Most people are by now familiar with the term genome — it's essentially a blueprint each person is born with. You might think of the genome as the complete instruction manual for building and maintaining a human being. Your genome is what dictates everything from your physical traits like height or hair to how your cells repair themselves, and much more.
The exposome is the dynamic, lifelong ledger of every non-genetic exposure a person encounters. It includes thinks like air pollution and pesticides, dietary choices, lifestyle, and chronic stress.
Growing research is beginning to better understand this "other half" of the health equation, and working to map how the outside world might be altering our inner biology and ultimately our health and susceptibility to diseases.
One such group of researchers is at Brain Chemistry Labs in Jackson, Wyoming. It’s led by ethnobotanist Dr. Paul Cox. Their mission is, in part, to discover new cures from plants, and just better understand the world in which we live and how it connects to our health. Their team includes world leaders in disciplines including neurology, physiology, epidemiology, oceanography, microbiology, and even physics.
We chat with Dr. Cox to learn more about this emerging notion of ‘the exposome’.
Guest:
Dr. Paul Cox, Executive Director of the Brain Chemistry Labs in Jackson, Wyoming
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Transcript created with Copilot. Please forgive any spelling errors or mistranslations.
Transcript
Mike Kiniry
This is Gulf Coast Life. I'm Mike Kiniry. Thanks for joining us. Most people are by now familiar with the term genome. It's essentially a blueprint each person is born with. You might think of the genome as the complete instruction manual for building and maintaining a human being. Your genome is what dictates everything from your physical traits, like height or hair, or how your cells repair themselves, and a whole lot more, I'm sure. The exposome is the dynamic, lifelong ledger of every non-genetic exposure a person encounters. Think air pollution, pesticides, dietary choices, lifestyle, chronic stress. Growing research is beginning to better understand this other half of the health equation and working to map how the outside world might be altering our inner biology and ultimately our health and susceptibility to disease. One such group of researchers is at the Brain Chemistry Labs in Jackson, Wyoming. It's led by Dr. Paul Cox. He's an ethnobotanist. Their mission is in part to discover new cures from plants, but also just to better understand the world in which we live and how it connects to our health. Their team includes world leaders in disciplines ranging from neurology, physiology, epidemiology, oceanography, microbiology, and even physics. I'm sure there's more on that list as well. Dr. Cox joins me today to help us learn more about this notion of the exposome. Dr. Cox, welcome back to Gulf Coast Life.
Dr. Paul Cox
It's a pleasure to be with you, Mike. Thank you.
Mike Kiniry
I gave a sort of top-level explanation of what you all do at the Brain Chemistry Labs and you being an ethnobotanist, but can you give us just a bit more explanation of the scope of the research that you all are doing?
Dr. Paul Cox
We're very focused on neurological diseases, particularly ones that progress and get consistently worse. Our major focus is ALS, Alzheimer's, and now Parkinson's disease. We also have some deep interest, and we're making real strides on studying glioblastoma. We felt for these diseases having a international and interdisciplinary focus is the best way to move forward.
Mike Kiniry
You guys are a non-profit. Is that typical for a lab such as yours if you're not attached to a university or something?
Dr. Paul Cox
Yeah, we get offers from VC companies. In case of people want to buy us, I have to say, no, we're a not-for-profit. And when people see our patent estate, which is around 60, 65 patents, They said, why didn't you start a biotech company? The answer is because we're interested in patients, not profits. The reason we patent our findings is that pharmaceutical firms require that as sort of a cost of entry to do advanced studies so they can get a return on their investment. But being a not-for-profit organization, particularly in a remote part of Wyoming in Jackson Hole, allows us to think different thoughts, take deep dives, not worry about sunk costs. Our sole concern is finding ways to improve patient outcomes for these terrible diseases.
Mike Kiniry
How did I do with the intro when it comes to our genome as compared to our exposome?
Dr. Paul Cox
I really wanted to write that down. That sounds like a good introduction to a graduate biology chapter on this. You did awesome. You get an A-plus, Mike.
Mike Kiniry
So I've been hearing a lot of stories about gut health, and I've been hearing them talk about the various kinds of things that not only you eat, but maybe you're exposed to. And that reminded me of the last time you were on the show to talk about your research in Guam with the cycads and the cyanobacteria stuff. And at the end of that, you just mentioned kind of in passing this idea of exposome. And so I did a bit of Googling. And so I thought this would be a great time to get you back on the show. So, talk about or, define exposome and how emergent this idea is in the scientific understanding.
