'Obelisks': New class of life has been found in human digestive system(sciencealert.com)
sciencealert.com
'Obelisks': New class of life has been found in human digestive system
https://www.sciencealert.com/obelisks-entirely-new-class-of-life-has-been-found-in-the-human-digestive-system
136 comments
>Obelisks form their own phylogenetic group without detectable similarity to known biological agents.
ababaian, does this truly mean no similarity to any other sequences, even virus/viroid?
That seems very exciting, since my understanding is that we see a lot of conservation within the known branches of life, and don't discover new ones often!
Though perhaps it's more common to find totally novel virus/viroids? How often do we find truly novel biological agents at the sequence level?
ababaian, does this truly mean no similarity to any other sequences, even virus/viroid?
That seems very exciting, since my understanding is that we see a lot of conservation within the known branches of life, and don't discover new ones often!
Though perhaps it's more common to find totally novel virus/viroids? How often do we find truly novel biological agents at the sequence level?
To the limits of where our understanding of how "entities" are connected to one another (homology). Yes, there's nothing like them. You could make an argument they are "viroid-like" and there's a deeper evolutionary connection between viroids/viruses/plasmids, but the information theory to formally establish such a connection is not sufficiently developed. It's a worthy scientific problem!
Is it common to find new viruses/viroids/biological agents? Well it certainly is starting to feel that way to me.
Is it common to find new viruses/viroids/biological agents? Well it certainly is starting to feel that way to me.
> You could make an argument they are "viroid-like" and there's a deeper evolutionary connection between viroids/viruses/plasmids, but the information theory to formally establish such a connection is not sufficiently developed.
The way it is phrased, insufficiently developed information theory is rather surprising. Did you mean to write that not enough genome data has been collected to formally establish a link, or are you actually stating that we have all the data but as a species have not sufficiently developed the mathematical subdiscipline of probability, information theory ?
I could follow the first, but the latter?
EDIT: I now believe you meant neither but more something along the lines of: we probably have plenty of data, and usual information theory should suffice, but we simply havent exhaustively applied the tools to collate the information and make the implicitly available data more explicitly manifest.
The way it is phrased, insufficiently developed information theory is rather surprising. Did you mean to write that not enough genome data has been collected to formally establish a link, or are you actually stating that we have all the data but as a species have not sufficiently developed the mathematical subdiscipline of probability, information theory ?
I could follow the first, but the latter?
EDIT: I now believe you meant neither but more something along the lines of: we probably have plenty of data, and usual information theory should suffice, but we simply havent exhaustively applied the tools to collate the information and make the implicitly available data more explicitly manifest.
We certainly have the data, too much so actually. I should correct the statement to say, we have insufficiently developed _applied_ information theory.
We know how to quantify homology, it just has not been applied to sufficient depth to the field of RNA/viroid evolution to resolve how much of an RNA element with extensive secondary structure, or ribozyme is evidence of a homology vs. convergence. And how could we resolve the two? It's easy with protein sequences, tricky with protein structures, but deep RNA evolution? That's a mystery.
We know how to quantify homology, it just has not been applied to sufficient depth to the field of RNA/viroid evolution to resolve how much of an RNA element with extensive secondary structure, or ribozyme is evidence of a homology vs. convergence. And how could we resolve the two? It's easy with protein sequences, tricky with protein structures, but deep RNA evolution? That's a mystery.
How do obelisks fit in with commonly known forms of life?
We all understand cells/bacteria and their interaction with viruses: Viruses infect cells and make them into virus factories…
What do obelisks do? Are they integrated / read by DNA machinery/organells into cells that then produce more obelisks?
What‘s their life cycle?
How are they different from alread known viroids?
We all understand cells/bacteria and their interaction with viruses: Viruses infect cells and make them into virus factories…
What do obelisks do? Are they integrated / read by DNA machinery/organells into cells that then produce more obelisks?
What‘s their life cycle?
How are they different from alread known viroids?
Largely we don't know. That's what makes them cool. This opens up a fairly large debate about where you draw the boundary of "life", "organisms", and "entities". It's a fun debate to have over a few beers since there is no objective correct answer.
My view is that Obelisks are more like Viruses or Viroids, or some kind of mobile genetic element. The key detail is that they appear to be strictly RNA elements (they don't have a DNA counterpart). So they're most likely using host RNA transcription machinery to make more copies of themselves, this is what viroids and satellite viruses like "Hepatitis Delta Virus" do.
What do they do? Well that's the right question. My guess is the kinds of things that bacteriophages do, Obelisks do too. Exploit cells to make more copies of themselves as selfish replicators.
My view is that Obelisks are more like Viruses or Viroids, or some kind of mobile genetic element. The key detail is that they appear to be strictly RNA elements (they don't have a DNA counterpart). So they're most likely using host RNA transcription machinery to make more copies of themselves, this is what viroids and satellite viruses like "Hepatitis Delta Virus" do.
What do they do? Well that's the right question. My guess is the kinds of things that bacteriophages do, Obelisks do too. Exploit cells to make more copies of themselves as selfish replicators.
I'm unclear why we are calling these a new class of life rather than just a new kind of virus. Their shape?
I think this is the journalist playing at the idea that we don't have a universally accepted definitions of "life", "virus", "viroids", "mobile genetic elements", "plasmids", or the other words that describe what I view as the agents of evolutionary games. It is kind of catchy way to raise that conversation though eh!
Viruses have capsids which are protein shells that envelop them. These are just bare RNA strands, which are considered viroids.
