199: Is Generational Toxicity Real?

Transcript of Episode 199: Is Generational Toxicity Real?

With Dr. Daniel Pompa, Meredith Dykstra, and Dr. Michael Skinner

Meredith Dykstra:
Hello everyone, and welcome to Cellular Healing TV. I'm your host, Meredith Dykstra and this is episode 199. We have our resident Cellular Healing specialist, Dr. Dan Pompa on the line. Today, we welcome very special guest, Dr. Michael Skinner. Dr. Skinner has been doing some very interesting research on something Dr. Pompa talks about a lot on this show, generational toxicity, which actually Dr. Skinner calls epigenetic transgenerational inheritance, so another name. He's bringing some really, really interesting research to the forefront to bring this information to people who really need to know it because it can really have major effects on our lives, but help us to live better lives as well when we talk about some of the solutions.

Before we jump in, let me tell you a little bit about Dr. Skinner. Dr. Michael Skinner is a professor in the School of Biological Sciences at Washington State University. He did his BS in chemistry at Reed College in Portland, Oregon; his Ph.D. in biochemistry at Washington State University; and his post-doctoral fellowship at the CH Best Institute at the University of Toronto. He's been on the faculty at Vanderbilt University and the University of California at San Francisco.

Dr. Skinner's research is focused on the investigation of gonadal growth and differentiation with emphasis in the area of reproductive biology. His current research has demonstrated the ability of environmental toxicants to promote the epigenetic transgenerational inheritance of disease phenotypes due to abnormal germline epigenetic programming in gonadal development. Dr. Skinner has over 250 peer-reviewed publications and has given of 260 invited symposia plenary lectures in university seminars. His research has been highlighted on BBC, PBS, and Smithsonian documentaries, and selected as one of the top 100 discoveries in 2005, and 2007 by Discover. In 2013, he received the American Ingenuity Award from the Smithsonian. Dr. Skinner has served on numerous journal editorial boards and as an officer for several scientific societies. In addition, Dr. Skinner's been actively involved with the startup of several biotech companies. A very impressive resume Dr. Skinner. We're so excited to have you on Cellular Healing TV to share your research.

Dr. Skinner:
Thanks very much. I appreciate the -inaudible-.

Dr. Pompa:
That's quite the resume. I sure appreciate your work because it really has been something I've been speaking about for many years. In 2017, I have been blessed to go on the road even in the public and talk about this problem of toxicity. Like you, I've made a lot of enemies in the chemical world. I don't think they like our message too much. I'm not the science guy. I take your studies and others, and I present them showing people a problem that really, again, it's a generational problem. The title of my talk this year, as Meredith will tell you, it's been generation toxicity. I talk about how we're inheriting physical toxins from our mom in utero. The number of silver fillings that she has in, the [Jurass] study showed how much mercury is in the baby’s brain in utero, the amount of lead she has carries on physically to the baby. However, the second part, and potentially the bigger issue is that the toxins are turning on genes that get transferred from mom and dad, and those genes are turned on. Talk about that because those are the studies. Transgenerational epigenetics, what is it? How is it affecting us and why should we care?

Dr. Skinner:
Sure. Alright, so the classic concept for inheritance that's developed over the past 100 years is that your DNA sequence, it's passed from generation to generation. That's what creates the traits you have, the characteristics, what kind of diseases you might develop and so forth. All of that is DNA sequence based. Essentially, the only cell that's going to transfer anything from one generation to the next is your germ cell, your egg or your sperm. It's going to transfer this DNA to the next generation.

About 15, 20 years ago, what we found was that there's another source of inheritance called epigenetic inheritance, where it's in addition to the DNA sequence. It's these molecular factors that are around the DNA, chemical modification of the DNA that also get transferred from generation to generation. This is called epigenetic inheritance. It is probably equally as important in transmitting phenotypes, and disease susceptibility, and all sorts of things to the next generation as genetic inheritance, which is just your DNA sequence. Essentially, it's a non-genetic form of inheritance. It's called epigenetic inheritance.

