Unlocking the Cannabis Genome

Humankind’s understanding of cannabis genetics is about where the knowledge of human DNA was 20 years ago — a few juicy snippets of information have begun to trickle out, but the immense, industry-changing potential still lingers on the horizon.

Today, genetics scientists can determine only a few things, like whether a seed will be male or female and how much THC or CBD a plant is likely to produce. But in the future, the science could be used to dramatically increase plant yields, create new strains with specific cannabinoid and terpene ratios and eventually to tailor custom cannabis strains specifically to treat an individual patient’s illness.

“By the end of this decade, breeders will be creating new cultivars we haven’t even dreamed of,” Alisha Holloway, director of bioinformatics at Phylos Bioscience, told a crowd at the Cannabis Science Conference, held in Portland in November. “This plant is possibly the most useful plant I can think of … but really we’ve only begun to unlock its medical potential.”

Funding issues

How soon those monumental breakthroughs occur depends on how much funding is devoted to research. For now, that research is in the hands of a small number of companies like Phylos Bioscience, Steep Hill Labs and Medicinal Genomics. But to reach the full potential, a lot more researchers — and a lot more money — will be needed, says Reggie Gaudino, vice president of scientific operations and director of intellectual property at Steep Hill.

“Right now, people who are doing this are mostly working on their own,” Gaudino says. “We have a few groups, and maybe if we put all of our data together we can start doing higher-level things. But to really get there, people need to understand the level of commitment and money it will take.”

Gaudino compares the challenge to the mapping of the corn genome. That mapping project took five years at a cost of $32 million dollars, with efforts from 157 researchers at 33 labs. And the corn genome is much less complex than the cannabis genome.

Fully mapping and understanding the cannabis genome will likely cost a lot more than that, and getting to that level will require some sort of national commitment that is nearly impossible while marijuana remains federally illegal, Gaudino says.

“We (at Steep Hill) try to raise money every few months to try to sell the genomics science we do to investors,” Gaudino says. “And they think it’s a phenomenal deal, until they look at the price tag.”

What’s really needed is university involvement. But many universities also ban cannabis from their campuses — even when it’s for research purposes; and that problem makes it even harder for trained scientists to conduct peer-reviewed research on the plant.

“Not a lot of real biological scientists are in this because there’s no real funding because of the status of cannabis,” Gaudino says. “And so doing this in private industry means we have to make a product to sell in order to get money for our next research project – and that makes things move slowly.”

Where are we now?

That’s not to say the science isn’t moving forward.

So far, there are no completely sequenced DNA strands from any cannabis plant – which is thought to have 800 million to perhaps a billion base pairs, the building blocks of the DNA double helix.

Standard DNA sequencing equipment can read about 300 base pairs at a time, but it also breaks up the larger DNA strand into pieces — sort of like a jigsaw puzzle — and then scientists have to put those pieces back together to build a map of the DNA, says Kevin McKernan, founder and head of scientific operations at Medicinal Genomics.

“So we have millions of pairs that have been sequenced in bits, and we put those together at the end,” McKernan says, noting that the effort to fully sequence and put all the pieces together could take many years.

But even the bits and pieces that scientists have discovered are proving useful.

By looking at DNA from certain types of plants — species with high yields or specific flowering times – scientists can correlate those properties to match with sequenced DNA building blocks called single nucleotide polymorphisms (also known as SNPs or “snips”).

Those snips can be used like a control panel that tells a plant to grow with those specific properties, allowing breeders to genetically build new plants that could be pest-resistant, have larger buds or resist drought, among a host of other factors.

“Having that information early on means that breeding can accelerate,” McKernan says. “And that means you can predict what a plant is going to do.”

So far, scientists have found snips that determine whether a seed will be male or female, snips that can predict THC or CBD percentages and snips for a few terpenes. Some scientists are finding snips for THCV — a lesser-known cannabinoid that bears some similarity to THC.

But that’s only the beginning, McKernan says.

“I think we’re going to find dozens of markers fall out of the cannabis genome in the next few years,” McKernan says.

Strain identification

One of the more interesting efforts in cannabis genetics is finding a way to match specific cannabis strains to a DNA profile. Through the science, a chunk of plant DNA could be used to confirm what strain it is.

“DNA sequencing can provide a link that people trust,” McKernan says. “And that gives people confidence in what they’re buying. Once a strain rises to a trend, people in the industry tend to rename other strains to capitalize on that — and if we have DNA sequencing and can confirm strains, it will help with that.”

McKernan says Medicinal Genetics can test for a handful of specific strain types already, with tests costing between $300 and $1,000.

That might sound like a lot for one plant, but if breeders test a mother plant and use it for cloning, they only need one test to confirm an entire line.

“Eventually that could also be used to genetically certify new strains, and companies could use that to defend intellectual property,” he says.

Still, there’s some error potential in that science, Gaudino says.

“It’s a very low probability, but the way the DNA sequencing equipment works, you could end up with some cuts (snips) in the wrong places,” Gaudino says. “And if that happens, you could end up telling two people that they have different strains, even if they’re the same, because the output doesn’t match.”

Phylos Bioscience takes a different approach to genetics and strain identification — by using snips to trace and connect cannabis families through history.

What the company has found so far is that identifying categories such as indica or sativa don’t really match up with the genetic families of the plant. The same can be said of so-called “landrace strains.”

In her speech at the Cannabis Science Conference, Holloway said Phylos Bioscience has determined seven distinct cannabis populations. They are: OG Kush, which includes strains like White Fire and Platinum OG; Skunk, which includes strains like Jack Herer and Jack Flash; CBD, which includes strains like Cannatonic, ACDC and Remedy; Berry, which includes strains like Berry White and Blackberry; Purple, which includes strains like Purple Kush and God’s Gift; Landrace, which includes strains like African, South American and Southeast Asian; and Hemp, which includes strains from Russia, Hungary and Brazil.

“If you look at thousands of samples, you find a lot with Kush in the name, but there’s a lot more variation than that going on,” Holloway says.

Phylos has used its data to create a 3D representation called the Phylos Galaxy. The company has developed a genotype test kit that can place a plant in its Phylos Galaxy map and associate it with one of those families.

“We want this to be part of the cannabis industry, and we’re turning the tools we’re developing into tests that breeders can use,” she says.

Medicine

Advances in cannabis medicine may be the furthest away, but the potential remains exciting.

To make personalized cannabis medicine a reality, scientists will have to do a significant amount of study on how different cannabinoids and terpenes work with human biology and genetics.

“That’s really our Holy Grail,” McKernan says.

That’s a long way off, in part because a good chunk of the research and testing requires advancements in chemistry and chemical sciences, Gaudino says.

“We need to understand flavonoids, isoprenes and other components that are medically important,” Gaudino says, adding, “we have to get better at understanding chemistry first, and then we can look back and find out what parts of the chemistry trace back to the plant.”

Eventually, there could be strains specifically engineered to fight seizures, PTSD, pain or a host of other ailments.

“If we can identify those things that are cancer affective or anxiety affective, then we can trace that back and make sure the genes in the plant make more or less” of a specific chemical compound, Gaudino says.

Scientifically tailored, personalized cannabis medicine may some day be a reality. But the potential depends on how much support and financial backing scientists get to develop those tools, Gaudino says.

“If we get Human Genome Project levels of interest and investment, we could actually see some of that in a few years,” Gaudino says. “But if there’s no other investment beyond what we have now, it could take 20 years or longer.

“It could be a very long wait.”

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