Biotech: A Brave New Cannabis World

The word spread quickly in August 2011 after Medicinal Genomics sequenced the cannabis genome for the very first time and then published the raw data on the Internet. The genome, from a sample of Chemdog, was very complex, consisting of about 400 million base pairs. Medicinal Genomics announced that it was releasing the data to promote a deeper understanding and exploration of the therapeutic potential of cannabis, in the hopes that the medical cannabis industry could someday create strains specifically developed for certain diseases and precise cannabinoid profiles.

Conservative observers panicked, fearing that genetically modified cannabis boasting twice as much THC as the current A-list strains might devastate unsuspecting consumers and drive people psychotic. Others voiced concerns that the seed business would face a hostile takeover by corporations like Monsanto, who would seize huge market shares with their genetically engineered and patented cannabis strains.

These fairly unrealistic projections won’t be coming true anytime soon, if at all. For starters, the cannabis genome that Medicinal Genomics published is an “unedited” raw version with millions of fragments—one that has created more questions than answers, essentially leaving us with a giant jigsaw puzzle to assemble.

As a result, genetically engineering the cannabis plant doesn’t have any viability—yet. A multitude of questions still remain about what functions each gene carries out, when and how each gene is activated, and how they are regulated within the plant.

Some crucial genes and their functions have been identified, but by other scientists. Only two months after Medicinal Genomics’ data dump, a team of researchers at the University of Toronto, led by botany professor Jon Page, became the second group to have sequenced and published a cannabis genome, or in this case two: one for the THC-rich strain Purple Kush, the other for an industrial-hemp strain called Finola that has almost no THC. With the genomes for both types of cannabis on hand, the scientists managed to determine certain things by comparison—for example, that a simple genetic switch is responsible for the production of tetrahydrocannabinolic acid (THCA), the precursor of THC. “The THCA synthase gene is turned on in marijuana, but switched off in hemp,” Page reported.

The professor and his team are now hard at work refining and improving their results. Page founded his own company, Anandia Laboratories, with the aim of putting these findings into practice by breeding cannabis with improved therapeutic properties. Interestingly, Page doesn’t foresee a bright future for genetically modified pot. He points out that the attempts at creating transgenic cannabis thus far haven’t had much success. And even if researchers obtain better results in the future, he still harbors doubts about whether it’s a desirable direction to move in. “I’m not convinced that it is,” he says, “given the power of selective breeding to create plants with optimized traits.”

Medicinal Genomics and Page’s team aren’t the only two groups studying the cannabis genome. Another band of scientists joined the party in February 2014 and is determined to surpass all the others. At the University of Colorado, Boulder, the highly ambitious Cannabis Genomic Research Initiative launched with the goal of pursuing the deepest-ever exploration of the ganja genome: not only those for Cannabis sativa and indica, but also for hybrids of these two species (provided they’re actual species at all; that age-old question of whether cannabis is one species or three—sativa, indica and ruderalis—could one day be settled by this work).

Nolan Kane, the project leader, wants to provide precise genomic blueprints for researchers, hemp farmers and cannabis growers in order to accelerate and optimize the process of selective breeding. His Cannabis Genomic Research Initiative could one day lead to more powerful and finely tuned medicines. Kane says that the work of Medicinal Genomics laid a “strong foundation” for his project, but he likened the results to a massive book with its pages out of sequence—and Kane aspires to put them all in order. “They got it down to 60,000 pieces,” he explained. “We want to get it down to the 10 pairs of chromosomes.”

Kane stressed that the Colorado-based initiative isn’t interested in conducting or promoting genetic modification; it merely aims to enhance traditional breeding approaches. “The ability to assay for specific genes within the crop is equivalent to superpowers for a breeder,” he notes. So Kane and Page seem to be very much in agreement about the desirability and advantages (or lack thereof) of genetically modified cannabis.

Outside the world of academia, right within the recreational cannabis industry, yet another person is working hard to systematically sequence the cannabis genome. He’s doing so because his employer—a major Dutch seed company—has a huge interest in using such genomic data for its business. Breeders around the world, whether in the US, Canada, Spain, the Netherlands or elsewhere, could use such a high-tech tool to accelerate and perfect their work. All of them strive to breed the most potent, high-yielding, aromatic, stable and homogeneous strains possible, and all of them would like to get their hands on such a powerful tool, which would set them apart from their competitors.

However, a seed company also needs someone who knows how to use such a tool—and in almost every case, that certainly won’t be the seed bank’s owner or breeder, because these guys are usually self-taught and don’t have the years of education and training necessary to work with genomic data. That type of endeavor requires the skills of a geneticist or biotechnologist—and that’s precisely why a well-known Dutch seed company decided to hire one a while ago, securing the services of scientist Marko B., a.k.a. Blitzo.

Blitzo has worked on a self-employed basis in the field of biotechnology for years, while his open-minded attitude toward cannabis completed the requirement profile. Blitzo set up a molecular-biology laboratory for his employer in the hopes of establishing a revolutionary new base for cannabis breeding. Next, using one of the “unedited” cannabis genomes recently made available, he plans to focus on the generation of actually applicable genomic data, while at the same time generating still more data on another platform and with another methodology that will make it possible to also decipher the epigenome.

