The Hidden Chemistry of Plants: How Nature’s Survival Strategies Became Our Medicine

Dustin Grinnell (00:00:00 --> 00:02:44)
I'm Dustin Grinnell, and this is Curiously.

What do you think about when you think about plants? Maybe you think about your garden, what you hang in your window, maybe a flower you give to a loved one on Valentine's Day. You probably don't think of plants as an intricate system of biochemical pathways containing a galaxy of compounds that help sustain vital metabolic processes and defend against insects and challenging environmental conditions. You also might not think about plants being a rich source of of natural compounds that have a variety of beneficial effects on humans. In short, plants are remarkable chemists.

Unable to flee from threats or environmental pressures, they must rely on chemistry to endure. Some of these chemicals have potent medicinal properties capable of addressing human health issues. It's now well established that a significant portion of prescription drugs have origins in plants or are directly derived from natural compounds found in plants. For instance, many widely used medications are synthesized versions of compounds found in plants. Examples include aspirin, originally derived from willow bark, morphine from the opium poppy, and Taxol from the Pacific yew tree.

In 2013, I began working as a science writer at the Whitehead Institute for Biomedical Research in Kendall Square in Cambridge, Massachusetts. Not long after starting, the institute hired an exciting new faculty member, Jingke Wang, a biochemist and plant biologist whose research sought to understand the chemical diversity of plants and how it evolved over time. Jinka and I shared the same office suite and ran into each other often in my work capacity as a writer of development materials to help publicize his work as well as encourage funding for his various research projects, one of which involves studying the chemistry of medicinal plants to understand their potential for medicines. It was this project that inspired me to travel to China in 2015 to visit with organic chemists who were studying traditional herbal remedies at the molecular level. I worked at the Whitehead Institute for 2 years, but Jinka stayed for a decade.

Last fall, he left the Whitehead for his dream job to become the founding director of the Institute for Plant-Human Interface at Northeastern University. As head of the innovative organization, Jinka's in the process of recruiting new faculty members and getting his research projects off the ground. I asked Jinka to come on the podcast to talk about his fascinating research, the role traditional Chinese medicine played in his early life, how science is done and how scientists think, and so much more. I hope you enjoy this conversation with a truly brilliant scientific mind.

Dustin Grinnell (00:02:47 --> 00:02:48)
Jinka Wang, welcome to the show.

Jingke Wang (00:02:48 --> 00:02:51)
I'm glad to be here. Thank you for inviting me.

Dustin Grinnell (00:02:51 --> 00:03:08)
I was hoping that to start off our discussion of plant science and plant biology, I was thinking maybe we could talk about, or you could tell me this kind of legendary story of the Chinese botanist. Is it Tu Youyou?

Jingke Wang (00:03:08 --> 00:03:13)
Yeah, Tu Youyou, that's how you call her name in Chinese. Yeah. The last name always goes first.

Dustin Grinnell (00:03:13 --> 00:03:14)
That's right.

Jingke Wang (00:03:14 --> 00:03:14)
Yeah.

Dustin Grinnell (00:03:14 --> 00:03:28)
Because it relates so deeply, I think, to your work and inspiration for your work, I was wondering if you could just kind of talk about how that project that she did and how it went from kind of herbal remedies in the search for a cure for malaria.

Jingke Wang (00:03:29 --> 00:03:46)
Sure, yeah. So Tu Youyou or Youyou Tu in Western calling, she's a remarkable woman from many aspects. Youyou Tu, so she's known for her work in discovery of artemisinin who saved then that saved millions of lives.

Dustin Grinnell (00:03:46 --> 00:03:48)
This is a malaria cure.

Jingke Wang (00:03:48 --> 00:04:50)
Yeah, that's an anti-malaria drug. And she's the first scientist, first woman to win Nobel Prize from China, born in China. She's also inspirational scientist and she works in my field. So at multiple levels, she's been an inspiration for me. So this name probably is known to many people now, but I think people probably don't know where her name comes from.

You know, Youyou. This Youyou is actually how the Earth bleat. This is kind of how her parents, coming from a line in Chinese poem saying there are wild deer bleat, yew yew is the sound, and the deer eat the wild Artemisia, so which many, many years later is the plant that produces Artemisinin, this magical drug. So I think it's just a little story that many people didn't know about. So she was assigned to this so-called Project 523.

Dustin Grinnell (00:04:50 --> 00:04:51)
This was what time period?

Jingke Wang (00:04:51 --> 00:05:10)
This is during the Vietnam War. So in the mid-'60s, the VM-9 just went to China, Chinese government, then asking for help in developing a drug for malaria, which is really kind of a very, very severe disease for local people during the wartime.

Dustin Grinnell (00:05:10 --> 00:05:12)
Because soldiers were succumbing to malaria.

Jingke Wang (00:05:12 --> 00:07:13)
So Youyou at the time was the head of her institute studying the pharmacology of traditional Chinese medicine. So she was assigned on this task. And before that, many people had tried a lot of compounds. I think over 200,000 compounds. By then there's no effective treatment.

So she kind of went into traditional Chinese medicine and going through a lot of ancient texts and trying to find something that may be relevant for this treatment. Eventually she went to this book authored by Ge Hong. So this is thousands of years ago, and there was a description of Artemisia annua or sweet wormwood, this plant, for treating a symptom that's really similar to malaria infection, which is intermittent fever. So she went into there together with thousands of other things, and she found, you know, this is the plant, the extract of that can cure malaria in a mouse model. But she was kind of stuck from that point because she then went in trying to identify the single molecule, the plant natural products that can cure the disease, but she couldn't succeed.

Eventually, she went back to that original text, actually describes exactly how the plant should be prepared. So it talked about a handful of the plant material, squeeze in cold water and drink that water, which is somewhat unusual because for typical Chinese medicine, herbal medicine preparation, you have to cook it. So then she felt, oh, maybe it's the heat that's preventing her from identifying the compound, so she switched the extraction method to cold ether. So that was a breakthrough. You know, from that, she kind of followed on the extraction, fractionation, eventually identified this single molecule called artemisinin, which is the malarial-killing agent.

