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Can “pharming” be sustainable?

Tobacco plants being grown by Guelph, Ontario-based Plantform for production of an Ebola vaccine. Source: Plantform

Per capita, Americans smoked nearly 150 cigarette packs a day in the mid-1970s. Forty years later that number has plunged by more than two-thirds, and a similar decline has been observed in Canada.

Use of “coffin nails,” as they’re sometime called because of their known contribution to lung and heart disease, is even on the decline within the companies that make them. Just this week, cigarette maker Reynolds American, the second-largest tobacco company in the United States, told its employees they can no longer smoke at work. The company said the new policy was “the right thing to do.”

The trend may be positive for our collective wellbeing, but it has left North American tobacco growers scrambling to find new markets and uses for their crops. Part of the answer, according to one Canadian company, is not what you’d expect: using tobacco plants to help fight the spread of the Ebola virus.

According to one report, health agencies in Canada and the United States have asked Guelph, Ontario-based Plantform to develop preventative vaccines for Ebola strains by genetically engineering tobacco plants. The company’s use of tobacco plants as a living pharmaceutical factory isn’t limited to Ebola. Plantform is also using the plant to make drugs for treating breast cancer, protecting against nerve agents, and fighting HIV/AIDS.

Tobacco plants are known for having unique properties. For example, when bugs land or crawl on a plant its leaves release chemicals that paralyze and kill parasitic insects. For Plantform, tobacco plants are ideal because they grow fast. On its website, the company says it can produce its plant-based vaccine or other drugs in as little as eight weeks, and at a fraction of the cost of using cells from animals or bacteria.

Experimental vaccine produced using genetically modified tobacco plants as the host "pharmaceutical factory." Source: Platform
Experimental Ebola vaccine. Source: Platform Corporation

Indeed, even Reynolds American is getting into the business. Its subsidiary, Kentucky BioProcessing LLC, is working with San Diego-based Mapp Biopharmaceutical on a tobacco-derived drug for treating Ebola, using a cocktail of antibodies developed at Canada’s National Microbiology Laboratory and licensed to Toronto-based Defyrus.

That experimental drug, called ZMapp, was given to Dr. Kent Brantly and Nancy Writebol, two aid workers who became infected by the virus this summer while in Liberia. Both have made a full recovery, which is probably encouraging to the doctor in New York City who reportedly tested positive Thursday for Ebola.

On its own, it’s a good news story. But the plant-derived Ebola treatment is symbolic of a new area of science that isn’t immune to controversy. Its critics consider it the antithesis of sustainability, while proponents paint it as a more sustainable path to drug development in a growing world filled with pain and poverty.

 

Health and Social Benefits

Manipulating plants to produce pharmaceutical compounds is a relatively new technique called plant molecular farming, and the results of early experimentation date back about 25 years. More colloquially, the practice is referred to as “pharming” – and it’s not limited to tobacco. Corn, rice, canola, alfalfa, safflower, tomatoes, and potatoes have all been used in laboratory settings as hosts in drug production, tackling everything from cystic fibrosis to tooth decay.

In essence, scientists isolate or synthesize a specific gene that creates certain proteins, such as those in insulin. This DNA is then inserted into a seedling plant, which as it grows creates the proteins as if it were their own. The plants can also be modified so that the target proteins become concentrated in leaves or seeds. The leaves, for example, can sometimes be dried and taken orally, or the proteins can be extracted, refined and used in the production of pills or liquids that can be injected.

In 2012, the first plant-derived drug approved by the U.S. Food and Drug Administration for human consumption was produced from carrots, which were genetically modified to carry an enzyme that alleviates painful symptoms related to Gaucher disease.

Plant pharming not only allows for faster turnaround of vaccines and other drugs. Biotech companies are lured to its promise because the process is relatively low-tech and, as a result, much less expensive. It doesn’t require the costly and complex bioreactor vessels typically used when working with bacteria and yeast.

This holds great promise for the research of pharmaceutical products for illnesses that, because they are so rare, don’t represent an attractive market for drug developers. The potential for lower-cost manufacturing of drugs would also benefit poorer countries that lack affordable access to medicines and vaccines.

It’s also easy to scale production up or down as demand requires. “It has been estimated that 250 acres of greenhouse space would be sufficient to meet all of South Asia’s requirements for hepatitis B virus vaccine,” according to the Pharming the Future research project, conducted through the University of Calgary. A 2011 study from microbiology researchers at the University of Central Florida contended that an “acre of tobacco could yield up to 20 million daily doses of insulin per year.”

