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Episode 8: Epigenetics | From controlling addiction to behavior to obesity

Posted by Manoj Perumal on

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About Episode 8

Epigenetics | From Controlling Addiction to Behavior and Obesity with Moshe Szyf

In this episode of The Discover | Dr. Dan Proactive Health, Dr. Dan is joined by Moshe Szyf, a pharmacology professor and author of over 300 papers on the topic of DNA methylation. He is also a pioneer in epigenetic pharmacology and is helping to use this science to help treat and prevent cancer. As one of the most authoritative scientists on epigenetics, he and Dr. Dan discuss the science of epigenetics and everything that it can affect from behavior to obesity and addiction tendencies. Listen to the full podcast below.

The Study of Epigenetics and the Questions it Answers

The study of epigenetics is transforming the medical world. However, to first understand what this study is, Moshe starts by explaining what genetics are. The DNA that we inherit from our parents is what is considered our genetics. These genes are passed down from generation to generation. However, epigenetics goes even farther than that to explain how even though every single gene in our body is the same, they are able to perform different functions. Moshe provides the following explanation to help the listener really understand this concept:

Your smartphone has two components in it. It has an operating system … but the operating system by itself, doesn’t do very much unless you write apps. … So the same phone, the same operating system could do so many different things. And essentially what happens to us when we develop in the womb is that apps are written on our DNA. The operating system we inherited from father, of mother; that’s genetics, the operating system. But the software that programs that operating system, that writes those different programs is epigenetics.

Epigenetics is then the study of the different markers or “apps” on our genes that make them do certain things or perform specific functions. So understanding this process is helping scientists understand which markers to look for to detect cancer cells or other genetic problems and tendencies. 

This study of epigenetics also might be the answer to one of the world’s oldest questions: Nature v Nurture. When scientists started to recognize that some genes are marked differently, they started to look into what marks those genes. Moshe and Michael Meany performed experiments on some rats to understand how life experience and specifically childhood experience affect our genes. After their experiments and analyzing the data, they found a connection, and Moshe states, “for the first time we had a biochemical explanation for the connection between early life experience and what happens to DNA.” So, maybe it is not just nature or nurture, but a combination of the two. 

Epigenetics and Obesity and Addiction

While there are some marks on our DNA that indicate cancer, there are other markers on our DNA that can be brought about by several circumstances that can indicate propensities for obesity and addiction. Epigenetic machinery is responsible for some of these tendencies. On the subject of addiction, Moshe notes that there could be genetic markers due to early life experiences that make a person more susceptible to addiction. When asked about epigenetics and obesity, Moshe states, “Children of obese parents have a higher risk of being obese or children who were starved early in life have a high risk of being obese and so on. And so this is a big field today in sciences, understanding how early life nutrition affects later life, metabolic health.” In summary, understanding the epigenetic machinery and how our genes are marked could help individuals understand how and why their bodies work or don’t work the way that they should.

How to Deal With and Treat Marks on Our DNA

There are so many genetic markers that are not good. Dr. Dan asked Moshe if there is any way to get rid of these detrimental genetic markers so that our bodies can work better. Moshe, going back to his software and operating system analogy, notes that just like a program that is written, it can be unwritten. “The methylation and other epigenetic’s marks are reversible. They are introduced by writers and removed by erasers … and they can be changed. So if you do certain drugs or certain behaviors or certain nutritional supplements, you can change the way these erasers or writers work and modulate them.” There is so much more to learn about epigenetics and Moshe and his team are dedicated to doing the research to better understand the science behind our genes.

To learn more about epigenetics and how it could be impacting your health, check out the Discover | Dr. Dan Proactive Health podcast episode below, and be sure to subscribe for new episodes each Tuesday. 


Transcription

Dr. Dan Gubler: (00:09)

Welcome to Discover with Dr. Dan | The Proactive Health Podcast. Epigenetics and how it can influence all aspects of our lives is a topic we will address today. With us is renowned epigeneticist Professor Moshe Szyf. From the Ted stage to giving lectures all around the world, Moshe is an expert on how the way our DNA is expressed can influence all aspects of human health. Moshe my friend, it’s a great pleasure to have you on the podcast today.

