'Useless specks of dust' turn out to be building blocks of vertebrate genomes | Hacker News Reader

'Useless specks of dust' turn out to be building blocks of vertebrate genomes

sciencealert.com

262 pointsgeorgecmu133 comments

"Not only are they the same in each species, but they crowd together in the center of the nucleus where they physically interact with each other, suggesting functional coherence,"

If there truly is some sort of functional interaction going on then this is a very profound observation. As it implies the close spacing is for some kind of mechanical/electrical mechanism within the core of every cell’s nucelus.

Surely nobody was under the impression that detail stops at the nucleic level, right? It's small machines and complex systems the entire way down, ad infinitum. Our ability or inability to render or understand these increasingly small systems does not negate their existence.

I agree with your general sentiment, but I don't see why we should expect "machines and complex systems" (as related to life) to exist at the level below molecules and atoms. If that was the case then we should expect otherwise identical organic molecules to have differences when they're created by living things and synthesis in the lab (ok, ok, there's chirality and carbon-14, but you get what I mean).

I get what you're trying to say, however this is a flawed assumption right up there with just getting an FTP account, mounting it locally with curlftpfs, and then using SVN or CVS on the mounted filesystem. Time and innovation are both not on your side, in this case. Complex systems are complex and extend far beyond the focal depth of our squinting.

Wöhler proved in 1828 that there was nothing special with organic molecules by synthesising urea.

I guess you could view molecular formation as a complex system involving atoms and atoms as a complex system involving quarks. That would define chemistry and particle physics as the study of said complex systems which makes sense to me. Still at that level that’s not generally viewed as the study of organisms. What we view as biology, the study of the mechanisms of life, really starts at the molecular level. If you go lower, things stop being specific enough.

I genuinely don't understand what your analogy is supposed to convey, could you elaborate?

It's a reference to an old HN comment back when the creation of Dropbox was announced here. Someone commented something along the lines of "you could just" do that whole thing with the FTP server etc. It's lived on as an example of "peak HN" attitude.

So any form of disagreement with someone can be reframed as being dismissive and missing the point, and therefore "peak HN".

That's quite the non-starter for any discussion about whether an idea holds up under scrutiny.

Individual atoms and molecules are identical in a vacuum. Are they in context? They at least have quantum degrees of freedom, which is quite a lot. But whether that has functional value is tbd

A statement like "complex machines all the way down" implies precisely that molecules would be different without context because of some lower-level machinery that forms a more fundamental building block of life. This is what I am skeptical of.

There is an emerging subfield "quantum biology" that studies biological systems under quantum mechanical influence [0]. Photoreceptor systems seem to be a prominent example.

[0] https://quantum.ch.ntu.edu.tw/ycclab/wp-content/uploads/2015...

I guess my issue was more with the implication that we'll find more fundamental building blocks of life.

Are you more comfortable with the implication that we won't?

Comfortable or uncomfortable doesn't even enter the discussion. You can't go down much further without entering the domain of high-energy physics. Which is not the domain of life.

How so?

It's hard for structure to form in burning hot plasmas. But hell, we only know about ourselves. That's the flaw in all the dogmatic thinking about what life is. Life is after all, just structured computation, and computation is just action, and action..just the passage of observer time:

https://www.youtube.com/watch?v=Q_CQDSlmboA

Before we go into the discussion of whether life may or may not be able to exist in hot plasmas (which is fine, in a speculative hypothetical physics kind of way), the point is that we are talking about the building blocks of our form of life. Which is not the kind that exists in hot plasmas.

I'm reminded of an early machine learning experiment where a system self-trained to perform a certain task on a piece of dedicated hardware did so unexpectedly. The researchers "knew" the solution but wanted to learn how their project solved it.

At some point, the sensing for analog effects became the most efficient way to achieve the result by exploiting flaws or unique properties in the individual components, sort of like that inductance backdoor where a particular set of instructions in a certain circuit leaks into another until it's energized enough to trigger it like a relay. Anyway, the result was unintuitive but worked.

Anyway, there's no doubt that after millions and millions of years, there are natural principles at the quantum and atomic levels that biologics are taking advantage of that we're basically only at the "allegory of the cave" level of understanding.

