The Cancer Journal - Volume 5, Number 2 (March-April 1992)
To smoke or not to smoke?
While hardly anybody doubts that smoking is hazardous to our health, it is not at all clear whether this can be proven by epidemiological arguments. This issue that splits the epidemiological community was recently raised in its prestigious journal (1-4). Does smoking cause lung cancer? "Of cause it does not! " exclaimed the late R.A. Fisher, one of the greatest statisticians of our century, creator of statistical genetics, analysis of variance and maximum likelihood. The observation that lung cancer is associated or correlated with smoking can be interpreted in two ways. Either smoking causes lung cancer, or lung cancer causes smoking. In other words, patients carrying lung cancer may tend to smoke more than others. One ought to also consider the person's constitution. For some, smoking may be dangerous, while others may benefit from it. Fisher was particularly suspicious of case-control studies and refused to accept their evidence.
Half a century later it appears as if the issue has been finally proven, and one wonders what were the reasons for Fisher's error (1). "When Genius Errs", exclaims Stolley in his commentary on Fisher, attributing failure to his personality. A "political conservative", "taking fee from the tobacco industry", "holding certain ideologic objections to mass public health campaigns" etc. Finally, Stolley concludes that "a genius can lack insight and fail to develop a sense of proportion about evidence", failing to realize that this may also be applicable to himself.
"Were we really wrong?" replies Eysenck apologetically (3). Should we abandon Hume's philosophy according to which proof of causation in the absolute sense is impossible? Referring to epidemiological studies on the relationship between smoking and lung cancer, Eysenck says: "We did not demand absolute proof... What we have found are serious methodological weaknesses in the design of these studies quoted in support of these theories, statistical errors, and unsubstantiated extrapolations." "Epidemiology is a complex discipline", "Risk factors interact in complex ways and univariate analysis is quite inappropriate to the elucidation of causality".
As in the previously described "Cancer Wars" (5), eminent epidemiologists contradict each other on the interpretation of their observations. If one is ready to adopt case-control studies, one may prove that "smoking causes lung cancer". Yet with case-control design it is possible to prove virtually anything, since the design uses retrospective observations that cannot be randomized. More rigorous statistical methods are less conclusive.
It is not epidemiology that is complex, as conceived by Eysenck, but the human organism. Cancer and smoking are complex processes evolving with time. Instead of considering their entire complexity, epidemiology reduces them to two observations, cancer mortality and smoking frequency. When confronted with each other they are correlated. This is where epidemiology should stop, since the interpretation of this relationship cannot be done with epidemiological reasoning. Either smoking initiates cancer or cancer triggers an urge to smoke, or the two may never interact and their observed association results from a third process that was not considered in the study. Epidemiology lacks the means to distinguish between the three and should leave the decision to medicine. Only medicine is capable of interpreting complex biological processes and their interaction. Instead, epidemiology borrows medical reasoning, applying it to two arbitrary points of a complex process, and finds this practice even justified to denounce its geniuses. Fisher did not err! He realized the limitation of the method that he created.
1. Stolley PD. When genius errs: R.A. Fisher and the lung cancer controversy. Am J Epidemiol 133, 416, 1991.
2. Vandenbroucke JP. Invited commentary: How much retropsychology? Am J Epidemiol 133, 426, 1991.
3. Eysenck HJ. Were we really wrong? Am J Epidemiol 133, 429, 1991.
4. Greenland S. Invited commentary: Science versus public health action. Those who were wrong are still wrong. Am J Epidemiol 133, 435, 1991.
5. Zajicek G. Cancer wars. Cancer J 4, 4, 1991.