eMalick Njie, Ph.D | Part 2: Answering the Question “What is Memory?”

Intro - 00:00:01: Welcome to The Biotech Startups Podcast by Excedr. Join us as we speak with first-time founders, serial entrepreneurs, and experienced investors about the challenges and triumphs of running a biotech startup from pre-seed to IPO with your host, Jon Chee. In our last episode, we spoke with eMalick Njie about his journey from Gambia to Brooklyn, his undergraduate studies at Northeastern, his research at MIT under Alice Ting, and a pivotal internship at Millennium Pharmaceuticals. We also spoke about his PhD work at the University of Florida, where he studied neurobiology and neurosciences. If you missed it, be sure to go back and listen to part one. In part two, we continue our conversation with eMalick, talking about his move from Boston to Florida, the cultural differences he experienced, and how the move revitalized his passion for research. We also hear about his research focus on the cellular and genetic causes of Alzheimer's disease. eMalick shares his insights into the critical role of microglial cells and his experiments with stem cells and plaque-busting proteins, highlighting some challenges and breakthroughs in Alzheimer's research.

Jon - 00:01:24: So you're now at UF. And it sounds like this is like a stars aligning, just like I'm thinking about the hangover, just like calculations. You stuck the landing here. You're now in Florida. I guess my first question is, how was the move just personally from, in the Northeast down to Florida. How was that for you? 

eMalick - 00:01:46: So coming from Boston to Gainesville, it's almost like moving to a different country.

Jon - 00:01:53: Yeah.

eMalick - 00:01:55: The one thing that what struck me was, I actually was an attractant was the weather change. I was quite homesick at the time that I was moving. Like it was so bad in my apartment in Boston. I had spent much of my millennium pharmaceutical internship money going to Home Depot and just buying all of these like big ferns and put them in my room just to replicate like a more warm environment in February in Boston. So it was quite wonderful to go to Florida where it was green everywhere. There was palm trees left and right. And extra warm weather in the summertime, I totally was able to handle. And then it never got too cold in the winter. So just spiritually, it was great for me.

Jon - 00:02:43: Awesome. 

eMalick - 00:02:45: Yeah, it was really wonderful. Culturally, it was quite interesting. So at the time, while in Boston, I think there was this big sign near Fenway Park basically saying stop. This is not going to go political, but it was basically stop guns or stop no more guns or sales or something like that. So we went to Florida where-

Jon - 00:03:04: Very different.

eMalick - 00:03:05: I'm not joking. When I moved into my roommate's place, after we said hello and, you know, this is your room, da-da-da, okay, let's hang out and watch TV, they then invited me to help them clean their guns.

Jon - 00:03:18: That's starkly different. Starkly different.

eMalick - 00:03:23: Okay, it was pretty cool. It's like shut up, SMS machine, you know?

Jon - 00:03:26: Yeah, that's so funny. You're like, where am I right now?

eMalick - 00:03:31: Where am I?

Jon - 00:03:32: Yeah, not only the weather changed, it's like a complete cultural change. 

eMalick - 00:03:36: Many things have changed, yeah.

Jon - 00:03:38: Yeah, I was actually, I was in Gainesville recently at UF with Innovate and Sid Meier. And exactly, I was like, and I don't go there often, but when I do, I'm always just like, how can it be so green? I'm like, it is so lush out here. It is crazy. So I can imagine that you're talking about like having the ferns inside your, in the Northeast. You're just like, yes, like I don't need to go to Home Depot anymore. It's just here.

eMalick - 00:04:06: It's just like here. It grows naturally there, yeah.

Jon - 00:04:08: Yeah, amazing. Okay, so now to kind of the lab experience, can you talk a little bit about the research that you were doing and your experience in this lab? 

eMalick - 00:04:20: Yeah. So again, working with David Burchelt, as well as Wolfgang Jake Strait, they're all in the same building, like two floors. So Michelle, the co-mentor, was both great, amazing scientists and also a ton of amazing colleagues that I had in both those laboratories who now have done wonderful things and continue to inspire me, actually, in their own ways. So my central question at that time. Was what is memory? And one way to explore that is by looking at the extreme edges of memory. So on one end of that spectrum, you could have folks that are super learners, folks that compete in memory competitions as like a hobby, for instance. I'm sure you may have heard of those. You know, they literally get together and give each other a deck of cards, and then you have to memorize the order of those cards. Or a deck of words, you have to memorize the order of those words, and these could go into the hundreds or something like that.

Jon - 00:05:21: It's crazy.

eMalick - 00:05:23: Yeah, and they have clubs and associations. It's quite a wonderful or very interesting space to know about. So that's like one end of memory, folks that are just able to... Perform feats that the rest of us just, we just don't have that kind of space to recall. The other end of that spectrum is Alzheimer's disease or the newer degenerative diseases, but I'll say Alzheimer's to start with. So to understand memory, or any study, usually it's best to spend more of your time on the extreme edges of it. And it just so happens that there's a lot more funding for the Alzheimer's side compared to the super memory side. Yes, yes. Those guys on the super memory side are doing okay, right?

