{"id":29139,"date":"2018-09-07T05:00:23","date_gmt":"2018-09-07T13:00:23","guid":{"rendered":"http:\/\/cannabiscultivatornews.com\/home\/index.php\/2018\/09\/07\/editing-the-cannabis-genome-with-ebbu\/"},"modified":"2018-09-08T00:47:33","modified_gmt":"2018-09-08T08:47:33","slug":"editing-the-cannabis-genome-with-ebbu","status":"publish","type":"post","link":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/2018\/09\/07\/editing-the-cannabis-genome-with-ebbu\/","title":{"rendered":"Editing the Cannabis Genome with Ebbu"},"content":{"rendered":"<p><img loading=\"lazy\" src=\"http:\/\/cannabiscultivatornews.com\/home\/wp-content\/uploads\/2018\/09\/tissuecultures-3.jpg\" width=\"1600\" height=\"960\"> <\/p>\n<p>Inside the drug discovery lab at Ebbu, I peer into a cup that\u2019s about the size of a Big Gulp at 7-Eleven to look closer at the slimy substance within. This cup isn\u2019t holding an unreasonable amount of soda, it\u2019s housing the makings of thousands of genetically identical hemp plants.<\/p>\n<p>\u201cEach of these little green dots is potentially a plant,\u201d says Robert Roscow, Ebbu\u2019s director of genetic research, pointing to the tissue culture in the cup. He explains that <a href=\"https:\/\/www.ebbu.com\/\" target=\"_blank\" rel=\"noopener\">Ebbu<\/a> has plans to grow hemp on an unprecedented scale by taking internodes \u2014 small pieces of living hemp stems \u2014 and growing them in hormones.<\/p>\n<p>\u201cNo one else is doing what you\u2019re seeing,\u201d he says, as I look into the cup, which is just one among two shelves of similar containers.The concept of tissue culturing, a method of biological research that takes stem cells from a plant or animal and places them in an artificial environment, is a method of clonal propagation used in other agricultural industries, but has yet to be commercially applied to hemp or cannabis. That is, until Ebbu started their project in 2013.<\/p>\n<div id=\"attachment_36864\" style=\"width: 1610px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" class=\"wp-image-36864 size-full\" src=\"http:\/\/cannabiscultivatornews.com\/home\/wp-content\/uploads\/2018\/09\/tissuecultures-2.jpg\" alt=\"Tissue Cultures Ebbu Cannabis Now\" width=\"1600\" height=\"960\" \/><\/p>\n<p class=\"wp-caption-text\">Ebbu Director of Genetic Research Robert Roscow points out hemp tissue cultures within the genetics lab.<\/p>\n<\/div>\n<p>\u201cAll of these little balls has the potential to become a plant with the correct hormone treatment,\u201d says Roscow, \u201cso there could be thousands of plants actually in this vessel and they\u2019re all <a href=\"https:\/\/cannabisnow.com\/?s=clones\">clonable<\/a>.\u201d<\/p>\n<p>Ebbu\u2019s General Manager Damon Michaels explains the potential destiny of the minuscule substances sitting on the shelves.<\/p>\n<p>\u201cWe could propagate thousands, if not millions of different clones under our roof and then into a greenhouse,\u201d Michaels says, mentioning that Ebbu plans to use the greenhouse space of <a href=\"https:\/\/www.hardyboyplant.com\/\">Hardy Boy Plants<\/a>, a partner company also based in <a href=\"https:\/\/cannabisnow.com\/?s=colorado\">Colorado<\/a>. \u201cThen, from there, we could take those clones and bring them out to large fields and then grow out thousands \u2014 if not millions \u2014 of plants of that same clone in acreage farms outdoors.\u201d<\/p>\n<p>This tissue culture project for cloning is unprecedented and ambitious, but perhaps most incredibly, it is just one of the experiments taking place at Ebbu that has the potential to change many aspects of the cannabis plant as we know it.<\/p>\n<h4>Cannabinoids as a Commodity<\/h4>\n<p>In the Ebbu offices upstairs, the company\u2019s CEO and founder Jon Cooper outlines the goals of his company, which is heavily invested in a state of research and development to secure data and intellectual property.<\/p>\n<p>\u201cOur entire approach is asking, \u2018What does it take to create mainstream cannabis?\u2019\u201d he says. \u201cEven for myself, one of the challenges that I had getting into this industry was that I didn\u2019t trust cannabis, which really came from the fact that I didn\u2019t know what I was going to get, I didn\u2019t know what my reaction was going to be. That caused a person like myself to really have major trust issues with the plant.