ISO Releases Standard Genome Editing Vocabulary

By Allison Proffitt 

September 6, 2022 | The International Organization for Standardization—ISO—last year released the genome editing standard vocabulary, comprising 42 terms and definitions covering genome editing concepts, tools, and outcomes. An updated version of the standard was released at the end of last month, and now, says Samantha Maragh, leader of the Genome Editing Program at the National Institute of Standards and Technology, the goal is adoption.  

Maragh leads NIST's programs supporting genome editing technologies with a primary focus on innovation in genome editing and measurements for the field of gene and cell therapies. In 2016, she started working on a consortium around genome editing. “The goal was to bring together a program that could really help with the measurements and standards that are needed for the field of genome editing,” she explained.  

The first two areas of focus for the consortium—controls and standards for wet lab genome editing, and standard datasets people could use to test their informatics tools and data analysis strategies—were an easy sell, Maragh says. Focusing on a standard lexicon and definitions took a bit more conversation and convincing.  

The value of a foundational vocabulary, Maragh says, is that, “Anybody using genome editing as a technology—it didn’t matter what kind of organism that you were going to apply it to—that these terms and definitions would be applicable.”  

Consensus Voices 

The list includes basic terms—genome editing, edit, indel, target, off-target, RNA edit, specificity—and more technical terms like TALEN linker, ZFN recognition helix, Cys2His2 zinc finger, and microhomology-mediated end joining repair. While Maragh initially imagined defining 20 words; that list grew to 42. And now—four years after the list was “locked” in 2018—Maragh acknowledges that new terms could be added.  

“There were not textbook, technical definitions for this field that were agreed upon across the field,” Maragh said. In less technical areas, new technologies are sometimes adopted easily with broad understanding, but, Maragh said, “that didn’t exist for genome editing as a field.” Other groups had worked on internal glossaries or vocabularies specifically aimed at physicians or the public, but Maragh saw a void in a technical lexicon for scientists themselves.  

To build consensus around the lexicon, the consortium worked in several phases. First the consortium members worked together to develop “reasonable definitions” to serve as starting points. They then invited “targeted expert feedback” from scientists in the field who were not part of the consortium. Here Maragh says they took care to invite gene editing experts in plant genomics, animal genomics, and microbes as well as human. The consortium also conducted targeted outreach to international regulators and the World Health Organization as well as any industry or academic stakeholders who were not already members of the NIST consortium.  

The process revealed some surprising biases. For instance, some team members defined a “genome” as the DNA code that makes up a creature until other researchers pointed out that viruses—while not technically cells—have genomes made of RNA. “Oh right!” Maragh recalls the response. “Because that’s not my technical area I, too, can have blinders on.” They settled on including “nucleic acid” instead of DNA or RNA.  

Next, there was a completely open and public review period on the list of terms and definitions. The list was shared via a Google Document and any member of the public could give feedback.  

Seeking Harmonization 

But the consortium didn’t stop there. “Genome editing is a global community,” Maragh pointed out. “The best good is if we can get formal, global harmonization.” Submitting the list to the very detailed ISO review process sets a higher bar for international acceptance, Maragh explains. “It’s a very low bar to actually get them visible publicly, but that formal international standard that’s been harmonized officially through ISO is a very different bar and process!”  

The ISO approval process began in December 2019 when Maragh—representing NIST as an ISO Technical Committee on Biotechnology member—proposed the project to ISO. In 2020 the project became an official ISO effort. More feedback and votes were gathered; international bodies contributed to and verified the evolving content. The standard was released in 2021, but widely publicized after an update in July 2022.  

Maragh knows that—even with extensive international review—everyone may still not agree on the definitions. She recommends letting the standard definitions serve as a baseline. “If you decide to use a word differently, you can at least say, ‘Ok, differently than the standard definition, I’m using this word like this in this particular case,’” she explains.  

But there is still great value in having a standard list of terms and definitions.  

“Terminology is underlying to and foundational to a scientific field,” Maragh says. “The key here is adoption. A document now exists, and we think it would be very helpful to the community—we [being] the many of us that worked on it, the many countries that worked on it. But if the community of genome editing scientists and those close enough to want technical definitions don’t know about it, don’t adopt it, it can’t do the good it was intended for.”