 a buzzword, not just in the ancestral health community, but even among mainstream researchers. Hi everybody, thanks for hanging in there. I realize it's the end of the day and our cortisol levels are really declining. And you guys have absolutely no idea who I am and I'm talking about this weird epigenetics thing and not only that, but I'm talking about it in a multi-generational context and oh my gosh, who am I, what am I talking about? Let me start there. It is an honor to be here. I respect this movement a lot and very much believe in what you are all doing. And this epigenetic stuff is a really cool, the coolest area of science right now and you might see here, however, there's some letters after my name, Jill Escher, and I'm not a scientist. I in fact got my law degree and my master's degree right here at UC Berkeley about 20 years ago and it's really great to be back here on campus a little bit spooky, but fabulous. What I am is kind of an oddball niche, if you will. I'm a science philanthropist. That means that I fund studies, I kickstart studies, I try to get scientists to collaborate, I dream up some possibilities for science. I also engage increasingly in science education and also in advocacy work. So our plan, we're gonna start off with, I don't know, maybe it's about 15 minutes with a kind of biology lesson, but I was told that you guys really like to geek out, so I don't feel bad about it. And this is a university, so we're gonna cover some basic biology that pertains to epigenetics. And then we're gonna look at how some of this biology lesson might relate to real life and real life health problems. And finally, we'll wrap up with more practical advice, I hope, both from a clinical practice point of view and also for public health, paradigm shifts. I think that that is an understatement. Right now in the field of biology, I think we are experiencing what really could be considered something of a Copernican revolution in thinking. Old dogma is dying day to day and new ideas are creeping. And now that said, I do wanna say that there's real time and then there's science time. And like science time is like, slow mo. It's super slow, like in molasses, like super slow. But that said, there's really no debate that there's some very, very important, very fundamental changes that are going on in biology right now that are gonna rewrite textbooks within a couple years. Let's talk about three of these areas. One area is in the realm of evolution. Now, if you're like me and you took AP Bio or whatever, you were taught that evolution occurs by the mechanism of random mutation and natural selection. I mean, how many of you kind of learned that? I mean, and not only did we learn it, now if you can read research papers today and they'll pretty much echo that same sentiment, that's the driver of evolution. But we're learning that that is really not the whole story and it's probably really not the whole story in a really big way. And that's because, and in fact, Barbara Natterson Horowitz this morning actually referred to this. It's not nature or nurture. There is actually a feedback loop from our environment that affects our genes. Sometimes it affects how our genes work. Sometimes eventually over time affects our genes structurally. So this idea of randomness is a little passe. There is some, I won't say intentionality, right? But there is some influence, molecular level influence from our environment that affects our genes. Second, when we are talking about disease causation, the traditional paradigm has been genes or environment. Now, my primary area is in the realm of autism philanthropy. I've been in autism philanthropy for at least a decade. I have been to many conferences, good Jillian lectures and speeches. Every time, every time, every lecture, the scientists will get up with a big PhD on his name and he or she will say, autism has got to be genetics or environment, right? But now we know similar to the realm of evolution, this isn't really true. There is at least a third way and that is that environment can dysregulate our genes, right? So we can have genes, right? We're all, you know, we started with a sperm and an egg, right? And that's our genetics, but maybe something could have happened to our sperm and egg somewhere along the line. Maybe something in the 20th century, something crazy happened that could have influenced our genetics. So it's kind of genetic, it's kind of environmental, right? But it's not genes or environment, that is dead. That paradigm belongs on the trash heap of scientific history as far as I'm concerned. And third, the conventional wisdom in risk assessment has been that we look at short-term risks on our bodies, right? I'm a somatic body, I take arsenic, I die. It's toxic, there's a risk assessment, don't take arsenic. But there's a whole bunch of other stuff going on that risk assessment really has not looked at. Note to EPA, by the way. There are long-term effects of some of these exposures, right? That may not happen today, tomorrow, in a month, in a year, in two years. It may happen decades from now because of an exposure long ago. And not only that, but we can have adverse effects on future generations based on exposures today. Now, is the EPA doing this? Is the FDA doing this? No, they aren't doing this. But is the science demonstrating this? Yes, it's slow, slow-mo, slow-mo, we're getting there. So those are three areas where we're seeing a tremendous amount of change. And why is this happening? What's the root of all this? Well, in a large part, it's epigenetics. What is epigenetics? And why do we care? Epigenetics is susceptible to a number of different meanings almost depending on which scientist you talk to. But generally, it means heritable changes in gene expression caused by mechanisms other than alterations to underlying DNA sequence. And then there's this thing called environmental epigenetics, which is sort of a subcategory of genetics, which really looks at how outside influences of various types can influence our gene expression. So in that sense, our epigenome acts as an interface between our environment and our genome. Now, how is this? Why is this? Let's talk about it. Let us banish forever the image that we have, again from our high school textbooks, of DNA as this unadorned kind of straight, smooth, and sleek double helix. You know that image, don't