Dirk Hoffmeister: Biochemistry of Psilocybin Production, Psychedelic Tryptamines & Magic Mushrooms
Updated: Sep 14
Full episode transcript below. Beware of typos!
Which is pretty much in the center of Germany. Not that it's not that much of a you know, it's too small for for a big city and it's too big for a small town. 100,000 inhabitants college town, quarter of them being students and Fan Fan city.
Nick Jikomes 4:48
Yeah. And you're from Germany originally? Yes, I am. Excellent. And can you just kind of give everyone a little bit of a background in terms of what your scientific training is and What you study very, very generally?
Dirk Hoffmeister 5:02
Oh, absolutely, sure. So I'm currently I'm a professor of pharmaceutical microbiology. And by training, I'm a botanist, and mycologist there's my, these were my majors. And so basically, I, back then 25 years ago, a lot longer, even 30 years ago, I didn't really, you know, think about the things and the subjects I'm thinking about today. So, botany and mycology, this was my training. And I then went on for a PhD degree in, in basically in bacteriology on an antibiotic related topic, which took me a little bit away from, you know, from from my, from my fungi, and from my mushrooms, which I was interested in before. And then later on, after I finished my PhD degree, but I should say, all the time now from you know, from being an undergrad, throughout my PhD, time as a PhD student, I was interested in, in small molecules in in all these these wonderful molecules that nature came up with, as antibiotics as something that tastes spicy, or hot or sweet, or, or the other the various art, I mean, just look around in your kitchen. You know, just think about your kitchen, what's, what's there, what's what's what's tasteful. And so nature basically has evolved, so many, so wonderful molecules. And this interest was kind of, you know, has been constant all over the years. And so when I was done with my PhD degree, I went to the United States for for my postdoc training, and to the Midwest, Madison, Wisconsin. And there, I kind of got reintroduced to fungi. So it's been it was kind of a of a circle I made. And which then, you know, took me back to the, to the fungi and their small molecules, their natural products. And so, this was about the time when I had to think about my own independent research program, I had to basically I was kind of decided to follow an academic career. And so, I had to think about what what kind of niche what kind of research I would like to do as my own independent program. And notice that mushrooms are little understood in terms of how they make these natural products is the correct term, the technical term natural products, small molecules, often bioactive. And when you think about mushrooms, and what what are the you know, most prominent and most well known molecules you think about toxins and so I thought about oh, I should I should do research on the on the death cap, you know, this, this, this incredibly toxic mushroom that appears in the fall. And that could even kill you. And so this was one one thought I had the other thought this was back in 2003, four ish. And there's more than one choice and the other obvious thing and I believe this was the reason why you introduced me to the, to your episode today. The other the other obvious choice was the where the magic mushrooms. And
from today's perspective, I was fortunate to, to choose neither one nor the other, because the techniques and the methods were not as advanced as they are today and I would have miserably failed. But anyway, that the idea was was, you know, in my mind, so I went on with other molecules, went back to Germany, accepted a junior group later position, then move back to the United States, again to the Midwest, even further north to Minnesota and accepted a faculty position there a tenure track position there, and then relocated as well to my current place to, you know, to expand on that topic and and same with with more resource available and with the, with the methods being more advanced than they used to be 1015 years ago.
Nick Jikomes 10:36
What, uh, what initially drew you to mycology, my apologies. It's not, I mean, it's become sort of famous recently with the whole psilocybin mushroom thing. But it's never, you don't typically it's not considered a big or sexy field. So how did you get into mushrooms and mycology to begin with? Was this a lifelong interest?
Dirk Hoffmeister 11:00
Well, I mean, this is kind of an individual perspective, whether it's a sexy topic topic, I guess. Yes, yes, definitely. It this is a tough one. What drew me to my ecology this is a, I think this is a combination of two of two aspects. First of this, it has to do with with a lifelong interest. So as a kid, I grew up in a, in a rural area, rural place, and in the far southwest of Germany. And nature was readily available, you know, I just left my parents home and it wasn't in the forest. The forest and you know, found the mushroom investor as a as a kid, and I knew the most important ones, as a as a kid. And that the Chandra rounds and the boletes and so, so this was, I think, this was one aspect that caught my interest very early on. And the second the second thing was one of my academic teachers of the most influential ones, probably of my academic teacher, who now passed away a few years ago who was such a brilliant, such a talented teacher and researcher, and this kind of, you know, so I just got hooked again, after, you know, 15 years as an undergrad. And so, I took all the classes, all the other courses and this is kind of, you know, lay the foundation of, of, of my interest, although his his research back then was was completed differently oriented, was was more about evolution and systematics and, and taxonomy. And, whereas, my research is more into into, you know, molecular biology, chemistry, biochemistry, so the direction is a different one, but that the basis is the same it's about mushrooms.
Nick Jikomes 13:15
Yeah, and from from a taxonomic perspective, so you said you start you majored and you studied early on botany and mycology, where do you fungi sit relative to plants and animals in the in the tree of life
Dirk Hoffmeister 13:29
much closer to animals, much prefer that I mean, traditionally, the the animal biologists had more, you know, to think about more animals than the botanist about plants. So, the kind of that they kind of you know, took took my ecology to plant it, so the the tree of life. So, if you have said that the plants are branching here so all evolutionary biologists who are listening now please forgive me if I simplify the Tree of Life with just my 10 fingers. So plants are here, basically and that branch that direction, then later off, branches off here into VeriSign in very simple terms now into fungi and, and, and, and animals.
Nick Jikomes 14:27
I see. Yeah, so superficially, a lot of people think of fungi as closer to plants, because, you know, they kind of grow out of the dirt like plants and they like vaguely look like plants, but they're actually more closely related to us
Dirk Hoffmeister 14:39
that they cannot kind of walk away that night, like animals are most most of them. But there's, but you should keep in mind that that the relationship between plants and fungi is a very, very close one. It's coevolution has been acquired. In addition, over 500 plus millions of years, probably even even before before the messy the plants, you know, went by basic went out of the sea and conquered the land. And so what we see today is, or what it resulted in is that plants and fungi have very close relationships be a symbiotic one, so that each partner or multiple partners benefit from each other, or plant or fungi use plants as a, as a host for parasitic fungi use plants as their host, and which is kind of, you know, a one way street now that the benefit. And so the notion of plants and fungi being very close to each other is kind of kind of justified, not from an evolutionary perspective, but from from, you know, just going outside. And then yes,
Nick Jikomes 16:12
yes, when you look at the genetics, and the literal familial relationship of fungi are closer to animals and plants, nonetheless, they are closely intermingled with plants in terms of their actual, like ecological interactions.
