Precision medicine — tailoring a treatment to an individual’s disease — requires understanding the individual’s biological characteristics. Although medicine and biotech are making significant progress in this area, they have historically been limited by few genetic samples and insights from patients of diverse backgrounds, particularly in therapeutic categories including cardiometabolism, inflammation, and other diseases with a disproportionate incidence among underrepresented racial and ethnic groups.
More than 80% of genomics studies have been conducted in people of European descent. If this imbalance is not fully addressed, a lack of diverse DNA sampling has the potential to hold back the pace of drug discovery and the development of, and more equitable access to, the promise of precision medicine.
As scientists with more than a half-century between us studying human disease, first as practicing clinicians — an oncologist (D.R.) and a neurologist (K.S.) — and now in the biotechnology field, we believe our industry is at an important transitional point: It must increase large-scale collection of medical and genetic information from diverse populations; study the data in an unbiased way to detect associations, then develop medicines tailored to the molecular and clinical features of illnesses and the biological characteristics of each patient.
It is important to understand disease through the context of human diversity, which isn’t just about genetic heritage but also about how different people respond to disease. Studying genomics from individuals of various backgrounds can help researchers not only better understand the many ways humans diverge from each other — genetically, biologically, and physiologically — but also are alike. Genomics can get us only so far. It is essential to use data — molecular, clinical, proteomic, phenotypic, and environmental — from diverse groups and then apply insights gleaned from them to drug discovery and development to benefit the broadest range of patients.
Bringing to life the vision for understanding human diversity
The first step we and our colleagues have taken to solve this problem is gathering population-scale human data achieved in part through the ability of deCODE genetics, a company one of us (K.S.) founded in 1996, to collect, store, and mine human data on a scale that was once considered impossible. When Amgen acquired deCODE in 2012, the dataset included the genotypes of about 100,000 individuals primarily from Iceland, and 2,000 whole genomes had been sequenced. Since then, deCODE has amassed genetic and medical data from populations in the U.S., Europe, and Japan, resulting in a more diverse database that includes 2.5 million genotyped individuals and 350,000 sequenced whole genomes, including whole-genome sequence data available from almost 20,000 individuals of African and Asian ancestry.
Data from other biobanks are also providing information about the whole genomes of large and diverse populations. All of Us, being conducted by the National Institutes of Health, aims to gather data from 1 million Americans of different backgrounds. We, along with industry partners, support Our Future Health, the United Kingdom’s largest health research program, and the UK Biobank, the most ambitious genome sequencing project of its time, following 500,000 older volunteers of various ethnicities.
Human diversity research also includes the challenge of studying the complex interplay of genes and the environment, such as diet and education, among different populations. This research is essential to understanding the biology of disease incidence and progression and identifying new drug candidates.
One way researchers have been able to understand these interactions is to search for levels of proteins in blood that correlate with a disease. From there it is possible to determine whether the gene variants that affect the levels of these proteins also correlate with the disease. Proteins that are participant in pathogenesis are attractive targets for research and development. To advance this effort, we are working with the UK Biobank on a proteomic study measuring proteins circulating in humans’ bloodstreams.
Preliminary progress of how a more complete understanding of human diversity can apply to drug development and precision medicine are coming to light in our work on investigational therapeutics to lower lipoprotein (a), an independent and genetically-determined risk factor for cardiovascular disease. Levels of lipoprotein (a) are disproportionately higher in Black Americans and we are working to study this biomarker in a racially representative group of people to understand the biological characteristics of those affected by cardiovascular disease.
Reason for optimism
Since the human genome was fully sequenced in 2022, researchers have learned an enormous amount from the information contained in the diversity of the 3 billion base pairs that make up the human genome. The next step is to incorporate additional layers of data — from molecular and medical to environmental — and work to change decades-old practices of focusing on people of one ancestry to include people of many.
The biotech industry and research institutions are rising to this challenge; the result will be one of the most detailed pictures ever of disease incidence, progression, and response to treatment.
Achieving the goal of precision medicine for all requires continued study of what makes us different. But if human diversity research has shown one thing, it is that what separates us is so much less than what joins us together.
David Reese is the executive vice president of research and development at Amgen. Kári Stefánsson is the founder of deCODE genetics, a subsidiary of Amgen.