Epigenetic Transgenerational Inheritance with Dr. Michael Skinner

I hate to break it to you, but yes - what your grandmother did directly influences how your DNA is regulated today. 

This is called epigenetic transgenerational inheritance. 

Epigenetic transgenerational inheritance refers to the transmission of epigenetic marks from one generation to the next. This phenomenon can occur through the germline and affect the development and health of future generations.

To further explain, it is possible for environmental factors that affected our grandmother to influence our epigenetics through epigenetic transgenerational inheritance. For example, if our grandmother was exposed to a toxin that caused changes in her epigenetic marks, those changes could be passed down to subsequent generations. This could lead to an increased risk of disease or other health conditions in her grandchildren, even if they were not directly exposed to the toxin themselves.

Additionally, lifestyle choices such as diet and exercise habits can also have epigenetic effects that can be inherited. If your grandmother had a poor diet or was sedentary, for example, this could have altered her epigenetic marks and potentially contributed to a higher risk of obesity or other metabolic disorders in her grandchildren.

In this week’s Everything Epigenetics podcast, Dr. Michael Skinner speaks with me about just that - epigenetic transgenerational inheritance, a term he coined in 2005. We discuss how Dr. Skinner and his team have shown that exposure to certain environmental factors, such as chemicals, nutrition, and stress, can cause changes in the epigenome that can be passed down through multiple generations. Dr. Skinner and I also chat about the mechanisms underlying this transgenerational epigenetic inheritance and the implications for human health and disease, including developmental disorders, obesity, and reproductive problems.

In this episode of Everything Epigenetics, you’ll learn about: 

• Dr. Michael Skinner’s history and how he became interested in things that cannot be explained by classical genetics
• The history of Epigenetics starting with Conrad Waddington who coined the term “Epigenetics” in 1942
• Epigenetic mechanism and marks (DNA methylation, histone modifications, chromatin structure, non-coding RNA, RNA methylation, and DNA adenine)
• How Dr. Skinner discovered epigenetic transgenerational inheritance 
• Epigenetic transgenerational inheritance 
• The role of the germ cell in this type of inheritance 
• The limitations of genetic data in determining phenotypic outcomes 
• Classical examples of epigenetic transgenerational inheritance
• Generational toxicology 
• The work Dr. Skinner is performing now (F10 generations in rats) 
• Environmental toxicants that have been shown to be associated with the transgenerational inheritance of increased disease susceptibility
• How

Transcript

[hannah_went]: 0:01

Welcome to the Everything Epi Genetics podcast, Dr. Skinner. I'm excited to have you here today.

[michael_skinner]: 0:06

Well, thank you very much. I appreciate the invitation.

[hannah_went]: 0:09

Yeah, and you know you have quite the resume. I remember originally hearing you speak at Preventative lifestyle medicine Institute in Seattle, Washington, last year at the conference run by Dr. Jeffrey Bland, and really knew I wanted to have you on the show. You're an expert, I would say in epigenetic transgenerational inheritance, which will be our main point of discussion today, and before we really dive into it, Can you just talk about your story? Give our listeners a little bit more. You know, I gave The common introduction and over view, But what made you interested in this field? And you know where how did you end up landing where you are today?

[michael_skinner]: 0:48

So I've been at other universities Vanderbilt University. I was in the faculty there, University of Southern California, San Francisco, and then I've been here over twenty five years at W, at Washington State University, and I've always been interested in things that could not be explained through classic genetics, And you'd be surprised if you think about it. Most of the stuff we see, And just then typic variation disease, and so forth, it's very very difficult to explain them with classic genetics because classic genetics is exceedingly low frequency for any kind of genetic mutations, So that really span my interest in epic genetics and we've been studying it for thirty years. Basically

[hannah_went]: 1:42

Yeah, definitely, it's always interesting to note. of course, genetics definitely doesn't give you the best picture, Which is the main point of my podcast is you know, looking into more of these Epi genetic factors, so I want to break it down and start with the basics. I think a lot of my listeners are familiar with the Pi genetic modification of Dan Metholation, But again, I want to start with these primary factors,

[michael_skinner]: 2:07

Sure.

[hannah_went]: 2:07

so there's you know. Several other Epi genetic mechanisms marks that I think are are Bviously worth discussing. Would you be able to describe those those other factors? I know. When you you gave your presentation, you have this really nice you know photo with the his modifications, Croatan structure, Non quoting Ran, and of course the Dnmethlation. But do you want to walk us through some of that?

[michael_skinner]: 2:27

Sure, let me give you a little history

[hannah_went]: 2:31

Yeah,

[michael_skinner]: 2:32

went with your audience. And so it was the nineteen fifties.

