How Did We Discover Smoking Causes Cancer?

In 1964, the president of the American Cancer Society went on television to say this.

At last, the relationship between heavy cigarette smoking and the increased incidence of lung cancer in men has been established as a fact. There can no longer be any doubt that the heavy smoking of cigarettes is a serious health hazard.

Earlier that year, the US Surgeon General published this report, over 300 pages explaining the overwhelming evidence showing how smoking causes different diseases. Over the next few decades, the US kicked off anti-smoking public health campaigns, made tobacco companies put labels on cigarette boxes, and made 10-year-olds across the country listen to cops tell us how bad drugs are. But getting to the point where the Surgeon General could say that smoking causes cancer took a long time. Like, by the '50s, we had lots of studies pointing to a link between the two, but not a causal relationship. So how did we get to the point where scientists could say that smoking for sure causes cancer? This video was made with the support of viewers like you on Patreon. The story starts in North America, where indigenous people had been using tobacco medicinally for thousands of years. When Columbus came over, he and his crew saw the Taino people in the Caribbean using tobacco smoke like a kind of disinfecting air freshener, and the snuff as a way to knock someone out before surgery. As more Europeans came over, they noticed indigenous folks in modern-day Mexico using it as an antidiarrheal or as a wound remedy. They also noticed that people in modern-day California would crush up tobacco leaves to make creams for skin conditions like eczema. So the explorers took a bunch of tobacco seeds and plants back to the Old world, and they went wild with it. They used it for everything from coughs to worms to, and this is foreshadowing, tumors. And they were so enthusiastic about tobacco because their list of drugs, or pharmacopeia, was essentially useless, so tobacco was hyped to high heavens. Like finally, there was something that might actually do something helpful. One of the biggest converts was Jean Nicot, the French ambassador to Portugal and namesake for tobacco's genus, Nicotiana. This dude was obsessed with tobacco's medicinal properties, and introduced it to French aristocracy and, uh, Unconsenting patients, we'll say. I found a story of Nico running his own ad hoc experiment where he made a crushed tobacco paste, rubbed it on some random man's tumor, and witnessed the tumor shrink. A little dubious. But that was about as experimental as doctors got back in the 1600s. Scholars could write whatever they wanted about a plant, print it in a book, and that just became medicine. If y'all want to see an extreme example of this, by the way, Google Pliny the Elder's Natural History. He was hundreds of years before this, but The point stands. Now, eventually someone made stuff up about tobacco, and it wound up in the 1612 printing of the Pharmacopeia Londonensis. The textbook described tobacco as a treatment for cold and lethargy— again, with no evidence to back it up. And while it sounds unscientific to us today, that kind of pharmacology lined up with popular concepts of medicine back then. European healers mostly subscribed to the humoral theory, a system that said health came from the balance of 4 bodily fluids, or humors: Blood, phlegm, black bile, and yellow bile. You got sick when those humors were out of balance, so treatments were meant to restore that balance. That's where bloodletting comes from, by the way. Too much blood is making you sick, so let's let some out. They also believed in something called the miasma model, which said infections and diseases spread through invisible, bad-smelling vapors called miasmas. And since bad smells spread disease, good smells might prevent them. This is how the plague doctor became a thing. They'd put nice-smelling flowers, potpourri, or tobacco in their beaks and hoped it would keep them healthy. But if you didn't want to wear whole getup, you could just smoke a pipe to keep yourself from catching plague. And this belief lasted for centuries. You'd find people in the 1800s smoking pipes in anatomy labs with the same logic. They thought a smelly corpse carried disease, so tobacco smoke would protect them. This combination of humoral theory and miasma model also lent tobacco to some of the dumbest treatments in medical history. This textbook from 1747 recommended blowing tobacco smoke in someone's ear to treat earache, or injecting tobacco for a twisting of the guts. Whatever that means. I dunno, it sounds like innuendo to me. My absolute favorite of these dumb treatments though comes from 18th century England. Back then, people in London regularly drowned in the River Thames, so people needed to figure out ways to revive them. The solution was tobacco enemas. Literally, it was a hose that let you blow tobacco smoke up someone's butt. Supposedly, it worked once and it became a thing after that. By the end of the 19th century, we'd moved past the idea that tobacco was purely good for us. The story starts getting more complicated, when we start talking about cancer. Superficial tumors can be easy to find, so doctors have been diagnosing cancer for thousands of years, way before modern mammograms and biopsies. Hippocrates was the first to name the disease karkinos, which means crab in Greek. Nobody really knows why he called it that, maybe because a lumpy tumor can be hard like a crab shell. Regardless, 500 years later, a famous Roman doctor named Claudius Galen dissected a breast tumor, saw all the branching blood vessels, and thought, huh, yeah, I guess that does kinda look like a crab. And thus, Cancer got its modern name. But scientists didn't have good evidence for the cause of cancer until the 18th century. In 1775, a doctor named Percival Pott noticed that chimney sweeps were getting scrotum cancer way more often than other men. So he proposed that something about their job was giving them cancer. He didn't know what