How The Cannabis Genome Got Mapped: Q&A With Dr. Jonathan Page

(Photo: Carlos Gracia/Flickr)

With interest in marijuana research at an all time high, we spoke to the scientist who mapped the first cannabis genome.

Canadian botanist Jon Page, Ph.D, was one of the lead investigators in the first, and so far only, cannabis genome project.

Published in 2011 in the journal Genome Biology, Dr. Page’s findings unraveled the sequencing of some 30,000 genes that make up the genome of Cannabis sativa, using the popular Purple Kush strain as the source.

The genome has since been available online, and has served as a tool for other cannabis researchers around the world. Dr. Page took the time to answer some of our questions about the project and what lies ahead in the field of cannabis genomics.

Q: What inspired you to pursue the cannabis genome project?

From the time I was an undergrad, I’ve been interested in medicinal plants and plants that have beneficial effects on human health. I focus on the biochemistry of medicinal plants, and study the active chemicals and how these chemicals are produced.

When I was a postdoctoral researcher in Germany in the late 90s, I had already started doing some work on cannabis, mainly trying to figure out how the plant makes THC.

I established my own lab at the National Research Council in Saskatoon when I returned to Canada in 2003 and continued research on cannabinoid biosynthesis and things relevant to the Canadian hemp industry. Hemp is a large acreage crop, but it’s still cannabis and has a lot of similar properties to marijuana.

I was doing small scale genomic studies on cannabis when, around 2009, I was contacted by Dr. Tim Hughes, a professor at the University of Toronto who studies genomics in many different organisms including humans and yeast. Tim basically said, ‘this is a fascinating plant and nobody has even attempted to do a whole genome sequencing project on it, yet it has so many uses and so much history with humanity.’ And medical marijuana was gaining more recognition in both the US and Canada at the time.

So we decided to collaborate on the sequencing of the cannabis genome, which merged my interests in plants, enzymes and cannabis specifically and Tim’s interest in genomics. And also, with cannabis being so important culturally, we wanted to focus on a project that would have some impact for society.

Q: What did the project involve?

Our two teams got together and we were able to obtain DNA of the marijuana strain Purple Kush. The reason we picked Purple Kush was that it was a widespread medical and recreational strain being grown in Canada at the time.

I also had access to various hemp cultivars, so we did the sequencing on Purple Kush, but also some re-sequencing of the hemp genome in order to compare the two types. One of the primary goals of our study was to identify the differences between marijuana and hemp on the genomic level.

Q: What were the major findings?

One major finding was that marijuana type cannabis and hemp type cannabis don’t actually differ by that much. For example, there are no extra copies of the genes for the enzymes of the cannabinoid pathway in the marijuana genome. And yet the plant makes much more THC and other cannabinoids. For example, we think Purple Kush contains around 20% THCA, the acid precursor to THC, and the hemp types contain approximately 5% CBDA.

So the differences don’t seem to be in the number of genes for these enzymes, but the fact that the expression of the cannabinoid pathway is turned up in the marijuana type. We suspect that there are specific regulatory controls, called transcription factors, that increased the expression of the genes for the cannabinoid pathways in marijuana. What this points to is that humans have probably been breeding for more potent marijuana by selecting for transcription factors that turn up the expression of these enzymes.

(Photo: Gagne et al., 2012)

The other major finding, which wasn’t new but was reinforced by our genomic analysis, is what really differentiates the cannabinoids found in marijuana versus hemp is a single enzyme at the last step of the cannabinoid pathway. In marijuana it’s the THCA synthase enzyme, and it’s the CBDA synthase enzyme in hemp.

Up to that point, the metabolic pathway is the same. But then there’s a genetically encoded switch, in which the allele that dominates differs in marijuana versus hemp. Sometimes you get both. For example, if you cross a THCA type plant and a CBDA type plant, the offspring will have each allele.

Others had described that at the genetic level, but they hadn’t really done it at the genomic level. So we proved that it was the split in the pathway at the last enzyme step that was responsible for this important chemical difference.