you? Yeah. That's not at all what's going on in our nucleuses of ourselves, right? What's actually happening is that DNA is enmeshed in a vast, incredibly complicated matrix of structural proteins and a whole bunch of chemical switches that tell our genes what to do, when to do it, where to do it. Now, if we were to strip the epigenome from our DNA, in the words of one scientist I heard, we would basically be baker's yeast, right? It's not our DNA that is making us so special. We need all this apparatus around it to make it work. So our chromosomes are really only about 50% DNA. The rest is all that other stuff that makes stuff happen that makes us not baker's yeast, all right? So this epigenome is a somewhat malleable layer that can shift depending on signals from within, right? The epigenome can be regulated by the genome itself, but also we know by outside forces. All right, let's go on. All right, one analogy that some of my favorite scientists like to use is a computer. The genome is the hardware, but it's impotent without software. The epigenome is the software that's telling the hardware what to do, and that's a really good analogy. I kind of prefer this one though, and I will go over it. Our genome, I think, can be seen as comparable to a piano keyboard. A keyboard has 88 keys, 88 pitches, that's all you got, but they can be played in infinite variety of ways. Now if I were to break a key or break a string, that's a mutation, we lose that pitch, we can't make that protein, right, in our genes. The composition, right, is like the epigenome. Okay, fingers, press here like this, soft light, slow, fast, CDE, switch to minor key, take a pause. That's our epigenome, right? But you need another layer, and that is, who's playing, right, what's the input? Well, here, that's my favorite Beethoven interpreter, Andre Watts. He's a virtuoso. He started playing when he was like three years old. He can play, you know, the Emperor Concerto, like nobody's business. He's a pro, he's been practicing forever, he's wonderful at it, right? I kind of think of him like ancestral foods, you know, like this is a great input. This knows how to play those keys. It's been doing it forever, it does it good. If I were to try to play Emperor Concerto, you guys would be like, oh my God, make it stop. It's horrible, I don't have practice at it. I'm no good at it, I'm like junk food, right? So how does this epigenetics stuff work? Well, this would be, you know, a 10 hour lecture if I were to even start to scratch the surface. So I'm just gonna give you two examples, because they're the ones that are most often talked about, they're the ones that are best understood, best researched. First is called DNA methylation. And in DNA methylation, these little chemical tags, these methyl groups, attach right onto our DNA at the cytosine, I'm not gonna go over genetics right now, but in specific places, and they're usually in groups along the genome, it's not random. And what those tags usually, but not always do, is send a signal to the gene to turn off, silence, no funcione, stop, that's methylation, DNA methylation, there's other kinds of methylation. Histone modifications, now I said before that our DNA is enmeshed in a vast matrix of proteins, and the DNA is actually wrapped around these ball-like histone proteins. And those histone proteins, depending on what are attached to them, can open up or they can close. Now when they're all closed and they're holding their DNA tight, no transcription, right? No gene expression, nothing. But when they're kind of cranked open by these different enzymes really, they're like, transcribe me, I'm open for business, come on in. So that's two mechanisms that help influence the way our genes work, there are many more. And actually one that's kind of interesting for all of you nutrition people out there is microRNAs. I mean, this is sort of parenthetical. It's so cool because they're finding that microRNAs directly from plant sources can affect our own gene expression. The food we eat can directly influence our gene expression, not through some metabolite business, but through their genetic workings. It's crazy stuff, I mean I told you 10 hours that would barely scratch the surface. All right, so what are some of these epigenetic mediators? I said Andre Watts, he's like, you know, ancestral diet, and I'm like junk food at piano. And so what are some of these inputs that should matter at least to this group? Well the most obvious one is hormones. Hormones, it's their job to alter gene function, that's what they do, right? They can up-regulate genes, they down-regulate genes. They can change us at the right time of life from a female to a male. I mean, they're incredibly powerful, powerful, tiny little molecules that get in everywhere, they go right, well the steroid hormones, go right into our nucleuses, and they can attach to certain parts of the DNA, the promoter parts of the DNA, and start this cascade of molecular events to change what our cells do. So there's no question that hormones are very active epigenetically, and transcriptionally too, and in other ways. Methyl donors, you guys are all smart nutrition people, you guys know about methyl donors. We talked about methyl groups, right? We need methyl groups to have our epigenome functioning correctly. So methyl donors include things like folate, B vitamins, betaine, choline, methionine, and there are more. And when we don't have them, enough of them, there can be serious consequences, especially at the fetal level. We've heard of spina bifida, that's when we have a lack of folate. There also could be too much of a good thing. Women are given folic acid, pregnant women, like there's no tomorrow, but there's a lot of reasons to believe that that will have adverse effects for various reasons. So we have to be a little careful about our methyl donors. That, by the way, is my typical breakfast. And I was seeing the picture, I'm like, oh my gosh, I didn't realize I have such a methyl donating breakfast. And so maybe that'll be my first book, I don't know. All right, so then there are other ones, including oxidative stress can affect our epigenome and neurochemicals can be epigenetic mediators and even ketone bodies, which I know is a hot topic at this conference. Now I said we're not just talking to epigenetics, we're talking multi-generational epigenetics