The micro is very much relative.

I don't completely understand what you are saying; the information encoded at the nucleic level does not have any analogy at the sub-molecular level (IE there is no biological information stored using subatomic particles or quantum tricks), nor do there seem to be any functional contributes to non-information molecular mechanisms.

I interpreted the parent comment as: Artifacts of the virtual machine that physics / biology / chemistry "executes" on (i.e. the universe and potentially minute physical properties we aren't aware of) may be reflected at the macro-scale in the "output" (life).

That doesn't make any sense from a scientific perspection, and reality is not a virtual machine that physics executes on.

What would be the difference?

> reality is not a

A. You don't know this, because it's (quite possibly) unprovable

B. Charitably, it was meant as a metaphor

I assume they were referring to emergence.

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

Yes, if the word 'complexity' falls then emergence is inevitable to be mentioned alongside.

> there is no biological information stored using subatomic particles or quantum tricks

This is correct, but only because "biological information" is utter gibberish without meaningful interpretation, from you not the comment that you criticize.

The more general statement was that people's horizon seems to be severely limited (except that the comment phrased it in an acceptably ironic mood). You practically proved them right

There are some known subparts of the nucleus, in particular the Nucleolus [1], and that link discuss a few additional subparts.

I'm not an expert in biology, so I don't know if this is a new part, or it's a part that we already know but in mammals is made by small areas of the big chromosomes and in this animals this areas are on their own.

[1] https://en.wikipedia.org/wiki/Nucleolus

Edit: nucleolus -> nucleus

> There are some known subparts of the nucleolus, in particular the Nucleolus

I think you meant "known subparts of the nucleus", right?

Thanks. I fixed it now, because my typo made the sentence very confusing.

Reminds me of…

The Vermin only teaze and pinch

Their Foes superior by an Inch.

So, Nat'ralists observe, a Flea

Hath smaller Fleas that on him prey,

And these have smaller yet to bite 'em,

And so proceed ad infinitum:

Thus ev'ry Poet, in his Kind

Is bit by him that comes behind.

-Swift

> -Swift

Taylor or Jonathan?

> Flea

> prey

> bite'em

> ad infinitum

What is this telling us about former pronounciation rules?

> , in his Kind

this feels like it's only there to force the rhyme

> As it implies the close spacing is for some kind of mechanical/electrical mechanism within the core of every cell’s nucelus.

It is interesting, but not for the reasons you may be imagining. And not a mysterious electrical mechanism.

It's well-known in the field that (e.g., in humans), chromosomes fold in on themselves in structured ways [1,2]. The functional consequence is not precisely mechanical or electrical -- rather, these folds bring regulatory domains close in 3D space to the sequences which they regulate (which may be far in 1-D sequence distance). These can be elements like "enhancers", which increase the level of transcription (DNA->RNA copying, the first step of gene expression); "insulators", which break up coherent blocks of gene regulation, etc. One of the mediating mechanisms is that regulatory proteins bind to these particular sequences; bringing them together in 3D space allows the assembly of a protein complex that actually carries out the relevant process (eg, transcription).

So, what's interesting here? There is extensive evidence of these contacts within mammalian chromosomes, but limited evidence _between_ different chromosomes. Insofar as the paper shows that mammalian macrochromosomes have homology to multiple reptile/avian microchromosomes (really, to their most recent common ancestor), it may be (speculation alert) that intra-chromosome contacts recapitulate contacts and organization seen in the ancestral microchromosomes.

(There are also "simple" interactions like wrapping of DNA on protein complexes called nucleosomes, like string on beads, but that's less interesting in this context.)

[1] https://en.wikipedia.org/wiki/Nuclear_organization#DNA_loopi... [2] https://en.wikipedia.org/wiki/Nuclear_organization#Chromosom...

Maybe we should use the word "use unknown" instead of "useless" when dealing with things we don't fully understand.

History has humbled us countless times. I recall a recent Veritasium video wherein famous mathematicians of centuries past labelled the concept of negative numbers "useless" (because they didn't understand how they could be useful). My high school bio teacher confidently claimed that the appendix was a "useless organ".