\u201d<\/p>\n<p>Cooper explains that, from a pharmacological perspective, the multitude of chemicals inside the resinous <a href=\"https:\/\/cannabisnow.com\/breaking-bud-zoom-trichomes\/\">trichome<\/a> heads found on the cannabis flower are known as \u201cdirty compounds\u201d because instead of targeting one cell receptor, they act in congruence to target many at once. \u00a0This means the exact effects of a given cannabis flower are extremely hard to predict or provide on a consistent basis.<\/p>\n<p>\u201cReally what it represents is chemical chaos,\u201d he says of using the properties found in trichomes for either medicinal or recreational products. \u201cThis is a really hard combination and equation across 100-plus cannabinoids and 200-plus <a href=\"https:\/\/cannabisnow.com\/?s=terpenes\">terpenes<\/a>, against 300-plus receptor sites in the body.\u201d<\/p>\n<p>To better understand how cannabis works, Ebbu is examining and restructuring the plant on a cellular level.<\/p>\n<p>\u201cWhat I care about from the input is how much am I paying for each one of those compounds that just happen to be in that plant and I really don\u2019t care if it\u2019s Blue Dream, Green Crack or Tangerine Haze or whatever it is,\u201d Cooper says. \u201cI care about how much I\u2019m paying for each one of those compounds.\u201d<\/p>\n<p>Because of this directive, Ebbu is in the business of isolating cannabinoids and then testing them on DNA sourced from human cell receptors to understand how they work. The Evergreen, Colorado-based Ebbu lab is also heavily involved with genetic research in order to get the plant to produce more of the compounds they are looking for.<\/p>\n<p>\u201cWe take the plant, we tear it apart and then the question is if we can put it back together,\u201d Cooper says. \u201cMother Nature is interesting from a formulation perspective in that it gives us some clues, but the reality is that everything we put together really is different, because we can get outside of the constraints of what Mother Nature has given us and create something that\u2019s more efficacious.\u201d<\/p>\n<div id=\"attachment_36866\" style=\"width: 1610px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" class=\"wp-image-36866 size-full\" src=\"http:\/\/cannabiscultivatornews.com\/home\/wp-content\/uploads\/2018\/09\/unprocessedcbd-2.jpg\" alt=\"\" width=\"1600\" height=\"960\" \/><\/p>\n<p class=\"wp-caption-text\">Cannabinoids change colors as they go through the refinement process. This CBD sample will be further refined to create products that include CBD isolate.<\/p>\n<\/div>\n<p>And in doing so, Cooper explains, Ebbu is focusing on treating cannabinoids themselves as a commodity.<\/p>\n<p>\u201cAt the end of the day, from our perspective, the plant is a wildly efficient way of producing complex compounds,\u201d he says. \u201cFrom a processing perspective, it\u2019s a lot easier if that plant is only producing one compound and so [we want to] kill that concept of these crazy strain names. What if we could just make a <a href=\"https:\/\/cannabisnow.com\/cbg\/\">CBG<\/a>-only plant?\u201d<\/p>\n<p>That\u2019s not a hypothetical question. Cooper says he expects this CBG-only strain to be complete in the very near future.<\/p>\n<p>\u201cMy vision of the world, for all the inputs, is that this should all just be a commodity,\u201d he says, noting his belief that the majority of the future cannabis market will be based on isolated cannabinoids. \u201cYou either need to push towards commodity or you need to push towards craft\u2026 You\u2019ll see flower become smaller and smaller and smaller and, I think most people agree, it will probably drop to about 20 percent of the marketplace.\u201d<\/p>\n<h4>Genetic Editing vs. GMO<\/h4>\n<p>Later, back in the lab, I\u2019m looking at a plant with speckles of fluorescent color visible from an ultraviolet light on the underside of its leaves. This particular plant, I\u2019m assured by all the Ebbu employees, is just a test subject. It includes the DNA from a jellyfish. Ebbu is using traditional genetic techniques that utilize the application of fluorescents to see how the plant has been affected. This is a genetically modified cannabis plant, but Ebbu says it is only using the plant as an internal control. The lab is not focused on genetic modification \u2014 like this cannabis plant expressing jellyfish proteins \u2014 but rather, genetic editing.<\/p>\n<p>\u201cThis is not GMO, this is genetic editing,\u201d Michaels says. \u201cWe\u2019re not taking any foreign DNA or RNA and adding it to the plant.\u201d<\/p>\n<p>Roscow clarifies that Ebbu just uses DNA sequences native to the cannabis plant. \u201cUltimately we\u2019re just making more of the protein that the plant is natively making, cutting and editing the genome,\u201d he adds.