60. Cassandra Quave Thinks the Way Antibiotics Are Developed Might Kill Us

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I've known a lot of scientists, and two things almost all of them have in common are an absolute uncompromising belief in the power of modern scientific thinking and a complete disdain for folk wisdom.

So I couldn't help but be intrigued when I first heard about Cassandra Quave.

She's a leading scientist working in antibiotic resistance who also believes in the power and wisdom of traditional traditional healers.

Is she deluded, or might shamans play a critical role in safeguarding the health of humanity?

We have this idea that modern medicine is the best medicine there ever is or ever will be, but what many people don't realize is that modern medicine is only possible because it was built off of traditional medicine.

Welcome to People I Mostly Admire with Steve Levitt.

Professor Cassandra Quave, an ethnobotanist at Emory University, tells her story in an amazing new memoir entitled The Plant Hunter.

Her right leg was amputated when she was three years old, and a subsequent staph infection nearly killed her.

Antibiotics saved her life as a child, and now she's on the hunt for new antibiotics and doing it in a way that's all her own.

I'd love to start with the issue of antibiotic resistance.

I've never really taken it very seriously until I started reading your book, The Plant Hunter.

Do you have the facts about how many people die each year because of drug-resistant bugs and what the projections are for, say, the year 2050?

Yeah, absolutely, Steve.

There was a report that came out in 2016 by the UK government, and this report estimated that there are around 700,000 deaths each year currently due to untreatable antimicrobial resistant infections.

But what was really shocking is that number is projected to reach 10 million a year by mid-century.

And if you think about the horrors that we've gone through in the first year of COVID alone, where we lost 2 million lives, we're looking at five times that by mid-century.

What really struck me as crazy is that right now

there are about 10 million deaths a year from cancer worldwide.

And you're talking about roughly the same amount or more deaths from antimicrobial resistance.

The obvious answer to antibiotic resistance is to just keep developing a steady flow of new drugs to stay one step ahead of the bacteria.

So how are we doing in that regard?

Unfortunately, we're not doing very well.

These are single-celled organisms that are incredibly wily.

They are able to outwit a lot of our new therapies.

And we experienced the boom in antibiotic discovery, especially in the 50s and 60s following the discovery of penicillin.

We haven't had a new class of antibiotic marketed that was discovered basically after the 1980s.

There have been new approved antibiotics that have come to market since then, but these are what we call redo drugs.

These are drugs in many cases that were already in the market, have lost a lot of their efficacy.

And then basically chemists and microbiologists make some small modifications to those chemical blueprints of the antibiotics.

And by doing so, restore or improve the activity so they can work once again against these pathogens.

The challenge is anytime you put that kind of direct selective evolutionary pressure on a microbe, it's bound to develop resistance.

Among the activities that we do that you think are probably most likely to increase antibiotic resistance, Where would you rate the use of antibiotics with livestock?

The use of antibiotics within our food system, both with livestock, but also on fruit trees, is a really big problem.

Also, antifungals.

The rampant use of antifungals in the tulip industry and in cultivation of roses.

We are putting tremendous amounts of these compounds out into the environment in order to support an agricultural system that's dependent upon this idea of monoculture, basically growing genetically the same things in one field.

It really opens us up to more and more threats.

We know, for example, in the soil, there are variations of different fungal pathogens that now are resistant to those fungicides that are sprayed on these fields.

And so we have to really treat these as the precious resources that they are and not abuse their use at such large scale.

As a lay person, what I learned in school is, well, we had these incredible successes with penicillin and streptomycin that back around 1900, infections were the leading causes of death, pneumonia and tuberculosis and syphilis and diarrhea.

And then we vanquished these diseases.

And I had thought we were just still living in that wonderful world where we were beating the bacteria.

But I'm just completely wrong.

If you think about life in the pre-antibiotic era, other forms of infection like malaria, just getting a scratch in your garden and getting an aggressive skin infection could kill you.

And when antibiotics came along, it was the game changer in medicine.

It made childbirth more safe.

It made cancer therapy safer.

It made elective procedures or other required types of surgeries safer.

We really haven't recognized the threat as it stands because as we lose these antibiotics, as we lose drugs that can help us to fight back these infections, it's going to undermine modern medicine as we know it today.

So tell me about drug development.

What are the scientists doing?

Where do they come up with the molecules that they expect will serve as antibiotics?