today. So the first step when we're talking about multi-generational is the next generation down, which is our fetuses. And here are some examples of adverse epigenetic effects owing to various forms of prenatal exposures. The first one, you've all heard of fetal alcohol syndrome. Yes, nod your head, yes. Well, it's coming to light that that really is an epigenetic phenomenon for I can't even go through the pathway, I'm not that smart, but it results in changes in brain development, it results in changes in facial dysmorphia, it causes myopia, which I have to, and various other problems. DES, raise your hand if you know what DES is. Okay, I'm gonna cry, but after I cry, okay, DES, everybody in the ancestral health movement has to know about diethylstilbestriol. You have to, you can't understand what has happened to our population until you know the history, the tragic catastrophic history of diethylstilbestriol. DES was a drug that was given to women for various women problems, beginning in about 1938 through roughly 1971. It is a synthetic estrogen that is more powerful than estrogen, but not really shaped like estrogen. But in the fifties, I think, it became very popular as an anti-miscarriage drug. Now it didn't work, right? It didn't work, in fact, there was a study done in the fifties that showed that it probably had adverse effects on birth outcomes, but it was given out like candy to millions of pregnant women during this era. This drug caused infertility, it caused cancer, it's causing an epidemic of breast cancer in women in their kind of fifties and sixties right now, in forties. It caused autoimmune disease and it caused depression and other issues. It was a disaster and it was given in very high doses for very long terms in pregnancies. So let's move on to something that's not a drug. Fetal starvation, we talk a lot about starvation. Maternal starvation has lasting effects on the fetus and we know that not from controlled studies, but because of various historical tragedies, including World War II, what was called the Dutch Hunger Winter, when there was mass starvation owing to blockades and there was a follow up of the children who were in utero at that time and they were more prone to heart disease, diabetes, overweight, et cetera. And other studies have actually confirmed that as well. All right, lack of methyl donors, what can happen? Well, this is a mouse model, but you can see these are genetically identical mice. When one was fed methyl groups, it remained non-obese and brown and the one that was on the other diet became obese and yellow. The coloration is because of a gene that only these mice have. We don't have that color gene, but it shows you the influence of the methyl donors. BPA exposure, there's an increasing literature on fetal BPA exposure and various adverse effects. This was one study in mice and it showed that the mice exposed, peonatally, to BPA. Human relevant doses of BPA developed liver tumors at much higher rates than the control group. Finally, the one that everyone knows is thalidomide. Thalidomide was another catastrophic drug but affected a much smaller population than DES from about 1960 to 1961. It was used primarily in Europe, not so much in the US for a certain reason, but what it did, there's just a study that came out like this year about it, is it epigenetically shut off certain genes that were involved in differentiation of the limbs and development of the fetus generally. It also caused mental retardation in a lot of the exposed. So you can see epigenetics can have profound impacts, especially on the next generation because that is when our cells are proliferating and differentiating and much more susceptible than we are in our adult state. All right, multi-generational. Well, I must be talking about more than one generation. So let's talk about the next generation down after the fetus. Here, this is kind of what we learned in school. This is the human life cycle, right? Wrong. This is not the human life cycle. Here it starts with a fertilized egg and it becomes a fetus and then a baby, then an adult, then we get old and we die, right? Well, where did this fertilized egg come from? Did the stork bring it? It's like getting a cake recipe. I know you guys don't eat cake, but getting a cake recipe and it says, okay, take your batter and stir it up. What's in the batter? What do I put in the batter? Okay, and it's sort of funny because people don't think about it. They don't think about what makes our sperm an egg. People, we're in this kind of somatic phase right now. I'm looking at all these bodies right now, but we spent anywhere from like 16 to 50 years in a molecular phase, right? This is only part of who we are. So the molecular phase is omitted typically from any representation of the human life cycle and this is a horrible omission. Let's talk about why. Okay, so this is kind of an ugly slide. I'll shorten, I'll make this short. The molecular phase, you, you started in your grandmother's wombs. The egg and sperm that made you started in your grandmother's womb. So I come from the 1930s, right? I was born in 1965, no, no. That's when my body emerged from my mother's uterus, right? But the sperm an egg that made me started in the 30s, all right, and that's important. It's not just this random kind of genetic thing going on. Remember, genetics is just one part of what's heritable, right? We have this whole epigenome thing going on that's vulnerable to environmental exposures. So all that stuff in the 30s, that was kind of important to the sperm an egg that made me, but what happened? Like, you know, here's an example. Is anyone here 24 years old? No, oh my God, you're all so old. Okay, I'll skip this example. But let's talk about this sperm an egg development because nobody knows this and it's important. Okay, so here it is in 1965, when I was conceived. Sperm an egg, meat, boom, right? What happens? Well, it's differentiated, it becomes a blastocyst, right? You guys know what a blastocyst is? And these cells, they're like in a huddle. Like, okay, we're in a huddle, we're a little ball. Okay, you, you cells over there, you're gonna become the placenta. Okay, you, you cells over there, you're gonna become the fetal body. And you, you cells over there, you're special. You're gonna become the gametes. Okay, that's called germ cell specification. Okay, so