Predicting and Preventing Disease with Precision Medicine with Dr. Jeremy Nicholson

Mark Hyman, MD

Full Transcript

Automatically generated. Please forgive any typos or errors in the following transcript. It was generated by a third party and has not been subsequently reviewed by our team.

Dr. Mark Hyman
Coming up on this episode of The Doctor's Pharmacy.

Dr. Jeremy Nicholson
The single best thing that you can do for your life is have a healthy diet and get a re do a reasonable amount of exercise. The biggest single killer of humans is cardio vascular disease statistically. 80% are premature death due to cardiovascular disease is preventable by healthy diet and exercise and not smoking.

Dr. Mark Hyman
Before we jump into today's episode, I'd like to note that while I wish I could help everyone via my personal practice, there's simply not enough time for me to do this at this scale. And that's why I've been busy building several passion projects to help you better understand, well, you. If you're looking for data about your biology, check out function health for real time lab insights. If you're in need of deepening your knowledge around your health journey, check out my membership community, Hyman Hive. And if you're looking for curated and trusted supplements and health products for your routine, visit my website, supplement store, for a summary of my favorite and tested products.

Hi. I'm doctor Mark Hyman, a practicing physician and proponent of systems medicine, a framework to help you understand the why or the root cause of your symptoms. Welcome to the doctor's pharmacy. Every week, I bring on interesting guests to discuss the latest topics in the field of functional medicine and do a deep dive on how these topics pertain to your health. In today's episode, I have some interesting discussions with other experts in the field.

So let's just jump right in. Well, doctor Nicholson, welcome to the doctor's pharmacy podcast. I'm so happy to have you. You've come all the way from Australia down under. You're here at the annual international conference for functional medicine.

I'm so privileged to be able to talk to you because you're one of the pioneers in a new field of medicine that is Joyce going to be what everybody's doing in a few years. It is. And and, and you've been the pioneer in this field, what we call phenomic medicine. Now we're gonna define what that is in a minute, but, you know, we're talking here about a new era, a new revolution in science and the science of medicine and the application of that science to treat complex chronic illness that doesn't lend itself well to a a single biomarker treated with a single drug to create a single outcome. Like high blood pressure, blood pressure pill, you know, lower blood pressure.

Biology is way more complicated than that. And in medicine, we kinda do what we do, but it's not really looking very deeply into the human body. And up until the last few years, we really haven't been able to understand what's going on. We do a blood chemistry panel of 20 or 30 analytes who might do a cursory physical exam, you might get a few x rays or imaging here and there. But it's kind of the dark ages when it comes to really what's what now is available to us to understand the complexity of the human biology and to understand this world of of the omic medicine, which is our genes, how they are expressed into what we call the phenome, which is the body's expression of all the influences that have washed over us through our lifetimes.

And we're gonna have you define it as well. And and we're we're entering an era where we're moving away from a one size fits all medicine to a highly personalized form of medicine that's based on your particular genes, biology, experiences, exposures, and that's gonna help us to identify patterns in your story, in your data, and a lot more data than we're capturing now, which we're gonna be able to capture more of over over time to be able to create a, a predictive model of where you're headed on the, continuum from wellness to illness. And so your work has really done a lot of of of the the sort of hard, sort of challenging work of making sense of an enormously complex array of of scientific advances that have happened so fast that we can't even imagine how profound it is. And it it's kind of akin in my view to sort of the discovery of the microscope or discovery of, like, the the even the the electron microscope to be able to see or the telescope to see what's happening in a world that we never saw before. So can you kind of before we get into sort of the omics and whatever, this, can you kind of talk about what what is precision medicine, personalized medicine, and how does it differ from what doctors are doing now in conventional medicine, what I was taught in medical school?

Dr. Jeremy Nicholson
Well, thanks for that interesting introduction. Covered a lot already. Yeah. So you're gonna I'm gonna be

Dr. Mark Hyman
I'm supposed to be learning from you.

Dr. Jeremy Nicholson
So, precision medicine. There's a there's it comes under a number of different, titles, terms of stratified medicine, precision medicine, personalized medicine. And all of those thing, they're different flavors of the same thing, but they're they're all about getting the right treatment for the right person based on some knowledge about their biology, some fairly deep knowledge about their biology. And and to a lot of people, these days, talking about scientists and doctors now, they they think of precision or personalized medicine as being very genomically orientated. So your genes will tell you what is going on in your body and what sort of things you should look out look out for.

But I think it was, you know, it was Francis Crick first described the genome as the blueprint for life, and that's an interesting and revealing, terminology count basically coined in 19 fifties. The blueprint blueprint is a set of plans for building something. So if you have a blueprint for a nuclear submarine, you can build that, but it won't tell you about nuclear power, about the the fact you're splitting atoms or anything anything like that or even what electricity is. It doesn't tell you how the thing works.

Dr. Mark Hyman
Right.

Dr. Jeremy Nicholson
And your genes, of course, are give you as a as an organism flexibility for living in a complex changing environment. The world changes all the time, and you're you have to have enough genomic genetic flexibility to be able to accommodate to the changes that exist. And when evolution occurs, it's your adaptability of your genes to go into new environments to capture new food sources. So there's an intrinsic variability in the genome, which has good parts. It gives you adaptability, but it also, allows you to go into new environments.

The thing that really changes whether you can go into an environment is is actually the microbes that live in you. The microbes are an interface between you and the environment. So all environmental influences, dietary sources, pollutants, whatever it is, come through a microbial layer on your surface of your skin, your lungs, in, of course, your gut, and that modulates what happens in your body. So for a start, the genomic hypothesis that, you know, have been able to predict medical outcomes based just on human genomes is in incomplete because it in it doesn't include all the microbial genomes Yeah. Individual to all of us.

I mean, it has maybe

Dr. Mark Hyman
a 100 times as much genomic material as

Dr. Jeremy Nicholson
our own. Maybe a lot more than that. But Yeah. So, a 100 a 100 trillion organisms living in us at any one time and about a kilogram of in mass of of microbial, you know, mass. So there's there's that extra bit that goes from the genome to the the metagenome.

That's all the bugs that live up with us. But all those environmental influences that you mentioned, including your differences in diet and your lifestyle, that is all continuous interaction throughout your life. So there's a conditional interaction between your genes, the microbes, and the world that happens from the time you're born to the time that you die. And those conditional interactions determine who you are. Yeah.

That you who you are is the result of everything. And, unfortunately, genomic medicine, it has some very powerful, applications, particularly in in some cancer medicine, things like that, and rare diseases. But in fact, for most people, it's the environment carries much more power in term determining your future and your future diseases than in many cases, your actual genome itself. So If

Dr. Mark Hyman
your genes are not your destiny, they may predispose you to something, but it's the expression of those genes that's based on what washes over them throughout the course of your life.

Dr. Jeremy Nicholson
And and we've got different sort of genomic potentials as well. So there are some people refer to them as Churchill genes. I mean, Winston Churchill got a Nobel Prize, was prime minister twice, and he drank and smoked heavily every day of his life until he's 90. And so we we think about the Churchill genes. You know, we'd all like to be able to do that.

Right, and he actually managed to tolerate that. So there are some people that have very resilient genomes, it doesn't matter what you do, they still live for a long time. There are other people who have inborn areas of metabolism, they tend to die young and there's not much you can do about it, and then there's the rest of us where it's your genes and your environment that determine what happens to you. And precision medicine is by trying to capture the gestalt of that, the whole the totality of that in order to make some judgments about you as an individual on how best to treat you going forward. Treatment isn't just treating diseases.

It's also preventive medicine. Right? So it's it's modifying your lifestyle so that you minimize the chances of getting disease in the future.

Dr. Mark Hyman
So really this is a a whole new way of thinking about health and disease based on, complexity and based on multiple variables that influence how your genes are expressed into the current health state that you are, and it's dynamic all the time and it's changing. It's changing based on everything you do, what you eat, how you move, what you think, your microbiome Mhmm. You know, environmental exposures, what we call the exposome, what you're exposed to throughout your life. Mhmm. And that, it seems like is responsible for 90 to 95% of all chronic diseases, not your genome.

Dr. Jeremy Nicholson
Correct.

Dr. Mark Hyman
And and yet, we've never really been able to look deeply into that until recently. And, you know, I I sort of when I started digging into all this, I was like, wow. There's, like, 37,000,000,000,000 per 1,000,000,000,000 chemical reactions every second in the body. And I don't know who counted them, but it's taken a while. But it's a lot of chemical reactions.

