American Journal of Epidemiology
© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of
Public Health. All rights reserved. For permissions, please e-mail: [email protected].
Vol. 183, No. 5
DOI: 10.1093/aje/kwv156
Advance Access publication:
February 10, 2016
Commentary
Epidemiology and the Tobacco Epidemic: How Research on Tobacco and Health
Shaped Epidemiology
Jonathan M. Samet*
* Correspondence to Dr. Jonathan M. Samet, Department of Preventive Medicine, Keck School of Medicine of USC, USC Institute for Global Health,
University of Southern California, Soto Street Building, 2001 N. Soto Street, Suite 330A, MC 9239, Los Angeles, CA 90089-9239
(e-mail: [email protected]).
Initially submitted May 14, 2015; accepted for publication June 10, 2015.
In this article, I provide a perspective on the tobacco epidemic and epidemiology, describing the impact of the
tobacco-caused disease epidemic on the field of epidemiology. Although there is an enormous body of epidemiologic evidence on the associations of smoking with health, little systematic attention has been given to how decades
of research have affected epidemiology and its practice. I address the many advances that resulted from epidemiologic research on smoking and health, such as demonstration of the utility of observational designs and important
parameters (the odds ratio and the population attributable risk), guidelines for causal inference, and systematic
review approaches. I also cover unintended and adverse consequences for the field, including the strategy of
doubt creation and the recruitment of epidemiologists by the tobacco industry to serve its mission. The paradigm
of evidence-based action for addressing noncommunicable diseases began with the need to address the epidemic
of tobacco-caused disease, an imperative for action documented by epidemiologic research.
causal inference; epidemiologic methods; smoking; tobacco control
Abbreviation: SHS, secondhand smoke.
The enormity of the disease epidemic caused by smoking, as
documented by epidemiologic research, was a powerful motivating force for action.
The epidemiologic evidence on the effect of smoking on
health is vast and well summarized in authoritative reports
and historical accounts. In the 50th anniversary report of
the US Surgeon General, which was published in 2014 (2),
investigators recounted the story of tobacco control in the
United States; monographs of the International Agency for
Research on Cancer and other resources provide the global
picture (3). The remarkable story of this tragic epidemic
and the tobacco industry’s role in causing it have been well
chronicled in such in-depth books as Ashes to Ashes (4), The
Cigarette Century (1), and The Golden Holocaust (5). These
resources describe the findings from myriad epidemiologic
studies that were completed as early as the 1920s and 1930s,
that span the full range of study designs, and that were conducted by investigators and institutions around the world.
They describe the efforts to control tobacco use that followed
Inevitably, an anniversary is a moment to look back and
take stock. In this instance, it is the 100th anniversary of Johns
Hopkins Bloomberg School of Public Health, which opened
in 1916. This time period nicely corresponds to the rise and
fall of the cigarette epidemic (Figure 1). Harvard historian
Allen Brandt referred to the 20th century as “The Cigarette
Century,” reflecting the once dominant place of cigarette smoking in mainstream American life (1). Cigarette smoking shaped
the disease patterns of the 20th century (Figure 2), driving
rises in the rates of lung cancer, other cancers, and chronic
obstructive pulmonary disease and contributing to the increase in cardiovascular disease as infectious disease mortality progressively decreased. The declines in rates of death from
lung cancer and cardiovascular disease, particularly in men,
followed the drop in smoking rates that began in the 1960s.
The findings in epidemiologic studies, some of which were
conducted by Johns Hopkins investigators, were key in characterizing the role of tobacco smoking in driving the rising
rates of noncommunicable diseases across the 20th century.
