Crispr Crittrs: a review of unnatural selection
Created and directed by Leeor Kaufman & Joe Egender
There was a wonkish phrase, buried in various molecular biology papers, seemingly designed to make readers’ eyes glaze over. Clustered regularly interspaced short palindromic repeats. In bacteria, they are sequences of DNA grabbed from invading organisms (viruses, or sometimes other bacteria) and added to the DNA of the host organism where they act as an antiviral agent. Basically, it’s acquired immunity, something fairly common in lifeforms.
Humans have it, too: it’s why we don’t usually get a case of the mumps twice and why vaccinations are effective.
But in bacteria, the genetic environment is comparatively simple, allowing scientists to follow what was happening. A Japanese team, headed by Yoshizumi Ishino, first figured out the basic mechanism, clear back in 1987. Research proceeded incrementally from there, until an American / French team, headed by Jennifer Doudna and Emmanuelle Charpentier figured out how to use the RNA part of the mechanism to cut a specific part of the DNA of a host organism, and replace it or simply eliminate it.
Clustered regularly interspaced short palindromic repeats. Or, as it’s better known, CRISPR.
With relatively unsophisticated lab equipment, it was possible to take a DNA molecule, change it as desired using CRISPR, and reinsert it into the host organism, where the changed DNA would suffuse through the body of the organism, and make the desired changes. Born with a genetic disease? Suddenly it was possible to replace the damaged DNA with healthy DNA. Have an incurable viral infection? CRISPER could create DNA that repels the virus, causing it to starve. CRISPR could potentially cure anything from multiple sclerosis to AIDs.
Want blue eyes? Or want a baby with blue eyes, black skin and an IQ of 150? With CRISPR, it was possible.
It gets even more daunting when you realize CRISPR gives us the power to change entire species. Want mosquitoes that cannot carry the malaria virus? Or even reproduce? Glow-in-the-dark dogs. Humans without the ‘god virus’. It’s all possible now.
It is, perhaps, the most powerful tool humanity has come up with. And the more powerful the tool, the bigger the benefits, and the bigger the chances for catastrophe.
Netflix, determined to bring intelligent documentaries to American television, has, in the four-part, 4½ hour series unnatural selection, brought the ethical and social implications of this new technology to the fore. The first episode introduces us to biohackers, people determined to keep this technology open source and available to all. While they have a very solid rationale for this approach (along with altruism, a deep distrust of the rapacious medical industry which is intent on preserving this technology for the rich and powerful), honesty, competence and foresightedness vary wildly, from those who see a clear path to saving humanity from itself to flat out scam artists. One fellow is selling DIY kits with everything you need for at-home genetic hacking for $140. He strikes me as both utterly sincere and extremely dangerous.
The series focuses on people drawn to the biohackers; a young man with AIDs, a boy with a genetic eye defect that is blinding him, a fellow with a horrific mitochondrial disease known as SMA-1. From there, the series follows the effects of gene therapy on those three (ranging from spectacular success to nothing to a significant setback) and expands out to look at scientific teams looking to eradicate rats in New Zealand, or malaria in Burkina Faso. The teams want the local populations to have informed ability to consent or not, and it’s intriguing watching the debate, colored by the need for change and tempered by the regional mores.
It’s a fascinating overview, not of the science behind this massive development, but the cultural, social, environmental and political implications. It could make humanity stronger, faster, more intelligent and even more compassionate. Or it could be used to create a permanent slave underclass. It’s every bleak science fiction dystopia writ large, or beyond Asimov’s wildest optimistic dreams for the race.
In the meantime, the science has not stopped. I had just finished the second episode when news broke of a new type of CRISPR, called ‘prime editing’ (below). Where CRISPR-Cas9 was the technology examined in unnatural selection, which has about a 70% implantation success rate, this new development is effectively 100%. Eliminating random error.
Given the stakes, we need to be faster, stronger, and more intelligent now, because this technology could make us gods—or make us extinct.
The research, published in the journal Nature on Oct. 21 and led by Andrew Anzalone, describes the new technique, dubbed “prime editing,” in a series of elegant experiments using four human cell lines and mouse brain cells. Performing 175 different DNA edits, the researchers show prime editing can change DNA with incredible precision and, importantly, introduces errors at a much lower rate than previous gene-editing technologies. To demonstrate this, the team corrected the genetic mutations for two human genetic diseases, sickle cell and Tay-Sachs disease, in human cells. They showed the necessary edits could be made to the DNA to reverse the genetic mutations causing those diseases.