At the Second International Summit on Human Genome Editing, held in Hong Kong on November 27-29, 2018, the room is buzzing with uneasy chatter. The audience already knows, at least to some degree, what Dr. He Jiankui, the most talked-about speaker of the event, is going to discuss. They are aware of the burgeoning controversy surrounding his experiment. In the last few days, his work has been called “criminally reckless,” “profoundly disturbing,” and a “grave abuse of human rights.” Some have speculated that it “will push bioethics into a dark new era.”
“Just to remind everyone here, we want to give Dr. He a chance to explain what he has done in terms of the science in particular, but also other aspects of what he has done. Please, can you allow him to speak without interruptions,” implores David Baltimore, a notable American biologist and Nobel laureate, who has been tasked with introducing Dr. He. Baltimore speaks from a podium on a wood-paneled stage. The audience, an unusually rowdy crowd of researchers, ethicists, policymakers, and medical representatives, does not quiet down. But Baltimore continues: “We didn’t know the story that was going to break over the last couple of days when he accepted the invitation to come and speak to us.”
When the audience finally settles, Dr. He steps up to the podium. “Do you see your friends, your relatives who may have a genetic disease? The way I see it, those people need help,” he says. His conception of “help” is the source of the controversy taking place at the summit. When Dr. He used CRISPR gene editing technology to modify the DNA of human embryos, his intentions were good––however devastating and far reaching the consequences.
CRISPR gene editing allows scientists to harness the naturally-occuring immune systems of bacteria to genetically modify other organisms. CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, refers to repetitive sequences of nucleotides (the molecules that form the basic structural unit of DNA) found in bacterial DNA. These sequences assist bacterial immune systems; when viruses attack bacteria, the bacteria produce Cas9 enzymes which in turn seek out the viruses, killing them and subsequently slicing up their genetic material. As a matter of survival, the enzymes cache specific fragments of those viral genetic codes in the CRISPR sequences of their own DNA, which allows the bacteria to later identify the same viruses in the event of reinfection.
Sudden breakthroughs in gene-editing technology occurred when biochemists discovered that the Cas9 enzyme would chop up and collect any foreign genetic sequence, as long as the enzyme recognized the RNA sequence. Once scientists realized that they could trick the Cas9 enzyme into cutting up any genetic material, not just that of viruses, they struck gold. Humans now had the power to manipulate any genome. Gene editing had been possible before CRISPR’s arrival, but the technology was expensive, time-consuming, and imprecise. Now, scientists could slice up DNA with unprecedented precision, deleting unwanted sequences and potentially adding in new ones.
Since CRISPR’s discovery, scientists have most notably used the system to mitigate hearing loss in mice and produce mushrooms that stay fresh much longer than other natural fungi. Each scientific breakthrough has demonstrated the revolutionary potential of CRISPR technology, tempting scientists with boundless opportunity in a world littered with biological imperfections. Despite the far-reaching ramifications of these experiments for the public, they received minimal coverage by mainstream news outlets, and the understanding and discussion of their significance largely remained insulated within the scientific community.
But CRISPR is far from perfect. In fact, within the last year, scientists have published research suggesting that CRISPR editing can cause serious, previously underestimated damage to DNA. Last July, Nature revealed that gene editing with CRISPR/Cas9 can inadvertently cause significant deletions and rearrangements in genetic material (the consequences of which remain unknown), while two other studies published in the same summer suggest that CRISPR-edited cells can become cancerous.
So while the potential benefits of CRISPR excite many scientists, most deem the risks too high to make its usage on humans in the near future advisable or even plausible. And the prospect of human genome editing, because it touches on profound cultural fears about evolution, eugenics, and overreach, has received far more attention in popular discourse than most scientific innovations. For much of the public, until Dr. He’s experiment, the prospect of a genomic revolution for humans seemed terrifying, but still far in the future.
Before November, He Jiankui was a 35-year-old biophysics researcher at Southern University of Science and Technology in Shenzhen, China with very little distinction in the gene editing community. He grew up in a family of rice farmers in an impoverished area of the southeastern Hunan province. From a young age, He demonstrated an individualistic streak, and science gave him a sense of independence and upward mobility. Dissatisfied with his high school’s opportunities, He built a laboratory at home to conduct his own physics experiments.
Earning his undergraduate degree in physics in China at the University of Science and Technology in 2006, He went on to pursue a Ph.D. at Rice University, where he studied the application of physical and mathematical modeling to biological systems. Not long after, He caught the eye of the Chinese government, which enticed him back to China with a state-of-the-art lab, liberal funding, and a position as the youngest associate professor at Southern University. But his work after graduate school garnered little recognition—he did not publish any papers on CRISPR or work in any notable CRISPR labs. Established CRISPR scientists considered his research imprecise, unnecessary, and not particularly innovative. According to Jennifer Doudna, one of the pioneers of CRISPR technology and a highly respected gene editing researcher, “he wasn’t seen as a major player.”