394
Am J Epidemiol. 2016;183(5):394–402
Epidemiology and the Tobacco Epidemic 395
5,000
1964 Surgeon General’s report
on smoking and health
Per capita number of cigarettes smoked per year
Broadcast ad ban
4,000
Synar Amendment
enacted
U.S. entry
into WWII
Nonsmokers’
rights
movement
begins
3,000
Master Settlement
Agreement
Federal cigarette
tax doubles
Confluence of
evidence linking
smoking and cancer
2,000
Nicotine medications
available
over-the-counter
Fairness Doctrine
messages on
broadcast media
Cigarette
price drop
U.S. entry
into WWI
1,000
Family Smoking
Prevention and
Tobacco Control Act
1986 Surgeon
General’s report on
secondhand smoke
FDA
proposed rule
2006 Surgeon General’s report
on secondhand smoke (an update)
Great Depression
begins
Federal $0.62 tax
increase
20
2010
12
00
20
90
19
80
19
70
19
60
19
50
19
40
19
30
19
20
19
00
19
19
00
0
Year
Figure 1. Per capita cigarette consumption and major smoking and health events in adults (≥18 years of age as reported annually by the US
Bureau of the Census), United States, 1900–2012. FDA, US Food and Drug Administration; WWI, World War I; WWII, World War II. Reprinted
from the Department of Health and Human Services (3), with permission from the Government Publishing Office.
confirmation of smoking as a powerful cause of disease and
premature death and also the actions taken by the tobacco industry to weaken tobacco control and sustain profits.
In the present article, I provide a different perspective on
the tobacco epidemic, describing the impact of the tobaccocaused disease epidemic on the field of epidemiology and
adding to prior discussions by Colin White (6), Alfredo
Morabia (7), and others. The initial conclusion that smoking
causes lung cancer and subsequent conclusions related to
smoking as the cause of other diseases are widely viewed
as some of the first successes of epidemiology in addressing
the etiology of noncommunicable diseases; the causal connections represented a “proof of principle” for the field,
showing that observational epidemiologic evidence could
support causal inference. The research on tobacco sparked
methodological advances. Early criteria for causal inference
that were based on observational evidence were elaborated
and applied in the 1950s and 1960s as evidence of the link
between smoking and disease mounted sufficiently to require
synthesis and interpretation (8). In the 1964 report of the US
Surgeon General (9), the authors described systematic review
methodology long before the subsequent elaboration of such
approaches. Other methodological and conceptual advances
were derived from epidemiologic research on smoking; for
example, the description of the odds ratio, the concept of attributable risk, the concept of the empirical induction period,
Am J Epidemiol. 2016;183(5):394–402
and methodology for exploring synergism between smoking
and other causes of disease.
Epidemiologic research also motivated a series of actions
by the tobacco industry that have had both positive and negative impacts on the field. The powerful findings of epidemiologic research about the effects of smoking led to systematic
efforts to counter them; strategies for creating doubt about
scientific evidence can be directly traced to the tobacco industry, beginning in the 1950s and possibly earlier. Initially
directed at active smoking, the industry’s doubt-creation
efforts became even more aggressive as exposure of nonsmokers to secondhand smoke (SHS) was linked to adverse effects.
Public health researchers were sometimes lured into working
as consultants to the industry and participating in industrydesigned strategies to undermine epidemiologic evidence.
The industry also created entities to fund researchers, strategically supporting studies that would deflect attention from
smoking as the cause of disease. However, the tension created
by the tobacco industry’s actions assured that epidemiologists carefully explored bias in studies and possible alternative
causes for associations of disease with active and passive
smoking.
In this paper, I trace the story of epidemiology and tobacco,
following the historical timeline of Figure 1. In recognition of
the 100th anniversary of the Johns Hopkins Bloomberg
School of Public Health, major contributions of the School
396 Samet
300
No. of Deaths per 100,000 People
250
200
150
100
50
10
19
15
19
20
19
25
19
30
19
35
19
40
19
45
19
50
19
55
19
60
19
65
19
70
19
75
19
80
19
85
19
90
19
95
20
00
20
05
05
19
19
19
00
0
Year
Figure 2. Selected age-adjusted mortality rates in the United States, 1900–2005. Rates are shown for infectious diseases (green), cardiovascular
diseases (red), all cancers ( purple), lung and bronchus cancer (blue), stomach cancer (orange), and chronic obstructive pulmonary disease (black),
with squares representing rates for men and circles representing rates for women. Data on infectious diseases and cardiovascular diseases are from
Cutler et al. (48). Data on stomach, lung, and bronchus cancers are from the American Cancer Society (49). Data on all cancers are from the World
Health Organization (50).
and its departments of epidemiology and biostatistics are acknowledged in this account.
