Welcome to Stuff to Blow your Mind from how Stuff Works dot com. Hey, welcome to Stuff to Blow your Mind. My name is Robert Lamb and I'm Joe McCormick and Robert. Today we are going to be talking about undead jeans. Yes, undead jeans, as they've been called in some of the headlines making the rounds. Some have even dared to call them zombie jeans. But I like to think even even those headline writers feel a little bit dirty actually calling them zombie jeans. I think zombies is a metaphor that
has just invoked too often. Now. I used to love zombies. Uh ten years ago or so, or maybe even a little before that is when it was like peak zombie for me. In two thousand four, I saw a Knight of the Living Dead and Dawn of the Dead that year, and and that was enough. And then suddenly we're in this zombie world where everything is zombies all the time. Yeah, it's been. I'm tired of it. It's been. It's been rolled out just far too often in science headlines. So yeah,
I think we should do more. Just undead genes or undead could be a vampire, it could be a litch, yet litch genes would be good. I would like that, or even uh even something like um necro genes. I could be over that as well. But the cool thing is is what we're talking about here is not completely out of keeping with these concepts, you know. It's that there is there is a strong enough thread connecting even the more outlandish headlines to the really cool science that's
going on here. Yeah, and so specifically, this is going to be referencing a paper that was pre published this summer in June. I think we're actually still waiting on it to come out in in a journal form, but it was pre published on a pre publication server bio archive, and and it's been covered in that form. So just be aware that that, you know, we don't have all the opinions in yet, right, But back back to undead gene So we of course probably don't have to say this,
but just to be clear, this is a metaphor. We're not talking about any kind of magical or supernatural resuscitation. Instead, we're trying to communicate what's very unusual about the activity of genetic structures that have been discovered to continue after what's known as organismal death. The death of the overall body and uh. And it's not unusual, of course to use metaphors to think about what the body does, but
it is helpful to find the right ones. Yeah, we depend on a number of metaphors to understand the human body. Machine is a big one, you know, the biomechanical man um. I I'm always partial to horse and rider versus centaur. Who's the rider? Well, horse and ride, horse and rider, the rider's the brain. Okay, the horses the body. And this is a faulty way of looking at the at the mind body connection. Centaur makes more sense where the tour are joined. Um. And in addition to that, you
also see vessel every now. And I think we've talked about like spaceship, the spaceship human body before. UM. But if you think of it as a civilization, as I did in looking at this paper, you know what is death about the apocalypse civilizational extinction exactly because you have in the human body essentially have a vast kingdom of somewhere in the neighborhood of a hundred trillion cells, thirty thousand genes, eleven distinct systems, and on top of all
of this, just the the the manifestation of cognition, environmental sensitivity, navigation, and self awareness, all of these systems, this this wondrous manifestation of consciousness, all of it working together and ruled over by genetics and epigenetics. So the genes and then the way the genes are expressed, at least until what happens everything falls apart, right right, Okay, yeah, I'm kind
of seeing this. So maybe in this metaphor, you can think about genes as what the constitution that governs the society or the council of elders in their roads and the servants that that rule over the fabulous city. Uh I guess you could probably say that no real civilization is as thoroughly prescribed by any kind of written document that says how everything's going to work as the body is by the genes. Yeah, and then of course that's
not to say that everything works perfectly. Certainly the kingdom of the human body has its issues and has its problems. But sometimes you might get a cancerous rebellion. Yeah yeah, cancerus rebellion, or just things that don't particularly work right, But we kind of we evolved into it with the current system of government is based on old systems of government and and therefore the legacy is still there. Yeah.