Jon - 00:06:13: Yeah, yeah.

eMalick - 00:06:13: They tend to be very successful in life because of that skill. On the other end of, however, with Alzheimer's, people are actually robbed of their livelihoods, robbed of their most precious memories, memories of their own children, of important moments that they went through in life, capacity to take care of themselves, which is not just in old age. Like Alzheimer's, the most extreme, the forms of Alzheimer's. Thank you. Impacts people in their mid-30s. So what are the cellular and physiological, as well as the Good to hear, Mike. And I would even say the genetic causes of Alzheimer's disease and how can we treat them was my big question. And at the University of Florida, I was able to explore two of those spaces pretty intensely. The cellular as well as the proteomic aspects of Alzheimer's disease. So with the cellular aspects of it, you know, within the brain, there's several different types of cells. There's astrocytes, there's neurons, there's microglia, and like a few other cell types, but these are the primary ones. The neurons are thought to be the electrical conveyors, the communication conveyors within the brain, while the other cells, such as astrocytes and the glial cells, are thought to be support cells. So they sort of take care of the Michael Jordan cells, so to speak. And at the time I was beginning my studies, there was this debate as to, do they have any impact on Alzheimer's? And there was a school of thought that these glial cells cause inflammation that causing neurons to die. So that was a prevailing hypothesis. Jake's right, though. He had a sort of a counterfactual. His counterfactual was that... These support cells are actually quite critical. The loss of these cells means that the neurons themselves cannot survive. So this is a larger hypothesis that he operated under. So we worked on experiments together that investigated the movement of amyloid protein that was thought to be important in the disease course of Alzheimer's disease. And the movement of amyloid in microglial cells, which are a subtype of glial cells. And we looked at them within an Alzheimer's space, as well as just elderly, aged brains. So this involved like pure wet lab work, tons of ELISAs and so forth. And I would say the take home, from those studies was that Microglial cells are indeed critical. They, within a normal state, very actively recycle the amyloid protein. They absorb it, ingest it, and then recycle it back out. To the extracellular amyloid. However, within a disease state or a very aged state, this becomes this capacity to recycle the amyloid protein or peptide becomes markedly reduced. In fact, peptide itself seems to be hurting the microglial cells and therefore the different measures of aliveness of the microglia cells gets reduced when they're exposed to the amyloid person. So this became like a sort of like a small pillar within like a larger story of this is one of the ways that these key support cells become compromised and therefore cannot continue providing the support to the neurons and therefore you start having loss of neurons in Alzheimer's disease. So that was the cellular studies for my PhD. And on the other end, I wanted to not just understand what was causing Alzheimer's disease, but how can we do something about it? And so this was the second arm of my work that I did mainly with David, where we investigated different proteins that were thought to be plaque busters, is the best way to put it, that destroy the amyloid plaques. So neprolysin, heparinase, and so forth. There's like a few of them that at the time were thought to be, at least in the test tube, break down amyloid plaques. So in stem cells where at the time... Quite new and thought to be excellent delivery vehicles of these proteins. So what I did essentially was purify stem cells, then genetically engineer them to overexpress. The proteins that we, the plaque buster proteins, and then inject them into mice that had a version of Alzheimer's disease. And I look into their brains to see if there was reduced plaque load down the line. This may sound familiar to you because that's called CART therapy today. Yep. C-R-T. Yep. Literally the exact same thing. So that's what we were doing then. And there were some mixed results from the study. What was quite fascinating to see stem cells just navigate all around the brain once injected into. For, you know, mice live about two years. And I think in some of the studies that we did where the young mice were injected with the stem cells, their stem cells survived nearly two years. So they were long-lived, which is quite interesting to see. However, they didn't, at least in our hands, didn't reduce plaque load by that much. And the reason is the stem cells just migrate to wherever they feel is like the most best niche for them. And that's not necessarily close to where the plaques are. So while they were secreting their plaque bus and proteins that we, you know, that they were genetically engineered to do, those were not going to the plaques themselves. So we didn't see much plaque load, which is like a lesson that's actually something that I continue to think about to this day as far as the movement of heart therapies, how efficacious they will be. And versus like competing methodologies such as lipid nanoparticles and so forth. But that's a whole other chapter.

Jon - 00:12:49: Yeah, exactly. Exactly. Very interesting. I mean. It sounds like this was like, you're kind of at the frontier, kind of at this point in time. I'm curious, you know, I have a sense of what the MIT kind of lab environment was like, but what was this specific lab environment like? Was it a larger lab, similar size? 

eMalick - 00:13:12: Kind of what

Jon - 00:13:13: was that like?

eMalick - 00:13:15: Both the MIT as well as the Burchard Lab were, I would say, medium-large labs. You know, MIT, it was me and Mark and Alice, it was three of us. By the time I finished, we were pushing 15, maybe close to 20 people. Similar thing, David brought his team from Johns Hopkins. So that's like a team, at least like 10 or 12 deep, really wonderful folks. And then he added some graduate students and some postdocs. So we're covering between 15 to 20. Individuals and he was given like a lot of space to do what, you know, for us. So. That's another experience where I think you mentioned 300 before, where I would say I was quite fortunate, again, to have a lot of freedom to operate. Not just physically, but also mentally. Hypothesis behind the studies I guess described all came from me walking down the street or taking a jog or, you know, shower, I don't know where these things come from, from the ether. And then honed by discussions with the professors. But it gave me, they gave me freedom to think and to shape and to execute. And this wasn't just me, like all of us were given that freedom because David really trusted in our capacity. And he had like a abundance of knowledge to help shape whatever crazy ideas we have into something potentially useful.