It turns out, in contrast to DNA sequence, which environmental factors really can't change DNA sequence very easily. In fact, vast majority of environmental—or exposures and chemicals cannot change that. However, the epigenetics, the DNA methylation, these small methyl groups that are attached to DNA or the non-coding RNAs. There's a number of different types. They can actually get dramatically modified by these environmental stressors or signals. During development of the individual, both early on and then later on, if the germ cell develops an altered epigenetics, that gets transferred to the next generation, gets programmed, and that one gets transferred to the next generation, and slowly this becomes going forward. Just to clarify, in plants we've actually demonstrated, or other people have demonstrated that an environmental exposure of heat can alter an epigenetic programming of a germline in the plant that gets passed for 100 generations.

Dr. Pompa:
Wow.

Dr. Skinner:
In insects, it will go for 15 to 100 generations depending on the insect you’re looking at. In humans, and rodents, and things that we study, we've actually taken it out about 10 generations and we don't see a decline. This is a long-term effect generationally. This is a new form of inheritance. The difference is environmental exposures and environmental chemicals like toxicants can have a significant impact to promote these epigenetic inheritance phenomena.

Dr. Pompa:
I had the opportunity to go to Flint, Michigan. I was teaching the doctors the right way to get lead out of the body. It was very frustrating for me because what I was up against was them seeing lead in blood, and then they’d fix the water issue. Then they didn't see lead in blood anymore. My point was okay, the problem is two-fold. Number one, what's bioaccumulated in the tissues? Number two, what genes were already triggered? Unfortunately, and we know that Flint—there's many Flint, Michigans around the country right now. These kids, whether it's ADD, ADHD, all these different conditions that were now triggered, it’s not just going to affect that generation. We're affecting multiple generations. I'm just bringing that home. We're being exposed to so many different toxins today. Your point is yes, we as a generation are being exposed, but now these future generations are going to have conditions and things that are turned on genetically whether it's a psychological thing, bipolar, maybe diabetes. It's endless, is that correct or are there specific diseases or conditions?

Dr. Skinner:
No, essentially, if you think about this, all tissues are affected. For example, let's say your germ cell, your egg or sperm, gets passed to your offspring in the early embryo when the sperm and the egg come together. Then it creates what's called embryonic stem cell after that, which then generates all the different cell types in the body. If the germline is passing forward an epigenetic shift that then changes the epigenetics of the stem cell, every single cell that develops from that stem cell early embryo, whether it be your brain cell, your bones, whatever else, all the cell types are actually affected. We'll have a shift in their epigenome, and a shift in their gene expression, what genes are on and off. That’ll change the phenotypes and disease susceptibility of your offspring later in life. Then if it's programmed into the germline, when that individual that your offspring grows up to becomes an adult, reproduces, has your great-grandchildren, it gets passed to your great-grandchildren. When they grow up, it goes to your great-great-grandchildren. It keeps going in your germline being passed, so that's the transgenerational effect. This is not just for the generation exposed. This can go for all generations to come.

Dr. Pompa:
Absolutely, I think one of the frustrating things is most doctors today are still functioning from an old paradigm or at least an old dogma of well you have diabetes because your father had it, thinking it's the inheritance of the gene, not the epigenetics. Most doctors, really they don't know the science. They may have heard the words, but they don't really get the fact that we have the ability to turn on and turn off these genes. It wasn't just your doomed because your mother had diabetes and now you have it. It doesn't work that way. This is a gene that was triggered, typically by a stressor of some sort, and mostly I see the chemicals that we're being exposed to. Are there other stressors that you see that can turn on these genes?

Dr. Skinner:
Oh, yeah. The number over the past—Our initial ones we showed the phenomena with were environmental toxicants chemicals. Since then, there's now dozens of other labs that have found other things. It depends on the organism, but for plants, it's drought and heat; for humans or mammals, your diet. What you eat is your largest exposure every day. What you take in in your diet and what you drink is basically your biggest exposure. Essentially, there's lots of stuff your taking in through your diet. The other thing is, basically, it's environmental chemicals. Things we breathe or just touch and basically get exposed to. Another major one that's been found over the past five, six years now is stress. Your stress, either maternal stress, fetal stress, early and postnatal stress, pubertal stress, all of these stressors can then actually influence this process as well. Essentially, everything we have around us, including our stressful situation can be involved as well.

