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Niko McCarty.

@NikoMcCarty • 52,471 subscribers

Biotechnology for flourishing. Founding Editor @AsimovPress. Podcast, essays, occasional microgrants. Site: https://t.co/GabLJnLEnG Prev: Caltech, Imperial, NYU, MIT

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We've rebuilt the entire Asimov Press website. We experimented with dozens of fonts and type sizes, column widths, and color palettes to find options that felt comfortable to read. JavaScript is also much easier to embed; many of our articles will include interactive elements. Footnotes, too, are now (finally!) visible in the margins.

We've rebuilt the entire Asimov Press website. We experimented with dozens of fonts and type sizes, column widths, and color palettes to find options that felt comfortable to read. JavaScript is also much easier to embed; many of our articles will include interactive elements. Footnotes, too, are now (finally!) visible in the margins.

10,911 views

I've been editing this article about "brain mapping" and connectomics, and I'm just stunned by how quickly the cost estimates to map, say, a mouse brain have plummeted in just the last couple years. It actually seems feasible that we could map the entire human brain -- all 86 billion neurons, and their connections -- in this lifetime. In the 1970s, Sydney Brenner started mapping all the connections between neurons in C. elegans. His team sliced the worm into thin pieces, took photos using an electron microscope, and manually traced and reconstructed each synapse for 302 neurons total. This project took more than a decade of work, and it cost about $16,500 to reconstruct each neuron. Scaling this up to a human brain boggles the mind. Electron microscopy remained the norm in connectomics for decades, because it was the only option available to see synapses at a resolution high enough to be able to trace their paths. Each electron microscope costs several hundreds of thousands of dollars, though, and you need lots of them to map even a mouse brain in a reasonable timeframe. In 2023, the Wellcome Trust released a report estimating how long, and how expensive, it would be to map the mouse connectome (~70M neurons). They estimated that imaging alone would cost $200-300M, and that proofreading (or ensuring that traces between neurons are correct) would cost $7-21 BILLION. (A human can only manually trace about 1 mm of neuron per hour.) Also, the images would occupy about 500 petabytes of data, and getting those data would require 20 electron microscopes running in parallel for about 5 years, continuously. They estimated the whole project would take about 17 years of work. This is, understandably, insane. But now it seems like there's an actual path toward mapping the full mouse brain in about five years for ~$100M dollars. There have been three major breakthroughs in the last year or so: 1/ Expansion microscopy, first developed in 2015, showed that it's possible to "enlarge" the brain by about 5x using a swellable polymer. But an improved method increases this number to >20x expansion, meaning we can now expand brains and image neurons much more easily using cheap light microscopes, rather than expensive electron ones. 2/ E11 Bio (a nonprofit research org) developed protein barcodes that get delivered into brain tissue; each neuron gets a unique combination of barcodes. These cells are then stained with colorful antibodies, which stick to a matching protein barcode, causing each neuron to light up in a distinct color. This makes tracing neurons so much easier. 3/ Google Research released PATHFINDER this May, an AI-based neuron tracing tool that can proofread about 67,200 cubic microns of brain tissue per hour, with very high accuracy. It works on electron micrographs, but something similar could be presumably be developed for the E11 / colorful tag approach. This is an extremely exciting time for neuroscience. (C. elegans connectome below.)

I've been editing this article about "brain mapping" and connectomics, and I'm just stunned by how quickly the cost estimates to map, say, a mouse brain have plummeted in just the last couple years. It actually seems feasible that we could map the entire human brain -- all 86 billion neurons, and their connections -- in this lifetime. In the 1970s, Sydney Brenner started mapping all the connections between neurons in C. elegans. His team sliced the worm into thin pieces, took photos using an electron microscope, and manually traced and reconstructed each synapse for 302 neurons total. This project took more than a decade of work, and it cost about $16,500 to reconstruct each neuron. Scaling this up to a human brain boggles the mind. Electron microscopy remained the norm in connectomics for decades, because it was the only option available to see synapses at a resolution high enough to be able to trace their paths. Each electron microscope costs several hundreds of thousands of dollars, though, and you need lots of them to map even a mouse brain in a reasonable timeframe. In 2023, the Wellcome Trust released a report estimating how long, and how expensive, it would be to map the mouse connectome (~70M neurons). They estimated that imaging alone would cost $200-300M, and that proofreading (or ensuring that traces between neurons are correct) would cost $7-21 BILLION. (A human can only manually trace about 1 mm of neuron per hour.) Also, the images would occupy about 500 petabytes of data, and getting those data would require 20 electron microscopes running in parallel for about 5 years, continuously. They estimated the whole project would take about 17 years of work. This is, understandably, insane. But now it seems like there's an actual path toward mapping the full mouse brain in about five years for ~$100M dollars. There have been three major breakthroughs in the last year or so: 1/ Expansion microscopy, first developed in 2015, showed that it's possible to "enlarge" the brain by about 5x using a swellable polymer. But an improved method increases this number to >20x expansion, meaning we can now expand brains and image neurons much more easily using cheap light microscopes, rather than expensive electron ones. 2/ E11 Bio (a nonprofit research org) developed protein barcodes that get delivered into brain tissue; each neuron gets a unique combination of barcodes. These cells are then stained with colorful antibodies, which stick to a matching protein barcode, causing each neuron to light up in a distinct color. This makes tracing neurons so much easier. 3/ Google Research released PATHFINDER this May, an AI-based neuron tracing tool that can proofread about 67,200 cubic microns of brain tissue per hour, with very high accuracy. It works on electron micrographs, but something similar could be presumably be developed for the E11 / colorful tag approach. This is an extremely exciting time for neuroscience. (C. elegans connectome below.)

67,157 views

This is beautiful. Making one protein, from one mRNA, takes minutes. This method images single mRNAs as they are translated by ribosomes. And can do it for >1 hour. Translation is start-stop; not continuous. (mRNAs = red; translation sites = green).

This is beautiful. Making one protein, from one mRNA, takes minutes. This method images single mRNAs as they are translated by ribosomes. And can do it for >1 hour. Translation is start-stop; not continuous. (mRNAs = red; translation sites = green).

168,771 views

There's a bacteriophage that turns bacteria into “liquid crystals.” Specifically, Pseudomonas aeruginosa bacteria make Pf phages, which are rod-shaped, negatively-charged, and measure about 2 micrometers in length (roughly the length of an E. coli cell). These phages leave the cells and enter their surroundings. There, they mix with polymers, also secreted by the cells, to form a crystalline matrix. Surprisingly, this is good for the cells. Although the phages kill some of them, it also makes their biofilms stickier and able to withstand certain antibiotics. These bacteria + phages are prevalent in cystic fibrosis patients; they've formed a sort of symbiotic relationship. The Pf phages are made from thousands of repeating copies of a coat protein, called CoaB, which wraps around a single-stranded, circular DNA genome. These genes are integrated directly on the bacterial chromosome. The bacteria “turn on” these phage genes when placed in a viscous environment with low oxygen levels. This is like a trigger to start forming a biofilm. And the cells make a lot of phages; about 100 billion per milliliter. These liquid crystals form because of a physics principle called “depletion attraction.” If you just mix a bunch of loose or flexible polymers together (such as long carbon chains) they will not form a liquid crystal. But if you mix stiff rods (the phages) with loose polymers at a high enough concentration, the polymers will force the phages close together to create a material that flows like a liquid despite being ordered like a crystal. See the video below. These liquid crystal biofilms are hard to get rid of. The negatively-charged phages block many antibiotics (like aminoglycosides, which are positively-charged) from entering cells. Liquid crystals also retain water, so these biofilms can survive on drier surfaces. I first heard about this from Malmesbury’s excellent newsletter, called “Telescopic Turnip.”

There's a bacteriophage that turns bacteria into “liquid crystals.” Specifically, Pseudomonas aeruginosa bacteria make Pf phages, which are rod-shaped, negatively-charged, and measure about 2 micrometers in length (roughly the length of an E. coli cell). These phages leave the cells and enter their surroundings. There, they mix with polymers, also secreted by the cells, to form a crystalline matrix. Surprisingly, this is good for the cells. Although the phages kill some of them, it also makes their biofilms stickier and able to withstand certain antibiotics. These bacteria + phages are prevalent in cystic fibrosis patients; they've formed a sort of symbiotic relationship. The Pf phages are made from thousands of repeating copies of a coat protein, called CoaB, which wraps around a single-stranded, circular DNA genome. These genes are integrated directly on the bacterial chromosome. The bacteria “turn on” these phage genes when placed in a viscous environment with low oxygen levels. This is like a trigger to start forming a biofilm. And the cells make a lot of phages; about 100 billion per milliliter. These liquid crystals form because of a physics principle called “depletion attraction.” If you just mix a bunch of loose or flexible polymers together (such as long carbon chains) they will not form a liquid crystal. But if you mix stiff rods (the phages) with loose polymers at a high enough concentration, the polymers will force the phages close together to create a material that flows like a liquid despite being ordered like a crystal. See the video below. These liquid crystal biofilms are hard to get rid of. The negatively-charged phages block many antibiotics (like aminoglycosides, which are positively-charged) from entering cells. Liquid crystals also retain water, so these biofilms can survive on drier surfaces. I first heard about this from Malmesbury’s excellent newsletter, called “Telescopic Turnip.”