Within every ecosystem, bacteria are at war with other organisms to defend their space, to fight for resources, for food.

And so mid-century, scientists discovered that there are certain compounds that bacteria and fungi can produce as part of this defense process.

Traditionally, many of these drugs came from what we call natural products, any compound that is produced by a living organism.

So, natural product scientists today look at chemicals found in soil microbiota.

They might look at chemicals produced by extremophiles, these are microbes that live in extreme environments, but they also look at marine organisms like sponges.

They can look to large fruiting bodies of fungi, what we know as mushrooms, and they can also look to plants.

The original antibiotics all came from the soil microbes, and there were soil samples being sent to pharmaceutical companies from all over the globe in the search for these novel compounds.

So initially, the scientists looked to other living creatures that were fighting the bacteria and seeing what we could extract from them that was useful.

But I would have suspected that in the modern age with artificial intelligence and computer modeling, that we'd be doing something very different now with computers trying to guess.

Is that not true?

Well, now where they've taken a lot of this process has been to looking at what they call cryptic genes.

So genes of these organisms that are not typically expressed unless they're put under certain selective pressures.

And this process of genome mining.

So looking deeper into some of these different microbes to stimulate them basically to produce different types of compounds.

There are a lot of compounds produced in nature that can be very effective at killing bacteria that harm us or slowing down their growth.

The challenge though is in finding those compounds that not only act against the pathogen or the bad bacteria, but also can do so without causing a lot of harm to our human cells.

There's a lot of toxic material out there.

The trick is finding the ones that are safe for us to use as well.

And how important is the human microbiome?

It's amazing.

We're probably more microbe than we are human when you look at all the genes that are in our bodies.

And by the way, there are lots of different types of microbes depending on what part of the body that they're colonizing.

If you think about the surface of your skin, maybe your forearm is dry like an arid desert, but your armpit, that's almost like a humid rainforest, right?

So you have different microbes that grow there.

And that is also one of the challenges that we've faced in in how we use antibiotics today is because in the past, many of those microbial natural products that were preferred to develop as antibiotics were those that had what we call broad spectrum activity, meaning that they were effective against many different types of microbes that could be causing disease in the body.

Imagine if a patient's extremely ill in the hospital and you don't know what the cause is of that infection.

You have to take an educated guess based on symptoms.

Having a broad spectrum antibiotic can be really useful in that case to ensure that you grab a broad array of things that could be causing the disease.

The challenge, though, is, of course, those broad-spectrum antibiotics are also attacking all of what we call your good bacteria or those members of your microbiome that are really important to helping you maintain a state of homeostasis.

With really long-term antibiotic therapy, you can essentially wipe out a lot of those commensal microbes or good microbes and then open up ecological niches for some of these quote-unquote bad bacteria.

I'm curious, is it really that the science isn't working or somehow the economics broken?

Because I have more faith in science than I have in economics.

Are there compounds out there that could be great, but the economic realities make it not worth the trouble of developing them?

The science has some definite challenges, but the economic model is really a mess.

There have been examples of companies that have brought out new drugs which were FDA approved, and then not long after the company's folding due to bankruptcy because of the extreme economic burden of post-approval monitoring.

So, when a new antibiotic comes out, your typical infectious disease doctor isn't going to want to use that brand new drug right away because there is a necessity to save back your best tools for the most extreme patients.

And so, they're going to go with the drugs that are already probably off patent first and see if that will work against against the infection and they use those as a reserve.

So economically, that's not great because you've just invested a lot of money into a drug that's going to sit on the shelf.

And developing these, by the way, is no trivial matter.

I've heard numbers ranging from 800 million to over a billion dollars to bring a new antibiotic to market.

If you look at other spaces within the pharmaceutical world, Economically, it makes much more sense to focus on drugs that treat chronic disease.

So heart disease, hypertension, diabetes, things that people will need to take every day for most of the rest of their life.

Antibiotics really don't fit the mold when it comes to the current way that we market these drugs.

Reading your amazing book, The Planhunter, it seems like you've embraced a radically different vision for finding new antibiotics than most of your colleagues.

Tell us about that approach.

Well, to me, it just makes common sense, though to others it's kind of, like you said, a radical approach.

Our existing antibiotics work by either slowing down the growth of the microbes, they kind of stop their ability to replicate.

And there are other antibiotics that work as bacteriocidal agents.

So these are drugs that kill the microbes outright.