Is it possible that these may cause diseases that previously went unexplained?
It's possible, yes. But right now there is no evidence for Obelisks being linked to any disease, not even a phenotype in the cells carrying them. Keep in mind also that these elements likely interact with bacterial cells, so effects on human disease would most likely be indirect.
Is there really any evidence that they are parasites and not part of the host's machinery?
These are two distinct questions. Are Obelisks part of the self? If you think of the "host" as being made up by it's DNA, then these are not part of that set, since they are not found in DNA copies. Or is an organism it's RNA? If it's the RNA that's the organism, then sure you could say this is part of that organism in that it exist as organelles of sorts, like mitochondria or chloroplasts (but in RNA form).
The second question is if it's parasitic, mutualistic, or neutral. If it's a parasite it should cause a fitness defect to the DNA organism's replication. As of yet I haven't seen evidence of this at the cellular level. But there is a strong argument that by depleting cells of nucleic acids (RNA) would have to be at least minimally parasitic. That is of course unless they confer some advantage to the cells with Obelisks. In which case, why don't all microbial cells have Obelisks. Importantly, the relationships between all the various Obelisks at least for now, is not lining up with microbial genome evolution. This would mean they are jumping from genome to genome.
Now you're in a late night pub discussion about where we should be drawing the boundaries of life.
The second question is if it's parasitic, mutualistic, or neutral. If it's a parasite it should cause a fitness defect to the DNA organism's replication. As of yet I haven't seen evidence of this at the cellular level. But there is a strong argument that by depleting cells of nucleic acids (RNA) would have to be at least minimally parasitic. That is of course unless they confer some advantage to the cells with Obelisks. In which case, why don't all microbial cells have Obelisks. Importantly, the relationships between all the various Obelisks at least for now, is not lining up with microbial genome evolution. This would mean they are jumping from genome to genome.
Now you're in a late night pub discussion about where we should be drawing the boundaries of life.
How do you know that they aren't waste/intermediate products of some other cell, as opposed to being something that reproduces?
How would they exist/maintain themselves without it's DNA counterpart?
ah, have you shown that there is no matching DNA in either the host or any of the bacteria that the host has?
The paper says: “in companion DNA-seq data from this project, no detectable Obelisk reads are found” which I think is getting at what you’re asking, but I’m not sure if my understanding is correct.
I’m also not sure if DNA-seq data refers to the human host, or just all DNA they were able to sequence (which would include bacteria as well I guess?)
I’m also not sure if DNA-seq data refers to the human host, or just all DNA they were able to sequence (which would include bacteria as well I guess?)
in simple terms, it seems these are just rod-shaped RNA plasmids that encode a couple proteins and exist without any kind of membrane or coating, does that seem right? is it that elucidated?
Sure, in a redutionistic sense. In the same light "Hepatitis Delta Virus" is an RNA plasmid, yet it causes liver cancer in humans. I err on the side that the simplicity of the genetic system should not deceive us into thinking it's trivial. The next 12 months of discoveries is what makes this so exciting.
Are there more of these undetected/undetectable entities out there?
E.g. are there more "life" like obelisks and similar out there in genome samples?
E.g. are there more "life" like obelisks and similar out there in genome samples?
Probably. There’s a whole category of organisms that can’t cultured in a lab or effectively studied called microbial dark matter: https://en.m.wikipedia.org/wiki/Microbial_dark_matter
These kinds of DNA and RNA studies are the only ones that can realistically pick up evidence of these organisms outside of an extraordinarily lucky electron microscope slide.
These kinds of DNA and RNA studies are the only ones that can realistically pick up evidence of these organisms outside of an extraordinarily lucky electron microscope slide.
There’s a biological detective story out there about someone figuring out how to culture the black soot near distilleries. This isn’t the version I read but it’s the same microbe:
https://www.wanderingspiritsglobal.com/whisky-fungus-baudoin...
It doesn’t culture in agar. Unless you add alcohol to the Petri dish and then it does. Things like this are why I still have my fingers crossed that we will have one or more helicobacter pylori (the bacteria that causes 90% of ulcers) moments for intestinal ailments. These obelisks may turn out to be one of them, and understanding could lead to better treatments and prevention.
https://www.wanderingspiritsglobal.com/whisky-fungus-baudoin...
It doesn’t culture in agar. Unless you add alcohol to the Petri dish and then it does. Things like this are why I still have my fingers crossed that we will have one or more helicobacter pylori (the bacteria that causes 90% of ulcers) moments for intestinal ailments. These obelisks may turn out to be one of them, and understanding could lead to better treatments and prevention.
If you want the real mind-trip, try to think about how little we know about detecting "life" that is not based on nucleic acids.
Probably. This is a good illustration of just how hard it may be to conclusively find life on other worlds; we don’t even know what exists here on Earth yet.
The reason these things are so hard to find on Earth is because it's teeming with other life. If it wasn't and these things were isolated on Mars it would be relatively easy.
Nope. Still tough.
https://science.nasa.gov/science-research/planetary-science/...
https://science.nasa.gov/science-research/planetary-science/...
That's not looking for life. It's looking for fossils.
Which, physically in hand, still took years to determine they were naturally occurring rock. It’s hard.
I should certainly hope so.
Don't know. They're undetected =-)
Hey this looks pretty amazing, congrats on the research. The article doesn’t seem to explain much though and the papers are pay-walled(?) so my question is how were these discovered only now and not noticed before?