Dr. Pompa:
I remember the video. I thought it was well done. It was a study at Duke University. They took two groups of identical twin mice, so exact same DNA, separated them. They feed them the same, same environments, same stressors, nothing different. They exposed one group to a toxin. It triggered the agouti gene. They became obese with some other conditions. Now, I think what they showed in this study was is the next generation that was born with that gene turned on. They became obese without any dietary changes. The one group didn't. It proves what you're saying. In that study, they actually did some things with methylation and they turned off the gene. Talk about this because right now we've doom and gloom. We've presented that you're not only what you eat, you're what your grandparents ate, and what they did, and what they were exposed to, and you don't feel well because possibly of what's been turned on in them. Can we turn these genes off and what are some of the strategies? This is a lot of what I teach, but I want to hear what you have to say.

Dr. Skinner:
What the Duke University, Randy Jirtle's group showed was yes, you could alter it with the environmental toxicant, which is phytoestrogen that was actually promoting this, if you put folate in during the exposure, which is a vitamin basically, a supplement. Essentially folate would suppress the ability of the genistein to actually promote the transgenerational or the next generational effects. What that suggests is your nutrition, supplements, and things like that will be very critical to suppress your response to an environmental stressor that may influence you and potentially your germline of future generations.

What we have found more recently though is once the generation gets defected, and you go forward a couple generations, and it's programmed, those supplements that have negligible effects to actually change that. Therefore, we’re not able to—It's really during the actual exposures that that's the critical thing. Once it programmed, it's programmed, and you really can't reverse it per se. We're not aware of any way to do that at this point, and on a molecular level, we also can't really fix it. It is doom and gloom, but it turns out by knowing that these phenomena exist, what we're right in the process of doing is showing that we can identify epigenetic biomarkers. We can actually map on your genome, on your DNA sequence, where these methylation marks are. We can use those marks to diagnose specific diseases, to diagnose whether you’re susceptible to get this as you get older, whether you're going to have these characteristics potentially going forward. We can use those things as diagnostics to then put in place a preventative strategy, whether it be through diet and supplementation, lifestyle changes to then basically delay the onset or suppress the onset of the disease later in life.

We also know there's a series of therapeutics like Tamoxifen with breast cancer can be used to suppress or delay the onset of the breast cancer by a significant amount of time. The problem today is we don't know which women that are potentially going to get breast cancer, to give the Tamoxifen to because they don't have it yet. If we know from the epigenetic marks that they had a susceptibility they were going to get it, we could give them Tamoxifen for a period of time, which would delay the onset 10, 20, 30 years. Essentially, I think we won't be able to necessarily fix it, but we definitely will be able to treat it through a variety of lifestyle changes, potential therapeutics and so forth going forward.

Dr. Pompa:
We have a large and growing doctor group where we do a lot of these things. We get the epigenetic component. Through some more dramatic I would say dietary things, feast/famine cycles, emulating what our ancestors were forced to do. We see dramatic changes, which we know are affecting the epigenome. More so than like you said just giving the one nutrient so to speak. When we do these feast/famine cycles and fasting and different things, we have a dramatic effect on stem cells and the epigenome. My work, which I call True Cellular Detox or taking the toxins out; it's working. Like you said, there is hope beyond that. I have to ask this question. The testing that you mentioned is this different? Who has access to this testing? The SNIP testing became popular for a while, but we realized epigenetics was going around a lot of the SNIPs. Where can you get this testing and really what kind of testing is it because people are thinking the ancestral testing, the 23 and Me, they’re thinking SNIP testing? Define that a little bit.

