What got you into science?
This is one of the hardest questions to answer, and people try to come up with something that sounds cool, but there really isn’t. I’ve always been drawn towards observations that are exciting. Not just wanting to know what was underlying that observation, but getting excited about things that happened around me. When I was a kid I used to go catch frogs and other critters and became fascinated about how they looked and what they could do.
I think step two for me was having really good teachers who could put more depth to those observations. When you make an observation, a good teacher can help you think through beyond the observation and try to understand what it means. Starting with my mother and a few teachers that I have had the pleasure of having, I would have them share credit for getting this passion in me.
Also, trying things out and fail. At your stage, I didn’t know what I wanted in my career. In fact, for many years after that, I didn’t know what I wanted. I would be lying if I told you I knew exactly what I wanted to do when I was in high school– I had no clue. I think being clueless is an asset at this stage. Gathering as much information as you can, through an internship like this one, for example, will help you answer that “What should I do?” question in a more informed way. I was under the impression in the country I grew up in and culture I was brought up in that careers were something with a set path, that I realize now is such a wrong way to think about careers. And so I started this program so students can come in and I said they should come and talk to everyone here to see how diverse the set of skills can be and yet we can work together in a research organization. Appreciating the diversity is key. For me, it wasn’t so obvious, it came the hard way. I planned to go to medical school because I liked biology and I thought that if you were really good and you like biology, medicine is the only career path. I was just completely wrong. And then I didn’t get into medical school and I was devastated. I spent probably the next 2 years just recovering from the devastation. This was not just me, many people go through this, the way the system was set up in India. Then I fell in love with microbiology just because I enjoy it and it came naturally to me. But I still didn’t know what a career in microbiology looked like.
It wasn’t just one thing, it was a series of things if I were to recount what got me excited eventually. What I’m doing now, there’s no way I would have predicted when I was at your stage. It’s OK not to have that one thing that says “Aha! I’m going to solve this and win a Nobel prize.” I don’t know if this was a disappointing answer to your question.
Everyone has blind spots, and if someone criticizes me, I take it objectively, try to understand and try to get better at that. Role models help a lot in that, for me: where I want to be, and how to get there.
How has your background and upbringing in India affected your life?
I spent my first 24 years in India and all of my schooling was done there. It’s a system that the British left behind so it is very content heavy and there is a lot of rote learning that gets rewarded, not as much creativity. As a consequence of that, you really don’t have a solid basic science innovation culture. There are pockets of excellence, and certainly a lot of talent. The only reason I left and the only reason all the people at the top of the class left India is that there was no innovation culture. I still remember, these challenges and am eager to help address them, and I hope to do that by replicating the SEE education program there and by establishing research collaborations, such as on tuberculosis. I’m trying to give back in a way that I can help the system get better.
So I did all of my schooling there up until graduate school–I got a masters in microbiology and marine biotechnology. This happened by accident. When I got my Bachelors there was a national entrance test. Everything in India happens via tests. If you are good you qualify and when you qualify there’s an opportunity and who would give up an opportunity, right? I took this test, I didn’t even know what this test was about. It was a national entrance exam and everyone in my class was taking this exam so I thought I would take it too, just because you have to be part of the group think, of course. And I ended up being the only one who qualified and it turned out that only a fraction of a percent in the whole country qualified. I was like, “Wow! I have to do something with this because I qualified!” They said I could do marine biotechnology, and I said, “What is that?” I did that for 2 years and learned a lot of skills that I still use. I brought in statistics and computation, programming, things that I wouldn’t have traditionally done. There was a program that the central government set up to bring in those kinds of cross-disciplinary expertise, but I’ve never done anything marine ever since until about 10 years ago when I started working with Monica Orellana on ocean acidification.
Then I tried to work in malaria for a year and a half, and that turned out to be a total disaster. The lab I was in didn’t have enough resources, but I wanted to take on some really meaningful research. I realized that it was much harder than I’d expected. That’s why I tell you guys, “expect research to be difficult.” My expectation was all romanticized and unrealistic, so I got disillusioned. You guys already mentioned the waste aspect. I don’t think the animals were treated well enough. I had to breed mosquitoes, and there wasn’t really a good setup to do to that. You need a specialized system to feed them animal blood, but they need to feed directly from the animal. You can’t just keep blood. The mosquitoes have to pierce the veins and drink the blood. I had to shave rabbits to expose their skin… There was a lot that I wasn’t expecting, and the lab wasn’t set up well to do those things. So then, I moved and got a Ph.D. in microbiology. Then I was collaborating with Lee Hood, and he convinced me to come to Seattle. That was a difficult decision, and I think in everyone’s life you’ll have a few opportunities where you have to take risks. This was one of those opportunities for me, to either go the traditional route of going deep–and I had a lab in Harvard that offered me a position, and I said, “Everyone wants to go to Harvard!”–but I looked at that opportunity, there was also a very well-known lab in San Diego working on gene regulatory networks, and then there was Lee’s idea of, “Let’s figure things out. We need to do systems biology.” So, I gave up on Harvard and the other places, and I came to Seattle. That was one of the best risks I ever took.