50,450 views

A single E. coli cell, placed on a dish, will become 70 billion cells in just 12 hours. That’s exponential growth. But a new preprint shows that it's possible to engineer E. coli to grow linearly instead, where only one daughter cell continues dividing and the other stops. First, some context. In nature, there is a bacterium called Mycobacterium smegmatis (initially discovered in 1884 in ulcers scraped from syphilis patients.) M. smegmatis is weird because it divides asymmetrically. These cells grow only from one end, and all their cell wall biosynthesis machinery is located on that one end. So when the cell divides, one daughter gets this machinery and the other gets nothing. The daughter that gets the machinery can keep dividing immediately, but the other daughter has to remake all that machinery from scratch, so its growth is delayed. E. coli doesn’t grow like this. When it divides, it pinches in the middle and splits everything evenly. Enzymes, metabolites, and proteins get partitioned more or less randomly between the two daughters. For the new preprint, though, researchers engineered E. coli to behave more like M. smegmatis. Here is how they did it: First, they deleted a gene called cyaA, which encodes an enzyme (adenylate cyclase) that makes a molecule called cAMP. cAMP is SUPER IMPORTANT! It is a nutrient sensor that instructs E. coli to switch on genes that help it digest non-glucose carbon sources when glucose is scarce. Without cAMP, E. coli cells growing on alternative carbon sources will starve; they won’t know how to eat the food. Next, they added back a “split” version of the cyaA gene into the cells. In other words, they split the gene in two so that each half of the enzyme is made separately. Cells can only make cAMP, and thus eat non-glucose carbon sources, if these two halves come together. To facilitate that “coming together,” the researchers also fused the split cyaA proteins to sticky proteins that clump together, and to a fluorescent protein (to make it easy to track these molecules in the cell.) So now some interesting things start to happen if you grow E. coli on a growth medium lacking glucose. As the cell grows, its cyaA “halves” start clumping together into a giant ball. Inside the aggregate, the two enzyme halves come together and make cAMP. And when the cell gets big enough and divides, the clump of cyaA RANDOMLY goes to either daughter cell #1 or #2. The daughter that gets the aggregate (called PA+ in this paper) can keep dividing. The daughter that doesn’t (PA–) cannot. It still grows a few times — about four divisions — because it inherits some leftover cAMP from its mother. But after that, the metabolite is diluted away, and the cell stops growing. PA+ cells went through about 23 divisions on average before their aggregate decayed. And the population of cells, as a whole, grew linearly. This paper is cool because there are many applications where exponential growth is too unpredictable and, perhaps, unsafe. If you want to engineer bacteria to deliver drugs, clean up waste, or live in the gut, you don’t want them to double uncontrollably. This paper shows you can make them expand in a controlled, linear way. Alas, mutations could break this whole engineered system. A mutation that restores cyaA, for example, would give cells a new way to make cAMP. Mutations that make the aggregates split between daughters would break the asymmetry, too. But still, I really enjoy proof-of-concept engineering papers like this.

A single E. coli cell, placed on a dish, will become 70 billion cells in just 12 hours. That’s exponential growth. But a new preprint shows that it's possible to engineer E. coli to grow linearly instead, where only one daughter cell continues dividing and the other stops. First, some context. In nature, there is a bacterium called Mycobacterium smegmatis (initially discovered in 1884 in ulcers scraped from syphilis patients.) M. smegmatis is weird because it divides asymmetrically. These cells grow only from one end, and all their cell wall biosynthesis machinery is located on that one end. So when the cell divides, one daughter gets this machinery and the other gets nothing. The daughter that gets the machinery can keep dividing immediately, but the other daughter has to remake all that machinery from scratch, so its growth is delayed. E. coli doesn’t grow like this. When it divides, it pinches in the middle and splits everything evenly. Enzymes, metabolites, and proteins get partitioned more or less randomly between the two daughters. For the new preprint, though, researchers engineered E. coli to behave more like M. smegmatis. Here is how they did it: First, they deleted a gene called cyaA, which encodes an enzyme (adenylate cyclase) that makes a molecule called cAMP. cAMP is SUPER IMPORTANT! It is a nutrient sensor that instructs E. coli to switch on genes that help it digest non-glucose carbon sources when glucose is scarce. Without cAMP, E. coli cells growing on alternative carbon sources will starve; they won’t know how to eat the food. Next, they added back a “split” version of the cyaA gene into the cells. In other words, they split the gene in two so that each half of the enzyme is made separately. Cells can only make cAMP, and thus eat non-glucose carbon sources, if these two halves come together. To facilitate that “coming together,” the researchers also fused the split cyaA proteins to sticky proteins that clump together, and to a fluorescent protein (to make it easy to track these molecules in the cell.) So now some interesting things start to happen if you grow E. coli on a growth medium lacking glucose. As the cell grows, its cyaA “halves” start clumping together into a giant ball. Inside the aggregate, the two enzyme halves come together and make cAMP. And when the cell gets big enough and divides, the clump of cyaA RANDOMLY goes to either daughter cell #1 or #2. The daughter that gets the aggregate (called PA+ in this paper) can keep dividing. The daughter that doesn’t (PA–) cannot. It still grows a few times — about four divisions — because it inherits some leftover cAMP from its mother. But after that, the metabolite is diluted away, and the cell stops growing. PA+ cells went through about 23 divisions on average before their aggregate decayed. And the population of cells, as a whole, grew linearly. This paper is cool because there are many applications where exponential growth is too unpredictable and, perhaps, unsafe. If you want to engineer bacteria to deliver drugs, clean up waste, or live in the gut, you don’t want them to double uncontrollably. This paper shows you can make them expand in a controlled, linear way. Alas, mutations could break this whole engineered system. A mutation that restores cyaA, for example, would give cells a new way to make cAMP. Mutations that make the aggregates split between daughters would break the asymmetry, too. But still, I really enjoy proof-of-concept engineering papers like this.

58,094 views

The bacterial flagellum looks like a simple tail, or whip. But it’s actually a rotating motor, and perhaps the most sophisticated protein complex nature has ever evolved. In e. coli, these motors are capable of astonishing speeds; about 15,000 rpm. (The world record, according to one study, is for a Vibrio cell that was “clocked at 100,000 rpm by laser microscopy.) The flagellum propels the cell forward at speeds of 20-30 microns per second, or roughly 15 body lengths per second. If scaled up to the size of a cheetah, E. coli would *nearly* be the fastest land organism. The darting movements of a microbe were first observed in 1676 by Antony van Leeuwenhoek, a Dutch cloth merchant. Antony was delighted by the motion of his “animalcules,” writing: “I must say, for my part, that no more pleasant sight has ever yet come before my eye than these many thousands of living creatures, seen all alive in a little drop of water, moving among one another, each several creature having its own proper motion.” But Leeuwenhoek did not see flagella. He assumed, rather, that these animalcules must be “furnished with paws” instead. Christian Ehrenberg would not properly describe flagella until 1836. But amazingly, all the way up until the 1970s, nobody actually knew how the flagellum spun! In 1973, there were two competing models people argued over: the helical-wave (bending) model and the rotating (corkscrew) model. The first model suggested that the flagellum whipped back and forth, side-to-side, to propel the cell like paddle. The corkscrew model suggested that the whole flagellum instead spins around like a screw. In 1974, the corkscrew model finally won out. For two separate studies, scientists affixed flagella to glass slides using antibodies, and watched as the cells spun around and around like corkscrews. And finally, in just the last year, high-resolution structures of the flagellum have revealed a LOT more about its intricate assembly. The tail is made from ~20,000 self-assembling copies of a single protein, called flagellin. A “driveshaft,” or rod, spins the tail and is itself made of 26 protein subunits. Each “motor” in E. coli consists of 11 stators, each of which is made from 7 proteins.(Other types of cells have even more stators, and swim with much higher torques.) The flagellum spins when protons flow into the cell through tiny channels in these stators; akin to water running through a turbine. Each proton makes a small part of the stator change shape and push against the rotor, nudging it forward one step. With dozens of stators working at once, these nudges quickly spin the propeller. I'm writing an essay for Asimov Press about this now, and am really enjoying learning about the flagellum and its history. It's an extraordinarily complicated structure, though, and has been a challenge to understand!

The bacterial flagellum looks like a simple tail, or whip. But it’s actually a rotating motor, and perhaps the most sophisticated protein complex nature has ever evolved. In e. coli, these motors are capable of astonishing speeds; about 15,000 rpm. (The world record, according to one study, is for a Vibrio cell that was “clocked at 100,000 rpm by laser microscopy.) The flagellum propels the cell forward at speeds of 20-30 microns per second, or roughly 15 body lengths per second. If scaled up to the size of a cheetah, E. coli would *nearly* be the fastest land organism. The darting movements of a microbe were first observed in 1676 by Antony van Leeuwenhoek, a Dutch cloth merchant. Antony was delighted by the motion of his “animalcules,” writing: “I must say, for my part, that no more pleasant sight has ever yet come before my eye than these many thousands of living creatures, seen all alive in a little drop of water, moving among one another, each several creature having its own proper motion.” But Leeuwenhoek did not see flagella. He assumed, rather, that these animalcules must be “furnished with paws” instead. Christian Ehrenberg would not properly describe flagella until 1836. But amazingly, all the way up until the 1970s, nobody actually knew how the flagellum spun! In 1973, there were two competing models people argued over: the helical-wave (bending) model and the rotating (corkscrew) model. The first model suggested that the flagellum whipped back and forth, side-to-side, to propel the cell like paddle. The corkscrew model suggested that the whole flagellum instead spins around like a screw. In 1974, the corkscrew model finally won out. For two separate studies, scientists affixed flagella to glass slides using antibodies, and watched as the cells spun around and around like corkscrews. And finally, in just the last year, high-resolution structures of the flagellum have revealed a LOT more about its intricate assembly. The tail is made from ~20,000 self-assembling copies of a single protein, called flagellin. A “driveshaft,” or rod, spins the tail and is itself made of 26 protein subunits. Each “motor” in E. coli consists of 11 stators, each of which is made from 7 proteins.(Other types of cells have even more stators, and swim with much higher torques.) The flagellum spins when protons flow into the cell through tiny channels in these stators; akin to water running through a turbine. Each proton makes a small part of the stator change shape and push against the rotor, nudging it forward one step. With dozens of stators working at once, these nudges quickly spin the propeller. I'm writing an essay for Asimov Press about this now, and am really enjoying learning about the flagellum and its history. It's an extraordinarily complicated structure, though, and has been a challenge to understand!