A START: STUDYING SMOKING AND LUNG CANCER
Epidemiologic approaches have been applied to research
throughout the tobacco epidemic, beginning with detection
of the occurrence of the epidemic through tracking the impact
of tobacco control on the disease burden attributable to smoking. As early as the 1930s, there were several studies in which
lung cancer was addressed (10), and careful efforts were taken
to assess whether the rising rates of lung cancer were artefactual and possibly reflected trends of detection and labeling
(11). With that alternative to a true epidemic set aside, epidemiologic research was initiated to study risk factors for lung
cancer; tobacco smoking was the principal agent considered,
although in 1950, Doll and Hill (12) gave equal credence to
air pollution, which was a serious problem at the time.
The initial etiological studies on lung cancer were of the
case-control design, although this design had been little
used in the first half of the 20th century, (7, 9). This design
was feasible and could be implemented through hospital- and
clinic-based ascertainment of cases. The lifetime profile of
use of tobacco products could be readily captured using a
questionnaire; for example, cigarette use could be assessed
by inquiring about smoking status (never, current, or former),
age at initiation of smoking, amount smoked daily (which
varies across a relatively narrow range centered at approximately 20, the number in a pack), and age at cessation for former smokers. In fact, Wynder and Graham (13) provided their
full questionnaire, which contained 15 items, in their 1950
paper in the Journal of the American Medical Association.
Generally at the time of these studies, once the pattern of cigarette smoking was established in adolescence and young
adulthood, it tended to be quite stable. Information bias from
misreporting of smoking behaviors was not of great concern at
the time because smoking was part of the social norm. However, a reading of these early studies from today’s methodological perspective can readily identify potential sources of bias.
Serious concerns about the case-control method were voiced
by prominent methodologists, including Joseph Berkson and
R. A. Fisher, who were later known to be tobacco industry consultants; consequently, cohort studies were implemented soon
after the initial reports from the case-control studies (14).
These studies were started with remarkable rapidity; Doll
and Hill implemented the cohort study of British physicians
in 1951 and reported the first results in 1954 (15). Hammond
and Horn followed with a study of 188,000 men in 9 states that
began in 1952 (16). Together, the case-control and cohort
studiesprovidedconsistentevidencethatcigarettesmokingwas
very strongly associated with the risk of lung cancer in men.
As the evidence accumulated, a causal association seemed increasingly likely given the strength of the association, the use
of multiple study designs, and the replicability of results across
Am J Epidemiol. 2016;183(5):394–402
Epidemiology and the Tobacco Epidemic 397
studies conducted in different countries and carried out by
multiple investigators. The consistent evidence from these
studies of lung cancer reflected the strength of cigarette smoking as a cause, the paucity of other equally strong causal
factors, and the relative simplicity of obtaining high-quality
exposure information. For these same reasons, epidemiologic
research proved equally useful for identifying many other
diseases caused by active smoking.
IDENTIFYING CAUSES
As the evidence linking smoking with lung cancer mounted
during the 1950s, the question as to whether the association
was causal was of increasing societal importance and a source
of rising controversy. Unlike infectious diseases, for which
microbes are necessary causal agents (e.g., tuberculosis is specifically caused by Mycobacterium tuberculosis), chronic
diseases,suchaslungcancer,cardiovasculardiseases,andchronic respiratory diseases, generally have multiple sufficient sets of
causes with no single cause more likely. As results were reported in the 1950s and 1960s, frameworks for establishing
causation for chronic diseases were not in place, unlike for infectious diseases for which the Henle-Koch postulates were
long established (17).