We have a 100,000 terabytes of data in our microbiome alone. And and, and how does, you know, one doctor or one, you know, practitioner ever come to understand how all those things relate to each other, how they connect to each other, what what to do about them, how to navigate that in a in a in a patient who's sitting in front of you. It's not something we learn all about in medical school. And so this whole field of phenomic medicine is actually encompassing all the omics, right, your genes, your metabolome, your microbiome, your transcriptome, your proteome, all the omics, right, and there's probably more.

Dr. Jeremy Nicholson
Yeah. I found a 257 things ending in the word omic.

Dr. Mark Hyman
Yeah. Your immune, right? And and all of those things are things that we have profound influence over, and there are things that get deranged or or dysregulated by by how we live and what we do. So it's a very empowering message, but it's also, like, daunting. How does how does someone think of, like, oh, gosh, you know, I go to my doctor and I get my 20 lab tests or 3 lab tests and my chem screen, my blood count, my cholesterol, checks my blood pressure, you know, my weight, and I does a cursory exam.

How is that even coming close to figuring out what's going on? And it's not. It the truth is it's not. We're looking for pathology. We're looking for end stages of problems that are picked up by these tests.

And what you're now able to do and what you've done in your, in your, phenom center in Australia is to help us to kind of map the landscape. It's almost like a new frontier of how we should be looking at human biology, not through the lens of diseases, but by the lens of the phenome. So can you kinda talk about what is the human phenome, and how how can we use it to guide a more personalized approach to health care? It's not a

Dr. Jeremy Nicholson
one size fits all issue. Sure. So as you point out, there's a lot of things you can measure, literally millions of variables in that the human body that are measurable now. In the real world, which is

Dr. Mark Hyman
I know that quote. And not everything that can be measured matters. Not everything that's measured measured matters.

Dr. Jeremy Nicholson
That's why Einstein said that.

Dr. Mark Hyman
Einstein. Right. So so I think it's, like, what do we measure that matters. Right?

Dr. Jeremy Nicholson
Yeah. Exactly. So, so it's it's a it's a multistep process. The first thing is we have extraordinary technologies now that expand almost every day. So the number of things that we can measure about the body, the number of ways we can describe the body in, let's call it, a multivariate, biology space.

So there is a mathematical part of reducing this dataset into something that is more manageable. But all of the different technologies are not really practical for the clinic, or, you know, a a a doctor or, even a major hospital. Those are just we're in the process of discovery at the moment, and discovery leads to ultimately to translation, which is what we want. So our Phenome Centre, which is a collection of very expensive, instrumentation designed to discover new human biology through chemistry, but also do it at high throughput so we can look at 1,000 100 of 1000 of people if necessary, but we also are interested in once we've discovered out of the million things we measure, the 200 or things or maybe even 50 things that are new that are informative about the biology that you of the the disease state that you either wanna prevent or you want to treat, then to make new translational technologies from that, which can be deployed in a a clinic or even potentially in the future in a doctor's surgery. So you take this vast space of human biology, describe my chemistry.

You find statistically what the most important things are, and then you create a new mini technology. So it could be a lab on the chip sort of technology. It could be some even a those as simple as even a dipstick, which measures a new metabolite, or we use a lot of spectroscopic tools, miniature spectrometers, which you could which cost a fraction of the discovery technologies, which you could deploy in a clinic.

Dr. Mark Hyman
Remind me of the, like, coloring books I have in the kid where you had to connect the dots and there's all these random dots on the page. I had to link them up together and these, oh, this looks like a duck. Yeah. This looks like a boat. Right?

And that's what you're doing. You're seeing all these random, literally, dots of biological data Yeah. And you're connecting them to see where they're related and how they influence disease and what to do about them.

Dr. Jeremy Nicholson
So that that so that's absolutely true. Right? But, your analogy is slightly simplistic in the in the duck is covered in a lot of other dots which are irrelevant. Right. But you don't know that when you're measuring them.

So so the the the the the art and the science and the mathematics is designed to extract the shape of the duck from the background of the noise of

Dr. Mark Hyman
of the dots. Where AI and machine learning

Dr. Jeremy Nicholson
comes from. Isn't well, we used to we did we've been doing this for sort of, like, I've been doing this for 40 years now. I didn't call it AI then. We call it AI now, but the multivariate statistics. AI is is a is a way of doing multivariate statistics.

But, so that is AI is not new.

Dr. Mark Hyman
Yeah.

Dr. Jeremy Nicholson
It's just we can do it better now.

Dr. Mark Hyman
Yeah. We can do it better. This is, you know, kind of a staggering when you think about the complexity. Right? And you think about the amount of data we have and, you know, we we now actually can measure a human genome pretty affordably.

We can measure the microbiome to, you know, test. You can get through various functional medicine and other doctors. I I just did a panel the other day. It was a metabolomic panel. It was a commercial lab that just sent me out a kit to draw my metabolome.

And and these things are starting to kinda hit the consumer health market. They're quite not in the doctor's office yet, although some genetic testing is. But I I find that that, that if we if we really look at disease, what what we're we're actually doing in in medicine today is is waiting till people have something serious or something that's measurable on a pathological basis. And we all we know, and this is from my original textbook in medicine called Robbins and Cochran, the Pathologic Base of Diseases. It's every every pathological change.

I mean, anything you see on a microscope or, or on an imaging scan is always preceded by some biochemical change. And what you're looking for is these early biochemical signals that precede disease and the patterns in that data that can tell you about that particular person's unique thing. And I believe it's gonna blow up our whole notions of disease because through the lens of systems biology and systems medicine, which is essentially what you're doing, it's what we try to do at the Institute For Functional Medicine and with functional medicine is apply this, take learnings from the work that you're doing and others to try to kind of say, okay, where where can we kind of try to accelerate the adoption without hurting anybody of this medicine to help understand these patterns in the data? And so I I wondered if you kind of talk about, how we begin to kind of sift through all that because, you know, when I when I when I look at a patient, I do a lot more in detailed analysis of of lab testing, but it's still just on the surface. Right?

And and I I'm just so excited for the moment when we're able to actually do these tests at scale, see these patterns that it happening for you and realize that we we're all different in our manifestation. So 2 people with depression or 2 people with Alzheimer's or 2 people with autism or 2 people with, autoimmune disease or whatever, diabetes are not the same. And we're treating them all the same today in medicine. This is where precision medicine comes in. So, how how does how does the the role of of doing some of these diagnostics, like the metabolome, the microbiome?

How how do we start to think about learning from this? And what are you learning in your research that that that that can actually start to make sense for people clinically?

Dr. Jeremy Nicholson
Yeah. Well, let's let's just start the going on a little bit more about precision medicine aspect first. I mean, the idea of one size fits all comes very much from the pharmaceutical industry. Yeah. Right?

The blockbuster drug. So, and this is not that long ago. You know, 25, 30 years ago, drug companies were trying to discover that drug which they could treat, you know, everybody with ulcers, everybody with arthritis, whatever, and find that drug which is a, you know, a $10,000,000,000 a year thing, and we know that's difficult to do. And, actually, all the easy ones have been found. So the pharmaceutical industry is in a bit of a they're in a hard place now because it's looking still for blockbuster drugs, and they they don't really exist so much anymore.

And in fact, precision medicine is the opposite of that. We're trying to divide people down, and, actually, ultimately, we're all individuals. There is an exact treatment for you, right, irrespective of what disease you've got because of your background physiology, which is made throughout the whole of created throughout your life. And the pharmaceutical industry is not interested in that because it cannot make vast amounts of money out of one chemical product. Right.

Right. But on the other hand, we still have this enormous task of measuring all of the things that we need need to measure. And one of the reasons I spend a lot more time, working on metabolism is that the metabolic phenotype, is actually incredibly useful because it captures a lot of the gene environment interactions that you need to know Yeah. About precision nutrition, about health prevention, disease prevention, and about stratifying, patients when they actually do do get a disease. So a a phenome is the expressed output of all the gene environment interactions in terms of things you can physically measure.

So your height and your weight, you know, phenomic properties, but so is your blood cholesterol, so is your urinary creatinine, and, literally a million other things as well. All of those things

Dr. Mark Hyman
Probably a 1000000000.

Dr. Jeremy Nicholson
Whatever it is, it's a bigger number than you thought it was.

Dr. Mark Hyman
Maybe a trillion thing.

Dr. Jeremy Nicholson
Yeah. But you the the important thing is you don't have to measure a 1,000,000,000 things or a 1,000,000 things because there's a lot of redundancy in the data. So Yeah. There is there is there are things that are what one metabolite might capture might capture the information that you need about a whole pathway or 1 or 2 metabolites. It's becomes the ratios of those things that tell you about differential activities.