The video in question, for those curious: https://www.youtube.com/watch?v=cUzklzVXJwo

I agree, but note that the title of the research article is "Microchromosomes are building blocks of bird, reptile, and mammal chromosomes".

It is difficult to imagine a system of evolution where "useless" survives in successful iterations.

Your point of view in evolution is called Adaptionism, but there are those who believe otherwise, and use the term "spandrel" to talk about the "useless" things that evolution carries along.

https://en.m.wikipedia.org/wiki/Spandrel_(biology)

Of course, something that is currently useless may become useful as the environment changes. Or it may not. Personally, I find a healthy sense of detachment from purpose, and certainly from any sort of teleology, is necessary to become philosophically consistent with the evidence from evolutionary biology.

Thanks for the rabbit hole ( I've never really studied evolution outside of CS applications ).

Your point of view about detachment makes quite a bit of sense to me, and if the spandrel idea proves true I guess we (Homo sapiens) will just have to take it on the chin...

This is quite interesting! Thanks for sharing! So might it be that a species, as a whole, benefits from carrying around a certain amount of “spandrels”? A genetic insurance policy of sorts to protect against/quickly adapt to unforeseen changes? Has there been any research into the prevalence (or absence) of spandrels in species that have gone extinct?

I'm not sure if there's much research in evolution about species that have gone extinct versus extant species, or at least I haven't encountered it.

The human genome carries around a massive amount of spandrels, in the form of what is called "selfish DNA." About 15% of the human genome consists of repeats of a single sequence: the Alu gene, which seems to primarily exist to replicate itself in the genome. This is part of a class of genes called transposable elements:

https://en.m.wikipedia.org/wiki/Transposable_element

And when discovered in corn, accounted for 85% of the genome. Barbara McClintock, their discoverer, hypothesized that they serve as a growth bed for evolution. And over the years it has indeed been found that individual transposable elements can serve as the seeds for new control sequences that coordinate when to turn genes on and off. The major forces of evolution in vertebrates are not big changes in proteins, but rather changes in when and how various proteins get activated, and transposable elements serve a big function in allowing that sort of evolutionary change in genomic sequences.

Does most repetitive DNA in the genome seem to be useless, in that its deletion or replacement have little effect on the genome? Probably! But all that fluff also facilitates more easy rearrangement of the genome, because if every part of the genome was essential, randomly moving a chunk of DNA into a new spot would likely kill off some useful stuff. But if there's a bunch of stuff that is useless, randomly copying some stuff into a random spot is less likely to disrupt something. If the genome is a hard drive, there's no "free list" or file system for the genome, so random writes are less likely to be disastrous if there's nothing of importance on most of the drive.

I used to get upset at the term "junk DNA" but I don't really care one way or the other now. One cell's junk is another's treasure.

I very much appreciate you taking the time elaborate! It’s quite interesting and now I have a new rabbit hole to explore :)

I find it difficult to imagine a system of evolution where useless code is reliably removed.

Presumably there is a cost to carrying the DNA, if it gets removed by chance and the cost was high enough the useless part will disappear.

That however hinges on the cost being high enough, if the cost is negligible then there is no real pressure either way.

this cost of "DNA size" is a long and ongoing argument in biology with no clear answer. Here's the strongest straw man argument in favor of "there are large amounts of non-funcitonal DNA which has zero evolutionary cost": https://www.cell.com/current-biology/pdf/S0960-9822(12)01154...

Certainly there are thing that formerly had a use but are less useful now. I'd be careful calling something useless, but if there isn't an advantage to getting rid of a feature, I see no reason it would be gotten rid of.

It depends on the cost of carrying vestigial stuff around vs the time required to make such changes (thousands of years? millions of years?)

Sometimes organisms carry things not very useful anymore for a looong time.

Evolution is not that ruthless. Useless but neutral traits can just stick around, if there's no selection pressure to get rid of them.

It looks like the only person who described them as useless is the editor who wrote the headline, and they did it in an incredibly disingenuous (and grammatically incorrect way) by putting quotes around it. That implies that someone in the study used the word useless, which doesn't actually appear to be the case.

> My high school bio teacher confidently claimed that the appendix was a "useless organ".

