EXECUTIVE SUMMARY

The first-known experiment creating genetically modified human embryos in the U.S. using a gene-editing tool called CRISPR reignited ethical debate on this type of research. Some ethicists voice concerns about the following:

• unknown and potentially unacceptable risks to individuals modified in this way;

• off-target effects, which can introduce mutations in other genes;

• the potential to use gene editing for trivial reasons.


The first-known experiment to create genetically modified human embryos in the U.S., using a gene-editing tool called CRISPR, has reignited the ethical debate on this type of research.1

“Science and technology usually, and often correctly, hate ‘no’ for an answer. But the modification of human embryos is special and worrisome,” says Kenneth W. Goodman, PhD, FACMI, director of University of Miami (FL)’s Institute for Bioethics and Health Policy.

There are unknown and potentially unacceptable risks to individuals modified in this way, says Goodman. “There are no clear review criteria for separating traits from maladies, or human enhancement from disease prevention.”

Clinical trials on genome editing of the human germline might be ethically permissible, but only for serious conditions under stringent oversight, concluded a recent report from the National Academies of Sciences, Engineering, and Medicine.2 Goodman says a “time out” is needed to gain insight into the complex ethical, legal, and social issues at play: “That is not a ‘no.’ It’s a plea for caution.”

Charis Eng, MD, PhD, FACP, chair of the Genomic Medicine Institute and director of the Center for Personalized Genetic Healthcare at Cleveland (OH) Clinic, says, “CRISPR/CAS9 gene editing has captured the imagination of clinicians and the public alike, for its promise in editing gene mutations that cause fatal diseases.” Ethical concerns center on off-target effects, which can introduce mutations in other genes, and the potential of using gene editing for trivial reasons, such as good looks.

“A recent paper from a multinational collaboration might address the early generation CRISPR/CAS9 off-targeting effects,” says Eng.3 In this paper, the investigators were able to show minimal to trivial off-target effects by introducing the enzyme and guide RNA at the gamete stage. “I suspect that as this technology, and even next generation CRISPR/CAS9, is developed, the off-target effects will become nonexistent,” says Eng.

Eng sees a parallel with the way in vitro fertilization (IVF) was initially viewed as shocking and controversial, but now is commonplace.

“When they announced the first IVF baby born, cries of ethics, ‘test tube baby,’ and ‘designer babies’ were heard around the world,” says Eng. Over time, IVF was shown to be safe, successful, and performed within accepted guidelines. “The accusatory cries died down quickly, and an obstetrical standard of care was born,” says Eng.

As more research is conducted, concerns about clinical trials for gene editing for devastating diseases may be similarly alleviated. “When a disruptive new technology emerges in clinical care, skepticism and controversy often greet it,” says Eng.

The U.S. has currently barred clinical usage or clinical trials for CRISPR/CAS9 editing of embryos.

“Should safety be shown, and investigators and clinicians demonstrate that they follow agreed-upon ethical guidelines, then one day such gene editing could become standard of care,” says Eng.

Eng says the technology should be thought of for somatic, not just germline, gene editing. “Imagine being able to take out malignant stem cells and editing the driver somatic mutations to the normal gene sequence,” she says. “We might be curing cancer without any chemotherapy or targeted therapy.”

REFERENCES

1. Lenford H. CRISPR fixes disease gene in viable human embryos. Nature 2017; 548(7665):13-14.

2. National Academies of Sciences, Engineering, and Medicine. 2017. Human genome editing: Science, ethics, and governance. Washington, DC: The National Academies Press.

3. Ma H, Marti-Gutierrez N, Park SW, et al. Correction of a pathogenic gene mutation in human embryos. Nature 2017; 548(7668):413-419.

SOURCES

• Charis Eng, MD, PhD, FACP, Chair, Genomic Medicine Institute/Director, Center for Personalized Genetic Healthcare, Cleveland (OH) Clinic. Phone: (216) 444-3440. Fax: (216) 636-0655. Email: engc@ccf.org.

• Kenneth W. Goodman, PhD, FACMI, Director, University of Miami Miller School of Medicine Institute for Bioethics and Health Policy. Phone: (305) 243-5723. Email: kgoodman@med.miami.edu.