<\/p>\n<p>Within the lab, Roscow points out some of the DNA chains Ebbu is examining in order to successfully produce cannabinoid-specific strains.<\/p>\n<p>\u201cWe know the genes that are causing the assembly of CBG and we know the genes that are taking CBG and then shuttling them into THC or THC synthase or CBG synthase,\u201d he says. \u201cWe can very much go and say, \u2018OK, if we want more CBG, the solution there is to reduce the plant\u2019s ability to make the terminal products [of THC or CBG synthase].\u201d<\/p>\n<p>He explains his work to edit the plant\u2019s DNA is similar to closing a road or creating a construction barricade.<\/p>\n<p>\u201cAll the traffic goes down the roads that are open,\u201d he says. \u201cIt\u2019s the same exact thing, just with molecules and the genetic steps that are shuttling them around.\u201d<\/p>\n<p>In order to edit the cannabis genome, Ebbu is utilizing CRISPR-Cas9 technology, a groundbreaking gene editing technology that was first commercialized in 2012. The science behind CRISPR is complicated. In short, CRISPR uses Cas9, an enzyme that cuts through DNA,\u00a0in tandem with RNA, a molecule in living cell nuclei that can read DNA. Scientists using CRISPR start by programming the RNA to match the DNA code of the genes they want to alter. Then, the RNA and the Cas9 are injected into the cell.<\/p>\n<p>\u201cOnce the RNA and the Cas9 are inside the cell, the two molecules sort of stick together,\u201d <a href=\"http:\/\/www.latimes.com\/science\/sciencenow\/la-sci-sn-crispr-cas-9-20151218-story.html\" target=\"_blank\" rel=\"noopener\">the Los Angeles Times wrote<\/a>, in a 2015 article describing the process. \u201cThe RNA guides the Cas9 to a particular part of a gene, and the Cas9 acts like a pair of scissors, breaking both strands of DNA at that specific spot.\u201d<\/p>\n<p>Roscow clarifies the method as we look at computer imaging that displays long strands of DNA sequencing.<\/p>\n<p>\u201cWe have a mechanism that allows us to go in and cause a small cut in the genome and so it basically acts as a control, find, delete,\u201d he says. Using this technology, Ebbu is able to take the DNA experimentation process from a computer model to a live plant in about two weeks.<\/p>\n<div id=\"attachment_36870\" style=\"width: 1610px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" class=\"wp-image-36870 size-full\" src=\"http:\/\/cannabiscultivatornews.com\/home\/wp-content\/uploads\/2018\/09\/hempebbu-1.jpg\" alt=\"Hemp Ebbu Cannabis Now\" width=\"1600\" height=\"960\" \/><\/p>\n<p class=\"wp-caption-text\">Hemp grows in the Ebbu genetics lab.<\/p>\n<\/div>\n<p>\u201cOur ability to do this within cannabis is unique in the space,\u201d Roscoe says. \u201cIt\u2019s a technique that\u2019s commonly used in cell culture for medical research and cancer research.\u201d<\/p>\n<p>It\u2019s also used in crop science on plants like coffee for companies like Nestl\u00e9, which Roscow tells me produced a report that said they could create about 4 million coffee clones in four months.<\/p>\n<p>And, I ask, is there any chance things could go terribly wrong, along the lines of the plant-eating scenarios depicted in \u201cLittle Shop of Horrors?\u201d Absolutely not, he says.<\/p>\n<p>\u201cBeing able to do something like that, where it\u2019s not what you designed, it\u2019s such a low likelihood. Instead of going in purposely after one thing, you\u2019d have to \u2014 by accident \u2014 be going after the perfectly wrong thing to be going after. The likelihood is that it just wouldn\u2019t work. It\u2019s essentially a thousand times more likely to just not work than to have any sort of negative or off-target effect.\u201d<\/p>\n<h4>The Pharmacological Approach<\/h4>\n<p>After a touring Ebbu\u2019s extraction facilities containing hyper-advanced cannabinoid distillation methods such as supercritical fluid chromatography, I find myself back in another lab, examining a machine that helps Ebbu come up with its product formulations. One of Ebbu\u2019s products, known as Genesis, comes in an oil form and contains a formulation of three cannabinoids and terpenes. I can figure out that two of the cannabinoids are THC and CBD, but the third is kept secret as part of Ebbu\u2019s proprietary blend. Michaels says it is designed to produce an energetic, clear headed \u201cuplifting\u201d feeling.<\/p>\n<p>\u201cIt just makes you feel alive,\u201d he says.