Are we thinking about genetics all wrong?
Today we are joined by genomic analyst Lynda Sedley to tackle the controversial subject of nutritional epigenetics, modern genomic technologies and why clinicians need to be optimistically open to evolve epigenomics into personalised medicine.
Covered in this episode
[00:49] Welcoming Lynda Sedley
[04:06] Epigenetics: New medicine for old concepts
[07:55] How bypassing pathways may be turning genes off completely
[18:20] Diurnal variations in gene expression
[20:51] Whole-genome sequencing
[26:18] Methylation in viral activation
[27:54] Modulating genetics through nutrition
[31:48] Controlling inflammation
[37:37] Individualised treatment based on genetics
[41:59] The role of the natural therapist moving forward
Mark: Hi, everyone, and welcome. Today, we're talking with Lynda Sedley, genomic biotechnology expert and genomic analyst at GenHx Australia. Lynda has moved from natural healthcare to high-tech genomics and all the way back again, and sees nutritional genomics as an area of opportunity for all natural healthcare practitioners. Hi, Lynda, and welcome. How are you?
Lynda: I'm very well. Thank you. Thank you very much for having me.
Mark: It's a pleasure. In fact, it's an area that I'm really keen. A lot of our listeners are practitioners. In fact, probably the majority are, and a lot of the natural therapists are in this area of change where we're taught natural therapies. I'm a doctor but, you know, we're taught the natural therapies, and then a technology like genetics comes along and it's a melding of those two, which can be a bugger of a thing to get right.
Lynda: Absolutely, yes.
Mark: So I'm really keen to take this kind of picture. I believe you've been through quite a bit in your development. Tell us a bit about your background, just about the past and how you've come to this area of melding genetics with natural therapies.
Lynda: Of course. Yes, so I started my career in the pharmaceutical industry, and this was in my early 20s. And I ended up getting quite ill, unfortunately. So, you know, I was struck down with chronic fatigue syndrome…
Lynda: …which pretty much had me out of action for almost 20 years. Throughout this time, I jumped from doctor to specialist to doctor, and I just couldn't find any definitive answers that were able to help me. So, I took it upon myself to go and study nutritional and dietetic medicine, and I got a degree in that. And, you know, I was extremely passionate, you know, I always felt that it was my diet and lifestyle that influenced me to suddenly fall ill at, you know, the age of 20.
Mark: That and working for pharma, I suppose.
Lynda: Oh, yes, and that, too.
Mark: It could be pretty intense.
Lynda: Absolutely. I felt that the environment and the stress level, there was lots of things that weren't taken into consideration from a conventional medicine perspective.
Lynda: So, I went down this path, and you know, I tried and tested absolutely everything, you know, all of the things that are normally recommended for these kinds of conditions, and I just got progressively worse. And you know, I figured there had to be something else to my story. Then I started looking into genomics or nutrigenomics, and I found the concept of methylation extremely interesting.
Mark: Interesting, isn't it? Yes.
Lynda: Yeah, and I went...I sort of got really stuck into those pathways and modulation of those pathways. And then I got worse again, and I was like, “why am I getting worse?” I had to get to the bottom of these problems. So I started looking at the information that was provided regarding methylation, and I found lots of holes in the theories and in the concepts. So, you know, I took it upon myself to jump ship again…
Mark: It is, isn’t it?
Lynda: However, it's a very old concept, you know? These concepts of epigenetics and nutritional epigenetics have been around since the '40s, so DNA methylation and histone methylation, you know, have been around for a very, very long time. But you know, when the Human Genome Project was completed in 2003, all these genes and all these technologies got patented.
Lynda: So you know, we had no access to a lot of these things, and the epigenomics and the nutritional epigenomics kind of got forgotten about for some time, and we kind of got stuck into phenotyping and SNP analysis…
Lydna: …and all this kind of stuff. And then, when the patents expired in 2015, there was this boom again, and there was a much greater understanding of epigenomics and nutritional epigenomics. And you know, we're at this stage now where we're kind of ready to introduce this new form of medicine. However, a lot of what we know is backwards. So, it's about leaving a lot of what I had learned behind and pretty much starting all over again, which is why I find that a lot of practitioners who are right into nutrigenomics don't really share my optimism for a future of nutritional epigenomics, for that reason.
Mark: Yeah. The optimism, I do see that when you move from natural therapies, especially, even in medicine, when you move into an area that's brand new, there's an overwhelm, a feeling that this is too much, how can we possibly integrate that?