Jon - 00:14:53: That's so cool.

eMalick - 00:14:54: That's really cool, man.

Jon - 00:14:56: I mean, I'm thinking back to your childhood, honestly, right? It's that freedom to explore the curiosity. I think it's awesome that you found it at UF2 in David's lab, because I think those

eMalick - 00:15:10: environments are rare.

Jon - 00:15:13: And something, again, I'm going back to the Rick Rubin book, and he called it the ether. Rick Rubin calls it the source, like capital S source.

eMalick - 00:15:21: It's kind of like you're tapping 

Jon - 00:15:21: into the source, whatever it may be. And it's like you could be in your shower, shower thoughts, or you're on a, this is when you kind of have a little bit of just like breathing room and you're not just constantly just like going, going, going. Which is really cool. And having the kind of leeway to explore that to its logical conclusion is very cool. And so I know, like, you know, after you left, you ended up back at Columbia. How did you end up, you know, choosing Columbia for your postdoc work? Can you talk a little bit about that transition?

eMalick - 00:15:57: Well, I mean, coming to Columbia, Columbia, um, It was a bit of a... I cannot refuse this potential to do this, but it required a lot. So this I'll bring back to the first time I met Martin Shelfie in person. He had come to Florida. To give a talk. And he had just won another prize, I believe that year, for green forest and protein. So I also tie back to Roger Chan. From yeah yeah yeah um and he came and gave a talk at our school and this is a little quirk i don't especially my friends know um back when i was in graduate school i used to play this game called professor

Jon - 00:16:45: Okay.

eMalick - 00:16:46: So stumbling professor is pretty, well, maybe it was me compensating for the fact that I slept a lot in lectures. So one question that comes to you, then like, I'm good. Yeah, yeah, yeah. But... I would do this routinely. I would ask the professor something that would just be on their... Within the immediate capacity to answer. And it was always fun. And Marty came. He was giving us a lecture. You know, it's like a Nobel Prize winner coming to your university. Everybody's. Best behavior, biggest auditorium, you know, it's like a stage. And Marty is such a great speaker and he really engaged the audience. And I played Stomping Professor with him. I love that theme. 

Jon - 00:17:41: Mario, now

eMalick - 00:17:42: you know. Yeah, I think he knows. I must have told him at some point. But he was talking about this low-powered GFP that was important for not light bleeding some sort of multimers that he was associated with. I can't remember what my question was, but it caused him... Pause and then led to him asking professors, after the talk, asking professors about me, which then led to... Me being invited to his second talk the next day at a different location in Florida. Yeah, and then I had a one-on-one with him that was quite extended. And he told me about C.Elligan's research. And I told him about the stuff that I was doing in the laboratory with these, you know, plaque busting materials. And so we are coming from two different spaces. He's basic research and I'm pure translational, right? But there's like a difference though. He knows about translational and I don't know anything about basic. I really didn't know anything about C. Elegans, but we had like a good rapport. And he said, and I complained to him about some of my thoughts on the studies on Alzheimer's disease. Specifically, remember how I said I studied the cellular and the proteomic aspects of the disease? Yep. But we weren't really strong in the genetics of the disease, right? I call this a radical question because I really was annoying people at the time when I was like, well, if we know that Alzheimer's disease is like a disease that's passed on through families, why are we only studying the genetics of it? Why don't we just put all of the funding only on the genetics? Like sort of this extreme way of thinking. And, you know, I didn't find many audiences for this, right? But folks knew of this thinking and sort of like snowballed to this, I guess, annoying West African guy yapping about.

Jon - 00:19:36: Yeah, yeah. 

eMalick - 00:19:38: But what I was doing was asking about the ground truths of not just our laboratory, but of the entire field of Alzheimer's disease. At the time, most folks were following the amyloid hypothesis, and even the tau hypothesis and so forth, but mainly amyloid. And I was curious about what are the ground truths here? How true are they? And should the genetics be more explored? Because we know that is true. You could trace down Alzheimer's families now from the 1100s until now. Moving across different continents and so forth? What is that genetic element that is moving across those human beings as they move across different places, right? So I shared this with Marty, and at the end of the conversation, what he said was, well, if you're really serious about learning genetics, you should consider coming to study with me for your postdoc. But you have to learn about C elegance first. Why don't you take a look at that and get back to me? Yeah then he said one more thing he's like so if you do find it interesting For you to get into the lab, you have to do the same thing that every single graduate student and postdoc has had to do since the beginning of the lab. You have to write a proposal that impresses me.

‍

Jon - 00:20:55: The game is on. 

eMalick - 00:20:57: The game was on.

Jon - 00:20:57: The game was on. You're just like, here 

eMalick - 00:21:00: you go.