yet, but he kickstarted this idea that the cause of cancer could be found. And over the next century, other doctors noticed more cases of mouth, nose, and lip cancer among smokers. So at this point, some red flags are going up. But these were just anecdotes still. And lung cancer wasn't even on the public health radar yet, in part because smoking wasn't that popular. Most American tobacco users preferred chewing, snuffing, or smoking a pipe. And they usually didn't inhale the smoke. That's because the type of tobacco plant that's native to America, Nicotiana rustica, is really strong. It's like 9% nicotine. But by the mid-1800s, people started asking for a milder tobacco. It's like if the only drink in America was a triple imperial IPA, Americans just wanted a White Claw. Like, yeah, it's less potent, but you could actually enjoy it. So farmers cultivated a few different species and preparations that were less intense. The most popular was, and still is, Nicotiana tabacum, which is closer to 1% nicotine. The new tobacco was much easier to smoke, but cigarettes still weren't common yet because they were so expensive. It would take rollers a full minute to roll a cigarette by hand, which made the final product more of a luxury item than a commodity. Then in 1880, An American inventor named James Bonsack filed a patent for a cigarette machine that could roll 200 cigarettes a minute. Cigarettes became affordable and available everywhere, so smoking rates shot up in the late 1800s. But doctors didn't see lung cancer shoot up right away, for 2 reasons. The first: we still didn't know a ton about lung cancer. We knew it existed before cigarettes got popular, but diagnosing it was really difficult. Doctors would've confused it with tuberculosis or other lung diseases, so your average physician wasn't really familiar with lung cancer from a clinical perspective. And scientific research didn't have much to add. In 1890, there were only 142 cases of lung cancer in the entirety of medical literature. And even if you suspected that one of your patients had lung cancer, you couldn't confirm it until after they died and you did an autopsy. Some doctors in Germany did this on a group of miners in the 1870s, but that was the only postmortem lung cancer study for a long time. The invention of the X-ray in the 1890s helped get more accurate diagnoses while the person was still alive, but until then, the diagnosis was inconsistent and extremely rare. And this points to the second reason lung cancer wasn't an emergency yet. Statistics about death. Between the late 1890s and early 1910s, we were in this period where smoking was getting way more popular, but not enough time had passed for a ton of people to develop lung cancer. In 1878, the University of Dresden's Institute of Pathology estimated that, of all the cancers they'd found on autopsy, only 1% were lung cancer. But the field of epidemiology was really young at that point, and data collection wasn't standardized, so our baseline rates of lung cancer were really fuzzy. But a few years into the 20th century, and the data was overwhelming. Between 1922 and 1947, deaths from lung cancer increased 15 times in the UK. And between 1930 and 1950, deaths from lung cancer increased 9 times in the United States. Whatever the baseline was, we were above it. People blamed the increased cancer rates on pollution from cars, or maybe it was the aftermath of the 1918 influenza pandemic, or maybe men were inhaling dust from their industrial jobs. Either way, lung cancer was getting out of control, and we had no good idea where the disease was coming from. And that's because cancer didn't behave like any disease we'd beaten before. The humoral theory and miasma model of disease weren't getting us anywhere. Medicine in mid-19th century Europe did nothing at best, and could kill you at worst. The biggest change came in the late 1800s, when microbiologists like Louis Pasteur, Joseph Lister, and Robert Koch showed that microscopic organisms cause infectious disease. So tuberculosis is caused by Mycobacterium tuberculosis, and anthrax is caused by Bacillus anthracis. Little microbe guys. This idea was called the germ theory of disease. And it was a huge deal because scientists could finally identify the cause of a disease, which meant they could figure out treatments or prevent diseases with vaccines. That helped germ theory become the most popular model across allopathic medicine by the end of the 19th century, and it became the basis for the most effective public health campaigns in the early 20th century. Medicine and public health based on germ theory worked so well that eventually, people started living long enough to die from chronic diseases like heart disease or cancer. And this shift in the leading cause of death is part of something called the epidemiological transition. It usually comes with an increase in life expectancy and decrease in birth rates too. But importantly, it didn't happen everywhere, and it didn't happen all at once. Just like everything with public health, wealthy countries benefited more. To this day, infectious diseases like tuberculosis are still enormous health problems in African nations. So germ theory was this powerful thing that worked great against infectious diseases, but it couldn't explain how chronic diseases worked. It wasn't as simple as finding the single virus that caused heart disease. scientists would need a completely different approach to figure out cancer. So let's come back to the 1930s. Doctors around the world were seeing more cases of lung cancer, and they had to start with the most basic question: are there any noticeable differences between people who have cancer and similar people who don't have cancer? This kind of question lends itself to something called a case-control study, which involves taking a group of people with a disease and a similar group of people who don't have the disease and looking for any differences between the groups. The researchers might look for differences in medications they take, exposure to other sick people, or