By mapping the cannabis genome, Medicinal Genomics founder Kevin McKernan hopes to unlock the mysteries of marijuana DNA.

 

By Chris Simunek

 

The breeding of cannabis for medicinal purposes has come a long way since California’s Proposition 215 was passed in 1996. The aboveground status of growers, dispensaries and patients has enabled the sharing of testimonial evidence as to which strains work best for which ailments. With medical marijuana now a quasi-legal, multimillion-dollar industry in 16 states, scientists are looking forward to the day that a serious genetic study of this plant is finally allowed, including clinical studies of all its cannabinoids. Ironically, this longstanding prohibition on marijuana has made it difficult for scientists to gather the empirical data that might one day raise medical cannabis from the status of “folk medicine” and place it in the same approved realm as the myriad pharmaceutical drugs (many of them known to be far more dangerous than marijuana) consumed by millions of Americans every single day.

 

In this respect, Kevin McKernan is a visionary. His company, Medicinal Genomics, is headquartered in Marblehead, MA, and has a laboratory in Amsterdam where its researchers can freely and openly study the many unknowns of this plant, which has been used medicinally throughout the world since at least 2737 BCE (when the Chinese Emperor Shen-Nung prescribed it for “beri-beri, constipation, ‘female weakness,’ gout, and rheumatism” according to the 1972 report by the US National Commission on Marihuana and Drug Abuse).

 

In August 2011, McKernan announced that his company had successfully mapped the genomes for both Cannabis sativa and Cannabis indica. Medicinal Genomics then made its work on Cannabis sativa public via Amazon’s EC2, a cloud-computing service that gives free access to the scientific community. Medicinal Genomics intends to make its work on Cannabis indica publicly available later this year.

 

At just 38 years old, Kevin McKernan has already amassed an impressive résumé in the field of genetics. A graduate of Emory University, he worked on the Human Genome Project from 1996 to 2000, running a research-and-development group at the Massachusetts Institute of Technology’s Whitehead Institute that programmed and designed liquid-handling robotics and engineered a new DNA purification chemistry that was easier for the robots to manage. In 2000, he started a company called Agencourt Bioscience that sold its DNA purification technology to the scientific community and also developed a method for sequencing DNA that made the process 100,000 times faster than was previously available. After selling Agencourt to Life Technologies and managing its DNA-sequencing R&D for five years, McKernan turned his eye and considerable resources to the cannabis plant.

 

After a career spent squarely in the scientific mainstream, what made you want to study cannabis?

A lot of my friends either had friends with cancer or had cancer themselves and were asking us about how these sequencers were being used in cancer. We were working at the time with a lot of oncologists. If you sequence a tumor’s DNA and sequence the patient’s DNA, usually you find these differences in the tumor that weren’t in the people’s DNA, and a hopeful few of those become druggable targets. So I got involved and my friends were asking: “What’s going on with medical marijuana?” We know cancer patients are using this, and that’s when I started looking at it – and the more I dug, the more and more I thought there are myriad uses for this plant. And that it’s a real crime that they kept it illegal, for patient access at least.

 

And so, this summer, I decided to go and sequence the genome, because it looked as if the components of the plant that are medicinal aren’t just about THC. I mean, THC seems to do wonders for tumors and for pain, but there are another 84 cannabinoids in the plant. THC synthase and CBD synthase are the genes in the genome that code for an enzyme that helps fold these hydrocarbons into cannabinoids. And those two have been known for a while, the sequence has been known – the Japanese, I think, actually weeded those out in 2004. But what governs the other 83 cannabinoids and the hundreds of terpenes in the plant are still a mystery. Nobody knows which genes are governing that, so we figured if we sequenced the genome, we could probably find those genes. And some of them, we suspect, could get resurrected – because when the federal government pro- hibited cannabis, everybody started breeding for higher and higher concentrations of THC.

 

Was that necessarily at the expense of other cannabinoids?

I don’t know that we have proof of that, but just having looked at this pathway, some of the precursors are the same for all the cannabinoids, so these enzymes are in competition with the precursors – the fuel. So if one of the enzymes is hogging up all the activity, then there’s not enough of those precursors to make the other cannabinoids. So I think that’s going to be the case ... have fun proving it. But the challenge the [illicit] markets had [was that] all the penalties were based on weight, not weight adjusted with THC concentration. So, naturally, they bred this for higher and higher THC concentrations, and I think that’s been at the cost of some of the other cannabinoids being sort of bred down to, not extinction levels, but perhaps some very, very basal levels of expression. We’re hoping by sequencing the genome, we can start to find what those are and maybe help guide breeding some of that stuff back into the plant.

 

In the articles that I read in preparation for this interview, a lot of scientific journals were making reference to cannabis’s ability to shrink cancerous tumors, and they weren’t using words like “allegedly” or “supposedly,” they were just basically referring straight to it. Is it, at this point, an established medical fact – that cannabis has this property?

You know, it’s interesting, because the NCI [National Cancer Institute] actually put that on their website, and somebody from the government made them take it down. They initially had a statement about palliative care, which is pain and anti-nausea, and they also put on their website in that same statement that there were potential anti-tumor effects. And like a month or two later, I think the DEA asked them to modify the language. But for right now, the anti-tumor effects have been shown in cell cultures and in rats – they’re just now looking at this in clinical trials on people. So I think the jury is still out on whether they would call this clinically real.

 

But the reason I’m excited about it is because I’ve been involved in sequencing people’s tumors to better pick drugs for them to take, and with some of these chemotherapeutic drugs, you’re threading a needle between killing the patient and killing the tumor. And when you look at the therapeutic index of the cannabinoids, very few compounds have that forgiving of a therapeutic index.

