2015: CRISPR-Cas9 Gene Editing in Humans Proposed (2015)

In 2015, a series of pivotal papers and conference proceedings coalesced around the question of
whether CRISPR-Cas9—the bacterial adaptive immune system repurposed as a programmable genome editor—
was ready for therapeutic application in humans, marking the opening of intensive scientific and
ethical debate that would reshape medicine within a decade. Jennifer Doudna, Emmanuelle Charpentier,
and their colleagues had described the essential biochemistry of CRISPR-Cas9 editing in a landmark
2012 Science paper, and Feng Zhang at the Broad Institute and George Church at Harvard
simultaneously demonstrated its use in human and mouse cells in January 2013.

The 2015 milestone was precipitated by reports—published by Huang and colleagues in Protein & Cell—
that Chinese researchers had attempted CRISPR editing of non-viable human embryos to correct
mutations in the HBB gene responsible for beta-thalassaemia. Though the embryos were non-viable
tripronucleated zygotes and the editing efficiency was low, the report provoked an international
response: leading scientists including Doudna, Baltimore, Berg, Lander, and others called for a
moratorium on heritable human germline editing pending ethical and regulatory review.

The International Summit on Human Gene Editing convened by the National Academies of Sciences,
Engineering, and Medicine in December 2015 established principles distinguishing somatic (non-
heritable) CRISPR therapy—deemed acceptable to pursue—from germline editing, for which a
moratorium was recommended. Simultaneously, early work demonstrated that CRISPR could precisely
correct disease-causing mutations in patient-derived haematopoietic stem cells for sickle cell
disease and beta-thalassaemia ex vivo, pointing directly toward the therapies eventually approved
in 2023.

The CRISPR editing tool was recognised with the Nobel Prize in Chemistry in 2020, awarded jointly
to Jennifer Doudna and Emmanuelle Charpentier.