Category: Science

More Waste From Toys Than Vapes: Study

Image: Przemek Klos
New research from the United Nations suggests that toys are a much larger contributor to electronic waste than vaping products, according to New Scientist.
The Waste Electrical and Electronic Equipment (WEEE) Forum recently collaborated with the United Nations Institute for Training and Research to quantify how much electronic waste the world disposes of without realizing it has the potential to be recycled.
According to the analysis, 9 billion kg of so-called “invisible” e-waste, worth nearly $10 billion, is thrown away yearly. Around one-third of this waste comes from children’s toys containing some 3.2 billion kg of hidden electronics.
Toys contribute 77 times more to the world’s invisible e-waste than vapes, which account for 42 million kg annually. The U.N. estimates that 844 million vapes are thrown away every year.
“Electronic waste is our fastest-growing waste stream,” says Oliver Franklin-Wallis, the author of Wasteland, a book on waste disposal. “It’s also by far our most valuable waste stream when it comes to household waste.”
However, very few people realize that many common items they dispose of contain e-waste. Magdalena Charytanowicz, at the WEEE Forum, highlighted that this was the purpose of the research.
“We’re trying to make people understand that the items they may not suspect are electronics actually do contain a lot of precious materials, like copper and lithium,” Charytanowicz said.
November 10, 2023
No Added Harm from Vape Substitution: Study

Photo: fedorovacz
A new systematic review conducted by the Center of Excellence for the acceleration of Harm Reduction on the available scientific research showed no difference in respiratory parameters in human clinical tests on the respiratory effects of electronic nicotine delivery systems (ENDS) use in participants who smoke tobacco cigarettes.
In their study “Respiratory health effects of e-cigarette substitution for tobacco cigarettes: a systematic review,” the researchers analyzed 16 studies from 20 publications. They found that the large majority of the studies showed no difference in respiratory parameters. According to the authors, this indicates that electronic nicotine delivery systems substitution for smoking likely does not result in additional harm to respiratory health.
One of the problems the researchers found during their evaluation is that many studies were not of sufficient duration for observing any harmful or beneficial effects because these may take time to manifest. In fact, the researchers observed a general low quality of the studies included in the review, with 10 of 16 studies rated at high risk of bias.
In light of the findings of no change in respiratory function plus the presence of reporting spin bias, the researchers call for long term studies that include diverse participants and to assess smoking behavior and history. Furthermore, they note that exclusive ENDS use and dual use with cigarettes should be identified as separate categories for analysis and findings. They also stressed that additional studies are necessary to assess the potential benefits or risks of e-cigarette substitution for tobacco cigarette smoking.
November 8, 2023
Tobacco Used to for Cancer Antibodies

Photo: Baiya Phytopharm
Thailand researchers have successfully used tobacco plants to develop antibodies that have inhibitory effects on the growth of cancer cells in laboratory animals, according to News-Medical.
“Our research team has developed the technology and system to produce plant proteins to make antibody drugs, with the hope to help reduce the cost of drug production so that cancer patients in the country can access drugs more easily and widely,” said Waranyoo Phoolcharoen, associate professor in the Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences at Chulalongkorn University, where the research is taking place.
The potential of the research was recognized with a 2023 research award from the National Research Council of Thailand.
The researchers are using an Australian species of Nicotiana benthamiana.
“We use plants as factories to produce the proteins we need,” said Phoolcharoen. “We insert antibody-producing genes into tobacco plants in order for the tobacco plants to produce the antibodies (drugs) we need. The extracted protein (antibody) is then purified. We found that the antibodies produced by the plants can bind to proteins on the surface of immune cells.”
“The antibodies that the research team produced from plants can inhibit the growth of cancer cells in laboratory animals,” Phoolcharoen said. “The size of the tumor cells in mice decreased. This ability to make cells shrink in size is comparable to that of the drugs used in the market.”
The next steps in the research are testing for safety and toxicity and studying the structure of the drug.
“If this research is successful, we will be able to produce our own medicines locally, reducing the cost of drug production and lowering medicinal expenses. More people will then have access to cancer medicines,” said Phoolcharoen.
The technology used in this research could also be used to produce antibodies to develop drugs or vaccines for many other diseases.
Phoolcharoen has also been involved in a venture to produce a Covid-19 vaccine using tobacco plants.
August 11, 2023
Red Algae Protein Doub Boosts Tobacco Growth