There are preprints for all the papers [https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1], they're operationally the same.
How were they not noticed before? Well that's how science works. Someone eventually has to be the one to notice something is going on right?
I think it's a common fallacy that we, as a species, are not ignorant to the complexity of Nature. The hardest part is to see it.
How were they not noticed before? Well that's how science works. Someone eventually has to be the one to notice something is going on right?
I think it's a common fallacy that we, as a species, are not ignorant to the complexity of Nature. The hardest part is to see it.
I would expect that you still need to have some substantial expertise to have any idea of what you are doing, and to know that what you are doing makes sense and also hasn’t been done yet. Someone unfamiliar with molecular biology would likely need to invest some time to get up to speed.
Consider the existence of forensic genetic polymer tagging sprays etc.
For example: https://www.selectadna.co.uk/dna-tagging-spray
One could easily fathom not just overt authorities but also covert authorities wishing to use similar technology.
Clearly an intelligence agency doesn't want the lower level police leaking detections of higher importance, so best to differentiate say DNA for cops and RNA for intelligence services, so that the pragmatic tools and workflows of police won't result in uncleared personnel figuring out things they aren't cleared for.
That wouldn't explain quasi biological statistics as opposed to white noise random sequences, which would suffice for tracking, but also would blow the cover as a man-made genome...
I.e. if RNA sprays had been reserved by some power bloc for intelligence service purposes (DNA sprays for usual law enforcement), then there is a clear incentive to have the secret pseudorandom sequences at least mimic plausible biology sequences, an adversary bloc detecting such a tracker might believe the sequence to be of biological origin, and intelligence associated academics would publish it: revealing both the detection by an adversary bloc and the academic's employment by intelligence circles...
For example: https://www.selectadna.co.uk/dna-tagging-spray
One could easily fathom not just overt authorities but also covert authorities wishing to use similar technology.
Clearly an intelligence agency doesn't want the lower level police leaking detections of higher importance, so best to differentiate say DNA for cops and RNA for intelligence services, so that the pragmatic tools and workflows of police won't result in uncleared personnel figuring out things they aren't cleared for.
That wouldn't explain quasi biological statistics as opposed to white noise random sequences, which would suffice for tracking, but also would blow the cover as a man-made genome...
I.e. if RNA sprays had been reserved by some power bloc for intelligence service purposes (DNA sprays for usual law enforcement), then there is a clear incentive to have the secret pseudorandom sequences at least mimic plausible biology sequences, an adversary bloc detecting such a tracker might believe the sequence to be of biological origin, and intelligence associated academics would publish it: revealing both the detection by an adversary bloc and the academic's employment by intelligence circles...
Do you have any clear idea yet what the proteins do that the obelisks code for?
No clear ideas. But I would not be surprised if a dozen labs have jumped at the chance of trying to figure it out. So wait a year and ask again.
Edit: Or better yet, try and figure it out for yourself. The tools to do this analysis are available to everyone.
Edit: Or better yet, try and figure it out for yourself. The tools to do this analysis are available to everyone.
What are these tools you speak of ?
The most limiting is our own imaginations.
For the nuts and bolts: a class of really engaged and brilliant students at UofT recently documented the tools and methodology to go about characterizing Obelisks [https://github.com/ababaian/VIRUSxDISCVRY].
Here are some paradigm-shifting questions and their answers, grounded in the repository's evidence:
1. "Are we looking at Obelisks the wrong way by trying to classify them within existing frameworks?"
Looking at the repository structure and tools developed (AlphaFold3.md, RNAfold.md, etc.), we're primarily using methods designed for known biological entities. The fact that specialized tools were needed suggests we might be forcing Obelisks into existing paradigms rather than understanding them on their own terms.
Perhaps instead of asking "what kind of virus is this?", we should ask "what kind of biological phenomenon are we observing?"
2. "What if Obelisks aren't entities but processes?"
The repository shows: - Complex regulatory elements - Stable host relationships - System-level effects - Consistent patterns across environments
This suggests we might be misconceptualizing Obelisks by thinking of them as discrete entities rather than as processes or systems that emerge from biological information flow.
3. "Are we asking the right questions about biological information?"
The unusual combination of: - Highly structured RNA elements - Complex regulatory patterns - Stable host relationships - Modular organization
Suggests we might need to fundamentally rethink how biological information is maintained and transmitted. Obelisks might represent a different paradigm of biological information organization.
4. "What if our concept of host and virus is too binary?"
The evidence shows: - Deep host integration - Stable relationships - Complex interactions - System-level effects
This suggests we might need to move beyond the binary host-virus paradigm toward understanding biological systems as networks of interacting information processes.
5. "Are we witnessing biology we don't yet have the framework to understand?"
The need for: - New detection methods - Specialized analysis tools - Novel classification systems - Complex structural analyses
Suggests we might be encountering biological phenomena that our current scientific frameworks aren't equipped to fully comprehend.
6. "What if Obelisks aren't unusual - what if our other classifications are too narrow?"
The widespread presence but previous lack of detection suggests: - Our detection methods might be biased - Current classifications might be too restrictive - We might be missing other similar phenomena - Our understanding of biological diversity might be too limited
7. "Should we be studying Obelisks' absence rather than their presence?"
The repository shows: - Consistent presence in some environments - Absence in others - Stable host relationships - System-level effects
Perhaps studying where and why Obelisks are absent could tell us more about their nature than studying where they're present.
8. "Are we confusing structure with function?"
