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Personalized CRISPR

Personalized CRISPR

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 This week we talk about gene-editing, CRISPR/Cas9, and ammonia.We also discuss the germ line, mad scientists, and science research funding.Recommended Book: The Siren’s Call by Chris HayesTranscriptBack in November of 2018, a Chinese scientist named He Jiankui achieved global notoriety by announcing that he had used a relatively new gene-editing technique on human embryos, which led to the birth of the world’s first gene-edited babies.His ambition was to help people with HIV-related fertility problems, one of which is that if a parent is HIV positive, there’s a chance they could transmit HIV to their child.This genetic modification was meant to confer immunity to HIV to the children so that wouldn’t be an issue. And in order to accomplish that immunity, He used a technology called CRISPR/Cas9 to modify the embryos’ DNA to remove their CCR5 gene, which is related to immune system function, but relevant to this undertaking, also serves as a common pathway for the HIV-1 virus, allowing it to infect a new host.CRISPR is an acronym that stands for clustered regularly interspaced short palindromic repeats, and that refers to a type of DNA sequence found in all sorts of genomes, including about half of all sequenced bacterial genomes and just shy of 90% of all sequenced archaea genomes.Cas9 stands for CRISPR-associated protein 9, which is an enzyme that uses CRISPR sequences, those repeating, common sequences in DNA strands, to open up targeted DNA strands—and when paired with specific CRISPR sequences, this duo can search for selected patterns in DNA and then edit those patterns.This tool, then, allows researchers who know the DNA pattern representing a particular genetic trait—a trait that moderates an immune system protein that also happens to serve as a convenient pathway for HIV, for instance—to alter or eliminate that trait. A shorthand and incomplete way of thinking about this tool is as a sort of find and replace tool like you have in a text document on your computer, and in this instance, the gene sequence being replaced is a DNA strand that causes a trait that in turn leads to HIV susceptibility.So that’s what He targeted in those embryos, and the children those embryos eventually became, who are usually referred to as Lulu and Nana, which are pseudonyms, for their privacy, they were the first gene-edited babies; though because of the gene-editing state of the art at the time, while He intended to render these babies’ CCR5 gene entirely nonfunctional, which would replicate a natural mutation that’s been noted in some non-gene-edited people, including the so-called Berlin Patient, who was a patient in Germany in the late-90s who was functionally cured of HIV—the first known person to be thus cured—while that’s what He intended to do, instead these two babies actually carry both a functional and a mutant copy of CCR5, not just the mutant one, which in theory means they’re not immune to HIV, as intended.Regardless of that outcome, which may be less impactful than He and other proponents of this technology may have hoped, He achieved superstardom, briefly, even being named one of the most influential people in the world by Time magazine in 2019. But he was also crushed by controversy, stripped of his license to conduct medical research by the Chinese government, sent to prison for three years and fined 3 million yuan, which is more than $400,000, and generally outcast from the global scientific community for ethical violations, mostly because the type of gene-editing he did wasn’t a one-off sort of thing, it was what’s called germ-line editing, which means those changes won’t just impact Lulu and Nana, they’ll be passed on to their children, as well, and their children’s children, and so on.And the ethical implications of germ-line editing are so much more substantial because while a one-off error would be devastating to the person who suffers it, such an error that is passed on to potentially endless future generations could, conceivably, end humanity.The error doesn’t even have to be a botched job, it could be an edit that makes the edited child taller or more intelligent by some measure, or more resistant to a disease, like HIV—but because this is fringy science and we don’t fully understand how changing one thing might change other things, the implications for such edits are massive.Giving someone an immunity to HIV would theoretically be a good thing, then, but if that edit then went on the market and became common, we might see a generation of humans that are immune to HIV, but potentially more susceptible to something else, or maybe who live shorter lives, or maybe who create a subsequent generation who themselves are prone to all sorts of issues we couldn’t possibly have foreseen, because we made these edits without first mapping all possible implications of making that genetic tweak, and we did so in such a way that those edits would persist ...

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