[hannah_went]: 2:36

Hm,

[michael_skinner]: 2:36

There was a Fin Cardarand Watington, and he was also doing things that were not following classic genetics too, So he took fruit flies, exposed them to heat, and it changed the wing structure and it would just pass for sixteen generations, and so clearly it couldn't be genetic process, this, or Rope. that. And so that was what he coined the term epigenetics, and studied it on a more sort of phenitypic sort of level. For another the next twenty years. It wasn't until the seventies that the first epigenetic bio marker sort of came available, and that was Dan Methalatian, And it really wasn't until the seventies and eighties eighties was really, when it went started going sort of heavily, and then we found other types of epigeneticmarks, So Ebygenetics is defined as molecular factors and processes around the n A that regulate Gnome activity with what gens are on and off completely independent of the N. A sequence. This is a non genetic cross process, And then last part of that definition is that this is also mitodically stable. So when a cell divides into two Or cells, not only is the D and A replicated to the both datisels at the same d, n, A, the epigenetics that's in the cell. All of those epigentic marks on the d n A also are exactly replicated. Okay, And so it's molecular factors and processes around the d n around the Dana that regulate Gnome activity independent of the N a sequence, and it's methodically stable, so it's a very defined sort of thing, and over the years, The past thirty years, forty years, they've realized that there's right now five, potentially one new new one Six, but there's five well known sort of epigenic components as you mentioned, Dan. A methalation, historom, modifications, Curmatan structure, non coding as which is a major one in the new one is sort of. there's also ran methalation and there's a new methalation called Adnimetlation. That's reltivay.

[hannah_went]: 4:58

Perfect. Yeah, I missed that Ran Metholatian, And what do you say? The new one was

[michael_skinner]: 5:03

There's a d n A. There's anine

[hannah_went]: 5:06

A din.

[michael_skinner]: 5:07

based Par in the d n A. It's not really frequent. It's very much more developed mentally and it's not quite as frequent as Dnmcidsnvesilation. But that one is sort of one of the newer ones basically in the last few years. Basically

[hannah_went]: 5:23

Perfect. Thank you for that And you mentioned. when you went over the non coding ran a point. You said. this one is really important. What made you say that?

[michael_skinner]: 5:32

So, Um,

[hannah_went]: 5:34

Whoa,

[michael_skinner]: 5:36

and this was another big surprise. I mean, the Nobel Prize was given in the two thousand. Because of this, we have twenty thousand, maybe twenty five thousand gins. Okay and everybody gets all excited about the fact we have twenty five thousand gins. We could do lots of things with that. So forth there's two hundred and fifty thousand oncodingrnes. They're all different And so just in sheer mass, there's a lot more going on with the non coating n. S. Then then we sort of realized, and so essentially they are very important Epi genetic component And these things that we just talked about, all of these epigenetic marks are highly conserved evolutionarily. So they are in a microbe up to a human, and they were here in the beginning, just like d n a d, N, A wasn't like there. Before then was Evolved. They co evolved at the same time, and this is what is what was evolved to regulate Tan function. N can't regulate its own function without having epygenetics involved.

[hannah_went]: 6:46

Yeah, thank you for for that that explanation something I also didn't know, so I'm sure we'll see a lot more research in the future, Hopefully with that non coding r. N. you know that Epi genetic modification and then the anine methalation, To now, like I mentioned, your main point of focus and something I'm super interested in for many reasons, is that epigenetic transgenerational inheritance. It's a little bit of a mouthful.

[michael_skinner]: 7:13

Yeah,

[hannah_went]: 7:13

But what is this? Why is it important? Why do we care? And yeah, What makes that a big part of your our research and focus?

[michael_skinner]: 7:22

So if you ask anybody off the street and say what, what's

[hannah_went]: 7:27

M.

[michael_skinner]: 7:27

inheritance? they will tell you you inherit your d n A from your parents and that's genetic inheritance.

[hannah_went]: 7:34

Hm,

[michael_skinner]: 7:34

And that concepts been around since the late eighteen hundred, early nineteen hundred. Basically and basically Mendelian phenomena was based on this inheritance sort of concept. We didn't really appreciate the fact that there was this thing called D N at the time, but basically Even then that this genetic sort of inheritance sort of came up. So so that's been around forever and everybody's taught that in school. And so So it's not like I went looking for this separately. I'll tell you this story. We were doing a study in in a rat model. Okay and we were. We wanted to study sex determination that tested an over development in the early fetal development period. So there was a pregnant mat rat and we exposed it to what's called chemical. That was an indicandestructor, blocks Ander And actions, the male hormone, And so I wanted to see if we could interfere with sex determination And test is mostly the testis By putting in this thing right during chemicduring, al sex determination,

[hannah_went]: 8:47

Hm,

[michael_skinner]: 8:47

a short term exposure. the animals to be born and loinbhold. The result was, there was no effect,

[hannah_went]: 8:56

Yeah,

[michael_skinner]: 8:57

no effect on sex termination. Nothing. so it was a really good example of Failed experiment, so we couldn't really manipulate sex termination. So Um, what we did do is we aged those animals up to be about a year of age, And then we looked at the tests and found that this from atagenics, This, developing the cells that will develop in to sperm, were dying at high rates. They're basically undergoing a process called Program call death or eight proptosis, And so there was significantly hire in the exposed animal and there, not exposed animal, which was interesting, And so we actually put all that together in public Paper. And and that was it. A few months later my post thought came in and she was very upset and she said I accidentally bred these animals to the next generation. They were aging, and so forth, and she was all upset And don't worry about it. Go look at the next generation and you know, do the analysis and see what you're fine. So she came back and said It's the same thing. The next generation has the same effect. Even though the exposure was back here Two generations later. we saw the effect. Of course, I

[hannah_went]: 10:11

M.

