Ghost in the Genetic Machine: Animals

before and uh. And it can be in a way a very dense topic because you are getting down to um, how the genome corresponds to the phenotype, how the contents of our genes is expressed, the phenotype is the expression of our genes. Um. So we can get a bit technical when you get into that, but ultimately we are talking about how the secrets written in ourselves, how thoseterialized as the person we are, both in terms of our

our our body and in terms of our mind. Uh. And we ultimately really get into the conversation about nature and nurture concerning animals and humans. So we're splitting it up, we have this first episode about the animals. It's often a little easier to to look at the that something as uh as complex as this with the animals first, and certainly that's where most of the experiments are gonna

taking place. And then after that we'll get into the human realm and the various human ramifications when we complicate things with all of our human baggage. Yeah, the idea here is we want to recast our ideas about evolution and also disease and how we can gain phenotypes the expression of these genes, uh, for for the better really.

And in order to really get into this discussion, we have to talk about this guy named Gene Baptiste Lamarck or Gene eighteenth century French scientists and naturalists and and uh. He had some some very interesting ideas about how animals change over time, essentially about evolution, and he's most cited example is that of the giraffes. He argued that, okay, you look at the draft wanted to draft of a

long neck. Well, Darwin's answer would be that they're all these various mutations over time, and some of those mutations involved longer necks. And since the longer necks were a better survival adaptation. Those are the ones that survived and flourished wanted on. The mutations with the shorter necks didn't pan out so well. Right, So longer neck naturally selected for taking a long time to be selected. Right. We're

not just talking about one or two generations. Lamark's idea, though, is that you have this giraffe, imagine the short neck giraffe, and he looks up or she looks up at the call. Cindy looks up at the at the fruit in the tree. Yeah, Cindy's and Cindy's and her cohorts have already eaten all the low hanging fruit. They want the high hanging fruit, right, They want to reach up higher. So she's straining her she's looking up there. I want to eat those top fruit.

And then Cindy's offspring have the same desire, and the offspring after that. There's this there's this need to reach the higher hanging fruit from generation to generation, and from generation to generation. The neck longands enough coffee this morning. Long, So already I'm thinking about Cindy from Brady Punch, whispering her desires to to reach the foliage length right, and then her offspring all lispening their desire to reach the

foliage too and getting there. Because here's the Lamark deal. In his view, some giraffes managed to stretch their necks over out over the course of their lifetime, giving them an advantage of other giraffes, which then what we're talking about is passing on to their children. This is a really quick acquisition of traits here, and this is really what the story comes down to, acquiring traits versus genetic mutations.

Now out with Lamarck right when he was talking about these droffs, well for a while, no, for he was dead wrong in this example. Yeah, I mean he was pretty much. This was considered the archaic idea, and we're not archaic, but an outdated idea that was that was it was far outperformed by Darwin's theory of evolution. So Darwin's theory becomes the predominant way that we make sense

of these changes over time. But it does turn out that Lamarck was onto something um and his you know, his theory was dismissed for a long time as malarkey, Like, how I did that? Lamar Malarkey Lamarca malarkey. Yeah. But when epigenetics really came onto the scene in the seventies and more lately in the last ten years, people have been looking at Lamarky and evolution again because our better understanding of epigenetics makes what he was talking about possible.

So epigenetics, Okay, you have genetics with the geno, and then you have this thing called epigenetic, which literally means in addition to genetics. Um, and this exists, and these changes exist between the genome and the phenotype. Now I like to think of this in terms of video games. It works for me, it'll work for some of you guys. Um, think of a flight simulator. Okay, you you put a load of flights that simulator up on the computer, right and uh, and you can go in there and you

pretend to fly this airplane. Now, if you go in there, you go into the settings for this particular game, you can alter the realism of the flight experience. Okay, So think of it. Think of this way. The game engine, the game itself, This is the genome. Your actual game playing experience is the phenotype the expression right, and in

between there you have epigenetics. You have the settings menu where you can where you can click on or click off all these little things like, oh, you don't want planes to be able to collide and there you don't want to ever run out of fuel. You want you know, unlimited uh, emma whatever. You can adjust those settings to have any anywhere between a highly realistic flight simulation and an arcade shoot them up, depending on how those settings are gamed. And so with an organism, you see a

very similar thing. You have the you have the genome, which says this is what the organism is going to be like, this is what the phenotype is going to be, this is what the experience, the game experience that we live every day is going to consist of. And then you have all these various settings in between, these ways, these epigenetic changes that affect the way that the genes

