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New viruslike entities found in human gut microbes (science.org)
156 points by drooby 10 months ago | hide | past | favorite | 82 comments



It’s amazing how RNA pops up everywhere we look. As our tools get better and better we find simpler and simpler RNA based things floating around, apparently being replicated by some chemical or biological processes.

It’s hard to see the trillions of other planets in the known universe along with its age and apparently limited chemistry and not imagine how similar RNAs should’ve have popped up over and over again.


"Some chemichal or biological processes" seem to always be living cells, isn't it. So any kind of RNA depends on already existing living cells.


I mean it's a bit more complicated, since ribosomes are themselves mostly made of RNA. Which gives RNA a kind of unique property that it can not only be transcribed into new proteins but also build the machinery to do this transcription.

Given a bath of amino acids you can easily use RNA to bootstrap a whole self-replicating system, which is probably what happened by accident at some point.


"Probably" - yet the real calculations of probability say it is not going to happen at all, ever. And then when we observe the natural world...lets take things that are alive and then die. Well, are they not essentially a soup of everything one would possibly need for life to arise, even with external energy source from the sun (think road kill as an example)...and yet we know of no instance in which life, by chance formed out of it; all the dead bodies seem to degrade into dirt. Of course if it did happen even once - how would we know as we can't possibly observe all occasions of such things. Anyway - just some thoughts I had on the matter.


Every dead body you've ever seen is teeming with life. Now, it's probably impossible for a novel life form to arise in a dead body, because the existing life (bacteria) that takes over has been optimized by billions of years of evolution to consume the resources around it better than any novel self-replicator possibly could. But that's not really evidence that a self-replicator couldn't get going if there weren't much better ones already around.


Calculations don't matter if they are based on faulty premises. There is nothing all that special about earth that what happened here couldn't have happened on trillions of planets across billions of years in the known universe. I think that's why biologists and just generic humans like me posit that there has to be life elsewhere in the universe, no woo woo or gods needed.


I’m curious why you say “easily”. Has this ever been done in a realistic environment? AFAIK it takes over 100 base pairs to produce a single self-replicating RNA, and prior to its ability to self-replicate there is nothing which would favor its creation over other random RNA.


I mean 'easily' is very much relative. It's easier than trying to build a cell from scratch, but much harder than say writing a quine in lisp.


Well you gonna be excited when you learn about proteins.


>we find simpler and simpler RNA based things

>In the early 20th century, plant pathologists came across viroids

>some of the obelisk sequences encoded proteins involved in RNA replication, making them more complex than standard viroids

I don't mean to interrupt your narrative but you seem to be getting information from other sources and I was wondering what they are.


This sentence captured my mind:

> Scientists still debate whether viruses are alive—they can’t replicate independent of a host cell’s molecules—but there are even simpler “creatures.”

We have varies "definition" and "categorization" saying virus is not "alive".. you can see many biologist saying this definition does not capture the essence and need changes... There are published paper for that every few other years.

Look like this is what the "AI is sentient" thing going... We will get a textbook definition for sentient AI, but nothing could end that debate.


My background is philosophy of language. The vagaries of definitions are exactly how many get communication backwards. It’s jut important to remember that language is effectively just pointing at things, and that the words we use are effectively arbitrary.

The distinctions in taxonomy should be reflected by the language, and we should very much not try to conform our taxonomy to our existing terms… beyond, say, shorthand.


  we should very much not try to conform our taxonomy to our existing terms
I see this stunting imagination everywhere. Economics, science, nature, etc. Humans generally feel they've "captured" knowledge with a brief overview and disdain any messiness that might allow that knowledge "to escape".


Some humans are curious to be exploratory of knowledge that "escapes" these classifications, as you say :) this is, in some definition, the criteria of an artist of sorts. Maybe artistic minds are just scientists of another cloth, investigating the features of linguistic creatures that escape the boundaries that other (more "particular") types of minds create and impose


This is maybe the most beautiful description linking the arts and sciences that I've ever read. A good scientist is one who extends the envelope of our external knowledge; a good artist is one who pushes the boundaries of our inner qualia and interpretations


>It’s just important to remember that language is effectively just pointing at things, and that the words we use are effectively arbitrary.

I think the success of transformer-derived LLMs suggests that Wittgenstein was more correct about contextual “family resemblances” than the “pointing at things” school of language philosophy.


