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Chapter 4 The Search for a "Safe" Cigarette
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Chapter 4
The Search for a "Safe" Cigarette

Any work undertaken must be with a commercial or political motive as well as a scientific motive. The object is for the company to be able to say that, in the light of all available knowledge, it "... is doing its best to supply a 'safer' smoke."
Letter from BAT to B&W president Ed Finch, 1964 {1804.01}


Introduction

Throughout most of the 1960s, the tobacco industry was convinced that it could make cigarettes safe—that is, that it could discover the toxic components of cigarette smoke and eliminate them. In the lab the tobacco industry's scientists quietly worked on reducing the toxicity of cigarettes by various means. To this end, they developed an array of biological tests, using mouse skin painting (cigarette tar painted on the skins of mice) as the gold standard for testing carcinogenicity. At the same time, in its public statements the industry challenged the validity of this test as evidence that tobacco poses any harm to human consumers. In fact, we now know that mouse skin painting underestimates the total carcinogenic action of tobacco smoke. Some of the most important carcinogens in tobacco, such as nitrosamines, are in the gas phase of the smoke, not in the particulate phase that makes up the "tar" painted on the skins of mice (1). As with its research on nicotine, the secret research being conducted by the tobacco industry was at least as high in quality as the work reported in the open scientific literature at the time. Despite the importance and quality of this research, little of it was ever published in peer-reviewed scientific journals.

B&W and BAT's early work seemed motivated by a genuine concern over the health effects of smoking and a belief that, if the toxic components of cigarette smoke could be identified, these agents could be removed and a "safe" conventional cigarette created. By the late


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1970s, however, the tobacco industry had largely abandoned the search and turned to a more defensive posture. This chapter describes what the documents reveal about the industry's effort to develop a "safe" cigarette. The industry did not disclose these research efforts to the public, and it was simultaneously engaged in two campaigns: an internal research campaign to develop a "safe" cigarette and an external public relations campaign to convince the public that cigarettes had not been proven dangerous to health.

As discussed in chapter 2, in the 1950s, in the wake of the rapidly growing scientific evidence that cigarettes cause lung cancer (2), cigarette companies created brands with filters and claimed that these brands gave "health protection" to smokers. These claims were not based on proof of "health protection"; indeed, some filter brands had higher tar deliveries than unfiltered products from the same manufacturer, and smoke from filter cigarettes was shown to be just as carcinogenic as smoke from unfiltered brands (3). Nonetheless, the hype worked, and by 1960 filter brands were well on their way to replacing nonfilter cigarettes in the marketplace. At the same time, cigarette companies conducted serious research to see whether they could lower the toxicity of their products.

"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:

 

(i)

Tobacco smoke contains a substance or substances which may cause ZEPHYR [.]

(ii)

Substances which can cause ZEPHYR are inhaled from the atmosphere, e.g. in the form of soot.

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


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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).


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Southampton Research Conference, 1962

As mentioned in chapter 3, BAT held periodic research conferences so that its scientists from around the world could meet to discuss research developments and other issues facing the industry. Such a conference was held at Southampton in early July 1962. The documents include a detailed set of minutes from a major session that dealt with a wide range of smoking and health issues. These included reaction to the recently issued report of the Royal College of Physicians on smoking and health, the company's research program, and research that was being undertaken through an industry-wide consortium in the United Kingdom known as the Tobacco Manufacturers' Standing Committee (TMSC; see chapter 2). As discussed in chapter 2, the British Royal College of Physicians issued its first report on smoking and health in the spring of 1962. That report concluded that cigarettes cause lung cancer and recommended that government take "decisive steps' to control the rising consumption of cigarettes.

The Southampton conference was attended by twenty-nine executives and research scientists from BAT offices and laboratories in five countries (including the United States and Canada, which sent four delegates each) {1102.01, front matter}. The record of the conference shows that, despite its public statements contending that the evidence on smoking as a cause of lung cancer was inconclusive, the British tobacco industry was moving aggressively to examine the problem with sophisticated toxicological testing.

In addition, a special session was devoted to a major problem that had arisen in the United States about six weeks earlier, when a B&W competitor announced its development of a cigarette filter that selectively removed phenols, a group of compounds suspected of enhancing the carcinogenic activity of cigarette smoke.

The documents include a detailed set of minutes from a major session dealing with a wide range of smoking and health issues. In a keynote speech Sir Charles Ellis, an executive in BAT's Research and Development Establishment at its Millbank headquarters in London, presented an overview of the smoking and health issues faced by the company and explained how the TMSC was responding to these issues. The full text of his remarks is included in the minutes. (The parts of his comments related to nicotine were discussed in chapter 3.) Sir Charles reviewed public and scientific perceptions of the cancer issue with a variety of rationalizations, but he also outlined a well-planned, comprehensive research program designed to reduce the toxicity of cigarettes.


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Lung Cancer And The British Royal College Of Physicians Report

In his speech Sir Charles tries to downplay the Royal College of Physicians' conclusion that cigarettes cause lung cancer, calling it an emotional reaction based on an incomplete examination of the data. He does, however, acknowledge that smoking causes bronchitis.

After reading the Report of the Royal College of Physicians and the debate in the House of Lords the dominant impression I received was that of people who had reached an emotional conclusion in which they believed passionately and sincerely. This report provided the occasion for statements of faith by people who seemed to find it necessary, however, to silence their own self-criticism by repeating phrases like, "conclusive proof beyond the shadow of doubt" [,] ... "devastating effect of the marshalling of cold scientific facts", and so on. Yet we who have been immersed in the subject for many years know that this report produced no new fact, produced no new arguments, indeed, except for the contribution of an emotional gloss, left the subject untouched. We know only too well that there are no conclusive proofs; that there are few, if any, cold scientific facts.

However, emotional conclusions cannot be disregarded. They may not be right, but they are not necessarily wrong. Emotional judgments are often the basis for national thinking, and since a national attitude to smoking may be building up it is essential for us to consider what are the components in this emotion.

The most important is the dread word "cancer". Most people cease to be able to reason once it is mentioned, and you will all be aware how difficult it is for doctors to overcome the reluctance of people to admit the possibility of having cancer and to present themselves for early examination. Lung cancer carries with it all of these associations, and also shares some of the aura of dread connected with tuberculosis. I can well remember how pneumoconiosis in the coal mines had much of this emotional background and was correspondingly difficult to deal with in a rational manner. Smoker's cough is a real phenomenon and obvious to everyone , and we should recognize that it is a factor in the emotional build-up [emphasis added]. {1102.01, pp. 3–4}

"Smoker's cough" is a symptom of lower airway irritation caused by cigarette smoke. "Bronchitis" is the clinical term that is implied by the phrase "smoker's cough." This irritation occurs as a result of smoke inhalation, which, in turn, is necessary for nicotine absorption from a cigarette (see chapter 3). Where there is a smoker's cough, there is some degree of bronchitis.

Sir Charles states that the evidence directly implicating cigarette smoking as a cause of lung cancer was epidemiological except for a single study by Blacklock (4). Blacklock had injected cigarette smoke con-


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densates mixed with the adjuvant eucerin, a material to amplify the effects of smoke condensate, into the lungs of rats, guinea pigs, and rabbits. The animals lived out their natural lives and then were examined. Cancers were observed in six of seventy-two rats and in one rabbit.

In saying that Blacklock's work was the only biological study in the literature that addressed the question of smoking as a cause of lung cancer, Sir Charles is framing the issue very narrowly. A decade earlier, the young US physician Ernst Wynder had shown that cigarette smoke tar condensate caused cancer in a mouse skin model (5, 6). The test involved repeatedly painting smoke condensate onto the skin of mice and observing the animals over a long period of time to see whether cancers developed at the exposed site. Although Sir Charles does not mention the mouse skin–painting model as relevant to the question of whether smoking causes lung cancer, BAT was to use this very model in Project Janus (discussed below) as its gold standard for determining whether specific product modifications could reduce the dangers of smoking.

Joint Research by British Tobacco Industry

Sir Charles then describes the new tobacco toxicology laboratory at Harrogate, which was to be run jointly by tobacco companies in the United Kingdom through the Tobacco Manufacturers' Standing Committee (TMSC). In the course of his discussion, Sir Charles explains the BAT board's policy on the smoking and health issue:

The Board recognises that this problem must be tackled from two sides, the first being medical research on the origin of lung cancer and bio-assay on the biological effects of smoke, and the second being the composition of smoke and the possibilities of modifying it. The Board has decided that if this Company makes any significant scientific discovery clearly relevant to health it will share its knowledge with its co-members of TMSC and not seek to obtain competitive commercial advantage. The Board has therefore decided that they will whole-heartedly support TMSC to carry out and co-ordinate all research on smoking and health. TMSC will do this by itself carrying out biological work at its establishment at Harrogate and by sponsoring biological and medical work at Institutions. TMSC will depend on member companies for physical and chemical work [emphasis added]. {1102.01, p. 5}

While the BAT board made a commitment to share information on how to reduce cigarette toxicity with other tobacco companies rather than "seek[ing] to obtain competitive commercial advantage," there is no mention of making research information available either to the public or to public health authorities.


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More important, as of July 1962, BAT was committed to cooperative investigations and product development when they were "health-oriented." A "health-oriented" product, as it would later be defined at the Hilton Head research conference in 1968, was one that reduced the actual hazard of smoking. In contrast, a "health-image" cigarette only appeared to provide a health benefit (see below). The fact that the company had decided to share any promising results with the industry as a whole strongly indicates that the company now realized that its products did, in fact, present a hazard. If the company regarded the evidence that smoking causes cancer as false, misleading, or inconclusive, it is difficult to see why it would have seen the possibility of a competitive advantage and adopted the policy that it did.

Sir Charles couches the rationale for conducting "health-oriented" research in the following guarded terms:

The central fact in this subject is that in sufficient doses tobacco condensate acts as a carcinogen when painted on the backs of mice, or when injected subcutaneously into rats. In sufficient dose it also acts as a co-carcinogen in mouse painting tests. On present evidence the amount of the known carcinogens in smoke are insufficient to make it plausible that these experiments could be extrapolated to support the view that smoking is harmful to human beings, but at least they serve to indicate a group of substances which require intense investigation and which, even if we do not know why, we would be pleased to see less of [emphasis added]. {1102.01, p. 7}

Despite this cautious attitude toward the implications of the mouse skin model, mouse skin painting had by this time become the test used by BAT to examine whether a particular manipulation of cigarettes reduced the risk of cancer. Indeed, discussion later on at this research conference demonstrated the hard-nosed attitude within R&D at BAT that the company would rely primarily on mouse skin tests in estimating the value of any maneuver to remove toxins from cigarette smoke. Mouse skin painting was, then, the definitive assay for cancer at BAT—even though, in public, the tobacco industry minimized the value of data from mouse skin–painting experiments. The public posture was that this model was not at all relevant to a determination of whether cigarettes cause cancer in humans.

The TMSC laboratory, which was to open at Harrogate on September 1, 1962, was to be capable of running mouse skin–painting experiments at twenty-five to fifty times the size of in-house efforts. Two thousand mice were to be used in the initial experiment, instead of the forty to eighty that were conventionally used. The start-up costs were put at


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£250,000, and the annual budget was estimated to be £100,000. Research results of this and other studies were to be published as a matter of policy {1102.01, p. 33}. In determining the sample sizes to be utilized in the initial experiment, the planners had done calculations of how small a difference could be detected between the activities (i.e., carcinogenic potential) of different condensates. Sir Charles notes that the experiment at Harrogate "should with almost certainty show up a difference of 30 per cent in the two condensates and will give good information about possible differences of 15 per cent" {1102.01, p. 9}.

One of the criticisms of earlier work was that the smoke condensates used were not "fresh"; that is, they had been stored for some time prior to being painted onto the mice. People inhale "fresh" smoke, not old smoke, and any chemical changes that made the stored smoke more toxic to mouse skin might skew the results. So the first experiment conducted at Harrogate was to be a comparison of "fresh" and "stored" condensate.

Besides looking at carcinogenic and cocarcinogenic activity in smoke, Harrogate was also charged with investigating the mechanisms whereby tobacco smoke causes irritation of the respiratory passages. A cocarcinogen is a material that amplifies the action of a carcinogen but is not itself carcinogenic. This research was relevant to the work at Harrogate, rather than simply a matter for competitive improvement of consumer acceptance, for three reasons. Sir Charles notes that irritation could

 

[a]

cause chronic bronchitis,

[b]

be responsible by itself for carcinogenesis,

[c]

act as a co-carcinogen or promoting factor in association with specific "carcinogens". {1102.01, p. 10}

The term "chronic bronchitis" is a specific diagnosis of some importance. In 1962 British investigators of what we now call chronic obstructive pulmonary disease (COPD) called the disease "chronic bronchitis," while investigators in the United States used the term "emphysema." The term "COPD" was coined to encompass both major phenomena of the condition, the narrowing of airways and the destruction of lung tissue, so that the literature would be easier to follow. Nearly all COPD seen in the United States is caused by cigarettes (7).

At Harrogate researchers would be able to conduct two kinds of tests: (1) by looking at the proliferation of mucus-secreting goblet cells in the lung (a response to irritation), they could determine the potential of smoke to produce bronchitis; (2) by looking for hyperplasia of the epithelial cells lining the bronchi, they could determine the presence of carcinogenesis


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and cocarcinogenesis (the stimulation of these cells to divide is an early action of carcinogens). Harrogate was to have the capability to set up both of these experimental models and then to test specific smoke constituents in these systems.

Sir Charles emphasizes the importance of the studies on irritation with the following comments:

I regard the attempt to probe more deeply into the cause of irritation as equally fundamental [to investigating the cancer problem]. Some smoke is irritating, smoker's cough is a reality, and it cannot be good for health to cause this irritation whether or not this irritation has any effect on the incidence of lung cancer . Some of you may regard irritation as so important that you are willing to make a guess and attribute it with but little evidence to a class of compounds such as aldehydes, or you may be ready to take a short cut and attempt to identify irritation by an organoleptic technique [subjective report of people exposed to potentially irritating materials]. This is a matter on which I hope you will express your views. Personally I think the TMSC policy is right; this subject of irritation is just too important to incur the danger of reaching a wrong conclusion due to a faulty technique. Once we have solved the problem of establishing a quantitative test[,] progress in identifying irritating components will be rapid. Whether their removal will be easy is another question, but to identify them will be a good first step [emphasis added]. {1102.01, p. 22}

Sir Charles also describes other work supported by TMSC outside the Harrogate facility: an examination of the relative carcinogenicity of smoke from tobacco that has been cured in different ways; a large, prospective epidemiological study on susceptibility factors (other than smoking) for cardiac and pulmonary disease among 200,000 men; a study of the carcinogenicity of aliphatic lactones (material found in plants that was thought likely to occur in cigarette smoke); an epidemiological study of lung cancer in South Africa and Australia; and the psychological work of Dr. Hans Eysenck. (Dr. Eysenck later received support through the special projects of the Council for Tobacco Research; see chapter 8.) TMSC also funded work on viruses and immunogens as causes of cancer and on the effects of tumor transplants treated in various ways in experimental animals. Taken as a whole, this work plan has a defensive tone: most of these projects sought explanations for the diseases at issue other than that they are caused by cigarettes.