And in this sense, I guess you could look at death as if death in the body is energy bankruptcy. Suddenly cells can't get the energy they need in order to do what they need to do. That's sort of like in a civilizational sense, if there's a total collapse of resource distribution, Suddenly you can't get food and energy, you know, power, water to the people who need them exactly. And when that when that happens, say in a kingdom, in a in an empire, we it's not like everything
just completely falls apart. I mean, the things may fall apart, the center may not hold, but everybody doesn't just vanish into nothing. Um. And and we see a similar right, yeah, yeah, we see a similar thing happened with the body, just as certain factions in a post apocalyptic scenario would would try and hold onto power or carry out their duties, you know, bravely delivering the mail no matter of what has happened, while other populations, such as microbiota and in
our body riot and rampage. So just as warlords and bandit kings rise up in the wake of a kingdom's fall, so too, do certain genes come to life after death, some manifesting in ways that they haven't since the womb. And that's the crazy thing here we have to have. You know, what is happening here. We tend to view death is this great unraveling the system after sift system just going dark? So why would certain genes activate on
the other side of death? I wanted to be an uptick and activity from certain genes after the organism has technically died. Well, that's a good question. Eventually, we're gonna look at this paper, specifically that it's been pre published this summer and discuss its findings. But first I think we need to set a little bit of context about what exactly is happening in the body with with genes and how they're expressed. So a question you might have
wondered before. Maybe you already know the answer to this, Maybe it's a little bit kind of vague. How do you get from genes to bodies? We all know this metaphor that genes are the blueprints, right, You know that genes have some sort of information encoded in them that will allow you to build a body that does what your body does. But really a gene is a molecule.
A gene is a tiny molecular structure in DNA, and it's a chain of nucleotides, which are organic molecules made of a nitrogenous molecule based and usually got a phosphate group and a carbon sugar. But bodies are these big macro structures, relatively gigantic machines, and they're made primarily of cells full of proteins and protein structures that determine what the cells can do. And ultimately this collection of cells works as a sort of vehicle for gene replication, basically
by being a gigantic energy trap. Now, how do you get from one to the other. This tiny molecule has to build your whole body well. In order to get from this tiny chain molecule to create an effect in the outside in in the the outer world the body at large, the gene has to be expressed. This is the term gene expression, and it's the name for the process that gets you from DNA to cell function. And then of course cell function at large determines what your
body is and what it does. But at the ground level, this process is just biochemistry. You might remember these words from sometime learning them in school. Will transcription and translation do they ring a bell? Gene gene expression is what these words refer to. So you have a chain of nucleotides in your DNA and it's a gene for I was trying to think of what I could say a gene for maybe fingernails growing really fast. Could that be
a thing that's gene regulated? Perhaps? Uh so. First, in order for that gene to be expressed, there's what's known as transcription, and this is going to be key to the paper that we're looking at in a bit. Transcription is where an enzyme called RNA polymerase latches onto a section of the DNA molecule and it starts pulling together all these other molecules to create a copy of that DNA section out of this substance RNA, which is similar to DNA. Now, sometimes that RNA copy alone does something
useful in the cell. You've just made this RNA copy and it goes off and does its job. Other times, RNA is what's known as messenger RNA and essentially acts to take that that gene and carry it to a structure inside the cell like a ribosome, and there at the ribosome which arrives. Zome is a tiny molecular machine.
It's a nanomachine that does work inside the cell. At the ribosome, we get to the process of translation, and that's where the rb zome essentially metaphorically, it reads the RNA photocopy of the gene and then translates into proteins that assume a function within the cell. These proteins determine what the cell can do, so that that's how you
get from genes to a cell doing something to a body. Um. So, of course we speak metaphorically in terms like copies and reads, but keep in mind these are all chemical reactions, just like you know, Robert, did you ever make a science fair volcano? Oh? You bet I have, and I will make a few more before I'm done. Oh yeah, they are fun. I've never made one just for fun at home. I guess maybe when I have Well, there's a you know, there's a lot of set up with the with the
volcano itself. But yeah, what's the classic recipe for the science fair? So you need vinegary, you need a little food coloring, uh huh, and then you get volcano. Right. I never thought of food coloring that would make it more lava issue. If you make it orange, you've gotta make it orange or red otherwise, Um, otherwise you're just doing bacon, soda and vinegar. Right. Well, so that's a very simple chemical reaction. But this is a much more
complex chemical reaction. And these chemical reactions are taking place between highly specialized molecules shaped by biochemical evolution. But back to those macro characteristics, the you know, the body as a whole, the big characteristics you see, all those observable characteristics of an organism, uh that emerge as a product of genes expressing themselves in an environment. All that together is known as the phenotype. You've got your genotype, that's
your genes and they make your phenotype. So your hair is a part of your phenotype. Your toes are a part of your no type, and your ability to run, and your fear of clowns, and you're you know, delightful craving for deviled eggs. All of that is part of your phenotype. So one would typically assume that, well, the death is sort of the end of the phenotype being able to do its job right. The death of the organism means well, I can't get energy to my cells anymore.