Photo: YanaKho
Researchers out of Cornell University have successfully transferred key regions of red algae into a tobacco plant using bacteria as an intermediary, resulting in doubled photosynthesis and plant growth compared to tobacco grown with the unaltered protein, according to a story in the Cornell Chronicle.
The study centers on Rubisco, the most abundant protein across ecosystems. The protein performs the first step of photosynthesis by fixing carbon, but it is slow and struggles to differentiate between carbon dioxide and oxygen, often limiting plant growth and crop yield.
The researchers found a species of red algae, Griffithsia monilis (Gm), that contains Rubisco that is 30 percent more efficient at fixing carbon than Rubisco in other organisms. Laura Gunn and her co-authors of the study used the 3D structure of GmRubisco to successfully graft a small number of regions from Rhodobacter sphaeroides (RsRubisco) into a bacterial Rubisco.
“RsRubisco is not very efficient, but it is very closely related to GmRubisco—they’re like cousins—which means that unlike land-plant Rubisco, it accepts the grafted sequences,” said Gunn. “RsRubisco also doesn’t need any special chaperones for it to fold and assemble in land plants.”
Using the altered Rubisco increased the carboxylation rate by 60 percent, increased carboxylation efficiency by 22 percent and improved RsRubisco’s ability to distinguish between carbon dioxide and oxygen by 7 percent. When transplanted into tobacco, it doubled photosynthesis and plant growth compared to tobacco with unaltered RsRubisco.
“We’re not at the point where we’re outperforming wild-type tobacco, but we’re on the right trajectory,” said Gunn. “We only need fairly modest improvements to Rubisco performance because even a very small increase over a whole growing season can lead to massive changes in plant growth and yield, and the potential applications span many sectors: higher agricultural production; more efficient and affordable biofuel production; carbon sequestration approaches; and artificial energy possibilities.”
The research was supported by the Australian Research Council Centre of Excellence for Translational Photosynthesis, Formas Future Research Leaders and the European Regional Development Fund.
July 26, 2023
Plant-Based Biologics Market Thriving

Photo: Kentucky Bioprocessing
The global plant-based biologics market is anticipated to generate a revenue of $182.9 million by 2031, expanding a compound annual growth rate of 4.8 percent from 2022, according to a new report published by Research Dive.
Plant-based biologics are medical products that are produced by utilizing bioengineered plants to create complex molecules like proteins, antibodies, and vaccines. These biologics are produced more sustainably and economically than conventional animal cell-based biologics. The use of plant-based biologics may have substantial effects on the pharmaceutical industry by lowering the costs of medicine development and production and addressing ethical concerns about the use of animals in medical research.
Tobacco continues to be the most widely used plant for the manufacture of pharmaceuticals. Due to their high biomass yield, ease of genetic modification and quick growth rate, tobacco plants are well-suited for biologics production. Several companies, including Medicago, Baiya Phytopharm and Kentucky Bioprocessing have used tobacco to developed vaccines and other medical treatments.
According to Research Dive, North America dominated the global plant-based biologics market in 2021. Not only does the continent offer a sizable market, but it also offers a supportive regulatory environment and strong research infrastructure.
Tobacco Reporter explored tobacco’s potential as a “green bioreactor” in its April 2022 issue.
July 6, 2023
Tobacco Plants Used to Make Medicines

Image: valya82 | Adobe Stock
The tobacco plant Nicotiana benthamiana is being used to create pharmaceuticals more sustainably than industrial manufacturing methods, according to a report in EurekAlert!
University of Queensland researchers have used the plant to create a drug to treat multiple sclerosis.
“We are using the natural ability of plants to produce cyclotides—strings of amino acids in a circular shape—which makes them very stable and suitable as oral drugs,” said David Craik, professor at the University of Queensland’s Institute for Molecular Bioscience.
“Using modern molecular biology techniques, we can effectively instruct the plant cell to produce the molecule of interest.
“The wild tobacco leaves are then harvested, freeze-dried, and the molecule is processed to be turned into oral medication.”
“Harnessing plants as ‘biofactories’ is more cost-effective as it uses fewer resources and is less wasteful, with a much simpler production process,” said Mark Jackson from the Institute for Molecular Bioscience, comparing the process to industrial manufacturing methods. “This method can also scale up very sustainably—using just light, water and nutrients.”
“We have shown it is possible to scale up production of cyclotides in plants, providing a platform for growing other medications for pain, cancer or obesity,” Craik said. “There is also an opportunity to build capacity for biomanufacturing in Australia with advances in vertical farming—where we can easily have a controlled environment to grow the plants.”
Tobacco Reporter covered the potential of tobacco as green bioreactors in-depth in its April 2022 issue.
June 2, 2023
World Vape Day:

Photo: BAT
A new scientific study on Vuse underscores the contribution vapor products can make toward tobacco harm reduction.
By James Murphy
Almost 20 years ago, I joined BAT as a scientist motivated by the positive change that tobacco harm reduction (THR) can achieve. We have made great strides since then, and on days like World Vape Day, it is encouraging to see continued innovation in this area. This ambition to support THR is embodied by BAT’s release today of one of the largest vapor product studies ever conducted, further supporting the role that Vuse, BAT’s flagship vapor brand, can play in tobacco harm reduction.
Science and research have been fundamental to the progress that I have witnessed over almost two decades at BAT. Together, they form the cornerstone of consumer and regulatory confidence in our brands. This confidence is essential for our new-category products to be able to both support THR and provide reduced-risk*† alternatives for consumers who would otherwise smoke.
Early in my career, I had the opportunity to lead product development for BAT’s first vapor product, which would subsequently turn into Vuse: a billion-pound brand and the No. 1 global vaping brand by market share.¹ Now, in 2023, there is wide acceptance that vaping continues to grow in importance as adult smokers seek reduced-risk alternatives to continued smoking.
As director of research and science at BAT, my priority is to develop and publish science-based information needed to better understand the real-world impacts of our products.
Our latest study, published today in the peer-reviewed journal Internal and Emergency Medicine, is intended to do just that. By comparing clinical measurements from exclusive Vuse consumers with current smokers, the results of the study show that adult consumers using BAT’s vapor brand Vuse² had significantly better results for biomarkers relevant to smoking-related diseases than smokers.
For priority cigarette smoke toxicants identified by the World Health Organization, levels of exposure were significantly lower in the Vuse consumers compared to the smokers. Additionally, favorable differences between the Vuse consumers and smokers were found across all seven measured biomarkers of potential harm relevant to smoking-related diseases.
We believe these results underscore the contribution that vapor products can make toward tobacco harm reduction and how, by using a robust evidence base to substantiate the role of reduced-risk* products, we can give adult smokers who would otherwise continue to smoke access to satisfactory reduced-risk* alternatives.
While World Vape Day brings together a global community to converse and learn about tobacco harm reduction, there are significant barriers and challenges facing companies involved in the vaping industry. I believe a core component to overcoming these barriers is evidence-led and science-backed regulation and leadership. These two areas are key to ensuring that reduced-risk* products are only made available to adult consumers and that consumers feel confident about the quality and safety standards governing the development of alternatives like vapor products.
In countries where the concept of tobacco harm reduction has been embraced, we have seen accelerated declines in smoking rates as smokers migrate to noncombustible products. Sweden, for instance, is on the cusp of becoming the first European country to become officially smoke-free—with smoking rates at just 5.6 percent—a 51 percent drop in a decade. Low smoking rates have also had direct benefits for Swedish public health, with cancer rates that are 41 percent lower than the rest of Europe. However, many countries are yet to offer consumers legal access to reduced-risk* products as alternatives to widely available conventional cigarettes.
I am more convinced than ever that tobacco harm reduction has the potential to be transformative for our consumers and significantly lower currently projected smoking rates worldwide.
There is a clear opportunity to use the scientific evidence we now have available to substantiate the benefits of reduced-risk* products for those who would otherwise smoke. Looking ahead, I am increasingly confident that the quality of ongoing research from us, other manufacturers, academics and public health authorities—combined with open and honest debate with a diverse range of political, regulatory and public health stakeholders—will accelerate tobacco harm reduction.
James Murphy is the director of research and science at BAT.

* Based on the weight of evidence and assuming a complete switch from cigarette smoking. These products are not risk-free and are addictive.
† Our products as sold in the U.S., including Vuse, Velo, Grizzly, Kodiak and Camel Snus, are subject to FDA regulation, and no reduced-risk claims will be made as to these products without agency clearance.
¹ Based on Vype/Vuse estimated value share from recommended retail price in measured retail for vapor (i.e., total vapor category value in retail sales) in the U.S., Canada, France, the U.K. and Germany. These five markets cover an estimated 77 percent of global vapor closed-system net turnover, calculated in June-July 2021.
² The study focused on self-reported exclusive users of commercially available Vuse ePod or Vuse ePen3. Thus, references to “Vuse” in the context of the study means either Vuse ePod or Vuse ePen3.
May 30, 2023
The Pharmacology of Nicotine

