The Climate Biotech Podcast
Are you fascinated by the power and potential of biotechnology? Do you want to learn about cutting-edge innovations that can address climate change?
The Climate Biotech Podcast explores the most pressing problems at the intersection of climate and biology, and most importantly, how to solve them. Hosted by Dan Goodwin, a neuroscientist turned biotech enthusiast, the podcast features interviews with leading experts diving deep into topics like plant synthetic biology, mitochondrial engineering, gene editing, and more.
This podcast is powered by Homeworld Collective, a non-profit whose mission is to ignite the field of climate biotechnology.
The Climate Biotech Podcast
The Power of Curiosity with Shuguang Zhang
In this special episode, we sit down with Shuguang Zhang, Head of the Laboratory of Molecular Architecture in the MIT Media Lab and a mentor to countless biotech explorers. His personal story has at least one literal "1 in 100 Million" moment and demonstrates the power of curiosity, kindness, and always asking questions.
We trace how Shuguang's stubbornness to pursue questions long after others give up has taken him around the world and reshaped biology. "Why is some DNA left-handed?" is a question he couldn't stop asking as a young man in China. It led him to work with one of his heroes, Alexander Rich at MIT, where he discovered zoutin (from the Chinese word for left, 左, zuo), the critical protein for mysterious Z-DNA. When he purified this new protein, he became fascinated by how it self-assembled into structures visible to the naked eye—a discovery that became PuraMatrix, now used in wound healing worldwide, and sparked generations of curiosity about self-assembling peptides.
Similarly, wondering why there are both hydrophobic and hydrophilic alpha helices led to the QTY code: a beautifully simple method to convert any membrane protein into a water-soluble form. By swapping hydrophobic residues for polar look-alikes (Q, T, and Y) without breaking geometry, this unlocks dense high-signal sensors, "molecular trap" therapeutics targeting cancer metastasis, and a fresh way to treat receptors as modular parts rather than fragile mysteries.
The pattern repeats with S-layer proteins: nature's two-dimensional crystalline lattices that orient engineered receptors 100% upright at nanometer precision. Combined with QTY-solubilized proteins, these create clean bioelectronic interfaces, ultrasensitive arrays, and new possibilities for separations and chemical monitoring.
We widen the lens to climate: industrial-scale kelp systems for carbon capture and feed, biotech routes for ocean-based materials, and practical paths to planetary solutions that borrow from biology's atomic precision and self-assembly. Kelp's exceptional photosynthetic efficiency and rapid growth make it a promising system that biotechnology could enhance through genetic engineering.
Threaded through it all are lessons from mentors like Francis Crick ("ask big questions, you get bigger answers") and Alexander Rich ("it's equally important to know what not to do"). As Shuguang puts it: "In doing science, we see a lot of things, but don't observe. To observe is to pay attention." We also talk frankly about funding setbacks, debt, persistence, and the role of AI: powerful at pattern completion, weak at original curiosity.
If you care about proteins, materials, sensors, climate biotech, or simply how a life of questioning can bend reality, this conversation is a field guide.
If the story resonates, subscribe, share with a friend, and leave a review with the one question this episode inspired you to ask next.
Read Shuguang's powerful essay "Life Has Ups and Downs, but Always Ask Questions": https://www.researchgate.net/publication/363521718_Life_Has_Ups_and_Downs_but_Always_Ask_Questions
So after joining army, I didn't know that soldiers supposed not to ask any questions. I continued to ask questions, and initially I was seeing called a communication unit, had access to the captains and the colonels. So asking the question, all kinds of questions, political questions, military questions. Soon I found I had been demoted to feeding horses. And interestingly, those guys did not know. It's all the generals and then colonels and captains. Those guys are riding horses. And so I still have opportunity to ask questions. Then I was demoted further to feeding pics.
SPEAKER_00:This is a very special episode for me, so this intro is gonna be a little bit different than normal. I've tried to make this an essay and have failed. And I'm really glad that we get to do this as a conversation today. Normally I don't talk about myself much, but the best way to introduce Shu Wong is to tell the story about how he's impacted me. Near the end of my PhD at MIT, I was pretty lost. I had done great work in the context of neuroscience, but I'd done this two-year slog with journal reviewers, and it really made science just become more of a grind than a passion. And I asked around, and I was talking to my friend Adam Marblestone, who listeners might know Adam as one of the founders of focused research organizations, and I asked him, What is one of the best classes I could take to rediscover science? And Adam didn't even need to think. He said, Go find Shugong. He is the best mentor at MIT. So I took Shugong's class, and a wonderful friendship emerged. His brilliance and his passion for exploring life and biology, and his unrelenting desire to always ask questions, it changed me. He renewed my curiosity. And then when he started sharing his own incredible personal journey as we became friends, there's things I never would have guessed, and it has inspired me to do more and to do better. His emphasis on questioning is strongly present in what Homeworld calls problems. But you in this conversation, I hope everyone can see part of the origin, for at least what I've pushed for. Whenever I have a moment of feeling tired or frustrated, I bring up one of my personal mantras, which is my parents did more with less. And I say this to be grateful for my parents who came from England, just as students. And Xu Gong's story is exactly like this. So when I say my parents did more with less, you're going to hear an amazing story about Xu Gong. I hope Xu Gong listeners will appreciate how much he's done, both scientifically and in his own journey of constant exploration. So today we're going to go through some of Xu Gong's life, his discoveries in really amazing parts of biology, and learn what he is he is excited about moving forward. So before we get to him, let me just give a couple quick lines and then I'll get out of the way. Shu Gong Zong is a researcher at the Massachusetts Institute of Technology, where he leads the Laboratory of Molecular Architecture. He has published over 200 scientific papers, which together have been cited more than 40,000 times with an H index of 97. He has won many awards, Guggenheim, Exner, etc. But I think my personal favorite is how he has a massive international footprint. He's elected to the Austrian Academy of Sciences in 2010, the US National Academy of Inventors in 2013, and the European Academy of Science and Arts in 2021. This is a conversation I've really wanted to have, and I'm so grateful for your time, Xu Guang. So let's just jump into it now. Shu Guang, who are you? Where did you grow up?
