The Genie Is Out of the Bottle

The Genie Is Out of the Bottle 150 150 IEEE Pulse

In my July/August 2014 editorial in IEEE Pulse [1], I opined on the very real possibility of genetic editing of human embryos with the newly discovered CRISPR/Cas9 gene editing system. My opinion was based on reported research in the Yunnan Key Laboratory of Primate Biomedical Research to create surrogate models of human neurological disease by CRISPR editing of macaque embryos. It was clear the step would be small from a macaque to genetic editing of a human embryo, but I predicted at the time that technical challenges may slow progress, and it would likely be several years before CRISPR editing of human embryos would be possible.
Obviously, I was wrong! Junjiu Huang, a researcher at Sun Yat-Sen University in Guangzhou, reported recently in the online journal Protein & Cell [2] on his team’s attempt to edit mutations with the CRISPR/Cas9 system in the HBB gene of in vitro fertilized human embryos. The embryos were nonviable based on the presence of an extra set of chromosomes. HBB encodes the human b-globin protein, and mutations in this gene are responsible for b-thalassemia, a potentially fatal blood disorder. Gene editing with CRISPR/Cas9 in human adult cells and animal embryos is well studied and has been shown to be an easy-to-use, high-efficiency, high-precision gene editing tool. Yet, the researchers reported the process in human embryos was relatively inefficient, with a surprising number of “off-target” mutations assumed to be from the CRISPR/Cas9 complex acting on other parts of the genome.
Despite these shortcomings, Huang and his team have blazed the trail forward. It will not be long before the technical challenges met by Huang are overcome and gene editing of human embryos becomes routine. The implications of human germline editing are transformative, unpredictable, and far reaching. Optimistically, this ability could be applied to eradicate a devastating genetic disease before birth. However, germline changes are inheritable and could have an unpredictable effect on future generations, particularly if off-target mutations are not fully eliminated. The elegant simplicity and ease of gene editing via CRISPR/Cas9 substantially lowers the technical barriers that normally would impede widespread adoption, thus making the technique broadly accessible to anyone with knowledge of genetics and access to basic molecular biology tools. Having this powerful gene-editing technology within easy reach of many of potential practitioners raises hope that the technology will find applications that better humankind but at the same time heightens the concern that gene-editing research on human embryos could be a slippery slope toward unsafe or unethical uses of the technique. In response, leading genetic researchers have called for a moratorium on human embryo editing to offer time for reflection on the ethics of such research and set up guidelines for its conduct [3].
It is our collective responsibility as biomedical engineers and scientists to join the conversation and be active in leading the dialogue on the moral and ethical implications of this powerful new technological ability. We must not be passive bystanders in this debate as the implications of this technological advance on humankind are simply too great. It’s imperative that we act now and not wait, as the genie is clearly out of the bottle and won’t be put back anytime soon.


  1. C. J. H. Brenan, “The brave new world of reproductive health,” IEEE Pulse, vol. 5, no. 4, p. 4, July/Aug. 2014.
  2. P. Liang, Y. Xu, X. Zhang, C. Ding, R. Huang, Z. Zhang, J. Lv, X. Xie, Y. Chen, Y. Li, Y. Sun, Y. Bai, Z. Songyang, W. Ma, C. Zhou, and J. Huang, “CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes,” Protein & Cell, vol. 6, no. 5, pp. 363–372, 2015.
  3. E. Lanphier, F. Urnov, S. E. Haecker, M. Werner, and J. Smolenski, “Don’t edit the human germ line,” Nature, vol. 519, pp. 410–411, 2015.