Listen to the Podcast:
Notes for this week's Podcast
This week's Transcript
Speaker 1: (00:06)
Okay. It appears that we are alive on Facebook and my face is now moving into a Picasso painting. Well, this will be interesting. Um, I, with Dr. Michael Skinner for the second time, and if I keep breaking up into a Cubist painting, we may have to start this again. Can you see that I'm a Cubist painting. Does it look like that? Do you remember if I moved my head like this? I, it was reminiscent of the 1960s.
Speaker 2: (00:37)
Just don't move. All
Speaker 1: (00:39)
Right. Um, let me do this. I will stop my video and give you the floor. Okay. And I want to say that, uh, I'm with Dr. Michael Skinner, who we've spent some time, uh, in LA in 2019. Speaking about your amazing research on how exposure of rats to glyphosate caused damage in the great-grandchildren correct. And you just published something new in the journal, epigenetics, uh, where you discovered the mechanism, how exposure to the pregnant rat was passed down to the next generation, to the next generation and to the next generation. And what it is is not only a sobering demand on us, living in organic and glyphosate free lifestyle, but you actually have shed an understanding of a whole new way that disease is created, not from our genome, but from our epigenetics. So we're going to dive into the dangers of Roundup, like we haven't before, but also a new understanding of disease and how it relates to genes. And I'm going to see if I'm still breaking out, breaking up like a, a, there we come back. Okay. So first of all, let's review what you did. You were at university of Washington or Washington, Washington state, or she state international state university, sorry, wrong, wrong place. And so if you could tell us what you did at your lab, uh, to make the discovery first about the intergenerational effects, and then we'll get into the mechanisms and the nitty gritty. Sure.
Speaker 2: (02:30)
So, um, a few years ago we published this glyphosate paper and, uh, for about 20 years ago, let me step back. We'd identified the concept that there was this non genetic form of inheritance. In other words, most inheritances thought to only be genetics and coauthor through your DNA sequence, to your next generation. And this requires the sperm and the egg to come together. That, that DNA then sort of co has certain mutations and things in it. And that causes this genetic sort of inheritance. So about 20 years ago, we identified the fact that using and other environmental chemical called clotheslined, which is the most commonly used fungicide in the world. In agriculture, we exposed some, uh, outward rat models to these enclosed. And, uh, we initially intentionally exposed to gestating female, pregnant female at a very specific time of sex determination for the fetus, whether they're going to get ovaries or testis, and then basically found that the offspring had phenotypes.
Speaker 2: (03:40)
But then when he bred those out two or two more generations to the great grand offspring that essentially the disease that we saw in the first generation kept being passed generations, even though the only exposure was the F zero generation. So we termed that epigenetic transgenerational inheritance, and it wasn't mediated through genetics. So we caught and B we knew it was actually epigenetics because what the environmental chemical did is it changed the epigenetic makeup of the sperm or the egg. And that actually that make that epigenetic change is what was being inherited. It's not a sequence thing. It's more small molecules and factors around the DNA that regulates how it works like chemical modifications and so forth. Those become permanently sort of, uh, put in place in the germline. And it keeps going inherited from multiple generations and a plant species, for example, had been shown that that can be inherited a hundred generations, that there was a key to exposure, changing a flowering phenotype, and hydrogeneration is the same flowering phenotype. And it was an epigenetic shift. It was doing it in rusafa the fruit flies. It can go a thousand generations. And so it was a wing structure change, and it goes a thousand generations in this non-genetic inherited the mechanism.
Speaker 1: (05:04)
Let me, let me just jump in here and make it clear that the genome did not change the genome sequence of the gene did not change. It was what was being expressed as a result of the, of the molecules hanging around,
Speaker 2: (05:23)
Right? The chemical modifications of DNA, like DNA methylation chemicals, right, right. Or the protein modifications, chemical modifications of the proteins. The DNAs are wrapped around called histones, uh, those types of things, or the really small RNs that hang around that actually help things work. So these epigenetic components is what was changing and it was becoming permanently programmed. And that's what you were inheriting going forward. Now we realize that a significant, if not equally important form of inheritance, uh, phenotypes and traits and forth comes from the epigenome and the environmental induced epigenome versus the genetic sequence that we inherit
Speaker 1: (06:04)
Now from a, from a practical standpoint, before we get into the glyphosate research, which by the way, from what I understand when they evaluated the social media coverage of your discovery from 2019 within a week, and I had 115 million mentions propelling it to one of the top five of all time of the scientific papers that in terms of, uh, social media devouring. So you're, you were known, it was the shot heard round the world, and I'm sure Monsanto and the other months, the glyphosate makers were not happy about that. Um, so we're coming back now to the concept that if something happens to your great-grandmother, if they go through a trauma or if they have a feminine, or if they have something in their life, it may be affecting you and you don't have to believe in consciousness as a field, or even if you do, you don't have to believe in, um, some kind of energetic, psychic, uh, inheritance. It could be the way his stones are wrapped around your DNA. That happened because your grandmother was in a trauma. Is there, is this, am I getting this right?