SPEAKER_01:Than you. Thank you for inviting me to this podcast. My personal story is unlike most other people. I grew up in the cultural revolution in China. Before that, was my parents, especially my father, was purged in 1957 for the anti-rightist system. Because he asked questions and to the authority. He was sent to the labor camp for two years. Because his experience, he did not want me to ask many questions. But how can you not ask your child not to ask questions? It's intrinsic for children to ask questions. And so I grew up then in the cultural revolution, I did not go to college. So I had six years elementary school education. And then in 1966, the cultural revolution started, all school was closed for 10 years. And I did not go to junior high, maybe for a few months, and did not go to, really did not go to high school. The country was a dictator, country China, and burned all the mathematics, physics, and chemistry textbooks. Why? Because it comes from Western Europe, it was not invented in China. What a tragedy. By the time I grew up, it was 10 years later, could not go to school anymore. And in the meantime, I went to my father's farm, spent a year in the farm, learning farming stem. It's not a farm, it's a peasants. Really have to carry water and 50 kilograms water and then to give water to the vegetables. And then after that, I went to the military. Because in 1968, Russia invaded China. Typical Russia. Huge land, still invading other countries. So the government asked us young people, I was 17, to join the army. I joined the army. So after joining the army, I didn't know that soldiers supposed not to ask any questions. I continued to ask questions. And initially, I was in called a communication unit, had access to the captains and the colonels and higher hierarchies in the army. So asking the question, all kinds of questions, political questions, military questions. Soon I found I had been demoted to feeding horses. And interestingly, those guys did not know. It's all the generals and then colonels and captains, those guys are riding horses. And so I still have opportunity to ask questions. Then I was demoted further to feeding picks so we'll be alone. And finally, you were assigned to feeding to be a cook in the military. So luckily in the military, as a cook I have a lot of time to read books. I told you there's no mathematics books, no physics, no chemistry, but I could read any other books, especially the Frederick Engels' book and Karl Marx's books and other things. It's from there and learned natural science from Engels, to everybody's surprise. Not Karl Marx. Karl Marx doesn't know anything about the natural science, but Engels knows. So it's from there and learned some natural science. But when I was young, very young, and I wondered to watch, which in China didn't have dog and cats, but we're allowed to have pets, silkworm pets, yeah. Silkrum, I take leaves, mulberry leaves, feed the silkworm, and I watch the silkworm eat the green leaves. And a few weeks later, then changing to white, the body changing white, and spinning out the silk, it's transparency, almost white and transparent, translucent stuff. Not green, but white. And later, of course, at the time I didn't know, it's a leaf, it's carbohydrates, it's cellulose. And the silk is protein. And how could the silk worm convert cellulose, which is carbohydrates, into protein? That was totally amazing at the time. Furthermore, we I also had a chicken, yeah? Chicken lay eggs, the hen, lay one per day. And I was fascinated. They did not eat any chicken, something, but chicken has a shell, the egg has a shell. How could it make the shell? Yeah? And then of course they eat other convert, again, carbohydrates into proteins. So it's truly amazing. No dogs, no cats, but hyper sucorb and chicken. It truly stimulates my curiosity. And from that point on, and also looking around, just ask some very simple questions in the surroundings that elicit my early scientific interest. My mother subscribed a magazine for me called Childhood Time. And it's a very interesting full of the natural phenomena and also stimulates young people to ask questions. That's a book series called Asking 10,000 Questions. Yeah. So that's truly stimulated me to wonder about the nature. So I believe that also plant a seed for me to eventually become a scientist.
SPEAKER_00:Amazing. And if I could jump in here just because I'm gonna be pulling from this amazing essay you wrote called Life Has Ups and Downs, but Always Ask Questions, which you published in the Molecular Frontiers Journal. And I have to be very honest that I knew you well before I read it. And so when you tell the story about your father got taken away when you were five, when I was reading this last night, I was crying because it's so sad. But then the story of you getting constantly demoted for asking questions is hilarious. And I was laughing, and it it you the through line goes exactly to all the amazing molecular work you later did. Now, when you get into proteins, thinking of animals so as silkworms and then chickens, pig hair also ended up becoming a very interesting uh through line into proteins. So I'd love to start there. What how did you end up working with pig hair?
SPEAKER_01:Ah, okay. In 19, I told you China University essentially stopped for 10 years, 66 to 75, 76, Mao Zedong died. Yeah. So university opened again. And I spent four years in the army as a cook, yeah, or three years as a cook, and then a year and for something else. And after return home, and I could not find a job, and military people, but they still have a better chance than other people to get a job. So we are signed either to work in Picker Factory or some other job because a driver, driver. Driving cars is high prestigious in China, in some bureaucrats place. So I did not want to be a driver for some bureaucrats. So I selected Pick Air Factory. To my parents, especially my father's astonishment, because that his concern is a dead end, that place. Once you go in, you can never come out. So after two years and China University opened, and in those days, 76, we didn't, this whole exam system was gone. Because nobody has an advanced study either. So I was called elected to join this university. Why? Because I was signed peak hair factory to clean pic hairs, spent two years clean pig hairs. And because peak hair is so cheap in China, there's so many millions of pig being slaughtered each year. There's a very dirty, full-smelling stuff, and but you have to clean them for export, make brushes or making other things. But pig hair is too cheap, cannot generate much income. So this unit becomes interest because pick hair has a lot high concentration cysteine, one with amine acids, older hair, like your hair too, my hair too. So amino acid, if you digest peak hair into amino acids, the added value per kilogram is much higher. I would say a hundred times higher or a thousand times higher. For I mean one kilogram amine acid, it's worth probably thousand times higher than one kilogram peak hair. So how to do that? So then send me to the Susan University to study biochemistry. So biochemistry is one to learn how proteins are made and how proteins are degraded, as well as how the sugars are made through photosynthesis and how the sugars are degraded through what we eat, digestion by enzymes. And so that's how I went to Susan University to learn. However, I mentioned to you I did not go to Junya High in high school. I had no mathematics background, no physics chemistry background. So when you go to university, first you learn is calculus, yeah, and analytical chemistry, organic chemistry, and basic physics, mechanism, Maxwell equations, and so on. But meantime, in 1976, after Mao Zedong died, China study published physics, chemistry, and mathematics books again. Yeah. So we could then have a series book called the self-guide, mathematics and chemistry and physics, so on. So I my mother brought me a set of those books. So I studied this. During the day, I take a mathematics class and whatever calculus in the university. In the evening, I study high school textbooks. And luckily, I have a very sympathetic professor in organic chemistry. He really took me on his way and very helpful to see my if my uh answers are right for this chemistry, physics, and mathematics. So I will benefit greatly from that mentor and when I was young. I was not so young. I was already 24 years old. 24, first time going to university. In the US, 24, many people already received master's degrees. And occasionally, Ed Boyden already his PhD.