Dustin Grinnell (00:07:13 --> 00:07:15)
And she won the Nobel Prize for that work.

Jingke Wang (00:07:15 --> 00:08:20)
Yeah, exactly. And the work carried on for decades. The action mechanism for the molecule was just discovered back in a few years ago in 2018. There's a very unusual chemical feature to Artemisinin. So it's called a peroxide, essentially two oxygen atoms linked together like a bridge. You don't see this very often.. And this particular peroxide bridge can be activated by iron, which is very rich in blood. So as you know that malaria is a blood-sucking parasite living, you know, in people's body. So when the malaria cell is really enriched with blood, it tends to activate artemisinin. So then becomes a free radical, then will inactivate many of the proteins. So it's really dangerous or it's fatal for the parasite, but doesn't hurt human. Mechanism itself is also a quite novel discovery in terms of the development of this saga over the past many decades.

Dustin Grinnell (00:08:20 --> 00:08:27)
And you said this story is particularly inspirational for you. Her work is inspirational. Why is that?

Jingke Wang (00:08:27 --> 00:08:45)
I think before that, you know, we kind of live upon thousands of years of tradition. People who were born and raised in China, including myself, We kind of just enjoy that as an outcome of thousands of years of wisdom, but without really thinking too much about it. It's just part of your life.

Dustin Grinnell (00:08:45 --> 00:08:54)
For thousands of years, these herbal remedies have been used and they have proven successful, but we didn't know the mechanisms.

Jingke Wang (00:08:54 --> 00:09:21)
Exactly. Or we kind of just felt, oh, these are natural. These are sometimes even thinking these are magical when they work. But Yu Yu Tu is one of the pioneers who went in and really to show that it's not the magic of the plants. Are specific molecules that are present in these plants, and we can use modern scientific approach to isolate that and make— turn that into modern medicine.

Dustin Grinnell (00:09:21 --> 00:09:57)
And these specifically, these chemicals within plants, these are metabolites? These are— maybe you could talk about kind of in general what kind of research questions you ask. I think it's probably useful to think about plant chemistry as like the primary metabolism, the secondary metabolism, and kind of talk about how plants have evolved to create metabolites for like a whole myriad of different things because they can't move. They have to deal with changing environmental conditions with their chemistry. And then that chemistry has led to all sorts of other things.

Jingke Wang (00:09:57 --> 00:12:12)
And you kind of touched upon the lifestyle of plants. So they are known as so-called sessile organisms. That means once they're seeded and rooted, they're just trapped in this one location. And if you think about the plant world, there are over 400,000 species we know, and they really spread across the whole planet. Some have to survive very harsh winter, some live and thrive in desert, some have to face challenges of pathogens, herbivores, day in and day out, and they have withstood the four seasons.

So to do that, it's really kind of hard for us and human beings and other animals to think about because we can put on gear, we can make shelters. Yeah, the plants can't. Yeah. So over hundreds of million years, that's also a really, really long period of time. They just evolved ability to make all sorts of weird, but in my eyes, beautiful natural products.

These are chemical compounds, and we also call them metabolites, and each one of them has its unique function, and it's really their language to interact with the world. Somehow humans just discovered their medicinal properties, and that's a really, really recent story. If we think about us, we kind of emerged around maybe less than a million years ago, and the history of using plants plants as medicines probably only in the last tens of thousands of years. So plants have been around doing this chemistry for the majority of the time. They're the main show for planet Earth.

Dustin Grinnell (00:12:12 --> 00:12:15)
They've been doing this for a lot longer.

Jingke Wang (00:12:15 --> 00:12:16)
Hundreds of million years.

Dustin Grinnell (00:12:16 --> 00:12:22)
And so they've seen a lot in that time. They've seen different 8 epochs, you know?

Jingke Wang (00:12:22 --> 00:12:23)
Exactly, yeah.

Dustin Grinnell (00:12:23 --> 00:12:40)
Talk a little bit more about kind of the diversity of metabolites. Like, you know, they have to attract pollinators, they have to fight off herbivores. Right. There's really like a universe of functions, universe of metabolites, isn't there? Yeah. If you think about all those species of plants.

Jingke Wang (00:12:40 --> 00:13:34)
Right, so I think many of us are familiar with metabolism. You know, animals have metabolism. Metabolism involves metabolites, so these are the compounds, and they are interconverted by enzymes. So these are proteins that catalyze chemical reactions in cells. So most of the metabolism we talk about is people think about primary metabolism. So primary metabolism does two things. One is supply the fundamental building blocks for cell. If you have a cell, you have the cell membrane, the lipids, we have DNA, so Primary metabolism supplies the DNA basis to construct our DNA. It also generates energy. So we know ATP, which can be converted from sugars we eat from food. So these are essential. Housekeeping.

Dustin Grinnell (00:13:34 --> 00:13:34)
Housekeeping.

Jingke Wang (00:13:34 --> 00:14:18)
Yeah. And you mentioned secondary metabolism. So it's an older term. Now these days we call it specialized metabolism because nobody wants to study something that's secondary, so the field comes up with this term specialized. So these are the type of metabolic systems you only find in certain species. And for example, a plant, you know, coffee plant produces caffeine, and caffeine is a specialized metabolite, and you don't see caffeine in any plant you encounter. That's just one of the millions of examples of specialized metabolism you would find in plants.

Dustin Grinnell (00:14:18 --> 00:14:20)
And why was it making caffeine?

Jingke Wang (00:14:20 --> 00:14:42)
That's a good question. I don't think it's fully resolved. My sense is it has some defense function. Some humans are relatively large-sized mammals, so having some caffeine, you know, just gets us high, but for smaller animals, maybe insects, that dose of caffeine could be fatal.