Speaker 2: (07:27)
Correct. Yeah. The environmental exposures, whether it be trauma, nutrition, environmental chemicals, and so forth of an individual can change your physiology early in life. So it affects your disease later in life. But what it does do is it changes your, your genetics of your sperm and egg, you're getting germline. And that then becomes permanently program sets that then when there's a reproduction and you have a fertilization event that epigenetics gets passed to the next generation, as that individual grows up and reproduces to the next generation, the same epigenetics gets passed. And so this keeps going and it's called epigenetic inheritance. And you're right. It has nothing to do with DNA sequence. It's not mutations in the DNA or anything else. It basically it's, it's epigenetic inheritance the night. The unique thing about that scientifically is the environment can't really change the DNA sequence. The vast majority of things are not mutagenic. They can't change the sequence, but they have very significant impacts on the epigenomes. So the way the organism responds to environmental stressors shifting the epigenome is they will get phenotypic shifts that actually can cause diseases, or in some cases allow an adaptation to allow them to survive better. So that then evolutionarily those are actually selected through natural select or natural selection, a Darwinian. So essentially this impacts all of biology, just not, you know, um, little things like our disease and so forth, it's everything. And so, yeah,
Speaker 1: (09:04)
I, I have to say that it's one of the areas it's like, I've often said that biology is not rocket science is far more complicated. And if you look at how they evaluate genetic engineering, which I've looked at for 25 years, they, it takes them 20 years to look at low dose endocrine disruptor effects after that's been established, but they still avoid looking at these epigenetic effects. Finally, within the last few weeks, we discover, uh, an article where epigenetic impacts from CRISPR cuts and, and additions was found 10 generations out. That means that if you genetically engineered something, you may make a change that no current research right now will have, will be able to find, but it gets passed on generation after generation, which means it could theoretically take over the niche and with, uh, with an epigenetic change that can cause disease susceptibility to the plan or those who eat it, et cetera.
Speaker 2: (10:06)
Correct. Now to bring this back to your sort of focus here in glyphosate for the field of toxicology, okay, what toxicology is geared around it looks at is what's the effect of a compound or an exposure on the individual exposed. That's called toxicology direct exposure. Toxicology is the only way we do toxicology today. Every single government agency only looks at direct exposure toxicology. What we did, what we found with glyphosate is if you do the direct exposure, we don't really see significant effects in our, in our models. They, it looks like [inaudible] is exceedingly safe. And so this is the, this is the industry coming out and saying, this is a really safe combat, which it is for direct exposure, what we did
Speaker 1: (10:58)
Well, you inject it into a pregnant rat and that particular rat didn't have any adored, correct?
Speaker 2: (11:06)
Correct. And so essentially, or males that being exposed to through diet or whatever. And so essentially, but if you take that individual and it gets bred to the next generation, or maybe another generation, essentially the disease rates go significantly higher. So it's 90% of the animals are developing disease. This is called, this is what we're calling this generational toxicology. It's not necessarily the direct exposure. That's a problem. It's your effects on your great grandchildren. We need to worry about. And so do we have a responsibility for our grand grandchildren's health? I think most people would say yes. And so we need to actually expand our view of what toxicology is beyond the simple, direct exposure effects to a gen X and the next generation. So this, so essentially the way this works is it's through these epigenetic inheritance mechanisms. And so w and so it's not like Monsanto knew about this, because this is very new science, essentially, this is new stuff, but it may, we should step back and try to reevaluate the way we do things and whether certain things, and there's, it turns out there's a number of environmental chemicals that are agriculturally based, like, uh, atrazine does the same sort of thing where there's no effects in the first generation.
Speaker 2: (12:34)
It only appears in the second or third generation. And then the disease incidence is very high.
Speaker 1: (12:40)
So I want to go into the specifics of what happens in the cells that allow this to occur. But first let's catch everyone up. You mentioned 90% of the great grandchildren of the rats that were injected, which was greater than the grandchildren, which was greater than the children. So there was a multiplication of the impact generation to generation. Just, can you mention those diseases that you found of, uh, in the great-grandchildren of the exposed?
Speaker 2: (13:11)
Sure. We see a Kennedy disease in both males and females, prostate disease, uh, in the males test is disease in the males. We use the ovarian disease in the females. We also see some oftentimes in behavioral effects. And one of the bigger is by the time the third generation comes around, usually we see increases in obesity, uh, susceptibility for obesity. So two animals that have this, basically one animal on the same diet, same exercise and so forth. This one will develop obesity and the other one doesn't. So this one has a susceptibility. It's not inducing the disease. It's a susceptibility based on their environment. And so we, we see a number of different things. When I say 90% they'll have one or more of these diseases in that third generation.
Speaker 1: (13:59)
All right. Now tell us the magic sauce. How did it go from grandmother? Great grandmother to the great-grandchildren.
Speaker 2: (14:10)
So the direct exposure of the India, like the gestating female. Okay. Essentially the female, uh, is directly exposed. That's the F zero generation. Okay. So all toxicology associated with that deals with direct exposure, your organ systems are responding to whatever compound you're looking at. Okay. And so that's causing them signal, transduction things and things in the cell to actually alter. And then that potentially can promote a disease in a toxicology. Okay. That's direct exposure, toxicology, the fetus F1 generation at all the only diseases you're going to see in that when it's born direct exposure, toxicology of the fetus. So they offspring the F1 generation generally have much lower disease, because again, it's a direct exposure on the fetus. There's no germline media at event. Okay. It's the F1 generation that has this now programmed into the germline, the sperm or the egg, but then it's, then that the next generation, the grand offspring are great at a grand offspring.
