Aside from the anthropocentric view that cells are relatively small because we are made of many of them, the increases in size of lifeforms past that of individual cells is a matter of exceeding thermodynamic and informational limits. I highly recommend the book _The Vital Question_ as an intro to the systemic view of this kind of biological complexification
I've recently gotten into microscopy as a hobby and comparing the relative size of microbes is really interesting. There are entire animals (tardigrades for one) which can be smaller than some single celled organisms.
There are even single celled organisms which will prey upon and eat multicellular animals.
"The allocation of all metabolic resources to maintenance purposes limits the size of the smallest prokaryotes and largest unicellular eukaryotes, whereas an inability to meet the ever-increasing biosynthesis rates limits the largest prokaryotes and smallest unicellular eukaryotes. Metabolic constraints for larger eukaryotes are relieved by alternative reproductive strategies and multicellularity."
That framing makes the article feel even more interesting, because it's not just "cells are small because diffusion gets slow". There's also an energy budget behind it
Nice article! There is another interesting perspective:
Anything selfreplicating kinda needs to be as small as possible (compared to the smallest internal mechanisms required), otherwise the replication time grows out of control:
Consider a 3D printer that can fully selfreplicate by depositing individual molecules: If this was the size of a regular printer, the replication time would be hopelessly long (>billion years even if it could deposit billions of atoms/s).
This applies somewhat universally, and is one of the reason why our current industrial tech is so unsuitable for selfreplication: Any "printing" like process (books, metal stamping, lithography) requires internal features that are much smaller than the output it produces.
On Being the Right Size turned 100 this year. It's not entirely the same topic as this essay, but this reminded me of it and it's a pretty famous short essay that's worth reading if you haven't seen it.
FWIW I wrote a paper on nutrient-limited growth rates of cells and how that depends on their shape. one of the interesting findings was that elongated cells can grow exponentially quickly (as observed) while spheres quickly max out.
All life started from procaryotic cells. The step from macromolecules to the first cell cannot be big, otherwise it could not happen spontaneously. On the other side, it must be big enough so that the cell have enough flexibility and functionality to support complex life.
That is, the cell is small enough in order to be produced directly by molecules but large enough in order to be a full living organism (reproduction, metabolism etc). This sweet spot seems to be the cell size we observe.
Later in evolution the size disparity grew because a procaryotic cell swallowed another one to become an eucaryotic and the eucaryotic ones specialized even further.
> Cell sizes are not fixed, however, even within a single species. Cells often swell as they increase their production of proteins and metabolites in preparation for division. This is in line with biology’s only rule: namely, there are exceptions to every rule!
> Case in point: a giant bacterium called Thiomargarita magnifica can extend about one centimeter in length, so large that it can be seen by the naked eye. It does so by breaking the surface area-to-volume rule, filling between 65–80 percent of its internal volume with an empty vacuole. In other words, it pushes most of its molecules to the cell periphery, thus shortening diffusion distances.
There is also a captioned image of bubble algae in the post.
Collected and stored sediment samples were found to have surviving T. namibiensis cells after over two years. The cells had no access to any added sulfide or nitrate during this time. In the surviving cells, there was a notable size decrease. To survive without growing the cells depended on the nutrient stores of the central vacuoles.
Indeed. It says they rely on two different substances which normally don't mix (nitrates and sulfites), presumably because if they were both present at the same time they'd react with each other directly without the bacterium extracting any energy from that. So they live in places that sometimes have one and sometimes the other, and have to store one of them until the other comes along, which can be years. Or that's how I read it.
Agreed. Humans draw rather arbitrary distinctions. It was quite funny in regards to viruses, aka parasite. Mimivirus are still a parasite, of course, but they even encode genes for metabolic pathways and are larger than some bacteria.
See:
"The Mimivirus is a giant virus that infects amoebae and was long considered to be a bacterium due to its size."
Although for me, I always used the definitions through the genetic information available (genome). So as long as a virus still is a parasite, I'd hold up that definition. It will be interesting when viruses are found that are even closer to a cell, e. g. some life cycle where they could switch between parasitism and stand-alone metabolism (or some hybrid in between; I mean if they can encode whole metabolic pathways, at the least some or some parts of it, the threshold here should not be impossible to overcome, and then the whole definition of a virus also has to be adapted since it would no longer make sense).
Granted, they are grouped both in Thiomargarita. 2cm is pretty gigantic. What I always found more interesting was that they don't merely have just one genome.