[michael_skinner]: 10:11

didn't believe, and we went out

[hannah_went]: 10:13

Yeah,

[michael_skinner]: 10:13

Pete to this thirty different times, and we took it out to the third generation, and essentially found that we had a very reproducable effect going out three generations. Where here's a chemical that came in. This chemical cannot change the n a sequence. It's not a muted mutigen, Just an inderconabnormality was put in place and it went out three generations, so wet Repeated this and we, basically I was very conservative, so we've actually sat on the data for a good four or five years, and did the experiment multiple different ways, in different chemicals and things, and basically then published in two thousand five, the first paper where we coined the term by genetic transgeneration inheritance. And the reason I was a little bit concerned was what I'm proposing, or what I proposed at the time was a non genetic form of Eritance, something

[hannah_went]: 11:09

Hm,

[michael_skinner]: 11:09

that nobody even considered because we were so ingrained and genetic We still are. That genetic inheritance was the only thing being inherited. Well what we just showed was Epygenetics can actually get inherited, and there's this whole phenomena is mediated by alterations in the dandamsolation, and pass forward and so forth through the germ line through the sperm. So the only thing that you're going to ever inherit is comes from your either sperm or Of your parents. It has to be through mediated through the germ line. There's nothing else that can actually do this that has to go through the jormalis, And so that was the explanation, So as going through a germline sort of process, and then basically the next generation would be re programmed accordingly like the parent was, And then essentially you carry this for multiple generations. So since that initial observation, I'm just to clarify, within

[hannah_went]: 12:03

Kay,

[michael_skinner]: 12:04

that paper got a lot of press. Within a year. there was another article that this was in science, and there was another article in science a couple of years later, where I was. I was labelled an Epi genetic heretic.

[hannah_went]: 12:18

Empigenetic heretic,

[michael_skinner]: 12:21

I was proposing that this weird thing by genetic inheritance that nobody had even sort of thought about before. Since then I don't know. thousands of papers have been published document just about every single species that you can examine from plants to humans. Everything that they've ever examined has this by genetic inheritance. And and this is really designed to oh, The environment, and most of the studies, Then, after ours we're done with nutrition Th high fed diet and chloric restriction. We've done it with thirty or forty different environmental chemicals, And then there's lots of people that have done everything from temperature to toxic, like alcohol. I mean, Pretty much anything you can think about in the environment is tested

[hannah_went]: 13:11

Hm,

[michael_skinner]: 13:12

to promote this sort of phenomena. There's critical times of development where it's more sensitive than others And but this evolution Really is how the environment has an impact on the individuals development. To give it its fina types later on now, if you do a genetic type of experiment for this, so let's say you were looking at a given pena type as later in life, And this animal has a different type than this animal, But it's the same species. Now

[hannah_went]: 13:43

Hm,

[michael_skinner]: 13:43

We know if you try to do genetics to actually find that through Geno Mart Association studies where you look for mutations There, Generally not there. there's not now some diseases they've done. Actually, most of the diseases they've looked at always have a positive gas mutation. The issue is that it's really only in one out of a hundred people with with a disease, so it's a one percent frequency at best. Usually it's less so. genetic mutations are such a low frequency that it's hard to explain how they could have an impact on on Algy, and in the major way we think about it in terms of genetic determinism by genetics. However, when we look at those those phenomena generally, it's greater than ninety percent of the individuals have the by genetic mutations to have the epignic change that give you that chenitypic variation. So it's an environmental thing going through the epigenetics To then the ebigenetics can regulate the gnomwhat. Gens are on and off and so forth, So it's not that the dean is not important. Just basically it's not So. it's certainly not responding to the environment. It's the epigenetic kids. and then you get the finito make short, shipped, or the disease developed. And so so this, this is really this epigenetic transgenerational. Inherit is a whole new way of thinking about. You Know what your great grandfather or grandmother was exposed to is going to affect your disease, And you're fnitized because of that epigenetic shift that you're inheriting and you're going to pass it on to your grand kids as well. So this changes how we think about the environment and also what we're doing to ourselves in terms of our exposures s human,

[hannah_went]: 15:30

Yeah, definitely, I remember hearing you speak again at that conference, not knowing anything about this epigenetic transgenerational inheritance and when you spoke, I was scared like you know, vicerally. I was kind of analyzing everything I did within the past week, you know, month years to to my body, and you know, especially for people who want to have children, passing those signatures on to your children as well, so it really made me very analyze, Kind of what I was doing from from a health standpoint and everything you know. the toxic environmental factors that we're surrounded with daily. So yeah that I love how you told a story there, So you really couldn't believe it When your you said you're grad student. I believe or student came to you and said You know I'm seeing this. You know, and you, you just couldn't believe. And then that's so profound. Holding off the data doing multiple studies, making sure that you're seeing this change through these Orations. Of course, it's not being a genetic factor, but some type of external stimuli. You could say Yeah, and just to kind of wrap that tack up as well, So that was the very first example you saw of epigenetic transgenerational inheritance. That was when you had the rats and you gave them that antiandrogenic endicrent disruptor, Correct,

[michael_skinner]: 16:53

Correct, Correct,

[hannah_went]: 16:55

and

[michael_skinner]: 16:55

And we've done it with everything we can think of.

[hannah_went]: 17:00

M,

[michael_skinner]: 17:00

More recently we did glifesae, which is the most heavily used herbicite sed world wide. Now it's pretty much in most of our food products and it can a very nice transgenerational effect, M. life. It's interesting in the sense that it has no effect with direct exposure. The F zero or one generation don't have any effect. It's not until you get The grand children, they have two or three generation, the great grandchildren that you actually see very significant increase in disease. So it's a very. so, We call that concept generational toxicology. There is no sense essence toxicology with direct exposure, but it appears two or three generations later we didn't know that compounds could do that, And so

[hannah_went]: 17:48

Hm,

[michael_skinner]: 17:48

this really does make us sit back and think about, first of all, No govern, And including our checks for trans generation toxicology, that all they look for is direct exposure toxicology. Companies don't test with that type of thing. They just look at direct exposure, And so they essentially design relatively safe compounds, like like a site for direct exposure. But if you don't look several generations later, you don't realize that it's just as harmful. It's just not.