51,977 views

Beauty should be a core pursuit of biotechnology. There should be companies and nonprofits that engineer organisms solely for the sake of crafting beautiful things. A few reasons why: 1/ Biotechnology has historically worked in reductionist ways, but many useful functions only emerge at the systems level. By engineering a systems-level outcome, like beauty, we will get much better at engineering organisms in predictable ways. When I say "reductionist," I mean that most useful things in biotechnology (drugs and tools) were discovered by stripping molecules from their natural contexts. Scientists collect organisms from soil or wherever and then study their molecules in isolation. This basic approach has yielded everything from rapamycin to antibiotics and CRISPR. This reductionism, though, means that that we know disturbingly little about how life actually works at a systems-level. My core argument is that, by studying beauty, we can remedy this. Beauty has persisted through tens of millions of years of evolution because it is functional; bright colors help attract pollinators to a plant, for example, which helps the plant breed. If evolution has created all of this beauty for functional reasons, then it stands to reason that by trying to create **new** forms of beauty, we'll be able to discover and understand how these systems-level functions work! Indeed, we may even be able to create entirely new functions that biology hasn't evolved yet. These functions will not possible to understand via isolated molecules or reductionism. Therefore, a company pursuing engineered beauty for the sake of beauty will probably make many fundamental discoveries about how organisms develop, interact, adapt to their surroundings, and so on. 2/ Beauty is a way to grow the field and bring more people into biotechnology. Nick Desnoyer’s flower design work, for example, has probably reached hundreds of thousands of people. The glowing plants from Light Bio, too, were featured in the mainstream press. You may not think that these examples are “important” for the universe relative to, say, an incrementally better cancer therapeutic, but there’s no question that they are way more popular to mainstream audiences and good, overall, for the field. 3/ The market is huge! Breeding is already widely used to engineer beauty, or at least to select for aesthetic preferences. Pugs are evolutionarily suboptimal, but they've been bred precisely to satisfy a certain aesthetic desire are now a multi-billion dollar industry. The Juliet Rose, developed via breeding over a 15-year period, debuted at the 2006 Chelsea Flower Show and is enormously profitable today. Why should deliberately engineered forms of beauty be any different? If you are building a biotech company or nonprofit that is pursuing beauty, please reach out! I’d love to help.

Beauty should be a core pursuit of biotechnology. There should be companies and nonprofits that engineer organisms solely for the sake of crafting beautiful things. A few reasons why: 1/ Biotechnology has historically worked in reductionist ways, but many useful functions only emerge at the systems level. By engineering a systems-level outcome, like beauty, we will get much better at engineering organisms in predictable ways. When I say "reductionist," I mean that most useful things in biotechnology (drugs and tools) were discovered by stripping molecules from their natural contexts. Scientists collect organisms from soil or wherever and then study their molecules in isolation. This basic approach has yielded everything from rapamycin to antibiotics and CRISPR. This reductionism, though, means that that we know disturbingly little about how life actually works at a systems-level. My core argument is that, by studying beauty, we can remedy this. Beauty has persisted through tens of millions of years of evolution because it is functional; bright colors help attract pollinators to a plant, for example, which helps the plant breed. If evolution has created all of this beauty for functional reasons, then it stands to reason that by trying to create **new** forms of beauty, we'll be able to discover and understand how these systems-level functions work! Indeed, we may even be able to create entirely new functions that biology hasn't evolved yet. These functions will not possible to understand via isolated molecules or reductionism. Therefore, a company pursuing engineered beauty for the sake of beauty will probably make many fundamental discoveries about how organisms develop, interact, adapt to their surroundings, and so on. 2/ Beauty is a way to grow the field and bring more people into biotechnology. Nick Desnoyer’s flower design work, for example, has probably reached hundreds of thousands of people. The glowing plants from Light Bio, too, were featured in the mainstream press. You may not think that these examples are “important” for the universe relative to, say, an incrementally better cancer therapeutic, but there’s no question that they are way more popular to mainstream audiences and good, overall, for the field. 3/ The market is huge! Breeding is already widely used to engineer beauty, or at least to select for aesthetic preferences. Pugs are evolutionarily suboptimal, but they've been bred precisely to satisfy a certain aesthetic desire are now a multi-billion dollar industry. The Juliet Rose, developed via breeding over a 15-year period, debuted at the 2006 Chelsea Flower Show and is enormously profitable today. Why should deliberately engineered forms of beauty be any different? If you are building a biotech company or nonprofit that is pursuing beauty, please reach out! I’d love to help.

18,726 views

We made a huge poster that illustrates all of the major genome editing tools in one place. You can download a copy for free from the Asimov Press website.

We made a huge poster that illustrates all of the major genome editing tools in one place. You can download a copy for free from the Asimov Press website.

40,627 views

Some microbes carry a protein, called SNIPE, that "chops up" phage DNA as it's being injected into the cell. This is a new mechanism for phage defense! CRISPR–Cas and restriction enzymes also evolved to fight against phages, but they work by recognizing sequences. SNIPE works, instead, by sensing "touch." SNIPE is a protein with about 500 amino acids. After it's made by the ribosome, it latches onto ManYZ, two proteins which sit on the cell's inner membrane. (ManYZ is an importer; it brings mannose and other sugars into the cell.) Once attached to ManYZ, SNIPE sits and waits for an invading phage. Some phages, including lambda, actually infect cells by pushing their DNA through this ManYZ channel. Lambda uses its "tail" to reach inside the protein channel, basically, and inject its DNA. When this physical touch happens, though, SNIPE is waiting. As soon as the phage DNA starts entering the cell, and passes through ManYZ and SNIPE, it gets immediately destroyed. This means that SNIPE is the first phage defense system discovered, so far, that uses spatial positioning at the injection site to destroy invaders. But there are caveats, of course. If you untether SNIPE from ManYZ, such that it can freely diffuse through the cell, it will chew up the bacterium's genome. It is not a highly discerning nuclease! Also, SNIPE is not found in most bacteria. A prior pangenome study, which sequenced lots of different microbes, found that roughly a third of well-studied bacterial lineages had at least one member with a SNIPE-like protein. (For this paper, they just ported one of those homologs into an E. coli laboratory strain.) And finally, because SNIPE's mechanism is tightly tied to ManYZ, it cannot be used to defend against phages that enter the cell through different routes. T4 phages, for example, inject their DNA straight through the cell membrane and into the cytoplasm, without interacting with ManYZ. This is a nice basic science paper. Applications TBD. (Just remember that scientists figured out that bacteria had a phage defense system, called CRISPR-Cas, many years before it was repurposed into a gene-editing tool.) P.S. The video below shows how cells with the SNIPE gene (middle row) kill invading phages, and thus continue growing and dividing. Empty vector (top row) refers to bacteria carrying a plasmid with no SNIPE gene; this is a control group. And SNIPE E414A refers to cells which received a mutated SNIPE gene, where the glutamate at position 414 has been changed to an alanine, thus destroying the protein's nuclease activity. These cells also die when they get infected with a phage.

Some microbes carry a protein, called SNIPE, that "chops up" phage DNA as it's being injected into the cell. This is a new mechanism for phage defense! CRISPR–Cas and restriction enzymes also evolved to fight against phages, but they work by recognizing sequences. SNIPE works, instead, by sensing "touch." SNIPE is a protein with about 500 amino acids. After it's made by the ribosome, it latches onto ManYZ, two proteins which sit on the cell's inner membrane. (ManYZ is an importer; it brings mannose and other sugars into the cell.) Once attached to ManYZ, SNIPE sits and waits for an invading phage. Some phages, including lambda, actually infect cells by pushing their DNA through this ManYZ channel. Lambda uses its "tail" to reach inside the protein channel, basically, and inject its DNA. When this physical touch happens, though, SNIPE is waiting. As soon as the phage DNA starts entering the cell, and passes through ManYZ and SNIPE, it gets immediately destroyed. This means that SNIPE is the first phage defense system discovered, so far, that uses spatial positioning at the injection site to destroy invaders. But there are caveats, of course. If you untether SNIPE from ManYZ, such that it can freely diffuse through the cell, it will chew up the bacterium's genome. It is not a highly discerning nuclease! Also, SNIPE is not found in most bacteria. A prior pangenome study, which sequenced lots of different microbes, found that roughly a third of well-studied bacterial lineages had at least one member with a SNIPE-like protein. (For this paper, they just ported one of those homologs into an E. coli laboratory strain.) And finally, because SNIPE's mechanism is tightly tied to ManYZ, it cannot be used to defend against phages that enter the cell through different routes. T4 phages, for example, inject their DNA straight through the cell membrane and into the cytoplasm, without interacting with ManYZ. This is a nice basic science paper. Applications TBD. (Just remember that scientists figured out that bacteria had a phage defense system, called CRISPR-Cas, many years before it was repurposed into a gene-editing tool.) P.S. The video below shows how cells with the SNIPE gene (middle row) kill invading phages, and thus continue growing and dividing. Empty vector (top row) refers to bacteria carrying a plasmid with no SNIPE gene; this is a control group. And SNIPE E414A refers to cells which received a mutated SNIPE gene, where the glutamate at position 414 has been changed to an alanine, thus destroying the protein's nuclease activity. These cells also die when they get infected with a phage.

20,578 views

This video shows a subset of ribosomes inside a cancer cell actively translating mRNA molecules. Each point of light is one ribosome. An image was taken every 3 minutes over a 4-hour period.

This video shows a subset of ribosomes inside a cancer cell actively translating mRNA molecules. Each point of light is one ribosome. An image was taken every 3 minutes over a 4-hour period.

35,219 views

Scientists made a robotic system that tracks honey bees 24 hours a day. Cameras track the queen and individual drones, while algorithms track their movements, egg layings, grooming interactions, and more. Really cool.

Scientists made a robotic system that tracks honey bees 24 hours a day. Cameras track the queen and individual drones, while algorithms track their movements, egg layings, grooming interactions, and more. Really cool.