Dr. Paul Cox
Basically, the way to think of it is the complete record of all exposures, actually from in utero, right till you die of environmental toxins, stress, other biological and physical factors. And this is really a new paradigm in disease understanding that's really taking off now among a bunch of young Turks, which I like to include myself with. What sort of led to this was, I mean, partially I work in Guam, where we found this terrible neurological illness suffered by the Chamorro villagers with symptoms similar to ALS, Alzheimer's, Parkinson's disease. was triggered by exposure to an environmental toxin produced by bacteria in their food. One sort of striking statistic that everybody in neurology knows, but often laypeople don't, is that if you take Alzheimer's or Parkinson's or ALS, only about 10% of the cases have a genetic cause or a familial history, possible genetic cause. 90% of the cases are considered sporadic. We don't know why. I think in the 80s and 90s and the early 2000s, there was a real focus on linking gene expression to diseases. And that's true for 10% of the cases. But what about these other 90% of the cases? They're sporadic, where people don't have an identified mutation or a family history of the disease, where they come from. We began working in Guam, but other people, and I'd like to signal out here, my friend Ray Dorsey, who's a Parkinson's expert, has a best-selling book on the New York book list on Parkinson's disease. It's really quite clear that Parkinson's also can be triggered by exposure to environmental chemicals like Roundup or glycophosphate or aging or those sort of things. So there's a whole new looking thought now about What are the exposures that can lead to this? Are some people more vulnerable than others to these exposures? And if true, if that's the sort of fount of some of these diseases, can we design therapies to counteract that?
Mike Kiniry
Would it be fair to say that one of the big challenges is we are, over our lifetimes, being exposed to so many things that we aren't either being tested for or maybe that we don't even really have a good way to test for?
Dr. Paul Cox
That's absolutely true. I mean, it's a very interesting hypothesis, and it makes you start wondering. I mean, there's clearly been an increase in autism in the United States. And this is more than just case finding. I think most of us that studied the stats believe that there is, for some reason, an increase in that. We can see that Alzheimer's, even age-adjusted, because we're living to be older now, is increasing. So is ALS in some countries. I mean, And it varies by geography in Sweden, this is quite an example of that, because I worked a lot in Sweden. In southern Sweden, the incidence of ALS is five times what it is in northern Sweden. And there's a family up in northern Sweden, this is up in Lapland, where the whole family has an SOD1 mutation. This is a risk factor for ALS, and none of the family members have come down with ALS. So What's different between northern Sweden and southern Sweden? Of course, we immediately think of the cyanobacterial blooms in the Baltic and other lakes down in the south. And people in the north don't have that. They have free-flowing rivers in their water source. But it really can structure scientific investigations in a different way. And that's why we got so fascinated with dolphins in Florida.
Mike Kiniry
Yeah, give us the short version of that, or let me try to give the short version of that. Doctor, is it Walter Bradley?
Dr. Paul Cox
Yes.
Mike Kiniry
They've been studying, they're doing necropsies on dolphins that died around areas where cyanobacteria blooms happen, and they found Alzheimer's-like changes in their brains. How did I do?
Dr. Paul Cox
Well, I did pretty well. We did the analysis of the neurotoxins in the dolphin brains right here in Jackson Hole, and Dr. David Davis, some great marine biologists, SeaWorld and other places really pitched in. But the frightening thing is that of beach dolphins in the Indian River Lagoon on the east coast of Florida, they have Alzheimer's disease. I mean, they have Alzheimer's type neuropathology. They have 536 genes that are activated in human Alzheimer's patients are activating these dolphins. And when we look at their brains, we find massive amounts of these cyanobacterial neurotoxins. So I think we've made a pretty strong case that these dolphins are actually getting beached and suffering from Alzheimer's or an Alzheimer's type disease. And what worries us about us is that there's people live all around where these dolphins live. So could they be canaries in the mine shaft?
Mike Kiniry
Is there any work being done where, because it's pretty hard to track a person from in utero throughout their life to what they've been exposed to, but I can imagine a study where a person might wear something that collects data. Is there anything being done like that with, you know, human beings long-term living life and collecting data?
Dr. Paul Cox
Well, that's what's interesting about the neurotoxins that we've been studying that are produced by cyanobacteria, sometimes called blue-green algae. because they insert themselves into proteins. So if we can get access to post-mortem autopsy tissue, we can see sort of a history of exposure in people right from their brain tissues. We've also used human hair as a way of seeing exposures. So it may be that we carry within us a little bit of a record of our exposures. The other thing that we're finding with BMAA, and it's isomers, and I should explain for listeners that an isomer has the same chemical formula, it's just that the atoms are hooked together a little differently. For BMAA and it's isomers, we're finding that there is really a clear record within the human body itself of these exposures. It's cleared out of the blood pretty fast, but if we look at brain proteins, or sometimes in hair we can see this.