After describing the overall research activities sponsored by TMSC, Sir Charles returns to the experiment on fresh versus old condensate.

[If] fresh condensate has a smaller biological effect than old condensate we do not of course at one stroke destroy the emotional conclusion [that smok-


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ing causes cancer]—in fact it remains unaltered—but we do clear the decks of a great deal of previous experimentation and smoke condensate will then be accepted as such a weak carcinogenic agent that other explanations of the association of smoking and lung cancer assume greater importance. Conversely, and this is always a possibility, the biological effect may increase as the condensate is used fresher and fresher. This possibility need not dismay us, indeed it would mean that there really was a chemical culprit somewhere in smoke, and one, moreover, that underwent a reaction fairly quickly to something else. I feel confident that in this case we could identify this group of substances, and it would be worth almost any effort, by preliminary treatment, additives, or filtration, to get rid of it. We should have brought the problem out into the open where it could be attacked. I feel sure you will give your full support to this experiment [emphasis added]. {1102.01, p. 21}

Sir Charles's willingness to accept the possibility that something intrinsic to cigarette smoking could cause cancer—and that, once identified, this "group of substances" could be removed—reflects a greater level of scientific openness than the tobacco industry has evidenced in recent years.

Ultimately, the experiment showed that "fresh" condensate (twenty-four hours old) actually had more carcinogenic activity than "old" condensate (one week old) (see below) {1105.01}.

The Bat Research Program

BAT's intramural research activities, Sir Charles explains, are devoted mainly to a detailed investigation of the physics and chemistry of tobacco smoke.

Now, as regards work in our own laboratories on chemistry and physics. Our objective must be to prepare ourselves as fully as possible to utilize any result the moment it appears from these biological and medical experiments. In effect, this means that we would like to know the origin of all the compounds that we currently think may be important, whether they are wholly or partially distilled from the tobacco or formed in some of the pyrolytic reactions, and at what temperatures. We might then hope to be in the position of being able to enhance or suppress certain classes of compounds by either pre-treatment or additives once we knew which compounds had to be so influenced.

This of course is precisely what we have been doing and are doing, and in my opinion progress is excellent. {1102.01, p. 24}

These comments indicate that a goal of R&D at BAT in 1962 was to reduce the toxicity of its cigarettes as rapidly as possible.

Sir Charles concludes his conference remarks with the following analysis and exhortation:


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We must admit that the threat to our industry is serious and very real, and it is of little help to us that it is based on an emotional guess and not on reasons. I believe we are now starting on a sound programme of investigation that in a few years will make it possible to see the situation and judge the future much more clearly. I hope to-day's discussion will start your active participation in this particular section of Group Research, and that the measures we propose will enable it to continue and grow. {1102.01, p. 25}

Unfortunately, this optimistic view that cigarette toxicity could be largely eliminated through research and engineering proved to be wrong.

Participants at the conference also discussed the feasibility and development of a safer cigarette. It emerged that BAT knew how to make a cigarette with low levels of what was regarded at the time as the major carcinogen (benzpyrene) but had not marketed it. There was concern about how to make claims for safer products that would not indict other products, and there was a keen appreciation of the difference between product innovation for public relations purposes and product innovation to reduce the hazard of the product. Finally, there was an appreciation of the spirit of sharing and comity among the British companies as regards "health-oriented" innovations in contrast to the competitive turn that had just emerged in this area in the United States.

The following exchange, during the discussion following Sir Charles's talk, illustrates the tension that knowledgeable spokesmen for tobacco companies were under at the time, because they were denying the scientific evidence that smoking is dangerous while, at the same time, they knew that the evidence was sound and that internal studies such as mouse skin-painting experiments were consistent with the publicly available results.

Mr. Reid suggested that no industry was going to accept that its product was toxic, or even believe it to be so, and naturally when the health question was first raised we had to start by denying it at the P.R. level. But by continuing that policy we had got ourselves into a corner and left no room to manoeuvre[.] [I]n other words if we did get a break through and were able to improve our product we should have to about-face, and this was practically impossible at the P.R. level. If we could ease the approach a bit, then when we did make positive contributions we could at least say so without having to crawl behind the door .

Mr. McCormickdid not quite agree that we in this country had got ourselves into that position, although it might be true of other countries [presumably, the United States]. We had more room to manoeuvre because, whatever we had said initially, in the last year or two we had been prepared to admit that there was a working hypothesis which ought to be examined. The fact that we had started with a donation to the MRC [Medical Research Coun-


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cil] had indicated that we thought there might be something in it. But it was very difficult when you were asked, as Chairman of a Tobacco Company, to discuss the health question on television. You had not only your own business to consider but the employees throughout the industry, retailers, consumers, farmers growing the leaf, and so on, and you were in much too responsible a position to get up and say: "I accept that the product which we and all our competitors are putting on the market gives you lung cancer", whatever you might think privately [emphasis added]. {1102.01, p. 45}

The Phenol Crisis

On May 22, 1962, the P. Lorillard Company precipitated a crisis within the cigarette industry: it announced that it had introduced a modification to the Micronite filter of its Kent brand that selectively removed 90 percent of the phenols from mainstream smoke (8). (The filter Lorillard had announced for Kent had been produced in collaboration with Dr. Ernst Wynder of the Sloan-Kettering Institute for Cancer Research.) The fallout from this announcement was still being felt in July, and the phenol problem was a major topic of discussion at BAT's 1962 research conference in Southampton.

The phenols were regarded as irritants and probable cocarcinogens. The irritating effects of phenols were thought to account for paralysis of normal ciliary function in the tracheo-bronchial tree that cigarette smoke causes. The cilia, little hairs that line the windpipe, help cleanse the lung by moving mucus up to the throat. As reported in the Wall Street Journal , Lorillard's public relations firm issued a statement claiming that "studies on the cilia in frogs show that the workings of the cilia are unaffected by smoke from Kents with the new filter. ... Smoke from another brand of filter cigarette, it claims, slowed the cilia down by 67 percent, while smoke from an unfiltered cigaret slowed action of the cilia by 85 percent. There is no mention made [by Lorillard's public relations firm] of any research or theories on the possibility that phenols may be cocarcinogens. The statement also claims that in smoke from an unfiltered cigarette there are about 105 micrograms of phenol. By comparison, it claims, there are 35 micrograms in a filtered cigarette, 24 micrograms in an old-style Kent and 12 micrograms in Kents with the new filter" (9). Lorillard's announcement, then, meant that it sought a competitive advantage from a product that seemed to offer a genuinely "health-oriented" benefit.

Ernst Wynder had made numerous contributions to the scientific understanding of cigarettes and disease in the 1950s and 1960s, initially at


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Washington University and then at the Sloan-Kettering Institute. He participated in major epidemiological and laboratory studies of smoking and health. In the mid-1950s he developed the mouse skin-painting model that was to become the cigarette industry's standard for assessing the carcinogenicity of cigarette smoke condensate.

In testimony before Congress in 1957, Wynder had pointed out that the cigarette filters of the day were not selective. That is, they did not remove toxins to any greater degree than they removed harmless smoke components (3). He also criticized some cigarette manufacturers for blending the tobaccos in their filter cigarette brands so that they produced smoke with higher levels of tar than came from the nonfilter brands of the same manufacturer. The year before Lorillard's announcement, a paper Wynder and Hoffman had published in the journal Cancer had drawn attention to the fact that the phenolic fraction of cigarette smoke had cocarcinogenic activity (10). This finding provided a rationale for seeking the selective removal of phenols.

The problems that the new Kent filter created for BAT—and, particularly, B&W—are reflected throughout the general proceedings of the Southampton conference {1102.01}. The matter was of such urgency and importance that a special session at the conference was devoted to the problem, and a full transcript of this session, including both the presentations and the discussion, was made {1102.02}. The mood at this session suggested that BAT was about two years behind Lorillard in the development of selective filtration. In his opening remarks at this session, Sir Charles Ellis acknowledged the profound embarrassment the BAT scientists had felt as well as the challenge that lay before them.

Gentlemen, we must all recognise that it is natural for our Boards to wonder why scientists of another Company should have brought to their Board's attention the possible importance of the problem of the selective filtration of phenols and that we ourselves unfortunately did not. I suspect that this has already been mentioned in their discussions and they are now awaiting anxiously for the next surprise to burst upon them. It is precisely to avoid such unpleasant situations that they provide themselves with expensive research establishments. Let us admit that it would be both natural and reasonable for our Boards to think in this way and irrespective of whether they do or do not, as may be the case, there is definitely something for us to answer. I personally feel this responsibility very keenly for I am in as good a position, if not better, than anyone to know the facts and to guess trends. If there were to be any kicks to be distributed I think they should first land on me. I suggest that this morning anyone should feel free to job [sic ] backwards and say what in their opinion should have been done. If this involves the suggestion that someone should have done some-


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thing different or acted more quickly then let it be said openly and frankly—straight speaking—we are all friends.

Now the reason for raising this point in rather a direct manner is because of the overriding importance of making our Group Research a successful reality—a reality which can grapple with situations like this. Obviously, it can be successful Group Research if it expresses joint opinions of you all acting as equals with equal responsibilities. I hope our discussions this morning will help that onwards. {1102.02, pp. 1–2}

These opening remarks were followed by presentations by H. D. Anderson from Millbank, who gave an overview of the situation; by T. M. Wade, Jr., who presented the problem from the B&W perspective; and by Mr. Laporte, who commented on the problem from a Canadian point of view. In his presentation Anderson emphasized the political importance of Lorillard's going public with the connection between phenol and ciliatoxicity, since the impairment of ciliary activity was, in his view, "implicated in the cancer problem" {1102.02, p. 8}.

How important is phenol? There are two sides to this—the scientific side and the political attitude. Let's be quite certain about this: the political implications have at the moment by far the greater importance and they have been summed up very adequately in a letter from Add [Addison] Yeaman, the lawyer at B. & W. Now that Lorillards have come right out into the open and made it publicly known that the [sic ] connection between phenol and cilia activity, and because cilia activity goes back a long way and has been implicated in the cancer problem, the argument would run like this—I quote from Yeaman's letter:

 

"1.

The uninhibited movement of the cilia tends to eject from the lung (or impede entering into the lung) particulate matter.

"2.

It is known that phenol inhibits the action of the cilia.

"3.

It is known that phenol occurs in the inhaled smoke.

"4.

It is now known that phenol content of the smoke can, by use of certain additives in the filter, be very substantially reduced.

"Query: In this state of knowledge is it negligence on the part of the cigarette manufacturer either

 

(a)

to fail to remove phenols, or,

(b)

to fail to warn consumers of the product of its potential danger?" [italic emphasis added]. {1102.02, p. 8}

Yeaman was suggesting that B&W had legal vulnerability if it did not act to remove phenols or warn smokers of the problem. Of course, these discussions took place before the advent of warning labels, which, ironically, have had the effect of largely protecting the industry from liability under a failure-to-warn theory.


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The phenol crisis presented a real-world example of the competitive problems that would arise if a tobacco company were to develop a "safe" cigarette—most notably, that all other cigarettes would be admittedly more dangerous. The potential liability issues were formidable (see chapter 7).

In his presentation Tom Wade, of B&W research and development, complained about the absence of a cooperative approach in the United States.

This is a typical example of too little, too late. This situation of ours [B&W's] is somewhat different from yours [BAT's] over here as it is now proven that certain elements of the industry will go it alone, rather than through T.I.R.C, in spite of the fact that they are members of the T.I.R.C. That leaves us in a very awkward situation in the States. Of course, we don't know the level of activity of phenols or the importance of them, but the Reader's Digest can make a powerfully good case of this; in all practical purposes they are anti-tobacco to begin with—thanks to their association with our boyfriend (Wynder). Secondly, it increases the circulation [of the Reader's Digest ] by having a good scare ..., and on top of that, they are very much insulted at the United States Government and the Federal Trades [sic ] Commission in particular for having stopped all kinds of reference to filtration in terms of total tar; we can talk about the foolish side if we want to, taste and flavour and so on, but the implications from the medical standpoint are being carried by the Reader's Digest in opposition to the Federal Trades [sic ] Commission. ...

We have gone through to the battle of the total tar and we are now in the battle of the phenols—tomorrow it will be something else. Of course Wynder does not believe that a cigarette will ever be completely safe. {1102.02, pp. 15–16}

The Reader's Digest had a long history of publishing articles about smoking and health, and since the mid-1950s it had published important articles about the relative tar and nicotine deliveries of various filter and nonfilter cigarettes. In 1955 the Federal Trade Commission put a stop to the most obvious health claims in cigarette advertising. References to "health protection" and to "reduced irritation" disappeared and were replaced by what Wade calls "the foolish side," an emphasis on taste and flavor. Wade's complaint, in part, was that although the FTC had barred the manufacturers from making the most flagrant health claims in their cigarette advertising, the Reader's Digest was still publishing articles on the relative benefits of various cigarette brands in terms of tar delivery (11). These articles were, inevitably, detrimental to some particular companies' brands, and the companies could not respond in their advertising.


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The phenol crisis illustrates the complex environment in which the R&D scientists operated. Most important, it illustrates the fact that the tobacco companies' scientific agenda was set by competitive and public relations needs as much as by scientific priorities.

Industry-Wide Research In The Uk, 1965

A report of a site visit in June 1965 to tobacco industry research facilities in England by Dr. R. B. Griffith, head of R&D at B&W, provides a glimpse at what had happened in the three years since the Southampton research conference. Dr. Griffith presented a report in person to high-level B&W executives on July 1, 1965, two days after his return. This presentation is summarized in a "Report to Executive Committee," marked "STRICTLY CONFIDENTIAL " {1105.01}.

Dr. Griffith reported that the first set of mouse skin–painting studies from the Tobacco Research Council laboratory at Harrogate was scheduled for publication within the year. The results demonstrated once again that tobacco smoke condensate is carcinogenic to mouse skin. Contrary to hopes expressed at the Southampton research conference in 1962 {1102.01}, fresh condensate was found to be actually more carcinogenic than old condensate. Griffith notes,

Scientists with whom I talked were unanimous in their opinion that smoke is weakly carcinogenic under certain conditions and that efforts should be made to reduce this activity [emphasis added]. {1105.01, p. 2}

Griffith stops short of saying that this "weakly carcinogenic activity" commonly leads to cancer in humans. By this time, statistician Sir Ronald Fisher, a consultant for the British tobacco industry, had conceded that epidemiological evidence established that there was a real association between smoking and lung cancer (12).

"Most people" Dr. Griffith spoke with in the United Kingdom were also worried about the potentially adverse impact of the reports from Harrogate {1105.01, p. 2}. At least one person expressed concern "that the Harrogate report may bring about some type of industry regulation by agencies of the British government" {1105.01, p. 2}. Moreover, "The personal opinion was expressed that the Harrogate report, and the possible repercussions in England, would have a significant impact on the American tobacco industry" {1105.01, p. 2}.

At the same time, industry scientists at Harrogate were actively working on ways to reduce the toxicity of smoke by various means. They


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had found, for example, that a charcoal filter and a PEG (polyethylene glycol)-treated cellulose acetate filter substantially reduced carcinogenic activity when equal weights of tar were tested. These results offered some hope of a safer cigarette.

