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Your 'runtime' is physics.

A protein is a chain of concatenated amino acids.

The chain will "ball up" into a 3-dimensional shape.

Its shape = its function.

Why does the balled-up chain function the way that it functions? Because other balled-up protein chains bump up against it in a certain way and suddenly an iron molecule can be contained within the confines of this mega-structure that has formed, and you now have hemoglobin.

Why does the chain ball up the way it does? Can we predict how a protein chain will ball up? Well, protein folding is an NP-Complete problem. Solve it and you will get at least $1M USD, change the world, etc.

- Software Engineer with a B.S. Degree in Biological Science w/ a focus on genetics + minor in Chem.

But physics is the 'runtime' for everything at some level of interpretation. I point out this other hypothetical system because it's possible for 'higher-level' runtimes to emerge from lower-level physicals rules, and this looks like it might be one of those cases. (To clarify, by 'emerge', I mean another consistent set of behaviors appears which are capable of formal description and which can be viewed as consequences of a lower-level system without actually resembling that system.)

I had a discussion about this a few days ago. If the current state of DNA programming is done at the physical level, that's like writing your code by doing photolithography on silicon: not very productive. A level up, maybe the Von Neumann architecture for genetic engineering is the world of DNA and the various proteins like transcriptase. When will we come up with the equivalent Structured Programming? Or Object Orientation? Or Operating Systems?

Each represents an abstraction over the others, and increases productivity.

The level up from DNA is proteins, the molecules that actually do stuff. These are relatively structured: Primary structure is the amino acid sequence.

Secondary is the structures that from out of the primary sequence: Helices coil, like DNA except except only a single helix not double. Double and triple helices (see keratin and collagen respectively) are more like winding 2 or 3 single helices around themselves, and Sheets: two or more strands that bond to each other either parallel or antiparallel.

Then it starts to get interesting. These secondary structures form domains which are the functional subunit of proteins that actually do (or are in the case of non-enzymes) stuff. These are the equivalent of structured programming. E.g. join an antibody variable domain (the bit that stick to stuff) to an enzyme, inject it into the bloodstream and you get expression on the enzyme wherever the antibody happens to bind (e.g. to a cancer cell).

(Tertiary and quaternary structure refer to the complete protein and to proteins that form a functional unit with other proteins respectively.)

The OO analogy is like the OO analogy for HDLs, the protein _is_ an object. OS is whole organism level.

Although it doesn't alter the analogy much, there is also the even higher level of 'quinary structure' - although it is disputed:

https://www.ncbi.nlm.nih.gov/pubmed/23943406

It's what we do!

https://serotiny.bio/notes/pinecone/ :: http://biologylabs.utah.edu/jorgensen/wayned/ape/

as

C :: assembly

We'd even hope it's a bit like 'basic' rather than C, to the point where motivated non-scientists could even start to use it: https://serotiny.bio/notes/support/tutorials/

My understanding is we got programmable computers in large part because: 1) a bunch of scientific/engineering advances we were in a position to make were bottlenecked by massive amounts of 'boring' calculations 2) Some of those affected areas related to the war effort in critical ways, so lots of money and resources were poured into solving the problem.

Seems like we're in a similar position with '1' above, in connection with genetic engineering, so demand exists to abstract over and automate the boring stuff. But maybe the problem is significantly harder, or maybe we're just lacking the pressure that would lead to focused/cooperative effort and lots of resources pouring in, like we had in '2'.

> lacking the pressure that would lead to focused/cooperative effort and lots of resources pouring in

Until literally a few months ago, hacking at the level of the protein abstraction was relegated to academics. Then Chimeric Antigen Receptors cured children of cancers, and were approved by the FDA. And so in August, Kite got bought by Gilead for $12B. Then in November Gilead bought another class of multi-domain protein biotherapeutics called SynNotch for $0.5B from an 18 month old startup. And Juno got purchased yesterday for $9B again for their work on CARs - multi-domain protein biotherapeutics.

We'd like to think that such cooperative effort and resources are just starting to pour in. But up until very recently, it was not obvious what the commercial value was when working at such an abstraction layer.

That's interesting to know, thanks. Regarding the 'cooperative' aspect, though—acquisitions might be falling a bit short of the ideal imo ;) But maybe it will be enough.