<\/p>\n<div id=\"attachment_36868\" style=\"width: 1610px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" class=\"wp-image-36868 size-full\" src=\"http:\/\/cannabiscultivatornews.com\/home\/wp-content\/uploads\/2018\/09\/ebburd-1.jpg\" alt=\"Ebbu lab Cannabis Now\" width=\"1600\" height=\"960\" \/><\/p>\n<p class=\"wp-caption-text\">Ebbu\u2019s Director of Clinical Pharmacology Jon Martin looks for patterns within human cells to determine how they are activated with different combinations of cannabinoids and terpenes.<\/p>\n<\/div>\n<p>This product has also been made into \u201caqua drops\u201d and can be dissolved into water. It\u2019s similar to what Ebbu is using in its <a href=\"https:\/\/cannabisnow.com\/blue-moon-creator-prepares-to-launch-first-ever-thc-beer\/\">non-alcoholic beer through CERIA beverages<\/a> with the former brewer and creator of Blue Moon Brewing Company, a company which is now a subsidiary of Molson Coors.<\/p>\n<p>To create its product formulas, Ebbu purchases tissue cultures filled with human cell receptors and then tests them against precise blends of cannabinoids and terpenes through a \u201cliquid handling robot.\u201d I watch in the lab as the robot delivers the compound combinations onto plates of cells.<\/p>\n<p>The formulations created using Ebbu\u2019s advanced extraction methods, which utilize liquid chromatography \u2013 a method for separating a mixture of chemical substances into its individual components \u2014 to isolate individual cannabinoids like <a href=\"https:\/\/cannabisnow.com\/what-is-thc\/\">THC<\/a> and CBG.<\/p>\n<p>\u201cWith chromatography and formulation, you can break barriers,\u201d Ebbu\u2019s Director of Clinical Pharmacology Jon Martin says.<\/p>\n<p>This method, Martin explains, allows the scientists at Ebbu to see the cell receptors responding to different cannabinoids, such as THC and CBD, and better understand how they work. Observational studies in the lab have demonstrated that different formulations of these compounds can change effects and moods. He says one big question Ebbu is seeking to answer is, \u201cCan cannabis become something new?\u201d<\/p>\n<p>That\u2019s when Roscow jumps in.<\/p>\n<p>\u201cThe answer is yes,\u201d he says.<\/p>\n<div id=\"attachment_36873\" style=\"width: 1610px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" class=\"wp-image-36873 size-full\" src=\"http:\/\/cannabiscultivatornews.com\/home\/wp-content\/uploads\/2018\/09\/ebbulab.jpg\" alt=\"Ebbu lab Cannabis Now\" width=\"1600\" height=\"960\" \/><\/p>\n<p class=\"wp-caption-text\">A liquid handling robot applies precise amounts of cannabinoids and terpenes to human cell receptors in order to come up with optimal product blends.<\/p>\n<\/div>\n<h4>Annual vs. Perennial<\/h4>\n<p>In a market dominated by product formulations, Cooper explains Ebbu is all about making the base materials, or cannabinoids, more effective.<\/p>\n<p>One strategy for more efficient cannabinoid delivery is growing cannabinoid-specific strains, such as the CBG strain Ebbu will soon finish \u2014 which Cooper points out is legally considered hemp because it contains less than .3 percent THC. The other strategy is finding ways to produce more trichomes, which hold the cannabinoids, on different parts of the plant, rather than only on the flowers.<\/p>\n<p>\u201cWhat if we could smother the fan leaves in trichome crystals and what if we could do that outside of the flowering cycle using the same basic simple techniques that we\u2019re doing?\u201d Cooper asks. \u201cWell, then you\u2019d be able to increase the output somewhere between two times and 10 times.\u201d<\/p>\n<p>Downstairs in the genetics lab, I get a further explanation.<\/p>\n<p>\u201cWe\u2019ve had fan leaves on test plants that are 10 percent cannabinoid content by dry weight, the standard for trim essentially,\u201d Roscow says. \u201cSo you could turn the whole plant in a vegetative state into trim.\u201d<\/p>\n<p>If you can get cannabinoids without needing to send the plant into a flowering state, then the base nature of the plant\u2019s growth cycle \u2014 a process in which flowers are prized for their resinous trichomes \u2014 \u00a0is fundamentally altered.<\/p>\n<p>\u201cTheoretically, if you prove it works out successfully, then we just changed the plant from an annual to a perennial, which changes everything about cannabis as we know it,\u201d Michaels says. \u201cThe cost that is now going into flower production is now cut out overnight. You just keep things in a vegetative state, you just shuck leaves, they regenerate and keep growing back and back. The root cycle will probably go through three or four cycles of that shucking process and then we replant the plant from the clone process again from the mother clipping.