The Harrogate lab was being doubled in size, and new machinery for the manufacture of condensate and smoke was under development. The lab staff was seeking the ability to process tobacco and to make its own cigarettes, but the R&D staff at BAT (Southampton) and at Imperial Tobacco (Bristol) were concerned that the Harrogate lab might thereby become too independent of the sponsoring tobacco companies.

The Imperial Tobacco laboratory at Bristol was in a rapid growth phase as well. (Imperial Tobacco was, and is, one of the largest tobacco companies in Great Britain.) Dr. Griffith notes:

Their entire laboratory facilities are operating on a "crash" basis on the smoking and health problem and activity was evident at the Director level. Two more floors are already planned for their new smoke research facilities (less than two years old) and every project in their new process development facility was concerned with this research. Their approach seems to be to find ways of obtaining maximum nicotine for minimum tar. Approaches being used include:

 

(a)

P.E.I. [polyethyleneimine] treatment of filters

(b)

Nicotine fortification of cigarette paper

(c)

Addition of nicotine containing powders to tobacco

(d)

Alteration of blends

I was told that they were making moves to be in a position where 30% of their production could be dual filter production by June 1966. Arrangements had been made with Cigarette Components for production of P.E.I. treated filter cigarettes which will be submitted for biological testing this August [emphasis added]. {1105.01, p. 2}

The Imperial scientists at Bristol were approaching the problem by concentrating on boosting nicotine dose to achieve a lower dose of tars. As discussed in chapter 3, PEI, when used as a filter additive, boosts free nicotine delivery {1205.03}. This research strategy is consistent with the view that people smoke in order to receive a dose of nicotine. The real task, then, was to reduce the delivery of other combustion by-products that cause cancer.

The German tobacco industry was developing a lab similar to the one at Harrogate. In addition, BAT had arranged for biological testing at Battelle in Frankfurt, Germany, while Imperial Tobacco had made similar arrangements with a private lab in England. Dr. Griffith felt that these


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latter two operations would be used for commercial purposes. The Battelle operation was a branch of the same industrial laboratory that had conducted BAT's nicotine research in Geneva a few years earlier (see chapter 3). Battelle's work on tobacco carcinogenesis for BAT was known within the company as Project Janus (see below).

Ed Finch, the president of B&W, had been away when Dr. Griffith presented his report to the executive committee on July 1. Dr. Griffith briefed Finch upon the latter's return. A July 19, 1965, memo from Dr. Griffith to Finch, with copies to J. G. Crume and to the general counsel, Addison Yeaman, reviews this meeting {1106.01}. In this memo Dr. Griffith indicates that, in his opinion, the adverse information from Harrogate—that fresh condensate is more carcinogenic than old condensate—will not provoke a "significant" public reaction but might precipitate government intervention. Therefore,

The company should take steps to place itself in best possible position to minimize chances of government intervention by

 

(a)

Having at least one brand on market which is "safest" possible cigarette on basis of knowledge to date.

(b)

Obtaining biological test data to indicate the degree to which the cigarette is "safer." {1106.01, p. 1}

The memo continues,

In the discussion of these points it was agreed that a modified LIFE [brand of cigarette] would represent the best company approach to a "safer" cigarette and that work on such a cigarette should be started as soon as possible. Approaches discussed were:

 

1.

Filter . AVALON type with acetate mouthpiece treated with P.E.G., bondex charcoal center section and paper treated with Polyethylene Imine (P.E.I.) or potassium carbonate next to tobacco.

2.

Tobacco . Blend changes will probably be required and it is possible that fermentation may be used to improve smoking qualities and decrease biological activity. A fermented burley blend was considered one possibility. {1106.01, p. 1}

The filter modifications were those that research at Harrogate had indicated would reduce carcinogenic activity of smoke condensate. The PEI additive increases the proportion of free nicotine. Potassium carbonate was used to reduce benzpyrene levels {1109.01, p. 2}. (By 1967, though, it was suspected that, despite the reduction in resulting benzpyrene level, potassium carbonate treatment resulted in increased carcinogenicity in mouse skin tests.)


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Dr. Griffith also argues that B&W should have its own biological testing program, preferably based in the United States. Moreover, B&W should maintain control over the publication of any results, doubtless to avoid other instances of the expected embarrassment from the publication of the Harrogate results:

Changes in biological activity must be measured by a reputable organization willing to make the results public only upon request. {1106.01, p. 2}

The memo closes on an unresolved note:

No decisions were made and the question of biological tests was tabled for further discussion at a later date. {1106.01, p. 2}

There is no evidence in the documents that Dr. Griffith ever got his wish that B&W conduct biological testing as part of product development in this country.

Report On Southampton Research, 1967

The documents include a detailed report on research activities at BAT's Southampton facility as of July 1967, two years after Dr. Griffith's visit to England {1109.01}. Dr. Robert R. Johnson from R&D at B&W had spent two weeks in residence at BAT's Southampton facility, and the file note summarizes his findings.

Current studies on the design of "safe" cigarettes fall into several main approaches. These are (1) synthetic tobacco substitutes, (2) cigarettes incorporating a large percentage of air-cured tobacco, (3) smoking products delivering smoke with a high nicotine/tar ratio, and (4) selective filtration. Ancillary research is also proceeding in areas of biological testing, human smoking patterns and smoke absorption, and smoke analysis. The supposed paramount importance of nicotine is evident in almost all of this research. {1109.01, p. 1}

Five years after the phenol crisis, selective filtration work had become a major function of the Southampton laboratory. The lab was also exploring a variety of additives and modifications to tobacco, including changes in the tobacco blend to reduce toxicity. Nicotine pharmacology was under study, and methods were being developed to look for nitrosamines, the most potent carcinogens in tobacco and tobacco smoke. Some work continued on Ariel (discussed in chapter 3), but in the main the emphasis of this wide-ranging but integrated research effort seems to have been on finding ways to make conventional cigarettes safer.

Ed Finch, CEO of B&W, read Dr. Johnson's report carefully enough to raise a question about it with Dr. Griffith {1110.01}. Why did "tu-


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morigenicity" increase even though the 3,4-benzpyrene content of smoke had been reduced after treatment with potassium carbonate {1109.01, p.2}? In his memo to Finch, Dr. Griffith explains that benzpyrene is by no means the only, or even the most, carcinogenic compound in cigarette smoke.

Actually, the data from the initial Harrogate experiment would indicate that the benzpyrene fraction can account for, at most, one third of the [carcinogenic] activity of the total condensate.

I personally feel that far too much attention has been given to 3,4-benzpyrene and other polycyclic hydrocarbons in England and elsewhere and not enough attention has been given to other materials which are probably of greater importance. {1110.01}

The more industry scientists learned about the toxicity of cigarettes, the more complex the problem seemed to become.

Montreal Research Conference, 1967

At the research conference held in Montreal in October 1967, participants discussed, among other topics, the applicability of mouse skin painting in their research.

The meeting agreed that it would be worthwhile to make a cigarette with lower biological activity on mouse skin painting, provided this did not adversely affect the position with respect to irritation and other factors. It was recognized that this implied certain assumptions about the relevance of mouse skin painting. However, it was agreed that it was unlikely this test would be replaced by cheaper, shorter and more meaningful tests for the next few years. In the light of this, the biological testing of new cigarettes must only be applied to those which have already satisfied the requirements of taste, cost, etc., and which are, therefore, considered viable commercial products. {1165.02, p. 3}

The participants agreed, then, that a less hazardous product must be similar enough to existing products that consumers would readily move to using it. Reduced toxicity in mouse skin painting was desirable, but secondary to marketing considerations. They considered a possibly "more meaningful" test, an inhalation test, but dismissed it because it was unlikely to become available.

The difficulties associated with inhalation studies were discussed and it was agreed that in the likely event that no satisfactory inhalation test could be found, it would be necessary to make an intuitive judgment based on cellular biochemical studies. {1165.02, p. 4}

Public statements from the industry have often pointed to the paucity of studies showing lung cancer from tobacco smoke inhalation as evidence


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against a causal link. In contrast, these company scientists did not look on the lack of an inhalation model as evidence of the lack of a causal link. Rather, they saw it as a technical problem. They were prepared to make an "intuitive judgement" about the toxicity of specific materials in the absence of such a test.

The likely impact of the publication of results from independent research groups was also discussed. Specifically mentioned were programs at the University of Kentucky and at the Environmental Health Unit at Research Triangle in North Carolina. The minutes note,

[T]he fact that they will[,] of necessity, publish their results should lead to a reconsideration of our own policy on publishing and it was agreed that where results which we had obtained were likely to be covered by such publication, we ourselves should publish first. It was also agreed that we should cooperate in such programmes as far as possible. ...

It was felt that Kotin's work [at the Research Triangle facility] could well provide the occasion for the cooperation of the American industry at the scientific level, preferably without any involvement of the company lawyers. It was mentioned that these programmes could also be supported by the industry, perhaps at the expense of contributions to CTR [Council for Tobacco Research] or AMA [American Medical Association]. {1165.01, pp. 5–6}

The minutes acknowledge that research results from R&D ordinarily were not published but should be published in this instance to ensure that the company would receive credit for results that were going to become public in any case.

The expressed wish that scientific exchange could take place without lawyers is interesting, as is the preference for channeling B&W resources for external research away from the public relations—driven outlets of the CTR and the AMA. As described in chapter 8, lawyers were heavily involved in most tobacco industry—sponsored research. These comments seem to indicate friction between the scientists and the lawyers; later minutes from research conferences demonstrate that the scientists came to accept the lawyers' supremacy as a matter of fact.

Hilton Head Research Conference, 1968

A dozen company scientists from various countries, including Sir Charles Ellis and Dr. R. B. Griffith, attended the 1968 research conference, held at Hilton Head, South Carolina. The conclusions reached during the proceedings on a wide range of topics were summarized by the conference chairman, Dr. S. J. Green of BAT, in a six-page set of minutes {1112.01}. The documents also include a thoughtful letter to Dr. Green in which


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B&W's technical manager, Dr. R. A. Sanford, comments on these minutes {1112.02}. The mood that comes through the conference report is one of cautious optimism. The R&D labs seemed to be making incremental but important progress in developing the capacity to make cigarettes that had reduced activity in biological tests but still would deliver nicotine (see chapter 3).

Dr. Green's minutes and Dr. Sanford's letter describe the contrasting concepts of "health-image" and "health-oriented" cigarettes {1112.01, p. 2}. This discussion goes to the heart of the company's approaches to the problems posed by the toxicity of their products. In the official conference summary, Dr. Green expresses the consensus of the delegates on this subject.

Research staff should lay down guide lines against which alternative products can be chosen in everyday operations. Although there may, on occasions, be conflict between saleability and minimal biological activity, two types of product should be clearly distinguished , viz:

 

a)

A Health-image (health-reassurance) cigarette.

b)

A Health-oriented (minimal biological activity) cigarette, to be kept on the market for those consumers choosing it [emphasis added]. 1112.01, p. 2}

In his letter to Dr. Green, Dr. Sanford suggests this clarification of the discussion and the consensus:

We find [this conclusion] confusing. Would it be better to say "A new product development might give undesirable biological test results, and the research staff should lay down guidelines insuring, in context of present understanding, a new product would have no greater activity in biological testing than current products. Preferably, the new product would give lower values. It was also recognized that there are two types of health products possible and that they should be distinguished.

 

a)

Health image (health reassurance cigarette) such as a low tar—low nicotine cigarette which the public accepts as a healthier cigarette and

b)

Health-oriented cigarette which has minimal biological activity; for example, one which would yield a near zero reading in a mouse skin painting test"? [emphasis added]. {1112.02, p. 1}

The term "biological activity" is a euphemism for toxicity and, especially, for carcinogenicity.

The "health-image" cigarette meets public relations needs, while the "health-oriented" cigarette serves a public health function (2). This interchange suggests that the company's scientists believed that low-tar and low-nicotine cigarettes conferred few, if any, actual benefits on the


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smoker, and that these products were mainly a marketing device because the public "accept[ed]" the view that these cigarettes were less toxic (see chapter 2). Also striking is Dr. Sanford's remark that, in the opinion of those at the conference, any future product should have no greater biological (carcinogenic) activity than existing ones. This consensus is, of course, an implicit recognition of the fact that cigarettes are actually toxic.

The minutes summarize other key conclusions of the Hilton Head Conference:

 

1.

It is clear that a number of features of cigarettes can modify the biological activity of smoke condensate. These include the incorporation of PCL [processed cigarette leaf] and CRS [cut, rolled stem], the form of the smoking vehicle, the type of tobacco, the presence of additives and the volume of puff taken in smoking the cigarette. These factors will become increasingly important when future cigarettes are designed.

2.

The biological results are also indicating the importance of both [cancer] initiators and promoters in smoke and this lead should be followed up vigorously in the biological research .

3.

Studies in instant condensate are showing a biological activity towards mouse-skin of the same order as that of stale condensate, suggesting that the biological activity is not time-dependent. The clear possibility of producing cigarettes with reduced mouse-skin biological activity therefore becomes of greater importance and a research solution to the whole problem is more likely.

4.

There was general agreement that a cigarette with such reduced mouseskin biological activity should be produced; other biological features, e.g. irritation, ciliastasis, must also be satisfied simultaneously [emphasis added]. {1112.01, pp. 1–2}

A number of other topics received attention during the discussions—among them, the development (at BAT's contract lab in Frankfurt) of reliable short-term tests to screen for carcinogenic activity; the merits of a noninhalable cigarette to protect smokers from developing emphysema, bronchitis, or cardiovascular diseases, conditions that depend on the inhalation of cigarette smoke for their development; the possibility of making a less irritating cigarette by lowering the proportion of nicotine compared to tar in the smoke (a filter from Germany, identified as the R6-acid filter, is mentioned in this connection); and the possible reduction of carbon monoxide levels in mainstream smoke through filtration or tobacco rod modifications with reconstituted tobacco. While these ideas apparently were not major focal points of product development at the time, their discussion reveals that BAT scientists thought that cigarette smoke inhalation was related to a number of diseases in addition to lung cancer and that nicotine was an irritant in cigarette smoke.


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The conference participants' commitment to making cigarettes less dangerous, as measured by bioassay, is clear in the following conclusions:

 

13.

Following discussion of the specific examples, it was agreed that no synthetic smoking material can be considered for product development unless the biological activity of its condensate is less than that of modified tobaccos or PCL. Despite the disappointing results reported by Montreal and Southampton on the Bell and Laing modified cigarettes—with an axial channel through a tobacco column of increased packing density—it was agreed worthwhile to attempt to acquire the patent for a reasonable sum, because it represents an alternative approach to cigarette design, in which B-A.T. already has some patent protection [i.e., Ariel].

14.

The adoption of an objective to make cigarettes which yield condensates with lower biological activity (but which must sell on their ordinary qualities) reduces the degrees of freedom in terms of taste, acceptability, economics, etc. in cigarette design. Because of its importance in smoker preference, there is a need to expand the systematic examination of the effects of casings and flavours on the flavour and aroma of cigarette smoke.