I've had the great honor to work with many different healers from many different medical traditions around the world, whether it was in the Amazon rainforest or in the high mountain ranges of the Balkans or in Mediterranean islands.

And I've learned that for them, medicine is not just about kill and destroy a threat.

Instead, it's about how do they use the resources in their environment, in many cases plants, to restore balance in the body.

And that kind of perspective really led me to think deeper about whether could there be other ways of addressing these types of aggressive antibiotic resistant infections.

There are two kind of key areas where my research has taken a different path.

Number one is I'm really interested in microbial behavior.

All the listeners can probably identify with this concept of a bacterial biofilm.

When you wake up in the morning and you run your tongue over your teeth and you feel that kind of slimy, gritty texture on your teeth, that's an example of a microbial biofilm.

What can happen in certain types of infections is that these microbes can attach to surfaces in your body.

They can attach to your heart tissue or to your bones, or if you have an implanted medical device, such as a knee replacement or some artificial pins or even an IV catheter, they can attach to that.

And when they do, they will exude that kind of slimy substance that you feel on your teeth.

And it's really difficult for antibiotics to penetrate that.

And it takes antibiotics more time to get through that kind of sticky substance.

So let's say that if we had a drug that could stop those microbes from sticking to surfaces, would that allow our antibiotics to be more effective in the body?

And would that allow your immune system to more rapidly take out those pathogenic invaders?

So instead of trying to kill the bacteria, you're trying to work on the biofilm so that it's just harder for them to stick to anything.

Yeah, that's one approach.

If you think about it from the perspective of evolutionary fitness, can I make them less fit?

Or can I also target their offensive measures?

Microbes will actually communicate with each other using the release of these chemical signals.

So I'll give you the example of the pathogen Staphyloccus aureus, which many people may know by its other acronym of MRSA or MRSA.

So MRSA can basically release these peptides into the environment and when you reach a certain density of those signals, all the cells recognize that as, okay, there's enough of us present.

Let's ramp up production of toxins.

Bacteria produce toxins not only to defend themselves from attack by the immune system, but also to access food from your body.

By destroying your body's tissues, that's releasing nutrients that are important to their survival and enables them to spread more throughout the body.

And so I'm interested in looking for ways to block those systems.

When you're talking about going after the biofilm or going after the way in which the bacteria communicate with one another, those are novel.

Those are new approaches that haven't yet been proven.

Exactly.

There's been a lot of great groundbreaking science in this field, really trying to develop a better understanding of these systems in labs labs across the world.

And some of these labs, including my own, have even discovered new molecules that specifically target those systems.

The challenge is there's no established regulatory pathway to get such a type of drug approved, and there are no examples of drugs that do this that are already out on the market.

I know lots of people who believe in natural medicines and alternatives to Western approaches, but they are invariably unscientific or even anti-science.

And of course, I know lots of doctors and medical researchers, and virtually all of them have complete disdain for traditional approaches, folk wisdom, shamans.

You've got one foot in each of these two worlds, and somehow you don't see the contradiction that almost everyone else feels.

We have this idea that modern medicine is the best medicine there ever is or ever will be.

But what many people don't realize is that modern medicine is only possible because it was built off of traditional medicine.

Some of our most important pharmaceuticals, these are drugs that are listed by the World Health Organization as essential medicines.

Many of these originated in plants.

And those plants, by the way, were those species that were being used by healers to treat similar diseases.

So when we think about some of our major therapies for pain, aspirin from the willow tree, codeine, morphine from poppy, when you think about therapies for cancer, many of these came out of plants that were used to treat a number of different diseases.

You have etopicide inspired by compounds from the mayapple.

You have taxol from the yew tree, campothesin from the Chinese happy tree, vincristine, vimblastine from the Madagascar periwinkle.

I could go on and on.

Human medicine has developed over centuries and centuries of trial and error.

And if we're going to find the medicines of the future, we have to recognize, number one, where our current medicines come from.

And number two, take a really hard look at what our future holds, because we are in a biodiversity crisis right now.

We're losing species faster than we can study them.

We have 374,000 species of plants that are known to be on Earth.

And out of those, humans have sorted that 9% of all plant life on Earth has some medicinal purpose.

So there are around 33,000 species that we have documentation of that have been used in some form of medicine.

These have not been studied for the most part.

I would estimate that we're still in the low hundreds of species that have been evaluated with any level of rigor.

