Annals of Oncology 11: 909-914. 2000.
Editorial
The regulation of tobacco and tobacco smoke
Apparently the first epidemiological associations between
tobacco smoking and lung cancer came in the first half
of the (last) century from the UK [1], Austria [2], the US
[3] and Germany [4, 5]. Following the publication of five
epidemiological studies in the early 1950s [6-10] this
association was progressively accepted by the medicalscientific community [11]. In 1962 the Royal College of
Physicians in Great Britain produced their first landmark report [12].
It is reasonable to conclude that we have known with
some certainty that cigarette smoking caused lung
cancer for between 40 and 50 years at least [13], have
understood the reality that it causes the large majority
of lung cancer for 30-40 years, and that it has been one
of the world's most consequential, avoidable causes of
death for at least 20-30 years. Further we now know
that smoking causes a number of other types of cancer
[14, 15], and is a major avoidable factor involved in
causation of heart disease and many other fatal and
non-fatal conditions [16-18]. Unsurprisingly, given the
strength and complexity of the mixture, the adverse
effects of second-hand smoke have been progressively
demonstrated over the past 15 years [19].
Watershed
Recent years have been a time of tumult for the tobacco
industry, leading, in the US at least, to expensive settlements of state based lawsuits and vulnerability to class
actions. Further, denials have turned to acceptance that
cigarettes cause lung cancer, certain other diseases and
that nicotine is addictive [20].
Although the industry lacks credibility, it still has
profits, power, and is far from penitent. However, the
forthcoming European Directive (of 2000) contains the
beginnings of regulation of tar, nicotine, additives and
further advertising restrictions and other countries are
looking at these issues. Serious disclosure by law is under
way in Massachusetts and British Columbia, which can
be seen as a precursor to regulation.
So examination of the ways in which tobacco smoke
should be regulated is timely.
The size of the problem
The actual size of the global tobacco problem is increasing at a startling rate. There are several reasons
for this. One is the development of new markets and new
generations of smokers, not by accident but by design
for which the industry is responsible. The second is the
predictable effect of long duration smoking in such
countries as China and central and eastern Europe
where the smoking of past decades is still to wreak its
full havoc. The third is the maturation of the tobacco
epidemic among women.
The most important determinant of lung cancer risk
is the duration of smoking: long-term smokers have a
20-30-fold increased risk compared to non-smokers
[21]. Risk varies also with other aspects of daily exposure including number of cigarettes smoked, depth of
inhalation and smoke composition (tar components
and nicotine). Lung cancer is the major tobacco related
site and is the leading cause of cancer death in men
in almost all developed countries. Annual incidence
rates are between 80-100 per 100,000 in the highest
incidence rate groups such as Afro-Americans [22] and
rates exceeding 200 per 100,000 have been recorded
among middle aged (35-64) men in cities of central and
eastern Europe [23]. Lung cancer being frequently and
rapidly fatal, mortality rates are high and, consequently,
the social costs are high. Smoking among women in
some developed countries has had the same effect as
in men, with lung cancer now exceeding breast cancer
as the most common cause of cancer death in the US,
Canada, Denmark, Scotland and in many other countries the gap between the two is decreasing rapidly.
Indeed, in Glasgow in Scotland, the incidence of lung
cancer in women now exceeds the incidence of breast
cancer [24].
Cigarette smoking kills half of all those who adopt
and persist with this addictive habit with half of these
deaths occurring in middle age and each losing over
20 years of non smokers life expectancy [17]. Tobacco
smoking kills effectively in twenty-four different ways [17].
It can be estimated that, whereas it will cause 3,000,000
deaths per annum in the last half of this decade, by 2025
it will cause 10,000,000 deaths annually [18].
This global epidemic can only be ameliorated, and
only to a limited degree, by controlling the tobacco
industry's commitment to market expansion and by
regulating the cigarette itself. Policies to reduce sales
and consumption of cigarettes have been established
for decades [25]. They include abolition of tobacco
advertising both direct and indirect, increased taxation,
education programs, smoking cessation programs and
limits on tar and nicotine yields.
Public Health policy has not hitherto included detailed
control of tobacco or the additives which go into modern
cigarettes. This is remarkable. It now seems only a
matter of time before these items are regulated.
910
seen in smokers was demonstrated by Russell in 1980
and many others [37-43].