Everything's fallen apart, So the phenotype just ends. It's kind of like one like it's kind of like the the genotype. They are the hands creating the shadow puppet, right, and then the phenotype is the shadow on the wall that looks like a barking dog. Right. If the flashlight goes out, that you can't make the shadow on the wall anymore. But the hand, the hands are still there. Yeah, So
the hands are still there. And so the phenotype is not necessarily based on the brain being conscious, or the heart circulating blood, or the lungs pulling in oxygen and purging CEO two. Even though we think of these things as the primary signs of life from a purely chemical standpoint, if you're just some you know, cosmic chemistry professor looking at what we do and you're not very concerned about the experience of being alive, these are not the primary systems.
These are support systems, and they're all in service of gene replications. So genes make these systems to do the things they do because they help trap, conserve, and judiciously spend energy that can be used to make gene replication happen.
More often and more successfully. So, even though your brain goes inactive and your heart stops beating and your lung your lungs stop pumping, you know, the genes in your cell are still in some sense independent machines that can continue to do things as long as they have the energy to do them, and they would go on without you if they could. They don't care about you. Even though you, the organism are gone. The genes, as independent
machines are, are still trying to do their thing. So does your core biological essence live beyond the death of your mind and body at large? Is their gene life after body death? The answer appears to be yes, and the details can get a little bit creepy. Yeah, let's get into the undead genes that that here. So we knew from previous day Like this isn't just completely out of nowhere. So we knew from previous studies looking at blood and liver tissue that a few human genes remain
active in the cadaver age. That's like after the Bronze Age, you're still continuing your civilization metaphor after the life age into the cadaver age. It continues. But recent work from microbiologists Peter Noble of the University of Washington, Seattle and his team have revealed a number of genes that that seemed to activate after death. So again, the kingdom fall on apart, the walls are crumbling, barbarians flowed the street. There's no going back to order life, bread and circuses.
But there are certain certain groups in the city that are still going to do their job. They're still going to deliver the mail, They're still gonna enforce the law. You have maniac cops roaming the streets. Yes, the civilization has collapsed, but but some of the machines within it still continue to do their thing. Yeah, and so, but since there's no going back, since the organism is organism is dead, since the human body is dead. At this point, it's not an raw area that we really knew that
much about. As the authors themselves point out, quote, it is not well known whether gene expression diminishes gradually or abruptly stops in death, nor whether specific genes are newly expressed or upregulated. Upregulated means, of course, uh an increase in their activity. So they decided to check it out. Yeah, So the paper that they have in pre publication now is known as Thanato transcript home my new favorite word, the NATO transcript Dome genes actively expressed after organismal death,
And that's pre published in bio Archive. Last I read, it's still under peer review at a journal somewhere. I think, um, though, if it's already come out and somebody knows about it, please contact us and let us know. But anyway, this refers to this collection of genes that continue to be expressed after organismal death, as as the Fanato transcript Dome from the Greek Thanatos for death and transcript dome for
the genes that undergo transcription. But I guess the question is, how could you actually examine this, Like, what would you do to find out if there are genes that are certainly suddenly starting to be expressed or continuing to be
expressed after death happens at the total body level. Yeah, because experiments on humans that involve, you know, getting right in their close at the death point, generally those are those are the kind of experiments that either very hard to carry out or they're a little unscrupulous in nature.