Dustin Grinnell (00:14:42 --> 00:14:56)
Because everything has a dose in biochemistry. So for us, it would be really hard to take a lethal or toxic dose of caffeine, but that's something very small. Oh, interesting. So it's like a sort of defense chemical.

Jingke Wang (00:14:56 --> 00:14:57)
Yeah, I think it has to be.

Dustin Grinnell (00:14:57 --> 00:15:07)
But for us, it happened to be, to have like sort of like a psychomotor benefit, like a cognitive benefit. What does it do?

Jingke Wang (00:15:07 --> 00:15:33)
It's, doesn't it like— Adrenaline receptor. Yeah, yeah. So I think it's a receptor in our body to sense tiredness. So adenosine is a metabolite of ATP. So once you consume ATP, the side product becomes perceived by this receptor that tells your body to kind of slow down. You should go to sleep. But if you block this receptor, it makes you wake up.

Dustin Grinnell (00:15:33 --> 00:15:56)
Do you think like an early human bit, like accidentally bit a plant and felt less fatigued and sort of ritual turned into drinking it? Like, how does— I mean, I'm really interested in how, like, humans just kind of co-opted plants and some, like caffeine, and then of course we'll talk about medicines and things like that.

Jingke Wang (00:15:57 --> 00:16:54)
But yeah. Yeah. So I think there are also observations of animals munching on plants that cure themselves. I think it probably was even earlier than humans. There's one kind of thought experiment I have during my meditation is to think myself as a hunter-gatherer because it's deep in our root and we were hunters and gatherers. Most of the time we kind of forage weird things we kind of find for food. And occasionally you may encounter something new. Hopefully your ancestors have passed down the knowledge to you that certain certain plants to eat, certain things not to eat, but you always kind of want to experiment. And what if you just chewed upon some coffee beans and that wake you up? This will be so remarkable experience, you would try to keep it and pass down generations about that knowledge.

Dustin Grinnell (00:16:54 --> 00:17:02)
What happens in this thought experiment? Do you think about potential benefits that a plant could have in your— do you mentally play that out?

Jingke Wang (00:17:02 --> 00:17:39)
Yeah. So I think we live in such a modern, in a way, artificial life. Sometimes you kind of lose sight of what would be the best way of living in terms of mental and physical health. Our genetic makeup was pretty much shaped by a hunter-gatherer lifestyle because that probably lasted hundreds of thousands of years and we're built for that. So, when I choose foods to eat, I kind of think about is that combination of diets will be something comparable of me being an hunter-gatherer.

Dustin Grinnell (00:17:39 --> 00:17:41)
Can you give me an example of that?

Jingke Wang (00:17:41 --> 00:18:15)
Yeah, so if I'm eating hamburger, right, so it'd be so much high fat, high carb that would never come about. And maybe once in a while if we kind of hunted a mammoth, so we will have a feast, but day in and day out, I'll be eating a lot of plant-derived materials. Yeah, some fruits, occasionally roots, and once in a while some meat. And I think that's probably the best kind of combination for me in terms of dietary health.

Dustin Grinnell (00:18:15 --> 00:18:27)
So you're not likely to eat a lot of boxed foods that have dozens and dozens of chemicals in it and that would never be present in our evolutionary past.

Jingke Wang (00:18:27 --> 00:18:56)
Right, yeah, there's so many additions of compounds to our food chain and mostly through processed foods that we, we means human beings' bodies, have never seen in our evolutionary past. And that only occurred in the past maybe few decades. So we're probably the first couple generations that are going through this and we'll see the consequences in the years to come.

Dustin Grinnell (00:18:56 --> 00:19:28)
We are, aren't we? I mean, I think Obviously with obesity, we live a very chemical life, don't we? Like, we're the byproducts of chemical creativity, especially with our food, but consumer products right down the line. I feel like it's a very chemical life. Coffee, melatonin if we take it at night, and all the food, everything that's in it, everything we know and don't know that's in it. We're just awash in chemistry.

Jingke Wang (00:19:28 --> 00:21:30)
Yeah, there's a recent study about microplastic, which is very concerning. You know, we— I think we know it's present in bottled water, anything that's in touch with plastic, actually in our drinking water because it has— there's just so much plastic we've generated. So it's in the tap water. So there was a recent study done by Italian physicians on people who suffered heart attack and from the plaque that has been retrieved, they found a very large percentage of patients that contains microplastic. And then they followed with these patients, hundreds of patients.

They found that the patients who have higher microplastic content in the plaque have 4.6-fold higher chance of dying after this. So the hypothesis is there is accumulation of microplastic in heart over a very long period of time that scaffolds those plaque that will eventually cause heart attack. So this is just being realized, and that's just one example. And we have added so many artificial chemicals, the food preservative, flavor fragrances in food, even in cosmetics, in shampoo we use. We know very little about the long-term impact on our health.

Dustin Grinnell (00:21:30 --> 00:21:57)
One thing I wanted to talk about a little bit too is like your past, your origins. You're Chinese and you came here, was it after college, I think? Yeah, that's right. I wanted to just briefly trace the origins of your interest in plants and natural products. I understand when you were young, your household, your mom would use traditional Chinese medicine and that involved herbal remedies and things. I wonder if you could talk about that a little bit.

Jingke Wang (00:21:57 --> 00:23:54)
Oh, that's really cool. I'm a little bit over 40 years old and I think I just spent almost equal amount of time in two countries, China and the US. As you said, I was born and raised in China. And I did my K-12 education and college there. And after that, moved to the States.

I kind of realized it was a really great experience. And looking back, it's a long time, but I did get really significant exposure in two very major cultures of the world. And I think that really shaped me today, my worldview about the world and how I find interest in science. Yeah, so I told you that Chinese traditional medicine is just part of the culture. There's nothing weird about it because you go to the hospital, you get both options.

You can go see a traditional Chinese doctor and also the Western doctor. And there's many incidences I can tell you. So one time I think I had an eye infection when I was probably in 5th grade, and weeks later I kind of had a bump near my left ear. So I went to— my mom was very worried. Very worried, took me to the hospital.