Jon - 00:21:01: Here's it. What was that feeling? Like, oh, goodness. 

eMalick - 00:21:07: Yeah, I was, I mean, again, starstruck and being like, is that an invitation or telling me to buzz off? Yeah, yeah,

Jon - 00:21:14: yeah. I wouldn't know how to read it.

eMalick - 00:21:16: Yeah, right. But he seemed very genuine. And he was actually. Like quite like he didn't i just remember we were having this conversation i did he didn't seem to want to leave the conversation to go to his talk right so i read that as him being interested um in sort of my complaints regarding genetics within the translational space. So, well, I went back and started to learn C. Elegans. I was doing my dissertation at the time. So I literally cut the time of dissertation in half. So half dissertation, half proposal. Half dissertation, half proposal. And it was more than that. This proposal was, I wasn't smart enough to just go into an entire new, like basic research space and make something cogent. So I dragged all of my friends into this.

Jon - 00:22:10: It's like crowdsourced.

eMalick - 00:22:14: Crowdsourced. Yeah, yeah. Thank you to them, to Wilton and Andrew and company that read revisions of this proposal. And also, there's like a cost to everything. It's not, nothing's free. I'm supposed to be sending them my dissertation for them to review, but I'm sending them the proposal. Yeah. That's amazing. 

Jon - 00:22:34: Yeah, yeah, yeah, yeah. They're trade-offs.

eMalick - 00:22:37: There's a trade-off. But I was one of quite fascinated by C. Elegans research. Just for anyone listening to this, and it's not a deep and basic research or into sciences, C. Elegans is a model organism. It's a worm, about a millimeter or two of length, that lives underneath trees and feeds on rotten fruits and so forth that fall off trees. And has become one of the organisms best to study the best genetics from multiple different researchers across the last 50 to 70 years of science. And I didn't know anything about this. I didn't know that, I don't know, it was like one in three Nobel Prizes that have gone out. Two researchers had one, two folks that basically were playing with C elegans. Yeah. One and four, some crazy number like that. I was in my own bubble. Yeah. Yeah. So he opened up this door, which I just ran into headfirst with curiosity once again. And wrote a proposal, again, together with the help of my friends. Thank you, guys, if you guys are listening to this. You guys know who you are. And I sent it to him, and he was actually interested. Let's go. Amazing. Yeah. So this is how I ended up in New York City at Columbia.

Jon - 00:24:00: Very cool. I'm envisioning the stump the professor during the talk, like just like how that went down. But also like I see how there's like also, I don't know, you know, at least what I'm

eMalick - 00:24:11: kind of pattern 

Jon - 00:24:12: matching here is like. It almost goes back to like Millennium Pharma. When a CEO is meeting with you, they're also human. Like he is also human. Like Mark is human despite being on a stage, but he's also human.

eMalick - 00:24:25: We can 

Jon - 00:24:26: also be stumped. So like anyone can be stumped. We're all figuring it out.

eMalick - 00:24:31: We're all figuring it out. Yeah.

Jon - 00:24:32 Which is cool. That's like super cool. And I think I, you know. As much as there's a lot of, you know. Like you can revere all these kinds of people who are like, you know, foundational and kind of leaders in the industry, but like, just don't forget that. Like, you know, people are people at the end of the day. We all, we're all doing this, you know, in this together. So, okay. So now I

eMalick - 00:24:56: just realized that I'm setting myself up to be stumped.

Jon - 00:24:59: Exactly. Exactly. That is now an open invitation. You're like, you will start getting stumped. That's amazing.

eMalick - 00:25:07: Bring it on.

Jon - 00:25:07: Yeah. Yeah. Yeah. And so, okay. Now. You're in New York. Now I'm curious, how was New York itself, New York City, personally for you, moving to New York?

eMalick - 00:25:19: I mean, it's a great question. New York is such a fascinating city. I had visited multiple times when I was in Boston for spring break. I actually didn't like it that much. I thought it was a dirty city. Obviously, I'll ask you. But Living here changed my thoughts on New York. It's a city that has so many different things to offer, so many surprises that when you think that you know everything, it's guaranteed to surprise you again, which has happened to me again and again and again. And each time that happens, I fall more and more in love with the city. So it's like a wonderful place to live. And again, I'm moving from Gainesville, Florida, back to one of the biggest cities in the world. The different types of food that are available, the variety of people that are here. One thing that folks don't talk about often, but I guess it's sort of implicitly known, the level of people that are here is quite remarkable. It's pretty common to just go get a beer at a bar and then you meet somebody that's at the top of whatever the space that they are in. That could be like an ice cream maker or ice cream trucks. And you learn this guy at the top of ice cream trucks. He's got like 17 parking lots.

Jon - 00:26:46: Yeah, yeah, yeah, yeah, yeah, yeah. I know exactly that. I know exactly what you're describing. I know exactly that.

eMalick - 00:26:52: So inspiration in itself is like part of the milieu of New York. And that was really welcoming, inviting, and also wonderfully entertaining to be here.

