Genome Editing & the Ethics of CRISPR-Cas9

Description

This historical case uses the April 2015 publication on editing the genomes of non-viable human embryos by Junjiu Huang et. al. to explore the ethical issues surrounding the development of gene editing technologies and application to humans.

Body

In April 2015, scientists in China published a paper in an online journal, Proteins & Cells, about experiments editing the genomes of non-viable human embryos (Liang et al. 2015). The research team, led by Junjiu Huang, used an engineered enzyme complex, called CRISPR-Cas9, to target and edit the HBB gene that codes for human β-globin protein. Defects in that gene can lead to β-thalassaemia, a heritable blood disorder that can be fatal.

In 2012, scientists Jennifer Doudna and Emmanelle Charpentier developed the CRISPR-Cas9 bioengineered complex that was used by the researchers in China. The technology has been used in previous research on animal and adult human cells. The technology allows researchers to target a specific gene by binding and splicing the DNA at specific locations, and replacing or repairing the segment by inserting other molecules (Cyranoski & Reardon 2015).

In their research, Huang and his team used non-viable, single-cell human embryos, which they obtained from a fertility clinic. The embryos possessed an extra set of chromosomes because they had been fertilized by two sperm and thus could not develop beyond the first stages of development. Huang and colleagues' aim was to test whether the technology could reliably target defective genes and replace these genes with repaired sequences. Their results showed that only a small fraction of the 86 embryos used in the study had the replaced genetic material at the targeted gene. The researchers also found that there were many "off-target" mutations that might have been introduced in the genome as a by-product of the technological intervention (Cyranoski & Reardon 2015). These results led the researchers to conclude that clinical applications of the technology to human embryos were still premature.

The authors of the paper also claimed that the prestigious journals, Science and Nature, rejected their paper because of ethical objections to their research on human embryos, and specifically, because of ethical objections to any kind of germ line genetic modification. The editors at the journal, Proteins & Cells, justified publishing the paper by claiming that they verified the researchers' institutional approval and the consent forms from the embryo donors, and confirmed that the study was compliant with Chinese laws and the Declaration of Helsinki's set of ethical principles on human experimentation (Cressey & Cyranoski 2015).

Were the editors at Science and Nature right to decline to publish the research paper? Should the editors at Protein & Cells have refrained from publishing the paper? Should the individual scientists have conducted and reported their research at all? Did they violate any moral duties or obligations? Given the paper is now published, what should members of the scientific community do?

Discussion Questions:

  • Leading scientists called for a moratorium on research on human embryos using genome-editing technologies, such as CRISPR. What sorts of ethical concerns does a moratorium address? What are some goals that could be achieved? What do you think are the likely outcomes or consequences of a moratorium and of the technology?
  • Why did the editors at Science and Nature decided not to publish the paper? Were the editors at Protein & Cells too hasty in publishing the research on embryos? How should academic journals deal with potentially controversial research? What are their moral and social responsibilities?
  • Should non-scientist members of the public be included in the decision-making process about whether or not, and to what extent, research with genome-editing technologies should be restricted? What kinds of concerns might be overlooked if the decision-making process included only scientists? What sorts of insights may non-scientist members of the public bring to the discussion?
  • What should be the social and ethical responsibilities of the individual scientists involved in research with genome-editing technology? How can they best fulfill those responsibilities?

Bibliography

Baltimore, B. D., Paul Berg, Michael Botchan, Dana Carroll, R. Alta Charo, George Church, Jacob E. Corn, et al. "A prudent path forward for genomic engineering and germline gene modification." Science 348, no. 6230 (2015): 36-38. doi: 10.1126/science.aab1028

Cressey, David, and David Cyranoski. "Human-embryo editing poses challenges for journals." Nature. April 25, 2015. Accessed December 10, 2015. http://www.nature.com/news/human-embryo-editing-poses-challenges-for-journals-1.17429

Cyranoski, David, and Sara Reardon. "Chinese scientists genetically modify human embryos." Nature. April 22, 2015. Accessed December 10, 2015. http://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378

Doudna, Jennifer A., and Emmanuelle Charpentier. "The new frontier of genome engineering with CRISPR-Cas9." Science 346, no. 6213 (2014): 1258096. doi: 10.1126/science.1258096

Jasanoff, Sheila, J. Benjamin Hurlbut, and Krishanu Saha. "Human genetic engineering demands more than a moratorium." The Guardian. April 7, 2015. Accessed December 10, 2015. http://www.theguardian.com/science/political-science/2015/apr/07/human-genetic-engineering-demands-more-than-a-moratorium

Lanphier, Edward, Fyodor Urnov, Sarah Ehlen Haecker, Michael Werner, and Joanna Smolenski. "Don't edit the human germ line." Nature 519, no. 7544 (2015): 410. Accessed December 10, 2015. http://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111

Ledford, Heidi. "CRISPR, the disruptor." Nature 522. June 8, 2015. Accessed December 10, 2015. http://www.nature.com/news/crispr-the-disruptor-1.17673

Liang, Puping, Yanwen Xu, Xiya Zhang, Chenhui Ding, Rui Huang, Zhen Zhang, Jie Lv et al. "CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes." Protein & cell (2015): 1-10. doi: 10.1007/s13238-015-0153-5

Reardon, Sara. "Ethics of Embryo Editing Paper Divides Scientists." Nature. April 24, 2015a. Accessed December 10, 2015. http://www.nature.com/news/ethics-of-embryo-editing-paper-divides-scientists-1.17410

Reardon, Sara. "US science academies take on human-genome editing." Nature. May 18, 2015b. Accessed December 10, 2015. http://www.nature.com/news/us-science-academies-take-on-human-genome-editing-1.17581

Sarewitz, Daniel. "CRISPR: Science can't solve it." Nature 522. June 23, 2015. Accessed December 10, 2015. http://www.nature.com/news/crispr-science-can-t-solve-it-1.17806

Vogel, Gretchen. "Embryo engineering alarm." Science 347, no. 6228 (2015): 1301-1301. doi: 10.1126/science.347.6228.1301

Links

Embryo-Editing: The Ethics of CRISPR on Flipboard: https://flipboard.com/@naturenewsteam/embryo-editing%3A-the-ethics-of-crispr-27j1164kz

The National Academies of Sciences, Engineering, and Medicine - On Human Gene Editing: International Summit Statement: http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12032015a

Notes

The author wishes to acknowledge the contributions of Karin Ellison, OEC - Life and Environmental Sciences Editor, and Joseph Herkert, OEC Engineering co-Editor. They provided valuable input in selecting topics and crafting the resources.

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