I'm a bit confused by your statement.

I'm a bit ignorant of the actual math/logic for modern LLMs (I took Andrew Ng's course on machine learning, but that just gets you to basic neural network architecture).

I'm also confused as to why you would put Wittgenstein in opposition to the concept of language as "pointing at things," as I would put him very much in that school. I'm a bit rusty, but I've been through the Philosophical Investigations a couple times, and I'm almost certain he's opposed to platonic forms.


He thinks some words rely on ostensive definitions, colour for example. Otherwise, though, his view of language can roughly be summarized as "meaning is use". You're correct to read him as opposed to platonic forms and ideas; however, he argues that language and meaning has its roots in behaviour, or as he puts it: "a form of life". So for him meaning is relative but not arbitrary. It's a crucial distinction.


I only wish I could have heard him lecture. His two books, while interesting, have always seemed, well, a bit odd in their structure (less so with PI). Beyond that, that people use some random notebooks like his published texts also seems odd.


This is clear to many of us with no formal training in language.


I completely agree, and wouldn’t suggest otherwise. I’m mainly referring to the concept of platonic ideals, which seem to be at least somewhat instinctual.


Yes, that was my original understanding of your meaning. There are other experiences and traditions as well that illuminate this way of thinking.


People like definitions that have clearly defined boundaries but biology is not like that.

There can be a messy continuum between is and is not. Things can match a definition strongly by some measures but miss some that are critical to how other things meet the definition. At best, a definition is a constellation of semi-related characteristic where some organism meet some subset and other meet another subset, but there isn’t a 100% match and may not even be an overlap.


> There can be a messy continuum between is and is not.

Exactly--concepts like "life" were invented long before we had an inkling of what viruses were...is it surprising that it's not a perfect abstraction for what we find in reality?


I think people have no qualms about fuzzy boundaries or continuities. The problem arises when those get subsequently mapped onto discrete sets with wildly different consequences.

My work in computational ontology led me to believe people are fast to come to a conceptual joint agreement in a given model when the outcome is not consequential, but find it nearly impossible to settle when there are strong implications attached to a labeling.

Language only works between people that ultimatly want to agree.


If labeling has fuzzy boundaries, perhaps it shouldn't have strong implications. If it does, the boundary cases behave chaotically, which is usually not acceptable behaviour. I mean, if the labels have no consequences, what is the point of labeling in the first place?

Organizing everything in the world into neat boxes feels so early 20th century to me. Back when we still thought that human reasoning can be applied to achieve a complete understanding of the world and everything in it. Putting things into boxes is a coping mechanism for the feeling of chaos; people do it because it makes them feel good, not because it actually reflects how things are.


>If labeling has fuzzy boundaries, perhaps it shouldn't have strong implications.

Well, it's tricky because labelling is so useful (oftentimes crucial for communication purposes), but we would be hamstringing ourselves if we either a. held off on labeling things with fuzzy boundaries altogether or b. refused to entertain possibilities with strong implications because a labelled phenomenon has fuzzy boundaries.

Best to remember that labels are useful but with very important limitations. Ultimately, when we get out to the edge of our understanding the boundaries will always be fuzzy, at least until a breakthrough (and sometimes long after). Whenever you are at a boundary, continually remind yourself that the label is less important than communication and exploration of what actually appears to be going on.

Are viruses alive? This is a very interesting question to try and answer from different angles, but arriving on a definitive "yes or no" here is not at all the most important thing about viruses to be worrying about.


We label because we need to compress reality before we can reason and make sense. Is this a limitation of human intelligence? Sure, but I would hypothesise it is even more fundamental. Irreducible complexity can only be observed and reacted to, it takes away the proactive. So we make do with reduced models that are definetly wrong, but sometimes usefull.


In a way, a virus is not too far off from a complex prion. Simple single cell organisms aren't too far off from complex viruses.

There's a line of thought that metabolism is the defining feature of biological life, and viruses do not have any metabolic activity of their own. This is essentially the only real distinguishing characteristic that holds true between viruses and organisms.

Once a virus has a host cell, however, it uses metabolic events to do its thing. That use of those events to drive its own reproduction is very life-like, and is very unlike a prion. In terms of behavior, it really is more like life than not. It uses metabolism, even if it doesn't innately perform glycolysis like everything else.