lifestyle habits like smoking. Scientists did a lot of these in the '20s and '30s, so I'll give you just one example. In 1928, Lombard and Dohring published a case-control in the New England Journal of Medicine. They sent questionnaires to hundreds of patients with different cancers, and sent the same questionnaire to similar people without cancer. They asked some of the expected questions like, how much tobacco do you smoke? And how much salt do you eat? But they also asked questions that seemed completely out of left field, like, how good are your teeth? Do you take laxatives? What's your conjugal state? Again, they had no idea where to start. They had to cast a wide net. Some of the questions showed no differences between groups. But the authors did notice that almost all of their patients with lung, lip, cheek, or jaw cancers, and 78.8% of all their cancer patients were heavy smokers. Only 20% of their non-cancer controls and a third of American men smoked that much at the time. And that seems like a huge difference, but case control studies still aren't the best evidence. They're academically interesting and encourage more follow-up study, but they're retrospective. They look back at patients who have different lives full of confounding variables that could shape the results. Now, while European scientists were starting to understand the epidemiology, Scientists in Latin America especially were gathering pathological evidence, information that helped them understand how the disease worked on a cellular level. In 1922, an Argentine scientist named Ángel Roffo opened the Institute of Experimental Medicine in Buenos Aires, and over the next few decades, he dedicated his career to studying lung cancer. Assuming that smoking did in fact cause cancer, he focused on finding the chemicals inside cigarettes that might cause cancer at the cellular level, mainly using rodents. And as much as I love the visual of tiny mice smoking tiny cigarettes, he used a different methodology. Roffo suspected that tar caused cancer, not nicotine. So he came up with an experiment where he distilled tobacco smoke into 3 different liquids, then smeared those liquids on rabbits' ears and recorded which formulas induced cancer. As expected, the tarry formulas induced cancer, while nicotine-only formulas didn't. It turned out it was these molecules made of hydrogen and carbon that were the primary carcinogens, the chemicals that induce cancer in cells. Roffo's research inspired more epidemiological studies in the '40s and '50s, but he also got the attention of scientists who worked for the American tobacco industry. In an internal memo to the president of the American Tobacco Company, Rotho was described as the chief protagonist of the theory that there is a causal relation between smoking and cancer of the respiratory organs. He was big tobacco enemy number one. Now while they were worried about Rotho, he wouldn't be a problem for too long. Not because somebody assassinated him, but because he published his work mostly in German in the 1930s. And scientific research published in German in that time has a complicated backstory thanks to— Nazi Germany hated tobacco. They hated anything that posed a risk to the future of the And by the late 1930s, plenty of people were on board with the idea that smoking wasn't entirely healthy. So they implemented huge anti-smoking campaigns throughout the '30s and '40s. They banned smoking in public places like movie theaters, public transportation, and schools, and banned the sale of cigarettes to pregnant women. They stopped short of outright banning smoking though, because they still needed those tax dollars. As part of the campaign, they also funded a ton of anti-smoking research. Their first big study was published in 1939 by Franz Müller. You don't have to speak German to recognize some of the familiar figures here. Lung cancer is going up, smoking rates are going up, let's see if smoking plays a role in lung cancer. According to Google Translate, Müller says that the increase in smoking was the single most important factor in the increase of lung cancer. He also pointed to a higher risk of heart disease, which we know today to be true. In 1941, the Nazis funded the creation of a research center at the University of Jena called the Institute for the Struggle Against Tobacco Hazards, which is not subtle. Like, they might as well have called it the Institute for Confirmation Bias if they already knew that their research was going to say tobacco is bad. 2 scientists working out of the institute published a case control in 1943. Among 109 cases of lung cancer, only 3 were found in nonsmokers, which was way fewer than in the control group. Other Nazi scientists would be the first to mention the harmful effects of secondhand smoke, or what they called passive smoking. But all of this German science didn't necessarily make a huge impact on the overall state of smoking research. I've read a paper from 2012 pointing out that Mueller's paper mostly repeated claims made by another German paper from 1931. Otherwise, it was mostly a review and case series, not high-quality research. Another historian pointed out that the 1943 paper was only cited a handful of times after the war. Plus, the study's methodologies received a good amount of criticism since, you know, the underlying motivation for all these studies was explicitly racist. Hitler was quoted as saying that tobacco was the wrath of the red man against the white man for having been given hard liquor. Depending on which source you read, read, the Nazi contribution to the science behind smoking was either the single defining moment in the scientific saga, or forgotten to the world of science. Either way, better science came just a few years later. Imagine it's the late 1940s. Lung cancer is now the most commonly diagnosed cancer, and second deadliest cancer after stomach cancer. World War II was over, so the governments of the UK and the US could finally put money into lung cancer research. This culminated in 1950 when 4 studies came out that all claimed smoking