Is cell-free Life possible?

Question

I think most of the people on this site know about the famous Baltimore paper describing the ability of the poliovirus to replicate itself without the need of cells but I want to expand on the issue and ask could it be possible to have truly "cell-free" Life-e.g. life forms that do not have cells in any form according to modern biology but yet can be considered "alive" by its standards? This is the first paper in historical context describing the possibility of creating a self-replicating molecule in the laboratory. Well, it's about a viral genome and it only can self-replicate so it's not like it's alive according to what we consider "true" living organism, but nevertheless it triggers an interesting chain of assumptions in my mind. What if we could design a system where nucleic acid can evolve outside of cells? Then, what if we managed to provide an energy source t drive this evolution outside of the context of cells? Would such nucleic acid evolving on its own in a test tube depending only on the energy source we provide and on the specific conditions in the test tube be considered equal to a gene evolving in a "true" living organism? What if then we managed to add more nucleic acid's molecules to the system, just enough to have all the components involved in the replication of the evolving nucleic acid molecules synthesized by the system itself? Then can we consider this system analogous to a living organism, e.g. truly alive? What if we continued adding nucleic acid molecules to the system to the point when it was able to produce ATP from organic molecules used by what we commonly consider to be "alive", e.g. entities we prescribe the name living organisms, like glucose, for example. Then what would be the difference between this chemical reaction system and a genuine living organism? What if we continued building up this "in vitro metabolism" to the point when we have a genuine "molecule laboratory" testing the fitness of new nucleic acid molecules to itself. A true evolving, replicating and self-organizing molecular "machinery" we could "grow" in a test tube. Would we then consider such a thing a genuine living organism and if so why?

Yes, I know it's a "fringe question" and out of the scope of almost all branches of biology but nevertheless I think it's one of those questions that can "capture our mind". So, do you think there could possibly be such a thing that we could deem "alive" but have no cells at all? Something organized in such a way that we can readily call it a life form but yet not organized in the "way we think" about Life in general? If this is possible, when do you think this system of reactions could be called genuine living organism?

To the moderators-my question is different than the question "Why isn't a virus alive?" because it has a much broader perspective than it-a cell free form of Life can be anything-from a self-replicating "grey goo" to an evolving tornado. Viruses are only one small particular subset of possible answers. Plus the question you are referring to isn't about synthetic biology and the possible diversity of life forms as is mine but is only about a particular aspect of what we call a virus-its pertaining to the set of life forms or not. My question has both different direction and different set of objects it's aimed at. How can the two be identical, then?

Answer 1

Your updated question, as I said in a comment is much more precise but also describes a biologically and thermodynamically absurd scenario that betrays deep misconceptions about how cells work and what they need to work. Having said that I've realized it has an answer, so I'll give it:

Would we then consider such a thing a genuine living organism and if so why?

As in every case in science where previously-sharp categories become fuzzier through the discovery or creation of entities that fall in previously-empty intermediate zones, "we" would debate ardently about whether those things should be considered "genuine living organisms" or not. There would be several possible outcomes to these debates:

1) All of the new intermediate entities demonstrate that in the space of characteristics things can have, the old category as previously defined no longer forms a sharp cluster, but a sharp cluster still does exist that is pretty close to that old category; in that case the old category gets a new definition, and as a result some entities might change their classifications, or not. Real-world example of this kind of definition change (though not necessarily caused by the appearance of intermediate steps): how stars and planets went from their antique definitions of "stays put in the sky vs moves around" to their current very-different definitions.

2) The new entities demonstrate that what was thought to be a sharp cluster in the space of characteristics is just... not. A clear, universal, unambiguous definition is thus impossible. One possibility is that the cluster dissolves entirely; the category as a whole is thus abandoned (many abandoned taxonomic terms can be seen as examples of this).

3) The old sharp boundaries no longer exist, but there is still a definite cluster in the space of characteristics that can be pointed to, it just has fuzzy borders. Like colors, which blend into each other but we still know there is "red" and "blue" and they're not the same. In that case, like with colors we might abandon the edge and focus instead on doing like we do with colors; defining the entity by looking at what "a good representative of this category is" and "what an ambiguous representative of this category is", thus giving a reliable idea of where the cluster is, where it isn't, and where the boundary is, even if it's fuzzy.

4) Sometimes you do need sharp definitions though, especially in science. In that case there are two possibilities:

4a) Use different definitions in different contexts, depending on which characteristics of the cluster interest us at any given point. "Species" is an excellent example of this; a paleontologist, a vertebrate biologist, a plant biologist, and a bacteriologist will use the same word to talk about similar concepts (a grouping of organisms with specific ecological and evolutionary significance), and they will use different criteria to determine what a species is in each case, meaning they have different definitions.

4b) Settle on an arbitrary boundary based on certain criteria that cuts through the fuzziness, with the understanding that it is arbitrary, other criteria would have yielded a slightly different boundary and different classifications for given entities that exist in the fuzzy zone, but it is useful for whatever purpose to have that boundary and thus a boundary will be chosen. Debate might continue a long time over where the boundary is, and potentially involve different people using different boundaries as in 4a, or not. Classic recent example is the definition of planet, and the process that led Pluto to no longer be considered one. This can also involve the creation of new categories, like "dwarf planet" in the case of the redefinition of "planet".

So to answer your question "would this be considered genuine life?", the answer will be "yes", "no", "it depends" or "neither" depending on which of those outcomes the debate ends up settling on. And we cannot know which outcome it will be, because the choice that will be made will entirely depend on what the space of characteristics will be like that makes a currently-sharp boundary fuzzy... And obviously we do not already know what the space of characteristics is like because those discoveries or inventions that will prompt us to revisit what we think of as "life" hasn't happened yet ! (well, not the ones you posit. Obviously the definition of "life" itself has already undergone the processes I describe many many times as it got better understood !).

(note I'm not even getting into the vernacular, and whether it will follow scientific usage or not and at what rate if so. It's interesting to note it still in many ways hasn't caught up with (or is just unrelated to) today's biological definition of "life" !)

(I will also add that I cannot posit an outcome even based on the specific scenario you describe, for two reasons: first, the decision would be a communal one made by professionals in the field, and I am a single person and not a professional biologist. Second, the specific scenario you describe already goes against everything we currently know about life, so, yeah.)