Eureka, Eventually: The Power of Slow Science
Manganese oxide nodule generated by the bacteria discovered by the Caltech team. These nodules are generally about 0.1 to 0.5 millimeters in diameter. Image is a scanning electron micrograph with false colorization. Credit: Hang Yu/Caltech
by Andrew Moseman
Bacteria live and die in the blink of an eye, at least compared to the lifespan of a human or the long creep of geologic time. Their short lifespans—and exponential rate of reproduction—make microbes ideal test subjects for the microbiologists who study them. Scientists can set up an experiment on Friday afternoon and plan to analyze the results on Monday knowing their microorganisms will be fruitful and multiply over the weekend.
Nature, though, does not always conform to a scientist’s schedule. Sometimes, the only way to a breakthrough is to hurry up and wait or to set aside an experiment entirely.
Consider the case of bacteria that grow by taking energy from the metal manganese, which were discovered by Caltech environmental microbiologist Jared Leadbetter described in a 2020 Nature study. For him, a summer of neglect succeeded where decades of best-laid plans could not.
It was clear that manganese-eating bacteria could exist. Scientists knew that microbes, in theory, could gain energy from the oxidation of manganese (in which they take electrons from the manganese atoms) just as humans gain calories from the oxidation of carbohydrates such as sugars.
Jared Leadbetter
The more tantalizing prospect was that these microorganisms should exist. The earth abounds in manganese oxide, the compound created when manganese is oxidized, Leadbetter says, and circumstantial evidence pointed to bacteria as the most likely explanation for all that material. Then, about 30 years ago, researchers discovered bacteria that drive a reaction in the opposite direction: they reduce the manganese oxide back into minerals that can be oxidized into manganese oxide all over again.
“When you discover half of a cycle, like we did in the ’80s with manganese being reduced,” Leadbetter says, “then you say, well, why is there manganese oxide anywhere unless it's being generated?”
Nevertheless, the existence of manganese-eating bacteria proved elusive. How could such a ubiquitous planetary process be impossible to find in the lab? The missing ingredient, he discovered, was time.
Leadbetter likes to joke that his fateful manganese experiment had an ending but no clear beginning. As a New Year’s resolution for 2015, he vowed to take on a new challenge in the lab. Sometime that spring, Leadbetter began to tinker with manganese as a side project with little expectation he would make progress where so many others had not. During those early lab sessions, he was correct. Little happened with the pink samples of manganese aside from the fact that they stuck to his glassware. Faced with gunk unwilling to detach from a dish, Leadbetter did what many people would do: he left the glassware to soak in his office sink.
Quite by accident, he left it for months. That summer, Leadbetter and Dianne Newman, the Gordon M. Binder/Amgen Professor of Biology and Geobiology, taught at the Marine Biological Laboratory in Woods Hole, Massachusetts. When Leadbetter returned to campus after 10 weeks away, he found the sample had turned a dark brown, a clue that something had transformed the manganese in his absence.
He gazed at the dirty dish and wondered whether it might be the vessel of his long-awaited discovery. And if he had indeed stumbled upon success, why? What had others missed that he had accidentally found? Perhaps his sample was just a little bit easier for bacteria to digest, he thought. Or, maybe, the waiting is the hardest part.
“It's not like I have this special green thumb or that the essential piece was Jared Leadbetter,” he says. “No, I think the attribute I have of patience and realistic expectations was actually part of the solution.”
The possibility intrigued him. Leadbetter’s imagination drifted to inherently slow studies he’d read about: painstaking work such as the classic research on corn genetics by Barbara McClintock of Cold Spring Harbor Laboratory. She had studied corn genetics over the winter to decide which plants to place in which plots the following spring, then waited out the year’s growing season to see the results and decide what to plant the following year. McClintock was locked into the glacial pace of one experiment per year, Leadbetter notes. Compare that to microbiologists, who are accustomed to data arriving in days, not years.
It turns out that manganese-eating bacteria move at their own speed. Even though they multiply more slowly than other microbes, their exponential growth rate, as observed by Leadbetter, would be enough to generate the entire Earth’s mass of manganese oxide in just three and a half years. To find them, Leadbetter just had to (accidentally) work at their pace.
“I just had to embrace the idea that the answer might be yes, but it might not be yes for a while,” he says. “If the field has been moving at zero miles per hour for a century, three months doesn't seem like that long to wait.”
Following that fateful day in 2015, Leadbetter marshaled reinforcements. He and Hang Yu, Sherman Fairchild Postdoctoral Scholar Research Associate in Physics, repeated the long, slow experiments to prove bacteria were truly the engine of manganese transformation and then to identify and classify the bacteria in question. Five arduous years passed before the pair published their study in Nature.
However, the crucial first finding happened because Leadbetter had the freedom to mess around.
“Maybe there are a number of research questions out there in science that people just totally ignore because of the danger of it taking seven years and producing nothing,” Leadbetter says. “Maybe there are certain research questions that Caltech faculty work on that only Caltech faculty could work on.”