesus moment about this where, oh, we’ve got to start supporting these Indigenous communities. We have to be giving a portion of our profits to these Indigenous communities. It’s not happening now. I don’t think it’s going to happen. They have no sense of responsibility. And that’s unfortunate. 

[Jeffrey Gerst]: And I agree entirely on that point. And I think that’s something that also plays out at the end of the book. I think this is something we have to have. We have to have a good housekeeping seal of approval on whatever commodification psychedelics in terms of production has. And I think this is, you know, an informed consumer is a good consumer. And they will buy things which are prepared in a way which they’re maybe sure that the Indigenous communities benefit somehow. I mean, there is laws to protect these Indigenous communities and their resources. But the laws have not been, I mean, there’s a number of UN conventions on it. There’s conventions to protect the species themselves, societies. There’s a UN convention to protect Indigenous resources. There’s the Nagoya Protocol, which is supposed to allow for their remunerations for these Indigenous societies on the basis of the use of their materials as they develop it or their knowledge. But as you said, these things are not necessarily followed. But if consumer advocacy is going to be strong, it could hold these companies to it, especially when legalization happens. Right now when there’s no legalization, everything is, you know, it’s sort of partly underground, partly chaotic, and it’s not clear where everything’s coming from, whether it’s coming from factories in China or Europe or wherever that’s where the United States is not. So you’ve touched on an extremely important ethical problem. But I would just say go back to the beginning when you talk about the moral neutrality. Yes, genetic engineering, just like a lot of things, are morally neutral. It all depends on the user, the person who informs it, whether they’re talking about AI or nuclear energy or genetic engineering. It can be fantastic material for helping the environment and helping the human species, and just as much it could be a detriment. So, I mean, I agree with you, it would be nice to get artists [all of it] from nature, but it’s just organisms that grow very slowly and it’s just not scalable to me. If suddenly the world population wants to have psychedelics, what if a billion people wants to have MDMA? Are we going to cut down every sassafras tree just to make enough staff [safrole] for all to do it? I mean, it would be a mistake. And I understand that we can’t eliminate natural sourcing. We may not be able to eliminate chemical synthesis, but we have to be able to scale up in a way which to make things sustainable. And this is true, again, for a lot of these very slow growing plants and animals, that their species number is so low that they will never be able to support a very large population. And look at the growth of the psychedelics that we’ve had just in the last 10 or 20 years. I mean, it’s amazing. And hopefully that this incredible demand that we have is because we want to have more self-awareness, we want to have more social connection between people, psychedelics are the pathway to get there. And the question, of course, is how do we generate enough for everyone if that’s what it’s going to be? If it’s going to be just based on cut notification [commodification] that only wealthy people in wealthy countries can take advantage of it, then we failed already.
 

[Dennis McKenna]: Do you think that even following legalization, do you think that the demand for these psychedelics is going to be so great that the need can’t be met by simply fostering sustainable production of things like ayahuasca? Ibogaine maybe is an exception. Mushrooms can certainly be grown on gigantic scales at any scale. I mean, just about the techniques of micro-cultivation to psilocybin mushrooms, you can grow gigatons of psilocybin mushrooms. That’s not a problem. And that’s ecologically compatible. I don’t think that indigenous communities are going to set up biotech labs in their communities to make these things. It’s not their mindset. They don’t have the capabilities and they’re not interested. What they are interested in doing is just growing plants. And in the case of ayahuasca, ayahuasca is interesting because it is the focus of a lot of ecotourism and so forth. So there is pressure on the species, but then these communities, a lot of them that do cater to Westerners, they’re beginning to step up and develop sustainable production. And with ayahuasca, this is practical because it’s a vine. You can start to harvest it at a fairly young stage. And Chacruna, the other plants, they grow fast. So why not just work with these indigenous communities to develop agroforestry protocols to produce enough vine and enough admixture plants to meet the need and preserve that cultural connection, which is so important. 