Moshe Szyf: (00:43)

Thank you for inviting me.

Dr. Dan Gubler: (00:45)

So I want to give our listeners a brief bio sketch of you and your accomplishments. Moshe is a professor of pharmacology and held a GlaxoSmithKline and James McGill Chair in pharmacology at McGill University in Montreal, Canada, and is a fellow of the Royal Society of Canada and the Canadian Academy of Health Sciences. Moshe has pioneered research and DNA methylation for the last three decades and published more than 300 papers on the biological role of DNA methylation that spans a broad spectrum from basic mechanisms to cancer diagnostics, and therapeutics, as well as behavior, chronic pain, and addiction. Szyf pioneered epigenetic pharmacology and cancer, as well as the field of behavioral epigenetics. Szyf’s studies provide a molecular link between environment and genes, between nurture and nature that had a wide impact on the social sciences and psychiatric. Szyf founded the first pharma company in the world dedicated to developing DNA methylation drugs, Methyl Gene Inc. Last year Szyf founded HKG Epitherapeutics at the Hong Kong Science Park, which develops a novel class of epigenetic diagnostic markers for early detection of cancer and other diseases aimed for routine checkups in the general population to prevent disease and increase health and wellbeing. So amazing accomplishments. Moshe again, so grateful to have you on the show and that you would take time out of your busy schedule.

Moshe Szyf: (02:12)

Thank you. Happy to be here.

Dr. Dan Gubler: (02:16)

So grateful to have you. So Moshe, how did you get into the field of epigenetics and DNA methylation specifically?

Moshe Szyf: (02:24)

Just by serendipity. As most things in science happen, we don’t wake up in the morning and decide to make a great discovery. It just happens. I was a student actually in dentistry at the time, and I needed to write a thesis and I was looking for a supervisor and the first supervisor encountered in the corridor was a young professor. He just came back from a postdoc at Caltech and he discovered the first methyl group in a bacteriophage that infects E. Coli. It’s not, it wasn’t very important, but it introduced us to the field of epigenetics.

Dr. Dan Gubler: (03:07)

Wow. How cool is that? Like you said, it’s amazing when you do science, you start out on one path and it’s amazing how it weaves and winds to something completely different.

Moshe Szyf: (03:16)

Right.

Dr. Dan Gubler: (03:17)

So, a lot of our listeners, they might know the name epigenetics, but why don’t you explain to us in simple terms, what is epigenetics?

Moshe Szyf: (03:29)

A simple meaning of epigenetics is beyond genetics. Genetics is the DNA that we inherit from our parents, half from our father and half from our mother and we inherited from our ancestors in human lineage and ancestors before we became humans. This is what we call genetics.

Dr. Dan Gubler: (03:51)

Okay.

Moshe Szyf: (03:52)

But to understand what epigenetic is or beyond genetics, we need to understand why this concept developed. And the problem that scientists have encountered in the middle of the previous century was the fact that they already knew that every cell in our body has exactly the same genes, the same DNA, but every cell in our body is doing different things.

Dr. Dan Gubler: (04:19)

Right.

Moshe Szyf: (04:19)

For example, some of our cells make a retina and others make a heart, and then some make a lung and the brain and so on and so forth. So scientists started asking the question, how is it possible that exactly the same genes do so many different things?

Dr. Dan Gubler: (04:36)

Right.

Moshe Szyf: (04:38)

And a scientist in the United Kingdom called Waddington, in the late forties, developed this concept epigenetics which was a combination of different terms in the embryology and genetics. But the idea was that something which they had no idea what it is, happens to genes as a baby or an embryo develops from the egg and the sperm into a whole human being or a whole animal. One DNA is going transformation during the process of development so it becomes multiple, numerous possibilities of a function. And so the field of epigenetics developed from the attempt to explain how one DNA, how one genome can do numerous different things.

