CharonY

It is not helpful to use your own definitions. In evolutionary sciences, conventional wisdom is not limited to natural selection for close to a hundred years. You are conflating multiple concepts here. I will try to disentangle them from you. The gene pool is the unit on which evolution happens. That is the definition, if you want to talk about something different, you need a different concept, but then we are not talking about evolution. Survival is not a part of evolution itself. It is one of the factors, but not the main factor. Organisms need to survive to the point of reproduction, after that it does not matter. So for example a factor that increases survival dramatically but results in sterility, will have no impact on the gene pool, and therefore evolution. As such, factors changing survival, but not changing the gene pool do not impact evolution. For epigenetics, let's also use more precise definitions. Specifically, in terms of gene expression, epigenetics typically refers to DNA modification. While some modifications are hereditary, they are not stably inherited. As such, they are considered yet another mechanisms that can shape evolution (i.e. the gene pool) but due to their transient nature, they are not considered the element to be measured (i.e. the gene pool). That being said, there are some efforts underway to investigate whether certain modification patterns could be stably inherited, in which point the idea of gene pool might be modified with the addition of these chemical modifications. Taking a step back: the idea of evolution was never as narrow as OP makes it seem to be. Again, if you focus on the concept of gene pools, there was already early the realization that there are many mechanisms that could shape these pools. Natural selection was one that was considered early on (i.e. the Darwinian concepts) others, such as Lamarckism were also considered, then largely discarded, and then gain integrated in a modified form due to the recognition of epigenetics (if it is not entirely clear, I can elaborate on that). Biological sciences have never been dogmatic and formulaic and we are cognizant that more mechanisms will be discovered eventually. After all, we still have not really figured out some of the fundamental aspects of life. Heck, even what was considered to be the dogma of molecular biology has been remodeled from when I started studying biology. But nonetheless, the basic concepts still rely on certain definitions, which might or might not fully reflect biological complexity. Either way, they are the best models we got to date. If we want to discuss them, we have to follow those concepts, otherwise there is no basis for discussion. As such, it makes no sense to expect a meaningful scientific discussion on the topic if you keep focusing on your personal definitions and concepts. Inevitably the discussion will keep trying to introduce you to established concepts, an exercise which is often is tiring for everyone involved. You are correct in details, but I would offer a slightly different perspective for biological sciences. In contrast to (I think) areas of physics (especially theoretical physics), biological models are far more open-ended. They tend to be more qualitative (to the frustrations to many statisticians), and generally only smaller, highly specific elements, have quantitative models (e.g., models for calculation mutation frequencies at specific loci). Conversely, large concepts, such as evolution (or even like a cell) can be defined pretty narrowly, but does not specifically enumerate all relevant parameters. There is a recognition that we do not have a full understanding of biology, which is why discovery is always going to be a core element of biological sciences. If, at one point we have a full understanding of all relevant elements, I fully expect a transformation of biology to something closer to chemistry and/or physics. But this seems so far away that I cannot even see the path.

That is the exact issue/question: what is needed to make it alive? We don't know and have not been able to achieve it. It is the same as FTL- we merely have to find a way to overcome the speed of light limit. Naively, it is just bending time and space. How hard can that be? Again, until someone actually figures out how to build a cell from scratch, we are talking hypotheticals here. Not that this might not be important at some point in the future, but in contrast to many other things that are a risk right now, it is still a hypothetical. Honestly, if we wanted to prevent us dying from infections, someone should figure out how to restore trusts in vaccinations and go from there. Mirror or not, organisms will have a 3d structure to work on.

This is a false dichotomy and not one considered by the scientists (in the field). You won't find an evolutionary scientist claiming either. What you might hear is that evolution is probabilistic. You can find determinism in small scale on specific elements and they are highlighted because they are unusual, not because they are the rule. Conversely, there can be elements that are mostly random that determine the fate of a group (e.g. drift). Again, it is one of the elements that folks look at in order to understand a particular history. What it says, though is that your premise is faulty and will unlikely go anywhere when you keep maintaining it.