Speaker 2: (15:16)
Where now think about this as a little complex, the sperm and the egg are coming together. And one of them, or both of them have an altered epigenetics, okay. That sits over the top of the DNA to regulate what genes are on and off. So when you have a fertilization event through the germline, the STEM cells that are generated from that early embryo, developing what we call a STEM cell now has a different epigenetics and a different sort of gene expression profile that STEM cell generates every single cell type in your body, your brain, your heart, your lungs, your liver, all the different cell types are coming from that embryonic STEM cell, every single cell type in the body now has it shifted epigenetics and transcriptome. Some tissues like the kidney, the prostate, the ovary, the test is those are sensitive, fairly sensitive to those shifts.
Speaker 2: (16:15)
And so we have a higher incidence of disease, other tissues, like the heart or liver and so forth that doesn't really develop diseases that we've seen. So some tissues are resistant and some tissues are more sensitive. And so essentially because of that germline transmission, all the cells in the body now have this shift and you have a higher incidence when that individual reproduces to the next, the great grand offspring, the same thing's happening again. And it keeps going basically. And so essentially, a germline mediated event, a sperm or egg mediated event has a very different mechanism to induce disease. Then the direct exposure FCR or F1 generation. Okay. And so that's why glyphosate is very safe for direct exposure. It doesn't really promote a lot of diseases in our animal models. There are some things that people have sort of identified in humans and other animal models that if it's high enough, it actually can induce things.
Speaker 2: (17:13)
But for the most part, it's, it's, it's one of the more safe compounds that we've actually generated, but it has a variability to change that epigenetics, that germline, so that the grand offspring, a great grand offspring have higher disease rates. That's a different mechanism. Okay. So that's how, and then the thing is it's permanent. So then as we saw with the plants going out a hundred generations and their fruit flies for a thousand generations, it just keeps going, okay. And so essentially this, this is why we need to start thinking about this generational toxicology, because this is probably where the bigger impacts of these exposures really are not so much on the people today. Now, back in the fifties, when we used DDT, those had big effects because they were used so much. And the, and so we did have direct effects and that's the whole field of toxicology was developed in the sixties from those types of exposures, DDT, and other things. And so that's why they only focused on direct exposure before now with this new information, new science, we need to sort of start thinking about this generational sort of thing.
Speaker 1: (18:21)
And I, my area of in collecting data and sharing it and interviewing scientists I've come across different sets of data than you and your studies in terms of the F zero for glyphosate. Um, I could probably spend 15 minutes just recounting various F zero impacts whether it's damaging the actin in the cell causing collapse or the mitochondria, the gap junctions, the tight junctions, the Geno toxicity, the antibiotic nature, the binding with, um, uh, minerals, making them unavailable, um, the et cetera, et cetera. So I, even though you could dismiss it as relatively little compared to some acutely toxic compounds, I would consider it to be significant. And yet where we can meet is if you think that's bad, you just wait, because then it's going to change. It's like, it's, I've found it fascinating. And you were very clear in the description, how the embryonic STEM cells become everything.
Speaker 1: (19:31)
And if they're messed up the scientific depth of scientific word messed up in a certain way, skewed in a certain way, they'll pass that on. They'll whisper that same mess up to everything that they become, including the germline, which gets passed onto the next offspring, which gets panned out, passed onto the next offspring. Now, when I ran the last interview with you doctor, I was, I got a comment from a friend of mine, Dr. Michelle pero a pediatrician, and she said she really enjoyed the interview, but disagreed with you on one thing. So I'm just going to lay that out there. I basically said, I asked you the question, so what can we do to reverse the trend of an epigenetic genetic issue that we've inherited? And you said, there's nothing that in her awareness, there are things that we can do. And that the medicine is getting to a point where if we could see how the environment can cause a change in one direction, we can see how to create a new environment to undo that change. So in that case, she was not taking it as a sentence for all future generations and that slum smart flute, fruit fly, if they just knew the right medicine would have stopped at somewhere in the thousand generations.
Speaker 2: (20:55)
Yeah. Well, for example, I don't disagree with her, but I think we're 50 to a hundred years off from having the technology to make those decisions. And this is why there are, she's absolutely right. There are some therapeutics that can be used. It's there right now used in stage three cancer patients for a number of cancers. They take this therapeutic and they can extend their life for two or three months. Okay. So it's not, it doesn't make them survive, but it extends their life. Then they die after three months, you might ask why they die. It wasn't because of the cancer or something. The therapeutic that they were using, the epigenetic changes that were so severe that were going on eventually killed the patients. Okay. So yes, it extends it, but it has its costs. We today can't target therapeutics at a specific site in the genome or, or, or a certain cell type and things like that.
