A vision for the next decade of human genomics research

Since the launch of the Human Genome Project 30 years ago, genomics has become deeply woven into research, medicine and, increasingly, daily life. In roughly 10,000 days, genomics has blossomed from a boutique discipline associated with a moonshot project into a scientific area now vital for areas as diverse as microbiology and oncology.

Numerous genomic applications—noninvasive prenatal genetic testing, DNA-based forensics, direct-to-consumer ancestry sleuthing, genetic disease diagnostics and SARS-CoV-2 virus surveillance, among others—are common practice.

What’s next for genomics, especially in its applications to human health and disease? For the past several years, the broader genomics community has worked with the U.S. National Human Genome Research Institute to formulate a vision—a “2020 vision”—of what lies at the forefront of human genomics for the next decade.

The vision represents the strong consensus that we heard about the key guiding principles and values that now undergird human genomics, such as those related to diversity, equity, social justice, data sharing and team science. The broader biomedical enterprise increasingly depends on a strong foundation for genomics (consisting of infrastructure, resources and dynamic areas of technology development), and so the vision articulates the need to sustain and improve this foundation.

The new vision identifies barriers that impede progress in genomics—with a call to action for high-risk pursuits to break down such barriers. And, because we are scientists, there are also ambitious and compelling research projects in human genomics that serve to stretch our imaginations and pique our curiosity.

The vision for the next phase of human genomics is bolder than ever, and continues to embrace many of the original promises of the Human Genome Project. It does so even as some of the previous predictions about genomic advances are still to be fully realized.

Critics may say such genomics boldness is disingenuous and breeds overpromises, but at every encounter during our recent strategic planning process, we found the optimism and exuberance of our colleagues to be both inspiring and metaphorically intoxicating, pushing us to be even bolder and more willing to take risks in describing where genomics might lead us. That is why the vision’s capstone is a set of 10 bold predictions for human genomics by 2030.

Bold Predictions for Human Genomics by 2030

Generating and analyzing a complete human genome sequence will be routine for any research laboratory, becoming as straightforward as carrying out a DNA purification.

The biological function(s) of every human gene will be known; for non-coding elements in the human genome, such knowledge will be the rule rather than the exception.

The general features of the epigenetic landscape and transcriptional output will be routinely incorporated into predictive models of the effect of genotype on phenotype.

Research in human genomics will have moved beyond population descriptors based on historic social constructs such as race.

Studies that involve analyses of genome sequences and associated phenotypic information for millions of human participants will be regularly featured at school science fairs.

The regular use of genomic information will have transitioned from boutique to mainstream in all clinical settings, making genomic testing as routine as complete blood counts.

The clinical relevance of all encountered genomic variants will be readily predictable, rendering the diagnostic designation ‘variant of uncertain significance (VUS)’ obsolete.

An individual’s complete genome sequence along with informative annotations will, if desired, be securely and readily accessible on their smartphone.

Individuals from ancestrally diverse backgrounds will benefit equitably from advances in human genomics.

Breakthrough discoveries will lead to curative therapies involving genomic modifications for dozens of genetic diseases.

From Green, E.D., et. al., “Strategic vision for improving human health at the Forefront of Genomics,” Nature 2020.

Innovation is inspired by reaching for seemingly unreachable goals. When early naysayers predicted that the Human Genome Project would fail, we ignored the pessimism and generated the first human genome sequence in less time and for less money than originally planned. Had we not been overly ambitious for the past 17 years since the end of the Human Genome Project, we would not have reduced the cost of DNA sequencing by more than a millionfold, made genome sequencing routine for the diagnosis of rare genetic diseases, or, most recently, generated a truly complete, end-to-end sequence of a human chromosome. As a physician-scientist, I was drawn to genomics because of its potential for changing medical care, never dreaming that genomic medicine would begin to be implemented in my lifetime (and I’m only 60!).

During the Human Genome Project, we mapped and sequenced the human genome to the best of our ability with the then-available methods, which shockingly started with handwriting DNA sequences onto notebook pages and then faxing those pages to collaborators. Little by little, we found that our step-by-step evolution of approaches was in fact the revolution that we needed for success.

Similar patience and tenacity will be needed in striving for the vision’s bold predictions. Even if two or three of them are realized, we will have accomplished the incredible.

Among the boldest of the 10 predictions are those that rely not only on the tools of genomics, but also on advances in society—a reminder that the science can only take us so far. To fulfill the full potential of genomics, researchers need to push the boundaries of science while every one of us—scientists and nonscientists alike—need to continually examine what we know to be true and know to be possible. Each of us must raise awareness of health inequities and develop the empathetic will to address them, caring for others’ genomes as much as we do our own.