these cells get together and they kind of take different roles, even though they're kind of identical at the beginning, right, we all come from one cell, right? The fused sperm an egg. Well, these special cells, these future gametes are kind of sent off to a corner, while other stuff happens to the placenta and the fetal body. And eventually, these cells that are outside of the fetal body have to migrate, this is weird, into the developing gonads of the fetus, the ovaries and the testes. It's like, you know, the March of the Penguins for germ cells, all right? And so they gotta go, they have to like travel to the fetal body. And as they're going, down what's called the gonadal ridge, as they're going, they're multiplying and they're being epigenetically reprogrammed, all right? It's not this like light, easy, passive, mitosis, it's all, we're all the same, no, they're being reprogrammed. Methylation is being stripped off and other tags are being put on and this is incredibly important. You know, I'm gonna go into a little PhD moment here, I'm sorry. But Dr. Blaisdell, today he talked about child's brain development, early brain development, from birth through the early years and how really what we're seeing is this interesting differentiating expression of genes in different phases of brain development. Well, actually that all is true and it all can be traced back to this, to all of these weirdo chemical tags that are being put on our germ cells because there is a special, sorry, PhD moment, I'm really sorry to do this. There's a special subset of genes, 1% of our genes are called imprinted genes. Anybody here heard of imprinted genes? I knew you did, okay. So these are very special genes because they to a large extent will tell our brains how to develop if they are dysregulated, if they are mismarked in this March of the Penguins period when all these little proto germ cells are going into the gonads, that can have very adverse consequences down the line. No one knows this stuff, but we're learning. We're learning. All right, let me move on because I'm gonna run out of time. All right, so I just talked about, you know, to what we call critical windows of development, right? We're vulnerable to exposures in different ways during different phases of our life cycle. I talked about the fetal body and then I talked about these germ cells that start in our grandmother's wombs when our parents are little tiny fetuses and grow in their gonads. But those are just two critical windows. There are other windows, early childhood in males, pre-puberty, kind of before spermatogenesis kicks into high gear. And of course, during spermatogenesis over the rest of their lives, spermatogenesis takes about 74 days. And that's a very vulnerable period. And it drives me nuts, drives me nuts is that no doctor ever seems to say to their male patients, by the way, if you're on like a drug or something, you probably don't wanna conceive a child in the next 74 days. That's a really weird thing. I don't know why doctors don't do that. I think they don't know about spermatogenesis. Females, para-ovulation, and then again, of course, para-conception, there's a whole other wave of reprogramming that goes on. Okay, so we've reached the conclusion of our foray into molecular and reproductive biology. And let's move a little bit into exposures and what's going on in the world today. So ancestral health focuses on nutrition, but it seems to me to be increasingly attuned to the impacts that chemicals and pharmaceuticals are having on our bodies. After World War II, we had this chemical revolution. There was an absolute explosion of chemicals and explosion of pharmaceuticals. And I do wanna address just something pretty simple. It should be obvious to you. We talk about chemicals, we talk about pharmaceuticals as if they're two different things. It's all the same, right? A lot of chemicals start their lives as pharmaceuticals, a lot of pharmaceuticals start their lives as chemicals. Something like pesticides, although started as agents of chemical warfare. It's very fluid. They're just molecules given different marketing labels and given different uses, but there's really no difference. So when I say chemicals, it really includes pharmaceuticals as well. And we use this stuff like it's going out of style. More than four billion prescriptions written in the United States each year, that was four billion with a B, 42 billion pounds of synthetic chemicals produced or imported each year. This is a lot going into our bodies, sometimes very directly and sometimes very indirectly. All right, we just heard about, I guess two lectures ago, a theory of obesity. And have you guys ever seen this, the chubby David on the internet? It came with a meme and it said, dear Italy, thanks so much for loaning us, loaning us the statue of David. We've enjoyed having it in the US for this past year. Now we return it back to you. I was like, okay, that's what happens today when it comes to the US. But there's emerging, and somebody asked this question of the speaker. There's emerging this idea that these chemical obesogens are playing a role in the development of this obesity epidemic. And I have to say, having read a lot of these papers, I'm pretty convinced that it is playing a role. Do I think it's everything? No, I think sugar and carbs deserve the knocks that they're getting. In fact, I wrote a book about sugar addiction. Jimmy Moore wrote the introduction to it a couple of years ago. So I'm a big fan of that theory as well. But we have now identified at least 20 obesogens and those come from both the chemical and pharmaceutical worlds. They include in the chemical category, BPA, phthalates, organotins. That includes some paint and chemicals that are applied to the side of boats. Fish are often polluted with these organotins. DDT, there is a slide at the very, very beginning on a picture of DDT. DDT was used pervasively around this country in the 50s and into the 60s pervasively. No one was immune from DDT. DDT accumulates in our fatty tissues. It persists in the environment. It continues to be a menace today even though we are no longer spraying it here. In the drug category, some known obesogens are synthetic hormones. Oh, like the birth control pill, maybe people, like that millions of people are taking. Smoking, not for this generation, but the next