In the absence of systematic on-going analysis of
Regulation of the content and yield of cigarettes will be
complex. The complexity arises only partly from the what has been going into smokers lungs, we are left
mixture of compounds in cigarette smoke. Difficulties with biological outcomes as an index of what has been
arise from the need to consider and regulate nicotine in happening. There are three potentially important obserthe context of addiction en masse, and as a second issue, vations in this regard.
First of all, it is very difficult to imagine that the large
the need to reduce the disease causing potential of the
fall in the tar content of cigarettes sold in the UK over
mixture.
Regulation may reasonably be expected to render the the last fifty years [44] has not directly influenced the
cigarette less disastrous, it cannot be expected that lung cancer death rate which has been falling for two
modifying the products of combustion of tobacco can decades in men in that country.
ever produce an even moderately safe cigarette.
Secondly, and somewhat paradoxically, mortality from
Historically the tobacco industry in the US has lung cancer in men increased between the first (CPS-I)
largely escaped regulation, although pressure has been and second (CPS-II) Cancer Prevention Studies of the
applied to what is a global industry via voluntary agree- American Cancer Society [45, 46]: these studies recruited
ments in the UK and Canada requiring reduced yields men from birth cohorts approximately 30 years apart.
of tar, nicotine and carbon monoxide. The European At first glance, the decrease in mortality promised by
Community (EC) currently mandates an upper limit for the yield reductions of the 1950s and 1960s has not been
tar of 12 mg [26]. In the US, however, the industry has substantiated over the 1970s and 1980s. However, this
been free to make its own decisions, and the results are may be too simple an interpretation.
Information of the number of cigarettes smoked at
apparent both in the marketplace and in the mortality
rates among smokers. Although sales weighted tar is time of enrolment to both studies may not mirror the
below 12 mg [27] the range of tar is up to 27 mg [28, 29]. lifelong patterns of smoking that cause lung cancer [47]:
However, the means of achieving reduced yields of data on smoking in early life, which critically determines
tar, nicotine and carbon monoxide to the Federal duration of smoking, are sparse in both studies. CigaTrade Commission (FTC) machine have not necessarily rette consumption during adolescence and early adultdelivered lower yields of carcinogens to the smokers. The hood was probably heavier among smokers in CPS-II
FTC machine produces measures of tar and nicotine for several reasons. Manufactured cigarettes were more
abstracted from a cigarette using a machine taking fixed readily available in the 1940s and 1950s than in the 1930s
'puffs' and fixed intervals of time. Since there are funda- and 1940s, eras when smoking was likely to be initiated
mental differences between smokers in the frequency in the CPS-II and CPS-I cohort, respectively.
and strength of puffs, this technology can only provide an
Birth cohort analyses show that the prevalence of
index. Furthermore, the addition of ventilated filters can smoking among white men increased with each succesfurther lead to reducing observed tar and nicotine levels. sive birth cohort born from 1900-1929 and decreased
While the FTC method is quantitatively misleading, thereafter [48]. Age-specific lung cancer death rates have
there have been qualitative changes too. Hoffmann and decreased in those born after 1930 [49, 50].
Hoffmann [28] have shown that the smoke of a leading
The increases in lung cancer death rates from CPS-I
US non filter brand shows a decrease in benzo(a)pyrene to CPS-II probably reflect unmeasured heavier smoking
(BaP) by 60% between the mid sixties and late seventies, among CPS-II during the 1940s and 1950s as well as the
while the tobacco specific carcinogen 4-(methylnitrosa- measured increase in daily consumption and duration
mino)-l-(3-pyridyl)-l-butanone (NNK) has increased of smoking. In addition, CPS-II may include a more
addicted 'hard-core' smokers, who find it virtually
by 50% between the late seventies and the nineties.
One must pause to ask whether, if cigarettes were impossible to quit smoking, and CPS-II smokers, partly
regulated like pharmaceuticals or foodstuffs, any regu- to compensate for lower nicotine content of modern
lator would have condoned such an increase in a known cigarettes, may inhale more deeply, take more puffs
per cigarette and retain smoke larger in the lungs than
carcinogen.
The early concept that simply reducing tar and nico- did smokers in the past. The impact of lower tar and
tine would reduce cancer risk was well founded on nicotine cigarettes is difficult to elucidate with all these
epidemiological studies, which showed a reduction in other changes in effect.
lung cancer risk, but not cardiovascular disease, of
Thirdly, and what is clear, is that there has been a real
between twenty and fifty percent in association with the swing towards higher rates of adenocarcinoma of the
move to filter cigarettes which occurred over the fifties lung both in the US and elsewhere [51-60] which is
and sixties [30-36]. It was therefore logical that public consistent with the hypothesis that qualitative changes
health authorities should press for further reductions. in cigarette smoke have led to a change in the observed
However the reductions which appeared in the yields as pattern of lung cancer but not to a substantial decrease
measured by the FTC system do not reflect, in a quanti- in mortality.