Q: Why map the cannabis genome as a whole?

Cannabis is an amazing plant: it produces fibre, edible seed, oil and of course cannabinoids like THC. Sequencing the cannabis genome is an important step in understanding the plant’s properties, and improving them for agriculture and medicine.

We felt making the genome itself available for researchers worldwide could really benefit research on all forms of this plant, both the hemp and marijuana types.

There are a lot of limitations on doing research on cannabis. It’s not an easy plant to have in your lab, as you need to obtain a special exemption or license to work with it. But we made the data available publicly through the web, so other researchers interested in things like cannabis evolution, sex determination, etc. could study aspects of the plant’s biology, even without having to grow the plant.

We really think it was an important step to make the genomic resources available and we hope it encourages others to do research on the plant.

The paper has been read by many people since being published, in the sense that it has been accessed more than 47,000 times through the journal website (genomebiology.com/2011/12/10/R102). It’s also been cited by a number of other papers. For example, a recent study from the UK, where they were attempting to breed hemp for different oil profiles.

Q: Is there anything particularly unique about the cannabis genome?

Cannabinoid production is unique to cannabis. No other plants that we know of have that capacity. So the genes that encode the enzymes required to produce cannabinoids are absolutely unique to the cannabis genome.

But overall, there wasn’t anything in the genome that we found exceptionally different from other plants closely related to it. For example, apples and strawberries are in a similar group as cannabis, and their genomes are known and cannabis was comparable to those.

Also, cannabis is closely related to hops. Humulus (hop) and Cannabis are the only two members of the Cannabaceae family. So those two plants are really, really close.

Q: What applications are there for cannabis genomics?

Plant breeding more and more relies on genomic tools. So as plant breeders want to develop new varieties of plants – whether they work on crop plants like wheat or medicinal plants like marijuana – the genome can be used to identify variations in the plants that are desirable. For example, you could breed for specific cannabinoid profiles if you knew the combinations of genes that are involved.

The other application is being able to sort out different strains and different variants in the hemp and marijuana areas. Marijuana in particular has thousands of strains, which have all sorts of interesting names, smells and shapes. What underlies all that variation are differences in the genome.

So applied genomics could be used to understand what makes different strains useful and interesting or also to identify them. For example, understanding the difference between Indica versus Sativa, which scientifically is not very well known at this point.

(Photo: kindgreenbuds.com)

Q: What about genetically modified cannabis?

I can say it hasn’t been achieved yet, in the sense that there is no genetically modified cannabis plants. As a scientist, I’m not opposed to genetic modification as a general concept, it just hasn’t been successfully applied in cannabis.

Also, a lot of what we’re finding is modern techniques of breeding can achieve many of the same outcomes of genetic modification. So I’m not 100 percent convinced that we need genetic modification in cannabis. But it’s probably something that will be attempted, and we may be seeing it in the next 5 years or so.

Q: Are you pursuing more projects in this field?

Yes. Our team who did the first study are going to be continuing to refine and improve the genome. We have a newly funded CIHR grant to continue this work. My new affiliation is with the University of British Columbia’s Botany Department, where I am an Adjunct Professor.

I’m also starting a company, Anandia Laboratories, to attempt to apply some of these genomic findings towards cannabis with improved therapeutic properties. The name Anandia derives from the endocannabinoid molecule anandamide.

Q: Is there more interest in cannabis genomics now than before?

Oh yeah, it’s amazing. For a number of years, I slogged along as kind of a lone voice in the wilderness working on cannabinoid biochemistry. Everyone was always interested in that work on the scientific level, but it’s a controversial plant and you always got the pot jokes whenever I gave a seminar.

But just in the last 6 or 8 months, there’s been a lot of interest in the genomic and biochemical research that I have done. I think there are two things that are driving it: the changes in regulations in Canada, which seem to have spurred a ‘green rush’, and the changes in Colorado and Washington State.