Speaker 2: (21:58)
And so I think I don't disagree that eventually we will be able to potentially get there, but we're quite a bit off of that. Now there's another thing where there's a compound called full plate, which is a vitamin, basically Foley is a methyl donor for the DNA methylation that we measure that's changing. Okay. So you'd think the, basically there's two little Foley and you just gave enough folate that you might actually shift the epigenetics, which can occur. You can actually measure that. Unfortunately, you get too high in the full, late guess what it becomes toxic causes. The epigenetic changes to actually cause more disease than what you were trying to treat. And so essentially if you take fully above maybe 200%, the daily dose recommended it becomes toxic. And so we just don't know enough science around these manipulations of their genome yet we're just in the early days for us to take any kind of measures like that. I w I think we will get there in 50 or a hundred years, but it's down the line. So we have to
Speaker 1: (23:05)
So possible that the ancient wisdom of health had an understanding of the impacts of food. They talk about food as intelligence or as knowledge, and it gets that information gets transferred. And I remember hearing about Iyer Veda with this concept, and then reading about the RNA because of food and herbs and how that can modulate gene expression. And it, it fit hand in glove with the description of the ancient understanding of food. Now, what's interesting here is we constantly upgrade well, in this case with food, it's not constant it's with these big leaps, it was vitamins and vitamins and minerals, and then phyto chemicals. And now we realize that the food that we eat has RNA and the RNA may help reprogram or program cell gene expression. It might have, um, other ways, as you mentioned, the methyl groups and also the histone, which was part of your research. So it becomes much richer when you look at the quality of the food, as well as the quality of the toxins. So it can cut both ways that maybe there's qualities of the food in terms of ability to inform our epigenetics, to, to chill and release the impact from the toxicity.
Speaker 2: (24:28)
It's not necessarily, I mean, you're absolutely right. Do you understand that RNA is, but it's all these non-coding RNA is these smaller and NAS, that's an epigenetic component, right? The epigenetics, one of the major components of epigenetics is those small non-coding RNA. And that's what you can actually ingest from food and have it maintained in text. It's very stable and that's, what's actually causing the effects, the big RNA, as you think about from a protein or something, those get degraded very quickly. It's the small RNs, which are epigenetic and function. They have nothing to do with the DNA sequence and they basically regulate things completely independent. So that essentially it's the epigenetics from the food. In addition, nowadays, there actually is a pretty, uh, uh, re uh, resurgence in Chinese medicine and so forth Asian sort of medicine that there's a lot of these medical approaches taken out of Chinese medicine, classic sort of traditional Chinese medicine, which have the same type of thing you think about in terms of food. There are herbs and so forth in there actually. And they now realize that epigenetic sort of modifications and so forth. They're a part of those mechanisms that they're looking at. So I agree totally in the future, we probably need to be a little bit more open-minded to our classic and traditional approaches, uh, and bringing that into modern medicine sort of approaches to bring, have a better sort of eventually medical approach.
Speaker 1: (25:55)
Now, having talked about the epigenetic impact of, of small pieces of RNA, um, you could probably understand why I'm a bit upset about the genetically engineered Apple and potato engineered with double-stranded RNA to silence the gene that produces Browning, because now you're have a epigenetic, uh, stable molecule and the food that we eat, that's known to reprogram genetic expression and doesn't necessarily limit itself to the Apple or the potato, but we eat the Apple or potato, or the RNA interference sprays that have been approved to be pesticides, or you can spray it and imagine the poor person who gets sprayed because he's the actual sprayer. And he gets full of that spray, and it might have epigenetic effects on his own genome. But now what you're saying is, and his, or her children and grandchildren, and great-grandchildren,
Speaker 2: (26:53)
So, um, you can genetically engineer in organism, okay. To make it different, like the CRISPR, Apple, okay. The basic genome and the basic RNA message RNA that's actually generated. Okay. If you eat that Apple, it's degraded in your stomach and doesn't go any farther. Okay. It's essentially normal sort of diet has lots amount of DNA. We ingest lots of RNA and lots of DNA. And we just, whether it's from a cow, whether it's from an Apple, whatever it is, and we did a digest it. So that is not, should not be seen as a foreign hazardous sort of thing. Okay. Now, if the genetic engineering generates a product that is toxic, then we potentially are ingesting that toxic. Now the CRISPR Apple is much more of a genetically engineered plant where it's in the basic DNA sequence and there's different sort of RNA generated that actually is causing sort of the taste in or whatever we're getting out of it.
Speaker 2: (27:59)
So that's really doesn't have the capacity to necessarily be harmful. It sounds very science fiction like, but in terms of that, you have to understand that when we ingest things, we are going to digest classic DNA in classic RNA. Now, if they make a small ne a non-coding RNA, most things are species specific in terms of their function. And so just because it's in an Apple, it doesn't really, it's going to have a function in the, in the, in the human. It doesn't mean that we shouldn't test its toxicity. And that's something that probably has not been done extensively. And so we needed to test the toxicity of some of these things that are generated. Uh, if we actually test them when there's not major effects, then it's probably not an issue. Okay.
Speaker 1: (28:45)
Well, if we had more time to dive into this, I would point out some research that that comes from a different angle. I did some research on RNA interference with, uh, I interviewed Jonathan Landsman who used to work at the USDA, who talks about how RNA from one species can impact another. And Dr. Jack Heinerman from New Zealand who points out that the regulatory agencies and the biotech industry claim that because RNA is break, gets broken down during digestion, we don't have to worry about it. And yet they use it for regulating DNA expression in such a way that it has to survive to some degree in order for it to even do that. So, and there was also some very specific research that shows that it is in fact stable and that there are some of the research that was, that showed that it was stable, was later attacked by Monsanto.