But Dr. He’s intentions were good: he believed he could do something profound with CRISPR. Like many scientists, He saw the potential in gene editing to revolutionize treatment for genetic diseases, particularly HIV. What made He different, though, was his unwavering drive to take action. After a devastating epidemic in the 1980s and 1990s, HIV remains a significant problem in China. The Chinese government estimates that over 500,000 people in China are currently HIV-positive, and infection rates have jumped in recent years. He had visited villages where more than 30 percent of the population was HIV-positive. There, he spoke with parents who dreaded passing the disease to their children. And in his speech at the Hong Kong summit, He cited this personal experience with the HIV crisis as one of his primary motivations for his gene-editing experiment: “They need this protection. [The] HIV vaccine is not available… They had lost hope for life.”
In 2017, Dr. He recruited seven sets of hopeful parents for a new clinical trial. Choosing couples in which at least one partner was HIV-positive, He attempted to use CRISPR/Cas9 to remove a gene called CCR5 from the genomes of their offspring. CCR5 is significant because those who lack the gene due to a naturally-occurring mutation are highly resistant, sometimes even immune, to HIV. Likely aware of his flouting of general scientific agreement, He concealed the true nature of his experiment. He took an unpaid leave from Southern University in February to work on the project without oversight, and only registered the experiment on the official list of China’s clinical trials in November 2018 (though experiment documents have been found that date back to March 2017).
Leading up to his experiment, Dr. He reached out to distinguished CRISPR scientists, asking for meetings, lab tours, and advice. In particular, he forged relationships with UC Berkeley biologist Mark DeWitt and Stanford bioethicist William Hurlbut, seeking advice from them about the use of CRISPR for human embryos. Both men urged Dr. He against the experiment, warning him of its potential dangers and ethical implications. Dr. He ignored their advice.
On November 25, two days before Dr. He was set to talk about his research at the Hong Kong summit, his research team made a stunning announcement in a YouTube video: the first two babies whose embryos he had edited with CRISPR/Cas9, a set of twins named Nana and Lulu, had been born healthy. The video itself shocked most scientists; typical protocol calls for researchers to present their work at conferences or in peer-reviewed journals. Perhaps anticipating a controversial reception at the summit, Dr. He likely wanted to defend himself and his project uninterrupted. So he initiated the dialogue on his own terms.
The video is staged against a sterile, well-lit background that appears to be a laboratory. Dr. He’s remarks are measured, and seemingly meticulously rehearsed. He describes Nana and Lulu’s “gene surgery” and embryonic development, and highlights their parents’ reactions. “When Mark saw his daughters for the first time,” He says, “he said he never thought he could be a father. Now he’s found a reason to live, a reason to work, a purpose.” He asserts that Nana and Lulu were born “safe and healthy as any other babies,” which he had confirmed by deep sequencing, or scrupulously documenting, their genomes. The girls seemingly lacked any abnormalities or unpredicted deletions caused by the CRISPR editing.
Dr. He’s manner is stoic but earnest. His posture remains rigid; his only movements are an occasional sweep of his hands, which he mostly keeps clasped. But his calm veneer cracks sometimes, when he speaks quickly or smiles, or gestures emphatically, reflecting his excitement about his experiment. He likens his work to the first IVF pregnancy in Manchester, England. At the time, he says, IVF sparked a media “panic,” but has proven to be a powerful tool for those who have difficulty conceiving, and has become acceptable over the last forty years as “regulations and morals have developed.” Dr. He thought his research could provide a similar boon to China by laying the groundwork for editing HIV-resistance into the genome of a new generation of Chinese babies, posing a solution to the problem he had seen developing for so long.
Anticipating some of the debate about eugenics that his work would provoke, He explicitly states in the video that Nana and Lulu’s parents do not want a “designer baby,” but simply children who will not suffer from a preventable disease. Any eugenic practices, such as selecting for desirable physical traits, “should be banned,” He states. Gene surgery “is and should remain a technology for healing.” But He’s idealism had blinded him to the consequences of his experimentation.