\u201d<\/p>\n<p>And all of this could have happened naturally, it just would have taken time.<\/p>\n<p>\u201cAll of these are normal processes \u2014 there are actually mutant strains that make a lot more trichomes,\u201d Roscow says. \u201cYou can end up getting to these same outcomes through natural breeding, but the path to get there would take decades, if not hundreds of years, where you would need to be genotyping every single plant you\u2019re dealing with times millions of each generation. So we\u2019re basically creating the very, very rare things that you could collect with natural breeding over a very long period of time.\u201d<\/p>\n<div id=\"attachment_36875\" style=\"width: 1610px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" class=\"wp-image-36875 size-full\" src=\"http:\/\/cannabiscultivatornews.com\/home\/wp-content\/uploads\/2018\/09\/hemptissueculture.jpg\" alt=\"Hemp Tissue Culture Cannabis Now\" width=\"1600\" height=\"960\" \/><\/p>\n<p class=\"wp-caption-text\">A hemp tissue culture rests in hormones at the Ebbu genetics lab.<\/p>\n<\/div>\n<p>All the plants Ebbu is experimenting with in-house are considered hemp, but the lab also partners with marijuana companies in Colorado to look into the potential of dropping the price of the THC compound.<\/p>\n<p>\u201cI think there is a tremendous amount of opportunity on a global scale,\u201d Cooper says of the future, while returning to the idea of consistent cannabis experiences.<\/p>\n<p>Following my visit to Ebbu I sample the Genesis drops over the course of a few days and find the blend of 10 mg THC doses, which come on fast and strong after dissolving them in water, does deliver a pretty reliable experience. The high, once I recognize it through regular use of the product, is pleasant and places me in a positive headspace. Songs sound better, nature seems just that much more vibrant and alive. This brings me back to further unwrapping a hypothetical question Cooper asked himself at the beginning of my day-long tour.<\/p>\n<p>\u201cHow do I make a Coors Light of cannabis? How do I make a consistent product that I would be willing to consume?\u201d<\/p>\n<p><strong>TELL US<\/strong>, are you searching for a more consistent cannabis experience?<\/p>\n<p><em>Originally published in Issue 32 of Cannabis Now.\u00a0<\/em><a href=\"https:\/\/cannabisnow.com\/print-digital-magazine\"><strong><u>LEARN MORE<\/u><\/strong><\/a><\/p>\n<p>The post <a rel=\"nofollow\" href=\"https:\/\/cannabisnow.com\/editing-the-cannabis-genome-with-ebbu\/\">Editing the Cannabis Genome with Ebbu<\/a> appeared first on <a rel=\"nofollow\" href=\"https:\/\/cannabisnow.com\">Cannabis Now<\/a>.<\/p>\n<p>&#013;<br \/>\n&#013;<br \/>\nRead More: <a href=\"https:\/\/cannabisnow.com\/editing-the-cannabis-genome-with-ebbu\/\" target=\"_blank\">Editing the Cannabis Genome with Ebbu<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Inside the drug discovery lab at Ebbu, I peer into a cup that\u2019s about the size of a Big Gulp at 7-Eleven to look closer at the slimy substance within. This cup isn\u2019t holding an unreasonable amount of soda, it\u2019s housing the makings of thousands of genetically identical hemp plants.<span class=\"more-link\"><a href=\"https:\/\/cannabiscultivatornews.com\/home\/index.php\/2018\/09\/07\/editing-the-cannabis-genome-with-ebbu\/\">Continue Reading<\/a><\/span><\/p>\n","protected":false},"author":46,"featured_media":29140,"comment_status":"false","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[50,3944,21,5,5741,1380,5693,306,85,5279],"tags":[],"_links":{"self":[{"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/posts\/29139"}],"collection":[{"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/users\/46"}],"replies":[{"embeddable":true,"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/comments?post=29139"}],"version-history":[{"count":1,"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/posts\/29139\/revisions"}],"predecessor-version":[{"id":29141,"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/posts\/29139\/revisions\/29141"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/media\/29140"}],"wp:attachment":[{"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/media?parent=29139"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/categories?post=29139"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cannabiscultivatornews.com\/home\/index.php\/wp-json\/wp\/v2\/tags?post=29139"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}