Speaker 1: (29:44)
When I interviewed the woman and she was outraged because it was clear that what Monsanto was doing with double stranded RNA was dangerous based on her research. And they were trying to discredit her research because it showed that there were playing, they were playing with regulatory fire. Um, so in addition, like when honey bees were fed double stranded RNA for a meal, they had over 1400 genes that became dysregulated over a few weeks, but it came from a jellyfish and it was, it was cross species. Anyway, I, as I say, I'm, I know enough. I have, I have steep walls where at a certain point, I'm like, Oh, I don't, I can't talk to you about his stone. You know, his stone differentiation and all that, because that's not where I have the background, but I'll just say that there's my concern. Is that what we learned here in talking to you about the multi-generational effects about the epigenetic effects, they are the small pieces of RNA, et cetera. And we compare that to the regulatory reviews, whether it's toxicology and the F zero or GMOs, which has even less than a standard toxicological review, it shows that we're, we're playing with fire here.
Speaker 2: (31:02)
Well, I would say that you're absolutely right. There's not a lot of science done in these toxicology analysis, and it's not in depth enough to actually make some of the conclusions that, that it's not present or something, and it needs to be investigated, but there's lots of normal examples of non-coding RNA or just RNA in general, which they're not sort of the toxicity that you're suggesting. And so you need to be cautious of not overact reacting with these types of things. So for example, uh, engineered, uh, yeah. Have to understand that we, when we engineer plants, we've been doing that for thousands of years. Okay. When they actually look out over a corn field and they have one plant that actually is a little higher, bigger, and has higher production, and you go out and pull that out of the ground and you propagate that in the next farm, that's a form of genetic engineering. Okay. We didn't go in and actually do something experimentally, but we've selected those types of things for literally a thousand years. Okay. And so, to a degree, some of these are some are natural products that are just shifted. And so therefore you get the creature, that's an ingrained form.
Speaker 1: (32:17)
And I have no problem with natural selection and, and wide cross breeding. I have no problem with that. I am aware that the process of genetic engineering done in laboratories introduces specific risks that are different than those that are injectables.
Speaker 2: (32:31)
I wouldn't disagree and they need to be tested. It doesn't mean we determinate them. We need to be tested as to if there is health down a lot. I agree. You know,
Speaker 1: (32:40)
We we've, we've stepped out of the box. I mean, I could, I've been doing the evaluations of these things for 25 years and traveling 45 countries and interviewing, you know, some of the regulators and the scientists and whatnot, and compiling them in books. And I love talking about this stuff, but I actually would prefer in terms of talking with you, learning from you in areas that I don't know for sure. And that this is an area where you are one of the world's experts. And I would like to just share before we finish, I would like for those of us who are really into the science, if you could explain very specifically how the epigenetics works in the sperm cells that you tested. So the histone and the methyl groups, and then finally how we need to rethink in terms of genes as expressions of diseases. We had a little bit of that, but let's just, let's just burn that, that myth completely and introduce a new understanding, but let's start with the simple mechanics that most people never get to.
Speaker 2: (33:53)
Okay. Sure. Okay. All right. So epigenetics is defined as molecular factors and processes 30 or around the DNA sequence that can regulate what genes are on and off genome activity, completely independent of the DNA sequence. The sequence has no impact on epigenetic regulation that doesn't care. Okay. If there was a sequence dependent, if there was DNA sequence dependent, the process would be genetics. Okay. So by having it completely independent, then essentially it has nothing to do with genetics. It's just now that the main types of epigenetics is there's a chemical modification of DNA in it, a methyl group, a small, uh, uh, carbon group with a couple of hydrogens gets attached to, uh, the DNA, right? And that attachment can actually change the structure of the DNA slightly, but it can also interfere with proteins and things binding to the DNA. So it completely changed thing.
Speaker 2: (34:57)
Okay. So DNA methylation is what we study extensively. And so that's, that was the first epigenetic component identified. The second one was called histones. There's a core of eight histones that get together and actually form this spherical structure. And the DNA gets wrapped around it, just like a bead, a string wrapped around a beat, okay. It takes a couple of hundred nucleotides to get it wrapped around it. And so essentially DNA is not like this naked strand of DNA. It's DNA is wrapped around these histones. So you get this bead and then this bead and this bead. And so it's on a string and then those get twisted and the whole thing comes together and it forms this double helix. And you get these basically everything's comes together with these hits, with the histones supporting this DNA structure. Okay. So it turns out that the proteins make up these histones.
Speaker 2: (35:55)
If you chemically modify these histones, guess what? You can actually turn genes on and off based on the histo modification, it doesn't care what the sequence is. So that's epigenetics. So the first one is DNA methylation. The second was histone modifications. Okay. The third one identified was the chromatin structure. If you have, let's say the DNA is going along. And all of a sudden you have a loop that goes around this thing on this piece of DNA can interact with this DNA. And it turns out if there's a gene sitting there, it can turn the gene on or off. Okay. And if you break down that loop, you can actually have an effect as well. So the structure of the DNA, we called chromatin structure has a significant impact on genes going on and off. And that's the third sort of epigenetic component identified. The fourth one that we identified was these non-coding RNA, not the, not the message RNA that are making proteins.