Finally, in the case of vaccines and other temperature-sensitive drugs, the end product can often be in the form of a freeze-dried, edible plant that doesn’t require refrigeration. Its natural “packaging” can be in the form of seeds and fruit, not capsules or vials. The fact it can be stored without needing to be kept cold is a huge benefit in the developing world where electricity is unreliable or non-existent.

 

Environmental Question Mark

When it comes to genetically modifying any organism, however, there’s always a tradeoff that many are not willing to make. We’re stuck with an enduring question with no easy or obvious answer: Do we take advantage of fairly certain social gains, such as better access to medicine and potentially more affordable drugs, knowing there are environmental and health uncertainties we may regret over the medium and long term? Do we accept what risks exists or fall back on the precautionary principle, as Europeans have when it comes to genetically modified foods?

The controversy came to a head in 2002 when it was revealed that a corn crop engineered to make a protein for a pig vaccine was plowed into the soil, which was used a year later to plant 500,000 bushels of food-grade soybeans. The soybeans became contaminated, and while the problem was discovered before it could affect food supply, it still fed the fury of environmental and food-industry groups strongly opposed to pharming.

Friends of Earth accused the U.S. Department of Agriculture of “endangering the U.S. food supply.” The Grocery Manufacturers of America warned there was “no room for trial and error.” A consumer, environmental and farmer coalition ended up suing the government, calling its subsequent attempts to strengthen regulation too weak and ineffective.

The biotech industry didn’t think so. The new rules proved too heavy-handed – many clinical trials were discontinued and startups working in the area collapsed. “That ended most entrepreneurial interest in biopharming,” Henry Miller, a molecular biologist and fellow at Stanford University’s Hoover Institution, wrote in a recent column on Forbes.com. It created a chill north of the border, too. To this day, pharming still hasn’t been approved in Canada on a commercial scale, though more tightly controlled research trials have been permitted in recent years.

A greenhouse used to grow tobacco for Ebola vaccines. Source: Plantform
A greenhouse used to grow tobacco plants for drug production. Source: Plantform

The risk to food-grade crops was and is real, and potentially serious. But Miller dismissed this fear as “overblown” and easy to avoid with certain measures. “Production in a non-food crop is an obvious one,” he wrote, pointing out that one developer of a Norwalk virus vaccine used tomatoes at first but then switched to tobacco plants to avoid tussling with regulators and environmentalists.

“The risk of plant-made drugs getting into food products is now virtually non-existent because the companies involved have switched to production in facilities with rigidly controlled environments, using mainly tobacco,” Miller added.

The move toward highly controlled facilities, such as greenhouses and labs, is crucial. The use of open-air fields doesn’t just risk contamination of nearby food or animal feed crops through the spread of pollen and seeds, it also threatens wildlife or livestock that might be grazing in the area. It could also harm or negatively alter organisms that live in the soil, not to mention pollinating and plant-eating insects – and it’s not like bees and butterflies don’t have enough problems with which to deal, such as insecticides sprayed on “normal crops.”

“Compounds from plants developed for plant molecular farming purposes may have physiological effects on humans and other organisms,” warns the Canadian Food Inspection Agency on its website. And while research so far shows no significant behaviourial and reproductive impacts on the pollinators and other organisms that have been studied, it’s still early days. The Canadian government will eventually allow commercial pharming – it seems all but inevitable – but currently it will only say it is “investigating policy options.”

 

A Net Gain?

Nuclear power. Genetically modified food production. Manipulation of algae to create biofuels. All carry risks. It comes down to what risks we are willing to accept in exchange for the known benefits, such as preventing an Ebola pandemic. It also comes down to the trust we have in the people in charge of limiting those risks.

Clearly, much can be done to minimize any health or environmental threats posed by plant-derived pharmaceutical production. Crops can be grown in specially constructed greenhouses that prevent entry by rodents and insects and stop pollen and seeds from escaping. Such structures can have air-lock entry systems for workers, who can be made to wear protective suits and required to shower down when departing.

There has even been talk of building these facilities in underground caverns and mines, and work has been done to grow sterile plants that can’t reproduce, even if seeds somehow enter wild fields or the food system.

As environmental journalist and Cornell University fellow Mark Lynas once wrote, “this application of modern technology to agriculture need not be remotely scary.”

Some precaution and good old common sense can go a long way. But like the GMO controversy generally, the debate seems destined to continue indefinitely. When it comes to pharming specifically, crisis is what will likely drive us – in one direction or the other.

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