Interview with Manu Prakash

Manu and his lab members on a lab retreat in Puerto Rico.

Let's start at the beginning, could you tell me what first inspired you to become a scientist?

That's a tough question because I do many types of science, and depending on the thread, the inspiration was different. My very first inspiration was nature, and when I look at nature, I realize that we don't actually understand much of it. That framework is really at the heart of everything that I do, particularly in life sciences, but thinking about understanding nature is also intimidating as a scientist. I mean, do we even have the capacity to ask these big questions? Then growing up in India, I often felt this notion of haves and have nots. I've felt this very explicitly in my personal life with lack of access to scientific tools. So, the other big piece of the puzzle that inspires me and keeps me going, is asking whether we can deliver scientific tools and bring the capacity to be curious to a much larger group of people. In the lab, we do that very explicitly by building programs and building instruments openly, so we can share them. In the end, I think it's two sides of the same coin and both inspirations are about magnifying curiosity.

Can you describe your career path and what your lab works on now?

My undergraduate degree was in theoretical computer science, so I was doing abstract math as an undergraduate at the Indian Institute of Technology. I transitioned to MIT for a PhD in applied physics, where I did a lot of continuum mechanics and fluid solid mechanics. My PhD was focused on a strange idea that I wanted to pursue, which was ‘could you build computers out of bubbles?’ That's what they gave me a PhD for! Quite literally, I played with bubbles and proved that it's possible to build a completely functional Turing complete computer using little drops of water and bubbles. Then, I got a fellowship at Harvard, which was my first foray into biology. I started thinking about physical principles and the rules of biology, asking how you organize the biological world. I think of every organism in the tree of life as an idea, and I can explore new avenues by studying almost anything in this vast span of the tree of life. This means that it's often not about choosing a question to research but instead choosing an organism, and that drives a lot of the work that we do. When I started my lab in 2011, I remember somebody telling me that I needed to have a lab website to recruit students. I was struggling, as I'm struggling right now to tell you what we do, because I didn't know what to write on our lab website. At the time I coined the phrase, we do ‘curiosity-driven science, and anybody who's curious and interested come talk to us’, and that's still written on our website.

Over the years, we've explored questions asking, what are the bounds of living systems. One big question that we've been thinking about is how does biological material compute. We do a lot of work in the ocean, and we've been able to connect ideas between how cell biology and principles of cell biology are organized in the ocean, and more recently, showing how they couple to carbon sequestration in the ocean. A lot of our current work is connecting climate change to cell biological principles, because it turns out that most of the current climate models don't have any detailed cellular or biological parameters. I'm interested in the extremes of biology. How fast can things go? How cold can things be? What is a minimum animal? Together, these types of questions make up the first founding principle of the lab, that we're going to do curiosity-driven work.

The second principle of the lab is that we will do research in a manner that enables and allows a larger group of people to engage in science – people who have never had the chance to engage before. So, the second anchor of the lab is frugal science. In a biological context, the Foldscope is probably the most famous tool that we've developed, but there are a dozen or more other tools. More recently, we've been automating a significant portion of biological observations by building farms of completely robotic microscopes that we call ‘Squid’. These microscopes are open source and allow researchers to push the bounds of high-throughput observation with minimum resources. Of course, these two principles of the lab are intertwined – because we are tool makers, we are able to observe things that very few people observe. For example, in the Arctic we built a microscope on a boat that can image inside ice at sub-zero temperatures. So, of course, we were the first one to see what was happening there and ended up discovering cell motility at very low temperatures.

Can you tell us about the inspiration behind the Foldscope project?

I think we were really driven by the question, could we create a microscope for $1 that had the capacity to image single bacteria. The goal stems from the desire to distribute these microscopes at global scale, which is at the heart of why we started the initiative. I often compare Foldscopes to pencils or pens. For a mathematician or a writer, pens and pencils are powerful objects, and the equivalent for a biologist or life scientist is a microscope. Our aim is for every single child in the world to be carrying a microscope in their pocket, because if we believe curiosity is at the heart of all of science and we deeply value it, we should share it. I remember having an exam question at school where we were asked to draw a microscope, but we hadn't even seen a microscope. How ironic is that? Over the last 10 years, the Foldscope program has grown to reach 6 million-plus children, with 2.5 million physical Foldscopes distributed across 150 countries. It allows people to share the microscopic wonders of nature. A big part of the program is our online platform called Microcosmos (https://microcosmos.foldscope.com/), where our Foldscope community come together to share their observations, images and scientific discoveries. There are literally hundreds of thousands of examples of people sharing curiosities, and you can very quickly go from a simple observation to arrive at the edge of knowledge, including discovery of new species, utilizing microscopy to monitor our changing and degrading environment, and applications in agriculture, animal and one health.

