The Man Mapping The Marijuana Genome Is Changing The Weed Game

[Norby]

http://www.newsweek.com/2016/03/25/marijuana-scientist-mapping-cannabis-genome-changing-weed-game-436526.html

 

 

Because he’s a scientist, not a back-slapping venture capitalist, Mowgli Holmes loathes using the term networking to describe even the portion of his job that entails shaking hands in the cannabis industry. But it was networking that brought the chief scientific officer of Phylos Bioscience in Portland, Oregon, to Las Vegas in November 2014 to attend the Marijuana Business Conference and Expo—and to smoke a massive joint with one of the cannabis movement’s legends, Ohio lawyer Don Wirtshafter.

Holmes had it on good information that Wirtshafter was sitting on a collection of hundreds of very old apothecary bottles filled with antique cannabis tinctures—relics from before marijuana prohibition came along in 1937, courtesy of the weed-criminalizing Marihuana Tax Act. Holmes, a 43-year-old geneticist with a doctorate in microbiology and immunology from Columbia University, desperately wanted those bottles—at least what viable strands of DNA might lie inside of them—for a project that has become his life’s work: an ambitious effort to sequence the DNA of every different kind of cannabis in the world.

It’s a quest that could change almost everything we know about marijuana. At this point, most cannabis is produced in the dark, then sold to recreational consumers and medical patients with catchy labels that are nearly always misleading. When Holmes completes his mission, he’ll be able to take any sample of pot DNA and compare it with the most robust database of cannabis strains ever assembled, bringing unprecedented clarity to the marijuana market, from the grow to the dispensary.

 

First, though, Holmes needed to do a little more networking. And in the cannabis industry, that can sometimes mean getting very high.

Wirtshafter wanted to know the scientist wasn’t a Monsanto in sheep’s clothing. When the two met in the lobby of the Rio Casino, Wirtshafter had already heard of Holmes and his project. Still, the best way to prove yourself in the marijuana world is age-old and simple—you burn one. So on the last day of the conference, Holmes found himself and his business partner, Nishan Karassik, in Wirtshafter’s hotel room, burnishing their street cred with childhood tales from the hippie mecca that is the Oregon Country Fair and puffing on an enormous joint. Seven weeks later, Holmes packed his lab coat and tweezers, then caught a flight to Columbus, Ohio.

Political Extermination

Holmes grew up in Eugene, a small city in Oregon’s Willamette Valley, home to conservative types descended from logging families and ultra-liberals who drape “Free Tibet” rainbow flags on their porches and wear tie-dyed T-shirts to the Saturday market. Holmes went to Vassar College, majored in philosophy and then moved back to Oregon to play the drums in several rock bands in Portland. After five years of that, he headed to New York once more to study microbiology at Columbia University.

In graduate school, his focus was on viruses, specifically HIV research. But when he returned again to Oregon, which in 2013 was a year away from becoming the nation’s fourth state to legalize marijuana for recreational use, he found a new career path staring straight at him: cannabis genomics. “There’s a whole new industry exploding all around it,” he says. Plus, “in every other academic field, you have to find the tiniest little corner of the world to study. It’s almost impossible to find something nobody else has done, and immediately someone is competing with you. Here, we have an entire organism that there’s basically no body of knowledge on…. This doesn’t happen in science, where you have a plant like this that’s been cordoned off from research.”

 

It was a risk to link his career to the study of marijuana, even with weed legal in Colorado and Washington. Would he still be taken seriously as a scientist, or would he be forever pigeonholed in pot? Plus, there were major roadblocks: Because cannabis is illegal at the federal level, the only way to legally research it is to use cannabis grown by the National Institute on Drug Abuse in Mississippi. That pot is “notoriously crappy,” Holmes says, and useless to his project. Researchers are also required to get approval from the U.S. Drug Enforcement Administration and the Food and Drug Administration. Federally funded universities are reticent to allow laboratories they host to have anything to do with cannabis.

Holmes’s lab and its 10 full-time employees are housed by Oregon Health and Science University, which does rely on federal funding. But he and Karassik, who have been friends since they were 4 years old, have found a clever way to avoid legal trouble: They don’t handle marijuana itself, just its DNA. As for his reputation, Holmes says, “people don’t even giggle anymore,” he says. “They just go, ‘Tell me about the financials.’”

The samples come from all over the world, via often fascinating treasure hunts conducted largely by word-of-mouth research. There are two or three other labs working on cannabis genome projects, but none have collected nearly as many specimens as Phylos, and most of their samples come from marijuana dispensaries, not from original landraces, Holmes says. He has collected nearly 2,000 specimens so far and entered 1,500 of them into a software program that organizes the DNA into clusters, outputting a visual representation that looks like a constellation of stars. Each dot represents a strain, and the distances and lines between the dots show how they’re related to one another.