Consequently, during the 1950s, there was a vigorous scientific discussion about the handling of scientific evidence
for causal inference, as more and more studies linked smoking
to lung cancer and other diseases (18–21). The evidence of the
association between smoking and lung cancer was evaluated
systematically and results were published in several reports
and publications during the 1950s, beginning early in the
decade (22). A notable review by Cornfield et al. (23) was
published in 1959 in The Journal of the National Cancer Institute that represented a starting point in the systematic evaluation of evidence of the effects of smoking on health. In this
comprehensive assessment, investigators found the available
evidence to be highly consistent with a causal association and
inconsistent with various noncausal explanations that had
been proposed.
This starting point was followed in 5 years by the landmark
1964 report of the US Surgeon General on smoking and
health, in which researchers reached the conclusion that
smoking caused lung cancer (in men) (9). The report’s methods chapter offered a pragmatic definition of cause, along
with guidelines or criteria for evaluating evidence for causal
inference (Table 1). Similar guidelines were proposed at approximately the same time by Sir Austin Bradford Hill in the
United Kingdom (8). Of these guidelines, only temporality
(i.e., cause must precede effect) is mandatory; however, the
others are critical in bolstering the case for causation and are
fundamental to the weight-of-evidence approach used to
evaluate the totality of the evidence available. The methodology was updated and terminology for strength of evidence was
standardized in the 2004 report of the Surgeon General (24).
The approach to causal inference has credibility based on a halfcentury of use, extending beyond the Surgeon Generals’ reports
to many other domains in which causal determinations are
requisite for decision-making. The “Surgeon General’s guidelines” are still widely taught in introductory epidemiology
courses.
Am J Epidemiol. 2016;183(5):394–402
Table 1. Criteria for Causation From the 1964 US Surgeon
General’s Report and Sir Bradford Hill
US Surgeon General’s Report
Criteria, 1964 (9)
Sir Bradford Hill’s
Criteria, 1965 (8)
Consistency of association
Strength
Strength of association
Consistency
Specificity of association
Specificity
Temporal relationship of association
Temporality
Coherence of association
Biological gradient
Coherence
Experiment
Analogy
SYSTEMATIC REVIEWS AND META-ANALYSIS
Systematic review is now a starting point in evidencebased public health practice and medicine; its use in summarizing evidence in medicine and public health is usually
dated to the 1970s (25), although arguably the 1959 paper
on smoking and lung cancer by Cornfield et al. and the 1964
report of the Surgeon General constituted systematic reviews.
These reports substantially antedated the 1972 publication of
Cochrane’s book Effectiveness and Efficiency (26), which is
considered a starting point for evidence-based medicine. Before 1950, a few studies were published on the effects of smoking on health, but after the 5 case-control studies on smoking
and lung cancer were published in 1950, the numbers of publications grew quickly and expanded to cover additional types
of cancers and other noncommunicable diseases. Implicitly
acknowledging the need to consider jointly the findings of
all studies, the authors of early reviews attempted to identify
the complete body of epidemiologic evidence. In their influential paper, Cornfield et al. (23) covered 21 “retrospective”
(i.e., case-control) studies and described the full scope of the
evidence from “prospective” (i.e., cohort) studies.
Five years later, the landmark 1964 Report of the US Surgeon reviewed all extant epidemiologic studies, comprising
29 case-control studies and 7 cohort studies. Using clearly articulated and hence transparent methods, an attempt was
made to identify the full set of studies. Additionally, the
methodology for the report specified that the Advisory Committee preparing the report would provide: 1) “Judgment as to
the validity of a publication or report”; 2) “Judgments as to the
validity of the interpretations placed by investigators . . .”;
and 3) “Judgments necessary for the formulation of conclusions within the Committee” (9, p. 19). The report covered
what might now be termed “quality assessment” and “risk
of bias assessment.”
Key features of the approach used to develop the Surgeon
General’s report are listed below.
• The report was prepared by a multidisciplinary advisory
committee made up of people considered bias-free with regard to the review’s potential outcome.
