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 Hayes
Transcript
Back 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 throughout the generations.
What I’d like to talk about today is another example of a similar technology, but one that’s distinct enough, and which carries substantially less long-term risk, that it’s being greeted primarily with celebration rather than concern.
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In early August of 2024, a gene-editing researcher at the University of Pennsylvania, Dr. Kiran Musunuru, was asked if there was anything he could do to help a baby that was being treated at the Children’s Hospital of Philadelphia for CPS1 deficiency, which manifests as an inability to get rid of the ammonia that builds up in one’s body as a byproduct of protein metabolism.
We all generate a small amount of ammonia just as a function of living, and this deficiency kept the baby from processing and discarding that ammonia in the usual fashion. As a result, ammonia was building up in its blood and crossing into its brain.
The usual method of dealing with this deficiency is severely restricting the suffer’s protein intake so that less ammonia is generated, but being a baby, that meant it wasn’t able to grow; he was getting just enough protein to survive and was in the 7th percentile for body weight.
So a doctor at the Children’s Hospital wanted to see if there was anything this gene-editing researcher could do to help this baby, who was at risk of severe brain damage or death because of this condition he was born with.
Gene-editing is still a very new technology, and CRISPR and associated technologies are even newer, still often resulting in inaccurate edits, many of which eventually go away, but that also means the intended edit sometimes goes away over time, too—the body’s processes eventually replacing the edited code with the original.
That said, these researchers, working with other researchers at institutions around the world, though mostly in the US, were able to rush a usually very cumbersome and time-consuming process that would typically take nearly a decade, and came up with and tested a gene-editing approach to target the specific mutation that was causing this baby’s problems, and they did it in record time: the original email asking if Dr Musunuru might be able to help arrived in August of 2024, and in late-February of 2025, the baby received his first infusion of the substance that would make the proper edits to his genes; they divided the full, intended treatment into three doses, the first being very small, because they didn’t know how the baby would respond to it, and they wanted to be very, very cautious.
There were positive signs within the first few weeks, so 22 days later, they administered the second dose, and the third followed after that.
Now the research and medical worlds are waiting to see if the treatment sticks; the baby is already up to the 40th percentile in terms of weight for his age, is able to eat a lot more protein and is taking far less medication to help him deal with ammonia buildup, but there’s a chance that he may still need a liver transplant, that there might be unforeseen consequences due to that intended edit, or other, accidental edits made by the treatment, or, again, that the edits won’t stick, as has been the case in some previous trials.
Already this is being heralded as a big success, though, as the treatment seems to be at least partially successful, hasn’t triggered any serious, negative consequences, and has stuck around for a while—so even if further treatments are needed to keep the gene edited, there’s a chance this could lead to better and better gene-editing treatments in the future, or that such treatments could replace some medications, or be used for conditions that don’t have reliable medications in the first place.
This is also the first known case of a human of any age being given a custom gene-editing treatment (made especially for them, rather than being made to broadly serve any patient with a given ailment or condition), and in some circles that’s considered to be the future of this field, as individually tailored gene-treatments could help folks deal with chronic illnesses and genetic conditions (like cystic fibrosis, Huntington’s disease, muscular dystrophy, and sickle cell), but also possibly help fight cancers and similar issues.
More immediately, if this treatment is shown to be long-term efficacious for this first, baby patient, it could be applied to other patients who suffer the same deficiency, which afflicts an estimated 1 in 1.3 million people, globally. It’s not common then—both parents have to have a mutant copy of a specific gene for their child to have this condition—but that’s another reason this type of treatment is considered to be promising: many conditions aren’t widespread enough to justify investment in pharmaceuticals or other medical interventions that would help them, so custom-tailored gene-editing could be used, instead, on a case-by-case basis.
This is especially true if the speed at which a customized treatment can be developed is sped-up even further, though there are concerns about the future of this field and researchers’ ability to up its efficiency as, at least in the US, the current administration’s gutting of federal research bodies and funding looks likely to hit this space hard, and previous, similar victories that involved dramatically truncating otherwise ponderous developmental processes—like the historically rapid development of early COVID-19 vaccines—are not looked at favorably by a larger portion of the US electorate, which could mean those in charge of allocating resources and clearing the way for such research might instead pull even more funding and put more roadblocks in place, hobbling those future efforts, rather than the opposite.
There are plenty of other researchers and institutions working on similar things around the world, of course, but this particular wing of that larger field may have higher hurdles to leap to get anything done in the coming years, if current trends continue.
Again, though, however that larger context evolves, we’re still in the early days of this, and there’s a chance that this approach will turn out to be non-ideal for all sorts of reasons.
The concept of tailored gene-editing therapies is an appealing one, though, as it could replace many existing pharmaceutical, surgical, and similar approaches to dealing with chronic, inherited conditions in particular, and because it could in theory at least allow us to address such issues rapidly, and without needing to mess around with the germ-line, because mutations could be assessed and addressed on a person-by-person basis, those edits staying within their bodies and not being passed on to their offspring, rather than attempting to make genetic customizations for future generations based on the imperfect knowledge and know-how of today’s science, and the biased standards and priorities of today’s cultural context.
Show Notes
https://www.nejm.org/doi/full/10.1056/NEJMoa2504747
https://www.nih.gov/news-events/news-releases/infant-rare-incurable-disease-first-successfully-receive-personalized-gene-therapy-treatment
https://www.wired.com/story/a-baby-received-a-custom-crispr-treatment-in-record-time/
https://www.wsj.com/tech/biotech/crispr-gene-editing-therapy-philadelphia-infant-8fc3a2c5
https://www.washingtonpost.com/science/2025/05/15/crispr-gene-editing-breakthrough/
https://www.npr.org/sections/shots-health-news/2025/05/15/nx-s1-5389620/gene-editing-treatment-crispr-inherited
https://interestingengineering.com/health/first-personalized-crispr-gene-therapy
https://www.nature.com/articles/d41586-025-01496-z
https://www.nytimes.com/2025/05/15/health/gene-editing-personalized-rare-disorders.html
https://www.nytimes.com/2025/05/31/world/asia/us-science-cuts.html
https://www.livescience.com/health/genetics/us-baby-receives-first-ever-customized-crispr-treatment-for-genetic-disease
https://en.wikipedia.org/wiki/He_Jiankui_affair
https://en.wikipedia.org/wiki/CCR5
https://en.wikipedia.org/wiki/Berlin_Patient
https://en.wikipedia.org/wiki/CRISPR_gene_editing
https://en.wikipedia.org/wiki/CRISPR
https://pmc.ncbi.nlm.nih.gov/articles/PMC6813942/
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