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Vol 23, No. 05, May 2019   |   Issue PDF view/purchase
The journey towards a smoke-free future
Tobacco Heating System a better alternative for smokers than cigarettes.
by Professor Manuel Peitsch

Smoking is a global problem. Today, there are more than one billion people who smoke, and this number is expected to increase, despite ongoing efforts to discourage non-smokers from starting to smoke and to encourage current smokers to quit.

On a global scale, the number of smokers is stagnant1 and the World Health Organization (WHO) data show that annually on average, only 2.5 per cent of smokers quit. This means that vast majority of smokers continue to smoke.2

Smoking is the leading cause of preventable diseases such as cardiovascular disease, respiratory disease and lung cancer,3 and smokers who quit are more likely to live a healthier and longer life while decreasing the risk of these diseases.4 There is a growing consensus that the harmful chemicals and ultrafine solid particles (small, inhalable particles identified as a cause of diseases such as respiratory disease) that are emitted when tobacco is burned are the main cause of smoking-related diseases.

Burning, or combustion, occurs at temperatures above 400°C and when a smoker puffs on a lit cigarette, the temperature can rise above 800°C at the cigarette tip where the tobacco is burned and creates smoke.5 The smoke of a cigarette contains close to half a trillion ultrafine solid particles and more than 6,000 chemicals. Almost 100 of these chemicals are toxicants that are classified as harmful and potentially harmful constituents (HPHC), including arsenic, benzene, benzo[a]pyrene, carbon monoxide or heavy metals.

Decades of scientific research show that these toxicants as well as the solid particles in cigarette smoke are the main cause of the toxic and carcinogenic effects of smoking. 6 Experts, including the U.S. Surgeon General and the U.K. Royal College of Physicians, agree that nicotine, while addictive and not risk-free, is not the primary cause of smoking-related diseases.7

Designing a smoke-free future

Philip Morris International has embarked on that journey to build a smoke-free future through science and innovation. The guiding principle for this journey is to develop and scientifically assess a portfolio of less harmful products that can reduce the risk of smoking-related diseases compared to continued smoking and constitute acceptable alternatives for adult smokers who would otherwise continue to smoke. It is important to recognise that these products are not risk-free and the best option for smokers is to quit and for non-smokers to never start using nicotine or tobacco products.

One example of a smoke free product is the Tobacco Heating System (THS), that heats the tobacco to a maximum temperature of 320°C, below the temperature needed for combustion.

Furthermore, the THS aerosol does not contain ultrafine solid particles. Cigarette smoke, on the other hand, contains more than half a trillion of such ultrafine solid particles per cigarette. The significant reduction in levels of toxicants and the absence of ultrafine solid particles, is due to the absence of combustion. These differences in the composition of cigarette smoke and THS aerosol can easily be made visible by collecting cigarette smoke and THS aerosol on a filter pad (Figure 1).

Lung cancer risk reduction potential of THS

Lung cancer can be induced through chronic exposure to carcinogens and other toxicants in cigarette smoke. Carcinogens contained in cigarette smoke can cause genetic damage that can lead to the loss of normal cellular growth control mechanisms and cell proliferation. Cigarette smoke exposure also causes chronic inflammation, which promotes tumour formation (Balkwill 2001).

Lung cancer takes decades to develop in humans, which makes the assessment of the risk reduction potential of Heat-Not-Burn products, such as THS or e-cigarettes in humans difficult.

PMI has developed an approach based on three important questions that can be answered using a combination of non-clinical and clinical studies:

  1. Does switching from cigarettes to a smoke-free product reduce genetic damage?
  2. Does switching from cigarettes to a smoke-free product reduce inflammation?
  3. Does switching from cigarettes to a smoke-free product reduce the lung cancer risk?

PMI has conducted scientific studies9 that provide solid evidence that THS significantly reduces inflammation and genetic damage. PMI’s 6 month clinical Exposure Response study demonstrated a significant reduction in systemic inflammation as demonstrated by the reduction in circulating white blood cell count (WBC) for subjects who switched to THS use compared to those who continued smoking. Furthermore a substantial reduction in additional markers of inflammation such as high sensitive C-reactive protein (hsCRP) was observed in the THS use group compared to the cigarette smoking group. In addition, THS aerosol has been shown to be significantly less genotoxic in vitro.10 Moreover, human organotypic epithelial tissue cultures exposed to THS aerosol showed considerably lower responses to DNA damage in the causal network model analyses than cultures exposed to cigarette smoke as demonstrated in oral, nasal and bronchial cultures.11,12,13,14,15

Lastly, the results of the urinary Ames test (a test for genotoxicity) from participants in PMI’s 3 month clinical Reduced Exposure study further supports the observation that THS aerosol is significantly less genotoxic than cigarette smoke.

PMI also conducted an animal study in A/J mice, a strain of mice known to develop lung cancer in response to cigarette smoke exposure.16 This study shows that cigarette smoke exposure increases the occurrence and number of lung adenomas and carcinomas compared with fresh air exposure. In contrast, lifelong exposure to THS did not result in an increased occurrence and number of lung adenomas and carcinomas in this animal model.