Lynda: Of course, yes.
Mark: How can we bring it together? And yet you go back a few thousand years in my field of medicine, Hippocrates was doing nutritional epigenetics, whether we think of it that way or not.
Lynda: That’s right.
Mark: The environment, the life, the diet, the water, the air, that these were the factors that created health, or real health. And the genome has not changed all that dramatically over that couple of thousand years, so it belonged in this field to begin with. Then, we put the technology over the top of it, make it sound complicated, and I agree with you, lots and lots of practitioners lose their confidence about that. They think, "Oh, I've been bypassed by the new technology," and it's really important not to forget that people are still people, humans are still humans, and we're talking about how you can modify the environment to make the genetic structure that we inherit work for us.
Lynda: Absolutely, absolutely. So the word epigenetics has changed so much over the last 50 years. We once thought it was just an environmental influence that changes us out, our genetic expression over the long-term. But now we're learning that it's pretty instantaneous. Like, you can change the expression of the genes right here, right now depending on what your environment is.
Lynda: So this is, you know, huge. But absolutely, you're correct in saying that it's very daunting. I certainly felt that myself when I finally had all the answers that I needed, but where do you start, you know? Like, it is very, very complex. As much as it's complex to look at at the time, now that I've got my head around it, I find it so much simpler in comparison to, you know, what I have learned in the past because it's very, very straightforward once you kind of get your head around it. So, I think it's very, very exciting, and I think it's a pretty amazing future for nutritional epigenomics or nutrition as a whole. I think it's very exciting.
Mark: Well, tell us...you said it's very straightforward. It still, to me, doesn't seem that straightforward. How do you make sense of this, that a person has their 23,000 genes, they are your inheritance. Whether they're expressed or not, it's almost like then a miracle happens. Some of them are, some of them are not, you get bad outcomes, you get good outcomes. How do we even start to think about it? You know, you can't put 23,000 data points and 10,000 SNPs together in a clinical practice. How should we be thinking about the genetics that we inherit and the epigenetic expression of that? Is this part of what we've been doing right, the way through natural therapy history? Or is this something that gives us a new perspective, a new way of thinking of doing something about it?
Lynda: Yes. So, it's a very new way of thinking. But you know, so let's go back to the SNPs and the phenotyping.
Lynda: So, we've got a very good understanding of, you know, whether you're a slow COMT or a fast COMT…
Lynda: …but we also now know that the epigenome is the control centre of all of those SNPs. So, it doesn't matter whether you have a fast COMT or a slow COMT, if that SNP isn't even active or that gene isn't even active in the first place. So, it all comes back to how the genome is governed and how the genes are expressed. So, we kind of need to take a step back a little bit…
Lynda: …and sort of look at the whole picture, look at what is governing the genome before we look at the SNPs themselves. This is what makes it slightly simpler, because you know, there are only so many ways that the genome can express genes, and that's either on or off. So you know, a lot of the time we're finding that most of our environment is hypermethylating as opposed to hypomethylating. So, this means that a lot of the time our genes are actually turned off instead of turned on.
Lydna: So you know, it's a pretty simple fix, the idea is to turn the genes back on. So it comes down to what we know about the epigenome in each individual person. So each individual case is different, you know? Everyone has a different set of SNPs, and has a different way in which their genome operates those genes, so to speak.
Mark: Right. These are the protein-expressing genes, these are the ones that are actually capable of building the messenger RNA and going out and constructing proteins. So there’s...
Lynda: Correct, correct, yes.
Mark: …we’re talking about those 23,000, roughly, genes.
Lynda: Absolutely, absolutely. So you know, when I say things that we've learned in the past need to be, I guess...you know, we need to put those things aside and start all over again, I'll use a couple of examples. One of the examples is the MTHFR gene.
Lynda: So you know, we all learnt that we had, if we had a pathogenic version of this gene, that we were essentially hypomethylating. So you know, we would bypass this particular gene and speed up that process, so we're increasing methylation. But when you look at it from a nutritional epigenetic perspective, we're finding that this particular gene is actually positively selected, which means that it has acquired this particular SNP to slow the process down…
Lynda: …because there has been environmental influence of hypermethylation. So people who live at high altitudes, people who have exposed to lots of UV radiation, and even the American population too, who have lots of fortification in their foods have more...there is a greater incidence of this particular type of SNP.