are expressed. That's right, because at the heart of epigenetics is really the study of these changes in gene activity that don't involve alterations to the genetic code, right, but they still get passed down to at least one successive generation. So again, think about the flight simulator that you just talked about, and think about um let me see it. Let's think about the genome is the hardware, and epigenome as the software. Okay, so you can load Windows if

you want on your Mac. Okay, I think about it that way. So I think now about this epigenome, that extracellular material that is sitting on top of the genome, and it's these epigenetic marks or proteins that tell your genes to switch on or off. And it's through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on those genes that are passed

on from one generation to the next. So we're we're talking about this because this is really amazing stuff because what you can do is you could you can impact your your future offspring in a very significant way without changing your own DNA. And we essentially see Lamarckian evolution return in this or some semblance of the idea, only we call it transgenerational epigenetic inheritance. So it's the settings that to end up being put in place in one

generation passing on to subsequent generations. UM. So it's like you know, a father had the realism settings on his flight simulator set to about and then that same those same settings pass on to the offspring, even if you know they're in a more arcade culture. I'm kind of stretching the metaphor, but I think you get what I'm saying, all right. So you're probably saying, well, how in the world does this happen? Anyway, what is the mechanism for

delivering these changes? And that is something called DNA methylation. Okay, So that's how you game gene expression, the phenotype, how a gene is expressed turned on or off in an epig genome. So it takes only the addition of a methyl group to change an epigenome. And a methyl group is a basic unit in organic chemistry. We're talking one

carbon atom attached to three hydrogen atoms. And when a methyl group attached to a specific spot on a gene, this is what we call DNA methyl ish methylation, and it changes that genes expression, turning it on and off, dampening it, making it louder. The choices are all there, right, So think of methylate and as chemical bundles that enzions hitch a ride to DNA on and then they have

the ability to manipulate jeans. You with me here, all right, You guys out there with us UM in the methylization patterns can be affected by again external environment and then get passed on to offspring because they are maintained through cell division. Yeah, they can change drastically in the course of a lifetime, but they can also as well discussed they can be said permanently during embryo development. So it depends on various factors and that affect the distribution of

methyl groups. So we have an example here of um one sort of DNA methyl methylation in process in nature, and this is with mice. This is in a two thousand and three Duke University study by oncologist Randy Jurtle in one of his postdoc students, Robert Waderland. They tinkered with genetics using mice with a uniquely regulated a Goudy gene. Okay, so this a Goudy gene gives mice yellow coat and

propensity for obesity and diabetes when expressed continuously. So what did they do to to these mice, Well, they gave them a one group of them a diet rich envitamin B, so we're talking about folic acid and B twelve. Another group they did nothing to. What they found is that the vitamin B acted as methyl donors. They caused methyl groups to attach more frequently to that Goudy gene, essentially

dampening it, turning it off, altering its expression. So without even messing with the d NA, what happened is that those mice with the gouty gene produced healthy offspring that had brown coats. They were normal weight, and they were not prone to diabetes. Just with this one aspect of nutrition. There's another really cool example that is often sided involving

water fleas in a predator heavy environment. The creatures developed these large defensive spines on their bodies, all right, because the world has become danger so they they load up, you know, they develop these spikes. It's a harsh world, so they they grow the weapons they need to defend themselves, and then the trait will pass on to the offspring, even if those offspring are raised in a predator free setting. So it's another example of to personify evolution a bit

here and and personify genetic expression. The fleet, the water fleet body is saying, all right, it's a it's a bad world. Let's grow these spines, and then the offspring is gonna be born into what can only be presumed to be a bad environment as well, so it better have the spines right out of the gate. Yeah. So, I mean if La Mark was alive today, he would say, who's laughing? Now? Right? You know it's correct in some sense.

