Georeactor Blog

A Twitter thread led me to find out about a cutting-edge concept in genetic engineering: the Genomically Recoded Organism (GRO).

The term originated in a 2013 paper in Science. Researchers replaced UAG stop codons in the E. coli genome with another type of stop codon (UAA). This didn't change the end proteins, but it demonstrated the possibility to rewrite a codon throughout the genetic code. If this were replaced with a codon which does not exist in nature (Wiki covers this in articles on unnatural base pair or expanded genetic code), then genes would be rendered illegible to all natural cells. The fears of GMOs spreading by horizontal gene transfer, hybridization, and so on could be nullified.

Over the past ten years, the technology has only rarely appeared in the biotech press. One company - GRO Biosciences - is working on therapeutics, and another -Pearl Bio - recently came out of stealth mode with a patent portfolio (website says they can make "template-directed biomaterials").

In the early-to-mid 2010s, researchers were developing a related concept in mirror life - biology with flipped chirality for all amino acids, ribosomes, etc. This may have fallen out of favor or press coverage, though related work was covered in Science last year.

In 2018, researchers gave E. coli a genetic firewall by removing one natural codon from tRNAs, preventing reproduction of transferred genes or viruses which enter the cell. Earlier this year, a paper in Nature took on some challenges with this approach. Invading genes and viruses might facilitate their own translation, so they gave the cell "viral tRNAs" which swap one amino acid's codon.

The futurist Tweet that I saw projected this to the far future, suggesting humans move to this new genetic OS and become immune to viruses, or maybe there were enough combinations that humans could each have their own codon:amino-acid mappings and prevent any commonality.
Genetics Twitter was less impressed. Dr. Angela Rasmussen, a virologist, quote-tweets it with:

I hate to unblow anyone's mind, but this isn't how DNA, codons, or viruses work.

I couldn't shake out whether Rasmussen was criticizing making everyone's DNA unique, applying the research to the human genome, or something more core to GROs existing in complex organisms or outside a lab. The comments did not expand on this, though they seem to deal out a dollop of skepticism of a common author in the GRO, firewall, and mirror-life papers: Dr. George Church.

As an outsider, it was difficult to suss out why Church was a red flag within this community. A 2016 /r/science AMA was mostly praise and curiosity. Wikipedia summarizes only two controversies: funding from the Epstein Foundation, and a thought experiment about reactivating genes for a Neanderthal baby. After more research the issue may be that Church, and Harvard projects and spinoff companies in his orbit, are chasing trends in so many directions: life-extension, Neanderthals, mammoths, data-sharing, cross-species organ donation, dating apps, blockchain, and biofuels.

For an extended rant on this guy's willingness to be interviewed on just about any topic in genetics: https://forbetterscience.com/2023/06/26/george-church-colossal-wnker/

At the end of the day, this is a fascinating glimpse into a type of GMO which I didn't know existed. Considering there is only a smattering of research replacing a few codons in the popular reference species E. coli, the technology may be still in its infancy or walled off by patents. As an outsider I can understand the basic mechanics of what's being proposed. It may still be viewed as unrealistic to add more codons, or to have a GRO in the real-world environment without any tRNAs getting exchanged between GRO and natural cells. Or maybe it's all about personal reputation. Would love to know more.