The opening scene of "Unnatural Selection," a four-part docuseries released recently from Netflix, depicts scientist Jennifer Doudna showing off a tiny sample of a colorless liquid. It contains, she says, an enzyme that allows her to add or remove any piece of DNA from any living organisms. This scene launches an exploration of the people who are taking up — and talking up — that opportunity, which Doudna did much to bring about. In this scene though, as in the remainder of the series, there is scant pushback on the hyperbolic narratives tracked over the four episodes. But, having built up the potential of gene editing, "Unnatural Selection" fails to explore the qualifications and correctives that call into question the whole project of gene editing. One wonders, in fact, if the filmmakers were even aware of the larger existential questions it raises.
The protagonists of the series span an extraordinarily wide spectrum. Spark Therapeutics claims to have invented a gene therapy cure for a special kind of inherited blindness. The biotech company has chosen its smooth-talking and sharply dressed company spokesman well, but his special challenge is to defend the pricing of their product. For a treatment that will likely cost just a few thousand dollars, the company wants to sell it for $425,000 per eye in the first year of production.
On the other end of the gene editing spectrum is a diverse community of self-styled biohackers (diverse if one discounts the fact that those featured by Netflix are all male and all white). Josiah Zayner became famous for becoming the first person to attempt to gene edit himself, though there is no indication it worked. In our first glimpse of Zayner, he’s challenging a classroom of students to tackle the thorny ethical issues involved in gene editing. In the next scene, he talks to the camera as he packs up the home gene editing kits he sells online through his company, The Odin. Zayner collaborates with David Ishee, a Mississippi dog breeder hoping to breed the first gene-edited fluorescent dog. Ishee serves as an exemplar for the ingenious amateur, tinkering away at his workbench. Both team up with Tristan Roberts, who is attempting to cure himself of HIV by editing his own cells to produce an antibody against the virus. When we meet him Roberts is already working with startup Ascendance Biomedical, who provide him with the reagents he needs and who guide his self-experimentation.
Some of the complexities of such relationships emerge early. The Ascendant crew, including its CEO, Aaron Traywick, are present at Roberts' home on the day he first injects himself. One of them asks whether he has surgical gloves, which he does not. There is a brief discussion, on camera, as to the necessity of gloves in these circumstances. It is a discussion that neatly encapsulates a certain naiveté among all the parties in this relationship.
Interspersed with this biomedical narrative is a very different one about the possible gene editing of wild species. Gene editing is a technology that creates the possibility of releasing organisms that can edit the genomes of their own offspring. Because of this, at least in principle, a single individual organism can be released that can spread a desired mutation to all their offspring and eventually convert the entire population into ones containing only the intended mutation. This technology is called "gene-drive." The property most discussed by the designers of these gene drives is population destruction through the forced spread of mutations that produce only males. All-male populations eventually crash and go extinct.
Gene drives are so controversial that the United Nations recently discussed a moratorium. The moratorium was eventually rejected, but "Unnatural Selection" delves into gene drives mainly through the lens of MIT professor Kevin Esvelt, one of its pioneers, as he travels the world looking for local human populations willing to host gene drive experiments on their lands. Esvelt presents himself as neutral in the debates he instigates, but he tells the camera too that without gene editing there is no hope for humanity. While he lacks the libertarian swagger and DIY gusto of Zayner and Traywick, Esvelt reminds us more than once that our present economic arrangements are not sustainable. We may not like the idea of genetically altered rodents, but with ecological collapse looming we don’t get to jettison a technology just because it makes us anxious.
On the island of Nantucket Esvelt wins outline acceptance, but in New Zealand he is greeted by a more skeptical audience. One Maori man tells him, "over the millennia we have heard a whole lot of fine words from the colonizers, which turned out to be hollow. You're a little bit like the missionary coming with a good story, but behind you are a whole lot of fellas with some rifles. It's not you personally that we are talking about, it's your ilk as a whole." The people behind Kevin Esvelt are, it turns out, the Pentagon, through its Defense Advanced Research Products Agency, known as DARPA. The filmmakers’ leave this startling revelation hanging in the air, instead of asking the many questions that it should prompt.
Back in the biomedical world, the narratives play out differently in each case. For the most part this is because what the protagonists initially construe as a narrow issue of personal freedom to follow their own paths begins to take on broader manifestations as their activities become more concrete and better-known. Zayner is questioned by the biological weapons division of the FBI for practicing medicine without a license (though the investigation was later dropped), David Ishee runs short of money and panics about the fate of his kids if it turns out he’s run afoul of the law, and Tristan Roberts begins to consider what happens if he succeeds in altering an infectious agent that may come back stronger.
But for one child featured in the film, Jackson Kennedy, who becomes a patient of Spark Therapeutics when his insurance agrees to cover the treatment, gene therapy is an impressive success. He regains much of his failing sight. From seeing mostly in blurs, we observe him at the end of the series leaving his glasses behind to climb into a go-kart.
The narrative of Jackson Kennedy successfully regaining his sight forms the lynchpin of the series. Without his success, "Unnatural Selection" is simply a story of (so far) unfulfilled expectation. Yet the filmmakers omit context that would place Jackson's treatment in a more ambiguous light. First, Luxturna, the commercial name of Jackson's treatment, is a viral gene therapy. It is not gene editing, the ostensible subject of "Unnatural Selection."
Second, his treatment is far from a cure; in trials, some patients experienced no benefit at all. Crucially, none have been fully cured, and some experts believe that the effectiveness of Luxturna will wear off over time. Jackson's therapy may therefore have to be repeated, at phenomenal expense.
Third, his illness is very rare. Only about 15 people per year are born with Leber Congenital Amaurosis. Why, one might ask, are gene therapists targeting rare diseases and not common ones? The reason is that very few diseases are suited to gene therapy–type treatments.
There are three important reasons why this is so, and they are not widely appreciated. Unlike the eyeball, most body organs are physically inaccessible to syringes and the medical instruments needed to accurately introduce DNA to the required cell types and cell layers. Secondly, unlike retinal cells, most human cell types are short-lived, meaning that applying gene therapy to them is virtually pointless. The third general obstacle is that, to the initial surprise of many geneticists, very few diseases can be remedied by restoring single genes. The ones that can be treated this way are mostly rare. Therefore, the market for gene therapies, collectively, but also individually, is small. In terms of gene therapy, therefore, the eye is one of the bodies' lowest hanging fruits. Treating low hanging fruit is not a failsafe recipe for subsequent rapid progress. It arguably implies the opposite.
Jackson's treatment, then, is not the gene therapy we have been sold. So while Zayner and Traywick — the biohacker and the entrepreneur — rhapsodize about the limitless potential for gene editing to put cures in the hands of ordinary people, bypassing insurance companies and busybody regulators, what unfolds instead is a profound twist in that utopian narrative. Instead of a low-cost cure, our solitary success story confers partial relief at a cost that far exceeds what most people will save in their lifetimes. Gene therapy, as it stands, does not disrupt the business model that the gene therapists and the biohackers seek to replace. It reproduces it.
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