Gold Rush: Measuring Nicotine Mortality by the Millimeter

 

The New Yorker magazine recently published an article, “Zyn and the New Nicotine Gold Rush,”  that included a remarkable passage from a discussion between the author and Thomas Ericsson, a former Swedish Match employee.  It perfectly describes the risks of using snus and nicotine. 

“I asked Ericsson whether he had any concerns about the possible harms of nicotine itself. ‘Of course you should have concerns,’ he told me. ‘Or you should do risk analysis.’ He walked out of the room and returned with a large ball of string. The string was exactly ninety-five metres long, each millimetre representing one of Sweden’s approximate ninety-five thousand annual deaths. Ericsson slowly unravelled the string until he reached a piece of tape representing the people who die early from smoking each year. He moved his fingers down to another marker, a few meters shorter, which represented the people who die from drinking. He continued shortening the string, indicating the number of deaths by suicide (fifteen hundred), drowning (a hundred and fifty), car accidents (two hundred), and workplace accidents (between fifty and seventy).

“‘You can ask yourself, What are Swedish people most afraid of? They’re afraid to fly. They’re afraid of wolves. They’re afraid of deer and other things,’ he said, holding a short length of string. ‘But what you should be afraid of is the wasp. It kills five to ten people every year.’ Finally, Ericsson reached the very tip of the string. While working on Nicorette, he and his colleagues did a risk-analysis calculation that estimated that fewer than two people per year would die of heart illnesses exacerbated by nicotine use. Compared with other hazards, he said, ‘this is not a big risk.’”

I have recognized the minuscule risks of snus since 1995, when I first described the Swedish experience in a peer-reviewed publication:

“Sweden has been the world's largest per capita consumer of smokeless tobacco (ST) throughout the 20th century, without a resultant oral cancer epidemic.  On the contrary, the age-adjusted mortality rate for oral cancer from 1960 to 1990 in Sweden was low and remarkably stable at 2.3 to 3.6 per 100,000 person-years.  A retrospective study of 200,000 male snuff dippers in Sweden found only one case of oral cancer per year.  This is in marked contrast to most other European countries where ST use is essentially nonexistent and where increases in oral cancer mortality have mirrored earlier increases in cigarette consumption.  The greatest increase in oral cancer mortality has occurred in France (13.4/100,000 person-years in 1955-59 to 32.3/100,000 person-years in 1985-89). 

“It is not surprising to find that Swedish lung cancer mortality rates have been the lowest in Europe over the past 40 years.  These large scale vital statistics from Sweden and France strongly support the suggestion that if tobacco is to be used, it should be in the form of ST and not cigarettes. The population that uses ST in lieu of smoking is, in effect, protected from lung cancer and other major smoking-related diseases and suffers little or no increased risk of oral cancer.” (emphasis added, references removed)

In 2004, following my research sabbatical at Sweden’s Umeå University, I published this:

Rodu B, Cole P.  The burden of mortality from smoking: comparing Sweden with other countries in the European Union.  European Journal of Epidemiology 19: 129-131, 2004. https://www.ncbi.nlm.nih.gov/pubmed/15074568  

In that article, epidemiologist Philip Cole and I described “the mortality currently attributable to smoking in the European Union (EU), and the change that would result if all EU countries had the smoking prevalence of Sweden.  Almost 500,000 smoking-attributable deaths occur annually among men in the EU; about 200,000 would be avoided at Swedish smoking rates.”

More than 20 years after our estimates were published, the Swedish Tobacco Experience has become a Gold Rush, meaning that more people are consuming nicotine and tobacco in a safer fashion.

Conducting Tobacco Harm Reduction Research Despite Constant Headwinds

 

Sensible Medicine is a website “featuring the voices of leading physicians, scientists, and thinkers.  The goal of Sensible Medicine is to showcase a range of ideas and opinions about all things bio-medicine.”  Recently I was honored when the editors published my article, “Six Urban Myths About Smoke-Free Nicotine.