36,389 views

I just moved to Berkeley, and unpacking was a good excuse to catalog the books in my library. I currently own 450 physical books, of which 18% are fiction and 82% are nonfiction. About 25% of my nonfiction books are about biology, which was surprising to me because I don’t really enjoy reading about biology in my spare time. When I shared my bookshelf with Claude and asked for recommendations, it suggested The Invention of Air by Steven Johnson, The Making of the Atomic Bomb by Richard Rhodes, and The Metaphysical Club by Louis Menand. The first two were already on my list, but I had never heard of the third. Overall, I think a digital bookshelf is a useful way to find more books based on my interests. My full bookshelf is here:

I just moved to Berkeley, and unpacking was a good excuse to catalog the books in my library. I currently own 450 physical books, of which 18% are fiction and 82% are nonfiction. About 25% of my nonfiction books are about biology, which was surprising to me because I don’t really enjoy reading about biology in my spare time. When I shared my bookshelf with Claude and asked for recommendations, it suggested The Invention of Air by Steven Johnson, The Making of the Atomic Bomb by Richard Rhodes, and The Metaphysical Club by Louis Menand. The first two were already on my list, but I had never heard of the third. Overall, I think a digital bookshelf is a useful way to find more books based on my interests. My full bookshelf is here:

14,486 views

In 2007, physicist Freeman Dyson wrote an essay called “Our Biotech Future” for The New York Review. In it, he wrote: “I see a bright future for the biotechnology industry when it follows the path of the computer industry…becoming small and domesticated rather than big and centralized.” Dyson had recently visited the Philadelphia Flower Show, “the biggest indoor flower show in the world, where flower breeders from all over the world show off the results of their efforts.” And he pondered a future where genetic engineering would enable these breeders to make entirely new types of flowers, unencumbered by the biological limits of evolution. It seems that Dyson’s “biotech future” is now becoming reality. Nick Desnoyer, a postdoctoral fellow in the United Kingdom, has already designed and created more than a dozen bespoke flowers. Desnoyer imagines phenotypes in his head and then uses a combination of breeding, CRISPR, and pathogens to manifest those phenotypes in his flowers. He’s currently working to add new colors to his design palette, including streaks of yellow, amber, purple, and green. All of his flowers are sculpted on nights and weekends, after lab mates have shuffled home for the night. I’m writing an essay about Nick and his process for Asimov Press, called "The Flower Designer." More to share soon! Video below is from Nick's website -->

In 2007, physicist Freeman Dyson wrote an essay called “Our Biotech Future” for The New York Review. In it, he wrote: “I see a bright future for the biotechnology industry when it follows the path of the computer industry…becoming small and domesticated rather than big and centralized.” Dyson had recently visited the Philadelphia Flower Show, “the biggest indoor flower show in the world, where flower breeders from all over the world show off the results of their efforts.” And he pondered a future where genetic engineering would enable these breeders to make entirely new types of flowers, unencumbered by the biological limits of evolution. It seems that Dyson’s “biotech future” is now becoming reality. Nick Desnoyer, a postdoctoral fellow in the United Kingdom, has already designed and created more than a dozen bespoke flowers. Desnoyer imagines phenotypes in his head and then uses a combination of breeding, CRISPR, and pathogens to manifest those phenotypes in his flowers. He’s currently working to add new colors to his design palette, including streaks of yellow, amber, purple, and green. All of his flowers are sculpted on nights and weekends, after lab mates have shuffled home for the night. I’m writing an essay about Nick and his process for Asimov Press, called "The Flower Designer." More to share soon! Video below is from Nick's website -->

21,845 views

A 3D map of mRNA transcripts in a zebrafish embryo. This video was not made using a microscope. Researchers tag nucleotides with barcodes, which then "link" together in the tissue. Sequencing those links can then be used to computationally infer the 3D positions of genes.

A 3D map of mRNA transcripts in a zebrafish embryo. This video was not made using a microscope. Researchers tag nucleotides with barcodes, which then "link" together in the tissue. Sequencing those links can then be used to computationally infer the 3D positions of genes.

24,543 views

Cable bacteria are long, "filamentous bacteria that conduct electrons via internal wires." New study: Anaerobes — in lakes and ponds — swarm around these cable bacteria & give electrons for respiration. Cut the cable, lose the microbes. Beautiful. 📽️

Cable bacteria are long, "filamentous bacteria that conduct electrons via internal wires." New study: Anaerobes — in lakes and ponds — swarm around these cable bacteria & give electrons for respiration. Cut the cable, lose the microbes. Beautiful. 📽️

33,755 views

This is what Ebola viruses look like inside of infected cells. They look like tubes because the viral capsid is formed from proteins that directly bind to the linear, viral genome. "Until recently, it was impossible to reveal protein structures directly inside of virus-infected cells, except for very thin peripheral parts of cells or budded virus particles. Therefore, we had no structural insights into how the Ebola virus replicates and how nucleocapsids assemble in infected cells prior to budding and release." This paper is a big deal, because it finds several highly-conserved regions in the Ebola virus structure that could be targeted by antiviral drugs.

This is what Ebola viruses look like inside of infected cells. They look like tubes because the viral capsid is formed from proteins that directly bind to the linear, viral genome. "Until recently, it was impossible to reveal protein structures directly inside of virus-infected cells, except for very thin peripheral parts of cells or budded virus particles. Therefore, we had no structural insights into how the Ebola virus replicates and how nucleocapsids assemble in infected cells prior to budding and release." This paper is a big deal, because it finds several highly-conserved regions in the Ebola virus structure that could be targeted by antiviral drugs.

17,683 views

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Breaking: PioneerLabs has engineered a microbe able to live on Mars, consuming solely nutrients found on the planet to create building materials. I interviewed Erika Alden DeBenedictis, the CEO, to learn how they did it and what might come next. Much of the interview was about bottlenecks to growing life on Mars; the planet has tons of water, but only in the form of ice. (If you melted all that ice, it would create an ocean 100 feet deep across the entire planet!) Similarly, we talked about the dirt. Martian regolith has salts, heavy metals, and perchlorates that are toxic to many organisms. Some microbes on Earth are able to break down these toxins, though, so Pioneer is engineering them to make them better at eating those toxins while adding nutrients back into the soil. This could possibly help support plant life in the future. Watch the full episode and subscribe to Asimov Press for more. 0:00 A first microbe engineered for Mars 5:03 Simulating Martian chemistry 8:27 The five "pioneer species" 17:20 Water, warming, and nitrogen 26:39 Radiation, growth rates, and poor measurements 35:49 Starship 41:05 Why create a second biosphere?
50:31
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Breaking: PioneerLabs has engineered a microbe able to live on Mars, consuming solely nutrients found on the planet to create building materials. I interviewed Erika Alden DeBenedictis, the CEO, to learn how they did it and what might come next. Much of the interview was about bottlenecks to growing life on Mars; the planet has tons of water, but only in the form of ice. (If you melted all that ice, it would create an ocean 100 feet deep across the entire planet!) Similarly, we talked about the dirt. Martian regolith has salts, heavy metals, and perchlorates that are toxic to many organisms. Some microbes on Earth are able to break down these toxins, though, so Pioneer is engineering them to make them better at eating those toxins while adding nutrients back into the soil. This could possibly help support plant life in the future. Watch the full episode and subscribe to Asimov Press for more. 0:00 A first microbe engineered for Mars 5:03 Simulating Martian chemistry 8:27 The five "pioneer species" 17:20 Water, warming, and nitrogen 26:39 Radiation, growth rates, and poor measurements 35:49 Starship 41:05 Why create a second biosphere?

Niko McCarty.

97,770 views • 26 days ago

Video of myosin proteins "walking" along actin. Insane that we can image this! It was made by Toshio Ando's group using atomic force microscopy. All of their papers are a goldmine; they've also recorded a Cas9 protein cutting DNA and ATP synthase spinning.
0:39
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Video of myosin proteins "walking" along actin. Insane that we can image this! It was made by Toshio Ando's group using atomic force microscopy. All of their papers are a goldmine; they've also recorded a Cas9 protein cutting DNA and ATP synthase spinning.

Niko McCarty.

94,504 views • 2 months ago

Out today: Researchers have made the first cell capable of “feeding, growth, replication, division and selection...entirely using components scientists put there.” In other words, a cell that self-replicates and was made entirely from the ground-up, molecule by molecule. The cell is called SpudCell. And although it is definitely a cell (in that it has a membrane with molecules inside) it is definitely not alive, because it cannot grow indefinitely, survive without human help, make its own ribosomes, or recycle waste. It "dies" after a few divisions. But it's a starting point! And these same researchers have raised $6-8M+ in philanthropic funding to scale their efforts with a new nonprofit for synthetic cell research, called Biotic.
1:29
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Out today: Researchers have made the first cell capable of “feeding, growth, replication, division and selection...entirely using components scientists put there.” In other words, a cell that self-replicates and was made entirely from the ground-up, molecule by molecule. The cell is called SpudCell. And although it is definitely a cell (in that it has a membrane with molecules inside) it is definitely not alive, because it cannot grow indefinitely, survive without human help, make its own ribosomes, or recycle waste. It "dies" after a few divisions. But it's a starting point! And these same researchers have raised $6-8M+ in philanthropic funding to scale their efforts with a new nonprofit for synthetic cell research, called Biotic.

Niko McCarty.

124,148 views • 3 months ago

New Episode: How to Design Flowers Nick Desnoyer uses genetic engineering, breeding, and pathogens to design and then create flowers that don't exist anywhere else on Earth. We talked about how he does it, in a room surrounded by many of his creations. At the start of the episode, Nick reveals his next project, called Paintunia, which is an engineered line of petunia that acts as a living canvas. He has engineered these petunias to include an inducible gene; when he lightly touches their buds with a molecule called dexamethasone, the molecules seep into cells, switch on the gene, and cause them to make a pigment. The result is a paintable flower, where molecules literally control which colors show up in particular places. Nick’s plan is ultimately to engineer these petunias to express three separate colors, for cyan, magenta, and yellow. Nick's ultimate dream is to build a botanical garden full of weird and wonderful flowers that exist nowhere else. We filmed this episode surrounded by flowers, and he patiently explained to me how each one gets its shape and pigmentation; how he combines breeding and genetic engineering to make new flowers; and how he searches scientific papers for mutations to figure out which plant crosses to make next. I think he convinced me that designing new kinds of flowers makes us look more closely at nature, and appreciate it more deeply. After all, all the genes and variations he uses in the laboratory are based on designs that have evolved elsewhere. Hope you enjoy!
1:24:30
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New Episode: How to Design Flowers Nick Desnoyer uses genetic engineering, breeding, and pathogens to design and then create flowers that don't exist anywhere else on Earth. We talked about how he does it, in a room surrounded by many of his creations. At the start of the episode, Nick reveals his next project, called Paintunia, which is an engineered line of petunia that acts as a living canvas. He has engineered these petunias to include an inducible gene; when he lightly touches their buds with a molecule called dexamethasone, the molecules seep into cells, switch on the gene, and cause them to make a pigment. The result is a paintable flower, where molecules literally control which colors show up in particular places. Nick’s plan is ultimately to engineer these petunias to express three separate colors, for cyan, magenta, and yellow. Nick's ultimate dream is to build a botanical garden full of weird and wonderful flowers that exist nowhere else. We filmed this episode surrounded by flowers, and he patiently explained to me how each one gets its shape and pigmentation; how he combines breeding and genetic engineering to make new flowers; and how he searches scientific papers for mutations to figure out which plant crosses to make next. I think he convinced me that designing new kinds of flowers makes us look more closely at nature, and appreciate it more deeply. After all, all the genes and variations he uses in the laboratory are based on designs that have evolved elsewhere. Hope you enjoy!