[hannah_went]: 18:17

Right. Yeah, and what's the? how many generations have you? You studied in a single? I guess you know, cohort or kind of research experiment? How far have you gone?

[michael_skinner]: 18:28

So we were doing a long term study. Now we've taken about ten generations, and we see some very similar phenomena. If anything, the farther out you go, you get more and more disease and we're now pushing twenty and it's very scary in terms of some of some of the effects were seeing. There's major disease affects and this is ter ten generation. move now just to clarify, probably the first time the first time this was ever done was there's a fall. His name was Lens and lines, Um said he was a plant and he actually came up with the concept of talktaxonomy, where he actually took all the plants and organized them into families, And so that was the first time that it had ever been done well. He did a heat exposure of a plant and it changed the flowering fine type of the plant, And then he took in another generation and saw the same flowering fin type. So this is kind of cool. So that was, But

[hannah_went]: 19:28

Hm,

[michael_skinner]: 19:28

aside, nobody really paid attention to it. So there was a scientist in around two thousand that actually was also a plant scientist. He knew about this flowering china type. So he and this plant that lens generated was actually propagated for a hundred generations, So that's what the guy did in two thousand, and essentially, he then looked at the plants, found an Epi genetic change and went back to the original plant. So that was a hundred gene Ation. Now there's organisms like Clegans, or of dusoflis, a fruit fly, and essentially Gans is little tiny worm, and those have such a rapid generation Al times those have also been exposed to an environment Al thing have a shift in the pena type and it's taken out a hundred generations, and you still see the type a hundred generations later, And so even and so mammals. We've not taken it out as far because it's hard to do that much. Um,

[hannah_went]: 20:28

Right?

[michael_skinner]: 20:29

but we definitely can take it out and there's a number of publications that have taken it up Fo or five generations and done the same thing, but I think it's going to be as permanent as we've seen in other organisms like plants, and so forth, Going forward,

[hannah_went]: 20:43

Sure,

[michael_skinner]: 20:43

it's not necessarily a short term phenomenon.

[hannah_went]: 20:47

Yeah, definitely. and is that F. ten generation you mentioned? Is that study currently on going with rats? Is that what? it is?

[michael_skinner]: 20:55

We're just in the It's in rat study and we're finishing up the molecular work, so that's not been published yet,

[hannah_went]: 21:01

Perfect? Perfect, And what are some? while we're on this, the subject of you know being exposed to these different toxins. Can you name some of the other toxins that you looked at? You know again, what kind of effect can this this really have on our health? You know, we're talking real life impact here. I kind of would almost think the opposite that the health effect would lessen over time right, like if you're passing it on, I definitely didn't think that would have a larger effect, which again is Yeah, very scary.

[michael_skinner]: 21:34

So it's because the Epi genetic inheritance, the Epi genetic shift in the germ line. It doesn't go away. In other words, that's that's the new program. That's the new base line. And so essentially that's what gets past for now. If another compound comes along, then you can actually amplify that and so forth. And so, but yeah, we thought that potentially, as you got out farther now, the people to doing the worm studies or the fly studies. they didn't. They saw this Same thing. The Pena type either stayed the same or got worth. As you went out. It didn't definitely didn't go away. Okay

[hannah_went]: 22:11

Hm.

[michael_skinner]: 22:11

And so we've studied compounds. I mean, we started out with integradisruptors. like been closing. We've also done d d t, which is an astrogenic sort of compound, heavily used pestiside. In the nineteen fifties, we've done. We've done literally. about thirty of them. We've done anti plastics, heavy metals, Uh, like the bisfanal, actually promotes a very strong transgenerational impact and epigenetic effect, and so literally everything from heavy metals to to estrogenic, Any inderconserted destructor, And then there's things like dioxine, That's not really a indercon compound, but it's just a toxic compound. It ill do the same thing, so we've not really found any chemical we've tested that doesn't promote the phenomena, So all of all, basically environment a toxicnownow. I don't want to leave leave, thinking this is just a toxic sort of thing. Like I said, caloric restriction or diet are just as impactful promoting a transgenerational effect. Smoking and alcohol will do the same thing. And one of the about two years after we probably start studying about in two Thousan five, there was a woman in Europe in the Univers Zeric, Isabel Manso, that did a St. She did it, basically a stress study in an atom mouth model and essentially found that there was an epigenetic effect due to the stress that became going. I got transgenteratinally transmitted as well, and since then there's been lots of post trermatic stress in Drum is now thought to definitely be an environmentally induced, every genetic sort of thing, and so stress, just environmental stress can actually do the same sort of thing, and so pretty much. And then If you look at plants and so forth, and even some animals, you know, sunlight or high temperatures, and all of those environmental sort of things associate with climate change can do the same thing as well. To our biology is being shifted by our environment through this environment.

[hannah_went]: 24:22

Yeah. And what? I want to hang on to a point that you said. there, you said. caloric restriction and diet change Now Because of of my work and position with true diagnostic, You know, we talk a lot about life style recommendations and different things. Are you saying caloric restriction actually has a negative effect with that translational Epi genetic inheritance?