So what is actually happening is we're bypassing this SNP, which is supposed to slow it down. We're increasing more methylation and we're taking methylation to the next level, which is histone methylation and DNA methylation, which is essentially turning the MTHFR gene off, and then you're turning the methylation cycle off. And then, they actually get relief from actually activation of genes.
Lynda: So you've got to understand that the MTHFR gene needs to be active. So we need to have, like, active processes to increase the expression of this particular gene just for the methylation cycle to function in itself.
Mark: The SNPs are the naturally evolutionarily selected variants.
Mark: I mean, nature has an interest in a wide variety of possible responses rather than a monoculture. And so there are presumably the, you know, the single-base variants, the single amino acid variants and those. There are changes that apparently worked to allow some groups to evolve with variations of the common or wild gene variety. And they must have had a benefit, or you would suspect that they would not have been perpetuated, that they would not have made it through in the evolutionary cycle.
Lynda: Absolutely. Yeah, yeah. So our body has this really innate, and our genome especially have this innate way of protecting us from our environment. And that's just evolution in itself. We acquire these minor changes in our genome just to adapt to our surroundings.
Lynda: And the MTHFR gene is one of those examples. So, and it's one of those things that really grinds my gears because…
Mark: I know.
Lynda: …you know, it is such a huge part of nutritional epigenomics. However, what we know about it is somewhat backwards.
Mark: When you say what we know is somewhat backwards, you're meaning that we're looking for a problem and then assuming that is a problem to be solved? Or what do you mean, "We're looking at it backwards with the MTHFR?" Because it hopped on the radar, it's got an interesting...you know, the way that you pronounce MTHFR often means something to people and they remember it. But it's only a variant of one pair of genes out of an entire spectrum, and we've focused on that to an obsessive extent.
Mark: Why should we have focused on that? Was it so big in, say, gene expression, switching on and off genes, methylating of histones? Was it such a big thing that it was an "aha" discovery, or is this just one of a whole line that we're picking up, now that we've got the COMTs and we've got the whole genome?
Lynda: The concept of epigenomics and DNA methylation has been around well before phenotyping.
Lynda: But because we couldn't access it, we kind of jumped with the phenotypes. We found key genes that were associated with things like spina bifida and, you know, chronic diseases like that, and worked out that they were associated with a particular type of condition. However, its association with condition doesn't necessarily mean that it needs more methylation, it’s inactive, it means that there's probably a situation of hypermethylation…
Lynda: …that has acquired this gene, and that's the association. And that's what I mean by it being somewhat backwards, is because, you know, we look at the methylation process and we go, why are we making these methyl groups? What is the process beyond the methylation, one carbon cycle? And this is DNA methylation and histone methylation, which control absolutely everything. So if we increase that, and we increase the methyl groups, then essentially, we're turning off genes, we're creating what's called heterochromatin, which means the structure of the epigenome closes up so that no genes can be expressed in that particular region.
Lynda: So, it changes the whole structure, the whole gene expression. When, you know, when you look at all the different potential epigenetic marks, which are acetylation, phosphorylation, ubiquitination, you know, there's so many of them that change the way the genome behaves.
Lynda: Methylation would probably be the last one we should have been focusing on because that's the one that's turning off the genes,…
Lynda: …when, essentially, we want to turn them on. So you know, the methylation cycle has, say, 30 genes that we're focused on, for example. Each one of those genes needs to be turned on for the methylation cycle to work. But if we produce too many methyl groups, then we're actually turning these genes off through DNA methylation, which means other genes in other areas are actually being activated.
Mark: Right. So you've got to take down the methyl groups to allow for the gene expression that you may want to see in a given individual, so that what you're really doing is allowing a process to occur by demethylating?
Lynda: Absolutely. So, the many processes of our body, a lot of the cyclic ones, say the menstrual cycle and the circadian rhythm, you know, all of these processes need a fluctuation of both methylation and acetylation…
Lynda: …as well as phosphorylation and ubiquitination and citrullination. All of those post-translational modifications change the way our genes are expressed, but the problems arise if we have too much methylation and not enough acetylation. So for example, we need acetylation to wake us up in the morning. We need activation of the CLOCK gene that gets us out of bed and gets us motivated for the day, wakes us up with the sun. But if we're hypermethylated of an evening, we don't actually get that wake-up feeling, we don't get that jump out of bed full of energy feeling that we are supposed to get.
