2023 Science, Technology and Environment

Adam M. Phillippy, Sergey Koren, Arang Rhie and The Telomere-to-Telomere Team

Conducted the first complete assembly of the human genome, sequencing the most difficult, final part of our genetic makeup, advancing our understanding of our biological blueprint and opening up scientific frontiers that could revolutionize the treatment of a multitude of diseases.

After seven years of painstaking research, three scientists from the National Institutes of Health were instrumental in cracking the last 8% of the human genetic code, providing new insights into the complexities of DNA and its relationship to health.  

The breakthrough research was conducted as part of the Telomere-to-Telomere Consortium, now a group of more than 300 international scientists led by Adam Phillippy, Sergey Koren and Arang Rhie of the NIH’s National Human Genome Research Institute. Using cutting-edge technology, the team studied the most hard-to-reach and complex parts of our DNA, creating a complete picture of the human genome that has enabled scientists to discover more than 2 new million variants—or changes—in our genetic makeup, many of which can cause serious health problems. 

“This is historic,” said Eric Green, director of the National Human Genome Research Institute. “Now we can say, as a species, that we have our entire genetic blueprint in front of us.”  

Unlocking the most inaccessible parts of our DNA  

Phillippy had just graduated from college in 2003 when the Human Genome Project finished mapping 92% of the human genome. An aspiring computational biologist, he became fascinated by the idea of discovering the last 8%—a set of repetitive DNA sequences that had been inaccessible to the Human Genome Project using the computational technology that existed 20 years ago.  

In 2018, he co-founded the Telomere-to-Telomere Consortium with Karen Miga, a fellow geneticist at University of California, Santa Cruz, to defy conventional wisdom. Koren and Rhie, two of Phillippy’s first recruits, developed computational algorithms for the project and verified the team’s results, respectively. 

Despite skepticism that the team could crack the most impenetrable parts of our DNA, Phillippy and his colleagues plunged forward, leveraging modern technology that deciphers long stretches of DNA at once to make startling discoveries.  

“It took courageous pioneers to say, ‘this is about understanding our biology, our health and our disease. We should never say that 92% is good enough,’” Green said. 

Shedding light on the genetic mysteries of autism, cancer and Down syndrome  

The team’s complete human genome sequence has already yielded new insights, including showing genetic material in chromosomes’ tightly wound centers that may be associated with conditions such as autism.  

Additional findings include repetitive DNA sequences at the ends of our thread-like chromosomes—telomeres—that may explain how cells age, and the development of certain types of cancer, chromosomal activity that could predispose people to Down syndrome, and information that could lead to better gene therapies for people with spinal muscular atrophy. Other findings could show how humans evolved certain traits over time, such as our large brain size and ability to live at high altitudes.  

Phillippy said the consortium is sharing its technological methods and findings across the world, including with Indigenous communities in the Americas, Australia and New Zealand, to map genomes that “better represent global genetic diversity” and inform diagnoses and treatment for people of all backgrounds.   

This approach is emblematic of a team that, according to Rhie, followed in the spirit of the original Human Genome Project and shared its findings with the public from the start.  

Today, the consortium is a global enterprise that has provided scientists with an authoritative reference for investigating genetic differences between humans and informing medical care.  

“This is a great step toward an era in which there are no questions about the genetics behind any disease and the rational treatment for it,” said David Haussler, scientific director of the University of California, Santa Cruz Genomics Institute. 

Phillippy believes this work emblemizes the impact public servants can make in government.  

“Our data is getting picked up by other scientists and by industry, and being turned into new therapies or treatments,” he said. “It is really easy to get up and go to work in the morning because our work is making a difference.”