In our field expeditions, we are doing the same thing – starting with an observation and then using our imagination to explore extreme mechanisms in biology. As a lab, one of our big focuses is using high-throughput tools to generalize and bring physiology-based experiments and live microscopy into the field. This means taking the scientific tools, like home-built confocal microscopes, that we have developed in the lab out into the field. We've been all the way to the Arctic, to Antarctica, probing depths of the ocean. We make observations and push the bounds of what we can achieve while working in the field. We recently posted a paper on BioRxiv (doi:10.1101/2024.11.18.624199), where we found a eukaryotic cell in the Arctic that still had the capacity to be motile at −15°C. It's the coldest ever recorded motility in a single cell. We found it lodged inside the Arctic ice sheets. If we look back in history to when our planet was completely covered with ice during Snowball Earth, maybe surviving these temperatures, or even thriving at these temperatures, was a normal thing. Perhaps in all of our genomes, we have the capacity to thrive in cold, we just don't express it. This is a great example of how we can very quickly go from an observation to completely new ways of thinking. This has allowed us to bring ideas from thermodynamics and explore the broader role of state parameters like temperature in the living world.

How did you build your research team?

I don't really respect disciplines; I respect questions, and the people that join the lab are people that are adventurous and explorers. They have in-depth training in one field, and then they're excited about learning something new. I have pure mathematicians in the lab who have only worked with pencil and paper. I have biochemists in the lab who have never done field work. I have engineers in the lab who love building things. I have an architect in my lab who used to design houses, and now she works on a lot of tools we make for the community. I've also had a resident artist in the lab for the last 12 years, and we have several long-term art projects that we will be unveiling soon. This is not art at the service of science, but art as a way of thinking. I have realized that artistic expression can lead you to new places and a deeper appreciation of a question that you might not have thought about before. Overall, I think that training young people in a breadth of fields is important because it is when ideas collide in your own head that you can appreciate the breadth of science and ask the important and right questions. To appreciate what other fields bring to the table, you must pursue ideas in as many fields as possible, and I think that's the purpose of training rather than becoming too specialized.

You sound very passionate about seeing and doing the science yourself. Are you still able to get in the lab or out into the field?

Yes, I'm a lab scientist. I have my own bench. I have my own projects. I have my own experiments. I have my own critters that I'm trying to crack! I don't think I can be who I am without running experiments. I have a lot of projects in the lab that started as observations that I had made in the field or as something I was looking at when mucking around on a Foldscope. Then, 7 years later, with an incredible amount of work as a team, we might finally understand that principle. Observation is so deeply ingrained in how I think, and I almost need to be observing and tinkering to be able to think about what might be going on. But it is hard, life gets busy in many ways and with many sets of roles, but I work very hard to preserve that personal time for me. Protecting time to do your science is really the best gift that you can give yourself. It's easier in the context of field expeditions where we will spend a month at sea together as a lab. We'll be at the bench working very long hours every day.

Has it been difficult to get funding for your curiosity-driven science?

Yes, I often say we run the lab on fumes, and that's a harsh reality of this type of research. We write a tremendous number of grants, but very few funding bodies seem to appreciate or care about this approach in science. Of course, when the work is done, people appreciate that, but that's when the discovery has already been made. My hope is that we are now providing enough evidence to show that true curiosity and exploration are at the heart of some of the best ideas. Unfortunately, so far that hasn't transformed into programs and funding. I am not aware of any programs in life science or in biology where they say we're looking for curious people. Some days, you're not mechanistic enough for someone, another day you are exploring too many things and not focused enough. Some days funding agencies have a problem with the fact that beyond basic science, we also engage communities or build and scale solutions in global health. There is always a label that can be used to find a flaw in somebody else's approach to science.