[Jeffrey Gerst]: Right. And I would agree with that entirely. Like I said, I don’t think the idea is to eliminate natural production or obviously or to make the indigenous communities bereft from their knowledge and their traditional practices. I think the idea is to do in a very complementary fashion where we can combine aspects of agriculture, we can combine aspects of genetic engineering and combine even chemical synthesis if we have to for typical compounds. In other words, it’s all a question of scalability. How do we reach a very large population? If we’re 10 billion people and I’m not saying everyone’s going to take psychedelics, that’s not going to happen. But if we’re only talking about a few million people or 50 million people in the world today, what happens when that’s increased 10 times or maybe 100 times? I mean, it’s not really clear to me if we’re able to meet that and whether the natural resources, the land will be able to do that. One of the problems with the indigenous communities is that they’re unable to protect their own lands as countries that usurp the land from underneath them. Or what other means, it could be extractive practices like mining or lumber production, or it could just be agriculture and cattle production. For example, as I pointed out in the book, a lot of territory in the world is being converted from natural forests or natural habitats into, again, these human modified habitats which are very different. And we’re losing basically on a scale of the size of the area of Greece each year to these changes in the natural environment in terms of those communities, these natural plant and animal communities as well. And so we’re fighting a war against nature. World War III has been going on for a while and it’s our battle against nature. And that’s the problem. We’re not going to win a war like this. We’re going to lose a war like this. And we’re smart enough to be able to alchemize our fear and to love and actually work on trying to help the land as opposed to just to exploit it. And this is the problem where we are in evolution, human evolution, is we’re totally controlled by this mentally egoic state of ours where materialism runs rampant. More is more and we want more and we’re just not satisfied until we get more. And this is the problem of getting into scalability of the psychedelics. If so many land is being diverted for other uses, will the indigenous societies have land to be able to do in the first place? I mean, I would like to think that they could. But I mean, I think we have to be very practical here and assume the worst because sort of this is the way the world in the 21st century is still going in this very unregulated sort of rampant exploitation of nature’s resources. And it’s been going on for a hundred years if not more. We have to be very open-minded here. I agree with you entirely. It would be great if the indigenous societies could provide all the natural, naturally sourced psychoactives, whether they’re psychedelics or other psychoactives, doesn’t matter. But I’m not sure that’s going to happen.

[Dennis McKenna]: But don’t there, I think another approach, there obviously needs to be policy changes, right, on that level to set aside these lands to recognize the indigenous right to their habitats where these plants grow, their traditions to the biodiversity that depends on it. I mean, this goes back to something that’s been an ongoing conundrum in the pharmaceutical and drug discovery industry. You often hear, for example, the statement that there are all sorts of undiscovered cures in the rainforest, right? Somewhere in the rainforest, there’s a cure for every disease that we can imagine. Why isn’t the pharmaceutical industry trying to develop those? Basically, it’s because they want to own it. They want to patent it. They don’t want to make deals with indigenous communities to supply these plants. Again, it comes back to this sort of corporate perspective that we need to own everything. We need to patent everything. We’re not going to put resources into supporting indigenous production of these natural medicines because it’s outside the control of the corporate sphere. They’re not really interested. The mindset is, well, we can make everything in the lab. We can use recombinant DNA and that sort of thing. Of course, that’s been a real flop because natural products still have a very good track record in terms of compounds being discovered that actually eventually make it to the clinic. The same thing in a sort of microcosm applies to the psychedelics. Why don’t governments recognize that psychedelics are important medicines work with indigenous groups to set aside land and set aside environments to produce them sustainably and then make deals with pharmaceutical companies or maybe even go around the pharmaceutical industry, go directly to therapists in North America who need these things? There’s a direct way to do it without necessarily invoking the genetic changes without applying this technology. I’m conflicted about this, Jeffrey. I see the beneficial potential applications. I’m also very cynical about corporations and the way that they have historically always misused technology, always stolen indigenous knowledge. I’m cynical. I’m worried that there’s not going to be some big ethical turnaround. They’ll basically take these genes. They’ll install them into biotechnology, grow everything in vats, hopefully not tomato plants, but they’ll produce them. As far as the indigenous communities are concerned, they’ll just basically say thank you very much and that’s all that they’ll get for it. No recognition. In some ways, it contributes to our increasing estrangement from nature. It seems like a move like this removes us from nature. If you produce these psychedelics in these artificial systems, these biotechnological systems, that may fulfill a need, but by having the capability to produce them this way, don’t you really take away the incentive to preserve these plants and these environments? We don’t need the plants anymore. We’ve got the biotech produced psychedelics.
 

