The worth of ‘worthless’ ideas

Manu Prakash, PhD, came into focus on my laptop for a Zoom meeting. It was early June, and blue and white waves behind him caught my eye. Bright sun lit his face and jacket, and wind buffeted his curly hair. Then the blue horizon behind him slowly tilted, and I felt a hint of sea sickness.

For Prakash, it was the first week of a 30-day cruise off the coast of Northern California. In coming hours and days, the U.S. Navy research vessel Kilo Moana would follow the California Current, allowing the researchers to drag giant, ultrafine nets as deep as 1,000 meters and pull aboard ocean microorganisms.

The microscopic beings wouldn’t survive long out of the ocean, often dying in just a few hours, so Prakash and his colleagues had to hurry them to a shipboard laboratory for study. Prakash, an associate professor of bioengineering, was searching the North Pacific for extraordinary one-celled organisms that tell surprising stories about how life solves puzzles, survives and thrives in the deep dark ocean.

Many people believe research should always be in the service of new technology and the public good, to produce, for example, a vaccine or a better battery. Prakash rejects that idea out of hand. There is science, he said, and then — maybe — applications will come later. He’s not against utility by any means, but he believes utility is not the point of science.

“Science is about understanding. It’s centered around being able to explain this world. And so when you see something beautiful, there is something lurking behind it. It’s beautiful because of the mystery. It’s beautiful because it’s almost outlandish.”

That beauty and outlandishness fascinate Prakash. And he wants that joy, fascination and surprise for scientists of the future. Inspired by recreational mathemetics, he’d like to establish “recreational biology,” a science of mysteries and paradoxes.

In June, Prakash was the Stanford lead on an ocean expedition funded by the National Science Foundation to study both marine pandemics and how viruses promote carbon sequestration in marine environments.

Back out on the research vessel, Prakash was staggering around with his laptop. A hundred seconds into the interview, he interrupted himself. “Oh, my goodness! This is insane right now!”

“What’s happening?” I asked, safely at my desk.

“I think we have 12-foot waves and they are generating this massive plume. This boat is very special. It is a double-hulled boat. And the waves get trapped and it reverberates like an angry dragon!

“Do you hear the rumble at the back?” He paused. “Right there?”

I didn’t. The Zoom app was helpfully blocking out the roar of the waves smashing between the two hulls of the big research catamaran, so I couldn’t hear any of it. Unsatisfied, Prakash quickly recorded the roar on his phone and later emailed the recording to me.

Prakash, a fellow of the John D. and Catherine T. MacArthur Foundation, was embarking on his 17th voyage to study the strange and beautiful microorganisms that populate our oceans. Also aboard the 186-foot catamaran were four members of his lab from Stanford University, collaborators from around the world, plus a crew of 20 to run the ship and “keep us safe,” as Prakash put it.

Prakash has an eclectic range of interests and inventions, including corralling tiny bubbles to execute computations in much the same way as a traditional electronic computer and a paper microscope that’s cheap, portable and durable enough to be invaluable in any village in the world.

Lately his research focus has been different kinds of protists — one-celled organisms that thrive in all kinds of damp places, from warm, shallow ponds to the near-freezing depths of the Pacific Ocean. Like big game hunters of the microbial world, Prakash and his students have snagged an amazing number of trophies.

In the past five years alone, these include:

• Tiny starfish larvae that can stir seawater in one pattern to bring nearby food closer and in another pattern to propel themselves toward better feeding grounds (Patiria miniata).
• Bacteria living in biofilms that feed a whole colony by gliding in spiral patterns to create flows of nutrients (Oscillatoria).
• Juvenile sea cucumbers able to form beautiful patterns of crystalline rocks in their skin (Apostichopus parvimensis).
• Bioluminescent cells that make half-kilometer-long journeys in the open ocean by increasing their volume six times, like tiny balloons floating through the water (Pyrocystis noctiluca).
• Colonies of cigar-shaped aquatic cells that can talk to one another by way of pressure waves and then, in unison, contract to release toxins that drive away predators (Spirostomum).

Another of Prakash’s longtime passions is the one-celled Lacrymaria olor. Under a microscope, the teardrop-shaped microorganism appears innocuously hiding among debris. But when it’s ready to hunt, it whips out a long neck — up to 30 times the length of its body — and nabs other protists. Over and over, it extends and retracts its astounding neck while ambushing and engulfing prey. It would be as if your house cat suddenly extended a paw 50 feet down a hallway to seize a mouse.

How “Lacry,” as Prakash calls the cells, could extend their necks so far at first seemed inexplicable. All cells are enclosed by a cell membrane that is flexible but not stretchy. Pull on it hard enough and it will tear like paper. That Lacry’s cell membrane could stretch to 30 times the length of the cell was impossible.

And there was another surprise. Lacrymaria olor’s neck doesn’t get thinner as it stretches out, as a rubber band would; it gets fatter, enabling it to engulf its often relatively hefty prey.

