Sat. Sep 24th, 2022
Promotional image from documentary Human Nature
enlarge An artistic rendering of a Cas9 protein that instantly interrupts and alters the genes of a living being.

Here’s a poorly kept secret: The internal chatter at a particular research and scientific institution is usually more interesting than what emerges in the public record. Published papers and newspaper interviews don’t come with the banter, pop culture references, or sheer humor that pumps through most geeks’ veins.

I thought back to all that geek humor when I thought about it Human nature, a documentary about gene editing and CRISPR that had its world premiere at South by Southwest 2019. There’s a lot to be said about such a subject, and the film, co-produced by Dan Liever, does quite well through existing research and studies , and then basing them on context and equal parts optimism and pessimism. But Human nature is also the rare science film that isn’t afraid to let its clever talking heads be funny, goofy, or just plain sharp.

Meaning: If you already know all about CRISPR (and if you read Ars Technica, maybe you do), Human nature has something for you.

“A word processor for DNA”

They saw a very peculiar pattern.
enlarge They saw a very peculiar pattern.

The film seems to know this about itself, as the credits list each participating scientist and talking head in order of appearance, all identified with a weird or humanizing quote. It’s as close as I’ve seen to a documentary that ends with its own yearbook page, but Human nature deserves it.

Before we get there, of course, the movie should set the stage by describing what the heck CRISPR is and why it has fascinated, excited, and/or terrified so much of the scientific community.

The film opens in 1966 with a talk by Robert Sinsheimer, a biologist at the California Institute of Technology, summarizing the understanding of the human genome of his time. “We’re going to get to the point where humans will be able to change their own genes,” he explains, and we jump-jump-jump through time to that point.

The film highlights a critical, difficult moment between the description of individual genes that began in the early 1970s and the modern understanding of gene editing: early gene therapy, which has been described as an “essentially random process.” A French research study in 2002 focused on leukemia patients who had run out of viable treatment options. But enough of the trial members suffered thanks to the uncontrollable, random nature of where the gene therapy DNA was introduced. The resulting cancer cases brought the process to a halt.

Again and again

From there, the film focuses on the work of Francisco Mojica, a researcher who had studied the DNA of bacteria in salt pools. These genetically simple microorganisms make it easier to study phenomena at the DNA level. In 2003, he noticed something that turned out to be a breakthrough: certain pieces of DNA would repeat over and over in the bacterial chromosome. This in itself was not necessarily a new phenomenon. (It had already been given the awkward term “Clustered Regularly Interspaced Short Palindromic Repeats”. Or, for short, CRISPR.)

But Mojica came up with a brand new reason for the reruns: The replay wasn’t junk. The sequence matched perfectly with viruses that had previously infected the bacterium. And as Fyodor Urnov, one of the film’s most sympathetic sources, explains, the reason is that something in the bacterium acts like a “word processor for DNA.” After identifying a DNA line that corresponds to an invading virus, the cell copies that sequence into RNA.

A protein, known to scientists as Cas9, then goes on the hunt for any DNA sequence that matches the RNA under lock and key. At the site of a match, the protein “cuts” the offending DNA. This kills the virus. (As we see in the film, one of the first applications of this phenomenon was to remove viruses from yogurt cultures for Danisco, a supplier of dairy products.)

“Fight without fear or pain”

It's all nice and fun until Putin shows up and says: "Nice research you have there.  Shame if something happens to it."
enlarge It’s all fun and games until Putin shows up and says, “Nice research you’ve got there. It’s a shame if something happens to it.”

My colleagues at Ars detailed the subsequent work. Labs have figured out how to deliver specific genetic information to Cas9 proteins that can then pass through an organism’s cells and cut specific information from their DNA. Human nature doesn’t offer nearly as comprehensive an overview of all the trial and error that followed as researchers developed this process. The animated sequences and friendly voices of the film make it simple and clear why this method of gene therapy is indeed feasible.