But I mean, depending on how you look at it, at some level of interpretation everything can be a higher-level runtime.

Yes, protein-protein interactions are a higher-level runtime emerging from lower-level physical runtimes.

But on the same vein, Hacker-news is a higher-level runtime emerging, in part, from protein-protein interactions, emerging from lower-level physical runtimes.

Can we describe the runtime without invoking some notion of purpose nor questioning free will?

> at some level of interpretation everything can be a higher-level runtime.

I don't see how everything can be considered a higher-level runtime. The concept of an execution environment just doesn't map to everything, unless you want to use a definition of it so general as to make it useless. If someone drops a glass and it shatters, would a higher level system describing the mechanics of glass shattering be a runtime? I don't see it.

> Yes, protein-protein interactions are a higher-level runtime emerging from lower-level physical runtimes.

That's pretty different from what I was describing. See my other comment for more details: https://news.ycombinator.com/item?id=16235639

> ... Hacker-news is a higher-level runtime emerging, in part, from protein-protein interactions, emerging from lower-level physical runtimes.

I think we disagree on the meaning of the word 'runtime'. I would not consider Hacker News to be a runtime. I do agree with your main point there, though, if you just replaced 'Hacker News' in your statement with, say, the Java runtime environment, then yes, I think it is a higher-level system, usefully described as a runtime, which has emerged as a consequence of the laws of physics doing what they always do.

> Can we describe the runtime without invoking some notion of purpose nor questioning free will?

My usage of 'runtime' does not involve free will nor purpose.

> If someone drops a glass and it shatters, would a higher level system describing the mechanics of glass shattering be a runtime? I don't see it.

It can be a runtime, if some interface is built on top of the phenomenon of the shattering of glass.

Because humans.

In that regard, the protein programs exist and interact with each other in a runtime environment/OS that is 'physics'. Which is cool.

Especially, because those programs, when run together, along with all sorts of other small molecule/lipid/temperature conditions are sufficient to output, well, me.

I was somewhat avoiding bringing that up just because, in theory, every physical 'system' in the universe just boils down to physics—and this question gets pretty close to the line between where it's useful to start talking about a higher-level system, versus thinking in terms of chemistry (and/or physics). So it could get confusing.

If there is a higher level system analogous to a runtime-environment which could be abstracted from actual genetic machinery, I would bet the rules of its operation would still be at least partially in terms of chemical rules (in other words, you couldn't abstract over it entirely).

My justification for it is that I think the system is split between the decentralized behavior of proteins and enzymes etc. just following the rules they always follow, combined with the external 'system' which sets up conditions constraining and otherwise directing the proteins. That second system could maybe be higher level, but it's still central to its operation that it interfaces with a 'raw' chemical system. (Just an idea of course—my confidence that it means anything is ~12%).

Edit: another analogy to maybe clarify (or confuse) things. I see the proteins/enzymes etc. which I described as decentralized as operating like a cellular automaton (e.g. Conway's GoL), but then the 'external'/centralized system as like another layer of rules which sort of pushes around clusters of cells in the grid in various significant ways, while all those clusters are still locally just executing the simple automaton rules.

Very much. We've actually tried to capture some of those runtime variables within proteins and break down the programs into smaller compossible units. And start to keep track of which conditions are required for particular functionalities of which components. Life has already made a bunch for us to look at.

Ultimately, in our hands, those properties are strongly linked to physical associations, locations within a cell, enzymatic capabilities, and i/o (light, heat, chemical concentrations, force, etc.).

Then you start (re)building little i/o robots from reusable components for use by and within cells that are regulated by their location and associations (in a wet Brownian environment). All by coding using that same genetic source.

> Makes me curious about the 'runtime' which makes their impressive execution possible

https://en.wikipedia.org/wiki/Ribosome

If DNA is the source code and proteins are the compiled programs, the Ribosome is the compiler, not the runtime.

It's an analogy. You could also say that DNA is the program, the Ribosome is the interpreter and proteins are the output, which is much closer to the truth.

Reflections on Trusting Trust...

Wouldn't the ribosome be the compiler, that translates codes to proteins?

Yes.