Speaker 2: (36:55)
It's these really small, the smallest ones are, let's say, 15 to 20 base pairs. They're really small, short, bigger ones are maybe a hundred and a long arm. Non-coronary Hesperia. You're a few hundred. Okay. So these small ones is really where they, again, they don't make proteins, but they bind to proteins or they bind to DNA, or they bind. They have structures associated with them that facilitate protein, protein interactions, lots of things going on. And so they can actually go in and directly turn genes on and off independent of sequence because they're interacting with proteins and things in the DNA. So that's, that was the fourth one identified. And those are probably just a tip of iceberg. I think we're going to see lots of new epigenetic components that we don't even know about today because the fields that young, that I think we're going to see a whole plethora of new epigenetic components.
Speaker 2: (37:46)
Okay? So these different epigenetic components get together, they interact with each other, actually then turn genes on and off completely independent of DNA sequence. Okay. You have to have a gene there you'd have to have a promoter there. And basically the epigenetics is what basically turns them off. So in your neuron, you can have this set of genes turned on and your liver cell you'd have this set of genes turn on. And the reason they're turned on in this cell and this cell is because the epigenetics in those two cell types is different. And so they regulate different genes. You have 200 cell types in your body. Every single cell type in your body has completely the same DNA sequence. So why is it? You have 200 cell types in your body. If the sequence is exactly the same, I'm sorry, the genetic sequence can't drive 200 different cell types.
Speaker 2: (38:40)
This doesn't do that, but the epigenetics and every single cell type is completely different and unique to that cell type to give it that cell specificity. So what generates the genome, the expression pattern in the neuron versus the liver is not the DNA sequence, as much as it is the epigenetics in those two cell types. So the way to think about it is I'm not going to say one's more important than the other, but basically the DNA sequence is just as important as the epigenetics in terms of regulating biology. Okay. We just never paid attention to the epigenetics before for the past hundred and 20 years always thought about is genetics and the DNA sequence, all of our, most of our science gears towards looking at gene genetic mutations. And there's nothing wrong with that, but it's like you get this small piece of a really big story here, and you're not paying to pay attention to the rest of it. Okay. So this is what we have a paradigm shift in. Science are occurring right now, and it's been occurring for the past 10, 20 years. And it probably take another 20 years to get a complete shift in the paradigm, but the, where we're going is equal having equal contributions of every genetics and genetics in terms of our thinking about evolutionary biology or disease etiology, or just basically how things work. Okay. So that's basically sort of a quick discretion of the field of epigenetics. Okay. Okay.
Speaker 1: (40:10)
We have the genome and we have the epigenomes. Now I know that when a gene creates a protein, well, it creates first the, uh, RNA, and then the RNA, the RNA can get alternatively spliced, right. Form different sequences, which can then produce different proteins. Correct. And what in the cell determines that alternate splicing, is that also the epigenetics or is that a third field?
Speaker 2: (40:42)
No, it's basically epigenetics. That's determining whether the splicing occurs at this point or this point. And so therefore it's epigenetics and genetics are completely integrated. You can't really separate the two, the way the genetics works is by having epigenetics, how many of these functions turning things on and off and so forth. And without the DNA sequence, the epigenetics is somewhat pointless. And so they really are sort of this integrated things. It's not like one's more important. The other, they, they, they're a unit and you really can't separate them. Now we need to start thinking about these epigenetic things that we haven't really thought about before, like epigenetic inheritance. We talked about that's completely new concept. When we first identified the phenomena for 10 years, I fought this because this is heresy. This is genetic literacy, essentially to say that there's a form of inheritance that to genetics.
Speaker 2: (41:34)
It took about 10 years. And finally people, other people started doing the experiments and realizing, Oh, this looks like it's actually working. And now hundreds of labs and like probably almost a hundred different species have done the same thing. Okay. And basically identified epigenetic inheritance is basically a real thing, but it took that long. And so I think paradigm shifts, there was a fellow and basically the 1970s, he came up with the theory that essentially a paradigm shift in science takes at least a generation of scientists because the current scientists are so ingrained in that dogma. They're not going to change. And the new scientists coming up, they realize, Oh, this is a better way to think about it. They have no restrictions. They have no invested interest. And so they'll step in essentially. And they create the new science called moving forward. So it's the same thing with epigenetics. We've just sort of in the nineties was it's really pushed forward in 2000, we got a little bit farther. So we, we need another 20 years and we'll probably be there where, where it needs to be, sort of looked at
Speaker 1: (42:39)
Now, one thing that you found in your study that was just published in the, in the journal epigenetics was that when you looked at the rats where the great grandchildren of the injected female rats, they had, what was passed down where certain, um, histones or methyl groups on particular genes associated with the particular diseases suffered by the rat and the prostate. You had mentioned obesity, you had mentioned the ovaries and the testes kidneys, I believe. And so this shows that they specific you can look at and evaluate, cause right now it says, okay, I have 23 and me, and I've done the medical thing, or I have ancestry.com and I've done the medical thing. So now I know what I am successed susceptible to, but there may be in, according to your research, a future at looking at our epigenome to see where these methyl groups are. And if they're sitting on top of specific genes that are related to certain diseases, is that right?