Dirk Hoffmeister 16:27
Absolutely, absolutely. And they couldn't survive. Without the other one. I mean, we were talking about fungi now. Mushrooms, and many, many mushrooms are, you know, living in close symbiosis with with look at all the, you know, the, on a global scale, that the northern hemisphere is dominated by forests, I mean, so don't don't think about deforestation, don't think about, you know, humans that destroy habitats, but just leave the planet, as it would have developed, without without human influence, without human impact. And then the northern hemisphere, in, in temperate areas in let's say that that's, that's North America, United States. Also, in boreal forests, Canada, and, you know, further north, or Scandinavia, for the North, in Europe, these are dominated by trees, that depend on mushrooms, as a partner in the in the soil in the ground, they have a very close, you know, interaction, physical interaction between plant roots and the fungal hyphae, that the filamentous cells and of other mushrooms, for exchange of nutrition, and so that the one couldn't live out without the other one, without the other partner. And this is why why we and so so as we walk through a forest in fall, you know, and then see all the various mushrooms that that pop up and grow out of the soil. We obviously think about this, this, they must have had something to do with each other. I mean, not from it from an ecological sense, from an evolutionary standpoint. As we know, now, or many years ago now,
Nick Jikomes 18:32
yeah, like, I think when people think about mushrooms, they're thinking of the fruiting body, the thing that actually comes out of the ground from time to time, yes, what you're alluding to, is there's this vast network underneath the ground
Dirk Hoffmeister 18:43
in the ground. Exactly. Yeah.
Nick Jikomes 18:46
Can you talk a little bit about like, what that is? What what is the lifecycle of a mushroom? And in, you know, when it's underground, what is that called? And what is that sort of form of the mushroom? And then why does, why don't these things periodically make these very, very big fruiting bodies that pop up from time to time.
Dirk Hoffmeister 19:05
So, the fruiting bodies like like this one here, this is just for reproduction. So they, this is what we see that that's right. And so, this is what we see as a as you know, how we how we perceive mushrooms, and this is just a temporary thing, ephemeral thing, these are formed for a reproduction for sexual reproduction. So the the sports you know that that that that are ready to grow out and you know, make the next generation they would be formed here, here at the cap. And the this happens once in you know, in fall so that they are the fruiting bodies they appear quick and are there for a couple days. And, you know, in the soil in the ground, there's kind of a web like structure of long filamentous high fee. Really like Like, like, like filaments very long and, and they are very thin. So much thinner than a tree root. So in other words, they can, they can access little niches and pores in the soil that other plant couldn't grow into. And so they can, they can take up nutrients and supply the tree with nutrients. And this kind of relation, and this, this, this, this this Hi Fi, and the entirety of it would be called mycelium from from like mucus peel, mushroom or fungus. And so this Mycelium is stays there, year round. And supplies the tree with with with with elements with nutrients, phosphorus, nitrogen, protects the basically real if this is a plant root here, and then the mushroom hyphae that these these underground cells, they would you know, wrap around, wrap themselves around the root and also offer some some protection and drought resistance. So this is the benefit that the tree has the tree in return can make sugars nutrients, by just taking co2 fixated co2 and reduce it into into sugar. This is what we live from, you know. So I will have dinner soon you maybe you will have breakfast. Assuming you will eat you know, cornflakes or
Nick Jikomes 22:03
mushroom coffee is all I've had so far. Okay.
Dirk Hoffmeister 22:10
And and so the benefit the mushroom has is that it can it has access to, to to nutrients to sugars to carbon to
Nick Jikomes 22:23
our service, or is it fair to say that basically, so these mycelial networks are providing the plants with micronutrients, like certain elements, also physical protection, and I think we'll maybe we'll talk about antibiotics and things like this. And the plant is giving the fungus primarily macronutrients like sugars.
Dirk Hoffmeister 22:41
Yes. Yeah, that's, that's correct. Okay. And this a case for it for a symbiotic relationship. So, both partners, in some cases, that there are multiple partners involved, but keep them both partners are they they benefit from each other and in case of a parasitic of a parasitic mushroom, there are many out there, they attack a tree, maybe a limp broke off or a thunderstorm hit hit the tree. And so there's kind of an injury and then that the the mushroom can enter the tissue that the tree tissue and cannot degrade living matter living tissue in the in the tree. And this This is a process you know, whoever is stronger and that can go on over over decades. And eventually the mushroom will win I would say and that the tree will die. And when and then serve at that and this this this dead wood will then serve as substrate also as a macronutrient for new life. Think think about think think about how think about a forest maybe somewhere in in no east coast or Canada or Minnesota forest without any human influence. It just develops over centuries over millennia. And during that time, many many many generations of trees will will die they will fall off or maybe a storm hits hits a forest and then they just take over but still after after The decades and centuries and millennia that the dead wood the dead trees, they will not you know, reach the sky, but they will have been degraded in the meantime. Why? Cuz degrading fungi are not the symbiotic ones, but the degrading ones did their job. And it takes about maybe 100 years for for, you know, a whole set of of mushrooms to degrade a tree a big, you know, substantial maybe oak tree that fell off or fell fell over to degraded into powder.
Nick Jikomes 25:46
So, there's, there's a couple different broad types of mushrooms, there's the ones that want the plants to stay alive to engage in a symbiotic exchange than the ones that want to degrade them. And they're, they're always in some kind of, you know, cyclical balance in the whole ecosystem.
Dirk Hoffmeister 26:03
It's kind of what what scientists call carbon cycling. So we have co2 in the air as a as a substrate of something beneficial for plants, because they live from from from co2, carbon dioxide. And so this is what the trees, fix a car, the co2 make biomass, they grow. And the best example, at the West Coast is these wonderful sequoia trees. I mean, they, you know, they hit the sky. And, and, and then degraders need to come in to raise it to disintegrate this biomass, this wonderful biomass that be called trees to disintegrate it again, and make it available to new life, then, you know, close the cycle.
Nick Jikomes 27:03
Yeah, interesting. Yeah, they're literally disintegrating structures that have been that have been grown, that are sort of bound up all of this energy and all of this carbon and they make them they make them useful again, through this physical disintegration process. Interesting. So when we think about the fruiting bodies, the reproductive organs, these things sprout up from time to time, part of the year, and they release spores, and this is how the mushroom network is reproducing itself. And of course, we've got medicinal mushrooms that make things like antibiotics or other nutrients that have medicinal properties. We've got gourmet mushrooms that people or other animals eat as nutrients. And then of course, we have toxic mushrooms. So we sort of have this monopoly of different options that sprout up on the forest floor, some of them can kill you, some of them can nourish, you know, nurture. Yeah. Why? Why do we see that kind of diversity in from the mushrooms perspective? Why is it making Why do different mushrooms make these types of things that can affect animals when they eat the fruiting body?