Photo: Richard Villalon
The fascinating workings of a widely misunderstood chemical
By Grant Churchill
In this article, I will describe the pharmacology of nicotine. I will guide you along nicotine’s journey, starting with how it gets into a person, explain what it does once inside by interacting with specific receptors and finally, how it is inactivated and leaves.
Due to its chemical properties, nicotine can exist in two forms, depending on acidity, which controls its ability to be absorbed and, in turn, the effectiveness of delivery by different routes of administration. For example, certain forms of smoked tobacco must be inhaled to absorb nicotine, such as cigarettes, whereas others, such as cigar and pipe tobacco, are not inhaled but nicotine is still absorbed.
It might be useful for the reader to know where I’m coming from in writing this article. I’ve got a professional interest in how drugs work as I do research and teach in this area and find the pharmacology of nicotine fascinating and convey this to medical students. I’ve also got a personal interest as both my parents smoked and died from cancer. So, I wonder if vapes were available 40 years ago, would my parents still be alive? And now, should I be concerned that my adult son is vaping?
Routes and Rates
I’ll now describe in more detail how nicotine gets into the body and then the brain. This depends on the fascinating interplay between the route of administration and the chemical formulation, for example, free base or salt of nicotine. Regarding the route of administration, one can have an intuitive and qualitative understanding by considering the number of barriers and distance from the site of application to the brain.
When inhaled, nicotine has a short journey with few barriers as it is absorbed into the oxygenated arterial blood and goes from the heart to the brain within 10 seconds.
When swallowed, nicotine has a much longer journey with several barriers as it has to make its way through the stomach on to the small intestine before it can be absorbed into the bloodstream. Then it is in the deoxygenated venous blood that goes to the liver, then through veins to the heart, then through the lungs, where it finally meets the starting point for the inhaled nicotine. Importantly, the liver acts as a paper shredder for drugs and metabolizes them before they are delivered to the rest of the body.
When applied by a patch, the skin provides an additional barrier before nicotine can enter the bloodstream. Surprisingly, an intravenous injection of nicotine results in a slower route to the brain than inhalation.
For the intuitive understanding of the routes and rates, one can think about the physiological role of each system. The job of the lungs is to absorb large amounts of oxygen and quickly deliver it to the brain, the importance of which is driven home by considering that consciousness is lost within tens of seconds if inhibited. In contrast, the job of the gastrointestinal tract is to absorb food for energy, which is not needed at the pace of oxygen. Moreover, the job of the liver has evolved to protect us from the remarkably diverse and potentially harmful chemicals we consume in our diets, and in this regard, a drug is just another nonfood or non-nutrient to be inactivated and removed.
The uptake of nicotine can be more precisely studied quantitatively by monitoring nicotine in the blood and graphing this over time. This reveals an initial increase, a peak and then a tapering off, and numbers can be put to the time and concentration at the peak and the area under the curve. The hit comes from a combination of the speed of the peak and the maximum concentration, and the craving comes from when the concentration falls below a critical activity threshold. The different routes of administration show characteristic concentration over time profiles, with inhaled nicotine showing a fast peak within minutes whereas a patch-delivered nicotine shows a slow increase, taking an hour to peak. This has implications in the user experience and the success of nicotine-replacement therapies for tobacco harm reduction. The rate of decrease in nicotine concentration is similar for all routes of administration due to the same elimination mechanisms: a combination of metabolism by the liver and excretion by the kidney into the urine.
Crossing Barriers
The chemical formulation of nicotine as a salt or free base has a major impact on its uptake into the body as only the latter gets in. The chemical basis of this can be understood by considering a vinaigrette, which forms two layers, with the oil floating on a layer of vinegar and table salt (sodium chloride) dissolving only in the vinegar. This demonstrates that molecules can be watery or oily and only mix with their own kind, as summed up by the adage that oil and water don’t mix. Bringing this back to biology, the barriers to uptake of nicotine are cells that form layers like brick walls to separate the contents of our gastrointestinal tract from blood and blood from the organs. The cell’s barrier is its surface membrane called a bilayer, which is an inside out soap bubble with a watery surface and an oily interior forming the barrier. A water-loving nicotine salt cannot cross the oily interior whereas the oily free base of nicotine easily crosses.
The ability of nicotine free base to easily cross cell membranes is the mechanistic explanation of why nicotine can be absorbed from pipe and cigar smoke held in the mouth whereas cigarette smoke must be inhaled. The processing of the tobacco alters the chemical composition and acidity, resulting in cigarette flue-cured tobacco being acidic with nicotine salt whereas air-cured pipe tobacco is alkaline with nicotine free base. For a fuller explanation, we must again consider how chemistry interacts with biology. Smoke from acidic tobacco (nicotine salt) is less harsh and irritating and can be inhaled deeply into the lungs, where the large surface area (approximately the size of a tennis court) compensates for the inability of the salt to cross membranes.
Nicotine is always present in both forms, and the acidity controls the relative amounts of salt to free base with only a tenth of a percent in cigarette smoke being the free base compared to 50 percent in pipe smoke.
The trade-offs between the amount of nicotine that is bioavailable and how deeply it can be inhaled to take advantage of the large surface area of the lungs can also explain the nicotine salt craze in vapes. Nicotine salt formed by adding benzoic acid leads to a “smooth” taste, enabling deep inhalation of higher concentrations of nicotine.
How it Works Inside
Now that nicotine is in the body, I’ll describe its effects and how it is active. Nicotine affects cognition, body function and mood. The effects of nicotine on cognition relate to attention and memory and it has been suggested to be a “work” drug as opposed to what most of society would think of as a recreational or “fun” drug. The effects of nicotine on body function mostly relate to heart rate and blood pressure. The effects of nicotine on mood are relaxation and euphoria, arguably two of its major effects as nicotine stimulates a reward pathway in our brains the causes one brain region to stimulate other regions involved in emotion by releasing the neurotransmitter dopamine. Neurotransmitters are chemical messengers that enable communication between the brain cells termed neurons. Very generally, dopamine signals reward or the anticipation of reward—think sex, drugs and rock ’n’ roll, and these days, smartphones—which leads to pleasure and risk of dependence. Nicotine itself acts by mimicking the neurotransmitter acetylcholine, which is involved in learning, memory and attention, which fits with its subjective effects mentioned above.
Remarkably, all the diverse actions of nicotine arise from it acting on the same pharmacological target: the nicotinic acetylcholine receptor. This receptor spans the surface membrane of a cell and acts as a gated pore that allows ions such as sodium to flow through and trigger a wave of voltage change that sweeps from one end of the cell to the other. The binding of acetylcholine, or nicotine, results in opening and turning on the signal—but with prolonged presence, the gate on the pore jams shut in what is termed “desensitization.”
So, nicotine has time-dependent effects: Over a period of minutes, the nicotinic acetylcholine receptors open and release dopamine, but after several hours in the presence of nicotine, many of the receptors desensitize, dopamine levels fall, and more nicotine is required to return to the higher level of dopamine. Over a period of weeks, the neuron responds by increasing the number of nicotinic acetylcholine receptors, but most are desensitized, and if nicotine is no longer present, dopamine levels fall, giving rise to physiological withdrawal and addiction. Addiction at the molecular level is related to the structure of the nicotinic acetylcholine receptor, which is made up of five cylindrical subunits arranged side by side in a circle to form the pore. Each subunit is given a Greek letter designation, and in a mouse model, addiction relates to the presence or absence of the beta subunit.
Chemical Inactivation
The pharmacological effects of nicotine wear off with time, not from the above desensitization mechanisms but through chemical inactivation and excretion. Nicotine in the blood has a half-life, the time for a given concentration to be reduced by half, of about two hours. Nicotine declines over time through processes common to all drugs in which the underlying principle is to convert a drug from an oily compound to one that is watery. Water is watery due to it being composed of hydrogen and oxygen, therefore introducing oxygen into nicotine makes it watery.
This chemical transformation occurs in the liver by the enzyme (a molecular machine) cytochrome P450, which forms the major metabolite cotinine. As cotinine has a half-life of about a day, it can be used to examine past nicotine exposure, often by health insurance companies. Cytochrome P450 is a family of enzymes, and different forms are more or less active in converting nicotine to cotinine; the specific form varies between individuals, and certain forms are more frequent in a given ethnic group. For example, a less active form of the enzyme is more prevalent in individuals with Black or Asian heritage. Cotinine or its metabolites are finally removed from the body through the action of the kidneys and excreted into the urine. Again, the effect of acidity on nicotine can be employed by acidifying the urine to increase the fraction of salt, which cannot be reabsorbed back by the body, which thereby increases nicotine excretion.
Addressing Misunderstandings
Lastly, there are many controversies surrounding nicotine based on misunderstanding, half-truths and myths. The major health consequences of smoking are due to chemicals other than nicotine produced during combustion of tobacco, so other methods of nicotine delivery provide for tobacco harm reduction. For example, the relative health harms are such that vaping is a method for smoking cessation endorsed by the National Health Service in the U.K. and promoted as such by the government based on the best current scientific evidence.
Nicotine was used as a pesticide and can be toxic, but as Paracelsus famously stated, the dose makes the poison; any chemical can be toxic, including seemingly innocuous water, or an exceptionally toxic substance such as Botox can be used safely at a lowered concentration. Nicotine may have bona fide therapeutic use beyond smoking cessation in Alzheimer’s disease, Parkinson’s disease, schizophrenia and obesity. Intriguing evidence has been published regarding all these disorders, but the studies were small, leading to equivocal results.
Larger studies are needed, but the demonization of the tobacco industry for past wrongs is tainting and hampering the ability of scientists and physicians to obtain funding and conduct large, definitive trials. Given that psychedelic drugs, which were made illegal and vilified in the 1960s, are experiencing a renaissance to treat depression and post-traumatic stress disorder, there is hope that nicotine can be separated from smoked tobacco and used or not based on the evidence.
Grant Churchill is a professor of chemical pharmacology at the University of Oxford.