All Right, we're gonna take a quick break, and when we get back, we're going to talk about some very cool examples of this in round worms and uh, mice and wrap Okay, we're back. Uh. We're talking about genetics. We're talking about an expression in a large sense. We're talking about nature and nurture and how these these different genetic factors in different environmental factors effect who and what an organism happens to be in life. So we're looking

at animals in this episode. In the next episode we'll get into humans. We're talking about a lot of the different organisms that we experiment on and then we analyze and attempt to understand the genetics better. And this brings us, of course to the roundworm. Yeah. This, Uh, These roundworms are of great interest to researchers because it turns out that they have a built in immunity to viruses or

whether they can cultivate this built in immunity. So researchers at Columbia University found that these roundworms were able to develop a resistance to a virus and then they were able to pass along that immunity for successive generations UM. According to an ION nine article, they do this through r in a interference or are in a I. And this process is used by cell to mute certain genes and is often used to beat back viruses and other

threats to the genome. This is really cool. This is like a defense system right here, sitting outside your your genome. UM RNA I destroys messenger RNA or mr rna, which is really important here because that's what's needed to communicate with various genes. So without their mr NA, genes basically

shut down and become inactive. Yeah. And it was particularly interesting with study UH two thousand eleven Columbia University study because they set it up so that the roundworms couldn't gain immunity in the Darwinian fashion like they had they had to do. It was it was Lamarck or nothing if this is gonna happen, and they did and they

actually observed this transgenerational process. So what's really cool here is that the researchers found that even a hundred generations at the initial effects infection, the round worms still carried the immunity acquired by their distant ancestor. Yeah, hud. Now, granted a hundred generations is a little different and around than in a human but still you can definitely see the survival advantage in ensuring that subsequent generations benefit from

the same protection against a viral enemy that's still out there. Well, and you can also see why researchers would be chumping at the bit to study this more because how could you gain this for humans? Right? What what sort of defense system could we UH create for ourselves if possible? So of course it leads to more tinkering there. Um. And speaking of tinkering and UH studies experiments, we will

have to of course go back to mice. So, yeah, there was a tough University School of Medicine UH study in two thousand nine. And what they did is they took some mice that they genetically engineered to have memory problems, and then they raised them in U an enriched environment. So there's an environment full of toys and exercise social interaction. Um,

you know, so like working at Google or something. For these four mice, UH and they did this for two weeks during the adolescence for the for these animals, and they found that the animal's memory improved. Uh. And granted this is expected to a certain degree because we know that enrichment has been shown to boost brain function. That's why you you want to enrich young children, you want to enrich the lives of indoor pats. I mean, it's it's it's what enrichment is about. That's why we seek

out knowledge as we're doing right now, right um. But what they found specifically is that the memory gene here that carried the mutation is called r A, S, g r F are the genes that regulate a signaling pathway that's involved in brain cell communication. So that's what was improved here. But the coolest thing is that the next generation, even though they had this gene, they had this mutated gene,

they had better memories. So again, what we saw here is that DNA methylation process occurring, dampening the gene for the next generation. So we're not going to keep a running score for the nature versus nurture battle, but this one would certainly be victory for for nurture. So yeah, TuS University neuroscientists. Larry five had said that a striking feature of the study is that enrichment took place during pre adolescents, months before the mice were even fertile, yet

the effect reached into the next generation. So that was surprising. And we'll talk a little a bit about that more with humans. UM, but we know that when UM, when an organism is going through its prenatal period, that what the mother does can't affect it. But what this is telling us here is that even before the mice were able to reproduce, that was affecting the genes of their

eventual offspring. Yeah. I mean it makes sense again when you've stripped down all of our human expectations of life and get down to the basic genetic mission of any organism to spread its genes and pass it onto offspring, like right out of the gate. That is what it is here on earth to do. So we look at another aspect here of memory, and this is called long term potential ation, and again we look at it in mice and Larry Fogg's team did a secondary study on this.

The same research group looked at this. They wanted to look at LPT, long term potential ation LPT strengthens communication between neurons and it increases memory. So again they had mice with a genetically faulty LPT expression and these, uh, this LPT was essentially fixed again when they were put in an enriched environment. So of course, what do we see happen with offspring? They turned out better even and

this is the crazy part. The puffs demonstrated this improved the same improvemental process even when they were raised by memory deficient mice that had never had any of the or these are rich enrichment benefits. So in this you kind of see a little bit of the like the victory maybe not of nature but of nurtured nature, so a little bit of both. Yeah, you're right, both of

them are definitely entangled here. But again, the big news here is that, um that this gene was switched off and game fixed it in one generation through enrichment and then bad parenting in the next generation didn't just automatically turn it off. So it's it shows that it's a little more complicated than that and also a little more fool proof. Now yeah, now these are all touchy feely examples, right, because we're improving things. What what if you're a researcher,

