🎧 Ethnobotany and Medical Discoveries with Dr. Paul Alan Cox

We chat about foods of the Blue Zones and how cyanobacteria are linked to neurodegenerative diseases like ALS and Alzheimer’s disease.

Nov 13, 2023

From the discovery of an HIV/AIDS drug candidate to uncovering the secrets behind a neurotoxin responsible for neurodegenerative diseases, we have a lot to share this week on the show! Our guest is Dr. Paul Alan Cox, ethnobotanist and Executive Director of the Brain Chemistry Labs in Jackson, Wyoming, where he and his colleagues are searching for new treatments for ALS and Alzheimer’s disease. Dr. Cox has lived for years in remote island villages, searching for new medicines. He was named one of TIME magazine’s eleven “Heroes of Medicine” for his discovery of a new HIV/AIDS drug candidate. He was also awarded the Goldman Environmental Prize, sometimes known as the Nobel Prize for the Environment. Visit this website to learn more: https://brainchemistrylabs.org/

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About Paul

Dr. Paul Alan Cox has lived for years in remote island villages searching for new medicines. He was named one of TIME magazine’s eleven “Heroes of Medicine” for his discovery of a new HIV/AIDS drug candidate. He was also awarded the Goldman Environmental Prize, sometimes known as the Nobel Prize of the Environment. Seacology, the island conservation not-for-profit he founded, has set aside over 1.5 million acres of rain forest and coral reef in 69 countries around the world.

Cox was both a Danforth Fellow and a National Science Foundation Fellow at Harvard where he received his Ph.D. He was then appointed as a Miller Fellow at the Miller Institute for Basic Research in Science at the University of California, Berkeley. After serving as professor and dean at Brigham Young University he became the first King Carl XVI Gustaf Professor of Environmental Science in Sweden.

He serves as the Executive Director of the Brain Chemistry Labs in Jackson, Wyoming, where he and his colleagues are searching for new treatments for ALS and Alzheimer’s disease.

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Yours in health, Dr. Quave

Dr. Paul Alan Cox's Background and Achievements

[00:00:44] Dr. Cassandra Quave: Our guest today is Dr. Paul Alan Cox. He's lived for years in remote island villages, searching for new medicines. He was named one of Time Magazine's 11 Heroes of Medicine for his discovery of a new HIV/AIDS drug candidate.

He was also awarded the Goldman Environmental Prize, sometimes known as the Nobel Prize of the Environment. Seacology the island conservation, not-for-profit he founded, has set aside over 1.5 million acres of rainforest and coral reef in 69 countries around the world.

Paul was both a Danforth Fellow and a National Science Foundation fellow at Harvard where he received his PhD.

He was then appointed as a Miller Fellow at the Miller Institute for Basic Science Research for Basic Research and Science at the University of California Berkeley. After serving as a professor and dean at Brigham Young University, he became the first King Carl 16th professor of environmental science in Sweden.

Today Paul serves as the executive director of the Brain Chemistry Labs in Jackson, Wyoming, where he and his colleagues are searching for new treatments for ALS and Alzheimer's disease. Thanks so much for coming on the show, Paul. It's great to see you.

[00:01:51] Dr. Paul Alan Cox: It's an honor to be with you. Thank you.

[00:01:52] Dr. Cassandra Quave: Yeah. Well, I've been wanting to get you on the show for a while. We share a common academic heritage. You trained under Richard Evans Schultes and I was trained, several generations below that. But, I think we, we share some common interest in Ethnobotany for sure. And, you know, when I was in graduate school, I very clearly remember reading your very inspirational book on Nafanua, Saving the Samoan Rainforest.

Oh. So I thought maybe that's a good place to start to kind of introduce folks to the work that you've done and kind of how you've taken . You know, your experience in Ethnobotany to address some of these medical challenges. Maybe we start there.

Dr. Cox's Journey into Ethnobotany

[00:02:30] Dr. Cassandra Quave: How did you start with Nafanua? Tell us a little bit about that.

[00:02:33] Dr. Paul Alan Cox: You know, it was a interesting experience because I had spent a year, with my family down in Island, very remote island, where I was trying desperately to find any possible new treatments for breast cancer, which had taken my mother's life. I'd done a little bit of back of the envelope stuff.

After she died, I thought about going back to medical school and becoming an oncologist, but then I was reading a book by Robert Coles called The Call of Service Robert Coles, the Harvard sociologist and Coles writes, if your passions and interest intersect with a deep societal need, then you're hearing a call.

So I went down to see my friends at the US National Cancer Institute. Dr. Gordon Craig was the director. And I said, you know, I'm guessing that if I really devoted my life to medicinal research based on ethnobotany, that there's about a 1% chance I could discover a new drug. And they said, well, we've been talking about you, Paul. We actually think you have a 3% chance. I thought 3% . That means there only needs to be 32 other ethnobotanists like me and one of us can hit. So, I was pretty excited about that. So we went for a year and just took the children's school books that their school teachers had my research gear went into a village I'd never been into before.

Lived in a little tiny thatch hut. No electricity, no running water in the whole village. The kids would have Hutt school. They just and just and then go out and play in the tide pools for recess. And I apprenticed myself to a couple of healers there. just trying to understand. The sad thing is that I didn't find anything that showed, promise for the treatment of breast cancer. Turned out in their language, the Samoan language, they don't even have a word for cancer. The closest I could find was Lumpy Breast. And the treatment they used for lumpy breast was inactive in the National Cancer Institutes bioassays.