The publication drew several courteous and intelligent comments, including an inquiry about my funding:

“…transparency around funding is important. A quick search suggests your research has received support from tobacco and nicotine companies. While that doesn’t necessarily impact the validity of your conclusions, some might see it as a source of bias. Of course, I may have missed something, but I’m curious…Should researchers with industry ties be more upfront? And how do we ensure strong research isn’t dismissed solely because of its funding source? I’d love to hear your thoughts.”

My response:

“I have conducted and published research on tobacco harm reduction since 1994 (https://louisville.app.box.com/file/1793592529260?s=ztqsq1ue1bdisllarvhpmi2ogrrvvjzj), and my funding has been a matter of public record for the entire period. From 1999 to 2018 my research was supported by unrestricted grants to the University of Alabama at Birmingham (UAB, 1999-2005) and to the University of Louisville (UofL, 2005-2018), which were publicly acknowledged. I now report no conflict of interest (COI), as six years without industry funding is a longer period than specified by the COI policies of professional journals and other relevant organizations. I have no personal or other professional conflict of interest.”

University research funding has been a hot topic in the national press recently due to a Trump Administration proposal to reduce indirect cost payments to universities to 15% of direct research costs.  I won’t comment on that proposal, but I will explain basic facts about faculty life in a research university medical school.

Medical school faculty members are expected to contribute to the university’s mission: teaching, service and research.  Their salaries are partitioned according to their percentage time commitment to those three components.  While the first component, teaching, is ostensibly paid for by tuition money and/or state support, teaching is low on the mission list because it doesn’t generate income; service and research are the income-earners.  Faculty prestige and salary are based on how many dollars one can generate from outside sources.

I started at UAB in 1979 in a cancer fellowship, and in 1981 I was an assistant professor in the department of pathology.  I had a heavy teaching load: hundreds of hours of contact time all year long with dental and dental hygiene students, as well as dental, oral pathology and medical residents.  Fifty percent of my time was paid by the university for teaching; I had to cover the other half.  A quarter of my time was spent providing service.  I saw hundreds of clinic and hospital patients and examined 2,000 specimens a year under the microscope, producing modest amounts of money for the school.  The final 25% was for research, and this is where I struggled.  I never was the principal investigator of a coveted R01 research grant from NIH, which provides money for supplies, salaries and lucrative indirect payments to administrators.  I survived with a small salary offset as co-investigator on other faculty members’ grants, and I conducted and published research on my own time.

My first study on tobacco harm reduction, which I did on my own time with no financial support, was published in Nature in 1994.  Epidemiologist Philip Cole and I found that the average loss in life expectancy from smokeless tobacco use was 15 days, compared with a loss of eight years for smokers.  One colleague noted, “A publication in Nature can make a career!” and he was right.  The publication made my career… miserable. 

My surprising, counterintuitive Nature report conflicted with mainstream medicine’s opinion that smokeless tobacco was a mouth cancer death sentence.  A point-counterpoint appearance on Good Morning America (here) was quickly followed by denunciation of me and of UAB by the nation’s primary source of research funding, the National Cancer Institute (complete story here).  NCI, asserting that telling smokers about safer ways to consume nicotine/tobacco was unethical, suggested that UAB was wrong having me on its faculty, and the agency filed a complaint with the federal office protecting patients from undue research risk.  It was an existential allegation that was proven baseless, but it led to three dreadful years of intense scrutiny (story here).

After my credibility and reputation was restored at UAB, it was clear that my important research was never going to be funded by NIH.  Using minimal financial support from the university, I continued to publish studies until around 1998, when my chairman gave me an ultimatum: while he was supportive of my work, I had to attract outside funding or my career would suffer.

I was at a crossroads.  Either obtain outside funding and continue to work on tobacco harm reduction, or abandon the field entirely.  After long discussions with Dr. Cole, I chose the former.