SPEAKER_00:Well, Ed Boyden is pretty singular, and I think he's actually going to be on soon. But uh so Professor Ma was his name, right? Who really went out of his beautiful the story progresses in kind of a series of unbelievable turns, right? First of all, you risked a dead-end job in pig hair, which ended up being your break into biochemistry. And then probably one of the, I mean, just numerically unbelievable moments is that you were the first person of Sichuan province of a hundred million people to ever receive a private passport. Yes. And which is itself an amazing, just from a statistical point of view. And so that was your by studying under Professor Ma and learning biochemistry, you were able to come to the United States. Was it easy? How did it go?
SPEAKER_01:Ah, this is story by itself. And I never when I was in university, Sichuan University, which is one of the top ten in China nowadays, yeah, and we never heard journal nature, never heard journal science. It's so forbidden. Why? Because in the front part, nature and science has a lot of political commentaries. Yeah. And also other things not directly related to science. So we never have those. By the way, we never had a textbook either. So I told you they burned before. So how we study biochemistry, mathematics, and chemistry is all copied teachers' notebooks. We found from them on the weekend, and always we copied from the blackboard and then to study. And it was very difficult and then to study on your own without the textbooks. In 1978, we now study biochemistry. I entered into university 77, and during the class, biochemistry class, we learned about uh cellulose, sugars, and uh proteins, alpha helix, DNA, double helix. So then I asked my teacher, biochemistry professor, the question why it seems most molecules, proteins, DNA, and cellulose are right-handed. Why are there any left-handed helices? And my professor did not know. And but I was curious, because nature frequently has a symmetry, our eyes, right? Our ears, and nose has the two, hands and feet and so on. Symmetry. Why is this only right-handed? In 1979, December, a paper published in Nature on the Cover, of course I didn't know that, by Alexander Rich at MIT. He later became a mentor. In 1979, after Carter, Jimmy Carter formally normalized relationships between US and China, and China allowed the magazine called Science News to be imported into China. So I subscribed that journal with my very little money. By the way, working in pig hair factory is$20 per month, not per week, per month. So 10% of my salary, no more than that, 20% of my salary went to subscribe to this magazine. Yeah. And so on the last issue, 1979, end of December, has a story about Alexander Rich. It's life handed the DNA. Now the only story And also has a picture of Alexander Rich with his left-handed DNA. So it's for me a philosophical question. We ask, we know, and my teacher didn't know there's no left-handed form. Here he is on the left-handed DNA. In 1979, after reading that, I got so excited, I said, I want to work with the professor at MIT. I knew MIT was impossible, like a Himalaya, to go to the top. It's the top, MIT. And I know how difficult it's to get through. I knew I had zero chance to get to MIT. Right? And also I didn't learn English. And only reading English, not listening, it's impossible. It's no tapes. And then all the teachers, a Chinese teacher, local teacher, those teachers used to learn Russians and changed into English. But I could read English. And I thought I'd determined at the time to work with Alexander Rich. Because in that time, 1979, my father received a letter from the United States, from Portland, Oregon. My father's aunt wrote him because after Jamie Coded normalized relationship between US and China, then could write letters. My father could receive letters. And in before, she had written before 1950s, 60s, all the letters disappeared. Nobody knows where they went. But 79 and he received letter. So and I asked my father to see the letter. He was very, really reluctant. By the way, my father really did not want me to go to university. Because once you get educated, you start to ask more questions. And in the culture revolution, many professors during the other 10 years sent to the farm, get re-educated. So my father truly did not want me to go to university, blocked me. But my mother, who had a degree, went to university, Fudai University, one of the best universities in China, she went to the 1946 to 49. So she encouraged me to go to university. For the first time, I saw my parents had a conflict. My mother supported me, my father tried to block me. But I said I want to go. And later, when I saw the letter, my my father's aunt wanted to invite me to the United States to study. My father again tried to block me. My mother again supported me. So I truly owe a lot to my mother to come to the United States. And that is how I came to the United States. When I came here, I did not speak much English. And I learned first to learn English at Portland State University.
SPEAKER_00:His name meant honest man.
SPEAKER_01:Yes, yes.
SPEAKER_00:Right. And he was called a writist for standing for doing something that was unequivocally good, right? He refused to denounce somebody. And for that, the state threw everything at him. So I empathize, I can both imagine empathizing with your father, and then also you wanting to ask questions and that. So I mean, I there's not much to say there. I just want to celebrate this, and I really urge people to read this essay. When you so there just kind of hop forward because there's so much talk about with you know ultimately getting to work with Alexander Rich. But you know, so you show up, you have to challenge, people think you're dumb because you don't speak English, right? You learn to speak English, and then you finish up and it turns out well, and then you get a break to start working on cancer, right? Yes, and then kind of another one of just the worst things that could happen to somebody happens to somebody, and that's where I wouldn't, you know, somehow that in this awful tragedy, it ends up being this bridge to meet your hero. And I'd love just kind of how have you pick up the story there as it takes you down my tea.
SPEAKER_01:Yeah. So I had set my site in 1979 come to MIT. But I also knew there's zero chance I could do it. I have to learn English. Like going to mountain, you cannot go take an elevator or take a helicopter to go to the mountain, you have to go zigzag.
unknown:Right?
