"Keep it a secret": leaked documents suggest Philip Morris International, and its Japanese affiliate, continue to exploit science for profit.

INTRODUCTION: The tobacco industry has a long history of manipulating science to conceal the harms of its products. As part of its proclaimed transformation, the world's largest tobacco company, Philip Morris International (PMI), states it conducts "transparent science". This paper uses recently leaked documents from PMI and its Japanese affiliate, Philip Morris Japan (PMJ), to examine its contemporary scientific practices. METHODS: 23 documents dating 2012 through 2020 available from Truth Tobacco Industry Documents Library were examined using Forster's hermeneutic approach to analysing corporate documentation. Thematic analysis using the Science for Profit Model was conducted to assess whether PMI/PMJ employed known corporate strategies to influence science in their interests. RESULTS: PMJ contracted a third-party external research organisation, CMIC, to covertly fund a study on smoking cessation conducted by Kyoto University academics. No public record of PMJ's funding or involvement in this study was found. PMJ paid life sciences consultancy, FTI-Innovations, ¥3,000,000 (approx. £20,000) a month between 2014 and 2019 to undertake extensive science-adjacent work, including building relationships with key scientific opinion leaders and using academic events to promote PMI's science, products and messaging. FTI-Innovation's work was hidden internally and externally. These activities resemble known strategies to influence the conduct, publication and reach of science, and conceal scientific activities. CONCLUSIONS: The documents reveal PMI/PMJ's recent activities mirror past practices to manipulate science, undermining PMI's proclaimed transformation. Tobacco industry scientific practices remain a threat to public health, highlighting the urgent need for reform to protect science from the tobacco industry's vested interests.Implications: Japan is a key market for PMI, being a launch market for IQOS and having the highest heated tobacco product use globally. Our findings, in conjunction with other recent evidence, challenge PMI's assertion that it is a source of credible science and cast doubt on the quality and ethical defensibility of its research, especially its studies conducted in Japan. This, in turn, brings into question the true public health impacts of its products. There is urgent need to reform the way tobacco-related science is funded and conducted. Implementation of models through which research can be funded using the industry's profits while minimising its influence should be explored.

Seeking to be seen as legitimate members of the scientific community? An analysis of British American Tobacco and Philip Morris International's involvement in scientific events.

INTRODUCTION: For decades, tobacco companies manipulated and misused science. They funded and disseminated favourable research and suppressed research that showed the harms of their products, deliberately generating misinformation. While previous work has examined many of the practices involved, their engagement in scientific events has so far not been systematically studied. Here, we examine the involvement of British American Tobacco (BAT) and Philip Morris International (PMI) in scientific events, including conferences, symposia and workshops. METHODS: Our analysis involved two steps. First, we collected all available data PMI and BAT provided on their websites to identify events. Second, we extracted information about the nature of tobacco industry involvement from event websites and materials. RESULTS: We identified 213 scientific events that BAT and/or PMI representatives attended between April 2012 and September 2021. Most events took place in high-income countries in Europe and North America. They covered a diverse range of fields, including toxicology (n=60, 28.1%), medicine (n=25, 11.7%), biology (n=24, 11.3%), chemistry (n=23, 10.8%) and aerosol science (n=18, 8.5%), as well as dentistry (n=9, 4.2%), pharmaceutical science (n=8, 3.8%) and computing (n=8, 3.8%). We identified 356 posters provided by BAT and PMI that linked to 118 events (55.4%) as well as 77 presentations from 65 events (30.5%). Industry involvement through sponsorship (nine events), exhibition (three events) or organising committee (one event) was rare. CONCLUSION: BAT and PMI representatives attended a large number and wide range of scientific events. Given that scientific events could be a crucial platform for building connections in the scientific sphere and disseminating industry's messages, this work highlights the importance of denormalising the tobacco industry's involvement in scientific events.

Bolaamphiphile Analogues of 12-bis-THA Cl2 Are Potent Antimicrobial Therapeutics with Distinct Mechanisms of Action against Bacterial, Mycobacterial, and Fungal Pathogens.

12-Bis-THA Cl2 [12,12'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride] is a cationic bolalipid adapted from dequalinium chloride (DQC), a bactericidal anti-infective indicated for bacterial vaginosis (BV). Here, we used a structure-activity-relationship study to show that the factors that determine effective killing of bacterial, fungal, and mycobacterial pathogens differ, to generate new analogues with a broader spectrum of activity, and to identify synergistic relationships, most notably with aminoglycosides against Acinetobacter baumannii and Pseudomonas aeruginosa, where the bactericidal killing rate was substantially increased. Like DQC, 12-bis-THA Cl2 and its analogues accumulate within bacteria and fungi. More hydrophobic analogues with larger headgroups show reduced potential for DNA binding but increased and broader spectrum antibacterial activity. In contrast, analogues with less bulky headgroups and stronger DNA binding affinity were more active against Candida spp. Shortening the interconnecting chain, from the most lipophilic twelve-carbon chain to six, improved the selectivity index against Mycobacterium tuberculosis in vitro, but only the longer chain analogue was therapeutic in a Galleria mellonella infection model, with the shorter chain analogue exacerbating the infection. In vivo therapy of Escherichia coli ATCC 25922 and epidemic methicillin-resistant Staphylococcus aureus 15 (EMRSA-15) infections in Galleria mellonella was also achieved with longer-chain analogues, as was therapy for an A. baumannii 17978 burn wound infection with a synergistic combination of bolaamphiphile and gentamicin. The present study shows how this class of bolalipids may be adapted further to enable a wider range of potential applications. IMPORTANCE While we face an acute threat from antibiotic resistant bacteria and a lack of new classes of antibiotic, there are many effective antimicrobials which have limited application due to concerns regarding their toxicity and which could be more useful if such risks are reduced or eliminated. We modified a bolalipid antiseptic used in throat lozenges to see if it could be made more effective against some of the highest-priority bacteria and less toxic. We found that structural modifications that rendered the lipid more toxic against human cells made it less toxic in infection models and we could effectively treat caterpillars infected with either Mycobacterium tuberculosis, methicillin resistant Staphylococcus aureus, or Acinetobacter baumannii. The study provides a rationale for further adaptation toward diversifying the range of indications in which this class of antimicrobial may be used.