Dirk Hoffmeister 28:18
So, this this question is why why do mushrooms are more generous and why do fungi or plants make all these wonderful compounds be toxic compounds or you know, whatever? This is kind of the, the holy grail that the most most important question of of my research area, natural product research area. And only in very few cases, we know why. And then in I mean, to be honest, in most in those cases, we simply don't know why. An organism invests all the energy all the metabolic power and multi step reactions to come up with with a particular compound that that we think of as, as a toxin or as as an antibiotic, I mean, that does is that the purpose for which this compound or particular compound was evolved for Is It wasn't ready to make an antibiotic or maybe something else. We use it as an antibiotic because we you know, isolate, we extract we test and see bioactivity against whatever it was, it's really the purpose of, of having been involved. And now coming back to the to the toxic in quotes, toxic mushrooms that I mean, in textbooks you would or you would consider the magic mushrooms also to be toxic as they interfere with your neurotransmission and and cause hallucinations and stuff. So on first glance, you would consider them toxic. And this is actually also a question that I, I'm trying to answer have been trying to answer still I'm trying to answer is what why why was psilocybin evolved? I mean from from part of it, maybe I mean, one theory would be you interfere with with the neurotransmission of, of a predictor of kind of a small animal that nibbles on you and tries to feed on you. So this would be a more general concept. This is protection. Like, like other, maybe other other toxins are what we consider to toxins simply as a protector. And this may be may be true in many cases, some cases that they are simply made for protection, so you don't get the producer does not get eaten up, chewed up by animal.
Nick Jikomes 31:32
Yeah, one thing that jumps to mind there is when you think about something like psilocybin, in the philosophy mushrooms, one pattern that seems to be true to me is, when you look at psychoactive drugs that come from plants, they typically seem to be made for defensive purposes to protect the reproductive organ. And I wonder if I mean, do you think is that a general trend in botany, that a lot of these things that happen to be psychoactive when an animal like a human eats them, are actually being used by the plant for defense to kill insects or to interfere with an animal that might want to eat it?
Dirk Hoffmeister 32:17
Tough question. I can't I can't really answer your question. I'm afraid. If this is a general principle. I'd rather think I mean, so let's talk about plants. In case of, of opium, opium poppy, I would say yes, this is this is protection. But there's my personal guests. So please, all pharmacologists now in the audience, they may they may look at that differently. So I would say yes, in the case of, of cannabis. Not sure. Not sure. I mean, it's the female flowers, obviously, that are, you know, rich in THC, which is actually not not the only compound, which is another question related to yours. Why not one party or why in one, in some cases, one particular compound? Why in other cases, this this entire set of many, many compounds? How many, how many THC related or congeners F and isolated from him that 50 or 60 or 80 or even more? And so it's probably it's not not about one particular compound, but more a mixture of of them also that the true ecological reason why they have been involved is maybe the mixture not not the isolate, I mean, we think about as so as, as, you know, from from impairment, pharmaceutical perspective or pharmacological perspective, we think in individual pure compounds with defined properties, with defined interactions with a with a, with a receptor in our brain, but But nature maybe thought differently. And now, coming back to, to psilocybin, what I think is the case and what what our research, you know, points to well, this is this, it's hypothetical, but at least an idea to keep in mind is that, that, that psilocybin or the capacity to make psilocybin has in fact to do with protection, but not by interfering with with the with the pre dangerous neurotransmission but much more simpler by just making a protective agent on demand. Think about you're familiar with that, of course, and many in the audience's as well, I believe, with the bluing reaction of the magic mushrooms. Yeah, when
Nick Jikomes 35:19
you touch them or you you physically injure them
Dirk Hoffmeister 35:23
or cut them, they turn immediately that they turn blue. Yeah, it's
Nick Jikomes 35:27
beautiful. Yeah, like almost iridescent color.
Dirk Hoffmeister 35:32
And, and what I think is the case that the magic mushrooms do not make, I mean, from from from our anthropocentric perspective, and with with this, you know, powerful and, and, and, and wonderful pharmacology that has a combinate you know, human kind for for centuries and millennia in, we think about the set such that something said such a such a wonderful phenomenon, this must have something to do, nature must have evolved this for for, you know, whatever purpose to to interfere with, with with your transmission or with with our brains and our our thinking and behavior of animals behavior for dangerous behavior, then I think that the the answer is much, much simpler, that the mushrooms are not interested in psilocybin itself, it's just a storage form. It's about chemical defense, but it's not that not to to interfere with with with our brains and our behavior, but to have a compound and inert compound that can reactivate it quick upon attack upon demand for on demand, and then turn into that that blue pigment that is that binds to a protein that that can precipitate proteins that is that is that kind of can can can react with proteins, and keep predate us from feeding on the mushroom. So it's a defense on demand. This is my hypothesis, a defense on demand kind of a melanin, protect a protective polymer. And psilocybin is just the monomer that's stable and safe to store.
Nick Jikomes 37:42
I think so. So the bluing, when the bluing happens, it's a bunch of psilocybin individual molecules that have physically started to stick together.
Dirk Hoffmeister 37:52
Yes, indirectly. So what happens so psilocybin is a stable molecule, that you can actually store in the lab, that can be stored. And it has very, as one very unusual feature. Now, a few technical terms will will, you know, come in, he has a very from, from a structural perspective, a very unusual feature, and that's a phosphate ester. So, a phosphate group is basically sticking on an on an alcohol group of the molecule with a phosphate we call it psilocybin without the phosphate because it slows the molecule, which is the actual bio active or neuro active compound, psilocybin itself is inactive or lacking, as soon as we ingest the mushrooms, the molecules will, the psilocybin will be cleaved into psilocybin and that is what causes the the pharmacological effects and the psychedelic effects. And psilocybin is highly reactive. And it will, it will connect to other cells and molecules, it will polymer oligomerize or polymerize, into that wonderful blue color. And this is kind of the same, in full of fulfills the same role. That is my hypothesis, it fulfills the same role than melanin in, in other you know, other organisms.
Nick Jikomes 39:24
I see. So, so the psilocybin is made in the fruiting body, the psilocybin can turn into silo Osen, which happens to be the psychedelic compound that most people are familiar with, with magic mushrooms, but the silos and start to Iligan arise and polymerize meaning they start to physically attached to each other. And that's where that bluing comes from. So is this is this providing like a physical barrier? Is it almost like a physical protection, like a wound healing or something like that? Or is there some kind of chemical deterrent to an insect or something like this?