Speaker 2: (43:43)
Yeah, absolutely. So what we've been talking about, put it in simple terms, um, what's your great grandmother got exposed to, or grandfather is going to cause a disease in you and you may never see that exposure, that environmental sort of factor, but you still get a disease and then you're going to pass it onto your grandkids. So I'm sorry, this is pretty doom and gloom. Thank you. So, in other words, you know, you can't control anything your grandparents did and you CA it's difficult to actually control what your grandkids are going to do. And so essentially this is pretty doom and gloom. So, so I've been thinking about this for decades. And so to say, okay, how do we go to the next step? How do we take this basic and take it to the next step? Okay. No. So the initial steps were, we started looking at, we have, we've looked at the effects of 16 or so different environmental toxicants and that we've promoted models with all three, all of them, the promo, they all promote transgenerational inheritance, but the epigenetic changes for each exposure.
Speaker 2: (44:52)
It turns out to be unique to that exposure. In other words, there is hardly anything overlap. Okay. And so that gave us the idea that, Oh, so you got kidney disease coming up with all of them. And so why is it coming up? So we're starting to get a better understanding of basically how disease develops, but what we started to doing is getting biomarkers for exposure. So the next thing we ended up ended up doing is sort of starting getting biomarkers for the given diseases. So the recent study is we used glyphosate model that we generated in 1990 and 2019. And we actually take those animals out. We analyze all the diseases they have, and then we actually isolate all of the animals with kidney disease, just Canadia, these nothing else, just kidney disease. We take those. And as from analysis from the father, that's causing the kidney disease and we basically get a biomarker for just kidney disease, epigenetic changes that are just kidney disease in the sperm.
Speaker 2: (45:53)
Okay. We do the same thing for obesity. We do the same thing for ovarian disease, I mean, and, and so forth. And so we have these disease specific biomarkers, and we did this with I think, six or eight different environmental exposures to actually show that indeed we have these epigenetic disease biomarkers. Okay. Some now these overlap a little bit more than the exposures did. So now it using that. So with glyphosate, we have epigenetic marker biomarkers for each of the diseases that the glyphosate was inducing. Transgenerationally three generations that's later. Okay. Now think about this. If you could, I actually use a biomarker epigenetic biomarker and determined what your great grandparents were exposed to. And by knowing that exists, what diseases you potentially are going to pass to your degree grandkids, we can actually use that biomarker to say, okay, early in life for your grandchild child or your child, you basically say, if you do the epigenetic tests, here's the biomarker that's present.
Speaker 2: (46:58)
We know you have a such and such percentage chance of developing breast cancer or, you know, basically kidney disease or whatever. And so because of that, now you can step in before the disease develops in the individual and actually come up with some treatment, either a lifestyle change dietary or whatever, or a therapy [inaudible] to actually treat the interview before they have the disease to delay or prevent the onset of that disease later. Okay. Now we weren't the one to show the feasibility of this. The first observations were done in the cancer field for breast cancer. Okay. So that breast cancer has had a number of chemotherapies developed to actually treat breast cancer after it develops. Okay. One of the treatments that were came about was called Tamoxifen, okay. Tamoxifen is a chemotherapy. It doesn't really work well to treat disease that breast cancer after it develops.
Speaker 2: (47:55)
But what they found was if you actually were in your thirties, most breast cancer occurred, as we say, between 50 and 60, maybe up to 78 years. And so if you went into your thirties and you took Tamoxifen for two or three years as sort of a preventative therapeutic, it would delay the onset of the breast cancer by 10 or 20 years. And sometimes then a hint of it inhibit it from happening in the first place. Okay. That's called a preventative therapeutic. The reason we don't have more therapeutics like that is we do not have any way to test whether you're susceptible to get the disease later in life, epigenetic diagnostics will give us that capacity. Okay. So this is what this particular study did. It said that with the glyphosate induction of this transgenerational, we have these biomarker specific disease to show the proof of principle.
Speaker 2: (48:51)
We could have those. And then basically now in the future, it won't be that useful in a rat model, but in an era, in the human model, we could actually develop those types of things like the Tamoxifen treatment for breast cancer. So what epigenetics is going to do and genetics actually thought that it would in 2000, when they sequenced the genome, they thought that they would get these sorts of things from the genetic mutations. But it just didn't, it wasn't realized because the mutations turned out to be extremely low frequency events. Every genetics is a very high frequency sort of issue. And so that doesn't have that problem. And our models are telling us that we can actually use those diagnostics to treat so, so we may not be able to fix the problems that glyphosate has induced, but we, to be able to treat them in our subsequent generations as a preventative treatments to actually treat the diseases.
Speaker 2: (49:43)
So we won't give a get rid of it, but we can treat the diseases to improve our health accordingly. So now it's not quite as doom and gloom. In other words, we, because of the technology, we might be able to do something about it in the future and take basically ushering in this preventative medicine approach and preventative therapeutics that we really couldn't do efficiently until now. So I think that, so that the current glyphosate paper is really giving that first sort of proof of principle that indeed those types of epigenetic sort of diagnostics exist. And now going to the human now we've recently published this last week that we could do this in autism, in humans. We could take a father sperm basically, and actually assess their epigenetics and potentially tell whether they have a susceptibility to have an autistic child. The nice thing about that is if you can catch autism early in life before the age of one and two and do some treatments, then you could actually decrease the severity of the autism direct dramatically.
