A Closer Look at the ‘Gene-Edited Babies’ Controversy
Author: @cheeze molecule (translator)
Practical questions that Professor He Jiankui and other genome-editing researchers must face.
In late November, the reported birth of twin babies whose genes had been edited to make them resistant to HIV caused an uproar. It also ignited fierce debate over experiments using CRISPR, the laws governing them, and the ethical issues involved.
The controversy drew opposition, neutrality, and support. At the Second International Summit on Human Genome Editing, held a few days later, the organizing committee called the event “unexpected and deeply disturbing.” Researchers in the life sciences had mixed reactions, but most believed the experiment had been conducted prematurely and questioned its legality and safety. Nature recently led with six unresolved questions about He Jiankui and the gene-edited babies. Here is a closer look at those questions.
1. Is He Jiankui in trouble?
On November 27, the day before He Jiankui spoke at the Second International Summit on Human Genome Editing, the National Health Commission urged the Guangdong provincial government, where his institution, Southern University of Science and Technology, is located, to investigate. Two days later, China’s Ministry of Science and Technology ordered him to halt all scientific research. His actions had violated guidelines issued by the Ministry of Health in 2003, but at the time they did not fall under any explicit law or regulation. A university representative told an interviewer that the institution was “waiting for an official statement from the university” and offered no specific response, underscoring the complexity of the case. He Jiankui’s personal page was removed from the university website, and several links to information about him on departmental pages and in his profile stopped working.
He Jiankui responded: “I will remain in China, my homeland, and cooperate fully with all inquiries.”
Note: The original article was written in early December 2018. On December 30, 2019, the People’s Court of Nanshan District, Shenzhen, issued its first-instance judgment. It found He Jiankui and two other defendants guilty of illegal medical practice for jointly conducting human-embryo genome editing for reproductive purposes and carrying out reproductive medical procedures without authorization. All three were held criminally liable under the law.
2. How can the accuracy and authenticity of He Jiankui’s claims be established?
Many scientists said that verifying He Jiankui’s claims would require detailed comparisons of the babies’ genomes with those of their parents to determine what edits had been made. The identities of the babies and their parents were kept strictly confidential. Along with China’s stringent rules on human genetic resources, this gave He grounds to withhold the experimental data and prevented an independent investigation.
He Jiankui said his team could provide anonymized samples and open laboratory data, invite other researchers to investigate with them, and submit the raw data for third-party review.
3. How did CRISPR alter the twins’ genomes?
CRISPR consists of repeated sequences in prokaryotic genomes that also provide recognition sites for Cas nucleases. It is an immune defense that evolved through the long conflict between bacteria and viruses. Put simply, viruses can integrate their genes into bacteria and use bacterial cellular machinery to replicate. To remove these invading viral genes, bacteria evolved the CRISPR–Cas9 system, which can cut viral DNA out of their own genomes. After discovering this mechanism, researchers adapted it into CRISPR–Cas9 technology for editing human genes.
After analyzing the raw sequencing data discussed in He Jiankui’s presentation, Australian National University geneticist Gaetan Burgio concluded that the babies’ cells contained several different edited forms of CCR5, one of the main coreceptors used by HIV to enter cells. If CRISPR edited some early embryonic cells differently from others, or left some cells unedited, the babies would be mosaics: individuals with two or more genetically distinct cell populations.
The rationale for He Jiankui’s experiment was also questioned. In his presentation, he said that his approach to editing CCR5 with CRISPR was based on the Δ32 mutation. Some people naturally carry a 32-base-pair deletion in CCR5, and this defect can confer resistance to HIV infection. Sean Ryder of the University of Massachusetts Medical School argued, however, that the CCR5 deletions introduced into the babies differed from Δ32. The structure and function of Δ32 have been studied extensively since its discovery. The edits identified in He’s experiment did not match Δ32, and the introduced changes had not been tested in animals or other preclinical studies.
4. When will the next gene-edited person appear?
He Jiankui’s decision to conduct the experiment and announce the results without adequate preparation alarmed many people. If unethical researchers used the technology without restraint, it could have grave consequences for science and for humanity. Concerns about genome editing in humans predated He’s experiment. In 2016, a physician from New York performed a procedure in Mexico, without approval from the relevant authorities, that replaced disease-causing mitochondrial DNA in an embryo with healthy mitochondrial DNA. At the summit, scientists discussed the possibility of creating a new human germline through such work and agreed that authorities should be notified of every experiment in this area.
5. Will He Jiankui’s experiment affect the future of genome editing?
The announcement met with strong opposition, and some people called for a complete ban. Such a ban would be devastating to genome-editing research. An official from the U.S. Food and Drug Administration said governments had to respond. In any event, the international community must reach a binding consensus that sets limits on this research, such as restrictions on women donating eggs for experiments. Such rules are a prerequisite for genome editing to gain broad public acceptance.
6. How can we ensure that genome editing leads to a better future?
Most researchers want the parties involved to coordinate, reach a consensus, and impose reasonable limits. The organizing committee of the Hong Kong summit also proposed an international forum and a registry for clinical research. Some bioethicists, however, explicitly oppose human trials of this technology and have called for mandatory penalties.
After reading these six questions on Nature’s website, I voted for the one I most wanted answered.
The poll results show that the public is most concerned about whether genome editing will help or harm the field and society at large. No one can predict its future. With the technology still immature and ethical disputes unresolved, these babies will face extensive debate and resistance. It may take years or even decades before we understand the effects of the changes He Jiankui made. For now, researchers can conduct extensive animal and preclinical studies to improve the technology and establish the conditions required before it is used in humans. Until then, researchers must not cross ethical boundaries in pursuit of personal gain, while the public needs better science communication to dispel rumors.
Only then might we be ready to take this step safely.
References
Citation:
First CRISPR babies: six questions that remain
https://www.nature.com/articles/d41586-018-07607-3
爱发电(点击图片跳转)