Lynda: And then we feel like we have to take more B vitamins to turn our methylation off, even though we think we're turning it on, to get that boost again in the morning. I know it sounds quite confusing to begin with, but the way I see it is, or the way I try and explain it as simply as possible is that we need to have gene expression, and it's all about that fluctuation and when we should be taking methyls and when we should be acetylating and vice versa.
Lynda: Oh, sure.
Mark: …so we could turn on and turn off on a daily, monthly, any other cycle that the body has. It sounds like there should be an awareness of what is required for gene expression at a particular time of day, month or even year, I would guess, for annual cycles.
Lynda: Absolutely. So, this has been my research focus.
Lynda: My research focus is the complex interaction between, you know, the hormones, the circadian rhythm, the immune system, and the epigenome, and the neurological system, which is all pretty much chronic fatigue syndrome picture. And you know, there is this very, very exciting pattern in post-translational modifications, which change the way each gene behaves throughout the menstrual cycle and throughout the circadian rhythm. So, absolutely. Yes. And then, I'm finding that with hypermethylation, there are a lot of people who take B vitamins that have the problems of, you know, early morning fatigue, you know, excessive day sleepiness and all that kind of stuff. So, and B vitamins are generally one of the first things you give to someone who has fatigue…
Mark: Ah, yes.
Lynda: …and circadian rhythm issues. However, you know, that is not the way I would treat.
Mark: That may not be indicated.
Lynda: No. No, I don't think so. No.
Mark: As a practitioner, though, how can you pick one from another? So you've got patients or clients turning up, saying, "I'm tired in the mornings, I'm forever tired in the mornings. I've had by MTHFR done, you know, I'm on a methylation treatment." Where do you take them from there? What happens?
Lynda: Yeah. So, if they say that they are actually positive for a pathogenic MTHFR, I immediately think hypermethylation,
Lynda: …which is quite the opposite to what most practitioners would say.
Lynda: But I see that as an evolutionary exposure to hypermethylation, and generally epigenetic inheritance from ancestors along that line. So, that's probably the first sort of clue to a hypermethylated state.
Mark: You are the ones that carry this epigenetic expression for a purpose rather than it's an accident that just happened to you badly.
Lynda: Yeah. Correct, correct.
Lynda: Absolutely. Yeah. So, I guess each individual case is different, which is why I'm a bit of an advocate for genomic sequencing or high-quality genomic sequencing, although it's in its infancy as far as cost goes. So since, you know, the expiration of the patents, you know, we had this boom in genomic sequencing…
Mark: I know.
Lynda: …we can now afford to do it in our practice. We can afford to do it, all researchers can afford to do it, you know? I guess a good quality, whole-genome sequencing is valued at around $1600, but you know, that price is going to go down, and it's going down every day.
Mark: It's been dropping for a couple of years now…
Lynda: Of course.
Mark: …quite a number of years, by orders of magnitude, hasn't it?
Lynda: Absolutely. And eventually, everyone will be able to afford these kind of technologies. So, my idea is to kind of prepare, I'd love to prepare the practitioners for when that time comes. Because I really believe that, you know, quality treatment of chronic disease kind of has to start with gene expression and gene analysis.
Lynda: We can, like I've used myself as a guinea pig and I've tried and tested lots of different epigenetic modulation on myself. But you know, it's a lot more effective if you have a blueprint of what is actually happening in that person.
Mark: Okay. So, you know where the trap doors are, you can figure that out by the whole genome.
Lynda: Absolutely. Yes.
Mark: So, rather than doing just, you know, I'll do methylation SNPs, I'll do VDR SNPs, rather than picking and choosing, you're thinking that the future is really, gather the whole of genome. Are we reliant, then, on big data and the kind of algorithms for the future to make sense of all those interactions, or can we make sense of it already?
Lynda: Yeah, I think the technology is there, especially with high coverage sequencing. There's definitely a lot of qualities of genomic sequencing that I wouldn't say are good...yeah, they're just not up to the standard as of yet.
Lynda: But there are definitely very high-quality sequencing technologies these days. But in an ideal world, you know, I would like to see gene expression analysis, a whole-genome coverage, high coverage of a particular condition, as well as looking at the epigenome and looking at the methylation marks in those particular cases as well.
Lynda: So, that would be the overall, ideal sort of initial analysis of a chronic disease patient.