Dr. Dan Gubler: (05:36)

So how many genes do we roughly have in the human body?

Moshe Szyf: (05:39)

So between 20,000 to 30,000, and they have to do so many different things. If you think about the billions of cells, just think about the brain. Almost every neuron in the brain carries different memories, does different tasks. So we have to express probably billions of different programs from only those 20 to 30,000 genes. That’s an enormous task.

Dr. Dan Gubler: (06:06)

Right.

Moshe Szyf: (06:06)

And the way it’s achieved is by programming these genes in many different ways. The way I explain it to people is, think about your smartphone, and your smartphone has two components in it. It has an operating system, it could be Android, it could be Apple OS, but the operating system by itself doesn’t do very much, unless you write apps. And if you take one operating system there are maybe great thousands or maybe tens of thousands or millions of different apps. So the same phone, the same operating system could do so many different things. And essentially what happens to us when we develop in the womb of our mother is that apps are written on our DNA. The operating system we inherited from father, of mother; that’s genetics, the operating system. But the software that programs that operating system, that writes those different programs is epigenetics.

Dr. Dan Gubler: (07:07)

Oh, that is so beautiful. Yeah, my mind is blown, right? I know what epigenetics is, but I wasn’t — yeah. The way you describe it — oh, that is so beautiful. So now that we know epigenetics, why don’t you give us some examples of how epigenetics can impact various aspects of our lives.

Moshe Szyf: (07:28)

So when I started investigating epigenetics, as I mentioned before, it was DNA methylation. This is the most, and what I call proximal, the closest mark on the DNA. There are multiple epigenetic marks, and I don’t want to confuse our audience, but just, they should appreciate there are multiple of those marks, which gives the fineness and the beauty of the exquisite programs that that system can create. But the basic level is essentially a little chemical mark, actually, one of the smallest marks that are added to our DNA as we developed. And so I investigated this mark, how it’s added, what are the proteins that are added, and I discovered very early in the early nineties that in cancer, for some reason, they’re doing overtime of adding those marks and removing those marks. And we found that cancer cells have a completely different way of marking the DNA than normal cells.

Dr. Dan Gubler: (08:30)

Interesting.

Moshe Szyf: (08:32)

And actually it makes sense, right? If the liver cells become a liver cancer, it’s a different app. It has to do different things. So, because it’s a different app, it has to write different programs. And then you ask yourself the question, “Okay, what do I do with this information?” And actually, you can do three things with this information. First, you can ask yourself the question, “Why does it happen? Why does our DNA start being marked in a very different way? Who is writing those cancer apps in our DNA?”

Dr. Dan Gubler: (09:03)

Right.

Moshe Szyf: (09:04)

The second question is, of course, “How do I fix it?” And there are different ways pharmacological and today, even, epigenetic editing ways to fix those marks. And this is when I start thinking about using DNA methylation, modulating drugs as anticancer drugs. And the third way that is exciting me a lot today is using those marks as early detection markers. So as soon as we can mark and find those changes in blood, we can detect cancer early and that’s becoming the most exciting area I think in early detection. Early detection is going to change medicine completely.

Dr. Dan Gubler: (09:47)

Right. Non-invasive, medical diagnostics, such an important build. Wow. Very cool. So Moshe, I know you’ve done some really interesting research related to epigenetics and certain experiences in life. Can you tell us some of that, that you’ve found?

Moshe Szyf: (10:05)

Yes, this is what’s really the most exciting, I think, aspect of our work is finding that it’s not just chemicals that affect us. And it’s something that looks subtle and not as physical as we think things are important. It has a huge, profound impact on us.

Dr. Dan Gubler: (10:29)

Okay.

Moshe Szyf: (10:30)

And actually people knew it for a long time, that the way a mother takes care of her child or paternal care has a large impact on the health of the offspring. Economists knew that, sociologists knew that, psychologists knew that, but hard scientists didn’t care because we consider this kind of ephemeral, hard to define, what do you mean maternal care? What does it mean?

