CANNABIS VILLAGE - Where do cannabinoids come from?

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CANNABIS VILLAGE - Where do cannabinoids come from?
...and how much do they cost?
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THC Producing Genetically Modified Yeast
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Kevin founded a startup focused on opening up the potential of cannabis-derived medicine, by replacing plant growth with engineered microorganisms. His side projects include Bricobio - the DIY bio/biohacker/indie science community in Montreal - and he’s also a director of Helios Makerspace. Kevin will speak about his work hacking the genome of yeast to make it produce THC. Being that this process is more in alignment with current pharmaceutical practices and is able to scale much more effectively, he hopes this approach will enable many to explore the benefits of Cannabis-related medicine and products more consistently.
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all right I think I'll get started and tell you guys a bit about my work with engineering strains it used to produce various cannabinoids my name is Kevin I'm from Montreal this is my first Def Con and it's yeah enjoying it a lot my backgrounds primarily in biochemistry but I am the CEO of hyacinth and I do a lot of the fundraising stuff and on the side I also do some like bio hacking and DIY bio sort of stuff so I've been to hope another I guess I've been to a couple times and so somewhat familiar with hacking things but I'm not very good at any any hacking stuff so hopefully today and tomorrow I'll learn something from you guys a little closer denike yes so to get things started I guess the 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 or what the chemistry looks like we had some fantastic talks earlier about that I'm gonna shift the focus away from maybe Canada's plant stuff and talk more about specifically the cannabinoids which are the name for the active ingredients in cannabis so like THC is one cannabinoid CBD is another cannabinoid and there's about 100 others and the basic question to start things off is like you know Wade where they come from and and also like how much do they cost of course you know most intuitive thing is to grow plants and get THC and that's that's pretty good and as far as like you know costs go for growing plants you guys people who have done their own growing would know their own estimates but I think if you had pure THC maybe like ten dollars a gram kind of thing if you really want to like you know get your cost down my name is plants are just one way of getting THC and as we saw earlier you can also synthesize THC in chemistry and that's kind of what you know you would see in the middle image there is like a big chemical plant that's producing all this THC 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 so
it's 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 you know sugar all the way to something called a lava taluk acid then to cannabis rolek acid and eventually to THC or a tetrahydrocannabinol ik acid and CBD and these chemical reactions are driven by enzymes which are the molecular machinery of the cell and and I don't know how what kind of backgrounds people have been like biochemistry and stuff like that but these enzymes are our genes inside cannabis that you can cut and paste and move around if you wanted to and so our goal is to kind of take
these genes from cannabis and like those segments of DNA that are responsible for producing THC 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 and have a really big like industrial scale kind of system for producing pure THC that's a lot more efficient than chemistry and and growing plants what
this looks like from I guess overview standpoint is that you know you're when you're thinking about what a yeast is doing and it sells it takes in sugar and it grows that's that's what I use does then produces co2 and or produces ethanol if you want it to make a beer or something like that and our job as a [Music] 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 lava taluk acid and eventually to to THC so this involves a lot of like 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 you know way of thinking about this you know we add three or four enzymes you know they convert from sugar to to THC in the end and that's you know the easy like you know way to think but the problem but and then if you want to make something like CBD then you remove the THC producing enzyme and you add a CBD producing an enzyme and then you're making CBD and C of THC and this is one of the advantages of you know manipulating genetics it can switch things on switch things off you control this stuff like a program the challenge comes in as things get more complicated when you're talking about like 100 different cannabinoids and and all these other metabolites that get made alongside of it where it's not you know as easy as adding just three or four genes to a yeast and then you get THC oh you're gonna playing around with maybe hundreds of different genes and for us you know we've gone through hundreds of thousands of combinations of different genes to optimize and to improve always on our yields and to try and get two different producing different cannabinoids and yeah so it's kind of you know 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 like 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 like an interest in these things right now 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 and we're making the ones from plants but we're not growing plants and anyways yeah alright so after we've made
cannabinoids and the question is okay where do we go and and this comes to you know talking about why we're doing this whole thing as as we would have seen earlier as well and probably because know like cannabinoids go into your brain they react with your plan with receptors and then you get you know the various effects like you know feeling high or having an appetite or whatever else and all kinds of different things or as Mark Lewis said this morning maybe you know tweaking your entire personality apparently as part of this this system but it's yeah super interesting system to manipulate and there's all these different cannabinoids that are going to affect it and that's ultimately you know what we're working towards
and because Kannamma does 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 even glioblastoma is like the 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 appetite Buster in cancer therapy is another that one is what Marin all that exists on the market right now is prescribed for and there's also another product called Sativex that's cannabis extract that's so a prescription drug so a lot of newer cannabinoid stuff kind of points in that direction so I guess out of these two 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 you know thing that people will try to use cannabinoids for and there's the famous
