Precision medicine should be seen as being synergistic―or at a minimum additive―to population medicine.
Perhaps no debate is more intense in all of clinical investigative medicine than the one on the relevance of focusing studies on population based versus molecular-based strategies. Certain academic commentators have even used the coronavirus disease 2019 (COVID-19) pandemic to highlight their arguments that the National Institutes of Health and other funding agencies should spend less on understanding disease entities at the molecular level and far more on illnesses affecting large populations. This never-ending argument misses the most critical point, which is the basic observation that these 2 approaches to human disease are complementary rather than in conflict or opposition.
To be clear, there can be absolutely no rational “debate” about the societal impact of population-based strategies conceived with scientific rigor and successfully implemented versus individual molecular approaches to disease management. Hands down, population-based strategies have always won, and will continue to do so. Who would argue with the magnitude of societal benefit of the multidecade smoking cessation efforts in the United States in reducing the incidence of lung cancer and other tobacco-associated illnesses versus the degree of impact resulting from the delivery of EGFR tyrosine kinase inhibitors in the presence of an activating EGFR mutation in patients with metastatic lung cancer?
Another example of the absurdity of arguing against the importance of population-based efforts centers on the benefits of a successfully implemented human papillomavirus (HPV) vaccination strategy among male and female adolescents to prevent cervical and other HPV-related cancers versus the effectiveness and adverse events associated with surgery, radiation therapy, and antineoplastic drug therapy in the management of these local, advanced, or metastatic malignancies.
In fact, when the Centers for Disease Control and Prevention (CDC) highlighted its “10 great public health achievements” in the United States during the 20th century, all were in the domain of population-based strategies, rather than the management of disease based on knowledge of the unique molecular profiles of individuals.1 Items listed were vaccination, motor-vehicle safety, safer workplaces, control of infectious disease, decline in deaths from coronary heart disease and stroke, safety and healthier foods, healthier mothers and babies, family planning, fluoridation of drinking water, and recognition of tobacco use as a health hazard.
In oncology, specifically, in addition to tobacco use, obesity is increasingly recognized as a major factor in the pathogenesis of a number of malignancies and population-based efforts are unquestionably where the focus must be to deal with this serious societal concern. I hope that when the CDC lists the major health achievements of the 21st century, it will include reversal of the obesity epidemic in the United States.
At the same time, however, the medical community has increasingly recognized that events at the molecular level can substantially influence our understanding of observations made at a population level and may have a major positive impact on efforts to improve societal health.
For example, in relation to the COVID-19 pandemic, several unique germline variants, including an individual’s blood type, may influence the severity of symptoms in individuals who become infected with this virus, according to a recent report.2
Similarly, investigators are now exploring specific molecular variants of COVID-19 in strategies to effectively find contacts who may be responsible for spreading the illness in a given location. Another recent report noted that public officials were able to identify that a health care worker’s infection originated from a social event rather than from a patient within the hospital based specifically on the molecular analysis of the isolated viruses.3
Turning our attention back to cancer, a provocative report regarding the presence of somatic mutations within the human bronchial epithelium induced by tobacco provides potentially critically relevant information for societal efforts in smoking cessation.4 This study, published earlier this year in Nature, revealed that tobacco smoking adds from “1000 to 10,000 mutations per cell” within the apparently normal bronchial epithelium. However, perhaps somewhat unexpectedly, even within this toxic milieu, a population of cells existed that had no larger number of abnormal cells for individuals with a smoking history than for never-smokers. Finally, the investigators found that this apparently normal population of cells was 4 times more common in former smokers than in current smokers.
The authors critically observed that “quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.”4 These data provide solid support at the molecular level for population-based efforts to strongly encourage smoking cessation with its associated clinical benefits, regardless of how long an individual has been a cigarette smoker. It is not difficult to imagine using this basic scientific information to effectively communicate to young or older adult smokers the impact of this habit on their lives and how stopping smoking could potentially reverse the terribly damaging effects.
A final brief example of a role for precision medicine within the realm of population-based health efforts is our increasing knowledge of how our genes influence obesity.5 Efforts to help individuals successfully reduce and subsequently control their weight will likely be favorably influenced as we develop a firmer understanding of relevant biological factors in obesity.
In conclusion, precision medicine should be seen as being synergistic―or at a minimum additive―to population medicine. Hopefully, we can quickly move forward on both fronts in relevant areas to improve individual and societal health.
1. Centers for Disease Control and Prevention. Ten great public health achievements―United States, 1900-1999. MMWR Morb Mortal Wkly Rep. 1999;48(12):241-243. https://www.cdc.gov/mmwr/preview/mmwrhtml/00056796.htm
2. Zimmer C. Genes may be reason some people get sicker. New York Times. June 5, 2020: A7.
3. Watson C. How countries are using genomics to help avoid a second coronavirus wave. Nature. 2020;582(7810):19. doi:10.1038/d41586-020-01573-5
4. Yoshida K, Gowers KHC, Lee-Six H, et al. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature. 2020;578(7794):266-272. doi:10.1038/s41586-020-1961-1
5. Thaker VV. Genetic and epigenetic causes of obesity. Adolesc Med State Art Rev. 2017; 28(2):379-405.