These both feature large central vacuoles, lending support the thesis of the article that the cubic growth in volume outstrips the quadratic increase in surface area for transferring nutrients and waste across the cell membrane.
Those still seem kind of small? Why not the size of an mature olive tree for example? I'm guessing the article may answer this, haven't gotten that far yet.
there is likely evolutionary pressure against large cell size (selfish genes; larger cell takes energy away from replication, provides more opportunity for infiltration by other genes, fewer gene backups in other cells, etc) while occupying a niche puts pressure to be a certain size. it lands somewhere in the middle.
I feel like keeping the amount of molecules the same within the simulation needs to be justified.
How would it look like if the average amount of molecule was the same across a um?
I never bought into the egg thing. There’s clearly a distinct cell in the center that’s going to divide and grow inside the egg. The egg itself isn’t undergoing mitosis.
I had to go look this up, as I had heard the egg thing my whole life and just accepted it.
It turns out the oocyte is the single cell inside the egg, which for birds is significantly larger than a typical cell. So in that respect, the cell in a bird egg is very large. However, compared to the egg itself, it's tiny. The yolk and whites in the egg are all to provide nutrients as it grows, if fertilized.
One of the fascinating things about biology I think is this - that if the cells of your body were the size of an egg, they'd be way, way too big and you'd probably die.
I also find it interesting that if your spleen were to go prompt critical, it would irradiate you and you'd probably die. That is my favorite fact about nuclear physics.
I don't know for sure here, but isn't the ostrich IN the egg a multicellular animal? I would assume the first point where the egg contains anything that will become the ostrich, mitosis is happening to make more ostrich cells. I'm assuming there's always cell walls and nucleuses every step of the way here, and the egg and ostrich are never just one big cell.
I could be off base here though, I'm really channeling grade 9 bio class from decades ago!
The trick is that the egg is a ball with one small cell (the ovum) that happens to have also a huge reservoir of food for the future ostrich. There is a moment when there is only once cell in the egg, just after the fussion of the ovum and the sperm cell.
Surrounded by a bunch of stuff that isn’t the ovum. “There is at most one cell in an unfertilized bird egg” is not the same as “an unfertilized bird egg is one cell and nothing more”.
Nitpick maybe, but I don't think oocytes are the largest cells, it pretty much has to be some sort of neuron. A sensory neuron for eg. someplace in the foot will be almost as long as the person is tall, and even if the neuron is extremely thin, it's gotta beat the oocyte for volume.
Some back of the envelope math says this is true. A conservative estimate for the size of an alpha motor neuron axon is 10μm diameter and 1m long, which already puts it over an order of magnitude larger than the 4,000,000µm³ oocyte quoted in the article.
In addition to what mbauman said, hair follicles and the hair itself are not single-cell. I can't immediately find the composition and average cell size, but even a long and thick strand of hair is less than 2 orders of magnitude larger than the largest neurons. I doubt any individual hair cell is very large.
Giraffes neurons can be up to 15 feet long. Blue whales are speculated to have neurons up to 100 feet long, though they've never been directly observed (dissected).
They've been catastrophically dissected at least once, which we know due to the detailed field notes made by Paul Linnman, and subsequent citations by Dave Barry.
It's possible some of them were observed, given the likelihood of striking someone's glasses or windshield.
edit: Huh. Actually not a bad read. It even mentions ' On Growth and Form' which is interesting, if outdated. There are more modern texts like 'Shapes', 'Flow', and 'Branches' by Philip J Ball.
Such sleeper accounts, slowly acquiring clout and time on the platform are often used by botnets. One day they (or their actions) will be sold to the highest bidder to upvote a comment, support an idea, ideology, politician or party or some virtual product, stock or coin.
Possible and that is definitely a thing, but I personally I would not rule out, that there still can be a human behind it, just with that specific style and careful about his privacy.
Perhaps cells are small in the first place is for efficiency. It's more efficient to perform a set of tasks with trillions of these cells in unison than one big blob.
Aside from the anthropocentric view that cells are relatively small because we are made of many of them, the increases in size of lifeforms past that of individual cells is a matter of exceeding thermodynamic and informational limits. I highly recommend the book _The Vital Question_ as an intro to the systemic view of this kind of biological complexification
I've recently gotten into microscopy as a hobby and comparing the relative size of microbes is really interesting. There are entire animals (tardigrades for one) which can be smaller than some single celled organisms.
