CANNABIS VILLAGE - Where do cannabinoids come from?
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Transcript: English(auto-generated)
00:00
Alright, I think I'll get started and tell you guys a bit about my work with engineering strains of yeast to produce various cannabinoids. My name is Kevin, I'm from Montreal, this is my first DEFCON and yeah, I'm enjoying it a lot. My background is primarily in biochemistry, but I am the CEO of Hyacinth and I do a lot of the fundraising stuff.
00:25
And on the side I also do some biohacking and DIY bio sort of stuff, so I've been to Hope a couple of times and so I'm somewhat familiar with hacking things, but I'm not very good at any hacking stuff, so hopefully today and tomorrow I'll learn something from you guys.
00:47
A little closer to the mic, yes. So, to get things started, I don't know if you guys were here for the rest of the day and saw the other talks, but maybe you got a bit of a primer about cannabis and how it grows and how to tell if it's sick or not,
01:01
or what the chemistry looks like. We had some fantastic talks earlier about that. I'm going to shift the focus away from cannabis plant stuff and talk more about specifically the cannabinoids, which are the name for the active ingredients in cannabis, so THC is one cannabinoid, CBD is another cannabinoid, and there's about 100 others. And the basic question to start things off is where do they come from,
01:25
and also how much do they cost? Of course, the most intuitive thing is to grow plants and to get THC, and that's pretty good. And as far as costs go for growing plants, you guys, people who have done their own growing would know their own estimates,
01:43
but I think if you had pure THC, maybe $10 a gram kind of thing, if you really want to get your costs down. But anyway, plants are just one way of getting THC, and as we saw earlier, you can also synthesize THC using chemistry, and that's kind of what you'd see in the middle image there, is a big chemical plant that's producing all this THC.
02:04
I think that plant in particular is for some other pharmaceutical or antibiotic or something like that. But I'm here to talk about a third way of doing this stuff, which is to engineer strains of yeast to produce THC and other cannabinoids, which has its own set of advantages compared to chemistry and compared to plants.
02:28
So as a bit of an introduction to what this is all about, we're talking about biosynthesis here, which means that there are chemical reactions happening inside the plant cells that will take sugar all the way to something called olivotolic acid,
02:44
then to cannabidriolic acid, and eventually to THC or tetrahydrocannabinolic acid and CBD. And these chemical reactions are driven by enzymes, which are the molecular machinery of the cell,
03:02
and I don't know what kind of backgrounds people have in biochemistry and stuff like that, but these enzymes are genes inside cannabis that you can cut and paste and move around if you wanted to. And so our goal is to take these genes from cannabis, those segments of DNA that are responsible for producing THC,
03:25
and put those into a strain of yeast. And then that yeast we can grow using just sugar and water and really big steel tanks that go up to hundreds of thousands of liters and have a really big industrial scale system for producing pure THC that's a lot more efficient than chemistry and growing plants.
03:47
What this looks like from an overview standpoint is that when you're thinking about what a yeast is doing in its cells, it takes in sugar and it grows. That's what a yeast does and it produces CO2.
04:01
Or it produces ethanol if you wanted to make a beer or something like that. And our job as metabolic engineers and genetic engineers is to look at this pathway and add on things that are going to get us to making something like a levitalic acid and eventually to THC.
04:22
So this involves a lot of changing around the genome of yeast and tweaking certain things and figuring out different ways to grow it so that it does optimize for production of THC. And in the simplest way of thinking about this, we add three or four enzymes, they convert from sugar to THC in the end,
04:41
and that's the easy way to think about the problem. And then if you wanted to make something like CBD, then you remove the THC-producing enzyme and you add a CBD-producing enzyme and then you're making CBD and THC. This is one of the advantages of manipulating genetics, that you can switch things on, switch things off,
05:01
you can control the stuff like a program. The challenge comes in, as things get more complicated, when you're talking about a hundred different cannabinoids and all these other metabolites that get made alongside of it, where it's not as easy as adding just three or four genes to a yeast
05:20
and then you get THC out, you're going to be playing around with maybe hundreds of different genes. And for us, we've gone through hundreds if not thousands of combinations of different genes to optimize and to improve always on our yields and to try and get to producing different cannabinoids.
05:41
So that's kind of how we think about this stuff. And just to clarify one thing I guess, we saw a bit of this earlier too. We're not thinking about synthetic cannabinoids at all, we're just interested in the ones that the plants make. You could possibly engineer yeasts to produce some of these synthetic cannabinoids, but there's not as much of an interest in these things right now.
06:06
So I don't usually use the word synthetic when I talk about what we do, because people get sometimes confused about synthetic cannabinoids versus ones from plants. We're making ones from plants, but we're not growing plants in any ways.