 

It was agreed it would be unreasonable to hold up the introduction of a new development of a significant nature until it had been proved conclusively to be of lower biological activity. Provided that available short-term tests had been passed, and the development was judged to be in the right direction, the meeting agreed that the development could well be introduced subject to the immediate initiation of long term testing procedures. {1112.01, pp. 4–5}

The invention referred to in paragraph 13 may be described in a US patent issued in 1971 and assigned to B&W (13). The patent, filed a few weeks before the conference, describes an article that arranges tobacco in a cigarette-like device around a central core. The core contains material capable of removing toxins such as polycyclic aromatic hydrocarbons from the smoke. The tobacco is lit. As puffs are taken, tobacco smoke is channeled through the central core on its way to the consumer.

Finally, the conference report includes a reminder of the need to increase communication among the laboratories. There is also a veiled reference to limits on communication for some information because of "special legal agreements." This restriction may be a reference to trade secrets or, perhaps more likely, to efforts to insulate B&W from receiving reports that might be embarrassing for it to have in its R&D files (see chapter 7).

The various changes in organisation were outlined and their effects in terms of communication links [between laboratories at the several operating companies] were discussed. It was concluded that there is still a need to strengthen these links in addition to personal visits, but it must be recognised that there


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can be occasions when these must be restricted to certain channels because of special legal agreements entered into by individual companies. {1112.01, pp. 5–6}

Kronberg Research Conference, 1969

Nine delegates from various affiliated companies, including delegates from England and from Kentucky, attended the 1969 research conference, held in Kronberg, Germany. The draft agenda {1113.01} covers a range of topics similar to those discussed at the Hilton Head conference: (1) reports of ongoing research projects, including Hilton (an inhalation experiment at Battelle), Lokstedt, and Janus (mouse skin painting to test for cancer); (2) discussions of nicotine pharmacology, carbon monoxide, solids in smoke, nontobacco materials, reconstituted tobacco, coumarin, black-fat tobacco, PEI, and "the current safest cigarette"; (3) product development; (4) process R&D, including leaf tobacco developments, freeze-drying, tobacco treatments, additives, reconstituted tobacco, and microbiological flora.

The minutes of the meeting include a lengthy discussion of the biological testing program. A major conclusion of this discussion is expressed as follows:

The conclusion of the Conference was that at the present time the Industry had to recognise the possibility of distinct adverse health reactions to smoke aerosol:

 

(a)

Lung Cancer

(b)

Emphysema and bronchitis

and present and future bioassay tests could usefully be classified according to their applicability to one or other or to both. {1169.01, p. 3}

The careful wording here is in keeping with industry dogma, but the statement is, nonetheless, far more forthright than the Zephyr document of the previous decade. A yet more frank assessment was to appear in the minutes of these meetings in the 1970s (see below). Despite this wording, the relative frankness of the comments on smoking and cancer in these minutes led to a strong letter (discussed in detail in chapter 7) from David Hardy at the law firm of Shook, Hardy, and Bacon to DeBaun Bryant, B&W's general counsel, warning that such admissions could lead to serious liability problems for the company {1840.01}.

Participants also discussed the mouse skin—painting experiments at Harrogate and the relative value of short-term biological tests as compared to mouse skin—painting studies. Cooperative industry studies in


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the United Kingdom had revealed important differences in carcinogenic activity between two preparations of tobacco condensate:

This appears to be a significant alteration in mouse-skin bioassay reaction brought about by an alteration in tobacco composition. {1169.01, p. 1}

Unfortunately, though, a difficulty had arisen in specifying the precise compositions of the two condensates, so it was not clear how to replicate the finding or what changes to make in blending to carry this result further. The participants suggested that those in charge of this work should get in touch with the University of Kentucky to explore ways in which conventional strains of tobacco could have such marked differences.

The conferees endorsed fractionation experiments at Harrogate to see what subfractions of condensate act as promoters and initiators of cancer. Mouse skin painting remained the standard for carcinogenesis:

In the foreseeable future, say five years, mouse-skin painting would remain as the ultimate court of appeal on carcinogenic effects. {1169.01, p. 4}

At the same time, short-term biological tests, such as a test of hyperplasia (an abnormal increase in the number of cells), were of interest both for their potential to act as predictors of mouse skin–painting results and as indicators in their own right of important toxicities of tobacco smoke. The conferees agreed, though, that there would be no consensus on what the results of short-term tests meant: any interpretation of short-term bioassay results as predictive of carcinogenic potential was "the responsibility of the user" alone {1169.01, p. 4}. Meanwhile, the tobacco industry's public position was that mouse skin painting is an unreliable way to test whether cigarette smoke causes cancer.

Biological Testing Committee Discussions, 1970

The Biological Testing Committee at Southampton provided oversight, review, and direction for the BAT toxicology research program. BAT-funded contract research as well as work funded by the UK industry group as a whole was discussed at these meetings. Committee membership usually consisted of BAT scientists in the United Kingdom, but individuals from other BAT companies in the UK industry group occasionally were present. Minutes from some of the meetings held between 1968 and 1977 are available in the documents. The minutes involve technical issues and it is often difficult to understand what is being discussed


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apart from the context. However, the general subject is the experiments on various product modifications and innovations to learn what maneuvers might lower the carcinogenic potential of cigarettes.

Two notes, one concerning inhalation, from a meeting held in May 1970 (the eighteenth meeting of this committee), and one on carbon monoxide, from a meeting in October of the same year, are included here as examples of these discussions.

The minutes of the discussion of inhalation tests read,

There was an extensive discussion of inhalation tests. Dr. Sanford [B&W], Dr. Fordyce [UK] and Mr. Wade [Canada] urged that BAT should be actively engaged in inhalation tests in the near future. It was agreed, however, that at present an inhalation test which led to the production of cancer and which could be used for the comparison of different cigarettes was not available. Dr. Green [UK] suggested that the development of these tests could be left to the industry [cooperative laboratory at Harrogate]. With regard to shorter-term tests, [the Imperial Tobacco Company laboratories at] Huntingdon were obtaining encouraging results on the mouse-irritancy screen, a goblet cell test and a macrophage test. Dr. Bentley suggested that these should be available within about 12 months. It was agreed that BAT should wait for these tests to be developed rather than attempt to duplicate the work at the present time. Similarly, the development of the "monkey-smoking" programme at Huntingdon would be followed with great interest. {1164.06, pp. 3–4}

In its public statements, B&W was insisting that the evidence did not support the hypothesis that smoking caused cancer {2110.06, pp. 6–10}. Here, a group of BAT scientists clearly stated their expectation that an inhalation test would be developed that "would lead to the production of cancer" and expressed an eagerness to have such a test available as a tool for comparing different cigarettes. Thus, the issue was a comparison of how different cigarettes caused cancer, not whether smoking caused cancer. In addition, the industry position was that even a successful inhalation test showing cancer causation in animals would not be indicative of cancer causation in humans. Yet the BAT scientists embraced animal inhalation tests for this very purpose. In the meantime, they continued to use mouse skin painting for purposes of evaluating human toxicity.

The brief mention of work under way at Imperial's laboratory in Huntingdon reflects an information-sharing arrangement between BAT and Imperial. The agreement covered exchanges of research results on smoking and health issues as well as on leaf characteristics, agronomy, and machinery evaluation {1171.02}. The documents do not contain any information about the monkey-smoking work, but chapter 3 discusses


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a series of experiments at Imperial on the pharmacology of nicotine; monkeys were used as subjects in these experiments.

Carbon monoxide was discussed at a committee meeting in October 1970.

It was considered that it was still very important to reduce the level of carbon monoxide in cigarette smoke. It is a known poison present in relatively large amounts and, despite the lack of success in developing a suitable filter, efforts should be continued. {1164.06, p. 4}

As will be described later, carbon monoxide was to continue to be a problem. However, as time went on, the nature of the problem became more one of public relations and the avoidance of regulatory oversight than the reduction of toxicity for its own sake.

Health Versus Public Relations, 1970–1982

St. Adele Research Conference, 1970

The group research conference for 1970 was held in November at St. Adele in Quebec {1170.01}. The group consensus about the potential for achieving a "safe" cigarette was significantly tempered in 1970 compared to conclusions the group had reached in 1967. According to the 1970 minutes, the 1967 meeting had concluded,

The smoking and health problem is amenable to a research solution. This is a significant change in thinking and is a direct result of research [emphasis added]. {1170.01, p. 1}

By 1970 the conference participants (nearly the same group of individuals) reached a different conclusion:

The smoking and health problem is at least partially amenable to a research solution [emphasis added]. {1170.01, p. 1}

Underlying both statements is the assumption that constituents of tobacco products have toxic effects. The statements represent an important shift between 1967 and 1970 in the degree to which BAT scientists believed there was a technical fix for the problem of smoking-induced cancer and other diseases.

Chelwood Research Conference, 1972

The minutes of the 1972 conference, held at Chelwood, England, include a specific statement of the "main objective" envisioned for R&D at the Southampton facility.


136

The main Southampton objective was stated 'To design cigarettes which are preferred by smokers either generally or in significant special cases. The products are to conform to policy requirements with respect to composition and biological activity.' The main criticism was not with the objectives but that these might be too difficult to achieve. {1171.02, p. 2}

A comment later on in the minutes, following the presentation of a paper by Dr. Green, the head of the Southampton laboratory, suggests what a measurable goal for an acceptable level of biological activity might be.

One suggestion was that our aim should be to provide smoking pleasure accompanied by risk no greater than that with comparable habits, such as alcohol. This may already be the position achieved in some countries. {1171.02, p. 5}

New products, first of all, had to be commercially successful. Hazard reduction was couched in relative terms. This stance acknowledged both the reality of the hazard and the practical impossibility of eliminating it.

Duck Key Research Conference, 1974

Twelve delegates from five countries, including the United Kingdom and the United States, attended the 1974 research conference, held at Duck Key, Florida {1125.01}. Discussions concerned work on tobacco substitutes (see below), smoker compensation to achieve a consistent nicotine intake (see chapter 3), puffed (expanded) tobacco, carbon monoxide, caffeine as an additive, selective filtration, sidestream smoke (see chapter 10), and the financing of research, among other topics.

Puffed (expanded) tobacco was being investigated in Germany and Austria. The problem was that cigarettes made of expanded tobacco yielded fewer puffs per cigarette. In expanded tobacco, the layers of the tobacco leaf tissue are forced apart by physical pressure provided by the rapid vaporization of a liquid (such as freon) or solid (such as carbon dioxide in the form of dry ice) that has previously been saturated into the leaf. Expansion increases the volume per unit weight of tobacco. Cigarettes made of expanded tobacco reduce tar delivery because there is less fuel in a given volume if some of it has been puffed up. Carbon monoxide in smoke was recognized as a problem, but available means to reduce CO (such as a lithium hydroxide process) tended to increase the levels of polycyclic aromatics and to increase "tumorigenic activity." The direction of future combustion studies at Southampton was to be directed toward controlling both CO and polycyclic aromatics. Caffeine


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was noted to reduce "tumorigenic activity" of smoke condensate, but concern was expressed about the public relations problems that the use of caffeine as an additive might engender {1125.01, p. 3}.

Product development throughout the company in 1974 centered on "selective filtration and constant puff by puff deliveries." Constant deliveries are most important pharmacologically, since the customer then gets a predictable dose of nicotine with each inhalation. When cigarettes were merely cured, cut leaves wrapped in paper, the product was uneven and nicotine deliveries unpredictable (14). With technological innovations introduced in subsequent decades, cigarettes became much more consistent products. In this connection, a program within BAT of systematically analyzing commercial and technical information on Philip Morris products from around the world was mentioned as worth continuing.

Advertising restrictions attracted discussion. At the time, the only actual restrictions were on broadcast advertising. However, broader restrictions were feared. The conference summary notes,

With increasing restrictions in advertising, there will be less opportunity for the creation of brands in traditional ways (imagery) but an increasing requirement for products to have new visible, demonstrable or detectable attributes. {1125.01, p. 4}

The Duck Key conference highlights the priority that R&D continued to place on making cigarettes safer. Issues of smoker compensation and environmental tobacco smoke appeared for the first time in this series, and a major portion of the conference report was devoted to the search for tobacco substitutes, which is treated in a separate section (see below).

Merano Research Conference, 1975

At the 1975 conference, held at Merano, in northern Italy, much of the discussion centered on tobacco substitute materials such as Cytrel and New Smoking Material (NSM) (see below). The conferees expressed concern that the tobacco substitutes might themselves contribute to the toxicity of cigarettes, resulting in a greater toxic impact than that of regular cigarettes.

The implications of the initiation-promotion hypothesis [of carcinogenesis] on the risks of smokers changing to cigarettes containing substitutes was discussed. It was agreed that this was important and that the mouse skin painting experiment proposal for TRC [the industry research group in the UK] (the so-called cross over experiment) should be supported. If it was not


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agreed at TRC to undertake this experiment it is recommended that consideration should be given to B.A.T. undertaking these or similar experiments. {1173.01, p. 3}

The conference participants recognized that the "smoking and health" issue was never going to go away.

The meeting agreed that the earlier conclusions that cigarette smoking is now irreversibly associated with health issues is still valid. {1173.01, p. 3}

Moreover, the assembled BAT and B&W scientists recognized that their potential contribution could never offer more than a partial solution to the problem. Apparently, some in the group felt that the R&D group had, however, understated its role in prior statements.

It was felt by some members that the assumption that there would be no R & D 'breakthrough' in smoking and health had been misinterpreted in some ways. It was emphasised that this does not mean that there are unlikely to be important R & D contributions. It is believed that considerable and continuing progress will be made leading to a progressive series of product improvements. {1173.01, p. 3}

Technical improvements would never make a cigarette safe; the only credible goal was to make the product less dangerous.

The R&D objectives in the "smoking and health area" were explicitly set forth. These objectives represented a decided departure from the optimism of the 1960s, when it seemed that smoking might be made safe, and revealed a predominantly reactive, defensive posture.

The immediate objective is to provide a scientific contribution in those territories where pressures in relation to smoking and health require such a capability. This function is carried out locally where adequate R & D establishments exist and from G.R. & D.C. [Group Research and Development Centre at Southampton] in their absence. Specific services include:

 

1.

Design of products having attributes dictated by the attitude of local health authorities, e.g. control of smoke constituents considered harmful.

2.

Advice [to management] regarding the health implications of product design and constituents.

3.

Interpretation [for management] of smoking and health discoveries.

4.

Assessment of health implications and availability of materials and processes under development and purported to have a bearing on the smoking and health issue, e.g. N.T.M.s [new tobacco materials].

As a longer range, and perhaps never ending, objective R & D has a goal of developing products that respond positively to scientific information having relevance to smoking and health.

...


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Until such time as assay methods already developed, or to be developed, are given authoritative endorsement by medical experts, the longer range work will remain as basic research. {1173.01, p. 5}

The immediate goal was to provide assistance to management in responding to public relations and regulatory demands. The provision of a less dangerous product for its own sake was relegated to a secondary role.

Sydney Research Conference, 1978

The minutes of the 1978 research conference, held in Sydney, Australia, reflect the acceptance by BAT and B&W scientists that smoking causes serious disease. Moreover, they expressed hope that the generation of low-tar cigarettes already on the market would prove to be far safer than those having higher-tar deliveries.

The first conclusion of the meeting affirmed the absence of any scientific controversy on smoking and health.

There has been no change in the scientific basis for the case against smoking. Additional evidence of smoke-dose related incidence of some diseases associated with smoking has been published. But generally this has long ceased to be an area for scientific controversy. ... The meeting affirmed that cigarettes acceptable on all counts can probably be achieved by research and, indeed, may in fact be available [emphasis added]. {1174.01, p. 1}

This frank statement stands in marked contrast to the industry's public posture that a substantial controversy still existed.

