"ZEPHYR" And Its Causes, 1957

One of the first references in the documents to the tobacco industry's effort to identify carcinogenic elements in tobacco smoke appears in a memo dated March 1, 1957, and titled "Smoke Group Program for Coming 12–16 Week Period" {1100.01}. The memo describes research under way at the BAT laboratory in Southampton, but it uses code words for lung cancer (ZEPHYR ) and for the suspected carcinogens (BORSTAL and 3,4,9,10-DBP) in tobacco smoke.

As a result of several statistical surveys, the idea has arisen that there is a causal relationship between ZEPHYR and tobacco smoking, particularly cigarette smoking. Various hypotheses have been propounded, from time to time, as explanations of this conception. The two which seem most important at present are:

Because of the way in which these causative agents are bound to the soot, they are in an inactive form; but the inhalation of compounds with solvent properties leads to the elution of the agents and their subsequent activation into a

form which readily causes ZEPHYR . This "Elution Hypothesis" may account in part for a subsidiary relationship claimed between ZEPHYR and the level of urbanisation (and consequently of atmospheric pollution). {1100.01, p. 1}

Both of the working hypotheses presented in this document assume that cigarettes are an important link in the occurrence of lung cancer. The first hypothesis is that one or more carcinogens are present in cigarette smoke; the second is that carcinogens which enter the lung from other sources are activated by their dissolution into the tar fraction of cigarette smoke as it is inhaled. Either way, cigarette smoke is hypothesized as part of the directly causal chain in the occurrence of lung cancer. The Smoke Group took these hypotheses seriously, as evidenced by their use of code words, and pursued internal studies based on these hypotheses.

As mentioned, the major suspected carcinogens are called BORSTAL (thought to be arsenic by the compiler of the 1988 chronology of B&W's smoking and health research {1006.01, p. 3}) and 3,4,9,10-DBP (thought to be dibenzo(a)pyrene).

Until very recently the most suspected compound was BORSTAL . Most values for BORSTAL content of cigarette smoke are held to be too low to reach a biological threshold value for ZEPHYR causation, even on a basis of continued dosage; this conclusion was published by one who is, nevertheless, one of the strongest proponents of the hypothesis under discussion. Very recently, a second compound has been claimed to have been detected in cigarette smoke and this has been stated, independently, to be twenty times as active as BORSTAL . It is 3,4,9,10-DBP. This work still requires confirmation and meanwhile BORSTAL remains as the most widely suspected component in smoke and atmospheric pollution. {1100.01, p. 2}

The research plan describes examinations of cigarette combustion temperatures under different puffing parameters and analyses of smoke fractions for BORSTAL and for polycyclic aromatic hydrocarbons (PAH), of which 3,4,9,10-DBP is an example, using smoke from the "front" and the "back" of cigarettes {1100.01, p. 6}. Some of the cigarettes to be studied were to be made of tobacco leaf lamina (the conventional cigarette material) or CRS (cut, rolled stem) {1100.01, p. 6}. This plan means that the lab was looking for the presence of carcinogens in cigarette smoke and also trying to determine whether different starting materials produced different amounts of these carcinogens. This work was an early attempt to reduce toxicity of cigarettes by attempting to reduce the levels of suspected carcinogens. It fit in precisely with recommendations from experts such as Ernst Wynder that tobacco product manufacturers should seek ways to lower the levels of toxic constituents in cigarette smoke (3).