Dirk Hoffmeister 39:56
It's a it's a chemical, it acts on a chemical basis, cause The this this blue oligomer this this Ciloxan oligomers, multiple Maalik, multiple individual molecules now being linked to each other. They bind to two other proteins, say in the in the intestinal tract of an animal that feeds on the mushroom. And so it's kind of a it precipitates proteins, it binds to protein attaches to proteins, and then harms the potential for danger.
Nick Jikomes 40:37
I see. So maybe like the insects literally just get physically sick or something.
Dirk Hoffmeister 40:41
Yes. Yeah. interested, they won't continue feeding on this. That's my theory. Yeah. I see. Okay. So think think think about, think about a hand grenade. Kind of a strange, strange comparison. I know. It has a, it has a pin that the security pin that keeps the grenade from you know, going off. It's called psilocybin, with the phosphate group still attached. So once you cleave off the phosphate, you pull out the pin. And now you know it goes off and boom.
Nick Jikomes 41:24
I see interesting. Yeah, so the psilocybin, the psilocybin has this sort of like little safety mechanism on it, when you take that off, and you get the silos, and now you can have this oligomerisation reaction, all of these compounds connect to each other. And then you get this bluing reaction that we see, which is a just a physical manifestation of what might be this kind of protection mechanism mechanism. Exactly. Is it primarily so so from the mushrooms perspective, the fruiting body of Salafi mushroom? is the primary predator for this insects? Or is it animals as well?
Dirk Hoffmeister 42:03
I would say it's insects, or maybe some helmets and some helmets and some warms, living in the ground. Maybe some some slacks or like,
Nick Jikomes 42:17
Dirk Hoffmeister 42:19
Not necessarily. Not necessarily. I don't think I mean, that, again, that this is hard for for for humans to believe. But I don't I don't think that that, that this this little magic mushrooms anymore. The psilocybin for, you know, for us?
Nick Jikomes 42:38
Yeah, yeah, one thing that that makes that a little tricky. In my opinion, the idea that the mushroom evolved it with animals in mind is you have to eat enough of the mushrooms to get a psychoactive effect. And of course, there's a delay. So it would make it quite difficult for an animal to learn by association, that, you know, if, if you're a small animal on the forest floor, nibbling on mushrooms and other things, it would be very difficult to learn that it was those particular mushrooms that caused some psychoactive effects, two hours later.
Dirk Hoffmeister 43:11
In case of the brewing blue in reaction as a as an immediate, you know, protection mechanism are to put prefer to have a predictor. I mean, this happens within seconds, that doesn't send
Nick Jikomes 43:24
immediate action. Interesting. Yeah. And
Dirk Hoffmeister 43:27
this basically related to what what chemists called protection, protection groups, or protection chemistry. So this is a strategy in when you do a synthesis, a chemical synthesis has nothing to do with nature now. And you want to do a particular reaction at a particular position, but you got multiple reactive positions in the molecule, then you need to protect the others that you don't want to see react, and to just work on one possession, and then once you're done with your, with your synthesis, you then need to de protect, take off the protecting groups, again from the molecule. And this is kind of a similar strategy. I believe this this relationship is between Ciloxan and psilocybin. It's natural protection, group chemistry. This is something now it's getting a bit more technical. Because I was I was intrigued by this by this phosphate as to why nature doesn't do that very often does it? This is very rare. And there would have been other options and lists less energy intensive and less cost intensive options to stabilize a molecule. Why do i Why did the fundraiser phosphorylated and the ads I mean in the light of this of the theory It's clear because you can't just stick something on, you need to make sure that it it comes off again, when it needs to get out needs to come off.
Nick Jikomes 45:09
So it's protective chemically, but it can easily be removed referring
Dirk Hoffmeister 45:13
reversible. It's protective chemistry, but it's reversible chemistry. And this is, you know, more makes makes more sense to me.
Nick Jikomes 45:25
Yeah. And that would be, I guess that would be the perfect kind of protection that reversible, protective chemistry, is why that bluing reaction happens so quickly, you can very quickly change the molecule and let it do what it needs to.
Dirk Hoffmeister 45:37
Yeah, absolutely. Interesting. That the second thing is, as we as we basically work on the, on the biosynthesis, so that the metabolic steps how the mushrooms actually make psilocybin is that there's been kind of a proposed biosynthetic route that was devised in the in the late 60s, by brilliant chemists that they did brilliant work, and they were really, you know, they were ahead of their time back then. And which kind of proposed that that's psilocybin is an intermediate a precursor to psilocybin. And when we saw when we did our research into the biosynthesis, we, it slowly dawned on us, that the mushrooms do not make psilocybin, but they they have evolved the entire pathway in a way to avoid by all means, that psilocybin ever occurs as it sits ilosone Sorry, cellos and Mo occurs. So the complete opposite and, and even, that even so, this, this biosynthetic, you know, mechanism step by step by step even has a built in Mega a built in repair mechanism. So it should ever say hello Sun occur in the cell, you know, in the intact cell, not when when it, you know, gets bruised or something, but in the in taxa. So if ever Cielos and should occur in the cell, there's a protection mechanism as a safety switch that protects Ciloxan again, and makes it become psilocybin again. So the fungal cell tries to avoid by all means, by all means it tries to avoid that Tilos. And, of course, got it's too reactive that because otherwise, it would, you know, exert the toxic effect on on itself. If you pull the pin out of your hand, and store it in your garage,
Nick Jikomes 47:50
I mean, there is kind of an analogy with cannabis here because you know, the cannabis essential oil, which contains THC acid, it's always put in the trichomes out at the external surface of the plant, the plant kind of doesn't want it on the inside. And it actually at least there's some evidence to suggest that that is also offering a kind of, in this case, physical protection, because apparently the THC acid, the acidic group can absorb photons apparently. And so it might be, you know, some people think that it might be acting as a kind of sunscreen for the plant to basically to help absorb some of the UV radiation that the plant is going to be exposed to. So anyways, so the plant is making psilocybin or excuse me, the fungus is made. So the philosophy mushrooms make this compound is very interesting. It's got this protective phosphate group over one part of the molecule. And as soon as you pull that off, that was your hand grade. And now hand grade analogy. You need analogy,
Dirk Hoffmeister 48:55
kind of brutal analogy. But yeah, but it's interesting to base the message.
