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Molecular Ethics: CRISPR Genome Editing

The capacity to edit human genomes is at our doorstep. As societies debate the relevant ethics, the scientific community should focus on informing the public about the complex biotechnology involved.

Five years ago this month, Jennifer Doudna and Emmanuelle Charpentier published their landmark paper describing a novel and powerful strategy for programmable gene editing—CRISPR/Cas9. It signified a monumental leap forward in the field of molecular biology, with applications for research and medicine alike. But while CRISPR has been readily adopted in laboratory research, there are many ethical concerns associated with its use in treating human disease.

As societies continue to debate the ethics involved, numerous and diverse groups—policymakers, religious institutions, clinicians, legal experts, the general public—will all have an interest in the outcome. For its part in the debate, the scientific community has a responsibility to ensure the public has the necessary awareness to understand and debate gene editing. As tomorrow’s scientists, ECRs must therefore be committed to understanding and communicating the relevant science underpinning the issue as well. This is especially critical since it is likely that genome editing will become reliable enough for general use in humans within the career span of today’s young scientists. What follows is hardly a comprehensive review of the ethical complexities at play, but rather, an overview of their special significance for those in the ECR community.

Nonmaleficence (first, do no harm)

The foremost tenet of the Hippocratic Oath, nonmaleficence underpins a frequently raised concern regarding use of CRISPR in humans: the risk of patient harm due to off-target gene editing. While highly precise, CRISPR is not yet perfect, meaning that undesirable mutations could unknowingly be introduced. For researchers, this concern is especially prickly—evoking memories of the Jesse Gelsinger case (in which unanticipated consequences led to a patient’s death in the first gene therapy trial). But this technical hurdle is likely to be resolved by future fine-tuning, meaning that ECRs will be tasked with evaluating ongoing progress and determining the technology’s eventual readiness for various clinical trials.

The germline problem

At the heart of the debate lays concern over germline editing. By altering the genome of an embryo, not only would all of the resulting individual’s somatic tissues be changed, but all germinal tissue as well. Consequently, all descendants will be irrevocably modified (without their consent). The ethical implications posed by such a scenario are difficult to overstate. Hence, the U.S. has been cautious in pursuing human embryo gene editing—reminiscent of Paul Berg’s 1975 Asilomar Conference (which placed a self-imposed moratorium on recombinant DNA research). This month, however, in the first open break with deferment policy, two U.S. research groups published a study which utilized CRISPR to alter human embryos. Recognizing the significance of this work, many news media outlets reported the findings as a breakthrough.

Numerous commentators, both scientist and non-scientist, have decried attempts to edit the human germline, reflecting widespread antipathy toward the issue. Therefore, to limit unnecessary delay in its clinical application, ongoing research should investigate uses for this technology that are not ethically objectionable. For example, two approaches which avoid the germline pitfall include directly injecting the system into affected tissue of a patient or editing the genomes of biopsied adult cells ex vivo. As a historical example, consider the stem cell research controversy from the previous decade. After a firestorm of public debate over the ethics of harvesting human fetal tissue, scientists ultimately reverse-engineered stem cells from adult tissues, enabling stem cell research to proceed without requiring fetal tissues. Through dialogue and efforts to find alternatives to ethically sensitive scenarios, the science community can help to limit unnecessary ethical controversies in the future.

Human enhancement: insight from Star Trek

Using CRISPR technology to edit human genetics in ways beyond what might reasonably be considered “curing disease” is a highly provocative ethical concern. Thinking on this issue lately, I was struck while viewing Star Trek: The Next Generation on television one evening. In the episode “The Masterpiece Society” the U.S.S. Enterprise encounters a planet in a state of seismic turmoil. The inhabitants request assistance to save their crumbling world and the crew agrees. Beaming to the surface, they find a colony of individuals attempting to create a utopia through genetic engineering. In their population, there is no disease and every individual is perfectly attuned for a designated purpose. Yet still unable to save their planet, it takes the Enterprise’s chief engineer, Geordi La Forge (LeVar Burton), to stabilize the planetary fractures and rescue the colony.

The crux of the story lies in the sad irony that their savior, La Forge, is congenitally blind and sees using a prosthetic visor. Being thus genetically flawed, he would never have been allowed to even exist in their world. In the episode’s poignant final exchange, a colonist explains: “our founders wished that no one have to suffer a life with disabilities.” La Forge’s response captures the central message of the story: “Who gave them the right to decide whether or not I should be here? Whether or not I might have something to contribute?”

In evaluating how to proceed in the era of human gene editing, we’d do well to recall this sentiment. Simply because we can act doesn’t always mean we should, especially with our genome at stake. We can never know all the eventualities which follow the alteration of a person’s genome for future generations; thus, we must take great care making even the most well-meaning of alterations.

The fiduciary scientist

CRISPR isn’t the first and won’t be the last bioethical quandary. There may be an even greater challenge to our ethical conscious just over the horizon, one which we cannot yet even conceive. Then, as now, it will require scientists to engage in civic discourse and offer their expertise to enable others to make informed decisions. Those in the profession should consider it their fiduciary duty to serve as mediators between the complex world of science and their communities. For ECRs, this responsibility will remain as imperative as ever.

 

Featured image: Geordi’s Visor. Obtained via flickr under a CC BY-SA 2.0 license

References

Jennifer Doudna faculty webpage. University of California Berkley website.

Emmanuelle Charpentier faculty webpage. Max Planck Institute for Infectious biology website

Jinak M. et al. (August 17, 2012) A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science. Vol 337, Issue 6096

Genome Editing with CRISPR-Cas9. YouTube media by McGovern Institute for Brain Research at MIT

Rodriguez E (March 24, 2016) Ethical Issues in Genome Editing using Crispr/Cas9 System. J Clin Res Bioeth 7:266. doi:10.4172/2155-9627.1000266

The Hippocratic Oath. Wikipedia page

Jesse Gelsinger Wikipedia page

Zhang, S. (December 1, 2015). Crispr Is Getting Better. Now It’s Time to Ask the Hard Ethical Questions. Wired website

Human germline editing. Wikipedia page

National Academies of Science (2017) Human Genome Editing: Consensus Study Report.

Kaiser, J. (February 14, 2017) U.S. panel gives yellow light to human embryo editing.  Science Health Policy. 10.1126

Asilomar Conference on Recombinant DNA. Wikipedia page

Hong, M. et al (August 2, 2017). Correction of a pathogenic gene mutation in human embryos. Nature doi:10.1038/23305

Beasley D. (August 2, 2017). U.S. scientists able to alter genes of human embryos. Reuters

Lanphier, E. et al (March 12, 2015). Don’t edit the human germ line. NATURE COMMENT

Foht, B. (December 4, 2015) The Case Against Human Gene Editing. National Review

Bioethics Observatory – Institute of Life Sciences UCV (February 3 2016). Genome editing CRISPR-Cas9 technique. Biomedical, ecological and ethical considerations

Cyranoski, D. (November 15, 2016) CRISPR gene-editing tested in a person for the first time. NATURE NEWS

Takahashi, K. and Yamanaka M. (August  25, 2006). Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell. Vol 126, Issue 4

Star Trek: The Next Generation Wikipedia page

IMDb Website. “The Masterpiece SocietyStar Trek: The Next Generation

 

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