[Jeffrey Gerst]: Anything that humans do that there’s going to be people who use it the right way and will be able to funnel money into indigenous societies in order so that they can expand their own cultural use and growing it in form for people to come and use or just to be able to harvest it. As well as people come from pharma, which is going to commodify it. You’re going to see a whole range of activities and it’s really up to us to really not divine the future, but direct the future in the direction that you’re talking about. I agree with you entirely in this case. The idea is not to pull the rug out from the indigenous underneath the indigenous societies taking their knowledge, their wisdom, and the materials that they’ve developed and then just sewing it as pop tarts in the corner store or in this case psychedelic pop tarts one way or another. But the fact of the matter that will happen. The question is how do we correct that? The reason I wrote this book is a form of advocacy needed by you reading and saying, I don’t want this. I want my naturally sourced material, which has spirited individual as the efforts of the indigenous societies that develop them for rituals and ceremonial practices. I want that. I agree with you entirely. But people need to know that there are other options because what happens if we do cut down all the sassafras trees and we do cut down all the capybara vines and we do pull up all the peyote in northern Mexico and we do capture all the buffo toads, the southern desert toads, and the southern United States. When they’re gone, they’re gone. I mean, how many species have we already driven into extinction already? The basic reality is that these species are beneficial to us. We’re not so beneficial for them necessarily. Maybe for psilocybin mushrooms, we spread them out through the world even more than they were already spread. Maybe from the evolutionary point of view, it’s a big success for them. These other species, which are very slow-growing, which take five to ten years.

[Dennis McKenna]: That’s the critical difference. I mean psilocybin mushrooms have been very good at colonizing the world, both colonizing and spreading to other species. If you look at the distribution of species in Paul Stamets book or iNaturalist.org, there’s about 220 psilocybin species in the world. They are a very successful species. Now, things like peyote and iboga and the sonoran toad, these things are more problematic, it seems to me, because peyote is a slow-growing plant. Obviously, it takes about 17 years to reach maturity, but do you really have to apply biotechnology? I mean, a simple technique like tissue culture could be used to vastly increase production in greenhouses, and then those plants could be deployed out into the wild. This is pretty simple stuff. As you know, plant tissue culture is no big deal. I had a colleague at UBC. We were working on a project on iboga. We were considering using something called hairy root technology. You probably heard of it, to produce ibogaine in vitro. For that, we needed the plant. Well, we never got funding for that. Nobody put any money into it, but in the process of doing that, he developed tissue culture for iboga plants. It was very easy to grow whole plants using tissue culture. It got to the point where he had so many iboga plants growing in his greenhouse that the managers came and said, look, your iboga plants are crowding everything else. You have to get rid of them. It is possible to apply things like tissue culture. In the case of the sonoran toad, it’s a whole other thing. This is really a tragedy. I think the over-exploitation of this toad is a real problem. A couple of things that are not very often said. One is it’s not really tied to any indigenous tradition. The idea it’s used traditionally is made up by people who want to commercialize the toad. The other thing is, and I rarely see this mentioned in discussions about this, 5-methoxy DMT is not a rare compound. There are lots of plants that contain 5-MeO DMT. There’s a species of virola. Virola is the sap that’s very rich in tryptamine, but there are some species of virola, which is a fast-growing tree that basically contains only 5-methoxy DMT. This could be a suitable substitute for the sonoran toad in that respect. There are many other more fast-growing plants that have 5-methoxy DMT, something like phalaris grass and that sort of thing has a spectrum of tryptamines. There are these special cases where the genetic engineering approach might be good, but it seems to me that in the case of mushrooms or ayahuasca, with the right kind of production infrastructures, you could just use the genes in their native setting in the plants or the fungi. It’s good that one can do this. Also, another point that your books make is that with the proper genetic tweaking, you can get these genes to produce psychedelics that are not natural because they’d be produced in the genetic system but have never been evolved. But that may be okay. Like you mentioned, using this technology to make the precursors for MDMA, I don’t see any ethical problems with that because MDMA is a synthetic compound. It doesn’t occur in nature, and it’s obviously useful therapeutically. So I’m not here to attack you, but I’m here to kind of let us focus on some of these issues which are really complex and difficult. 