There are even single celled organisms which will prey upon and eat multicellular animals.
Tardigrades are really cute.
https://i.imgur.com/9BoxjK8.jpeg
Some call them water bears. I am not quite sure they look like bears (six leg bear?) but the stubbly legs are indeed cute.
> I am not quite sure they look like bears
From the front, they somewhat do. See https://uconnladybug.wordpress.com/wp-content/uploads/2013/0...
This reminds me also of this paper: https://www.pnas.org/doi/pdf/10.1073/pnas.1115585109
"The allocation of all metabolic resources to maintenance purposes limits the size of the smallest prokaryotes and largest unicellular eukaryotes, whereas an inability to meet the ever-increasing biosynthesis rates limits the largest prokaryotes and smallest unicellular eukaryotes. Metabolic constraints for larger eukaryotes are relieved by alternative reproductive strategies and multicellularity."
That framing makes the article feel even more interesting, because it's not just "cells are small because diffusion gets slow". There's also an energy budget behind it
Nice article! There is another interesting perspective:
Anything selfreplicating kinda needs to be as small as possible (compared to the smallest internal mechanisms required), otherwise the replication time grows out of control: Consider a 3D printer that can fully selfreplicate by depositing individual molecules: If this was the size of a regular printer, the replication time would be hopelessly long (>billion years even if it could deposit billions of atoms/s).
This applies somewhat universally, and is one of the reason why our current industrial tech is so unsuitable for selfreplication: Any "printing" like process (books, metal stamping, lithography) requires internal features that are much smaller than the output it produces.
On Being the Right Size turned 100 this year. It's not entirely the same topic as this essay, but this reminded me of it and it's a pretty famous short essay that's worth reading if you haven't seen it.
https://teaching.hkaiser.org/fall2025/csc7103/course/papers/... (PDF 50 KB, 5 pages essay + 3 pages commentary)
FWIW I wrote a paper on nutrient-limited growth rates of cells and how that depends on their shape. one of the interesting findings was that elongated cells can grow exponentially quickly (as observed) while spheres quickly max out.
https://arxiv.org/abs/1312.0674
All life started from procaryotic cells. The step from macromolecules to the first cell cannot be big, otherwise it could not happen spontaneously. On the other side, it must be big enough so that the cell have enough flexibility and functionality to support complex life.
That is, the cell is small enough in order to be produced directly by molecules but large enough in order to be a full living organism (reproduction, metabolism etc). This sweet spot seems to be the cell size we observe.
Later in evolution the size disparity grew because a procaryotic cell swallowed another one to become an eucaryotic and the eucaryotic ones specialized even further.
Reminds me of: "Gravity plays a role in keeping cells small" [0]
[0] https://www.princeton.edu/news/2013/10/24/gravity-plays-role...
Not all are?
Largest eukaryote:
https://en.wikipedia.org/wiki/Valonia_ventricosa
largest prokaryote:
https://en.wikipedia.org/wiki/Thiomargarita_namibiensis
> Cell sizes are not fixed, however, even within a single species. Cells often swell as they increase their production of proteins and metabolites in preparation for division. This is in line with biology’s only rule: namely, there are exceptions to every rule!
> Case in point: a giant bacterium called Thiomargarita magnifica can extend about one centimeter in length, so large that it can be seen by the naked eye. It does so by breaking the surface area-to-volume rule, filling between 65–80 percent of its internal volume with an empty vacuole. In other words, it pushes most of its molecules to the cell periphery, thus shortening diffusion distances.
There is also a captioned image of bubble algae in the post.
> This is in line with biology’s only rule: namely, there are exceptions to every rule!
Nice paradox
Interesting topology. How empty is the vacuole?
empty in terms of normal cell components, apparently it stores relatively huge amounts of nitrates that are a necessary energy source for it
Rather large gas tank:
Collected and stored sediment samples were found to have surviving T. namibiensis cells after over two years. The cells had no access to any added sulfide or nitrate during this time. In the surviving cells, there was a notable size decrease. To survive without growing the cells depended on the nutrient stores of the central vacuoles.
Indeed. It says they rely on two different substances which normally don't mix (nitrates and sulfites), presumably because if they were both present at the same time they'd react with each other directly without the bacterium extracting any energy from that. So they live in places that sometimes have one and sometimes the other, and have to store one of them until the other comes along, which can be years. Or that's how I read it.
It uses container based virtualization under a single host kernel instead of VM based virtualization.