Mike Kiniry
Is Gulf Coast Life. My guest today is Dr. Paul Cox. He's the Executive Director of Brain Chemistry Labs in Jackson Hole, Wyoming. At its core, the Brain Chemistry Lab's mission is to discover new cures from plants. Dr. Cox is an ethnobotanist. Their work includes research in the worlds of neurology, physiology, epidemiology, oceanography, microbiology, mostly brain science stuff. Today we're learning about an emerging concept called the exposome. It's essentially an accounting of a person's entire exposure profile, including things like pollution and toxins and even environmental stress. That all adds up to potential for increased risks for brain diseases like ALS and Alzheimer's and perhaps even more. I mentioned that the reason I reached back out to you was because all the stuff we're hearing about gut health. Is there a nexus or vector between the exposome and our gut health and brain health.
Dr. Paul Cox
Yeah, I mean, absolutely. We now are talking a lot about the bacterial flora that we carry within us. I think last count, there's about 4,500 bacterial species that have been documented. Most of these are benign. They're fine. They help us. They protect us. That's why sometimes people that take a very strong antibiotic course suddenly are vulnerable to infectious diseases in ways they weren't before, because it's sort of like, you know, you've got 4,500 bacteria and they're fighting any sort of new pathogen that wants to show up. But I think where this has become really in focus is first of all our work and then the work of Professor Elijah Stommel in New Hampshire and his colleagues who found that if you live next to a cyanobacterially contaminated lake, your risk of getting ALS goes up 25-fold. And of course, we've been very focused in our research on Lake Okeechobee. and very concerned about release of cyanobacteria-laden water down the St. Lucie River and down the Caloosahatchee to the east and west coast. And we've cautioned the Army Corps of Engineers to try alter the schedule of those releases so they do not occur during the times of year when the cyanobacteria blooms cover large swaths of Lake Okeechobee.
Mike Kiniry
You mentioned Dr. Ray Dorsey. He's, or I guess what I'm getting at is maps. There are, researchers are putting together maps that show what prevalence for certain diseases are versus what they're proximate to. Can you just go through the scope of what those maps are doing? And I presume there's even more that are trying to be finished up.
Dr. Paul Cox
No, absolutely. Mapping is really a key issue because, again, Professor Elijah Stommel, who's at the medical school at Dartmouth, he's a professor of neurology, read our early work on Guam and started mapping his patients' addresses were ALS patients. And they found this astonishing feature that if you live next to a lake or river that has cyanobacterial blooms chronically, your risk of getting ALS goes up. It doesn't mean that you will get it. just means, because fortunately, ALS is a very rare disease, but your risk goes up. And so it's sort of like looking at a balance sheet of risk and benefits. Some people, unfortunately, believe that if they have a, for Alzheimer's, for example, an APO4 gene, that means you're going to get Alzheimer's. No, it doesn't mean that at all. It is a risk factor. On the other hand, if you exercise or eat a Mediterranean diet, try to learn a new language, or in our case, take health searing, that reduces your risk. So it's just sort of a balance of factors. And what Ray Dorsey's done, I think in a beautiful way, he's a professor of neurology at the University of Rochester, a real internationally renowned Parkinson's expert. He's basically arguing that Parkinson's is mostly an environmental disease. That if you get exposed to certain types of agricultural herbicides or pesticides, a road known to be a great example of this, that is a definite risk factor for Parkinson's. Now the good news about the exposome is that if you understand these things, you can avoid exposure. And that's one thing we've been hoping would happen for Florida, is that the Florida State Health Department, if they see cyanobacterial blooms in waterways, say in the Caloosahatchee or St. Lucie River, that they would put the warning out. When I first went down, I think it was 2016, when they had a big cyanobacterial incidence in St. Lucie River in Stewart, I mean, the cyanobacteria were so viscous, the locals were calling them guacamole. As soon as I saw that, I jumped on a plane and went straight out to sample the water. And when I got the St. Lucie River, there were 11 dead manatees. And that's very frightening because Many of these marine mammals, manatees, dolphins, whales, have neurological systems that are very similar to ours. And I was really concerned about all the people living along the shores of the St. Lucie River. When I started sampling in Lake Okeechobee, some local people came up and said, why are you wearing all this stuff? I was wearing hazmat gear. I said, well, these cyanobacterial toxins are very dangerous. And they had their kids out picnicking, swimming, And they said, nobody told us. So just like now, I think it's well accepted for paralytic shellfish poisoning. There's alerts. I think the health authorities should give people information on potential environmental dangers. And then people decide, well, maybe we won't go to the beach Thursday. Maybe we'll go next Tuesday when it clears up. And they can make informed decisions to prevent exposures.
