American Journal of Epidemiology Advance Access originally published online on September 15, 2008
American Journal of Epidemiology 2008 168(7):816-818; doi:10.1093/aje/kwn145
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Commentary: Dr. George W. Comstock—A Primary Care Practitioner of Public Health
From the Prevention and Research Center, Mercy Medical Center, Baltimore, MD
Correspondence to Dr. Kathy J. Helzlsouer, Prevention and Research Center, Mercy Medical Center, 227 St. Paul Place, Baltimore, MD 21202 (e-mail: KHelzlsouer{at}mdmercy.com).
Dr. George W. Comstock, a specialist in the treatment and prevention of tuberculosis, was also a cardiovascular disease epidemiologist, a cancer epidemiologist, and a molecular epidemiologist. In short, he was the equivalent of a primary care practitioner—"a generalist" in the field of public health and the science of epidemiology but expert in all. He was "ahead of the curve" in many ways, doing "translational research" before it was called "translational research," just as he did molecular and social epidemiology before those terms were coined or came into vogue. He has left a legacy in almost every aspect of public health. A well-done literature search on almost any topic will produce at least one reference authored by Dr. Comstock. The range of topics is astounding, from church attendance and impact on mortality (1) to genetic polymorphisms and cancer risk (2).
Dr. Comstock thought "out of the box" but kept ideas "in the box." He was the "go to" person for students in need of a topic. I was one of those students searching for a thesis topic. He would pull out his "idea box" containing 3- x 5-inch index cards, and a plethora of research topics would be at your fingertips; all were topics that would make a difference in public health. He had a topic for me that was feasible and novel, and it launched my longtime association with Dr. Comstock and the CLUE cohort studies. It was one of the best choices for my career, not for the impact of that particular study but for the valuable lessons I learned for "out of the box" thinking and my subsequent transition from student to colleague.
His breadth of activities made choosing which of his papers to republish in this special edition a daunting task. When preparing to speak at his memorial service, I was asked to list two or three articles of his in the area of cancer epidemiology to be on a total list of articles that would be highlighted. I found that to be impossible and prepared a list of 14 articles, placing them under categories such as "shows insight to do critical methodological investigations—not glamorous or fundable but necessary for research" or "shows foresight to store buffy coats for genetic investigations." For this special issue of the American Journal of Epidemiology, it was even more challenging as space is limiting and choices are many. Two of the articles I initially considered were already chosen to represent his seminal work pertinent to cardiovascular disease epidemiology but with applications to cancer. This not only shows the commonality across many topical areas of epidemiology but also emphasizes the impact that Dr. Comstock's career and work have had across many fields of study. The final list was chosen for several reasons: to represent a complete body of work; to republish older works and reviews that should not be lost because they are not easily accessible in this day of online literature searches; and to highlight his wonderful writing style. All are relevant to science today.
As a wonderful teacher and mentor, he passed on valuable lessons. One of his most valuable lessons was the value of "recycling" data—never throw anything out—especially data. New applications could always be found, as demonstrated by the study of subcutaneous fat and association with mortality. Information obtained from screening chest radiographs was used to examine the association between obesity and cause of death (3, 4). Similarly, he used community mental health surveys to examine the association between depression and cancer (5). Dr. Comstock, also a firm believer in replication, conducted several investigations of the association between bacille Calmette-Guérin (BCG) and subsequent cancer in different populations (6–8). In addition, he perhaps holds the record for conducting some of the longest follow-up studies ever recorded. One of these in the cancer field is the association between tonsillar and adenoid radiation and subsequent cancer (9, 10), a study made possible because of guarding the data and realizing how it could answer a variety of research questions.
Dr. Comstock was one of the first to look at the association between religion and health (1), an association now being pursued in the broader field of spirituality and health. In the historical article "Church Attendance and Health" that follows in this issue, data from the 1963 private census conducted in Washington County, Maryland (11), were used to examine the association between church attendance and cause of death. Infrequent church attenders had a twofold risk of arteriosclerotic heart disease deaths among both men and women. Death rates from emphysema, cirrhosis, and suicide were also higher among infrequent attenders than those attending once a week or more (1). The Discussion is a wonderful example of his straightforward and enjoyable writing.
More exciting hypotheses can be generated from the inverse association of church attendance with arteriosclerotic disease. Does this association merely reflect the ‘good guy’ or ‘Leo Durocher’ syndrome (‘Nice guys finish last’)? Is it related to the sense of identification with a supportive group? Are churchgoers likely to have Type B personalities ...? Or is the effect mediated through peace of mind and release of tensions?