Nick Jikomes 48:59
As soon as you pull that off, you've got silos in which is not very reactive, and it can Iligan arise, you can come together with other silos and molecules, and that offers potentially some kind of protection. But in any case, that's where the bluing the very fast bluing reaction comes from. Yes, yes. So if we back up into the biochemistry here, Can you unpack where the psilocybin is coming from? So what are the starting materials for the psilocybin and how do you get to that?
Dirk Hoffmeister 49:26
Pretty, pretty simple. So the starting point is amino acids that we all have in our, in our proteins that all organisms have in their proteins. That's called L tryptophan. It's the heaviest amino acid and the rarest amino acids among the 2020 most cases amino acids that we basically consists of. And so it begins with, with this. Now general building block that's available everywhere, in your, in your food and in the meat or steak or whatever you eat or plant, you know, vegetarian food. And, and the first step is that it gets that it, it loses co2 to make tryptamine out of tryptophan, so tryptophan is what's going in. And the first you know, processing step is that the tryptophan loses co2 carbon dioxide, and, and produces or an enzyme does that produces tryptamine step number one. Step number two is another quite unique feature that doesn't occur very often in natural product chemistry, which is now it's getting very technical. This is that you install an alcohol group O H, and oxygen atom now comes in at a particular position of the of triptan in the position for a very good choice, a choice by by nature to to put the put the oxygen there, I'll come back to that later. And this occurs very, very infrequently, very rare, this is very rare feature. And interestingly, it happens as well with kratom. So that the matter again in the crowd and molecule features are for hydroxy for hydroxylated endo system as well. Anyways, so now we've installed the alcohol growth. And the the next step is the phosphorylation because it may cause now that the molecule is kind of in stable and reactive, prone to oxidation. And now, the fungus immediately phosphorylates to this alcohol group is for four Oh H group to stabilize the molecule to basically to push in the security pin. And the final, the final step is also technical terminal to transfer methyl groups, one carbon units to the molecule, which then completes psilocybin biosynthesis. And this is also one of the questions. We were asking ourselves why this methylation, that it's getting methylated twice. It's not necessary, because it would bind to I mean, the psychedelic effect or the the polymerization effect the bluing effect would happen with or without, without this methyl groups on. And the reason this again, what I think is the reason, so others may think differently is that it is required to slow down to to slow down basically are trying to make the to make this this, this this protection mechanism possible, from Ciloxan to back to psilocybin, this this this protection mechanism, mechanism that, that keeps the cell clear of syllables and so and it kind of helps slow down slow down reactivity to make the protection mechanism faster.
Nick Jikomes 54:13
I see. So, so basically, the fungus starts with tryptophan, and it gets it through food just like we do. So it gets this amino acid from its diet, and then turns this tryptophan amino acid into tryptamine, which is presumably the basic building block have all of the psychedelic tryptamines and other tryptamines. Exactly. You go from tryptamine to psilocybin and the chemistry there is such that you've got this phosphate group on one piece that is a protection. It's a protection thing to stabilize the molecule but it's also easy to come off and you've got these other modifications that make it really easy for the fungus to do this bluing reaction through Sylow silos and but also easily convert the solution back To psilocybin inside of the cell if that needs to happen, yes, I see. So I guess the name of the name of the game here is the fungus silo sin, the thing that we we is the psychedelic compound that's psychoactive in our brains. It's a very reactive molecule. And the fungus simultaneously takes advantage of that reactivity for the bluing reaction, potential protective mechanism to protect itself. But also because it's so reactive, it doesn't want too much tylosin inside of the cells. So there's some other chemistry there. That's that's protecting the fungus from that happening.
Dirk Hoffmeister 55:36
How harmful to that to the producer? Yes. Absolutely. Interesting. Yeah. So you summarized it brilliantly.
Nick Jikomes 55:44
Thank you. Thank you. So that's really interesting. But also, before you mentioned, you know, we talked about cannabis a little bit, it produces THDA, but it also produces this sort of constellation of other things. And there's this sort of, you know, branching pattern of biochemical pathways that get you this cocktail of compounds inside of that psilocybin synthesis pathway. Is it just sort of one single pathway that goes from tryptophan to psilocybin? Or are there other branches that the fungus can use to make other tryptamines as well.
Dirk Hoffmeister 56:15
So within that tryptophan to psilocybin pathway there is almost no no branching very, very minor branching, we discovered one one branch, which was in very, very minor quantities. So that there's this is a pretty, pretty straightforward and linear thing. But the fungus that the magic mushrooms or the mushrooms as well as the organisms as well as the plants as well, they can make other compounds out of tryptophan. And, and interestingly, the magic mushrooms can make compounds that are referred to as better Karpeles. Like so did the harmala. alkaloids. And they kind of they are, these are also bioactive molecules, that is better carbon liens. But in a completely different way, they inhibit a human enzyme that helps degrade, for example, Cillessen. So this is kind of a synergism, you know, the mushroom makes a compound that exerts a certain effect in US or in other organisms. And at the same time, it produces a compound that inhibits that degradation of another mushroom compound.
Nick Jikomes 58:06
Yeah, so the mushroom, at least certain species of philosophies are making both psilocybin and these beta carboline. Carbonate ma allies
Dirk Hoffmeister 58:16
Exactly. I'm gonna mean oxidizing.
Nick Jikomes 58:19
And as many people will know, this is kind of interesting, because this is, you know, in one organism, you have this cocktail coming together, which is very similar to what the shamans in the Amazon do by combining two different plants to Alaska.
Dirk Hoffmeister 58:33
I WASC. Exactly. Yeah, exactly that that's exactly the same, same principle, use a tryptamine and use Mao y monoamine oxidase inhibitor, in a cocktail, but the mushroom basically produces in with all all at once in one organism. But one cautionary note, we publish that work. And we wrote it in this publication as well but it was kind of maybe a little bit you know, in the background. That first of the beta carboline contents in the mushrooms are very, very low. I would say too low for for true pharmacological effect. That's the first thing the other thing is the, the the highest if you want to call them high at all. The highest better Karbolyn contents were found in again in the in the Hi Fi in this fluffy mycelium in the white thing not not in the fruiting bodies themselves, so that the fruiting bodies they are full of psilocybin one thing and that the mycelium that the white you know, cotton wool, fluffy thing is a little bit richer in the in the better carbon lanes, so they don't necessarily co occur at the same time. I'm at the same place.