The "are viruses alive" is really more a medical philosophy question than a practical one.


In what way is a virus remotely like a prion? Both the structure and function of the parts are completely different.

Just because a virus interacts with a metabolism doesn't mean it's closer to having one of its own. That's like saying humans use gasoline combustion for our biology because we drive cars instead of walking sometimes.

You're not wrong that whether viruses are alive is not a very practical question, but none of the rest of your post meaningfully addresses it either way.


A viral capsid is certainly an evolutionary benefit, but the disease known as "scrapie" astonishingly seems to be able to survive without one for long durations.

We are quite lucky that nothing like that targets humans so effectively.


Yeah, because scrapie doesn't resemble a virus, so it doesn't have the same survival concerns. A protein in an exceptionally low-energy conformation is more robust than a ring of RNA, film at 11.

Anyway, fun fact, the prion that causes scrapie is extremely similar to the ones that cause mad cow disease (transmissible to humans) and Creutzfeldt-Jakob disease (human disease). So yes, we're very, very lucky, so far. Sleep tight.


Actually, the worst cases were from Kuru.

It has a ghastly origin.

https://en.m.wikipedia.org/wiki/Kuru_(disease)

(I will upvote you now.)


Sure, but Kuru doesn't transmit anywhere near as easily as scrapie does in sheep, which seemed to be the relevant comparison.


>That's like saying humans use gasoline combustion for our biology because we drive cars instead of walking sometimes.

I imagine you are speaking more in terms of molecular biology, but if we zoom out into evolutionary biology this is not such an unreasonable statement if we are talking in terms of the extended phenotype.

Especially as we get closer to a robust hypothesis that humans lack free will on a biochemical level, it really could be that our genes making use of gasoline, because the "we" that we like to think of as making use of it through intellect and choice is more a hallucination (perhaps useful in some way, perhaps mere side effect) than a biological reality.

Humans using petroleum isn't necessarily all that different from how a parasite modifies host behavior as an essential part of its lifecycle, or how a beaver builds a dam to have a much more survivable environment.


And then on the other side of prions, you get things like asking whether self-catalyzing crystal formations are alive.


I like to think of a virus like code. It’s nothing more than a series of instructions in a file that, when executed (by the cell), does something. Is code complex enough to be called life?


We call self replicating programs viruses when they're unpleasant and quine as curiosities.

Is the game of life, life?


Something is getting lost in translation here, because scientists are not literally "debating" whether viruses are alive.

Scientists "discuss" the boundary between alive and not, which is an interesting question because it doesn't have a super clear and obvious answer. It becomes more a question of semantics and ontology than anything else.

What's really happening is that the words "alive" and "not alive" have outlived their usefulness: we need to think about things differently, and use better words, to fully capture how the world works. That's the discussion, and yes it's similar to what's happening with words like intelligence and consciousness in relation to AI.


A virus usually encodes for, and definitely utilizes, many processes of living things.

Part of the breakdown here is recognizing independent life requiring only a nutrient and energy source, and various consortia (e.g. can you say that a mitochondrion is alive without the host cell, and vice versa).

Basically, as mentioned by another commenter, the fact that "life" started out as a Platonic ideal that's being sussed out.

I'd say just change it to an adjective entirely and don't bother with a categorical noun.


"nutrient and energy source" is an interesting perspective: we certainly can't live off radiation (or heat, or electricity, or whatever one might consider as direct energy input) plus all the atoms contained in a lifetime worth of food arranged in simple monogamous molecules. We are no less dependent on other organisms arranging atoms into molecules our bodies can use as fuel and building blocks than a virus is dependent on a host cell for reproduction. I suppose that we can't really want a definition of life that excludes everything that isn't a plant?


As you state, the carbohydrates, fats, and proteins in our food sources function as energy sources. Photons are great for plants, but comparatively high-energy chemical bonds are fine, too.


> nothing could end that debate

Oh yeah, it could. If AI is textbook-defined technically “sentient” then that is perfectly enough to put an end to unethical abuses of sentient beings. (Imagine what that will do to the industry.)

It doesn’t matter if people still debate it. People still debate race supremacism, slavery, etc., that doesn’t mean a single thing as far as law is concerned.


[flagged]


>Koch's Postulates where redefined and then abandoned entirely by virologists as they couldn't find a way to apply them to viruses.