Discovering New Treatments for Diseases

[00:04:25] Dr. Paul Alan Cox: But then I got a letter from Dr. Craig at NCI. saying, Hey, you know, is there any chance you could find any new antiviral compounds? We're very interested in HIV. The healers I'd apprenticed with two healers had told me about the tree of a, the bark of a tree. Homalanthus nutans. Again, translating indigenous disease concepts into Western concepts is sometimes a difficult process, as you know. But as I listened to the symptoms and signs, I wrote acute viral syndrome in my notebook, and with the permission of the healers and the Prime Minister Samoa, the Village Chiefs. I exported samples back to Bethesda, where we found they were rich in a compound called prostratin, 12-deoxyphorbal, which showed a really new mechanism of protection from the HIV virus.

And I was really thrilled to be able to negotiate with the village the Prime Minister government of Samoa, that any commercial development of this would result in a return. I. Significant return to the families, the village, and the government. And this was before the convention biodiversity had been signed so or even negotiated.

So, it was pretty exciting times.

[00:05:40] Dr. Cassandra Quave: Yeah, I think that's, I think that's great.

The Importance of Indigenous Knowledge and Intellectual Property Rights

[00:05:42] Dr. Cassandra Quave: I mean, for the listeners out there, the conventional biological diversity in the Nagoya protocol. Are established really to ensure that we have equitable access and benefit sharing things like this where you have agreements in place to return benefits if something becomes you know, enters into commercial development from these discoveries.

[00:06:00] Dr. Paul Alan Cox: Yeah, and I think Cassandra, you would've been really proud of the National Cancer Institute because Oh yeah. The patent lawyers they hired, there was no provision in the original patent documents for the healers. So I refused to sign and they said, well, what You want us to put a witch doctor on the panel?

I said, yeah, sure, because. I'm just the guy with the notebook here. I'm just listening. To the women who tell me what their mothers and their grandmothers going back centuries have learned. And so my feeling is that they have an indigenous form of intellectual property rights and I refuse to go forward unless they're gonna be recognized.

Well, the National Cancer Institute stood right up behind me on this. It was really great. Wonderful. And we actually

It's quiet folks. So yeah. So the, that's worked out really well. Let me just sort of update the story there.

The Discovery of a New HIV/AIDS Drug Candidate

[00:06:53] Dr. Paul Alan Cox: the AIDS Research Alliance. Licensed it from the national cancer Institute, at the request going to Samoa with me to negotiate additional returns to the Samoan people.

And an interesting thing the Samoan government declared sovereignty over the gene sequences in the plant that produced the compound. They negotiated returns to the people. And now Paul Winder really gifted chemist, a great soul at professor chemistry at Stanford, and his colleagues have now tinkered with the molecule.

So it's even a thousand times more active. Than what's found. And I've you know, had an article in Science magazine arguing that any analog of the Prostratin molecule should also recognize indigenous intellectual property rights. So, as you know, you know, pharmaceutical development is glacial.

It takes a long time. It does. is still in play and it shows potential action clearing people from virus. So it's still not in clinical trials yet, but I'm very excited about what the Stanford team's done to and this is a typical sort of thing that happens historically, a product has found.

A natural product and a plant used by indigenous people and the molecule is optimized and tinkered with to make it even more active. So, this is a story that may maybe isn't over yet. We'll see.

[00:08:14] Dr. Cassandra Quave: Yeah, that's that's really exciting. Yeah. It does take time and it takes, you know. I think many of our best drugs that have come from nature have gone exactly that path where they're optimized through Derivitization to either increase activity or potency or reduce toxicity like this is.

So that's exciting that Prostratin is still in play and it's really exciting that there are mechanisms to bring back benefits to these people.

[00:08:37] Dr. Paul Alan Cox: Well, they're set in stone. Very interesting. In fact in the negotiations, UC Berkeley, on commercializing the gene sequence. One of the sticking points was where are discussions if there's problems gonna be held, and, you know, what do you do? Because they said well, we want it in Berkeley, California. And the chiefs in Samoa were saying, what's this Berkeley thing? We've never heard of it. And the compromise was that it would be held on Samoan soil at the United Nations, at the delegation, the United Nations.

So, wow. And this made the front page of the Financial Times in London, um, you know, drug development returns, going back to Samoa and, but I was saddened by this. Why should that be newsworthy? Yeah. It seems to me common sense, anybody that participates, particularly these people who are the indigenous custodians of this knowledge, definitely should be considered as co-equal partners in development and, so I think it's moving that way pretty much now, but that's not the way it used to be. A lot of times contributions from indigenous people were basically ignored, and I think that's a travesty. So isn't it sad that it makes a newspaper that we're doing the right thing? It should not be a newsworthy event.

[00:09:52] Dr. Cassandra Quave: Yeah. I feel like we're still kind of coming out of the colonial era, right? I mean, all of these major products of plants, if you're talking about whether it's coffee or vanilla or quinine, I mean, those all share the same story of yeah. Of being taken in indigenous peoples not being recompensed for those crops.

[00:10:09] Dr. Paul Alan Cox: Well, the genius of the convention biodiversity is that it sought to encourage partnerships between technology rich countries like most countries in Northern Europe, per se, in North America. And biodiverse rich countries, which often are in the south or in, in tropical places. Here's a case where it really worked. Yeah.

Government led by the Prime Minister. Totally. Were behind this, all the Village Chiefs. I mean, it was interesting. Somebody wrote in a a mean letter. You know, I mean, there's always a view that ethnobotanists are sort of somehow covert, exploiters. In, in the paper in Samoa and, 56 chiefs from the village wrote a response.

