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A bioethicist breaks down the first human germline genome editing experiment

CRISPR People: The Science and Ethics of Editing Humans

Henry T. Greely
MIT Press
2021
400 pp.
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On 25 November 2018, He Jiankui, a biophysicist at Southern University of Science and Technology in Shenzhen, China, announced that his laboratory had pulled off a previously unthinkable achievement: the successful modification of the germline genome of two living humans. Two children, female fraternal twins known by the pseudonyms Lulu and Nana, had been born with altered copies of the C-C motif chemokine receptor 5 (CCR5) gene, having been subjected to a CRISPR-Cas9–based genome editing protocol.

The purported purpose of this feat was to protect the children from contracting human immunodeficiency virus (HIV). Packed with facts and analysis, Henry Greely’s CRISPR People examines what He did, explains why Greely believes it was wrong, describes the world’s reaction, and details what we can and should do about work like this in the future.

Greely draws a parallel between the birth of Lulu and Nana and the 1996 birth of Dolly, the cloned sheep, noting that in both instances, the respective breakthroughs underlying each achievement were unimaginable right up until they were attained. Before Dolly, we could clone frogs with some success, but mammalian biparental reproduction just could not be replaced. And then, suddenly, it had been done.

The scientific feasibility of He’s experiment was not necessarily in question. We had known for some time that human eggs could undergo in vitro fertilization, for example, and that the resulting embryos could be genetically manipulated. What we did not know was that someone would ignore the consensus of every major scientific and medical organization and forge ahead with an experiment in humans. And then, someone did just that.

“I stand by the comments I made to the press just after the news broke [of the twins’ birth],” writes Greely. “[T]he experiment was ‘criminally reckless’ as well as ‘grossly premature, and deeply unethical.’” Citing the Nuremberg Code and the Helsinki Declaration, he argues that the risk-benefit ratio for such an experiment is simply too high.

CCR5 Δ32, the naturally occurring CCR5 mutation that He sought to replicate in his experiment, is a 32–base pair deletion in the coding sequence of the gene, an alteration that produces a nonfunctional protein. Such mutations afford significant, although incomplete, protection against HIV infection in individuals with two copies of the deletion. But He’s experiment did not replicate the natural variant: One twin had two different mutations, and the other had one normal copy of CCR5 and one copy containing a different mutation.

Even had He succeeded, Greely notes that HIV transmission can occur via non-CCR5-mediated pathways, that there are potential side effects of the CRISPR editing process, and that some benefits are conferred by wild-type CCR5. Furthermore, the CCR5 Δ32 mutation may increase one’s risk of death from influenza (1), which is a more likely cause of death in China than HIV infection.

“Evolution has been working toward optimizing the human genome for 3.85 billion years. Do we really think that some small group of human genome tinkerers could do better without all sorts of unintended consequences?” summarized Francis Collins in 2015 (2). Greely appears to feel similarly, although he does not go so far as supporting a total ban on such technologies. “I think this argument cannot be based directly on the consequences of human germline genome editing but instead must be founded on the belief that such a procedure is inherently wrong,” he writes. “I accept that people may hold such a position, but I do not see how they can hold it consistently with acceptance of a great deal of modern life, modern medicine, and modern reproduction.”

Trained as an attorney, Greely is among today’s best thinkers in the field of bioethics. His writing is straightforward, conversational, and technically accurate. What it does not, and perhaps cannot, provide is a simple answer to the complex questions posed by human genome editing. Indeed, his penchant for considering every argument and counterargument precludes a simple conclusion or a straightforward way of assessing similar ethical dilemmas that we will no doubt be faced with in the future. Meanwhile, readers seeking a broader view of the genome editing landscape may wish to consult Kevin Davies’s Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing (3). Nevertheless, with CRISPR People, Greely provides an exquisite view of the wide-ranging issues at play in this particular case.

About the author

The reviewer is at the Department of Biology, San Francisco State University, San Francisco, CA 94132, USA.