SPEAKER_01:Go zigzag, climb the mountain. That's what I did. So first learned English at Polish state, then later went to UC Santa Barbara to learn biochemistry and genetics, molecular biology in UC Santa Barbara. So spent almost six years, and five years and nine months, got my PhD from there. But I never waived to not do company MIT. During that time, and I knew Tom Check, who discovered the RNA self-splicing. He was in our small group, like 100 people in researching in this community and took Tesou Hymana community. And later on, also Elizabeth Blackburn discovered the telemaries, right? Also in our community. So I knew both of them when they were assistant professors. And because then received Tesla Hymana the strain, the ciliate, and from our laboratory to study them, and then eventually winning the Nobel Prize. We knew already, 1980s, and when they discovered, we knew the US guy won the Nobel Prize. So people also suggest me I should go work with Tom Chet or work with this Blackburn because I'm going to get the Nobel Prize. So then I still want to work with Alexander Rich. I want to study the left-hand DNA. So it didn't wave, didn't change. So after finishing my PhD, I wrote the American Cancer Society and a fellowship. And I received the fellowship. After me wrote up, I did this a dozen different fellowships, and the American Cancer Society awarded me the fellowship. And during the fellowship, interestingly, the subject was to study chromosomes translocation on the influence of left-handed ZDNA. Yeah, what Alexander Rich called the left-handed ZDNA, Z backbone. And I became expert on chromosome translocation. And the tragic struck, my son, Nicholas, at three years old, he also got leukemia. Turned out he had in his cell, single cell, had two pair chromosome translocations. And six and twenty-one, luckily it's not twenty-two, twenty-two be Philadelphia chromosome, it's a death sentence. And six and seven and nine. So at the time I wrote to the leading cancer researchers in the world, and including Jeanette Raleigh, Chicago, Karen, Sharon Murphy, and George Klein at the Karlinska Institute, and Daniel Farber, Stephen Sullen, and so on and so forth. And several people replied to me, including George Klein from Karlinska. I had zero idea how important how big it was. Absolutely no. I was just graduate student. Yeah. Turned out George Klein has been on the Nobel Committee for 10 years, has been selecting Nobel Company in medicine. And finally I met him in person in 1999 in his office at Karlinska Institute. So go back to this, I with Alex Rich, I spoke with him, and Alex Rich called me 9 o'clock California time, which is midnight here in the East Coast. And I was so astonished, Alexander Rich, like a god in science, called a person, a graduate student, and then I was fully astonished and excited, of course. I told my PhD advisor the next day. So we essentially wrote this grant fellowship application, I received a grant. So by the way, my son is still alive and well, he's now already 41 years old.
SPEAKER_00:Amazing. So there's so I mean there's so many layers of beauty here, but you know, just to reiterate, nine years after you happened to see this in this journal that you were spending 20% of your income with, and you never left this curiosity to one day work with Alexander Rich in the middle of the biggest personal tragedy I think any of us can experience, which you work, you fought through, you get the call from your dream, and then you get to go work with Alexander Rich. And I think I mean, I hope people listening to this have this moment of wow, if there's not a story of just never ever give up, there it is. And I'm also gonna call out I really hope people read this story of your life because you put the box, you have boxes of when how asking questions have changed your life, and this was a big part of saving Nicholas too. But to move into the science, and you know, people who know your work technically will know all the amazing contributions you've made through proteins. And so it's a it I had to go back through your history to realize how left-handed DNA turned into a study of proteins. And so, you know, just to go in how you so you get to go to MIT, you get to work under your hero. How did we end up getting to proteins from left-handed DNA?
SPEAKER_01:Ah, okay. That's a serendipity. Well, the grant this fellowship application is to work on chromosome translocations. That requires leukemical cell lines, and cell line has translocation, the tumor cells can't continue to grow and then don't stop. Unfortunately, in 1988, so this MITUs have a tissue culture center, you can provide literal cells, you can study. That year when I arrived at MIT, the center was closed by NIH. Yeah. So then have no source of cells. And then you cannot grow in a P2 dish to grow liters in the cells. It's impossible. And Alex said, maybe you should work on another organism, you can grow in the laboratory. That is yeast. So I use East as a model system because East can also do recombination. Yeah. Genetic recombination East is one of the model systems to study genetic recombination. So I use East. My goal at the time is to purify a protein that binds left-handed DNA. And not bind if bind the DNA other right-handed B DNA, but we use 400 access B DNA, syndicated samusperm DNA, as a cleaning solution. That's all the DNA binding protein binds the BDNA bind to samusperm DNA. What is left, and you have to develop very good assay, sensitive assay, took me half a year to develop the assay. So have to turn the BDNA into ZDNA and use ZDNA, which is not very stable, and have to use that unstable DNA as a aside to select the protein, DNA binding protein. So after this developed assay, then I did a serious experiment and eventually found a protein, Ephon yeast. So the protein, this batch of protein had been used previously by another colleague to select the BDM binding protein, AT-rich protein. By the way, I don't know how much you know about genome. In human genome, East genome, most genome, the gene coding sequences has high content GC, and everything in between the coding sequences is AT rich. So that batch protein, this x-ray has been used, East nuclear X-ray has been used to purify AT-rich binding protein. So I mean already it works. So I use the same fraction to purify it and then ZDM binding protein. So one stone got two birds. But gut mass back got only 15 residues, that's enough to make a corresponding DNA. So use called the southern blood. Nobody uses that anymore. Everybody uses PCR. Southern blood, northern blood, western blood, and so on. We use the oligos to fish out the protein that binds to this left-hand DNA. Well, the first the DNA binding protein purified. So I discovered, so that's why I get the name, the gene, and the protein. It's like my baby. And what was it called? Called the sorting. Z-U-O-T-I-N. So means left in Chinese. It's a half-Chinese name. But if right Chinese character has a Z in this Chinese character. So that given sorting. Yeah. You can go to Wikipedia, type sorting, you can find it in Wikipedia. I did not make the page. Somebody else made a page. Turn out sorting is a multi-functional protein. Depends where it is in the cell nucleus or cellular function has a very different function. So I believe in general, protein, each protein has multiple functions, depends where it is and what time it is in the cell cycle. So I even wrote an article, compare the thought in another like Mozart. Mozart can compose, can conduct, can play violin, can play piano. Right? Depends what he's doing. He can fall different duties. The protein, I believe, most protein have such a functions. Otherwise, cannot explain why only have limited number of protein, but human beings can produce, can come with all kinds of things.
SPEAKER_00:Yeah. Wow. I mean I'm very moved by this story. And I think the way I understand that your scientific arc is that for people that know your work today, they'll know QTY code, they'll know self-assembly. But it's, and I think we're going to get to that, which is very kind of it's more platform, it's technology approach of kind of broadly across all proteins. But it started with this very specific discovery, you know, that was 15 years in the making, if you start from when you first heard about Z DNA. And so I'd really love to kind of continue with the story where you discover Zwotin, and then somehow that turns into self-assembling peptides, which then be has a billion-dollar punchline. And so would love to kind of continue on the story there. How did Zwotin get to self-assembly? Good, very good question.