story of Charlotte's Web and this whole thing where CBD is now like being used for treating epilepsy and there's a really interesting timeline where this stuff kind of came out in 2013 and then 2014 like a pharmaceutical company g2b from sucrose started their first trials of CBD with epilepsy and now it's as of a few months ago on its way to the market and approved by the FDA and yes so when it comes to thinking about like
why we're doing this we're really interested in looking at different ways of producing THC and CBD and not just thinking exclusively about growing plants as like this has to be the be-all end-all solution because it does take a lot of energy and and time to grow plants and if I think in in terms of numbers it's like yeah three months to grow plants 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 this like lighting energy and stuff like that so it's really not that you know environmentally friendly or economical to grow th season that method and then with chemistry you're working with petroleum-based compounds having multiple different reactors and always interesting temperature controls and and reagents has to go into that process and that also becomes quite complicated and can take you know weeks as well to do but with yeast it's more like you know you add sugar you add water you got the yeast you wait a week these grows up then you do an extraction and get your thdf or CBD or whichever one that you're interested in and that's the process that we're you know aiming for and there's a few different advantages to this but as far as you know the impact that this is going to have on the industry 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 like a little bit of a bit of place but I'll bring it back I'll keep going and then I'll bring it back and then you guys can ask questions and everything will be okay
so yeah it's quite hard to grow cannabis plants and I haven't tried going to myself and I mean it maybe it is easy kind of easy to do it in your closet if with the right amount of investment but once you start scaling things into like agricultural level and you're starting to build out you know acres of greenhouses that yet you know entirely contaminated with powdery mildew and then you lose like millions of dollars of crops at the same time instead of like you know 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 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 a good good reason because you're you're lighting this product on fire you're inhaling it and if you're nailing pesticides and that's different from when you're eating pesticides and so there's there's a really you know restrict 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 not sure where things are at as far as pesticide use exactly but I'm glad that in Canada this was discovered it was enforced and that might not necessarily for all the different US states and now with California's legalization coming up there is expected to be some kind of bottleneck in cannabis testing labs where they just aren't and labs to test all the cannabis that's gonna go on the to the market so how are you supposed to know if your cannabis does or does not have these pesticides in it but it's 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 not having you want to add any pesticides or antibiotics or anything like that
the other key advantages is in diversity of products so like was mentioned earlier we I see these things kind of
like Lego blocks where you know there's gonna be a hundred different ways it's gonna be a whole bunch of terpenes and they're all these different like molecular compositions that you could build and put together to create these optimal experiences for when you use cannabinoids or cannabis product and to kind of dismiss the idea of like getting down to that finer grain stuff and discovering what all these things do is like we have to know these things and it's super interesting to know you know which perfect combination will be the best treatment for epilepsy or which perfect combination will be the best treatment for like a Friday night you know at night out or something like that and and this is also part of the reason why you know yeast is so interesting is because you can manipulate the genetics you can clone new things you can build new cannabinoids or very quickly you know scale up new kinds of products using this technology and then as I
mentioned earlier the question of scale is the other one and this may be 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 is if you think about the scale that is needed to treat something like epilepsy like there's 50 million people in the world who have epilepsy and now there's like between CBD and CBD V some new drugs being developed for treating epilepsy and if you if you add that up to like the you know how much the dosage is and what this is gonna take then you're getting into the range of like you know 1,500 tons of pure CBD or CBD v like the pure cannabinoid product and I think you could compare that against like a cannabis growth operation and maybe the
total amount of cannabis in the world right now it's still maybe a hundred or a thousand times away from getting close to that kinds of numbers and if you're willing to bet some money on like you know what's going to be the scalable best way to grow cannabis it's gonna 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 and you can do more like 750 tons per year and so you know this is the reason why East is so interesting because it has this established industrial scalable model of manufacturing and this is my last slide
and then excited to go to questions in Canada I'm from Canada so he can ask me about the Canadian law system and what's going on there cuz I know quite a bit about that but it's actually funny just to share a bit of perspective where Canada has this like you know very well defined objective of like you know cannabis being illegal as a health risk because it exists as a black market and so on so forth and there's access to you that they want to be they want to control and so they're they're motivated in this way to create legalization and to create a framework for a kiss getting access to cannabis legally and so you know instead of us dealing with the DEA like the Drug Enforcement Agency or that the FBI or whoever else that you know manages it where it's a kind of a Narcotics 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 so you're welcome to ask me more questions about that and maybe you can write into your own governments about you know this perspective because I think it's it's kind of one of these ruling arguments forward towards cannabis legalization [Music]