• The evidence then available was systematically assembled
and reviewed for potential methodological concerns and
the implications of such concerns for study interpretation.
398 Samet
• Multiple lines of evidence were considered, including the
nature and components of cigarette smoke, findings from
toxicological research, findings from epidemiologic research, and data showing coherence with the hypothesis
that smoking causes lung cancer, such as parallel trends
in smoking and lung cancer rates in the population.
• The causal guidelines were applied (Table 1).
• Extensive narrative analysis of the evidence and its interpretation was provided using the guidelines to lay out in
a transparent fashion the basis for the causal determination.
The 1964 report reflects many elements of the methods of
current systematic review: Evidence tables were prepared
that captured critical features and findings of the studies,
and the potential for bias to have resulted in the observed association of smoking with disease was explored. Consideration was also given to how to summarize the results of the
7 prospective cohort studies. The alternatives considered were
summing the overall observed and expected deaths to estimate the overall mortality ratio and using the median mortality ratio as the summary to eliminate the instability for
categories of cause-of-death with small numbers.
Beginning in 1981, reports from cohort and case-control
studies linked exposure to secondhand smoke (SHS) to lung
cancer in nonsmokers. Unlike the strong association of active
smoking with lung cancer, this association was much weaker
and the evidence was far more mixed than for active smoking
and lung cancer, which motivated researchers to conduct one
of the first meta-analyses of observational data. In the face of
continuing questioning of the evidence by the tobacco industry, a systematic review approach was taken to deflect
criticisms of selective gathering of the evidence, and metaanalysis was used because of the seemingly mixed evidence,
some of which came from small studies. In an early (1986)
application of meta-analysis to data on the association of
smoking with health, the National Research Council’s Committee on Passive Smoking pooled data from 13 studies and
estimated that nonsmokers who were married to smokers had
a relative risk of lung cancer of 1.32 (95% confidence interval: 1.18, 1.53) (27). Subsequently, investigators from the
Environmental Protection Agency completed a meta-analysis
of 31 studies in their assessment of the carcinogenicity of
SHS; their use of a meta-analysis prompted the publication
of multiple reports from tobacco industry consultants in
which they questioned the use of a meta-analysis for this purpose (5, 28, 29). The 2006 report of the Surgeon General,
which addressed SHS exposure, incldued meta-analyses for
a number of health outcomes (30).
METHODOLOGICAL ADVANCES
Epidemiologic research on the associations between smoking and disease was the “leading edge” for the emerging field
of “chronic disease epidemiology” in the 1950s. Methodological advances motivated by data on smoking and health
were numerous. The initial studies on lung cancer refined
case-control methodology; the study by Doll and Hill (11) has
been acknowledged for its methodological rigor and attention
to information bias. Several years after the Framingham Heart
Study was launched, major cohort studies were initiated to
study the associations between smoking and lung cancer.
The British Doctors’ Study, which was launched in 1951 and
maintained by Doll for 50 years, became a model for cohort
studies of populations that could be readily ascertained and
successfully followed. Its example was followed in the wellknown Nurses’ Health Study, which was implemented by
Harvard’s Frank Speizer, who trained with Doll. The American Cancer Society’s study of men in 9 states was the precursor of Cancer Prevention Studies I and II (16).
Two key contributions were made by Jerome Cornfield
and Morton Levin, who were researchers on the faculty of
the Johns Hopkins School of Hygiene and Public Health during their careers. Cornfield’s 1951 paper (31) in the Journal
of the National Cancer Institute, in which he described the use
of the odds ratio for estimating association in the 2-by-2 table,
was motivated by the new case-control studies on smoking
and lung cancer. He noted that a “ frequent problem in epidemiological research is the attempt to determine whether the
probability of having or incurring a stated disease, such as
cancer of the lung, during a specified interval of time is related to the possession of a certain characteristic, such as
smoking” (31, p. 1269). Recognizing that the relative frequencies of exposure in cases and controls did not estimate
the strength of association, Cornfield derived the odds ratio
using the example of smoking and lung cancer.
