Smoking Research on Animals

Dr.Ian Higgins writes: "Animal experiments using skin painting, tracheal instillation or implantation, and inhalation of cigarette smoke or its component compounds have confirmed the presence of complete carcinogens, tumor initiators, and tumor promoters in tobacco smoke..."(2)

Is it true, as this statement implies, that animal experiments have led to the positive identification of cigarette smoking as carcinogenic to man? The historical facts speak for themselves.

Investigation of the relationship between cigarette smoking and lung cancer was launched in the 1930s from observation of human beings. Researchers were puzzled by the precipitous rise in the lung cancer rate in men since 1920. In seeking to explain the general increase in lung cancer after 1920, the thoughts of researchers often turned to the Joachimsthal miners, who suffered an increased rate of lung cancer from inhaling radium in the mine dust (as demonstrated by Peller). Scientists began to search for a substance which might explain the lung cancer epidemic. Based on the studies of the Joachimsthal miners by Peller, the researchers determined that the "mystery" substance must fit the following description:

1. It must enter the human lung.
2. It must have come into common use in countries like England and the U.S. about 1900.
3. It must be in very common use in countries where lung cancer rates are high but less common in countries where lung cancer rates are low.
4. It must enter men's lungs more than women's lungs. Cigarette smoking was the primary candidate.(4)

In order to show that cigarette smoking was causing the increase in lung cancer, investigators began to undertake retrospective studies of lung cancer victims. These retrospective studies all consist basically in starting with a group of lung cancer victims and asking the question: What has occurred in their past histories which might explain their lung cancers? 

Perhaps the earliest answer came from an English physician, Dr. F E. Tylecote. In 1927, he reported in the British medical journal Lancet that, in almost every case of lung cancer he had seen or known about the patient was a regular smoker, usually of cigarettes. In 1936, Drs. Aaron Arkin and David H. Wagner of Chicago reported that of 135 men with lung cancer they had examined, 90% were "chronic smokers". While suggestive, this study did not constitute proof of the link between smoking and lung cancer. For example, it did not rule out the chance that 90% of the men of the same age, occupations, and residence in Chicago who did not die of lung cancer might also be "chronic smokers". In order to prove that smoking causes lung cancer in humans, epidemiologists began to undertake controlled retrospective studies of human populations. To do this, the scientists studied a group of lung cancer victims and a group of healthy men, which were similar in every conceivable way. The scientists then asked: Is there a difference in the histories of the two groups that might explain why one group suffered lung cancer while the other did not? One early controlled study was reported by Dr. F. H. Muller of Cologne, Germany, in 1939. Muller compared 80 male lung lung cancer patients with 80 healthy men and found much more smoking among the cancer patients. He concluded that smoking must be resposible to a marked degree for lung cancer. One of the first well-controlled studies was reported from England in l950 by Drs.W. Richard Doll and A. Bradford Hill.(6) The researchers began with 1,465 lung cancer patients, mostly from London hospitals. Each ofthe patients was matched by age and sex with a hospital patient who did not have lung cancer. Like the earlier studies, the Doll and Hill study reported a significant association btween smoking and lung cancer. In the U.S., the second major controlled study was also published in 1950. Drs. Ernst Wynder and Evarts Graham found that "Excessive and prolonged use of tobacco, especially cigarettes, seems to be an important factor in the induction of bronchiogenic carcinoma."(7)

Despite the positive findings from the two major British and American controlled retrospective studies, critics continued to deny the association between cigarette smoking and lung cancer. One of the major arguments against the cigarette-cancer theory was that an "X-factor" (e.g. a gene) causes people both to smoke cigarettes and to contract lung cancer. To counter this criticism, Drs. Wynder, Lemon and Bross studied Seventh Day Adventists (who seldom, if ever, smoke cigarettes) in Seventh Day Adventist Hospitals around the country.(8) The study sought to answer essentially one question: is there a lung-cancer difference between Seventh Day Adventists and others treated in the same hospitals? The answer was clearcut. Lung cancer was almost entirely unknown among the Seventh Day Adventistsenth. In contrast, those patients at the hospitals who were not Seventh Day Adventists had the same lung cancer rate as the general population. This finding made the "X-factor" extremely implausible. If such a factor exists, it must have the two characteristics already noted: it must be associated with cigarette smoking and it must cause lung cancer. In addition, the X-factor must be present in Catholics, Methodists, Baptists, and Jews - but not in Seventh Day Adventists (!) The results of the 27 major controlled retrospective studies of cigarettes and lung cancer were extraordinarily consistent. All 27 studies showed a strong association between cigarettes and lung cancer.