generation. Antidepressants and under nutrition, which is not, that's actually not a pharmaceutical, but sometimes it's related to something like smoking. So what happens? How do all these chemicals, these synthetic molecules that are foreign to our bodies, that are foreign to human evolution, how do these actually cause us to accumulate adipose tissue? Well, there seems to be a whole variety of mechanisms and we're really not sure what they all are. But in some cases, there's a direct interference with hormonal action, direct endocrine disruption. Sometimes it's an up regulation or down regulation of the receptors for our hormones. Sometimes there's sort of a blockage, right? A blockage of proteins, basically that control, kind of a hormonal levels. So it can be a whole number of things, but we're pretty sure that this is playing a role. And what's really interesting in animal studies, like for example, I think DDT is a great example. You don't see much effect on obesity in the first generation. You don't in the second generation, but you see it in the third generation. Remember the germline generation? You're seeing it in that generation. So there may be some old exposures that really in ancestral health, we have not been thinking about at all that are feeding some of these epidemics we're seeing today. All right, but these animal studies that look at these endocrine disruptors and other toxicants, they find a whole bunch of other pathologies, impaired glucose metabolism and diabetes, PCOS, fertility, reduced sperm quality, abnormal urogenital development. That's a really important subject. I wish I had time to talk about cancers, kidney disease, immune dysfunctions, including autoimmunity, behavioral abnormalities, including poor mating or parenting behavior, ADHD and anxiety, ADHD. Let me talk about this really fast. There's a great study this year on nicotine exposure in rodents. I remember there were rats or mice. And again, the third generation, the germline exposed generation developed rodent ADHD, rodent anxiety. Well think of all the pregnant women who used to smoke. All right, so let's talk a little bit more about these exposures of our past century and into today, so many pesticides. Pesticides are increasingly used. Agent orange was a powerful, horrible toxic endocrine disruptor, which many, many, many military people were exposed and also civilians as well. Plasticizers, of course, are still in use. Flame retardants, they're probably right there in all of your chairs, by the way, and you're picking up little doses as you're sitting there. PCBs, horribly toxic chemicals that don't degrade. And so these things, they build up in our fatty tissues and they remain in the ground. So sometimes we think, oh, I was exposed to that 10 years ago, or dioxin, like, Agent Orange, that's a great one. That'll stay around for like 30 years. Oh, God, Vietnam, that was so long ago. Well, yeah, that exposure's still in you. It's still in your body. It doesn't go away, right? Air pollution, oh my God, gajillion kinds of chemicals in there, and of course radiation, and of course there's a known mutagen, but it's also an epimutagen. All of these are known to have adverse epigenetic effects, and we've all been bathing in them to one degree or another, or our parents or our grandparents. Drugs, okay, this is what I do in my work. All right, after World War II, there was this thing called kind of like, you know, futurism, the Cold War, this belief in tomorrow, this sort of unremittant belief that science would make life better, and that applied to the world of pharmaceuticals and it also applied to the world of pregnancy pharmaceuticals. The labs could not produce pregnancy drugs fast enough, and pregnant women were routinely medicated. It really wasn't until the 70s that we started thinking, you know, maybe we really wanna be a little bit more careful about this, although we're still routinely medicating pregnant women today. So we talked about at least one synthetic hormone, which was DES, but there were about 20 other synthetic hormones that were given to pregnant women. There were barbiturates, 22 million U.S. women took pregnant women, took barbiturates in those decades, anti-nausea drugs, amphetamines. We used to give pregnant women speed. We gave them methamphetamine. Why? Because there was a myth that a pregnant woman couldn't gain more than like 20 pounds, and so, you know, if you looked at your gaining weight too much, your doctor would sometimes, sometimes he would tell you to smoke, and sometimes he would give you speed, okay? Really bad idea. This happened to millions of women. This was not small stuff, right? They're in about, I think in the 60s, it was something, there's one figure, 50% of pregnancies involved, two or more drugs, all right? And then there were diuretics, which have hormonal effects, anti-hypertensive. Anesthesia, very toxic, very toxic x-rays, analgesics, and of course recreational drugs, including smoking, which was pervasive, right in the 50s and 60s and the 70s as well, and like, let's forget synthetic sweeteners. Synthetic sweeteners came on to the scene in that area, and some of them were super toxic, and I think some of them still are, but pregnant women take them because they don't want to gain weight. All right, oh my goodness. Why should we be concerned? Because we are now learning that drugs, many kinds of drugs, can have adverse epigenetic effects. This is just a partial list, but we know anti-depressants, anti-depressants which are used pervasively, even the pregnant women, more than 5% of pregnant women are in anti-depressants, okay? Staten drugs, which you guys know are used pervasively, adverse epigenetic effects, are they worse than decreasing your risk of heart disease? I think so, oh, I definitely think so. Accutane, like any doctor, would give a teenager something as toxic as accutane when you guys know there's an alternative, I can't imagine. This stuff is so epigenetically horrific, but this is, you know, but it's medicine, you know, it's like standard of care stuff, it goes on. There's not much we can do about it. Oh, depicote and anti-convulsants, anti-seizure drugs, those are known to have very adverse epigenetic effects. In fact, in fetuses, it will cause neurological problems. All right, so let's go to some of the work that I do, and my work is a philanthropist, and why I