Chapter 2, Part 2

By Frank Tursi, Susan E. White and Steve McQuilkin
JOURNAL REPORTERS
© Winston-Salem Journal

Ernst Wynder was a medical student at Washington University in St. Louis in the late 1940s when he attended an autopsy of a lung-cancer patient during a summer internship at New York University. He was surprised by the absence of a medical history. Showing a brashness that some of his professors found infuriating, Wynder talked to the widow and learned that her husband had been a two-pack-a-day smoker. His curiosity piqued, Wynder crossed the street to Bellevue Hospital and interviewed lung cancer patients there. ''After 20 or so interviews, I knew I had something,'' he recalled.

The effect of smoking on health had been debated for hundreds of years. Dr. John Hill, a physician and botanist in London, was the first to suggest a relationship between tobacco and cancer when he reported in 1761 six cases of ''polypusses'' related to the excessive use of snuff. But the subject didn't attract much attention until after World War I.

The R.J. Reynolds Tobacco Co. was once the largest cigarette company in the United States with a powerhouse of best-selling brands: Winston, Salem and Camel. But times changed, and as the case against smoking became more pronounced in the 1960s, RJR failed to adapt to the marketplace. Its rivals would eventually rush past it, and RJR's efforts to catch up would have a profound impact on the company and the cigarette industry.

Before that war, most doctors spent their entire careers without seeing a lung-cancer patient. Only 371 cases were re-ported in the United States in 1914. More than 2,300 cases were reported 15 years later. By 1942, lung cancer was killing almost 9,000 Americans a year, a toll that would more than double by the time Wynder started his mouse experiments. It had by then surpassed stomach cancer as the most common form of the disease.

Tobacco was an inevitable suspect. It didn't take a medical degree to recognize that the alarming lung-cancer epidemic paralleled the increasing popularity of cigarette smoking. Colonial Americans smoked their tobacco in pipes; 19th-century smokers favored cigars. Neither form was normally inhaled. Cigarettes, on the other hand, were made primarily of burley and flue-cured tobacco, which produced a mild smoke that could readily be taken deep into the lungs.

Early researchers, though, had a hard time investigating lung cancer's possible sources because it took 20 or more years before symptoms began to appear. Devising studies to investigate diseases with such long latency periods was difficult. But enough preliminary work had been done by 1946 to cause a tobacco chemist at Lorillard to write in a letter to the company's manufacturing committee: ''Certain scientists and medical authorities have claimed for many years that the use of tobacco contributes to cancer development in susceptible people. Just enough evidence has been presented to justify the possibility of such a presumption.''

Wynder had a high-enough opinion of himself to conclude that he was just the guy to nail the case closed. He didn't consider his youth and relative inexperience or the fact that he wasn't yet out of medical school to be major drawbacks.

The son of a Jewish doctor, Wynder was born in the German town of Herford and fled with his family from the Nazis. They settled in suburban New Jersey, where Dr. Wynder resumed his practice. Ernest or Ernst _ he would alternate the spelling for the rest of his life _ graduated from New York University in 1943 and spent World War II with Army intelligence. By the time he entered medical school, he wore his black hair long and carried around a world-weary, dour expression that was highlighted by deep-set, caring eyes.

It was a look women apparently took to. Before his marriage, Wynder often attended scientific conferences with a beautiful woman clinging to his arm. The tobacco scientists gnashed their teeth in envy.

After interviewing the lung-cancer patients at Bellevue, Wynder returned to St. Louis, where Dr. Evarts A. Graham, a distinguished professor of surgery who performed the first successful removal of a cancerous lung, allowed Wynder to continue his interviews with Graham's patients. Graham, a heavy smoker himself, was dubious about the smoking-cancer link, but he saw no harm in allowing the eager, energetic researcher to ask his questions. As the evidence accumulated, Graham became a believer.

During his last two years of medical school, Wynder collected information from 650 lung-cancer patients in a dozen states. He and Graham published the findings in 1950 in the Journal of the American Medical Association. Their study showed that more than 95 percent of the lung-cancer victims had been smoking for 20 years or more. ''Excessive and prolonged use of tobacco,'' Wynder and Graham concluded, ''especially in cigarettes, seems to be an important factor in the induction of bronchiogenic carcinoma.''