And said, You don't know this guy. He's one of ours. And he's done everything. He's done with our permission. The other exciting thing is we're always, and this is a tricky business, we always want to make sure that there's equal sharing of benefits. But what if ultimately those benefits are delayed or there's nothing down the road?

Yeah. And we prematurely raise expectations. So in this case, this is where ecology, that's not-for-profit I set up came in, we build a aerial walkway over the forest that was threatened by the loggers. Now the people get more money from torch revenues going up on this walkway than they ever would.

Amazing loggers. I was figuring out the other day we've spent about half a million dollars there building trails and a little clinic and schools just simple things that we take for granted here. But and these remote parts of the world that you and I work in are not always provided.

So, this one fortunately, has been a success story and and I'm very grateful that, for my indigenous partners, including this entire Samoan government who's been very positive about this whole thing.

The Mystery of a Paralytic Disease in Guam

[00:11:52] Dr. Cassandra Quave: That's great. And so Paul, how long have you been working with the Samoan government, with these communities?

How many years has it been now on this project?

[00:11:59] Dr. Paul Alan Cox: Right. You know, I think the agreements with the age Research Alliance and uc, Berkeley date back to about 2000 2005, 2003. So that's what, 20 years? Yeah. But really my research began over a decade earlier. The good thing is that I I feel as ethnobotanists that we really have to rigorously adhere to a complete disclosure.

So. Before I even set foot in the village, I talked to the government, I talked to the village chiefs. Why are you here? I'm interested in medicine. My mother died of breast cancer. I Want to understand your medical traditions. Maybe something can help them. And we signed a formal covenant called the Folu Covenant with all of the chiefs and all the villagers, um, that codified this.

So, you know, I just feel lucky that we, we made the right moves. At the beginning.

[00:12:52] Dr. Cassandra Quave: That's great. That's great. Yeah, I think this is this is a path that is more and more being recognized as kind of the standard where it hadn't always been in the past. That's exciting. And I know, you know, you've done this work in Samoa with regarding, you know, with regards to discoveries of potential medicines.

But you've also done some important work in the region on trying to understand. Some unusual diseases, some neurologic diseases. What can you share with us about that and how your observations as an ethnobotanist led to these

[00:13:24] Dr. Paul Alan Cox: discoveries?

Sure. You back when I was a graduate student this Cassandra was an era when only two rows of the periodic table had been filled out.

The Role of Cyanobacteria in Neurological Diseases

[00:13:33] Dr. Paul Alan Cox: We had the hubris of sort of dividing the world up, you know? So went down to the Amazon and Wade Davis went down to Haiti. And I chose the Pacific Islands and Southeast Asian Islands. Island's. Interesting because there's sort of like a little natural experiment going on. And I became so close to the HIV/AIDS community during my research. That when that started moving, you know, through Stanford, through the pharmaceutical world, I wanted to find another indication to work on that had the same sense of desperation, uh, destruction of work and family relationships.

I mean, AIDS in the 1980s was a very different disease of is now. Oh yeah. People were losing their jobs, being thrown at God was awful. And so I chose ALS. Because I just felt there hadn't been any good drugs coming up. Fortunately, I didn't know any ALS patients. But I decided to focus on this and this took us to the ion of Guam.

I think we made six or seven expeditions there, uh, where in two villages UMMA and Maurizio, uh, up to 25% of the people were dying from this unusual paralytic disease.

[00:14:45] Dr. Cassandra Quave: And so what was, can you describe for us what this paralytic disease looked like locally? I mean, how was it being described by locals and what kind of observations did you make?

[00:14:53] Dr. Paul Alan Cox: Yeah. They used, the agent had a local name for, it was called ligo Bodi, but it was it had an unusual phenotype. I mean, many people had a paralysis in muscle wasting consistent with ALS, atrophic lateral Sclerosis or Lou Gehrig's disease. Other villagers had you know, rigidity or cogwheel, uh, tremors cogwheel rigidity consistent with Parkinson's disease, and other people had profound dementia, like Alzheimer's disease. So my thinking was that this disease was sort of like a neurological Rosetta Stone. If we could figure out what's going on into these in this village or the two villages , that we might gain deeper insights and how these very disparate diseases are related. So we went house to house.

We had a great neurologist John Steele who'd lived on the island, working with this Dr. Sandra Bannock who's now our senior scientist brain chemistry labs. we Had some medical doctors, Patricia Stewart, uh, a very gifted amino acid chemists. Dr. Susan Merch, who was doing a postdoc with me.

Now she's a very famous professor in Canada, it seems like. Yes. She's, I sort of, yeah. My students go on to great things. That's great. So that's exactly the way you want it. And it was like an Agathe Christie novel. Why is this killing these people in these two villages and what's going on here?

I mean, at its peak it was a hundred times more prevalent than ALS anywhere else in the world. Wow. So we're just going door to door.

The Impact of Cyanobacterial Blooms on Health

[00:16:25] Dr. Paul Alan Cox: Hutt to Hutt house, to house just sitting doing ethno botany. What's fascinating is that, first of all, we're not the first people to get interested in this disease. Early physicians army, US Army physicians, uh, identified this disease in the aftermath World War II and got fascinated in it.

Leonard Keland did, at NIH did a really careful pedigree chart. showing that it could not be a genetic disease. It's had no familial background. And so there are all these ideas, you know, and I used to get these letters. Carlton Gajdusek, the Nobel Prize winner of, for his discovery of crew and prion disease.