Niko McCarty.

11,547 views • 10 days ago

This robot is controlled by a fungus. The fungus' mycelia senses the environment and emits "action potential–like spiking voltages" to control the motors and valves.
0:29
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This robot is controlled by a fungus. The fungus' mycelia senses the environment and emits "action potential–like spiking voltages" to control the motors and valves.

Niko McCarty.

467,973 views • 2 years ago

A few months ago, researchers made a synthetic cell that grows, eats, and divides. But it only grows for about five generations, and then it “breaks down” completely and stops moving. This is the reason it’s not yet considered “alive.” When I asked Kate Adamala, the lead author behind SpudCell, why she thinks this happens, she said something really simple and somewhat surprising: The cell cannot break down its own waste. In other words, it has all these proteins and RNA and DNA, but has no way to break them down and reuse the building blocks when they inevitably fail. So when a ribosome stops working, it just sits inside the cell and remains there for many generations. With each generation, more of the cell is filled up with broken pieces. Now, you could add a protease to these cells, but proteases are blunt-force instruments. They would destroy both working proteins *and* the broken ones, and so probably kill the cell. And when I asked Kate why we can't just use the enzymes and chaperones that natural cells use, she said there are too many of them. If you try to recreate all of biology's quality control processes, you end up with a hugely bloated metabolism inside what is supposed to be a minimal cell. The issue, then — the fundamental bottleneck — is that we do not have good tools to recognize WHAT is broken inside a cell and *then* destroy them while leaving healthy variants unscathed. My hunch here is that we need better molecular sensors. If we could distinguish between different forms of a protein, without destroying a cell entirely, then perhaps we could couple that recognition to a selective protease and recycle only the things that are broken. We also just don’t understand, at a high enough level, what happens when a ribosome breaks, and thus we can’t design good probes to sense those broken molecules. In trying to create a synthetic cell, then, we might also arrive at ideas for much better tools. Trying to create life is a really good way to figure out all the obstacles and stuff we don’t yet understand. But when Kate says she thinks they'll achieve perpetual cell division by 2030 (in the interview), I'm kind of skeptical. There's a lot of work to do here, and the tools we tend to use as biologists are often much broader than the precise, highly-evolved systems we find in nature.
2:55
NikoMcCarty's profile picture

A few months ago, researchers made a synthetic cell that grows, eats, and divides. But it only grows for about five generations, and then it “breaks down” completely and stops moving. This is the reason it’s not yet considered “alive.” When I asked Kate Adamala, the lead author behind SpudCell, why she thinks this happens, she said something really simple and somewhat surprising: The cell cannot break down its own waste. In other words, it has all these proteins and RNA and DNA, but has no way to break them down and reuse the building blocks when they inevitably fail. So when a ribosome stops working, it just sits inside the cell and remains there for many generations. With each generation, more of the cell is filled up with broken pieces. Now, you could add a protease to these cells, but proteases are blunt-force instruments. They would destroy both working proteins *and* the broken ones, and so probably kill the cell. And when I asked Kate why we can't just use the enzymes and chaperones that natural cells use, she said there are too many of them. If you try to recreate all of biology's quality control processes, you end up with a hugely bloated metabolism inside what is supposed to be a minimal cell. The issue, then — the fundamental bottleneck — is that we do not have good tools to recognize WHAT is broken inside a cell and *then* destroy them while leaving healthy variants unscathed. My hunch here is that we need better molecular sensors. If we could distinguish between different forms of a protein, without destroying a cell entirely, then perhaps we could couple that recognition to a selective protease and recycle only the things that are broken. We also just don’t understand, at a high enough level, what happens when a ribosome breaks, and thus we can’t design good probes to sense those broken molecules. In trying to create a synthetic cell, then, we might also arrive at ideas for much better tools. Trying to create life is a really good way to figure out all the obstacles and stuff we don’t yet understand. But when Kate says she thinks they'll achieve perpetual cell division by 2030 (in the interview), I'm kind of skeptical. There's a lot of work to do here, and the tools we tend to use as biologists are often much broader than the precise, highly-evolved systems we find in nature.

Niko McCarty.

11,388 views • 12 days ago

A green alga cell can swim 100 microns per second. Scientists put little baskets on a wheel. As algae became trapped, they pushed and spun the wheel around.
1:21
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A green alga cell can swim 100 microns per second. Scientists put little baskets on a wheel. As algae became trapped, they pushed and spun the wheel around.

Niko McCarty.

351,800 views • 2 years ago

This video is one of the first times I thought biology was “cool.” It shows a neutrophil cell chasing a bacterium. Originally recorded in the 1950s by David Rogers at Vanderbilt University, the video gave me a deeper appreciation for life, even at the level of a single cell, because the neutrophil's movements seem so intentful, purposeful, aware. It wasn’t until recently, though, that I actually tried to demystify the neutrophil’s movements and understand how they happen. Here's what I learned: 1. The neutrophil's surface has thousands of protein receptors. Molecules secreted by the bacteria collide with these receptors. When that happens, the proteins change shape, slightly, and initiate a signaling cascade. 2. The neutrophil “knows” where to go because of a discrepancy in bound vs. unbound receptors. The side of the cell closest to the microbe will, probabilistically, have more "bound" receptors than the other side (because the molecules secreted by the microbe have a concentration gradient). This is how the neutrophil figures out which way to move. 3. Each bound receptor activates several G proteins located inside the cell membrane. Each G protein, in turn, switches on PI3K enzymes. In this way, the original signal is amplified; a single "activated" receptor might cause ~100 copies of PI3K to get switched on downstream. 4. The PI3K enzymes stick phosphates onto lipids in the cell membrane. The side of the neutrophil facing the bacterium now has more phosphates than the "back" side. Phosphate-binding proteins, such as GEF, accumulate and then recruit Rac, thus activating it. Rac, in turn, acts like a molecular switch, ultimately recruiting Arp2/3. (TL;DR: A bunch of proteins get activated, and the high phosphate concentration at the leading edge is the key signal for all this.) 5. At any given moment, the neutrophil has millions of actin molecules. These are the proteins used to build the cytoskeleton. Half of the actins are already “assembled” into filaments, but the other half are just floating around. Arp2/3 acts as a nucleator, grabbing onto actin and then starting a new cytoskeletal branch. More actin is assembled at the leading edge (where the Arp2/3 has accumulated), where they each push on the cell membrane with ~2 piconewtons of force. Hundreds of actin chains, pushing together, causes the cell to form protrusions. 6. The assembling actin chains push the cell at a speed of ~20 micrometers per minute (the length of about ten E. coli cells placed end-to-end.) As all of this is happening, another signaling cascade, nucleated at the back end of the cell, is dismantling actin filaments and recycling them. All this happens over a span of about 30 seconds. Much of this process is invisible; what we see, instead, is "just" a cell chasing its prey. But that's the wonderful thing about biology: A singular observation is usually more than enough fodder for a lifetime of work. The well is deep. There is always more to learn.
0:28
NikoMcCarty's profile picture

This video is one of the first times I thought biology was “cool.” It shows a neutrophil cell chasing a bacterium. Originally recorded in the 1950s by David Rogers at Vanderbilt University, the video gave me a deeper appreciation for life, even at the level of a single cell, because the neutrophil's movements seem so intentful, purposeful, aware. It wasn’t until recently, though, that I actually tried to demystify the neutrophil’s movements and understand how they happen. Here's what I learned: 1. The neutrophil's surface has thousands of protein receptors. Molecules secreted by the bacteria collide with these receptors. When that happens, the proteins change shape, slightly, and initiate a signaling cascade. 2. The neutrophil “knows” where to go because of a discrepancy in bound vs. unbound receptors. The side of the cell closest to the microbe will, probabilistically, have more "bound" receptors than the other side (because the molecules secreted by the microbe have a concentration gradient). This is how the neutrophil figures out which way to move. 3. Each bound receptor activates several G proteins located inside the cell membrane. Each G protein, in turn, switches on PI3K enzymes. In this way, the original signal is amplified; a single "activated" receptor might cause ~100 copies of PI3K to get switched on downstream. 4. The PI3K enzymes stick phosphates onto lipids in the cell membrane. The side of the neutrophil facing the bacterium now has more phosphates than the "back" side. Phosphate-binding proteins, such as GEF, accumulate and then recruit Rac, thus activating it. Rac, in turn, acts like a molecular switch, ultimately recruiting Arp2/3. (TL;DR: A bunch of proteins get activated, and the high phosphate concentration at the leading edge is the key signal for all this.) 5. At any given moment, the neutrophil has millions of actin molecules. These are the proteins used to build the cytoskeleton. Half of the actins are already “assembled” into filaments, but the other half are just floating around. Arp2/3 acts as a nucleator, grabbing onto actin and then starting a new cytoskeletal branch. More actin is assembled at the leading edge (where the Arp2/3 has accumulated), where they each push on the cell membrane with ~2 piconewtons of force. Hundreds of actin chains, pushing together, causes the cell to form protrusions. 6. The assembling actin chains push the cell at a speed of ~20 micrometers per minute (the length of about ten E. coli cells placed end-to-end.) As all of this is happening, another signaling cascade, nucleated at the back end of the cell, is dismantling actin filaments and recycling them. All this happens over a span of about 30 seconds. Much of this process is invisible; what we see, instead, is "just" a cell chasing its prey. But that's the wonderful thing about biology: A singular observation is usually more than enough fodder for a lifetime of work. The well is deep. There is always more to learn.