Koch's Postulates have since found new life among conspiracy nuts as indisputable proof that viruses aren't real.


Great...


I don't think the question is whether viruses are real, the question is whether scientific studies have yet to show transmission of infection that leads to disease.

There isn't a scientific definition for "real" that I'm aware of. Do you know of any studies that have isolated a virus, or a virus plus host cells, and successfully introduced those into a novel population to reproduce disease? All I've ever managed to find are epidemiological studies after an assumed viral outbreak, but I really am interested to see a more controlled study that helps prove a more direct link.


I agree with the people saying this is impressively kooky, but just in case here's a pretty overwhelming number of examples of common viruses in mice, how they're isolated, and how laboratory populations are then directly infected with them: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150319/

(There's plenty more out there, but that source is just so dense with examples that it seemed like a nice go-to.)


To be clear, there are a ton of studies listed there but all the ones I chased down (maybe 25%) they aren't isolating the virus.

My message you were replying to specifically called out Koch's Postulates [1] and the fact that virologists had to first redefine it then abandon it for epidemiological and modelling studies.

You effectively proved my point here, everything I see in the survey you linked fits into that description. I'm not arguing that viruses do or don't exist, only that I've never seen a study successfully isolate viral particles in a substrate, introduce it to a novel population, and re-isolate the virus from the novel population after they begin showing signs of disease.

[1] https://en.m.wikipedia.org/wiki/Koch's_postulates


> the question is whether scientific studies have yet to show transmission of infection that leads to disease.

We literally make adenovirus derivatives for cell therapy, and a lot of technical and engineering effort went into making the derivatives non-disease agents. I, personally, have made baculovirus derivatives for protein expression. E.g. https://www.addgene.org/kits/peters-bigbac/#?

The same with vaccine-induced polio and the like from attenuated live virus vaccines. How do you think scientists made those attenuated live viruses in the first place without isolating, engineering, bulking up, and then "infecting" (vaccinating) people with them?

Edit to add that baculovirus has been massed produced and used as an insecticide: https://www.ncbi.nlm.nih.gov/books/NBK543459/


I'm specifically referring to Koch's Postulates here, and as far as I'm aware the viruses you're referring to weren't isolated. I've always seen them being used either in models or in some other host cells from cows, monkeys, etc. though I've never worked directly in the field so please point me to a study if you've seen one truly isolate a virus.


Here's a simple isolation protocol for a fish virus. The isolated virus is imaged in figure 3.

https://www.researchgate.net/publication/50409110_Cardiomyop...

> Virus propagation in cell culture. Heart tissue from freshly dead Atlantic salmon (Salmo salar L.) was collected from a clinical outbreak of CMS (the diagnosis was confirmed by histopathological examination). The heart tissue was homogenized, followed by centrifugation at 4,000  g and 4°C for 20 min to remove cellular debris, before being processed through a 0.22-m filter. The homogenate was subsequently inoculated onto GF-1 cell cultures (5). The GF-1 cell line, derived from the fin tissue of orange-spotted grouper, Epinephelus coioides, was grown in plug seal cap culture vessels at 15°C after inoculation in Leibowitz 15 supplemented with 1% L-glutamine (2 mM final concentration), 0.1% gentamicin sulfate (50 g/ml final concentration) (all from Sigma Aldrich), and 10% fetal bovine serum (Invitrogen). Development of cytopathic effect (CPE) was monitored at 6, 14, and 21 days postinoculation (p.i.). At 21 days p.i., the supernatant was harvested and passaged further in cell culture.

Notice that since this wasn't a stringent purification they used a subsequent passage to further dilute out anything carrying over. As stated in the other comment it would also be possible to use something such as tangential flow filtration or size-exclusion techniques in order to get an even purer first sample.


> the viruses you're referring to weren't isolated

They're made de novo (adenovirus and baculovirus derivatives, and yes, I've done this for baculovirus), which is better than isolation as even with isolation it's difficult to prove a pure sample. Even Koch couldn't prove an isolated sample back in the day. Not to our standards, at least.

Throw a GFP protein in the modified adenovirus or baculovirus genome and you can literally see the exact specific virus that you made move from cell to cell while the cells start dying.



Human challenge studies are used to test the efficacy of therapeutics and vaccines, not to test the pathogen itself. I was specifically referring to the abandonment of Koch's Postulates in virology, which again has nothing to do with challenge studies where the virus is not isolated from the host.


