“You can go down many different roads before discovering what it is you actually want to do . . . it’s often an unpredictable, winding path.”

“What is your current project and position here at ISB?”

“I’m an ISB fellow. I graduated from college a little over a year ago with a degree in physics, after which I wanted to transition into biology. I was given the fantastic opportunity to come here, essentially, to become a biologist. I am the inaugural ISB fellow, which has been an extraordinary thrill and privilege and honor.”

“My research focuses on Mycobacterium tuberculosis, the bacterium responsible for tuberculosis, which is currently the deadliest infectious disease in the world. Typically MTB infects people by burrowing in their lungs in a deactivated, latent state, where the bacteria slow down their metabolism and can persist for years, undetected, before some ancillary illness distracts the immune system, allowing the bacteria to activate, wake up, and wreak havoc in the body. How it is that MTB enters and emerges from this latent state is a major question in infectious disease research. My project is to understand those transitions, to discover the genetic program—the genes that get sequentially turned on and off—through which MTB adapts to the host environment. The hope is that once we figure out the architecture and logic of these genetic circuits, we will be able to target combinations of genes that stall the latency program, which could lead to new drugs. I work on both the computational end, developing predictive quantitative models of MTB’s gene regulatory network, as well as on the experimental end, designing and performing elaborate experiments that can validate whether those models represent the reality of MTB’s biology. I do these experiments in a Biosafety Level 3 lab, dressed in something resembling a hazmat suit. There’s often months of training you have to go through to get into one of these labs by yourself. Inside, you have to be extremely careful and vigilant—the organisms you’re working with are highly dangerous—but the science that goes on in these labs is crucial, not just for our basic, curiosity-driven biological understanding of this organism, but in helping find cures for the almost two million people who suffer horribly and die from tuberculosis every year.”

“How have you found your unique physics background applicable to your study of tuberculosis?”

“Not at all in an obvious way. In physics you are taught about fundamental laws that govern the behavior of matter and energy in the universe. From these laws you can construct mathematical models to understand all sorts of the things that happen in the world around us, but underlying that understanding are always those few, general, governing principles. Except for perhaps the theory of evolution by natural selection, there isn’t much resembling law in biology. There are, however, a few ideas, a few basic models, that seem to govern life across all scales, from bacteria to human beings. The lac operon model, for example, helps us to understand how it is that genes are turned on and off in an organism. The MWC model for allostery, another example, gives us a picture of how proteins assume different conformations, essentially contorting themselves to bind other molecules and perform specific functions. While both of these ideas are descriptive and not exactly mathematical, as physical laws typically are, they certainly resemble physical law in the extremely wide range of phenomena that they explain across the whole span of living organisms. In fact, the brilliant guy who helped discover both of those ideas—to my mind, the smartest biologist since Darwin—was a Frenchman named Jacques Monod, who used to say: “What is true for E. coli is true for the elephant.” So if you find a genetics or cell biology textbook, you’ll see hundreds, often well over a thousand, pages of detailed information about cellular processes. But my training in physics gave me an ability to hone in on the really fundamental ideas, which are often very simple and easy to state, but that in no small part undergird the reams of details that fill those textbooks. In light of these principles, the details become a lot less bewildering.”

“I think this perspective has fed directly into my style of research. I’m interested in the details of a problem insofar as they help lead me to construct a model whose components consist of much more fundamental notions. The power of these models, then, is that they are predictive. Not only do they describe what we already know, but they describe things that, until that point, we might have had no idea of. This is the kind of thinking that physicists are experts at. In my own research, I’ve been constructing models that we believe underlie the phenomenon of latency in MTB. These models are in the form of genetic circuits that, if they behave the way we think they do, should not only explain what people have learned about the genetics of latency over the last few decades, but also should be able to predict exactly which genes to target in order to prevent the bacteria from being able to enter into latency in the first place. This is a prediction that we will have to go and test in the lab, and if it’s right, it’ll say something about not only the validity, but also the predictive power, of our model. This is an unusual form of biological research, certainly pretty remote from the way MTB has largely been studied in the past; but this is the kind of biology I’m most interested in, and it is directly inspired by my training in physics.”

“Do you have any type of graduate school plans?”

“Yeah, definitely! I didn’t want to go straight to graduate school after college because, I don’t know, I’m a master procrastinator. I thought as an intermediate step I could get shoulder deep in research. I’m not and never have been much of a classroom student, but I do love research. I like tussling with a really hard problem over the course of months and years. So I knew I wanted to go straight into research. Now as we’ve made significant progress on this project, and we’ve started to reach conclusions, we’ve been brought closer and closer to the point of publication. After wrapping up this project my next destination will likely be a doctorate program. I’m applying this fall for PhD programs in biology.”

“Do you wish you had taken biology right at the start as an undergrad or do you like that you got your physics background?”

