Unnatural Selection review: captivating mind-bender but needed more science

Today’s post is a review of Unnatural Selection, the new Netflix science docuseries focused on CRISPR and other disruptive genetic and reproductive technologies.

The show is an interesting mix of personalities and stories from patients, scientists, biohackers, and more. One patient thread is the story of a wonderful little boy named Jackson Kennedy. He wants to be an astronaut. He also happens to have the random misfortune of two mutant copies of a gene that together are causing him to lose his vision. Unnatural Selection follows his story as he and his family find out that a new FDA-approved therapy might help him.

He ultimately gets the treatment and we see his initial therapeutic response. More on that in a bit.

So what’s my big-picture take on this show?

Netflix series Unnatural Selection with patient Jackson Kennedy, one of the few people who gets a happy ending in the show.
Netflix series Unnatural Selection with Jackson Kennedy pictured here, one of the few people who gets a kind of happy ending in the show.

Unnatural Selection takes the viewer on an emotional and intellectual rollercoaster ride. At various times watching it, I went from disliking some of it to finding other parts quite compelling. Generally, it improved as it went along. After watching episode one, for example, I would have given it only 2.5-3 stars out of five mainly due to too much hype in that episode, but later episodes were closer to the 4-5-star range.

Overall, I give the series 3.5 stars out of five. It’s a mind-bender that is captivating and at times disturbing. However, we need to be disturbed because the reality here is unsettling in some ways and what’s going on out there is real whether we know about it or not. Better to know, think, and engage. 3.5 stars out of 5

The show covers a lot of ground, maybe too much for a four-part series. I wondered at times while watching if the producers would have been better served by focusing on fewer topics as they didn’t always all coherently come together. The show goes through everything from biohacker attempts to make genetically modified dogs to an effort to possibly extinct malaria-causing mosquitos in a region to a literal stab at human DIY HIV therapy.

It also features some rigorous clinical trial efforts like gene therapy for vision loss for Jackson (which, good news, preliminarily seems to have potentially helped him see better) as well as Spinraza an oligonucleotide therapy for spinal muscular atrophy, which was not successful for the patient in the series, Nicholas Piazza, who tried it and reportedly had a side effect. Nicholas and his family were a moving part of the show too.

There are in addition some segments on anti-aging and “3-parent babies”. Readers of The Niche here will know I’ve been skeptical of “3-parent” (aka “mitochondrial transfer”) technology and I’ve discussed some of the risks it carries. If memory serves, the show mentioned no risks for it other than maybe social. Yikes.

The cast of real-life characters on Unnatural Selection includes in some ways most prominently certain biohackers like Josh Zayner and David Ishee, some compelling patients like Jackson and Nicholas mentioned earlier, bioethicist Jeffrey Kahn, an assisted reproduction doctor and personnel, CRISPR pioneer Jennifer Doudna, gene drive scientist Kevin Esvelt, scientists working to eradicate devastating disease-associated and ecologically damaging pests (think mosquitoes and rats) out in the real world potentially using gene drive, everyday people contemplating gene drive and other cutting-edge technologies, and many more.

At first, the heavy emphasis on biohackers left me concerned. I was scratching my head a bit because frankly some of what the various biohackers out there are doing is really dangerous including potentially to other people and, I wonder, do they have a clear sense of the risks? Comments from Zayner on the show in the heat of various moments like, “There are no mistakes to be made” (did I hear that right?) suggest a kind of hubris or naivete at times. Some of this may just be frustration at “the system”, but the reality is that science, especially cutting-edge stuff, has tons of mistakes, and some can be very costly on multiple levels.

However, as the show went along I felt that it provided a somewhat broader context for the biohackers and they were fleshed out as complex people better by the end. It may be that when Zayner made the comment on mistakes he was still amped up from a long period of FBI questioning. I wasn’t totally clear on that.

Also, my impression was that Ishee has a deeper sense of the big picture than your average biohacker. In addition, Zayner is shown by the end as having some concerns about the impact of what he’s doing. Still, I’m sure some academic watchers will be disturbed by the depiction of the biohacking efforts. It got a huge amount of airtime on the show.