I tried to figure out what OP sees as a contradiction to "conventional wisdom" but ultimately failed. Part of it is that different mechanisms in evolution keep getting mixed up, but also the introduction of "control" as an element. The latter plays no elevated role when it comes to the conventional wisdom of evolution. It is helpful to recall what evolution really refers to: the change of the gene pool of a population over time. It does not matter how it changes, whether changes are reverted or not. Even epigenetic elements do not matter for that aspect. Formally we can describe evolution as a change from Hardy-Weinberg equilibrium, which describes the conditions needed for a static gene pool. So in short, conventional wisdom on evolution describes a condition that violates that Hardy-Weinberg equilibrium. A teleological approach to evolution would therefore suggest a system, that moves the gene pool to a predetermined composition. Selective pressures shape the gene pool, but they do not predetermine it. Even in a highly artificial conditions it is can be almost impossible to predetermine how the final gene pool would be. Say there is a strong selective pressure for size, while certain genes that favour size will be overrepresented, there are going to be broad variations in the final gene pool. In part because the existing population can change the overall selective pressures (e.g., in a population with large birds, some smaller individuals might find some advantages that didn't exist when the average population was smaller). Even in highly artificial conditions you can only somewhat control the gene pool, if you use highly inbred lines (and thereby inch your system closer to the Hardy-Weinber equilibrium.

It simply doesn't. What we know is that the a lot of more is needed. There is a list of things folks assume is needed, but so far putting them into a membrane has not yielded a viable cells. This is why I mentioned that we need to figure out what is needed minimally first, as obviously we are still missing critical elements. Again, what you proposed is early thinking about cells and as it turns out again and again, it does not result in viable cell. That is why with enormous financial investment at that time, the only thing folks were able to come up with was to remove DNA and then put a reduced version back into the cell it came from. The graph is basically ignoring all the critical steps. It is a bit like: Build rocket-> develop system for FTL-> explore different star systems. Also, while the authors acknowledge that those very theoretical organisms would need to compete with existing organisms for molecules with the more common chirality, they actually just speculate that they will somehow overcome that. This suggest that you would need to bioengineer all the contingencies into the system, which normal bacteria are able to do from the get go. The authors are skipping a lot of steps, and from my perspective, these steps are the actual challenges.

Gibson et al. 2010 described a cell with an artificially synthesized genome injected into an existing only. However even that one was based on the existing one, just pruned down and reinserted. This essentially was feasible with different and more inconvenient methods since the 2000s. The challenge is, as mentioned earlier, that to our current knowldge we do not know how we can prune down cells to its essential co ponents to live and replicate. Most work still focuses on DNA, not because it is so essentisl, but more because it is easier to msnipulate.

That is a big if. We have been just a few years away from synthetic life for a few decades now. And you have to read carefully, they say it is at least a decade away. My contention is that we are looking at a much longer timeline, we first need to be able create synthetic life, before being to create a mirror of that. So far, in biology we have not seen a clear path to that. In contrast, simplified approaches which are conceptionally old, such as replacing DNA have repeatedly been sold as artificial life, which is really just overhyping things for laypersons (and the easily excited). Also, I think you have still a fundamental misunderstanding of mirror molecules. Just because of their reverse chirality, molecules do not suddenly become more toxic. Many building blocks, such as amino acids exist in both orientations naturally, it is just that organisms exclusively use one for protein formation (and convert the other form before usage). For example, bacteria, D-amino acids may serve a role in stress related signaling. So the only thing that does not exist in nature are D-proteins synthesized from D-amino acids. But in labs, those have been produced for decades for structural investigations. Again, the issue is not the presence of those mirror-molecules, especially as they also exist in nature. What the authors argue is more of a biohazrd risk which, in my opinion and with our current knowledge is overstated. It is not unlike the worries folks had (and still have) regarding biowarfare agents, which, theoretically, could be easily produced with modern biotech capabilities. And while those are far more realistic, they have not really been realized (we apparently are much better at spreading disease the "natural" way with the help of anti vaccination efforts).

