History
In 1998, Joseph Pandolfino founded 22nd Century to provide funding to North Carolina State University (NCSU) for a research and development collaboration on nicotine biosynthesis in the tobacco plant. Mr. Pandolfino’s hypothesis: If it were possible to produce tobacco cigarettes without nicotine, smokers could use these extraordinary cigarettes to successfully quit smoking.
A paradox to be sure. Nonetheless, Mr. Pandolfino’s hypothesis stemmed from his careful observation of real smokers. As an importer of tobacco-free herbal cigarettes, Mr. Pandolfino had come to realize that some consumers were using nicotine-free herbal cigarettes to successfully quit smoking. Anecdotal evidence suggested that this approach was actually quite effective; the biggest problem with the novel “therapy” was the fact that herbal cigarettes have distinct taste and aroma characteristics which greatly limit their consumer appeal and acceptance.
Indeed, though various processes were developed to improve these herbal products, it became clear that their peculiar taste and aroma characteristics would never appeal to mainstream smokers, thereby greatly limiting their purpose: smoking cessation. If, on the other hand, a tobacco cigarette without nicotine could be developed, Mr. Pandolfino believed it could prove very attractive to any and all smokers desiring to quit. With this in mind, Mr. Pandolfino set out to investigate the feasibility of efficiently producing tobacco cigarettes without nicotine.
Already Philip Morris had developed a proprietary process to extract nicotine from tobacco; however this process, similar to that of producing decaffeinated coffee, proved very costly. What’s more, these “denicotinized” cigarettes (test-marketed from 1989 to 1991) simply did not taste very good. Philip Morris concluded that in the denicotinization process, various other leaf compounds important to tobacco’s taste characteristics were extracted along with the nicotine. The denic process is not selective for nicotine and “resulted in a dramatic change in the taste of the original tobacco” (Philip Morris 1994).
Therefore, Mr. Pandolfino concluded, the key to producing a cigarette with virtually no nicotine—that smokers would find acceptable—is the ability to grow tobacco plants whose intrinsic nicotine content is a tiny fraction of that found in conventional tobacco plants. This conclusion led Mr. Pandolfino on a journey to acquire and develop the know-how and technology, including formal intellectual property rights, to block nicotine biosynthesis in the tobacco plant through genetic engineering.
To this end, in 1997 Mr. Pandolfino met Dr. Mark Conkling, Director of the Biotechnology Programs at North Carolina State University. Dr. Conkling had recently cloned a key gene in the tobacco plant responsible for nicotine production. Dr. Conkling believed expression of this gene could be blocked to produce tobacco plants with virtually no nicotine. Mr. Pandolfino concurred and the result of their meeting was a successful 5-year research collaboration between 22nd Century and NCSU that resulted in a patented very low nicotine (VLN) tobacco variety (Xie et al. 2004). This became the first genetically modified tobacco variety deregulated by the Animal Plant & Health Inspection Service (APHIS) of the United States Department of Agriculture.
In 1999, 22nd Century exclusively sublicensed this proprietary technology and VLN tobacco to Liggett Group, the fifth largest cigarette company in the United States, and shortly thereafter to other subsidiaries of Vector Group Ltd. (Wall Street Journal 2001). In 2003, Vector Tobacco Inc., an affiliate of Liggett, marketed in eight U.S. states Quest®, a novel cigarette brand containing 22nd Century’s proprietary tobacco, to gather data for the FDA approval process of Quest® as a smoking cessation aid. Quest® also utilized Mr. Pandolfino’s product concept comprised of a series of cigarettes with the same “tar” yield but progressively reduced nicotine content for use in smoking cessation.
In 2006, Vector Tobacco sponsored a multi-center Phase II smoking-cessation clinical trial to evaluate the effectiveness of Quest® alone or in combination with nicotine replacement therapy. (Becker et al. 2008). This trial was performed under Vector’s Investigational New Drug Application (IND) filed with the FDA in 2004. After conveying that it intended to proceed with Phase III clinical trials, Vector Group Ltd. announced that Vector Tobacco was no longer pursuing FDA approval of its smoking cessation aid in development. Accordingly, 22nd Century’s licenses to all affiliates of Vector Group Ltd. were terminated. Subsequently (in 2008), 22nd Century obtained rights to use and reference at the FDA all data in Vector’s IND, including all results from the Phase II clinical trial, relating to cigarettes containing 22nd Century’s proprietary tobacco.
From 2005 to 2009, 22nd Century partnered again with NCSU and with other public institutions in Japan and Canada in research projects to clone additional genes responsible for nicotine production in the tobacco plant. 22nd Century’s contracted R&D partners were first to discover certain nicotine biosynthesis genes and several transcription factor genes that regulate expression of all nicotine biosynthesis genes. 22nd Century’s model of outsourcing R&D to world-renowned plant biotechnology centers has enabled our company to maintain strict control of our R&D costs, while providing our company broad access to large public institutions’ infrastructure and transdisciplinary expertise. As a result, 22nd Century obtained exclusive rights to all key genes that can be regulated to produce viable commercial products with modified nicotine content.
In 2010, a University of Minnesota clinical trial demonstrated that VLN cigarettes (made exclusively with 22nd Century’s proprietary tobacco) used alone over a 6-week treatment period are an effective tool in smoking cessation (Hatsukami et al. 2010). 22nd Century also completed development of an improved VLN cigarette to continue clinical trials with the company’s proprietary VLN cigarettes for use in smoking cessation.