Dr. Dan Gubler: (11:07)

Right.

Moshe Szyf: (11:07)

We believe in chemicals and these are the things that we can study in our experiments. But this has bewildered humanity from very early days. Is it nature, the physical matter of our lives that defines our trajectories, our life trajectories, how healthy we’ll be, how smart we’ll be, how successful we would be? Or is there an impact of the experience that a human or an animal goes through early in life, or even later in life in defining life trajectories. Since we know that almost everything is encoded in the DNA, then how on earth could early life experience like maternal love or maternal care affect my blood pressure or my heart rate when I’m 50 or my IQ and so on? So that was kind of a mystery, but epigenetics offered for the first time, a perspective that could connect experience, which is kind of spiritual, ephemeral, as I say, in the hardcore of chemistry of the DNA. And because epigenetics doesn’t change the DNA, it just marks it. And the first study we did with my colleague Michael Meaney, was to look at a model of maternal care in rats and rats like humans do maternal care. They are mammals. All mammals do maternal care. And they do it in different ways. And there is a natural distribution. Some mothers do a lot of it, some mothers do very little and most mothers do something in between. And when you look at what happens to the animals as they grow long after the mother is dead, is that mothers — animals that received high quality maternal care from their mother are less stressed, they are less aggressive, and they’re less obese, et cetera, et cetera, than animals that went through very harsh childhoods if you want to say. And we asked the question, “How?” This was real, you couldn’t deny it.

Dr. Dan Gubler: (13:36)

Right.

Moshe Szyf: (13:36)

But what is the mechanism? How does it work? And so many many years of work established that the care, the maternal environment alters pathways in the brain or the way our chemicals react in the brain. And one of the important chemicals, so we have in the brain is serotonin. This is the kind of chemical that is released when we are happy or when we’re successful, et cetera. And when the mother licks and grooms the pup and takes care of the pup, the pup releases serotonin. Serotonin interacts with receptors in different brain regions and activates a whole cascade of events that result in epigenetic modification of very critical genes that control stress, control anxiety that control depression, et cetera.

Dr. Dan Gubler: (14:30)

Wow.

Moshe Szyf: (14:31)

So for the first time we had a biochemical explanation for the connection between early life experience and what happens to DNA. And what’s important is that not that there’s any needed response, we all know that if you’re stressed, you have a response. If you’re happy, you have a response. But that response is registered in the DNA and stays there and defines how your life will move forward. Epigenetics provided this information because epigenetic is on one hand, dynamic. On the other hand, it’s extremely stable. So the changes that happen early in life are not changes in the gene, but nevertheless, they can stay for a long time and they can define a life trajectory for a long time.

Dr. Dan Gubler: (15:23)

Wow. So is it possible for these markers, due to these stressful experiences in the past, can they be removed?

Moshe Szyf: (15:31)

Of course, that’s the basic difference, right? Our genes are fixed. And now we talk about gene editing, but these are very sophisticated ways of playing with a genome. But the genome that you inherit, you’re going to pass to your children and to your grandchildren and so on. And the methylation and other epigenetic’s marks are reversible. They are introduced by writers and removed by erasers. And so these erasers and writers that add or remove those, the guys that write the software, the programmers. And they can be changed. So if you do certain drugs or certain behaviors or certain nutritional supplements, you can change the way these erasers or writers work and modulate them. This is what we tested. We asked the question, exactly your question is, well, let’s take a rat that had a low maternal care, had adverse experiences when that pup was an infant and now the pup is an adult and it behaves in a certain way that reflects the adverse experience when the pup was a baby. But can we now add an epigenetic drug and change it? And amazingly we could. So we could actually reverse not only the epigenetic marks, but also the behavior that was registered by these epigenetic marks.

Dr. Dan Gubler: (17:11)

Wow.

