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Lander Weighs in on Issues Raised by Germline Genome Editing

This article has been corrected to clarify Eric Lander's position on the 1975 Asilomar conference, the subsequent recombinant DNA research moratorium, and his support for continued CRISPR/Cas9 laboratory research.

NEW YORK (GenomeWeb) – Eric Lander is the latest voice to chime in on the ethics of human germline editing. In an essay published yesterday in the New England Journal of Medicine, Lander, the director of the Broad Institute, laid out four issues whose resolution he thinks will be key to determining whether or not humans should edit the human germline.

With an international conference scheduled for this fall by the National Academy of Sciences and the Institute of Medicine to discuss wide-ranging implications of human germline editing, Lander voiced the need for a framework to evaluate the topic. He was careful to point out that the 1975 Asilomar Conference led to a moratorium on laboratory research; Lander wrote that research on CRISPR/Cas9 should continue and that the current debate concerns only "clinical applications to human beings that result in permanent changes to the human gene pool."

He offered four key issues to consider on that topic: technical feasibility, compelling medical need, the rights of parents over their children's genetic makeup, and morality, which he loosely defined by enumeration. His comments on these issues largely argued against the modification of the human germline at this point in time.

His essay follows several high-profile essays calling for restraint in using genome editing technologies, namely CRISPR/Cas9, to make heritable changes in the human germline. The journals Science and Nature published opinions from leading scientists in the field in anticipation of studies rumored to be using CRISPR/Cas9 to edit human germlines.

In April, scientists led by Puping Liang of Sun Yat-sen University in China proved the rumors to be true when they published a paper in Protein & Cell demonstrating that they had used CRISRP/Cas9 in non-viable human zygotes to edit the gene causing beta-thalassemia, but noted a concerning amount of off-target activity. The study was evidence that germline editing technology is far from ready, Lander said, adding that "even with improved accuracy, the process is unlikely to be risk-free."

Lander wrote at length about whether a medical need could outweigh the risks involved with germline editing.

"Though avoiding the roughly 3,600 rare monogenic disorders caused by known disease genes is a compelling goal, the rational for embryo editing largely evaporates under careful scrutiny," he said.

Pre-implantation genetic diagnosis offered a much safer alternative in the rare cases presented, he said. Eliminating (or adding) genes that could reduce risk of more common, chronic conditions like cancer or diabetes is another potential application of germline editing; however, the universal effect on the body of many gene variants is unknown and in some cases genes may be both beneficial for one condition and deleterious for another. Still, Lander said that eliminating the ε4 variant of the APOE gene, which might lead to lower risk for Alzheimer's and cardiovascular disease and providing null alleles at the PCSK9 gene, which could reduce the risk of heart attack could be beneficial.

Lander also considered whether synthetic biology could engineer new, beneficial gene circuits and whether non-medical traits might be changed, but backed off of any endorsement.

"Mistakes would be inevitable, and there would be no way to recall novel genes from the human population," he said. "Nonnatural genetic modifications hold even bolder prospects — and risks."

The "right to decide" and morality were also issues Lander raised, but he did not elaborate on them, leaving questions about the consent of future generations and privilege of access to such a technology for others to answer.

"It has been only about a decade since we first read the human genome," Lander, who was a top lieutenant in the Human Genome Project, wrote. "We should exercise great caution before we begin to rewrite it."