A woman samples the scent and stickiness of various strains at a marijuana dispensary. With a robust cannabis genome database, buyers would be able to fine-tune their relationship with different strains and have a better idea of what they're using. Lynn Johnson/National Geographic Creative

The rarest and most valuable samples are old and original—landraces compiled from herbariums, museums and collectors in countries like Colombia, Thailand, Mexico, Afghanistan, India, Uruguay, Namibia and South Africa. After months of coaxing, Holmes convinced legendary breeders David Watson and Robert Clarke to let him take samples from their collection in Amsterdam. Now he is trying to acquire a 2,700-year-old strain from northern China.

Holmes arrived at Wirtshafter’s white Victorian in rural Athens County, Ohio, on a sunny, ice-cold January day, wearing a lab coat and carrying a box filled with tweezers, a scalpel, a digital scale, sample tubes and blue rubber gloves. He had a flight to catch, which left him only a few hours to collect all the samples. “You’ll never have enough time,” Wirtshafter told him.

Wirtshafter acquired his collection from the wife of a former federal employee. These jars were supposed to be destroyed after prohibition, but the rogue government worker decided to keep a huge collection of the tinctures. He made his wife promise not to sell them until 10 years after his death. Whatever the motive for that decision, the man’s collection was extremely valuable. Back in the 1880s, breeders recognized the distinct medicinal value of cannabis, but they didn’t have the sophisticated tools to tease apart the active compounds. Still, by the 1920s, growers had by virtue of significant trial and error begun to breed plants that might balance paranoia-inducing effects with sedating ones, and marijuana was widely sold on pharmacy shelves by major pharmaceutical companies, as medicine. “People don’t know how respected this was, how many mainstream companies were involved with it, how sophisticated they were,” Wirtshafter says. Then came prohibition, and “the work of millions of our ancestors was lost in a sheet of political extermination. Not only did we try to wipe out the plant, we tried to wipe out all knowledge of the plant.”

 

When Holmes saw Wirtshafter’s collection, he was ecstatic. There were bottles with pills, powder or gooey black viscous residue mixed with opium. Some were labeled as “aphrodisiacs.” Others claimed to treat anxiety, insomnia, glaucoma. It was one of the best single collections of ancient cannabis DNA he’d ever seen. “Jackpot,” Holmes said.

A Pot Stud Book

Holmes’s lab, Phylos Bioscience, opened in 2014. The lab’s director of research, Jessica Kristof, a horticulturist and biochemist, is tasked with what’s perhaps the most difficult part of Holmes’s endeavor: designing a method to extract DNA from each sample collected. It’s an excruciatingly time-consuming process because each substance requires a different protocol for DNA extraction and purification. Each of Wirtshafter’s samples needed to be handled differently to dissolve whatever substance was in the way of getting the DNA out. “Ancient DNA is very fragmented,” she says. “There’s may be 1 percent of cannabis material in these samples, and they’re already diluted by whatever buffers that have been added to make it medicinal. Then, on top of that, there’s yeast and E.coli and stuff growing on it for years.” With 1,500 strains sequenced, the constellation is slowly taking shape. “What 23andMe does for humans,” says Karassik, “we’re doing for cannabis.”

Mowgli Holmes looks at samples in a laboratory on August 11, 2015. Winston Ross for Newsweek

Once complete, Phylos will hand over its data set to the Open Cannabis Project, a nonprofit effort to build an archival record of all cannabis strains, to ensure they stay in the public domain. Then, Holmes says, they will create a testing program that will allow growers and dispensaries to stamp “certified” on the products they sell to consumers, who can then have a better idea of what they’re using and can fine-tune their relationship with different strains. Robert DeSalle, who studies genomics at the American Museum of Natural History, imagines a “stud book” of different strains. “This is going to lend a lot of legitimacy to the industry,” he says. “It’s kind of a black book now.”

Pot is often categorized in two overly simplistic ways, as either an indica or a sativa strain. The indica makes you sleepy, the sativa, hyper. But that nomenclature is based on old information. Back in the ’70s, narrow-leaf sativa strains tended to produce a more euphoric plant, and broad-leaf indica a more sedating one. We still use those terms to describe characteristics of pot, regardless of whether a given strain actually has any indica or sativa lineage. “People talk about strains that are good for sex, or eating food, or playing with your kids,” Holmes says. “Some are good for arthritis.” But because strains are so frequently mislabeled today, it’s nearly impossible to know whether the Sour Diesel that once relieved your migraines is going to be the same Sour Diesel next time you go looking for it. “Very rarely do even the growers know what they’re growing,” Holmes says. Once his DNA map is complete, Holmes believes it will give growers a better way to understand their horticulture and consumers a better way to understand their product.