Clearly cigarettes are different but still seriously
tative way, what passes into the lungs of smokers. That
more intensive ('compensatory') smoking patterns are harmful after decades of self-regulation.
The regulation of tobacco smoke
911
The carcinogenic component
itself. Such a proposal does not have to, and should not,
provide carte blanche immunity for past actions but
must enable publication and discussion of existing and
future research. In this era of new-openness, the time may
be ripe for the establishment of the tobacco-equivalent
of the 'Justice and Truth' Commission employed in
South Africa.
It is possible to conceive a system for regulation of
carcinogens and other toxins in cigarette smoke which
could follow the precedents set by the regulation of
the automobile industry. The Environmental Protection
Authorities around the world did not allow the automobile industry to set standards. Dialogue occurred and
standards were set, initially as targets and ultimately as
standards. The result has been a progressive reduction Nicotine regulation
in air pollution achieved with the active assistance of
the automobile industry's research facilities, and can be To consider regulating nicotine means considering
seen as a public health triumph. Regulation has been addiction. Benowitz and Henningfield [63] have proposed
common-sense. Lead could only be reduced by removing a gradual diminution in the weight of nicotine permitted
it from petrol. Other emissions depended on engine in the actual cigarette. The idea has the merit of simplicity
design and the manufacturers were set targets and and practicability and is analogous to limiting the lead
standards which they could, and have, met.
in petrol. If watched over by a competent regulatory
With regard to the many components which make up agency, it would constitute a practical ongoing experitar, we should look to the EPA model with targets to be ment which (duly monitored) should in due course
followed by standards. Analysis of the top twenty brands reveal whether a non addictive, or less addictive, cigafor the major toxins /carcinogens would show the upper rette can be manufactured, whether it is saleable, and
and lower limits of the present market. As a starting how customers react to it, not merely in terms of sales,
point it would show what is practical now. Setting target but in patterns of use. This is not prohibition by stealth,
levels in the middle ranges would be a beginning and it is a reasonable approach to making the cigarette less
research over time would show which targets could be addictive.
met, and converted to industry standards, and which
The alternative approach, which might be to allow
could not [61]. This may mean telling the manufacturers nicotine content to be unregulated so that the smoker is
of specific brands that they must, over time, bring levels nicotine satisfied, rather than encouraged to suck harder
of, say, polyaromatic hydrocarbons or nitrosamines, and thereby inhale more carcinogens, is not a long-term
down to those of other brands on the market, or vice solution to the problem of tobacco addiction.
versa. It may also require sharing of manufacturing
There are three important points.
secrets.
The first point is simple. The index of nicotine delivery
This approach is compatible with that described as by the cigarette ought not to be the amount yielded to a
the 'Selective Reduction of specific toxic constituents' machine running under one set of fixed conditions.
pursued by RJ Reynolds in the development of their Ideally, it ought to be a better reflection of what goes
recent 'heated tobacco' cigarette (Eclipse/Premier) [62]. into the arterial blood of the smoker and will surely
This product delivers lower levels of some 37 'biolog- involve a series of tests conducted under a range of
ically active' compounds thought by the industry to be smoking conditions. Failing this a simpler and more
worthy of testing. Review of the material presented in practical index could be the actual weight per cigarette
favour of 'Eclipse' establishes that the industry has the [63]. In addition it is necessary to reduce nicotine bioskills and knowledge to work in this way, although only availability so control of pH needs to be considered.
a few outside the industry would have the detailed Since some additives both facilitate nicotine bioavailknowledge possessed by it.
ability and themselves lead, when burnt, to carcinogen
Such regulation is practical and in accord with estab- formation [64], they need to be either abolished or
lished drug control and air quality control precedents. subject to the same safety testing (in burnt and unburnt
Drugs with carcinogenic activity are already regulated. form) as nicotine replacement products are.