I'd get these letters from Carlton and they, I'll be in caps in exclamation mark. Paul, what are you doing in Guam? Because Carlton espoused that it was exposure to aluminum. That was caused Alzheimer's disease. And this was not such a bad guess because on examination postmortem brain specimens from Alzheimer's patients shown excess of aluminum.

And when that got out, I mean, all of a sudden people threw away their aluminum pots and pans here in North American stop using deodorant and things like that. But this was not a satisfying explanation in Guam, because it's a limestone island, they have a deficiency of aluminum.

But then we got really fascinated in an observation made by Marjorie Whining. Marjorie was at the Burns School of Medicine. She was a nurse. Spent a couple months on Guam and she made a really fascinating observation that of, you know, you've lived in the tropics Cassandra, I know you've a lot of work there and elsewhere. Any sort of food stuff you have up on the shelf. Gets bugs in it. Well she had some flour made of cycad seeds and there are no bugs, and so she actually said, Hey, maybe there's something going on with these cycads.

Now the one thing we found out is Ethnobotanists and you know, I mean, what's your guess, Cassandra? I mean, how many of us are sometimes introduced as one of the top 50 ethnobotanists in the world? 'cause there's only 25 or 30 of us. There we go in our boots, muddy, you know. But one of the powers we have is we learn the people's language or we do our best.

We adapt ourselves to their culture. We don't wear a white coat and a stethoscope. We're not in a clinic. We're sitting with them in their houses or huts. And I think because of our training and our background, we hear things from the people that they're uncomfortable telling. Clinicians of course.

I mean, have you found that in your work?

[00:19:19] Dr. Cassandra Quave: Absolutely. A hundred percent. Yeah.

[00:19:20] Dr. Paul Alan Cox: And we found out something really amazing that nobody had heard before in the clinic. And it came from a card sort program. What I did, 'cause you know, we're interested is it is infectious disease. Doesn't look infectious.

Genetic doesn't look genetic. So I had a card sort thing where I had. Everybody we're talking to, I say write out all the food things you eat. And then I hand the card, I say, would you put these in order of priority? And people start getting frustrated. 'cause one thing they eat and nobody at NIH should figure this out.

They eat flying foxes. These are large bats. Genus Pteropus with like four foot wingspans. And one guy, an elder got frustrated with me. He said, you know, I don't get you white boy. Why are you asking these questions? He said, flying foxes is the most important thing we have to eat. He said, and if there was one right now I'd lock the doors, I'd eat it myself 'cause people break in trying to get in here. So we got extremely interested in this. Extremely this idea of these people eating these flying foxes because we knew that flying foxes fed on cycad seeds. So we thought, well, maybe the flying foxes can show us what's going on. And then there's been a lot of work on toxins and cycad seeds long before us.

So, with Dr. Bannock, our lab then was on the Island of Hawaii. We had a you know, some chromatography equipment, HPLC, this sort of thing. I thought, well, let's get some flying fox specimens from Guam, from the Smithsonian. Or from Berkeley a museum comparative zoology.

Let's see what toxins they have in their flesh. And we just started down the list alphabetically. The first one was called BMAA Beta methyl alanine. I was at home at two in the morning. Sandra was still in the lab. Boom, the phone rings. I picked it up, said, Paul, it's here. I said, are you kidding me? He said, no, it's this giant peak I raced over and here's this giant BMA peak.

Okay, so we suddenly realized that these people are eating the flying foxes. In addition, they're eating flour from the cycad seeds and tortillas and dumplings. . They're getting this massive dose of this neurotoxin. So then we work to get autopsy specimens postmortem specimens, people's brains 'cause people eat this stuff so highly in Guam.

We went to Canada to get control samples blinded at all. Broke the blind. The people that died of this disease had this massive amount of neurotoxin their brains, but so did two of the control patients from Canada. What they're not eating bats in Canada? What's going on? So we got the clinical details.

Those were the two, only two Alzheimer's patients and

[00:21:58] Dr. Cassandra Quave: Interesting. So they also had high levels of BMA,

[00:22:00] Dr. Paul Alan Cox: Which not a high size of people, but they had high and yeah, went higher than controls. So. What how do you get that seen In Canada, they don't have cycads, which is tropical. They don't eat bats. They, and so we started doing a lot of research.

I did anyway, a crash course on cyanobacteria and suddenly we realized. And I can remember the day I was driving the Land Cruiser with the Dr. Bannock and I said, you know, there's cyanobacteria as blooms in reservoirs, estuaries. Lakes, they're all over the world, and it felt as if we were staring into the abyss.

So we called up all our buddies around and you know, around the world and I can't remember how many we, we ran samples of cyanobacteria collected from all over Sweden, Spain, France. And almost all of 'em had this neurotoxin in their BMAA and we knew that it grows in the roots of the sica trees.

Then it bio magnifies up through the bats. And I mean, my heavens. So we published in PNAS and it was really moving fast and once you get on their circuit, boy there, and I called up there, he said, Hey, can you slow down? I need to talk to some people before this publishes. And he said, Dr. Cox, my entire career, I've never had an author call me up and say, slow down publication. Yeah, I'd be really grateful if you could delay it. We flew back to Guam. We went to every house, every family. Because I wanted him to hear it from us and not from a press account. And I told them that we felt they were getting sick because of their consumption of these flying foxes.

It coupled with the Cycad flower. Yeah, and I just waited here because as you know, Cassandra, this is sort of like violating the prime directive for ethnobotany. We were not there to change a culture. We're there to document a culture, not change it. Yeah. But here we're telling people our research. Shows that this is the cause to the person, the Chamorro Villager said, thank you.

