The Rise of Marijuana™ (Patent Pending)

To the cannabis industry, a patent granted last August was either doomsday or the dawn of a new era, depending on who you asked.

U.S. Patent No. 9095554 covered the “compositions and methods for the breeding, production, processing and use of specialty cannabis.” Filed by a group of California marijuana growers, it covers any cannabis plants with a certain chemical profile, including THC (the main psychoactive chemical in marijuana) and terpenes (the molecules that give different varieties their distinctive odors). Although the government had issued patents on certain compounds derived from the cannabis plant, this was the first time a patent had been issued for the plant itself.

“It’s seen as the big guys versus the little guys. There are a lot of people who are afraid of Big Ag and Big Pharma coming in and taking over,” says Jennifer Martin, a cannabis grower and consultant.

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In a grow house in Colorado, marijuana is raised for sale in legal dispensaries.

The patent comes as social norms around marijuana are loosening and cash-strapped states turn to the drug to alleviate their budget crises. Today, 20 states have legalized medical marijuana, and pot has become a business valued at $6.7 billion. Although the federal government still classifies cannabis as a Schedule I drug with “no accepted medical use,” the industry’s reach—and revenue—is still expected to climb as more states loosen their restrictions on the drug.

As the industry’s supply chain has transitioned from underground growers to legally recognized suppliers, it has caught the attention of scientists and entrepreneurs interested in cataloging and capitalizing on marijuana’s medicinal potential.

In 2011, a group of Canadian scientists published the first full genome sequence of the marijuana strain Purple Kush. In the five years since, both researchers and biotech firms have begun classifying and standardizing marijuana strains so that customers may one day walk into any marijuana dispensary around the country and know that the Girl Scout Cookies strain they bought last week is the same one they’re buying today. The results are transforming the cannabis industry into a potentially high-tech, high-stakes business.

Meanwhile, long-term breeders like Martin fear that if small-time hobbyists can’t compete, they’ll lose the soul of the industry to the likes of Monsanto and Pfizer. These fears have led scientists like Mowgli Holmes of Phylos Biosciences to use DNA sequencing to document as many existing strains as possible and release them into the public domain in an attempt to block more possible patents.

“Whether it wants to or not, the cannabis industry needs to start looking at itself as an agricultural industry. But it’s also a pharma industry. We have a very uniquely placed plant,” says Reggie Gaudino, vice president of scientific operations at Steep Hill Labs in California.

From Shaman to Geneticists

In 2008, a team of scientists announced the discovery of a 2700-year-old cache of medical marijuana in an ancient grave. Located in the mountainous Xinjiang province of far northwestern China, the group says the stash likely belonged to a shaman of the Gushi culture. They strongly suspected the cannabis was used for its psychoactive properties rather than hemp grown for food or fiber because of its unusually high levels of THC. (Their efforts to grow seeds found in the grave were unsuccessful.)

Though the Xinjiang discovery is the oldest physical sample of marijuana yet found, genetic and evolutionary evidence points to a much earlier domestication of the plant, likely around 10,000 to 12,000 years ago. We still don’t know which culture first started using marijuana, but Daniela Vergara, an evolutionary biologist at the University of Colorado who studies marijuana, says that it was probably independently domesticated several times in India and China.

“It’s clear that lots of people were interested in breeding cannabis for its particular traits,” Vergara says.

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The terminal bud, also known as the cola, of a cannabis plant is where the flowers form.

Cannabis has been a popular medical remedy throughout history, being used for pain, nausea, and more. In the late 1800s and early 1900s, cannabis was frequently found in patent medicines, those over-the-counter cure-alls that not infrequently contained everything from morphine to arsenic. The creation of the Food and Drug Act in 1906 made these home remedies harder to find, though they persisted until the 1930s when marijuana was formally criminalized. While it remained legal to conduct scientific research on cannabis, the amount of red tape discouraged all but a few scientists.

Botanist Jonathan Page was one of those few. By 2010, he had spent nearly a decade using a plant’s genome to decode its ability to make a range of complex chemicals. So when a friend saw an email from Tim Hughes at the University of Toronto looking for someone to help sequence the cannabis genome, they immediately forwarded it to Page, who was on sabbatical from the University of Saskatchewan.