What is the hardest part of your job, on a day-to-day basis?
There are quite a few things. One is multitasking. You hear from people that multitasking is bad, but the reality is that you have to multitask at some level. As you pointed out, in research, there are many different elements. It’s not just being in the lab and doing experiments… You have to interact with people, communicate your research, raise money, publish papers, manage people… There are all of these aspects that require you to be a “jack of all trades.” In a typical day, I’ll be guiding my staff on doing experiments and research, working with someone on a manuscript, working with someone else on a grant proposal, or doing some administrative duties because I’m a director here … So it’s not that I’ve selected these activities because I like to do them, but it’s because I have to do them. I do happen to enjoy them because I see their importance, but they do pose a challenge–because in a day, how do you focus on one thing and then shift gears to focus on something completely different? Then you have meetings that interrupt. You do get better at that with time, but it continues to be a challenge.
The second thing is, managing people can be a challenge. We all know what we need, and how we need it, and what works/doesn’t work for us, but everyone is different. When you hire different people and you teach each one of them, they all have different interests, career goals, backgrounds, and styles. Being able to reconcile those differences in a way that you can approach them where they’re at–there’s joy in it, but you also make mistakes. Acknowledging that you might have erred at times is step one. I’m still trying to get better at that. That happens on a day-to-day basis. When someone comes into my office, I immediately shift my thinking so that I can communicate most effectively with them.
A new challenge for me is going beyond my lab and impacting the people and communities for whom we’re working, essentially. If you come up with a way to deal with tuberculosis, how will you get it in the hands of people who will benefit from that approach? A lot of my talks to foundations and trips to India have been about trying to get some of these capabilities to the right people. Education is a big passion of mine. This whole program came from my naive approach to what it would take to transform education. I had two high school students come to work in my lab over 15 years ago, and boy, did I learn a lot. The first year, it was just them. Now you have teachers and everyone else here.
I got a grant from NSF and brought two students to ISB. One of them is a hand surgeon in Seattle, and one is a Ph.D. student. I think she may have graduated and well past that. So one day I come into my office and I find that one of them is entirely packed into the shelf of my bookshelf, and the other is looking at her, just kind of nodding. I said, “What are you guys doing?” And the one on the bookshelf said, “Well, she challenged me that I couldn’t get into the bookshelf, so I showed her that she was wrong.” So then I said, “Okay, I need some adult supervision here,” and I brought in some teachers the next year.
So yeah, different challenges day today, but I find fun in all of them.
How do you balance your work and personal life, or do you?
I like to think I do. There are times when I travel a lot and it can become difficult to go far and need to come back the next day. But I also have some rules about not working when I come home in the evening, and I don’t work on weekends. For the most part, I always abide by those rules. I also love cooking, so I do all the cooking at home. It’s not as though I do it because it’s my role. Anything I do in life, I do to have fun. Otherwise, I can’t do it. So that’s how I balance it. I find joy in things that don’t work. I went camping this past weekend, and I had a full menu planned for the six meals. It was remote. There was no connection at all, so I had no option but to have fun. So you have to have personal goals and take joy in those. Take joy in spending time with your family. Make sure you don’t just work all the time. I think I do balance work and home life.
What’s the best part of your day-to-day work?
Interacting with students is one of the best parts! When interacting with students, I get enormous joy watching how you guys progress. Students from ten years ago write back from where they are, and that’s just so much fun. Some of them are not scientists, like one of my students who became a banker. He still relates to the experience by interacting with people, and he did a lot of database work when he was here. That might’ve influenced his thinking about data services that he provided when banking. Students come back, and they tell us how we’ve influenced their careers. That’s one of the best parts.
Among the other best parts is like how just last week, someone from MIT reached out to us. He reached out and said, “I loved your paper; we’ve been trying to develop this technology.” So we had essentially scooped this guy, but that wasn’t his concern. He was happy that someone had solved the problem, and I just loved that attitude. So he’s more conscious of the problem that this technology can help progress. Instead of being bitter about being scooped, he was looking forward to doing the next thing with us. I was thrilled to see someone with such a giving attitude. He had some additional data that would help us, and he said, “I’ll just give it to you if it’ll help you.” And he is a junior scientist. Typically at an early stage, scientists tend to be very cutthroat, because they have to establish themselves and establish a track record so that they can make money, blah blah blah. He’s an assistant professor barely starting his lab, and maybe he’ll change in a few years, but at least for now he’s a role model for me, and he’s fifteen years my junior.
