CharonY

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.

One could ask a different question: is gender identity innate for cis-gender folks? I.e., one could look at the broader population and try figure out when and how gender identity is established. If one e.g. identifies a genetic mechanisms for gender identity, then one could take a look at possible differences between cis- and trans-gender folks. However, there is decent likelihood that it is a developmental process (i.e. genes interacting with the environment) which would make the study more difficult. But then it also means that cis-gender identity is not innate. Perhaps surprisingly, our knowledge of a genetic basis of gender somewhat sketchy. Twin studies suggest at least some genetic component, especially if one tries to link traits more quantitative (i.e., using grades of masculinity and femininity vs. binary measures). However, so far molecular studies, such as GWAS have only found suggestions with varying degrees of usually fairly low specificity. There was a good review on this topic from a genomics consortium sometime 2018/19, though I cannot recall the citation of the top of my head. If there is interest I can likely dig it up.

For sure. There are a plethora of journals catering to specific needs and their formats (and content) are reflective of it. One important element of it is is that original papers are often a discussion platform, where evidence for competing hypotheses are presented and discussed.

Publishers do not change the text, but they might e.g. highlight typos and such. Some also make suggestions, but the authors control the text fully (they have to, as they are the subject experts). Some journals have page limits or page limits for certain types of articles, others simply charge more if the article is too long, especially as digital publishing becomes more common.

Conversely, sometimes drugs are administered in a less active form (prodrugs) and are then metabolized into the active form. Beside oxidation there also many other metabolization pathways (codeine is demethylated to the more bioactive morphine, for example, but most glucuronidated, IIRC).

Obviously, though there are some folks who think that drugs somehow safer or less harmful than, say, vaccines. Yes, and I think that there are some animal studies that suggested that thinning of the blood might play a role in improving blood flow and might improve healing (and potentially more than offset the disruption of inflammatory signaling). As you said, things are complicated. As well as other potentially unrecognized parameters that can interact with the drug in question. Sometimes in ways that we do not really understand. For example, Aspirin has been identified as a risk factor for Reye's syndrome (mostly, but not exclusively in kids), typically in conjunction with viral infections.

I agree that side effects are a bit of misnomer. As I mentioned, any drug has a plethora of effects (though not necessarily symptoms) and it is basically convention to label effects that are not the intended purpose as side effect. Hope you are feeling better soon. With regard to broken bones, aspirin is anti-inflammatory and can help somewhat against inflammation-related pains (though it should do less against pain signals from the fracture itself, I would think). But on the downside, inflammation is apart of a signaling cascade related to healing processes. Based on that, there is the hypothesis that using too much aspirin could delay bone healing. But OTOH I think I saw a more systematic study on operation of some sort of fracture and no delayed healing was observed there (but I also don't recall what the age of the cohort was, as that would also play an outsized role). Another related thought I forgot to add to my earlier post: for treatment, the medication ideally only targets the affected tissue/region. However, in most cases there is no way to achieve that relying instead on flooding the body with the medication in sufficiently high dosages so that the target region gets enough of the medication. That also means that non-target areas will be exposed to the drug and also affecting healthy tissue. Drugs are, generally speaking, not precision instruments.

What do you mean? There are tons of books on writing research papers. There are general books on the craft of paper writing and specialized ones for each discipline.

Unfortunately, we already had those years. And a couple before that (if perhaps a bit less blatant). I think, at this point folks are swimming in coffee but not noticing anything.

It is because of biology. Even if a compounds specifically targets, say, a receptor and nothing else, inhibiting/blocking that receptor can have many effects. Some of these effects are beneficial in dealing with a disease, others may not. Think about it that way: even in a single cell, the functions of molecules are interconnected. If you inhibit one enzymatic function, it has impact on many levels as up and down-stream pathways can be affected. Now increase the complexity from single cell to tissue, organ and organism and you have a host of non-target functions that will be impacted. Even if you eat things, you have a host of effect on your body, even if you do not think of it as medication. Actually antibiotics are frequently disagreeable as they also interact with eukaryotic cells. Just not as fatally as with prokaryotic ones. Fluoroquinolone antibiotics for example can also interact with GABA-A receptors, for example. But as I said, even if they manage to find a highly specific ligand, the interaction itself can kick off a plethora of other unintended effects. The key for good medication is that it has a net benefit to the patient. It is exceedingly rare that some drug will have only one effect, even if you do not feel any symptoms. However, as long as there is a dosage where the primary issue is alleviated and the side effects are manageable it is a net benefit. But I don't think that we should think of drugs as highly specific agent that targets the source of a disease specifically. Rather, it is something that interacts with our biology on multiple level and hopefully during that course the issue is alleviated. That, of course depends on the mechanism and complexity of the disease to be treated, of course.

Fictional characters are not alive. Unfortunately that is what folks believe, contrary to all evidence but also simple logic (i.e., differences in outcomes, priorities, goals, mechanisms, procedures etc.).

Define "small". I think it is more accurate to say that it is written for experts and not the general public. No amount of random notes will change that. In fact, it will only confuse folks more as you need knowledge of specific laboratory/group conventions to make sense out of notes. We often use shorthand that is not used much outside of our lab for example. Again, that "supporting" information won't help you. Look, the bottom line is that to papers are for advanced audiences and the only way to understand them fully is to gain at least some level of expertise. There is no simple or convenient way to convey expert level knowledge to a layperson without losing information. If that was possible, we wouldn't need higher education in the first place. Look, this is an entirely different discussion and it goes exactly against your point of broader audiences. The folks interested in why certain approaches are a specialized sub-section of an already specialized sub-section. And in 90% of the cases in the wet lab it is because someone messed up during pipetting, or got distracted during the process. Again, if we added each failure as supplementary information you could have a ten-page article with 800 pages of supplements. Add to that discarded raw data you would need a few gigs of downloads for each simple thing. Now, I will say that there are some journals who try to publish negative outcomes and I do think that there is some value in that. But again, these would be well-vetted experiments and not just a bunch of random outcomes. I have no idea how your thought on AI ties into any of this, though. It is not like that the AI can make sense of these things easier. I suspect you would change your mind if you have actually seen how records are done in the lab.

I think you have no idea how many notes are generated in the course of a writing a paper and how much is not included because it would make the whole thing unreadable. There is a bigger point in putting somehow preserving even failed experiments into a repository to ensure academic integrity. But again, considering how much work really is just random thoughts and failed experiments (most of the time due to inexperience) it would be take a huge amount of time to create a dump that no one ever looks into. Folks look at Einstein's note because he is famous and folks are curious about him, not because it is necessary to understand the science. What I take away form the average student lab book is that they really need to learn to read and write better. Not everything is information and a key element of science is to condense meaningful information. If you want fluff to distract you from information, you got the internet.

As a former D&D player, I do not really see the issue here.

I don't understand that. I am not that familiar with math papers, but I would assume that any paper with a proof would report on it in a way that can be followed. Why would you put anything in the margins? if it is relevant it should be in the paper. I have no idea why the comparison with high school is supposed to do.