do it. Autism rates have exploded, and this is not funny. This is not funny. This is serious, horrific, horrible stuff. California has the best records of any state in the nation. It's because we have something here called the Lanterman Act, you don't have to worry about it, but we've been keeping closed tabs on every person with developmental disabilities in our state, I live here in California. You know, since the, you know, 60s, kind of. And we know how many people have substantial autism, and these numbers have been looked at, and it's not because of better diagnosis, it's not because of Temple Grandin, it's because we have more people with neurodevelopmental abnormality. So you can see actually from, it's about a 3000% increase from the 1980s, all right. In the 1980s, you could fit almost all the people with California with substantial autism, that's a, I say substantial, it means they're, they can't care for themselves, they're really disabled. You know, kind of into this, maybe two of these rooms. Now you can fit them into two major league baseball stadiums. This is not small, this is a giant explosion of an unexplained neurodevelopmental disability. And it started with births in about 1980. Again, we know that because our data here in California rocks. And why, why is this happening, why? Well, it's not better awareness, we know that because of the California data and all the PhDs who've looked at it. I mean, if you had a small effect, but not so much on the substantial, we're just looking at the subset of autism with that graph, just the people who can't care for themselves. So we're not talking about the Asperger's, you know, kind of goofy people. We're not talking about that. At least for this purposes today. And it's not vaccines. I know that people in natural health are very concerned about vaccines. It's not vaccines. We've looked at it, it's not that, it's not postnatal events. We are not finding that in the research. But we are finding some risks. As I just said, fetal anti-convulsant exposure, fetal antidepressant exposure, not talked about enough. There have been study after study after study after study that shows early embryonic development to SSRIs and other antidepressants increases the risk markedly for up to, I think, fourfold for autism. We talked about thalidomide exposure. There's, you know, some epidemiological work like you can get pesticides and smog exposure is pretty suggestive. Prematurity, perinatal complications. And then, you know, a little bit on parental age, advanced, you know, age, but that's not a big effect. Maternal infection is one as well. But most of the epidemic remains unexplained. So I, you know, have some ideas about what will explain some of it. I don't pretend to have all the answers. I wish I did, I don't. But let's talk about me. Because it was my story that kind of sent me down this path looking for what is happening here. As I said, I was born in 1965. I was born in Los Angeles. Actually, I grew up right near Barbara Natterson Horowitz. I didn't know her then, but I know her now, down in LA. I have three beautiful children who are genetically normal. And I had from three very normal pregnancies, no assisted fertility, no drugs, full term, you know, high apgar scores, two of them were basically natural childbirth. There's no risk factors. Nothing in my family history, no abnormal, you know, mental impairment, no developmental disability. Same in my husband's side, nothing. No risk factors. Zilch, right? None. But two of my children are severely autistic. They're nonverbal. They can't, they go to school, but they don't really go to school, right? They don't really learn. They don't understand stories. They don't, they wouldn't, they would never follow a direction except for maybe the most simple direction. My son is more severe behaviorally. If he was here right now, he'd be kind of jumping up and down and kind of flapping and kind of making some noises. And Sophie looks, she's gorgeous first of all, but she looks totally normal, but you know, you talked to her and she wouldn't even know that you were talking to her. Okay, I hope that some of you in the audience think that this is a little odd that here I am, and my husband who's not here, that we would have two beautiful, perfect children whose brains didn't develop. And that not just my kids, but that this is happening in families all over the country, especially in LA, Dr. Blaisdell, especially twice the autism rate, two times in LA County. I hope you think it's a little odd. I certainly think it's a little odd. Why is this happening? Why did it happen to me? We went to like every clinician and expert we can think of to ask and nobody had a clue. We don't know Jill, it's weird, it must be genetic. You have two of them, it's gotta be genetic, but we can't find the gene, but I don't know. All right. Then something happened. In 2011, I was listening to a podcast. How much time do I have? How much time? Oh, I ran out. Okay, I'm gonna make this really super fast. Take my time. Okay. Oh, there's no one coming after me. Okay. I was listening to a podcast. We're almost to then. And Sean Crockston was talking to somebody gates, Donna Gates. I wasn't really listening, but Donna Gates says, you know, the nutrition that a pregnant woman takes in affects not just her fetus, but also her grandchildren. Because as you know, a girl is born with all her eggs. So if the eggs are affected, that will affect the development of the grandchild. Something like that. At that moment, I thought, oh my God, maybe something happened to my eggs. Now, there's backstory here that I'm not gonna tell you and why I thought that could be. But through a miracle, I obtained my prenatal records from 1965. How many have you have seen your own prenatal records? Meaning your mother's, no one has. No one has. This is a miracle. I got my records. I not only got records, I got incredibly detailed records about all my exposures. And I had no idea this was true, but as it turns out, I was exposed to five different synthetic hormone drugs that were used in an anti-miscarriage protocol that was kind of popular in West LA at the time. And if you do the math, it's roughly equivalent to about 20 to 30,000 of today's birth control pills worth of synthetic hormones. It was massive. These people believed, these doctors back in the 60s believed in a super