Who Invented Nicotine Gum?

Sweden has given us ABBA, Volvo cars, IKEA meatballs and, possibly more impressively, nicotine gum.

Granted, it may have been an American inventor, Carleton Ellis, who first had the idea for nicotine gum – or at least, he was the first to file a patent. This is the same guy who invented margarine, polyester and long-lasting house paint [1]. He was inspired to design a nicotine-containing gum to be used by tobacco chewers in 1907, but the patent went nowhere. Sixty years later, a Swedish chemical engineer, Dr. Ove Fernö, never saw Ellis' patents before he created a prototype that would become NICORETTE®'s successful nicotine gum.

Fernö studied at the Royal Institute of Technology and took up smoking during his military career, going through 20 – 30 cigarettes a day for more than twenty years. In a twist of fate, it was his smoking that led him to his post as head researcher at AB Leo, the company that would eventually become NICORETTE®. In 1941, he was in a smokers' tram carriage on his way to the Royal Institute of Technology, when he saw his professor sitting nearby. As they sat together and shared a smoke, the professor asked Fernö if he was interested in taking an entry-level job at AB Leo [2].

Fernö's early work at the company was in creating new pharmaceutical polymers that are still in use today. He become research director in the late 1940s. Twenty years and another twist of fate later, Fernö's career was directed towards nicotine replacement gum when he received a letter from a close friend, Dr. Claes Lundgren.

Lundgren was performing research on the respiratory health of submariners and aviation crews at the Lund University. His study environments had a strict ban on smoking and he noticed that his participants would use snus to curb their cravings for cigarettes. Snus is a popular chewing tobacco in Sweden – sticky, brown pellets of tobacco that are placed under the lip where they deliver nicotine directly into circulation. Lundgren realised that snus could supply nicotine without harming the respiratory system – a great therapy for troops and submariners who needed to go for long periods without a smoke but couldn't risk the withdrawal symptoms. He also recognised the harmful effects of tobacco on the oral cavity and wondered if nicotine could be delivered without tobacco. Who better to share his idea with than his friend and head researcher of a profiting pharmaceutical company, Dr. Ove Fernö?

Fernö's interest was immediately piqued – he had been a heavy smoker himself during the war and had tried nicotine-free replacements when tobacco had been strictly rationed. The replacements did nothing for him and he recognised that nicotine was the key ingredient he had been craving. Reading Lundgren's letter decades letter, he had no doubt that nicotine was a driving force behind smoking addictions and that finding a tobacco-free delivery method could save thousands of lives.

Before meeting with Lundgren, Fernö began with preliminary trials. His first experiments in 1967 were with aerosol sprays that contained nicotine, but they tasted foul and were too complicated to use. The idea was quickly abandoned. If nicotine replacements were going to be popular and effective, they had to be discreet, convenient, and tasty. The product would need to stay in the mouth for as long as possible to allow the nicotine to pass directly through the mucus membranes, and to be released slowly to avoid a huge spike of nicotine in the body. Gum was the logical answer. Fernö stated, “From chewing tobacco to chewing gum is not a large step.” [2]

Lundgren joined the team, the experiments continued and the gum's recipe was refined. The first primitive nicotine gums released their nicotine too quickly and they tasted terrible. To slow down the nicotine delivery, Fernö bound the compound within a resin that worked with ionic exchange. This meant that sodium from saliva was the only way to release the nicotine from the gum. In short: you had to chew to get your nicotine, and how hard and fast you chewed would impact how much nicotine was released. This resin technology was the step that the American inventor, Ellis, hadn't taken in 1907 and why his original patents never get off the ground.

For Fernö, manufacturing processes were set up in the late 1960s and clinical trials began to roll out. The most notable early trial was on Fernö himself – after decades of failed attempts, he began chewing the gum in 1969 and completely quit cigarettes within one year [2]. With this personal experience behind him, Fernö had confidence to present his product at conferences the push his product within AB Leo. Chewing gum isn't a typical product for a pharmaceutical company, but Fernö soon found the scientific backing he needed to make it a marketable product.

Lundgren saved the day again and introduced Fernö to a colleague at the Lund University, Dr Hakan Westling. Westling was coordinating clinical trials on smokers who were struggling to quit smoking while hospitalized, and he agreed to use Fernö's nicotine gum in the studies [4]. The gum trials showed very promising results with dramatic individual experiences of patients who reversed their smoking-related illnesses. Westling himself was a pipe smoker but quickly gave it up once he started chewing the gum. The press and AB Leo were impressed, but Fernö thought the gum wasn't performing as well as it should. He wanted the nicotine replacement product to have a flawless success rate. By 1975, Fernö had adjusted the pH of the gum by adding sodium bicarbonate, increasing the absorption of nicotine by well over 100% – and he'd worked on the flavor, too [3]. By 1976, Fernö had created NICORETTE®'s trademark gum. In 1978, Switzerland was the first country to approve its use as a prescription drug, followed in 1981 by its homeland of Sweden.

By the turn of the millennium, NICORETTE® was a household name and nicotine gum had become the principle treatment for smoking addiction. In 2005, 2.6 billion packets of NICORETTE® were manufactured and distributed to 88 countries, along with patches, inhalers and nasal sprays.

Dr. Ove Fernö retired from AB Leo in 1981. Five years later he was awarded with the Polhems Prize for technological innovations. AB Leo was bought by Johnson & Johnson in 2006, and Fernö died in 2007 at 91 years of age.

References:

[1] Zorina, K. (2005) The Democratization of Invention: Patents and Copyrights in American Economic Development, Cambridge University Press, 1790-1920, 209-210. https://econpapers.repec.org/bookchap/nbrnberbk/khan05-1.htm

[2] Fernö, O. (1994) Conversation with Ove Fernö. Addiction., 89:10, 1215 – 1226. https://www.ncbi.nlm.nih.gov/pubmed/7804082

[3] Fernö, O. & Ohlsson, B. (1974) Buffered Smoking Substitute Compositions. US Patent No. 3,845,217, 29 October 1974. https://patents.google.com/patent/US3845217

[4] Brantmark, B., Ohlin, P. & Westling, H. (1973) Nicotine containing chewing gum as an anti-smoking aid. Psychopharmacologia, 31, 191-200. https://link.springer.com/article/10.1007%2FBF00422509