How Paradoxical Questions and Simple Wonder Lead to Great Science

In recreational biology, the questions come first, and Prakash practices what he preaches. For example, after spending time aboard a research vessel, he wondered — because it seemed paradoxical — whether photosynthetic cells exist in the deep, dark ocean. Before long, he reeled in Pyrocystis noctiluca, a species of photosynthetic algae, and described its inflation mechanism, which it uses to spring from deep to shallow water off the Hawaiian coast “like a yo-yo,” he said — a feat previously considered impossible for a single cell. Through his process of explorative wonder, Prakash has also characterized the geometry of cells that hunt by unfurling dense membrane pleats — which he called “a mathematical puzzle but hidden in a living creature” — and the “comet tails” of bits of falling matter in the ocean, known as marine snow, which affect global carbon cycles.

Prakash grew up in Meerut, India, where he had an affinity for getting lost outside and satisfying his curiosity with simple tools. He went on to study computer science and engineering at the Indian Institute of Technology Kanpur, and in 2008 he completed graduate studies in applied physics at the Massachusetts Institute of Technology. In 2011, he started his lab at Stanford, where his initial goal was to develop tools to diagnose malaria “under a tree,” he said — that is, to make identification of the deadly infection simple in the places where it is needed most. That mission has evolved, and now he and his students interrogate the boundaries of biology by studying unconventional organisms and democratizing access to science.

When he’s not on a boat reeling in curious cells, Prakash works on large-scale public health problems, such as malaria and poor sanitation. He has pursued field research in India, Rwanda, Senegal, Tanzania, Kenya, Madagascar and Uganda, and his work includes training clinicians to use his “frugal science” tools. Often his two research modes inform each other. The Prakash lab built an automated microscope that runs on a cell phone battery and diagnoses malaria 30 times faster than a human can — an invention that was possible only because he was “bumbling around in astronomy literature, not looking for a solution,” he said.

While he’s fashioned his philosophy into a profession, Prakash believes anyone can be a recreational biologist. That’s why he prioritizes expanding science education around the world, and through his Foldscope effort has cultivated a community of recreational biologists who support and challenge each other to look into the hidden world with wonder.

“We all have a debt to pay for our time on this planet,” Prakash said. “And then you are free to explore.”

Quanta spoke with Prakash about his research philosophy, the hidden wonders of microscopy, and cellular origami. The interview has been condensed and edited for clarity.

How do you describe your body of work?

I do two types of expeditions. Some of them are about health and ecology-oriented technologies, and the others are about open-ended curiosity — seeing how life works. They are connected. Half the time, I don’t care whether a piece of knowledge is useful. But the other half, it’s about studying the most urgent problem that nobody’s working on. Will capitalism bring it to the world naturally? If not, how can we bring it to the world? How do we scale it? During that process, we also ask and solve scientific puzzles.

The Foldscope put you on the map. How did you come up with that?

Almost 12 years ago, while we were building a microscope to find malaria parasites in rural clinics, we ended up inventing Foldscope — the world’s most frugal microscope that people can carry in their pockets. It wasn’t practical to diagnose malaria with, but it led to the educational context immediately because then, for a price point of a dollar, anybody could observe the microscopic world. We’ve reached around 3 million kids now in 150 countries, and it’s become the largest amateur microscopy community. There are Nobel Prize winners in the community, but we call it amateur in the sense that anybody can join.

In science, many people feel that they don’t have a voice, and the Foldscope community is a way that you can use creativity to distinguish yourself — not your status, who you know or where you published your paper.

Why is a paper microscope a good addition to a recreational biologist’s toolkit?

Let me show you. [Over Zoom, Prakash folds the paper microscope, taking it from flat to functional in 30 seconds, tapes a mosquito larva to the glass slide, and holds the microscope up to his camera to reveal the larva’s guts.] That’s the heart, and those are the immune cells.

When we look through the Foldscope together, suddenly we’re not talking in hypotheticals. We just saw the heart of a mosquito. Once people see these things, they can start asking questions. We should be allowed to build questions that come from our experiences, not just a textbook. It doesn’t matter who described the mosquito heart for the first time; what matters is that you just saw it. If we teach how to observe and ask questions that are emotionally relevant, people will have the passion to solve them.

Observation is a practice, and if you don’t practice, you lose it. You can walk in the most beautiful reserve, or even just in your garden, and not actually notice the complexity of what’s unfolding around you. I think we forget how to ask questions, so as adults we have to relearn it.

Recreational biology relies on broad curiosity to make connections between fields. How did studying astronomy lead you to make Octopi, a diagnostic tool for malaria, for example?