Nick Jikomes 1:00:01
Yes. And this is the beta carbons are more prominent in the mycelial network, the
Dirk Hoffmeister 1:00:06
mycelium Yes, in the groin, magnesium towards the tip, we also did some some work on my students. And collaborators did some some beautiful work to localize that, to localize the contents with with, you know, imaging techniques or mass spectrometry imaging techniques. And they seem to be localized towards the the ends towards the tips of the of the growing hyphae. But they don't really co occur at the same as place and at the same time, in that arena from the lifecycle. So, this is what you know, when under a little bit in the in when people read the, the publication, because it sounded too good, you know, yes,
Nick Jikomes 1:00:53
yes, I see. See the Wascana? Yeah, people were immediately thinking, Oh, okay, this could be why certain mushroom species may be more potent, because Samsung is potentially to buy the amuigh. But basically, what you're saying is the fruiting bodies got all the psilocybin very little beta carboline content. Yeah. mycelial network is the opposite. Yes. And it's got higher ma wise, any, is there any hint at what the function of the beta carb liens are in the mycelial? Network?
Dirk Hoffmeister 1:01:22
Not that I'm aware of that not not the my router? This brings us back again, to the Twitter questions. Why are all these beautiful molecules are what what are they made for? I wouldn't really, I cannot really tell. You know, at least not in in a well founded way. What what what is better? Carlene says my wife are good for for the, for the mushrooms.
Nick Jikomes 1:01:53
And now for the philosophy mushrooms. What is their ecological relationship to plants and trees do Are they one of the species that is symbiotic with certain plants,
Dirk Hoffmeister 1:02:04
that these are the graders, these are our degraders, which is actually the reason why it's relatively easy to you know, throw them in your backyard. Because there's absolutely simple you need, you know, wood chips, or, or, you know, just get organic matter. You know, plant beds that are marked with, with, you know, these these wood wood chips. So, these are simple, the greatest or they are even copper philic, which means that they grow on done, which is probably one one of the routes how they were, you know, distributed globally, that they were introduced, for example, to, to the, or some species that were introduced to the newer, simply with with cows and cattle. And with with the dawn,
Nick Jikomes 1:03:04
I see, I see. And so, so going back to the the, the psilocybin, in the fruiting bodies of these things, are they unique? Is psilocybin uniformly distributed throughout the entire fruiting body or is it more concentrated in the cap or the stem of the fruiting body? Is there any localization there?
Dirk Hoffmeister 1:03:25
Well, I know that there are investigations and it seems to be more to my knowledge more concentrated in the in the caps and in the subtypes. And the spores basically are, are relatively, you know, free and clear, clear of the trip domains. But I so out of our own research, we haven't really made this, this differentiation yet. So I can tell so, so we didn't do any, any, any research to confirm that.
Nick Jikomes 1:03:59
And so what are the what are the natural types of environments that you tend to see Salafi mushrooms? I think we just alluded to it a little bit. Some of them grow directly in like wood debris, and some of them are copper philic as you said, dung loving mushrooms on matters. Yes. And so what types of environments like natural environments does that mean that they're commonly found in
Dirk Hoffmeister 1:04:24
various metro areas environments, including into basically human human made environments. I mean, just walk through through a parliament we have that in Central Europe as well in or in cemeteries that are, you know, well maintained with with all the plant beds that are that are, you know, well maintained and and and covered with With you know, wood material, which is a perfect substrate and provides a perfect habitat for for these, for example, one of the of the potent species it's called psilocybin sign essence, sign essence the one that turns blue, the one that develops a blue collar, what's the meaning of sign essence? And, and it grows, you know, really gregarious ly on on in parks and and artificial environments. The other one that's so I'm now from from from a central Europe, European perspective. The other one is called St. Helens Yeda a very small one tiny one grows on in on higher altitudes in the Alps. Again, close to an on meadows and pass them and maybe close to cow them. So there's this kind of kind of the habitat but it's not not a case. So so the psilocybin mushrooms is not a case that you really need to search for in a forest as you would do to your to pick some mushrooms, some some some bullets, and chanterelles or whatever that are associated with with trees in it somewhere. Deep, deep down in the forest. This is not the case with suicides. It's more more about open habitats. I see. Even on roadside Yeah.
Nick Jikomes 1:06:45
Rotax Yeah, so the fact that they're degraders. And the fact that humans human activity often procreate the environment, you know, break up trees to make mulch and things like those environments. So is there you know, there's been some speculation that, you know, humans and mushrooms, you know, philosophies may have co evolved in the sense that, you know, actually humans create so many environments that are the right environment for some of these degra degradative mushrooms to grow, than through just us moving around the world and doing human stuff, like making paths and gardens and stuff through the woods, that we've actually facilitated their dispersal throughout the world.
Dirk Hoffmeister 1:07:26
We facilitated this person, but I wouldn't call it a coevolution because I mean, the mushrooms have been around for many, many more millions of years, then we humans do. So it's, I, I'm a bit skeptical that that isn't really a coevolution. But we basically create an environment that helps them grow more abundantly. And and that brings us back to the anthropocentric perspective. I mean, if there is a mushroom that will never get extinct, it's psilocybin. Right? I mean, this kind of
Unknown Speaker 1:08:11
Yeah, and same same
Dirk Hoffmeister 1:08:13
with with with cannabis with him, I mean, think of a plant that that humans really care about and care for. And then it's probably you know, him.
Nick Jikomes 1:08:26
Is it. So when you're studying these fungi in the lab, how advanced are the genetic and molecular techniques? Like can you make transgenic mushrooms?
Dirk Hoffmeister 1:08:37
Mm, no, it's, it's pretty, it has to do with with the lifecycle of these mushrooms, which is a little bit complicated from a cell biology perspective. So the answer is no or say not not yet.
Nick Jikomes 1:08:57
I saw in one of the things in industry in
Dirk Hoffmeister 1:09:00
general, so it's a mushrooms generally are are pretty, are not easy to manipulate genetically, that there are some some techniques, but we've never applied them, at least not successfully, to the to the, to the magic mushrooms.
Nick Jikomes 1:09:17
And how, how abundant is psilocybin or philosophy mushrooms in nature, like how like roughly how many species of philosophies are there and is psilocybin produced anywhere else in nature? Is it only the Salafi mushrooms or does it show up anywhere else and other fungi or other plants?
Dirk Hoffmeister 1:09:34
Not in plants. So so it's so the the number of species about psilocybin and other other genera very roughly, I would say 200 species globally, very rapidly depends a little bit on taxonomical issues as sometimes one one species is split up in five or many spaces. Sometimes they are then consolidated again back to one species. So it varies a little bit, I will say roughly 200 species, and where else does it occur? That definitely not in plants, although plants are very talented and good at making tryptamine bioactive compounds, but not psilocybin. And there's there's some, there have been some reports that psilocybin can also made by, say, Basil fungi which still need to be confirmed. So, so mostly, basically, it's about this these higher.
