How CRISPR Actually Works: From Bacterial Immunity to Gene Therapy

In November 2018, He Jiankui announced at a conference in Hong Kong that he had used CRISPR to edit human embryos that were subsequently implanted and carried to term. Two girls, referred to as Lulu and Nana, had been born with edits to the CCR5 gene — a co-receptor used by HIV to enter cells. A third child was subsequently born from the same program.

The scientific and ethical response was immediate and nearly unanimous condemnation.

The distinction that matters here is between *somatic* editing and *germline* editing. Casgevy is somatic: it edits blood cells in one person, and those edits don't pass to their children. Germline editing — editing embryos or gametes — means the changes are heritable. Every cell in every future descendant carries the edit.

The concerns about He Jiankui's work were multiple. CCR5 editing doesn't provide complete HIV immunity (HIV can also use an alternative receptor, CXCR4). The editing was mosaic — different cells had different edits. Potential off-target effects were not adequately characterized. And the medical need wasn't urgent — the girls' HIV-positive father could not have transmitted the virus through IVF procedures. He had, in essence, conducted an unauthorized human experiment on children who could not consent.

He Jiankui was convicted of illegal medical practice in China in 2019 and sentenced to three years in prison.

The broader question remains unresolved. Germline editing *could*, in principle, prevent inherited conditions from being passed to children. Parents who are both carriers of a severe recessive disease — say, Tay-Sachs, or cystic fibrosis — might one day have the option to prevent the disease from appearing in their children at the embryo stage, rather than relying on selection (PGT) or accepting the odds.

The scientific community has called for a moratorium on clinical germline editing until safety and societal consensus questions are resolved. The International Commission on the Clinical Use of Human Germline Genome Editing (2020) concluded the field is not ready — technically or ethically — for clinical use.

What "ready" looks like, and who gets to decide, is the open question. The technology won't wait for perfect answers.

Germline Editing: He Jiankui, Lulu and Nana, and Where the Line Gets Drawn

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