In Quebec City, a greenhouse is chock full of alfalfa whose slender, green bodies contain antibodies to fight cancer.
Outside of London, Ont., rows of tobacco plants are manufacturing a potential edible drug that could trigger the body’s immune system to fight type I diabetes, Crohn’s disease, multiple sclerosis and organ transplant rejection.
In Calgary, the common safflower — grown in Canada only as bird feed — has been altered to produce either insulin or a drug to prevent arteriosclerosis.
Welcome, city slickers, to the pulsating, if not quite realized, world of biopharming.
The scientific basis for what is also called molecular farming is research first done more than a quarter century ago that showed that a gene is a gene is a gene. For example, when a gene for human insulin was put in the E. coli bacteria, the bacteria happily started producing human insulin.
“Plants, although they look a lot different than humans, are actually a lot closer to humans than bacteria are,” says Maurice Moloney, co-founder and chief scientific officer of SemBioSys Genetics Inc. in Calgary, which is developing protein-based pharmaceutical and non-drug products in safflower crops. “Add a foreign gene and a plant with high fidelity will do what the original host did.”
Insertion is achieved with a variety of processes ranging from tiny, gene-shooting guns to bacteria that “infect” a host organism with the foreign DNA. One virtue of a plant is that you can do all this insertion in a cell culture and then grow the whole plant from it.
There is a three-fold impetus behind the efforts to grow drugs in plants.
The first is that it already happens in nature: Aspirin, for example, from willow bark and codeine from the poppy, not to mention Chinese and western herbal medicines that rely on healing drugs naturally appearing in plants.
Second, the drug industry already uses bioengineered microbes and animal cells to produce a number of drugs. E. coli and insulin is a classic example. Since you can do it in other living creatures, why not in plants?
The third, and maybe the most important, reason is that producing drugs by other bioengineering means is super expensive.
At a conference on plant-made pharmaceuticals in Montreal earlier this year, speakers estimated that it cost $500-million (U.S.) and more to build each facility that houses the drug-expressing bacteria or animal cell culture, including two 10-metre-tall, stainless-steel 50,000 litre tanks. For a fraction of that the same drugs could be produced and extracted from plants.
Dr. Moloney estimates that two average-size Prairie safflower farms — somewhere between 4,000 and 8,000 hectares — could supply a quarter of the world’s 14-metric-tonne needs of insulin in 2015.
Even better, if there was a change in the market, the plant-based manufacturing process could quickly respond.
For example, researchers at the University of Guelph have been working on a tobacco-based “plantidote” for possible bioterror attack of the botulism bacteria. They’ve calculated that four to eight hectares of genetically engineered tobacco would provide enough antidote to treat a million people — and the treatment could be available in a few days.
So why have no plant-derived biopharmaceuticals made it to market yet?
A key technological issue is finding the best plant — technically called a “platform” — to use in making given drugs.
As part of the worldwide effort to produce plant-grown drugs, researchers have tried corn, rice, barley lettuce, flax, tobacco, sugar cane, alfalfa, potato, tomato, banana, moss, duckweed and cowpea.
Why so many? In choosing a plant host for a drug, several issues collide.
One is that the plant must produce the drug in a large enough quantity to make refining worthwhile. If only a millionth of a gram is expressed per plant, the process won’t be economical.
Another is that when animal genes are inserted into plants, sometimes the plant adds sugars to the proteins the inserted genes produce. The process is called glycosylation and there are worries this might affect how the human body responds to some plant-made drugs.
But overriding everything is the considerable political resistance to bioengineered plants, particularly in food crops.
One fear is that the drug-laced crops could pollute the general food supply. In 2002, for example, a pharmaceutical-bearing corn sprouted in a Nebraska soya field after the tests for the corn had finished. As a result, about 500,000 bushels of soybeans were quarantined and then bought and destroyed by the biopharming company that created the corn.
Another fear is that genes carrying the drugs will be spread via pollen to food crops in nearby fields.
Because of the ecological concerns, “people fear that [plant-made pharmaceuticals] will never be released or only grown in greenhouses or in very limited field trials,” says Shengwu Ma, co-founder of Plantigen, a London, Ont., based company growing drugs in tobacco in greenhouses.
To head off those concerns, SemBioSys, which plans to grow its bioengineered safflower outdoors, has developed strict guidelines, including not growing a pharmed crop within 80 kilometres of a food crop or another biocrop. Because insects and not wind spread safflower pollen, Dr. Moloney believes that will cover pollution concerns.
Quebec City-based biopharmaceutical company Medicago Inc. — the name comes from the Latin word for alfalfa — acknowledges that it grows its test alfalfa, with antibodies for cancer in them, only in greenhouses because of public concerns over GM contamination.
“Because of the way we structure our growing there is no risk of gene disposal, because we are not in the field,” says Medicago president Andy Sheldon. “. . . I don’t think it [gene dispersal] is really a problem but from a public relations perspective we have solved this worry.”
However, using greenhouses add expense to the process. “You have to grow high-ticket things to offset the costs of greenhouses,” says Paul Arneson, general manager of FAAR Technology, who recently wrote a report on the state of the industry in Canada.
Mr. Sheldon responds that while greenhouses are more expensive, his company hopes that the ability to grow up to 10 harvests of alfalfa in a year will offset the cost.
Canada is not alone in trying to make biopharming something more than a cool idea. In the United States, five or six small companies and some Big Pharma corporations, including Syngentia and Dowpharma, are actively involved in the field.
Last year, the European Union allotted $12-million to a consortium of researchers from 11 member countries and South Africa toward Pharma-Planta, a five-year project aimed at using plants to produce vaccines and other treatments against such diseases as AIDS, rabies, diabetes and tuberculosis.
Both Medicago and SemBioSys have formed alliances with drug companies interested in seeing whether they can grow new drugs, and they hope to have products on the market in less than five years. The first commercial product will be the real test of how well biopharms can compete in the cutthroat world of drug production.
That breakthrough day may be sooner rather than later. Last year, a review article listed nine plant-made drugs that were in clinical trials.
The French company Meripase has announced that corn bioengineered to produce a drug for multiple sclerosis had passed the second stage of clinical trials — that is, has shown itself to be more effective than a placebo in mitigating some of the worst effects of the disease. Plant Biotechnology Inc. in California also has an antibody against tooth decay that is in phase II clinical trials.
If the ecological and technical hurdles can be overcome, its advocates believe that the future of medicine must include the manufacture of drugs in plants. “Plants are the least expensive way on the planet of making protein,” Dr. Moloney says. “We believe we can reduce the price of making insulin by more than 50 per cent and we might be able to bring it down to a third of the present figure.”
One ironic upshot of the drive to get something to market, is that instead of being rivals, the various plant-made pharmaceutical firms are cheering each other on.
“Any success for Medicago would be a success for us,” says Dr. Maloney, “and vice versa.”