Two years later, Morton Levin (a graduate and a faculty
member of the Johns Hopkins School of Hygiene and Public
Health) published the paper “The Occurrence of Lung Cancer in Man” (32), in which he described the measure generally
referred to today as the population attributable risk or the etiological fraction. Concluding that smoking was likely a major
cause of lung cancer, he proposed an index for estimating
“. . . the maximum proportion of lung cancer attributable
to smoking” based on the assumption that the smokers, had
they not started smoking, would have experienced the same
incidence of lung cancer as nonsmokers (32, p. 536). This
approach remains in use today, underlying the Centers for
Disease Control and Prevention’s Smoking-Attributable
Mortality, Morbidity, and Economic Costs model (3) and
the Estimation of the Global Burden of Disease, Injuries,
and Risk Factors Study (http://www.healthdata.org/gbd).
Numerous other methodological advances were motivated
by research on the effect of smoking on health. Tobacco and
alcohol are both powerful causes of upper airway cancers,
raising the question as to whether these 2 causal agents act
synergistically. As early as 1957, Wynder et al. (33) explored
the joint effects of these 2 risk factors for oral cancer using a
multiplicative model. In a 1972 paper, Rothman and Keller
(34) also used the example of alcohol, tobacco, and oral cancer but gave emphasis to considering the joint effect of the
exposures on the additive scale. They linked models of interaction to attributable risk and began a consideration of effect
(measure) modification and public health. The strong associations of smoking with many diseases and the availability of
large cohort studies facilitated modeling of dose-response relationships and of the time course of change in disease risk
after smoking cessation. Rothman (35) used smoking as a
key example in an effort to bring clarity to the concept of induction and latent periods. Pioneering analyses were carried
out, for example, of determinants of the rate of change in lung
Am J Epidemiol. 2016;183(5):394–402
Epidemiology and the Tobacco Epidemic 399
function (36) and of the quantitative risks of lung cancer in
relation to amount smoked and the duration of smoking (37).
CREATING DOUBT
For the tobacco industry in the 1950s, the powerful findings of epidemiologic research needed to be countered. A now
well-chronicled 1953 meeting at the Plaza Hotel in New York
brought together the chief executive officers of the major tobacco companies, including Philip Morris, in response to the
emerging evidence on the risks of smoking (5, 38). By then,
the epidemiologic studies were providing convincing and coherent evidence linking smoking to lung cancer (12, 13, 39–
41). The mouse-skin painting research by Wynder et al. (42),
in which they applied cigarette tar condensates to the shaved
skin of mice, showed the development of skin papillomas and
histologically proven carcinomas in the painted mice. At the
1953 Plaza Hotel meeting, a strategy was orchestrated by
John Hill of the advertising firm Hill & Knowlton, which
had been hired by the industry to devise its defensive communications tactics. The strategy included the creation of
controversy and doubt, the founding of the Tobacco Industry
Research Committee (which later became the Council for Tobacco Research), and the initiation of illegal collusion among
the tobacco companies (38). The strategy also resulted in the
release of a public announcement, now referred to as “The
Frank Statement,” which proclaimed the industry’s interest
in people’s health and denied health consequences of smoking while stating, “We always have and always will cooperate
closely with those whose task it is to safeguard the public
health” (43, p. 1).
From that point onward, the industry’s efforts to subvert
tobacco control became even more intense. Much of the initial attack focused on epidemiology and the results of epidemiologic studies. Industry spokespersons and consultants
spoke to the weaknesses of observational studies, which
were cast as only able to generate hypotheses that required
testing in animal models and confirmation of mechanisms before causality could be inferred. The biases that can affect epidemiologic evidence were presented as insurmountable, and
research was funded by the industry with the purpose of deflecting attention away from smoking as a cause of disease.