Some modern scientists and medical practitioners just don't see the value of herbs.

And then you have on the other side, practicing herbalists that don't recognize the need for the science.

And there's also a lot of misconceptions around the power of herbs.

There are some things in nature that will definitely kill you.

And then there's also this idea that some plants can cure everything.

I can't tell you the number of people that come to me with questions about cannabis.

And cannabis is a great plant, and it's been used by humans for a very long time, but it's not a cure-all.

I think many Western scientists would say, of course, plants and herbs are a valuable resource for finding new molecules that can help humans.

But you go further in that you take very seriously the role of traditional medicine and of healers.

Social sciences and the natural sciences have this artificial barrier between them.

We just don't know how to communicate across these different areas of science, across the humanities, and into the medical sciences.

Communicating that way opens up so many more creative ideas.

I also really value having a very diverse team.

To do the kind of work that we do, we really have to have a mix of expertise.

So I have pharmacology students that are studying the mechanisms behind how these drugs work.

We work with microbiologists.

We have natural products chemists that can look into the details of how to read those chemical signals of nature.

And then we have more on the anthropology side and folks that look at historic text and the botanist, of course.

If we're going to make breakthroughs in the future in medicine, we have to be more open to these kind of multi-disciplinary angles of looking at problems.

Cassandra, could you go into detail about some of the traditional healers who've influenced you?

One of the first healers that I worked with was Don Antonio Montero Pisco, who is an ayahuasca shaman from the Peruving Amazon.

Don Antonio started training as a healer, as an apprentice under a shaman when he was eight years old.

His entire life was dedicated to learning the wisdom that others had gained from ancestors.

I met Don Antonio just after my 21st birthday, and it was my first trip to the Amazon.

And I was there to work as a research intern, helping him out around his garden.

But he really took me under his wing and taught me a lot about plants.

Up until that point, I had been a pre-medical student in the mindset that medicine is surgery, medicine is pharmacy.

And he really taught me not only about the amazing pharmacological potential of nature, but also about how he related with his patients and how he related with the natural world when looking for ways to heal his patients.

He also consumed a hallucinogenic beverage known as ayahuasca.

Now, ayahuasca has this cult following.

There are ayahuasca cults in cities, in the U.S., in New York, Atlanta, and LA.

But from what I learned from Don Antonio, ayahuasca wasn't something that you gave to the patients.

On occasion, he would, but more commonly, it was something that he prepared as a way of communing with the forest spirits, as a way of understanding how to diagnose the problems that his patients were suffering from, and also how to talk to the plants plants and find which medicines would heal the patient.

Of course, this all sounds way out there, right?

But this idea that people would take this in some apartment in the city outside of its true medical context is just for me really a bastardization of what this formulation of plants is all about.

On the other hand, I understand why people are curious about psychedelics.

And as a scientist, I'm fascinated with where the science is going.

It's all about putting the science first to really see what we can gain from these therapies, but also to do it with a deeper level of respect for where these medicines came from.

Yeah, and it must be a race against time if you're trying to draw up the wisdom of traditional healing, because my guess is that it's all in the older generations, not written down, and that the younger generations in most places probably have very little interest in it.

Yeah, I've seen that in the Amazon.

I've also seen that, ironically, in Europe.

When I met Zia Elena, she was in her 90s, someone I would call a master healer.

She lived in an ethnic minority village known as the Arboresh.

These are descendants of Albanians that fled the Ottoman invasion of the Balkans five centuries prior.

And they speak their own language in addition to Italian.

She treated people with a wide array of dermatologic conditions, different types of rashes, including bolus rashes, fluid-filled pustules on the skin.

And she was using both prayer and plants in her rituals.

She didn't have an apprentice, and so she urged me to record a lot of the details around these therapies.

And those have been published in a journal of folklore research, but we're seeing a loss in the transmission of these oral traditions of knowledge from one generation to the next.

This also is coinciding with a linguistic crisis.

We're losing a lot of the variety in languages that we have across the globe.

And as those languages are no longer spoken, you also lose a lot of the cultural wisdom, including medical traditions that aren't being necessarily recorded.

You're listening to People I Mostly Admire with Steve Lovitt and his conversation with Cassandra Quave.

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Hey, Levitt.

Hello, Morgan.

So our listener, Mari, wrote in with a question.

When to fight and when to give up.