“No, I’m really glad that I didn’t take any biology at the start because I’m just not good at memorizing lots of facts. That’s not what biology is, but that’s often how you’re taught and evaluated in biology. You’re tested by whether you have memorized all the different detailed points across some number of chapters in a monstrous textbook. That’s just not how I learn, and I hated biology in high school. Most of the biology I know now, I’ve taught myself, often in an on-the-spot and haphazard way. Research works in a far less linear way than classes, and so my learning through self-study has been unsystematic, but often more thorough than if I’d learned the same things in a classroom. I find that trying to do good research is a far, far greater incentive to learn with depth than trying to get a good grade on some tedious exam. I’ve learned through an intense reading of review papers and monographs and a few really excellent textbooks (I find most textbooks to be unreadable and awfully written, but there are exceptions). Learning in this way has been, I’m sure, far more fun and fulfilling than had I majored in biology in college and been bored to tears by lectures and Powerpoints and the inevitable cram for multiple choice exams. That might have killed any nascent interest I had in the subject.”

“So you talked about how you came to work at ISB. How do you think you balance your work and personal life? Is there a balance or?”

“*laughs* Oh man, um… I’m working on it. The truth is, science is just one among many of my interests. All of my other passions matter a great deal to me, but when I first got here I had to subdue them for a bit. Earlier on, I was spending a lot of nights in the lab. I was nervous and anxious and afraid: I had no background in this stuff, I had no idea what on earth I was doing. I’d never been formally taught sterile technique, so I was contaminating my bacterial cultures for weeks, and there was nobody to tell me so. I was learning everything from scratch. So during that initial period I was very intimidated, and I spent all my time here thinking about the science, thinking about the problem I was trying to solve, even if I didn’t yet know a whole lot of the biology and wasn’t making much progress on my project.”

“Eventually, after lots of hard work and lots of thinking, I had a few lucky breaks, a few times where I discovered something conceptual or experimental that was really cool, and seemed to solve the complicated problem at hand. And that finally put me at ease. To take a very insignificant but recent example, there was this great moment, just two days ago. Did you see those Eppendorf guys? At those tables over there? They were showing off these fancy experimental platforms they were trying to sell, and after asking about them, I said, ‘That’s exactly what I’ve been doing! What you have right there, is exactly what I’ve been building for our experiment!’ I didn’t even know there was a commercial version of this thing that you could just go out and buy. We thought what we’d made for our experiment was on its own really expensive; after all the troubleshooting, we’d probably spent upwards of $6,000 on the equipment. And seeing these Eppendorf guys, I was wondering, Oh boy, how much money, how much time, would we have saved if we’d used their platform? So I asked one of the representatives, ‘How much does this cost?’ He said, ‘Well this one starts at $160,000.’ At that moment I realized that all the flailing around that I’d been doing for weeks and weeks, and those late nights that I’d been spending in the lab—all of it paid off.”

“So earlier on my time at ISB was a lot more intense. I remember once I went on a date with a girl, and in the middle of the date I needed to check the growth of my bacterial culture. So I brought her into ISB (I’m not even sure if that’s allowed) and said, ‘Hey, I need to check the growth of my microbes for a second.’ So… probably something like that wouldn’t happen anymore.”

*laughing*

“That’s, uh, that’s work-life balance, right? There wasn’t so much balance then, unfortunately… *laughs* Now there’s more. After making headway, you feel more secure about your position, and about what you can accomplish, and what’s within your control and what’s not. Then you start valuing your free time much more and making good use of it.”

“When you got to ISB, did you learn anything about yourself? Besides thinking, ‘Oh my gosh, I’m so intimidated.”

“I think there’s a few traits which have brought me farther than I might have otherwise gotten. One of them is an ability to be beaten, defeated, floored, then to get back up on my feet, and to try again, over and over. That’s because when you suddenly come here with no training, not only in the particular project you’ve been assigned but in biology in general, and you’re suddenly given all these responsibilities—it’s been such a privilege because they gave me the responsibilities of being able to go to the meetings and make decisions with the rest of the group, and right now, for example, I’m helping to write a grant proposal for something like a one-and-a-half million dollar grant. They gave me a lot of responsibilities and assumed a lot of maturity, and, at the same time, I didn’t know any biology! So sometimes I would say something in the middle of a meeting, and people would look askance at me and think, ‘…What?’ At some point I developed an ability to recover from humiliation, to tell myself, ‘Ok, next time I’m going to do this better.’ Now I feel utterly at ease with biologists, and I love talking with them, speaking in their language. At first I had such a difficult time reading papers. Someone would give me a paper and I would sort of pretend like I had read and understood it, when in truth I found it totally opaque. Now I can read them far more easily. So, just an ability to get my butt kicked, over and over again, and get bummed out, but nevertheless to stubbornly refuse to give up, and keep pushing myself until things change. And eventually, things get better, much better. You learn, you grow, you mature.”

“When you were in undergrad, high school, did you find that trait in yourself? Or did you admit that you didn’t understand?”