[Jeffrey Gerst]: I agree. They do touch on a lot of different aspects of ethical aspects, and again, sustainable production of these things is very important. I don’t want to backtrack, but I was saying that even for mushrooms, you know, you couldn’t grow in one liter of yeast to express the psilocybin before psilocybin producing genes. You can grow in two days the amount of psilocybin that would take you two months to grow from basically 600 grams of wet weight mushrooms. I’m not saying we have to substitute mushrooms, but there are places in the world where mushroom production could be very difficult. Maybe Somalia, maybe, I don’t know, you know, all sorts of places where you have human trauma and conflicts going on that they may not be able to afford that. And I’m not saying that this is necessarily the best place to do psychedelic assistance hypotherapy, although that may be the best place to do it. The thing is that we can do this. What’s nice about using the bioengineering approach is it is sustainable. It’s scalable. There is a way to funnel money back into Indigenous societies if it’s done the right way, which depends on us to determine what is the right way. And it’s not going to be a substitute for natural sourcing. I don’t recommend it to be a substitute, but we have to find a balance that we can, a comfortable balance that we can benefit from all these different practices. And it also neglected to mention regarding chemical synthesis is that a lot of these psychedelic compounds from their natural sources, whether it’s fungi, plants or animals, they all contain the entourage molecules, which are necessary or important to perpetuate the psychedelic experience by stabilizing the psychedelic, preventing its oxidation within the body, interacting with other receptors in the brain, which can also, again, perpetuate or extend the experience. You don’t get that from chemical synthesis. Chemical synthesis is basically looking for GMP pure material. And at least the bioengineering aspect reconnects that synthesis back to the more natural products, the plants that we would use to produce these psychedelics. And again, it’s already been done in many cases. The DMT pathway for five methoxy DMT and for psilocybin is already put into tobacco plants. It’s put into potato plants. So the technology is already there. I’m not inventing something new. It’s something that it’s already been harnessed. There’s a question of where do we go from here with it? I agree. If it just falls into the hands of pharma, we’re not going to advance very far. We’re basically just enriching a small sector of society. We don’t want to do that. But on the other hand, we don’t want to deprive people of the potential worldwide of being able to have access to them as well. And maybe there won’t be enough natural production around yet or at least to meet the immediate need. And maybe this is where we can fit in here with doing bioengineering. And then again, if it’s done the right way, where there is some kind of remuneration or reciprocity regards to indigenous societies, we may be able to compensate for the fact that we are still exploiting what they discovered originally. So I think I understand exactly where you’re coming from. Some people could argue that we’re removing the spirit of the molecule by taking out of the endogenous species. There’s no argument here. But on the other hand, chemical synthesis has already removed the spirit completely from whatever it was. And so if it works even as good as the purified material, then we’re already onto something which could be, again, scalable, sustainable, and eco-friendly, at least in this case. 

[Dennis McKenna]: Yeah. You won’t really get an argument for me on the spiritual side. I’m basically a panpsychist. I think that there’s spirit in these molecules. Not only the plants and the fungi have spirit and the people, but I think even the molecules have a certain kind of intelligence. Alex Shulgin used to talk about his compounds, all of which were synthetic. He talked about their little drug souls, which was kind of interesting. But I think what we’re at here is we have a very powerful technology here in this biotechnology ability to transfect these genes into other organisms. It raises enormous ethical issues and policy issues about giving the indigenous people a place at the table. We have to develop very clear-eyed policies and very fair policy. The thing that worries about me is that this has never guided our relations of the first world with the indigenous world. Fairness has not really been the main criteria. It’s basically what could we get from you without giving much back. We have to get clear-eyed. I think the policymakers actually need to take these medicines and get some perspective on this because really it does give you a perspective on our connection with nature and the importance of these traditions. I don’t know if the drug by itself will do what it will do to our physiology, but context is important. I don’t think Western people can necessarily imitate or appropriate indigenous practices and try to instantiate those in the third world. What they can do is listen and observe the way that indigenous communities have used these things and try to develop something similar that maybe borrows from it, but not steals from it. If you know what I mean, there would be more of a collaborative kind of relationship here. Are you doing anything in that regard in terms of policy? 