SPEAKER_01:Most people, and when they discover new gene, and got very excited, right? Myself included, and we pursue to study this. Then I discovered, observed, that's the one sequence, unique sequences, is every other one is hydrophobic amino acids, alone, called AGAG AKAK, and repeat AGAG AKAK. That aroused my curiosity. Most people call gene and go on to do this kind of other things. I think in science, one of the most important things is curiosity and also very careful observations. Ask questions, yeah, observe. People can see stuff, can see, but do not observe. How many of us remember the side roads? Not many. Yeah, because we don't observe. We just see it. Don't observe. So in doing science, we see a lot of things, but observe. Observe is pay attention. So once you observe, then start thinking about things. The same thing for hearing. Hearing, you hear something, you can have background music. But only you do is listen. Listen is pay attention. When you go to concert, you don't hear the concert, you listen to music. So pay attention, listen and then observe as pay attention. So in science, those two are absolutely important to once you have those, observe and listen, you start to thinking about. Just see, just hear, it doesn't do justice. Yeah. So you observe that the sequence, this repeating pattern, just like Mozart, mainly music has uh melodies, had to repeat melodies. You can go to Mozart here, mainly this repeating the sequences. That exactly the sequence aroused my interest. In 1989, 1990, several people just published by people from Stanford. They showed 16 residual peptides with the same composition, alanine, gluten, and lysine from a very stable alpha helix. Very stable. So I thought this one would be very similar to stable alpha helix. I went to Alex Rich, asking, can I make a peptide do the study? He did not say yes immediately, did not say no. And then a week later I went back to him, Alex, can I make a peptide to study this? He did not say yes, he did not say no either. The third time, the third week, I went asking again, I said, Alex, can I study this? peptide he said are you sure you want to study this it's not your main focus my fellowship is to study genetic recombination to study and recombination there's nothing to do with that and but third he asked me are you sure I said yes so later Alex said to me something very profound I think everybody should listen to the device he said in science it's very important to know what to do then he said again it is equally important to know what not to do very important yeah so and as I decided to do this I knew I have to give up to study the Z D and genetic recombination but somebody else picked on people Johns Hopkins from University Wisconsin medicine and then in France in other places then keep on working on zotine. And in the end other people working on more zortin than I did but the self-symmetric peptide was first observed sixteen lucid peptide form some material visible with naked eye that's unheard of at the time how could the peptide form something visible with naked eye but turn out it's a salt induced salt without chloride without other judging water it doesn't see that and also initially have to see under Normarsky microscope which Alex doesn't have only a face contrast microscope in the neuron science and Bobitz has one so I use Bobitz Nomarski microscope to say face contrast system and that we made the peptide we did a study everything is totally contradicted to the literature everything. So it's not alpha helix is a beta sheet is very stable beta sheet very little change changed pH from pH 1 to pH 14 how did it change and the heat very stable you can stable 90 degrees nothing happens. So that's why MIT found a pattern on this and Alex asked take out the license office we don't understand what's going on but it's new material so that's how we met I met Bob Langer in 1992. MIT asked Bob Langer, Nita Nelson asked Bob Langer, and I asked me to explain to this observations I explained to Bob he said it's based it's made of amylacids and it's harmless and it's it's new material we should file so I may file I two years later not file in 1992 two years later was licensed to a company for$1.2 million dollars for the patent which he not made partner get licensed. Made partners just filed get died and then but this one gets the license to$1.2 million dollars. However the company licensed then didn't continue to do the work on this so MIT has a clause after five years it don't develop you should give part and bike so MIT insisted company to give pattern bike so asked me to form a company and then I form a 3D metric company I didn't know anything about forming company and hire first CEO from Sloan School big disaster everything on paper has no experience in practice. So hire another one another one soon took over and did not study science and took over for me hire consultant to read my paper and explain to him but in the end the company was saved by one investor in Japan and brought from Cambridge to Japan and went IPO so that now that product called Pure Matrix and has been used for wound healing and selling more than 20 million dollars per year for many years now. And it's clinic and the Cleveland clinic mayor clinic and MGH and also Europe in UK in Europe and in Singapore Japan and Australia elsewhere selling very well it's like toothpaste. And toothpaste you seal in the wound once you have surgery you instead you seal the wound very quick. Why? Because that is nanofiber what we see in the material is the gel type but like she didn't understand nobody understood so we got the pattern granted because nobody understood but we explained we explained how it worked what the mechanism it worked it was Francis Crick advised me to look at it. I told him we did do x ray diffraction because Alex Rich the laboratory is x-ray diffraction laboratory.
SPEAKER_00:We did and but we Alex which could not do fiber diffraction so quick Francis Crick the same click discovered DNA double helix he told me you should look on the EM so then I looked MIT had the EM scan the EM and look at EM all the nanofiber showed up that's the first time we saw protein material from a nanofiber so that was got very excited in 1992 that was uh yeah product yeah it's an absolutely unbelievable story so once again you know from a boy working in a pig hair factory to now working with Alexander Rich and Francis Crick on a discovery that you made is amazing. And as one of your students I remember sitting in your lecture showing that it's pretty interesting to see a camera photo of a hydrogel right which is self-assembling peptides. And as a technologist I kind of like collecting tricks right or approaches and just the idea that a small repeating peptide sequence can self-assemble into a macrostructure that in this case can retain water you can functionalize it you can deliver drugs with it it's really it's really an amazing story. And I'm gonna push us kind of forward now I'm gonna we're gonna jump about 15 years. So you it's ups and downs but this is a huge discovery for you. There is this moment that I think is also just another great story and then I want to do I do want to make sure we're looking forward but one of the moments that really stuck with me as beautiful in your career is things are going bad in 2011. You have this and it's this is all in in your public essay but you get your funding cut you're having issues with the MIT administration they make you move your office twice for no good reason and your lab was so broke that you borrowed$4000 and you put$1000 of your own money probably from 3D Matrix to keep your lab alive. And you know so in my mind I'm reading this and I was like why didn't he just quit but then on the other side of that was the QTY code which kind of sounds like quit which is funny. So I think this is just a great story of perseverance and you know so I think people want to understand the QTY code but maybe we just start with what you were trying to accomplish why you went into debt to keep your lab alive and then what the discovery on the other side meant.
