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Cannabis genome project in news

Levitationofme

Well-known member
THE MAN MAPPING THE MARIJUANA GENOME IS CHANGING THE WEED GAME
BY WINSTON ROSS ON 3/14/16 AT 10:02 AM
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A Seattle cannabis worker cradles the resin-dusted bud of a strain called Blueberry Cheesecake, a sativa-dominant hybrid. Pot is often categorized in two overly simplistic ways, as either an indica or a sativa strain.
LYNN JOHNSON/NATIONAL GEOGRAPHIC CREATIVE
TECH & SCIENCEMARIJUANAGENOMESWEEDCANNABIS
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.

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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.

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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.”

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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.
 
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