In this case the whole process must be seen for what it is,
The second point is difficult. How to deal with coma huge human experiment. The authorities must have the pensatory smoking? This phenomenon has been known
right to allow what seems to be best practice on the basis since the early work of Russell in the seventies. The
of existing knowledge. They must also be immune from tobacco industry has discovered a way to deal with this
litigation over their efforts. Ongoing monitoring by ani- - delude the smoker into thinking the amount printed
mal tests, laboratory tests and some cohort studies will on the packet means something (light?) and make the
be needed. The changes required will probably be more nicotine more bioavailable by a variety of clever engioften based on what comes out of the cigarette than neering techniques [64]. The knowledge that reducing
what goes into it. The manufacturers will have to use nicotine to low levels drives deeper inhalation is the
their substantial research skills under regulatory scrutiny justification for the experimental approach proposed.
instead of in secret. This latter point may require some
The solution to the controversy surrounding the effects
legal protection which will allow the industry to tell what of addiction and compensation has to be an ongoing
it knows, at least for the future, without incriminating epidemiological analysis of smoker behaviour in relation
912
to nicotine content, as the nicotine content of cigarettes
is progressively reduced en masse. Only in such a way
can we develop a clear long term approach to the
reduction of tobacco addiction. The fact that this is a
population based, experimental approach should not be
surprising. No ethical alternative is possible as the
present cigarette is too dangerous to be allowed to
remain on the market unchanged. Nearly all the important data we already have come from analysis of a
massive (uncontrolled) human experiment, conducted,
initially unwittingly, by an industry. Mass weaning of
populations will not occur, on present experience, with
the present cigarette. It may be, and probably is, possible.
It will not happen while the tobacco industry is responsible for deciding what will be delivered by the cigarette.
Neither will it happen unless there is a co-ordinated
legislative program, preferably global, aimed at the progressive reduction of the addictive (and carcinogenic)
properties of cigarettes.
The third point arises here. There is a strong case for
regulating all forms of Nicotine, both nicotine coming
from tobacco smoking ('dirty') and that from nonsmoking sources ('clean'). The pharmaceutical industry is
experienced in collaborative regulation, but the tobacco
industry is not. However, the drug needs to be considered
at a societal level. So regulation of nicotine in cigarettes
needs to be considered together with the existing regulation of alternative nicotine delivery systems, and by
the same agency. While cigarette regulation needs to
progressively tighten, the regulation of 'clean' nicotine
could usefully be substantially loosened. The time is
right to consider whether more efficiently absorbed forms
of clean nicotine are needed and should be allowed to
compete freely with tobacco derived nicotine.
The issues canvassed here are topical. There is now
an opportunity to assert regulation over cigarettes in
Europe, and indirectly to influence what happens elsewhere. While the concept of the Global Cigarette [65] in
terms of maximum allowable limits of 12 mgms tar and
1 mgm nicotine has immediate validity for the developing countries where historical yields have been extremely
high, a more sophisticated system is needed for developed, and eventually all, countries and this needs to
become global as it evolves. With the global industry
under pressure and the power to regulate incipient,
Public Health Authorities and Governments which let
slip the present opportunity to inhibit the epidemic will
be judged harshly by history.
What can the oncological community do today?
Oncologists see daily the unforeseen consequences of
cigarette smoking in their clinical practice. They are in a
strong position to have an influential role in Tobacco
Control although, surprisingly, they have never as a
group exerted this potential.
It is important that oncologists set an example: it
defies logic that oncologists continue to smoke knowing
what they know, and see, about the long-term adverse
effects of cigarettes. Oncological meetings should be
completely non-smoking, smoking cessation advice and
education should be available at these meetings and
through learned societies, and oncologists should be
trained in the methods of smoking cessation. However,
smoking cessation is difficult and special efforts should
be aimed at this professional group to increase the
number of smokers who want to stop smoking and increase the probability that a quit attempt will be successful.
Oncologists have the potential to be a large and
important group of activists. Currently there is a new
Tobacco Directive being discussed in the European
Parliament which proposes, among others, to further
reduce tar ceilings and to introduce ceilings on nicotine
and carbon monoxide; to obtain disclosure of the type
and nature of tobacco additives to cigarettes; and to
eliminate the use of adjectives such as 'low', 'mild', and
'ultra mild' which could be construed by the general
public as implying a safer product. This Directive deserves the active support of European oncologists who
should leave their elected representatives in no doubt
about the importance and value of such legislation to
public health.
Acknowledgements
This work was conducted within the framework of support from the Associazione Italiana per la Ricerca sul
Cancro (Italian Association for Cancer Research).
N. Gray l 2 & P.Boyle1
'Division of Epidemiology and Biostatistics
European Institute of Oncology
Milan, Italy
2
Past President, UICC
Geneva, Switzerland
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