Lynda: But that would be...you know, that's quite a bit in the future because it's quite expensive to do that all at once now. Although, the technology is to standard.
Mark: Yeah. In practical terms, what happens is we have a patient walk in with a 23andMe report, and they dump it on the desk and say, "Why am I sick?"
Mark: As if, you know, 125 pages of genome sections, individual segments taken out with red dots and green dots. We have this problem that we're expected to interpret that and make sense of the phenotype of the illness expression, and I think that's almost impossible. In fact, literally it's impossible when they dump it on the desk at the beginning of a consultation…
Mark: …because there's not the time to go through it. So we're talking about different things here. You're seeing a future where the whole of genome and interpretation is available to the practitioner rather than a set of data points which say, an MTHFR is a 1298 variant, and a COMT 2 is a low-function...
Mark: So, we're just getting data points now, trying to put them together. But the future is not that, I'm hoping.
Lynda: Yeah, no, it certainly isn't. Unfortunately, you know, the information that we have on phenotypes is very, very skewed. There is a lot of missing pieces, and the missing pieces sort of come with the epigenetics.
Lynda: So, yeah, certainly you know, you can gather a picture of methylation.
Lynda: For example, I see it as being hypermethylation, and you can sort of see where there are some roadblocks in certain areas. But I look at those 23andMe reports, and I look at key genes that are involved in the epigenome. So, we need key genes to activate genes.
Mark: Something that we can do something about. Is that...?
Lynda: Absolutely, yes. Except, unfortunately, the 23andMes are cherry-picked. So, these key genes that I'm looking for aren't actually there.
Lynda: They’re not visible, you can't see them. And a lot of the time, these patients that come to me, that have chronic disease, especially things like chronic fatigue syndrome, their epigenetic issues lie in deletions and insertions, and you know, these kind of things.
Lynda: And these are very important because if you hypermethylate a deletion, for example, what's left of that deletion, you know, gets wiped out completely.
Lynda: And this is where, you know, illness sort of starts later on in life. You might not have...you may have that deletion all of your life, but not acquire it until later on, when it gets silenced.
Mark: And we don't do them any favours by hypermethylating, by bringing up the high methyl donors and acceptors. In those circumstances, what would be your approach? So, you've got...so, I'll give you an example. Because I have been in the field of chronic fatigue syndrome quite a bit, we have evidence of lots of viral activation.
Mark: Which the assumption has been that's a failure of methylation as a technique to sabotage a virus's replication, or a failure of the histone methylation to sabotage the virus. Therefore, we think okay, if we methylate, methylate, methylate, maybe we can stop these viruses. Is that reasonable, or is that a misinterpretation of the thing that we're looking at?
Lynda: Well, I understand the concept, and I can see where you're coming from. However, a viral genome needs to have active gene expression for latency as well.
Mark: Right. Okay.
Lynda: So, you know, it's very important that you analyse every single genome in the virus, you know, to determine whether that person stays in latency, or whether the virus is reactivated. Yeah, so every gene needs to be either activated or deactivated, but the virus has so many different pathways. It's about which one you're going to be modulating, which one's a priority. And for me, you know, I would like to see a virus stay latent…
Lynda: …which is essentially making sure that those genes can be expressed because it can very much backfire and go the other way.
Mark: So, talk about the nutritional aspects of this. The epigenetic modulation that is available to us all is certainly able to be done through dietary changes. I recall when you were saying, you know, things can change very rapidly, a single meal seems to be able to change epigenetic expression, at least in some animal models that I've seen. If we can change things from a nutritional perspective, can we get a lead from the genomic analysis to say what, nutritionally, should this person...what's their natural diet? What is their way through evolutionary history that they would have been modulating gene expression?
Lynda: Absolutely. And this is where things like 23andMe and Ancestry do come in handy…
Lynda: …because you can have a look at your evolutionary history and, you know, you can see what your ancestors ate. And as far as evolution is concerned, you know, the slower we make changes to our diet and lifestyle, the better our epigenome and our genome can adapt, and the less chance we have of having mutations and things like that. It's when we're exposed to major environmental change or major dietary change that we end up having to adapt…
Lynda: …and you know, that's when our genome, you know, modulates itself so that our genes can express to fit in with our lifestyle.
Mark: So, the major changes of the last few hundred years, where we eat food-like substances from supermarkets rather than food…
Mark: …those have got to have played a part in what we see now as chronic disease, chronic inflammatory states.
Lynda: Absolutely. Yeah, yeah.