How was a single cell able to do this? For Prakash and his graduate student Eliott Flaum, one clue was a helical pattern of pleats just under the cell’s membrane. When the helix of pleats unfold, the cell’s neck extends — and with a girth that can accommodate morsels nearly as large as Lacry itself.

Lacry’s beautiful, pleated neck is made of a helix of molecular filaments, capable of folding and unfolding, closing and opening. Prakash first realized how Lacry evolved the capacity to pull off this magic trick while he was on a trip to Japan with his kids. Lacry, he suddenly realized, had mastered the ancient Japanese art of folding paper, or origami.

Lacry’s neck is the first known example of “cellular origami.” As Prakash said, “It’s the first time a single cell has been shown to ‘invent’ a new kind of origami to achieve this shape-shifting dance.”

Flaum’s and Prakash’s discovery inspired the lab to begin building a pleated surgical robot that can expand 100 times in length to reach far-flung corners inside the body.

In June, Flaum’s and Prakash’s seven years with Lacrymaria olor paid off with a paper in Science magazine and a beautiful image of Lacrymaria on the cover. By then, though, the entire lab crew was at sea, pulling miracles from the deep.

Whatever seems beautiful, intriguing or paradoxical in the microscopic world becomes Prakash’s joyful obsession. For him, more than for many scientists, science is so much fun he thinks of it as play. But the joy comes with a tinge of feverish haste and a portent of loss. For one thing, cells don’t live long out of the water.

“When we’re on board, I’m gonna throw a net out, and there is a fleeting moment of, I would say usually two or three hours, that there’s a possibility that I might have these deep-water cells alive and I can watch them. And then it’s gone, and I have to wait for that next fleeting moment.”

One extraordinary finding this summer for Prakash was a single-celled organism the size of a small grape, the radiolarian Cytocladus, which had been last documented in 1898 during the Valdivia expedition and never before photographed or closely studied. Prakash spotted the “fuzzy grape” by chance among a haul of tiny shrimp and other plankton pulled from 600 meters below the Pacific’s surface.

Anxiously, he kept it alive for two days to study and then reluctantly dunked it in liquid nitrogen, flash freezing it for posterity. Weeks later, after obsessively filtering nearly 100,000 tons of water — as much water as might flow over Yosemite Falls on a spring morning — he found three more of the cells. With his first safely frozen, those three precious living cells occupied him day and night, all the way to the end of the cruise. Finally, as the Kilo Moana sailed under the Golden Gate Bridge into San Francisco Bay, Prakash dropped the three extraordinarily rare cells into liquid nitrogen.

Not knowing if he or, really, anyone in the world would ever again see these remarkable deep-sea organisms, he sailed into the bay with a great sense of sadness.

Besides cells’ short lives out of water, there’s another reason for Prakash’s persistent sense of haste. A senior fellow at the Stanford Woods Institute for the Environment, he’s aware that many of the planet’s most miraculous organisms are literally going extinct before we even know they are there, let alone know enough about them to appreciate their beauty and inventiveness.

At least some of their activity is deeply important to the entire world. On board the Kilo Moana this summer, Prakash came to understand that some of the deep-sea organisms he is studying are accelerating ocean carbon sequestration. Organisms we are barely aware of are helping keep climate change at bay.

Saving the world, one carbon atom at a time

We already know the world’s oceans absorb vast amounts of carbon dioxide, keeping Earth’s atmosphere from heating more than it already is. We also know that photosynthetic plankton in the ocean use sunlight to snatch carbon atoms from carbon dioxide and link the atoms into long carbon chains to form carbohydrates, fats or proteins — the building blocks of life. All those chains of carbon make up the mass of every cell.

In the ocean, once individual cells and other organisms die, they slowly sink to the bottom, so slowly that it might take a year for the carbon in a single cell to fall the 4 kilometers to the bottom of the sea. There it lies inert as sequestered carbon.

But cells often clump together and plummet through the sea much faster than individual cells ever could, reaching the bottom in weeks instead of months. “And that,” said Prakash, “is how 30 to 40% of anthropogenic carbon is actually being taken up by the oceans. The ocean is both a great savior and a gigaton technology for carbon sequestration that already works.”

But what makes the cells clump together?

Enter viruses! That’s right, there are viruses in the ocean, just like on land, and they can infect everything from marine mammals to one-celled organisms.

Virus experts already knew that when viruses infect a cell, they need to be able to stick tightly to the cell. (When the infected cell bursts open later to release new viruses, those viruses need to not stick to the cell.) It was reasonable for the team to wonder if infected cells in the ocean might be stickier and more likely to form rapidly falling clumps, known as “marine snow.”

“So that,” said Prakash, “is what our expedition was about. We were studying how viral infection impacts the formation of these clumps.” Prakash and colleagues tentatively hypothesize that stress induced by a viral infection might cause more snow formation.

Meanwhile, Prakash’s lab has long studied other radiolarians — in part entranced by their breathtaking beauty and intricate crystalline structures. As fate would have it, many radiolarians turned up in the Kilo Moana’s nets this summer. Because radiolarians have stone crystal skeletons, they are both lovely and incredibly heavy, at least for one-celled organisms. When they form marine snow, their weight and density make them fall even faster to the bottom of the sea, accelerating marine carbon sequestration. Prakash is excited to begin writing a paper describing how that works.