Jon - 00:27:08: Absolutely. And before we hit record, when I was talking about like that, that experience of like never finding the bottom, like when we go to Tokyo and we're just like. Basically going on a food adventure and there's like levels to it just like exactly what you said i was like there's a dude in tokyo who dedicated his life to making one kind of pizza and we happen to just like walk in just like holy crap like this exists i i get the same whenever i visit new york it's a similar energy where it's like you this person is dedicated to their craft to like the, to the extreme. And that's super, at least for me, super inspirational to see someone who's like, whatever it may be. It could be like ice cream trucks. It can be pizza. It can be finance. It can be science. And you can just like bump into people and like the ability. I'm a bit jealous of you guys because. Our subway out in the Bay Area, not as extensive as you guys. So it's like harder to have kind of that where you just like, it's like walkable. Everything's far more kind of like feels within reach. And you can just like bump into people. In the Bay Area because it's like, you know, a little bit, you know, not as robust in terms of like transportation walkability. You don't get exactly that. There are definitely people or leaders in their industry here, but a bit more spread out. So it's kind of, it requires a bit more kind of concerted energy to like pull it together. Whereas whenever we go visit New York,

eMalick - 00:28:33: holy crap,

Jon - 00:28:34: there's like a meetup for like AI here. There's a meetup for pizza here or like, and so on and so forth.

eMalick - 00:28:41: AI pizza. 

Jon - 00:28:43: Yeah, yeah, exactly. It's like, now we just join forces. Like, how

eMalick - 00:28:46: can we 

Jon - 00:28:47: just run, like, models to just increase the level of pizza to the next? 

eMalick - 00:28:51: Also, just a note, we have to share that the pizza maker in Japan, in Tokyo.

Jon - 00:28:57: Yeah, yeah. Here's the model. Let me know what you think. Let's run it. Okay, so now you're at Columbia and your presentation has, you know, kind of gotten you into the lab. Can you talk a bit about your research with C. Elegans and what was the experience in that lab?

eMalick - 00:29:18: So when I said earlier, nothing is free, it's real. So now I'm in not just a basic science laboratory, not just an Nobel Prize winning laboratory, but one of the most hardcore basic science laboratories.

Jon - 00:29:32: Yeah, you're just like, what did I get myself into? It's a mentality,

eMalick - 00:29:36: right? We do not like translational science people like that mentality. And I'm walking in like with my white coat from the laboratory. It's like, no, no, no, we don't do white coats here. We wear sandals. 

Jon - 00:29:48: Yeah, open toe shoes. Open toe

‍

eMalick - 00:29:50: shoes. You wear shorts, right? And everyone here is very smart. And you don't have to openly present yourself as being the smartest person in the room. It's just like. It's chill and it's like high level, right? There's no posturing basically, right? Or at least not in the same way, because there's posturing, it's just different subjects, right? Yeah. And then I had to drop another thing, which was everything I knew about science or translational science, I just had to let go. To be able to operate at the levels. That the C. Elegans community was, which was and to this day leads in genetics, right? It's like a triangle of C. Elegans, Drosophila, and I think yeast people that I, I would say plant people as well, so a quadrangle of the leaders in genetics. And I had to learn the language. It's like an operating system. It's like literally a new operating system. Things that I knew that you for granted, PPS, right? Phosphate Buffered Saline. Couldn't find a single bottle of phosphate buffered saline PBS in the laboratory. This was called like everywhere things were taken for granted. Yeah. Instead, there was these bottles of N2 everywhere, like literally number N and number 2, N2, everywhere. And I just walked around and was like, what is... One, where's the PBS? What's wrong with you people? And two, what is this N2 thing over here? And why is it called N2? It's called N2. So, and, um, It's N2 because it was a second version.

Jon - 00:31:37: That's amazing. You're just like, what? Like, what? Is that really what it is?

eMalick - 00:31:44: Yeah, it's the second. This gives you insight to the thinking of how, of CLA against people, which now I'm full, 120% blood, but at the time I'm just, you know, getting into it. 

Jon - 00:31:55: Yeah, yeah. 

eMalick - 00:31:56: So N2 is the equivalent of PBS. It's a similar, it's like a salt-based solution. And has phosphates and things like that that allow C. Elegans to live well. And it's just like a different, like, awkwardness, a different design language. So genes, like, naming genes is very different. So in mammalian world, in mice, you know, humans and so forth, somebody discovers a gene, they'll name it some long-winded name. Yeah. And Drosophila, they'll name it some very descriptive name, like sleepless. Like if this fruit flies on sleep. Much or the sleep, no arm, less than normal for fights. We call it sleepless, you know. In C. Elegans, you have three letters to choose from and then a number. That must have helped

Jon - 00:32:49: with the memory.

eMalick - 00:32:51: Exactly. It's like a convention. It's like three notes. Depending on the number, right? So a great one is this gene that causes more males to be made compared to females. And just some background, C. Elegans is a hermaphrodite species, or you could call them sort of female, extra female plus. And for every 700 females, there's one male that's made. So it's like a heavily dominant, like hermaphrodite population. So genes that impact this ratio cause great amounts of males. So the first gene to do this was called HIM.

Jon - 00:33:32: So on the nose, just

eMalick - 00:33:33: so on the nose.