> Human challenge studies are used to test the efficacy of therapeutics and vaccines, not to test the pathogen itself.

Actually, you're wrong.

https://www.gov.uk/government/news/worlds-first-coronavirus-...

: Published 17 February 2021

: Due to begin in the next few weeks, it will involve up to 90 carefully selected, healthy adult volunteers being exposed to the virus in a safe and controlled environment.

: The safety of volunteers is paramount, which means this virus characterisation study will initially use the version of the virus that has been circulating in the UK since March 2020 and has been shown to be of low risk in young healthy adults.

Note that this study was in 2021, after the virus had already mutated. In order to ensure that the volunteers are infected with a specific virus version they would have to have cultured it.

: Once this initial study has taken place, vaccine candidates, which have proven to be safe in clinical trials, could be given to small numbers of volunteers who are then exposed to the Covid-19 virus, helping to identify the most effective vaccines and accelerate their development.

As shown here, the first cohort would not have been given a vaccine. But would have been used to characterize the activity of the virus on healthy humans.


> Human challenge studies are used to test the efficacy of therapeutics and vaccines, not to test the pathogen itself.

These are the same thing. The only way to demonstrate the efficacy of a vaccine is if the control group gets sick, otherwise there can't be a relative improvement.

(That's why reported vaccine efficacy goes down over time; as people naturally get the disease it appears to be relatively less effective as some of them get natural immunity.)


> These are the same thing. The only way to demonstrate the efficacy of a vaccine is if the control group gets sick, otherwise there can't be a relative improvement.

That's simply not true. A vaccine efficacy study specifically validates how well the introduction of a vaccine prevents disease, it does nothing to show the specific link between disease and the pathogen itself.

Prior studies are needed to link the pathogen to disease, and the most accurate way to do this is to first isolate the pathogen then show that introducing it to a novel population recreates the disease. After symptoms show up, if the pathogen can again be isolated from the newly infected hosts you have a pretty strong case for causation. Moving on to reproducing the results in follow up studies would go a long way. At that point you know the likely pathogenic cause and can move on to developing a vaccine based on that pathogen and run efficacy studies to see how well the vaccine works to prevent infection, disease, or transmission.


> and the most accurate way to do this is to first isolate the pathogen then show that introducing it to a novel population recreates the disease

Yes, that's what the control group is doing in the challenge trial.


This is very kooky.

One of the first virus discovered was Tobacco mosiac viruses. If nothing else, there's no question that viruses cause diseases in plants.


Are you questioning whether viruses can infect organisms or whether they can cause disease?


In general this line of argument is questioning how we can know that a particular virus causes a particular disease. It ignores decades of technological improvements developed toward actual viral bulkup, purification, and infection.

Is it easy to know that a particular virus causes a particular disease? Not always, particularly if the disease syndrome is complex. Is it possible to link particular viruses to particular diseases? Definitely. For the more straightforward diseases it's even relatively straightforward to show that a particular virus causes that particular disease, with enough work.


> For the more straightforward diseases it's even relatively straightforward to show that a particular virus causes that particular disease, with enough work.

I'd be really interested what this work would look like. Koch's Postulates have always made logical sense to me and I've never understood why they where abandoned for virology. How can we prove a high likelihood of causation when at best we only have data of hosts that already showed signs of disease?

Aside - this thread seems to have gone down a rabbit hole where many are assuming I'm claiming viruses don't exist or don't cause disease. I get that viruses have been made a political topic these days, but I'm only raising that as far as I'm aware viruses have never been isolated in the same way as bacteria or fungi. We've never, again as far as I'm aware, isolated a virus from a sick person, exposed a healthy person to it, and seen the same disease symptoms show up with the virus now present in their system.

One could point to vaccines for this proof, but even those include other adjuvants that are present specifically to inflame the host and help promote a stronger immune response. I'm not claiming that including those adjuvants is a problem as far as the vaccine goes, only that it doesn't fit the definition of introducing an isolated virus.

Have we found plenty of evidence that a specific virus is present in a host after symptoms are shown? Absolutely. But have we ever successfully checked the box on Koch's Postulates with a virus? Not that I know of.


Perhaps, a better way to traverse this would be to look at the history of virology, trace main events, starting from the discovery of bacteriophage, and check out associated work. It is hard to say what kind of evidence would satisfy you. Viruses have been isolated many times, and transmissibility has been shown on cell cultures and animal models.