Dr. Skinner:
I think right now we're at the early stages of research to show the presence of these epigenetic signatures that are associated with disease, both in animal models and now we're moving to humans and then validating these signatures. I think eventually probably with within the next five years, you're going to see a number of companies come up like 23 and Me, but they will be mapping the epigenome instead of the DNA sequence. What we're starting to find is there may be a finite number, maybe it seems like a large number, but it’d be 40 or 50,000 sites in your genome that are sensitive to these shifts. We can actually analyze them. If you have this set, you go with this disease. Where if you have this set, you're going to go with this disease susceptibility, or you're going to have these—so we think we'll be able to actually get to that place hopefully within the next five years. It would be more of a publicly available so that medical community could use it to help diagnose and manage it's -inaudible- better, but it's not available today.

Dr. Pompa:
Yeah, I mean I knew that was the answer. When the SNIP testing started, and just to give people a relevance what I'm talking about is the MTHFR genotype, where the I don't methylate well. All of this SNIP testing became popular. I, like many, jumped on the bandwagon; was very excited about it so I studied. Then I brought it into the clinical world and realized this is not holding up like I thought it was. It's not as clean as we thought. Oh, you have this SNIP. You have this genetic type. Then this is going to be the treatment or the outcome. Didn't work out and I believe epigenetics is a big reason why some of these SNIPs aren't as clean as we thought. Am I right on that?

Dr. Skinner:
Not necessarily; to a degree you're right. The way to look at it is this. In 2000, when we sequenced the human genome sequence, the prediction was that we could sequence your DNA, and from looking at mutations, we would diagnose what disease you were going to get, all this stuff. For the past 18, 17 years, we've been doing that. Literally, it's the most expensive—we put more money into that than any other area of science. NIH funds, probably 90% of everything it funds through the National Institute of Health, is to do genetics and this type of thing. They've been doing it for quite a while. They've done every single disease you can think about, neurodegenerative, every disease you want to think about.

Across the board, most of the diseases do, not all but most of the diseases do have a mutation like the SNIP or something that they find. The problem is that all across the board, it's in less than one percent of the people that have the disease. If you have 100 breast cancer patients, and you have these SNIPs, or prostate cancer, or whatever, you're going to have 1 out of 100 with the association. The other 99% don't have any correlated mutations. It was a useful exercise. It shows that genetics is involved, but it's not the mainstream.

Now, when we do an epigenetics analysis on a population with disease, we see 90% or plus that actually have these epigenetic shifts. It's not a minor thing; it's the majority of the population. That's going to be the switch on why the genetic testing didn't really come through as much as we thought. I think epigenetics is actually going to do it because we do see it across the board. It's the driver basically.

Dr. Pompa:
I couldn't agree more. Yeah, I mean because clinically the SNIPs really wasn't what we thought. I believe the epigenetic testing will be what really matters. Again, you’re the expert here. That's just my opinion clinically.

Dr. Skinner:
Just to clarify, I think what this does, it opens up this whole area of preventative medicine. In other words, there's a reason you have a susceptibility to get breast cancer when you're in your 50s and 60s. More than likely, it was an early life exposure or an ancestral exposure that actually promoted this, and you have this shift in your epigenome. If we can diagnose that, and we have therapeutics and lifestyle changes, and so forth that you can do in your 30s or late 20s to actually then prevent this from developing for another 10—shove it out there for 10, or 20, 30 years. That what we've been talking about for preventative medicine becomes a reality. We can actually do it. Today, we simply don't know which patients are susceptible to disease until they get the disease.

Dr. Pompa:
Michael, I don't know if your work crosses into the microbiome and the role that the microbiome has on epigenetics. There's a lot of research here. I've been reading and following it. We get that the microbiome is a major player, bigger player than we thought. What's it role into the epigenome and turning on and off these genes?

Dr. Skinner:
The microbiome doesn't directly turn on and off genes. They're like a symbiote. In your body, you have this microbiome in your gut that basically will produce things. Those things that are produced will interact with your cells in your body. There's this communication that we now are realizing exists. How healthy your biome is will determine how well that communication goes. It's more the factors produced and so forth. If you have a certain microbiome that produces negative type factors, then you may be having some problems. If you have a good biome that's producing more positive type factors, then you're going to have those types of things happen. It's more of an external environmental influence, not an internal molecular influence. It's more the things that are produced by the microbiome. I would treat it like nutrition. The diets you have is going to directly impact your health. The quality of your microbiome will do the same thing. It's giving you things that your body then takes and uses.