The tobacco industry was particularly concerned by the evidence on the association between SHS and lung cancer,
which had the potential to motivate smoking bans because
of the harm inflicted involuntarily on nonsmokers. Numerous
attacks on the evidence were made that were based around the
rudiments of epidemiologic methodology. The attackers proposed mechanisms by which selection bias, differential information bias, and uncontrolled confounding could introduce
an association of SHS with lung cancer risk in never smokers.
One recurring argument, which occasionally still surfaces in
other contexts, posited the existence of unknown confounding
factors that were yet to be identified but resulted in associations
judged to be causal. Such strategies based around potential
known limitations of epidemiologic information were widely disseminated through publications in the peer-reviewed literature and in scientific meetings, some organized by the
tobacco industry and its surrogates; these strategies were also
used in regulatory settings and in the courtroom (44).
Am J Epidemiol. 2016;183(5):394–402
The history of the industry’s efforts to create doubt is now
well documented, particularly because of the access gained to
the industry’s internal documents through the Minnesota tobacco litigation. Other sectors have learned from the tobacco
industry’s playbook and similarly strategized to undermine
epidemiologic evidence, particularly around environmental
pollutants. The strategy has spread more broadly and is actively in play at present with regard to climate change. Notably, some scientists who worked with the tobacco industry on
the issue of SHS later became involved in attacking climate
research as surrogates for the energy industry.
RECRUITMENT OF RESEARCHERS
In its campaign to create doubt, the tobacco industry recruited researchers, including epidemiologists and biostatisticians, to undermine the scientific evidence on the association
of smoking with health. Some were directly recruited as spokespersons for the industry’s messaging, and others were indirectly recruited through the research support offered by the
industry’s Council for Tobacco Research and Center for Indoor
Air Research. These funding agencies solicited proposals that
met their research agendas, framed to deflect attention away
from the adverse effects of active and passive smoking, respectively. They also supported special projects intended to create
doubt about particular topics and slow policy measures. Now,
because of the availability of the tobacco industry’s documents,
the names of persons who are working with the industry can be
readily identified, as can the names of those funded by the industry through its Council for Tobacco Research and Center for
Indoor Air Research. The Legacy Tobacco Documents Library
houses these documents (http://legacy.library.ucsf.edu/). A
quick search readily shows a lengthy and disappointing list
of public health researchers who worked with the tobacco industry, sometimes without disclosing their connection. For
example, Joseph Berkson, R. A. Fisher, Alvin Feinstein, and
Nathan Mantel, all of whom were important contributors to
public health research, were paid consultants to the industry.
Robert Proctor lists 29 statisticians who have been experts for
the industry in legal proceedings (5). Unfortunately, the tobacco industry ensnared researchers at many institutions, including Johns Hopkins.
THE CONTRIBUTIONS OF THE JOHNS HOPKINS
BLOOMBERG SCHOOL OF PUBLIC HEALTH
Faculty members of the Johns Hopkins Bloomberg School
of Public Health have written countless papers related to the
association between smoking and health and to tobacco control (Table 2). Interestingly, the early studies on smoking and
lung cancer were not carried out by investigators at schools of
public health but rather primarily by researchers in government and research institutes. Table 2 lists some of the landmark contributions from Johns Hopkins faculty. One key
early contribution did come from a school of public health:
the report by the biostatistician Raymond Pearl, chair of the
Department of Biostatistics, that was published in Science in
1938 (45). Pearl was carrying out a follow-up study of families
in East Baltimore and made a comparison of the survival curves
for what he termed “nonsmokers,” “moderate smokers,” and
400 Samet
Table 2. Selected Notable Contributions From Johns Hopkins
Faculty to the Literature on Smoking and Health
First Author, Year
(Reference No.)
Description
Pearl, 1938 (45)
Pearl reported diminished lifespan in
smokers compared with nonsmokers
based on longitudinal data from East
Baltimore.
Levin, 1950 (39)
Levin detailed findings of a case-control
study on smoking and lung cancer
carried out at Roswell Park. Findings of
this study and of the study by Wynder
and Graham (13) were published in the
same issue of the Journal of the
American Medical Association.