[Jeffrey Gerst]: Because you’re exactly right. We’re talking about creating policy which is basically in a very amorphous state right now. As you said, there’s really very little going back, despite the Nagoya Protocol that was signed by the United States, for example, or Canada, for that example, which would allow indigenous societies to benefit in terms of remuneration from the use of their technologies, whether it was medicines or otherwise. We have to force governments to actually enact policies which allow this to happen, and that’s why at least at the end of the book, there would be some sort of own fund, which would be sort of a good housekeeping seal of approval that any therapist or producer in the psychedelics would give a percentage of their profits back to indigenous funds, which would then distribute these monies to indigenous societies so they can hold on to their land, so that they would be able to hold on to their land so they can have legal representation, especially in countries where they’re denied that, for example. So they can protect the species that they develop from the first place. 

[Dennis McKenna]: It’s a beautiful vision. I’m too cynical to think that it might happen, but I mean, governments haven’t even got to the point where they’ve legalized these things. I mean, that would be step one, would be to put them in some reasonable regulatory class so that therapists can use them, research can go on. And importantly, if people want to go out and collect these mushrooms or grow these mushrooms or grow these plants and use them, have them in their gardens, there should be no interference with that. That’s a direct symbiosis with another organism. And lately, I’ve started talking about symbiotic rights. I think symbiotic rights are important, and people should have the right to form any symbiotic relationship with any plant or organism that they want to. And it goes beyond human rights, because it’s really about all organismic rights. But we’re coming up to the top of the hour here, not that we have to end. There’s no deadline, but I did want to touch on a couple other things you talked about in this book of interest. And one of those is you talked a bit about the stoned ape theory. And you made some very interesting observations about how that could potentially be approached through the application of molecular biology to the sequencing of some of these hominid genomes and looking for particular markers that indicate basically an increase in serotonin. And the genetics cover the serotonin and the serotonin receptors. Do you want to explain a little bit about that? Can you explain about that in the short term?
 

[Jeffrey Gerst]: Sure. I would love to. I mean, of course, the Terence’s stoned ape hypothesis is an interesting hypothesis. The fact is that these societies did discover these psychedelic materials. And the question is, if they were around in nature, isn’t it logical that early hominids and later hominids gave them in this felt advanced human evolution? I mean, it’s a really nice hypothesis, but it’s not falsifiable. There’s no way I can go back in time to prove or disprove this. 

[Dennis McKenna]: Unfortunately. 

[Jeffrey Gerst]: Unfortunately, right? So yeah, exactly, unfortunately. And there are experiments that one could do today, but they’re never going to recapitulate what happened a million or two years ago in terms of the evolution of Australopithecus to Homo habilis and all these things like that. That’s an experiment that I guess we’re not going to be able to replicate. But it turns out that one could use, again, genetics as a detective story and sort of undercover what are the differences between our genomes and genomes of, say, Neanderthals or Denisovans where we have full genome sequences and maybe only from a few individuals. So we don’t really know what an entire population looked like in terms of the genetic variations between within the population. But we can compare human sequences for serotonin receptors, for the monoamine oxidases in the body, for other enzyme systems which are involved in sensing or mediating the signal from psychedelics by just looking at the sequences and comparing that to what was found, again, in these earlier genomes, the Neanderthal genome or the Denisovan genome, for example. And it turns out that there are differences in these genes, but there are small differences and there’s no difference, for example, between humans. Let’s take the 5-HT 2A [5-H2 2A] receptor, which is the basic receptor thought to be mediating most of the psychedelic actions. We’ll look at the 2A receptor, which, again, is very state-oriented, the 1A receptor, which may be involved in preventing depression and things like that. If you look back in evolution at these two receptors, who are prominent ancestors, you see there’s really no difference between our receptor in terms of the protein level between us and the Neanderthals. And there’s only one mutation with the Denisovans. And the question, of course, is, do these mutations, one mutation is actually by the HT1A receptor. So there’s no mutations in the protein. However, there are mutations which would be single nucleotide variants, single nucleotide changes between that Neanderthal and humans, which could be important from terms of how much receptor is made or the stability of the RNA for that receptor, for example. And this is places where there are differences, and maybe this is how we can find out whether the consumption of psychedelic materials somehow might have played a role in the selection for these particular variants. Now, you could say, I’m not saying that these are the mutagens, but because of bioculturalism, the consumption of these psychedelics and bioculturalism is basically the effect of culture on biology and the effect of biology on culture. If our early ancestors, the archaic ancestors, were consuming these psychedelics, and presumably that they affected them in one way, maybe a positive way or a negative way, it had an effect in terms of which variants were maybe selected from the population. And that made a difference in terms of allowing increased cognitive capacity, increased perception, social bonding, all these things. And so it may have not made big changes in terms of, it would be simplistic to think that just the consumption of psychedelic mushrooms alone, provided that even the species had access to them, would be sufficient because a lot of these evolutionary changes took place over many millions of years. So it’s not really clear, of course, when this happened, but at least in terms, especially as we don’t have genetic material for Australopithecus or Homo erectus or any of the early species, where we could maybe monitor these changes in the receptors very early. But nonetheless, we could get a fairly good idea of what mutations or variants that exist within the DNA, and then now take these genes and maybe exploit them in the laboratory by taking these Neanderthal variants and putting them into the human 5HT2A or 1A receptor, and then putting it into neurons and culture and seeing how that affects neuron excitability, for example, or neuronal growth. These are testable hypotheses, for example. Good for a PhD student, for example. 