She's talking about the tiny injustices of everyday life and is wondering if there's some scientific or mathematical approach to standing up for yourself.

If your food delivery is missing an item and they refuse to refund your money.

Or, for example, the other day she was on the phone with UPS for an hour in an attempt to recover her $11.38 for a missing package pickup.

Well, I don't know if I have any magic bullets on this one, but I do know how I approach these kind of situations myself, very much like an economist, and maybe there's a hint of something interesting in there.

I have three rules.

The first rule is that I worry a lot more about people who are intentionally ripping me off than when it's happening because of incompetence.

I'm much more forgiving about incompetence.

On the other hand, when I feel like I'm actually a mark where someone's actually targeting me, then I get much more outraged.

The second one is I think about is this a one-time case or will this happen over and over?

If it's just one time, it's not nearly so important to fight as if you think that this is gonna happen again and again and again.

If there's the equivalent of a a bully out there who's going to figure out that you're weak and come after you over and over and over, then you really need to fight.

And this actually harkens back to our episode with Robert Exerod on the repeated prisoner's dilemma, where one of the three key rules for life was being provocable.

Now, it doesn't make any sense.

If it's a one-time event, you don't have to fight back because you don't have to defend yourself against future infractions.

But if it's going to happen over and over, then that's where I really want to stand up for myself.

And what's the third thing?

The third third thing is, and this is just a rule I adopted for myself when I was maybe 23 years old.

And the rule was, I'm going to take some dollar value, which started out at $5,

and I will not worry about any transaction that's less than $5.

When I was young, every single decision I made, I put time and effort into trying to get it right.

If I thought it was a dollar versus 50 cents, I would take a moment and I'd ponder, is it really worth 50 cents to me?

And then at some point, I'd say, wait, I'm wasting so so much mental energy.

If you add up all of these decisions over an entire year, it just doesn't add up to real money.

And I could do more valuable things with my brain power than worry about these little things.

Essentially, you're putting a dollar value on your time.

Yeah, but somehow it's even deeper than that.

It's the idea that you don't need to optimize.

And I have to say, it is one of the most surprising, happiness-enhancing decisions I've ever made.

And it frees me up to do things I care much more about.

I think another thing Mari's worried about is this accumulation of tiny injustices.

It's not just any one

thing that's bothering her, but it's maybe when she has to deal with five moments where she feels like she's getting beaten down or walked all over.

So there, I would say, to the extent that she's being injusticed by five different companies or people or settings, then I would do my best to not worry about that.

To the extent that the same person

or organization is doing multiple injustices over and over and over, then that's where, Mari, you got to be provocable.

You can't let people walk on you over and over.

Right.

I think there is some power in walking away, though, if things aren't serving you.

That's also a good point, Morgan.

There's one choice to accept the injustice.

There's another one, which is to fight it.

And there's a third one, which is just to walk away and say, I'm going to have nothing to do with this organization ever again.

Well, Mari, I'm not not sure if you can walk away from UPS, but good luck fighting other tiny injustices.

If you have a question for us, we can be reached at pima at freakonomics.com.

That's p-i-m-a at freakonomics.com.

It's an acronym for a show.

Steve and I read every email that's sent, and we look forward to reading yours.

I've learned a ton from our conversation so far, but somehow I've done a really bad job of opening up Cassandra's human side, which I suspect will be fascinating.

So that's where I'd like to take our conversation now.

And also, all this talk about bacteria has got me wondering whether her approach might also help with viruses, maybe even COVID-19.

Your early years were not easy.

You were born missing missing some bones in your leg.

That leg was amputated below the knee.

You almost died of a staph infection when you were three.

How many surgeries have you undergone in your life?

Oh my gosh, I've lost count.

On average, it was usually one or two a year from the age of three to around 18 or 19.

And then I've had, thankfully, fewer in adulthood.

I had issues with bone spurs.

My bone would basically grow out of my skin where my amputation had happened.

I only had a very thin layer of scar tissue there because of the infection.

So that really had lifelong consequences for my mobility.

In a way, these experiences of dealing with really serious illness and really serious recoveries throughout my childhood shaped me in the ways that I'm able to communicate with people that, for lack of a better word, have also suffered in some way.

And for the healers that take care of them, there's a shared sense of experience.

And that's really helped to serve as a map of how I engage with people when talking about these very difficult subjects.