The new U.S. farm bill also allows research on hemp in 9 or 10 states, which they never were able to do before. So everything is sort of coming together, where cannabis was hot before, but now it’s suddenly white hot in terms of a research area.

Source Leaf Science

Kentucky Moves First On Hemp Research Projects

Hemp seed plant (Photo: D-Kuru/Wikimedia Commons)

The Kentucky Department of Agriculture has announced plans to conduct some of the first U.S. hemp studies, which are now legal under the new farm bill.

The state will partner with universities to investigate different aspects of hemp cultivation, Kentucky Agriculture Commissioner James Comer said on Monday.

A provision in the farm bill that passed this month allows research on hemp in states that have legalized the crop. So far, that includes Kentucky and nine others.

Comer is investigating the legality of commercial production under the farm bill, but says the first year of the program will likely be devoted to research and development.

The Department of Agriculture and various research partners will oversee the five hemp projects.

The projects are expected to begin March 31 and will include:

University of Louisville – A study of hemp’s potential to detoxify polluted soil on former industrial land.

Kentucky State University – A study of the cultivation potential of a “Kentucky heirloom hemp seed.”

Murray State University – A study of the cultivation potential of European hemp varieties.

University of Kentucky – A study of hemp cultivation for medical applications.

University of Kentucky, Eastern Kentucky University – A study of the basic agricultural aspects of hemp production, including production cost and machinery requirements.

Source Leaf Science

Scientists Develop New Line Of Cooking Oil From Hemp

(Photo: fdmount/Flickr)

A major breakthrough now allows hempseed oil to compete with other vegetable oils for cooking.

Scientists at the University of York have developed a new line of hemp that produces oil with a much longer shelf-life and higher temperature stability.

The breakthrough, published this week in Plant Biotechnology Journal, is believed to be a major step towards making hemp a commercially attractive oil crop.

“The new line represents a major improvement in hemp as an oil crop. Similar developments in soybean and oilseed rape have opened up new markets for these crops, due to the perceived healthiness and increased stability of their oil,” said study co-author Professor Ian Graham in a university release.

While standard hemp oil has a nutritional profile that tops other vegetable oils, its high polyunsaturated fat content makes it an unstable oil that turns rancid quickly. It is also unsuitable for frying due to its low smoke point.

But by using selective breeding processes, Graham and his team were able to develop a line of hemp plants that lacked the enzyme responsible for such high levels of polyunsaturated fats. The oil produced by these plants contained high levels of oleic acid, a monounsaturated fat, instead.

Oil from the new line, called “High Oleic Hemp”, was almost 80 percent oleic acid, compared with typical values of less than 10 percent.

This increases the oil’s shelf life by 5 times and also improves its usefulness for cooking and high temperature industrial processes, according to the team.

Trials conducted by the researchers found similar flowering time, yield and growth habits between the new line and the standard Finola hemp line.

The new line will begin trials across Europe this year in order to evaluate its cultivation performance and prepare for a commercial launch.

Source Leaf Science

For The First Time, U.S. Law Allows Hemp

(Photo: Gage Skidmore/Flickr)

On Friday, President Barack Obama signed into law the new farm bill, which includes an amendment allowing industrial hemp to be grown for research purposes.

While the farm bill only permits research in states with existing hemp laws, advocates still celebrated the turning point in federal policy.

“This is the first time in American history that industrial hemp has been legally defined by our federal government as distinct from drug varieties of Cannabis,” said Eric Steenstra, the president of Vote Hemp, in a press release.

Now, academic institutes in ten U.S. states will be able to study different varieties of the crop in order to guide future farming practices. The pilot program could pave the way to a legal hemp industry in the U.S.

So far, few farmers have been brave enough to try growing hemp, even in states that have legalized it.

Under the Controlled Substances Act, hemp is still considered the same as marijuana – a Schedule I substance – though it only contains trace amounts of the psychoactive chemical THC.