So does the Encyclopedia Brittanica, Healthline, and any number of other sources:

> appendix, formally vermiform appendix, in anatomy, a vestigial hollow tube

If the appendix truly serves no function and isn't developmentally required, then selection pressures would tend to remove it.

It likely has some complex purpose, such as a reservoir for microbiome.

This is a common misunderstanding.

The same logic would apply to male nipples. It's a flawed logic.

Nipples are used by female mammals for feeding their young, so this logic does not apply to nipples.

It certainly does apply: why do men have nipples? Likely for reasons similar to why we have an appendix.

Fundamentally, natural selection and evolution are models that help explain general biological processes, to help us comprehend a bigger picture. Around the edges of that picture, it's not fully clear.

The truth is that the universe is governed by laws that are deeply unintuitive: general relativity and the standard model. Each layer of abstraction on these makes the periphery of the image fuzzier, but allows us to make more sense of the part of the image that we're focusing in on.

Genes to turn off development of the nipples would cost more. The same body plan is used until sex hormones cause sex characteristics to develop.

Many females also find male nipples attractive.

That's only if the gene's to express an appendix ever go away.

I always think back to Richard Dawkins explaining how a particular vein in a Giraffe's neck is wrapped around a lower neck bone and has grown 2x to accommodate the long neck instead of regrowing in a more efficient way (not wrapping).

I believe you're talking about the laryngeal nerve!

And I don't think it's just giraffes, it's all mammals, which also points to a common ancestor.

The recurrent laryngeal nerve is actually common to all tetrapods, not just mammals. Birds have it, probably dinosaurs had it.

https://bioone.org/journals/acta-palaeontologica-polonica/vo...

Nature’s billion dollar mistake?

> selection pressures would tend to remove it.

A person born without an appendix has no actual advantage over a person who has one, so selection doesn't really influence it.

The human body is full of things that truly serve no function, and it's also full of detrimental things, such as genetic diseases.

As long as it does not impact reproduction, selection has no impact.

> A person born without an appendix has no actual advantage over a person who has one

Untreated appendicitis is quite deadly. I would say there is definitely some advantage.

That's true, but untreated cardiomyopathy is potentially deadly too, yet that isn't enough pressure to cause us to not have hearts...

Good idea but bad example. Something needs to fulfill a heart's role, but we can live without an appendix just fine.

Oh sure, it was reductio ad absurdum, just pointing out that the possibility of appendicitis wasn't by itself an argument against its continued existence - I don't know anyone personally who has ever been diagnosed with it...

> just pointing out that the possibility of appendicitis wasn't by itself an argument against its continued existence

Except that yes it is an argument against it.

Your reduction breaks down because it conflates "a reason" with "all reasons".

Unless it is widespread deadly before breeding age, it doesn't make much difference.

See: dementia, cancer.

Natural selection only pushes towards the removal of things that harm reproduction, not things that harm survival at all ages. If appendicitis mostly happens after the average age of reproduction, then there's not really a big evolutionary pressure to remove the appendix. Sure the person will die of appendicitis, but if at that point they've already had all the kids they're likely to have during their life, then the appendicitis doesn't have an effect on the process of natural selection.

You yourself gave the answer. “Tend to” means it is likely, not that it will always happen.

This is a widely held misconception. Mammalian genomes contain about 50% of their DNA as repeated sequences, and although there are people who can imagine uses for those sequences, there is no evidence that they are required or even evolutionarily advantageous.

The idea that modern higher organisms have been "optimized" so that every part is essential is not well supported by evidence, and there are many examples of features that simply are historical artifacts or "not-sufficiently harmful". Many evolutionary biologists are comfortable with neutral theories consistent with the idea that large portions of the genome are not under strong (or perhaps even moderate) selection.

biological version of dead code with no time allocated in the roadmap for cleanup and refactoring?

Only vaguely. If the DNA was to be compared with our programming languages, it would be like INTERCAL, but a million times worse.

Sections of the genome interact not only with the code right around them, but also with code far away, as a result of the chromosomal folding. So a section of 100 nucleotides might not do anything if you splice it out and throw various enzymes and other chemicals at it, and it might not even matter that much which nucleotides they are, but if you remove them and change the shape of the chromosome, it might not work the same way.

A lot of our knowledge of genetic is limited to the things that are easy to test.