[michael_skinner]: 24:43

Sure, this is a somebody the general public doesn't know very well as well. Um, the original observations on this were made in the sixties.

[hannah_went]: 24:55

Okay,

[michael_skinner]: 24:56

And what they did is they took a couple animal models. I think Fox was one and a wolf was another one, and they basically monitored these animals during really really bad weather where there was essentially caloric restriction of the population. Okay, And essentially what happened is the Epi genetics would change the metabolism of the developing fetis such that when it was born, it could survive on less calories. And this is called the thrifty pena type, And that's what they call the thrifty peaty, and was then in several different species, And and then so then, if there's several years of this bad weather type or situation or a basically chloric restriction, those young offspring now could survive better than their parents could. Okay. So if you caloric restrict an individual O to basically have weight loss and stuff like that, and you did this during pregnancy, or your offspring would have that programming. Okay And maybe, and if you look at the human population and the seventeen hndredeighteen hundred, we didn't live on high caloric diets anywhere near like we're doing today, and so essentially humans were designed with this caloric, this thrifty fine type. Unfortunately, if you take those same animals okay and then put them A high fat diet, what do they do? They develop obesity. Much higher susceptibility to get obesity than the regular individual doesn't have the thrifty punitype. And so this is a really well established phenomena. And now, in more recent times we've realized that this is an Epi genetic programming. It's modifying your metabolism and it gets program and it's mediated through the germ line, so you can inherit it, and so through a genetic inheritance. And so it's it's There's Reason to a degree, So we did a d d T. exposure. Okay, We took the animals out three generations. The number one fenitype we saw was over fifty percent of the males and fifty percent of the females in the third generation had obesity, matoollic disease and obesity from three generation previously, D d T exposure, so human population, first of all, D T was the first agricultreal come Made synthesized in the late forties, and there fell in one price for that in the nineteen fifties. Then they used t. d t H for trying to get rid of milaria in both Europe and North America. Unfortunately, in the nineteen fifties, for the whole decade there was no concept of toxicology, There was no concept of epdemiology. These things didn't exist, and so they just figured well, The more we Is the better, and so they literally use thousands of times higher than what they should have used to basically try to. And they did get rid of the malaria disappeared and it worked, but the entire population. in the nineteen fifties, there is not an individual that wasn't exposed and all children born were exposed. So were three generations from the nineteen fifties, and our obesity epidemic in the United States is fifty per cent of our population As obesity. It's not not that diet, and how much food you eat is not a factor. It is a very bit important factor. but what we're saying is the Epi genetics drives your susceptibility to get obesity. and if you, because of those exposures today we are, have a increased susceptibility to go City. And what we found in our study was there were their litter mates, the liter mates, that on the same exact diet, same exact exercise and half of them will get a bit and half them wouldn't. So this is a programming of your metabolism that basically is involved on the same diet, sort of situation. Now there are individuals certainly that eat accessively, and that will certainly promote their obesity, and so forth, but I think the general population, we don't realize that there is this melecial Basis for the susceptibility to get obesity. And so, yeah,

[hannah_went]: 29:18

That's amazing, so profound because you always hear about. Yeah, this obesity epidemic right in that could have Ben. because of that d d t exposure that happened in the nineteen fifties, So it's you know, coming back full circle and making some more more logical sense, But then, also, like you said, you know, does play a part of. you know what's our diet? Our fitness regiment, et cetera That definitely adds a layer or component in there as well, Um, Dr. Skinner. what about you? What? What? From your research has changed. You know your life style or hasn't had an effect on it at all. You know what? what would be? some recommendations that you know you would give unsolicited to people, Or does that make you think about your own health differently?