“I wrote to Hughes and said, ‘Hey, I’m your guy,’ ” Page says. Hughes agreed, and the two began collaborating.

The team didn’t sequence weed alone; they also compared the marijuana genome to several varieties of hemp. Just as broccoli, Brussels sprouts, and cabbage all originated from the same plant and developed their unique characteristics through hundreds or thousands of years of plant breeding, so had marijuana and hemp. Starting with the same cannabis plant, humans increased levels of THC to optimize the buzz they were seeking from marijuana while taking hemp down a separate road for its fiber. Page and Hughes settled on one variety of marijuana, the popular Purple Kush strain that they purchased from a Canadian dispensary, and two varieties of hemp which are legal to grow in Canada.

Page, Hughes, and their team published the first draft genome of cannabis in 2011 in Genome Biology to wide scientific and public acclaim. Their work showed subtle but important differences between the three plants. Purple Kush had a copy of a gene called Δ9-tetrahydrocannabinolic acid synthase used to make THC. Hemp lacked this gene.

“We got a lot of attention. But think about this remarkable plant breeding success, especially since the people who have been doing this are not professionals. These are crowd-sourced methods to increase THC levels that worked in a short period of time,” Page says.

Just as having the raw data from the sequencing of the human genome gave researchers an unprecedented ability to understand and perhaps manipulate what makes us human, the cannabis genome will do the same for marijuana. Knowing which genes control the production of compounds like THC, cannabidiol, and terpenes will help breeders make better decisions about how to create new strains.

To that end, Vergara has recently started a non-profit called Cannabis Genomic Research Initiative to create a genetic map of cannabis. Right now, she says, the genome data that Page and Hughes generated back in 2011 is sort of like a directory of addresses without a corresponding map. Vergara is working to show where different genes are located on different chromosomes, which will give breeders a better idea how likely they are to obtain a certain trait when they cross two strains.

“What we’re doing in cannabis is not new. It’s been done in soy and wheat for years. We want to develop the same types of tools for cannabis, so you can know with precision whether you will get the desired results,” Vergara says.

It’s relatively basic information about a plant’s genome, and in this respect, marijuana is decades behind other crops like corn and soybeans, says Dale Hunt, a molecular biologist turned patent attorney at Hahn Loeser & Parks LLP in California. Cannabis breeders and growers are now just beginning to tap into tools that other plant scientists have relied upon for years.

Striving for New Strains

Page and Hughes’s early genetic work showed what even the most rudimentary breeding programs could create, given enough time. Even now, breeders use the same general strategy to create new strains as before, says Martin, who operates Marijuana Cultivation Consulting. By fertilizing the flowers from one strain with the pollen of another, a breeder will create a diverse panoply of offspring with different suites of traits. The breeder then grows these seeds and again fertilizes the plants with the desired traits. They repeat this process over and over, frequently ten or more times, until the offspring contains the right characteristics. Then, they take cuttings from the winning plant to plant and grow clones for growers like Martin.

The process is difficult and time-consuming. “It can take years to get the right combination,” Martin says.

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Seedlings take root inside a Colorado grow house.

In response, a suite of cannabis testing labs like Steep Hill Labs have popped up, primarily in the Pacific Northwest. Gaudino coordinates testing for Steep Hill, which can rapidly analyze a plant to determine the levels of THC, terpenes, and other cannabinoids. The goal is to speed up and simplify the process of creating new marijuana strains. “We’re working to develop the tools to help breeders make new varieties more quickly and not end up getting trampled by Big Ag,” Gaudino says.

This process has extra benefits for breeders who are trying to develop new strains of medical marijuana. Many who use marijuana regularly do so for a combination of both recreational and medical purposes. Someone with anxiety, for example, may smoke a joint not just to have a good time, but also because they find that the chemicals in cannabis help them relax. They don’t necessarily need a strain specifically for medical purposes.

Others, however, do. Anecdotal reports and small scientific studies have found that cannabidiol and cannabis oil can help benefit children with severe, intractable epilepsy. For these children especially, parents want treatments that have very low levels of THC and high levels of cannabidiol. Charlotte’s Web is the most famous strain with these properties, but scientists, breeders, and even parents themselves are searching for new options. The ability to more rapidly develop these strains could have tremendous benefits. Even the California growers who obtained one of the first marijuana patents made this argument in their patent application.

