Special issue: Applying research in the human genome -- progress and potential

“Although some hoped having the human genome in hand [as of two decades ago] would let us sprint to medical miracles,” writes Science Senior Editor Laura Zahn, in an introduction to a special issue of the journal, “the field is more an ongoing relay race of contributions from genomic studies.” In a Policy Forum, a Perspective, four Reviews and two related News stories, the special issue examines well-earned successes in applying research in the human genome to understanding human evolution, cancer, polygenic traits, and functional genomics. It also highlights research ground yet to cover.

A Perspective in the issue by Jennifer E. Rood and Aviv Regev reflects on the progress since the publication of the first draft sequence of the Human Genome Project (HGP). The initiative forever altered biomedicine, they say, but work remains to fulfill its true potential. “The HGP has also left us with a major mission—still incomplete 20 years later—to understand how genomic information leads to the development, function, and malfunction of cells and organisms and to fully leverage this knowledge to promote human health and treat disease,” say Rood and Regev.

In a Policy Forum, Natalie Ram and colleagues highlight the first law in the United States—and in the world—that comprehensively regulates law enforcement’s use of consumer genetic data to investigate crimes. It was enacted in May 2021 in Maryland. Before that, the primary restraint on law enforcement’s use of consumer genetic data had come from consumer genetics platforms themselves, with some declining to cooperate. The new law’s success, say the authors, “provides a roadmap for regulating genetic genealogy in a way that balances privacy and public safety, and its terms include six critical features that others should model moving forward.”

Four Reviews cover topics including the value of the polygenic (risk) score for identifying people at increased risk of disease, thereby facilitating prevention or early intervention; the importance of integrating different types of data in understanding the molecular evolution of malignant cell states across the cancer life cycle; the importance of understanding the biological mechanisms by which genetic variants influence phenotypes, using new methods; and the way recent advancements in DNA sequencing technologies and laboratory preparation protocols have expanded the scope of ancient DNA research over the past decade.

A story from Jocelyn Kaiser, a reporter in Science’s news department, reviews the promise of newborn genome sequencing, which still faces a host of ethical and practical obstacles. Even so, one company in the United Kingdom is pushing ahead with a major test: Genomics England is planning a large pilot research project, involving as many as 200,000 babies. In a separate news story on human genomics, reporter Mitch Leslie profiles researcher and physician Dan Kastner, who became the scientific director of the National Human Genome Research Institute in 2010. Kastner is known for having defined autoinflammatory diseases as a category of illness, and for having collaborated to identify 14 defective genes that trigger these conditions. By identifying what drives these diseases, Kastner’s work opened the door for life-changing and even life-saving treatments for patients. What’s more, the gene-hunting methods he and other scientists have pursued could change the approach for identifying and defining diseases; doctors have traditionally recognized new illnesses based on clusters of symptoms, but Kastner proposes to first sequence genomes to pinpoint mutations and then determine if people who carry these glitches suffer from unexplained health problems. This approach could allow for discovery of diseases scientists didn’t imagine occurring, Leslie writes. In fact, Kastner and his colleagues have already revealed one such unimagined disease, and he plans to search for more.