Moshe Szyf: (17:12)

But if we go back to your app and software, if you know how to write the script, you can change the script at any point. And this is exactly what we did.

Dr. Dan Gubler: (17:23)

Interesting. Wow, fascinating. It’s cool that the situation, bleak as it might be in the past, can be modulated via science in the present.

Moshe Szyf: (17:34)

Right. That’s the optimistic message. So I always say that genetics is pessimistic, epigenetics is optimistic.

Dr. Dan Gubler: (17:41)

Oh, I love that.

Moshe Szyf: (17:42)

Because genetics is predetermined, right? It’s very hard to change the genes you inherited, but how you take care of your inheritance, that’s epigenetics and that’s up to you or to society and your parents and et cetera.

Dr. Dan Gubler: (17:59)

Oh, wonderful. How cool is that? I know you’ve also done some great research and you might’ve already touched on it a little bit, but related to epigenetics and behavior. Is there anything else you would tell us about that?

Moshe Szyf: (18:14)

So epigenetics is involved heavily in behavior. And one sign that epigenetics is extremely important for behavior is the fact that when the genes that encode the epigenetic, what we call machinery, the erasers, the readers, the writers of the marks, if they are effective, most of the symptoms that people see are mental behavior — mental health symptoms, suggesting that the brain is really critically dependent on a functional epigenetic system. And therefore it’s highly susceptible to alterations that can affect the epigenetic system. So for example, addiction is most probably written in our DNA through epigenetic mechanisms.

Dr. Dan Gubler: (19:14)

Wow.

Moshe Szyf: (19:15)

And we have shown that could be removed at least in animals, by epigenetic interventions. And so addiction is a classic example of an experience and in this case, it’s the experience of experiencing a drug, and the long-term consequences that it has. So for example, if you take an animal that was trained to self administer cocaine,  that animal, if it’s removed let’s say to a rehab facility, put in a cage without being exposed to cocaine, it’s okay. But if you, after a month or two months, you show that animal anything that reminds the animal of the cocaine experience, the animal will start craving cocaine. And if you’re provided with a way to self administer cocaine it will just do it in a very addictive way, similar to humans.

Dr. Dan Gubler: (20:15)

Right.

Moshe Szyf: (20:15)

And we found out that this whole process involves changing and the way genes are programmed in the brain and that it’s defined by epigenetic machineries. The other interesting thing in addiction is why some people become addicted and others not. Are there early experiences that program our DNA in the brain to be more susceptible to addiction?

Dr. Dan Gubler: (20:43)

Hmm. Wow. So what you’re saying is that traumatic experiences earlier in life can lead to some of these health issues that we have, that people can have later on.

Moshe Szyf: (20:56)

Exactly.

Dr. Dan Gubler: (20:58)

Wow. That is really fascinating. Are there any other examples you would give us on how epigenetics can impact aspects of our lives based on the research that you’ve done?

Moshe Szyf: (21:09)

Of course the best example is nutrition. And there’s a lot of evidence that the early nutritional restriction will reprogram our brain and our body towards obesity and bingeing. Yes. And if you think about it, it makes absolute sense, right? When a baby is born, a baby gets cues, what kind of life it’s going to live. And based on these cues, the body is writing the proper codes to cope with, to fit into that anticipated situation, right? And so if you anticipate hunger because you were nutritionally restricted in the womb because something happened to your mother or was it stress, or she didn’t feed well, or she fed too well, all these things send signals through the baby to program the DNA, in the brain, in fat tissue, in muscle tissue, to adjust to those anticipated environments. So if the anticipated environment is famine, you better binge, right? Because you never know when your second meal will come. Not only that, turn everything into fat, which is the most stable way of saving energy. However, if what happens is that this was a false signal because you live in the United States and whether you’re poor or rich, you can get many, many calories for one or two dollars. And so what happened in Western society is there’s a disconnect between this very useful programming early in life, are you going to be poor or rich, which meant throughout evolution, it meant that you won’t have enough food or you have a lot of food so be ready for these two possibilities. And now it doesn’t mean the same thing anymore because poor people can have access to high calorie diets. And therefore you see that we start developing obesity because we have those signals from early life that are now in a very maladaptive kind of environment, these signals become maladaptive. They’re not useful anymore.