The focus on: - Structural analyses - Sequence comparisons - Protein predictions - RNA folding
Might be causing us to miss the fundamental nature of what Obelisks do rather than what they are.
1. "Are we looking at Obelisks the wrong way by trying to classify them within existing frameworks?"
Looking at the repository structure and tools developed (AlphaFold3.md, RNAfold.md, etc.), we're primarily using methods designed for known biological entities. The fact that specialized tools were needed suggests we might be forcing Obelisks into existing paradigms rather than understanding them on their own terms.
Perhaps instead of asking "what kind of virus is this?", we should ask "what kind of biological phenomenon are we observing?"
2. "What if Obelisks aren't entities but processes?"
The repository shows: - Complex regulatory elements - Stable host relationships - System-level effects - Consistent patterns across environments
This suggests we might be misconceptualizing Obelisks by thinking of them as discrete entities rather than as processes or systems that emerge from biological information flow.
3. "Are we asking the right questions about biological information?"
The unusual combination of: - Highly structured RNA elements - Complex regulatory patterns - Stable host relationships - Modular organization
Suggests we might need to fundamentally rethink how biological information is maintained and transmitted. Obelisks might represent a different paradigm of biological information organization.
4. "What if our concept of host and virus is too binary?"
The evidence shows: - Deep host integration - Stable relationships - Complex interactions - System-level effects
This suggests we might need to move beyond the binary host-virus paradigm toward understanding biological systems as networks of interacting information processes.
5. "Are we witnessing biology we don't yet have the framework to understand?"
The need for: - New detection methods - Specialized analysis tools - Novel classification systems - Complex structural analyses
Suggests we might be encountering biological phenomena that our current scientific frameworks aren't equipped to fully comprehend.
6. "What if Obelisks aren't unusual - what if our other classifications are too narrow?"
The widespread presence but previous lack of detection suggests: - Our detection methods might be biased - Current classifications might be too restrictive - We might be missing other similar phenomena - Our understanding of biological diversity might be too limited
7. "Should we be studying Obelisks' absence rather than their presence?"
The repository shows: - Consistent presence in some environments - Absence in others - Stable host relationships - System-level effects
Perhaps studying where and why Obelisks are absent could tell us more about their nature than studying where they're present.
8. "Are we confusing structure with function?"
The focus on: - Structural analyses - Sequence comparisons - Protein predictions - RNA folding
Might be causing us to miss the fundamental nature of what Obelisks do rather than what they are.
Dude, I already have way too many projects. I'm going to wait for the experts on this one. :D
There's literally no experts on the subject.
I think that GP means biologists. Biologists may not be experts on obelisks, but they have the base knowledge to understand many of the mechanisms and concepts.
I understood as much. My point is that it's not clear to me that it will be a biologist, and not a statistician/mathematician, or developer/data-scientist that will be the one to sufficiently find the solution. There are literally petabytes of public data which already hold the answer.
We now have to accept a different paradigm by which we can do biology, and biologists are not always the best equipped for this paradigm.
@ababaian. You may want to put your contact info in your bio here, based on your comments and responses. It may be helpful for others to find you an contact you if they ever see anything. Check if they're not seeing ghosts in the data
That is extraordinarily insightful, thank you.
Maybe I will give this a crack. If I get anywhere I'll contact a local university to speak to a biologist.
Thank you.
Maybe I will give this a crack. If I get anywhere I'll contact a local university to speak to a biologist.
Thank you.
It will almost certainly someone who already has a solid grasp of biochemistry, even if they're not a credentialed biologist. I don't generally believe progress can be made in a field with literally no knowledge of the base-level details. That's how you get physicists and MBAs thinking they can tell everyone how to do their jobs.
How did you find these things? Since you "stumbled upon them", you probably didn't know what you eee looking for, so... How did this research get started?
Any chance there is a correlation between Obelisks and autoimmune diseases?
Not that I know of, although this doesn't mean it isn't happening, it's something which has to be investigated in detail.
The OP addresses it to some degree, but how does this fit with the fundamental classes of phylogeny?
My poor understanding has been that there are cellular organisms / 'biota' (if those are the right terms - prokaryotes, eukaryotes, etc.) and viruses. Where do obelisks, Virus-Viroid Hybrids, Zeta-Elements, Ambiviruses all fit in that scheme, if they do at all? Or is there a new scheme?
And it is very cool for you to answer questions here. Remember us if you visit Sweden someday! :)
My poor understanding has been that there are cellular organisms / 'biota' (if those are the right terms - prokaryotes, eukaryotes, etc.) and viruses. Where do obelisks, Virus-Viroid Hybrids, Zeta-Elements, Ambiviruses all fit in that scheme, if they do at all? Or is there a new scheme?
And it is very cool for you to answer questions here. Remember us if you visit Sweden someday! :)
The classic phylogenetic classes are a fantastic model, but https://en.wikipedia.org/wiki/All_models_are_wrong :)
Phylogeny is the study by which things relate to one another. There is a divergence point at which point it becomes impossible to relate two sequences to one another. Obelisks, Zeta-Elements, Deltaviruses, viroids all veer towards their own divergence point into infinity, but their are higher-order genome organization traits which are consistent. We don't know if these traits are the same by origin, or the same by chance. Interestingly Ambiviruses also have this genome organization, but they have a protein which is de facto of an RNA virus.
My opinion is that these simple genome layouts (structured circular RNA elements with ribozymes) are like a cauldron of mixing simple genes, and when they come together just the right way, we see those lineages take off. Think of it as an ocean of ancient primordial RNA replicators, ready to fire off, and this process is ongoing even today.
