This is really smart. By making it impossible for the cells to generate Thymidine, they can not create more DNA which is needed to produce the genome of two (possibly malignant) daughter cells. Why Thymidine? Because there is a key difference between DNA and RNA: DNA has Thymine while RNA has Uracil. Both DNA and RNA share the other 3 bases: Adenine, Cytosine and Guanine. The cell only needs additional DNA if it goes into cell division, but it needs RNA all the time for many cellular processes. Singling out Thymidine is a really cool idea!

wouldn't this cause issues with dna repair?

I expect that, yes. The cell might die if the DNA damage occurred in a critical position.

Yep - cells would die. ...UNTIL they accrue enough dna damage to accidentally either:

- create a new way to generate thymidine

- fall into a proliferation strategy that no longer needs thymidine

Human cells did the same thing and created checkpoints to preclude malignant growth. There are a number of checkpoints already employed in your own bodies. But if you accrue enough DNA damage, you can get around each of those checkpoints (and get cancer):

- IF too much DNA damage, then die

- IF divided too many times, then die

- IF committed to die, actually die

But if a cell collects enough damage, it can get around ALL of the checkpoints. And evolution has shown us that there is no perfect watcher of the watchmen. Still pretty cool to create a new checkpoint this way.

If I was in an environment where such strong mutations can happen in a single generation of non-reproducing cells, I'd ve very worried about the health of my original cells.

What about the heterogeneity of the original cells?

In Jurassic Park there is a Lysine Contingency which was a genetic modification to prevent the dinosaurs from producing a key molecule, which in turn would prevent their escape and propagation in the wild.

I think that the original Jurassic Park book mentioned that the dinosaurs found a way to get around the lysine issue.

After all, humans can't produce lysine either, and we propagate in the wild just fine!

This page didn't load for me, so here is the original article:

https://www.cell.com/molecular-therapy-family/molecular-ther...

So would using these cell modifications, in the case of growing organs perhaps, require germline modifications?

Or what are other types of uses for these cells?

These cells won’t divide because they will fail to replicate their DNA due to the lack of thymidine. The use case is cell therapies, where you give the patient cells grown in the lab but you don’t want those cells to potentially divide and cause cancer. For example, CAR T therapy to treat cancer, or dopaminergic neuron replacement therapy for Parkinson’s disease.

Hmm. "Life finds a way."