So what we call now artificial intelligence or pattern recognition methods are actually designed to extract those principal features in the complex dataset, multivariate dataset, and say, well, of all the things that you've measured, there's it's these 15 or 20 that describe pretty much all the biology, difference between a normal person and a person with a particular sort of disease or all the different subtypes of a particular disease.

Dr. Mark Hyman
And it might not be things we're measuring at all clinically now. Right?

Dr. Jeremy Nicholson
Mostly you wouldn't. No.

Dr. Mark Hyman
Right. Like David Furman at Thousand Immune Project, which basically got a thousand people look at their cytokines and their immune he calls it the immunome. Yeah. And found that there were 4 cytokines, 4 markers that I never heard of that are, you know, probably buried in my immunology textbook or maybe discovered after I graduated medical school.

Dr. Jeremy Nicholson
Yeah. Yeah.

Dr. Mark Hyman
And that they were highly correlated with, advanced aging and chronic disease. And and those things now can be available as a clinical blood test, which you can use to track over time. You know, I was I was talking to, Richard Isaacson last night who you might know is Alzheimer's researchers doing a lot of innovative work around a systems biology approach to Alzheimer's. He said, they've come up with this new, new diagnostics, all the p, I don't know, something, something, p Tau, some number, I don't know what it was. But he said it's like a biomarker that actually found changes as you change people's lifestyle habits that affect their brain.

So you can see the increasing or worsening of Alzheimer's or the improvement in Alzheimer's through this biomarker, but you might have looked at a 1,000 things before you end up with this one thing. So that's what you're talking about is signal from noise. How do you detect the signal from the noise?

Dr. Jeremy Nicholson
Absolutely so. So, and the answer is statistics and a lot a very large n. Right? So you have to be able to sample.

Dr. Mark Hyman
N would be a lot of people.

Dr. Jeremy Nicholson
N is the number of people. Yeah. And in order to make these sorts of discoveries, you really need to be looking at thousands and thousands of people to build the the basic mathematical models. That's for most disease. I mean, if it's a rare disease, I mean, or an inborn area of metabolism where the number of people might be very, very small, but the effect is very, very large, so you don't necessarily need a big end to discover what is wrong.

Yeah. But for most diseases, things that kill most of us, then you do need you need literally thousands of people to make those sorts of discovery using, the appropriate sort of technology. And what's the appropriate technology? Well, it's one that gives you the right answer. And, unfortunately, there's quite a lot of different technologies, so you have to look at thousands of people with a number of different technologies to do the the the sort of discovery that's, that's necessary to be able to refine out of that the small number of markers that you could then productize, if you like.

Because, ultimately, it's a commercial angle on all of these things. Anything that's gonna be successful clinically and in the in the big world will have a will have a commercial angle to it because somebody's gotta validate it, and it's gotta be made and manufactured. So tolerance, etcetera, etcetera. So when we think about precision medicine and the sort of discovery biology we need to do, we need to think about all the possible problems that are going to come up in order to make that work in the real world. So you have to take a very long view into the into the future about what's gonna stop.

So I've got this great new marker. Is it gonna be practical to measure it in the real world? Is it gonna cost $15,000 per time you analyze? Right. And if it is, it's probably not gonna work generally.

If it's gonna cost $5, then you're then you're talking business. So we're looking for that magic bit that's not only good science, good biology, and good medicine, but it's also cost effective.

Dr. Mark Hyman
Yeah. It's true. I mean, and I think I think we're well on the way to doing that. It's it's amazing how much medicine has changed us in the last even decade. You know?

Sure. I mean, when I graduated medical school, we hadn't even decoded the human genome.

Dr. Jeremy Nicholson
Yep.

Dr. Mark Hyman
You know? Sure. Right? And and now we we not only can decode the human genome, but we can do large throughput analysis of, you know, just tens of thousands of molecules that are in our body. And, you know, like, just people don't even understand that that probably half or a third of the metabolites in your blood are from your microbiome.

Right? So it's like, wait a minute. You're gonna check your poop by checking your blood and it's like, wow, this is such a different world. And and it allows us to sort of look at this continuum phenomenon. You know, the, 2009 White House, I'm sorry.

The 2009, White White Hawk 2 core cohort study was published in The Lancet looked at a whole series of factors that we could look at that would precede disease. So what were the sort of predictive things that you can actually measure that show what's happening? And one of the things that they found was that high insulin levels precede, high glucose by as much as 13 years. So doctors just check glucose. And this is something that's sort of an easier thing to understand for people and they check it.

It's like, okay, well, your blood sugar seems all right. I must, you must be all right. You don't have diabetes, fine. But the insulin levels go up before glucose. And I've seen this for decades because I measure insulin, but it's less than 1% of doctors that measure insulin.

Right? And but it's actually probably one of the most important biomarkers. Now there's a new and you mentioned these ratios is a new test. It's been now developed that looks at insulin and something called c peptide, which is the sort of a precursor molecule for insulin and the ratio of insulin and c peptide through mass spectrometry, which is a very, very accurate test. And that test is is highly predictive of someone's degree of insulin resistance, which is one of the biggest drivers of all chronic disease.

So this is something, you know, one of the tests that could be like more like 5 or $10

Dr. Jeremy Nicholson
Yep.

Dr. Mark Hyman
That tells you a lot that kind of the other data might not be as important. Can you kinda talk more about this whole idea and what you're finding around this continuum concept of disease from from optimal health to presymptomatic disease to symptomatic to full blown disease to death?

Dr. Jeremy Nicholson
Yeah. So the the idea is that we all it can be considered to be existed.

Dr. Mark Hyman
Wait. So the reason I'm asking you is because I think phenomic medicine is the first time we've been able to think about actually looking at that continuum because doctors don't do that. They just wait till you got something and then they treat you.

Dr. Jeremy Nicholson
Well, and and doctors are very highly siloed, you know, gastroenterologists, nephrologists, neurologists, and stuff like that.

Dr. Mark Hyman
But one

Dr. Jeremy Nicholson
of that's one of the things that just systems biology really teaches you is that all those things are connected together, and it's very difficult to look at a patient just from one medical angle. There'll be other things that are connected. You know, the organ systems in the body don't work in isolation. They work together as part of the system. The immune system connects everything, together.

So looking at the a a multisystems is, is is very, important. But so from our point of view, we're thinking about we tend to think in the way we conceptualize it is thinking of people occupying a metabolic space or a phenomixed space. It doesn't just have to be metabolites, but I tend to measure metabolites a lot, so, you know, we think in metabolic spaces. So what what I mean by that is so if you've got, say, let's say, 3 parameters from your blood, you have glucose, creatinine, and urea, You'd have a three-dimensional space. That'd be your, you know, urea, creatinine, glucose space.

But, of course, there's thousands and thousands of things you can measure, so you can have 1,000 dimensional spaces. And you occupy if I took a blood sample from you now, you would occupy a particular plate position in space, and so would I. And it wouldn't be the same space. We would be separated by some hyperspace difference.

Dr. Mark Hyman
And then tomorrow morning, it might be different.

Dr. Jeremy Nicholson
Oh, yes. We'll what we'll do is we will be hovering around in our own within our own metabolic sphere, if you like, except the sphere isn't in 3 dimensions instead of 10,000 dimensions. So think about us oscillating that during the day, and you are oscillating in your space. And your space and my space, if we're both healthy, will be fairly similar. As soon as we get a disease, we're gonna move in the space because the different parameters are gonna change.

So the sort of advanced mathematical tools, including AI, are about looking at where we are in that space, the particular markers for us that make us unique, and also how that changes in time. And that's what that is essentially what what we do. So we build spaces in m dimensions, large number of dimensions, and we look about how how a disease impacts on that occupancy space, that position in space, and we look at a disease as a process of a movement, a trajectory through space. So you start in one space, let's call it your healthy space, which you're hovering around a bit in, you get some disease, and you move significantly in space. And when you recover, you should go back to where you started.

Now this is quite interesting conceptually, and we've learned interestingly, we've learned a lot from studying COVID over the last couple of years. You know, COVID has been the biggest hit in human biology that we've had since, you know, since flu in 1918 as a giant, you know, synchronised hit in human biology. So that produces population level, effects that we can see. And one of the things that we observe, from a a metabolic mapping point of view is when people get COVID nineteen, we've we've now got a lot of data on this, is they move in metabolic space. They actually move in lots of different dimensions.

COVID affects a lot of organs, makes it really interesting for people doing metabolism, right, which is nonobvious for that movement.

Dr. Mark Hyman
Not not not for people who have it.