So we're not talking about humans. And uh, though it does bring me back to those old experiments about the weight of the soul and all the painful average you had to go who to get a willing dying individual to set on your set, to lay down on a bed on a set of scales for you. But no, they did not bother with humans in this. They examined post mortem gene expression into model organisms, the zebra fish and the common house mouse, with a focus on examining
genes with expression increases after death. Again, we're not talking about um apoptosis or necrosis, but genes that suddenly light up with doomed life again like a band of waste wandering survivors. Uh So, So they expected the genes to shut down, but they didn't. But they did not in all cases. Although most of these upregulating genes up to their activity in the first twenty four hours after the animals expired and then tapered off. And in the fish,
some genes remained active four days after death. So that that's crazy, Yeah, thinking about four days after the organism has died, there are still some genes in some cells or a body that are still doing things. They're they're undergoing transcription, they're having this chemical reaction. That's the beginning of the process to create proteins. The fingers are still working furiously to make that dog shadow puppet on the wall. Now, they had to kill a bunch of fish and mice
for this. Uh that's how you get the specific time of death for the lab animals case. I think they killed the fish with ice water. Yeah, they Well, they have a pretty They have pretty exhaustive details about the methodology in the paper. Um, but suffice to say they gave them all an irrefutable death so as to study what came next. The mice, I know they killed by cervical dislocation, which is the humane way you're supposed to execute a mouse in the lab. You dislocate the skull
from the spine. They're just like in an action movie with like Geene Claude van Dam with his hands, Like Steven Seagal does that right, Oh yeah, he grabs somebody's head and just breaks it off, just this casual little movement. It always does make me a little bit sad to read about mice like that, but I think we are actually learning things from this kind of research that could potentially lead to medical research two very useful applications in
the real world. So after they euthanize these animals as as they said, Uh, they took samples and they leaned in for a closer look, observing the non random up regulation of certain genes. And that's important here because it's not just like, oh, the everything's out of order and things are clicking on and off randomly. Yeah, yeah, that that is worth noting. So it wasn't just like all the genes started just kind of lighting up as they
noticed specific genes are being up regulated at this time. Yeah. So it's not like, oh, the chicken's head is cut off and it's just running. It's no, it's more like the chicken's head is cut off, but it's running specifically to a bar across town to get a drink or something. Um. And so so they sorted the genes into several different categories.
So I'm just gonna and I and we're not gonna go through all of the genes in all of the categories, but just the categorization they rolled out, I think it's very illuminating stress, immunity, inflammation, apoptosis, solute ion, protein transport, embryonic development, epigenetic regulation, and cancer. Okay, so one part of their results that is not so surprising is that a lot of the gene expression that you see continuing
after death is related to emergencies happening within the body. Yeah, yeah, shock emergency. They're concerned with stimulating inflammation and the immune system. I think these are the police and firefighters that are swamping the post apocalyptic city, right. The genes performed tasks such as spurring inflammation, firing up the immune system, and counteracting stress in the organism, just doing their job in
the face of cataclysm, even though there's actually no hope. UM. Specifically, just give you a taste of some of the specifics. You know, that kind of makes sense, even though there's no hope. The cell doesn't really know there's no hope. It's not it's not his job. This is doing his job that all the other stuffs above his pay grade. Uh. Specifically, the stress response genes were assigned to three groups. UH, heat, shock, protein,
hypoxia related, and other responses such as oxidative stress. Hypoxia of course would be oxygen deprivation. Yeah, your cells know how to respond when they're not getting the oxygen they need exactly and also sorts not even in both organisms UM organismal death activated heat shock, hypoxia, and other stress genes which varied in the timing and duration of up regulation within and between organisms. But so they set off the stress responses death. Yeah, and all that that makes sense, right,