SPEAKER_01:I have been teaching the class and Daniel you took since 1999 and I've used a textbook by Carl Brandin and on page 17 this has three alpha helices one is the bullet hydrophobic and second in the middle is half hydrophobic half hydrophilic third one is so hydrophilic. So nature has done it and the alpha helices are no different when he discovered alpha helix he did not put a side chain on it only center axis yeah the geometry the rise amylasid and so on it did not specify the amylacid so people in protein science knew for decades that there are different kinds of alpha helix but nobody made an explicit classifications until I wrote this in 2022 specifically wrote this into so on the Alex asked a question in 2010 December 20th I know the exact time and date where on campus he asked me a question can you convert alpha helix hydrophobic alpha helix into hydrophilic one that's a very scientific question convert hydrophobic alpha I said of course I can I can and people have done this in use changing lecine into lysine into gluten to arginine and so on and so forth but I thought how to change convertin so I told Alex nature has done it because hemoglobin is all alpha helix it's highly hydrophilic yeah we can high soluble protein in in in our body 30 milligram per liter no per mil per mile 3% and but membrane protein it totally is also alpha helix it's water insoluble but question is how to convert them yeah so I uh so that's why I printed to writing NH grant application I print this a gene membrane protein or factor receptor a mouse to study to during the weekend write NH grant application. So I did on this how to change and so on and so forth. Leucine changed to arginine change to lysine and we change to aspartate change to whatever lysine and so on and change isophic into hydrophilic. But those size are different and even change to charge the protein becomes charged and is not neutral anymore. So I did it on the piece of paper finally I put uh writing down on this piece of paper leucine changed to lysine archinine glutamate and aspartame and so on and then q is glutamine and then valin changed to swelling searing and whatever stuff finally tyrosin in the phenoline change tyrosine. So once the road piece on the piece of paper I can see so I don't want protein kind of new charge. So Q is a no charge and the Q is glutamine. Yeah T is swelling low charge and the shape is the same finally is phenoline can be replaced by tyrosine which has a hydrophilic OH group on it. So each OH group can form three hydrogen bonds and each acid glutamine can form four hydrogen bonds that's why it becomes soluble. So now I look at the shape I discover by accident somebody's a teaching website David Eisenberg I used Los Angeles that has a website shows 20 amyl acids labeled change by size labeled as arranged by size the first time ever I have seen such an arrangement. So once you arrange by size you can see the wheeling and the swelling the electron density map identical almost identical and the leucine which is hydrophobic and aspergine aspartic acid glutamine and glutamate the density map is also very similar and finally is phenoline with the tyrosine and hasidin are also very similar so that's how QTY code was born. Wow it simple and but just look on paper not enough you have to experiment that's why I spent seven years doing experiment and then I did it.
SPEAKER_00:Wow okay so to to make a quick parallel here work study what became zootin studying ZDNA took you to self-assembling peptides and then studying olfactory proteins took you to a general strategy to take any protein and make it soluble.
SPEAKER_01:Yes and it took seven years of proof and seven years to to publish one paper seven years. It's like a whole nother PhD my meantime I wrote the three NH grant applications everything was rejected and the size it's impossible it's crazy it's unsound so also one was criticised me I'm very good at working peptides but no experience working membrane protein inexperienced membrane protein but the fourth application that wrote in 2023 review 2024 is that we know everything already of course you can change this so wrote for age grant didn't get any funding meantime got more than six million dollar funding from other places and now five companies focus on QTY code.
SPEAKER_00:Yeah five startups yeah I I hope for everyone who thinks about what new science structures need to be can listen to the story because I think there's something against consensus science right there's a story there's times for it and there's times where it can really push everybody back to you know everyone has to raise their hand and agree and I don't think a lot of good science comes from that what do you can you give maybe one example because I think this is another powerful idea and solubilizing a protein might not be immediately obvious to people. So I'd love to just maybe do one quick example of that and then I'd love to go to S layer proteins and you know how we fix climate.
SPEAKER_01:But what would you do if you could solubilize a protein the two companies would be formed found two publications one probably in 2023 we can solubilize XL4 is one of the chemical receptors we can use as a monitoring device or detector device and the paper has been published and you can make a device and anchor on the surface one trillion per square centimeter very high with 100% up uploading like SL protein on the down the bottom and that's one application that's one company will be formed in Hong Kong Hong Kong really wanted to get us to Hong Kong because as one of the sponsors gave his lot of money is from Hong Kong he just sponsored with an idea which NIH will never go do yeah he just got an idea okay we trust you we trust your science and we succeeded and other companies we published paper this year in August and August and August 21 2025 shows the same water soluble 6L4 can be injected into animal cancer model animal four different cancer multiple can stop or reduce cancer metastases. So that in my animal paper published just this year. So now another company will be formed in Songhai and the first company and as a detector called recensor receptor SL electronic nanoarray the second company called molecular trap because this water soluble receptor becomes like monocle antibody confined to this excessive ligand and can remove them and then like a sponge washing dishes soak up all the excess stuff and then remove them.
SPEAKER_00:If that could be redirected to metal separation I think that would be amazing right and so I'm gonna kind of go into quick digression but I do hope we kind of define S-layer proteins because that's another thing I've learned from you and but uh you know we think a lot about critical minerals and we think you know one of the major bottlenecks is separations so how you find you know both in a complex mixture but also in dilute mixtures how you bind you know rare earth elements especially the heavy rare earth elements are very hard to tell apart and that's one of the things that biology I think really has a premise like a lot of promise for is the atomic precision. And if you can build something from the nanoscale when can you get these incredible performance characteristics like you were just talking about with either you know sequestration or from initiating a you know an immune response. So so I think that is one area where I get really excited and you know when can something designed on the nanoscale really help? But I think this S-layer trick is also a self another self-assembling trick. And you know my joke is I'm a recovering mammalian supremacist because I started in neuroscience and so I only thought about mammalian biology. And so you never hear about S layer proteins when you come from neuro. So what are S layer proteins and you know how do you think they are useful in this situation?