 

You mean it’s a much healthier medicine to use?

Yeah. If it shows any signs of shrinking tumors and it’s that nontoxic, we have to basically go after it with guns blazing.

 

 

And so, medicinally, what will be the benefits of having the cannabis genome decoded?

With THC and CBD, there are already pharmaceutical companies pursuing those, and I’m sure those are going to do well. But the other 80-some cannabinoids, we’re hoping we will find the genes that encode those, and then we can help people up-regulate those by breeding. A lot of hemp plants that have not been bred for THC have high CBD expression. And we’re hoping we’ll be able to match mother and father much more accurately to bring out some of these other genes.

 

And I’m still a proponent of what GW Pharmaceuticals has been doing in this space, because they’ve gone with the plant extract, and I think that’s probably the right bet today – this plant being so complicated that if you tried to synthesize all 85 of the cannabinoids and balance them in some cocktail ... I mean, it’s cheap for pharmaceutical companies to make one or two compounds, but when you start getting into dozens, and the alternative is a plant, it doesn’t make much sense to continue to synthesize dozens of these things.

 

We have something that’s already there.

Yeah, exactly. [The companies] will always be questioning whether there will be a return if people can just resort to a plant. Even if it’s not the perfect ratio, it’s pretty darn close, and that’s a difficult thing to compete with.

 

Once you discover these other cannabinoids, what’s the process whereby you learn how they’ll affect cancer and various other ailments?

You would actually put them through a clinical trial. There’s a handful of cell lines from the National Cancer Institute that are cells derived in Petri dishes of different tumors. They’re not exactly what any given person’s breast cancer is going to behave like, but they are models, and people start dosing those cells with these types of compounds to see what types of activity occurs. Do the cells die? Do they continue to grow? Do they grow faster, slower? Now, we’re not set up to do that; we’d probably partner with somebody who’s already set up to do that and actually take it to this next step of bringing it to clinical trials and taking a look at these things in people.

 

You’ve mapped both an indica and a sativa. I’m wondering which strains you chose, and why those particular strains?

The two were Chemdog and LA Confidential. So Chemdog – I think it’s a sativa-dominated hybrid – we took a look at it because it’s a famous strain and there seems to be a lot of folklore as to what its actual history is.

 

I doubt there are too many pure indicas or sativas on the recreational market.

One of the reasons we went after LA Confidential is because we recognized what people were saying of Chemdog – that, hey, this thing seems to be a hybrid, which means it has two very different genomes in it. So we went back and spoke to Don at DNA Genetics about this problem, and he right away was like: “If you want something backcrossed to pure indica, your best bet is LA Confidential. It’s pure indica and it’s been triple backcrossed, and likely if you backcross a lot of these things any more than that, they start to show some really weird phenotypes. I don’t know if you want to have an unstable plant.” And the benefit with this is that they’ve done the triple backcross and the plant is stable – and, actually, I think it won a Cannabis Cup or two. So we figured that was a good candidate.

 

 

Okay, and why did you put all of your findings on the Web for free?

Well, one of them: We put the Chemdog’s genome up because, after speaking to a lot of people in the field, we felt that we would be vilified if we came in here, did the sequencing and said we’re gonna keep it all private. It just didn’t feel like the right way to start things off, so we put one of them public. And the other reason for putting it public is that we figured that we could actually leverage some resourcing and get some other minds on this. The moment we put it public, there was another two or three dozen people looking at this data and responding as to what they were finding in it. And it’s more data than a small company can possibly digest, so I didn’t want it to be held up in some company’s coffers for like another five years.

 

Now, we still have another genome that we sequenced that we haven’t put public yet, but we’ll be putting that one public once we’ve gotten our head around a few of these problems that we’ve been trying to solve ....

 

This is the LA Confidential?

Yeah – the LA Confidential is going to go up, hopefully, before the end of the year. And that one will probably have a link to it from an iPad app we’re putting out. It won’t actually fit on an iPad – it’s too much data – but we can have an interface that can educate people about, you know, what does this stuff mean? We’re trying to get the average person interested in this. We’ll also have some links in there to some medicinal papers that we’ve read and some explanations of what these papers mean in laymen’s terms. We’re hoping to target anyone who’s interested in genomics, cannabis or cancer. So it’s a pretty broad spectrum of people, and it’s meant to be more sort of a Wikipedia of information on what we’ve found with the plant. And our interest there is just to get it on a viral form of media that will get the word out as to what we’re doing and explain to people why this is an important field and why people should care about genetics when thinking about cannabis.

 

And, theoretically, someone could use your findings to make a plant with even more THC in it, right?

They could. I’m somewhat skeptical: The last 30 years of hyper-breeding has probably pushed the plant to express as much of that as it can. But, I mean, I could be wrong – someone might be able to dial that in. My general sense is that if you try and crank the THC any higher, I don’t know if the trichomes are going to remain stable.

 

So people are looking at CBD and CBN for medical applications, but you’d have to argue that for certain ailments – for instance, PTSD – the psychotropic effect of THC is part of the plant’s medicinal quality.

Without a doubt, without a doubt. Unfortunately, the US government doesn’t like to admit that, but the pharmacology will tell you and advise you to have some THC present. Complete elimination is probably a bad plan.

 

Do you think someone might eventually be able to use your findings to contest the US government’s classification of marijuana as a Schedule 1 drug with absolutely no medicinal value?

I hope so. I mean, part of our interest in putting [our findings] public was that it would make it so anyone in the world can research without having to get a license per se, and can answer certain questions without actually having to grow the plant.

 

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