Speaker 2: (50:46)
And so we might be able to click the clinical management of the disease, might be a preventative sort of approach to do the end of this from the epigenetic analysis of the father's sperm. And so I think in the human, we now have some indications too, that this is going to work, or at least the proof of principle. Now we need to do larger clinical trials and so forth and sort of move forward. But that's why we're spending a lot of time now, because now that we've identified the phenomena, the next step was, well, what can we do about this phenomena? Because it's basically now ingrained in our population and our, and the increase in disease we've seen over the past few decades is because of all these environmental factors. Sure. We should try to clean it up. Sure. We should try not to use them and so forth, but what do we do about the people that were exposed? And so this sort of starts to address that.
Speaker 1: (51:34)
I think we talked last time about we're a generation whose parents or grandparents were exposed to DDT, and that might explain, um, obesity or something like that coming, coming out now because of the epigenetic markers. So even though I wouldn't be even more optimistic than you and say that we're going to be able to do a kind of, uh, uh, treatment that may not even be, uh, pharmaceutical, but more holistic where we can use the intelligence of the body to restructure the, the, uh, environment around and inter twined in the DNA. So we could shed this stuff. But I also find it fascinating that like, I know people will say, well, I've got the particular genome or the, the gene for, for breast cancer. I've got the gene for Alzheimer's and, you know, pretty soon they're going to say, yeah, but do you have the epigenome sitting on top of that? So is it actually where there's the, you look at the particular location of the gene and you look at the, at the vicinity around the gene to see if the methyl group and the histone and the chromo tended all that right there at the place of the, at the suspect gene. And that's where you do your row. You're looking,
Speaker 2: (52:49)
Um, we do, when we do a epigenome map, first of all, we do genome-wide analysis. And so we identified, you know, and I think in the glyphosate diseases, there were three or 400 epigenetic sort of sites that we identified. So my opinion is it'll never be one site. It'll never be even a few sites. It's all two or 300 or a thousand sites. So we have to stop thinking about the fact that one thing can do something. And so that's a, that's called a reductionist view in science. And then a reductionist view is not getting us anywhere. We really need to step back and look at this as a system. And so when we do an epigenome map, we do the whole genome and the way you're going to think about this, this here's the diagnostic. And if you're going to do some sort of therapeutic treatment, it has to affect the entire epigenomes who had to fix this, this with genetics, w it was very difficult to do large numbers, and you have to understand if they get a genetic mutation for Alzheimer's or whatever, it's in one and a hundred hundred people have the disease it's in one individual it's that, that low it's usually less than 1% of any kind of disease biomarker like that, or mutation is within the population.
Speaker 2: (54:03)
It's a very low frequency event yet we can take in the case, we just did. We took 15 individuals that had autistic children, and we identified 800 of them that were present in every single individual. So it's a much higher frequency event. Okay. So we have to start doing more global, you know, genome wide stuff, and stop doing this reductionist approach. And we'll actually get someplace I think. And so, so I'm not sure if that answers your question, but
Speaker 1: (54:34)
It's even better. I mean, to me, I've been railing against reductionist thinking for a long time. In fact, I'm excited someday. I'd like to visit you when the pandemic is over, or at least get on another zoom call. And based on your understanding of the shortcomings of, of F zero toxicology and the impact, the potential impacts of manipulating DNA, which could change RNA and can change regulatory, um, impacts of RNA on the same and few other species. What I'd love to do with you is to map out what a more ideal assessment for, uh, GMOs would be, you know, so that in, unless it gets this, this, this, and this you're putting future generations at risk, you're ignoring. I mean, they don't even do genome genomics. They don't do any Omix right now, they don't look at anything. When they create a genome, a GMO for food, they just say, well, it seems to be creating the pesticide or add or resisting the herbicide.
Speaker 1: (55:35)
So we won't even sequence the protein that we expect it to be created. And then they found out later, it wasn't at all what they wanted. Anyway, I'm not going to rail against that. That's just my area. They're like doctor. I said, when we started, I said, the last time we talked for 47 minutes, I don't think it's going to be that long. We actually, I just love talking to New York. You are. So, first of all, as a scientist, you're not only on the cutting edge of what you do, but you're also brilliant at explaining it so everyone can understand. So I feel like that people like you and you in particular can speed up the way that the generation takes before the paradigm shifts, because it's not obscure. It's not held off on the far reaches of geekdom it held. And you're tied down by jargon. You're explaining it in such a way that feels right. And you're also creating, uh, most importantly practical steps, which can save lives, which always speed up implementation. So
Speaker 2: (56:39)
That's, that's one of the, uh, uh, problems with being a professor. You sort of basically have it because you're communicating it to people that, you know, have to start it from scratch. And so that's part of the, uh, it's a, like a, uh, professional hazard of being a professor basically, but I appreciate the comment.
Speaker 1: (56:58)
Okay. Thank you so much. Anything else you want to add?
Speaker 2: (57:01)
Well, no, but I think that that covered it and, um, yeah, I appreciate the interest in the study.
Speaker 1: (57:06)
All right. Thank you so much.