SPEAKER_01:S layer protein is here essentially every AHIA doesn't have like regular membrane like bacteria. Also some bacteria but E. coli don't have it salmon don't have it so people just ignore since it's not important. But here is another kingdom right it's very important all the high temperature and you got the PCR enzyme from you kind of high salt bacteria that grow in the Dead Sea and so on. They all have this the bacteria from the in the hot spring in in Yellowstone they all have this kind of S layer. So S layer is protein then soft symbol on the bacterial surface is like a checkerboard checker you think about the checkerboard and it's so rigorous it's a two-dimensional nano crystalline yeah think about the oh the your kitchen has a checker checkerboard type so each dimension each area is so defined it's a nanometer square nano square nanometer square so in this particular one we use is 13 nanometer square by each anchor you can anchor protein on onto top on each one can make recumbent protein and protein can anchor molecule 100% upward think about you drop cooking drop bottle water bottle on the ground how many bottles were standing not many right you drop from one meter high that's one meter high drop then how many standing? Very few. So SLA protein you drop the bottle on the front it's 100% upward. So that one sensitivity will be extremely high if binding on the first one you missed it go to the second one third one and so fourth one. Unlike antibody all the people doing ELISA right antibody on the surface is randomly coded if you have 10% coding with the the F FAB binding ligand is pretty good already, 10%. But with SL it's 100%. So that's what such a difference. Bacteria are really meant to demand crystalline. And Professor Uwe Sleiter in Austria and his colleagues had been studying for 60 years since 1968. Wow. And from curiosity, he discovered SL protein from the non-E. coli bacteria. And then he studied so for 50 some years, not 60. And then had developed into very useful technology. And then MIT had a joint and file partner with him for the sensor, with sensor the company will use SL protein. And it will be used for many other things. One my star company, new one, will also use S layer protein. Actually, two my staff companies will all use SL protein to for something else. Amazing.
SPEAKER_00:And just so I'm imagining this right. And I think the Wikipedia page is really good for this, right? It is a the S layer proteins are a self-assembling 2D surface. Yes, two-dimensional lattice. Covers the cell body, you know, the cell of and when you orient everything in the same way that clicks into this self-assembling array, you now have in 13 nanometer gaps any arbitrary function you want, which is very and also if calcium induces self-assembly. So you have an arbitrarily high concentration of something happening. Yes. So very good. So Xu Gong, I'd love to steer this a little bit just with the time we have is to talk about the planet and to talk about I see. So people are gonna be listening, and Shuguang is showing me the collapse of Western Civilization, a book which I think is really resonating with you. So why don't you want to just kind of tell us about you know what that book is talking to you and how biotech can help?
SPEAKER_01:Biotech should be very useful to help fighting climate change. And Daniel, you have been swimming in California seacoast. The kelp. Yeah? The calp grew so fast, it grew how many inches per day? The one with the exceptional is grow 20 inches a day. That's you can actually literally watch it grow, see the giant cup. And but we don't have because that's like cold water, done like hot water. If you can do recombinant this kind of cup, you cannot change into much better and grow because it suck off the carbon dioxide. And there's a company in Ireland, Ireland, that job is to grow large amounts of cup as a food and feed for animals. And large biotech can be very useful. We even spoke with people at Woodshof. Remember? We spoke with somebody at Woodshov Ocean Institute, then grow cup in Alaska. So on. And Norway and Maine also grow cup, but small scale. I think cup is very good for food feed for animals. And that can because it grow very fast, then can capture carbon dioxide much quicker than trees. And kelp the photosynthesis system is much more efficient than trees because on the water. One of the young boys asked the question why is there no black tree leaves, no black leaves, trees? Yeah, all green. But kelp, it's so dark green, almost like black, because photosynthetic system might be much more efficient on the water. Photon goes through the water, lots of get deflected, or could not go through the water. The kelp can capture them. So that's its one. So why I ask everybody to read the book. In this book, it describes what's happening in a hundred years from now, and historians looking for a thousand years from now. So humanity knowingly, knowingly in 20, 21st century, it's knowingly climate change, but didn't do enough to stop it. Yeah. So the water when you Green Line and Antarctica and all the glacier in Himalayas in the Swiss Alps melt will increase the water, the sea coast by 66 meters high, almost 70 meters high. So all the coast cities, New York, Boston, Washington, DC, Baltimore, San Francisco, Los Angeles, whatever, Ogan, Seattle, Portland, yeah. Most European cities will be also on the water. Imagine 66 meters. Singapore everybody's talking about AI is whatever, this and that, but if you don't stop climate change, everything will be on the water. And the US recently has cutting down clean energy on the current administration. All the clean energy has been cut. All the wind farms, solar farms have been stopped. Meantime, Europe, Australia, and China has been increasingly building, and Israel and Saudi Arabia, all those countries has been building solar panels in larger scale. US soon have to buy solar technology from other countries.
SPEAKER_00:Okay, so we so agreed. Clean energy is essential. You know, one thing that you stand for a lot, and I think we'll get to it in the closing questions, is always ask questions, right? And I think you're, I mean, you've lived the example. And the it's kind of a funny thing, but we were talking, we were talking before this about uh, you know, sea level rise when the glaciers melt, and you're using Gemini to send me this. And I really want to get your perspective, because this is actually one of the essays I tried to write about you, and I just couldn't land it. Is that in the age of AI, asking good questions is even more important because oftentimes it's having the idea, then you can get the amplification from the AI. I'm curious, you know, you I'm sure you ask questions to these things all the time. And I'm curious, yeah, what do you think about AI and the importance of asking questions? And what advice would you have for younger people listening?
SPEAKER_01:Well, AI needs a lot of big data to support it. And AS is trained on big data. If you ask a question in 2020, 2030's question, AI cannot answer you. And then you ask some four far-out questions, can elephant plays basketball? That's everything is correct, right? The sentence syntax, everything's correct. But elephant cannot put a basketball. So AI cannot, mostly AI cannot ask good questions. AI is not curious. Five years old, Daniel, you're five years old asks much better questions for about nature than AI. Yeah. So eventually AI needs to train. So far, AI cannot ask good questions, but then can other follow-up questions. Once you ask the first question, an AI can repeat you or ask you variation or on the same, those kinds of questions. But original questions come from the BI, which is the brain intelligence. And brain intelligence is absolutely important, and especially for children, for curious mind, and that it needs to be kept, it will be continued encouraged.