Dr. Pompa:
Okay, got it. Is there a generation that is hit the hardest? Meaning, let's just say I was exposed to a chemical, which I was. Is it my generation that’s hit the hardest, or the second, or the third generation? Has that been in any of your research?

Dr. Skinner:
In terms of development, these various times during development where there's more sensitivity versus not. Essentially, when you're a fetus is the most sensitive time. Your most effected by anything that comes in that's not supposed to be there: chemicals, whatever. Essentially, that's the most— Also, because all your organ systems are developing in the fetus. In that early part of development when it's going from a stem cell to a mature cell, that's when it's most sensitive to get shifted. Once we have the mature cells, then they're actually fairly stable. The fetal period is the most sensitive. Early postnatal for the for the first five years, we have a number of organ systems like your brain and stuff that's just rapidly developing. That's another critical time. That's probably the second one. The third one is actually, believe it or not, during puberty. There's a number of organ systems and things that develop, including your brain, during puberty. Pubertal exposures during that fairly long period are very critical. As an adult, then we get this more matured state. Everything's developed and we're much less sensitive to these environmental insults.

The generational impacts really are because of the critical windows of sensitivity. If you're exposed to it as a fetus, all your tissues are being affected, but also your germline. Once that germline gets affected, then when you reproduce it's going to go to the next generation, and so forth, and it will go in the next generation. The fetus is the most sensitive. However, recently we've found that pubertal alleles with an exposure can actually alter the germline, the sperm, and goes forward for the rest of that individual's life as well. That's also another -inaudible- period. The exposures are based on the developmental sensitivity and whether the germline’s affected, if it's going to go to generationally.

Now, for your question on is there a sensitive generation. Every generation we feel has a different set of exposures. In the 1950s, it was DDT. It was the major exposure in DDT. In the 1960s and '70s, it turned out there’s a whole bunch of different things: lead, mercury, lots of other things became really big. Now, we have all kinds of therapeutics, and other kinds of exposures, so every generation’s going forward. Essentially, this can happen in any of them. What we need to do is—this is why the diagnostic ability maybe— We won't be able necessarily to fix all these environmental things, but through the diagnostics we may be able to treat them much more effectively and keep things at bay going forward. In the future, but still, we need to clean up our environment and all sort of things to get rid of it.

Dr. Pompa:
Yeah, it's remarkable what you just said because I've experienced this. My wife got lead from her mother who grew up in that major lead generation. My wife's lead was off the chart. When my kids started having certain symptoms, we tested their lead; boom, off the chart. During pregnancy, you lose bone, out comes the lead where it's stored, obviously effecting their epigenome as well. My son was going through puberty, and all of a sudden, he starts getting these symptoms, different things happening. Test his lead; it's back off the charts. No doubt, he was then affected again by the lead. Now, here's my concern. You've said it so well. Each generation has a different concern. Today, what's your feeling on glyphosate. It's being sprayed on all our food. You and I weren't exposed to this, but the kids today are being just slaughtered with this chemical. What's this doing?

Dr. Skinner:
Let me clarify a couple things. That's a very good question. In the short answer, I think glyphosate is something we need to be seriously¬—look into. Now, we just published a paper with a compound called atrazine. Atrazine was the most commonly used herbicide worldwide and it's used in concert with glyphosate. Essentially, what we found was—

Dr. Pompa:
I'm sorry, what was it called?

Dr. Skinner:
Atrazine.

Dr. Pompa:
Atrazine, okay.

Dr. Skinner:
Heavily in the corn and soy industry. It's very similar to glyphosate in terms of its exposure. Essentially, what we found was, we just did the rodent study, as we exposed these gestating females at a critical first trimester period, when the first germline was developing. We induced these epigenetic shifts in the germline. Both the individual exposed mother and that first generation, all the animals generated, there was absolutely no toxicity, no pathologies. There was no effect. There was no effect basically. In a normal toxicology analysis risk assessment analysis, this would look like a completely safe compound. However, when we actually took this out two more generations, in the third generation, 90% of the animals had one or more pathologies. The major pathologies that were testes disease for the males. They were hyper-lean phenotypes, metabolic disease sort of situations. It was a very big turn up in the third generation. What we're seeing is this transgenerational toxicity going forward is really what we need to think about.