You can't purposely infect real people with disease-causing viruses in research so you won't find much studies like that. But there is no doubt that viruses are transmissible and can cause disease, and there is plenty of evidence to support that. Check out studies on yellow fever virus and flu done more than a hundred years ago.


If you read the Wikipedia page on Koch's postulates you'll see that Koch himself abandoned and modified them for various bacteria. https://en.wikipedia.org/wiki/Koch's_postulates#Postulates

Viruses, and some unculturable bacteria and other organisms, are simply unique with regard to Koch's second postulate, in that they literally can't be cultured in a pure manner. Hierarchical and tangential flow filtration can, however, get them incredibly pure (as quality controlled by electron microscope) after culturing. I'm not an expert here. This is probably not routinely done as it would be costly and to no purpose for the particular experiment. But it can be done, and I'd be extraordinarily surprised it it hadn't been done.

> We've never, again as far as I'm aware, isolated a virus from a sick person, exposed a healthy person to it, and seen the same disease symptoms show up with the virus now present in their system.

Yes, we also don't typically expose healthy people to disease-causing bacteria either. This is a hard sell post-WWII.

Typically when you culture a virus you'll also have a separate culture that is exposed to everything else minus the virus. You'll "purify" both in the same manner, expose some animals or cultured cells to the purified virus culture, and expose other animals or cultured cells to the purified control culture. The only thing that differs is the presence of the virus.

You can also literally view cells being infected by physical viruses in culture, and image or video what happens to them during this process. E.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330349/

Read the "Routine Diagnosis" part of this article.


> > For the more straightforward diseases it's even relatively straightforward to show that a particular virus causes that particular disease, with enough work.

> I'd be really interested what this work would look like.

A stringent example:

1) Replicate the virus in cell culture and ensure you're isolating the virus while doing so.

- A: homogenize and passage a virus containing sample.

- B: passage it through cell culture.

- C: dilute the supernatant from cell culture until the dilution, on average, has less than one virus per aliquot.

- D: Use these aliquots to inoculate further cell culture.

2) Analyze all cultures

- A: As, on average, some of the aliquots contained no virus, there should be a number of cultures which look identical to the uninfected controls.

- B: Any cultures which show morphology or pathology distinct from the uninfected controls should contain specific virus particles and show specific viral RNA/DNA on a PCR test. Likewise, any cultures which look like the uninfected controls should be free of virus based on these tests.

- C: If any cultures show morphology or pathology distinct from the uninfected controls but do not contain virus particles (given sufficient time for the virus to propagate and emerge from the cells), then you've got a thinker on your hands. Triage for contaminants or another disease causing agent.

3) After demonstrating that virus is the causal agent of the infected culture morphology or pathology, use multiple of these infected cultures to infect animals (and have control "infections" from the uninfected cultures). Then repeat this process from the infected animals to demonstrate that it is indeed the identified virus which causes the disease.

If you can't use an animal model for the disease then you're stuck doing this in cell culture and comparing the infected culture cell morphology and pathology to that of cells in biopsies of diseased people.

Pretty darn good evidence that it is a virus, and a particular virus at that, which causes the disease.

Realistically it's much more convenient just to use 2B as evidence. You get some issues with natural immunity and lysogenic versus lytic viral stages (these have different terms in Eukaryotic viral infection), but it's pretty decent for showing things like HIV being the causative factor of AIDS even prior to showing the effect of HIV presence in immune cells.


I skimmed the paper, and it's interesting that this seems like these were identified purely from scanning public RNA sequencing datasets and then finding things that look like they would make circles. As someone with only a rudimentary understanding of biology and bioinformatics, I'm wondering:

* Has anyone experimentally demonstrated that these RNA sequences actually form circles?

* Is it possible that these are the result of some reaction in the transcription process? (My understanding of RNA transcription is that we sequentially dump some enzymes into a petri dish, so it seems plausible that we could generate novel DNA/RNA not present in the source.)

* Is it possible these are actually ubiquitous, exist in every cell, but we don't have any reliable way to detect them?


>Is it possible that these are the result of some reaction in the transcription process? (My understanding of RNA transcription is that we sequentially dump some enzymes into a petri dish, so it seems plausible that we could generate novel DNA/RNA not present in the source.)