Dr. Jeremy Nicholson
No. It's well, I've had it a couple of times. It's no fun. I can tell you. Right.

And then the idea of of mapping that movement into the abnormal space, which in a highly inflammatory space, and then mapping the movement as you recover back. Now as as we know with COVID, particularly interesting example is because a lot of people don't recover. They end up with something called long COVID

Dr. Mark Hyman
Yeah.

Dr. Jeremy Nicholson
Or, you know, post acute COVID 19 syndrome, where they're actually physiologically abnormal. And then we start thinking about the ways of of of measuring that. We've done a lot of work on this. But we also start thinking about it from think from the point of view of reinfection because there's been lots of reinfections. People have it 3, 4, 5 times.

And the more times you have it, the more times you more likely are to get long COVID.

Dr. Mark Hyman
It's

Dr. Jeremy Nicholson
cumulative. So what we think about this now, and I think this is relevant for all of human diseases, let's say all most, I don't have I haven't done all human diseases, but let's say a a large number of human diseases, is they can be considered as miniature. Each time you get a disease, and it can be different diseases, you have a little journey in metabolic space from your normal space into abnormal space and then back again. The important thing is when you come back to your normal space, you don't come to it back to the exact of the space you started from. Yeah.

You shift slightly. And the effect of that over your lifetime is aging. So you're metabolically aging through a series of trajectories. And you the important thing is there are now ohmic measurements that you can make that map that space, and there's mathematics for reducing it. So we can start thinking about localized journeys due to an individual episode of disease and also potentially lifetime journeys as you age and be become sort of more biologically incompetent as you get older, which is is the, you know, is the aging process.

I mean, aging is it's it's not a disease. Aging is natural. It's, and death is the thing, that we all worry about, but it's premature death is what we're trying to avoid, right, through our technology. Precision medicine is effective, like, trying to avoid premature death averaged over the whole of your lifetime.

Dr. Mark Hyman
But you you brought up something really interesting. You said aging is not a disease. Right? Mhmm. But, you know, neither is having a high insulin, but it it definitely drives disease.

So where where where on that continuum do you sort of name the disease? And we had this arbitrary cut offs. If your blood sugar is 126, you have diabetes. If it's 125 or 24, you don't. Well, we know just that's ridiculous.

Right? So

Dr. Jeremy Nicholson
It's also population specific. I mean, what we're genetically, you know, what's true of Japanese isn't true of

Dr. Mark Hyman
For sure. For sure. For sure. So we have like this instead of arbitrary cutoffs where we say, you now have entered into a disease. But this phenomenon, this continuum of dysfunction and aging, for example, is is that there's there's breakdowns as normal physiological processes that don't manifest as a disease, but that make you get biologically older.

So we now know there are interventions that you can do to change that trajectory. So in a way, there are a lot of people talking about aging as a disease and treating it as a disease and understanding the underlying mechanisms of they call the hallmarks of aging, for example, the things that happen that are in common, with people as they age, like mitochondrial dysfunction or inflammation or change the microbiome or, our epigenetics or telomeres or zombie cells. These are things that we don't really typically measure in traditional medicine, but we can now. We can start to look at these things and see, okay, well, if I'm doing these 5 lifestyle things or taking this supplement or this drug, I can reverse my biological agent. I and I just did this.

It was so fascinating to me and, you know, I I still kinda worry about the validity of some of the tests and the reproducibility, but I did the, this lab called True Diagnostic where they do biological DNA methylation testing so they can look at your biological age. And and I did it 2 years ago, and and then I I was, you know, 43. M and M was 62 at the time. I just did it and I'm gonna turn 65 this year in a few months and I'm 39. And I did a number of things on purpose to see if I could move that.

Right? So I changed what I ate. I changed my supplement regimen. I added rapamycin, I, which I don't recommend everybody take. I'm a Guinea pig for myself.

I tried various technologies like plasmapheresis to clean my blood. I did a number of different therapies to see if I could move it and it moved and it wasn't, I wouldn't say, you know, having a biological age of 43 at 62 was bad. It wasn't a disease. Damn good. Right?

But what was I more on the continuum towards disease and breakdown at 43 biologically than I am at 40 39? I think so. Right? And so that's fascinating to me. It's like I'm not treat I wasn't treating a disease by doing these therapies.

I was trying to optimize, this status of my phenome essentially. Right? And that's that's what I think is super exciting is like is understanding this concept of the exposome. So maybe you can just take a few minutes and help people understand how much control they have over what happens to them in their life, through their health and understanding through the lens of the exposome and how that interacts with our genome and our microbiome. And you talk a lot about that.

Dr. Jeremy Nicholson
Yeah. You well, let's start with microbiome, which is is probably the most complicated part of it. So microbiome develops from the time that you're born. You are pretty much a, you know, aseptic before you're born. That's not absolutely true.

We now know. There are bugs that live inside you even when you're in utero, but you get a lot as soon as you're out out in the big, wide world. And that changes very rapidly over the 1st 6 months of life. The microbiome fully develops. It doesn't become like an adult microbiome till about 3.

It takes about 3 years

Dr. Mark Hyman
Wow.

Dr. Jeremy Nicholson
To mature even the microbes in in in you. And it's that early microbiological development that tunes your immune system. So your immunology is set up from the time, the first year or 2 of life. And in fact, when it comes to understanding long term chronic disease, a lot of the stuff that we've gotta fix is in those 1st 2 or 3 years. If those are bad years, then you're never gonna be able to fix it.

Right? So I I don't think there's that appreciation of the importance, of having a healthy, very young childhood, with the right sort of the minimizing very adverse, immunological, microbiological exposures. So there's all there's all of that, which is all part of your development, but we it's inevitable that we get infections in, in our early life. You can't can't avoid it. And that's part of building up your long term immunity and part of building up your long term, metabolism.

And all of these developmental processes have, metabolic signatures that go with them. And in fact, they turn out to be some of the easiest things. We talked at the beginning about Yeah. About there's so many things you can measure. But in fact, we would say that, of all the things you can measure, metabolic profile is probably the easiest.

You can get urine samples. You can get blood samples very, very easily. Those are easy samples to get is what clinicians look at all the time. So a lot of our technology is geared to getting the diagnostic and prognostic features out of things that are readily clinically available. And if not noninvasive, they're minimally

Dr. Mark Hyman
Yeah.

Dr. Jeremy Nicholson
Invasive. So, again, part of the science is mapping those sorts of changes in metabolism, in urine and plasma, peripheral fluids, if you if you like, back to much deeper things that are happening in the microbiome, your immune system, and actually also its organ specific, physiology and pathology, which develops over years.

Dr. Mark Hyman
And and it's really all the things that we do that affect this this interaction. Right? It's what we eat, it's exercise, it's our thoughts, it's sleep, it's environmental toxins, it's our microbiome, it's Yeah. I mean temperature, climate, weather, everything.

Dr. Jeremy Nicholson
And and when when I put my health care hat on, I mean, it's the simple things that are that are important. So we talk about all these incredibly expensive, complex technologies, but common sense is important too. So the the single best thing that you can do for your life is have a healthy diet and get a re do a reasonable amount of exercise. If you look at WHO statistics, now, you know, the biggest single killer of humans is cardiovascular disease statistically. 80% of premature death due to cardiovascular disease is preventable by healthy diet and exercise and not smoking.

Those are really 80% of the world's biggest killers.

Dr. Mark Hyman
And that's changing the exposome?

Dr. Jeremy Nicholson
Yeah. That it well, it is Like, yes, when you're diet is

Dr. Mark Hyman
is is That's right.

Dr. Jeremy Nicholson
Exactly. Right.

Dr. Mark Hyman
Yeah. Exactly. So you're basically talking about things we have in our control, which is a very empowering message. Yeah. And, you know, it's like not like we're waiting for some big gene discovery.

We're gonna get a gene, splicing editing technology that's gonna fix us and prevent us from being sick.

Dr. Jeremy Nicholson
That's a long, long way away from now and and may never be possible.

Dr. Mark Hyman
No. Because most of these conditions are polygenic. Right? It's like not just one gene like Down syndrome gene which could be affected or, you know, if you have Huntington's chorea or some rare condition like muscular dystrophy, great. You can edit your genes out.

But most of the stuff people are suffering from is just polygenic, it's complicated, and and it's influenced by our environment more than the genes. Absolutely. And what I'd love you to do sort of next is to help unpack the the story of long COVID because this this is something you focused on with your team, and it's an application of phenomic medicine that I think has real fruit to bear. I mean, I I'm a practicing physician. I can tell you I see a lot of cases of lung COVID.