Yes. We didn't know what was killing our family, and now we can protect our children. So, but I'd like you to opine on that for a second. Do you feel I committed immortal sin there by sharing that absolutely with the people?

[00:24:09] Dr. Cassandra Quave: Absolutely not. I mean, one of the things that we do with our return of knowledge is ask healers that we work with community members that we work with, what do they want out of this project?

And I would say nine times outta 10, they want to have the science explained to them whatever we find in our laboratory studies, you know, we're not looking at trying to determine causes of disease in my lab. It's more of like, how does plant X work against, you know, bacteria y? But there's definitely, yeah there's, I think it's it's a important part of the process.

I don't see it as changing. I think I see it as sharing of knowledge.

[00:24:45] Dr. Paul Alan Cox: So there's a democratization, a democracy of knowledge. Exactly. By holding the indigenous people in the same esteem, we hold our scientific colleagues. A hundred percent. Your view is share the knowledge.

[00:24:58] Dr. Cassandra Quave: Share the knowledge, absolutely. Especially, and they can make their own decision. And they can. Exactly. Yeah. There's no recommendations that, you know, you should use this or that. This is what we found. Yeah.

[00:25:09] Dr. Paul Alan Cox: Well I had a, you know, an anthropologist Pam, me on this one. Because you've changed the culture. Well, if the culture's killing people.

[00:25:16] Dr. Cassandra Quave: Exactly. No , you know, I mean, isn't that a, isn't that a privileged thing to say though? Is you're changing the culture. I mean, you, these are, that's...

[00:25:25] Dr. Paul Alan Cox: these are people that response, which I fortunately say is, well, do you think this is a zoo? Do you think these people doing animals? There are people just like me and you.

Yeah. And we value them. We care about them. We speak to them. So, but I have to tell you, there was, I think there could be an argument that Paul went and changed this culture or did something that could change the culture. It reminded me though, of Mina Mata Bay in Japan. As I got into that, you know, Mina Mata Bay was the first indication that methyl mercury causes Syrian serious neurological illness.

And in mean amount bay in Japan, there was a big factory dumping in mercury waste. Into the water it was going, it was bio magnifying in the ecosystem. So the poor Japanese villagers eating fish are getting this massive doses of mercury. Oh no. And the first indication that anybody had was a visiting neurologist trying to figure this puzzle out, and he saw a catwalk sideways.

Yeah. Boom. And suddenly his medical training came in. Oh, you know, this sort of GA effect is characteristic of mercury poisoning, you know? So anyway, I don't know, but the people were so kind, so gracious. They thanked us for sharing this with them. And then the article came out. We later then reproduced the village disease in Verit on the island of St. Kitts. These were introduced. They don't belong there. They outnumber the locals. Harvard made a really nice facility where it's all like a zoo. So, and we never forced any animal to take a diet take a dose. We just had some that had rice flour in a fruit, you know, a piece of the pie after the meal.

Others had BMAA, all the ones that had BMAA developed. Alzheimer's neuropathology, they developed ALS neuropathology and they developed Parkinson's neuropathology, the ones that had the just rice flower didn't have any of that. So this really is evidence that neurotoxin triggers that disease in Guam.

And now there's two epidemiological groups come out saying that BMAA is the best supported environmental cause of ALS.

[00:27:29] Dr. Cassandra Quave: So I'm sure many of our listeners here are probably on their edge of their seats wondering how do they determine if they're getting exposed to the cyanobacteria? Like what do you have to be eating this to get exposure to BMAA or is it enough to live near a body of water where you have these cyanobacteria blooms?

[00:27:49] Dr. Paul Alan Cox: Those are really good questions. Yeah. We know that, I mean, cyanobacterial blooms are the sort of green scammer man. That sometimes you see in estuaries or sometimes in polluted lakes or rivers. And my advice is to stay away from them. They don't always produce BMA, but at certain times in the life cycle, we think any cyanobacterium can do it.

The place we've been monitoring very carefully now is, lake Okeechobee in Florida?

[00:28:16] Dr. Cassandra Quave: Yes. It's near my, not far from my home. Like an hour from where I grew up. Yes. Where did you grow up at? Cassandra. In Arcadia, along the Peace River.

[00:28:24] Dr. Paul Alan Cox: So, yeah. Well, what happens is there's a big dam there that sort of increase the size of the lake.

But when the water gets high during a wet season, the Corps of Engineers will release water down the St. Lucie River. Going to the east to Stewart. The Indian River Lagoon, and they'll re release it west to down the Caloosahatchee, going to port Charlotte, Fort Myers, that sort of area.

And you know, I was sitting watching television, a news broadcast when the first 2016 release came and I saw it. I thought, oh, good heavens. I jumped on a plane right then, boom, went straight down there. When I got there, Cassandra, there were 11 dead manatees. 11 in the St. Lucie River and the local people that live in trailer parks and then along the St. Lucie River. Yeah, were calling the sign of Bacterial goo because it was so, viscus, they're kind of guacamole. And the Stewart County people down. You know, were, I wanna be care, very careful how I say this, but sort of where the rich people live they had signs up saying, please avoid the beach.

But when I went up to Lake Okeechobee sampling, um, I. There were local people there. This is Central Florida moms and their kids are swimming, fishing. They came, oh the lake, why are you wearing this stuff? 'cause I'm wearing hazmat gear. And I said, oh no, this is very dangerous. And they said, well, nobody told us.

Yeah. Nobody. Yeah. Boom. We get back and they're off the charts in terms of sign bacterial , oh my gosh. 20,000 times WHO standards from Microcystin, which causes liver cancer.

