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Pediatric Bioethics

January 2019

The Ethics of Germ Line Gene Editing

Author: John D. Lantos, MD | Director of Pediatric Bioethics | Professor of Pediatrics, UMKC School of Medicine

The fundamental question in the debate about germ line gene editing (GLGE) is this:  Should we just accept as an unalterable fact that there will always be some babies who will be born with genetic diseases?

Attempts to tinker with the genetic lottery of human reproduction raise fears of dystopias, playing God, designer babies and other nightmarish scenarios. When scientists first developed in vitro fertilization (IVF), Leon Kass invoked Nazi horrors by accusing IVF pioneers of “seeking the final solution to the miseries of the human condition,” and warned of “limitless, no-holds-barred, self-modification.”1 Hurlbut worries that GLGE “denigrates that child and devalues the richness of humanity itself.”2 Eng worries that GLGE will increase genetic disparities.3

Such innovations also trigger utopian hopes. Metzl imagines that we soon will be able to “eliminate most single gene mutation diseases and likely increase children’s chances of living a longer and healthier life.”4 Harris hopes we will “avert the suffering and death caused by terrible single-gene disorders.”

Neither the utopian dreams nor the dystopian nightmares have come true in the past. We now live in a world where amniocentesis, IVF and pre-implantation genetic diagnosis are used safely and effectively to expand reproductive choice and improve child health.

The recent report from China of the use of GLGE stimulated two very different types of criticisms. One line of criticism focused on issues about the integrity and quality of the science.  Such critics pointed out that the study design was flawed, the informed consent inadequate, and questioned whether the results, which were released without peer-review, were fraudulent.  There were also concerns about the investigators’ financial conflicts of interest. Those are all important questions, but not unique to GLGE. 

A second set of concerns focused on GLGE itself, and whether reproduction is so sacrosanct that any attempt to alter it is straightforwardly unethical. I will briefly discuss both sets of concerns.

If Professor He’s research is shown to be fraudulent, this will go down in history as just another scandal in a long line of research scandals. On the other hand, if He actually safely altered a gene and conferred immunity to HIV, the implications will be more complex. If GLGE could be done safely and effectively, is there a coherent argument for not replacing those genes in germ line cells?

Arguments for and against germ line gene editing

Two quite different sorts of arguments are made against GLGE. One is that it might not be safe and, as a result, may harm the babies who we are trying to help. Such risk-benefit assessments are an irreducible feature of medical research. We usually respond to such concerns by careful oversight of the science with good pre-clinical studies, careful study design and meticulous monitoring for safety. Critics of GLGE argue that, in this case, the risks of the research are too great, the research subjects cannot consent, and therefore any research itself is unethical. Such concerns would make it impossible to do the science that could make GLGE safe. Taken seriously, though, they would make it impossible to do most pediatric research.  After all, children can never consent and all research has risks. But without careful, high-quality scientific research, there would be no medical progress and all children would be worse off. 

A second type of argument focuses on concerns that would arise if such interventions are studied and shown to be both safe and effective. Questions then arise about its proper uses.  Should it be used only to treat disease? Would it be used for enhancement? Darnovsky fears that the technology would “escape from regulatory limits” and be used for “market-based eugenics that would exacerbate already existing discrimination, inequality, and conflict.”5

A number of professional organizations have guidelines for the appropriate use of GLGE.6,7 They recommend that it only be used when 1) there are no reasonable alternatives; 2) we know that the genes to be edited cause or strongly predispose to a serious disease; 3) there is evidence that altering the gene will help; and 4) there is rigorous oversight of the trials and long-term follow-up. By these criteria, curing sickle cell would be acceptable. Enhancing intelligence would not. There will inevitably be gray zones. Decisions will need to be scrutinized and judgment calls made. Still, with such sensible guidelines, GLGE could be studied in a way that will allow us to understand and realize the benefits, and minimize the risks.    

References:

  1. Making Babies – The New Biology and the “Old” Morality. Kass L. Publ Int 1972. 16:18-56.

  2. The Chinese Gene Editing Experiment Was an Outrage. The Scientific Community is to Blame. Hurlbut JB, Jasanoff S, Saha K. Washington Post, Nov 29, 2018. https://www.washingtonpost.com/outlook/2018/11/29/chinese-gene-editing-experiment-was-an-outrage-broader-scientific-community-shares-some-blame/?noredirect=on&utm_term=.4cf58fd44728. Accessed 12-15-2018.

  3. Who Will CRISPR Benefit? How to Prevent this Life-saving Technology from Creating Gender and Geographic Disparities. Eng K, Siwo G. Genetic Literacy Project, July 10, 2018.  https://geneticliteracyproject.org/2018/07/10/who-will-crispr-benefit-how-to-prevent-this-life-saving-technology-from-creating-gender-and-geographical-disparities/.  Accessed 12-12-2018. 

  4. Is Sex for Reproduction About to Become Extinct? Metzl J. Leapsmag, 11/29/2018. https://leapsmag.com/is-sex-for-reproduction-about-to-become-extinct/. Accessed 11/29/18

  5. Con: Do Not Open the Door to Editing Genes in the Future. Darnovsky M. National Geographic, August 2006.  https://www.nationalgeographic.com/magazine/2016/08/human-gene-editing-pro-con-opinions/.  Accessed 12-14-2018.

  6. Human Germline Genome Editing. Ormond KE, Mortlock DP, Scholes DT et al. Am J Hum Genet 2017; 101: 167-76.

  7. National Academy of Sciences. With Stringent Oversight, Heritable Germline Editing Clinical Trials Could One Day Be Permitted for Serious Conditions; Non-Heritable Clinical Trials Should Be Limited to Treating or Preventing Disease or Disability at This Time. Feb 14, 2017. http://www.nasonline.org/news-and-multimedia/news/Human-Genome-Editing-Report.html. Accessed 12-16-15.