The doctor said, oh, it's likely a tumor. We can do surgical removal. It'll take very quickly, like a day or so and recover. But a surgery on the face isn't gonna be good. So then my mom took me to see the doctor, a traditional Chinese medicine doctor, took a couple trips because the first one who's younger said, oh, it's likely a facial tumor.

We'll just treat this using tumor recipes. So there are some turtle shells, seaweed. There's actually a science story behind that years later. I can come back. And I had it for a couple of weeks.

Dustin Grinnell (00:23:54 --> 00:23:56)
This is a brew or an ointment?

Jingke Wang (00:23:56 --> 00:25:35)
The place, the Chinese pharmacy you went in actually smells really great because there are thousands of different herbs. It's really a scene to see because they weigh materials, raw materials in those traditional weighing things. Actually, I don't know how to call it. Scale. Scale, yeah, exactly.

So that we went for 2, 3 weeks, nothing really happened. It didn't go away.. And then my mom kind of got an appointment with the expert. So really it's very hard to see her, but she's really well known in our city. And she kind of touched me on this thing and then asked around, did anything happen to you around that time?

So I told her about this eye infection and then she immediately said, oh, it's very likely a kind of lymph node inflammation. That's related to this. So I'll give you something that's anti-inflammation or kind of cooling down. So in the Chinese system, it's like the heat and the cold. And this thing, she said it's heat related.

You had too much heat. Heat, yeah. So I think it translates to inflammation. So, and she prescribed something really different. It's a set of plants.

I don't remember what they are. Anti-inflammatory properties. Exactly. So I had that for a couple of weeks It just disappeared so magically. It just gone.

Dustin Grinnell (00:25:35 --> 00:25:39)
And you thought of herbal remedies as magic almost.

Jingke Wang (00:25:39 --> 00:25:44)
Exactly. So I essentially avoided a surgery that would leave a scar on my face.

Dustin Grinnell (00:25:44 --> 00:26:01)
I often wonder how often we overreach in Western medicine using example like that. How often are we doing surgical interventions, doing medical interventions, doing pharmaceutical prescriptions when they're more or less unnecessary? There are natural products that could do the same work.

Jingke Wang (00:26:01 --> 00:26:30)
Yeah, so to respond to that, I think, you know, first I have to acknowledge that Western medicine is a huge invention to mankind. I think without it, we'll be living in much worse worlds. But oftentimes, we kind of forget about body's own ability to heal. And I think in a way, the traditional Chinese medicine, the herbal remedy, activate our own body in some way to heal itself.

Dustin Grinnell (00:26:30 --> 00:26:33)
Activate our own inner pharmacy.

Jingke Wang (00:26:33 --> 00:28:14)
It's blocking some receptor, let's say anti— histamine, which is really, really important medicine. But what it does is a single molecule that just blocks how histamine is perceived by your body. So the histamine is still there, and there is a source, there's an unknown source of generating that histamine. It's not being treated. The only thing you feel better is because we use a chemical to block how it's perceived.

So the root of the illness isn't resolved. It just like it helps you to feel better. And there are many of these Western medicines over time, you may develop a dependence on this by removing the drug. The symptom can totally come back and sometimes in much worse ways. So that's why we have dependency and addiction sometimes to certain drugs for a long time.

Dustin Grinnell (00:28:15 --> 00:28:15)
Right.

Jingke Wang (00:28:15 --> 00:28:15)
Yeah.

Dustin Grinnell (00:28:15 --> 00:28:59)
Preaching to the choir. So put, you know, what is it that an herbal remedy does to get to the root cause? Like if you use your inflamed lymph node as an example, was it that, you know, if you're taking an herbal remedy, it's not one, like one-to-one, one chemical hits one phenotype or one gene. It's more like there's thousands of metabolites in an herbal remedy. So it's not just hitting one mechanism, it's hitting many mechanisms. And is that really kind of helping to get to the root cause? Is that it's so kind of scattershot, or is it more precise, or is it more it just covers all the bases? How is it that an herbal remedy gets to the root?

Jingke Wang (00:28:59 --> 00:30:55)
So it's based on experience. So people get sick and there are very long history of people trying things and certain things do work. And as you said, each plant component contains thousands of natural products in it., and we also tend to combine them because of our experience of combining things. So at the end of the day, it's a systems biology treatment. Oftentimes disease is complicated.

Bacterial infection is complicated, but it's one of the easier things to think about. It's if you can kill off the invading bacteria or virus, any pathogen, and you're good. But there are other diseases like neurodegeneration, diabetes, cancer, you know, heart attack, it's not a single agent you want to eliminate. So it's much more complicated than having an antibacterial molecule that just kills off the pathogen. So you do need a systematic approach to it.

Dustin Grinnell (00:30:55 --> 00:30:59)
Is there a place to get herbal remedies in Boston? Could you go to Chinatown?

Jingke Wang (00:30:59 --> 00:31:20)
Is there like a pharmacy? There are traditional Chinese. Yeah, so there are complementary medicine people can seek. I do know some really good Chinese medicine doctors in Boston. You can find them online and you go to them and there are ways to get you really high quality herbal remedies.

Dustin Grinnell (00:31:20 --> 00:31:27)
I understand another thing that you related with when you were young was, you know, I think your dad was a geologist.

Jingke Wang (00:31:27 --> 00:31:28)
Yeah.

Dustin Grinnell (00:31:28 --> 00:32:00)
Yeah, and you always used to go outside. And I remember in our discussions, Years ago, you would talk about being out in nature, and I think that informs your mind as a scientist today, like playing with rocks and seeing tadpoles. And you talked a long time ago about a documentary you saw on Charles Darwin, and you felt like his naturalism was something that resonated with you. I was wondering if you could kind of talk about how nature informs your scientific work, informs your life.