Niko McCarty.

127,486 views • 9 months ago

For decades, biologists argued that birds migrate using magnetic fields, and that cryptochrome proteins in their eyes help them figure out where to fly. But the evidence for this has always been flimsy. In 1972, Wolfgang and Roswitha Wiltschko captured migratory European robins, put them in cages, covered the cages with a blanket, and wrapped electric coils around them. Once the birds lost their view of the sky, they still tried to move, or "hop," in the direction of their normal migration route. But when the Wiltschkos flipped the magnetic field around, the robins started hopping in random directions. They took this as evidence that, somehow, birds migrate using a magnetic sense. (Not bad!) In 2000, three theoretical biophysicists in Illinois, Ritz, Adem, and Schulten, proposed a mechanism for that magnetic sense. They argued that when blue light hits a receptor in the eye, it might create something called a "radical pair," locking two electrons into a spin state that a magnetic field could then nudge. They suggested that cryptochromes, light-sensitive proteins in the retina, might be responsible. (Speculative!) And then, in 2021, researchers apparently confirmed this! They took cryptochrome proteins from a type of migratory robin and put them in a test tube. They shone blue light at the proteins and found that this light induced them to form that transient "radical pair" state. And finally, they showed that magnetic fields could change this photochemistry where, in the presence of a magnetic field, the proteins formed fewer of these radical pairs, because the field forced a larger fraction of the excited molecules to ‘collapse’ back to their resting state. The experiment they used to measure this, though, has almost nothing to do with biology. You literally isolate the proteins, bombard them with a blue laser and, after each pulse, measure how much light the proteins absorb. For the robin cryptochrome protein, adding a magnetic field changed the absorbance *slightly.* But here’s the caveat: All of this was done in vitro, in a test tube, in a water-based buffer (rather than a cell). And, even worse, the experiment was done at 5 degrees Celsius (waaaay colder than the bird’s normal temperature) and at a low pH. And even after all this tinkering, they still *barely* saw a magnetic response! The news media didn't report many of these caveats. I randomly pulled one story from Science News and another from the University of Oxford, and neither even mentioned that the researchers ran the experiment at low temperature. The Oxford writeup actually hyped the result up more than the paper itself; that author wrote: “…the authors think the proteins involved could be significantly more sensitive in their native environment. In cells in the retina, the proteins are probably fixed and aligned, increasing their sensitivity to the direction of the magnetic field. Moreover, they are also likely to be associated with other proteins that could amplify the sensory signals." (Wow!) When Andrew York and Maria Ingaramo, two scientist working at Calico, heard about these results, they grew skeptical and decided to search for magnetically-responsive proteins — that actually work under physiological conditions — on their own. And that search, in turn, gave rise to Nonfiction Laboratories, a company that not only has created such proteins, but is now trying to commercialize them to make magnetically controlled cancer therapies that are only active near a tumor. The clip below is from my podcast.
2:53
NikoMcCarty's profile picture

For decades, biologists argued that birds migrate using magnetic fields, and that cryptochrome proteins in their eyes help them figure out where to fly. But the evidence for this has always been flimsy. In 1972, Wolfgang and Roswitha Wiltschko captured migratory European robins, put them in cages, covered the cages with a blanket, and wrapped electric coils around them. Once the birds lost their view of the sky, they still tried to move, or "hop," in the direction of their normal migration route. But when the Wiltschkos flipped the magnetic field around, the robins started hopping in random directions. They took this as evidence that, somehow, birds migrate using a magnetic sense. (Not bad!) In 2000, three theoretical biophysicists in Illinois, Ritz, Adem, and Schulten, proposed a mechanism for that magnetic sense. They argued that when blue light hits a receptor in the eye, it might create something called a "radical pair," locking two electrons into a spin state that a magnetic field could then nudge. They suggested that cryptochromes, light-sensitive proteins in the retina, might be responsible. (Speculative!) And then, in 2021, researchers apparently confirmed this! They took cryptochrome proteins from a type of migratory robin and put them in a test tube. They shone blue light at the proteins and found that this light induced them to form that transient "radical pair" state. And finally, they showed that magnetic fields could change this photochemistry where, in the presence of a magnetic field, the proteins formed fewer of these radical pairs, because the field forced a larger fraction of the excited molecules to ‘collapse’ back to their resting state. The experiment they used to measure this, though, has almost nothing to do with biology. You literally isolate the proteins, bombard them with a blue laser and, after each pulse, measure how much light the proteins absorb. For the robin cryptochrome protein, adding a magnetic field changed the absorbance *slightly.* But here’s the caveat: All of this was done in vitro, in a test tube, in a water-based buffer (rather than a cell). And, even worse, the experiment was done at 5 degrees Celsius (waaaay colder than the bird’s normal temperature) and at a low pH. And even after all this tinkering, they still *barely* saw a magnetic response! The news media didn't report many of these caveats. I randomly pulled one story from Science News and another from the University of Oxford, and neither even mentioned that the researchers ran the experiment at low temperature. The Oxford writeup actually hyped the result up more than the paper itself; that author wrote: “…the authors think the proteins involved could be significantly more sensitive in their native environment. In cells in the retina, the proteins are probably fixed and aligned, increasing their sensitivity to the direction of the magnetic field. Moreover, they are also likely to be associated with other proteins that could amplify the sensory signals." (Wow!) When Andrew York and Maria Ingaramo, two scientist working at Calico, heard about these results, they grew skeptical and decided to search for magnetically-responsive proteins — that actually work under physiological conditions — on their own. And that search, in turn, gave rise to Nonfiction Laboratories, a company that not only has created such proteins, but is now trying to commercialize them to make magnetically controlled cancer therapies that are only active near a tumor. The clip below is from my podcast.

Niko McCarty.

21,714 views • 1 month ago

The Magnetobiology Episode: A company in San Francisco, called Nonfiction Laboratories, is building proteins (like antibodies and enzymes) that can be controlled using small magnets. In this episode, co-founder Maria Ingaramo and scientific advisor Andrew York explain how they engineered a protein, MagLOV, that responds strongly to magnetic fields, why most prior attempts have failed to replicate, and how the mechanism of magnetically-controlled proteins actually works. They also get into the “dream” use cases, like cancer drugs that activate only at the tumor, which might have a lower toxicity inside the body. This podcast is made possible by Astera Institute. I'm happy with how this episode came out. I think my interviewing skills are improving, and I'm getting better at building up context throughout the episode. Enjoy! Search for "The New Biology" on YouTube, Spotify, and Apple Podcasts. Timestamps: 00:00 - Opening 00:54 — Introduction 01:35 — The dream 05:38 — Why magnets vs. light or ultrasound 10:05 — The physics 17:48 — On the name "magnetogenetics" 21:25 — Birds and cryptochromes 27:09 — Why is the field filled with so much junk? 29:51 — Adam Cohen's molecule 33:24 — Markus Meister’s debunking 38:06 — The experiment 46:22 — Finding the LOV domain 54:11 — Singlets, triplets, and cysteine 56:54 — What the magnet is actually doing 1:05:13 — The conformational-change red herring 1:12:46 — The Quantum Biology Institute 1:19:31 — Founding Nonfiction Labs 1:24:38 — How to convince skeptical investors 1:29:39 — What a magnetogenetic medicine might look like 1:38:50 — First clinical indications 1:45:12 — The regulatory path 1:48:01 — What the field needs 1:54:30 — Appendix: Whiteboard lecture
2:07:35
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The Magnetobiology Episode: A company in San Francisco, called Nonfiction Laboratories, is building proteins (like antibodies and enzymes) that can be controlled using small magnets. In this episode, co-founder Maria Ingaramo and scientific advisor Andrew York explain how they engineered a protein, MagLOV, that responds strongly to magnetic fields, why most prior attempts have failed to replicate, and how the mechanism of magnetically-controlled proteins actually works. They also get into the “dream” use cases, like cancer drugs that activate only at the tumor, which might have a lower toxicity inside the body. This podcast is made possible by Astera Institute. I'm happy with how this episode came out. I think my interviewing skills are improving, and I'm getting better at building up context throughout the episode. Enjoy! Search for "The New Biology" on YouTube, Spotify, and Apple Podcasts. Timestamps: 00:00 - Opening 00:54 — Introduction 01:35 — The dream 05:38 — Why magnets vs. light or ultrasound 10:05 — The physics 17:48 — On the name "magnetogenetics" 21:25 — Birds and cryptochromes 27:09 — Why is the field filled with so much junk? 29:51 — Adam Cohen's molecule 33:24 — Markus Meister’s debunking 38:06 — The experiment 46:22 — Finding the LOV domain 54:11 — Singlets, triplets, and cysteine 56:54 — What the magnet is actually doing 1:05:13 — The conformational-change red herring 1:12:46 — The Quantum Biology Institute 1:19:31 — Founding Nonfiction Labs 1:24:38 — How to convince skeptical investors 1:29:39 — What a magnetogenetic medicine might look like 1:38:50 — First clinical indications 1:45:12 — The regulatory path 1:48:01 — What the field needs 1:54:30 — Appendix: Whiteboard lecture

Niko McCarty.

45,502 views • 4 months ago

A 3D structural model of an entire bacterial cell. Biology is the coolest thing ever.
0:29
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A 3D structural model of an entire bacterial cell. Biology is the coolest thing ever.

Niko McCarty.

170,610 views • 2 years ago

Our second book is now available for pre-order. 🎉 Embracing the book's technology theme, we did something special: We encoded the entire book into DNA & packaged it into stainless steel capsules, where it will live for tens of thousands of years. 1,000 copies were made... 🧵
1:35
NikoMcCarty's profile picture

Our second book is now available for pre-order. 🎉 Embracing the book's technology theme, we did something special: We encoded the entire book into DNA & packaged it into stainless steel capsules, where it will live for tens of thousands of years. 1,000 copies were made... 🧵

Niko McCarty.