Do you have any major role models or heroes?
I always have role models. One of my current ones is Obama, and how he handles criticism. That’s something in science. You always get rejections, and your knee-jerk is to have an angry response: that these people don’t get it, that they’re people are out to get me, etc. But when I see people like Obama, I kind of take a step back and become more objective about it. I have a lot of admiration for that. There are people who’ve reached out to me, and they’ve told me how they’ve done things differently, and I think, “Oh my gosh! I should do it that way.” They’ve become role models for me–even when it’s for a short period of time. I also look at leaders around me, either at work or around me at the state or national level, and say, “What is it that they do that I would want to do?”, and then I try to bring that into my practice. But, I also know that not everyone is perfect, so I don’t hold role models to a godly status, and I don’t criticize them. I hope that’s true of me as well, in terms of knowing that there are some blind spots. Everyone has blind spots, and if someone criticizes me, I take it objectively, try to understand and try to get better at that. Role models help a lot in that, for me: where I want to be, and how to get there.
What’s something you’d recommend students who are interested in STEM to do?
I think you guys are doing a lot in terms of what I’d want to see a student doing, in terms of internships. I bet that this experience will stay with you for a lifetime. What I would want you to do is give it forward. When you have a chance, mentor. I don’t think enough people mentor. When you get into a position of giving back, do it. I think that’s the biggest contribution you would have.
Fail more. Try new things, and fail, and do not get dejected, but get more inspired by knowing that you will have to do things differently and how you could get better.
Acknowledging that you don’t know certain things. That openness will give you more confidence. If you say you don’t know something, then someone will take you more seriously when you say that you do know something. But, when you identify something you don’t know, figure out whether it’s important to know, and if it is, how you get to the right place. Students should do more of that.
Also, know two things:
One, education is about learning, and also that education is about making an impact. There might be people who say it’s one or the other, but I think it’s both. When you’re learning, and you’re passionate about something, it’s about making a difference at the end of the day. It’s not just being happy about knowing and understanding, but also applying it. That’s a personal choice, by the way. But I think it’s a lot more rewarding if you take what you’ve learned and you make other people’s lives better with that.
If you could change anything about the science or laboratory community, what would it be?
I would change the way that the community is viewed by society and by the government. I would expand funding. I think it goes both ways. We need to expand funding for research, but I think that scientists should also appreciate where the money comes from. They hold their own feet to fire in terms of asking if they’re moving their research in a direction that’s going to better humankind–maybe not their own work, but if the insights they get could be leveraged by others towards making a difference in the future. No matter how abstract it is, it would be good to relate. And I’ve struggled with that with postdocs in the past, where oftentimes they think writing the rationale for why this research needs to be funded is just an added burden. They think people should know. But no, in reality, people don’t know. People should know, but you need to help them understand why what you do is important. Scientists could become better communicators. Then, if there were more funding, then there could be more research careers made possible for students like you. That doesn’t mean research is the only career trajectory, but scientists are often caught quarreling amongst themselves about what research is more important that needs to be funded. That’s because the pie isn’t big, but the number of people for that pie is so many that you end up slicing it, and it’s a zero-sum game. If you make one slice bigger than someone has to give up their slice. That pits scientists against each other. That’s a big systems problem.
Earlier you talked about how young scientists have to establish themselves. Could you elaborate on that process and what it takes?
Some of it may be self-imposed, but the research enterprise imposes some expectations. Some of it is very artificial, but nonetheless, it exists. For example, if you’re an independent investigator and you start a lab, then there are some expectations of what you need to demonstrate in the first few years. Those things include independence. They have to demonstrate that they’ve created a program that is unique, independent, and adding value to the overall research operations of that institution. The way you do that is by one, raising money to continue research which is essentially an endorsement of the value and uniqueness of your research. It’s hard to get funding if you don’t have those elements. Second is in demonstrating that you are able to publish in high-profile journals. You also have to demonstrate that you’re good at teaching and training. Different jobs have different criteria, but generally, they fall into these three major areas. When it’s time for you to be considered for promotion, they look at your tenure dossier. Tenure is when you get a permanent, guaranteed position, wherein if you take on a very controversial research topic, they can’t fire you for that. To get to that level, you need to demonstrate the three capabilities that I’ve described. You have a committee, and they sit around a table like you guys are now, and they review your tenure dossier. It can be very stressful, because if you don’t get tenure, then you have about a year to find another job somewhere else. This has an unintended consequence of making people very insular and inward-looking, but this is a disservice to research at large because it doesn’t give a premium for collaboration. We do this differently at ISB because even if you only have three papers rather than nine published, we will look for whether you enabled someone else to become better–because there’s value to that. No matter what trajectory you go in, find out what your career goals are and what the trajectory of your career might look like in the context of the organization’s goals, and what the expected steps are for you to be considered for promotion within that trajectory. Even if you’re in school, you need to know how many credits you need to graduate. It’s the same idea.
