Enlarge / An artist’s representation of a Cas9 protein immediately interrupting and changing a living creature’s genes.

Here’s a poorly kept secret: the internal chatter at a given research and scientific institution is typically more interesting than what emerges on the public record. Published papers and newspaper interviews don’t come with the banter, pop-culture references, or sheer wit that pumps through most nerds’ veins.

I thought back to all that nerd humor when I reflected on Human Nature, a documentary about gene editing and CRISPR that had its world premiere at South by Southwest 2019. There’s a lot of ground to cover on such a topic, and the film, co-produced by Dan Rather, does quite well by identifying existing research and studies, then grounding them with context and equal parts optimism and pessimism. But Human Nature is also the rare science film that isn’t afraid to let its smart talking heads be funny, dorky, or just plain sharp.

Meaning: if you already know everything about CRISPR (and if you read Ars Technica, you very well might), Human Nature still 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 its ending credits list each participating scientist and talking head in order of appearance, all identified with one weird or humanizing quote. It’s as close as I’ve seen to a documentary ending with its own yearbook page, but Human Nature earns it.

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

The film opens in 1966 with a speech from Robert Sinsheimer, a biologist at the California Institute of Technology, in which he sums up his era’s understanding of the human genome. “We will come to the time when man will be able to alter his own genes,” he declares, and we hop-skip-jump through time to that very point.

The film highlights one critical, difficult moment between the description of individual genes that started in the early 1970s and the modern understanding of gene editing: early gene therapy, which was described as an “essentially random process.” One French research trial in 2002 targeted leukemia patients who’d run out of feasible treatment options. But enough of the trial members suffered thanks to the uncontrollable, random nature of where the gene therapy DNA was inserted. The resulting cases of cancer ground the trial to a halt.

Over and over

From there, the film focuses on the work of Francisco Mojica, a researcher who’d studied the DNA of bacteria found in salt pools. These genetically simple microorganisms make for easier study of phenomena on 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 itself wasn’t necessarily a new phenomenon. (It had already been given the clunky term “Clustered Regularly Interspaced Short Palindromic Repeats.” Or, for short, CRISPR.)

But Mojica figured out a brand-new reason for the repeats: the repetition wasn’t junk. The sequence matched up perfectly with viruses that had previously infected the bacteria. And as Fyodor Urnov, one of the film’s most likable sources, explains, the reason is that something in the bacteria is acting like a “word processor for DNA.” After identifying a line of DNA that matches an invading virus, the cell copies that sequence into RNA.

A protein, which scientists know as Cas9, then goes on a hunt for any DNA sequence that fits lock-and-key with the RNA. At the site of any match, the protein “snips” the offending DNA. This kills the virus. (As we see in the film, one of the earliest uses of this phenomenon was to clear viruses out of yogurt cultures for Danisco, a dairy-product supplier.)

“Fight without fear or pain”

It's all fun and games until Putin shows up and says, "Nice research you have there. Shame if something happen to it."
Enlarge / It’s all fun and games until Putin shows up and says, “Nice research you have there. Shame if something happen to it.”

My Ars colleagues have detailed the work that followed. Labs have figured out how to supply specific genetic information to Cas9 proteins that can then go through an organism’s cells and snip specific information out of their DNA. Human Nature doesn’t offer nearly as comprehensive a look at all the trial and error that followed as researchers developed this process. The film’s animated sequences and friendly voices simply make a basic and clear case for why this method of gene therapy is indeed feasible.

From there, of course, Human Nature takes us to the scariest extremes of what could follow.

That includes requisite footage of Vladimir Putin at a Russian science event describing what future CRISPR-driven gene editing might look like. After talking up the wholesome angle of medical care and eradicating diseases, he adds a pretty on-brand suggestion: “This could be for a soldier” to “fight without fear or pain.” His speech is followed by images of Aldous Huxley’s likeness and passages from his 1932 novel Brave New World.

“Every five years, we hear these horror stories,” one of Human Nature‘s researcher points out, asking viewers to belay their fear of the worst in terms of CRISPR ushering in a wave of eugenics. As one way to remind viewers that CRISPR could solve some real medical problems, the film tells the stories of a teen boy with a “milder” form of sickle cell anemia and a teen girl with severe myopia as brought on by albinism.

In both cases, the affected kids and parents remark upon the possibilities of those diseases having never emerged… and then offered their own shoulder shrug. “I learned patience,” the boy with sickle cell says about his disease. “I learned to be positive. I wouldn’t be me if I didn’t have sickle cell.” This is followed by an explanation that sickle cell’s prevalence in sub-Saharan Africa is a likely evolutionary reaction to the region’s scourge of malaria, as sickle-cell sufferers aren’t as likely to contract that disease.

“You say Jurassic Park, I say coral reefs”

Aspirational goals. (The film also stars some pigs, who may have a more immediate impact on human life.)
Enlarge / Aspirational goals. (The film also stars some pigs, who may have a more immediate impact on human life.)

Human Nature is careful to let advocates for every talking point get their fair share of screen time. A CRISPR-obsessed researcher named Stephen Hsu talks up his hopes for increased human intelligence as a result of wider access to gene editing. Other speakers opine, well, what metric of intelligence are we even talking about? Another gene-editing researcher, George Church, admits that his stated goal of resurrecting the woolly mammoth via the practice is “quixotic” but is positioned as a reminder that his work could apply to work on other endangered or declining animal and plant populations.

It’s around this time that Human Nature shows a few sequences from a certain 1993 film about a dino-filled theme park, to which one 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 might the scientific community believe is the best practice to preserve coral reefs by way of gene editing? Or bee populations? Or deciding which genetic conditions should be snipped out of people, either via “tissue line” applications (to mature cells, thus not affecting embryos) or “germ line” (meaning straight to the embryo and affecting future generations)?

The last point—researchers’ stance on germ-line gene editing—gets the most airtime in this documentary. This mostly reveals an evolving stance, from hard-line “nope nope nope” to a growing willingness to address serious genetic disorders at the embryo level. For the most part, however, Human Nature is a film about human history and ambition, not the research community’s exact next steps.

We see wide-eyed researchers trumpet their highest-level hopes or express fatigue with doubters. We see affected families talk about what illnesses they want eradicated forever or what illnesses might actually define the human condition. We see archaeologists and agriculturalists remind viewers that humanity already has a rich tradition of “gene editing” by way of artificial selection, via what we choose to plant, how we domesticate animals, and more.

Human Nature world premiere trailer

There’s just enough data in Human Nature—really, right on the edge of an information deficit—to make a case to casual viewers. As one of this site’s science novices, I admit that the film had me eager to hit up my colleagues’ articles and join the conversation. We’re potentially on the brink of wider CRISPR-driven gene editing in humans and other mammals (including a startup that wants to harvest human-compatible organs from gene-edited pigs), and the film made me hungry for more context—but it included enough smart commentators to respect my inherent skepticism.

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

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

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