Jingke Wang (00:32:00 --> 00:33:52)
So I kind of remember we spent a lot of time discussing different aspects of geological formation. You know, we go out for hikes and he will tell me, oh, what kind of mountain, you know, this is what kind of stones and rocks these are and talk about billions of years of Earth evolution. So it's really kind of eye-opening because as a kid, you don't think about this very large timescale and his passion in science, I think definitely planted a seed in me. I think when I transitioned into becoming a scientist, I think it's really natural. There was one point of time I almost became an architecture.

So this is just entering college. I had the option to become a biologist or become an architecture because I am actually very good with art. But eventually I chose biology. I think it's almost destiny. But I think thinking about my development in my life, that early exposure to nature, that curiosity that my dad seeded played a critical role in shaping me into a natural scientist.

Dustin Grinnell (00:33:52 --> 00:34:06)
Yeah. You talked about science as destiny in a way, and you almost went to architecture. Like, why are you a scientist? Is it curiosity? Is it— what are the natural traits that made it destiny? What is the anatomy of a scientist?

Jingke Wang (00:34:06 --> 00:35:20)
That's really great. I think the first one is the raw curiosity. About unknowns. You got to ask questions that you do not understand in a very independent way. So that curiosity should not be dictated by what people tell you, what you read.

It's really kind of to be able to observe the world around you and being able to ask insightful questions that have not been asked before. And so that's number 1. So number 2, resilience. So doing science isn't easy, especially if that becomes your career. You're essentially a professional scientist in a way.

You do science on behalf of the society. The society raised money to fund your exploration. So you carry this responsibility to do good science.. But oftentimes you have some ideas we call hypothesis. You test them 95% of the time.

It doesn't work the way you want. 95% seems low. Yeah, right. Sometimes higher. So you can't just give up.

Dustin Grinnell (00:35:20 --> 00:35:34)
You got to— What drives you then? If it's basically failure, why? It seems like that it's really just the kind of Thomas Edison thing, right? I just found another way. It didn't work. And that is the motivation.

Jingke Wang (00:35:34 --> 00:36:36)
So I have a very neutral emotional state. You're ambivalent about the outcome. Exactly. So that's the process. You go try something, and if it doesn't work, that's part of the process.

There's nothing sad about that. The second is when it works, because let's say 1%, chance. That's such a great reward. And I can describe this thing, maybe it's a little bit geeky for scientists. For a period of time, once you discover something really great, you and your colleagues, sometimes your students, postdocs, you hold this mystery of nature only a small number of people know before you publish that.

Dustin Grinnell (00:36:36 --> 00:36:54)
Oh, I imagine. You know, it's, you know, pre-publication, pre-publicizing, you have an answer to one of nature's mysteries that no one else has come to. You've essentially pushed the edge of the boundary of knowable knowledge, you know.

Jingke Wang (00:36:54 --> 00:37:44)
That must be an incredible thrill. Yeah. And you mentioned Charles Darwin. The third thing that drives me, which is I think it's at the core of science as a tradition, is you could share this knowledge with anybody on the planet, in the world, even across time and generation. You know, I can relate to Charles Darwin. He got onto a boat and seeing animals around the world. I study plants, looking at their molecules. I can relate the process he was doing discovery to mine, and it's a tradition that's passed down generations, and you can really communicate through the language of science, and it's such a beautiful thing for human beings to do all collectively.

Dustin Grinnell (00:37:44 --> 00:38:11)
Yeah, one of my favorite movies is Contact, and Jodie Foster plays a Her character is based on a real astronomer, and she said that the signal that was sent from outer space from an extraterrestrial species was sent in a universal language, which is the language of mathematics, so that no matter where the signal hit, our species would be able to interpret it because it wasn't dependent on language or nationality or whatever.

Jingke Wang (00:38:11 --> 00:38:13)
Yeah. Yeah, I think I've seen that movie too.

Dustin Grinnell (00:38:13 --> 00:38:54)
I really love it too. It's great. Yeah. It plays with like faith and science and all that too. You know, it's interesting because this idea that you're talking about of like passing down wisdom from the generations and doing it through the written word essentially, you know, the story that you shared at the beginning of Yu Yu's scientific discovery, that never would have happened had a botanist or herbalist written down and recorded those observations. Thousands of years ago said, "Oh, I've noticed that when people drink this juice, they have less prominent fevers or something." And then she was able to kind of think about that and then to take the next step.

Jingke Wang (00:38:54 --> 00:42:00)
Actually, I can tell you another story about modern medicine that's derived from traditional use of plants. Quinine, you know, that's another anti-malarial drug. It's probably one of the first single molecule modern medicines. So in the 16th century, the colonists from Spain traveled to live in Peru and they discovered the tree bark of cinchona trees can be utilized to treat fever and also malaria. So this became a huge sensation.

So then I think it happened to one of their princesses. So it became known to Europeans. So then the cinchona tree barks became so popular. They are traded back to Europe, starting Spain and then other countries. The kings and queens learn about this, so they want to study plants more because one motivation is to be able to recognize the correct plant material because there are so many tree barks that look the same.

So you have a lot of adulteration. So it was the development of botanical gardens and the development of plant systematics, being able to recognize what species plants are that kind of cultivated modern science from the botany side of things. Then years later, people realized, oh, it's not the bark, it's actually something in the bark. So a century later, scientists isolated A compound that they found, oh, this one actually treats malaria. You don't need the whole bark.

It's actually one compound. And then 100 years later, people developed analytical chemistry and they were able to crystallize this compound into crystals and do X-ray diffraction and there are other methods. So they figured out the chemical structure for quinine. So that became the early days of chemistry, modern chemistry, starting from botany. And then you go to the chemistry and starting from analytical chemistry, then 50, 60 years later, people use organic chemistry to be able to synthesize that.

Dustin Grinnell (00:42:00 --> 00:42:19)
Play that timeline out. Like, go 50 years from now, go 100 years, go 500 years. What is your lineage of scientists? Who's gonna be looking back at you and your work and saying, "He was one step in our pathway." Like, what does that even look like as you project out that logic?