May 1, 2023
Bad Science
Photo: olly
What is bad science, and why is there so much of it?
By Clive Bates
Every Friday afternoon, I receive the worst email of the week. It is an automated search on the PubMed database, an index of the biomedical literature covering over 30 million published papers. The search tries to pick up new studies relevant to tobacco harm reduction and typically finds 30–70 new papers each week. Once the email comes in, I look through the abstracts and write down hot takes on the ones that seem relevant to policy or practice. Then I share with public health and consumer advocates. To be honest, it is often a dispiriting experience. Despite the scattering of excellent “must-read” papers, many are truly awful. I have been doing this since 2016, and the volume of papers has roughly doubled.
So, what have I learned by going through this painful weekly ritual? There are distinct patterns repeated in the literature, including poor methodology, poor interpretation of results and, almost always, poor extrapolation from findings to policy. There are obvious biases and sometimes near-comical desperation to find fault in reduced-risk products. Let me provide a list of some of the most common flaws.
Poor toxicology. The 16th century Swiss physician Paracelsus coined a maxim now expressed as “the dose makes the poison.” The detectable presence of a hazardous chemical does not mean it is toxic. There must be sufficient exposure to the human body to cause harm. As an example, many studies find metal residues in vape liquids and aerosols, but usually at levels that create no basis for concern.
Lack of meaningful comparisons. Many studies will present data on the effects of smoke-free products without context, such as a comparison with cigarette smoke, or some objective risk benchmark, such as the standards used for occupational health exposures. Without such context, it is impossible to assess whether the findings are a basis for concern or for reassurance. So, the question is always, “how much exposure, and is that a little or a lot?”
Observations versus risks. Nicotine is a stimulant and has many effects on the body, but epidemiological studies do not generally show nicotine exposure to be harmful to health. For example, there are regular headlines reporting that nicotine can cause an acute stiffening of the aorta, the largest artery in the body. But is that bad news? It seems less disturbing when we find that coffee, exercise or even exposure to music can have the same effects.
Unrealistic operating conditions. A range of studies makes machine measurements of emissions from heated aerosol products in unrealistic conditions that no human user could tolerate because of the terrible taste. Using this unrealistic method, researchers often find high levels of toxic chemicals. But this is about as sophisticated as testing the residues from the surface of burnt and blackened toast—and concluding that eating toast for breakfast increases cancer risk.
Over-interpreting animal and cell studies. There are many studies of human cells tested in Petri dishes (“in vitro”), but these are tests on cells without all the defenses and regenerative capacity they have in the body. Test on animals (“in vivo”) must recognize that animals have very different physiology to humans and are sometimes bred to have vulnerabilities. In both cases, creating a realistic equivalent to the exposures a human would experience can be challenging. These studies can’t tell us much conclusively about human risk. At best, they can provide valuable clues. At worst, they can mislead.
The wrong counterfactual. Many studies beg the question, “what would have happened if vaping did not exist?”—without that, it is hard to determine what effect vaping is having. For example, if there were no vape option, would pregnant women who currently vape be abstinent, or would they smoke? That should affect the advice of health professionals. Many are concerned about youth vaping, but for the youth who would otherwise be smoking, maybe vaping provides a significant benefit. That should affect the approach of policymakers and regulators. These assumptions are known as “counterfactuals,” and they are hidden and hard to determine, which makes them open to bias.
Correlation ≠ causation. Many studies find a correlation (usually referred to as an association) between vaping and some harmful effect. But too many studies suggest that vaping causes the harmful effect. Take, for example, vaping and Covid-19. A 2020 study suggested Covid was abnormally high in young vapers, concluding that vaping is a “significant underlying risk factor” for coronavirus disease. But critics pointed out that people who vape may be more likely to work in occupations where they are more easily exposed. Are vapers the type of people who are more likely to ignore masking guidelines and stay-at-home mandates? These other risk factors that may be more common in vapers are known as “confounders” and are a pervasive challenge in nicotine and tobacco science.
Reverse causation. Some studies find that vaping is associated with, say, respiratory illness. But what if some people who smoke switch to vaping precisely because their respiratory health is deteriorating? There would be an observable association, but the respiratory illness would be causing the vaping, not the other way around.
Confounding by smoking history. There has been a recent spate of studies claiming that vaping causes heart disease or respiratory conditions like chronic obstructive pulmonary disease. Almost everyone old enough to both vape and to experience these conditions has a smoking history, usually decades long, contributing to the disease. In such studies, it is impossible to isolate the effect of vaping from smoking. In some cases, the vaping has even commenced after the event or diagnosis.
Misunderstanding gateway effects. Does vaping lead to smoking? If that were the case for significant numbers, vaping could be almost as harmful as smoking. There are studies that show that young people who vape are also more likely to smoke. But that does not mean the vaping causes the smoking. More likely, the characteristics of the individual (e.g., rebelliousness) or their circumstances (e.g., parents, peer group) incline them to both smoking and vaping. This is a rival explanation to the gateway effect and is sometimes known as the “common liability” theory.
Selection effects. Some studies will focus on people who are unusually dependent on nicotine and therefore find it harder to quit. For example, in some cases, it is more likely that vaping will be tried by people who have not succeeded with any other method. This doesn’t mean vaping is less effective, just that the people using the products find quitting harder. This is a common error in studies of concurrent vaping and smoking, often known as “dual use.” The dual users are more dependent and tend to be more intense smokers with higher toxic exposures.
Weird study populations. Not all studies conducted on social media are useless, but most are. The people discussing vaping or smoking on Twitter or Facebook are not representative of the vaping and smoking populations. Their views are not gathered systematically in the way surveys work. Trends over time might be helpful, but most snapshots tell us little.
Baseless policy conclusions. Policy conclusions like “ban e-cigarette flavors to protect kids” are disappointingly common in the literature. To justify a policy requires numerous considerations that will go beyond the findings of any single data paper and stretch into economics and ethical considerations. Such considerations would include, for example, the assessment of unintended consequences (will kids smoke instead?) and trade-offs (between the interests of teenagers and adults).
Such a list does not explain why there is so much bad science, given these errors are simple to understand and mostly avoidable. I believe the answer lies in the incentives of those doing the science. Major U.S. federal research funders are aiming for a “world free of tobacco use,” which also means free of nicotine use. Tobacco regulatory science funded by regulators will be inclined to find justifications for regulation and intervention, not liberalization. There could also be deeper drivers: without the significant harms of smoking, there isn’t much justification for the whole field of tobacco control. Perhaps the emergence of much safer smoke-free nicotine products threatens livelihoods, careers and entire university departments, and bad science is the reaction. Maybe researchers gain prestige from alarming media coverage. These are all subtle conflicts of interest that are never acknowledged or recognized, yet they are pervasive drivers of bias.
It will surprise some, but I have noticed that science from the tobacco industry rarely crosses these lines. That is also down to incentives. The tobacco and nicotine industry must satisfy skeptical regulators about the safety and effectiveness of its next-generation reduced-risk products. It conducts research for product stewardship reasons and, in part, to take precautions against product liability litigation. The industry is incentivized to do good science.
It is time to address these problems by establishing a more constructively challenging environment for tobacco and nicotine science. This is not just an abstract academic curiosity. Public health credibility and the lives of millions are at stake.
Clive Bates is the director of Counterfactual Consulting and the former director of Action on Smoking and Health (U.K.).
January 2, 2023
Committed to Science

