Race to the bottom

| February 1, 2017

Some scientists continue to support the idea of lowering nicotine levels. But is it a realistic harm reduction strategy?

By George Gay

Over the years, I have attended a lot of symposiums at which learned people have presented wide-ranging research on tobacco consumption and its effects. But because, in most cases, I have had little knowledge of the science they were describing, what I have usually taken away from these sessions is simply a feeling that the person who was speaking was not a tobacco consumer, had never been a tobacco consumer and had little “feel” for the product.

The question is: Is this lack of direct experience in the product under consideration important? Generally, I would say that it is a negative factor if the person in question is in a position of being able to influence policy in relation to fundamental aspects of the product—its formulation, say, rather than the way it is to be marketed. I say generally because, for obvious reasons, in some cases people have to help devise policies in respect of products that they have never consumed.

In the recent past, a good deal of research has been focused on examining the idea that cigarettes with a low level of nicotine represent a way forward in the quest to get people to quit smoking. As I understand it, such cigarettes would deliver a level of nicotine below that believed to be necessary to addict new smokers or to maintain addiction in existing smokers.

This research continues, and some of the people pursuing it readily call for more research to be carried out even though, as far as I know, low-nicotine cigarettes have been rejected by smokers wherever and whenever they have been launched. Many of the researchers, I’m certain, would happily sign up to the adage that smokers smoke for the nicotine but die from the tar. But here they are, on the face of it, advocating as a harm reduction strategy the launch of a product that would require a smoker to ingest hugely increased amounts of tar to obtain the nicotine she needs.

Why? I don’t really know, but one thought that has occurred to me is that some researchers seem to be possessed of the ability to live comfortably with opposing views firmly lodged in their brains. Some of these researchers, for instance, seem to believe that nicotine is the most addictive substance of all legal and illegal substances, but believe also that nicotine addiction can be broken by requiring cigarettes to be sold in packs that show the picture of a mouth with dental decay.

I’m not suggesting that all researchers don’t get it. Some get it right by asking the right questions of the right people. Toward the end of last year, the Centre for Substance Use Research (CSUR) in Glasgow, Scotland, published the results of a survey funded by the U.K. smoker group Forest that found that 95 percent of the 600 participating smokers gave pleasure as their primary reason for smoking. What is important here is that the academics carrying out the survey took the trouble to speak to committed smokers, and what they found was different from what we are usually told: that most smokers wish they had never taken up the habit and that all they ever think about is quitting.

“Minimally addictive levels”

nicotine photoAnd yet …. Despite my conviction that researchers often see only the cost of smoking and not the value of it, and are therefore probably incapable of looking at this subject in a meaningful way,
there remains for me the nagging doubt that learned people have devised and recently resurrected this low-nicotine strategy and that it is being considered by such bodies as the U.S. Food and Drug Administration (FDA) and the World Health Organization (WHO).

So in order to examine the positive side of the low-nicotine strategy, I tried, unsuccessfully, to talk with the people at 22nd Century Group, which describes itself as a plant biotechnology company that is a leader in tobacco harm reduction. But, no matter; an Oct. 13, 2016, press note issued by the group discusses some of the issues that I wanted to raise.

The press note, titled “22nd Century very low-nicotine cigarettes could reduce U.S. smoking rates by more than 75 percent,” said that a group of leading scientists in the U.S. and New Zealand had published a “special paper” in an international peer-reviewed journal strongly advocating for a national nicotine reduction policy.

The article, published in the September 2016 issue of Tobacco Control, outlined the “compelling and urgent case” for enacting a national nicotine policy in order “dramatically” to lower smoking rates. The authors were said to have cited results from many of the 15 major clinical studies conducted with 22nd Century’s very low-nicotine (VLN) tobacco.

“Drs. Eric Donny, Natalie Walker, Dorothy Hatsukami and Chris Bullen authored the special paper that asserts governments around the world should reduce the nicotine content of cigarettes to ‘… ≤ 0.4 mg per gram of tobacco, a 95–98 percent reduction in nicotine content relative to what is currently on the market,’” the 22nd Century press note said. “The Tobacco Control article reinforces the World Health Organization recommendation that member countries ‘mandate reductions in nicotine to minimally addictive levels.’