Except our machines are designed around the idea of isolating components and minimizing unintended side effects, while biology has no such compulsion.

Imagine if an extra semicolon in one of your unused files shifted electrical distribution on storage media and that had all kinds of downstream effects on unrelated systems and those effects were critical for multiple other functions.

Only increase complexity enough so the whole contraption is NOT brittle.

You’re talking about messiness in the genotype, but selection pressure happens to the phenotype. The latter I think controls more of what ends up in the former.

Which is what we see all the time in programming: software wins because of its effect, not usually the lines of code needed (or not) to get there.

I'm not sure I understand your argument, but if large portions of the genome have no effect on phenotype, then perhaps we can both agree that those regions would not be under selection. Pressure on the phenotype cannot directly alter the genotype (no Lamarkism), but it could select for or against the fraction of the population with a particular genotype. But only if the genotype produces a phenotype.

Wouldn't assuming a one-copy rule end state is natural cause immense issues with recessive genetic disorders (which could in turn select against it), and also make chromosomal-crossover produce sterilized but viable young at a much higher rate?

> This is a widely held misconception. Mammalian genomes contain about 50% of their DNA as repeated sequences, and although there are people who can imagine uses for those sequences, there is no evidence that they are required or even evolutionarily advantageous.

If you remove noncoding "junk DNA", you alter the higher level spatial configuration of DNA. Histone winding changes which promoter regions are accessible, gene dosing is altered, binding affinity and kinetics change, etc. These are dynamical equations you're dramatically altering.

Non-coding DNA also likely shields against several classes of random point mutations, base substitutions, transposition, etc. preventing cancer and cell physiological disease states.

It's also important for maintaining alignment during crossover.

If it truly served no purpose, it would be gone.

> The idea that modern higher organisms have been "optimized" so that every part is essential

Essential is the wrong word here. Relying on every part for survival would put us at risk. We have plenty of built in redundancies to support degradation, failure, and loss of multiple systems and functions.

I get your argument, but I still disagree. At the species / population level, we have been optimized as wholesale organisms as best as development and body plans will allow. Everything not subject to pressure will get washed away.

Despite our vestigial tails, the coccyx supports our weight while we are seated. As I postulated before, the appendix probably has a net positive function in supporting gut microflora and our "junk DNA" plays a role at the molecular level.

> If it truly served no purpose, it would be gone.

Why? Removing it serves no purpose either.

The statement that at some level species have been optimized is a religious belief, not a scientific one. Species are at the end of an evolutionary history that ended in the present. There is no reason to believe that that endpoint is optimal in any sense. It is certainly not globally optimal, and absent very strong selection, it may not even be locally optimal. Evolution explores an infinitesimal fraction of the possible states/pathways available. Without more thorough exploration and strong selection, there is no reason to believe things are optimal.

I think I’m not going out on a limb to say that no modern evolutionary biologist believes organisms are optimal. They simply survived.

Others have said this using different words, but evolution relies on the preservation of low-cost mutations. It took many mutations to get from photoreceptors to the mammalian eyeball.

If the cost is small enough that other factors dominate your ability to procreate, it will spread to all of your descendants. If other genes in your genome make you reproductively successful, that gene edit will spread and spread.

It’s a good thing these cheap changes are preserved, or viruses and bacteria would have wiped out all multicellular life early on by practicing patience. We all have genes that make us less susceptible to some pathogens than others and if a bad enough variant comes around, suddenly we are over represented in the next generation. If the hits keep coming eventually our family reunion may be the only one being held.

Can’t an inherited trait be “neutral”? By that I mean it confers neither a benefit nor a detriment? It’s my understanding that the baby toe, for example, isn’t particularly useful anymore. But having or not having the baby toe(s) isn’t likely to help or hinder a person’s ability to reach adulthood and reproduce. There must be a lot of traits like that, right? Like eye color or maybe wisdom teeth. No one (as far as I know) is selecting a sex partner based on whether their wisdom teeth were impacted or not.

That's not how selection works. If something doesn't decrease survivability, then there is no reason why evolution would get rid of it.

This is a profound misunderstanding of the driving forces of evolution.