caused cancer. They were published in prestigious journals, and had the highest quality epidemiological evidence seen to date. We'll go through them one by one, starting in the US. In the May 27th issue of the Journal of the American Medical Association, Wynder and Graham published Tobacco Smoking as a Possible Etiological Factor in Bronchogenic Carcinoma. That's jargon for smoking might contribute to lung cancer. They recruited over 600 patients with lung cancer into the study. They started by separating subjects by disease status. They either had lung cancer, or they didn't, which meant they'd be in the control group. Then the smokers in each group were classified by their smoking habits. Nonsmokers were those who averaged less than 1 cigarette a day, while chain smokers smoked over 35 a day. The questionnaire asked about habits over the course of 20 years, since the researchers hypothesized that lung cancer took years to develop, so long-term habits were more relevant than how much that person smoked last week. After running the numbers, they found that 96.5% of men with lung cancer were heavy smokers or chain smokers, while only 73.7% of the general population smoked that much. They also saw something called a dose-response effect. The more cigarettes a group smoked corresponded to more cases of lung cancer in that And this article was so impactful because that dose-response effect was seen across a lot of participants, which made it a powerful result. But this study alone still didn't show that smoking causes cancer. As Wynder himself said, it was an important factor in the induction of bronchogenic carcinoma, but he didn't say it was causal. In the same issue of JAMA, literally starting on the same page, Levin, Goldstein, and Gerhardt published Cancer and Tobacco Smoking: A Preliminary Report, which used hospital records to come to the same conclusion. It's a factor, but we can't show cause and effect yet. Also, they got well actually'd in a letter to the editor a few months later. These 2 research groups literally published the strongest evidence to date showing the link between cancer and smoking, and haters still wrote mean comments. Bet they'd fit in on YouTube. The 3rd paper, Tobacco Smoking as an Etiologic Factor in Disease, was published in Cancer Research and used data from a veterans hospital in Illinois. For the last decade, the hospital made it standard practice to ask patients about their smoking habits on intake. Then they'd file the intake form with the rest of the patient's medical record. At the end of their By the end of their data collection period, the research group had 5,000 patient records to work with. That left them with 82 patients with lung cancer and 73 with throat cancer, which they lumped together as respiratory cancers. They compared those patients' smoking habits to a control group of 522 patients with other tumors, and found that 85.4% of the throat and lung cancer patients were smokers, compared to 76.1% of the control group that smoked. The final study from 1950 came from these guys. And they're my faves, Richard Doll and Austin Bradford Hill, who published Smoking and Carcinoma of the Lung: Preliminary Report in the British Medical Journal. Bradford Hill and Doll were assigned by the Ministry of Health to figure out why lung cancer was going up, and neither of them knew where to start. Both of them were smokers, and they weren't automatically convinced of the link between smoking and cancer. They thought it could be cars, coal, industry, or maybe smoking, but these were the same ideas that people had 50 years earlier. In their study, they selected 20 hospitals in the UK, and whenever anyone was admitted with lung, stomach, colon, or rectal cancer, an assigned person would come interview the patient with a questionnaire. Then, that same person would walk through the same hospital, looking for a patient of the same sex and age and ask them the same questions. Then, after the patient was discharged from the hospital, they confirmed that the patient was actually diagnosed with cancer and asked how it was confirmed, which was mostly by biopsy or X-ray. Between April 1948 and October 1949, they got almost 2,400 patients. But they decided to exclude anyone over age 75, and patients who got a non-cancer diagnosis after admission. The group then shrank to 2,140 patients, since some of the group were discharged before they could be interviewed, some couldn't speak English, some were too sick, a few dozen died, and one was a liar. That's what it says, right there. Just like the Winder and Graham study, they categorized smokers by how much they smoked so that they could check for a dose-response effect. At the end of the research, they showed the dose-response effect, but they also showed something called specificity. Specificity, when the cause is associated with one outcome and nothing else. They found a clear association between lung cancer and smoking, but no association between any other cancers and smoking. In their own words, it must be concluded that there is a real association between carcinoma of the lung and smoking. Their results were so powerful that Doll stopped smoking in the middle of the study, while Bradford Hill kept smoking. Side note, I don't get involved in the pissing match of who was first in medical history, but I personally think that the British paper was the most convincing of the studies from They had all the best aspects of the 3 American studies, including a dose-response effect, specificity, and a large sample size. But it was published in September, while the Wynder and Graham study was published in May. So American writers tend to look at this study as supporting evidence instead of the best one. So it's 1950, and these 4 massive papers come out. But smokers around the world didn't quit overnight. Why not? Well, mostly because laypeople don't read technical scientific journals, but they were also getting mixed messages from everyone else, like doctors and the media. I'm gonna have my friend Knowing Better teach you a little bit about that one.