We did another study with DDT and basically showed that when the DDT was exposed to the gestating female, in the first generation, there was absolutely no obesity. By the third generation, half the population of both males and females had a susceptibility to get obesity and became obese. In the 1950s, for 10 years the entire population was exposed to DDT at such levels that there was not a woman that was pregnant in North America that did not get DDT exposure. It wasn't possible because of the levels of DDT used for over 10 years. Therefore, we are three generations now away from the 1950s. In the 1950s, our obesity rate was five percent. Today, it's close to 50%; three generations. These ancestral exposures really are bringing up what we're seeing in terms of today. The lead and the mercury in the 1960s and the early ‘70s, it's the same thing. We're basically seeing this -inaudible-.

Dr. Pompa:
Yeah, gosh, I feel like I'm the only one out there talking about this, right Meredith? I mean you're in there doing the studies. At least you have someone out there talking about it. That's exactly what I've been teaching. When you look at Stephanie Seneff's work; she's out of MIT. She showed that the glyphosate, it's doing a lot of things. Obviously, it's hitting the epigenome. It's opening up the gut barrier, the brain barrier. It's even making other toxins even more potent if you will, allowing them to cross deeper into the brain. This generation's getting hit, man. I guess my question is this. You put it all together, with a chemical like glyphosate, what you're saying. Is this just the perfect storm for disaster?

Dr. Skinner:
I mean I'll step back and say the direct risk assessment for glyphosate shows that it simply is not toxic for the direct exposure. Essentially, this is a very safe compound with all the studies really published in the classic toxicology sets. Unfortunately, nobody yet has done a transgenerational study with glyphosate. We would like to, but finding funding for that sort of thing is extremely difficult. Essentially, if we do indeed find, just like we did with atrazine, which shows that it's very safe for the direct exposure, but generational toxicology needs to be looked at. In the current field of toxicology today, it is not. It is not by the industry, or the governments, or anybody else at this state. The most they'll do is the F-0 mother, and then the F-1 offspring; that's it. They don't go any farther. Essentially, I think for glyphosate, I can't say whether it's going to be toxic at this point. Right now, for direct exposure, it's really not. If indeed it does show a transgenerational effect, then yes, you are absolutely right. It's probably just a major of deal as DDT was in the 1950s.

Dr. Pompa:
One of the things, Monsanto hung their hat on what you said, it's not a direct toxicant. Then what happened was, oh crap, we realized it's affecting the bacteria, their shikimate pathway. Oh geez, we realize now to produce certain brain neurotransmitters we need these bacteria, and glyphosate, unfortunately, is defecting their shikimate pathway and they're not producing them. It was more complicated than we thought once again.

Dr. Skinner:
I think the data's suggesting that we need to look. With compounds like that, it's difficult to get funding to look. Essentially, I think it will be looked at within the next year or two. My suspicion is there's a good chance it will be transgenerational. We just don't have the data yet and that's really the critical thing. You can deal with something that is a low level of toxicity with direct exposure, but if it becomes transgenerational, then it's a whole new ball game.

Dr. Pompa:
I mean, you look at mercury and lead that are both toxic directly and then transgenerationally. We know it's nasty, so that's why they're such bad guys. You're saying you believe then—the hope, and I agree a lot of it lays in some of the new testing. The epigenetic testing, looking at this genetic testing differently, being able then to prevent things, lifestyle, make these shifts in people based on that testing. That's basically where a lot of your future research is going?

Dr. Skinner:
Yeah, basically we are. We continuate to test, usually if we can get the money for it, once a year or something; glyphosate is something we'd like to. The government situation, political situation, the funding for those types of things are becoming more and more difficult. In addition, we are heavily in the area of looking for these epigenetic diagnostic signatures that potentially associate with disease because that's going to be the potential treatment part down the line. That's going to be the translational thing to actually do something about these transgenerational phenomena.

