Breaking the Rules

Four years ago, I grabbed a front-row seat in the Lee Shau Kee Lecture Centre at Hong Kong University in anticipation of the entrance of a young Chinese scientist at the epicenter of a media frenzy and global firestorm. Just two days earlier, the world was stunned to learn that He Jiankui (“JK”) had created the world’s first gene-edited babies, Lulu and Nana. The twins had been born prematurely a few weeks beforehand, supposedly healthy, carrying deliberately damaged copies of the CCR5 gene intended to render the children immune to HIV.

Bioethics conferences don’t usually attract the hoard of photographers, journalists, and camera crews jostling for space along one wing of the auditorium. Among them was director Cody Sheehy, who was making a film with producer Samira Kiani (a genome scientist now at the University of Pittsburgh) about the brave new world of human CRISPR engineering. A month earlier, Sheehy and Kiani had been filming interviews with Chinese scientists who had published research on CRISPR editing in human embryos. Traveling with them was Antonio Regalado, an intrepid reporter with MIT Technology Review.

The trajectory of that film—one might say the entire course of genome editing—changed irrevocably during that China trip. Sheehy, Kiani, and Regalado had serendipitously arranged an off-the-record meeting with JK that left Regalado convinced that JK was hiding his true intentions. On the eve of the Hong Kong conference, Regalado sensationally uncovered proof of a CRISPR-edited pregnancy under JK’s supervision. Although he didn’t know the outcome of that pregnancy, he boldly published the biggest scoop of his career. It was Thanksgiving Sunday, 2018.

That momentous episode is recreated in Make People Better, Sheehy’s riveting film about the JK affair. That this film is finally released four years after the “CRISPR babies” scandal erupted—with its central protagonist incarcerated for most of that time—suggests that the filmmakers have wrestled with the question of how best to frame their story. The final cut focuses squarely on the JK story, for the most part ignoring wider ethical issues and eschewing the deliberate pacing and academic experts seen in traditional science documentaries. The result is something altogether edgier and exciting, even if at times style overshadows substance.

In JK’s enforced absence, Make People Better revolves around four central characters. In addition to the charismatic Regalado and, almost inevitably, Harvard geneticist George Church, we meet J. Benjamin Hurlbut, a science historian at Arizona State University. (Not mentioned in the film, Hurlbut’s father William, a Stanford neuroscientist, was a member of JK’s inner circle who was informed about the pregnancy of the CRISPR babies.) Following JK’s detention, Ben Hurlbut recorded several long phone conversations with him that shed some light on JK’s motivations. These interview clips are presented without spin or sympathy, allowing viewers to reach their own opinions.

The picture that emerges is that of an ambitious scientist motivated by the success (and fame) of IVF pioneers Robert Edwards and Patrick Steptoe in the late 1970s. Hurlbut recounts a brief conversation JK had with James Watson, who tells him the reason to consider human hereditary genome editing (HHGE) is to “make people better.” On the phone, JK tells Hurlbut: “That gave me the courage to be the person to ‘break glass’.” Or as Hurlbut puts it, “cowboy now, Nobel laureate later.”

Another prominent figure is JK’s former press spokesperson, Ryan Ferrell. He signed on to help JK orchestrate the public release of the CRISPR babies’ birth, hoping the world could “ease into the idea” of HHGE. His conflicted emotions as JK rushed to submit a self-congratulatory manuscript (to Nature) and the story span out of control are plain to see.

For all JK’s flaws, the film makes a persuasive case that he was not the “rogue” scientist he was widely portrayed in the West. In addition to his “circle of trust”—including a handful of confidantes and mentors in the United States—JK felt protected, even encouraged, by the Chinese authorities, as long as he didn’t do anything too controversial.

Flaws in the sequence

Make People Better zips along with a running time of just 84 minutes. It is handsomely shot and briskly edited in a fashion that shares more DNA with The Bourne Identity and Westworld than a typical science documentary. But in rushing to present their story, I think the filmmakers miss some precious opportunities to paint a more complete and satisfying picture.

A recurring plot device (presumably to ramp up suspense) is a countdown of the days to “JK’s disappearance”. Sheehy poignantly captures JK’s exit from the Hong Kong conference, the arm of a security guard firmly ushering him out of the auditorium as JK casts a wistful glance back through the closing doors. In fact, his whereabouts only remained a mystery for a few weeks. A pair of journalists from the New York Times dramatically spotted JK on the balcony of a guest house belonging to his (former) university. The reporters valiantly try to visit JK but sensibly retreat down a stairwell after their efforts are blocked by multiple security personnel.

The film also treats the science in a disappointingly cursory fashion. Other than a fleeting glimpse of Doudna and Charpentier, there is no explanatory background given to the discovery or process of CRISPR gene editing – or editing in human embryos for that matter. (The filmmakers justify their choice by noting that CRISPR technology is moving fast and besides, documentaries such as Human Nature have covered this in rich detail.)

JK’s rationale for targeting the CCR5 gene is also given short shrift. In 2015, JK hears George Church give a keynote at a conference in Berkeley, in which he lists several genetic variants—including CCR5—that could in principle offer some form of human enhancement. There is a brief discussion of the HIV scandal in rural China in the 1990s, but no mention of the naturally occurring 32-base deletion in CCR5, associated with HIV resistance, that JK was attempting to mimic. Other than the documented mosaicism in one of the gene-edited embryos, viewers may struggle to grasp why the world reacted so angrily to the news of the CRISPR twins.

For a film that raises so many compelling ethical questions about the wisdom or otherwise of meddling with the human gene pool, there is surprisingly little effort to supply any answers. One might expect a succession of bioethical and legal experts weighing in on the merits of an HHGE moratorium, a recap of the blue-ribbon commissions that have released reports on HHGE, or some debate over designer babies. I suspect the filmmakers rejected those ideas as too lame or predictable, or perhaps they reasoned that it would needlessly date the film as the technology continues to evolve. Instead, we make do with a clip of Church being interviewed on television by Stephen Colbert.

Make People Better closes by posing some tantalizing scenarios that suggest that this story is far from over. Indeed, JK had barely left the stage in Hong Kong before conference organizers were talking of a “translational pathway” for HHGE. “The disaster lasted about five minutes,” quips Regalado. There is evidence that JK was venturing to launch a CRISPR clinic– Audrey Life Sciences (named after his daughter)—in China’s Hainan medical zone, in collaboration with prominent fertility specialist John Zhang. Released from prison in April 2022, JK has set up a new lab in Beijing and declared an interest in pursuing a (somatic) gene editing therapy for muscular dystrophy.

Despite these quibbles, Make People Better is an important and eminently watchable record of an historic moment in the history not only of CRISPR genome editing but also of humankind itself. My hope is that there will eventually be a longer Director’s cut, salvaging some of the material that has been left on the (CRISPR) cutting room floor.

Kevin Davies PhD is the Executive Editor of The CRISPR Journal and GEN Biotechnology, and the author of Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing (Pegasus Books, 2020). This essay was originally published in The CRISPR Journal.

The post Breaking the Rules appeared first on GEN – Genetic Engineering and Biotechnology News.

crispr
gene editing
medical
life sciences
device
shares