Intellia announced a new tool for gene editing. Academics said they rewrote history
David Liu, the Harvard biochemist, was sitting in a meeting last week when his phone started buzzing repeatedly.
Unbeknownst to him, minutes prior the CRISPR company Intellia had finished unveiling their approach to base editing at a Cold Spring Harbor Lab conference. First pioneered by Liu and his lab in 2016, the method allows you to change individual DNA bases without breaking the double helix, an advance that could prove critical for treating a long list of cancers and genetic diseases.
Intellia, though, didn’t cite or acknowledge any of Liu’s work, or any of dozens of papers produced by his students and outside researchers. Immediately after the session closed, former graduate students, postdocs and members of other labs started messaging Liu, asking if he had seen the apparent snub.
Liu responded publicly on Twitter four days later, calling out Intellia for failing to acknowledge the two then-postdocs, Alexis Komor and Nicole Gaudelli, who led the base editing studies. He then named 37 other researchers he said contributed to research Intellia “presented as its own.”
It was therefore disappointing to see Intellia present the development & application of cytosine base editors (CBEs) at last week's @CSHLmeetings conference with no attribution or citation of the many who previously developed and published this science./2https://t.co/4cWdURo4mW
— David R. Liu (@davidrliu) March 29, 2021
In an interview Tuesday, Liu said he hoped Intellia succeeded in bringing therapies for patients. But he argued the company’s decision to not cite early papers could be particularly damaging to young scientists’ careers.
“Whether somebody cites a paper I authored or not at a conference probably isn’t going to affect my career,” he said. “But it could really impact the opportunities for a graduate student or a post doc, or a recent graduate student or a post doc whose scientific accomplishments may largely [be that] work.”
Intellia never claimed in the presentation, a video of which was obtained by Endpoints News, to have invented base editing. But Sam Sternberg, a gene editing researcher at Columbia University unaffiliated with Liu or his companies, said Intellia presented their editors as new and exciting without crediting Liu or explaining how the editors were different.
It seemed “there was a calculated intent to present these as new,” Sternberg, who attended the conference, said in an interview.
Intellia declined to make the employees who made the presentation available for an interview. In an emailed statement, they acknowledged “Liu’s pioneering work” but said, “We believe our base editing system is differentiated compared to other systems we are aware of, and for this presentation we met all requirements for data disclosure as indicated by Cold Spring Harbor Laboratory.”
A Cold Spring Harbor Laboratory spokesperson said they were made aware of the issue through social media and are reviewing the situation with the committee who organized the meeting.
A screenshot of Intellia’s Christian Dombrowski walking through their base editor
Click on the image to see the full-sized version
The controversy notably comes after nearly a decade of bitter disputes over who should receive the credit and patents for inventing the first generation of CRISPR gene editing.
In 2016, when Broad Institute chief Eric Lander wrote a review article on the history of CRISPR, he was accused by some of trying to rewrite history in a way that minimized Jennifer Doudna and Emmanuelle Charpentier’s role and elevated the role of Broad researcher Feng Zhang. When the Nobel committee picked Doudna and Charpentier but not Zhang for the 2020 chemistry award, it was read as the committee’s verdict on who should claim credit.
Base editing has largely been free of such strife, in part thanks to conscious efforts by its leading figures. And neither Liu nor Komor are concerned about running into intellectual property issues with Intellia. In a statement, Beam Therapeutics, the company Liu founded with Zhang and Mass General scientist Keith Joung, said they had “a strong leadership position” in base editing and “an extensive patent portfolio.”
The pair feared, however, that Intellia was rewriting history in a way that could be detrimental to young researchers. Komor, who started her own lab at UC-San Diego after leaving Harvard, said the success of her new research group depends in part on others recognizing her graduate and postdoc work as important.
“You have no idea how difficult it is,” she said. “Any time I want to publish something, I need to leverage my previous accomplishments to get my foot in with this editor, to tell this editor, ‘I did this great work before, remember? So what I’m doing now is really great too.'”
Already, she said, she sees people on Twitter who are new to the field or who lack a strong scientific background talking about a new invention from Intellia called a base editor. “That’s sad to see,” she said.
Intellia titled the presentation, “Special Edition: Expanding Intellia’s Toolbox with Base Editing.” Christian Dombrowski, senior director of the biotech’s Gene Editing Platform group, walked through the company’s CRISPR efforts, including for cell therapy, before explaining that to “unlock the full potential of the T cells,” they might need new forms of gene editing.
“So this was sort of us looking to the future and saying, ‘What is the tool that we are going to need?'” Dombrowski said.
He said they settled on a base editor for the DNA base cytosine. He walked through the well-established components for such an editor: a deactivated Cas9 enzyme that can bind to but not cut the DNA, directed to the right location by an RNA strand; an enzyme called cytosine deaminase that can change a cytosine base to a different base; and a small protein that blocks the body from correcting that change.
Dombrowski then presented a series of slides showing how effectively their base editor could manipulate T cells and the advantages they offer over older CRISPR systems. But he didn’t mention Liu or his lab’s work, or explain how their approach differed from the ones he, Gaudelli, Komor or Kobe University’s Keiji Nishida laid out in 2016 and 2017 — a fact that didn’t escape Gaudelli, who was tuned into the presentation.
In a subsequent Q&A period, she asked in a message box how their approach differed, writing, “I didn’t see any references to all the work that has already been established.” Sternberg, speaking by video, echoed her question.
Intellia CSO Laura Sepp-Lorenzino, who was moderating the session, read out the question. Dombrowski demurred.
“As you can imagine, as it stands today, we aren’t disclosing the composition of the base editor that we’ve built,” he said. “Stay tuned.”
Sternberg said in the interview that he’s gotten used to companies refusing to disclose details for confidentiality reasons. And even as an academic, he said, he often has to choose what to present and what’s not yet ready to be disclosed, because CRISPR is such a hotly competitive field. But Intellia’s presentation was unusual.
“It was a bit surprising that there was no attribution,” he said. “These academic and scientific conferences are here to promote scientific exchange and transparent advancement of scientific knowledge.”
Most scientists in the gene editing world know the papers and academics that established base editing, Sternberg said. But conferences are also attended by non-academics or people who are new to the field. They might come away from such a presentation thinking Intellia invented a new form of editing, as Komor said she’s already seen.
Liu echoed the concern. And he wondered about how the various publications and presentations would look years later if early work goes unnoticed.
“We don’t want to rewrite history,” Komor said.