This last step is critically important. As Blitzo explains: “It’s a kind of missing link, as it hasn’t been explored yet—or at least has not yet been described. The epigenome is the memory or control unit for genes, determining which ones get activated and which are switched off.” Only the breeder who knows and understands the epigenome will be in a position to precisely target and influence a breeding process based on genomic data.

After Blitzo completes the genome sequencing (he also contends that the cannabis genome has 800 million base pairs, not 400 million), he’ll be able to develop a method to genetically trace any given cannabis plant back to its point of origin, through the determination of its respective parent strains. “I think that it will also be possible to one day conduct a sort of computer-based pair-mating,” he predicts, “genetically selecting and optimizing hybrids on the PC so that those big time, area and cost dimensions of classic phenotype selection would become a thing of the past. It would be like individual paint-mixing in the home-improvement store: With a seed company of the future, one could order a plant with certain desired properties and then receive accordingly mixed and compiled genetics from the database of already existing strains, accurately tailored to one’s needs.”

Blitzo acknowledges that it will take decades before his vision becomes a reality—and the seed company that hired him wants him to attain a couple of crucial short-term and midterm goals first. For starters, the cannabis industry still needs a 100-percent-reliable way to make female plants produce male flowers for the production of feminized seeds. Some strains suffer damaging stress and even mutations when exposed to the potent chemicals used to make female plants go hermaphroditic.

Blitzo is already looking at a surprising approach to solving that problem: With the use of special bioengineered microorganisms, he might be able to make any female cannabis plant grow male flowers with pollen. Such a method would be much more gentle and benign than using toxic and mutagenic agents like silver thiosulfate or gibberellic acid. Not surprisingly, Blitzo isn’t ready to reveal yet what microorganisms he has in mind or just how they’d do their job.

On another front, Blitzo is seeking a way to precisely target and activate (or deactivate) the flowering impulse of autoflowering plants. Epigenomic data will play a crucial role in this, since he needs to identify exactly which genes control the release of flowering hormones, and exactly what mechanism causes them to get activated when they do. Although indoor growers have long been familiar with the 12/12-hour light cycle that induces the flowering stage, scientists still don’t know the precise biochemical mechanisms behind this process.

Another important task already underway is the introduction of sterile-tissue culture to safely maintain a seed company’s precious genetics. Blitzo will also have to tackle the challenge of producing regular 50/50 batches of male and female seeds from strains that are currently available only as female cuttings, such as the legendary G-13 strain. In these cases, a breeder is confronted with a task contrary to the feminization process. As Blitzo explains: “For the production of regular seeds, a female and a male plant are required—that is, the sex-chromosome pairs XX and XY. But since, in case of G-13, the XY plant is missing, so far only feminized seeds could be produced with her. With some biotechnological tricks, though, one can generate a real male plant out of a female plant, afterwards producing regular seeds—XX and XY—by means of the then-available male XY pollen.”

Not content to rest there, Blitzo is also conceiving even more projects to launch in the future—for example, biological additives that could regulate the vegetative and flowering stages of a cannabis plant. Say that breeder has a bunch of strains with different flowering times growing in his garden, but he wants them to finish at the same time—using such additives, he could prolong or shorten the flowering stage of certain plants to synchronize the whole batch.

Prolonging the flowering stage of a plant beyond its natural duration would yield some very interesting biochemical possibilities, Blitzo argues. “Think of a plant with a regular THC content of 20 percent that normally takes 10 weeks of flowering to ripen. If one could extend the flowering stage to 15 weeks with the help of such an additive, the plant would produce more and more THC and, in the end, potentially achieve a THC content of 30 percent.”

Another possibility would be developing boosters and biological fertilizers with an entirely new principle of operation and an innovative approach—for example, they might contain rhizobia, soil bacteria that can bind nitrogen from the air and deliver it directly to the roots. Other symbiotic systems could also be integrated into cannabis cultivation, reducing fertilizer requirements and saving money while protecting the environment.

Over the long term, Blitzo has even set his sights on the medical sector: “At some point, I also want to research the human endocannabinoid system—CB1 and CB2 receptors, anandamide and 2-arachidonoylglycerol, etc.—and the impact that different endocannabinoids and their naturally occurring mimetics are having on the regulation of certain physical and psychological processes.” Mimetics are chemical compounds that bind to the same receptor as the actual agent. Other plants from the genera Echinacea, Acmella and Aster also produce some kind of cannabinoid-like substance and are therefore highly interesting as research subjects, as do other plant families and even other kinds of organisms. In that broad context, scientists will explore ways to transgenically produce a number of different compounds. This means that after a transgenic treatment, fungi, algae or bacteria might be able to produce specific cannabinoids much more cheaply than cannabis.

As one can readily imagine, all of these projects would keep a small army of scientists busy for many years. Blitzo is a kind of walking think-tank, a person from whom ideas gush forth like a fountain—though, of course, he and the company he works for pursue a more methodical, step-by-step process in bringing these ideas to fruition. At some point in the future, after Blitzo has achieved his short- and midterm goals, the company would need to develop more capacity for research. But if even a small part of these projects are realized, they would represent a quantum leap for professional breeding and cannabis research in general.

At that stage, it would be much more difficult for corporate giants like Monsanto to drive their competitors out of the market and take over, since the most important innovations would already have come from the cannabis industry itself. So will a brave new cannabis world emerge from a biotech laboratory in the Netherlands? As with so much else that’s interesting in life, we’ll just have to wait and see…

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