Nick Jikomes 1:10:43
So most mostly found just a nice philosophy mushrooms. Yes, yeah. But there's but there's quite a few species depending on how you count. Hmm. Interesting. And now, what about are there any other compounds that have interesting physiological properties for humans, that are related to psilocybin some of these other alkaloids that I know that some species produce basis the nor basis, then what do we know about some of these other compounds and how common are they?
Dirk Hoffmeister 1:11:11
So, BOC synovial system, these are intermediates on the way from that that we justice or just talked about from from tryptophan to tryptamine to psilocybin, so they are just intermediates. And they so they occur in you know variable amounts difference a little bit from species to species. And so research from from what I observe research into their role correlative and quantitatively has just began so we don't really understand yet the contribution or at least maybe that there may be some some literature but I'm in the moment I'm not aware of of any. So, we only you know, slowly begin to understand what role these other compounds play for the, for the pharmacology because Because from from a from a say from a pharmaceutical perspective, we think in pure compounds in homogenous pure compounds with a reproducible you know, ligand as a binding molecule, ligand receptor interaction, this is what what we can really can measure and, and quantitate. And, I mean that there have been reports related to magic mushrooms on the so called entourage effect that other compounds may affect and increase or decrease the the action of psilocybin there's this this mysterious would llamas paralysis
Nick Jikomes 1:13:07
Yeah. Can you explain Can you explain that for people who don't know?
Dirk Hoffmeister 1:13:10
Oh, absolutely. Sure. So, these are reports so it's a good lovers paralysis, these are reports more on an anecdotal basis, not not really in the scientific literature or a very small degree, the scientific literature that that that you know, people who consumed magic mushrooms as a recreational drug experienced paralysis kind of numbness or really, they are were heavily impaired in their in coordination of their of their muscles. And these are all these effects occur with those mushrooms that grow on wood, this one called wood lovers paralysis with with a wood inhabiting mushrooms, not with the ones that grow on done like psilocybin cubensis or a seminar Tiana later. And, and so this was kind of of or still is, kind of young America, what causes these, what what causes these paralytic effects that that we cannot, you know, move up, move our arms anymore or feel feel numbness and so on? And cause the effects that this paralytic effects that lasts much longer than maybe 18 or up to 24 hours, much longer than the psychedelic effects of psilocybin, which is maybe three or four hours until they subside. And that is number one. Number two is that that psilocybin causes central effects on our central nervous system. That whereas the paralytic effects are in effect our peripheral nervous system, so there's that there must be something different going on, but we don't know why this is America and try to you know, so there's or has not not much been research been done yet and that which kind of sounds like there are other compounds at least in some species some some particular species of mushrooms that are not discovered yet.
Nick Jikomes 1:15:47
I see. So, there are anecdotal reports that some of these would loving philosophies in contrast to the the copper philic ones that grow in dung, you can get this paralysis that far outlasts the psychedelic effects. So there's probably some other chemistry there but but we just don't know what it is. Yet. Yeah. Interesting. So what other stuff do you work on in your lab? It looks like you also work on things like terpenes produced by fungi so what are some of the other families of compounds that that your group is looking at?
Dirk Hoffmeister 1:16:21
The terpenes are not a focus in our group. It's more about did you are we talking about the magic mushrooms or the other projects that are going on?
Nick Jikomes 1:16:34
Yeah anything anything
Dirk Hoffmeister 1:16:35
else? Okay. Cuz I mean the magic mushrooms are one one project maybe the most visible one in my in my research, but But surely not the only one. And there are others for example, with the number move from from the magic mushrooms to the web cap, web caps, symbiotic mushrooms. So, we work on on on another on another group of natural products, which are called polyketides, which are distantly related to fatty acids, also a very prolific group of natural products, many bioactive molecules. So this is another focus how they and we recently found out that an undiscovered class of enzymes actually make these these mushroom polyketides are this Oliver cyclic match from cookie dad's. So this is another form is not necessarily the terpenes although I really liked the terpenes and that brings us back to the to the to the spices and herbs. In the beginning of our conversation I really liked like to spice up my materials with with time and stuff. So the webcasts business one thing and yeah, and another type of compounds are brings us back to two colorful and and colorful molecules. Our group which is called probiotic assets, has nothing to do with with with psychoactive molecules, but they seem to play a role in in interactions between bacteria and fungi. So they they impact upon biofilm formation and stuff. And so this is a so this terminal Quinones is palmitic acids. This is a group of compounds that that I've worked with for you know, many, which is basically that the one that I then embarked on when I thought about a postdoc, which which program should I develop as my my own independent program 15 years ago and this is still active in my in my home. So it's basically the three things it's the it's the magic mushrooms, it's the polyketides mushroom polyketides and the probiotic acids, which are very frequently found in boletes in foliage, mushrooms, and which are the molecules. So when you again, this is a phenomenon many many mushroom enthusiasts in the audience will be will be familiar with. So when you bruise a bullet, it will turn blue has nothing to do with the blowing reaction of the of the magic mushrooms, different chemistry and these these palmitic acids. My third project is about these these compounds. I see work.
Nick Jikomes 1:20:00
So there are mushrooms that will bruise blue but they're not psilocybin mushrooms. Exactly. Yeah. Well, that brings, you know, to maybe a practical question. There's you know, there's, there's a fair number of people in the world that like to go mushroom hunting, I live in the Pacific Northwest, I buy a lot of mushrooms at the market that people go out and they just pull right from the wild. And, you know, this can be if you're in the right environment, potentially dangerous, right? Because you might pick something that's toxic. If you're not a seasoned mushroom Hunter. So for a philosophy mushroom, if someone's hunting for magic mushrooms containing psilocybin are there, what are the characteristics that they look for that would distinguish it from other things? That that might be harmful for example?
Dirk Hoffmeister 1:20:48
Well, blooming blooming is one one feature but not all mushrooms, that I mean, are we talking about the the edible ones, or the psychedelic ones?