What’s your advice on productivity?
Set yourself a bar, and keep going at it. Set expectations for yourself, such as publishing, raising money, etc. You have to operate like a small business. You understand this as you look around ISB. There are small groups of research laboratories, and each one has a head who’s charged with the responsibility of paying everyone’s salary in the group. I have about twenty people under the operating budget of our lab, which requires about three to four million dollars per year, and I need to raise that money. Being a director for the last few years, I’ve come to appreciate the business aspect of running a lab. That’s helped me in terms of knowing what needs to happen in order to be successful. So, I can publish great papers, but if I don’t keep writing proposals, then I won’t have enough funding to support my lab. On the other hand, I might bring in a lot of money and support my lab, but if I don’t publish papers, then I won’t satisfy the grantees and then they won’t give me more money in the future. So, I think in terms of productivity you need to balance everything to make your lab successful. To me, I think productivity here includes publishing papers, communicating your research, getting grants, and having a good education program. Simplified, in order to find what success means, know what you’re doing and make sure you have enough information to define that success. If you’re in high school, your next big step is to get into a really great college. But, I’d recommend looking a little further than that. What would you like to accomplish in your career? Then find out what college training might help you get to that. Think a little more broadly, and then define the metrics of success for now, in terms of how you get to those colleges.
What was the project you were most excited about when working on it?
All of them! There was this one project on algae. These algae were dying out in huge numbers every evening, and then the following morning it would regenerate the population. We saw this in the lab and then we studied it extensively. The algae that were living in an environment with high salt where carbon dioxide didn’t dissolve as well because the salt takes up too much space. So then, the algae grow and consume all the carbon dioxide. They reach this conundrum where they can’t grow because there isn’t enough carbon dioxide, but then if they don’t grow, then they’ll be outcompeted by others. So, they’ve evolved this mechanism of killing large segments of their own population, and when the cells die they release carbon, nutrients, and other resources that are then used up for the next cell division. So you see the population crash and then come back up. That process then drives a lot of the other microbes that live with the algae, including halobacteria. We figured this out, and this was something we had not anticipated at all. That was one.
The second one was about TB. When I was in India, one of my friends got TB. We were at a university, and there was no cafeteria, so in the evenings we had no food unless we’d stocked up. As a result, our nutrition was just poor. This guy who’d been a bodybuilder had lost ninety pounds or something. He was very skinny, and one day, he started coughing up blood. We took him to the ER and realized he had TB. Then I spent a week or so in the TB ward–and saw people dying of TB. it was a life-changing experience. So many years later, I came back to do TB research and I wanted to see if the systems biology approach we developed would help in finding better drugs. We published a paper in Nature Microbiology two years ago where we showed a new way of finding drugs and making them more effective. That was one thing I was really proud of. It really came in a full circle, and I got excited by something that went way back. It’s fun to readdress that–and the same goes for cancer. There are some pockets of things that we’ve done that I’m still really excited about. They all stand on a body of work though, so any single piece of work we point out (like the TB work) is standing on the shoulders of dozens of papers and people who enabled a path towards that one delineation.
You mentioned the algae project earlier. Was the information that you discovered applied anywhere else afterward?
One application is making biorenewable products from algae. The day/night cycle is how the algae evolved. They do one thing in the daytime and one thing at night. However, in the biorefineries, they typically use photobioreactors that provide constant light. One thing we learned is that reduces productivity enormously because they could stall this enormous cycle.
Second, we have a patent on how you can modulate the process to improve productivity for harvesting molecules. If you can control cell life, you can essentially have this alga grow to large numbers and then induce cell death, so then we can have it release the products and harvest them.
The third is what we published last year in Nature Communications, where we showed that this cycle takes algae through complex physiological states, and they exert a lot of energy in doing that. We can exploit that to quantify how healthy they are. This is similar to a cardiac stress test in which you get on a treadmill and they make you run. They increase the elevation and speed, and then they look at how you’re functioning. Then they ask you to get off, lie down, and they look further at the dynamics of your heart. The test shows some characteristic curves and depressions if you’re at high risk for heart disease. That signal doesn’t show up until you’re at stress. So essentially, we put the diatoms on tiny treadmills and tracked their stress with different conditions until they collapsed. We simulated climate change one hundred years from now, which made them more resilient–which sounds like a good thing, but is not … Knowing how climate change interactions occur is crucial to the future in terms of influencing policy on pollution, certain leaks, and so on.
Do you have any regrets in terms of your career?
Never!