103,081 views • 1 year ago

The Bitter Lesson for Biology — Adam Green on Scaling Laws for Virtual Cells In this episode, the founder of Markov Biosciences, Adam Green, explains the "bitter lesson" for biology, the idea borrowed from Richard Sutton that large unbiased datasets and the right training objective tend to outcompete models with hard-coded rules and human priors. We talk a lot about virtual cells, sources of bias in data, and his evidence that virtual cells pre-trained on plain observational data show clean scaling laws, getting monotonically better at predicting unseen perturbations as the models grow, and beating a state-of-the-art model built specifically for that task. Our interview was about 3 hours long, but cut to 1.5 hours. My main goal was to understand Adam's perspective on virtual cells and his goal to "solve biology." Search for "The New Biology" on YouTube, Spotify, and Apple Podcasts. Timestamps: 00:00 — Cold open 01:58 — Clinical predictions from a virtual cell 05:38 — What is a "virtual cell"? 08:01 — The problems with single-cell RNA-seq 11:31 — The urns analogy 19:54 — Observational vs. perturbation 23:29 — The bitter lesson for biology 29:06 — Geometric Plackett-Luce 38:27 — Ablations and loss function 47:23 — Cells as specimens 59:26 — Antibody-Drug conjugates 1:11:16 — Will we ever understand the cell fully?
1:29:33
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The Bitter Lesson for Biology — Adam Green on Scaling Laws for Virtual Cells In this episode, the founder of Markov Biosciences, Adam Green, explains the "bitter lesson" for biology, the idea borrowed from Richard Sutton that large unbiased datasets and the right training objective tend to outcompete models with hard-coded rules and human priors. We talk a lot about virtual cells, sources of bias in data, and his evidence that virtual cells pre-trained on plain observational data show clean scaling laws, getting monotonically better at predicting unseen perturbations as the models grow, and beating a state-of-the-art model built specifically for that task. Our interview was about 3 hours long, but cut to 1.5 hours. My main goal was to understand Adam's perspective on virtual cells and his goal to "solve biology." Search for "The New Biology" on YouTube, Spotify, and Apple Podcasts. Timestamps: 00:00 — Cold open 01:58 — Clinical predictions from a virtual cell 05:38 — What is a "virtual cell"? 08:01 — The problems with single-cell RNA-seq 11:31 — The urns analogy 19:54 — Observational vs. perturbation 23:29 — The bitter lesson for biology 29:06 — Geometric Plackett-Luce 38:27 — Ablations and loss function 47:23 — Cells as specimens 59:26 — Antibody-Drug conjugates 1:11:16 — Will we ever understand the cell fully?

Niko McCarty.

28,362 views • 4 months ago

I've started writing my book: "Biology is a Burrito & Other Essays." It is an interactive and highly visual look into the beauty, speed, and complexity of a living cell. I'm planning to print hardcover books while serializing the essays online. The first essay is now available at This was inspired by Stewart Brand's latest book, "Maintenance of Everything," which he developed in serialized form with Works in Progress. One cool thing about that book was that he improved each chapter with reader comments before printing the physical copies! I'll be doing the same with this book. If you send me feedback that improves the text, I'll credit you online and in the final print version. You can also sign up to get email updates when a new essay launches. Hope you enjoy!
0:46
NikoMcCarty's profile picture

I've started writing my book: "Biology is a Burrito & Other Essays." It is an interactive and highly visual look into the beauty, speed, and complexity of a living cell. I'm planning to print hardcover books while serializing the essays online. The first essay is now available at This was inspired by Stewart Brand's latest book, "Maintenance of Everything," which he developed in serialized form with Works in Progress. One cool thing about that book was that he improved each chapter with reader comments before printing the physical copies! I'll be doing the same with this book. If you send me feedback that improves the text, I'll credit you online and in the final print version. You can also sign up to get email updates when a new essay launches. Hope you enjoy!

Niko McCarty.

34,308 views • 5 months ago

My first podcast is out today with Mark Budde 🦕🏆, CEO of plasmidsaurus. Plasmidsaurus took whole-plasmid sequencing from $600 to $15 and turned a "boring" service company idea into a hugely successful company that now serves >70,000 scientists. We talked about what it means to build a "boring" company, whether the Plasmidsaurus idea could apply to other technologies (like CRISPR screens), and why Plasmidsaurus isn't expanding into China. This podcast is made possible by Astera Institute. 00:00 – Enter Plasmidsaurus 01:21 – Reducing sequencing costs by 40x 04:17 – Scaling Oxford Nanopore technology 06:29 – Venture capital and building a "boring" company 13:03 – Plasmidsaurus vs. traditional CROs 22:25 – On selling customer data 30:10 – Building a moat 37:08 – 50-minute results 39:26 – Logistics and the UPS partnership 48:42 – The Chinese market 50:20 – Playbook for new biotech founders 52:31 – The future of biological reasoning and AI You can find the podcast, THE NEW BIOLOGY, on YouTube, Spotify, and everywhere else.
57:31
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My first podcast is out today with Mark Budde 🦕🏆, CEO of plasmidsaurus. Plasmidsaurus took whole-plasmid sequencing from $600 to $15 and turned a "boring" service company idea into a hugely successful company that now serves >70,000 scientists. We talked about what it means to build a "boring" company, whether the Plasmidsaurus idea could apply to other technologies (like CRISPR screens), and why Plasmidsaurus isn't expanding into China. This podcast is made possible by Astera Institute. 00:00 – Enter Plasmidsaurus 01:21 – Reducing sequencing costs by 40x 04:17 – Scaling Oxford Nanopore technology 06:29 – Venture capital and building a "boring" company 13:03 – Plasmidsaurus vs. traditional CROs 22:25 – On selling customer data 30:10 – Building a moat 37:08 – 50-minute results 39:26 – Logistics and the UPS partnership 48:42 – The Chinese market 50:20 – Playbook for new biotech founders 52:31 – The future of biological reasoning and AI You can find the podcast, THE NEW BIOLOGY, on YouTube, Spotify, and everywhere else.

Niko McCarty.

29,522 views • 5 months ago

I made an interactive enzyme simulator. Change the temperature, add or remove inhibitors, and tune the probability that enzymes bind their substrates. Watch as the reaction rate moves up or down in real-time. Maybe this will be a helpful teaching tool.
0:44
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I made an interactive enzyme simulator. Change the temperature, add or remove inhibitors, and tune the probability that enzymes bind their substrates. Watch as the reaction rate moves up or down in real-time. Maybe this will be a helpful teaching tool.

Niko McCarty.

60,605 views • 1 year ago

New book chapter: "How to Weigh a Cell." This chapter explains how scientists have weighed cells throughout history, often using simple equipment and back-of-the-envelope calculations. It has lots of interactives, so you can "repeat" the experiments directly in your browser.
0:24
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New book chapter: "How to Weigh a Cell." This chapter explains how scientists have weighed cells throughout history, often using simple equipment and back-of-the-envelope calculations. It has lots of interactives, so you can "repeat" the experiments directly in your browser.

Niko McCarty.

23,637 views • 4 months ago

The bacterial flagellum looks like a simple tail, or whip. But it’s actually a rotating motor, and perhaps the most sophisticated protein complex nature has ever evolved. In e. coli, these motors are capable of astonishing speeds; about 15,000 rpm. (The world record, according to one study, is for a Vibrio cell that was “clocked at 100,000 rpm by laser microscopy.) The flagellum propels the cell forward at speeds of 20-30 microns per second, or roughly 15 body lengths per second. If scaled up to the size of a cheetah, E. coli would *nearly* be the fastest land organism. The darting movements of a microbe were first observed in 1676 by Antony van Leeuwenhoek, a Dutch cloth merchant. Antony was delighted by the motion of his “animalcules,” writing: “I must say, for my part, that no more pleasant sight has ever yet come before my eye than these many thousands of living creatures, seen all alive in a little drop of water, moving among one another, each several creature having its own proper motion.” But Leeuwenhoek did not see flagella. He assumed, rather, that these animalcules must be “furnished with paws” instead. Christian Ehrenberg would not properly describe flagella until 1836. But amazingly, all the way up until the 1970s, nobody actually knew how the flagellum spun! In 1973, there were two competing models people argued over: the helical-wave (bending) model and the rotating (corkscrew) model. The first model suggested that the flagellum whipped back and forth, side-to-side, to propel the cell like paddle. The corkscrew model suggested that the whole flagellum instead spins around like a screw. In 1974, the corkscrew model finally won out. For two separate studies, scientists affixed flagella to glass slides using antibodies, and watched as the cells spun around and around like corkscrews. And finally, in just the last year, high-resolution structures of the flagellum have revealed a LOT more about its intricate assembly. The tail is made from ~20,000 self-assembling copies of a single protein, called flagellin. A “driveshaft,” or rod, spins the tail and is itself made of 26 protein subunits. Each “motor” in E. coli consists of 11 stators, each of which is made from 7 proteins.(Other types of cells have even more stators, and swim with much higher torques.) The flagellum spins when protons flow into the cell through tiny channels in these stators; akin to water running through a turbine. Each proton makes a small part of the stator change shape and push against the rotor, nudging it forward one step. With dozens of stators working at once, these nudges quickly spin the propeller. I'm writing an essay for Asimov Press about this now, and am really enjoying learning about the flagellum and its history. It's an extraordinarily complicated structure, though, and has been a challenge to understand!
0:05
NikoMcCarty's profile picture