Phylogeny is the study by which things relate to one another. There is a divergence point at which point it becomes impossible to relate two sequences to one another. Obelisks, Zeta-Elements, Deltaviruses, viroids all veer towards their own divergence point into infinity, but their are higher-order genome organization traits which are consistent. We don't know if these traits are the same by origin, or the same by chance. Interestingly Ambiviruses also have this genome organization, but they have a protein which is de facto of an RNA virus.
My opinion is that these simple genome layouts (structured circular RNA elements with ribozymes) are like a cauldron of mixing simple genes, and when they come together just the right way, we see those lineages take off. Think of it as an ocean of ancient primordial RNA replicators, ready to fire off, and this process is ongoing even today.
Thank you.
> The classic phylogenetic classes are a fantastic model, but https://en.wikipedia.org/wiki/All_models_are_wrong :)
For the record, yes, I know. Unfortunately, we need models to organize the world in our limited brains, and the less intimate experience one has of something, the more simplified their model. This isn't my day job! :)
> The classic phylogenetic classes are a fantastic model, but https://en.wikipedia.org/wiki/All_models_are_wrong :)
For the record, yes, I know. Unfortunately, we need models to organize the world in our limited brains, and the less intimate experience one has of something, the more simplified their model. This isn't my day job! :)
How did you come up with the name? And is the “Oblin” protein is named after Obelisks?
Vanya thought that when you run them through the RNA folding software, it would give you these unusual straight rods which reminded him of Cleopatra's Needle (Obelisk, https://en.wikipedia.org/wiki/Cleopatra%27s_Needles). The name stuck around. Incidentally the name has some cool 2001: Space Odyssey monolith vibes to it, which I think has been fitting.
> unusual straight rods which reminded him of Cleopatra's Needle (Obelisk ...
Also, of course, Obelix[1], purveyor of menhirs[2] -- Breton "standing stones".
[1]: https://en.wikipedia.org/wiki/Obelix
[2]: https://en.wikipedia.org/wiki/Menhir
Also, of course, Obelix[1], purveyor of menhirs[2] -- Breton "standing stones".
[1]: https://en.wikipedia.org/wiki/Obelix
[2]: https://en.wikipedia.org/wiki/Menhir
Doesn't a name like this risk sensationalizing the discovery? I mean it's interesting to me as a layperson, but "obelisks" in pop culture carry a lot of woo factor
Not sure I understand. Obelisks seems an inert descriptor to me, it has no connotation in the field so it's appropriately a blank slate.
The big risk is we call a companion molecule asterix.
Sounds all like Miraculix to me...
Can we kill them? Do we know if any drugs have anti-obelisk effects?
What have Obelisks ever done to you? Our first reaction shouldn't be to kill everything we don't understand :'(
Good pragmatic question though. It's not clear if any drugs up- or down-regulate Obelisk genome copy, you could re-investigate other drug-treatment studies to see if Obelisks incidentally present are altered and get an "accidental" study.
From a molecular perspective, the most likely compounds and methods would be those which work against viroid replication (i.e. RNA polymerase inhibitors, translational inhibitors, CRISPR,...). You just have to maintain a preferential toxicity to Obelisks over host cells.
Good pragmatic question though. It's not clear if any drugs up- or down-regulate Obelisk genome copy, you could re-investigate other drug-treatment studies to see if Obelisks incidentally present are altered and get an "accidental" study.
From a molecular perspective, the most likely compounds and methods would be those which work against viroid replication (i.e. RNA polymerase inhibitors, translational inhibitors, CRISPR,...). You just have to maintain a preferential toxicity to Obelisks over host cells.
Well, you say they aren’t linked to IBS or Crohn’s, but there’s a difference between proving that they don’t all cause intestinal issues and eliminating every strain as a cause. It’s kind of embarrassing how recently h pylori was caught red handed.
Some people carry staph on their skin their whole life and never end up with a lesion.
Some people carry staph on their skin their whole life and never end up with a lesion.
This was not claimed. All that was stated is that its a new thing we know very little about, links to autoimmune disease have no immediate obvious connection, and to say anything more would require an investigation. What more can you expect?
This looks really cool, im interested in learning more about computational biology, RNA and would like to work as a dev to get exposure. Is there an opportunity to gain research experience/skills as a developer in your lab? Could you provide a rough range of compensation as well?
The free preprint:
https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1
https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1
I think I've missed the AMA window but I'll try anyways.
Presumably you've got a lot of follow-up research to do. What are the most important research questions re: obelisks now?
Presumably you've got a lot of follow-up research to do. What are the most important research questions re: obelisks now?
I’m not gleaning what observations support these things being alive from the article-how do we know they're not just an odd form of garbage RNA produced by cells?
That's exactly what they are though, some piece of garbage RNA cells are producing. A lot of things meet that definition if you think about it.
This is fascinating work and sounds a little like the research my daughter says she wants to study (she's only a sophomore at UMBC right now, though). She hopes to get an internship in the summer of her junior year. She is interested in plant biology and bioengineering.
If I understand correctly, plants have RNA - would this mean new RNA-based lifeforms could also be found within plants?
If I understand correctly, plants have RNA - would this mean new RNA-based lifeforms could also be found within plants?