Dr. Dan Gubler: (23:25)

Wow. So epigenetics helps to explain the observation that obese parents, that children of obese parents have a higher risk of being obese.

Moshe Szyf: (23:38)

Yes. Children of obese parents have a higher risk of being obese or children who were starved early in life have a high risk of being obese and so on. And so this is a big field today in sciences, understanding how early life nutrition affects later life metabolic health.

Dr. Dan Gubler: (24:06)

Wow.

Moshe Szyf: (24:07)

And sugar tolerance, diabetes, obesity, et cetera, and that’s an important area where early intervention could make a huge difference.

Dr. Dan Gubler: (24:19)

Right. One thing I’m fascinated about when you mentioned nutrition, it seems like some of these small molecules, organic molecules in plants, maybe one of the reasons that they’re beneficial is they help to modulate gene expression or signal transduction pathways related to epigenetics.

Moshe Szyf: (24:34)

Right. Many, many, many small molecules can affect the epigenetic system. Some because they are a part of the natural pathway that regulates the epigenetic system, for example, S-Adenosyl-l-methionine which is a donor of the methyl group and others, because they signal on the pathway, right? This is a very complex web and signaling can happen anywhere on this web. And the trick is to figure out what combination of nutritional supplements is sending good signals that we want to have, right?

Dr. Dan Gubler: (25:13)

Right.

Moshe Szyf: (25:13)

And those signals could be different in different contexts, right? They might be different for somebody who lives in a wealthy fat society versus somebody who lives in a famine society. And so there’s no one solution for all, that’s what makes this whole area interesting. It has to be personalized. We understand that. And it has to be contextualized and —

Dr. Dan Gubler: (25:44)

Wow. Interesting. So, yeah. So if we were to help to regulate or support epigenetics and people, it’s not a blanket approach, kind of like a personalized epigenetics.

Moshe Szyf: (25:57)

Right.

Dr. Dan Gubler: (25:58)

Interesting.

Moshe Szyf: (25:59)

And it’s more a self-learning and self-reinforcement approach, right? I mean, we need to learn through experimenting with ourselves is what is working for us, right? And it’s a lifelong kind of commitment.

Dr. Dan Gubler: (26:21)

Wow. So, you talked about lifestyle factors that can alter epigenetics. What about pollution? Is there any research how pollution and — in the air —

Moshe Szyf: (26:30)

There’s quite a lot of research now on environmental pollutants and the impact they have on the epigenetic system. And of course the impact they have on our health. The classic example of course is smoking and cancer or, different pollutants that are found and can cause lung cancer which is probably driven by epigenetic modulations. But, almost every hazardous material will have epigenetic consequences. Some will be short-term, others can be long-term, others can be transgenerational.

Dr. Dan Gubler: (27:11)

Right. Wow. That is amazing. Let’s now move on to, I know you are world leader, you’re the father of the field of epigenetics and medical diagnostic applications for the detection of diseases and other health conditions. Can you explain to our listeners some of the research that you’ve done in that area and some of the applications that you’re doing?

Moshe Szyf: (27:34)

So if we go back to the metaphor we used early on, which is, we have different apps that run our programs, right? And each app has a script, right? A coder has to write the script. And if you know the difference between a diseased app and a healthy app, you can identify who is diseased and who is healthy. Right? So if, for example, we have a tumor growth starting to grow in our body, that tumor’s DNA is going to have different epigenetic marks than normal cells from the same tissue and normal cells from any other tissue. And usually what happens is that DNA is shed into the blood. And if we can fish it from the blood, like pulling the needle from the haystack, but because we know the difference between the needle and the haystack, we can immediately identify the needle. And even if there are very few molecules of this kind, we can start seeing them in the blood early on, and then use it to detect, for example, cancer early. Some of these markets can be markers of other damage that happened to the body, like diabetes, when there’s damage to the pancreas or heart conditions when there’s damage to the heart. DNA from these tissues will start floating in the blood, could be detected and using sequencing technologies that allow us to read exactly the script. We can say, “Wow, this is not a script of a normal DNA, this is a script of a cancer DNA.”