In a succinct, entertaining, and enlightened way, he outlined an entire research plan to explore the mind-body effects of these associations. He calls for further exploration and replication of the study but points out, as we often lose sight of, that even if the mechanism of the association observed is not discovered, it may be useful in identifying groups at risk. Researchers are still following through on his research program.
Dr. Comstock also was a proponent of doing the "not glamorous but necessary" research. This is exemplified by the historical article republished in this issue that first appeared in the journal Clinical Chemistry (12), "Effects of Repeated Freeze-Thaw Cycles on Concentrations of Cholesterol, Micronutrients, and Hormones in Human Plasma and Serum." Having established a specimen repository with the CLUE cohort, he sought to answer the practical questions of what happens to specimens with long-term storage or with repeated freeze-thaw cycles, necessitated by repeat preparations of aliquots for multiple studies (13–16). He lamented that these types of investigations were not the type to garner grant support but believed that they were fundamental to all the research that was being conducted. These studies, along with investigations of variations of temperatures within freezers (17) and methodological investigations of questionnaire reproducibility and response rates (18, 19), provide critical knowledge for long-term cohort specimen repositories.
Dr. Comstock established the CLUE cohort studies to study clues to cancer and heart disease. Never the traditionalist, he didn't just freeze serum or plasma but prepared a special aliquot of serum to preserve ascorbic acid that, without the addition of metaphosphoric acid, deteriorates with storage. The historical article on the study of micronutrients and lung cancer (20) republished in this issue demonstrates the contributions of the cohorts to the study of diet and cancer, as well as the value of making the extra effort in how specimens are stored. Additionally, his "out of the box" thinking comes through with investigating assays designed to get a global picture of association between antioxidants and cancer—the total peroxyl radical absorbing capacity. This study represents an enormous body of work looking at micronutrients and subsequent risk of cancer and heart disease.
George was frugal and practical. He emphasized clinical significance over statistical significance. He had the "30" rule. If a pilot study of 30 cases and controls did not show any evidence of an association, then larger studies, he maintained, were unlikely to find anything clinically relevant. His source for this was from the approach used in the smallpox eradication program (21). This approach couldn't be any farther from the approach today where the only science is "big science" and where the p value rules, not the estimate of risk, mostly evident in the current approaches in genetic epidemiology using whole genome scanning. We did many pilot studies with the CLUE cohorts. I don't believe there has been a case where the pilot studies missed a clinically relevant association when other studies were done. An example of both the pilot approach and the novel use of repositories is the historical article on prostate-specific antigen and prostate cancer (22) republished in this issue. The CLUE cohorts were designed primarily to examine biologic markers of risk of cancer and heart disease, but this did not stop Dr. Comstock from seeing the potential of using the cohorts to study cancer-screening markers (22, 23). The sensitivity and specificity of prostate-specific antigen for the detection of prostate cancer determined by the pilot study were later replicated in other prospective studies (24). The cohorts with repositories are a rich resource to answer many clinically relevant issues and overall remain underutilized.
The field of cancer epidemiology was extremely lucky to have had Dr. Comstock join the ranks of researchers, and Dr. Comstock as he always said was "lucky all his life" to have had such a rich career. He was an epidemiologist—a generalist—who was expert in many fields. We as educators, researchers, and practitioners should especially take note of the tremendous contribution Dr. Comstock has made across many fields. The pressures today from promotions committees to grant funding are many to subspecialize in research. A generalist is a problem for promotions committees: He/she is viewed as a "dabbler," diffuse and unfocused. Crossing from research in one disease area to another presents a problem for reviewers: Where is the "track record"? Who is now "stealing" our funds? Where is the expert? But just imagine what the fields of infectious disease, cardiovascular, cancer, genetic, and behavioral epidemiology (to name just a few) would have missed without the contribution of Dr. Comstock—the true primary care practitioner of public health.
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ACKNOWLEDGMENTS |
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Conflict of interest: none declared.
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References |
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 TOP References |
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- Comstock GW, Partridge KB. Church attendance and health. J Chronic Dis (1972) 25:665–72.[CrossRef][Web of Science][Medline]
- Huang HY, Thuita L, Strickland P, et al. Frequencies of single nucleotide polymorphisms in genes regulating inflammatory responses in a community-based population. BMC Genet (2007) 8:7.[CrossRef][Medline]
- Comstock GW, Livesay VT. Subcutaneous fat determinations from a community-wide chest X-ray survey in Muscogee County, Georgia. Ann N Y Acad Sci (1963) 110:475–91.[CrossRef][Web of Science][Medline]
- Comstock GW, Kendrick MA, Livesay VT. Subcutaneous fatness and mortality. Am J Epidemiol (1966) 83:548–63.