So let me just say, Cassandra, I'm so sorry that you had to face that as a child.

I suspect most people's spirit would have been crushed, but somehow you've emerged on the other side.

All these interactions with the medical system, Did it leave you with a positive feeling towards modern medicine or a negative one?

It's been both.

When I was very young, I felt very much like an object.

And I describe it in the book as, you know, here's the bearded lady in the circus for all the medical residents to come and talk about all of her weird abnormalities.

But I was so lucky that as I approached puberty, I was taken to a new orthopedist, Chad Price, and he was the first doctor to really engage with me as a person.

He took the time to to explain to me, not just to my mom or my dad, what he was going to do to my body.

And just that alone made a huge difference for me.

So in your book, The Planet Hunter, you describe a very different type of healing experience than a Western one when you were with Don Antonio and he noticed you were achy and moving more slowly than usual.

So it was part body aches, part just like mental angst, because this was near the end of my college career and I was

really torn and what I needed to do with my life.

I really always thought I would go on to be a surgeon.

My heroes had repaired my body and I wanted to do as they did.

I also had this feeling that maybe that's not the right path for me, but I still didn't really understand what the right path was.

And I'd also been suffering from phantom pains.

And phantom pains are kind of like electrical shots that shoot down your limb, basically where your body's looking for the limb that's not there any longer.

They can be really annoying and painful.

There's no solution, right?

There's nothing you can do.

Yeah, it's one of those things where you can massage the leg.

Some people try acupuncture and I can go months without having them.

And then all of a sudden it'll just be like all night long.

It happened to me just last week.

And so I was experiencing all of that.

And he said, Tuesdays and Fridays are good days for healing.

It's Friday.

Why don't you meet me at the edge of the woods?

And I'm like, okay.

And I came to the edge of the woods where the jungle began, and he had a stool set up and a bowl with some different herbs inside of it and water.

And he held in his hand this device known as this shikapa bundle.

So shikapa, it's a kind of hand fan that's full of leaves from a grass plant.

And when you shake it, it makes this amazing kind of whooshing sound.

And so he had me sit down and poured this bowl of herb water on top of my head and then began whistling and singing.

And then he made requests to the spirits of the forest to heal me, to make me feel better, and kept this kind of rhythmic whooshing.

I'd never been to a psychologist or therapy or even massage therapy at that point.

Those weren't really offered as something for me to take advantage of as a kid going through all these different surgeries.

And so this was really my first experience with something other than surgery or pharmacy.

This went on for a while and I just really felt all of a sudden very in tune with the sounds of the forest, with the monkeys that were crawling the tree above us, with the sound of the wind blowing through the leaves, the butterflies going by.

It just made me very aware of my surroundings and very aware of myself.

And I just felt incredibly grounded.

I would almost say like a religious experience.

When I returned to the U.S.

and had to make that final choice of whether or not I was going to go forward with attending medical school, I decided not to and decided to go in this completely other direction to study ethnobotany.

And my parents didn't even know what that meant,

but it was the right choice for me.

And it's ironic that I did end up back in a medical school as a professor, but not a practitioner.

Can you describe the process, the steps required to go from, hey, I wonder if some plants in the Amazon rainforest might hold the key to the next blockbuster antibiotic, to actually finding the right plant and eventually creating that antibiotic?

It's a long process.

It starts with permits.

You can't just go into another country and take plants without permits.

I haven't worked on a lot of plants from the Amazon because it's been really difficult in the past to get research permits to pull species out because there's been such a history of colonial exploitation where people have taken things and then not brought back the benefits to local people.

So we have to think about how to set up agreements with different partners in different countries that are under the principles of something known as the Nagoya Protocol on access and benefit sharing, which is part of the UN Convention on Biological Diversity.

And the basic premise there is that you get access to these materials under the terms of benefit sharing, that the people providing that access would also reap some rewards from it.

But that already presumes you know what you're looking for.

Like you've said, there are hundreds of thousands of plant species.

How do you know where to start?

In my scientific talks, I will often show this map on the wall.

So if you can imagine a map of the world, there are 36 areas that are shaded in brown, and these are known as the 36 hotspots of terrestrial biodiversity.

Each hotspot represents a region that has at least 1,500 endemic plant species.

So these are species that are only found in that part of the world.

And it also has to have at least 70% of that ecosystem under threat already threatened or removed.

So there's an urgency to start there.