totally totally on board. That makes total sense that these genes would be firing up in this time of chaos and unrest. But the really surprising thing was the embryonic gene activity. Developmental genes that normally helps scalp the embryo, but they aren't needed after birth, and that the possible reason here is because and this is according to the authors, is that cellular conditions and newly dead corpses resemble those in embryos. And there's something about that man that manages
to be both comforting and grotesque at the same time. Yeah. Uh yeah. So you might be wondering, like, wait a minute, why how could this happen? That you have developmental genes that are, you know, not normally expressed in life. So these genes that help you develop as an embryo, they remain a part of your genome. They're still there, but they're known, they're they're quote silenced, which means they're regulated in such a way that they no longer undergo gene expression. Uh,
they're still there. They're just turned off. But in organismal death, all those off switches just sort of get opened right back up. They switch back on. These silence genes are set free to be loud and proud. Yeah, it's just it's crazy to think about. But along with that, so we've got development genes, embryonic genes. You know, these are causing the development of body tissues, cell division. One thing you might not be surprised to see. Going along with
that is genes that are related to cancer. Yes, several cancer causing genes also activated and at this result, according to the authors, could possibly explain why some individuals who received transplants from the recently deceased have higher have a higher risk of cancer. Now I didn't actually know this fact,
I was. I was not really aware of that either, but yeah, according to the author is apparently people who receive like an organ transplant from a recently deceased person, you die in an accident, they take your organs, give them to someone who needs them. You're more likely to experience cancer like a tumor in those organs. So that that would seem to make sense if the death response in the overall body triggers some kind of genetic activity
within these organs that sets off the cancer program. Yeah. I mean, it's kind of like communication transfer between the two worlds, between the living world and the post death world, the post apocalyptic. It's kind of like if your local neighborhood was going to hire a neighborhood watch and they hired the Brotherhood of Steel from the Games. You know they're They're from a totally different time with a totally
different set of values. Okay, I wanted to read one quote from the paper that I thought was very illustrative of what we would have expected from this kind of study and what we found instead. So the author's right quote. We initially thought that sudden death of a vertebrate would be analogous to a car driving down the highway and running out of gas. For a short time, the engine pistons will move up and down, and spark plugs will spark, but eventually the car will grind to a halt end
quote die. Yet in our study we find hundreds of genes are upregulated many hours post mortem, with some e g. And then they give the names of some genes that are especially interesting here upregulated days after organismal death. This finding is surprising because in our car analogy, one would not expect window wipers to suddenly turn on and the horn to honk several days after running out of gas. So that that communicates the you know, the the energy
bankruptcy problem. You don't have energy to do anything with anymore at the at the total system level, so you would expect just nothing to happen anymore. But apparently if there's still energy within some cells in the body, you know, still some local energy that can be used to do something, the body is going to do something with it. And uh. This also they pointed out that since we saw this, uh, this post mortem up regulations, post mortem gene expression happening
in both mice and zebra fish, that's interesting. It happened in both of these very different organisms. It's reasonable to assume that other multicellular eukaryotes, so you know, uh, organisms with a cell nucleus that have multiple cells like us, will show the same kind of phenomenon. It's not just an artifact of one branch of the tree of life. And that's kind of weird, like, so what if that includes humans? So this continued gene expression after death leads
to some really bizarre questions. I want to quote one that they bring up in the paper. What would happen if we arrested the process of dying by providing nutrients and oxygen to these tissues they're talking about tissues that show continued gene expression after death. Quote, it might be possible for cells to revert back to life, or take some interesting path to differentiating into something new, or lose
differentiation altogether, such as in cancer. I'm imagining, Oh my god, the post death expression of the genome reawakened into a living organism. This would make a great sci fi movie.