[00:30:02] Dr. Cassandra Quave: Should the EPA a be monitoring this? This is insane. Or like letting people know, I mean, well, there's also the sugarcane cultivation there.

We have all these fertilizer, all kinds of stuff's being dumped into that river.

[00:30:13] Dr. Paul Alan Cox: You know, there's a lot of agricultural waste coming into, like. A lot of people have septic tanks. We have sewage coming in. And this makes heaven for cyanobacteria. Oh my. So we you know, we're we wrote the core of engineers and said, look, well, before you release that green goo, please think about this really carefully.

You need to change the management plan. The center center for the conservation organizations from the Everglades. Everybody came in behind us. Or in support of us. There was a film called Toxic Puzzle. I should have put that up. But people that click on our website can see that film done by

Bunch of European people every time that film screen In Florida, the standing room only 'cause people don't have enough information. There it is. Brain chemistry labs.org. If you click on that, you'll see a film called Toxic Puzzle, uh, which the director in Sweden made free of charge to view. People are terrified.

Emergency room docs are seeing people coming in. There's dead dogs. Dead fish, dead manatees, dead dolphins. It's really scary when these sin of bacterial blooms, and that's the scary part. The good news is to stay away from 'em. Yeah. If you see that , just don't go up and do, just stay away.

[00:31:27] Dr. Cassandra Quave: It's hard. It's hard if you're living there and if you don't really have the financial means to move away.

[00:31:33] Dr. Paul Alan Cox: Well, yeah, that's a neurologist at Dartmouth. A a member of the medical faculty there. Professor Elijah Staal read our papers. He started plotting on maps where his ALS patients live in New England.

. He figures if you live next to a lake that has cyanobacterial blooms. You increase your risk of getting ALS by 25 fold. Wow. So, we're monitoring the situation there. We're trying to encourage as best we can, the core not to release that goo out of Lake Oak, Shelby. And there and again, a really heartening thing.

There is a very strong bipartisan support in Florida. To clean up the water. And trying to, from Brian Mast who's who's been leading the way and both parties really and citizens are really concerned about this. So, so you know that's been a good story.

[00:32:20] Dr. Cassandra Quave: Yeah, no, absolutely.

The Connection Between Diet and Neurological Health in Okinawa, Japan

[00:32:21] Dr. Cassandra Quave: I mean, it's an amazing arc of discovery from work with villagers to flying boxes to blooms in the River or Lake Okeechobee.

I'm wondering, is it known what the precise mechanism of action is for BMAA? And this, I mean, do we know what its neurotoxic effects are on the brain?

[00:32:43] Dr. Paul Alan Cox: When I was a kid you know, they had something called Wonder Bread that said it builds strong body is eight way it was white bread. I mean, good heavens.

BMA has a number of negative actions, but the one we've been extremely interested in is that since it's a non-protein amino acid, our cellular machinery, when it builds our proteins in our brains mistakes it for a normal amino acid L-serine is one of the 20 amino acids we have in our brain.

And we found, and this is, and I really wanna give credit here to Dr. Ken Rogers. And Dr. Rachel Dunlop. Rachel now works in our lab. She's our senior research fellow. Together we discovered that if we increase in neuronal cell culture, L-serine, we can stop all protein misfolds and all neuronal death.

We did the same thing in laboratory animals, in, in these verts. If we fed the verts BMA at the end of their meal, but then added L-serine, we could block the neuropathology. We could completely block if FDA gave us permission to run or commission clinical trials. Our neurologists in Phoenix and San Francisco and back east and now Houston have been studying it and it's pretty exciting work.

It looks like this normal dietary amino acid L-serine may indeed help prevent these diseases. I think the jury's still out. I'd like to see it go through some more trials and a big . Phase three, but so far it's promising. So we haven't been beaten the drum really till the work's done, but of course pretty exciting.

We've got a trial now for mild cognitive impairment that we've sponsored at Houston Methodist, topnotch, a neurologist there. And up to a hundred people will be enrolled in this trial and. So far. I mean, if you've got a monkey that's having neurological problems, call me. 'cause I know exactly what to do for that.

Monkey . For the monkey . That's great. We even saved a dog . We even saved a dog. So poor lady brought in her dog and it had sort of the doggy version of ALS and wow. So we she said, and we fell in love with this little dog, Jake. It was a corgi, so it had legs play. So, we thought, well, are we gonna get in trouble for practicing veterinarian medicine without a license?

So we got a local vet in Jackson Hole involved. So, you know, it was all an up and up. Yeah. Actually the dog started getting better. And this lady, so there's, wow. Well, this lady was so sweet. Eventually the dog died, but we kept it in a prime of health for a while. And she gave us the $25,000 gift.

We're a not-for-profit. So I called my scientist together, said, now look in this town, it's a dog friendly town. I said. You never know how many $25,000 dogs are walking around out there . I said, there you go. Be really careful. That's amazing. But we should talk a moment about Ogime 'cause you mentioned before.

[00:35:31] Dr. Cassandra Quave: Well, yes. I was gonna, I was gonna transition to that because you know, I know I mentioned before we started recording, I was just there in May. For the audience, Ogime is a village located in Okinawa, Japan. It is the site at the greatest concentration of centenarians in the world. And I wasn't, I, unfortunately, I was only there for, you know, a few days.

I wasn't able to do an in-depth study. It was just while I was in Japan, I had to go and visit and see just see how, what things looked like. But I know that you've done a more intensive field study around diet and healthy aging and brain health. I'd love to hear about what you found from that study.