In the malaria problem, our challenge was that up until now, to find a parasite [living inside a cell], we had to use a 100x oil objective on the microscope, which costs $10,000. You just keep zooming in, but you can still only see a few cells. A health care worker needs to see between 3,000 and 5,000 cells and, from that view, to be able to decipher whether a person has malaria.

Astronomers have already solved this problem. When we look at stars, we can’t get much information from their shape. They just look like dots. The things are so damn far [away] that astronomers just keep building larger telescopes. So instead, they look at the colors of light that arrive from the star, because in those colors is hidden the chemistry and composition of what might be happening so far away. It’s this idea of spectroscopy — the chemistry of what’s burning is reflected in the light that it’s emitting.

So, we had all of these cells right in front of us, but we couldn’t see them. How could we find the rare ones with parasites? I didn’t want to buy a $5,000 microscope filter set, so I said let’s just see what [looking through] a piece of glass can do. It was not so good; it was leaking all these colors of light. But then we realized that the parasites were leaking a particular color.

It turns out, the light an infected cell emits is 10 nanometers off [compared to an uninfected cell]. We were working on the exact same problem astronomers already figured out. Now, we can build cheap microscopes with $10 to $15 objectives and a massive field of view that allows us to search 20 million cells in a drop of blood [and identify malaria parasites by their light signatures].

How do you come up with research questions in recreational biology?

The absurdness of cells drives this work.

Our first oceanographic expedition in Hawaiʻi took place because we had a hunch that we should look for photosynthetic cells in the deep. We know about whales. Whales can dive and go to deep waters in a single breath, so we wondered, could a cell do it? I didn’t have any grants or any funding for any of the oceanography. I met this wonderful person who offered a boat off of Hawaiʻi, and that was the first time that I actually went on an oceanography expedition. That’s like seven, eight years ago now, and I just fell in love with being on the boat. I just completed my 19th expedition, so we have come a long way.

I wanted to test if we could search for photosynthetic cells that were in the deep. Because that’s paradoxical, it would be interesting. We ended up finding these beautiful photosynthetic cells, but they have no flagellum. They have no cilia. No organelle to move. So how do they get there? And how will they ever come back? Because if you are deep, but you need light to survive, you or your progeny must rise.

We discovered that the cell has a beautiful buoyancy engine. It inflates like a hot air balloon and is a lot like a desalination plant. Aquaporins, [proteins that form pores in cell membranes], bring in fresh water that has a lower density, so it can suddenly skyrocket up 250 to 300 meters. It produces proteins and then goes down. Now this cell holds the world record for the longest cell migration. It’s a 100-micron object moving half a kilometer. When you do this in body length — I should be able to walk to the other side of the planet and come back. But it’s a migration that the cell does in seven days.

What other features of unique cells have you discovered?

Once, we were looking at this microbe Lacrymaria olor, which hunts by extending its neck incredibly far — the equivalent of a 6-foot human projecting its head 200 feet. We couldn’t figure out how it could do that.

Then, when I was in Japan with my kids, I was fascinated by these chochin paper lanterns. I started thinking about whether true origami can occur at a cellular scale. I realized this could actually be the cell’s architecture. We went into the lab and measured the hell out of the cell, and boom! — it was exactly what we thought. In this case, the question came first. It can be whimsical in many ways, and the answer deep below had a phenomenal biology.

Your curiosity-driven approach to research is fundamental or basic science, which is pursued not for application. What do you want the public to know about the importance of basic science?

Most of the challenges that we face in society, at their roots, are because we don’t have a fundamental understanding of the processes that we are messing with. In medicine, every drug that’s ever been invented has been us trying to meddle around in something that we don’t have a grip on. When we build solutions using only the knowledge that’s on the shelf, we end up being incredibly constrained about what we can do, at what price point and on what scale.

It’s not about investments. It’s far deeper in all of us. Basic science is not at the service of something, but the groundwork that is our entire society’s foundation.

So how do you train a recreational biologist?

You buy some rubber boots for them, and you bring them to the depths of the ocean or the swamps or the glaciers, and you teach them to observe. You give them the freedom to ask original questions without worrying about whether they are useful to someone else, and they’ll start seeing things that they never did before.

We should all be allowed entry into the mysteries of the living world, but people step away from it. They say they found science boring or dull, or it wasn’t their cup of tea, or they’re not good at it. But science is everything. It’s every emotion, everything that you have experienced, and all of our existence in the world. We have stripped away almost everybody from the wonder of the living world. Recreational biology, to me, is an answer to how we bring that back.

*Editor’s note: Foldscope distribution is supported by the Simons Foundation, which also funds this editorially independent publication. Simons Foundation funding decisions have no influence on our coverage. [back]