Near the end of the minutes from this meeting, a discussion of less dangerous cigarettes includes an important epidemiological definition of what such a product would be.

Cigarettes of substantially reduced biological activity (SRBA) can be made by product modification and will continue to present a range of marketing opportunities. By SRBA is meant cigarettes where epidemiology would show no greater incidence of disease for smokers than non-smokers. But there remains a need for credible biological tests to facilitate developments. Credibility will continually evolve but could be provided by outside independent medical and scientific advice.

As indicated in Note 1 [quoted above], we may already have an SRBA cigarette and it may be worth studying epidemiologically the current smokers of low tar products over the next decade . But until this evidence is available alternative products should be developed. To do this, research must provide a continuing basis for cigarette formulation and design for related process needs and better understanding of smokers' behaviour. Defensive research will need to be provided for as far ahead as can be seen and this may well include social aspects [emphasis added]. {1174.01, pp. 6–7}


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While the industry was publicly insisting that incidence of disease, as measured in epidemiological studies, is not a valid measure of disease causation, the BAT scientists privately adopted incidence of disease as the measure of degree of biological activity against which to evaluate the success of efforts to make a "safe" cigarette. There is no scientific controversy here. Cigarettes cause serious diseases.

The companies' scientists were saying that biological testing is only used as an indirect measure of what really matters—namely, whether customers of tobacco companies get sick and die more often than people who do not smoke. The official dogma, in contrast, is that epidemiology can never be used to reach conclusions, and that there is no animal model that proves causation. The absolute standard for measuring success of the R&D effort to make a less dangerous cigarette is whether fewer people get sick from smoking the supposedly SRBA product. In fact, the goal is that the SRBA smoke not cause any detectable excess incidence of disease. Unfortunately, the low-tar cigarettes that the group hoped were SRBA devices have not turned out to be substantially less hazardous than other cigarettes (7).

This passage sharply illuminates what is perhaps the most distressing aspect of the tobacco problem. Scientists at B&W and BAT were intent on developing a safe product. At the same time, tobacco products known to be dangerous were being continually produced by their employers and sold to the public. Even when the scientists believed (wrongly) that they might have developed a safe product, it was marketed for only a special segment of the market. That is, products known to be dangerous were kept on the market, whereas those thought to be safe were introduced only as niche brands. Moreover, the supposedly safe brands had not been adequately tested and therefore had not been proven safe. The tests that counted, the results of epidemiological studies of the companies' customers, were necessarily post-marketing research that would take many years to complete.

London Research Conference, 1979

The R&D conference held in London in the fall of 1979 was notable for the brief discussion in the minutes of the biological testing program.

The expenditure at Southampton on biological testing represents a significant portion of the total R&D expenditure (£0.54m internal and £0.37m external out of £5.3m gross total). Before agreement can be reached on the details


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on any proposed programme of work, it was thought essential to have established the current Board policy on research on smoking issues e.g. (a) for early warning, (b) as evidence of a responsible attitude by the Group, (c) as the basis for future positive support to Group products. {1176.02, p. 9}

At the time, then, BAT was spending £910,000 per annum on its biological testing program through the Southampton facility. As the references to "early warning" and "responsible attitude" indicate, the scientists regarded the value of the work as mainly defensive; possible product improvements based on this work seemed of secondary importance. This emphasis may simply have reflected their realization that a "safe" cigarette was not an achievable goal and that the company had other pragmatic reasons to do work in this area.

Pichlarn Research Conference, 1981

The 1981 research conference was held in Pichlarn, Austria, in August {1178.01}. Smoker compensation, the tendency for consumers to smoke low-delivery products more vigorously than higher-delivery products (see chapter 3), was a theme that came up in several places. For instance, the strategic objective for filters referred to "human smoking patterns."

To develop novel filters and novel filter technology aimed at the development of marketable low-tar products, paying particular regard to human smoking patterns. {1178.01, p. 3}

Similarly, in the discussion of carbon monoxide in cigarette smoke, "human smoking pat[t]erns"—that is, the way people actually smoke, in contrast to the way machines smoke—also are mentioned:

Though the political relevance of medical opinion on the importance of CO [carbon monoxide] varies between countries, it was agreed that GR&DC should continue to seek means of reducing the CO/tar ratio of the main types of products. Before any such products are offered commercially, it would be advisable that they should have been examined in the context of human smoking pat[t]erns. ...

It is felt that the time is close when Government agencies worldwide will take more notice of compensation—and of the scale of the differences, for a given commercial product, between smoking machine numbers and the dose of smoke actually obtained by smokers. This issue may well go beyond the simple technical measurement of deliveries. If for no other reason than defence, we must pay increasing attention as to how our products—especially new products—are smoked by different categories of smokers. {1178.01, pp. 13–14}


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Compensation, recognized by BAT and B&W scientists in the early 1970s, threatened to undermine the potential benefits of well-intentioned improvements in cigarette design. Instead of dealing with this threat as a problem in toxicology, however, company scientists seemed more pressed by its regulatory implications.

Montebello Research Conference, 1982

The minutes of the 1982 conference, held at Montebello, Canada, acknowledge that smoking and health problems had not been solved despite a quarter century of work on them. The following notes summarize discussions under the heading "Smoke Quality."

Despite intense research over the past 25 years, the biological activity of smoke remains a major challenge. In particular, it is not known in quantitative terms whether the smoke from modern low and ultra-low delivery products has a lower specific biological activity than that from previous high delivery products. Nor is it clearly established (other than in broad terms such as sheet and stem) what are the main factors that influence biological activity. In the UK, the Independent Scientific Committee is calling for information on the quality of smoke from modern products, but the formulation of an appropriate research programme will prove extremely difficult and will need very careful planning. The US Surgeon General has previously also drawn attention to the general need for a better understanding of biological activity.

In a survey of the current US scene, the broad area of smoking and health (less hazardous cigarette, additives, self-extinguishing cigarette [to reduce the risk of cigarette-caused fires]), the possibility was identified that a competitor could in the future well make competitive capital out of health-related attributes, eg low nitrosamines or even a biological index.

The Canadian contribution to the Group Biological Programme, which is closely co-ordinated with GR&DC [Group Research and Development Centre], will concentrate on factors that might influence mutagenic [cell changing] activity:

 

(a)

Different tobacco types including sheet.

(b)

Smoking regime—human vs standard smoking machine.

(c)

Product design features.

The research at McGill University, which is funded by the Canadian Tobacco Manufacturers Council, will also contribute to Group knowledge. {1179.01, pp. 4–5}

This passage acknowledges that BAT and B&W scientists did not know "in quantitative terms" whether the innovations they had pioneered were effective in lowering the biological activity of the products. Pressure from public health quarters continued unabated. Especially trou-


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blesome was the presence of nitrosamines, extremely potent carcinogens in tobacco. Nitrosamines also presented a possible competitive problem if another company made claims about low nitrosamine levels.

Concerns about nitrosamines are further emphasized in the outline of work to be undertaken in the following three years (1983–85). Since nicotine and other nicotinic alkaloids in tobacco combine with nitrates to form the tobacco-specific nitrosamines (15), removal of nitrates from tobacco (thereby reducing levels of this precursor of nitrosamines) was regarded as a priority {1179.01, p. 15}. A related investigation would try to determine whether "certain nitrogen-containing components [nitrates and proteins/amino acids {1164.26, appendix F}] are major precursors of smoke mutagenicity" {1179.01, p. 16}.

In addition to these veiled references, the specific discussion about nitrosamines is summarized as follows:

There was support for the identification of this [nitrosamines] as a new Work Area. It was emphasized, however, that the approach should be two-pronged, ie:

 

(i)

Understanding the routes by which nitrosamines in whole smoke are formed, and possible modification thereof by additives etc.

(ii)

Selective removal of nitrosamines.

Before starting experimental work on the environmental analysis of nitrosamines, the past work of Wynder and Hoffman, Philip Morris and the German Verband should be fully appraised. {1179.01, p. 17}

Stems, otherwise valued for their relatively low tar production, were high in nitrates and so could potentially contribute to nitrosamine formation. During the late 1970s and early 1980s, many patents were issued to tobacco companies on ways to remove nitrates.

Bat's Research Projects, 1960s–1980s

Project Janus

BAT did not rely solely on the UK industry-wide cooperative lab at Harrogate for its long-term toxicology program. In 1965 it set up a contract operation of its own, called Project Janus. Project Janus was winding down in 1977 {1164.23}, but continued at least into 1978. BAT contracted with Battelle-Institut Frankfurt am Main to conduct long-term mouse skin-painting experiments as part of BAT's product development program. This was another branch of the same laboratory that had conducted the nicotine projects Hippo I and Hippo II (discussed in chapter 3) a few years earlier. Battelle hired a staff of between twenty and


144

twenty-seven people for Project Janus and built a special building to house it {1138.03}. Battelle undertook a wide variety of studies under Project Janus. The core activity was mouse skin painting, and different ideas were tested to examine the toxicity of specific cigarette components and of different proposed modifications. In addition, Battelle developed a variety of short-term biological tests under this project.

The selection of projects initially seems to have been decided by the priorities of the BAT staff in the United Kingdom. Early on, before the project had even started, Dr. R. B. Griffith of B&W expressed concern that the initial testing was entirely related to British-type 100 percent flue-cured cigarettes and ignored the blended cigarette typical of the US market {1105.01}. B&W did, however, contribute materials for a variety of Janus experiments. The preparation of samples for testing at Harrogate and at Frankfurt consumed a good bit of time at the Southampton lab in the late 1960s {1138.01, p. 3}, but B&W was also involved in this work {1143.01}.

A glimpse at how Southampton contributed to Janus comes from an undated, two-page fragment of an annual report from about the late 1960s to the early 1970s {1138.01, pp. 3–4}. The lab's work is categorized into "(a) the reduction in biological activity, and (b) the understanding of consumer acceptance." The report indicates,

Additive-treated tobacco and sheet materials show considerable merit biologically, indicating that tobacco can be altered advantageously. It would appear that the tobacco type and the processing it receives may be the major factors. ... The formulation of non-tobacco materials has also been undertaken.

The investigation of additives to reduce aromatic polycyclic hydrocarbons has continued. Several have been found to be effective, and two have sufficient commercial potential to warrant detailed study regarding levels and methods of addition [emphasis added]. {1138.01, p. 3}

The preparation of samples for Project Janus testing at the Battelle facility in Frankfurt and at the Tobacco Research Committee (TRC) lab at Harrogate (TRC was the successor to TMSC) consumed a substantial amount of effort.

The results of a study of the toxicity of inhaled tobacco smoke at the Battelle laboratory are discussed in a 1972 report {1152.01}. Groups of male mice were exposed to the smoke of one of two cigarette types; their fertility then was compared to that of a group of mice that had not been exposed to smoke and to each other. Sexual activity was less in the experimental groups than in the controls, and the controls had a higher fertility rate than the smoke-exposed groups.


145

In 1967 Janus testing had established that the additive potassium carbonate, even though its use resulted in lower benzpyrene levels, was associated with higher rates of tumor formation in mice {1109.01, p. 2}.

Part of the Project Janus research plan in 1968 was to test the effects of different levels of cigarette ventilation on condensate carcinogenic activity and to test processed cigarette leaf (PCL) as a substrate {1112.01}.

In an overview of Janus mouse skin–painting experiments prepared in April 1971 {1138.04; 1163.13}, E. B. Wilkes summarized results from six different experimental test preparations. The rates of tumor production at the lowest of the three doses tested for each preparation are presented here in order of the size of the effect {1138.04, pp. 5–6}:

 

Condition

% Tumors at 25 mg dose

PCL, based on CN102 lamina and Canadian stem binder

16.9%

Flue-cured lamina (CN102) and Canadian Stem (as CRS), in equal portions

31.1%

"Typical" U.S. K.S.F.T. [king size filter tip] cigarette

33.6%

Flue-cured blend (CN102), lamina only

47.7%

Yeast treated flue-cured lamina (CN102), strand widths 30, 60 and 120 c.p.i. [cuts per inch]

59.1%

Flue-cured lamina (CN102) control for B6; strand widths 30, 60 and 120 c.p.i.

62.2%

By late 1971, however, BAT was expanding its options for toxicology testing. A progress report on Project Janus for 1971, written by a BAT scientist, notes that BAT expects to set up its own laboratory facilities within a year {1163.10}. Moreover, this new lab would concentrate on inhalation studies. The new inhalation work would feature precise control and measurement of the retained dose from different cigarettes. Nevertheless, the author of this report continues to expect that a role for mouse skin–painting experiments will remain.

[I]t is anticipated that mouse-skin painting experiments will be continued at Battelle and[,] although the demands are reducing[,] the next long-term test has already been planned. Future requirements are somewhat less certain but it is likely that such tests will be required for the examination of new technical developments in the reconstitution process and the incorporation of different materials or additives in the process. {1163.10, p. 10}

A Project Janus experiment on the effect of different puff volumes on tumorigenicity was reported by the Battelle lab to BAT in 1973 {1138.02}. At issue was whether cigarette smoke condensates taken at


146

puff volumes of 10, 25, and 50 ml were equally potent when the same amounts (50 mg) were applied to mice in the standard manner. While the eventual rate of tumor formation was similar in all three groups, there was a clear dose-response relationship in the time of appearance of tumors. The 10-ml puff volume was associated with the most rapid appearance of tumors, the 25-ml puff volume was intermediate, and the 50-ml puff volume was associated with the most gradual onset of the appearance of tumors. In this experiment, the carcinogens in the condensates seemed to be in higher concentration in the tar from the smaller puffs than the larger puffs. Combustion may have been more complete in the later stages of the larger puffs, resulting in a dilution of carcinogens from the first part of the puff. The report describes the results as showing a dose-response relationship. The presence of a dose-response relationship is very strong scientific evidence that the material being tested, in fact, causes cancer.

Janus, which continued for more than a dozen years, made major contributions to BAT's understanding of safe cigarette strategies. It utilized long-term and short-term assays to help the R&D staff make decisions about product design. Even though the work led at best to only marginal improvements in cigarettes, the goal of the work was always clear: to help make cigarettes less toxic. To achieve this goal, BAT was willing to support a large contract research operation in Frankfurt from 1965 until at least 1978.

Project Rio

A review of BAT's biological testing program was held at Southampton in May 1983 {1164.26}. The notes on this meeting contain the first reference in the documents to Project Rio, a project designed to organize the company's research on cigarettes having reduced biological activity. Additional information about Project Rio is found in the report of the Rio de Janeiro research conference held in August 1983 {1180.07}. (Chapter 7 discusses the concern that B&W lawyers had about the possible discovery of Project Rio by lawyers for plaintiffs in products liability lawsuits.)

Three distinct components were recognized in Project Rio:

 

(a)

Phase I would be the design of low activity cigarettes in the 5–10 mg [tar] range, using existing technology and tests.

(b)

Phase II would be the further investigation of such cigarettes with additional tests, possibly after their introduction onto the market. Within the


147
 
 

additional tests it is likely that there would be a requirement for a long-term study: Dr. F. J. C. Roe recommended that an inhalation study would be preferable, providing a viable test procedure was available.