[00:36:07] Dr. Paul Alan Cox: It's just a remarkable place. We've made seven expeditions there now. And I really wanna thank my colleagues, Maki Kishimoto and his brother Mahara Kishimoto Chiba, Kimi, other people who have assisted me. Ghia is on the northern tip of the island. Its most isolated place, a number of hundred year old people there.

I've now you know, I've completed 51 hour interviews with 50 of the centenarians. Again, you know, I initially thought, well, maybe this, these people just have gene, a genetic basis for being youthful. . I can't keep up with 'em. I'm crying. And they dance. They can remember, yes. Their childhood.

Wonderful people. So we brought samples, their entire diet, and again, doing card sort routines just like you learn ethnobotany. Back to our laboratories in Jackson Hole where we have a really strong analytical chemistry platform. I. Analyzed them, and we find these people have the richest diet yet recorded in the world for L-serine.

To put this in perspective the average American gets about three grams or so of L-serine from dietary sources. The average woman in Ogime, who's a hundred years old, is getting eight to 12 grams. Wow. They're getting it primarily from the Sea. They have, they eat 25 different species of marine algae of seaweeds.

And some of those are extremely rich. in L-serine, they eat a lot of tofu. Yeah. And very little rice, which is interesting. They might have a little rice in the morning as sort of a porridge, but they're eating tofu. And get this Cassandra there eating tofu as part of their religious. They have their own language, which is different from Japanese, different from now, and I've been learning it.

They always sort of think it's cool. Here's this guy that , you know, at least talk to him about the plants and language. But they have their own religion and they get together, oh, every week and a half and they dose themselves with, with seaweeds and with tofu we, they also eat a lot of pork, which is very rich in L-serine.

[00:38:08] Dr. Cassandra Quave: That's what I found that was really interesting. A lot of wild boar. I was staying with the farmer on my visit and he was lamenting how the wild boar eat his pineapples, but he would catch some, trap them and eat them and very, I was surprised. I think based on other things I've read about the communities that they had such a meat rich diet in that sense.

[00:38:26] Dr. Paul Alan Cox: Well, that's the only one they do though. It's very . Yeah. They don't eat shellfish. They eat sweet potatoes. They call 'em Bemo. Yes. And they're purple. And they're beautiful. Those are rich in L-serine. Yeah. Now, do the people know about L-serine?

No, of course not. But how could I distinguish if it was a genetic disease or not? Well, I was visiting with the matriarch. It's a matriarchal culture, which is cool. The women. Call the shots there. And the matriarch a 19 year old young woman brought out the punching cookies to greet me, and as I was hearing, to leave just on a hunch, I turned to her.

I said, how old are you to this 19 year old? She said, 54. She. I said were you born in this village? She said, no. I said, why are you doing here? She said, well, I married her son, the matriarch son. And then, and this is where praise the Lord, inspiration comes in. I said, do you have a sister? I said, where'd you come from?

She said, I came from Kashima up in mainland Japan, Island. I said, do you have a sister? Yeah. She's just a year or two years. Difference in age. Do you have a photograph? She brought it out. Her sister looked like a normal 56 year old Japanese woman, whereas this 54 year old woman looked like she was 19 years old.

Wow. And there's no way that she had any participation in the genetic, you basis of genes. So suddenly I got really interested in diet and we've analyzed that diet and I dunno if you had a chance to take some meals there, but when I'm eating that village diet I feel a little bit more spring in my step.

And yeah. , maybe psychosomatic, I don't know. But the women are just so amazing, you know? Yeah. But I was interviewing 2 98 year olds who lived together. One of 'em was bouncing. I couldn't even get the camera to slow down, you know? As I got ready to leave, she came up, she put her arm around me. Now this is not a typical behavior in Japan, in Japanese culture, okay?

No. She put her mouth up to my ear. That is also not typical and in Japanese. 'cause we speak in Japanese. Except when I'm talking about plants, I speak language. Yeah. She says, you're sort of cute.

So when I finally got down, there weren't any hotels that this was one of the first trips.

Got back down to the main city. I called my wife. I said, Barbara, I've got this 98 year old woman hitting on me, . And Barbara said, well, is she hot? I said, well, yeah. She said, be careful, Paul.

[00:40:58] Dr. Cassandra Quave: Be careful. I love it. I was so struck. I had a nice visit with a woman named Yuki. I don't know if you, if

[00:41:06] Dr. Paul Alan Cox: Oh, yeah. Yuki. I know Yuki in Japanese means snow. Okay.

[00:41:11] Dr. Cassandra Quave: Yes. She was like, just the whole time we're talking, she's folding origami for the schoolchildren. She says her hands are busy the whole time. She just baked like a thousand cookies for the schoolchildren. She's just, I mean, her energy. I was like, I need this energy. Whatever you have this mojo. was like, yeah. It was just,

[00:41:30] Dr. Paul Alan Cox: They're incredible. The exercise, they play their hin, these little three string. and dance. In fact if we can bring up that website again because on this film, the Swedish team made. Brainchemistry.org.

They spent a week with me in the, there we go. If you, it's great. There we go. There we go. So if you click on this toxicpuzzle.com or come into the brainchemistrylabs.org, you'll see some very nice film they made of these women in Okinawa. And I can literally not keep up with them when they're dancing.

Yeah, they're just and they're so amazing. I'm talking to this lady she was about 97, maybe 95, and I go through a whole. Carefully structured interview. You know, have you had any medical issues? Have you ever been to the hospital? She said, well, yes. I said, well, how long ago? 20 years ago? What happened?