[Dennis McKenna]: Well, several PhDs, I think, could be gotten. But let me ask you this. If we look at the various pieces of data here, if we look at paleoclimatic data for Northern Africa, going back about 8 million years, there’s data, and it was a wet place periodically. It had so-called African human periods where there were lakes. It was a place where mushrooms could grow, and we know where there were species of cattle growing. There’s fossil evidence of cattle being there and hominids, of course. Ecologically and environmentally, it’s a reasonable inference to say those mushrooms were probably there. If they were there and you’re hungry, hominid, you’re going to eat those mushrooms and maybe several times and maybe a lot. One of my questions is, knowing what psilocybin can do in terms of fostering things like neurogenesis and synaptogenesis and long-term neuroplastic responses to psilocybin, which is understood to be part of a big and important aspect of the therapeutic effect, could those changes be propagated through generations? Could they activate these genes for the 5-HT2A receptors that you’re talking about and propagate them multigenerationally through epigenetics or some sort of mechanism? Is that a reasonable supposition? 

[Jeffrey Gerst]: I would say that the question is, why did these variants come about? Of course, we don’t have a genetic time machine besides the DNA itself. We can’t go back and see what were the prevailing circumstances that encouraged these changes. Again, most changes within a genome are neutral changes. If there are deleterious changes, it’s probably eliminated from the population because they’re deleterious and not very healthy. I think we have to go back in time as well and ask, were these psychedelic mushrooms, psilocybin mushrooms, for example, were they an adequate source of meals for Australopithecus or whatnot? I even mention this in the book, either Australopithecus was hypersensitive and if it ate mushrooms, it might have knocked it out for a while and allowed it to become prey for some prowling predator nearby, which wouldn’t be too good, or it didn’t do anything to them at all. They ate them and they were perfectly happy. Only later in hominid evolution do they start affecting the neuroplasticity, obviously in the cognitive states of the later or more archaic species of hominids. Again, the only way to go back and to do that is to actually look at these variants individually. I guess it’s a lot of work to say, and maybe you would get some indication there, but I think it’s clear from the biocultural level that our genetics is profoundly influenced about how we interact with the environment. For example, again, using the book, for example, the lactase gene, which has a mutation which allows northern Europeans to drink milk all their lives and not suffer the consequences. Yet, all the species, including the Neanderthals and the other Denisovans [Venetians] and most of the other non-northern European humans had turned this gene off early in development, and thus they’re not able to consume milk products very easily. So it was actually the northern Europeans that they were pastoralists and grew sheep and cattle and goats and continued to drink milk and just selected for this mutation. Whether the mutation came about, whether it was a random mutation, or whether it was from epigenetics that hardwired into the system, we’re not going to really know that answer either. And the same thing is true in terms of our understanding of how psychedelics may have influenced our behavior through bioculturalism. In fact, they’re probably influencing it today. The question is, what are we selecting for? The people who are using psychedelics, what are they selecting for in their behavior? Does this ever get hardwired into the system? So there’s a lot of evolutionary questions here which actually also border on ethics in terms of what is actually going on with our population, especially today as we’re so polarized and so caught up in our mental egoic strategies of living that maybe the psychedelics will have a way of calming people, certainly bringing about more social connection, more self-awareness to act in a way which is contrary the way with most of humanity is going. It may be too late as far as I know. And again, in biology, numbers is what counts. Unless the psychedelic induces a very beneficial positive effect within the population, you could get a positive sweep of these mutations which would allow us to use psychedelics or even benefit even more so in terms of better cognition, better neuroplasticity. Otherwise, it might be missed. So I don’t know where we’re going. And maybe you know where humanity is evolving. I definitely do not know where we’re going.
 