David O’Reilly (Photo: BAT)
David O’Reilly, director of scientific research at BAT, shares his views on the roles of science and nicotine in tobacco harm reduction.
TR Staff Report
Science is instrumental as the tobacco industry transitions from combustible products to less risky smoking alternatives. Tobacco Reporter spoke with BAT’s director of scientific research, David O’Reilly, about the roles of science and nicotine in tobacco harm reduction.
Tobacco Reporter: You have been with BAT since 1991. Could you please compare the role of BAT’s science department at the time when there were only combustible cigarettes to the role it plays today?
David O’Reilly: BAT has a long history of conducting scientific research and has had an R&D facility in the U.K. for over 60 years. Throughout this period, we have seen the science significantly change.
Originally, the majority of R&D we conducted was focused on cigarettes and tobacco plant science, but the more we learned about combustion and the harm that burning tobacco causes, the more we shifted our efforts to exploring new ways to provide consumers with less risky alternative products.
Initially, our focus was on reduced-toxicant cigarettes, but, utilizing the growing body of evidence and the Institute of Medicine report that highlighted the negative impact of combustion, we shifted our activities to the development of noncombustible products.
This is now where the majority of our R&D efforts are focused: generating new evidence to support our new category products but also developing new or improved products.
To ensure that we are using the latest scientific thinking and cutting-edge techniques, we have increased our investment in science and expanded the number of scientists within BAT. We have recruited people from a broad range of backgrounds, such as genetics, neuroscience and data sciences.
With so much focus on the development of reduced-risk products (RRPs), does BAT still conduct research on combustible cigarettes?
Our primary focus within R&D is our new category products, as we know that consumer preferences continuously evolve, but also that science and innovation continue to change at pace. However, we do undertake some R&D on our combustible products. This is essential to ensure that they are produced to high quality and manufacturing standards.
What are your thoughts on very low-nicotine cigarettes with regard to their role in tobacco harm reduction?
Our belief is that tobacco harm reduction is the best way forward to reduce the health impacts of smoking. The evidence shows that most of the harm from cigarettes is caused by combustion and the burning of tobacco, not by the nicotine.
In fact, nicotine plays an important role in tobacco harm reduction. Since it is one of the reasons why people smoke, nicotine’s presence in products that, though not risk-free and addictive due to the presence of nicotine, are designed to be reduced risk¹ compared to cigarettes. These products can help adult smokers to switch instead of continuing to smoke.
As Professor Michael Russell said in his 1976 pivotal paper, “People smoke for nicotine, but they die from the tar,”² and we know if you take the nicotine away or offer very low amounts, consumers may not be satisfied and revert back to cigarettes rather than switching completely to a reduced-risk alternative that is backed by scientific research, such as vaping.

