CRISPR’s Icarus

By Robert Cook-Deegan

The documentary Make People Better is the result of three years of work by a team that witnessed the dawning of human genome editing using CRISPR, a breakthrough technique for precisely editing genes. The film is about He Jiankui, a Chinese biophysicist who defied international scientific consensus to orchestrate the editing of human embryos using CRISPR, resulting in the live birth of three babies in China in 2018 and 2019. The genomic change that He introduced in the first two children, born as twins, was intended to confer resistance to HIV infection and in the third child, a rare genetic disease. Because He edited their germline, those genetic changes could be passed on to future generations.

He aspired to follow the path of James Watson, one of the discoverers of the structure of DNA, or Patrick Steptoe and Robert Edwards, who developed in vitro fertilization—scientists whose accomplishments entailed scandal but resulted in Nobel Prizes. Instead, He found himself in the company of the disgraced geneticist Martin Cline, whose 1980 experiments tried unsuccessfully to introduce recombinant DNA into the bone marrow cells of children in Israel and Italy with the blood disorder beta-thalassemia. (When Science broke the Cline story in October 1980, it caused a furor that prompted sanctions by the National Institutes of Health, landed Cline in front of a congressional hearing where he was excoriated by then Representative Albert Gore Jr., and provoked the nation’s second bioethics commission to prepare a report on Splicing Life.) He, by comparison, ended up spending more than two years in prison.

The film’s title comes from an exchange between He and Watson at a genomics meeting. When He passed a note to Watson about whether it was a good idea to alter DNA in humans, Watson scribbled back “make people better.” Medicine is about making people better; new technologies such as CRISPR open the door to also making “better” people by design.

The documentary joins a longstanding debate—and a vast literature—about the wisdom of deliberately engineering human beings. Even before the discovery of DNA’s structure, which laid the foundation for molecular genetics, British scientist J. B. S. Haldane’s 1923 essay, “Daedalus, or Science and the Future,” anticipated that humans would one day have the power to engineer themselves through genetics. Philosopher Jonathan Glover queried What Sort of People Should There Be? in his 1984 bioethics classic that rekindled the debate. And I have reviewed newer additions to this literature by Robert L. Klitzman, Françoise Baylis, and Erik Parens and Josephine Johnston and by Henry T. Greely in these pages. This film chronicles what has now become the most prominent event informing that debate.

Medicine is about making people better; new technologies such as CRISPR open the door to also making “better” people by design.

Make People Better was criticized by the New York Times for having a muddy narrative line and spoiling the drama around He’s fate by revealing his punishment early in the film. Bioethicist G. Owen Schaefer took the movie to task in The Conversation for diffusing culpability and focusing on incentives in the research system rather than placing responsibility squarely on a rogue scientist. 

Both reviews miss the point, or rather, the many points raised by this complex story. The movie has no clear narrative arc and no clean moral message—but those are features, not bugs. The film is a nearly real-time account of a major event, and it studiously avoids tidy conclusions and lists of lessons. The result is that the filmmakers have produced a work that enables deep exploration of a highly complicated subject. I missed many of the subthemes on my first viewing, and the film will continue to stimulate new observations on subsequent viewings. 

Make People Better is a real story populated by flawed humans and fallible institutions and infused with politics, money, and ambition. Different viewers will find different themes. Those interested in emerging technologies and bioethics can use this film to stimulate discussion about the wisdom of human genetic engineering. Students of politics and global science have a case to illustrate how China’s technoscientific ambitions and authoritarian politics affect science and medicine. Those interested in science and science policy will focus on how the push for being first tempts researchers to jump the gun, and how the institutional constraints intended to protect people studied in human research can fail. 

Keeping with documentary tradition, archival footage and real-time video do hard work. Viewers see the actual 1978 birth of Louise Brown, the first human born after being conceived through in vitro fertilization. Chinese leader Xi Jinping addresses the Chinese Communist Party, and guards block a New York Times reporter from speaking to a caged He Jiankui. And we hear He’s voice through tapes made by Arizona State University professor Ben Hurlbut, a biomedical historian who met He in 2017.

This is an ideal film to use for teaching precisely because it raises issues that reach far beyond the injudicious choices of a naïve and overly ambitious young researcher. He does not appear to have been the rogue scientist portrayed by his critics. Hurlbut and Ryan Ferrell, a public relations specialist hired by He, compiled a list of over 60 Western scientists who were aware of He’s work; many of whom knew genetically engineered babies were in gestation before they were born—well before the story became public. Nameless Chinese officials and hospitals supplied the funds, permitted access to patients, and (at least partially) approved the experiment.

This is an ideal film to use for teaching precisely because it raises issues that reach far beyond the injudicious choices of a naïve and overly ambitious young researcher.

It becomes clear that He Jiankui was no secret Victor Frankenstein locked in a hidden laboratory, but a rising star who knew he was taking risks but was oblivious to their magnitude. Some of those risks fell on He, who deeply damaged his own career (although now is perhaps on the rebound) and tarnished the reputations of famous mentors. But more importantly, He altered the genomes of three embryos under conditions of sloppy and incomplete—that is, not fully informed—consent from the parents and without adequate plans for follow-up assessment of the resulting children. Promises of monitoring until adulthood to learn from the experiment will never be fulfilled because of the ruckus that ensued when the story broke. Even if the experiment does not have unintended health consequences, three children will now grow up as the living results of an embarrassing misfire; the story of their birth may haunt them as long as they live. That risk is real, and it was not assumed voluntarily; embryos cannot give informed consent.

The abandonment of the children and their parents was not Frankenstein’s heartless revulsion at the creature he created in secret, but rather a bureaucratic burial of bad news. He justifies the premature and technically flawed effort to create genetically modified people—who will live with his DNA changes and may pass them on—by claiming he was doing it for their benefit, to protect them from HIV infection in a culture that heavily stigmatizes those with the disease. Intense personal ambition combined with a national desire for technoscientific recognition begat the problem; knee-jerk suppression tried to bury it. The result will be a permanent stain and national embarrassment, with little technical learning from the actual biological experiment. 

Even if the experiment does not have unintended health consequences, three children will now grow up as the living results of an embarrassing misfire.

He Jiankui is no victim, but we should be wary of making him the scapegoat. He is a product of a scientific system that prizes priority. Pride of priority is true globally in science, but clearly a fortiori in China. He was following Xi Jinping’s exhortation to not let regulatory barriers and red tape slow the march of high technology. Although he is a moral agent, He is not fully independent of systems that sent mixed messages. 

This story is far from over, but the first chapter is ugly. Viewers are left wondering about the fate of the children resulting from He’s experiment. Their lives are surely affected. If medical benefit was the justification, its achievement is far from certain—the risk of social harm from being scrutinized as the first “CRISPR babies” seems much bigger and more likely than any medical benefits. We don’t even know if the children are protected from HIV infection, and we may never find out if the experiment even partially achieved its intended aim. 

What a mess. Make People Better presents that mess in a way that warrants careful consideration.