Mark: So, how do you pick the vulnerable? Can you from a whole of genome assessment, can you see who is vulnerable to, say, the inflammatory responses to particular types of diets? Are there people better suited to, you know, vegetarian, low meat? Are there anti-inflammatory type diets that you can base on the genome itself? Or is that a way, way ahead of us now?
Lynda: No, certainly this is the here and the now. This is the basis of nutritional epigenomics.
Lynda: So you know, my idea of evolution and nutritional epigenomics and inflammation is another, I guess, another way or another place that I see some holes in our current theories, especially when it comes to chronic fatigue syndrome and those kind of chronic ailments.
Lynda: So you know, like, we can look at things like the Italian evolutionary history. So these ancestors, you know, they ate basically plant-based diets…
Lynda: …and they were known to be quite fit. They were the gladiators, you know, they had high muscle mass, but they primarily lived on plant-based diets. And then you have other colonies that were meat-eaters, you know, they ate mostly meat, you know? And we have a bit of an understanding in regards to evolution, and you know, there's meat-eating kind of tribes, like the Paleo idea, you know?
Lynda: They eat these foods from those eras or from those times, and you know, they find that they're healthier, they have more muscle mass and all that kind of stuff. However, at those times, we didn't eat green, leafy vegetables. They were quite toxic back then.
Lynda: So, as much as we see, you know, the changes that have happened through the technological boom, and we had, you know, the processed foods and all that kind of stuff...
Mark: The food processing, and the rapid growing, and the agricultural revolution. Yeah.
Lynda: Yeah. Yeah, so we saw that change, but we also saw another huge change, which is the health craze, you know?
Lynda: And we all went to green, leafy vegetables and anti-inflammatory diets. And it certainly was the case for me. But this is, you know, a diet that can be hypermethylating and very anti-inflammatory. And we know that we need inflammation to heal wounds, we know we need certain types of inflammation for cognitive function. And you know, inflammation is something that is also very essential.
Mark: And it's moderated by our own genes and by the, you know, omega-3, the pathways. And so inflammation is, these days I think, considered much more a controlled mechanism. We, in the past, had to have inflammation to control infections as well.
Mark: Now, we seem to be stuck with the problem that the inflammation is the problem rather than the infection being the problem. I mean, we still have the antibiotic issue to address, but now, if you gave doctors a choice, “what would you like?” We'd, say, “control inflammation without the adverse effects of all the drugs that we use.” So that inflammation controlling part would interest every medical practitioner because we see it in heart disease, stroke, we see it in clotting disorders, we see it in arthritis. And we're forever using drugs that shut off a particular system, or poison an enzyme but are not sustainable. So, is there a sustainable model that we can gain? Do people with their, say, genomic analysis, can we see them these days and say, well, here's the diet for you? Here's the food you should be eating. Or is it just, you know, we keep on giving generic information?
Lynda: Yeah, it's definitely an area that could use some significant improvement.
Lynda: But absolutely, you can see your inflammatory profile in a whole-genome analysis.
Mark: You can? All right.
Lynda: Absolutely you can. So for me, and the reason why I was talking about my idea of anti-inflammatory is because the driving force of my chronic fatigue syndrome was a lack of inflammation.
Lynda: So, I actually needed inflammation to control my immune system. So, you know, if you...
Mark: Isn't that interesting?
Lynda: Yeah, yeah. And you know, as I got deeper and deeper, inflammation is the driving force of the menstrual cycle as well. So you know, you really need to have a basis of inflammation, it just depends on what type of inflammation there is. So, each cell has a different metabolic profile, so you know, in heart disease, you know, inflammation can certainly be confined to the heart or to the blood vessels. However, it's not to say that there is an excess of inflammation in every other tissue.
Lynda: So, it comes down to the genes, the gene expression, and the epigenome, which is the driving force of inflammation everywhere in the body.
Lynda: So as far as targeting specific organs, we have a very good database, and there's lots of information out there. However, as far as translating that to clinical practice is quite a long way off.
Mark: It still is, is it? So are we talking about 10 years away, or...will be in our lifetimes? Is it that kind of...is this a pipe dream is, I suppose, what I'm asking? Because my ideal would be to know whether the person in front of me is suffering from an excess of a pro-inflammatory profile, whether they're failing to meet, say, inflammation control areas in particular parts of the body, to see whether the gut...you know, I would love to be able to take a peer in and see what their diet ideal would be like to stabilise some of those inflammatory pathways. I think what you're saying is that's a way away, all we can do is take snippets of that information right in the present and work with the little bits that we do know.