Rich folks have realized that politicians are very cheap investment, and rather doing the lobbying dance, it is now alright to buy them outright, it seems. What is worrying to me are polls during the election showing that Trump is also gaining popularity especially among young men in Western Canada (and Ontario). Among conservative voters, Trump edged out Harris, compared to 2020, which again is a worrisome trend. But then, if the world is going to hell in a handbasket, Canada is unlikely to be immune.

I skimmed over parts the report and do not find it very convincing as a whole. Chapter 2 does a lot of handwaving and the main message is basically that with new tech, at some point mirror life might be possible. Given the challenges with actual synthetic life (as opposed to introducing synthetic elements into existing life) it has too many unknowns to call. We might all have died from antibiotic resistant infections before it comes to that. I found it also odd that they spent so much time on the immune system, and only little regarding the survival and proliferation of these hypothetical mirror organisms. The latter is way more relevant than the former. If they cannot establish a replication niche, the immune system would not need to do anything in the first place. There again, they waffle a lot and seem to suggest that the mirror organisms would not be fully mirrored, but instead be also designed to use more common nutrients. At this point the suggestion is apparently less about mirror organisms per se, but more about partially engineered organism. I.e. able to use abundant stereoisomers but have modified surfaces for immune evasion, for example. Where they are accurate, they determine specific mechanisms that could be escaped due to incompatibility, though they kind of go light on the mechanisms that "regular" pathogens already have access to. As a whole it seems that the main argument really is just about a pathogen with a tougher surface to recognize, though again, they do not talk much about the decoration that current bacteria are able to do. Again, too handwavy and not enough contextualization with current pathogen strategies. Combine that with the fact that they also have to make excuses how the mirror bacteria are going to survive in the first place, it does seem a bit sensationalized. They certainly do not make a stronger argument than other discussions on e.g. gain of function research, especially as they have to point out to hypotheticals to highlight potential dangers. To be fair, the keep mentioning parts that are unclear but then just conclude it could be bad, which, again is not terribly convincing.

To some degree, maybe. However, if you have enough numbers, some of the issues can be accounted for. Also, even values that can be measured objectively, can have poor predictive values. I believe the digit ratio is one of these. I think our thinking regarding genetics has changed due to the large GWAS conducted to date. When I started out some close to 30 years ago, many issues were thought to be traceable by genetics and the human genome project has just fueled these ideas. But with cheaper and more comprehensive sequencing we keep finding that many genetic associations are somewhat weak, or at least not as deterministic as believed. Add to that a higher appreciation of statistical statistical challenges when dealing with high dimensional data sets, it has increasingly challenged simplistic explanations of traits.

Isomerases in general, I probably should have said. I worked with racemases and it was the first thing that came to mind.

None of the examples in the review are true living and entirely synthetic cells. Also, how would these theoretical organism infect if their molecules don't interact with tge host? Host pathogen interaction goes both ways.

No, you can make bacteria use and create some uncommon molecules. That part is easy for the most part. Bacteria already produce metabolites with different chirality and use enzymes like racemases to convert them into a form they want. Many enzymatic reactions can produce molecules with different chirality, it is not like antimatter or something drastically toxic, as you seem to imagine. The worry, I presume that folks have is that entirely new organisms would compete with existing one in changing the distribution of stereoisomeres in the world. But again, there is there is a huge jump from producing a few unusual molecules to create synthetic life (mirror or not). The latter is still quite far out of reach.

The first issue is that we remain unable to synthesize life with "proper" chirality. Not sure why folks should panic about doing something with it. I think a lot of folks are skipping over the technical and conceptional barriers that still exist.

! Moderator Note This looks like an attempt to get someone to answer assignments for you. Locked pending review.