Jingke Wang (00:42:19 --> 00:44:39)
Just there's so many things that have occurred that's beyond our imagination decades ago. I'm sure it's gonna be like this, but I can throw out some wild ideas and see whether it holds true when we revisit this podcast. Yeah, it's like a time capsule. Yeah, exactly. So if you think about life, life forms, it doesn't have to be plants, but plants included, it's essentially a vehicle of very complex information.

I think the past decades we figured out the central dogma. There's the rules, how the information is recorded and it's being copied. Right, DNA to RNA to protein. Exactly how it gets translated, how it played out in the form of life. We're still kind of don't know how, let's say, consciousness of the brain, how that comes about.

But at least the other basic parts, you know, from DNA to RNA to protein to metabolites to the organs in our complex bodies that triggers the physiology movement. We have a very good grasp. I think we're on the verge of being able to simulate that. So I think AI is a big trend right now. I think it has huge impact on biological studies.

I think eventually we'll be able to simulate how different molecules come together, work together to produce outcome, the physiology, the phenotypes we see.. And that'll really accelerate discovery because before that, all the discoveries were made through physical experiments. People have to grind up plants, isolate compounds, and do measurements and determining their structures, identifying their functions. So it's a slow process. I think in the coming decades, this will be greatly accelerated with all the computational tools we're building.

Dustin Grinnell (00:44:39 --> 00:45:30)
And yeah, I think it's just really exciting to be living at this point in time. You can only imagine increased acceleration to an exponential rate, right? Because think about, say, an AI system, a database had just all of our species' accumulated scientific knowledge, and you just queried it and you asked, say you think of the story you told at the beginning, just ask it, Please go through all traditional Chinese manuals and textbooks across the centuries and look for entries on fevers. And just with a good prompt, with a good query, bang, you got it. You'll have a list, a nice list. You don't have to read through all the manuals. You don't have to go out to these locations and find the natural products on a mountaintop and bring it back and grind it up.

Jingke Wang (00:45:30 --> 00:46:27)
You already just saved potentially a whole lifetime of work. Yeah, yeah. This, this excess of knowledge is already happening. You have all the published works, literature that's been digitized, and we had older tools like Wikipedia, right? Essentially, it's many pages linked in a very funny way. There are a lot of links on each page you read. You can always click through. You can have a Wikipedia marathon following pure interest and then landed somewhere totally unrelated and discovered something really cool. And this data structure is being exploited by AI scientists. Essentially all the scientific knowledge at your fingertips and through a few prompts using language model, you can make seemingly unrelated connections. That's actually how creative process happens in science.

Dustin Grinnell (00:46:27 --> 00:47:16)
Exactly. And you put it together. Exactly. I want to talk about your current work. We met at the Whitehead Institute.

I was there for a couple of years. I was a science writer working in like a fundraising development capacity. And we shared a suite. We were right next to each other and we worked on a lot of projects. I was basically trying to to help edit some of your work, to get grants, and to raise money and things like that.

Jingke Wang (00:47:16 --> 00:47:26)
Yeah, the 10 years I spent at Whitehead is really special. We're talking about fraction of your life. This is probably one of the most productive years in my life.

Dustin Grinnell (00:47:26 --> 00:47:32)
This is a biomedical research institute in Kendall Square, Cambridge, associated with MIT.

Jingke Wang (00:47:32 --> 00:51:52)
I built a lab there starting with a few folks. By the time I left, I have a very sizable lab of about 15 researchers. I met some really great colleagues, mentors there, and some of them are founding members of the Whitehead Institute. So I was very inspired by this founding story. So it was late 1970s, and David Baltimore, who won the Nobel Prize in discovering reverse transcriptase at age 34,, and he led the idea of founding the Whitehead Institute with the philanthropic gift from Jack Whitehead, who's made his fortune by selling his company doing blood work.

So these two people came together and they had the vision to build an independent research institution focusing on fundamental biomedical research. And it wasn't really popular then. I think Jack Whitehead initially went to Duke medical school, and they just wanted that money for supporting the medical school, and it's not exactly what Jack wanted, and he met David Baltimore, and then David recruited 4 really outstanding mid-career scientists: Bob Weinberg, Harvey Lodish, Jerry Fink, Rudolph Janisch, and these 5 people came together and they built a new building in Kendall Square, Within 10 years, it became the top 1 most exciting research institute and had decades-long legacy. So I had a chance to work alongside of these people and just learn the culture. It's really kind of pushing the boundary and challenge the status quo, be really courageous in pursuing what's really interesting to you and have this environment to exchange ideas.

So it's really kind of a perfect place for scientists to be. So I think I spent really the best time there. Yeah, you mentioned I left Whitehead just very recently to join Northeastern University. It is an uprising university. It's a very strong university but has the ambition to do something even greater.

And there are two things that really attracted me. One is President Joseph Aoun's vision to create a network university. So usually you think about university, it's just one place, but Northeastern has more than 20 campuses around the world. So we'll create a network effect for higher ed, for people coming together to do important things. So that really attracted me.

The second is to very aggressively invest resources and capital to tackle the most interesting scientific problems and also the challenges facing the human beings in the 21st century. And I can definitely see my older Whitehead colleague Hazel Sif, who left a year ahead of me to join Northeastern to become Dean of School of Science, and she played a huge role in recruiting me to Northeastern to build a new institute. And essentially she told me, okay, Jingke, you've done really great plant biology work. How about building an institute around the thing you study? So not only I can continue to do the things I'm passionate about, but being able to create almost another Whitehead Institute, but working on plants.

Dustin Grinnell (00:51:52 --> 00:52:56)
Well, I wanted to go back to Whitehead real quick. So you talked— I was there, I was in the area of the scientists, not the administrative area. That was deliberate. I asked to be up with the scientists. It was in the air, you know, what you're talking about, this pushing boundaries.

These weren't platitudes. They weren't like things on a website. You guys really had a culture of pursuing wild ideas and pushing the boundaries. And it was a culture of, like, asking questions, blue sky thinking. I was wondering if you could just kind of talk about what that type of research is too.