Why do we have wisdom teeth? Just because something is useless doesn’t mean it’s eliminated

The appendix is used to reboot the intestinal biome in case of a catastrophic event.

It's pretty much an on-site backup for intestinal flora :)

They are wrong.

> The appendix has been identified as an important component of mammalian mucosal immune function, particularly B cell-mediated immune responses and extrathymically derived T cells.

https://en.wikipedia.org/wiki/Appendix_(anatomy)#Functions

Do we have data on COVID in people without appendix?

The first sentence of the article:

"Originally, they were thought to be just specks of dust on a microscope slide."

not to mention the perception of some organisms in ecosystems as "useless" only to discover their absence causes the system to collapse

To their limited knowledge, it was indeed useless. Scientist can make such statements if they feel up to, but they must also have the humility to later eat their own words when they are proven wrong.

> The exception is the platypus, which has several chromosome sections line up with microchromosomes...

Even at this level, the platypus is a strange creature.

One really has to wonder if we're all missing something with the platypus. Did some extremely unlikely gene transfer happen at a scale, and across taxonomic distances, that nobody has ever thought possible? There is some N where repeating the argument "it's just a quirk that they're so different" N different times starts to not feel like the simplest explanation any more. Are we absolutely certain there's no way a frisky duck-oid forced itself on an unlucky shrew-oid and in a one-in-a-billion stars-aligning miracle, managed to produce a viable offspring? (Edit: I guess they'd have to produce at least two ...)

Nah, this should be easily verifiable by simply comparing the DNA of a platypus to that of a bird. I haven't done that, but I bet I know how it would turn out.

> Are we absolutely certain there's no way a frisky duck-oid forced itself on an unlucky shrew-oid and in a one-in-a-billion stars-aligning miracle, managed to produce a viable offspring?

Yes.

Sometimes different (but related) species can reproduce... sometimes the offspring aren't sterile. Your comment makes me wonder what two most-different species have done this.

The playpus is basically an early fork of the tree before placentas and marsupials, and the entire commit tree is squashed under Antarctica, which use to be a life filled continent connecting Australia to South America.

https://youtu.be/rQRDc2SKw2I

So they’re saying we have chromosomes floating around in our cells? Outside the nucleaus? How do they get replicated?

The original scientific article says that mammals don't have the microchromosomes. And they are located inside the nucleus in other species.

They’re saying birds and reptiles and other animals have micro chromosomes, and that mammals have incorporated these micro chromosomes into their macro-chromosomes.

Per the Wikipedia page, Micro chromosomes are replicated the same way as other chromosomes - mitosis.

It's interesting how much variation there is even within mammals when it comes to number of chromosomes, even though so much of the genome is conserved. This points to chromosomes being a major factor on the grander scales of evolution.

> This points to chromosomes being a major factor on the grander scales of evolution.

Or, alternatively, that chromosomal-level organization is happenstance.

I agree though with your implication that it’s an interesting area of study. Perhaps there is an interesting mechanism to be learned or disproven.

Check out bio electrical regeneration research

If you haven’t come across it, the teams inject drugs that do nothing to cells but instigate an electrical field effect. What happens is regrowth of a limb to the correct “spec” even though that physical information is gone (limb amputated).

This suggests to me an equalizing effect exists, where fields and matter feed each other just enough to reach structural equilibrium.

Relativistic information network effects, proving what math objects create which field effects, and the social impacts, are going to become huge and blow away our current engineering goals of making hard silicon computers.

We might be able to use nature itself as our CPU.

A fascinating article. David Quammen's book "The Tangled Tree: A Radical History of Life" also has stories how DNA changes through more mechanisms than just mutation.

This seems to be another nail in the coffin of "DNA is Code" idea.

We do not know how life organises itself. DNA is involved. We have some knowledge.

But what we do not know matters much more than what we do know.

Blowing out of proportions a bit are we? This is still dna, just in another form elsewhere. And it doesn’t uproot anything, most of the important genes are still in the main chromosomes, we just don’t have the full picture and studies like this help us inch closer towards it.

I understand some of these words. Can someone explain this in layman’s terms?

