Path to a Nobel: Yale stop critical for gene editing pioneer

Jennifer Doudna’s scientific journey to the 2020 Nobel Prize in Chemistry passed through New Haven and Yale University. 

Those who worked with Doudna say her tenure at Yale, between 1994 and 2002, laid the early groundwork for the development of CRISPR, the revolutionary gene editing technology that she would later develop at the University of California, Berkeley along with French biologist and co-laureate Emmanuelle Charpentier. That innovation earned them the Nobel Prize on Oct. 7.

“The foundational ability to make a structural determination of RNA happened here in Jennifer’s lab,” said Scott Strobel, the Henry Ford II Professor of Molecular Biophysics & Biochemistry (MB&B) and University Provost.

In the early 1990s, Strobel and Doudna both worked at the University of Colorado-Boulder in the lab of Thomas Cech, who shared the 1989 Nobel Prize in Chemistry with Yale’s Sidney Altman for their discovery of the catalytic properties of RNA (ribonucleic acid).

While in Boulder, Doudna would also meet two visiting Yale biochemists, Joan Steitz and the late Thomas Steitz, Strobel said. Thomas Steitz would share the 2009 Nobel Prize in Chemistry for his work in determining the structure of ribosome, the cell’s protein-making machinery.

Thomas Steitz lobbied Doudna to come to Yale and, in 1994, she became assistant professor of molecular biophysics and biochemistry. At Yale, Doudna would make groundbreaking advances in visualizing the structure of RNA, the single-stranded copies of DNA segments that scientists now know are responsible for a host of crucial biological functions.

“Her career really started here, she became a member of the National Academy of Sciences while at Yale,” said Enrique De La Cruz, professor and chair of MB&B. “Yale has a history of developing young scientists. She arrived as an RNA biologist and left as an expert in structural biology as well.”

That expertise in structural biology proved crucial to Doudna’s eventual interest in exactly how the ancient immune system in bacteria and archaea fended off pathogens, said Joan Steitz, now Sterling Professor of Molecular Biophysics and Biochemistry at Yale.

Doudna and Charpentier, of the Max Planck Institute of Infection Biology, would eventually discover that components of the bacterial immune system could be retooled to act as a sort of genetic scissors to edit DNA, allowing scientists to essentially “rewrite the code of life,” as the Nobel committee wrote. 

“It was never a matter of if she would win the Nobel Prize,” Joan Steitz said. “It was a matter of when.”

Although her work at Yale was not directly related to development of CRISPR, the ability to frame novel solutions to scientific problems was developed by working with top-flight biochemists in New Haven, De La Cruz said.

And at Thomas Steitz’s memorial service in 2018, Doudna, who was awarded an honorary degree by Yale, paid homage to her colleagues at Yale, Strobel recalled.

“She celebrated Tom and said the working foundation of her career was established at Yale,” Strobel said. “It was a generous suggestion and we are extremely pleased to have participated in a portion of her tremendous scientific trajectory.”