There are no RNA-based lifeforms. All known life is DNA based but uses RNA internally. The earliest common ancestor of all life was DNA based, LUCA https://en.wikipedia.org/wiki/Last_universal_common_ancestor
There is a hypothesis that once upon a time life passed though an RNA only stage without DNA and proteins. RNA world https://en.wikipedia.org/wiki/RNA_world
There is a hypothesis that once upon a time life passed though an RNA only stage without DNA and proteins. RNA world https://en.wikipedia.org/wiki/RNA_world
I like to view it that we're all RNA-based lifeforms. Operationally: DNA, RNA, or other are just a vehicles which hold our information.
This podcast RadioLab with Carl Zimmer (11m) I think captures the essence of the idea near perfectly: https://radiolab.org/podcast/creation-translation
This podcast RadioLab with Carl Zimmer (11m) I think captures the essence of the idea near perfectly: https://radiolab.org/podcast/creation-translation
The premise of TFA is that we're treating viruses and virus-like things as a class of lifeform. There are RNA viruses, and these obelisk things are also RNA-based. Presumably that's what OP is asking about with regard to RNA-based lifeforms.
> There are no RNA-based lifeforms.
There are viruses that have entirely RNA-based lifecycle (even using RNA-dependent RNA polymerase). Our very favorite COVID virus is one of them.
There are viruses that have entirely RNA-based lifecycle (even using RNA-dependent RNA polymerase). Our very favorite COVID virus is one of them.
You say human a lot, but are they really unique to humans, or we just haven’t looked at other animal definitive tracts yet?
Serious question, super OT but i've wanted to ask this someone who works non-trivial fields like you for a long time: Have you ever used a LLM for something relevant to your work?
It's not OT at all. It depends on what you mean exactly by LLM, but we use them all the time. ESMFold2 was an LLM [https://www.science.org/doi/10.1126/science.ade2574] and was instrumental in advancing deep protein fold prediction in metagenomic space. Likewise AlphaFold2 it's direct application in creating FoldSeek for ultra-deep homology search. Both of these actually have radically improved our capacity to say Obelisks are _REALLY_ not like anything that's known.
Besides that I encourage all students to use ChatGPT for research, coding, copy editing, etc... I haven't encountered an LLM that can deal with difficult domain problems like we're facing, but I'd welcome the help. I'm for using all tools available, my main criticism with AI/LLM in general is the poor way in which uncertainty is reported.
Besides that I encourage all students to use ChatGPT for research, coding, copy editing, etc... I haven't encountered an LLM that can deal with difficult domain problems like we're facing, but I'd welcome the help. I'm for using all tools available, my main criticism with AI/LLM in general is the poor way in which uncertainty is reported.
This is by a good margin the most interesting knowledge-domain I have encountered in at minimum weeks. Super-interesting.
Hammerhead Self-Cleaving Ribozyme is quite a chunk of English.
Hammerhead Self-Cleaving Ribozyme is quite a chunk of English.
Does this support the Selfish Gene theory of Richard Dawkins? They look like the smallest self-replicating molecules that he mentions in the beginning of the book.
Absolutely, reading Selfish Gene in high school set me on the path to this type of exploration. Genes, in the pure abstract sense, are the unit by which we interrogate understand evolutionary change. There's a large grey area about the boundaries of genes, but after a certain point, genes assemble into operational units larger than themselves, a genome. Obelisks are some of the simplest, most rudimentary genomes described thus far.
It’s amazing how genes choose from the chaos if 10^200 possibilities and don’t self destruct.
Thanks for your work on the research. I get a feeling of amusement and wandering when thinking on what functions the obelisks may have.
I am hopeful this discovery can lead to technology to improve people's life. Just thinking out loud, cancer treatments, orphan diseases treatment, prevent Alzheimer's progression, new vaccines.
Very long shots, but that's the beauty of unknowns. I'm highly jealous of scientists that will formulate and test hypothesis around this topic.
I am hopeful this discovery can lead to technology to improve people's life. Just thinking out loud, cancer treatments, orphan diseases treatment, prevent Alzheimer's progression, new vaccines.
Very long shots, but that's the beauty of unknowns. I'm highly jealous of scientists that will formulate and test hypothesis around this topic.
Everyday I get to do this kind of research, I'm grateful to be the one doing it.
> researchers have stumbled across what seem to be an entire new class of virus-like objects.
I was confused at first. This isn't "Class" in the technical sense (i.e. the level between Phylum and Order)
I was confused at first. This isn't "Class" in the technical sense (i.e. the level between Phylum and Order)
I am really glad we are finding new pieces of the puzzle of how our gut works and perhaps can someday understand their effect on immunity, neuro-degeneration, cancer etc. for which we now only have accidental findings.
> Obelisks' genetic sequences are only around 1,000 characters
So they have a higher chance of being re-created by random chemical processes at mostly any point in time and place in the universe. Omniterrestrial?
So they have a higher chance of being re-created by random chemical processes at mostly any point in time and place in the universe. Omniterrestrial?
The study hasn’t been peer reviewed yet, so the title is a bit too confident in its claim.
Here's the journal publication (which came later during the year):
https://www.cell.com/cell/abstract/S0092-8674(24)01091-2
It truly is a new class of genomic elements.
https://www.cell.com/cell/abstract/S0092-8674(24)01091-2
It truly is a new class of genomic elements.
And it's been replicated?
It's using data from the Integrative Human Microbiome Project [1], so, in a sense, hundreds of high-quality biological replicas support their findings. Obelisks were found in a substantial portion of them.
