CharonY

Not only that, if genes only arose out of necessity, it would invalidate classic genetics as well as the fundamentals of our current understanding of evolution. It would suggest that inheritable units only arise after interaction with the environment in a Lamarckian way, which would obviously turn our understanding of genetics on its head. It would also to a large degree invalidate or at least heavily change the idea of selection, which postulates a shaping force on the gene pool, whereas a gene pool which would generate only beneficial traits is already magically pre-selected...?

Well, folks apparently got what they want. I suppose that many also think that bullying is a demonstration of strength. But then the internet has regressed everyone to highschool students again. I guess it is at least internally consistent...

Generally speaking no- DNA is a polymer consisting of nucleotide subunits. Each nucleotide consists of deoxyribose (the pentose sugar), a phosphate group and a base. That being said, some parts of the DNA can be modified by adding e.g. a methyl group. In vivo there is also water, but that is not really part of the DNA structure. If you are thinking of "filler" because the image makes it look that there is a lot of space there, this is in large part due to the schematic nature of the image. If you do an xray of a DNA crystal, you do not have a lot of space, the base stacks are sitting quite neatly on top of each other.

I don't think that the article is talking about companies per se. The article is about research funding, and while companies have access to certain portions of it (often they require academic collaboration), IIRC the vast majority was academic funding. I believe the NIH is the single largest organization for health research in the world.

Under Obama, there was a push to push cancer research forward under the auspice of the NIH (it was called a Cancer Moonshot). I assume that this did not happen in other countries. On the other hand, you have countries like Germany and Switzerland export more pharmaceuticals than the US (German pharmaceutical exports are double that of the US). It is true that In absolute production the USA dominates and they also have the largest market share. But I would not consider the countries to only have a handful. Many of the big pharma countries are not originally from the US, suggesting that the US is a highly attractive market. In part this is because the US also has the highest pharmaceutical consumption, despite being much smaller than China, the second-largest consumer.

That is not the only issue. Remember, most of the discovery in this field is not done by companies, but by researchers funded by public money. And the first hurdle is to develop something that is sufficiently advanced where a clear translation into commercial therapeutics is feasible. The alternative, of course, is a moonshot approach, with more funding from the government. But in either case, there are still technical challenges on multiple levels for both, stem cell therapeutics as well as tissue engineering. These include poor viability and lower regenerative abilities of transplants (I am not sure about the latest developments, but at least a few years ago, it remained an unsolved problem). At this point feasibility is more of an inhibitor than profitability. Both are obviously linked, and solving the technical challenges can move thing forward. That being said, other than financed by private sector or government, what alternative do you see to fund the necessary developments?

You keep missing my point. A cell does way more than synthesize proteins. Yet you insist that this is the hard part. If you ignore this issue, I don't see a reason to continue the discussion.

And this is especially apparent when we use a more precise definition of evolution focusing on gene pool changes. While behaviors influence reproductive success, they do not control as such how the composition of the next generation is going to be. That level of control is virtually only possible with specific and targeted breeding that overrides any other factor. With anything else, it becomes one of many factors, many of which are based on chance (such as, likelihood of finding a partner in the first place).

To some degree that might be true, especially with regard to billionaires, but there is a trend towards authoritarian parties which are financed by billionaires, but who portray themselves as for the working class. The Austrian far right (FPÖ has repeatedly won elections and, as many right-wing parties and they are (allegedly) supported by Russia. In fact an undercover report showed how the leader of the party was open to bribes from a fake Russian oligarch. That government collapsed but the same party won the recent elections again.... I think you are right that overt billionaire support is less attractive, but they can throw a lot of money around without people noticing.

I know that this thread is US-focused, but Musk is likely already interfering with other elections around the world. Not sure whether there are any regulations against that, though. https://www.reuters.com/world/europe/elon-musk-gives-nod-german-far-right-party-election-looms-2024-12-20/

Basically all the other functions of the cell? I think you might be hung up on the term "dogma". It is not the sole key element, just one that we understand better. So well that the term dogma of molecular biology was coined to highlight information flow in the cell. And now we know that even that is inaccurate. So we have metabolism, molecule turnover, sensing and all the other elements that makes a living cell. I keep repeating myself a bit here but essentially we know one part well and we don't even know how many parts we do not know. If we did, we would be able to create an artificial cell. The fact that we can't suggests that we don't understand it. Just for illustration, even if we only talk genes and ignore the increasing complexity resulting from the proteome and metabolome, Escherichia coli is probably the best studied organism out there. Every single gene has been investigated over decades. In the end, we only have an idea of the function of roughly 50% of its genome. Among the genes that have been annotated a sizable proportion the functions are still not fully clear. What I am saying is that functionally we are still unable to fully understand what a a cell needs to work. To take my previous analogy, it is like saying that we are able to build rockets, so why are we not settling other star systems yet? There is a big gap between these two challenges. Take a look at that. This is simplified diagram of the pathways in E. coli as far as we understand it. The nodes are metabolites with enzymes catalyzing the associated reaction. Each of the nodes has a layer of complex regulations (not depicted) to ensure that they move in the right way without seizing up and react to dynamic changes in their internal composition (we can ignore external challenges if we assume highly artificial conditions). Also missing are posttranslational activities that modulate the activities (plus other layers of control). This map, to be clear, does not represent all what the bacterium is doing, only the parts we figured out in the last 3-4 decades or so. And we are nowhere close to replicate that artificially because as it turns out, even if we created a soup with all these enzymes, it still won't work. There are more layers (one of which is regulation, as hinted above) and likely some not yet discovered elements that play important roles. My guess is that it might take decades to get to the point where we start to understand what we are missing. My timeline obviously can be wrong, but for the last decade or so I have not come across breakthrough research that would make me believe that we have overcome some of the fundamental challenges yet. Bacteriophages have never played much of a role in controlling diseases. From a competition viewpoint control for nutrients is likely a bigger factor in settling for niches, rather than phage resistance. It is not nothing, but I would not pick it out as as the key element shaping bacterial evolution and ecology. Even as targeted therapeutics they are much less useful than antibiotics. There are attempts to make them more useful due to the threat of increasing resistance, but it is unclear to me what level of impact it ultimately will have.

Among the many explanation why we have a capital-based economy which promotes an upward movement of wealth (Marx, anyone?), I also found an interesting observation regarding non-essential consumption. There was an argument that folks have more things than ever before (e.g. comparing to our parents and grand-parents) as many goods (especially electronics) are now mass consumed. To produce these goods, cost cutting and efficiency has spread through all levels of the support chain, leaving essentially labor cost as a non-reducible unit. There are therefore strong incentives to keep salaries low and companies successful in cutting costs this way are getting incentivized by shareholders as well as consumers.

The US Bureau of labor statistics has those data available, but I think the gap is widely recognized. Edit, some figures also from the EPI, slightly updated

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.