Animal Smoking Studies

Some seem to think experiments show smoking causes cancer in animals.  Not so, for mice or rats:

I review the results of a representative selection of chronic inhalation studies with rats and mice exposed to mainstream cigarette smoke. … Smoke-induced epithelial hypertrophy, hyperplasia, and squamous metaplasia were reported in the conducting airways in most of the studies, along with increased numbers of intra-alveolar macrophages that were occasionally associated with alveolar metaplasia. Lung adenomas and adenocarcinomas were reported in only a few of the studies. No statistically significant increase in the incidence of malignant lung tumors was seen. …

The 14 studies reviewed … [showed] significant increases in the numbers of malignant tumors were not produced in the respiratory tracts of rats or mice exposed chronically by inhalation to cigarette smoke.  The studies clearly involved the inhalation of very large amounts of smoke (usually from unfiltered, high-tar cigarettes) …  The results of this work clearly indicate that maximal amounts of smoke were inhaled into the lungs of the animals (blood COHb concentrations very close to those associated with lethality) daily for up to 2 yr with no carcinogenic effect noted.

Nor for hamsters, dogs, or primates:

This paper makes an identical evaluation as before, but, restricting the species being evaluated to representative studies of smoke-exposed hamsters, dogs (both by tracheostomy and by direct inhalation), and nonhuman primates. As was seen previously, no statistically significant increase in the incidence of malignant tumors of the respiratory tract was found in any of the 3 species, even though very long exposures and high doses of smoke were used.

Now the number of animals in these studies is a few thousand at most, and their duration is less than decades, but experimenters did have complete control over making animals smoke heavily.  Yes this review author works for a tobacco firm, but his papers seem professional.

Searching for “animal smoking experiments,” I found many sources admitting we haven’t found much evidence smoking hurts animals, and none saying the opposite.  Here is a ’97 Scientific American article “Animal Research is Wasteful and Misleading”:

In a striking illustration of the inadequacy of animal research, scientists in the 1960s deduced from numerous animal experiments that inhaled tobacco smoke did not cause lung cancer (tar from the smoke painted on the skin of rodents did cause tumors to develop, but these results were deemed less relevant than the inhalation studies).  For many years afterward, the tobacco lobby was able to use these studies to delay government warnings and to discourage physicians from intervening in their patients’ smoking habits.  Of course, human population studies provided inescapable evidence of the tobacco-cancer connection.

In fact, folks blame early animal experiments for distracting from human correlations:

The link between smoking and lung cancer was discovered by the British scientist Sir Richard Doll in the 1950s by means of a study of human lung cancer patients in twenty London hospitals. He used the epidemiological method, i.e. the statistical study of diseases in human populations. The practical application to medicine of this all-important discovery had been hindered and delayed by animal research. Why?

First, because animal experiments had previously failed to demonstrate this link and researchers had ruled it out. Medical researchers were dismissive of Doll’s discovery. They had already tried to trigger cancer in animals using tobacco tar but had failed, they pointed out. Only later was it shown that their experimental procedures contained serious errors.

And then, even after Doll’s theory was published, animal researchers tested it by trying to reproduce the carcinogenic effects of smoking in animals. Some of this animal research was funded (you may guess) by tobacco manufacturers.

And what were those “serious errors” of early animal experiments?

Animal experimentation is by its own very nature unreliable for application to humans.

Bob Unwin points us to a nice history of the early smoking controversy, written by philosophers.  It starts:

The fascinating history of the debates over smoking and lung cancer illustrates the difficulties of causal inference and prediction from policy studies, and also illustrates some common mistakes.  Perhaps no other hypothetical cause and effect relationship has been so thoroughly studied by non-experimental methods or has so neatly divided the professions of medicine and statistics into opposing camps.

It ends:

The real view of the medical community seems to have been that it was just too implausible to suppose that genotype strongly influenced how much one smoked, whether one smoked at all, whether one smoked cigarettes as against a cigar or pipe, whether one was a Mormon or a Seventh day Adventist, and whether one quit smoking or not.  After Cornfield’s survey the medical and public health communities gave the common cause hypothesis more invective than serious consideration.  And finally, in contrast to Burch, who was an outsider and maverick, leading epidemiologists, such as Lilienfeld, seem simply not to have understood that if the relation between smoking and cancer is confounded by one ore more common causes, the effects of abolishing smoking cannot be predicted from the “risk ratios,” that is, from sample conditional probabilities.  The subsequent controlled smoking intervention studies gave evidence of how very bad were the expectations based on uncontrolled observation of the relative risks of lunch cancer in those who quit smoking compared to those who did not.