[michael_skinner]: 30:05

Um, well, certainly people need to be worried about their health. Their diet is a big one. That axercise is a big one. Exercise is very critical for, for you know, so those are lifestyle sort of considerations that will definitely impact our health And we have lots and lots of data actually support that sort of thing. But for our purposes, I'm a scientist, and so what we've been doing is taking a different tact, And so, if this is Then essentially generationally and even an individindividual that has a certain life stuff early in life or season later, we should be able to identify epigenetic marks in the individuals. It would one potentially identify what diseases they may be susceptible to, and to whether there was this early life exposure that they're inheriting from their parents or grandparents, that kind of thing. And so, in other words, there the epigent Bio markers for disease for exposure, And basically So, the first one we did, we took sperm from men that were either infertile or fertile infertile sperm. They still have sperm, sometimes the same count, but their motility and structure and things like that of the sperm can be abnormal. So we took sperm from infernal man versus fertamen, and we found a very distinct bio marker for fertility and fertility. Okay, which is nice to have. If you go to an I v F. clinic, lots of the men's sperm numbers would be fine, and so they would use it in. I v F. This could actually tell them. Oh, your sperm is goin, be infertile because of these epigenetic things, So then you can make sorted decisions. Also one of the one of the pharmasuticals used to treat and get hired fertility. We actually found a bio marker for that as well, Kay, So essentially that was our first fore into it, but since then we've found epigenetic bio markers for pre term birth, Female are trite romaterorthritis, a whole series of different diseases, where some of these, If you, if you have these epigenetic bio markers, this could have a very big impact earlier. So for example, for the rumaterarthrit is, But if you took a analysis to whether you were going to be susceptible to get earth rites okay, And you did this in your twenties or thirties, and you had a positive sort of test. It turns out in your thirties and forties. Some of the farm suticales they used to treat Earth writers can also be used to be treated in the thirties, and when you're in the thirties and forties before you have arthritis. And if you do that, it will delay the onset or prevent it from developing later on, so that's called a preventative there. Peti. Okay today, we have a bunch of preventative therapeutics that we could potentially use, but we do not know who to give them to, and it's inappropriate just to give them to everybody. And so this will help usher in the era of preventative medicine, rather than the reactionary medicine we do now after the disease develops, and this will all be based on potentially epigenetic biomarkers. And so we were today. We spend most of our time. We still do Some basic research along the by genetic inheritance activities, but we spent well over half our work taking a specific disease and identifying so recently. We also did another one that got everybody's excited. Was we took sperm from men that had autistic children versus men that didn't have autistic children. Kay, and we basically found that and an autism, It's a three to one ratio from men to mothers. In other words, a paternal. it's a paternally transmitted disease. Predominantly mothers will be transmitted about, you know, third of the time or a quarter of the time. But it's a three to one ratio. Essentially, so it's primarily a paternally transmitted disease that's been known for a while. So when I, when I saw that I said, this has to be an Eve, genetic phenomena, So basically found this night Bil marker for this paternal transmission of Out. Now you can then decide well, if you know you're going to pass past the autism, you could potentially get a downer downer pert or something that doesn't have this, and use that instead, or by simply knowing that you have it when your child is born, there are clinical management practices in their first year of life that will reduce the severity of the autism from a really high severities, five or six, down to a one or two or three that is relatively low, and to man Well, And so that again is a preventative. You know therapeutic strategy. So I think in the future Epi genetics will usher this in, And so we may not be able to fix the problem of this generational sort of toxicology, but we may be able to treat it much more effectively through preventative medicine sort of approaches. So for me that's sort of our maiden push right now is to actually come up with these sort of epygenetic biroemarkers that we can Used for that purpose, which are oftentimes potentially inherited from your parents or grandparents through every genetic inheritance.

[hannah_went]: 35:43

So all about identifying. You know. I guess whatever outcome you're looking for right that area of interest and then being able to mitigate that effect you know, prolonging the disease progression or even diagnosis. So yeah, I'll definitely have to have to have you back on when you have more more research behind that right. Everyone wants to know what they can be doing,

[michael_skinner]: 36:04

Yeah,

[hannah_went]: 36:05

but for you all listening, this is. this is really the future. I'm learning. You know so much more. even from what Just heard you speak. you know a couple of months ago, So it's It's super interesting and I know you know there are tons of fertility based companies right now right trying to work on on this, you know, in fertile issue, So a lot of that I think does point back to your work and this Epi genetic mechanism that we can, we can look at, and then, like you mentioned, make decisions on kind of how that that pathway will move forward. Um, I know you mentioned it earlier, Dr. Skinner. I want to come back to. S. You know, from a policy standpoint you mentioned, the government just looks at. you know. the generational effect. Is there anything we can do? Is there anything you know in the future your future that you see happening with with the government for studying more of this transgenerational Epi genetic inheritance?

[michael_skinner]: 37:05

So it's a difficult question.

[hannah_went]: 37:10

Hm,

[michael_skinner]: 37:11

Some, our government is very, very much Conflicted with industry and government and designing rules for toxicology and chemical use, and so forth.

[hannah_went]: 37:28

Hm,

[michael_skinner]: 37:29

The current sort of strategy is, they tend to lean towards not doing something then doing something, even if there's some data going going forward. So there's a great deal of problems going on. It's partly due to the structure of our government the way we have it set up. Unfortunately, the Environmental Protection Agency, which is the one that's supposed to sort of do a lot of this is not set up, so it has an independent budget, like Many government agencies, like the National intitude of Health, has an independent budget built into the going into the government sort of budget. The Pa has basically a budget that's determined by Congress, and so, therefore, if there's industry lobby on the Congress, you're going to have problems with the P. A budget. So they have very significant limitations and are set up in the current Us. system. Has prob. Because of that, this is a very sensitive topic when talk about chemicals and things like that. And so there's not a whole lot of progress expected from the, and I think in the Us. it would take a significant public, sort of pushed to actually have anything happen. Now it's different in the in Europe. Europe actually has committees and so forth that are put in place to actually independent, the independent of industry, and that sort of stuff. They make Decisions, and so forth, And so they have vane many of the compounds we have tested going forward, and they sometimes do it really really quickly. One of the first times I gave a public talk in Europe on our work on in close land, which is the antiandrogen, which is a fungoid used in agriculture, we were in Switzerland, and they're very progressive And so since I gave the talk and there is lots of these Discussions around the politics, and so forth, and literally, within a month there was a proposal to band close line, which like and so I said. Well, you got. you can't be too reactionary. You actually have to get some support of science and that sort of stuff. But so that's just like the opposite. So they are the first sort of entity that's looking at banning Life is a. It's pretty close, but it's still not there for the same sort of purposes. The problem with the life sad, so heavily used in Culture today, it's hard to actually pull. And so, in terms of solving this on a government level, and so forth, it's going to take a significant amount of time, probably a few generations. And

[hannah_went]: 40:12

M.

