Creating the common language of genome editing
Last year CRISPR Medicine News interviewed Samantha Maragh, Leader at Genome Editing Program at NIST, to learn about the work on standards on genome editing. Since then, the world has experienced a pandemic which – similar to most other sectors – has influenced the work in positive and negative ways. On the backside, NIST has been limited in their ability to conduct lab experiments as their facilities were shut down earlier this year. Now the labs have slowly reopened, and the staff have been adjusting to the new normal.
»We’re still at limited operations, because we need to make sure that those who need access to the lab can operate safely. We are also hampered by delays in deliveries and manufacturing of laboratory necessities as for example plastic consumables. So, I think that one of the things we have learned this year is that science isn’t just science. Science is a lot of business and infrastructure that we don’t often think about«, Maragh says.
Accustomed to virtual meetings an advantage
While part of the work regarding standards for genome editing has been delayed, other parts have continued despite the pandemic set back.
The science community is used to meeting and interacting at live meetings, seminars and other events, and as the pandemic put a definite stop to these kinds of interactions, the communication has had to find new ways. The NIST community is used to working in alternative ways:
»For this NIST consortium, it has actually been an advantage that virtual meetings were already the norm. It was sort of that little bit of normality that we could keep going in the midst of all of these things that were changing and shifting. Some people could not do the physical experiments that they were planning, but we were able to put a little bit more energy in some of the experimental design and planning activities. So, I like to think positively that we might have benefited from people having that moment to think about other aspects of this work than they normally would have time to«.
Two areas of action continued at full power: The working group that focuses on data and metadata was able to move forward, modelling what could be an easy-to-use infrastructure for the description of an experiment. Also, the work on determining the terminology used in genome editing has continued as planned.
The realization of a lexicon
Whether speaking with a Japanese, a German or a British colleague, doctors use Latin terms to determine precisely what bone or ligament they examine. The same is necessary for people working in genome editing. They need a common language to ensure universal understanding of procedures and protocols.
With that in mind, NIST had formed a working group within the consortium to develop a lexicon for genome editing. In mid-2019 the consortium had prepared a list of terms and definitions in cooperation with targeted experts on genome editing. To ensure that these terms and definitions fit the landscape within global genome editing research, the organization made an open call to get global feedback in autumn 2019.
»With this open call, we invited anyone anywhere in the world to comment on the terms to make sure that we were capturing different viewpoints and to make sure the terms were really appropriate for our users«.
NIST Genome Editing Consortium
The NIST Genome Editing Consortium addresses the measurements and standards needed to increase confidence and lower the risk of utilizing genome editing technologies in research and commercial products.
The goals are to (a) Evaluate genome editing assay pipelines (b) Develop benchmark materials (c) Generate benchmark data (d) Develop suggested minimal information reporting for public studies (e) Generate a common lexicon for genome editing studies.
The NIST Genome Editing Consortium has extended its operation duration through 2025 and is still accepting new members.
The next step was to incorporate the responses from research groups or experts on CRISPR technology from countries all over the planet, to ensure that scientist in genome editing can share protocols from Alaska to South Korea. And in 2021 this year, NIST published on their website a lexicon, consisting of the terms and definitions agreed on. Maragh explains:
»For example, in any science field you often use the term specificity. But what does that mean in the context of genome editing? What are you describing? To us it seemed important to have a definition of that specific term, because it is such a common term across different fields«.
The lexicon includes notes and examples that are useful to prevent ambiguity about the definitions. In the case of the word specificity, which is such a general concept, the lexicon presents a note that clarify that »When using this term, the procedure is defined, intended target is defined, action or outcome is measured and reported, and limits of detection are reported«.
As a way to integrate the consortium lexicon with the data & metadata efforts and enhance ease of public utilization of these terms and definitions, the NIST Genome Editing Lexicon (NIST_GEL) has been made available on NCO BioPortal (an online repository of biomedical ontologies) as a standardised genome editing ontology for the technical community.
Progressing to ISO standard
That accomplished, the working group asked themselves: What is the biggest, most inclusive impact this work could have?
»We realised that it would be an internationalised formal standard definitions. So, what we did was we approached the International Organisation for Standards« Maragh explains.
An ISO standardisation will ensure that the terms and definitions within genome editing are deemed appropriate by different countries, so they are harmonised at a global level. One of the technical committees – the TC276 – is titled biotechnology. The goal of their terminology working group is to define international standards for key terms for biotechnology.
»One of the working groups within TC276 is about terminology. So, we approached the working group to propose a new project of genome editing terms and definitions as a standard« Maragh says, and stress that ISO will be used to better the very technical communication among experts within the scientific community – not communication in education or to the public.
As it turned out there was an interest in the ISO analytical methods as well as terminology scientific community to form ISO-standards for genome editing. The existing NIST genome editing lexicon could function as an advanced draft towards a formal international standard. And so, the process began, and an international drafting committee was formed on genome editing terminology.
Adjusting to a different way of sharing knowledge
An ISO standardisation is a formalised process, going through six stages: proposal, preparatory, committee, enquiry, approval and finally the publication stage. The NIST lexicon has made it possible to speed up the first stages a bit and is now in stage five.
»The work is still ongoing and in progress. So, stay tuned, hopefully we'll be able to bring out the news later this year, that there's an ISO standard published« Maragh reveals with a big smile.
NB We also spoke with Samantha Maragh in 2019, you can read that interview here: 'Setting standards in the CRISPR genome editing revolution'.
Poseida Therapeutics, Inc.
First Affiliated Hospital of Guangdong Pharmaceutical University