06:20
Alright, so after we've made cannabinoids, the question is where do we go? And this comes to talking about why we're doing this whole thing. As we would have seen earlier as well, and probably you guys know, like, cannabinoids go into your brain, they react with your cannabinoid receptors, and then you get the various effects like feeling high or having an appetite or whatever else and all kinds of different things.
06:45
Or as Mark Lewis said this morning, maybe tweaking your entire personality apparently is part of this system. But it's a super interesting system to manipulate and there's all these different cannabinoids that are going to affect it.
07:02
And that's ultimately what we're working towards. And because cannabinoids do this, that means that we can use them to treat various diseases. Whether that's for epilepsy or for mental health disorders like depression or anxiety.
07:22
Even glioblastoma is like, you know, late stage brain cancers has seen a lot of interesting results from using THC along with other cancer treatments. And then nausea, appetite loss during cancer therapy is another. That one is what Marinol that exists on the market right now is prescribed for.
07:41
And there's also another product called Sativex that's cannabis extract that's also a prescription drug. So a lot of newer cannabinoids stuff kind of points in that direction. So I guess out of these four pictures, maybe the biggest ones are epilepsy, which is fairly new. And then nausea, appetite and stuff is kind of the classical thing that people try to use cannabinoids for.
08:04
And there's the famous story of Charlotte's Web and this whole thing where CBD is now being used for treating epilepsy. And there's a really interesting timeline where this stuff kind of came out in 2013. And then 2014, the pharmaceutical company, GW Pharmaceuticals, started their first trials of CBD with epilepsy.
08:21
And now it's, as of a few months ago, on its way to the market and approved by the FDA. So when it comes to thinking about why we're doing this, we're really interested in looking at different ways of producing THC and CBD
08:41
and not just thinking exclusively about growing plants as this has to be the be-all, end-all solution because it does take a lot of energy and time to grow plants. And if I think in terms of numbers, it's like three months to grow a plant. And if you really want to get high levels of THC, then you have to grow it indoors in a very controlled environment. And how about those lighting energy and stuff like that?
09:01
So it's really not that environmentally friendly or economical to grow THC in that method. And then with chemistry, you're working with petroleum-based compounds. You're having multiple different reactors and all these interesting temperature controls and regions that have to go into that process. And that also becomes quite complicated and can take weeks as well to do.
09:23
But with yeast, it's more like you add sugar, you add water, you add the yeast, you wait a week, the yeast grows up, then you do an extraction and get your THC out or CBD or whichever one that you're interested in. And that's the process that we're aiming for. And there's a few different advantages to this, but as far as the impact that this is going to have on the industry
09:44
is that we're finally going to be able to have a reliable supply chain for CBD that's coming from a source that is industrially scalable. And what I mean by that is, now my thoughts are a little bit all over the place, but we'll bring it back.
10:04
I'll keep going and then I'll bring it back. And then you guys can ask questions and then everything will be okay. So yeah, it is quite hard to grow cannabis plants. And I haven't tried growing them myself. And maybe it is kind of easy to do it in your closet with the right amount of investment.
10:21
But once you start scaling things into agricultural level and you're starting to build out acres of greenhouses that get entirely contaminated with powdery mildew and then you lose millions of dollars of crops at the same time instead of a few leaves in your plant in your closet, then you're getting into problems. So there was a few cases in Canada where some of these big marijuana companies that were growing these huge amounts of product
10:45
were using pesticides that they weren't allowed to use because there's only a few pesticides that you're allowed to use because that's the way that Health Canada restricts things. And for good reason because you're lighting this product on fire, you're inhaling it, and if you're inhaling pesticides then that's different from when you're eating pesticides.
11:01
And so there's a really restrictive thing there. And so there's a few companies that got caught using these pesticides and that was causing some health problems in Canada. And I think this is still in the U.S. I'm not sure where things are at as far as pesticide use exactly, but I'm glad that in Canada this was discovered and this was enforced
11:23
and that might not necessarily be true for all the different U.S. states. And now with California's legalization coming up, there's expected to be some kind of bottom that can cannabis testing labs where there just aren't enough labs to test all the cannabis that's going to go on to the market. So how are you supposed to know if your cannabis does or does not have these pesticides in it?
11:42
All of these problems are associated with growing cannabis plants and not with yeast, of course, because when you grow yeast it's just in these very controlled environments and you're focusing just on extracting your THC and you don't have to add any pesticides or antibiotics or anything like that. The other key advantage is in diversity of products.