Jon - 00:33:34: That's amazing though.

eMalick - 00:33:40: Right. So, yeah, you get an extra, of course, you get a number at the end because you eventually find a second gene. So you have him one, him two, him four. That's amazing. This is the straightforwardest of things. Getting into the mind,

Jon - 00:33:55: getting into the mind.

eMalick - 00:33:57: Yeah. So I came into the lab with this proposal that I worked on for two years and it didn't really go far. And, you know, I won't say two years, I'll say, yeah, like 15 months, a year and a half. And that's when Marty came to my desk one day and told me, do you know that no proposal has ever worked?

Jon - 00:34:17: That's like, thanks.

eMalick - 00:34:20: You could have saved 

Jon - 00:34:21: me a year and a half.

eMalick - 00:34:25: But no, he insisted that I had to go through the process to learn with the confidence of my own ideas so I wouldn't give up too quickly. So he's correct. It's very 300.

Jon - 00:34:36: Clever. Very clever. Very clever.

eMalick - 00:34:38: It's hardcore. So after a year and a half, I moved on to the second project, which became my primary project, which was the achievement of neurons. We, as a laboratory, were hyper-focused on the six neurons that are needed for C. Elegans to be able to feel gentle touch. So these neurons have been studied extensively. These were the first neurons that green fluorescent protein actually was expressed in. And for the first time, you could see neurons live, which led to his Nobel Prize. And the developmental pathway of these neurons is a topic of investigation to this day. We know that they are born in a particular space and they migrate to very specific positions in the body. Then they then take on the function of the sensation of touch. And interact with the environment immediately around them for this function to take place. In the case of my studies, we were examining how these neurons, once they migrate to their final position, or where they're destined to stay for the rest of the animal's life, how the skin around the neurons, because they move towards the surface of the animal, the skin around the neurons wrap around them and sheath them. And what are the genetics. Enabling this in-sheetment. So we did several different studies using different types of mutagenesis as well as candidate screening to identify genes or confirm genes that we already knew. For instance, we knew some of the genes that essential for touch sensation, such as, I'm just gonna name a few, like MEK5 and so forth. These genes, without them, the neurons will not become encheathed. And then we discovered a lot more genes, like a lot, lot more genes that are also essential for encheathment. And they occupy multiple different spaces of function, from extracellular matrix proteins to genes that are expressed within the cell itself. So very, like, super curious results that have, like, widespread implications to things such as diseases, like multiple sclerosis is a disease where... The neurites that are coming from the brain into the body are not in sheet well and causes the incapacity to transmit neural signals properly to even more primordial aspects of development, such as when we're coming out of the 2, 4 to 8 cell stage, like within the zygote, there's folding that occurs of some cells onto other cells to sort of ensheathe them. And the genetic pathways that enable this ensheatment are really difficult to study at that early stage, but we believe that we've identified some of the genes that are essential there just by really looking closely at these touch-sensitive neurons.

Jon - 00:37:48: Very cool. And I'm going to imagine, was this lab also a similar instance where you were able to dislike explore and really just explore your curiosity? Or was it different?

eMalick - 00:38:02: Yeah, this was the most extreme version of freedom

Jon - 00:38:05: Oh, even more extreme.

eMalick - 00:38:09: It's just like, this lab

Jon - 00:38:11: doesn't even exist. 

eMalick - 00:38:13: It is just in the ether.

Jon - 00:38:16: It is in the...

eMalick - 00:38:18: Yeah, it was... You know, Marty is like a very curious and very brilliant human being. And. You know, has a very amazing and quite successful life that has. You know, had left and right turns between undergrad and grad school. I think he was selling like women's clothing door to door.

Jon - 00:38:43: No way. I love hearing that. I love hearing that. It's just like diversity. 

eMalick - 00:38:50: I probably have some aspects of that story, right? Also incorrect, but something to that effect. But in either case, though, he's been through enough to really have confidence in people. And. He loves... Seeing people grow. I would say Marty appreciates undergraduates more than any professor that I've ever seen. He's a quintessential, like, give water and watch it grow person. And he's brilliant at it. So he gave me, as well as others in the lab, so much space. Almost, for me, I abused it. I totally abused it. But I abused it, right? I was just too, I will tell you why in a second. But I just sort of pursued what I thought was the best and explored that space. And he, which led to sort of lots of interesting things, such as the word achievement itself came from me going to Albert Einstein's university here in New York and looking at these electron micrographs over an entire summer, just every single day. Just going and just flipping pages of looking at these neurons within electron micrographs and eventually realized the movement of the skin around it. And, you know, led to us naming this whole process achievement. So Marty gave me complete free space. Oh, you want to go across to Albert Einstein every day in a hot summer in a really crappy bus? Knock yourself out. Yeah. That's amazing. And he's just like, you know, please do. Like, he loves the effort. And I had also an unlimited budget. This is what people dream about. So there was like a period of time I was doing this lecture on physiology experiments, which I'm terrible at. I'm a big guy. I'm six foot seven. And I'm in a room operating these things. But I also was very good with electronics. And I remember, you know, buy some robots to help us do this manipulations to put like a patch clamp these neurons. And neurons are waste, like human neurons about 15 microns. That's about half the width of a human here. C. Elegans neurons about two microns. Yeah. So like a 25X, extra small, right? So I had to get these robots that were from like fertility clinics. And they were expensive, like $75,000 each or $80,000 each. And I was just able to just buy them without much thought. So I had full financial freedom in that way. And I, of course, explored the edges of it because I'm a curious person. But that led me to sort of push upon the boundaries of artificial intelligence. And I started to order GPUs, which they didn't think was important. And I would stop from ordering GPUs.