That the Thanato transcriptome man, I like it. The the the idea I'm kind of envisioning here based on this is essentially you could take a newly deceased individual and if not keep their body alive, at least keep certain tissues alive, keep certain there are certain aspects of their body remain living even though the brain is dead, even though the body is essentially dead as well. I mean, right now, I think the the organ preservation regime is well,
it's preservation. You know. They want to get the organ into very cold uh, too cold conditions so that it's uh sort of freezes up and doesn't undergo too much cell death. But yeah, what would it mean to to take tissues that are still showing gene expression and give them something to work with, put some energy back into
the bank. I live, I die, I live again. But anyway, we we can actually get some interesting ideas out of this that might be useful in in medicine or in forensics even I mean, first of all, just a broadsense. It allows us to better understand life itself, because despite humanity's tendency to define death is this outside force is a thing that happens to our body, even as a
personified force. Um. Despite all of this, death is something our bodies do, Okay, And to understand how life behaves at or even past the death point is to better understand how life works. I mean, I would say ultimately, understanding death is is one of the most important things in understanding what the boundaries of life are. I mean, if you think about it, our earliest understanding of what is necessary to sustain life must have come from observations
about what specific deprivations lead to death. Yeah, like oops that I held that guy underwater for a little bit too long, apparently, and he's no longer alive. I guess we can't live underwater. Yeah, exactly so. Deprivation of air leads to death within minutes, deprivation of water within day. His deputation of food or sleep can mean death within weeks. If I take this this bone from a taper and beat this other humanoid with it, they cease to function.
I guess we can't. We can't. That's actually a question you wouldn't normally think to ask. But why does that happen? Can you imagine at the troglodyte level, You know, we're very very early human trying to figure out what it is about massive blood loss and beating that causes a person to stop moving. It's it's one of This is the type of question I encounter a lot now with a four year old, not specifically about violent apes beating
each other to death. I haven't let him watch the two thousand and one yet, but but I get a lot of questions where I'm forced to reevaluate just basic realities of life. Uh, such as you know, my son will asked, why do we lock the door at night? Well, we don't want people coming in the house while we're asleep. Why not? Why not? And that's a terrifying question to be asked because you can't really answer it for a
four year old. But but questions like that about just every aspect of the natural world um as, as Louis c. K points out in his stand up, you you end up in a very existentially problematic place eventually, where you're making arguments like, well, some things are and some things are not, and then you just have to cut off the questioning and to change the subject ontological crisis brought
on by the questioning of children. Now, one of the other interesting areas here is of course, in the area forensics. Oh yeah, I didn't even think of when I first started reading this. Yeah. So one thing you'll notice if you look at this paper is that there are expression. There's gene expression charted onto time. So you can chart the transcription of certain genes after death by looking at the amount of m R and A or something like
that after certain periods of time after the organism dies. Now, one thing you could do with this is take those time charts and you know, do them enough that you have a pretty rigorous idea of exactly what the numbers should be at what points after death, how long it takes and you can figure out based on the amount of m R and A or something like that in the tissue sample, how long it has been since the
organismal death occurred, since this organism died. Yeah, you have you have kind of a timeline of genetic up regulation that you can look to and you say, all right, when did the when did John Doe here expire? Well, let's see what Let's see what his genes are doing, and and then we'll compare to the chart, and then we'll have a very definite idea potentially when he died. And of course that's something that now we don't always
have a great way of doing that. When one of the articles we read, I know pointed out that, you know, forensic investigators are often trying to like look at last made phone calls or texts or something like that in order to establish time of death. I think would be great to have a much more solid or the I think they might look at body temperature, but but it's not always solid. You would be great to have a really really reliable way to know exactly when somebody died.
So that's another big possibility here for this paper. In fact, there's an entire separate paper that that looks extensively at the forensic applications. Yeah, and so I imagine at some point there is going to be a whole blooming science of the Thanato transcript home. I have to imagine this is going to inspire a lot more research and hopefully a few horror movies as well. Yes, all right, so there you have it. Um, this is definitely a topic where we wanted to make sure we didn't go to
in depth. That the paper itself is is ultimately very readable, uh and fascinating, but it and it's and it's open. It's open so you can look it up by the side, readily available. But but it does go into into into depth. It does list out a lot of genes and to and specify exactly what they're doing, more so than it made sense to include here. But we wanted to give you a nice overview of these findings and uh can give you an appreciation for where it might be heading.
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