Look, everybody knows that cigarettes are bad for you, right? This isn't a secret. They figured that out as soon as people began smoking in the '20s, when the main issue was throat irritation and smoker's cough. The industry fixed that by adding menthol, which protected your throat with a cool, fresh sensation.

Great tobaccos and a light touch of cooling menthol. This new spud gives you a fresh taste in your mouth, like the smoke was air-conditioned.

Since not everybody is a fan of that flavor, they came out with king-sized cigarettes in the '30s, which traveled the smoke farther, making it smooth and mild.

Yes, Dunhill, thanks to its king size, its finer tobaccos, and its natural filtering qualities, screens out irritants to give you a far milder smoke.

These had already been on the market for decades when those so-called cancer studies were being published by fringe scientists. So most people weren't all that concerned, the industry will find a solution, just as they always have. And most doctors were regular smokers at this point, so they began endorsing brands which had proven themselves to be healthier.

What cigarette do you smoke, Doctor? Yes, surveys show more doctors smoke Camels than any other cigarette. Smoke Camels, the cigarette so many doctors enjoy.

Their faith was rewarded, the industry began adding filters to their cigarettes in the early '50s to make them even safer. Millions of consumers switched to filtered cigarettes, secure in the knowledge that they were protected from lung cancer and any other dangers the health fascists were complaining about.

Yes, the perfect marriage between a great new filter and a great modern blend. Now in new Old Gold Filter Kings. You get the fresh steam and pollen. You get the longest filter offered yet. Territon's got a charcoal tip and it's got a white one too. Yes, it's the filter that counts, and L&M has the best. You get much more flavor, much less nicotine. A light and mild smoke. This is it. L&M filters, just what the doctor ordered.