Dr. Dan Gubler: (29:20)

Wow.

Moshe Szyf: (29:21)

So what we’re doing is we’re developing the tests that are based on this and our goal, our hope is that tests of this sort will be a routine checkup. Like today, we’re checking our sugar and blood pressure and lipids, it will be able to check those things. And really, cancer becomes a very simple disease when it’s detected early. It’s a horrible situation when it’s detected late. So if people could routinely follow up the emergence of cancer cells and take care of it early on, it will have a huge impact on morbidity and mortality.

Dr. Dan Gubler: (30:05)

Wow. That’s amazing. I’m thinking about some of the tests that are offered today, the DNA tests and what a lot of people don’t know is those DNA tests they tell maybe something about propensity for, they tell you nothing about what’s happening in real time. And so that’s why, yeah, this is amazing. So you’re able to see in real time how things are changing, how things are progressing, digressing, degrading and those sorts of things.

Moshe Szyf: (30:34)

Exactly. Because what will happen is as the tumor grows, it will shed more and more of this kind of DNA. So, you can follow, or you can follow if your therapy actually work because that DNA will disappear from the blood. And so I think that that will change dramatically how we look at diseases like cancer and other bad diseases. I believe that maintaining your heart health and your cardiovascular health will also use similar tests, but we hope one day also psychiatry and stress and anxiety and PTSD will be tested by these kinds of tests. So early detection will allow early intervention before things deteriorate.

Dr. Dan Gubler: (31:25)

Right. Yeah. The field of psychiatry. I mean a lot of these things like schizophrenia and bipolar. So in theory with a test like this, you could see if somebody who has bipolar for instance, and is undergoing CBT, or they have OCD, and they’re undergoing CBT to try to fight back the tide, using this type of test you could potentially see if those therapies are working. Is that correct?

Moshe Szyf: (31:50)

Right. The only challenge with the brain is that the DNA that is found in the blood is different than the DNA that is found in the brain and what slows down this field of research is understanding how much of the things that are happening in the blood are informative on what is happening in the brain, because we don’t have access to the brain, right? We cannot get DNA from the brain. Although it is becoming clear that even for the, when there’s some damage to the brain, there is the DNA from the brain in the blood, which we can actually use to detect early, early damage to the brain.

Dr. Dan Gubler: (32:27)

Oh, so that’s promising. So Moshe what you’re saying is with this test where you can detect epigenetics and changes in real time, seems to me that perhaps with psychiatric conditions like schizophrenia, OCD, and those sorts of things, you might be able to see if cognitive behavioral therapies and other therapies could be improving the condition.

Moshe Szyf: (32:52)

You’re right. And actually, this is a very active field of research. Psychiatrists, epigeneticists are trying to find out whether we can find markers in DNA that are indicators of those conditions and could be followed up to find out whether we are changing something. And the only problem with psychiatry and epigenetics is that the DNA that is important for psychiatry, or most of it is in the brain. And the brain is very hard to access and with non invasive methods. And so the big question in the field, which is still controversial, is how much does the blood DNA represent what’s going on in the brain?

Dr. Dan Gubler: (33:41)

Okay.

Moshe Szyf: (33:42)

Definitely there are results that suggest that there are markers of what’s happening in the brain and the blood then, but it’s still not as strong as what we see in cancer. But another source of DNA that is relevant to the brain is if there is brain damage, they would be DNA from the brain into blood and might be useful for early neurological diseases like the detection of diseases, from stroke to Alzheimer’s and diseases of this sort. So this is a very early time in the field and technologies are still developing, but potentially there’s a huge opportunity there.