She said, well, I was bit by a hamus. That's a poisonous snake. I was bit by this poisonous snake. And I said, well, what did you do? She said, well. I killed it. Of course.

That's great. They're just a hoot. I used to, of course. I really have so much fun down there and Oh, I love it. I was so touched. 'cause the last trip I got ready to leave in the council, the chief's council, the mayor's council sent a messenger. He said Dr. Cox, could we please meet with you?

Before you leave. Sure. You know, so I go over and they said, we just want you to know something. They said, we have never met a foreigner who's shown us more respect than you. And they gave me a proclamation from the council declaring me as a friend of, oh, isn't that sweet? You know? That's amazing. I was so touched, you know, so touched, but amazing people, amazing stories.

When I was first there, I asked a woman Tell me about the war. Which war? The World war. Which World War? I'm dealing with a hundred year old people. So it's like, yeah. It's like being in a time machine, you know? Incredible to have them. Tell me about, I mean, and I think what happened is I actually teared up because I said to one of the women, she'd lost her son in World War II.

And I said, you know, I have so much respect for your culture. I mean, I've been learning Japanese and can speak a little bit and learning their poetry and just the stuff you do as an ethnobotanist. . And I said, I'm so sorry our country's went to war. I'm so sorry for the loss of your son.

I, and and I shed a tear and somehow word spread around and you know, that's the thing about the joy of ethnobotany that doesn't get into those so many papers is you, it's connections such affinity with these people. Yes. And you respect them and you admire 'em so much. And it turns out there's a little bit of that.

Reciprocity that they, yes. They look at us as being maybe a different sort of person than the Taurus they've met before or whatever, of course. But would you agree with that?

[00:44:11] Dr. Cassandra Quave: Oh, a hundred percent. Yeah. I mean, it's hard. People often ask me what's my favorite field site? And I'm like, it's not just about the landscapes or the plants, it's the people.

And each place is so uniquely wonderful and there's so many different stories. With people from different places where I've worked, it's, you know,

[00:44:29] Dr. Paul Alan Cox: it's and you don't even need to know to go to an exotic place. No. Yeah. To meet these sort of people. I mean, I was in Honolulu and I went to the Samoan bakery, asked, where do you go?

You're sick. Then I hear the name of the same woman. I go meet her in some little apartment. Here's this totally practicing Samoan healer. Wow. That's why I said, well, what happens when there's something in the Samoan floor they don't have in Hawaii? She said, oh, I just call, pick up the phone. I get it in 24 hours, somebody brings it up on the plane.

That's 24 hours. That's great. Emergency service. Yeah. You know, so it's it's really cool to meet these people and I, what I teach my students is the most important thing we can show is respect. Oh, absolutely. That if you walk into a new village, I've done that a number of times. I've never seen a foreigner before.

If you think these people are Ben knighted or savage, you don't have to open your mouth. They'll know that. But if you go there, you want to humble yourself, respect their culture, learn. I tell my students your goals and ethnobotanists to be like a little puppy that's soiled the carpet. We don't kill little puppies, that soil carpet, we put 'em on a newspaper and teach them.

And that's exactly position you want to be in because . Unwittingly, the second we walk in, we're violating their culture. Yeah. We basically want to tell them, look, here's why we're here. Please teach us, help us. And if you show that respect, that communicates to people, and that I think is maybe the most important part of an ethnobotanist toolkit, but the most difficult to teach.

Would you agree with that?

[00:45:53] Dr. Cassandra Quave: Absolutely. It is. I think that's so well put. You have to have the right mindset of openness and . And humility. That's the key. And those are not easy things to teach. I agree. It's but I just wanna thank you, Paul the, for sharing these stories, for sharing your wisdom and the, the journey that you've gone on really well to work in collaboration with people and make these great discoveries. I've long admired your work and it's been such a treat to speak with you. Yeah.

[00:46:24] Dr. Paul Alan Cox: Well, I'm honored to be here, but I just wanna be clear. I don't think this is my wisdom. I'm the guy with the notebook.

I just sit with these women who are a hundred years old telling me these amazing things, or I have these great colleagues. I mean, the scientist with me in my laboratory, I hardly know how to turn the machine on. I mean, there's these kids doing amazing things. So I just sort of feel like I'm the lowest leaf on the tree, but I.

I listen carefully and I like what you've done here, Cassandra, because what we listen to are stories. Ultimately, yes, we're with indigenous people and the truth is in the story. And if we can record the stories, just perhaps we not only understand their use of plants better, but we get a deeper sense into our shared humanity, and that's what makes it so fun to be an ethnobotanist.

[00:47:08] Dr. Cassandra Quave: That's a perfect way to end this show. Thank you all.

Conclusion and Reflections on Ethnobotany

[00:47:10] Dr. Cassandra Quave: You've been listening to Foodie Pharmacology, the Science podcast for the Food Curious recorded for you today on Restream. I wanna give a big shout out of thanks to our show's producers, to Rob Cohen and Christine Roth for bringing out a great show for you.

Each and every week. You can learn more about the work that's being done in at the laboratory. It is the, what's the website again? It's the Brainchemistrylabs.org to find out more about this work and also access those resources, including the additional film. And you can also learn more about the podcast by heading over to foodiepharmacology.com.

You can find links to our full video version of this on the Teach Ethnonotany YouTube channel. And of course don't forget to click subscribe so you don't miss any of our future upcoming shows. Thanks so much for listening. Stay healthy out there. I'll see you next time.