But importing hemp products, from countries like Canada and China, is not illegal. According to estimates by the Hemp Industries Association, more than $500 million (retail value) of hemp product was imported to the U.S. in 2012.

Source Leaf Science

Study: Hemp Seeds Show Promise In Managing Hypertension

Roasted hemp seeds can be eaten alone or added to dishes (Photo: Rubyran/Flickr)

New research suggests adding hemp seeds to one’s diet may help in both preventing and treating high blood pressure.

Researchers at the University of Manitoba believe hemp seeds could offer a safer alternative to drugs traditionally prescribed for hypertension. Previous studies, they note, suggest that proteins found in hemp seed possess a variety of cardiovascular benefits.

“Preliminary in vitro studies have shown that industrial hemp seed peptides possess both antioxidant and antihypertensive properties.”

In a new study, published in the European Journal of Nutrition, the team found that an 8-week diet of hydrolyzed hemp protein could slow the development of hypertension in genetically-prone rats.

What’s more, the diet was also effective at reducing signs of hypertension – plasma ACE and renin levels – in rats with already established conditions.

“The results confirm the potential of HMH (hemp seed meal hydrolysate) as a useful ingredient that can be used to formulate functional foods and nutraceuticals for the prevention and treatment of hypertension.”

While a number of foods have been found to help control blood pressure, the researchers suggest that the protein content of hemp seeds, as well as being easy to digest, make it an ideal choice.

“The presence of superior amino acid profile in hemp seed proteins (principally identified as edestin and albumin) and high digestibility promotes their efficacy as a source of health-enhancing bioactive peptides.”

Despite the positive results, more work still needs to be done. The team says the next step is to identify and purify the protein sequences responsible for its antihypertensive effects.

The study received funding from the Manitoba Agri-Food Research and Development Initiative (ARDI) and the Natural Sciences and Engineering Research Council of Canada (NSERC).

Source Leaf Science

U.S. On The Verge Of Relaxing Hemp Ban

(Photo V.H. Hammer/Flickr)

A provision that allows hemp research to be conducted in states where the crop is legal has a good chance of being passed as part of the new farm bill.

Congress released the final version of the five-year farm bill on Monday, which is set for a final House and Senate vote on Wednesday.

If passed, federal law would allow research institutes in 11 different states to import hemp seed and study its cultivation, explains Tom Murphy of Washington-based advocacy group Vote Hemp.

Climate differences between countries make this type of research essential, he adds.

“Agriculture colleges and other educational research institutions in states that have passed hemp farming laws would then be able to import seed from other places in the world, do research, and develop varieties that are well-suited to that state and to the United States in general.”

But what the farm bill won’t do is give farmers federal approval to grow the crop.

“We would still need to pass the Industrial Hemp Farming Act or have hemp removed from the definition of marijuana in the Controlled Substances Act.”

Murphy explains that industrial hemp is still defined as marijuana under federal law, even though it lacks the chemical that gets you high.

A bill introduced last year in both the House and the Senate, titled the Industrial Hemp Farming Act, aims to solve this problem by defining hemp as varieties of cannabis that contain less than 0.3 percent THC.

But while the bills sit in Congress, a number of states have already taken measures into their own hands.

In 1997, North Dakota became the first state to legalize hemp farming. Since then, the state has been joined by 10 others, Colorado, Hawaii, Kentucky, Maine, Maryland, Montana, Oregon, Vermont, Washington and West Virginia.

Yet only one farmer in the country, Ryan Loflin of Colorado, has been brave enough to plant a hemp crop, which he did last year.

According to Murphy, most farmers interested in growing hemp are still wary of the federal ban. Some have even been warned by the DEA of the consequences.

“If marijuana is defined as all varieties, then you would still have the mandatory minimums and you would still have the asset forfeiture proceedings that could be brought against a farmer for growing a crop that is illegal on the federal level.”

“So there’s still a whole lot of other things that need to be done,” he says.

Source Leaf Science