The scientist is also hoping to solve some intriguing mysteries. We know that much of the pot consumed today in the U.S. has roots in strains smuggled here from Afghanistan and Thailand in the 1960s, but there was cannabis in America before that, before prohibition. Where did that originate, and what can it tell us about ancient migratory patterns of the human race? Cannabis is one of the few plants carried all over the world, over the past 10,000 years. Tracing its genetics could tell us something we didn’t know before about where humans traveled and when.

Heady stuff. And even answering those questions seems like first steps. When he has a more complete picture of cannabis’s genetic makeup, Holmes intends to work with growers to create hundreds of new strains with specific genomic traits. The popular pot strain Blue Dream might have a particular array of terpenes—the compounds that impart flavor and aroma to the plant—directly connected to boosting energy in the user, for example. What if a new strain could be grown that enhances that particular effect? Cannabis is already the most hybridized plant on Earth. But its evolution has only just begun.

[Restorium2]

[imiubu]

The last few decades of cannabis breeding have been an unprecedented burst of horticultural creativity. No living plant species has as much richness and diversity as the Cannabis plant now does. Most of these cannabis varieties have been in the public domain for years. They have been widely circulated, and sold, and therefore cannot be patented. At present, plant patents and breeder’s rights are not available for cannabis in the US. But this also means that the federal government does not keep track of cannabis varieties. They cannot be patented, but there is also no legal proof that they exist. There is no documentation that today’s cannabis varieties are rightfully in the public domain. If the federal government changes course and begins to grant cannabis patents, then companies could rename existing strains, patent them as if they were new, and restrict their use. The OCP is building a database of genetic sequence data for every available cannabis strain. This data cannot be used to patent plant varieties – but it can be used to demonstrate that varieties are in the public domain and cannot be patented. In the future, any attempts to patent or restrict existing cannabis strains will be rendered impossible by this work.

 

http://opencannabisproject.org/

[Restorium2]

Breeding programme

GW's team includes experts in Cannabis breeding. In the genetic model used, the cannabinoid content of each chemical phenotype (chemotype) is controlled by four independent loci. By manipulating the genes at these four positions, our scientists can precisely control the cannabinoid composition of a plant. This is explained in the diagram below:

 

The gene at locus O allows the production of the initial phenolic precursors (resorcinolic acids). These combine with geranyl pyrophosphate to create the intermediate cannabinoids CBG and/or CBGV, the central precursors for the end-product cannabinoids THC(V), CBD(V) and CBC(V). The functional allele O is co-dominant; O/o hybrids have a low cannabinoid content and o/o plants are cannabinoid-free.

 

The ratio of propyl- and pentyl cannabinoid precursors is determined by a postulated locus A, which is still under investigation.

 

The CBG/CBGV intermediate is further processed by the alleles of locus B. BD and BT are co-dominant; the BD gene converts CBG(V) into CBD(V) and the BT gene converts CBG(V) into THC(V). In the BD/BT genotype, codominance allows the expression of a mixed CBD/THC chemotype. Also at this locus, non-functional alleles, designated B0 can exist; these are unable to convert the CBG(V) intermediate and leave the plant with a CBG(V) predominant chemotype.

 

Locus C is fixed so all plants have CBC synthase activity. CBC synthase competes for the same CBG(V) precursor as the synthases encoded by locus B (THC and/or CBD synthase). In 'normal' Cannabis plants, CBC synthase is only active in the juvenile state. However, our scientists have discovered genetic factors that induce morphological mutations that are associated with a 'prolonged juvenile chemotype'. Prototype CBC production plants carry these factors in combination with B0/B0 at locus B. In these plants CBC synthase has no competition from THC or CBD synthase.

References

Meijer EPM de, Bagatta M, Carboni A, Crucitti P, Cristiana Moliterni VM, Ranalli P, Mandolino G. 2003. The inheritance of chemical phenotype in Cannabis sativa L. Genetics 163: 335–346.

Meijer EPM de, Hammond KM. 2005. The inheritance of chemical phenotype in Cannabis sativa L. (II): cannabigerol predominant plants. Euphytica145: 189-198.

Meijer EPM de, Hammond KM, Micheler M. 2009. The inheritance of chemical phenotype in Cannabis sativa L. (III): variation in cannabichromene proportion. Euphytica 165:293-311.

Meijer EPM de, Hammond KM, Sutton A. 2009. The inheritance of chemical phenotype in Cannabis sativa L. (IV): cannabinoid-free plants. Euphytica 168: 95-112.

[+Malamute]

The last few decades of cannabis breeding have been an unprecedented burst of horticultural creativity. No living plant species has as much richness and diversity as the Cannabis plant now does.

 

 

Apples and Tulips.

 

;-)

 

But yea.... :-)

[Restorium2]

Ironically, the best strains I can find are from the 80's! No change in the last few decades.

[+Malamute]

Well, you can narrow down the heritage of most marijuana to about 12 races.