something's on fire all right yes carbon
footprints [Applause] [Music] yeah yeah I guess we'll sit tight for we can we can get up and go outside or something like that what are we supposed to do is it gonna be just give me like a minute longer okay we can talk while she's talking abut wean your arms we'll do it very quickly [Music] I do yes [Music] [Music] oh hey we're back all right hey all right questions then yes and back so like I said earlier the basic concept is to look at the genes in cannabis and take take those and I can speak more specifically I guess the cannabis genome is sequenced it's online somewhere along with the genomes of various other organisms along with the east of course and so you can look at the genomes and pull the segments of DNA out email those to a DNA since this company and they'll make it for you and send it to you in the mail and so you know we've never actually touched any kind of plant material we just used the digital DNA information and then just have it ordered online for us and that's the 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 cast nine stuff that you can use to engineer yeast it really depends on you know what your approaches and what gene you're targeting so it's a lot of hard work and a lot of sweat and tears and blood and everything that goes into engineering least but it'll take more time than it would take to you know grow a plant but to you know if you want to breed a plant that would have high amounts of THC 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 yes no my material um let's see if I go to I'm not unlike your mind alright we won't do a live demo but anyways you can go to ITT DNA calm or look up just DNA synthesis companies and you can write in DNA sequences and they'll 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 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 that's kind of how it how it goes so if you were 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 running from scratch of course and and this is where like what Mark was saying earlier about how you need to have isolated versions of plant cells that can be grown into plants and then you can cultivate new modified strains like all this technology that's involved that's part of what you would need to take synthesize 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 and then not yet one day maybe maybe like in maybe 10 years maybe like 100 years I don't know I don't know I think I saw any in the back first not specifically and that is one of the things that we will be testing like as soon as we are make the stuff and are authorized to do all the testing and whatever else needs happen for that but basically when when we're looking at and we're thinking about this we're talking about the chemical composition and what's gonna work the best and so when if you took THC that's been coming isolated into a hundred percent pure from the plant 100 percent pure from my chemical synthesis and maybe 100 percent pure from biosynthesis and compared to the site by slide you should have the exactly the same results no matter what and then the usually the finer detail 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 a computer platform 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 and doesn't work that well compared to the cannabis in many cases I saw this in yeah over there in the back yeah oh okay about twelve months kind of thing yeah told Eva's and refined you it's not for sale yet and maybe maybe on our website eventually hyacinth bio calm you can go there and try it yeah sorry hyacinth bio calm that's alright website I have business cards and stickers and stuff you guys can come up to the front and grab some - who would divide next MZ you next I think you've got your head you still have your hand up so let's go with you theoretically yes and and practically probably yes as well and and this has been done or poured a bit with the people who are trying to engineer yeast to make opioid stuff like they took it and try to brew a beer with it and then the I think their analysis was look look it doesn't make opioids which is like you know it wouldn't because the conditions are different because it's not very much east in there the so you might be up to bake your bread with it it might not have any - you see in it and that's just like the way it'll go and it might smell like flowers or something like that cuz that's alright thanks in the back all right 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 i think you can get from other sources like kind of cheaply and so or even like take a purified form of CBD that we make and mix that in with a hemp oil and then you have your your full spectrum thing that way is a few different ideas that are you know we've got in mind for when we get to that stage yeah yeah it's a bunch of things in parallel kind of thing so CBD we've done maybe the most work around but also like this kind of science does well when you try to do THC as well at the same time or THC B and so we've got like a whole bunch of tracks that are running through and like high-throughput kind of thing yeah all right I see somebody way in the back so when you're looking at like the East soup 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 DS next target we're not we're not there yet but like you know that's sort of what we're aiming for 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 every product is a bit different and it's in insulins like a protein so you need less of it 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 we're you know then they were getting like pretty 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 or even more than that maybe yeah so that's our kind of our goal yes so solvent extraction basically and there's a bunch of other techniques like we could try supercritical co2 stuff as well and do the same thing as is done with plants and I'm going I don't know from going over time but I guess recs are you up next yeah okay alright Rexel tell me when he's ready to present okay cool so that this will be maybe one more question after this well Rex gets it up and and your question was extraction yeah various methods and there's there's ones that are established pretty well for yeast like doing like column separation or or solvent extraction stuff it depends a bit on the product and depends if we're going for THC or one for CBD and depends on like other things and yeah yeah okay Rex yes all right cool and excited for Rex's talk to so stick around yeah [Applause]