One day after publication of a landmark study detailing the first-in-the-U.S. use of CRISPR (clustered regularly interspaced short palindromic repeats) to repair a germline mutation in human embryos created through in vitro fertilization, 11 genetics-focused professional organizations are calling for researchers to use caution in applying the technology.

The 11 organizations have issued a policy statement stopping short of calling for a ban on human germline genome editing. But the groups added that future clinical application of the technology should not proceed without at least a “compelling” medical rationale, a base of evidence that justifies clinical use, an ethical justification, and the solicitation and incorporation of stakeholder input through a “transparent public process.”

“Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing,” the organizations declared.

The policy statement also declared it “inappropriate” to use germline gene editing that would result in human pregnancy. However, the organizations urged against efforts to prohibit public funding of research into human germline genome editing.

The statement, “Human Germline Genome Editing,” was published yesterday in The American Journal of Human Genetics. The journal is owned and controlled by the American Society of Human Genetics (ASHG), one of the 11 organizations that crafted the policy statement. 

“While germline genome editing could theoretically be used to prevent a child being born with a genetic disease, its potential use also raises a multitude of scientific, ethical, and policy questions. These questions cannot all be answered by scientists alone, but also need to be debated by society,” Derek T. Scholes, Ph.D., ASHG’s director of science policy, said in a separate statement issued by his organization.

Debate Rekindled

That debate was rekindled this week, following publication in Nature on Wednesday of “Correction of a Pathogenic Gene Mutation in Human Embryos” by researchers from Oregon Health and Science University (OHSU), the Salk Institute for Biological Studies, and South Korea's Institute for Basic Science.

The team of 31 researchers—led by Shoukhrat Mitalipov, Ph.D., of the Center for Embryonic Cell and Gene Therapy at OHSU—carried out the first American study showing that modifying single-gene defects using the gene-editing technology CRISPR has the potential to be safe and accurate enough to use in human embryos.

“Overall, this is an impressive paper, but one that also raises the stakes on future CRISPR use in humans,” Paul Knoepfler, Ph.D., of University of California, Davis, School of Medicine, stated on his lab’s stem cell blog, The Niche. “Perhaps it will catalyze more research on CRISPR in human embryos. That could be both good in the sense of learning more, but also risky in terms of not everyone doing such a good job as these authors did in considering ethical implications and even in the technological level they used. Also, where will everyone get eggs and sperm for studies?”

Dr. Knoepfler noted the researchers’ expressed hope to use germline genome editing for human reproduction with specific clinical goals.

“While they also included some appropriately cautionary statements about future clinical use, at the same time some language such as envisioned possible “rescue” of embryos was potentially concerning,” Dr. Knoepfler added. “I am highly skeptical that gene editing in the human germline can make sense as a safe and more effective approach than embryo screening by PGD and PGS [emphasis in original].”

PGD and PGS refer to, respectively, preimplantation genetic diagnosis and preimplantation genetic screening.

Dr. Knoepfler also said the odds were “better than 50-50” that the Mitalipov-led research will spark a backlash and possibly proposed restrictions in the U.S. by conservatives and others who have faulted embryonic research on ethical grounds.

‘Unintended Effects’

In a statement to Catholic News Agency earlier this week, Rev.Tadeusz Pacholczyk, Ph.D., director of education for the National Catholic Bioethics Center, expressed moral objection to germline genome editing on embryos: “Their value as human beings is profoundly denigrated every time they are created, experimented upon, and then killed. Moreover, if such embryos were to grow up, as will doubtless occur in the future, there are likely to be unintended effects from modifying their genes.”

The 11 organizations acknowledged numerous ethical issues arising from human germline genome editing, including:

  • Exposing individuals to potentially harmful health consequences, since the magnitude of the potential risks of off-target or unintended consequences is yet to be determined.
  • Diverting public funds from the research, which the groups concluded could degrade or omit mechanisms that ensure that research is subject to ethical oversight, such as research ethics boards, and remains public, ensuring oversight and transparency.
  • Ensuring against eugenics, which the groups acknowledged “could be used to reinforce prejudice and narrow definitions of normalcy in our societies.”
  • Ensuring the technologies do not worsen inequalities within and between societies, noting: “Unequal access and cultural differences affecting uptake could create large differences in the relative incidence of a given condition by region, ethnic group, or socioeconomic status.”

“At a minimum, the potential for harm to individuals and families, ramifications on which we can only speculate, provide a strong argument for prudence and further research,” the policy statement asserted. “By proceeding with caution, we can ensure better understanding of the potential risks and benefits of gene editing from a scientific perspective and, as such, provide families with a more fulsome exercise of their autonomous decision making through the consent process.”

The statement added: “We encourage ethical and social consideration in tandem with basic science research in the upcoming years.”

Last October, You Lu, M.D., and colleagues at Sichuan University’s West China Hospital in Chengdu launched the first known clinical trial using CRISPR to treat patients—specifically, knocking out a gene encoding the programmed death protein 1 (PD-1) in patients with non-small-cell lung cancer.

Groups joining ASHG in issuing the policy statement included the Association of Genetic Nurses and Counsellors, the Canadian Association of Genetic Counsellors, the International Genetic Epidemiology Society, and the National Society of Genetic Counselors.

Additional groups authoring the policy statement were the American Society for Reproductive Medicine, the Asia Pacific Society of Human Genetics, the British Society for Genetic Medicine, the Human Genetics Society of Australasia, the Professional Society of Genetic Counselors in Asia, and the Southern African Society for Human Genetics.

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