It's basic research versus applied and how that kind of basic research that's asking just fundamental questions tends to be statistically, like where the breakthroughs come from. Is that right? It's like you're asking these questions that are fundamental. They're not directly applied to like maybe cancer or another disease. And yet that's where the breakthroughs for disease come.

Jingke Wang (00:52:56 --> 00:55:01)
Why is that? Yeah, I think people is the first. I think about Whitehead, I think about the people. I mentioned the founding members, and in the following decades, I think Whitehead Institute has done a really good job recruiting really innovative scientists who have the ability to do first principle thinking, which is oftentimes not a very common trait because it's very easy to get absorbed into some trendy topics everybody talks about, and then you can just do the obvious next experiment. Oftentimes the most creative ideas, discoveries are coming from unpopular topics or questions.

You ask something that there's no funding agencies actually funding that, but you still have the stubbornness and resilience to continue until you prove to the world, okay, it's worthwhile pursuing because you are finding something nobody ever know that existed. So it all comes from this ability to ask the first principle questions. And the Whitehead is an interesting place because it's not unified around a particular topic. It's not a cancer institute. It's not an institute for just technology.

Dustin Grinnell (00:55:01 --> 00:55:24)
Are you talking about like like rebels almost in a way. It's a type of independent thinking you're absolutely talking about, but it's something of a rebellious spirit as well. The ability to just go your own way because of your own— the conviction of your own beliefs, the conviction of your own curiosity. Is that what made Whitehead special in a way?

Jingke Wang (00:55:24 --> 00:55:33)
Is that people who are just following their curiosity with such, like, passion and conviction? Right. Yeah, you can say so.

Dustin Grinnell (00:55:33 --> 00:55:37)
I think this spirit started by the founding members.

Jingke Wang (00:55:37 --> 00:55:54)
Yeah. Bob Weinberg discovered the oncogene. Exactly. Yeah. Nobody knew cancer was caused by mutations. It's really so obvious now, but before that, it's such an unknown thing until he discovered the mechanism for that.

Dustin Grinnell (00:55:54 --> 00:56:14)
And right next to us on the third floor was David Sabatini. Right. And I think we know the impact of his work. Was it on mTOR? Exactly. Metabolism. We're talking about like major scientific advances happening in a tiny little building, you know, 400 people, you know, 20 or so faculty members.

Dustin Grinnell (00:56:14 --> 00:56:14)
Yeah.

Dustin Grinnell (00:56:14 --> 00:56:17)
So I remember— They always said they punched above their weight.

Jingke Wang (00:56:17 --> 00:57:38)
And these people I just met for a few weeks, they were legendary figures in the history of science, and now they are my neighbors. I actually was kind of nervous to enter that circle, but they are human beings. They talk to you. They are curious about your questions. Yeah, you just become one of them, and it's so inspiring.

I think just Watching how they think about their questions, how they mentor their students, how they run their lab played a huge kind of role in shaping how I kind of do science day in and day out. So I felt at this moment, this particular time point of my career, I can also exert my impact in helping younger people. So at the new institute I'm starting, the Institute for Plant-Human Interface, iPhi in short. We're recruiting 3 really exciting junior scientists to join as the founding members in the coming fall. And really exciting to work with them.

Dustin Grinnell (00:57:38 --> 00:57:55)
I'm just so happy to help them to realize their dreams in their scientific pursuit. What are the characteristics and traits and dispositions of these young scientists? And what kind of faculty members are you looking as you kind of staff up and build your own your own institute?

Jingke Wang (00:57:55 --> 00:58:16)
I think we talked a lot about the Whitehead Institute, as you can tell. My thinking is very much shaped by that experience. Definitely insatiable curiosity and the courage to ask unpopular questions or work on things nobody really cares but are truly interesting.

Dustin Grinnell (00:58:16 --> 00:58:22)
And these are the features I look, and yeah, resilience is something I also look to.

Jingke Wang (00:58:22 --> 00:58:22)
Yeah.

Dustin Grinnell (00:58:22 --> 00:58:31)
So, but you'll also be running your own lab and doing science. This is your life and life's work. What questions are you most curious about now?

Jingke Wang (00:58:31 --> 01:02:43)
We'll continue to discover more because it's just such a rich system. There are more areas in the lab that's to do with how plant chemistry interface with human physiology and disease. We're trying to study the action mechanism of the natural products. We study how they can be utilized to treat human disease or cause physiological changes. So there's one area of perception of potential danger by humans.

So we have to forage a lot of plant materials. Actually, we have developed a very sensitive mechanism to perceive what are potentially dangerous from the food we eat. When we put it in our mouth? Yeah, even before that. Oh, we smell.

We smell. Yeah. So human genomes contain hundreds of olfactory receptors. So we're very good at smelling. So before you put anything into your mouth, you pretty much have a good idea whether it's edible or not.

But if you still decide to put it in your mouth, then you have those taste receptors. So my lab recently got very interested into this family of bitter taste receptors. These are called T2Rs, and they are chemical sensors for potentially dangerous molecules. So things that are harmful usually taste bitter. And we found that they're not only expressed in your mouth, but also in other parts of your GI tract and even in other organs.

So the extraoral functions are also interesting to me. Let's say you accidentally swallow something and this toxin can still be sensed by the bilaterate receptors, let's say in your stomach or in your intestine, that will induce are discharged. Let's put it that way. Yeah, exactly. And there might be long-term consequences to that.

One is memory. So we're trying to link the initial activation of certain receptors to some long-term behavioral changes. You may have learned, okay, don't swallow that again. Or there's immunological consequences. We think some of the compounds may serve as adjuvants to trigger food allergy.

So if you ate something that makes you really unpleasant, maybe there is both neurological, immunological consequence to that event. So these are the questions we're quite interested in solving. Interesting. Anything else? Yeah, so that's that.

