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

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.

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}:

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

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.