A gene-edited tobacco plant created using the CRISPR technique has the lowest ever amount of nicotine. It could boost efforts to reduce nicotine in cigarettes to non-addictive levels, as the US plans to do.
Felix Stehle and Julia Schachtsiek at the Technical University of Dortmund in Germany used CRISPR to disable six enzymes involved in the production of nicotine in the tobacco plant. They started with a strain that usually contains 16 milligrams of nicotine per gram of dry tobacco, but their gene-edited version has just 0.04 milligrams of nicotine per gram – a reduction of 99.7 per cent.
It is almost undetectable, says Stehle.
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Low-nicotine cigarettes are just as dangerous as normal ones because other substances damage the lungs and cause cancer. However, such cigarettes prevent people becoming addicted and help them give up, according to a 2015 report by the World Health Organization (WHO).
Trials of cigarettes with very low nicotine levels show that existing smokers don’t smoke more to compensate. “That was a surprise to people,” says Alan Boobis at Imperial College London, one of the authors of the WHO report.
The report proposed reducing nicotine levels in cigarettes to non-addictive levels to eliminate smoking worldwide. That proposal was never officially adopted as policy, says Boobis, but he hopes the WHO will review it.
Meanwhile, some individual countries are pursuing this approach. In March 2018, to force manufacturers to reduce nicotine in all cigarettes.
“Approximately 5 million additional adult smokers could quit smoking within one year of implementation,” the then US Food and Drug Administration commissioner Scott Gottlieb said at the time. By 2100, more than 33 million people in the US would have avoided becoming regular smokers, the FDA said.
Before Stehle and Schachtsiek’s work, the lowest level of nicotine in any tobacco was 0.4 milligrams per gram. This is in a strain created by using conventional, non-CRISPR genetic engineering.
Even this level of nicotine could still be addictive, the WHO report noted. “It would be worth testing a lower nicotine content cigarette,” says psychiatrist Dorothy Hatsukami at the University of Minnesota, another author of the WHO report.
Stehle did approach one big tobacco company, but those he dealt with weren’t interested in the CRISPR tobacco. “Maybe they are not interested in selling nicotine-free cigarettes because they are less addictive,” he says.
However, Stehle says the pair’s work isn’t patentable, meaning anyone could use the same approach to make their own low-nicotine tobacco strains. “It’s really easy,” he says.
Very-low-nicotine cigarettes are quite different to the cigarettes that used to be labelled as “light” or “low tar”. These cigarettes are made from normal tobacco – they just have holes in the filter to dilute the smoke in each puff. There are also a wide range of cigarettes sold as “nicotine-free” that are made from plants other than tobacco.
Plant Biotechnology Journal