In RRP development, one of the most pressing challenges is youth initiation. To what extent can innovation help prevent underage consumption? Will it be necessary to sacrifice all nontobacco vaping flavors to achieve this goal?
We are clear that our products are for adult consumers only and that youth should never use any nicotine products, be it cigarettes or vaping products.
Our products are sold to adult consumers via reputable retailers that verify the age of consumers before sale and follow our youth access prevention standards, which include prominent 18-plus labels on the front of all packaging and on all communications.
This is in addition to robust age verification on our own e-commerce channels, our youth access prevention training and certification for retailers and our “iCommit” training for employees.
It is worth highlighting that alternative products need to be satisfying to prevent adult consumers from going back to cigarettes, and research has shown that flavors play an important role in encouraging adult smokers who would otherwise continue to smoke to switch to better alternatives. However, a priority for BAT is ensuring that our flavors and device colors are designed to appeal to adult consumers, not youth.
In order to switch away from combustibles, consumers need to like the alternative, less hazardous product. What still needs to be done to improve nicotine delivery and consumer satisfaction? Can you please give an example of how you improved one of your next-generation products in this respect?
When we develop any new product, we think holistically about the consumer experience, and we use science and consumer insights to guide our development programs and deliver products that consumers want and find satisfying. For example, when we think about a product, we think about many aspects, including the design, the feel, the power of the battery, ingredients of the liquids, taste, etc. BAT was one of the first companies to use nicotine salts, as we knew that consumer satisfaction is important to make vaping more acceptable to cigarette smokers. This is just one example of how science and consumer insights combine to enhance our products.
For tobacco harm reduction to succeed, product must be affordable, especially to customers in the low-income and middle-income countries where many of the world’s smokers reside. What solutions in addition to nicotine pouches are you researching in this regard?
Our purpose is to build “A Better Tomorrow” by reducing the health impact of our business. We are doing this by developing a wide choice of alternative products for adult consumers who would otherwise continue to smoke, tailored to meet their evolving preferences.
Two key components of every innovation program we undertake are sustainability and affordability. It is important that these aspects are considered from the outset and at every step of the way so that we deliver a product that consumers want. We continue to launch these in markets across the globe, and our aim is to switch 50 million consumers to our noncombustible products by 2030.
Sustainability is increasingly important. BAT has introduced a recycling campaign for its electronic nicotine-delivery devices and has begun replacing plastic elements of vapor products with pulp-based alternatives. However, vaporizers contain circuit boards, which in turn contain plastics and heavy metals, and they also use lithium-ion batteries. How is BAT tackling this issue?
Every product developed has sustainability as a key component of the development plan, and we are committed to carbon neutrality across our operations by 2030. In May 2021, Vuse became the first global carbon neutral vape brand due to our ongoing efforts, notably by offsetting its carbon impact.³
Also, in many markets where Vuse is available, there is a takeback scheme in place, which allows consumers to return products for responsible disposal.
As part of our ongoing Vuse “Cut the Wrap” initiative, Vuse Go packaging has no external plastic poly wrap. The initiative, which is our commitment to reduce single-use plastics in our packaging, has already saved approximately 250 tons of plastic, the equivalent to more than 10 million plastic bottles.⁴
Misconceptions about the relative risks of RRPs and misconceptions about the nature of nicotine also present major challenges to harm reduction. An increasing number of U.S. adult consumers believe that vaping is as hazardous or even more hazardous than smoking, for example, and there are also misperceptions in the scientific and medical world. Such misunderstandings are often fueled by flawed studies. What can the industry do to address this problem without being accused of lobbying and in an environment where many are skeptical about tobacco industry-funded research?
At BAT, we think that the solution cannot be delivered by industry alone. To the contrary, BAT needs to work together with the wider scientific community and other key opinion leaders to create a system that is clear about the harm caused by smoking yet recognizes, holistically and consistently, where real public health gains can be made. A system that encourages adult consumer choice. We want a “whole-of-society approach”—as referenced by the United Nations—to this important public health issue.
There is also a need for the ongoing generation of robust scientific evidence. BAT continues to invest in scientific studies and openly share the results to help build the evidence base that supports alternative tobacco and nicotine products and their potential role in tobacco harm reduction.
At BAT, we believe that adult consumers should have access to information that enhances their understanding and allows them to make informed choices based on the best available evidence.