(c)

A further stage in the development of low activity products could be envisaged, involving more speculative procedures such as the adventitious addition of materials to cigarettes. However, the work associated with the development and evaluation of such cigarettes would be substantial and might pose problems similar to those faced by the pharmaceutical industry [emphasis added]. {1164.26, p. 1}

The work was to be done through the laboratories in Hamburg, Montreal, and Southampton. The first two parts of the project sound very similar to the things that the R&D group had been involved with over the past generation. The third, though, was something of a departure: the use of additives to reduce biological activity. The document mentions one such possibility: Vitamin A.

The current status of Vitamin A as an anti-cancer agent should be reviewed in the context of the possible addition of Vitamin A (or some derivative) to tobacco. {1164.26, p. 2}

Such a proposal would make sense only if one believed that tobacco causes cancer. Compounds related to Vitamin A found in food had been related to reduced cancer risk, and this information was coming to public attention around this time. However, the use of such cancer-reducing materials as additives "might pose problems similar to those faced by the pharmaceutical industry" {1164.26, p. 1}. The reference here appears to be to FDA regulation.

Toward the end of the 1980s, a B&W marketing executive, Douglas Keeney, left the company to start a new company, CA Blockers. CA Blockers was set up to market a cigarette that used an additive, N-Bloctin, which promised to reduce the consumer's exposure to nitrosamines. The product, Spectra, was regulated as a drug by the FDA because of the implied health claim (2). The FDA regarded N-Bloctin as a drug, since it was intended to reduce the absorption of carcinogens from tobacco smoke, and the agency declared that any product containing N-Bloctin was also a drug. Therefore, it exerted jurisdiction.

By August 1983 the R&D scientists at BAT had decided against actively pursuing Vitamin A as an additive. The decision was based on the results of a literature review, which led to the conclusion "that Vitamin A (and closely related compounds) does not present an opportunity for the cigarette industry directly to influence human response to smoke" {1180.07, p. 4}


148

A fear expressed during the discussions about Project Rio in the initial 1983 concept paper was that competitors might publish a ranking of cigarette brands according to the results of mutagenicity tests such as the Ames test. (The Ames test uses bacteria that because of a defective gene are unable to make a particular nutrient that is lacking in a specially prepared growth medium. A mutation at this gene locus can permit the bacteria to grow in the deficient medium. The relative mutagenicity of a test material—such as cigarette tar—can be estimated by the rate at which the material induces mutations that permit the bacteria to grow.)

The possibility of competitors producing a biological ranking of brands e.g. based on Ames test data is real and we should be in a position to respond to such a situation. {1164.26, p. 2}

It is interesting that this threat was seen as coming from other tobacco companies and not from a source such as the Reader's Digest , which had previously caused such problems with its publication of tar and nicotine yields. Clearly, in a country such as the United States, the only competing company that would publish such a list would be one whose product had the least Ames mutagenic activity. In other words, the competitor would have to be a start-up company such as CA Blockers. Nonetheless, the concern that someone else might develop a brand-specific table of mutagenic activity led to a plan to evaluate the Ames test mutagenicity of company brands and those of competitors in selected countries from around the world {1180.07, pp. 3–4}. This work would actually have enabled BAT to publish a biological index table. The work was to be completed on this initial testing by mid-1984.

Project Rio was to be the company's major biological research activity for the 1984–86 period {1180.07, p. 18}. While the work would concentrate on the Ames test, the minutes reflect an attitude of caution about "over-dependence" on this single measure; "more direct tests" were preferred if possible.

Preliminary results from Project Rio are summarized in the minutes of the biological conference held at Southampton in April 1984 {1181.06}.

The Ames is the main screening assay and from the results to date it is clear that:

 

(i)

Cigarettebrandscan be readily distinguished. This is in contrast with the earlier mouse skin painting results. An unfortunate side-effect is that the sensitivity increases the probability of an Ames League Table


149
 
 

appearing. A further unfortunate examination is that, to date, it is not uncommon for BAT brands to have a higher result than those from the opposition.

(ii)

Important fractionation work in Montreal indicates that the Ames activity is associated with the basic materials in cigarette condensate. Again, this is in contrast to the mouse skin painting results, where the bulk of the activity resides in the neutral fraction. Any response to this observation must wait until the initial work in Montreal has been completed.

(iii)

Initial results indicate that reduction in circumference [of the cigarette] reduces activity.

(iv)

Early results from Hamburg indicate that the addition of casings and flavours can increase the Ames activity. Observations from Montreal suggest that certain other casings bring about a reduction in Ames activity.

(v)

Ventilation brings about an increase in mutagenicity which with Canadian cigarettes was not significant. German cigarettes however showed a significant increase. It could be important to evaluate changes in design features with a number of cigarette types as the interaction with the tobacco blend could well be important.

(vi)

Montreal is to produce a review examining variations in design parameters and mutagenicity.

Clearly we need tests in addition to the Ames test and Southampton is obtaining encouraging results with an enzyme induction assay. There was general agreement that the work should be actively pursued. Similarly it was agreed that the "yeast system" showed promise as a useful assay and should be followed up.

The eventual need for a long-term bioassay, preferably based on inhalation, was considered. The significance of such a test to the tobacco industry was discussed, particularly if the animals used were pre-treated with a known initiator such as radon. No firm conclusions were reached but it was agreed that Southampton should explore the feasibility of a long-term assay [italic emphasis added]. {1181.06, pp. 1–2}

BAT scientists had been able to stratify cigarette brands according to Ames activity, but not with mouse skin painting. The constituents of cigarette smoke responsible for the Ames test activity seemed to be different from those associated most strongly with carcinogenesis in the mouse skin–painting model. This result suggests that these were additional constituents of tobacco smoke with negative health effects.

A joint R&D/marketing conference held in Montreal in July 1984 included a report on Project Rio from the Montreal lab {1226.01, p. 85}. The report presents data showing that changes in smoker behavior (compensation effects) could alter Ames test results.

Traditionally, mouse skin painting has been used as an indicator of biological activity. Recently, short term tests such as the Ames mutagenicity test have


150

also been used to determine biological activity. With the increase [sic ] use of short term tests, there has been, within the BAT group, discussions focussing on the possibility of legislative bodies using the Ames or other short term tests to assess the "tar quality" or arriving at biological league tables. Project RIO is an example of BAT's response to a potential need for a reduced biologically active product.

...

In all cases, the biological activity of the human generated smoke condensate was compared to standard machine smoking condensate.

...

These results appear to indicate the following:

 

1)

that human smoking does influence biological activity relative to standard conditions.

2)

certain aspects of human smoking behaviour affect the biological activity of the smoke condensate more than others.

Further studies will revisit this area and investigate in more detail:

 

1)

those aspects of human smoking behaviour that appear to be most influential with regards to biological activity.

2)

whether these aspects can be modified through product design. {1226.01, pp. 85–86}

The study compared human and machine smoking of two Imperial Tobacco Ltd (Canada) brands, Matinée Extra Mild and duMaurier Light King Size. Matinée had a greater level of "specific biologic activity under human smoking conditions"; that is, Matinée smoke had a higher level of activity per microgram of smoke. In contast, deMaurier had a higher level of activity than Matinée when the data were examined on a "total" (per cigarette) basis. Human smoking profiles had greater "specific" and "total" biological activity associated with them than did the machine standard {1126.01, from overheads used in the presentation}. These data seemed to confirm the study hypothesis that human smoking behavior differs from machine-based smoking enough to be of practical importance.

All in all, Project Rio seemed to leave unresolved problems that had plagued the search for a safe cigarette from the beginning. The Ames test offered a credible short-term assay, but it measured different things from the mouse skin test that had been the standard for decades. The focus at this late stage, three decades on, was still on developing a good assay, when the technological difficulties involved in reducing toxins to safe levels while still delivering a satisfying smoke remained formidable. The whole matter was further complicated by the fact that people do not smoke like machines.


151

The bleak prospects for making meaningful progress on this front are reflected in the five themes for R&D found in the minutes of a Group R&D meeting at Wallingford, England, in September 1985 {1182.01}.

 

i.

Product/smoke quality to be as good as, and preferably better than, competitors.

ii.

Develop technology to be the lowest cost producer and others necessarily of a longer term nature.

iii.

Produce a recognised step forward on the S&H [smoking and health] issue.

iv.

Remove concern for passive smoking by various initiatives including superior products.

v.

Develop alternative products. {1182.01, p. 2}

Progress toward a safe cigarette had become the third objective, was regarded as a long-term objective, and had been diluted to the point that a reasonable goal was seen as merely offering management a "recognised step" in this direction.

Short-Term Biological Tests

In order to develop a cigarette that was less prone to cause cancer, BAT scientists needed an assay procedure to test out various possible product modifications. Mouse skin painting was BAT's standard test for carcinogens, but it required up to two years to get the results of a single experiment. This built-in delay and expense made rapid progress impossible. Accordingly, Sir Charles Ellis suggested that BAT develop a battery of short-term tests for use in-house. In January 1964, coinciding with the publication of the US Surgeon General's report, Sir Charles wrote Richard P. Dobson at BAT headquarters, recommending that BAT develop a set of short-term toxicological tests for the use of B&W {1103.02}.

Sir Charles suggested that Battelle, the contract research organization that did other work for BAT on both nicotine pharmacology (Project Hippo) and carcinogenicity of tobacco smoke (Project Janus), or some other organization be engaged to set up the ciliastasis test. He wanted to use it in assessing cigarette brands selected by B&W. In addition, he wanted to develop two other tests from among the five suggested, or to develop other sorts of short-term bioassays. The proposed testing program seems to have been mainly for the benefit of B&W. It is unclear why the work was to be done at Battelle rather than in-house, except that Battelle was shortly to do the company's mouse skin–painting work to


152

evaluate carcinogenic potency of cigarette smoke under the Janus project. Having the toxicology work done in an overseas, outside laboratory also provided B&W a buffer against discovery in legal proceedings (see also the section headed "Specific Strategies to Avoid Discovery" in chapter 7).

In his letter Sir Charles speculates that having such a battery of tests available would be of similar importance to conventional quality control:

If this project were to prove feasible it might lay the basis for a continuing health monitoring service on our cigarettes analogous to the Quality Control practised for physical characteristics. The work would be quite distinct from the researches into the relation between smoking and lung cancer which is carried out on a co-operative basis by T.R.C. [at Harrogate]. {1103.02, p. 3}

A week later, in Louisville, Tom Wade of R&D at B&W wrote an analysis of this memorandum for Ed Finch, B&W's president {1103.01}. A copy was hand-carried to Mr. Dobson of BAT when he was in New York on the following day. Wade endorses the concept of rapid tests without commenting on the technical feasibility of the specific proposals made by Sir Charles. Wade also blurs the distinction between tests to look for carcinogenic potential and tests for immediate toxicity. He concludes, "Naturally the whole purpose back of this is to get a reasonably rapid method to determine differences" {1103.01}.

The documents do not include further information on this attempt to establish short-term biological testing within BAT's research establishment. Nearly three years later, though, in October 1966, an internal progress report on a research project at the Southampton lab demonstrated that there was by then active work on the development of shortterm assays. In this case the goal was the development of a short-term test that would predict carcinogenic activity {1107.01}.

By November 1968, as a memo from Dr. R. A. Sanford, technical manager of research at B&W, to J. W. Burgard (with copies to the company president, general counsel, and the director of research and development) indicates, the contract lab operated by Battelle in Frankfurt, Germany, had achieved some success with a short-term test that measured hyperplasia in mouse skin as a predictor of malignant transformation {1111.01}. The test required only eight days to perform. It measured thickening of the skin on the backs of mice exposed to the test materials. This test had shown agreement with the mouse skin–painting test in most of the following situations:

The addition of certain PCL's, Celanese synthetic materials, or certain additives to the blend reduces biological activity rating.


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Filters containing charcoal, cellulose acetate, PEI (polyehtyleneimine), or paper do not affect tumorigenic results.

With the exception of one result, increasing puff volume progressively from 10 to 50 ml reduces activity.

U. S. cigarettes are less active [i.e., less capable of inducing cancerous changes in the mice] than English varieties. The addition of either burely or up to 50% CRS [cut, rolled stems] to flue-cured tobacco reduces activity. {1111.01, p. 1}

Dr. Sanford suggested that some experimental versions of Viceroy be submitted for testing in this system and that it be used in connection with an upcoming project called Project Hilton {1111.01}. Project Hilton was to be an inhalation study under the management of Battelle, with the goal of looking at the short-term toxicity of tobacco smoke in animals.

By the middle of December, Dr. Sanford had received clearance to send samples to Europe for the hyperplasia test {1112.04}. He sent current versions of Kool and Viceroy, the same brands with 28 percent WTS (water-treated system), and Life filters and Life filters without PEI (polyethyleneimine) but with a Viceroy tobacco rod. The mention of Life filters without PEI suggests that the normal filter for Life contained this additive, an ingredient that was known to increase the proportion of "extractable nicotine" in cigarette smoke {1205.03}. It had not, however, reduced tumorigenic activity of smoke condensate {1111.01}. By 1968, then, B&W had at its disposal a short-term bioassay that correlated reasonably well with the standard test for carcinogenesis, mouse skin painting.

Notes on the 1974 Duck Key, Florida, research conference refer tersely to a short-term bioassay test that the BAT lab in Germany had developed.

BAT (Germany) NMFI test is proving of significant value in rapid prediction of mouse skin activity. We propose not to make this test available to competitors at this time since it might be of considerable commercial advantage [emphasis in original]. {1125.01, p. 2}

This assay was the subject of a research report from the BAT affiliate in Canada three years later. A 1977 research report from Imperial Tobacco Limited (Canada) details the possible use of a test called "the nitromethane fraction index (NMFI)" as an indicator of "biological activity" {1129.01}. The NMFI test was designed to be an inexpensive and quick test that predicted carcinogenicity in mouse skin. The test involved the extraction of cigarette smoke in a way known to concentrate polycyclic aromatic hydrocarbons; this smoke fraction was then mixed with egg albumin, and the resulting degree of binding by fluorescence


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was determined. The degree of binding in turn showed a correlation with the biological activity of the smoke.

The test had been developed at the BAT lab in Germany and also was in use at Southampton. The test was found to be reproducible and to correlate well with the results of mouse skin–painting carcinogenicity tests conducted under the Janus program. Despite some reservations, the report recommends the routine inclusion of the NFMI test among the tests done "in future projects where there is a possibility of a change in the biological activity of the smoke" {1129.01, p. 4}. The report emphasizes that the NMFI test is for internal use only; it is not to be shared with other companies. In this context, the term "biological activity" is used as a euphemism for "carcinogenic activity." The development of this test is one more example of how the company knew its products caused cancer, and tried to do something about it, while publicly denying this fact.

US "Smoking And Health" Projects

Selective Filtration: The Fact Cigarette

Selective filtration, the approach first legitimized in 1962 by Lorillard's new filter for its Kent brand, is the focus of several of the documents. B&W developed the Fact brand of cigarette around a filter designed to selectively remove certain volatile compounds, such as acetaldehyde and acrolein, from cigarette smoke (16). Introduced in 1975, Fact was on the market for only a few years.