It's not a rare problem. And there are lung COVID clinics in medical centers all across the country that I personally think do a lousy job of actually helping people because they don't understand the condition. They don't they try to medicate the symptoms, but without really understanding the the biology of it.

Dr. Jeremy Nicholson
Sure.

Dr. Mark Hyman
And I think we are seeing data emerge around the biology of what's happening, but it's not stuff often you can get within sort of an average doctor's visit or, you know, into looking at sort of anti muscarinic or autoimmune antibodies or various kinds of cytokines or various biomarkers that are elevated. And and with the phenomic medicine that you're doing, you can sort of take this almost novel condition and say, what does it look like? What are the things that go wrong? How do we start to learn about why this is happening and what we can do about it? So can you tell us a story of 1, how you're using long COVID as a a way of really applying phenomic medicine and what you're learning from it and what you're seeing the patterns are that you're finding and what are the the therapeutic sort of hopeful things that we see on the horizon as a result?

Dr. Jeremy Nicholson
Right. Again, a lot of stuff to ask.

Dr. Mark Hyman
I know. I ask long questions. I'm sorry. I wanna know everything. My mother always asked me, you know, not what I learned in school today, but what what questions did you ask?

So I've been in the question business for a long time.

Dr. Jeremy Nicholson
Fair enough. Fair enough. So if we just think about that, from from the point of view of my laboratory, it's there's peculiar bits of history here. I was previously, as you know, at Imperial College London. And about 5 years ago, we moved to Australia so we can basically expand on the phenomic medicine, you know, program and build a new phenome center really just to to look at that.

Our new laboratory new laboratory was was ex was opened in October 2019. If you think about that where we are in relation to COVID, it's like 3 months before.

Dr. Mark Hyman
Holy cow. It's good timing.

Dr. Jeremy Nicholson
So we we we sort of put this this $50,000,000 laboratory together, and then we're looking for things to do, and COVID appears. And when you when you build expensive laboratories, you do you need to do important things with them. So we had a whole list of things, you know, cardiovascular disease, diabetes, and all the other stuff. And then COVID just went to the top of the list. So, what our our approach to the problem was to work with international collaborators.

And, Australia, as you may recall, was was one of the last out the gate with COVID because it's quite geographically isolated. And, also, they had we we could from Australia, we could watch it happening across the world. Australia shut down fairly quickly if you could get in or out. And it it basically prevented the disease in for for a couple of years. It kept pretty much kept it out.

And Australia still has the lowest mortality for, for for COVID than any other country in the world. It's quite extraordinary. But so we we started to build all these databases based on stuff from Harvard and Cambridge and all the other stuff. And we were studying, of course, initially, the the the acute disease, but you have to understand long COVID, you have to understand the acute disease and what it can do first.

Dr. Mark Hyman
Yeah.

Dr. Jeremy Nicholson
And the first thing that comes out of it is it's incredibly heterogeneous. So COVID is is heterogeneous in its expression in human populations. There are some people that get incredibly let's just go back to the original Wuhan variant. You you got you got people who had incredibly severe respiratory disease that would put them, from catching the bug to going into intensive care in in a week or less than that. And once you're in intensive care, you're in deep trouble.

As you know, you don't that's a place to avoid. And there are other people exposed to the same, you know, genetic subtype of of the of the bug, that have almost no effects. So you have this diversity of severity, and that still persists

Dr. Mark Hyman
And symptoms.

Dr. Jeremy Nicholson
And symptoms. And the yeah. So you can have respiratory symptoms, but they weren't more important earlier on, in terms of severity. But there's neurological symptoms, there's GI symptoms, there's kidney. There's almost body.

Yeah. A blood clotting skin lesions in children, you know, Kawasaki like, disease, and a whole range of things. Almost everything that you could think of. And what it for me is, you know, anecdotally, we were you know, I was it's a lung disease. And, I was thinking, yeah, what what does urine teach you about lung diseases?

Not that necessarily that much. And then we looked at the the first samples we saw from COVID, which would have been probably March 2020. Yeah. It it lights up everything. I've never seen any yeah.

What? Urine or plasma. I've never seen anything that lights up the body like this. Thought, oh, well, you know, we got a big story here.

Dr. Mark Hyman
So what do what do you mean lights up the body?

Dr. Jeremy Nicholson
I mean, every pathway was was abnormal. Right? So there was there were things related to renal metabolism, kid you know, liver metabolism. There were changes in lipoproteins. It's just wherever you looked wherever you looked, there was there was alterations.

Whichever technology you used, there were things that were different. Now normally we think of trying to find the right technology to get the right diagnostic. But because this is such a spectacular systemic disease, it it it's and the in fact, you know, the essence of the disease is really its systemic involvement and its immunological, involvement. And so we ask the question is, like, if you've got all these sub effects in renal liver, microbiome is altered as well. Well, how do you know when you how do you know when it's over?

Right? It's not when you stop coughing. Of course, some people didn't stop coughing. Right? But, it's not when you stop coughing.

It's when your system biochemistry goes back to normal. So we got samples from people who'd had this this is now a year or 2 later. Yeah. And we start to look at people with long COVID, people who for instance, people who had never been hospitalized that had COVID once, and we had that in Australia. We had pretty good control of of that because of the way that, the protection was politically implemented in in in Australia.

So we we ended up with people who only have mild infection, never hospitalized. But if you look at their biochemistry, they were still abnormal 6 months or a year afterwards, so a whole series of things that were different.

Dr. Mark Hyman
And Just the people who had long COVID or everybody? No.

Dr. Jeremy Nicholson
No. These were. Everybody.

Dr. Mark Hyman
Anybody. Right. So Anybody and everybody after COVID.

Dr. Jeremy Nicholson
For some fee biochemical features, there are things that do not return to normal even after a year, even if you have no symptoms.

Dr. Mark Hyman
Wow.

Dr. Jeremy Nicholson
And that's we call that occult long COVID. Right? It's something that's hidden.

Dr. Mark Hyman
Are you saying this is a 100% of people that you tested?

Dr. Jeremy Nicholson
There I think there will be a 100% of people ultimately that have some long term biochemical effects of having one infection Wow. Of COVID even if they didn't weren't ill to start with. And, also, somewhat alarmingly, this appears to apply to children as well.

Dr. Mark Hyman
Oh, wow.

Dr. Jeremy Nicholson
Right? So, I mean, if you recall, Donald Trump famously said you don't have to worry about children. They hardly get it because, of course, he was an expert on many diseases. Right? But, and that's that's actually not that's not true.

There are physiological effects in children which are potentially quite serious. So what we had was a whole series of different metabolic and immunological biomarkers, which indicate different subsystem failures, different organ failure, different levels of severity, etcetera. So we can take a panel of those and monitor any anybody from their blood, actually, or their urine, but the blood is is easier in this respect for functional recovery for kidney, gut. You name it, whatever it is.

Dr. Mark Hyman
There are

Dr. Jeremy Nicholson
biomarkers which have to normalize.

Dr. Mark Hyman
And these aren't the normal things you get on your blood panel when you go to the doctor. Right? There are a

Dr. Jeremy Nicholson
few things, but only a tiny percentage of them. So these are a lot of these things are things that we discovered in our lab. Other people have discovered them and verified those as well. So what we're thinking about now is taking a blood sample. And from that metabolic panel, metabolic profile, we can say, well, look.

You you whatever your symptoms are like, it looks as though you've still got liver damage, or you've got new onset diabetes, which is a common, effect. And long COVID is not really a disease in its own right. It's a collection of other diseases that we already know that have been accelerated by having exposure to COVID. And the important thing about that is, and that's this is also a hopeful thing, is if we find those markers of your disease, of your subset of long COVID from a a a a blood, you know, analysis, we say, well, okay. You're a diabetic now.

You need to have the but there are medicines already available for that. So this occult long COVID where you don't necessarily have to have symptoms associated with it, in most cases, there are things that are you've you've both gone from predisease into a state, accelerated like COVID, or you've gone into a pre disease state. So, again, an accelerated

Dr. Mark Hyman
terrifying.

Dr. Jeremy Nicholson
Yeah. It is terrifying, but the important thing is you can do if if you know it, if you've been if you've been screened, you can do something about it because there are already lots of therapies. The things that we don't know so much about, although we've been we know we are learning about them from the biochemistry, things like the neurological effects. Right? So there's there's a lot of neurochemical effects.

Fog and Yeah. That well, which is also is a really common part of long COVID, right, chronic fatigue. And and in fact so here's another sort of bright side to the story, is that COVID is now shining a light on lots of diseases that we already know, but we we find new things about those diseases because COVID is accelerating them in particular people who didn't have them before. So if you look at chronic fatigue, there is a, you know, a set of sim chronic fatigue syndrome. There's a a syndrome which is usually without an etiological agent.