Jon - 00:41:50: Whoa that's crazy first funny thing um yeah i was like i did rotations in labs where it was just like talking about undergraduates like i just glorified pipe batters this is basically a nudge which It's awesome to hear in this lab, Marty was like, no, no, no. We're going to, I'm going to water. You're not just the pipetter here. Obviously you're doing pipetting. You still are, but those are foundational. Having someone believe in you that you can be more than that is Super awesome to hear. But also that environment sounds like the dream where you have intellectual freedom and also the financial freedom to really pursue these things. And I, you know, I heard this story, whether it was like on the acquired podcast or just like learning about like NVIDIA and like the GPU type stuff where like. It's like Stanford, like a Stanford professor was just like. Yeah, like the supercomputer over here is like actually not that great. And I just used my son's GPUs to crunch the data and it was far better. And he like calls Jensen. He's like, I get more of those. And I love that kind of like application. Yeah. And so it sounds like you bought some for some of your work. Was this the start of... Kind of the AI kind of ML journey for you?

eMalick - 00:43:15: Yeah, it came from and she's my project. Through a series of steps, I navigated to this thing called artificial intelligence. So the first one, the first step was we were doing targeted sequencing for the most binary laboratories, or PCRs. You have a gene candidate and a PCR specifically where in the genome that is to confirm it or do some cloning or something like that. Whole Genome Seekers was coming online at the time. And I imagined a world where every one of those experiments with PCR would be replaced with whole genome sequences, like, absurdium. Just whole genome sequence everything. And I tried to convince some people in the laboratory towards it. And moreover, this is one of my first, like, early business moves. I got to triangulate several different whole genome sequencing companies to sort of get into a little price war. That reduced the sequencing of whole genomes that we needed to some ridiculous low amount. It's 2024 kids now. I got it to reduce it down to 350 bucks from about 4,000 or 5,000 bucks. And in return, I was opened up to, I

Jon - 00:44:31: promised the

eMalick - 00:44:32: winner of this bidding war, which was BGI, that I would introduce them or let them know of this world of basic researchers that are doing more sequencing on hospitals. She said they had no idea that we existed because we are a whole genome, right? I said, I want to introduce a whole new customer base, but you have to reduce this price to the point where you are crying. Yeah, yeah,

Jon - 00:44:57: yeah, yeah, yeah.

eMalick - 00:44:57: I like it. Um, so, so it worked out, they reduced it down and then I introduced them to the C elegance community. And then they were like, Whoa, this guy's like really are sequencing like crazy. And it worked out great for them. Right. But I didn't think of what was going to happen next. Right. Um, mainly I didn't think of the data deluge. Of whole genome sequences. So we just get these massive files sent to us from BGI with all the sequencing I was doing, and just like Excel just wasn't good enough. 

Jon - 00:45:34: I can just imagine how long this Excel file is taking to load.

eMalick - 00:45:38: They won't open most of the time, they'll crash. Yeah. So you have to find some other ways to sort of, yeah, basically go to a terminal to truncate the file, then open it into an Excel. From that surprise of the amount of data, I had to learn how to program. And I had to learn how to program. And then I was in search of tools that could handle this type of data easily. So I went through the whole, like going through Bolson machines, Monte Carlos, and all of the whole world of engineering. And eventually to this. Towards artificial intelligence. And I luckily was early enough because this was the same year that AlexNet came out, which I'm not sure you know, but AlexNet was the... It's considered sort of like an important point where neural networks outperform people, or at least begin to outperform previous models significantly and were destined to outperform people in image recognition. So I jumped on the boat just as it was coming offshore in the AI train. And he was like, okay, one, this could do the work that we needed to do as far as handle these full genomes. But two, these are universal approximators. Like literally universal approximators, that means they are widely... Across different spaces and fields. So I would play this game in my mind and also with some friends that would, you know, what can it not affect? This is 2014, 2015, 2013, 14, 15. Like what space can this technology not impact? And we just couldn't come up with one. We talk about fishermen. You find a way like how AI could help or change how fishing is done. Construction. Same thing. Harvesting. Same thing. Let's go rocket science. Same thing. Let's go plant biology, same thing. The choosing of Nobel laureates, same thing, right? So I started to just tell everybody that I could. That would listen to me that this thing called AI is gonna be very important. I started at a laboratory, at Shafi's lab. But we were all, as a group, we were all very biologically oriented or biological sciences oriented. So it was hard to get traction there,

Jon - 00:48:01: but

eMalick - 00:48:02: I continued and started to build these, I'm a pretty junior programmer at the time, just learning Python. But was enough to make these small models of, you know, convolutional nets that would be enhanced with GPUs as far as how fast they go. So it's putting genetic information in convolutional nets and then buying these GPUs to accelerate. Accelerate the processing of them. And then that's when my unlimited budget got flagged.