My lab team and our network of collaborators across the globe work in these biodiversity hotspots.

We've got work ongoing in eight of the 36 hotspots.

For example, in the Balkans, we're working with our research partners at the University of Pristina in Kosovo.

It's a long-term relationship with those communities that's facilitated by our research partners that are based in that country.

And the reason you're talking to people is because they have knowledge of the local

vegetation.

And it's from those conversations where you narrow down from the many endemic species to the handful that you'll put your attention to.

Exactly.

And we really look for communities that are isolated in some way.

The more isolated the community is, the more likely they're going to be highly dependent on their natural resources for their survival.

And so this is one of the reasons I like to work on islands or in isolated mountain range villages.

And some of these communities in the Balkans, they're basically cut off from the rest of the world for months and months out of the year because the snows are so bad, the roads can't be passed.

And so they have to grow or wild harvest all their food stores to last them throughout the winter.

And they have to do the same for all their sources of medicinal plants.

So working with them, we then go out with local people.

We collect what are known as herbarium voucher specimens.

An herbarium is a natural history collection.

And if cared for properly, these can last at least six centuries because that's how old some of our existing collections are.

We then collect like a grocery bag full of whatever plant tissue locals are saying they're using for medicine.

And this is where local knowledge is incredibly important

because if they say that they boil the leaves in hot water and then use it as a medicine, in the lab, it's important that we also replicate the way that medicine is processed.

Right.

So you found a plant that you think might be promising, but then even to go from there to understanding the specific chemicals, there must be a lot of work, a lot of science that goes into that, right?

Oh, absolutely.

I have the herbarium, which is where we keep our natural history collection of those pressed flat specimens.

We have the phytochemistry lab, which is where we make the extracts and study the chemical makeup of those extracts.

And then we have the microbiology and dermatology lab, which is where we examine their pharmacological properties, both against pathogens, but also against human cell lines.

Of all the plants you've worked with, do you have one that you think is most likely to change the world?

There's a couple I'm really excited about.

We have identified four compounds, three from the Brazilian pepper tree, which also grows in Florida, and also from the European chestnut or sweet chestnut leaves.

The one from the chestnut leaves is a brand new compound to science.

It was a new discovery.

The ones in the pepper tree fruits are known compounds, but the activity had never never before been reported.

And these all shut down completely the ability of staph bacteria to produce an entire suite of toxins.

So staph as a bacteria causes lots of problems in the body.

It can lead to sepsis, infections of the heart, the bones, different tissues, your skin.

And those are all very severe and aggressive diseases that rely heavily on their toxin production pathway.

So that's the long game I'm going to go after.

But on the short game, where I really want to go with it is to explore how we could use it to improve the treatment of a disease known as atopic dermatitis.

People know this disease is eczema.

You're constantly itchy and just uncomfortable.

We currently use immune therapies, we use steroids, and there's just a need for a new approach.

And I really believe that one of these compounds could be the answer to that approach.

That's great.

So we've been talking about bacteria, but of course, it's a virus, COVID-19, that has everyone's attention.

Would you expect a plant-based approach to be effective against viruses as well?

Oh, I think so.

Plants are also impacted by different viruses.

So they also have defense mechanisms against viruses.

And we've actually been working on COVID in the lab.

We have what's known as a pseudotype model.

So basically, we take a piece of the virus and use that to test against all of our extracts.

Wait, so you can buy on the market a part of the virus that you keep in your lab to experiment with?

Yeah, so to work on the virus responsible for COVID-19, that virus is called SARS-CoV-2.

And that virus is a biosafety level three virus because it is, as we all know, transmissible through the air as a respiratory virus.

So my lab is a level two lab.

Okay.

And so we're not able to work with the whole intact virus in my lab.

We have the piece of the virus that we're most interested in.

So you have the spikes.

Essentially, they send you the spikes without the bad stuff attached to it, more or less.

Exactly.

So if you think about the virus and the surface, it's the little spike that kind of pokes out.

And so we're looking at how that spike and the ACE2 receptor on cells engage in the presence of some of these different plant compounds and found that two of our extracts are actually quite potent.

So we're getting ready to submit this paper and I'm really looking forward to it.

It's also one of those things where I've been very cautious because I know that when papers like these hit the news and it's medicinal plant works against COVID, it's like, I have to be really careful to explain, this is in a test tube model.

This has not yet been shown to work in animals.