Mike Kiniry
You've mentioned L-serine a couple times, and we've talked to you about it on the show before, and I'll link those on the post for this show. But can you just give the short version of what you mean by that?
Dr. Paul Cox
Well, I started, we began our work in Guam, where we found that in two villages, up to 25% of the adults were dying of this very unusual neurological disease that sometimes looked like ALS, sometimes looked like Parkinson's, sometimes looked like Alzheimer's disease. People who died of it had neuropathology consistent with all those diseases. And then I started looking at a village in the northern tip of Okinawa called Ogimi, where there were no record of any of these diseases, trying to figure out what's the difference here, because they're both tropical environments. And we found that the people in Ogimi get about four to five times the amount of the amino acid L-serine that we get in North America. We, Dr. Rachel Dunlop and her team in Australia, Dr. Ken Rogers, found that this works in cell culture, that if you hit cells with this neurotoxin BMAA, they die. Human neuronal cells, if you add L-serine to the mix, it stops the death. And then we repeated this on studies in a vervet in St. Kitts. We've had now an FDA-approved clinical trial in Phoenix and San Francisco showing that L-serine can help reduce, slow the progression of ALS. We had a second phase two trial going on at Dartmouth. It got shut down during the pandemic because of rapid turnover in the clinical trial office and nurses not being able to show up in that. But we're trying to restage that right now. So we know it's safe and we believe it's efficacious. And if so, That's a simple way of reducing risk of some of these diseases. We also have a phase two right now, finishing at Houston Methodist for treatment of mild cognitive impairment. Mild cognitive impairment is a precursor to Alzheimer's, and we will have full data at the end of this year. But there's a lot of excitement. That's A 95-patient trial, so a big clinical trial. So that's why I think that L-serine is potentially a way of reducing risk of some of these diseases.
Mike Kiniry
The exposome concept is not widely known yet, but it is something that the U.S. Centers for Disease Control and Prevention actually does have a webpage called the Exposome and Exposomics, which I presume is the studying of exposomes. So this isn't just something that, you know, nonprofit labs like yourself are talking about. The CDC actually is at least has a webpage. I'm not sure if that means that they're doing research or not.
Dr. Paul Cox
Well, again, this is, how can I say it, science moves in waves, and this is a new wave, the exposome. A lot of sort of thought leaders are now talking about this, thinking about this. The exciting thing is that if you understand this concept, and as the research progresses, we can identify what exposures are dangerous, then it's easy to tell people to avoid them. And these are just common sense things. For example, we know that people that live in places of intense air pollution, say Mexico City or other American urban cities, certain times of the year, they're going to increase their likelihood of getting certain types of cancer or getting asthma. We're seeing if you're exposed to these cyanobacterial toxins, these blue-green algae, that you're increase, you have an increased risk of getting ALS and potentially Alzheimer's. And something I want to circle back to that you mentioned earlier, Mike, was mapping. Because mapping suddenly becomes really important because you look at a map, almost like a contour map of Colorado, you see these peaks where there's massive amounts of, or higher than expected amounts of, say, ALS. And then you can start asking, well, what's going on in this place? And we're very interested as I went to Google and spoke to them. I said, Could you draw me a map of Alzheimer's disease? They said, what? I said, yeah, if we could map number of cases per square kilometer, we might turn up some really interesting things. And Professor Wilder Bradley at the Miller School of Medicine, Miami, who's one of the world's greatest neurologists, has begun with his colleagues mapping Florida for different neurological illnesses. So These maps can really point out some fascinating things.
Mike Kiniry
Last question and a follow-up on that. we've really made rapid strides in recent years of being able to use machine learning on large data sets. Is that all feeding into this emerging exposome world?
Dr. Paul Cox
It's such a new technology. My understanding of digital technology, I'm an ethnobotanist. I'm more of a machete and notebook and pencil guy. But of course it's going to help us looking at very large data sets. for patterns is going to be fascinating. And here's where the work in Scandinavia is so fantastic because in Finland, they can actually geolocate everybody's birthplace and the place where they die within a couple of meters. So we were able to identify a lake in Finland as potentially being a source of cyanobacterial contamination because people surrounding that were getting ALS. Ditto in France, The Tao Lagoon in the south of France had a situation much like Lake Okeechobee, where there's agricultural chemicals being dumped into the, you know, fertilizers dumped into the Tao Lagoon, and there's a, sure enough, there's a cluster of ALS. So mapping, and I think, as you said, Mike, AI can really help us understand these things better in the future.
Mike Kiniry
Dr. Paul Cox is an ethnobotanist and executive director of the Brain Chemistry Labs in Jackson Hole, Wyoming. Great talking with you again, Dr. Cox.
Dr. Paul Cox
Thank you, Mike. It's a pleasure and please have a wonderful summer.
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