The bacterial flagellum looks like a simple tail, or whip. But it’s actually a rotating motor, and perhaps the most sophisticated protein complex nature has ever evolved. In e. coli, these motors are capable of astonishing speeds; about 15,000 rpm. (The world record, according to one study, is for a Vibrio cell that was “clocked at 100,000 rpm by laser microscopy.) The flagellum propels the cell forward at speeds of 20-30 microns per second, or roughly 15 body lengths per second. If scaled up to the size of a cheetah, E. coli would *nearly* be the fastest land organism. The darting movements of a microbe were first observed in 1676 by Antony van Leeuwenhoek, a Dutch cloth merchant. Antony was delighted by the motion of his “animalcules,” writing: “I must say, for my part, that no more pleasant sight has ever yet come before my eye than these many thousands of living creatures, seen all alive in a little drop of water, moving among one another, each several creature having its own proper motion.” But Leeuwenhoek did not see flagella. He assumed, rather, that these animalcules must be “furnished with paws” instead. Christian Ehrenberg would not properly describe flagella until 1836. But amazingly, all the way up until the 1970s, nobody actually knew how the flagellum spun! In 1973, there were two competing models people argued over: the helical-wave (bending) model and the rotating (corkscrew) model. The first model suggested that the flagellum whipped back and forth, side-to-side, to propel the cell like paddle. The corkscrew model suggested that the whole flagellum instead spins around like a screw. In 1974, the corkscrew model finally won out. For two separate studies, scientists affixed flagella to glass slides using antibodies, and watched as the cells spun around and around like corkscrews. And finally, in just the last year, high-resolution structures of the flagellum have revealed a LOT more about its intricate assembly. The tail is made from ~20,000 self-assembling copies of a single protein, called flagellin. A “driveshaft,” or rod, spins the tail and is itself made of 26 protein subunits. Each “motor” in E. coli consists of 11 stators, each of which is made from 7 proteins.(Other types of cells have even more stators, and swim with much higher torques.) The flagellum spins when protons flow into the cell through tiny channels in these stators; akin to water running through a turbine. Each proton makes a small part of the stator change shape and push against the rotor, nudging it forward one step. With dozens of stators working at once, these nudges quickly spin the propeller. I'm writing an essay for Asimov Press about this now, and am really enjoying learning about the flagellum and its history. It's an extraordinarily complicated structure, though, and has been a challenge to understand!

Niko McCarty.

51,977 views • 1 year ago

There is a new paper in Science proposing a mechanism for how homing pigeons navigate on cloudy days. (Hint: It's magnetic fields.) As with many magnetobiology papers, though, I'm skeptical of their proposed mechanism. These researchers, from Germany, found that pigeons have macrophages in their liver that accumulate lots of iron. They confirmed this with staining and other analyses. These macrophages also tend to cluster near nerve fibers in the liver (this is important for later). Then they did a really interesting experiment: - Train 34 pigeons to fly a particular 19-kilometer route. Ensure they all do this well. - Split the pigeons into two groups: treatment and control. - Inject the treatment group pigeons with liposomes loaded with clodronate. The macrophages eat these liposomes, and then clodronate kills the cells and scatters the iron. - Release the pigeons, from both groups, on an overcast day (it's thought that pigeons use magnetic fields to navigate when there is no sun). - All of the control pigeons reached their destination within 70 minutes, but the treated pigeons scattered in random directions. - (Important control experiment: The treated pigeons, released on a sunny day, flew like normal and reached their destination.) - This is taken as evidence that ??? macrophages --> iron --> navigation ??? via magnetic fields. But the mechanism is fuzzy. This experiment is super interesting, and it's clear that the treated pigeons really are unable to home to their destination using a magnetic field. But I'm not entirely convinced by the mechanism these authors propose. The main claim is that these iron-loaded macrophages "align" in a magnetic field, and that they shift according to the bird's orientation so that it can fix its direction. These macrophages (somehow) send signals to the nerve fibers in the liver, which then pass the messages to the brain, which allows the bird to navigate. The news coverage for this story suggests how this might happen: "One idea is that as the bird shifts its position relative to Earth’s magnetic field lines, the ferritin changes orientation and tugs on the web of fibers within a macrophage, possibly triggering the release of signaling molecules." (All you need to do is read the 2016 Meister paper, from the images below, to understand why such a mechanism is physically dubious.) The problem, though, is that the authors show (in their own study) that the iron in these pigeons' livers only act as a stable magnet at super low temperatures, below about 12 degrees Kelvin (or -260 degrees Celsius). At normal, physiological temperatures, the iron would be scrambled by the thermal motions of the tissue. Every measurement in the paper is taken at cryogenic temperatures, but a bird's body temperature is much higher, which means heat would likely destroy any magnetic alignment. The authors claim that MILLIONS of iron particles in the liver are all acting together to escape this effect, but they don't demonstrate the mechanism convincingly at all. If this claim is true, why not take homing pigeons (control vs. macrophage-depleted) and then rotate a magnetic field around them? You could record their neurons to see if there is some kind of signal coming from the liver.
0:22
NikoMcCarty's profile picture

There is a new paper in Science proposing a mechanism for how homing pigeons navigate on cloudy days. (Hint: It's magnetic fields.) As with many magnetobiology papers, though, I'm skeptical of their proposed mechanism. These researchers, from Germany, found that pigeons have macrophages in their liver that accumulate lots of iron. They confirmed this with staining and other analyses. These macrophages also tend to cluster near nerve fibers in the liver (this is important for later). Then they did a really interesting experiment: - Train 34 pigeons to fly a particular 19-kilometer route. Ensure they all do this well. - Split the pigeons into two groups: treatment and control. - Inject the treatment group pigeons with liposomes loaded with clodronate. The macrophages eat these liposomes, and then clodronate kills the cells and scatters the iron. - Release the pigeons, from both groups, on an overcast day (it's thought that pigeons use magnetic fields to navigate when there is no sun). - All of the control pigeons reached their destination within 70 minutes, but the treated pigeons scattered in random directions. - (Important control experiment: The treated pigeons, released on a sunny day, flew like normal and reached their destination.) - This is taken as evidence that ??? macrophages --> iron --> navigation ??? via magnetic fields. But the mechanism is fuzzy. This experiment is super interesting, and it's clear that the treated pigeons really are unable to home to their destination using a magnetic field. But I'm not entirely convinced by the mechanism these authors propose. The main claim is that these iron-loaded macrophages "align" in a magnetic field, and that they shift according to the bird's orientation so that it can fix its direction. These macrophages (somehow) send signals to the nerve fibers in the liver, which then pass the messages to the brain, which allows the bird to navigate. The news coverage for this story suggests how this might happen: "One idea is that as the bird shifts its position relative to Earth’s magnetic field lines, the ferritin changes orientation and tugs on the web of fibers within a macrophage, possibly triggering the release of signaling molecules." (All you need to do is read the 2016 Meister paper, from the images below, to understand why such a mechanism is physically dubious.) The problem, though, is that the authors show (in their own study) that the iron in these pigeons' livers only act as a stable magnet at super low temperatures, below about 12 degrees Kelvin (or -260 degrees Celsius). At normal, physiological temperatures, the iron would be scrambled by the thermal motions of the tissue. Every measurement in the paper is taken at cryogenic temperatures, but a bird's body temperature is much higher, which means heat would likely destroy any magnetic alignment. The authors claim that MILLIONS of iron particles in the liver are all acting together to escape this effect, but they don't demonstrate the mechanism convincingly at all. If this claim is true, why not take homing pigeons (control vs. macrophage-depleted) and then rotate a magnetic field around them? You could record their neurons to see if there is some kind of signal coming from the liver.

Niko McCarty.

22,441 views • 4 months ago

How to See Microbes from the Sky — Yonatan Chemla on Hyperspectral Biology Scientists have studied bacteria under microscopes for 400 years. But Yonatan Chemla, a postdoctoral fellow at MIT, has developed a technology that lets us see microbes from a drone 100 meters in the air. In this episode, we discuss the emerging field of "hyperspectral biology," which uses hyperspectral cameras (first built by NASA in the 1980s) to detect molecules with unique light-absorption signatures. With this technology, you could engineer a microbe to sense a landmine, for example, and release a pigment in response. A drone could then spot that pigment from hundreds of meters away, thus identifying the locations of the landmines. By spraying other types of engineered microbes over a field, they could similarly map heavy metals, report on soil health, or find gold deposits. But almost none of this can happen in the United States. The EPA regulates engineered microbes as chemicals under the Toxic Substances Control Act, a 1976 law that never mentions biology, and the agency seems to have approved just one product through it. As a result, many of biotechnology's most useful ideas — microbes that break down plastic, sense landmines, or remove pollution from water — never leave the laboratory. This episode is much more casual than other podcasts I've recorded. We talked for many hours, into the early morning, and so I also feel like my lines of questioning are not as good as it could've been. The video quality is also not great; sorry! Chapters: 00:00:00 Introduction 00:04:08 Applications for hyperspectral biology 00:07:33 How to build a biosensor 00:13:00 Molecular absorption data 00:22:12 How hyperspectral cameras work 00:38:15 Spatial resolution and satellite monitoring 00:51:04 Regulations around environmental release 01:08:44 Risk vs progress
1:23:23
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How to See Microbes from the Sky — Yonatan Chemla on Hyperspectral Biology Scientists have studied bacteria under microscopes for 400 years. But Yonatan Chemla, a postdoctoral fellow at MIT, has developed a technology that lets us see microbes from a drone 100 meters in the air. In this episode, we discuss the emerging field of "hyperspectral biology," which uses hyperspectral cameras (first built by NASA in the 1980s) to detect molecules with unique light-absorption signatures. With this technology, you could engineer a microbe to sense a landmine, for example, and release a pigment in response. A drone could then spot that pigment from hundreds of meters away, thus identifying the locations of the landmines. By spraying other types of engineered microbes over a field, they could similarly map heavy metals, report on soil health, or find gold deposits. But almost none of this can happen in the United States. The EPA regulates engineered microbes as chemicals under the Toxic Substances Control Act, a 1976 law that never mentions biology, and the agency seems to have approved just one product through it. As a result, many of biotechnology's most useful ideas — microbes that break down plastic, sense landmines, or remove pollution from water — never leave the laboratory. This episode is much more casual than other podcasts I've recorded. We talked for many hours, into the early morning, and so I also feel like my lines of questioning are not as good as it could've been. The video quality is also not great; sorry! Chapters: 00:00:00 Introduction 00:04:08 Applications for hyperspectral biology 00:07:33 How to build a biosensor 00:13:00 Molecular absorption data 00:22:12 How hyperspectral cameras work 00:38:15 Spatial resolution and satellite monitoring 00:51:04 Regulations around environmental release 01:08:44 Risk vs progress

Niko McCarty.

15,854 views • 3 months ago