But if we all took the same approach, we would all race to the same vista in science. Only by taking different approaches can we expect to find completely new folds in the scientific landscape. So, we keep applying and, once in a while, we get lucky, and it keeps us afloat. I think that it's crucial to think about the framework of how we evaluate sciences, especially knowing that if you look back at history of science, remarkable transformations and fields came along from very fundamental and often oddball observations. History is there to remind us, but unfortunately it has not found its way into science policy.

Your lab seems to address quite a few of the United Nations Sustainable Development Goals, so it seems surprising that it is difficult to get funding, given this is an internationally accepted framework

Yes, that's true, and the Foldscope project is a clear example of the difficulties we face in getting funding to scale up projects. Every 2 months, I feel like I have to figure out whether I'll have to shut the program down. This is the largest microscopy community in the world we're talking about. It has taken us 10–12 years to get to the point that 6 million children have access to Foldscopes, and it costs us ∼$1–2 per child to run the program. But there are 2 billion children on this planet, so we are orders of magnitude away from the dream of all children having access to Foldscopes, and that is driven by funding. We have built national programs; we've done hundreds of thousands of pilots, and hundreds of papers have been written on this approach of introducing science around the world. People have even discovered new species using their Foldscopes, so I don't know what additional evidence we need to prove this work is valuable, but when it comes down to funding, there is very little support for grassroots programs. Ironically, I would argue that Foldscope is the most applied project that I've scaled up. I just don't think we invest enough to support and scale programs. We work with UNICEF, we work with USAID, public libraries, school networks, we work with NGOs and entities across the world, but it's very piecemeal. We have also worked with governments. For example, I just came back after meetings with a Ministry of Education, and it's hard for them to really engage with creative approaches to bringing science to people. I've been thinking quite a lot about building this framework country by country, but it's going to take time, and it's also about finding the right people and funding from people that care about scale.

Meetings can be essential for disseminating research and getting input on ongoing work – how do you get the most out of attending meetings?

I have to balance meetings with field work, because I'm out in the field quite a lot. I do think that the joy of sharing your work with other people is very human, and to a certain extent, finding like-minded people in broader groups makes you believe that the approach that you're taking is valuable. I love meeting kindred souls who will challenge me, who will explore with me and who will value ways that I think. So, to me, that's why meetings are valuable. The scientific content is often available elsewhere. I can find and read the research, but the human is stripped away from it. One conversation with another researcher might make you think about your research in a different way. I'll give you an example: I've been working in the Arctic and on cells that survive ultra-cold temperatures for the last 5 years. We planned an Arctic expedition, and we now have a Human Frontiers Science Program grant, trying to understand how life thrives in ice. So, I've been thinking about ice quite a lot. Then, recently I had a chance meeting with a person that studies Europa, one of the moons of Jupiter which is completely ice. It was such a fun moment for me to just take a step back and think that everything we've been doing in the last 5 years is applicable to what people have been thinking about for Europa. The idea that we might have a mission to Europa, and what we have learnt here will help shape the sets of questions that mission might address is exciting. Sometimes chance conversations can mean that you can suddenly link to an intellectual space that was very near to you, but you didn't see it.

One of the things we're excited about for our Biologists @ 100 conference is that it is interdisciplinary; what are you excited about for the meeting?

I've had several conversations with people who are very excited about the program because of the breadth of what you are covering. I think that we should see biology and life as a whole and it's just not possible for us to divvy up research in the same way that we have divided up the living world. We can't expect to understand one piece of it without understanding other pieces. In a lot of our research, we've stripped away all context and become isolated. Having a broader framework of journals and communities that bring biology together is really where we need to go. I often feel an outsider in all fields of science but that's great because then I don't have to feel responsible for it and I also have a bird's-eye view. This view tells me that our obsession to keep subdividing our territories has truly gotten us lost. The interconnectedness in life is deeply rooted. For example, no question in ecology can be understood without molecular frameworks, and no molecular mechanism can be understood without an ecological framework. The unit of a cell is everywhere, and you can't understand molecules without understanding a cell. Having different disciplines under the same umbrella, as with the journals at The Company of Biologists and at the upcoming conference, is something that I value.

Manu Prakash was interviewed by Helen Zenner, Online Editor at Journal of Cell Science and Community Manager of FocalPlane. This piece has been edited and condensed with approval from the interviewee.