And my lab is working with Sas Reikhoff-Nochamn's lab at at Boston Children's Hospital on food allergy. And there are certain proteins, and many from plants, somehow can trigger very severe immunological response to our body, and we really don't know how it works. And we're trying to map out, for example, the biogeography of allergen proteins in the body. You know, if people with peanut allergy you chew a peanut, at what point the allergen protein in the peanut becomes perceived by your immune system that triggers the allergic reaction is actually not known. And it's actually to do with how protein is generally digested and absorbed in the body.

Dustin Grinnell (01:02:43 --> 01:03:06)
Wow. What do you hope to come like 5 years, 10 years from now at the plant-human interface? Like what do you hope comes out of it? Are we talking about Basic biological knowledge so that we can better understand things or applications, therapies? What kinds of things are— that do you hope for in the next 5, 10, 15 years?

Jingke Wang (01:03:06 --> 01:04:37)
Yeah, so we are charting out a plan to recruit 20 faculty members to join the institute in the next 10 years. It'll be a really exciting process. I want to 10x or maybe 50x what Youyou Tu has done during her lifetime. She discovered Artemisinin. Hopefully in the next 10, 20 years, we'll be able to discover 20 more nature-derived molecules as medicine. I want to advance bioengineering processes, how molecules can be made in sustainable manner, because many of the plant-derived medicines we use today are still being purified and isolate it from plant host, it's really a low-tech and unsustainable approach. We want to be able to engineer microbes to do that so we can produce a lot more medicines in a much sustainable manner. We want to be able to engineer crop plants so that they are more resilient to the changing climate and providing more yield and be able to adapt to different environments around the globe. Hopefully we could also contribute to sustainability of the planet Earth. We have some ambitious project in engineering the carbon cycle. So if we can turn plants to sequester a little bit more CO2 over the years, maybe that's a unique approach to reduce CO2 that's been pumping into the air.

Dustin Grinnell (01:04:37 --> 01:05:11)
One of the things I wanted to ask is, we kind of come closer to the end of the conversation is this idea of plant intelligence, right? We talked about this a little bit before, like plant communication, what is kind of going on below the surface of humans' awareness inside plants. And I wanted to ask about kind of like what form of intelligence you think plants have like root systems and how they communicate and things.

Jingke Wang (01:05:11 --> 01:07:00)
You look at an ant colony, bee colony, you would say it's smart. I think intelligence helps the host organism to survive better, fighting against entropy. If this doesn't occur, so basically we decay very quickly. Things go into disorder very quickly. So intelligence is a form that can help us to fight against that.

So plant intelligence, we have spoken about the chemistry. They use chemistry to communicate with each other, with other organisms, with the environment. I think it's a level of intelligence we don't fully understand. Once you have network and you can also say intelligence is an emergent trait of a network, which AI is a form. You have networks building computers.

Dustin Grinnell (01:07:00 --> 01:07:44)
I wanted to— I don't know if you ever heard of the book The Overstory. I don't think so. The author is Richard Powers. There's an excerpt that I want to just read and get your reaction to in this context of kind of like plant intelligence. He says, this is not our world with trees in it. It's a world of trees where humans have just arrived. Trees know when we're close by. The chemistry of their roots and the perfumes their leaves pump out change when we're near. When you feel good after a walk in the woods, it might be that certain species are bribing you. So many wonder drugs have come from trees, and we haven't yet scratched the surface of the offerings. Trees have long been trying to reach us, but they speak in frequencies too low for people to hear.

Jingke Wang (01:07:44 --> 01:07:48)
I wonder what you think about that. It's beautifully written.

Dustin Grinnell (01:07:48 --> 01:08:02)
That's exactly how I think about the world of plants. There's so much in there. I wonder, this is a funny question, but if trees are trying to talk to us, what are they saying?

Jingke Wang (01:08:02 --> 01:08:54)
My thinking is they probably don't care too much about us. Oh, indifference. Yeah, there are their own problems to work with., and we're just kind of discovering the tips of the iceberg, like how smart they are. Because if you think about this, they've been so successful in terms of adapting to almost every corner of the planet Earth, every bit of ecology that you can find plants. And human beings, if you count modern humans, we're just around for tens of thousands of years, and it's very early to tell whether we can even outlast dinosaurs. Dinosaurs were around for millions of years, hundreds of million years. And we have to see, I think there is some level of wisdom we can definitely gain from plants.

Dustin Grinnell (01:08:54 --> 01:09:43)
I do think about if, yeah, plants, trees, they've been here so much longer. They've seen so much more than us. They don't have our technology, but they've just, they have age, longevity. And I think of them as old wise men and women, you know, just having, they've seen it all. And they may sort of laugh at us. They may say, "We saw the dinosaurs for millions of years, and you're just a newcomer on the scene." Exactly. And you're— to get a sort of sustainability point in here, it's like we're damaging them at very high rates. We're sort of clumsy and reckless. And we're, yeah, inadvertently through our own ignorance, just kind of messing it up. Creating a big mess of it all in a very unsustainable way.

Jingke Wang (01:09:44 --> 01:09:50)
That's right. I think sustainability comes to mind. How can we outlast dinosaurs?

Dustin Grinnell (01:09:50 --> 01:10:07)
I think that's a goal to hit for human beings. Yeah, I'd say that'd be a good objective for our species. Well, this has been a great conversation, and I just want to thank you for sharing your work and your insights. And I can't wait to see what happens with the institute.

Dustin Grinnell (01:10:08 --> 01:10:19)
Yeah, my pleasure. Thank you for inviting me. Thanks for listening to this episode of Curiously. I hope you enjoyed this conversation with Jinko Wang. If you're enjoying this podcast, please consider leaving a review.

Dustin Grinnell (01:10:19 --> 01:10:22)
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Dustin Grinnell (01:10:22 --> 01:10:31)
If you like what you're hearing and would like to sponsor the podcast, please consider supporting me on my Patreon account. Thanks again for listening. And stay tuned for more conversations with people I meet along the way.