[michael_skinner]: 40:12

and sort of a hat, you know, a public sort of uproar about going forward. And but people are starting to pay attention. Even the farmers. I live in an agricultural area and the farmers have been using glifasate on their crops for a long time, and a lot of the men that now get older have diseases that are now Linked to the these agriculture chemicals, and so forth, so there sort of aware as well, So I think with time things will change, but my suspicion is trying to fix it at that level, is going to be very inefficient and fixing it at a level of preventative medicine. The induction of preventive medicine using these tests, and so forth, saying well, we know your your grandparents are exposed. You inherited. Therefore you're going to get this so we can give you this at an early time. So an example is that breath cancer, and one of the first Preventative treatment identified was for breast cancer. There was a chemotherapy called Temoxyphin which is not really efficient in terms of stopping. the. It's not a good chimo, but it's a reason compound. but they realized that if they gave the kimotherapy in your thirties or forties, you could delay the onset of the of the thing and maybe get get rid of it. It sort wouldn't develop later in life. And so that I actually ran a trial for a long period of time to actually do that And there are long studies. But and so so I think that's where we should focus our efforts and activities Is actually pushed towards preventative medicine, using tepygenetics as a diagnostic, because the government change in terms of chemical use, and so forth is, and it's not just chemical is our daily sort of activity. You have to realize that its stress. We get stressed all the time, but just through our daily

[hannah_went]: 41:57

Okay,

[michael_skinner]: 41:57

lives. I mean this is. this is across the board. It's not just the chemical industry. This is really our life Styles today. and so so yes, changing our life styles to try to minimize. That is certainly one big step. Hopefully the government would step up at some point, but really taking a slightly different view to medicine and moving it towards preventative medicine is probably going to be the biggest impact

[hannah_went]: 42:23

Sure, and the stress is not good to hear. I'm a naturally stress down person.

[michael_skinner]: 42:29

Every.

[hannah_went]: 42:29

I think I say that on like every body is like, I'm just one of those you know people who's always like hyper alert, hyper aware, and I'm very aware that it's not good for my health, so I see you're our pattern of thinking, though, take that preventative approach. Hopefully, the government cantreson can't be too reactive. Though to you now find means we. we need to you. look at all of the data so Philosophically this is very. you know, philosophically speaking, if you believe there was some massive change like in the next couple of generations to come where it's you know. you're super healthy and you're doing all of the things right and everyone becomes super pro active. Do you think we could eventually you know, flip those Epi genetic modifications or switches, and you know, reverse almost all of that damage that has become from. Like you said, the d. d T exposure, and all of these kind of Toxic that we're being exposed to.

[michael_skinner]: 43:26

Um. so I hate to be the bad news person. But no

[hannah_went]: 43:31

No. Okay, No, I want to hear it. you're You're the expert here.

[michael_skinner]: 43:34

Once once there is a programming. If you can take this out of hundred generations has been has been done in a number of species like plants. Um, and essentially it gets programme. We have a new physiological molecular sort of trait and that's this is our environment S driving it, and once it's put in place evolutionarily we have a certain fine type associated with it And so Oh, this is this. Really? It's not like you could do something to turn it around. Now during the pros, timing of the exposure. this has been shown that if you actually took certain diets and so forth during the exposure, you can reduce the impact of the exposure later on on epygenetics, and so forth, Going forward, and so those types of things could be done. But once it's programmed like if your great gram parents were exposed to some, They got programmed in their germ line and you inherited it. there's not Now

[hannah_went]: 44:41

Still still there?

[michael_skinner]: 44:42

correct. So so however, knowing that it's going to be there, knowing you're going, you're susceptible for obesity. knowing you're you know, you have nouratigenerative issues and so forth, you can take live style changes to actually reduce those fine types and delay the onset, and so forth, like the preventative medicine sort of approach, So I think there are things you can do. It's just that you're not going to necessarily fix it, and it's because this is not just in terms of What's going on in our lives, are on a daily level, or even during your life. This is. this. Epogenetics affects everything you can think about from disease, Deologyrapheni, types, your longevity, Als that sort. but it also affects things like evolution. In other words, we've had this genetic sort of concept for evolution, which is not inaccurate, but it's just not the whole story, but essentially when a phenitypic variation occurs within a population, Okay, there's a reason for it and it's environmental epogenetics. Okay, So then if there's a sub population that has an adaptive pena type and natural selection goes through to actually promote the evolutionary event, this is being controlled through environment, Al epogenetics to give you that adaptive pena type, So you can't change those things quickly. It takes. now you can. you can slowly. Over time, you know, have new sort of environmental sort of thing. You actually driving new epigenetics and so forth to get things to change, And that's how evolution so works, along with the genetic sort of change. so unfortunately, no, this is a sort of program event. It's It's almost a stable, if not the same as the stability of the d n sequence. Essentially which you can't ally, change you. You can't change your d n sequence, and unfortunately, some of your epigenetic program you're not going to change as well.

[hannah_went]: 46:41

Absolutely easy answer? Just no. So I, I like that explanation. because yeah, you know, philosophically I think I had some some hope there. but again the preventative medicine approach and focusing on on that. Um, now I know we're getting short on time here. One thing, I just, I just have to ask you you. You have this more recent twins study. Can you just give us the Cliff notes version or a little, you know, kind of introduction to the twins study, and what you found?