Dr. Dan Gubler: (34:30)

Wow. That’s really fascinating. So it seems like the sky is basically the limit when it comes to epigenetics and its ability or potential to give us information about various health conditions in the body.

Moshe Szyf: (34:44)

Because epigenetics is the dynamic picture of our body. Epigenetics is a movie. Genetics is like a book, but epigenetics is a constantly interactive movie, right? We’re holding the remote control and we’re changing how that movie goes. And by mapping this epigenome and mapping this movie, you get a good understanding of where you are in life and where you’re heading and what other kinds of changes you need to make.

Dr. Dan Gubler: (35:17)

Wow. What a beautiful analogy. So now that we’ve talked about all the incredible things that epigenetics can do and the information it gives on the body, I think all of our listeners are wondering, and I think we might be freaked out, right, about epigenetics and what’s going on, but what are actionable things we do to improve our epigenetics, maybe to remove some of these markers that are detrimental to our health?

Moshe Szyf: (35:44)

Right. So the actions, some of them we know from human social evolution, right? Certain behaviors that we developed are actually good for us, for example, maternal care. In maternal or breastfeeding and good dietary habits and exercise. There’s evidence that all these things are affecting the epigenome in a way that increases our well being. But what epigenetics allows us is to test those things and keep learning what is working better.

Dr. Dan Gubler: (36:28)

Right.

Moshe Szyf: (36:28)

And so the future that I see will be, we start with all these things that we know already from human history, from human social evolution, that they are good for us. And we keep learning how to improve and modify them using tools that allow us to get a quick measure of how our genome is changing. And so, for example, we definitely need a source of metal groups to sustain the epigenetic machinery. Deprivation of metal groups by certain diets that are poor in those mono carbons that will contribute like poor in folic acid, the vitamin B12. They will cause trouble. So these are certain things we know, but there are a lot of things to learn and I think we’ll learn by experimenting, by experience, by trial and error.

Dr. Dan Gubler: (37:33)

So it sounds like this field is just in its infancy.

Moshe Szyf: (37:37)

Yes. It is an infancy as far as scientific understanding of what’s going on. But I think it’s as old as human evolution, in fact of the behaviors that we have adopted that aren’t good for us. And we have to be respectful of human evolution. If we have certain behaviors, there’s probably a good reason for it, why they were selected. So one thing that epigenetics gives you is respect for your elders and respect for the history of humanity, because the best school is human history and figuring out what people have figured out by trial and error works for them. And of course what doesn’t work.

Dr. Dan Gubler: (38:27)

Right.

Moshe Szyf: (38:27)

But what science will do, it will provide an explanation that will speed up this learning process and focus it on getting better results.

Dr. Dan Gubler: (38:40)

Wow. Fascinating. So Moshe, it’s been incredible talking to you today. What final comments would you leave our listeners about epigenetics?

Moshe Szyf: (38:56)

Epigenetics is teaching us how much in our life is under our control, how much we have to learn and that by active, dynamic learning and relearning we have the opportunity and potential to improve our lives. And we should start moving from just protecting ourselves from disease to increasing the quality of our well being which is in the DNA potential. Our DNA has enormous potential because one genome can have billions of epigenetic programs, and this potential we can harness and by proper usage of learning from history, from experiencing, and from science.

Dr. Dan Gubler: (39:58)

Wow. Amazing. Moshe, every time I talk to you, my mind is just blown about your wealth of knowledge and the things that you share. So it’s been amazing talking with you. You’re an amazing scientist, a great friend, and you’re an incredible human being. Thank you so much for being here.

Moshe Szyf: (40:14)

Thank you. Thank you, it was a pleasure.

Dr. Dan Gubler: (40:14)

Pleasure. Thank you.

Moshe Szyf: (40:15)

Bye-bye.

Dr. Dan Gubler: (40:17)

Thanks for listening, my friends. This is Dr. Dan signing off. 

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