They then expanded the search to millions of sequences, which are publicly available, and found ~30k different classes(!) of Obelisk elements. One could argue that the quality of each of these "experiments" may not be as good as IHMP, but still, the signal is more than sufficient to clearly demonstrate the existence and implied significance of these elements.
1: https://pubmed.ncbi.nlm.nih.gov/31142853/
They then expanded the search to millions of sequences, which are publicly available, and found ~30k different classes(!) of Obelisk elements. One could argue that the quality of each of these "experiments" may not be as good as IHMP, but still, the signal is more than sufficient to clearly demonstrate the existence and implied significance of these elements.
1: https://pubmed.ncbi.nlm.nih.gov/31142853/
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"Please don't post shallow dismissals, especially of other people's work. A good critical comment teaches us something."
https://news.ycombinator.com/newsguidelines.html
No doubt there are valid concerns but the value of comments formed by internet clichés and dismissive tropes is... lower than what we want here. When it comes with a tone of entitled aggressiveness, that's even worse—that's enough to drive away the people who spend their lives working on a subject, and that would be the worst possible outcome for HN.
https://news.ycombinator.com/newsguidelines.html
No doubt there are valid concerns but the value of comments formed by internet clichés and dismissive tropes is... lower than what we want here. When it comes with a tone of entitled aggressiveness, that's even worse—that's enough to drive away the people who spend their lives working on a subject, and that would be the worst possible outcome for HN.
Thank you! I'll work on deeper dismissals
It's based on data gathered from scientific instruments that are well-characterized and whose results are validated by being used for other findings. They're not administering a questionnaire to someone's microbiome and doing sample statistics on the results. They found novel RNA sequences in microbiome sample data using well-understood and repeatable methods, and confirmed that the RNA sequences seem to exist. You can repeat the analysis yourself and make that determination.
I think you're trying to draw a comparison here between two things of completely different category, and I feel like you might not understand how different they are.
I think you're trying to draw a comparison here between two things of completely different category, and I feel like you might not understand how different they are.
Don't be a dick. It's totally normal to be skeptical and doubtful of some over-the-top claims. The onus is squarely on the person presenting the information to justify it. Your points about replication are accurate, but let's at least keep it to a pretext of civility.
I wasn't being a dick, I was being direct. It doesn't always come through online though.
The claim is not over-the-top at all though. They did a survey of funny RNA sequences in gut samples and didn't find anything that links them to known sequence from other organisms. Nothing spectacular was claimed.
It’s such a different thing entirely, the question of replication doesn’t make sense. See my other comment.
I think you’d be better served by trying to understand how psychological research has been done, why people go on about replication, what results are suspect from psych, and how they developed in the first place.
Bc it seems like you’re trying to justify the actions in psych world by other disciplines, but it just doesn’t make sense.
I think you’d be better served by trying to understand how psychological research has been done, why people go on about replication, what results are suspect from psych, and how they developed in the first place.
Bc it seems like you’re trying to justify the actions in psych world by other disciplines, but it just doesn’t make sense.
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The sequences they found are already in various databases and are not linked to any organisms we know. It's like discovering an interesting new insect in a national park. That's as different as it can be from psychological research. What is there to replicate?
I hold no prejudice against the 'soft sciences', or for literature, or for music, or for athletics or for any other human pursuit which demands merit.
I am genuinely curious as to how best to present the evidence. What would you like to see to tame your skeptic?
I am genuinely curious as to how best to present the evidence. What would you like to see to tame your skeptic?
Closer to "not yet". It's bleading edge scientific advance. Someone has to be the first.
It's good to wait until replication and then 5 years to let the dust setle down.
But if the research group had group had a good past history, it's better to trust them while the other teams verify.
It's good to wait until replication and then 5 years to let the dust setle down.
But if the research group had group had a good past history, it's better to trust them while the other teams verify.
What's your definition of replication?
The standard that people hold soft sciences to when they dismiss them.
I'm starting to realize that this may be a justification of their prejudice against these fields rather than a legitimate basis for dismissal.
I'm starting to realize that this may be a justification of their prejudice against these fields rather than a legitimate basis for dismissal.
So basically this study is “we looked at various publicly available data sets of information, and here is a thing we notice that has previously gone unnoticed”.
The noticed it in multiple datasets.
What would replication look like here besides someone else looking at the dataset and agreeing that they also see the curiosities?
Or do you mean someone measuring a new fresh set of data and looking at it?
Asking for replication in this case is surprising, because seemingly the entire value is to prompt other research to go figure out what’s going on with these things.
The noticed it in multiple datasets.
What would replication look like here besides someone else looking at the dataset and agreeing that they also see the curiosities?
Or do you mean someone measuring a new fresh set of data and looking at it?
Asking for replication in this case is surprising, because seemingly the entire value is to prompt other research to go figure out what’s going on with these things.
My reading is that the GP moreso takes issue with how social sciences are discussed, and is using an arbitrary replication-less finding in the 'hard sciences' (this one) as a podium to speak from--regardless of why replication doesn't exist for it, or whether that reason makes sense.
Is it falsifiable? What is H_0 in this study?
> Is it falsifiable?
Rather obviously, I'd think, if someone else looks at similar samples and sees no "Obelisks" at all. Or looks at their samples.
> What is H_0 in this study?
"The stuff we're seeing here doesn't exist"?
Or, IOW, "All the electron microscopes used have the same weird bug, showing obelisk-shaped pieces of RNA material where there really isn't anything at all"?
Feels a bit like what you want is really "We were all high on funny mushrooms when we saw that".