Doctors didn't quite know how to react to the first major study to link cancer and smoking. Most smoked. Some even endorsed certain cigarette brands in advertising. The medical journal that published Wynder's finding said weeks later that smoking's benefits outweighed any possible harmful effect.

More evidence, however, was on the way. From 1948 to 1952, Drs. Richard Doll and A. Bradford Hill interviewed nearly 5,000 patients in British hospitals. Out of 1,357 men with lung cancer, all but seven were smokers. Doll and Hill concluded: ''Smoking is a factor, and an important factor, in the production of cancer of the lung.''

Frank Colby couldn't help but be impressed. He and Wynder shared many traits: both were the sons of Jewish doctors in Germany, both fled Nazi persecution, both became scientists. Wynder, however, used his skills to indict smoking. Colby would spend his life defending it. In the early 1950s, Colby joined R.J. Reynolds Tobacco Co. to set up its scientific library. He would remain with the company for more than 30 years, and Wynder would become his main opponent.

''In 1950 Ernie Wynder and Richard Doll should have gotten the Nobel Prize in medicine because their work opened up the scientific literature to the appropriate way of treating long latency, chronic diseases,'' Colby said respectfully. ''The fact that they were wrong had nothing to do with it. At the time, it was a breakthrough discovery.''

Wynder's best was yet to come. Conducting experiments on humans to find the carcinogens in tobacco smoke was, of course, unethical. So researchers had to use animals. Large mammals were hard to handle and expensive to keep, and forcing smaller animals to inhale cigarette smoke presented problems. Unlike humans, most breathed exclusively through their noses, which had highly developed built-in filters to block or absorb irritants. Whole smoke never reached their lungs in quantities large enough to offer a meaningful comparison to human exposure. Compensating with large amounts of smoke usually killed the animals because of the carbon monoxide in the smoke.

Skin experiments, then, offered the most practical alternative, and mice were the most common test animal because they were small, short-lived and close enough anatomically to humans to allow researchers to reach reasonable conclusions.

Machines that mimicked human patterns smoked the cigarettes, and the smoke was cooled to extract the solids. Wynder shaved the backs of 86 mice from head to tail and applied 40 milligrams of the tar mixture with a brush three times a week. Forty-four percent of the mice developed cancerous tumors. The procedure was far from perfect, but Wynder noted in an article in Cancer Research magazine in December 1953 that it provided ''a working tool which may enable us to identify and isolate the carcinogenic agent(s) within the tars.''

Graham, Wynder's co-author again, was more to the point. He told a news magazine soon after the results were published that the experiment showed ''conclusively'' that something in cigarette smoke caused cancer. ''Our experiments have proven it beyond a doubt,'' he said.(Kluger footnote)

Wynder's mice were front-page news around the world and were featured in major magazines such as Time, Life and Reader's Digest, which had become very aggressive in running articles that attacked smoking.

Worried Reynolds employees approached Murray Senkus, the company's new director of chemical research. ''It aroused some apprehension,'' he said. ''I talked to a number of people in the plant. They asked, `Should I sell my stock?' ''

Publicly, executives at Reynolds and at the other tobacco companies were quick to cast doubt on Wynder's findings. The response from Edward A. Darr, RJR's president, was typical. He assured smokers that ''no real or substantiated evidence'' existed that linked smoking to lung cancer. ''The only claims have been made by just three doctors,'' Darr said. ''The vast body of other medical scientists do not agree with these.''

The company's annual reports would take the same reassuring tone. ''Many eminent medical authorities have stated that claims made as to a possible causal relationship between smoking and lung cancer are lacking in any real proof,'' the 1954 report said. ''Very little is known as to the true cause or causes of any cancer.'' Similar statements would appear in the company's annual reports for the next 15 years.

Company scientists insisted then as they do now that Wynder's experiment exposed the mice to extraordinarily large amounts of tar in a form that's chemically different from the tar inhaled by smokers. Painting one square centimeter of the back of a mouse with 40 milligrams, they say, is the equivalent of smoking 97,000 cigarettes a day.

''It's absolutely insane, but it was never adequately fought,'' Colby maintains. ''We knew that the established science -- the skin painting -- was bullshit.''

Despite the industry's criticism, tobacco scientists for the next 20 years would model their own research on Ernie Wynder's findings and pronouncements, and mouse painting remains a standard analytical tool.

Wynder's adversaries at the nation's tobacco companies knew that more than brave words were needed to counteract the fear welling up among their customers that cigarettes would kill them.