After an illustrious career including 12 years as director of the National Institutes of Health (NIH) and leading the international Human Genome Project (HGP) consortium, Francis Collins, MD, PhD, announced his sudden resignation from the NIH over the weekend.
He joined the NIH in 1993, a guitar-playing physician-scientist (and born-again Christian) who could not resist the challenge of helming the sequencing of the human genome. “How could I walk away from the chance to lead such an historic enterprise?” he wrote.
Collins served three presidents during his 12 years as NIH director, including the onset of the COVID-19 pandemic. He also served as chief White House science advisor to President Biden, accepting the position following the sudden resignation of his HGP ally, Eric Lander, PhD. Throughout his tenure, Collins maintained his research lab at the NHGRI, publishing a paper in GEN’s sister peer-reviewed journal, The CRISPR Journal, led by Lori Bonnycastle, PhD, 12 months ago on the generation of induced pluripotent stem cell lines using prime editing.
Collins released his resignation statement the day after officially retiring from the NIH on February 28. “It has been the greatest honor of my life to be part of this institution in various roles over the last four decades,” he said. He expressed his “gratitude and love” to his many colleagues “of extraordinary intellect and integrity” since he arrived on campus in Bethesda, MD, in 1993.
“They personify excellence in every way, and they deserve the utmost respect and support of all Americans,” Collins said.
Ashish Jha, MD, dean of the Brown University School of Public Health, praised Collins. “Francis helped usher in an era of genomic medicine whose fruits we are just beginning to reap,” Jha posted. “History will judge him as a legend who helped transform American medicine.”
Forty years at the top
Collins first made his mark in molecular genetics fully four decades ago. In 1985, working with Sherman Weissman, MD, and Bernard Forget, MD, at Yale University, Collins published his first Nature paper documenting a mutation in patients with hereditary persistence of fetal hemoglobin. The study helped pave the way for the fetal globin switching strategy used by Vertex Pharmaceuticals in the development of Casgevy, the landmark CRISPR-based cell therapy for sickle cell disease.
The year before, Collins had published a revolutionary method for positional cloning that essentially allowed researchers to jump or leapfrog over relatively large stretches of DNA as they crawled from a linked DNA marker to the putative location of a disease gene. That method proved crucial as Collins, joining forces with Lap-Chee Tsui, PhD, and Jack Riordan, PhD, at the Hospital for Sick Children in Toronto, capped an intense four-year search to isolate the gene mutated in patients with cystic fibrosis (CF).
The discovery of the CF gene was marked by three consecutive research articles in Science. Gunnar Esiason, son of former NFL quarterback Boomer Esiason and a CF patient, posted on social media that “because of people like [Collins], I’m alive today with kids of my own.”
Collins went on to have key roles in teams that identified other major Mendelian disease genes, including neurofibromatosis-1 in 1990 and Huntington’s disease in 1993. One that got away however was BRCA1—the hereditary breast and ovarian cancer gene, which Mary-Claire King, PhD, had mapped to chromosome 17 in 1990. Collins briefly teamed up with King to hunt down the BRCA1 gene, but both groups were scooped by Myriad Genetics in Salt Lake City in 1994.
By this time, Collins had left his Howard Hughes Medical Institute investigator position at the University of Michigan, to become a government official at the NIH, leading the fledgling genome institute (which was officially named the National Human Genome Research Institute in January 1997). Collins publicly confirmed his appointment at the first anniversary Nature Genetics conference in April 1993, taking over leadership of the HGP from Jim Watson, PhD.
Launched in 1990, the international HGP was making slow progress at the halfway mark when Collins was summoned to an urgent meeting with Craig Venter, PhD, in May 1998. Venter stunned his former NIH colleague by announcing his intention to launch a private effort to sequence the human genome. (What happened next is documented in several books including The Genome War by James Shreeve; The Common Thread by John Sulston & Georgina Ferry; and Cracking the Genome by Kevin Davies.)