and you want to see the opposite. You want to see what happens when you have rats that are abused, UM, that are raised by stressed mothers that neglect and physically abuse their offspring. UM. What will those offspring show in their epigenetic modifications. Well, sadly showed that the the abused my screw to be poor mothers as well and appear to pass down the same epigenetic changes to their offspring, which you know closely mirrors sort of the expected cycles

that one sees, you know, even in humans. Yeah, and the twist here too is that the offspring of the use of mothers was then raised by healthy mothers, and although that did help with some of some of their behavior, it didn't It did not dampen um the expression of that behavior as the other DNA effylation did and the other scene that we saw with mice. So it helped, but it did not fix it. Yeah, and it again underlines that we're talking about a complex interaction of nurture

and nature. That it's it's not just oh well, nature is gonna went out in this case and they're just gonna went out in the other. It's epigenetics is is a little more involved, and I think that you know that's that's the idea that you carry away from this is that it's not just one or the other. It's not just nature versus nurture. It is definitely a nuance of both. But it's also not just Darwinian evolution versus Lamarchian evolution. These also work in tandem, because we're still

living in a Darwinian world. We just have some Wamarki in expression. Yeah, there are various ways that our genes can be expressed in the final phenotype, and a lot of that is determined by environment, by the way we're brought up, by just whatever kind of situation that our

bodies are and ourselves are put into. But of course this, this UH is all very exciting because what does this mean for humans When you have such stark examples in nature of the epigenome um and its ability to to be expressed differently in subsequent generations, what does that mean to us? Well, there are two ways to look at and we'll get into more of this in the next podcast. But on one hand, it does give you the option to freak out about every little thing in life in

concerning your own upbringing. That you know that your your children, your children's children, you can really begin to to over analyze every little detail. Also, as we continue to map out the epigenome, it gives us an increased ability to potentially go in there and and adjust these settings uh as one potentially as one would the realism settings and flights and later instead of leaving it purely to environmental changes. Yeah, it's really cool is that the Human Epigenome Project UM

just like the Human Genome Project. They are trying to map it UM. Now that the Genome Project has done in the and the ability to do that is is um much more within grasp. The epigenome should be done fairly soon, and the kinds of stories that will come out of that will be I think of a mind blowing quality once they sort of passed through everything that they can unravel and everything that unfolds, and begin to

apply it to us. Yeah, and and figure out what they can turn on and what they can't turn off. I mean, who knows what's in there because I've I've read the examples of being able to um. It's it's like toy with chickens, so that they're a little more like dinosaurs just by tinkering around, what's various epigenetic changes? Um, you know, granted they're they're probably would not be able to go in and just suddenly make spines growing grow

out of our backs. But but we have spoken a good bit about some of the the various physiological things that that humans have left behind in their evolution, and uh, and I can't help but wonder, like which of them are still there, like the whole um, like the spiny penis thing that we discussed, Yeah, is that still on the table? I don't know, have genetics answer the question? I hope. So now I'm just thinking of urban chicken chicken coops and cities with with different phenotypes express and

it's sort of like dinosaur chickens running around. You have a little velocity raptor chickens. Yeah, that's the future, folks, wrap it up right there. Yeah, So definitely tune into the next episode because that's gonna be the one where we're gonna talk about some of the findings involving experiments about humans, about human epigenetics, how these various how these various environmental changes affect uh, the expression of of our

of our genomes in the final phenotype. And we'll also do a little pondering to a little more a little more philosophical stuff there at the end of that pticular episode. So let's call the robot over here and uh get a little listener mail. Oh now, this one's pretty exciting. Um, I mean, that's I find it exciting. We heard from Tim. Tim writes in in response to our nutmeg episode and says, Hi, guys, my name is Tim, and I come from Dutch parents.

Wanted to share with you something that I grew up with. My parents and grandparents used to put this stuff in everything. I'm not sure if you can even buy it in the States. They have it sent to them from a friend. It's a mixture of nutmeg and other things, and to be honest, it's excellent, wonderful of putting your hot chocolate or over Christmas drinks. Pick some up if you can. And he indeed sent a couple of photographs so that we might describe this product. It is called Let's let's see.

The brand is Silvo and it's cook and speculous cruden, and its ingredients appear to be cattle cruden, Aguellen Newton musket gimber warter, carda mom which is maybe cardaman yeah, and uh and white pepper so um which one of those was nutmeg muscott Do you think is nutmeg? That's what I was thinking. Yeah, but I think the crazy thing about that is uh. And why he says that he's not even sure if that you could buy that state side is because that is a massive amount of nutmeg.