In November 1977 B&W contracted with Celanese Fibers Company to analyze the vapor phase constituents of Fact in comparison with the following competing brands: L&M Flavor Lights (Liggett), Real Menthol (RJR), Merit (Philip Morris), and Kent Golden Lights (Lorillard). The Celanese report, dated January 1978, includes analyses of fifty-four different vapor phase constituents for the five different brands {1130.01}. The results for acetaldehyde, acrolein, nitrogen oxide, and cyanide are highlighted with handwritten marks in the results table. The Fact brand had lower values than the competition for acetaldehyde and for cyanide, but it ranked second highest for nitrogen oxide. Acrolein was not measured for Fact. The documents do not indicate what use was to be made of these data. Perhaps they were simply an internal check to see whether the competition had introduced filter additives that had effects similar to those found for Fact cigarettes; perhaps they were obtained to justify possible advertising claims of selective filtration.


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In 1979 B&W commissioned a survey of physicians to learn whether they would be responsive to claims of reduced gases in cigarette smoke (see chapter 9).

The Tobacco Working Group

The Tobacco Working Group (TWG) was a federally supported project, launched by the National Cancer Institute (NCI), with the purpose of developing a less hazardous cigarette. The documents show that the tobacco companies participated in the meetings of the TWG and attempted to influence the group's work. At first, the tobacco industry attempted to convince the members of the TWG that cigarettes are not dangerous. When this strategy failed, the industry gained unexpected assistance from Dr. Gio Gori, deputy director of the National Cancer Institute's Division of Cancer Cause and Prevention and chairman of the TWG. Gori publicized the idea that less hazardous cigarettes could be created. Gori's proposal ultimately became an embarrassment for the federal government, which was focused on getting smokers to quit, but was a boon for the tobacco industry. The tobacco industry took advantage of Gori's proposal in its marketing of low-tar and extra-low-tar cigarettes.

On February 8, 1973, the Department of Health, Education and Welfare issued a charter for the TWG, which made it a formal and multidisciplinary group consisting of researchers from academia, the government, and the tobacco companies. The group had actually begun meeting informally in 1968 to discuss generally research related to smoking and health, cancer, cardiovascular disease, and respiratory disease {1400.01}. The 1973 charter specified that the purpose of the group was to "identify the criteria and prescribe methods for the development of a less hazardous cigarette, and other methods to decrease the smoking hazard" {1402.02, p. 1}.

The TWG was chaired by Dr. Gori; the other members were "selected on the basis of their personal qualifications in the field of smoking and health, cancer, cardiovascular [disease], and respiratory disease" {1402.02}. In addition to academic and government researchers, the research directors of Liggett & Myers, R. J. Reynolds, Lorillard, and Philip Morris participated in the TWG meetings {1401.02}. The documents clearly show that the main purpose of tobacco companies' participation in the TWG was not to share information but, rather, to keep the tobacco industry informed about government policy and research direction and to attempt to influence such policy.


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A B&W file memorandum dated March 15, 1973 {1400.01}, describes a meeting of a subcommittee of the Tobacco Institute's Committee of Counsel and the research directors of the tobacco companies at which they agreed that they would probably not be able to influence Gori's work on the "safe cigarette." Because of this lack of influence, the scientific directors were instructed to distance themselves from the TWG because it could reflect badly on the industry. The file memorandum states:

It was generally felt that there is no chance that the tobacco industry can influence the Government to cut back on the proposal made by Dr. Gori for the Tabacco Working Group . If the industry makes a counter-proposal, it would be but for the record only.

...

After careful consideration of the views of the members of the Tobacco Institute staff with regard to the public relations and political effects of the public withdrawal from TWG [in original document CTR is crossed out and replaced with TWG], it was concluded that the research directors cannot withdraw. We should take steps to give the industry as much protection as is possible and at the same time remain in the Tobacco Working Group [emphasis added]. {1400.01}

To give the tobacco industry as much protection as possible from any TWG statements suggesting that cigarettes are dangerous, the memorandum describes a three-point plan:

 

1.

When called by Gori, scientific directors decline to concur with or comment on Gori's recommendations. ... Dr. Gori should also be informed that the scientific director does not accept the premise that smoking is harmful .

2.

Scientific directors will informally try to persuade Gori to eliminate or modify those proposals which are propaganda-oriented, rather than scientific—e.g., cessation clinics.

3.

Subcommittee of Committee of Counsel [a Tobacco Institute committee consisting of the chief counsels of the member companies] (with representation from ranks of scientific directors) re-examine previous letters from scientific directors to TWG stating their roles [emphasis added]. {1400.01}

Other documents show that the tobacco industry carried out the plan. Throughout the documents related to the TWG, the tobacco companies repeatedly state that they were just observing and were not fully participating in the meetings. A May 31, 1973, letter from I. W. Hughes (research director at B&W) to Gori states:

At the risk of repeating myself, I see my role as making available my knowledge of cigarette design and chemistry of tobacco and smoke, and not participating in approving the many research proposals proposed by the TWG


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and outside of my area of expertise. Finally, I would reiterate my view that my participation should not be construed as agreeing with the premise that cigarettes are hazardous or contribute to the development of human disease [emphasis added]. {1400.02}

It is interesting that representatives of the tobacco industry were now making a distinction between the animal studies and human disease.

Friction between the tobacco industry's researchers and other researchers in the TWG is described in an October 10, 1974, memo from Horace Kornegay of the Tobacco Institute {1907.01}. Kornegay reports an incident in which Dr. Phillippe Shubik, a member of the National Cancer Advisory Board, criticized industry-employed members of NCI's Tobacco Working Group by saying, "you [the industry-employed members] will go down in history denying facts well-known to the scientific community" {1907.01, p. 1}.

The September 10–11, 1974, meeting of the TWG concluded with a discussion by Gio Gori on the scientific foundation of the safe cigarette program:

In the projection of the future [it] is unlikely that Heart and Lung Institute will put much support in TWG in the development of safer cigarettes. On the other hand, the TWG work should not only be limited to reduced nicotine and tar, but at the same time should examine the other phases including CO [carbon monoxide], NOx [oxides of nitrogen], etc., which may cause other health problems. ...

Dr. Gori presented a rough draft of a policy statement which will serve as a guide for the TWG program. He presented a flow chart which indicates three stages of screening for the development of a safer cigarette. The first stage is mouse skin painting; the second stage is inhalation by hamsters or rats; and the third stage is dog (beagle) and/or humans if possible. {1401.02, p. 5}

As the TWG's work on developing a less hazardous cigarette began to be reported in the lay press, the tobacco industry took a proactive role by attempting to prevent publication of comments suggesting that tobacco is dangerous. Both Dr. I. W. Hughes (research director at B&W) and Dr. A. W. Spears (research director at Lorillard) commented on press releases that Gori sent to them in late 1975 regarding research to develop a less hazardous cigarette. The statements in the press releases were made by the directors of the National Institutes of Health's National Cancer Program, the National Cancer Advisory Board, and the National Heart, Lung and Blood Institute. The tobacco industry evidently convinced Gori to cancel at least one press release. The original press releases referred to three upcoming reports from the TWG (to be released


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January 1976): (1) a report on the first set of experimental cigarettes; (2) a report on the second set of experimental cigarettes; and (3) a report on an in vitro bioassay of cigarette smoke from experimental filters. The release contained the following statements that disturbed the industry:

Evidence gathered by research efforts throughout the work indicts cigarette smoking in over 300,000 premature deaths each year in the United States alone.

... calling upon the tobacco industry to adopt newly developed techniques to make cigarettes less hazardous ... {1404.08, pp. 1–3}

Because some people are unable or unwilling to quit, the cigarette industry should strive to offer the smoking public cigarettes that minimize the risk to the smoker. {1404.09, p. 1}

Hughes evidently sought advice from Ernest Pepples, general counsel for B&W, about how he should respond to the press releases. Pepples responded to Hughes's request as follows:

It is the classic "pig-in-a-poke" [referring to the fact that the three reports are unpublished].

...

[T]he TWG members from the industry need to dissociate themselves from the releases and any underlying materials which allegedly support the releases.

...

At bottom I think you should come off saying to Gori that such activity as these releases abuses the industry members of the TWG. It is a bad way to treat them. It makes continuing cooperation difficult or impossible. {1404.10, p. 1}

Hughes's letter to Gori (unsigned) states:

I have no choice but to urge you to try and convince the people concerned not to use them [the press releases]. ... from earlier discussions with you regarding the drafts of the publications you considered it important not to draw any firm conclusion from the work done to date. ... The whole attitude of the press releases in contrary to this. ... I certainly would dissociate myself from the releases. ... Lastly, I feel that such releases abuse my membership of the TWG. {1404.03, pp. 1–2}

Horace Kornegay, president of the Tobacco Institute, also commented on Hughes's response to the press releases:

Dr. Hughes' views are sound and, hopefully, they will be persuasive with Gori to be more careful in drafting news releases which purport to report on scientific work. {1404.01}


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Spears's comment to Gori (December 18, 1975) states:

I am surprised and disappointed by the dramatic nature of the language, over-interpretation of the data and what I consider to be false statements. ...

The press materials state that newly developed techniques and scientific evidence indicate that 'without question less hazardous cigarettes can be made today.' Less hazardous with respect to what? ...

Another statement asserts that 'people are unable or unwilling to quit.' I am unaware of any information that suggests people are unable to quit smoking [emphasis in original]. {1404.07, pp. 1–2}

Spears also says, "Based upon our recent telephone conversation, I understand that it is unlikely that there will be a press release from NCI along the lines of the material which you previously forwarded" {1404.06}.

After this press release incident, Pepples urged (in a January 19, 1976, memo) Dr. Hughes to keep his distance from the TWG.

I recommend you decline the proffered appointment [to formally join the TWG] and ask to continue in your present capacity—auditing, but not voting, present but not participating. {1405.01}

In October 1976 the TWG's safe cigarette project did make the press. An October 29 article in the Louisville Courier-Journal reported on a speech made by Gio Gori at the National Academy of Sciences in which he talked about safe cigarettes and the numbers of cigarettes that could be smoked without causing cancer (i.e., safe smoking standards) {1408.02}. A letter from Pepples to H. A. Morini of BAT comments on the Courier-Journal article and expresses the tobacco industry's concern about the safe cigarette project:

It must be kept in mind, however, that Gori is a man who claims to be building a better mousetrap with Government funds. Accordingly, he must continue pointing out that the mice are a hazard. ... The issue would seem now to be whether "safer" smokes should be legislative or the free market system should be permitted to operate. {1408.01, pp. 1–2}

An attached written statement made by Gori, entitled "Etiology and Prevention of Smoking Related Disease," outlines the rationale for his safe cigarette program:

It is unrealistic to expect a society of nonsmokers in a short time period. ... Tobacco use cannot be abolished easily; therefore, alternative solutions for disease prevention are necessary. Two such solutions are the selective removal of toxic elements from smoke and the reduction of total smoke


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intake. ... The technology required to reduce hazardous components in cigarette smoke has been established, ... the tobacco industry is beginning to utilize these procedures. Consumer acceptability of low hazard cigarettes can lead to intake limits that could make the resulting risk of disease virtually undetectable. These limits are defined as the smoke intake dose that would result in approximately the same disease risk for a smoker as for a nonsmoker. {1408.05, p. 1}

Gori later sent a paper entitled "Less Hazardous Cigarettes[:] Current Manufacturing Advances, 1977," written by Gori and Cornelius Lynch of Enviro Control, Inc., to the tobacco industry for comment {1408.08}. (Enviro Control was the main contractor with NCI for the safe cigarette project {1403.01}.) The paper describes how cigarettes have been made less hazardous, compares them by brand name, and recommends brand switching to achieve "critical values" of smoking, below which smoking is safe:

These critical values may serve as intermediate goals for a smoker who is intent on reducing his smoking habit through progressively less hazardous smoking stages.

...

The incorporation of these and other state-of-the-art advances, coupled with flavor acceptability characteristics, has resulted in commercially available cigarettes that can properly be termed less hazardous. {1408.08, p. 6}

In other words, Gori was recommending that smokers switch to low-tar brands in lieu of recommending that they quit.

On August 22, 1977, in a letter to Gori, I. W. Hughes commented on this paper.

The purpose, then, of your supplying the draft to me and of my commenting on it is not to rehash our differences in the smoking and health area, but merely to see whether, given these differences, a paper of the kind you propose would serve to advance the scientific debate.

For the reasons listed below, I feel that it would not:

 

1.

As scientists, we have to be careful to avoid having the fruits of our labor used in an unwarranted manner by the public or by various pressure groups whatever their persuasion. ... I cannot help but believe that the tables in your paper, especially since they list brand names, will be misapplied to the detriment of both sides of the smoking issue.

2.

It is the nature of man to seek simplistic solutions to complex problems. ... It is inevitable that the pulp press will, unfortunately, continue to oversimplify and distort scientific data, drawing conclusions where only caution and more study is warranted. In my opinion, your paper—con-


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taining as it does, specific brand names—will be used to suggest a standard which is both misleading and dangerous.

3.

... Table I lists average yields [of low tar and nicotine brands] over a twelve-year period on a sales-weighted basis. Surely, this is being unfair to the industry. It reflects smoker predilections rather than the industry's admittedly substantial effort in this area. ...

4.

Brown & Williamson, for its part (and I believe this is true of the other companies in the industry)[,] has deliberately stayed away from enticing non-smokers to smoke while the controversy over possible health implications rages. Could not your paper, as presently written, have the unintended and unwarranted effect of encouraging non-smokers to take up the custom [emphasis in original]? {1412.01, pp. 1–2}

It is ironic that a tobacco industry employee was worried about encouraging smoking. The main thrust of Hughes's letter, however, indicates that he was worried about the tobacco companies' using Gori's data to get into marketing wars for low-tar cigarettes.

The TWG was officially terminated on August 12, 1977 {1411.01}. However, The TWG continued to meet "unofficially" {1411.03}. The tobacco companies may now have been eager to continue their participation in the TWG so that they could remain informed about the development of less hazardous cigarettes. Such information would help the companies gain a competitive edge in the low-tar cigarette market.

In mid-1978 Lisher and Company, a marketing management consultant, submitted a draft proposal for a "low delivery project" to B&W {1203.01}, in line with emerging recommendations from the NCI under Gori. This proposal illustrates that the tobacco industry viewed Gori's work as useful for marketing purposes but was concerned about calling cigarettes "safe." The editing of this draft with regard to nicotine was discussed in chapter 3. The draft's statements on smoking and health issues were also edited. The following sentence was in the original draft:

The parameters of a "safe" cigarette have been defined by Dr. Gori of the Federal Government, although his definition of "safe" is believed to be as yet largely unrecognized by the medical community at large. {1203.01, p. 1}

The edited version reads:

Within the past several years, Dr. Gogio Gori of the National Institute[s] of Health has discussed guidelines for the potential reduction of selective cigarette smoke components. {1203.02, insert card}

The word "safe" was systematically excised at three other places {1203.01, pp. 2, 3, 4}:


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The phrase "Dr. Gori's (and other Government Agencies') parameters of safety" is edited to delete the last two words.

The phrase "low tar/safe" is changed to "low tar."

The phrase "a safe and satisfying cigarette" is changed to "a Goritype, satisfying cigarette."