Four days after the release of his video, the Chinese government banned Dr. He from pursuing his research any further. There are to be no more CRISPR babies. “The genetically-edited infant incident reported by media blatantly violated China’s relevant laws and regulations. It has also violated the ethical bottom line that the academic community adheres to. It is shocking and unacceptable,” said Xu Nanping, Chinese vice-minister of science and technology, in a statement a few days after the Hong Kong summit. As of now, Dr. He lives in university housing on his campus in Shenzhen. Plainclothes guards are stationed at his apartment. It is unclear whether they are there to protect him or to enforce his house arrest. Rumors have swirled in the media that Dr. He faces the death penalty, which he has flatly denied. He has made no substantive public statements since the initial turmoil.
In addition to the government crackdown, many scientists have raised serious concerns with Dr. He’s experimental design. They claim that Dr. He’s experiment was fundamentally unnecessary for the babies in his study—he was not addressing an unmet need, as the embryos in He’s trial had no medical issues. Editing their genomes did not cure them of any disease, but instead made them resistant. (Moreover, there are cheaper, pre-existing treatments for HIV.) This objective does not clearly align with Dr. He’s purported goal of use gene editing as a “technology for healing.” While Dr. He saw resistance as a form of healing, many others believe that his experiment crossed the line into enhancement (if there is any line to be drawn at all).
On a larger scale, the very notion of using CRISPR on humans has alarmed most scientists. Given the potential risks—the prematurity of the technology and the unknown consequences of accidental mutations—many scientists have questioned the informed consent of the parents in the study, let alone the ethical dilemma of the children. They are not just embryos, but humans who will have to live with genetic modifications they did not ask for, making bioethicists question whether parents’ consent in experiments like these can ever be sufficient.
Finally, it is unclear what will happen to Nana and Lulu. Dr. He did not execute the mutations perfectly: only half of Lulu’s CCR5 genes are edited, and Nana had some normal copies of the CCR5 gene. So while he claimed in the video that the babies showed no unplanned deletions, he neglected to mention the other unplanned results of the experiment. Dr. He’s mistakes aside, even if the editing had gone perfectly, Nana and Lulu have no medical precedent. Those of us watching the babies are left wondering: What might it mean to be the first of one’s kind? In uncharted biological and ethical territory, what kind of norm might this experiment, or these children, set?
As He’s experiment has moved into popular discourse, public anxiety over its ethical implications has subsumed his misguided crusade to eliminate HIV in China. Many people fear not only that the experiment crossed the boundary between healing and enhancement, but also that the very prospect of human genome editing has opened the door for a new kind of eugenics movement. In a theoretical world where scientists can slice and rearrange human genomes at will, a vision that has become increasingly conceivable recently, parents who can afford CRISPR gene surgery would be able to select for desirable or advantageous traits, intimately linked to hierarchies of race and ability, or weed out the undesirable or disadvantageous, creating "designer babies." Despite He’s denouncement of designer babies, these eugenic possibilities raise numerous ethical questions about desirability and the place of people with disabilities in this new, genetically-modified era.
But the public’s response has not only reflected these cultural fears that genome editing has, since its inception, evoked—overwriting nature, playing God, and recklessly altering the processes and trajectory of human evolution—but has also called into question the nature of the scientific community itself: How did the community fail to see something so out of line right under its nose? What terrifies many scientists is that there was no clear way to prevent this from happening within the community. Short of institutional oversight, which evidently can be circumvented, little can stop scientists from overreaching when the only method of regulation is the norm of protocol itself. David Baltimore alluded to this during his remarks at the Hong Kong summit: The problem, from his perspective, was “a failure of self-regulation by the scientific community because of the lack of transparency.”
He’s experiment, then, becomes not only a referendum on human genome editing—a practice which, when viable, will have significant (though certainly not unanimous) scientific, ethical, and public support—but also on the seeming lack of regulation, oversight, and enforcement within the scientific community, and thus modern science itself.
And so, much of this debacle centers around the figure of He Jiankui, who seems to be the perfect combination of reckless idealism and stubborn individualism: A contemporary Victor Frankenstein, the canonical overreaching scientist. This incident prompts us to consider the stakes of Mary Shelley’s warnings in the 21st century: How much agency should individual scientists have within a community so dependent on collaboration? And in a world where gene-editing technology seems like it will become more accessible, and more scientists will have the opportunity to ‘play God,’ will the scientific community learn from this mistake, or will more tragedies occur? With children’s lives, the future of bioethics, and possibly the trajectory of human evolution seemingly hanging in the balance, the need for answers to questions like these feels increasingly pressing. Standing at the podium on stage at the Hong Kong summit, He offers the audience this call to action: “If we have the technology and can make it available, then this will help people... It is up to society to decide what to do next.” Society gave him a resounding answer: Not on your terms.
GEMMA SACK B’21 is very wary about 23andMe.