abundance of hormones. So I started calling people, hey my friends, you autism mom, were you exposed to anything funky? Turns out I was exposed to something really funky that I never even knew about. And by the way, none of those drugs worked. They didn't work, but they used them anyway. And over time, this didn't happen in a day. Over time, I found family after family after family after family with similar stories. Now these are anecdotes and there's no control group. Kind of for my pseudo control group, I would say, do you have a sibling? Was the sibling exposed or unexposed to these drugs? If the sibling was exposed, there tended to be some sort of abnormality in the kids. If the sibling was unexposed, there tended not to be. So I'm like, okay, not science. I know it's not science. This is super sloppy. But it was a hint. It was an indication to me that there's something going on here that maybe nobody had been thinking about. So, is there research on this? Everybody says, Jill, where's the data? Where's the data? No one's even thought about this. There's no data. But there's a whole lot of research in autism that is pointing to epigenetic dysregulation as part of the puzzle. And I won't do this to you. You can email me, I'll give it to you. It's fascinating stuff. So what are the lessons from my story? First of all, probe the past. We always think about the here and now in terms of our health. But our health started a long time ago. It was influenced by factors a long time ago. Think about that. Ask your patients about it. Ask yourself about it. Did your mother smoke? Did your grandmother smoke? Et cetera, et cetera. Counsel people on risks. I just said that a grown man taking some kind of drugs, let's say it's a steroid hormone, God forbid, isn't counseled by his practitioner to maybe not bear children while he's taking that drug. Minimize medication. There are all kinds of epigenetic effects of these medications we aren't even thinking about that are long term. And we really want to restore hormonal normalcy. Noragad Gaudis was talking about avoid those hormone supplements. Let's normalize this thing. She's right. She's right. Let's normalize this thing. But that's not the attitude in conventional medicine, I'll tell you. For public health, really we have to look at toxicity across the entire life cycle, including the molecular phase. We need to be much better about our records. It is not fair that I am the only person in America who had access to her prenatal records. And it's a really long story as to why I did. It's a bizarre story. That is not okay. This is some of the most important medical information of our lives. I now know I'm at increased risk for cancer, right? For example, because I had all these drug exposures I had no idea I had, right? It's not fair that I'm the only one who knows this. It's terrible. And the precautionary principle, which seems to be stomped on and spat on by the FDA and EPA, it has to come back into style. So healthy DNA depends on healthy epigenetics, which depends on ancestral health in my opinion. We have to be very careful with some of these novel substances. Quickly, this is my last slide. I want to say, we're kind of talking about this stuff as if it's new, it's so not new. And anybody who has read Weston Price's book knows that it's not new. Weston Price left Cleveland as a dentist looking for the secret student health. But he came back, in my opinion, as the world's first epigeneticist. Because he noticed, and you read those last couple chapters, he goes on about how, he wasn't talking about chemicals, he was before the chemical revolution, but how poor nutrition is affecting the hereditary process. Just in 1939, as today, there was a strong paradigm of genetic determinism. He was fighting against that, and he was right. He was right, all these epigeneticists who've never heard of Weston Price, by the way, would agree with him. Rachel Carson, of course, who wrote Silent Spring, she warned about this in 1962, pesticides and all these other chemicals, you know, penetrate the germ cells that alter the very material of heredity upon which the shape of the future depends. If you're interested in more germline exposures is my funds website, and then Autism Epigenetics is a website that has a whole bunch of videos with some of these scientists I've been working with. Thank you very much, I've enjoyed talking to you. Well, thank you for a very stimulating talk. I know people have questions, so we'll take, and there's no talk after yours, so if you're a game, we'll have some questions. Sure, sure. All right, sort of a three-part question, but it all goes hand in hand. So, basically, you're saying a lot of it is based on your grandmother's sort of genetics in terms of that germline, and then your mother's, right? Yeah, I think so. That's certainly my hypothesis. Right, and then from what I understand that this may be incorrect is that once genes are turned on and off, they're not switching, right? Okay, that's a really good question, because a lot of people say, well, epigenetics, yeah, it's reversible, right? Is that kind of what you're saying? Is there a way to treat it if you know there's something that's wrong in your genetic code currently? Really good question, yeah, really good question. Again, I talked about, or at least referred, alluded to the fact that there are somatic cells and there are germ cells, right? Different actions, different kinds of epigenetics. There's a lot of evidence that when we adversely impact our somatic cells, our body cells, that can be reversible through things like good nutrition and removal of drugs or other substances. When it comes to our germ cells, uh-uh, there is no evidence that that's reversible. That's baked into our DNA. Baked in, it doesn't come out. It affects early development, it affects our developmental program. So the answer is sort of yes, sort of no. Gotcha, and then how much of your actions through life, can my day-to-day actions impact my germ cells or only my somatic ones? Oh, such a good question, such a good question. The answer seems to be, I had a slide about critical windows, right? Critical windows of development. And it's during these critical windows of your kind of rapid differentiation, proliferation, you know, and, you know, cell division really, you know, when our chromatin is open, that's when, you