Gene editing technology uses an adaptive defense mechanism from bacteria for a novel new purpose: the precise editing of isolated genetic defects in DNA. The technology, clustered regularly interspaced palindromic repeats (CRISPR)/Cas9, “has been widely studied in animals, and may one day be very beneficial in humans. But use of this technology in human beings is premature,” says Dennis M. Sullivan, MD, MA (Ethics), director of the Cedarville University’s Center for Bioethics.

In 2015, Chinese researchers used this method to treat beta-thalassemia in excess embryos from fertility treatments.1 “Even though they did this research in tripronuclear zygotes, which are not implantable, they received worldwide condemnation,” notes Sullivan.

The National Academies of Sciences, Engineering, and Medicine held a summit on human gene editing in December 2015, and called for an international moratorium on human CRISPR research.2

“Amazingly, within a few months, the Human Fertilization and Embryo Authority in the U.K. approved using CRISPR in human embryos up to 14 days, completely bypassing the ethical concerns of the Washington forum,” says Sullivan.

Charis Eng, MD, PhD, FACP, chair of the Genomic Medicine Institute and director of the Center for Personalized Genetic Healthcare at Cleveland (OH) Clinic, notes that many researchers use CRISPR/CAS9 technology as a tool to engineer mutations in cancer cell lines to study the effects.

“This is not controversial, nor unethical,” she says. “What is controversial is the research on human embryos, or even earlier stages, to alter genes to ‘play God.’”

The following are some frequently voiced ethical objections:

If human embryos are used, these will affect the germ line and all subsequent generations if the embryos are implanted.

“The central ethical concern relates to the unknown consequences for future generations,” says Sullivan.

Unwanted and unpredictable side effects are likely.

Eng explains, “When one edits, often there are ‘off target’ effects.” Other changes, or even mutations, might be introduced in the gene of interest, or even elsewhere.

Informed consent of any affected offspring will be impossible to obtain.

This can only be mitigated by ensuring that germ line therapies are as safe as possible. “But the full risks and/or benefits of such treatments will not be known until its first recipients grow into adulthood,” says Sullivan.

Sullivan cautions that, although CRISPR/CAS9 holds great promise, “we should not open this Pandora’s Box until we truly understand what we may unleash.”

Eng believes that the “hoopla” is best addressed by forming international committees for guidelines on appropriate use of the technology for the greater good.

Eng points to a similar controversy surrounding recombinant DNA years ago, which was resolved by adherence to guidelines.

“Much good has come, to the point that one doesn’t even think twice about using this technology in research routinely,” she says.

REFERENCES

  1. Liang P, Xu Y, Zhang X, et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & Cell 2015; 5(6):363–372.
  2. National Academies of Sciences, Engineering, and Medicine. 2016. International summit on human gene editing: A global discussion. Washington, DC: The National Academies Press. doi:1017226/21913.

SOURCES

  • Dennis M. Sullivan, MD, MA (Ethics), Director, Center for Bioethics, Cedarville University. Phone: (937) 766-7573. Email: sullivan@cedarville.edu.
  • 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.