“With ownership or exclusive control of more than 200 patents on the genes in the tobacco plant that regulate nicotine production, 22nd Century is the only company in the world capable of growing tobacco with up to 97 percent less nicotine than conventional tobacco plants. Company scientists believe that at just 0.04 mg per gram of tobacco [presumably yield], nicotine is nonaddictive and yet still present in sufficient amounts to stimulate a small number of bio-receptors in the brain, thus greatly reducing cravings in smokers.”

Left unsatisfied

nicotine photoThis last-quoted sentence is interesting. It seems to say that a smoker who converts to a low-nicotine brand would find some of her cravings satisfied, but not all of them, and this raises the question as to what she would do about her unrequited cravings. One obvious strategy that she might employ would be to increase her consumption of the low-nicotine cigarettes, but since they would be delivering also tar, the risky element of the product, this seems not to be a strategy that could be recommended for risk reduction. And it surely raises the issue of whether or not the smoker would start changing the way in which she smoked, possibly resurrecting some of the negative factors that apparently arose when smokers started consuming “light” cigarettes.

Another way to overcome the satisfaction deficit might be for the smoker to consume the low-nicotine cigarettes while applying to herself an appropriate number of nicotine patches, but I rather think that using patches and smoking at the same time comprises a strategy that would be frowned upon by health authorities, for at least one obvious reason. Of course, such an objection could be overcome if the low-nicotine cigarettes were supplemented not by nicotine patches but by nicotine from a vapor device such as an e-cigarette. But would the FDA, for instance, be able to sanction such activities? Could it recommend that a smoker of traditional cigarettes switch to low-nicotine cigarettes, presumably with all of the health implications of the traditional product, plus a vapor product that it seems to believe is riddled with potential, unseen dangers? It seems unlikely.

A third way would be for the smoker to supplement the low-nicotine cigarettes with traditional cigarettes, but, unless the low-nicotine cigarette had a taste hugely superior to that of any traditional brand, this development is going only in one direction: The smoker is going to rationalize her product purchasing by concentrating on the regular cigarettes that provide the satisfaction she craves. And one thing we know is that low-nicotine cigarettes do not offer a hugely superior taste. For instance, in its press note, 22nd Century says that its “proprietary very low-nicotine Spectrum, Magic and Brand A cigarettes have the taste and sensory characteristics of conventional cigarettes.”

Backdoor prohibition

nicotine photoOf course, there is more than one way of handling things, and the question arises as to what would happen if a government were to decide that all cigarettes sold on the market over which it had jurisdiction were to be low-nicotine products, thus removing the competitive element and the opportunity for smokers to supplement their low-nicotine cigarettes with traditional brands. Well, as a number of commentators have pointed out, this would simply be a case of prohibition by the back door because the government would be banning cigarettes as they are currently defined. And even if one is in favor of prohibition, it is obvious that there is a more straightforward way of introducing it.

Some people have suggested that, as above, governments should require, insofar as they are able (insofar as the illegal trade will allow), that only low-nicotine cigarettes be made available to smokers, and others have suggested that governments might do so. But it has to be said that 22nd Century seems to see its brands competing with traditional brands—certainly on the U.S. market. “We think the United States could—and should—be the first country to require all cigarette manufacturers to offer consumers a very low-nicotine brand style alongside their existing products,” Henry Sicignano III, president and CEO of 22nd Century, was quoted as saying in the October press note.

One way perhaps of getting over the competitive problem and the prohibition objection would be to introduce nicotine reductions gradually, so that the nascent low-nicotine brand had its nicotine delivery reduced by, say, 5 percent a year. This, too, would not be without its problems, however. In this case, for a good number of years the nascent low-nicotine brand would presumably still be addicting new smokers, and possibly encouraging its consumers to smoke more cigarettes than they otherwise would.

Additionally, the question would arise as to whether it would be technically possible to lower the amount of nicotine by a controlled, relatively small level from year to year. And if it were technically possible, would the cost of doing so allow the sale of such cigarettes at prices acceptable to smokers, with or without government excise concessions, given that governments were willing to make such concessions? I don’t know—partly because I don’t know whether low-nicotine tobacco can be produced simply through genetic manipulation of the plant, or whether the tobacco has to be modified during processing.