After two years of intense rivalry and public bickering over public data sharing and ownership of the reference genome, Collins and Venter agreed to make a joint announcement. On June 26, 2000, the two men followed President Bill Clinton into the East Room of the White House for the official announcement, with British Prime Minister Tony Blair appearing via satellite. “Without a doubt, this is the most important, most wondrous map ever produced by humankind,” Clinton said.
Beyond the Genome Project
A key to Collins’ success has been his rare ability as a public speaker and communicator. Whether addressing scientists, politicians, patients, or the media, Collins exuded a natural charm and an uncanny ability to know and respect his audience, aided by an eagerness to talk candidly about his faith and beliefs as a born-again Christian.
“[Francis] really could talk to Congresspeople from different sides of the aisle,” Ewan Birney, PhD, told GEN’s Alex Philippidis in 2021. (Birney, deputy director general of the European Molecular Biology Laboratory, had an important role in the British wing of the HGP.) “The fact that he wore his Christianity absolutely not on his sleeve but over his chest, I think, gave a lot of reassurance to people that were in the Republican Party.” In 2006, he published his first book, The Language of God, discussing his efforts to marry his strong Christian faith with his belief in science and evolution.
In public engagements, he frequently brought out an acoustic guitar, including at the Yale School of Medicine commencement ceremony last year. He made a series of bold predictions about the future of personalized medicine empowered by the HGP, many of which proved accurate decades later. Collins rejected notions that the completion of the HGP meant that biomedical research had moved “beyond the genome.” We are still in the human genome era, he liked to say.
Even before the official completion of the HGP—conveniently on the 50th anniversary of the double helix in April 2003—Collins oversaw the launch of several international projects, including the International HapMap Project in 2002 and the Encyclopedia of DNA Elements (ENCODE) in 2003. The NHGRI provided critical funding for advances in next-gen sequencing that drove the price of sequencing a human genome down to the $1,000 mark. Somehow, Collins also found time to write his first book, The Language of God.
After stepping down as director of NHGRI in 2008, Collins spent time writing a second book on personalized medicine, The Language of Life, before accepting President Obama’s nomination to return to government service as director of the NIH. He stayed in that role for 12 years, serving three presidents—Obama, Trump, and Biden.
Among Collins’ achievements at the NIH was the inception of the H3 Africa Project in 2012. In 2019, Collins threw his support behind a moratorium on human germline editing, following the “CRISPR babies” scandal that erupted in China in November 2018. “We should proceed not at all at the moment and only with great caution in the future,” he said.
The biggest challenge he faced was undoubtedly the COVID-19 pandemic in 2020. “It was my job,” he said in his resignation statement, “to pull together partnerships with the FDA, academia, and the private sector to produce what only America’s unparalleled biomedical sector could have: COVID-19 vaccines in just 11 months, a staggering medical achievement that saved over three million lives in the U.S. alone.”
That view is not universally shared, in part because of the scrutiny over federally funded gain-of-function research on viruses; Collins approved lifting a three-year moratorium on such research in 2017. Along with his NIH colleague Anthony Fauci, MD, Collins became a prime target in recent years for politicians and anti-vaccine activists.
The road to retirement
After retiring as NIH director in 2021, Collins briefly served as President Biden’s chief science advisor, a role that exposed him to projects beyond his usual portfolio including, as he told an audience in 2022, semiconductor shortages and wildfires. He then enjoyed a brief respite as an NIH distinguished investigator overseeing his research lab, focusing on long-standing interests in type 2 diabetes and developing a potential genetic therapy for a rare form of progeria.
In April 2024, Collins underwent a radical prostatectomy at the NIH clinical center, performed by urologic surgeon Peter Pinto, MD. He published an op-ed in the Washington Post to disclose his diagnosis, “to lift the veil and share lifesaving information” for other men.
Collins’ latest book, The Road to Wisdom, was published last year. In his NIH retirement statement, Collins vowed to continue to find ways “to bring together our fractured communities around the shared values of love, truth, goodness, and faith.”
Amen to that.