[Free Full Text] - Linkins RW, Comstock GW. Depressed mood and development of cancer. Am J Epidemiol (1990) 132:962–72.
[Abstract/Free Full Text] - Comstock GW. Leukaemia and B.C.G. A controlled trial. Lancet (1971) 2:1062–3.[Web of Science][Medline]
- Comstock GW, Martinez I, Livesav VT. Efficacy of BCG vaccination in prevention of cancer. J Natl Cancer Inst (1975) 54:835–9.[Web of Science][Medline]
- Kendrick MA, Comstock GW. BCG vaccination and the subsequent development of cancer in humans. J Natl Cancer Inst (1981) 66:431–7.[Web of Science][Medline]
- Sandler DP, Comstock GW, Matanoski GM. Neoplasms following childhood radium irradiation of the nasopharynx. J Natl Cancer Inst (1982) 68:3–8.[Web of Science][Medline]
- Yeh H, Matanoski GM, Wang Ny, et al. Cancer incidence after childhood nasopharyngeal radium irradiation: a follow-up study in Washington County, Maryland. Am J Epidemiol (2001) 153:749–56.
[Abstract/Free Full Text] - Comstock GW, Bush TL, Helzlsouer KJ, et al. The Washington County Training Center: an exemplar of public health research in the field. Am J Epidemiol (1991) 134:1023–9.
[Free Full Text] - Comstock GW, Burke AE, Norkus EP, et al. Effects of repeated freeze-thaw cycles on concentrations of cholesterol, micronutrients, and hormones in human plasma and serum. Clin Chem (2001) 47:139–42.
[Free Full Text] - Hsing AW, Comstock GW, Polk BF. Effect of repeated freezing and thawing on vitamins and hormones in serum. Clin Chem (1989) 35:2145.
[Free Full Text] - Comstock GW, Alberg AJ, Helzlsouer KJ. Reported effects of long-term freezer storage on concentrations of retinol, β-carotene, and
-tocopherol in serum or plasma summarized. Clin Chem (1993) 39:1075–8.[Abstract/Free Full Text] - Comstock GW, Burke AE, Hoffman SC, et al. The repeatability of serum carotenoid, retinoid, and tocopherol concentrations in specimens of blood collected 15 years apart. Cancer Epidemiol Biomarkers Prev (2001) 10:65–8.
[Abstract/Free Full Text] - Comstock GW, Norkus EP, Hoffman SC, et al. Stability of ascorbic acid, carotenoids, retinol, and tocopherols in plasma stored at –70 degrees C for 4 years. Cancer Epidemiol Biomarkers Prev (1995) 4:505–7.[Abstract]
- Helsing KJ, Hoffman SC, Comstock GW. Temperature variations in chest-type mechanical freezers. Clin Chem (2000) 46:1861.
[Free Full Text] - Helsing KJ, Comstock GW. Response variation and location of questions within a questionnaire. Int J Epidemiol (1976) 5:125–30.
[Abstract/Free Full Text] - Hoffman SC, Burke AE, Helzlsouer KJ, et al. Controlled trial of the effect of length, incentives, and follow-up techniques on response to a mailed questionnaire. Am J Epidemiol (1998) 148:1007–11.
[Abstract/Free Full Text] - Comstock GW, Alberg AJ, Huang HY, et al. The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acid, carotenoids, -tocopherol, selenium, and total peroxyl radical absorbing capacity. Cancer Epidemiol Biomarkers Prev (1997) 6:907–16.[Abstract]
- Henderson RH, Sundaresan T. Cluster sampling to assess immunization coverage: a review of experience with a simplified sampling method. Bull World Health Organ (1982) 60:253–60.[Web of Science][Medline]
- Helzlsouer KJ, Newby J, Comstock GW. Prostate-specific antigen levels and subsequent prostate cancer: potential for screening. Cancer Epidemiol Biomarkers Prev (1992) 1:537–40.
[Abstract/Free Full Text] - Helzlsouer KJ, Bush TL, Alberg AJ, et al. Prospective study of serum CA-125 levels as markers of ovarian cancer. JAMA (1993) 269:1123–6.
[Abstract/Free Full Text] - Gann PH, Hennekens CH, Stampfer MJ. A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer. JAMA (1995) 273:289–94.
[Abstract/Free Full Text]
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