CharonY

Not sure what you mean with mirror dogma, synthesis of D-peptides and proteins? We can already do that. Mirror bacteria are outside of our reach right now, as I mentioned earlier. I said it is unclear- much of what the authors argue are extrapolations, similar to the threat of GMOs. Empirically, those threats have not yet materialized. So basically a mirror bacteria that has the metabolic pathway of current ones? What would remain mirrored, then? That is what the authors speculate, but not clear whether chirality is sufficient. Again, existing bacteria are already doing that, some escape immunity, others do not. Your hypothetical bacterium would compete with bacteria already adapted to their environment. The most likely scenario is similar to many GMO bacteria released on the field. They get outcompeted and vanish. If that is the level of speculation you want to make then I would say no. Based on what we are seeing, the most likely scenario is that other civilizations developed something analogous to the internet, got stupid and died from preventable diseases. Why would they need something like mirror bacteria to achieve that. An automated troll farm in Russia is more than sufficient.

I don't think it is an issue of time consuming- AFAIK children grow roughly at similar rates everywhere. I.e., it would imply that folks in the developed world are busier than in developing countries, but I kind of doubt that. Cost may be something, but then I am wondering whether children are really only expensive (in relative terms) in developed countries. One could ask the opposite question- why would folks want children? There are social pressures (familial, religious etc.) which are diminished in many developed countries, for example.

I think screenshots or relevant excerpts would be fine. However, it is likely that you won't find folks with the specific needed expertise.

Those were the guys who have claimed to have created synthetic life at least twice (and again, they only took out DNA and put in a reduced version back in). So huge chunk of salt on that one. Pretty much similar fears were raised in the 2000s regarding GMOs, and so far nothing has materialize, despite abundant use of them. So far, I find empirical evidence for the risk of mirror organisms too speculative and in terms of infection risks, I would look more into zoonoses, AMR and decline of vaccination rates. Many of those are already able to escape our immune system and are increasingly resistant to therapeutics. There is just not enough evidence that would demonstrate that these speculative organisms would add meaningfully to the existing risks. I have no idea what the rest of the post has anything to do with it.

Many serious folks have claimed that, and it is one of the things that is only interesting after the achievement. Otherwise, I plan on curing cancer in a year or so.

So why do you think that compounds synthesized with uncommon chiralities are a bigger issue than, fully synthetic drugs, for example? If you are familiar with ADME, you do know that there are unspecific elimination routes? The supposedly mirror organisms would presumably consist of D-proteins. Even if the compounds are non-chiralic, it doesn't mean that the D-form enzymes would be able to process them. In fact, the whole premise of immune evasion is that the 3D structure is different and hence not recognized, isn't it? I guess there could be highly symmetrical configurations where it would work, but I would think that this would be rather rare. And conversely, if there is an active centre that is structurally similar, it would be a great epitope. Yes, as mentioned there are enzymes that are able to change the stereochemical configuration. Which means that (abundant) existing bacteria would compete with these mirror organisms. Plus they are well adapted to the dominant nutrient sources. It is unclear how these mirror organisms would persist under these conditions.

...? You do know the shape of the Earth?

Unfortunately, the "unusual" is always more attractive as it holds the promise of skipping the "boring" stuff everyone is doing and skip right to the secrets that experts somehow are not able to access. For books, Dough Futuyma "Evolution" is a solid read, I have heard it has been updated to provide more modern examples. Older editions are affordable and still provide a good intro and still highlights the scientific approach to evolution. Mark Ridley's Evolution is perhaps a bit more narrative-driven from what I have heard, which makes it more readable and a better intro, but is more undergrad teaching than research-oriented.

Yes, we can do in vitro protein expression, fairly easily and routinely. D-proteins are mostly used in structural investigations (I am not sure whether any with therapeutic value have been discovered yet). However, smaller peptides including either some or consisting of D-amino acids are either in use or being developed. DADLE is a synthetic peptide that has been synthesized in the 90s, for example. Edit to add: In isolation, mirror protein, amino acids, DNA and so on are not particularly more dangerous than any other drug or synthesized compound. The risk of mirror organism is entirely independent of that, and hinges on the ability on creating that in the first place. Just adding some chirality does not add much. Bacteria routinely use many tricks, such as sugars in many shapes and forms to confuse our immune system. In fact, in their O-antigens one can find D- and L-forms of their subunits to confuse our immune system. I.e., this is not fundamentally new chemistry we are talking about here.

Then how about the many unnatural drugs? Are you worried about those, too? Because that argument applies to to any newly synthesized compound and materials.

I am not sure what you think the issue is. There are plenty of drugs that are chiral often only or the other is used (or sometimes mixtures of both). Are you also worried about naturally occurring mirror molecules?

If I may make a suggestion: if there is genuine interest, it is always better to build your understanding from the ground up, rather on relying on articles that promise a shortcut to a concept that you might find drawn to. Pubsci articles heavily rely on the surprise factor, i.e. the promise that after reading that you will be privy to some insights that will somehow challenge existing knowledge. But consider this: existing knowledge is built on the work of many many folks, whereas any single article is the work of at best a handful for persons (or only one). It is exceedingly rare that one person will have some insights, missed by the whole community and even rarer to publish it in a no-specialist journal. This also applies to discussion forums. Ultimately, there is no shortcut to knowledge and picking up a good book is still the best way.

Producing chiral molecules have been done for over a decade at least (perhaps longer), so that is nothing new. The central dogma sounds pompous, but is really just transcription/translation and can be easily done in vitro without cells for a while, too. This is not what is tricky. Replication, sustainable metabolism and overall maintaining cellular integrity, are the tricky bits (plus a few I am missing, I am sure).

That is not how it works, generally. In graduate school you submit and defend your thesis to a committee and not for general publication (though the thesis itself becomes part of a repository). Ideally your work should be publishable, and some groups make it a requirement for a PhD, but that is not always feasible in experimental sciences. Conversely, publishing something is entirely independent of the degree. In many groups, most of the writing/editing is done by the PI and also undergrads can be on papers, without doing any writing on it. The only overlap is that if you are able to publish a few papers during your PhD, you can summarize those as part of the thesis, which saves time writing. But that is basically it.

Yes, assuming the quotes are not out of context, it does seem to me that it is possible that the author is overselling concepts to lay audiences. However, some of the later quotes are accurate: For example, this link with epigenetics makes sense- yet it was never an either or question, which seems to be implied. I presume that the typo was not part of the original article, though. Here it is acknowledged that there are separate mechanisms and I have no idea why the author would harp on about natural selection in the former quotes. But again, the presented quotes are not great representation of the basics and it seems that certain concepts are overemphasized which is again not great for laypersons.

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.