Not a scientist so I may be wrong in places, but here goes:

A chromosome is DNA folded up. What was previously thought to be specks of dust on a microscope slide turns out to be very small chromosomes. Their function is unclear. Between many birds and reptiles these microchromosomes seem to line up with the normal chromosomes fairly well. The difference is relatively speaking fairly small. In mammals however these microchromosomes are much more jumbled. These microchromosomes cluster together in the center of a cells nucleus. This means they physically interact. They touch.

Now what this all means is as of yet not entirely clear. They most likely have some important function since they got preserved very well along evolution. Mammals however did something weird to these microchromosomes for unknown reasons.

Ha, I though this was an article on useless crypto - https://uselesscrypto.com since my skim reading of the title came up with Useless + building blocks.

Little did I know.......

Someone should train an AI to find all the assumptions ("useless specks of dust") made in science. Then they should all be checked. Would likely result in a great leap in scientific discovery.

The spice melange

It's a legacy codebase. The default assumption should be "DO NOT DELETE THIS".

Jokes aside, I wonder if we actually know enough to safely meddle with genetic materials, e.g. with mRNAs vaccines.

mRNA vaccines are barely meddling with genetic materials. We know that lots of viruses are barely harmful; mRNA vaccines are basically just:

• take out most of the steps

• change the payload

• substitute one of the ingredients to trick the immune system.

If you said CRISPR, I'd agree – but we do know enough for mRNA vaccines.

To use a CS analogy, mRNA vaccines aren't Turing-complete, but CRISPR is. We understand both fairly well, but the implications of mRNA are much simpler than the vast, vast, vast implications of CRISPR.

I'm curious why you question CRISPR. I've worked with CRISPR; I've seen some very unexpected results from its use; I've also not really kept up with the science in the past few years.

Do you have experience working with CRISPR? Is there a study or set of studies that concerns you, or is it the reality that negative results don't get really get published?

There's nothing in the comment that "questions" CRISPR, it's just pointing out that due to the larger space of possibilities more care needs to be taken with it.

I interpreted the comments about CRISPR in the parent comment to be more or less cautionary, and I used "question" as a way to say "not sure about the benefits". Sorry if I was unclear, I will work harder on my communication.

CRISPR is basically find-and-replace with DNA. DNA expression is weird and complicated, and some bits do different things depending on the environmental context. There's a lot of potential for things to go wrong.

mRNA vaccines are injecting simple, engineered mRNA. This mRNA is expressed 100% of the time; what it does is very simple. I'd be confident using a new mRNA vaccine on day 1, so long as they're certain they picked the right protein, but I wouldn't be confident using a CRISPR treatment without a full medical trial.

I know what CRISPR is.

Like I said, I worked with it in grad-school. I agree with you in general, though I will say that if I was in a position to get CRISPR as a treatment, I would probably have a lot of questions for my doctor, but I wouldn't dismiss it outright.

I guess my point is that our understanding of how mRNA vaccines operate (or any other methods for manipulating genetic materials, for that matter) might prove incomplete, just like how we underestimated the importance of microchromosomes, as stated in the article.

The current generation of mRNA vaccines may be simple enough for the scientists to analyse, but I feel it will only be a matter of time before the complexity of such technologies grow to the point that it resembles art more than science. (I am looking at you, deep neural networks!)

mRNA's mechanism of action is trivially simple. There's a known gene that codes for a known protein, and they create a snippet of mRNA to codify it. It doesn't change your DNA, it's not a virus, it's not able to replicate in any way. There aren't any unknowns waiting to be discovered. The mechanism is fully-understood and easy and safe.

The complications with mRNA vaccines like this have to do with keeping the mRNA intact during delivery and getting it into the cell so the protein gets built. That's the hard part, and the focus of all the patented engineering that differentiates BioNTech and Moderna vaccines. And the delivery mechanism, while complicated, doesn't involve anything genetic; it's a mechanical problem.

> There aren't any unknowns waiting to be discovered. The mechanism is fully-understood and easy and safe.

I am sure many people felt that we had figured it all out w.r.t. planet motions etc. with Newton's law of physics :)

You are mistaken if you think I am anti-vaccine or something. I merely tried to point out that there are always unknown unknowns and that we should remain cautious when it is people's health that are at risk.

