Tobacco in the Service of Pharmacology

Nicotiana_tabacum

(This post refers to an article I co-wrote with James Hale for the October 2015 issue of Pharmaceutical Engineering. You can read the entire article by clicking on the image above.)

Our relationship with tobacco is fraught. Few plants have been as closely associated with humans, and for so long. Leaves of the wild plant were smoked 8000 years ago. Its cousin, Nicotiana tabacum, is one of the oldest plants grown purposely by humans, with evidence of cultivation in Mexico as long ago as 1400 BCE. Columbus came across indigenous people smoking tobacco in Cuba, and Hernández de Boncalo took seeds to Europe in 1559. It continues to be used ceremonially by the indigenous peoples of the Americas and many consider it a sacred medicine.

When I lived in Nova Scotia, I came across many Shambhala Buddhists, particularly when I lived and worked at Windhorse Farm. One of the challenging concepts that they tried to help me wrap my head around is the idea that things are inherently empty – devoid of meaning and value until we invest them with these qualities. We tend to believe that something is true or false, admired or hated, and that these are immutable qualities. Hamlet echoes this when he says to Rosencrantz, “for there is nothing either good or bad, but thinking makes it so.”

But what about tobacco? Isn’t it the exception that proves the rule, that it is one thing this is universally reviled. Worldwide, one billion people smoke tobacco, lung cancer accounts for 27 percent of cancer deaths and 80 percent of these deaths result from smoking. Many additional cancers of the GI tract can be attributed to smokeless tobacco products. Can any good come from tobacco?

The short answer is, yes. Nicotine from tobacco was used in the 17th century – and continues to be by some organic farmers – as the first plant-derived pesticide. Nicotine extracted from tobacco is used in nicotine replacement therapy. Using transgenic tobacco plants, biopharmaceutical companies are developing plant-derived monoclonal antibodies (mAbs), complex biologics that provide unparalleled specificity and targeting as pharmaceuticals. These biologics have been used for rheumatoid arthritis, transplant rejection and some cancers.

To date, only one biopharmaceutical extracted from a transgenic plant has been approved—Elelyso (Pfizer and Protalix) for the treatment of Gaucher disease. Many more are in the pipeline, including biologics for use in the treatment of breast cancer.

The 2014 Ebola outbreak in West Africa highlighted how ill prepared we are for such an epidemic. With neither vaccine nor other tested treatment available at the time (rVSV-ZEBOV is currently being tested by Merck), health authorities turned to experimental drugs. One of these, ZMapp, is a biologic cocktail (developed by Mapp Biopharmaceutical from research it conducted with the Public Health Agency of Canada, Kentucky BioProcessing and the National Institute of Allergy and Infectious Disease) designed to provide passive immunity against the Ebola virus. It consists of three human-mouse chimeric mAbs synthesized in Nicotiana benthamiana. Of the ten Ebola patients treated with ZMapp, eight survived. There were only that many doses because, at this point, it takes 6000 pounds of tobacco to make even a few dozen doses. To scale this in anticipation of a future epidemic, more research and development is needed.

Tobacco, so long a public health menace, may soon be a source of life-saving biopharmaceuticals.

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