12:03
So like was mentioned earlier, I see these things kind of like Lego blocks where there's going to be a hundred different cannabinoids, there's going to be a whole bunch of terpenes and there are all these different molecular compositions that you could build and put together to create these optimal experiences for when you use a cannabis product.
12:26
And to kind of dismiss the idea of getting down to that finer grain stuff and discovering what all these things do is that we have to know these things and it's super interesting to know which perfect combination will be the best treatment for epilepsy
12:40
or which perfect combination will be the best treatment for like a Friday night night out or something like that. And this is also part of the reason why yeast is so interesting is because you can manipulate the genetics, you can clone new things, you can build new cannabinoids or very quickly scale up new kinds of products using this technology.
13:05
And then as I mentioned earlier, the question of scale is the other one. And this is maybe the biggest kind of clear thing that is becoming more and more defined as we go along with the development of the bigger and bigger grow ups is if you think about the scale that is needed to treat something like epilepsy
13:22
like there's 50 million people in the world who have epilepsy and now there's between CBD and CBDV some new drugs being developed for treating epilepsy. And if you add that up to how much the dosage is and what this is going to take
13:41
then you're getting into the range of like 1500 tons of pure CBD or CBDV like the pure cannabinoid product. And I think if you compare that against like a cannabis growth operation then maybe the total amount of cannabis in the world right now is still maybe 100 or 1000 times away from getting close to those kinds of numbers.
14:04
And if you're willing to bet some money on what's going to be the scalable best way to grow cannabis it's going to cost you maybe 100 million dollars to get to 16 tons per year of product and if you pay more like 50 million dollars of investment then you might build a facility that grows yeast
14:22
and you can do more like 750 tons per year. And so this is the reason why yeast is so interesting because it has this established industrial scalable model of manufacturing. And this is my last slide and then I'm excited to go to questions.
14:43
I'm from Canada so you can ask me about the Canadian law system and what's going on there because I know quite a bit about that. But it's actually funny just to share a bit of perspective where Canada has this very well defined objective of cannabis being illegal as a health risk because it exists as a black market and so on and so forth
15:02
and there's access to youth that they really want to control. And so they're motivated in this way to create legalization and to create a framework for getting access to cannabis legally. And so instead of us dealing with the DEA, like the Drug Enforcement Agency
15:24
or the FBI or whoever else that manages it where it's a kind of a narcotic control board that's managed by the police we deal with Health Canada where it's like a public health agency that is oriented towards improving the health of Canadians and they see this as like the priority.
15:40
So you're welcome to ask me more questions about that and maybe you can write into your own governments about this perspective because I think it's kind of one of these ruling arguments towards cannabis legalization.
16:00
Something's on fire. All right.
16:23
Yes, carbon footprint.
16:46
I guess we'll sit tight or we can get up and go outside or something like that. I don't know, what are we supposed to do? Is it going to be like a minute longer? We can talk while she's talking between your alarms.
17:03
We'll do it very quickly.
17:23
I do. Yes.
18:17
Hey, we're back. All right.
18:24
Questions then. Yes, in the back. So like I said earlier, the basic concept is to look at the genes in cannabis and take those and I can speak more specifically I guess.
18:43
The cannabis genome is sequenced. It's online somewhere along with the genomes of various other organisms along with yeast of course and so you can look at the genomes and pull the segments of DNA out, email those to a DNA synthesis company and they'll make it for you and send it to you in the mail and so we've never actually touched any kind of plant material.
19:03
We just use the digital DNA information and then just have it ordered online for us and that's probably the fastest and easiest way to do this kind of stuff. And then there's like five or six different techniques including the CRISPR-Cas9 stuff that you can use to engineer yeast. It really depends on what your approach is and what gene you're targeting.
19:25
So it's a lot of hard work and a lot of sweat and tears and blood and everything that goes into engineering the yeast but it'll take more time than it would take to grow a plant but if you wanted to breed a plant that would have high amounts of THCV
19:45
or something like that then you're probably better off using a yeast than an engineering that instead of trying to breed a plant to do that kind of thing. Yes. Okay, you just said sorry. Yes.
20:05
No plant material. No plant material.
20:30
Let's see. If I go to... Oh, I'm not online. Never mind. All right, we won't do a live demo.
20:41
But anyways, you can go to idtDNA.com or look up just DNA synthesis companies and you can write in DNA sequences and they'll make them for you and it'll cost like 10 cents per letter that you order and then they send you the actual DNA sequence which will look like a clear powder or like a liquid or whatever and then that's what you work with
21:00
and that's, you know, the DNA is inside that liquid and that's all you're handling. So there's no actual plant material being moved around or anything like that. That's kind of how it goes.