Lynda: Yeah. See, as much as it's a long way away, see, the translation from research to clinical practice as far as drug manufacturer goes is about 20 years.
Lynda: So you know, it takes quite a considerable amount of time. So my idea is to have a research institution which is designed for practitioners that can do their own assessment of these kind of things, and get these things happening now. Because we cannot wait between, you know, that...you know, throughout that 20-year period.
Lynda: There’s just so many people who are suffering, and we can actually do something about it now. The problem with, you know, clinical trials and all that kind of stuff is because we're getting so many false negatives and false positives because of the sizes of the cohorts. Now, we know that each individual genome is different, so for personalised medicine, we should be able to test everybody, you know? I encourage everybody to, all practitioners, to be doing their own testing, you know? I'd love for you to, you know, have a look at whole-genome sequencing and analyse the inflammatory profile of your patients and see for yourself. Because if we wait, we probably will never get there because a lot of the researchers tend to get these postdoc positions, and kind of get lost in their...
Mark: Yes. More researchers needed.
Lynda: Yeah. And you know, we don't hear about it for a very, very long time. And my idea is to get this ball rolling now, and having all practitioners being able to access their own research and participate in our own research, which will hopefully build the nutritional epigenomic, like, industry as a whole.
Mark: All right. So, you do see the day of us being able to take the genomic information, look at the phenotype who's the person in front of us, our client or our patient, and be able to say, well, here's simple things that you can do to alter that trajectory of gene expression.
Mark: I mean, the ones that we say now is “fill your belly with vegetables,” because that's largely going to be better for you. But that's not always the case. If our ancestry comes from meat eaters, fish eaters, there may be differences, so that we're not just saying “everybody go on the Mediterranean diet,” we'd be able to be far more specific about your needs are best met by the following. And some of those may be supplements, and some food. Do you see that being the working model for a while now?
Lynda: Absolutely. So, my research is hormonal balancing. So I find that some cultures, they ate a lot of hormones, or they ate a lot of meat…
Lynda: …purely because they have a different epigenetic, different evolutionary makeup which makes them require hormones from their diet…
Lynda: …as opposed to manufacturing them on their own. So, absolutely. And this inter-ties with inflammation as well, but these kind of people absolutely need to eat more meat because they will suffer if they don't.
Mark: And then the "Woman's Weekly" will say, of course, in the next week, never, ever eat meat, and then "The New York Times" a month later will say meat is exonerated.
Mark: And we have all of these generic statements, all of which do not apply to individuals. They apply across populations, when you don't differentiate according to needs or genomes.
Lynda: And this is a problem. Yeah, and this is the problem that we're having. We really need to take an individual, personalised perspective for every single case. Because you know, evolution was there for a reason. We all come from different regions and ate different things, and we need to, yeah, continue to do that if we want the healthiest version of ourselves.
Mark: Right. So give me the practical example. A person turns up and asks your opinion, they do have, say, something simple, like chronic fatigue syndrome.
Lynda: Yep, yep.
Mark: How do you even start that? Is the phenotype, is the person presenting to you an important part of that, whether they're thin, they're tall, they're, you know, hypersensitive to sounds, noise and the like? Are we making a mistake in clinical assessments where we don't really need to differentiate people that way we do better in the genome? Or is the history, the family history, the physical examination, are those still important things in this world of genetics?
Lynda: Absolutely. I think you need to take everything into consideration. So, you know, their ancestry certainly plays a part on their genetic susceptibility…
Lynda: …but as far as chronic fatigue syndrome goes, that's generally...
Mark: I'm doing this for personal reasons, you understand? I would love to have a simple answer to a complex problem.
Lynda: So, as much as there are due… cell studies that have fine-tuned the key genes associated with chronic fatigue syndrome, it's very pheno-typical. So they've kind of like honed in on a couple of key genes, however, these key genes are certainly modulated by the epigenome. So from my experience, it was just a majorly hypermethylated area of my genome, which basically turned off all my essential inflammatory genes.
Lynda: So, that is a simplified version. However, because there are, say, 30 genes associated with chronic fatigue syndrome, every single case is different, and the expression of each one of those genes will be different. So as much as I say for me it was a hypermethylation situation, it's not always going to be that case. There are certainly other variations of that. And the way to determine that is through, you know, analysis. You really need to have a look at the environment still, you really need to look at, you know, the evolutionary history, and then their diet, and lots of different things. All of the things that we currently do, we would still need to do.