The art of observation

For a cell biologist, Prakash is a surprisingly enthusiastic advocate for field work. He and his lab members are always packing boxes of microscopes and flying these tools to expeditions around the world. When researchers study cells in the lab, he mused, “We strip away the relevant questions. We don’t even know what questions to ask, right?”

But out on the Pacific Ocean, with 12-foot waves tossing catamaran and researchers, the ocean environment speaks loudly. “Being here, knowing what the water looks like, I can think about, ‘How the hell does this delicate, fragile cell survive in an ocean that looks like this?” Being out on the ocean, staring at living cells fresh from the wild sea, is bound to suggest thoughts and questions that might not come to mind in a quiet laboratory.

Prakash recently taught a Stanford University course titled The Art of Observation. “For a while now,” he said, “I’ve been thinking about this notion that observation comes before ideas, even before any experiments.”

The scientific method, as typically taught, emphasizes hypothesis testing, rushing past simply observing the world, rushing past just wondering why or how. Yet virtually all science begins with observing and mapping. Before the great discoveries of modern astronomy, we mapped objects in the sky and noticed, for example, that stars and planets were different. Only then could we begin to ask why.

The first thing an ecologist wants to know about an ecosystem is what lives where. Likewise, geneticists spent years mapping thousands of genes on the chromosomes, even when they had no idea what the genes did.

Observation comes naturally to us. A 3-year-old will stare in wonder at a rabbit disappearing into a brush pile. But most adults learn to focus on our endless chores, and we often block out the wonders surrounding us.

“The purpose of the course was partly to help students understand what observation means and the history of observation, but also, just practically, to teach them how to observe acutely. And you observe acutely when you immerse yourself in nature,” Prakash said.

“I particularly like the small world, so I have acute powers of thinking about the small world.” But others may notice the way plants behave or the way sunlight filters through water. His students made at least one new observation a day, writing down what they observed, sometimes with drawings. “When you’ve done it for two months, you start feeling like it’s a practice. And then when you’ve done it for five years, you sort of feel like, oh, it’s a part and parcel of your life.”

Prakash has been keeping a record of his observations for 20 years. Sharing those observations is an important part of the practice, but it is often difficult, Prakash said. “I have some wild ideas that I am sometimes embarrassed to tell anybody,” he laughed.

Prakash’s dissertation topic at the Massachusetts Institute of Technology was one of his “embarrassing ideas.” He had noticed the way bubbles avoid one another or merge depending on conditions, and it occurred to him that it would be possible to construct a computer circuit with bubbles. “Like literally bubbles. And it’s something that I had thought about for a long time, but I would never tell anybody.

“But then I pursued it. And that was my PhD. I got my PhD,” he said, with a trace of wonder in his voice.

Even at 44, Prakash still hesitates to share some of his wildest ideas with people outside his inner circle. He conceded, “It’s easy to say it; it’s hard to do.”

Prioritizing wonder

In Silicon Valley, investors say things like, “Ideas are worthless; execution is king.” To the degree that ideas by themselves can’t be copyrighted or patented, that is true. But ideas are the fuel that powers science (and, ultimately, technology).

Prakash argues for the worth of worthless ideas. Historically, he said, the most important ideas come from scientific backwaters, areas of knowledge that may have been ignored for decades. “The most important ideas lie in places where very little has been pursued so far. Curiosity is a way to take that leap.”

Despite prioritizing wonder over utility, Prakash acknowledged that the fast pace of modern science leaves little room for rapt observation or the delight of noticing something completely unexpected.

“The next big project is always around the corner. There’s very little time to slow down, turn over rocks and just play. How do you write a grant about play? How do you write a grant about the most beautiful cell in the world? All scientists believe that if you pursue your curiosity, that’s the primary way to make discoveries. But in practical terms, it is difficult.

“Just because it’s difficult doesn’t mean we don’t do it. Play and curiosity are deep in our hearts,” Prakash said. “But there are no awards for observation. It’s just, you share it and lots of people build upon your observations and ideas. That’s at the heart of the scientific pursuit.”

Prakash calls his passion-driven research “recreational biology.” “What if we could create an entire field that’s associated with mysteries and paradoxes? Not because people 50 years ago were asking this question, so we have to continue that legacy, or because there is a disease that we are working on.” What if instead of plodding, he asked, we unshackled biology from utility and said we are just going to work on puzzles?

Just days after returning from exploring the depths of the cold North Pacific, Prakash and his lab were off to the Atlantic Coast to teach recreational biology at the Marine Biological Laboratory at Woods Hole, in Cape Cod, Massachusetts. He was planning two weeks of play, with students joining from around the world in one of the oldest continuously running cell biology courses taught in the world. “I’m packing tomorrow. I’m also packing a whole bunch of organisms,” he laughed.