An undeclared civil war is breaking out in biomedicine. On one side is precision medicine, with its emphasis on tailoring treatments to ever-narrower groups of patients. On the other side is population health, which emphasizes predominantly preventive interventions that have broad applications across populations.
Which vision will provide the most durable and efficient path to improved health for all?
Precision medicine is a merger of molecular genetics, the dominant vision in biology, and genomics, the expression of that vision in human health. Disregarding the “breakthrough” announcements that appear on a regular basis, the question of whether precision medicine will lead to better health for all remains an open one.
Advances in public health such as cleaner water, safer and more nutritious food, prevention of infectious disease, and the prevention and cessation of smoking had much to do with adding 20 years to the lifespan of the average American between 1900 and 1950. Advances in biomedicine, such as better diagnosis and treatment of cardiovascular disease and cancer, added another 10 years since then.
Enter molecular genetics and genomics. The launching pad for this new era was the Human Genome Project, led primarily by the National Institutes of Health at a projected cost of $3 billion. This massive project encouraged people in the genomics community to see themselves as transformational actors in all forms of medical research and to promise equally transformative benefits for health.
As President Bill Clinton said in a ceremony celebrating the completion of the Human Genome Project in 2000, it offered the hope that “genome science will revolutionize … the diagnosis, prevention, and treatment of most, if not all, human diseases.”
The development of genomics since 2000 has been accompanied by an enormous growth in resources devoted to research, training, technology development, and implementation. This new emphasis has required a substantial reallocation of resources that were once directed toward traditional biomedical disciplines. The NIH, with its nearly $42 billion budget for 2020, currently invests approximately half its resources in genomics-related research, but less and less on research into prevention and public health.
That the NIH is bullish on genomics and precision medicine is clear from a 2018 tweet by its director, Francis S. Collins: “We would expect to see more effective prevention of many diseases, fewer diagnoses of serious illness, and an extension in health span.”
— Francis S. Collins (@NIHDirector) May 8, 2018
Offering personalized medicine as the foundation for population-based medicine of the future, as well as the ongoing and proposed investments in it, means the time has come for open debate to achieve balance and consensus on the fundamental priorities that will drive further gains in healthy lifespan in the United States and other countries.
We believe that genomics and precision medicine have ridden a wave of hype without substance for far too long. Unless they are able to go well beyond their thin record of empirical success and demonstrate their effectiveness in meeting the actual health needs of populations, they will be marginal players with regard to any lasting impact on the health of the public.
Fortunately, it appears that the tide is beginning to turn toward population health, especially as a more balanced perspective of the value of polygenic risk scores — one of the most widely advocated innovations of the precision medicine movement — is beginning to emerge.
Initial studies using genetic markers to predict the future risk of coronary heart disease received widespread attention and the marketed algorithms have been used by numerous medical centers. However, back to back studies in JAMA — conducted using improved statistical comparisons with standard risk factor profiles — demonstrate little or no value for these scores. An accompanying editorial provides further context for premature acceptance of polygenic risk score tools and reaffirms the need for population approaches to the prevention of cardiovascular disease, which have proven to be so successful over the last five decades.
Genomics has clearly led to major advances in many areas of biomedical research, and has myriad clinical applications, such as improved screening for familial diseases, enhanced diagnostic capabilities for infectious diseases, targeted therapy of immune-related conditions, and the capacity to provide guidance for greatly improved therapy for a subset of cancers.
But the “grand vision” accompanying projects like the NIH’s All of Us Research Program, which is currently enrolling 1 million volunteers with what Collins promised would be more “effective prevention of many diseases, fewer diagnoses of serious illness, and an extension in health span,” far exceeds what can be supported based on current evidence. Genomics, as Nobelist Harold Varmus once pointed out, “is a way to do science, not medicine.”
The genetic variants we inherit in our DNA have little impact on common diseases, and we need to draw a sharp dividing line between the majority of illnesses that influence population health — which are driven overwhelmingly by lifetime exposure to harmful air and water, poor nutrition, infectious agents, physical trauma, and psychological insults — and the minority that are driven by harmful genetic variants.
As we argued recently in the journal Issues in Science and Technology, choosing which road to follow to achieve significant improvements in health — like the 75% decline in cardiovascular mortality since 1968 and the 30% fall in cancer death rates since 1990 — is of enormous importance to public health. Although genomics has arrived as a new and exciting frontier of science, the opportunity costs for biomedical research if we continue down that road are enormous.
With a substantial chunk of the NIH’s budget devoted to genomics-related research, landmark trials like SPRINT, which demonstrated that lower treatment thresholds for blood pressure could reduce cardiovascular deaths by 110,000 per year in the U.S. alone, can no longer be funded because of the diversion of funds to genome sequencing projects like TOPMed.
Perhaps more important, an entire generation of young scientists who are being trained in genome-related laboratory and statistical disciplines are coming to believe that this form of biomedical investigation is uniquely important, to the detriment of other forms of research.
Although advocates of a more public health focused approach to biomedical research are beginning to make their voices heard, and the failures of the predictions of genomic enthusiasts are becoming increasingly evident, the biomedical research establishment continues to dig in its heels.
A course correction is urgently needed.
Richard Cooper, M.D., is a cardiovascular epidemiologist and chair of public health sciences at Loyola University Medical School. Nigel Paneth, M.D., is a professor of epidemiology and pediatrics at Michigan State University.