[Dennis McKenna]: Roland Griffiths once quipped psychedelics make people more liberal. That’s why the government’s not going to fund research. I think there’s something to that. But something you said a few phrases back. I do have to push back a little bit. We know the importance of set and setting for positive outcomes for psychedelic experiences and the idea of hominids eating mushrooms and then they’re incapacitated so they’re easy prey and that sort of thing. That’s possible. It’s possible that they do. I mean, if you’re totally loaded, maybe you’re not so on guard against the saber-toothed tigers that are wanting to eat you. On the other hand, at lower doses, it can make you hyper vigilant and very much tuned into your environment. And in that sense, it increases visual acuity. There’s been studies on this. And I’ve often said psychedelics bring the background forward. That’s a lot of what they do is what’s going on in the background. They bring it forward to our attention. So if things are going on in the environment that normally through neural gating, we’re programmed to filter out, psychedelics demolish that filter, those neural gates, at least disable them temporarily. And you notice things in the environment that normally you don’t notice. And you learn from the environment psychedelics, especially psilocybin, can be used in some ways as a scientific instrument for looking at processes in nature that you’ve always examined but you’ve never examined them from that perspective and you notice things going on that you may not normally notice. So that can have survival. That can have an adaptive benefit. So yes, if you’re completely loaded on psilocybin, you want to be safe in your cave, right? But if you’re out there outside and you take a fairly moderate dose, you can achieve an extremely useful, rather surprising adaptation to the environment. I like people that take mushrooms and go helicopter skiing and this kind of stuff. I mean, I would never do it, but they say. And there’s this famous story, which I forget the details of, but the baseball player that took LSD and he had to, on a day that he was supposed to play a major game, they called him on short notice and said, you have to pitch this game. And he’d already taken acid. So he showed up and he pitched a no-hitter. He was completely loaded on acid. 

[Jeffrey Gerst]: Is that true? That sounds urban legend, but I’ll accept it.
 

[Dennis McKenna]: I’ll get the details. This is maybe a myth. This is a story about psychedelics. So basically, you don’t have to be disabled in the psychedelic state at a certain level. 

[Jeffrey Gerst]: No, I was just proposing that as just, again, the idea is that we don’t know if they were hypersensitive or completely desensitized to the psychedelics. And the only way we can do it is using, we can look back and, again, at the archaic humans and maybe do experiments with mice or cells and culture to get a better idea of what the effects are. These are falsifiable experiments. So it’s things we can do. And I agree with you entirely that psychedelics has certainly provided myself with clarity and it’s also provided me with this foundation now to write a book like this, which can discuss all these possibilities. And again, the idea isn’t to necessarily convince everyone. The idea is to put it out there that we can do it if we need to do it. And if you don’t want to do it, then let’s find another solution which is sustainable, is scalable, and is equal friendly. I think that’s the enlightenment here is that we have to be able to consider all possibilities. Obviously, we’d be better to choose the ones which is going to be less harmful to environment, less harmful to indigenous societies.

[Dennis McKenna]: Clearly, this genetic technology is one of those that can be used for benefit or can be used for harm. And it’s rather amazing that humans have become capable of this. Another example of how we’ve in some ways achieved dominance over nature. But we have to have the wisdom not to exercise it when it doesn’t make sense. We have to be partners with nature, not owners of nature. But we’ve unpacked a lot here. There’s a lot more we could unpack, but you probably have things to do, like maybe go to bed. Must be very late there. But this has been a wonderful conversation. I really appreciate this.

[Jeffrey Gerst]: Thank you for having me. I think this has been a wonderful opportunity to speak with you. I look forward to meeting you in person again.