Jon - 00:48:32: Yeah, you're like, wait a second. Wait a second. This one's especially big.

eMalick - 00:48:37: Yeah, it's a great GPU. So I think some admin thought that this was for Bitcoin miners. 

Jon - 00:48:43: Yeah, you're just like, what is this? So now it seems like you've kind of, it's like you found a

eMalick - 00:48:51: rabbit hole.

Jon - 00:48:52: And, you know, usually, you know, when you've done your graduate studies and postdoc, usually like academia, like, you know, professorships are kind of like on the horizon. But obviously, looking backwards, I know you

eMalick - 00:49:06: ended 

‍

Jon - 00:49:08: up being an entrepreneur, but... Did you feel like you were at a crossroads? Did you have,

eMalick - 00:49:14: I want

Jon - 00:49:14: to be a professor aspiration, and this is kind of a moment where you know, or did you know entrepreneurship was eventually where you're going to go back to to reminisce on the millennium experience? 

eMalick - 00:49:25: Yeah, exactly. Going back from the millennium thing, I was quite happy to be a leader in whatever the space, whether it's my own laboratory or in a company that I am a leader. I wasn't happy with being like the third or fourth person in any space. It just wasn't my personality, particularly after the conversation with the CEO of Millennium. It sort of highlighted to me that like, oh, you can't possibly do this. So during the postdoc, for the most part, it was very open to going to the professorship. However. AI changed that. Also another thing changed. Second, very, I cannot understate this. We were doing these experiments that are called rescue experiments. Which is... When you think a gene is causing some sort of ailment in an animal, you create the correct version of the gene and you inject it into the animal. And then you just wait a day or two. And what I witnessed was the animals recovered fully. They were cured. And we're doing this. Every single day. Like it was routine and nobody thought it was special because the elegance people. Do these incredible experiments all the time. They didn't know that in other spaces, this is called groundbreaking. So in the mice world, being able to inject a gene that can use an animal's course, you maybe do that once in your PhD, if you're lucky, so forth. And we're doing it multiple times a day. So this routine that's asked, you know, basically forced me to think, what does it look like the other side of it? What does it look like if we are able to do experiments like this that rescue ailments in people at scale? And that idea I couldn't let go of once it occurred. So then you're of course like, okay, how do you find out what is the actual correct gene to inject, right? This is the AI. So the other thing that I couldn't escape, once I opened the window of AI, I couldn't close it. Like it's just once you see the future in this particular way, you cannot move backwards from there. So you have one choice and only one choice, move forward. So to explore either of these, I had to quit my own company. There wasn't space in academia for those thoughts. Particularly to just to spread them

Jon - 00:51:57: out, right?

eMalick - 00:51:59: It's not enough to be able to write a paper like this could be done. You have to actually just do it. So that began the movement of my mind towards creating genetic intelligence.

Jon - 00:52:14: Very cool. And I had a similar experience like with founding Exceder, the is trying to figure out how to just like, empower research at scale. And for me, it was an experience was like, oh, didn't have like a lot of our lab, the labs that I was in, we didn't have the proper tooling. And I was like, I'm not the best. Like I'm not the best in the lab, in the wet lab. But my colleagues are. So like, how can I play my role to like support them? And I was like, this doesn't sound like an academic project at all. This is kind of like an industry thing. So I ended up leaving the academic laboratory to start Exceder. To like you know to help folks who are doing their work just can we do this more efficiently and i get a faster clip it's 

eMalick - 00:53:01: like you have once you had a mental movement you had to just start moving forward

Jon - 00:53:03: with it right yes i had to i had to leave the lab um and back then it was like 2011-ish so

eMalick - 00:53:10: like

Jon - 00:53:11: industry was like the dark side so i was like oh i didn't know i'm trying to help i didn't know it was the dark side but um you know obviously things have changed it's like 2024 now so like you know there's less stigma around it company

eMalick - 00:53:25: publish yeah

Jon - 00:53:26: exactly

Outro - 00:53:29: That's all for this episode of the Biotech Startups podcast. We hope you enjoyed our discussion with eMalick Njie. Tune into part three of our conversation to learn more about his journey. If you enjoyed this episode, please subscribe, leave us a review and share it with your friends. Thanks for listening and we look forward to having you join us again on the Biotech Startups podcast for part three of the Malick story. The Biotech Startups Podcast is produced by Excedr. Don't want to miss an episode? Search for the Biotech Startups Podcast wherever you get your podcasts and click subscribe. Excedr provides research labs with equipment leases on founder-friendly terms to support paths to exceptional outcomes. To learn more, visit our website, www.excedr.com. On behalf of the team here at Excedr, thanks for listening. The Biotech Startups podcast provides general insights into the life science sector through the experiences of its guests. The use of information on this podcast or materials linked from the podcast is at the user's own risk. The views expressed by the participants are their own and are not the views of Excedr or sponsors. No reference to any product, service or company in the podcast is an endorsement by Excedr or its guests.