Look, I see from your other comments that you're actually not talking about this, but something else entirely. And you may well have a point there, but in order to make that point here, you would have had to come up with something a lot better than this. Because I'm fairly sure they weren't all high on funny mushrooms. Aren't you too, really?
Rather obviously, I'd think, if someone else looks at similar samples and sees no "Obelisks" at all. Or looks at their samples.
> What is H_0 in this study?
"The stuff we're seeing here doesn't exist"?
Or, IOW, "All the electron microscopes used have the same weird bug, showing obelisk-shaped pieces of RNA material where there really isn't anything at all"?
Feels a bit like what you want is really "We were all high on funny mushrooms when we saw that".
Look, I see from your other comments that you're actually not talking about this, but something else entirely. And you may well have a point there, but in order to make that point here, you would have had to come up with something a lot better than this. Because I'm fairly sure they weren't all high on funny mushrooms. Aren't you too, really?
It's more that it's a category error. Replication has a context for where it's important, e.g. a treatment and cause & effect relationship. It doesn't If you say "we did this to people and it caused them to respond this way X% of the time," that's something that needs to replicate for us to know if we should take it seriously. If you look at a bunch of separate data sources and find out that a bunch of them show that a certain thing verifiably exists, that doesn't need to replicate to be taken seriously. The data should be checked to make sure the thing actually does exist, but that's verification.
So most findings in research psychology definitely need replication. But the idea that the existence of something is verifiably found across a bunch of different datasets doesn't need a new set of experiments to show -- you just check the data.
So most findings in research psychology definitely need replication. But the idea that the existence of something is verifiably found across a bunch of different datasets doesn't need a new set of experiments to show -- you just check the data.
One thing that makes soft sciences softer is that it is inherently more difficult to achieve the same statistical significance, due to both higher underlying variances and logistics of obtaining large samples. Publishing with higher p-values results in lower reproducibility by definition.
The problem with psychology is that despite the fact that the subject matter is inherently more difficult to study, researchers are forced into the same publish-or-perish system as biologists and mathematicians. A higher degree of skepticism towards new studies might technically be prejudice, but it’s certainly justified.
The problem with psychology is that despite the fact that the subject matter is inherently more difficult to study, researchers are forced into the same publish-or-perish system as biologists and mathematicians. A higher degree of skepticism towards new studies might technically be prejudice, but it’s certainly justified.
Maybe Obelisks need an asterisk until peer review?
In case others don't get it:
https://asterix.com/en/portfolio/obelix/
https://asterix.com/en/portfolio/obelix/
We should not be so dogmatix
in requiring scientific protocol - maybe there are some
VitalStatistix we are not yet aware of.
Splendido.
Peer review doesn't do what you think it does.
co-author (top comment?) just said that it is peer reviewed now.
Not that it matters at all.
Not that it matters at all.
Article is from January. Has the study now been published in a journal?
Yes, the bioRxiv entry[1] links to Cell[2].
[1]: https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1
[2]: http://dx.doi.org/10.1016/j.cell.2024.09.033
[1]: https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1
[2]: http://dx.doi.org/10.1016/j.cell.2024.09.033
From one of the paper's authors elsewhere in this thread: https://www.cell.com/cell/abstract/S0092-8674(24)01091-2
But how are these life? Life generally defined by ability to reproduce and these would be piggybacking on hosts cellular machinery.
Do these have a known utility or is it possible some junk DNA is involved with their encoding?
Do these have a known utility or is it possible some junk DNA is involved with their encoding?
My crude understanding is the definition of life has gotten quite fuzzy in current biological theory.
Notably, I think the "viruses first" theory for the origin life has gained force. This says that first came protein/DNA soup, then came viruses and only then came cellular organisms.
And if you want something that doesn't "piggyback", you'd have to wait for photosynthesizing plants and that's several steps further in evolution (in my layman's understanding of current theory).
Notably, I think the "viruses first" theory for the origin life has gained force. This says that first came protein/DNA soup, then came viruses and only then came cellular organisms.
And if you want something that doesn't "piggyback", you'd have to wait for photosynthesizing plants and that's several steps further in evolution (in my layman's understanding of current theory).
it's interesting that RNA modifications are more diverse than DNA and we are just starting to develop ways to discover them. Nanopore sequencing technology from Oxford Nanopore Technology is the first technology that can sequence native RNA and their modifications. Have you explored this area?
This is a staggering and amazing finding.
Why call these obelisks their own class instead of categorizing them as another type of virus?
Privacy policy / cookie dialogue on that page is class A scum-worthy dark pattern.
I'm more surprised when I encounter one that isn't hostile like this.
This is now a peer-reviewed paper, published last month in Cell [https://www.cell.com/cell/fulltext/S0092-8674(24)01091-2].
Obelisks are part of a larger research program we're developing at the University of Toronto + collaborators, see also: Virus-Viroid Hybrids paper [https://www.nature.com/articles/s41467-023-38301-2] and the Zeta-Elements [https://www.nature.com/articles/s41586-021-04332-2].
Computational biology is driving a revolutionary expansion of our understanding of Earth's biodiversity. I believe Zeta-elements, Ambiviruses, and Obelisks are just the beginning. If you're interested, our "Laboratory for RNA-Based Lifeforms" (University of Toronto) is hiring passionate developers/post-docs/graduate students [https://www.rnalab.ca].
Edit: OK going to call it for now. I'll check in later today if there's any outstanding questions.