Mark: And so that's the place of the natural therapist. The doctor may be focused more on infection, you know, pathogen, Epstein Barr. They may focus on particular stressors or stimulus for the expression of genes in a negative way. But you can go back to the individual and say what are their strengths, what are their weaknesses? Naturopathically, I think that leads to a broader concept of, you know, how do you manage stress, exercise, the diet?
Mark: What are the players in this that may take time for you to work out with the person?
Lynda: Of course. And there's the whole concept of adaptation as well.
Mark: Yes, I agree.
Lynda: So as much as we can turn genes back on, the person still has to adapt to the new environment all over again. And that can result in anxiety, depression. You know, these genes haven't been activated for a long time, so you know, there is a huge need for naturopathic or holistic therapies in those cases, especially chronic disease.
Mark: So, do you see the natural therapist as having to become mini-geneticists along the way? Is this something that can be tacked on to naturopathic education, that it can become, if you like, another tool like a stethoscope or something for a doctor? Is it another tool that expands the range of the things that they are doing? Or is this, you know, revolutionary, as in a displacement of old ways of thinking, and a new way of thinking about each individual? My feeling is that naturopaths dealt a lot better with personalised medicine than doctors did. We tended to think of diseases and treatment for disease, and the individual was not all that relevant, as you could see from randomised controlled trials.
Lynda: Yes, yeah.
Mark: Whereas the naturopath has always seemed to me to respect the person in front of them and their individual variations, which the doctors discarded as irrelevant.
Lynda: Absolutely. Now, I think that the incorporation of nutritional epigenomics is eventually going to be essential.
Lynda: You know, I look at different forums and things like that, and you know, these practitioners will ask a question in regards to a condition, and you know, will get 10 or 20 different answers. But when you incorporate nutritional epigenomics, you can fine-tune those answers to one or two…
Lynda: …that I know would be 100% effective. So you know, as much as the concept of naturopathy is absolutely, essentially, we hold all the answers for genomic modulation. But if we wait until...well, I see it as a window of opportunity. Because you know, in...you know, probably past our lifetime, you know, the genomics will take off, and they'll be able to snip and cut different genes out of our genome and insert new ones, which is a technology that's available now.
Mark: Ohh...I know, CRISPR.
Lynda: Yeah. And it's really scary. But people aren't going to want to do this. And as far as evolution goes, we don't know the consequences of these things. So for our industry, in my opinion, to stay alive, we need to stay on top of this because, you know, we are going to hopefully, you know, be able to incorporate that when these times come, and be the superior form of genomic modulation because of safety.
Lynda: So, yeah, I see it as an essential transition which will take some time. But you know, it should be really exciting for them because they do hold the answers.
Lynda: A lot of herbs are very, very effective genomic modulators.
Mark: Yes, and they have been around as long as humans have been around, and humans did pretty well under an evolutionary selective process. I just do see this last, you know, century, even just the time that I've been alive, that what we take for food and what we take for exercise and what we take for, you know, normal stressors have changed amazingly. And human DNA and their genetic expression and the epigenetic expression, it's almost like it's in a catch-up mode of how do you make massive changes to the world and the food and the gut and the microbiome…
Lynda: Oh, yes.
Mark: …and expect everything just to function normally without any challenges?
Lynda: Absolutely. Yeah, so biochemistry in itself is just a completely different to what it used to be, you know? Like, our bodies do not do what they used to do. And it just means really starting all over again, you know? Just having an open mind to change is really important in this day and age, I think.
Mark: Yeah. Look, I would love to thank you for taking us through that, Lynda. It's been delightful to get a perspective. And I think, you know, my deep down gut feeling is there'll be a technical side to medicine, and if we can bring those technologies in softly enough to value the other side, the phenotypic assessment, as we practitioners have always done, that the technologies that add to rather than displace are going to be the valuable ones. And how we bring those together, it seems to me that you've been on the forefront of that, changing from the natural therapies to the genomics, and then back to natural therapies. I want to thank you so much for guiding us through that today. Thank you very much.
Lynda: You're welcome. Thank you so much for having me.
Mark: It's been a pleasure. This is FX Omics, and I'm Dr. Mark Donohoe.