It's most people have agreed it's probably of viral origin, but we can be pretty much certain of that with COVID because people get this brain fog and other neurological problems, as a result of COVID. We know what that etiological agent was, and there are molecular biomarkers that go with that. So there's

Dr. Mark Hyman
with brain dysfunction.

Dr. Jeremy Nicholson
Well, one of the ones that we think is really interesting is the tryptophan kineurinine pathway, and that's got a lot in a lot of the tryptophan related metabolites and neurotransmitters. You know? There's a whole range of Serotonin. Serotonin. Yeah.

For instance. And that pathway is really, really disturbed. It also is one of the ones that stays disturbed for the longest after you've had your COVID infection. And so we're thinking about what this would you know, what this is about. And

Dr. Mark Hyman
And by the way, when you go to your doctor, you're not getting your tryptophan and urinate levels measured, but you're looking at these things with your deep phenomic analysis, and you're seeing that, oh, this seems to be a persistent pattern in these patients.

Dr. Jeremy Nicholson
But if you look at that pathway and things that are disordered in that pathway, there's actually loads of diseases, Huntington's disease, there's Parkinson's disease, there's, you know, HIV induced dementia. All of those things have got defects in the the tryptophan kynurenine pathway. It's a this is a really long list of disease. So that's actually something that we think is is probably important for medicine in general, that that irrespective of all the other stuff that

Dr. Mark Hyman
Yeah.

Dr. Jeremy Nicholson
Measuring that pathway is actually deeply insightful for a lot of diseases.

Dr. Mark Hyman
Well, because it's because it's it's the thing that responds and gets worse when there's inflammation Yeah. From any source

Dr. Jeremy Nicholson
Yeah.

Dr. Mark Hyman
Whether it's COVID or whether it's sugar or whatever.

Dr. Jeremy Nicholson
And that's because that pathway is very the the enzymology, if you like, is very immunologically controlled. So so for instance, things like TNF alpha, interferon gamma, etcetera, stimulate the indole dioxygenase enzymes, which convert IDO. Right. Yeah. Exactly.

The IDOs. Exactly. So the, the tryptophanokineurine transfer is very much modulated by that, you know, those those, immune factors.

Dr. Mark Hyman
Just to break that down a little bit for so we can because not everybody's a PhD in biochemistry here. The phenomenon you're talking about is inflammation interferes with a critical enzyme called IDO, just called IDO, that is involved in taking tryptophan from your diet, from, you know, turkey or whatever you're eating, and converting it into serotonin. And when there's inflammation, that process is affected and you end up creating molecular byproducts that are quite toxic to the brain like quinolineric acid that create inflammation in the brain and can cause any host of neuro inflammatory diseases which range from autism to Alzheimer's, from anxiety to OCD.

Dr. Jeremy Nicholson
Yeah.

Dr. Mark Hyman
All of which are brain inflammation conditions. So there's a final common mechanisms and pathways, but but variety of insults. Right? Because inflammation can come from your microbiome. It can come from COVID.

It can come from sugar in your diet. It can come from a million things. So I think I think this is such an important thing that you're bringing up, which is that there's a lot of stuff that we've never looked at that is where the problem is. You know, there's a there's a joke that I often tell when I'm giving a lecture, which is this guy's looking at on the street for his keys under this lamppost, and his friend comes by and says, what are you doing? He said, well, I'm looking for my keys.

He said, where'd you drop them? Well, I dropped them down the road. He says, why are you looking over here? He says, well, the light's better. So we're, we're used to looking where we can see the light, which is our typical chemistry and blood count and but it's actually not where the problem is.

And with phenomic medicine, we're actually, for the first time, be able to shine a light on a lot of other things that we didn't ever look at before in the history of medicine that can now help us predict what's going on.

Dr. Jeremy Nicholson
I mean, the the the thing you mentioned there, quinolinec acid, that's a really interesting metabolite. It's massively elevated when you you actually have the active COVID infection. So that's sort of the end it's sort of quite a few steps away from triptophan. Quinelic acid is used as a a striatal neurotoxin, an experimental one in rats. Really?

If you dose rats with quinolinec acid, you can make experimental Parkinson's. Yeah. Well, that's pretty worrying, isn't it?

Dr. Mark Hyman
Yeah. Right?

Dr. Jeremy Nicholson
So this is how, you know, one an infectious disease can lead to something totally different downstream as a complex interaction, which is immunological. It's also dietary related depending on and also potentially microbiome related because microbiome has a lot of activity in that pathway too.

Dr. Mark Hyman
Yeah. It's amazing. And when you're talking about all these overlapping diseases that seem to be separate, right, but actually have the same underlying common mechanisms, but just manifest differently in different people depending on their genetics and predispositions and how their body uniquely responds to it. So this is really what we're talking about around precision medicine.

Dr. Jeremy Nicholson
And, well, that is systems medicine to me. Systems medicine allows you to visualize the complexity of it so that you can be more efficient and precise in your interventions. Right. So that

Dr. Mark Hyman
It's great. It's amazing. And you you talk about this sort of patient journey phenotyping around COVID 19. Can you explain that as what you're talking about before of tracking what happens over time and if people progress to the Sure. More of a normal phenotype or

Dr. Jeremy Nicholson
Well, this is an on this is an ongoing job. It's a big job because you have to have to be statistically powered. So what we're trying to do is look at populations and the way that they respond to infections. COVID is one of them. So if you we have there's lots of epidemiological studies where samples have been collected for many, many years, framing them with the original one looking at heart disease.

There's a study in in Western Australia called the Bustleton study. It's a similar it's like bit like framing, where you're looking for, you know, heart disease and diabetes over a long period of time. And we've had access to the Bustleton from study, so we already had run thousands of people from Western Australia who were part of the normal population. So we're describing what normal Australian biology looks like. Right?

Dr. Mark Hyman
We got a lot of beer in

Dr. Jeremy Nicholson
the Yeah. Well, yeah, that is part of the metabolite in Australia. Beer metabolites? Yeah. Yeah.

Fosters. Yeah. But the and so when you're looking at so that's a reference point. So usually, you think about measuring taking these samples to try and create new biomarkers for future events by studying a population over many years, but we can also use it as a reference frame for the population biochemistry, but this is Australian biochemistry. So when somebody's had a journey due to COVID, they go out of that space, and we can measure whether they should where they should be within the population by by by mapping them biochemically through through time.

And in fact, we've just been given another $1,000,000 by the the state for extending the bustles in the study, and resampling people now after their last sample, which is probably 5 years ago, because almost all of the people have had COVID.

Dr. Mark Hyman
Right.

Dr. Jeremy Nicholson
So we can measure the before and after COVID status, and we can find all of those potential long COVID people that didn't maybe the occult long COVID. They don't even know they've got it, and we can make medical recommendations how to improve their health knowing that COVID has had certain knock on effects in different parts of their, their systemic metabolism. So we're this is very to me, this is very real. This is very translational. So we we're also mixing, for the first time, I think, ever, epidemiological studies with real clinical studies.

Yeah. Real time clinical studies where we're monitoring trajectories of people in and out of the normal population, the norm population being defined by an epidemiological, sample profile. And so that becomes and then to have that actionable so we can find people who have latent disease as a result of COVID or anything else for that matter, and then saying, right. Well, you need to go to the doctor and get this, this, and this tested and sorted out. That is very practical, part of translational So

Dr. Mark Hyman
what are what are you seeing with with the data you're learning? Because you're you're you're doing a phenotyping of long COVID where you're seeing these abnormalities that track across symptoms and explain how people feel, and there are actually biomarkers that you can use to track the trajectory of any treatment, whether you're not treating them or you're getting conventional approaches or other approaches. What what kind of things are emerging that help you think differently therapeutically about how to treat patients? Because it's not a single pathway that creates a single disease with a single drug.

Dr. Jeremy Nicholson
Mhmm.

Dr. Mark Hyman
Right? It's a very different you're talking about systems medicine.

Dr. Jeremy Nicholson
Yeah.

Dr. Mark Hyman
So how do you start to apply what you're learning to patients with long COVID? Because there's 1,000,000 and 1,000,000 and 1,000,000 anywhere from, you know, 6% to maybe up to 30% of people, and maybe you're saying a 100% of people have asymptomatic long COVID. You know? Wow. What do we start to do with that data?