SPEAKER_00:Yeah. Well, there's a lot I want to ask about this. But what I think the best thing we have to do now is go into the rapid fire questions at the end. And I hope, I really hope people are taking notes on the new approaches to biology that we've discussed here. So I'm gonna ask you four questions, and I'm gonna intentionally not respond much to keep them rapid fire, but really say whatever comes to mind, and you're gonna see a lot of your influence on me and these questions. And we've asked all our guests this. So the first question for you, Shuguang, is what's a single book, paper, art piece, or idea that blew your mind and shaped your development as a scientist?
SPEAKER_01:I read a book in China called One, Two, Three, Infinity. It's written by George Gaimov. Yeah, I've heard this guy, scientist. He is the same guy who coined the word the big ban. Same guy. He's the same person who was stimulated and Crick, Watson, and others to study genetic code. Same guy. He's also a physicist. He spent a lot of time in Washington University in DC. Later ended up in Boulder. He's a Russian Jew immigrant to the US in the 1930s. That book was written in 1948. He said, in another book, 48, he said the science would develop in two directions. Two directions. One extremely far away. Galaxies, astronomy. The other extremely small. It has to say in the microscope, and so on. That book has a tremendous influence on me. I had an interview with nature in 2003. They also asked me what books influenced me most. It's that book. So science is infinity in two directions. One infinitely large, the other is infinitely small. And then 1948, imagine this guy, all the books that drawing, the cartoon, he wrote his drawing himself. He wrote quite a few public and popular science books. George Guimar, 1, 2, 3, Infinity. The same book had a tremendous influence on Roger Penrose, who was Stephen Haking's PhD advisor. Also, Joe Jacobson also told me he also read the book, the same book, One, Two, Three, Infinity.
SPEAKER_00:Yeah, very profound. I love it. Alright, question two. What is the best advice line that a mentor gave you?
SPEAKER_01:Ah, well, Francis Crick, right? Even though he was not my mentor, but I met him four times personally. No, four times in California. He was heard in Boston twice. And visiting Alexander Rich. So he said you should always ask questions. The bigger, the better. He said, then said, if you ask big questions, you get big answers. I fully agree. Right? That's the best advice. Alex Rich also gave advice as I mean to you have already before. It's important to know what to do. It's equally important to know what not to do. And also, Alex frequently says, why not? That uh he why not is that two words, allow me to study the peptide. That's what he said, why not? Important advice. Because the called open mind, why not means open mind.
SPEAKER_00:And I hope people who listen to this go see some of your lectures online because it's filled with quotes and references to your mentors. And I really I've internalized that a lot into the way I do things. Question three: if you had a magic wand to get more attention or resources into one part of biology, which part would it be?
SPEAKER_01:I would just hope people put the resource to study the brain. So we don't understand, very little understanding between our ears. We don't understand what's the molecule of memory. We don't even understand what is the molecule of thought. Yeah. How you're thinking, what is the molecule? Is molecule doing the work? Is enzyme or whatever other things, other proteins, and what people call neurofilaments or microtubules, whatever, it's some kind of molecule, how it's be aggregated and keep the memory. We don't know. If we understand the memory, it'd be much more powerful. Yeah. To understand neural computer science, everything else. Yeah. Neural science. I think it's called a sense of the brain. But now functine have been cut and the eye devoid even not getting enough function to study the brain. So sad.
SPEAKER_00:I choose optimism that we're going to get it back, but I share this and I agree with this answer very much. Alright, and then the fourth answer, the fourth question is what is one aspect of personal development that you think biotechnologists need to spend more time on?
SPEAKER_01:I think you should spend a lot more time on AI. And then because AI needs the data, the bigger the data, the more powerful the AI. You still should to study some unusual animals, unusual systems. Think about the people start to soften, discover the home box, it's conserved entire living system. People study east and the cell cycle. Yeah, east and climb study cell cycle. People study the worm, say elegant, understand apoptosis, all the stuff are universal, not just one small unimportant organism, but human included. Study ciliate, hymela, and through the telomeres, and orange splicing. So I study on the study, very important study, unusual system. I if I were a young person now, I would study some the fish under the deep sea. Or some crap under those guys living 10 kilometers deep sea. The pressure in some ring has a hard time. But there's no problem there. How and why? And cuttlefish, this squid, squid has a brain, cut a distributed brain, squid. Not the brain only in the head, but all on the tentacles that have the calculations. The study unusual organisms would really help understand the real biology, how it's really sensitive to work. Yeah.
SPEAKER_00:Love it. I mean, yes, the fish that have blue blood and the cuttlefish, which can be genetically identical but live across 30 degrees of variation because of all the post-transcriptional modifications. Very cool. And I mean, Tetra Hyman is where a lot of your work started too, which is beautiful. Yeah. Um, I have to say this has been a total honor, uh pleasure to have this conversation and to talk about your history and to see the patterns in focusing on one thing unlocks a tool, and then the tool goes back into something, you know, studying something specific. And I think it's just been really beautiful. And just as we wrap, I want to make sure I'm saying huge thank you to you for your mentorship to me and many other people. And I'm just curious if you have any parting words or if people want to find you and learn more, where would you send them to?
SPEAKER_01:Well, I would study the sea creatures. I have written in my will how much money I would give to Utho. So because that remain to be discovered, there are so many things we don't know what we don't know. So we people say we know what we don't know. But other things we don't know what we don't know. So we can't even begin to ask questions. So I think it reveals quite a lot of sea creatures, the mystery will solve a lot of problems. The jellyfish, imagine you can't discover GFP. Without GFP, can you study neuroscience today? No. Right? So that's uh study the channel adoption. Yeah? Now have uh without optogenetics. And all this unusual place you have to look looking and developing a new tool for peer the mystery of science further down the brain or other sense. Yeah.
SPEAKER_00:Yeah. Well, Shu Gongzong, thank you so much for coming on the Climate Biotech Podcast. It's been an absolute blast.
SPEAKER_01:Sure, it's my pleasure, Daniel.
SPEAKER_00:Thank you so much for tuning into this episode of the Climate Biotech Podcast. We hope this has been educational, inspirational, and fun for you as you navigate your own journey and bring the best of biotech into planetary scale solutions. We'll be back with another one soon. And in the meantime, stay in touch with Homeworld Collective on LinkedIn, Twitter, or Blue Sky. Links are all in the show notes. Huge thanks to our producer Dave Clark and Operations League Paul Himmelstein for making these episodes happen. Catch you on the next one.