We don't know the safety in animals or especially in humans yet.

So we're very careful in how we communicate what our findings are so that people don't just go out and start digging these plants up to use.

So, you seem to be fearless at so many different levels.

You head off to the Amazon rainforest for long periods of time as a college student, knowing that you're at an elevated risk of infection with a prosthetic.

You chose to do iconoclast research.

You wrote a popular book before getting tenure, which can be queer suicide, at least in academic economics.

Do you lack common sense or what's the deal?

Sometimes I worry about that.

When I feel passionate about something, I go for it.

My fullest version of my life is doing the science I love, but also communicating that love for science with others and with the hope that this will, in the long run, help people that are dealing with infection or other types of illness in the future.

I interviewed B.J.

Miller for this podcast.

He's a doctor who's battling for people's right to die with dignity.

And he's also a triple amputee.

Very early on in his journey, he stopped trying to hide his damaged limbs.

He abandoned flesh-colored prosthetics.

And he described that as being really important for him emotionally.

How have you dealt with being perceived as different?

I went through something very similar to him.

As a kid,

I was always the odd disabled girl.

Imagine all the insecurities that teenage girls have about their bodies.

And then imagine, I'll say, having a prosthetic and being riddled with scars all over your body.

I spent so much time trying to hide that part of me through the clothing I selected or the ways I would engage with people, staying sitting instead of walking.

Over time, I became more confident.

And I went to my prosthetist, Will, who's just great.

He's been my leg man since, you know, college.

He's used to my crazy adventures and my weird needs for adaptations on my leg

but I remember going back to him and I said Will I'm like I'm tired of this I want you to strip all this fake plastic skin off and this foam stuff off the leg I just want a metal pole let him look at that he's known me for a long time and he said you know Cassie I have another idea for you he showed me these websites of two companies they had these amazing covers for the prosthetic legs they had designs that looked like Iron Man like a stormship trooper.

They had very like botanical ones.

My oldest son really pushed for Iron Man.

I was like, I don't know.

In the end, I went with this very kind of steampunk one.

I got in silver and it changed not only the way that I engaged with people about my leg, because all of a sudden, instead of being this thing that I felt I needed to hide, it was something that became a conversation starter and something that was viewed as art and beautiful.

And the way I thought about my scientific ideas really followed that same path.

And I stopped worrying so much about what other people thought of my ideas.

I still have to put a lot of effort into educating people about the value of natural products so I can get some grants funded.

But I let go of some of that angst because in science, you're so driven into different kinds of buckets.

You have to be this kind of chemist, or you have to be this kind of biologist, and you can't do things in between.

And I just said, you know what?

I'm going to do what I'm going to do.

I love people who aren't afraid to be themselves.

People who find the exact thing that excites them and they find a way to build a life around it.

It's a risky strategy, but when it works out like it has for Cassandra, it's a beautiful thing to behold.

Now, the younger version of me would have scoffed at Cassandra's approach.

What could folk remedies have to offer that isn't trumped by modern medicine?

But I have to to say, my experiences over the last 25 years have both greatly reduced my faith in modern medicine and greatly increased my faith in more holistic approaches.

Modern technology and the scientific approach, they're awesome tools, but I find that they're often wielded blindly and clumsily.

The need for thoughtfulness and wisdom and compassion has never been greater.

And hopefully with a little luck, Cassandra's combination of science and wisdom just might one day save your life.

Thanks for listening.

We'll see you next week.

People I Mostly Admire is part of the Freakonomics Radio Network, which also includes Freakonomics Radio, No Stupid Questions, and Freakonomics MD.

This show is produced by Stitcher and Renbud Radio.

Morgan Levy is our producer, and Jasmine Klinger is our engineer.

We had help on this episode from Alina Coleman.

Our staff also includes Allison Kreglow, Greg Ripon, Rebecca Lee Douglas, Zach Lipinski, Mary DeDuke, Ryan Kelly, Eleanor Osborne, Emma Terrell, Lyric Voudich, Jacob Plementi, and Stephen Dubner.

Theme music composed by Luis Garra.

To listen ad-free, subscribe to Stitcher Premium.

We can be reached at Pima at freakinomics.com.

That's P-I-M-A at freakonomics.com.

Thanks for listening.

So if someone wants to be socially responsible, they should throw their antibacterial soap in the garbage and just use regular soap.

Yeah, regular soap works great.

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