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Wednesday, May 22, 2024

In Human Nature, Crispr's Origin Story Comes to Life

Midday light streams through the windows of the Stanford Children’s Hospital in Palo Alto, California. In a bed too big for his child-sized body, David Sanchez sleeps among a tangle of tubes plugged into a port in his chest. A machine nearby draws blood out of his veins, exchanging his deformed red blood cells for a batch of plump round ones, donated by someone free of the genetic mutation Sanchez carries. Like other sickle cell disease patients, Sanchez requires one of these hematological tune-ups every four to six weeks. At least for now. Researchers at Stanford are testing a therapy to not just treat—but cure—his condition with the gene-editing technology Crispr.

This is the opening scene in the new documentary Human Nature, which will open on Friday in select US theaters and stream on Netflix this fall. The film tells the unlikely story of the discovery of one of the most revolutionary technologies of the modern era. Crispr makes it easy to rewrite the DNA of any living organism, handing humans the ability to profoundly alter the evolution of any species on the planet. But it didn’t arrive in a single burst of enlightenment. Figuring out what Crispr is, where its key bacterial genetic sequences come from, and what they could do with it took scientists scattered across the globe years of chipping away at a molecular mystery.

The thrill of incremental advances toward understanding Crispr’s true power underpins the central drama of Human Nature. Unlike prior efforts to acquaint the public with gene editing—including a Netflix docuseries called Unnatural Selection, which debuted in October with scenes of biohackers injecting Crispr into mastiff sperm—the new film takes its time with the science. After introducing us to David, it takes viewers to salt ponds and yogurt factories, tracing the early confounding days of Crispr research, when scientists kept finding its weird genetic pattern in bacteria, rather than plowing headlong into the technology’s most provocative potential uses. (It does eventually get there.)

The film’s focus on science as adventure can be traced back to the project’s beginning. Journalist and coproducer Dan Rather had conducted an interview with Crispr luminary and UC Berkeley biochemist Jennifer Doudna in the spring of 2016. He reached out to Elliot Kirschner, an executive producer at the Wonder Collaborative, a scientific documentary organization based in San Francisco, about making a short explanatory film to be released online. But after holding a meeting with Doudna, the geneticist George Church, Harvard Medical School dean George Daley, and microbiologist Rodolphe Barrangou, where they talked about Crispr’s arc from humble yogurt culture helper to billion-dollar disease-curing biotech investment, the filmmakers realized they had a feature-length documentary on their hands.

“We were just so struck by how willingly these scientists were saying this was a huge deal,” says director Adam Bolt. He had worked on science stories in the past and was used to hearing more hedging. “It quickly became clear that, to them, this was one of the biggest breakthroughs in biology ever.”

Bolt decided that a movie about Crispr deserved breaking with some conventional wisdom about how science is captured on film. He didn’t want to make a project that speaks to audiences at a fifth-grade learning level. Instead, he pushes deep into the nitty-gritty of how the technology actually works, with the help of glittering animations that feel like they actually surround the viewer. While little of this information will be surprising to people who’ve heard of Crispr, these sophisticated renderings offer a new layer of understanding to all but the most wizened gene editor. “We wanted it to feel like you’ve been shrunk down inside a cell and seeing it happen in front of your own eyes,” says Bolt.

Scientists have been pursuing Crispr since 2012 in the hope that it can be used to cure a number of genetic diseases, including sickle cell anemia. (Human Nature is dedicated to the memory of Shakir Cannon, a crusading sickle cell patient advocate who hoped to live to see the day Crispr would cure his disease. WIRED profiled Cannon in 2018, shortly after he passed away.) But it also offers possibilities for treating a multitude of inherited genetic conditions, cancer, and infectious diseases like HIV.

Human Nature lays out these tantalizing possibilities alongside some even more far-out applications, like Crispr-ing pigs to grow human organs. Then viewers spend time with Steven Hsu, the chief scientific officer at Genomic Prediction, a company that generates genetic scorecards for prospective parents’ IVF embryos. Hsu believes that using Crispr to create children free of disease will one day be routine, and that parents who leave their genetic recombination up to chance will be the ones deemed unethical by societies of the future.

Which is why audiences might feel let down by how Human Nature handles the birth of the world’s first Crispr-edited humans. The film was nearly finished in November 2018 when one of the movie’s subjects—MIT Technology Review reporter Antonio Regalado—broke the news that a Chinese scientist had used Crispr to edit human embryos in an attempt to make them immune to HIV. After it emerged that the scientist had crossed ethical lines to obtain consent from the babies’ parents, and had broken Chinese law to perform the editing itself, the researcher was sentenced to three years in jail. Further revelations about the poor quality of the editing revealed that the resulting children likely will not have resistance to HIV.

After spending the first hour of the movie building up the possibility that Crispr could be used to design future generations of children, and probing the ethical implications of doing so, the brief and sudden arrival of this much-anticipated outcome is jarring. The movie flashes a few slides showing relevant news stories before moving on to the future of Crispr technology, without dwelling on whether the rogue experiment will be a one-off or an inflection point in the history of gene editing. If you were hoping for a Crispr Baby exposé, this film is not it.

Asked about why the filmmakers didn’t take more time to refocus the documentary, Bolt says that they were worried they wouldn’t be able to do justice to such a complex story and that there were many things wrong with the experiment that didn’t have to do with the fundamental question they were exploring with the film: Whether or not scientists should make permanent changes to the human gene pool. While Bolt has questioned that decision in the intervening years as they brought the documentary to the end of production, ultimately, he says, he’s glad they didn’t try to rush something through. “At the end of the day, we still accomplished what we set out to do,” says Bolt, “which was to make a film that people will walk away from feeling like they understand Crispr and what the ethical questions are around its use.”

There’s no doubt Human Nature will contribute to improving the public’s literacy about Crispr, including the differences between editing cells that can pass down those changes to future generations (germline cells, like sperm, ova, and embryos) and ones that can’t (somatic cells, or those from other body tissues). That’s critical for the future of the technology, says Alta Charo, a bioethicist at the University of Wisconsin-Madison who appears in the film for her work on the National Academy of Sciences’ reports on the ethics of gene editing. “It’s unusual to see a film that’s as accessible as this one for a topic that’s so scientific and intensely political, and even theological,” says Charo. “I hope it leads people to understand that we need a nuanced response that regulates this, so that it’s available when it’s needed and done responsibly, and restricts it when it’s not.”

Perhaps no place is this need for nuance demonstrated more than toward the end of the film, when the now-adolescent David Sanchez reappears as a patient in a clinical trial for a Crispr-based cure for sickle cell disease. At one point, the interviewer says that it might one day be possible to use the technology to treat embryos, rather than kids, to prevent them from experiencing the pain David lives with every day. Then he asks David whether he would have wanted his parents to use this technology, if they’d had the choice. David says no. That decision should be up to the child, he believes. “There are a lot of things I learned having sickle cell,” he says. “I learned patience. I learned to be positive.”

Without sickle cell, he says, “I don’t think I’d be me.”

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