Dr. Pompa:
I can tell you a good way to get funding is coming on shows like this because we have a lot of people. I'm serious because there's a lot of people who watch this that we’re invested into this area. We got to get him on Joe's show, Joe McCullough. You've got to get on his podcast. Pam Greenfields, some of our close friends. We're reaching millions of people, but it's the people that will fund this stuff. It's the people who will—because I know. Thomas Seyfried, he wrote a book, Cancer as a Metabolic Disease. He knows this research very well. He said they get his funding from our group of people because the drug companies that fund that stuff, they're gone. Yeah, they're gone.

Dr. Skinner:
The government money, it's drying up very quickly. Essentially, any time you start pushing against industries, it's very difficult to get government money.

Dr. Pompa:
Meredith, you probably have some questions because this is a topic that you've heard me talk about so passionately, and here we have the man himself.

Meredith:
It's such a fascinating topic. I'm wondering if you could speak to synergistic effects of different toxicants? If you’ve looked at those or if it's been a more singular toxicant that you've looked at?

Dr. Skinner:
Yeah, it is interesting in the fact that we do have exposures with different toxicants. What we see is each one has a unique thing. Like atrazine didn't promote obesity, but it promoted a hyper-lean genotype, which is just as health harmful as actually being obese. Hyper-lean is not a good thing. Then DDT promoted a very obese phenotype and there wasn't any lean, so just the opposite. You see different things between them. There are given tissues: the mammary gland, the prostate, the ovaries, the testes, the kidney, and then your adiposities, your metabolism stuff, and your brain. Those are the most sensitive to environmental insults. The exact pathology in those tissues might shift a little bit, but it's going to be probably that set of organ systems that going to be the first thing where we end up with a disease. There is some differences, but there's also this going forward.

Now, if you've actually thought about—the other part of your question is maybe what if you had two or three exposures instead of just one type thing. We're just in the midst of a three or four yearlong experiment where we actually expose the first generation to Vinclozolin, which is a fungicide, the second generation to DDT, which is a pesticide, and the third generation to—this is the same set of animals. The first one was exposed to this one. The second generation was exposed to another compound. Third generation was exposed to jet fuel, which is a hydrocarbon mixture. Now, we've taken it out three generations from that, and now we're looking at the pathologies right now or over the next year. Then we're going to do the epigenetics. In other words, just like we talked about, each generation has this major exposure over a 10 or 20-year period and then it shifts to something else. What happens in that situation? Do we amplify things? Does it plateau out at the same disease rate? Those are things we don't know, but we're in the midst of doing that.

Meredith:
Wow.

Dr. Pompa:
Wow, okay. I so appreciate your work. I want to connect you to get on some other podcasts because I know you're going to reach the right people. You're work needs funded, just the testing alone.

Dr. Skinner:
That would be a—This area, the federal funding is starting to dry out. To allow the science to progress, we're going to have to get into more philanthropic situations because that's the future source of our research money I think.

Dr. Pompa:
I couldn't agree more. Dr. Skinner, we so appreciate you. Man, we appreciate you coming on. Obviously, we appreciate your work. We're going to make sure that this gets out to a lot of people because you're talking about something that I read about years ago. I probably stumbled upon your work and didn't even know it was your work frankly. Then as of lately, just keep seeing it, so it's getting out there. It's a message that people aren't hearing. It really is. It's a message that people aren't hearing. One of my goals is to teach and preach it, so thank you.

Dr. Skinner:
I very much appreciate the interest. Yeah, the more discussion and the more education to the public, the better. Hopefully, then people become more aware, and we can push things forward both scientifically and just lifestyle stuff too.

Dr. Pompa:
Yeah, absolutely. We appreciate you. Thank you.

Dr. Skinner:
Alright, thanks very much for the interest.

Meredith:
Thank you so much, Dr. Skinner. Thank you, Dr. Pompa. Thank you, everyone, for watching and listening. Have a wonderful weekend, and we'll see you next time, bye-bye.

Dr. Skinner:
Bye.