The concept of harm reduction has been widely accepted in fields such as substance abuse. Why does it face so much resistance when applied to tobacco, and how can this be overcome?
Firstly, it is important to recognize that there are some governments, such as the U.S., U.K., Sweden and New Zealand, who have adopted progressive public health policies that reflect the growing weight of evidence that supports the role of alternative tobacco and nicotine products in providing less risky alternatives to those who would otherwise continue to smoke. In these countries, although not all at the same stage, we see the continued decline in smoking rates and progress toward becoming smoke-free (under 5 percent of the population).
In other countries, many of whom have adopted policies that do not differentiate between cigarettes and alternative products, we see little or even a reversal in progress. Often the reason for such an approach is the “precautionary principle.” Essentially, in the absence of epidemiological data about alternative products, governments will not recommend them.
However, we believe, based on the already available evidence about alternative products and providing a complete switch, that these are reduced risk¹ compared to cigarettes. This is a view reflected through the work of independent organizations, such as Public Health England, who determined that based on current knowledge, vaping is at least 95 percent less harmful than smoking.⁵ However, it is important to note that these alternative products are not risk-free and contain nicotine, an addictive substance.
BAT has started to build an innovation hub in Trieste, Italy. What role will this hub play within the company’s global strategy for innovation and sustainability? What does this mean for your R&D site in Southampton?
The Trieste innovation hub will host a range of facilities, including a new manufacturing site for BAT’s New Category products, a digital boutique, innovation lab and Centre of Excellence for digital transformation and digital marketing. These activities, alongside the activities undertaken at our other R&D and innovation sites, complement and build upon the research and development work undertaken in Southampton, which is focused on generating the science needed to substantiate our products whilst ensuring they are produced to high standards.

What role should tobacco harm reduction play nowadays?
Tobacco harm reduction is one of the most important public health strategies. Science plays a critical role in delivering the alternative products that enable it but also allows us to measure the impact and outcomes of switching completely from cigarettes.
Work by scientific experts, using advanced computing and modeling, has shown us the potential for substantial life year gains and premature deaths caused by smoking-related diseases averted than can be delivered by switching smokers to vapor products.⁶ The longer these alternative products are on the market, the more real-world data we will be able to collect, which will be very powerful and reinforce our belief about the critical role they play in tobacco harm reduction and building “A Better Tomorrow.”
¹Based on the weight of evidence and assuming a complete switch from cigarette smoking. These products are not risk-free and are addictive.
² Russell MJ. Low-tar medium nicotine cigarettes: a new approach to safer smoking. BMJ 1976;1:1430–3.
³ Based on Vuse Go, [Vuse Go Max], Vuse ePod, ePen, eTankmini, Alto devices and consumables internal sales forecast (calculated March 2022) for 12 months starting from April 2022. Vuse will have reduced its carbon emissions by circa 55 percent (as of March 2023) through its internal sustainability initiatives since launched in 2019 and has now offset the remaining circa 45 percent.
⁴ Plastic saving was calculated from 2020 global sales volumes and 2021 forecasted sales, and the plastic bottles comparison was based on a 22.9 g bottle weight, representative weight of 500 mL commercially available soft drink bottles (May 2020).
⁵ Evidence review of e-cigarettes and heated-tobacco products 2018 (publishing.service.gov.uk).
⁶ Potential deaths averted in the U.S. by replacing cigarettes with e-cigarettes – PubMed (nih.gov).
January 1, 2023