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Comment by tmabraham | Hacker News Reader

While this top-down approach (removing unnecessary parts of an organism and keeping the essential parts) is really impressive, I personally find the bottom-up approach more interesting: building an "artificial cell" by adding all the transcription and translation machinery into a lipid vesicle, allowing for this "artificial cell" to produce proteins to do various tasks. For example, people have developed "artificial /synthetic cells" that communicate with each other [1] and even bacteria [2]. There has also been some recent study on dividing cell-sized lipid vesicles with membrane proteins [3]. I know there were some comments about science has achieving a biological “Hello World”, and I think this sort of work is what is going to get us there.

[1]: https://www.nature.com/nchem/journal/v9/n5/abs/nchem.2644.ht...

[2]: https://pubs.acs.org/doi/abs/10.1021/acsami.8b10029

[3]: https://www.nature.com/articles/s41467-020-14696-0

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The approach of removing unnecessary parts from a genome to find the minimum brings to mind Muntzing. In the 1940s, Earl Muntz was a TV seller who reduced manufacturing costs by cutting out unnecessary components. He walked around the lab with diagonal cutters and snipped out components until the TV stopped working. He'd put the last component back and have a new lower-cost design. The TVs only worked in high-signal areas, but were much cheaper than the competition and sold a ton.

https://www.electronicdesign.com/technologies/boards/article...

If you can create something living by a combination of non living parts, I think that would be an interesting first. All of the life we know of, presumably has living ancestors. Hence the notion of a "spark" of life that is passed on like the flame of a torch. If we can create life from raw parts and supply the spark ourselves, it increases the relevance of science. Suddenly the idea of sending seeds of ecosystems in the form of printers and data would become viable.

We didn't create life from nothing, but we can certainly get close. https://en.wikipedia.org/wiki/Miller%E2%80%93Urey_experiment

Close? Yeah no, I dont think so. The experiment was basically a complete failure. It just happens to be interesting to analyses what actually happened and why. Its also based on assumed condition on earth that are now consider extremely unlikely.

Once you have mastered the top-down ("is this really the minimum? Or is it a local minimum?") approach, then you could attempt to bottom-up with an end product very firmly in mind. This way, you could skip aiming for parts that you might have thought required which were in reality redundant, or secure the existence of a piece you had once thought superfluous.

After you had bottom-upped a few times, one might even try to figure out a necessary order for the steps and possibly gain some more insight into evolution that way.

As all engineering, it boils down to requirements. Mycoplasmata, from which JCVI-syn3A has been developed, is reported to "survive without oxygen", which means that it's not necessarily a "pure" anaerobic organism. We must assume that there has to be an existing mechanism that protects this bacteria from highly reactive oxygen. If the design requirements don't include surviving the natural environment, then that is one of probably many more areas to trim genetic "fat" from. However, I don't know much about their work on synthetic bacteria nor the environment used for it, so it's possible that the aforementioned mechanism to be already removed from its genes.

What do you mean? Like creating every protin without a ribosome? Why would you need to go to that lengths of artfical? Seams to like you have to start from the top up in one way or another. Starting from the complete bottom just seams over the top.

If you can figure out how to go bottom up, it will result in new innovations in microscopic manufacturing methods.

Or... you can just use the top up built cell to manufacture things. Why build your own nanorobots when there are pre made nanorobots that already works.

Because switching to a different chemical composition (not carbon based) is more likely that way.

I think it must be possible to create equvivalent functionality from more durable materials.

This certainly is scify, but imagine changing all your cells one by one to cells which can withstand wider temperature ranges, and corrode (rot?) half as easily.

Starting from the bottom means, you really did understand it all, once completed ..

If that is the ultimate purpose and you have a way to slowly progress towards full understanding sure.

Oh, I would say many researchers have that goal, but probably not many would consider it a realistic goal to be achieved in their lifetime ..

(all assumed, biology is not my area)

> Starting from the complete bottom just seams over the top. Is it really?

"What I cannot create, I do not understand." - Richard Feynman

And to clarify, currently the ribosomes are provided as part of the cell-free transcription/translation system. Additionally, amino acids, tRNA (plus tRNA synthetase), RNA polymerase, and a primitive energy source (ATP with some extra energy in creatine phosphate) are all provided.

Here are the components of the most common cell-free transcription/translation systems (PURE): https://www.nature.com/articles/nprot.2015.082/tables/1

Yes. Starting from the bottom, we might in the process discover that 90%-99% of cell components are cruft/inefficient, and discover how to make cells 10 or 100 times smaller. Imagine being able to inject neurons in the brain that are 100 times smaller.

Couldn't messing around with these artificial cells expose us to the risk of creating some second order mutations in humans from accidentally introducing these cells to our microbiome from the lab akin to the COVID-19 escaping a 'gain of function' virus lab theory?

It would be extremely unlikely that such an artificial cell could colonize humans in any way, and even more unlikely that such a cell would be pathogenic.

Source?

Look at the proportion of natural cells that can colonize humans versus those that can't. Similarly, look at the proportion of pathogenic organisms versus non-pathogenic organisms. Assuming the goal wasn't to produce a pathogen, I find it unlikely we'd produce one accidentally.

Here's hoping

Maybe that's the beauty of it. Maybe now's exactly the propitious time to play fast and lose with these things. The world today is more prepared than it has ever been - the overall impact may not even register as an independent event and be taken only as another wrinkle to current pandemic.

...but for the record, the above is not an advice. Here's the mandatory and responsible advice: kids, have fun (with science), but wear the things to keep it safe!

Meh, if you are not doing the atoms yourself from leptons and quarks then I am not interested.

Of course, there's a relevant xkcd: https://xkcd.com/378/

Man: “I shall create life from dirt, to show I am equal with you.”

God: “Get your own dirt.”

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