Dr. Jeremy Nicholson
Let's start with what the statistics are. I'll be there are a lot of statistics around and a lot of studies now on on on long COVID. The the the I think the correct number is about 67 6 to 7% of people have some sort of symptomatic, long COVID, maybe at 2 years, even 3 years now. And if you've got it at 2 or 3 years, you're probably not gonna get rid of it. It's a it's become a chronic disease.

So that's that's the first thing is putting biochemistry around that that allows you to say, well, look. It does look as though you have long COVID based on this biochemical profile. Now that's actually quite important to people because a lot of doctors, as you know Dismissed though. Do not know, well, they say, yeah, well, you're feeling tired, you know, it's your age, and it's easy to dismiss, and that's what a lot of chronic fatigue patients have actually experienced over here, a very poor response to the medical community.

Dr. Mark Hyman
And that's what I had, chronic fatigue syndrome. I had to cure myself, and that's how I learned all this.

Dr. Jeremy Nicholson
It's it's it's miserable, isn't it?

Dr. Mark Hyman
Yeah. It's horrible. The worst thing you could possibly imagine. It's like you haven't slept for 3 days, but you just woke

Dr. Jeremy Nicholson
up. Well, I had I did I had a long COVID, as a result of getting COVID in the first wave. I was one of the first people in Australia to get it because I've gone to a conference in Italy in February 2020. Do you remember? That was one that was one of the first ones that that kicked off, and I came back so tired when I got back.

It must be jet lag. It was jet lag that didn't go for 3 weeks or 4 weeks. And 2 months later, I we with our own technology, we diagnosed that I actually had had had COVID because my biochemistry, 3 months after I'd had my episode, was still the same as active COVID patients. So we so this live the lived experience, right, gave me a little bit of insight into what what might be might might be going on. But I can tell you you know, I don't have to tell you, chronic fatigue is truly miserable.

Right? I'm as yeah. Fortunately, I'm I think I'm I'm largely through that, but it but it did leave me with diabetes. So thank you very much.

Dr. Mark Hyman
Type 2?

Dr. Jeremy Nicholson
Type 2 diabetes. I was left with I also have atherosclerosis now, which I didn't use to have. Really? And in fact, the cardiovascular side, that's one of the that's one of the

Dr. Mark Hyman
of your blood vessels. Yeah.

Dr. Jeremy Nicholson
Well, and there's very strong biomarkers for that, actually, which is, we're we're very interested in at the moment because we Like what? Well, the apolipoprotein b 100, apolipoprotein a 1 ratio. Yeah. So the for those that don't know, the b 100 is a is a transporter, lipoprotein, a supermolecular complex that actually helps cholesterol get into blood vessels.

Dr. Mark Hyman
This is ApoB. You're talking about

Dr. Jeremy Nicholson
It's ApoB. Yeah. Yeah. And so it's atherogenic. And the the a one does the opposite called Protective.

Right. So the ratio is actually very predictive of your atherosclerosis risk because it's part of the active transport process of cholesterol, but it's also it's an it's an important long term risk for myocardial infarction stroke.

Dr. Mark Hyman
So you're saying that ratio changes with COVID?

Dr. Jeremy Nicholson
It's dramatically changed during the active infection. Right? I mean, you can you can there's this work goes back, you know, 30 years on the the the relationships between Apolipoproteins, b 1, and, and and cardiovascular disease. You go from being a normal person to being an intermediate to high risk within about 3 days, right, of catching COVID. It really changes the it's dramatic.

Right? And that then persists for some time. Right? And that's one of the things we monitor in the long COVID people. Is there ABA 1 normal or or abnormal?

And some people well, of course, if you're as as you get older, your ABA one tends to, you know, get worse, and it it it, gets worse with, obesity and things like that as well, unsurprisingly. But COVID causes an acceleration of that enormously. And when we were looking at samples from the UK, and they the UK got it really, really bad. The Wuhan Yeah. I mean, they they had people dying on in the corridors and Yeah.

Hospitals and stuff. The people that 6 months after their episode, we still have people in ultra high risk of, cardiovascular disease as a result of their of their COVID exposure. So that's another thing. So that's something that's the infection impacts on long term cardiovascular health. But there's a way of monitoring that, and that's something we could do now.

Dr. Mark Hyman
You can monitor all this stuff and you see these changes. What about treating it? Are you finding any therapeutic applications of phenomic medicine? In other words, were you not just treat diabetes because you have it after COVID, but where you can actually say, gee, there's these, you know, these these auto antibodies, for example, that are forming against your nervous system tissue, which we now can measure. And in, for example, Europe, they're doing studies looking at plasmapheresis where they filter the blood, clean out all the antibodies and all the crap from your blood and put in new protein and and put back your cells, and they're finding significant improvement.

I've personally seen with my long COVID patients, it's one of the things that really helps a lot. So I'm wondering if the biochemical profiles with the right therapies could actually go back to a more normal pattern and not even the occult long COVID pattern you're talking about.

Dr. Jeremy Nicholson
Yeah. So, I mean, so all those things like plasmapheresis, etcetera, I mean, it's difficult. When you're talking about millions of people, that's not really very practical.

Dr. Mark Hyman
No. It's capable.

Dr. Jeremy Nicholson
No. Okay. So for your patients, they're lucky. Right? Yeah.

Yeah. And and we're lucky actually in the west that we can do something Yeah. About this in the developed world, but there's a lot of people that can't do anything about it. So what was so one of the things we're thinking about so let's just come out of the tryptophan pathway for a minute. Right?

There are drugs. You know? The, indomethacin is a good old drug, an IDO inhibitor. It it's sort of banned certainly banned in Australia because it causes problems along sort of renal insufficiency, renal papillary necrosis, and things like things like that. But there are obviously, once you start to find particular molecular targets that are abnormal, whether it's in COVID or long COVID, then you can think about drug therapy to selectively try and change change that.

But we are actually interested in sort of dietary intervention. So for instance, you know, that you you get a lot of the, you know, tryptophan, etcetera, from the diet. Is just restricting tryptophan isn't is not the solution because one of the one of the one of the, effects of long COVID is actually having low low tryptophan. Yeah. Right?

Anyway, part of that is because its its metabolism is accelerating.

Dr. Mark Hyman
Doing right. Right?

Dr. Jeremy Nicholson
So so just adding more tryptophan does not help, especially if it's being metabolized to quinolineric acid, which is poisonous.

Dr. Mark Hyman
And maybe b 6 could help because it activates that enzyme.

Dr. Jeremy Nicholson
Indeed so. So, again, thinking about alternative drugs, which we might use, but, also, we found that there are sort of natural inhibit there's several natural inhibitory you know, natural products in certain food stuffs in plants

Dr. Mark Hyman
that Biochemicals.

Dr. Jeremy Nicholson
Yeah. Biochemicals, exactly, that, that inhibit some of those enzymes in that pathway. And we we haven't done it yet. The in the next year, we will do some sort of nutritional intervention study where we're adding these phytochemicals or the original material. It turns out that the the plant sage has got high levels of these things, so sage might be a natural, if you like, cure, for long COVID, but don't quote me on that because we haven't proved it yet, but but but we're thinking about this in this holistic way that you you learn about the biochemistry and think about, well, can you fix it with a drug or can you fix it with a dietary

Dr. Mark Hyman
Lifestyle diet, the exposure.

Dr. Jeremy Nicholson
All of those. All of those.

Dr. Mark Hyman
Your microbiome. Who knows? All these things can be start to be therapeutic tools, and then you can track how they're doing across this continuum to disease.

Dr. Jeremy Nicholson
But the solution for you might not be the same as the solution for me. Exactly.

Dr. Mark Hyman
That's why you have to kinda map out each person's individual

Dr. Jeremy Nicholson
Exactly. Yeah.

Dr. Mark Hyman
Kind of biology, which is what phenomic medicine really is about. It's to me, it's it's what I think is one of the most exciting areas in medicine, which is the finally the understanding that the way we're looking at disease is so outdated based on individual diagnoses that are all treated the same by conventional medicine. And that these patterns in the data that you're seeing with deep genomic analysis, even within long COVID, for example, they're not it's not a uniform condition, and different people have different manifestations of it. And the treatments are gonna be different depending on what it is rather than just a one size fits all treatment. So that's kind of the promise here.

I I wonder, you know, how how do you see this kind of 1, 5, 10 years from now? Like, is this gonna be in the clinic? Are doctors gonna be doing this? Are we gonna be able to get deep phenomic analysis of us? Because and I cofounded a company called Function Health, which is essentially designed to get a deep genomic analysis of each individual and use, sort of medical intelligence and computing power to help make sense of it, like you're talking through math.

Right?

Dr. Jeremy Nicholson
Yeah.