Quitting the use of all tobacco or nicotine containing products is and always will be the best option for smokers. However, for the millions of smokers who would otherwise continue to smoke cigarettes, better, scientifically assessed alternatives, such as Heat-Not-Burn products and e-cigarettes are needed to reduce the harm that smoking causes to health.

The totality of evidence to date on THS demonstrates that switching completely to THS, while not risk-free, presents less risk of harm compared with continuing to smoke cigarettes.

Rapid innovation and continuous research and development efforts present opportunities to create a larger portfolio of less harmful alternatives to cigarettes and accelerate the rate of smokers switching to them instead of continuing to smoke, therefore accelerating the journey towards a smoke-free future.


  1. www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60264-1/fulltext
  2. www.pmi.com/resources/docs/default-source/newsroom/pmi-cop-position-statement.pdf?sfvrsn=41ff9cb5_10
  3. www.pmiscience.com/library/publication/assessing-the-lung-cancer-risk-reduction-potential-of-candidate-modified-risk-tobacco-products
  4. www.expressnews.com/opinion/commentary/article/Beat-cancer-before-you-have-it-prevent-it-13692657.php
  5. www.pmiscience.com/our-products/combustion
  6. www.pmiscience.com/discover/technology/nicotine-without-burning-tobacco
  7. www.ncbi.nlm.nih.gov/books/NBK53017/
  8. www.pmiscience.com/discover/news/platform-1-on-average-emits-90-95-lower-levels-of-harmful-and-potentially-harmful-constituents-compared-to-cigarette-smoke
  9. In a laboratory setting and in humans
  10. Schaller J-P, Keller D, Poget L, Pratte P, Kaelin E, McHugh D, Cudazzo G, Smart D, Tricker AR, Gautier L, Yerly M, Pires RR, Le Bouhellec S, Ghosh D, Hofer I, Garcia E, Vanscheeuwijck P and Maeder S (2016) Evaluation of the Tobacco Heating System 2.2. Part 2: Chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol. Regulatory Toxicology and Pharmacology, 81 Suppl 2:S27-S47 and Thorne D, Breheny D, Proctor C and Gaça M (2018) Assessment of novel tobacco heating product THP1.0. Part 7: Comparative in vitro toxicological evaluation. Regul Toxicol Pharmacol. 93:71-83.
  11. Iskandar AR, Mathis C, Martin F, Leroy P, Sewer A, Majeed S; Kühn D, Trivedi K, Grandolfo D, Cabanski M, Guedj E, Merg C, Frentzel S; Ivanov NV, Peitsch MC and Hoeng J (2017a) 3-D Nasal Cultures: Systems Toxicological Assessment of a Candidate Modified-Risk Tobacco Product. ALTEX, 34:23-48.
  12. Iskandar AR, Mathis C, Schlage WK, Frentzel S, Leroy P, Xiang Y, Sewer A, Majeed S, Ortega-Torres L, Johne S, Guedj E, Trivedi T, Kratzer G, Merg C, Elamin A, Martin F, Ivanov NV, Peitsch MC and Hoeng J (2017b) A systems toxicology approach for comparative assessment: Biological impact of an aerosol from a candidate modified-risk tobacco product and cigarette smoke on human organotypic bronchial epithelial cultures. Toxicology in vitro. 39:29-51.
  13. Iskandar AR, Titz B, Sewer A, Leroy P, Schneider T, Zanetti F, Mathis C, Elamin A, Frentzel S, Schlage W, Martin F, Peitsch MC, and Hoeng J (2017d) Systems Toxicology Meta-Analysis of In Vitro Assessment Studies: Biological Impact of a Modified-Risk Tobacco Product Aerosol Compared with Cigarette Smoke on Human Organotypic Cultures of the Respiratory Tract. Toxicology Research, 6:631-653.
  14. Zanetti F, Sewer A, Mathis C, Iskandar A, Kostadinova R, Schlage WK, Leroy P, Majeed S, Guedj E, Trivedi K, Elamin A, Merg C, Ivanov NV, Frentzel S, Peitsch MC and Hoeng J (2016) Systems toxicology assessment of the biological impact of a candidate Modified Risk Tobacco Product on human organotypic oral epithelial cultures. Chemical Research in Toxicology, 29:1252-1269.
  15. Zanetti F, Titz B, Sewer A, Lo Sasso G, Scotti E, Schlage WK, Mathis C, Leroy P, Majeed S, Ortega-Torres L, Keppler BR, Elamin A, Trivedi K, Guedj E, Martin F, Frentzel S, Ivanov NV, Peitsch MC and Hoeng J (2017) Comparative systems toxicology analysis of cigarette smoke and aerosol from a candidate modified risk tobacco product in organotypic human gingival epithelial cultures: a 3-day repeated exposure study. Food and Chemical Toxicology. 101:15-35.
  16. The A/J mouse cancer model is the only accepted model in the medical and scientific communities for cigarette smoke-induced lung cancer.


Professor Manuel C. Peitsch is the chief scientific officer at Philip Morris International.


Disclaimer: This article does not promote or support smoking. THS and e-cigarettes are not risk-free. The best choice any smoker can make is to quit cigarettes and nicotine completely.

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