Cornfield, 1959 (51)
This paper included a thorough
assessment of the evidence of an
association between smoking and lung
cancer, anticipating the approach of the
1964 Surgeon General’s report.
Tokuhata, 1963 (54)
This was the first major paper in which
familial aggregation of lung cancer and
the possibility of genetic susceptibility
to tobacco smoke were explored.
Meyer, 1972 (53)
In this commentary, the authors provided
a careful analysis of the complicated
interpretation of the data on smoking
and perinatal mortality.
Howard, 1994 (52)
This study, based in the multicenter
Atherosclerosis Risk in Communities
Study, was one of the first in which an
effect of passive smoking on carotid
atherosclerosis was shown.
Wipfli, 2008 (55)
In this paper, the authors documented
exposure of women and children to
secondhand smoke in countries around
the world, providing evidence of this
widespread exposure.
“heavy smokers.” The findings are striking, showing a substantial difference in life expectancies when comparing the heavy
smokers with the nonsmokers. Inspection of the survival
curves indicates an approximate 10-year reduction in life expectancy for the heavy smokers, equivalent to that observed
at present. Notably, even in the 1930s, the tobacco industry
took steps to discredit the evidence and limit its impact (46).
George Seldes, an investigative journalist, wrote that the tobacco industry used its substantial influence over mainstream
media to suppress the publication of Pearl’s finding that cigarette smoking shortens the lifespan (47).
Other studies covered diverse topics (Table 2) related to
methods, cancer, cardiovascular disease, and lung disease.
Studies of passive smoking were carried out by various investigators beginning in the 1990s. Faculty members of the
Bloomberg School of Public Health contributed to the reports
of the Surgeon General as authors and editors.
LESSONS LEARNED
The long story of epidemiology and tobacco is not yet over.
Epidemiologic research is still needed to track the epidemic
globally and to quickly begin to assess the real-world consequences of the rapid rise in use of electronic nicotine delivery
systems, also referred to as electronic cigarettes. Tobacco
smoking has also afforded an unfortunate but useful opportunity to use molecular approaches to explore mechanisms of
disease causation, to identify biomarkers of susceptibility
and early disease, and to identify genes associated with nicotine addiction and disease risk.
Much has been learned and accomplished from decades of
epidemiologic research on smoking and health. The paradigm of evidence-driven public health intervention has been
established; epidemiologic findings have been key across the
rise and fall of the epidemic (Figure 1). Methodological advances were motivated by particular challenges of the research on smoking and health, and epidemiologists defended
their methods against attacks by the tobacco industry. Many
epidemiologists have engaged in the translation of their findings into action, participating in such activities as the development of the Surgeon Generals’ reports, litigation, and policy
formulation. They were motivated by their powerful findings
and the compelling case made for intervention.
The strategy of doubt creation was an unfortunate outcome
of the initial success of epidemiologic research in linking
smoking to lung cancer. The industry’s documents show its
origins and application within the United States and beyond.
The spread of this strategy to other environmental issues is
well documented. Epidemiologists need to be aware of this
strategy and its potential implications for translation of their
research; they also need to give consideration as to whether
they will become participants in efforts to discredit epidemiologic and other research.
In the case of tobacco and health, any distraction from the
case that smoking is an extraordinary public health threat
is dwarfed by the overwhelming evidence for causation and
the enormity of the resulting disease burden. Consequent to
decades of epidemiologic research on smoking, we have confidence in using epidemiology to address the noncommunicable disease epidemics and have models for moving from
well-formed research questions through rigorously designed,
conducted, and analyzed studies to collective actions that reduce disease and improve the public’s health.
ACKNOWLEDGMENTS
Author affiliation: Department of Preventive Medicine,
Keck School of Medicine, University of Southern California,
Los Angeles, California (Jonathan M. Samet); and USC Institute for Global Health, University of Southern California,
Los Angeles, California (Jonathan M. Samet).
I thank Drs. Stephen Cole and Alfredo Morabia for their
comments.
Conflict of interest: none declared.
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