From there of course Human nature takes us to the most terrifying extremes of what could follow.

That includes the required footage of Vladimir Putin at a Russian science event detailing what future CRISPR-driven gene editing might look like. After discussing the beneficial angle of medical care and disease eradication, he adds a sweet suggestion: “This could be for a soldier” to “fight without fear or pain.” His speech is followed by depictions of Aldous Huxley’s parable and passages from his 1932 novel brave new world

“Every five years we hear these horror stories”, one of Human nature’, the researcher notes, asking viewers to subvert their fear of the worst in terms of CRISPR ushering in a wave of eugenics. As a way of reminding viewers that CRISPR could solve some real-world medical problems, the film tells the stories of a teenage boy with a “milder” form of sickle cell anemia and a teenage girl with severe nearsightedness caused by albinism.

In both cases, the affected children and parents commented on the possibility that those illnesses never occurred… and then shrugged. “I’ve learned patience,” the sickle cell boy says about his illness. “I’ve learned to be positive. I wouldn’t be” me if I didn’t have sickle cell.” This is followed by a statement that the prevalence of sickle cell in sub-Saharan Africa is a likely evolutionary response to the scourge of malaria in the region, as sickle cell patients are not as likely to develop disease.

“You say Jurassic ParkI say coral reefs”

Ambitious goals.  (The film also features some pigs, which may have a more direct impact on human life.)
enlarge Ambitious goals. (The film also features some pigs, which may have a more direct impact on human life.)

Human nature ensures that advocates for every topic of conversation get their share of screen time. A CRISPR-obsessed researcher named Stephen Hsu expresses hopes for increased human intelligence as a result of wider access to gene editing. Other speakers think, well, what measure of intelligence are we talking about anyway? Another gene-editing researcher, George Church, admits that his stated goal of reviving the woolly mammoth through practice is “quixotic,” but is positioned as a reminder that his work could apply to working on other endangered species. or declining animal and plant populations.

It is around this time that Human nature shows a few sequences from a particular 1993 movie about a dinosaur-filled theme park, to which a researcher replies, “You say Jurassic Park† I say coral reefs.”

But that simple statement could itself weave its own web of an entire two-hour film: What, according to the scientific community, is the best method of preserving coral reefs through gene editing? Or bee populations? Or deciding which genetic disorders should be excised from humans, either through “tissue line” applications (to allow cells to mature, leaving embryos unaffected) or “germline” (i.e. directly to the embryo and impact on future generations)?

The last point — researchers’ stance on germline gene editing — gets the most airtime in this documentary. This usually reveals an evolving attitude, from a hard “no, no, no” to a growing willingness to address serious genetic disorders at the embryo level. For the most part though Human nature is a film about human history and ambition, not about the exact next steps of the research community.

We see wide-eyed researchers trumpeting their highest expectations or expressing fatigue with doubters. We see affected families talking about which diseases they want eradicated forever or which diseases could actually define the human condition. We see archaeologists and farmers reminding viewers that humanity already has a rich tradition of “genediting” through artificial selection, through what we choose to plant, how we domesticate animals, and more.

Human Nature world premiere trailer

There is just enough data in Human nature– really, right on the brink of an information deficit – to make a case for casual viewers. As one of the science novices to this site, I have to admit that the movie got me excited to read my colleagues’ articles and join the conversation. We may be on the cusp of broader CRISPR-driven gene editing in humans and other mammals (including a startup looking to harvest human-compatible organs from gene-edited pigs), and the movie left me hungry for more context, but it contained enough clever commentators to respect my inherent skepticism.

Is this the future of health? The future of a Putin-fueled super soldier nightmare? By anchoring both extremes with a funny, human touch, Human nature made me feel comfortable with a landing point somewhere closer to the center.

Human nature received its world premiere screening at SXSW 2019. The film does not yet have a United States distribution deal.

By akfire1

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