In 1999, the U.S. Tobacco Company signed an agreement with UAB to support my THR research for five years.  The funds constituted an unrestricted “gift” (in IRS terminology), meaning UST had no expectation or control regarding any work product.  While 100% of gifts go to the researcher’s program, and 0% to indirect costs, I was able to partition 50% of my salary for THR research, enabling me to transfer some of my teaching to my colleagues.  It also allowed me to conduct my research sabbatical in Sweden in 2002, resulting in a series of published studies examining how snus products made by Swedish Match, the major competitor of UST at that time, had made Sweden a THR model for the rest of the world. 

In 2005, I retired from the Alabama system and moved to a new position at the University of Louisville Brown Cancer Center.  My new boss, Cancer Center Director and THR supporter Dr. Donald Miller, duplicated my UAB support structure at UofL.  From 2005 to 2018, my research was supported by grants from industry to UofL.  I was fortunate to obtain funding for my entire program until 2018, when my last unrestricted grant from tobacco manufacturers to UofL ended. 

My groundbreaking work in THR would not have been possible without the support of leadership at two universities who believed in the validity and value of my research, and who had confidence in the legitimacy of accepting and administering grants from controversial sources.

Academia in the U.S. is a pressure cooker for faculty who are required to attract funding from external sources.  Excluding small grants from pharma and medical device companies, the only game in town is NIH.  When NIH makes a researcher non gratis, it poses an existential threat.  I took the only other opportunity, producing and publishing as much as possible, using the proceeds of unrestricted corporate gifts to my university employers.        

The Real Cost of FDA’s “Real Cost” E-Cigarette Campaign

 

FDA staff just published a study in the American Journal of Preventive Medicine titled, “The Impact of ‘The Real Cost’ on E-cigarette Initiation among U.S. Youth.” 

The authors describe the campaign advertisements in the study’s appendix:

“Scary Enough.”  Metal monsters representing toxic metal inhalation

“Addiction Isn’t Pretty: Toilet.”  A teen reaches into a toilet to retrieve an e-cigarette thrown there by another teen, then takes a hit before walking out.

“Toxic Taxidermy.”  The interior of a taxidermy shop showing badly preserved animals who talk about formaldehyde in e-cigarettes.

“Don’t Pollute Yourself.”  A serene natural landscape where a pipeline starts dumping sludge, portraying toxic chemicals, into a lake, which is shaped like lungs.

The FDA authors used a nonpublic survey dataset to measure children’s exposure to the ads, and then they performed a “discrete-time survival analysis… to examine the impact of the exposure index on e-cigarette initiation at follow-up by using logistic regression models that controlled for the above-mentioned demographic and environmental variables.”

In other words, they estimated how many kids age 11-18 did not start using e-cigarettes because of the FDA campaign.  They said the ads prevented 444,252 children from starting to use e-cigarettes in 2023-2024, with a 95% confidence interval between 73,639 and 814,866.

Given that their estimate was more like a guesstimate, the authors should have rounded to the thousands or ten thousands. But, for this exercise, let’s assume the authors’ approach is valid, and that the ads prevented people from using e-cigarettes.  We can also assume that the effect that the authors claimed for 18-year-olds – basically adults – applies to the entire adult smoking population of nearly 27 million, per the 2023 NHIS.

Applying the authors’ analytics to the adult population, the FDA Real Cost Campaign prevented 654,477 adult smokers from switching to far less harmful, even life-saving, e-cigarettes.  The 95% confidence interval is 144,770 and 1,164,098.

I don’t believe the FDA ought to be evaluating its own campaign based on a secret dataset.  Between 2023 and 2024, teen vaping declined, so it’s easy for the FDA staff to claim that a concurrent FDA campaign was responsible.  Even worse, these FDA employees attest that they have “no financial disclosures” and that “The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Food and Drug Administration.”  You gotta be kidding me.