Gori's support for the concept of a "safe" cigarette and a "safe" level of smoking became increasingly controversial. Gori left NCI in 1980 and became director of the Franklin Institute's Health Policy Center {1415.01}. Since 1980 Gori has been a paid consultant to the tobacco industry and testifies on the industry's behalf on issues related to smoking and health (17).

Tobacco Substitutes

In the late 1960s and early 1970s, many in the cigarette industry thought that the use of tobacco substitutes in cigarette blends would substantially reduce the toxicity of cigarettes. Consequently, various possible substitutes were tested for tobacco-like qualities on the one hand and for reduced toxicity—especially for reduced activity in mouse skin-painting experiments—on the other. Products containing tobacco substitutes were briefly marketed in Germany and in the UK, but they did not become established in either market.

Tobacco substitutes posed special problems for American cigarette companies because of the legal environment in the United States. Putting nontobacco material into the blend as a tobacco substitute would likely have raised a variety of awkward questions in the United States. To the extent that the substitute material replaced tobacco in a cigarette, the product would be less a tobacco product and more a drug, an article intended to prevent disease. This substitution, in turn, would have raised the risk of FDA scrutiny and would have drawn the attention of attorneys specializing in products liability matters.

On October 22, 1973, William Shinn of Shook, Hardy & Bacon sent the general counsel of B&W, DeBaun Bryant, a copy of a June 2, 1973, editorial from Lancet , a British medical journal {1124.05}, concerning a tobacco substitute that had been developed {1124.04}. The editorial described New Smoking Material (NSM), a product developed in Britain by Imperial Tobacco Ltd. (ITL) and Imperial Chemical Industries, Ltd. (ICI), as a less toxic, wood pulp–based, tobacco substitute for cigarettes.


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ITL research, as reported in this editorial, had shown that NSM "is less irritant to animal tissues and less carcinogenic for the skin of mice." ITL and ICI were building a factory to manufacture NSM, and the editorial writer speculated that if a government committee found NSM less hazardous than tobacco, the material might one day entirely replace tobacco in cigarettes. While the editorial recognized the importance of nicotine for the appeal of smoking, it did not point out the necessity of adding nicotine to an all-NSM cigarette.

Shinn may have sent Bryant the editorial in anticipation of a meeting between Ed Finch, B&W's CEO, and Malcolm Anson, ITL's CEO, in Louisville in the first week of November. Anson also met with the general counsel for B&W and the company's director of research. Following his return to Bristol, Anson wrote Finch a letter commenting on the concerns expressed by the B&W executives about substitute smoking materials.

You and your colleagues gave me some fairly unmistakeable messages on the subject of substitute smoking materials, and on the more general political and scientific aspects of the smoking and health question. This did not entirely surprise me because I know that American manufacturers approach this matter from a different legal and philosophical background, but it was very helpful to me to be exposed to the arguments at first hand, and I now have a much more vivid picture of the considerations which are upper most in your minds when these issues are raised. This is extremely helpful and I very much hope that we shall continue this kind of dialogue at regular intervals.

I particularly noted the reservations which you expressed concerning the National Cancer Institute [NCI]. I entirely understand your desire for us to be discreet but equally as I explained we shall not wish to forego making what capital we can out of any pronouncements which NCI may produce. {1124.01, pp. 1–2}

While ITL and its competitors did not put cigarettes containing tobacco substitutes on the market until 1977 (awaiting an official blessing of the British government through its Hunter Commission), Courtaulds, a small domestic British tobacco company, jumped the gun by test-marketing a brand called Planet in November 1973. The launch was greeted with substantial criticism in the press questioning whether Planet was "safer" and asking "safer than what?" {1124.03}. The criticism illuminated the potential difficulties that would confront the industry in trying to introduce a "safer" cigarette. The industry's interest is documented in a packet of press clippings {1124.03} that G. C. Hargrove of BAT's Millbank office sent to the CEOs of BAT subsidiaries around the world on November 8, two days after the introduction of Planet {1124.02}.


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The BAT R&D conference at Duck Key, Florida, two months later (January 1974) shed additional light on the thinking within the company about tobacco substitutes. The first conclusions of the conference involved the substitutes.

 

1.

The decision that B-A.T. would not use non-tobacco materials without a demonstrable advantage on health grounds has proved particularly effective in influencing Amcel [the maker of a tobacco substitute] developments—and since I.T.L. at that time concurred, probably in influencing the development of N.S.M. The interpretation by R. & D. of "demonstrable advantage" was a reduction in specific activity for smoke or condensate by most or all relevant biological tests available. It is now recognised that the development of the non-tobacco materials and their possible "acceptance" by medical authorities may change the position. Also the non-tobacco materials may become commercially very attractive on supply and price grounds.

 

It is therefore now proposed that, although reduction in specific activity across the board would be most attractive and reduction in specific activity on key tests desirable, in the absence of significant behavioural differences, reduction in activity per cigarette (in all relevant tests) should now be accepted as sufficient for alternative smoking materials, both tobacco and non-tobacco.

2.

New smoking materials now under development include N.S.M., Cytrel, N.C.F. (Batflake and B. & W. version), Ecusta, Sutton Research, Reemtsma (BASF), Gallahers, Rothmans, Brinkmann and Courtaulds. No information is available on Reynolds and Philip Morris in this field. The front runners are N.S.M., Cytrel, Courtaulds, with Batflake having advantages for taste and cost. Since Courtaulds material is being tested biologically, they appear to have failed so far to make a good cigarette and yet could be on big scale production before any others; B-A.T. should talk to Courtaulds if this can be arranged ...

3.

American Celanese have informed us that the proposed short tests by the Hunter Committee are sebaceous gland, hyperplasia, rat trachea, lung cell activity, macrophage, ciliastasis, mytochondria, mutagenicity, teratology and Goblet cell. Long term tests are mouse skin, rat inhalation, and possibly dog inhalation. It will be interesting (possibly alarming) if this list proves correct when Hunter outlines his proposals to the U.K. industry for the first time on February 8th.

 

Estimated cost to cover [test and bring to market?] four Cytel 324 and 361 variants is over $1 million p.a. [per annum] for 5 years. {1125.01, pp. 1–2}

In early 1974, then, tobacco substitutes played a substantial role in BAT's R&D effort, and there was at least some sharing of information among a variety of companies outside of the United States. Reduced toxicity, as measured in a variety of short- and long-term tests, was the goal. While the UK government–sponsored Hunter Committee might insist on a large battery of tests, at the least, BAT agreed with the principle that


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the value of a tobacco substitute was primarily its lower toxicity in such tests in comparison to tobacco itself.

A glimpse at BAT's internal R&D effort for its own version of a tobacco substitute, Batflake, is contained in the summary of a Southampton research report {1127.01}. The document, dated July 2, 1975, relates preliminary results of inhalation toxicology testing of cigarettes containing various proportions of Batflake Mark II compared to British-style cigarettes containing 100 percent flue-cured tobacco.

The study reported here involved preliminary range finding work to fix exposure conditions, a dosimetry experiment, measurements of respiratory function of animals and an extensive pathological examination, particularly of the respiratory system. {1127.01, p. 1}

The report indicates that the exposure system actually delivered cigarette smoke to "all parts of the respiratory system" of the rats and was similar for all the experimental cigarettes. Nasal filtration, often considered an obstacle in rodent experiments, "did not occur to a very significant extent" {1127.01, p. 1}. Carbon monoxide levels were similar in all groups. Smoke exposure led to reduced body weight and to an increase in the weight of heart, lung, and trachea. Lung and trachea weight increase was inversely related to the proportion of Batflake in the cigarette; Batflake also provided some protection against increases in heart weight.

Most rats survived to termination and the inhaled smoke caused:

 

1.

Squamous metaplasia in the larynx.

2.

Hyperplasia and keratinisation in the larynx.

3.

Goblet cell hyperplasia in the bronchi.

4.

Goblet cell hyperplasia in the nasal cavity.

5.

Increased macrophage activity in the lung. {1127.01, p. 2}

The presence of Batflake in the cigarette reduced the degree of effects 2, 3, and 5 in proportion to the amount of Batflake added. However, squamous metaplasia of the larynx was seen in every rat exposed to smoke, regardless of the proportion of Batflake in the cigarettes. So, by mid-1975 BAT had evidence from its own laboratory that cigarettes made with Batflake as part of the blend were less toxic than conventional cigarettes.

The Hunter Committee, chaired by Professor (later Lord) Robert Hunter, advised the Secretary of State in the United Kingdom on tobacco issues. In particular, its focus was on tobacco product testing and on research on less hazardous smoking. In 1975 the committee gave tobacco substitutes a lukewarm, preliminary endorsement:


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The product may be no more dangerous to health than a similar product containing tobacco only and could prove to be less injurious. (18, pp. 95–96)

In July 1977 Imperial, Gallahers, and Rothmans (other competing British tobacco companies) launched a dozen versions of cigarettes made with tobacco substitutes, either NSM or Cytrel. Health groups and the Minister for Health criticized these products as unsafe because they still delivered substantial doses of toxins. Their sales were minuscule—in part because the public health community criticized them as unproven half measures—and they were withdrawn within a few months (18).

So, in the end, the concerns at B&W about the risks posed by tobacco substitutes were much ado about nothing. However, the episode illustrates the company's fear that steps taken publicly to make cigarettes safer would expose the harmfulness of the basic product and therefore constituted a great risk. The tobacco substitute story also illustrates the fact that the essential ingredient in tobacco products is not tobacco: It is nicotine.

Abandoning The Search

By the late 1970s the tobacco industry had all but abandoned its search for a "safe" cigarette. The industry's scientists had found it much more difficult than at first anticipated to identify and remove the toxic elements from cigarettes. Perhaps more important, however, tobacco industry lawyers were becoming increasingly concerned about government regulation and litigation.

Sea Island Research Conference, 1980

BAT's 1980 research conference was held in Sea Island, Georgia. The documents contain a list of proposed topics for the meeting, along with the comments of Dr. R. A. Sanford, then vice president of research and development at B&W {1132.01}. Sanford rated the various topics on a scale of 1 to 3 (1 = top priority; 2 = definite interest; 3 = little or no interest). He gave the lowest priority to topics such as short-term biological assays and studies of smoke irritation, topics that had dominated discussion at earlier conferences.

Dr. Sanford actually discouraged additional toxicological testing, as his comment on short-term bioassays indicates:


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We need evaluation of externally developed methods for critique. We don't want GR&DC [that is, BAT itself] to develop methods [emphasis added]. {1132.01, table}

He has this to say about irritation and inhalation of smoke:

Dangerous area. Please do not publish or circulate. No more work needed on biological side [emphasis added]. {1132.01, table}

The initial enthusiasm for toxicology work to refine and perfect the product had been abandoned. In contrast, the areas ranked as top priority included the topics nicotine, basic combustion research, sidestream research, flavor research, and ventilated cigarette technology.

Sanford's choice of priorities suggests that by the early 1980s the tobacco industry had dramatically changed its focus: instead of trying to understand and eliminate the carcinogens and other toxins in tobacco smoke, it was now trying to avoid developing any potentially damaging knowledge of its products. Short-term bioassays remained of interest, but only if they were developed extramurally, possibly because of concern about the potential for discovery through litigation. By 1980 the R&D staff at B&W had seemingly come to regard continued research on the inhalation toxicology of tobacco smoke as potentially hazardous to the company.

Responding To The Market, 1985

The deemphasis of reduced toxicity as a primary factor shaping cigarette design at B&W is illustrated in an April 1985 letter from E. E. Kohnhorst, manager of the B&W Development Center {1136.01}. He wrote J. A. B. Kellagher of BAT (Millbank) in response to correspondence that Kellagher had sent to B&W about carbon monoxide reduction technology. The letter praises work that Kellagher had shared with B&W about a project that correlated "the more difficult sensory attributes to the smoke deliveries," a project that would be relevant "for cigarette designs in parts of the world where carbon monoxide (CO) delivery in cigarettes is under pressure of statutory regulation." Carbon monoxide is a colorless, odorless poison gas that binds to blood and reduces its ability to deliver oxygen to the body; the carbon monoxide in tobacco smoke is one element that damages the cardiovascular system.

Kohnhorst notes that there was no such pressure to lower CO deliveries of cigarettes in the United States, even though by the late 1970s the


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Federal Trade Commission's "tar" tables included a listing for CO. As Kohnhorst points out, "the CO delivery of Marlboro KS [king size] in 1979 was 15.5 mg/cig. and today it runs on an average 15.2 mg/cig." Consequently, Kohnhorst explains,

Within B&W, we have rarely attempted to develop new products specifically designed to deliver low CO, except perhaps a prototype of FACT that was kept ready on a turn-key basis in the event of a marketing need for such product. This was done through a combination of filter ventilation, cigarette paper permeability, and appropriate cigarette paper additive. Needless to say, such need did not arise. {1136.01, p. 1}

Although the addition of shredded dried stems (SDS) to B&W's tobacco blends in the fourth quarter of 1985 would incidentally lower CO yield by 10 percent with a 12 percent level of stem addition, the reduction in CO yield was not the company's primary purpose in using the additive:

Its benefit is process simplification, increased yield, reduced manufacturing cost, improved cigarette physical properties, and results in reduced CO generation.

...

Beyond these plans, the emphasis at B&W is on product amelioration. The major part of our resources is devoted to understanding what contributes to the harshness of cigarette smoke. Improvement of our products to achieve superiority over competitive products is a more pressing need. Therefore, I do not see involving ourselves in designing products with the limited objective of reducing CO in the near future unless marketing needs dictate otherwise [emphasis added]. {1136.01, p. 2}

Kohnhorst is blunt in telling Kellagher that B&W has more pressing things to worry about in product design than reducing a toxic constituent—beating the competition on mildness. This attitude markedly differed from that taken by BAT scientists in the 1960s, when they were trying so hard to reduce the "biological activity" of cigarettes.

Conclusion

In 1957 the BAT research department used code words like "Zephyr" for lung cancer and for the carcinogens thought responsible for lung cancer. At the 1962 Southampton research conference, there had been an enormous display of optimism and hope about the possible development of a safe cigarette. Sir Charles Ellis declared that, if cigarettes actually cause cancer, industry scientists would find a way to fix the problem.


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Throughout the 1960s reports of industry-sponsored R&D activities brimmed with energy and enthusiasm for getting on with solving the problem. The problem proved intractable, however. Certainly, it is a technically difficult problem to solve. In addition, any genuine solution contained an inescapable admission of harm from conventional products. By 1973 B&W was unwilling to participate even a little bit in work on tobacco substitutes. By 1980 an R&D scientist at B&W regarded work on tobacco smoke inhalation as "dangerous." In 1985 a B&W executive declared that the only product innovations of interest were those that gave a competitive advantage. If, by chance, they also reduced toxicity, that was a bonus, but it was not a reason to make the change.

While the internal R&D work shifted over the years from a gallant acceptance of the challenge to a cynical acceptance of an inevitably harmful product, the external posture of the company remained defiant. Publicly, the smoking and health question remained an open one, a controversy. Privately, the controversy was not whether Viceroy, Kool, Raleigh, and Belair are dangerous. The controversy was over what to do about the danger. For many years the companies tried, privately and quietly, to make things better. As it became evident that a safe cigarette was not achievable, the industry turned to creating a false controversy about the scientific evidence that smoking is dangerous.

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