It's like a deodorant stickful of nutmeg. And as we know, nutmeg has hallucinery or hallucinogenic properties when ingested in large quantities. So I don't know that stuff on the street quite a dime. Well, you know, as we discussed Penny, because remember we talked about it's not really the consensus was, but it's not really worth anybody's time. No, no, no no, not not in large quantities. And large quantities, it's a nightmare and it's awful, But of course, in small quantities.

On a regular basis, nutmeg has a number of positive health benefits. Lovely on your hot cocoa or latte. I've been having it on my coffee every morning pretty much since we did that episode because I like nutmeg and I'm and if there's any even remote chance that I'll have a health benefit from it, then why not. I even had a nutmeg infused root beer the other night. It was great. Did you brew the root beer yourself? No, it was like some brand, like they have a special

Bavarian nutmeg version of their root beer. You get a big They have it at that little market in near your house, so check it out, all right, all right, And here's one from Trevor. Trevor writes and says hello. I live in a on a twenty five ft sailboat near downtown Seattle, more specifically Lake Union. I don't have cable or internet, and I rely on reading books and listening to your podcasts streamed through Stitcher on my iPhone

for entertainment. I've avoided cabin fever and seasonal depression thanks to the information and knowledge I've gained through your podcast. Please continue your work because it's keeping me saying and informed.

Most importantly saying that that was a lovely email to get there because or actually that was on Facebook, I think, because I mean in my job, in our job, we're kind of shackle to the internet somewhat, so I know that I sometimes feel like it wouldn't be nice to be able to just really step away from the Internet a bit, which I don't think I've really done. And close to a decade now, well, Trevor is definitely living

my dream. I'm not kidding. Yeah, I mean, I've always wanted to live and this is gonna sound weird, but on a boat in a major city, so that you would have access to everything that a city provides, but you could just take off whenever. And here's a little weird thing is that I have had this fantasy in my mind for so many years that I mentally wanted to prepare myself and I would only use a pairing knife because I figured that if I ever lived in a boat and used the kitchen, I would only have

one knife. You've been training for this for years and I didn't realize to what extent. And tell my husband, who is always like, why do you why there's a bevy of nine, and I finally fessed up. I was like, because one day I might live on a boat and I have to get used to just this one knife. Wow. I have to admit that early on I never really

wanted that for myself. But occasionally I'll read a book, you know, they had someone living on a boat, like in the in Sutury mccorma McCarthy, he lives on a boat. And I was kind of attracted to that, and it made me think back, like why do I have the sort romantic idea about living on a boat that never

goes anywhere? And it's because of that the Highlander TV show, Because in the Highlander TV show McLeod um whichever his first name was in that show, because it was different, Connor McCloud, Connel McCloud, I don't know, but he lived. He lived on a boat that was was there in Paris, I think, and so he was always coming, you know. And he's just this brooding loner with a samurai swort that lives on a boat in Paris. And I was like, that looks like the life for me. Amsterdam another place

I would like to be boat bound. I wonder how many of you guys have these boat fantasy too. Maybe this is just particular to us. I know, I did get to go down the Thames. My wife and I um a friend of hers that she had she knew over the internet when we traveled to London years ago, and we he he had at a canal boat, and so we got to go go down the Thames a bit on that and that was delightful. And and when we spent the night in it too, so I could I could see where one would really fall in love

with it. Maybe not so much the chemical toilet, but but the rest of it is fine. Well, thanks Trevor for writing in. Well, if you guys would like to share something with us, be it about epigenetics, be it about chemical toilets on your romantic boat, or be it about not Meg, we'd love to hear from you. You can find us on Facebook, you can find us on Tumbler. We are stuff to blow your mind on both of those and uh and we also have a Twitter account where we used to handle blow the Mind, and there's

something a little bit acrossover. We're going to promote the show on all of those feeds. But then there's there's always gonna be something on the Twitter that's not on the Facebook. There's gonna be stuff on the Tumbler that's not uh not used on the other website. So so check them all out. There all pretty cool. Find the one that fits your your frame of mind best. And some people are more Twitter people, and then some people were well one over by the flashiness of tumblers, so

you make a nice tumbler too. By the way, I enjoyed the tumbler, I shouldn't really digging it, so yeah, that's very cool. Um. You can also send us a line by emailing us a blow the mind at discovery dot com for more on this and thousands of other topics because it how stuff works. Dot Com