Agreed. Humans draw rather arbitrary distinctions. It was quite funny in regards to viruses, aka parasite. Mimivirus are still a parasite, of course, but they even encode genes for metabolic pathways and are larger than some bacteria.
See:
"The Mimivirus is a giant virus that infects amoebae and was long considered to be a bacterium due to its size."
https://pmc.ncbi.nlm.nih.gov/articles/PMC9133948/
Although for me, I always used the definitions through the genetic information available (genome). So as long as a virus still is a parasite, I'd hold up that definition. It will be interesting when viruses are found that are even closer to a cell, e. g. some life cycle where they could switch between parasitism and stand-alone metabolism (or some hybrid in between; I mean if they can encode whole metabolic pathways, at the least some or some parts of it, the threshold here should not be impossible to overcome, and then the whole definition of a virus also has to be adapted since it would no longer make sense).
Perhaps what you are seeking "retrotransposons," an endogenous retrovirus.
https://en.wikipedia.org/wiki/Retrotransposon#Endogenous_ret...
relatedly, foraminifera are single cellular organisms that can grow up to 20 cm! https://en.wikipedia.org/wiki/Xenophyophorea
Isn't the ovum supposed to be a single cell? Eggs of various species can be substantially larger than this.
Yes. I remember reading that Ostrich eggs are the largest single cells (in terms of mass/volume; Blue Whale nerve cells are longer).
> largest prokaryote:
Actually the wikipedia article states:
"It is the second largest bacterium ever discovered"
> The largest T. magnifica cell Volland found was 2 centimeters tall
https://www.science.org/content/article/largest-bacterium-ev...
Granted, they are grouped both in Thiomargarita. 2cm is pretty gigantic. What I always found more interesting was that they don't merely have just one genome.
https://en.wikipedia.org/wiki/Xenophyophorea
These both feature large central vacuoles, lending support the thesis of the article that the cubic growth in volume outstrips the quadratic increase in surface area for transferring nutrients and waste across the cell membrane.
Those still seem kind of small? Why not the size of an mature olive tree for example? I'm guessing the article may answer this, haven't gotten that far yet.
When they invade your saltwater aquarium, you won't think they're small. They can get up just slightly larger than a marble
There’s also the one that almost ate the Enterprise. https://en.wikipedia.org/wiki/The_Immunity_Syndrome_(Star_Tr...
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Exactly
> A simplistic answer is that evolution has made each cell the size best suited to its function.
Yeah. That's probably it. Really, it probably is the right answer.
That just kicks the can forward one step. What parameters control the optimal size of a given cell?
there is likely evolutionary pressure against large cell size (selfish genes; larger cell takes energy away from replication, provides more opportunity for infiltration by other genes, fewer gene backups in other cells, etc) while occupying a niche puts pressure to be a certain size. it lands somewhere in the middle.
Why are things the way they are? Because it works better. Simple, really. :D
Great concepts, very well written, Kudos to the writer! I bookmarked your main site.
Also : as usual, lots of HN type nitpicking in the comments, most missing the main story.
I feel like keeping the amount of molecules the same within the simulation needs to be justified. How would it look like if the average amount of molecule was the same across a um?
Maybe the better takeaway is not "larger cells can't work" but "larger cells need to pay for increasingly elaborate workarounds"
What does amount of molecule mean?
Cells are small? compared to what? An ostrich egg is a single cell
I never bought into the egg thing. There’s clearly a distinct cell in the center that’s going to divide and grow inside the egg. The egg itself isn’t undergoing mitosis.
I had to go look this up, as I had heard the egg thing my whole life and just accepted it.
It turns out the oocyte is the single cell inside the egg, which for birds is significantly larger than a typical cell. So in that respect, the cell in a bird egg is very large. However, compared to the egg itself, it's tiny. The yolk and whites in the egg are all to provide nutrients as it grows, if fertilized.
The yolk is an energy/vitamin source, not a 'cell'. The division happens outside the yolk.
From Wikipedia:
> The yolk is not living cell material like protoplasm, but largely passive material
One of the fascinating things about biology I think is this - that if the cells of your body were the size of an egg, they'd be way, way too big and you'd probably die.
I also find it interesting that if your spleen were to go prompt critical, it would irradiate you and you'd probably die. That is my favorite fact about nuclear physics.
For sure. You should definitely avoid bioaccumulating fissionable radionuclides in your spleen, not even a tiny amount if you can help it.