Few people in the marijuana industry would question the need—or desire—for new cannabis strains. But patenting new strains has proved divisive. Historically, Martin says, growers have developed new types of marijuana for the love of the plant or a search for a better high. For most growers, it wasn’t a way to get rich or even earn much of a side income. “They did it because they loved the plant,” he says.

That ethos has governed the marijuana industry since the 1930s when the plant first became illegal, Gaudino says. Though it remains illegal under federal law, the decriminalization of cannabis in certain states coupled with a growing acceptance of marijuana use, especially for medical purposes, has propelled the industry. As a result, there is growing concern that Big Ag and Big Pharma muscle in and wind up controlling the industry, he says.

Still, it won’t be as easy as grabbing a plant and filing a patent, Hunt says. Companies need to show that they invested significant intellectual labor in the creation of a marijuana strain and that the strain is sufficiently different from existing strains.

The patent granted last August has generated a fair amount of angst within the industry. To Gaudino, the patent doesn’t satisfy either of these requirements. It’s not clear that the growers actually created a new type of cannabis plant, he argues, and the patent is far too broad. “It covers a broad swath of strains that are already in existence,” Gaudino says. Furthermore, terpene levels can vary dramatically within a strain depending on the environment in which they’re grown. A grower could raise the same strain in two places and unwittingly violate the patent in one of them.

Gaudino and Hunt believe that taking the growers to court would likely establish the fact that the patent isn’t actually enforceable. Doing that, however, will take time and money, something that most growers just don’t have.

Big Pot?

The patent issue worries Mowgli Holmes of Phylos Biosciences. His doctorate in molecular biology exposed him to the high-stakes biotech world, and he suspected that pharma was at the gates, ready to stake a claim in the marijuana industry. Small growers wouldn’t stand a chance against large pharmaceutical firms.

“Everyone is terrified of some big corporation with deep pockets coming in and taking over. They’re really scared about that, and they should be,” Holmes says.

In 2014, he founded Phylos Bioscience to give cannabis growers the genetic tools they’d need to compete. Holmes and his colleagues developed a cannabis genotyping test that would provide a DNA fingerprint for each strain, solving the age-old problem of strain confusion between different growers.

Then Holmes began collecting cannabis strains from around the world, including those being used today and those found in tinctures and elixirs in days past. He gave his genotyping test a dry run on the samples before the kit went public. Holmes, however, didn’t stop at genotyping. With the DNA sequences, he and a curator at the American Museum of Natural History began piecing together what he calls the Phylos Galaxy, a striking 3D visualization of how different cannabis strains were related to each other.

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The Phylos Galaxy is a visualization of the relationships between different strains of cannabis.

The Galaxy, however, wasn’t just a pet project for Holmes. It also provides incontrovertible proof of the marijuana strains that are currently in existence—and therefore not patentable, he says.

“If a plant clearly exists in the public domain, you can’t patent it. And if you have genetic information on the plant, it’s easier to protect it and keep it free and available,” Holmes says.

He also hopes his soon-to-be-released genotyping services will help smaller growers distinguish themselves in an ever more competitive marketplace, ideally giving them a jump start on developing new strains. Genotyped plants also pave the way for growers to certify their product, says Nat Buttrick, CEO of Madrone California, a cannabis farmer collective. The group already tests the marijuana they grow for potency, pesticides, and other chemicals. From there, Buttrick says, it’s only a small step to create a set of standards for different strains that would allow breeders and dispensaries to show they had the “real thing” and to make such verification a selling point.

It’s a long way from how people grew pot in the 1960s, when they freely shared cuttings and most grew relatively small amounts for themselves and their friends. Today, marijuana is a high-tech, big business. Holmes and other cannabis scientists say that small, backyard growers will always have their place in the industry, just as many home brewers enjoy creating their own beer.

The biotech boom has left an indelible mark on cannabis cultivation, though its full impact is likely yet to come. Whatever its future may be, Holmes and other scientists are working to make sure that pot’s diversity and heritage don’t go up in smoke.