For those other biohackers intent upon commercializing their efforts in humans and going beyond self-modification, the show demonstrates (rather than preaches) how that can go spectacularly wrong. A side note is that I didn’t realize until about halfway through the series that Aaron Traywick of Ascendance was that guy I had heard about who died some months back.

It seems that Ishee and Zayner are now working together on the dog genetic modification project. I still am not a fan of the idea of genetically modifying dogs with CRISPR to make them glow (or be huge), mainly because I think it’s likely you’re going to make deformed dogs that suffer in the process and there’s no benefit to the dogs. I do acknowledge for context that we should also look at the crazy stuff that humans have done to dogs as a species over the centuries just with standard breeding.

Even so, I wish the show had somehow conveyed how badly things could turn out with reproductive introduction of CRISPR into animals or especially people, in terms of leading to suffering or death, especially if it is attempted without doing a lot of homework and giving it some deep contemplation. I did like that the show showed Ishee literally doing his homework such as by reading papers. We scientists, no matter where we work or who we are, need to do tons of homework. I am constantly reading and learning new things as a professor.

More specifically for CRISPR, the show needed a deeper discussion of how it works and how it can go wrong. Viewers should have learned more about concrete known weaknesses and risks: off-target effects, indels v. true precision edits, mosaicism, and unintended outcomes. The show gives the impression that you inject and for better or worse, it just works. That’s a bit of a cartoonish view. It didn’t have to be that superficial.

I get it that scientists going into detailed explanations of cell and molecular biology or ethicists talking about risks isn’t always compelling television by itself for a broad audience, but still it’s very important context. Unnatural Selection overall just didn’t have enough science for me. Maybe there’s no surprise there since I’m a scientist, but I think they could have pulled off having more science without being boring at all.

One other thing that didn’t work was including Friends of the Earth as supposedly representative skeptics of CRISPR gene editing. I saw that as a major mistake.

In terms of other things that I did like, the coverage of costs on the show and how that negatively impacts patients and families was powerful. It’s so important. Note that I have heard criticism of the show for being exploitive of the patients it featured, but that wasn’t my feeling.

I also enjoyed the segments with Kevin Esvelt and he provided some nice balance for the show. You could feel him grappling with the complexities and weight of all that he’s doing.

I don’t know that he’s making the right decision to try gene drive (if you’re asking “What is gene drive?” see here or even better search for “Kevin Esvelt” on YouTube) in the real world, but this guy is a deep thinker and he cares. It looks like we’ll learn more about the impact soon one way or another of gene drive in the real world. Note that an early attempt at gene drive targeting mosquitos didn’t work so well.

I tended to agree with the Maori people featured on the show who were skeptical about the wisdom of using gene drive to wipe out invasive rats in New Zealand, but then again what about the native birds disappearing there due to rats? It’s not a straightforward decision.

For me, that kind of unsettling tension between differing views on the same question is the key strength of Unnatural Selection. You can end up agreeing with totally opposing sides as you watch. I did.

On another level I brought a unique sense as a viewer of the show. I couldn’t help but think at times about the somewhat satirical new book my daughter Julie and I wrote about how to use CRISPR and other tech like stem cells to try to make a real dragon (How to Build a Dragon or Die Trying). I think biohacker Josh Zayner even said at one point in Unnatural Selection something about how biohackers naively thought they could quickly DIY make a pet dragon. I still wonder if someone might be inspired by our book to try to make something like a real dragon. People have semi-jokingly (I think) told me they were.

Overall, I’d recommend Unnatural Selection, but I encourage you to challenge some of its assumptions as you watch and go do more reading to decide things for yourself.

2 thoughts on “Unnatural Selection review: captivating mind-bender but needed more science”

  1. I didn’t think the show was intending to show the exctual science of gene editing but rather as a platform to present the idea of gene editing and its future implications. It has also raised the questions of moral grounds by big pharma and corporates where they are trying to value a life and make unreasonable profit off it.

  2. I thought the series was informative for the 101 public education conversation for the scientific community to appreciate where that’s currently going.

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