21:26
So if you were starting with synthesized DNA then you would need to have also like a plant material to add it into. So you're not like growing from scratch, of course. And this is where like what Mark was saying earlier about how you need to have isolated versions of plant cells
21:41
that can be grown into plants and then you can cultivate, you know, modified strains like all this technology that's involved. That's part of what you would need to take synthesized DNA and make modified plants. So you wouldn't be able to order a plant online by just typing the DNA sequence of the plant. Not yet. One day.
22:01
Maybe in 10 years. Maybe like 100 years. I don't know. I don't know. I think I saw Annie in the back first.
22:20
Not specifically. And that is one of the things that we'll be testing like as soon as we make the stuff and are authorized to do all the testing and whatever else needs to happen for that. But basically when we're looking at and we're thinking about this, we're talking about the chemical composition
22:42
and what's going to work the best. And so if you took THC that's been isolated into 100% pure from the plant, 100% pure from like chemical synthesis, and maybe 100% pure from biosynthesis, and compare those side by side, you should have exactly the same results no matter what. And then usually the finer detail
23:02
of like how effective a cannabis thing is versus a synthetic thing is, is when you're talking about these compositions of cannabis oils where yeah, there's more stuff in cannabis oil and so you get different effects compared to just like a purified form of THC. And that'll be something that we consider when we go into our own testing is like we're not just wanting to make purified THC because that's kind of been done
23:20
and doesn't work that well compared to cannabis in many cases. I saw this in, yeah, over there in the back, yeah. How far do you go? Oh, okay. About 12 months kind of thing. Yeah, 12 to 18 months. And right behind you.
23:48
It's not for sale yet. And maybe on our website eventually. The highest in bio.com. You can go there and try it.
24:01
Sorry, highest in bio.com. That's our website. I have business cards and stickers and stuff. You guys can come up to the front and grab some too. Who did I have next? Is it you next, I think? You've got your hand. You still have your hand up, so let's go with you. Theoretically, yes. And practically, probably yes as well.
24:21
And this has been done or explored a bit with the people who are trying to engineer yeast to make opioid stuff. Like they took it and tried to brew a beer with it. And then I think their analysis was like, look, it doesn't make opioids, which is like, you know, it wouldn't because the conditions are different because there's not very much yeast in there. So you might be able to bake a bread with it.
24:40
It might not have any THC in it. And that's just like the way it'll go. And it might smell like flowers or something like that because that's... All right. Thanks. In the back?
25:04
All right. Yes. And there's some terpenes that could possibly be good biosynthesis targets like along with the cannabinoids. But also some of these terpenes,
25:21
I think you can get from other sources like kind of cheaply. Or even like take a purified form of CBD that we make and mix that in with like a hemp oil and then you have your full spectrum thing that way. There's a few different ideas that we've got in mind for when we get to that stage. Yeah. So your main focus right now is CBD.
25:48
Yeah. It's a bunch of things in parallel kind of thing. So CBD we've done maybe the most to work around but also like this kind of science does well when you try to do THC as well at the same time or THCB.
26:01
And so we've got like a whole bunch of tracks that are running through in like high throughput kind of thing. All right. I see somebody way in the back. So when you're looking at like the yeast soup
26:21
in like a liter of yeast soup, you would get like one gram of product kind of thing. And that's like our, that's our at least next target. We're not there yet but like, you know, that's sort of what we're aiming for.
26:40
And that's pretty good for a process. Yeah. Yeah, insulin is a, yeah, different, yeah. It's hard to compare I guess because every product is a bit different and insulin is like a protein so you need less of it
27:01
and also it's producing much lower amounts. But I guess the comparison that I can draw is when people were trying to do biofuels using yeast where, you know, then they were getting like pretty, a lot higher yield so they needed to get a lot higher yields in order to make it commercializable. And then you're talking about like, you know, tens or hundreds of grams of product per liter of yeast
27:23
or even more than that maybe. Yeah. So that's our kind of, our goal. Yes. Are you actually extracting it? So solvent extraction basically,
27:41
and there's a bunch of other techniques. Like we could try supercritical CO2 stuff as well and do the same thing as done with plants. And I'm going, I don't know if I'm going overtime but I guess Rex, are you up next? Yeah, okay. All right, Rex will tell me when he's ready to present. Okay, cool. So this will be maybe one more question after this while Rex gets set up.
28:01
And your question was extraction. Yeah, various methods. And there's ones that are established pretty well for yeast like doing column separation or solvent extraction stuff. It depends a bit on the product and it depends if we're going for THC or if we're going for CBD and it depends on like other things.
28:21
And yeah. Okay. Rex? Yes? All right, cool. I'm excited for Rex's talk too so stick around. Yeah.