CRISPR is not "turing complete", I'm not sure where you got this impression. You could build a pseudo-turing machine (finite memory, measurable but small error rate) with enzymes and DNA, but CRISPR is not sufficient to implement turing complete computation.

He did not try to say it was turing complete. He was making an analogy: CRISPR:mRNA::Turing Complete:Non-Turing Complete. Not sure how deep that analogy is, since non-turing complete systems can still be very powerful. But I think it gits the idea across OK.

OK, it was written very misleadingly. Further, the comparison doesn't even make sense. RNA molecules can fold into ribozymes and carry out activity. In principle, you could make a turing machine with RNA molecules, although the error correciton would be fantastically hard.

Computer scientists, please stop making CS/biology analogies.

But that's not how analogies work.

When someone says "A is to B as X is to Y", you're not supposed to start comparing B to X. Your post is comparing B to X.

Let me try to come up with another example... Let's say I make an analogy like "a house relates to a wall the same way a forest relates to a tree". (It's not a very good analogy, but that doesn't matter here.) If you look at that analogy and then start talking about how you can use a tree to build a wall, you are doing analogies wrong. The items on the left of the analogy are not supposed to be compared to the items on the right of the analogy. You're only supposed to compare the relation on the left to the relation on the right. Your discussion of RNA-based Turing machines is doing analogies wrong in the same manner. Turing machines are on one side of the analogy and RNA is on the opposite side.

That's also not what they wrote, they used it as an analogy - in the sense that mRNA can express one very specific thing, and CRISPR can express a much wider variety of things. It's not about literal turing-completeness.

mRNA vaccines don't meddle with your DNA. They inject mRNA in to cells that _temporarily_ instruct the cell to produce a specific protein. Once the mRNA is exhausted, the cell stops producing that protein.

So in that case the mRNA is more like printer ink than like a blueprint? Or both at the same time? Is it possible for a cell to still produce the protein when it runs out of mRNA?

I'm not an expert in this but... If DNA is like a blueprint, mRNA is like an email sent from the architect to the contractor to instruct them to carry out specific work.

It's a print _job_. The cell is printing more bits of cell all the time, we just slip in some extra messages that print foreign proteins. The immune system identifies the proteins as foreign and produces antibodies to destroy them, which primes it to destroy matching COVID viruses.

As an ex-biologist, this is the best analogy.

mRNA is "messaging" RNA. It sends the message to the protein factory to make more of a protein structure defined by the DNA, just like a print job sends the message to the printer.

If DNA is a blueprint, mRNA is a photocopy that's used as a working memory of it for a ribosome to use while making a protein. It's chemically unstable and soon falls apart. (The individual nucleotides night be recycled into other mRNA strands that the cells make.) Since the vaccine mRNA does not have any corresponding DNA to make more copies from, that's the end of it.

> It's chemically unstable and soon falls apart.

Thanks, that was the part that the others answers didn't cover.

The "ink" would be amino acids that are always floating around in the cell, the "printer" would be a ribosome.

The mRNA would be something like the print buffer that stores the currently printing document. DNA would be the document file stored on disk.

Watch out, your computer is using electricity that could potentially kill you.

mRNA vaccines don't modify your dNA. They provide a volatile blueprint of the corona-specific spike protein, so that spike proteins can be synthesized for a short time, analyzed and then discarded by the body.

One problem with mRNA is that 75% of its name is what it's built out of, and only 25% what it does. It'd be like if we called HTTP packets "hBits", flash memory words "mBits", text files "tBits", and OS kernel instructions "kBits". I can see how someone would be worried that putting tBits on their computer could potentially modify their kBits! What if all those bits got all jangled up!?

If we called mRNA a "protein print job" like pjc50 came up with, and we called our chromosomal DNA our "kernel instructions", etc., I think it'd be more obvious how silly it is to worry that mRNA is going to somehow alter your chromosomal DNA. The point is that there are a lot of different functional things and data structures made out of bits, and a lot of different functional things and data structures made out of adenosine, guanine, cytosine, and thymine/uracil.

To be fair (not trying to imply mRNA vaccines modify your DNA), there are a lot of systems, especially past but also present (with vulnerabilities), where the right (wrong) print job could end up permanently modifying your system's kernel instructions.

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