Dr. Mark Hyman
And and and we're going to get, you know, regular blood work now. We're measuring APO a and APO b and all these things that we're talking about. We're we're also gonna be looking at your omics and metabolome and microbiome, your genome. We're gonna be looking at biosensor wearable data, your medical history, looking at all that information, in in order to help create a kind of predictive model of where you're headed and what you can do along that continuum and helpfully get to a 100 healthy years. But, you know, we're we're doing it outside the healthcare system because it's it's so hard to change things from the inside.

Right? And people want it. You know, they want it with their data. So so where do you see this sort of going and how do we start to adopt this? And and, you know, you're doing a lot of the hard grunt work in this in the lab over decades that they've gotten at this point, but how do we get to kinda where this is available to everybody?

Dr. Jeremy Nicholson
Yeah. So, I was previously the head of surgery and cancer at Imperial in a big clinical academic department, which was immense fun for 10 years. But I I became limited. So this this is not as bad as it sounds, limited by the National Health Service. So the National Health Service is a fantastic institution.

I am a big fan, right, because it does so much good to so many people for no money, right, personally. But it's also like a it's like the a Leviathan. It's difficult to shift its direction. Yeah. Right?

And I became quite frustrated, and that was one of the reasons I wanted to move to to Australia to build a new lab more connected with Asia.

Dr. Mark Hyman
Wasn't it better weather?

Dr. Jeremy Nicholson
The weather is truly extraordinary. So it's a 101 outside in Las Vegas today, and that's that's pretty common for about 3 months in West Australia. But, but, anyway, but, one of the things was to set up a a a a phenome sensor that actually was trying to address not just clinical problems. It's on a hospital campus when our lab is, but also the epidemiological type problems, but also, you know, diet, healthy nutrition as well. So we're thinking about, you know, humans in in the total environment.

And there's a way of and the the Australia doesn't have a a a national health service in the way that UK has. It has a lot of of linked hospital services, but it's federally funded, and it's very well funded from the point of view of medicine. So so one of the things that we wanted to do is have this more holistic approach that we thought would be easy to implement in Australia. But we've already got 2, I think, 2 translational diagnostics that have come out of the COVID nineteen work that aren't actually really related to COVID nineteen at all. So we've found a better way of measuring ABA 1 on a really small NMR spectrometer.

So a lot of the work we do is on these discovery spectrometers, which are $2,000,000 each. Well, we've now got it working on a $100,000 machine, which is still expensive, but the actual reagent cost is 0. So it's a it's it's radio technology, so it's reagent free technology. And, we've patented that, that, and we're now looking at translating these miniature NMR spectrometers to the clinic for general cardiovascular assessment. Right?

So that's a translational step. The other thing is that she's really fascinating and, actually a discovery from, from acute COVID is we found a load of really weird and wonderful metabolites initially in the urine, but we found them in plasma as well that are all cytosine derivatives. And when you look at them, if you're in medicinal chemistry, you go, you know, that looks like an antiviral drug or that looks like an anti cancer drug. We've now found a dozen of them. They're completely new to human biology, right, published just a couple of months ago.

And it turns out that they're part of an ancient immune system, the viparin, the virus inhibitory protein, mechanism, that creates antiviral drugs when you have a virus infection.

Dr. Mark Hyman
Your own body.

Dr. Jeremy Nicholson
And so the drug companies think they invented combinatorial chemistry. Actually, nature did it about 3000000 years ago. Right? So we discovered a whole new piece of biology, right, from COVID 19 urine patients, and that turns out to be relevant for all viral infectious diseases. There's now a urine test for active viral infection, which come patented again, which, comes from our work on COVID 19.

When I when I was in Imperial, I'm the head of, intensive care academy one day and said, you know, if you've got a test that could distinguish people of active viral infections versus bacterial infections, that would be really useful because at the moment, it take we're gonna do lots of different testing, kind of sometimes a day. We've got something now could do it in 2 minutes. That's right. Which but that that came out of the COVID research. Right?

Dr. Mark Hyman
So it's not gonna be one single thing, but you're gonna you know, I it it means to me imagining a world of future where we're gonna be able to do sort of lower cost or or very low cost. Like, your human genome was, I don't know, $1,000,000,000 to first decode. Now it's $300. Where we're gonna scale these things up to be able to do deep analysis on individuals at scale. And from those learnings, see the patterns in the data, see what sort of signal from noise, and be able to then develop diagnostics and therapeutics that help to kinda restore the body to optimal function and reverse that continuum from disease backwards towards wellness.

That's kinda what the promise is of this.

Dr. Jeremy Nicholson
That is the promise. Yeah. But I I think the important thing is it's gotta be everything you do diagnostically has got to be on a clinically relevant time scale. So with genomics, you know, if you do deep genome sequencing, I know it's got cheaper now, but it's it can't be done on a a the same day. No.

I know. If you think about the way that most doctors work, then they need then they send something down to the pathway, and it comes back, you know, soon, and they say, you know, crap means this and whatever it is. You need to have something that where there's a ton turnover of just a few hours in order to make it clinically relevant for the actionability. There's no point in being able to diagnose something 6 months later. No.

Right. Right. And so we're very that's our we're very committed to the translational technology that gives you rapid data because that's really impactful in in

Dr. Mark Hyman
And it it feel like we're just at the beginning of this frontier where where first is understanding the biology and then is figuring out how to apply a novel therapeutics, which aren't gonna be, I don't think, a single targeted pathway or mechanism, but really understanding a systems approach. You know, what what Laakozia and Barbasi call a multimodal approach to multi causal diseases. Right? Using multiple kinds of things, like, if that you have to treat all the things that are going on, not just one. So, I mean, I'm just so excited about this.

I I I'm so excited about the work that you've done at at your institute and the ability for us to learn from that and particularly around long COVID. I think, it's it's one of those things that's causing so much disability, so much disease, so much suffering. It's little scared me a bit when you said that everybody who's had COVID has some biochemical signature that there's still dysfunction going on.

Dr. Jeremy Nicholson
It's probably true of influenza and other diseases as well. It's just that we don't know it.

Dr. Mark Hyman
Yeah. It's quite amazing. Well, again, thank you so much, doctor Inclis, for your work. We're gonna keep following it. I hope everybody learned something.

I think, you know, this is a fairly high level discussion, but why I wanted to bring it to you all was because this is where medicine is going, and this is what you're all gonna be getting hopefully in the next 5 to 10 years more and more. And I think with the advent of machine learning and AI and technology and our ability to do deep analytics and phenomic analysis, we're gonna learn so much. And and this is gonna be today what seems like the dark ages in medicine, and we're gonna have the light shown upon us to understand these the deep biology of what we're actually now understanding is the true nature of disease, which is a systems problem. It's a network problem, and and we have to treat things that way. So thanks so much for being here at the Institute For Functional Medicine.

You came a long way from Australia, and I I saw you're coming. I'm like, I gotta have you on the podcast. So thank you so much for joining us in the doctor's pharmacy and, and for your work and contribution to the betterment of humankind.

Dr. Jeremy Nicholson
Thank you.

Dr. Mark Hyman
Thanks for listening today. If you love this podcast, please share it with your friends and family. Leave a comment on your own best practices on how you upgrade your health and subscribe wherever you get your podcasts. And follow me on all social media channels at doctor Mark Hyman, and we'll see you next time on the doctor's pharmacy. I'm always getting questions about my favorite books, podcasts, gadgets, supplements, recipes, and lots more.

And now you can have access to all of this information by signing up for my free Mark's Picks newsletter at doctor hyman.comforward/marxpicks. I promise I'll only email you once a week on Fridays, and I'll never share your email address or send you anything else besides my recommendations. These are the things that helped me on my health journey, and I hope they'll help you too. Again, that's doctor hyman.comforward/marxpix. Thank you again, and we'll see you next time on The Doctor's Pharmacy.

This podcast is separate from my clinical practice at the Ultra Wellness Center and my work at Cleveland Clinic and Function Health where I'm the chief medical officer. This podcast represents my opinions and my guest opinions, and neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services.

Now, if you're looking for your help in other professional advice or services. Now, if you're looking for your help in your journey, seek out a qualified medical practitioner. You can come see us at the Ultra Wellness Center in Lenox, Massachusetts. Just go to ultra wellness center dot com. If you're looking for a functional medicine practitioner near you, you can visit ifm.org, the search find a practitioner database.

It's important that you have someone in your corner who is trained, who's a licensed health care practitioner, and can help you make changes especially when it comes to your health. Keeping this podcast free is part of my mission to bring practical ways of improving health the general public. In keeping with that theme, I'd like to express gratitude to the sponsors that made today's podcast possible.