See? Just what the doctor ordered. I don't know why everyone is so worked up over this cancer thing. They figured it out. It's fine. Don't stop smoking. It's fine.

People started taking the cancer risk more seriously after an article came out in Reader's Digest, but you'll have to watch Knowing Better's video for that story. Back on the science side of things, there were still plenty of people who smoked and didn't develop cancer. So how could smoking cause something if it doesn't have a 100% hit rate? Was there some other factor or confounder they didn't study? Just like the case controls before them, these new studies had all been retrospective. They looked at a snapshot of data which was influenced by all the messiness of life that you couldn't standardize. If you wanted to show a more powerful association, you'd have to do a prospective study. Like, you could recruit 2 sets of comparable teens and assign them to either a smoking group, or a non-smoking control group, and then see who got cancer at the end of their lives. But that kind of study isn't gonna happen because, you know, ethics. Bradford Hill and Doll knew that the next best thing would be finding a group of adults who were as homogeneous as possible, but some voluntarily smoked while others didn't. Luckily, they knew a group of people who fit that description to a tee. A group of people who all had similar socioeconomic status, were almost entirely white, and almost entirely men. Doctors. And even better for their study, doctors in the UK had to keep their contact information on file in order to practice medicine, so It would be easy to follow up with them. Bradford Hill and Doll decided their next paper would use British doctors as their subjects. In 1951, Doll sent a questionnaire to every available doctor in the UK asking the following questions: Number 1, do you smoke? If you do, how much and when did you start? If you quit, when did you quit? They classified the doctors into groups based on age, how much they smoked, how they smoked, and whether they quit or not. After sending out almost 60,000 surveys, they got 41,000 responses. Then, they excluded men under 35 and women of all ages since lung cancer wasn't as common in those groups. They were left with 24,389 participants that they would follow around for the next few decades. Then, they waited. Over the next 29 months, they saw 789 deaths, 36 of which were from lung cancer. They found that zero of their nonsmokers developed lung cancer, and saw the dose-response effect that they expected from earlier studies. They also saw a higher incidence of coronary thrombosis in smokers, what we'd call heart attacks today. They published their initial results in June 1954, and it finally got some attention from the scientific community. Not only did they present a ton of data, but they presented the first prospective cohort trial about the topic, which made it the best statistical evidence to date that smoking caused cancer. A few months later, the American Cancer Society funded a similar study that lent even more evidence to the causal link. That study's methodology was similar to the British doctor study, so I won't go into depth here, but they only recruited white men between the ages of 50 and 69.

Nice.

Now, the 1954 publication in BMJ was preliminary result. Bradford Hill and Doll brought on a younger researcher, Richard Petto, and followed up on their subjects multiple times from 1957 through 2001. At the 10-year follow-up, they reported that lung cancer caused 0.07 deaths per 1,000 nonsmokers, but 3.15 deaths per 1,000 in the heaviest smoking group. Then in the '80s, Doll led a similar study showing the same mortality effects of smoking on female doctors, because remember, they were excluded from the original British Doctors Study. Now, scientific studies can help inform individuals. But I argue that science is more impactful when it informs policies. The British doctor studies have collectively been cited over 17,000 times by other scholars, which means these studies were extremely impactful both for follow-up research and for science-based policy, which is what happens next in the story. In 1964, the Surgeon General of the United States released that big report I mentioned at the beginning of the video. They recognized that smoking was a cause of cancer. It's 155,000 words long, which Which is longer than The Hobbit, and it's not nearly as fun to read. This was regarded as the landmark moment in the public health battle against smoking. But as far as proving that smoking caused cancer, it wasn't all that exciting since that science was already 10 years old at that point. It did mark a new chapter in American public health though. Now that we had solid evidence showing smoking causes cancer, what do we do? Hey, before you go, I think you're gonna like this video I made about snake oil salesmen, or this one about how generic drugs became a thing. And if you want to keep learning about tobacco, make sure to check out this video from Knowing Better about the history of the cigarette industry. And subscribe to him while you're at it! And of course, thank you to my patrons on Patreon who make these videos possible. Have fun, be good, thanks for watching!