Nick Jikomes 1:21:01
The psychedelic ones, the ones
Dirk Hoffmeister 1:21:05
Okay, so So the psychedelic ones, they they should, Bruce blue, but not all mushrooms that do so are psychedelic. So it's, it's not, it's not working that direction. So that the psilocybin mushrooms are, are when you need to be an experienced mushroom Hunter. If you want to pick them for whatever reason is as a recreational drug. I shouldn't, you know, there's not something i i recommend or endorsement and by no means there's also also legal restrictions in some some states. So, just from a, from a psychological perspective, the psilocybin mushrooms are quite a quite variable in the way in their appearance, you know, in their, their morphology. From from cubensis I mean, what you are not very likely to find in the Pacific Northwest, which are you know, really, you know, tall, tall mushrooms down down to tiny, tiny species. So there's no real, you know, one feature fits all trade that would help you identify me with an egg, I mean, that there are microscopic features that then help you identify as a species. But for I mean, for the sign essence, which is basically one of the of the widely distributed mushroom wood loving mushroom. It has a, what's characteristic is that it grows in gregariously in clusters invest in troops. And, and, and the, the here the margin here, turns turns a little bit bluish as they as the fruiting bodies age. There can kind of wavy a wavy shade here, not not as straight as here.
Nick Jikomes 1:23:32
So basically, it sounds like you're saying that all psilocybin containing mushrooms should bruise blue, but just because something bruises blue doesn't mean it's a psilocybin mushroom, mushroom, so it needs to bruise blue and you also need to probably have good familiarity with the specific morphology of the species that is likely to grow in your area.
Dirk Hoffmeister 1:23:51
Yes, yes. replaster make it more complicated. There's a lot of psilocybin related mushrooms that do not make psilocybin
Nick Jikomes 1:24:07
so they morphologically look similar, but they
Dirk Hoffmeister 1:24:09
don't look similar, but don't do not make psilocybin they have been from from from a taxonomic perspective, they've been, you know, separated in or grouped into a different genus. Now so selasa B mushrooms are now you know, from a taxonomic perspective now are required basically to make psilocybin to really belong to that particular genius. But there are many many out there and that this is this is also the reason why why are you ready? Don't Don't Don't take any chances. Because similar looking mushrooms can be very very toxic and make so I'm not familiar or not familiar enough with with a with the microflora in In saying in North America or the Pacific Northwest at least from from the European one I can say that that's similar looking mushrooms make make the make the toxin that also makes the death cap toxic and fatal created
Nick Jikomes 1:25:17
what is that molecule emanating
Dirk Hoffmeister 1:25:24
which basically attacks your liver tissue and and and blocks processes in your in your liver inhibits your liver and which eventually may cost deaf and what most people don't know is that not just the Deaf caps make make m&r or Emma nitens is again it's a family of compounds but also other ones and among them you know, little brown kept mushrooms that made at least at first glance looks similar to to to psilocybin for example, sinus unexperienced you know, unexperienced people may may really confuse them. Yeah.
Nick Jikomes 1:26:13
So I guess that kind of recap what you've told us about psilocybin. There's really this one genus of mushrooms with maybe some minor exceptions. But it's the philosophies that produce psilocybin. It's produced in the fruiting body in the reproductive organ of the plant. It's got this interesting biochemistry where the fungi are eating tryptophan in their diet, they're turning tryptophan into tryptamine tryptamine to psilocybin. And you told us about this interesting chemistry where the molecule is stabilized and protected in certain ways. But it's done in this reversible manner. So it can very quickly make the silos and bluing reaction happen, plausibly as a way to protect itself from things that want to eat the fruiting body. And it evolved that biochemistry for its own reasons. And it just happens to be psychoactive when an animal eats it. You Yeah, it's a very, very interesting, very interesting organism. What do we know about like the genetics underlying this, are there particular genes that evolved in this lineage of philosophies to allow it to have that biochemistry.
Dirk Hoffmeister 1:27:24
So, so basically, this we need four enzymes to convert tryptophan into tryptamine, denorfia, symbiosis and psilocybin. And these four enzymes correspond to four genes, which are present in Peru, more or less the same arrangement, maybe sometimes some duplication happened in the psilocybin mushrooms, psilocybin and also in some, some other genera. So it's not just an aside, I mean, that, although they are most most familiar and well known, but there are also some, some other genera and that do contain a kind of a genetic locus of a portion of their of their genome. quantify that roughly 25,000 bases are necessary, and that that, you know, contains these four, or sometimes duplicated five or six genes to make psilocybin happen. And there's, there's one one study that came out almost five years ago, no doubt of my lab, colleague of mine, Jason sloth in Ohio, who basically basically elucidated how these how these genes found each other, and outside the genus and then psilocybin, and then how the how the, you know, the entire cluster of genes, you know, got transferred, and then radiate it out. Beautiful work. Interesting.
Nick Jikomes 1:29:09
What, what kinds of, you know, for the psilocybin group in your lab, what are some of the questions that you're working on today? What's what's on the cutting edge that that's top of mind for your group right now?
Dirk Hoffmeister 1:29:22
It's a balloon reaction still. Which, which is Yeah, kind of want one focus. It's also about the enzymes to to characterize the enzymes you know, in greater greater detail, for example, this this, this this protection mechanism to bring soloists and back to psilocybin. This is something we still focus on. And yeah, so it's still stuck. I'd like to project.
Nick Jikomes 1:30:01
Well, you've, you've shared a lot of interesting stuff with us, Dr. Hoffmeister, are there any final thoughts you want to leave people with about, you know, the biochemistry of psilocybin mushrooms or mycology? Generally?
Dirk Hoffmeister 1:30:13
Um, some final thoughts, it's maybe one or more general things that I've, I mean, we talked a lot about science and discoveries and theories hypotheses, which would not have been possible to discover with without very, very dedicated co workers. And, and group members. Yes, I would like to, to mention, Alex Robert of the Eastern Institute, Madison, Wisconsin. Who is fun guy and so it's so it's such a pleasure to work with. It's with Andrew Chadeayne. Of, of Camtech, who actually appeared on your in, I think it was episode number 71. Who is awesome. It's so inspiring to, to, to share thoughts with him and and cooperate with him with battle. He's an American Austrian protein chemist, I was a fun guy. And so they are it's, I'm really privileged to to cooperate with all them and and develop hypotheses and and share thoughts and get input and provide them with input. And also with with a very enthusiastic group and very dedicated group here, beyond the small who actually do the to the the creative work and and the lab work and really come up with with new knowledge. And so this is this really a privilege, I think, which I would like to emphasize it's not just one person who's standing in the front, but it's, it's, it's about the CO operators and the co workers that do all the work and, and, yeah,
Nick Jikomes 1:32:13
yeah, so just like the mushrooms, it's a lot of symbiosis. Exactly. All right, well,
Dirk Hoffmeister 1:32:21
and one day, there's very, very well working.
Nick Jikomes 1:32:26
Professor Derek Hoffmeister, thank you for your time, and I look forward to talking to you again at some point. It was a pleasure.
Thank you for having me.