Since the major retrospective studies were performed, several massive "prospective" studies of human populations have also proven that cigarette smoking causes lung cancer in humans. By following the lives of millions of people who smoke and millions of people who do not smoke, epidemiologists have shown that persons who smoke are far more likely to die of lung cancer than persons who do not smoke. Like the retrospective studies, there is not a single prospective controlled study that has failed to show that cigarette smoking causes human lung cancer.(10)

In stark contrast to the consistently positive findings linking smoking to lung cancer in humans, the results of decades of animal experiments are highly contradictory. Most animal studies failed to show that cigarettes cause cancer. The primary criticism of the cigarette-cancer theory advanced by several reknowned critics was that researchers had by and large failed to induce cancer in laboratory animals with cigarette smoke - despite more than a half century of research. In summing up the view of such critics, foremost among which was Dr. Clarence Little, the founder of the Roscoe B. Jackson Memorial Laboratory at Bar Harbor, Maine. Eric Northrup wrote:

"The failure of many investigators to isolate a specific human carcinogen from tobacco as well as their inability to induce experimental cancers, except in a handful of cases, during fifty years of trying, casts serious doubt on the validity of the cigarette-lung cancer theory. Unfortunately, negative findings rarely make headlines, so that the public is often placed in the position of confusing the exception for the rule ...."(11)

One of the most well-respected of the critics of the cigarette-lung cancer theory, Dr. W.C. Hueper, an expert on occupational cancers, wrote:

"The inconsistent results obtained by various investigators when tobacco or cigarette tar was applied to the skin of, or inhaled by, experimental animals, indicate that tobacco tar is apparently a weak carcinogen to the skin of mice and perhaps also to the skin of rabbits .... while the inhalation of cigarette smoke, even when successful in eliciting tumors in mice, fails to produce tumors which are histological equivalents to the human bronchiogenic variety of cancer... The development of pulmonary tumors observed in certain strains of inbred mice, moreover, depends upon the action of a primary hereditary factor which according to our present knowledge is totally absent in the causation of the great majority of bronchiogenic cancers in man."(12)

Though researchers are still forcing animals to inhale cigarette smoke, to this day, no scientists have succeeded in causing the human type of lung cancer in animals. Dr. Thelma Brumfield Dunn writes:

"... the induction of lung cancer by tobacco smoking has not been achieved. Almost every conceivable experiment has been devised to induce lung cancers in animals that would duplicate the lung cancers found in man. Chickens and dogs were made to smoke and to inhale, but no convincing lung cancers developed. Hundreds of mice spent a lifetime in smoke-filled rooms yet no increase in lung cancer was found..."(13)

Nonetheless, some scientists did succeed in causing certain forms of cancer in laboratory animals, often by directly painting the skin of rodents with tobacco tar. Proponents of the cigarette~lung cancer theory were quick to point to these few positive experiments (often conducted by the proponents themselves), while opponents of the cigarette-cancer theory pointed to the vast number of animal studies that failed to show a relationship between tobacco and cancer. One of the few unbiased reviews of the animal studies was written in 1961. It was obvious to the authors of the review that, as this monograph has repeatedly stressed, the animal studies were not scientific tools but "political footballs." Drs.P.S.Larson, H.B.Haag, and H.Silvette, wrote:
 

"Virtually all of the books appearing in recent years dealing with the subject of smoking and lung cancer have included more or less brief and, in consequence, more or less selective accounts of experimental carcinogenesis in animals, in which the several authors have attempted to correlate, or to demonstrate the irrelevance of, the experimental findings with clinical and/or statistical studies of the lung-cancer smoking relationship in man. Since space in these books is limited, such reviews of experimental "tobacco" carcinogenesis are necessarily circumscribed - one hesitates to say, by the particular predilection of the respective authors - and the authors' opinions, while interesting in themselves and perhaps of future historical importance, must be said to rest upon the incontrovertable fact that, at the time of writing, the question of the production of tumors in laboratory animals by tobacco carcinogens is controversial, if not downright chaotic." (Emphasis added)(14)

Thus, it is clear from the historical record that animal studies in no way proved or helped to prove that cigarette smoking or a chemical in cigarette smoke causes lung cancer in human beings. In fact, animal studies that failed to show that cigarette smoking causes cancer retarded wider acceptance of the cigarette-lung cancer theory, which was firmly based on studies of actual human populations. 

REFERENCES

1. Ochsner,A: Smoking and Cancer: A Doctor's Report (New York: Julian Messner,Inc., 1954), p.21.

2. Higgins,I: "Ill Effects of Tobacco Smoking." Maxcy-Rosenau Preventive Medicine and Public Health (New York: Appleton-Century-Crofts, Inc., 1980).

3. Carroll,K.K: "Influence of Diet on Mammary Cancer." Nutrition and Cancer 2:232-236, 1980-81.

4. Brecher,R: The Consumers Union Report on Smoking and the Public Interest (Mount Vernon: Consumers Union, 1963), p.23.

5. Ibid. p.25.

6. Ibid.

7. Ibid.

8. Ibid.

9. Ibid. p.31

10.Ibid. p.37

11. Northrup,E: "Men, Mice and Smoking." Science Looks at Smoking: A New Inquiry into the Effects of Smoking on Your Health (New York: Coward-McCann, Inc., 1957), p.133.

12. Hueper,W.C: "Environmental Factors in the Production of Human Cancer." Cancer (London: Butterworth and Co.,1957) Raven, R.W, Ed., v.1, p.462.

13. Dunn,T.B: The Unseen Fight Against Cancer (Charlottesville: Batt Bates and Co., 1975), p.61.

14. Larson,P.S., Haag, H.B., Silvette, H: Tobacco: Experimental and Clinical Studies: A Comprehensive Account of the World Literature (Baltimore: The Williams and Wilkins Co., 1961), p.427.