“So in undergrad if I didn’t understand something I was probably much shyer about it. Because I felt like I was supposed to understand, you know? Everyone else was at the same level as me. So it was very different when I didn’t understand there and I felt that my peers understood something; then I knew, ‘Oh, I better figure this out quickly because I’m behind.’ Whereas here, everyone I work with is at least a decade older than me. I think, by way of this position, I’m by far the youngest researcher at ISB, and so that helped me momentarily justify those earlier moments when I felt I was behind. It helped me forgive myself sometimes if I didn’t understand something, because I knew my being here was an unusual thing. I knew I was kind of a guinea pig. My position here was an experiment just to see, is this possible? Where you could just take some kid who studied physics and thrust him into the deep end of a research question and see if he does something significant. The defeats were definitely more frequent early in my time here, but I’m resilient. I recover from them, and I think that’s a good thing. That’s a trait I’ve learned about myself.”

Katherine: “That’s the important thing, right?”

“Yeah, just being able to look like a fool from time to time, and realizing that anyone who never makes a fool of themselves is probably an alien”

*laughing*

“Do you remember why you went into physics? Did you have a field in mind? Or like a job you thought you’d go into?”

“I knew I liked physics, I knew that I enjoyed it. During high school I had done a physics internship, I liked reading about the lives of physicists and solving problems, but when I went to college I really wanted to study English, actually. I spent much of my time taking classes on Shakespeare and poetry and things like that. So how did I get into physics? The truth is, there’s a lot about physics that I love, and certain classes that were really exciting and have been important in my scientific development. Part of why maybe I was drawn to English initially was that I felt like it came more easily to me. Physics, on the other hand, often involved a lot of difficulty and struggle for me. So I guess I was drawn toward what, to me, felt like the greater challenge.”

“How much do you still struggle now working every day in the lab, still answering your question?”

“All the time! I mean, it’s different: the struggles have to do with — it depends! Once you get into the field and you’ve really immersed yourself in the literature and you understand many of the techniques, new things will come to you faster, much faster than they did initially. You’re able to pick things up quicker, but sometimes when you’re trying to talk to someone who’s doing something quite outside of your area, then you’ll suddenly feel a lot less knowledgeable. As a consequence, I try to read a lot from fields that are not my own specialty. Over time, you get less intimidated! There’s this basic rule, which I think has entered my head, that anything is comprehensible. If there’s a paper, humans wrote that paper, and because I’m a human, I should be able to understand it… Right?”

Lauren: “That’s a quote we should put on the website”

“*laughing* I’m telling you this is not going to be a normal interview! This is not going to be — you have to let me cut out all the weird parts!

*laughing*”

“What would be your advice to someone who is our age who is thinking about going into a field in science?”

“So, I read a lot about the history of science, and about the lives of biologists, biographies, autobiographies, to know what were these people — these people who discovered these incredible things — what were they going through? You come across stories which utterly destroy notions which have infected our minds before we first go into science. There’s often the idea that you have to be that kid who is winning all the science fairs and competitions and whatnot. You know, who has the best grades in science, and who goes to college and knows exactly what they want to do, and graduates with flying colors. If you look at the people who’ve really made the most spectacular discoveries in science, they’re an extremely heterogeneous bunch, and often their lives often did not follow that trajectory at all. Strangely, many of the people in your own life who you think are prodigies and geniuses will just burn out. They won’t end up doing very much at all. Growing up, I knew people who bragged about their high IQ scores and joined weird, self-congratulatory organizations like Mensa who, now, are total layabouts.”

“To give you a concrete example of the kind of scientist I’m talking about, take Harold Varmus, the guy who basically discovered how mutated proto-oncogenes could lead to cancer. He’s a very famous biologist now. He went to college, majored in English, had no interest in science whatsoever, nearly failed his organic chemistry class, and graduated with an English degree. He then went on to pursue a PhD in English Literature. Eventually, when he realized his med school friends were having a lot more fun than he was, he decided he wanted to go become a doctor. When he was in his late 20’s, he got a trainee position at the NIH as a way of escaping the draft for the Vietnam war. You might have assumed by then he knew what he was doing with his life, that his course was set. But it was at this late stage that he first started learning about biology from other scientists, and finally himself got involved in basic research. He eventually figured out something that revolutionized our understanding of cancer genetics. He’s a Nobel Prize winner. He was the director of the National Institutes of Health. And there are many other similarly improbable stories I can tell you about people who went on to discover extraordinary things in science.”

“The point is, people can come into science from so many different directions, from so many different backgrounds; they can find out early or late. I just think, you don’t need to go into college with an absolute certainty about what you’re doing. You can go down many different roads before discovering what it is you actually want to do. You’ll meet many people who are really certain they want to do something, and then get deeply involved in it, only to find out somewhere down the line, ‘You know what, this is not for me.’ Then they find something else. This is a wonderful advantage of living in the United States; in other countries, where cultural pressures often predestine you for one career or another, or force you to choose very early on, you might not have that flexibility. Here, on the other hand, it’s not necessarily that way, and circumstances may require that you take an unpredictable, winding path towards your ultimate destination. That’s a privilege inherent in this society. We’re the lucky ones. Don’t be afraid of uncertainties. Take the plunge.”