The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

Doudna’s decision to go with a competing company may have contributed to her cooling relationship with Charpentier, but the two had been drifting apart for a while. When Doudna asked Charpentier to continue working on CRISPR-Cas9 as a gene-editing tool in 2012, Charpentier declined, preferring to work in the realm of pure science. Doudna felt that Charpentier viewed the CRISPR-Cas9 system chiefly as her project, though Doudna was a cofounder. From Charpentier’s point of view, Doudna had hijacked the limelight on CRISPR-Cas9 by focusing exclusively on its gene-editing potential.

Despite their differences, Doudna and Charpentier have been united by acclaim. In 2014, the pair received the glamorous Breakthrough Prize in Life Sciences, which awards $3 million to each recipient. This was followed by the Gainer Award in biomedical science in 2016 and the Kavli Prize in 2018, which they received along with Lithuanian scientist Virginijus Šikšnys.

A controversial Cell article published by Broad’s Eric Lander further divided the CRISPR camps. Lander’s apparent motive in the article, entitled “The Heroes of CRISPR,” was laudable: He wanted to show that CRISPR was an ensemble act. However, the piece had another cloaked aim—downplaying Doudna’s role in the development of CRISPR-Cas9. Lander’s narrative credited early players like Mojica and celebrated the work of unsung heroes like Šikšnys. It also praised Charpentier’s work in discovering tracrRNA. However, it largely glossed over Doudna’s accomplishments in the field. Moreover, it credited Lander’s protégé Zhang with many breakthroughs while citing little evidence. Though neither Lander nor Cell disclosed it, the Broad Institute was competing with Doudna for patents and prizes.

Doudna refuted the article online in a measured tone. Though Lander told Isaacson that Charpentier had criticized Doudna to him, Charpentier herself posted online that the article was “incomplete and inaccurate.” Church also refuted Lander’s claim that Doudna took information from the preprint he sent her in 2012. Doudna’s friends rallied to her cause, with Berkeley genetics professor Michael Eisen calling Lander “an evil genius at the height of his craft.” He felt Lander’s piece was a hatchet job aimed to win Zhang the Nobel Prize and Broad an insanely lucrative patent. However, Isaacson posits that Lander’s motives may have been protectiveness of Zhang, his mentee. Women scientists saw Lander’s article as a Rosalind Franklin moment redux, an attempt to wash out the contribution of an important woman in science.

When Zhang and the Broad Institute beat Doudna, Charpentier, and Chylinski’s patent application in 2014, Doudna was livid. In his application process, Zhang had unfairly implied that Doudna plagiarized Church’s preprint, an accusation Church categorically refuted. Further, Doudna felt it was her team that had actually discovered how CRISPR-Cas9 worked. From then on, figuring out how to transport the system in other cells was obvious. Another puzzling aspect of Zhang and Broad’s patent application was the ouster of Luciano Marraffini, Zhang’s collaborator.

Since Doudna’s application was still languishing at the Patent Office, she could request (within an year of Zhang’s patent) a contesting “interference” hearing. Doudna filed her interference claim in 2015, stating that though her team’s experiments were on bacteria, her application had clearly mentioned the CRISPR-Cas9 mechanism could be carried over to other organisms. Thus, Zhang’s claim “interfered” with hers. Moreover, this transition to human cells was obvious, not inventive. Zhang argued that the transition was not obvious: Bringing CRISPR-Cas9 into human cells required an extra inventive step, which was why he and Broad deserved to patent the technology for human use. The hearing for the contested patents began in December 2016. Doudna’s lawyer argued that since five labs had made CRISPR-Cas9 transition into human cells, this proved Zhang’s invention was obvious.

The three-judge panel rejected Doudna’s claim in February 2017, declaring Zhang’s patent inventive and original. Doudna took her case to the federal courts, which sided with the patent board. Yet, since the patent board had thrown out the possibility of “interference,” Doudna’s patent application was still valid. In early 2019, Doudna and Charpentier’s patent was accepted, existing in parallel to the Zhang-Broad patent. By now, Doudna had a powerhouse new lawyer named Edora Ellison, who was trained in both biotech and law. In June 2019, Ellison prodded the patent board into launching another case, this time on deciding which side had made the key discovery first. By late 2020, the case was still dragging on. In hindsight, Doudna’s business partner Andy May believes Doudna sometimes wishes she and Zhang had pooled their inventions instead of fighting prolonged court battles.