know, what we do really affects our somatic cells and our germ cells. But, you know, there's kind of a consensus that, you know, this stuff isn't unperturbable, right? It's kind of knotted up at other times, but they're not immune. So yeah, everything we do, different degrees affects. Last question, do you eat cake? Do I eat cake? You said we don't today. Yeah, on occasion, yes. Ha-ha-ha. Thank you for an incredible talk. When I read Weston Price's comment about intercepted heredity is what he called it, I almost fell out of my chair because of all this research that he anticipated by 70, 80 years. Also, I'd like to know how to, is that the way to get involved in what you're doing through the germline exposures? Oh yeah, so germline exposures is a, it's an educational website, they're interviews, lots of interviews with scientists that I've been doing some work with and some others. And, you know, the work I do as a philanthropist is basically I do educated grant giving. So I don't, you know, but yeah, if anyone wants to help me with the website, I'll take volunteers for sure. Well, the work was really incredible. Thank you. Thank you. Hi there. You spoke about the pregnancy exposures that put three generations at risk and when you touched on and highlighted that you wanted to talk about more was abnormal urogenital development. Urogenital development, yes. That's right. Could you say a little bit more about that? Yeah, yeah. Okay, you guys know about like hypospadius, cryptor, chidism, urogenital development is mostly in males. So you know, I think you guys probably know we kind of all start out embryonically as females. And then if there's some testosterone, depending on the hormonal signals, those tissues will differentiate into male reproductive organs, right? But if there is some endocrine disruption, some hormone disruption along the way, the male urogenital development will be incomplete or will be disturbed in some way. And what we've seen is that things like hypospadius, which is basically where the urethra pops out in the wrong place or undescended testicles, that those incidences are increasing rather markedly. And we think that they're related maybe to some drugs and maybe to some chemicals that are influencing these very early hormonal actions. Does that make sense? It does. Okay. Thank you. All right. So I have two questions, although the first is maybe a little bit more of an observation or a comment, which is that if all of the additional hormones that pregnant women were given a few decades ago are actually contributing to increases in autism, then we might expect a decrease over the next few generations as those were phased out. So that's more of a comment. Yeah, I want to make a comment on your comment really quickly. It's not just the synthetic hormones that we're worried about. All these drugs, as I kind of said, a lot of them have these hormonal actions, have these epigenetic actions. Synthetic hormones are an obvious one, but these sedative drugs, these anti-nausea drugs, other drugs, diabetes drugs, they all could potentially be involved as well. We don't know yet. We don't know yet. And pregnancy medications, although some have decreased, are increasing now every year. You should know that. So no, I'm not actually all that optimistic about it. Go ahead. Well, my second question, I'm trying to wrap my head around the critical times. Yeah. So if my grandmother does terrible things without knowing it during these critical times, and then she has my mother, do I have to worry about the critical times of my grandmother or my mother? No, they only worry. Yeah, we should all worry, number one, but number two. The biggest worry, I think, is what were you exposed to in utero? So have a conversation with your mom, right? I had never had this conversation with my mom. I didn't know. I had no reason to ask, right? Did you smoke? Were you on some medication or something? Did you have surgery, whatever? I mean, you should know that because that could affect the quality of your gametes. I mean, that's just the way it is. But also, you should think throughout your whole lives. Again, don't worry yourself to death. Remember, I was exposed to about 30,000 birth control pills worth of drugs, okay? So I'm a really weird example. Most people today aren't. So no, don't worry that far back. You seem pretty normal to me. No. I don't know for sure. I'm not going to address that. Okay, should we do keep going? No. Two more, okay. Sarkis mausmanian, Caltech, has done some interesting research into autistic mice and using some very specific probiotics to really change what's happening. His theory is that some individuals, including mice, can be more susceptible because of their beginnings. But interestingly, he's seeing some possibilities for this. He did a very interesting study that was in cell. Yeah, I know a little bit about the sort of the gut issues and the microbiome issues in autism. It's not an area that I do much work in, but I think it's really interesting. Clearly, there is an elevated rate of gut problems, GI problems in kids with autism. He basically cured the autism in these mice. Yeah, okay. I'll look, give me the name. I'm not sure that one's familiar to me. So later, give me the name. I'll find it. Okay, thanks. That was an awfully good scientific explanations from a non-scientist. Okay, and seriously, I was wonderful. I just kind of disagree with you on vaccines, though, because the heavy metals in the vaccines, the possible viral contamination of the tissue that's used to grow the vaccines, I mean, to me, they would all fit along with everything you've been saying, whether it's plastics in the environment or whatever, to me, that all fits together. Yeah, I'm just looking at the research that's out there and published, and I'm very open to all kinds of hypotheses. Some people say, well, maybe it's multiple hits, right? Maybe it's one thing happens here, one thing's happened here, and it makes you more susceptible, right, to some kind of abnormal exposure when you're an infant. And I don't know, maybe so. I'm just, I'm saying, I don't see the evidence. And so, therefore, I don't really spend time on that hypothesis, so. Okay, thank you. Thank you very much. That concludes day one of the conference. We reconvene back here, and also at Bancroft Hall tomorrow at 9 a.m., so see you bright and early.