Even if this was plausible, it wouldn't be there at a high enough copy level when using a DNA-dependent RNA polymerase. Let's say the RNA polymerase goes haywire and creates a random string of RNA. Well, you'd just get one exact copy of that string, it'd be unable to use it as a template to duplicate the string, since it requires a DNA template, not an RNA one. A single copy wouldn't be detectable above the noise, and so wouldn't show up in any datasets. (or would be discarded if it did, as noise).

>Is it possible these are actually ubiquitous, exist in every cell, but we don't have any reliable way to detect them?

There is so much more to the RNA world, especially the RNA virus world, than we realize, because RNA is so hard to work with. Humans secrete enzymes that degrade, and those enzymes are extremely durable and wind up everywhere. Also, RNA is generally not good for DNA processing, so lots of DNA prep kits degrade the RNA intentionally. So the overwhelming majority of nucleic acid work is done with just DNA, and RNA viruses are a huge blind spot. That's not to say no one is doing RNA work, just far fewer.


I can't watch it right now but IIRC this (amazing) video of the life cycle of an HIV viral particle demonstrates an RNA that forms a ring:

https://vimeo.com/260291607


It'll be great to learn more about these and see what diseases are associated with them. I still think it's crazy that an anti-fungal drug is very good therapeutic for Multiple Sclerosis: https://en.m.wikipedia.org/wiki/Dimethyl_fumarate


not fungal, but pathogen related: stanford researchers in 2022 identified how epstein-barr virus (EBV) could be one cause of MS. essentially, EBV proteins may mimic a human protein and induce the immune system to mistakenly attack the body’s nerve cells.

https://med.stanford.edu/news/all-news/2022/01/epstein-barr-...


Dimethyl fumarate is not an antifungal drug. It's an immunomodulator.


You're correct it's not an antifungal drug, it's a substance used for its antifungal properties. Furniture companies today still use it for that: https://www.leatherusa.org/dimethyl-fumarate-dmf you can Google "Dimethyl fumarate furniture". I'm not sure if it's mechanism of action is known.

It was originally used to prevent mold on furniture. The Germans notices that treated psoriasis when it was applied topically. After which the swiss(Fumapharm) was noticed that people who took it for psoriasis and had MS, had fewer MS symptoms.

https://en.wikipedia.org/wiki/Dimethyl_fumarate

==== https://pubmed.ncbi.nlm.nih.gov/36641891 Dimethyl fumarate ameliorates fungal keratitis by limiting fungal growth and inhibiting pyroptosis


Are you lost? You don't seem to have read the same article I just did.


We don’t know why human digestion is such a (pun not intended) shitshow right now. There are microbes that don’t culture in agar. There are histamine reactions from allergies. Detergents and rinse agents messing up protective layers. Or maybe the right bacteria are there but they’re sick with a virus and misbehaving.

We don’t know.

My brain went the same place as GP but without the anecdote. So I suspect did the people who greyed out your reply before I got here.


Or he just paid attention to it: "It’s not yet known whether obelisks affect human health, says Matthew Sullivan, an integrative biologist at Ohio State University, but they could alter the genetic activity of their bacterial hosts, which in turn could affect human genes."

And of course, even if there wasn't an explicit reference to that question, wondering how those new entities might affect our health is 100% compatible with the article.


"It’s not yet known whether obelisks affect human health, says Matthew Sullivan, an integrative biologist at Ohio State University"

We have no idea what these do. What if they could cause MS? Then drugs could kill these things and prevent MS.

Now that we know some cancers are caused by viruses, we've created vaccines to stop the viruses and the cancer.


It is probably best to destroy obelisks, and deny their utility to the Necrontyr.



Doesn't this support the theory that viruses are rogue cellular messengers that left their hosts and started a genealogy on their own


It is possible that some viruses have appeared in this way, though not very likely.

A large part of the viruses (if not all) appears to have an ancestor that was significantly further in the past than the common ancestor of all present cellular life forms, so they are much more distantly related to us than any bacteria.

While a part of the viral genomes has this distinct origin, many viruses have combined with various pieces of nucleic acids extracted from their hosts, so these can be considered hybrids that include fragments of DNA or RNA of various origins, possibly even human DNA for some.


Are obelisks supposed to be circular? I thought they were like towers or something.


RNA world is alive and well.




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