However, such a gradual reduction might—and I emphasize, might—be what the Tobacco Control paper was suggesting. “The Tobacco Control article authors suggest that such a national nicotine policy could be the centerpiece legislation necessary for New Zealand to reach its goal of becoming smoke-free by 2025,” the 22nd Century press note said. “Because the island nation has a clearly defined goal of becoming smoke-free (< 5 percent prevalence by 2025), and because regulators and tobacco control experts in New Zealand have well-developed tobacco control programs in place, the Tobacco Control paper recognizes that New Zealand presents a ‘unique opportunity’ to implement a nicotine reduction policy for combustible cigarettes.”

Global considerations

nicotine photoUp until now, I have been looking at the application of a low-nicotine cigarette strategy to a single market of modest size. But what would happen if it were to be applied to a big market or even internationally via the urgings of the WHO’s Framework Convention on Tobacco Control? Certainly, such a development would raise a number of issues. At the moment, as one company seems to hold the patents on producing the necessary tobacco, I presume that it would take a fairly long time to scale up production to cater for a large market or for an international one, given that tobacco is grown in many countries, presumably with different attitudes to the genetic manipulation of plants. And so I cannot help wondering why, since the world already has in place a number of promising products with considerable success at getting people to quit smoking, it would be considered a good idea to go down a road whose benefits seem to stretch into the distance?

I don’t know, for instance, whether low-nicotine tobacco has been produced and tested in respect of all the types and varieties currently being used around the world. And have the questions of the acceptability of and attitudes toward genetically modified tobacco been addressed? Clearly, in some parts of the world products with genetically modified ingredients are more acceptable than they are in others, and questions of acceptance will vary from individual to individual across all markets. It would be wrong to force—because of her addiction—a smoker to consume a genetically modified product if she had some ethical reason for not doing so. On the other hand, would we discover sometime in the future that some smokers read a “genetically modified” label as meaning “safer”?

One aspect of the 22nd Century note about the Tobacco Control paper is ironic given the extreme caution, verging on hostility, that the FDA and the WHO have applied to their dealings with products such as snus and e-cigarettes. Donny and his collaborators were said to have pointed out the cost of delaying policies to reduce nicotine: “Waiting for the results of [additional] trials before seriously discussing a [nicotine reduction policy] that is rooted in decades of research … could delay potential action and ultimately lead to a failure in efforts to more rapidly improve public health.”

What is being suggested here is that the FDA, for instance, should dispose of the niceties of further research and just get these low-nicotine cigarettes onto the market. But hang on; from what I understand, these low-nicotine cigarettes involve the consumer and those close to her in inhaling all of the products of combusted tobacco, and so presumably involve them in all of the health risks associated with users and secondhand smokers of regular cigarettes. Surely, the FDA is not suddenly going to act in such a cavalier fashion. The FDA is an organization that, in the case of one brand of snus, an oral tobacco product, the consumption of which is almost certainly more than 90 percent less risky than is smoking low- or high-nicotine cigarettes, took almost 2 1/2 years mostly to fail to reach a decision on whether to allow amendments to health warnings associated with this product that a prominent U.S. public health expert described as “egregiously inaccurate” (see “Trailblazer,” page xx). The FDA has suggested that the process of applying for the amendments should be dragged out—possibly for another two years.

On this basis, it beggars belief that the FDA could suddenly introduce a low-nicotine policy. And, indeed, this seems to be the case. 22nd Century’s wholly owned subsidiary, Goodrich Tobacco Co., submitted on the last day of 2015 a combined modified-risk tobacco product (MRTP) application and premarket tobacco product applications for 22nd Century’s “Brand A” VLN tobacco cigarettes. The MRTP application apparently seeks only to state, “as truthful and accurate in Brand A packaging and marketing, that the company’s proprietary very low-nicotine cigarettes reduce smokers’ exposure to nicotine.” But it wasn’t until Jan. 5, 2017, that 22nd Century announced that it had received from the FDA “helpful and positive feedback” on its applications.

I would like to quote one other section of the 22nd Century note. “Building on the results of previously conducted clinical studies, the Tobacco Control article authors summarize the highly attractive characteristics of VLN tobacco: ‘… In current smokers, very low-nicotine content … cigarettes decrease nicotine exposure, decrease cigarette dependence, reduce the number of cigarettes smoked per day, and increase the likelihood of contemplating, making and succeeding at a quit attempt.’”

This seems to echo the start of this story. It has to be noted that the “highly attractive characteristics” referred to are, I assume, highly attractive insofar as the researchers are concerned. But unless force is used, it is the smokers who will ultimately decide whether these products are attractive enough to consume.

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