What does that even mean? :D
Wouldn't this be true about any organ?
Another fun fact: if your ears were tomatoes, you'd be deaf.
I don't know for sure here, but isn't the ostrich IN the egg a multicellular animal? I would assume the first point where the egg contains anything that will become the ostrich, mitosis is happening to make more ostrich cells. I'm assuming there's always cell walls and nucleuses every step of the way here, and the egg and ostrich are never just one big cell.
I could be off base here though, I'm really channeling grade 9 bio class from decades ago!
Unfertilized bird eggs are single cells, fertilized eggs should be multicellular by the time they are laid.
The trick is that the egg is a ball with one small cell (the ovum) that happens to have also a huge reservoir of food for the future ostrich. There is a moment when there is only once cell in the egg, just after the fussion of the ovum and the sperm cell.
You're correct, but only for fertilized eggs. Unfertilized eggs are single cells.
Surrounded by a bunch of stuff that isn’t the ovum. “There is at most one cell in an unfertilized bird egg” is not the same as “an unfertilized bird egg is one cell and nothing more”.
skeletal muscle cells can be many cm in length
A neuron can be more than 1 meter long in humans, more than 20 meter in a whale.
Nitpick maybe, but I don't think oocytes are the largest cells, it pretty much has to be some sort of neuron. A sensory neuron for eg. someplace in the foot will be almost as long as the person is tall, and even if the neuron is extremely thin, it's gotta beat the oocyte for volume.
Some back of the envelope math says this is true. A conservative estimate for the size of an alpha motor neuron axon is 10μm diameter and 1m long, which already puts it over an order of magnitude larger than the 4,000,000µm³ oocyte quoted in the article.
This almost feels like cheating. Why not count hair follicles with hair attached then?
That's very different; hair doesn't perform membrane transport along its length. The surface of an axon is critical to the cell's functioning.
https://en.wikipedia.org/wiki/Axolemma
In addition to what mbauman said, hair follicles and the hair itself are not single-cell. I can't immediately find the composition and average cell size, but even a long and thick strand of hair is less than 2 orders of magnitude larger than the largest neurons. I doubt any individual hair cell is very large.
I agree, except the Squid Gian Axon https://en.wikipedia.org/wiki/Squid_giant_axon that can "1mm diameter and almost 1m long" https://www.understandinganimalresearch.org.uk/using-animals...
Giraffes neurons can be up to 15 feet long. Blue whales are speculated to have neurons up to 100 feet long, though they've never been directly observed (dissected).
They've been catastrophically dissected at least once, which we know due to the detailed field notes made by Paul Linnman, and subsequent citations by Dave Barry.
It's possible some of them were observed, given the likelihood of striking someone's glasses or windshield.
But neurons are electrical no? I suppose maybe that's why they're not in the comparison.
Or does that work with diffusion too?
Man that was great great great! Recommending for coworkers, I suscribed!
Thanks for the good work
Surface area to volume ratio?
That's literally the first thing in the article.
You got me. Usually I read them.
edit: Huh. Actually not a bad read. It even mentions ' On Growth and Form' which is interesting, if outdated. There are more modern texts like 'Shapes', 'Flow', and 'Branches' by Philip J Ball.
I like explanations like this because they make biology feel much less arbitrary
Am I getting overly paranoid, or does this account look incredibly unnatural?
Yes too much “it’s not X it’s Y”, and too few references to personal actions/biography.
I also got curious, this is the most personal comment I could find
https://news.ycombinator.com/item?id=44498083
Funny, but might as well be generic, trained from reddit comments. What a time we live in.
Such sleeper accounts, slowly acquiring clout and time on the platform are often used by botnets. One day they (or their actions) will be sold to the highest bidder to upvote a comment, support an idea, ideology, politician or party or some virtual product, stock or coin.
Possible and that is definitely a thing, but I personally I would not rule out, that there still can be a human behind it, just with that specific style and careful about his privacy.
maybe god is small too?
Another answer is: They're not - at least in some plants:
https://en.wikipedia.org/wiki/Valonia_ventricosa
https://en.wikipedia.org/wiki/Acetabularia
Perhaps cells are small in the first place is for efficiency. It's more efficient to perform a set of tasks with trillions of these cells in unison than one big blob.
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Cells are small compared to humans because we're made up by around 3×10¹³ cells.
An odd way to look at it.
Why do our bodies constrain everything else? Sure, WE are big in cell-units, but why are cell-units in the size range they are?