[michael_skinner]: 47:10

So so this one got a lot of interest unless more than I thought it would. So I had a colleague at the university who we have a twin registry, and in the state of Washington, where basically all twins are sort of registered, and then they can do studies on the twins and they like to do that because they contribute to the science. And so he's he was. He was oversaw the Washington State twin registry for a long time as a director of it. So he came to me and said We have these twins that essentially have different exercise, their discordant in their exercise. So one of the twins has really low sort of levels of exercise, and the other ones have vigorous exercise, and when we see this, we also see these metabolic sort of obesity type type. I see this changes going on, and everybody knows if you exercise a lot, you're going to lose weight and axtually be more physically fit. So for so, but we never really thought about before. Well, what's going on? What's the molecular mechanism behind those changes that you're getting from the physical exercise? So we did the study and basically found that the epigenetics was very different between the low exercising high exercise and the phenatypes were also in terms of eases associated very nicely, and so essentially so we put that together and published it, And within two or three weeks this paper had had had something like five hundred million reaches in rest. And so you know, I sat back, so you know we published the glifisate paper on epigenetics, and that got you know two or three hundred. You know a million, but this one even did better, and it turns out that a lot of these exercises sort of people in society as over come to me, And they said we never had a molecular Canis behind what the exercise did, And so the fact that we now have an understanding that if we do this exercise, we're changing our programming on the epigenetic level, and that will shift our you know susceptibility to get obesity and have all these obesity traits and metabolism and everything else. So really it was just another environmental sort of thing of exercise that was actually promoting this epigenetic shift, causing these pena types going forward, so that was Most recent studied. Basically so now we have a new new phenomena Of that's how exercise work. But now I think you could do things like take the ultra athletes that do the marathons and so forth, and actually see how these degrees could change based on their genetics and things, because now there's a molecular basis for that.

[hannah_went]: 50:02

Yeah, that's five hundred million views. That's a lot of wow. I was thinking. Yeah, your other papers I know are just so popular. very very famous. so I'm like there's there's no way, but you know, have the Google alert set up and I just saw that study over and over again and all of these different articles, which really again prompted me to to reach out to you and have you on here. So I wanted to give that twin study some some love,

[michael_skinner]: 50:28

Okay,

[hannah_went]: 50:29

And there's not a lot of yeah, N't think there's really any of epigenetic studies looking at exercise right. So now they have that information and hopefully we can look at different types of athletes and the epigenetic mechanisms behind that. So what's next for you? Are you going more in the twins route? I know you're looking at the rat models and different generations and that takes time. but you know what's on your radar.

[michael_skinner]: 50:55

So yeah, generation study will probably get out to twenty within the year. And so that will be interesting. and just from the penal types we're seeing, it's going to be a little scary, or in other words, I think if you you take this out, it's actually going to show that you end up getting more and more diseased as time goes on. Probably because there's subtle sort of environment, Al things that actually pro. So that's something we're in the process of doing. We have several of these disease states that we're actually going after In terms of bio markers, We have pre clamps project going on pre term birth, sort of induced thing, pre term birth. You have to understand. it's another environmental thing. If you're if you're a pre term baby, that just the pre term condition will shift the epigenetics very dramatically in cause a significant amount of disease Later in life just to do that. And then, unfortunately you have children, and you pass some of those things on to. And so the pregnancy issue Today, if we could reduce return birth would be significant impact on health of our society, So pre clams is one of the main, a main driver for that sort of process, Or we have a project going on them, and there's another one of the we've studied male in fertility quite a bit, because it's easier at Perm than it is in eggs From females. But one of the chief causes for the reduction and female fertility right now is known as policist. Very disease. It's a disease that we can't really detect really easily if we knew it was. if you're susceptible for it, They do have a few things he could do to actually prevent it. And so that one is another, so we have a couple of the diseases we're trying to get. But believe it or not, it's hard to get funding for these sort of things. And so that's the biggest Yeah issue for the funding levels there. Just so low. it's it's getting harder and harder to do the research in General

[hannah_went]: 52:59

Yeah, I just spoke to even a couple H students the other day and had them on the podcast. You know about the struggles with funding and that's something I don't think people really the general public. I would say, understand right. I remember being in college and like my professor is putting up, You know, no office hours to day working on a grant and I would get, so I would become so frustrated. I'm like What is a grant entail right? And now I know what it entails because you know we're doing a lot of those grants at true dig Stick, so it's definitely frustrating especially for all the F. the great work you do. So you know, I really appreciate your time, Dr. Skinner. I have one hurveball question

[michael_skinner]: 53:41

Kay,

[hannah_went]: 53:41

that I always asked on my podcast If you could be any animal in the world, What would you be? and why

[michael_skinner]: 53:47

An animal in the world.

[hannah_went]: 53:51

Anything?

[michael_skinner]: 53:53

Well, I'm quite a fisherman, so I wouldn't be a fish. That's for sure.

[hannah_went]: 53:57

Okay,

[michael_skinner]: 53:59

I don't know. I spent a lot of time in Africa, and I really, the wild life there is amazing, but I don't know if I could pick a specific animal. I've always had an affinity for a hawk, I guess, or an eagle, something like,

[hannah_went]: 54:15

Yeah, there we go. No process of elimination. working through through those thoughts. I like it. so thanks again, Dr. Skinner. I learned a lot. I know, my audience is definitely going to be interested in your work. I'll make sure I link out. You know all of your papers and put links. of course, giving extra attention to that twin study. So you know, thank you everyone for joining us at everything, Epigenetics Podcast. And remember you have control over your Epi genetic, so tuning next time to learn a little bit more, Dr. Skinner.

[michael_skinner]: 54:45

Thank you.