Bacteria and other microbes have ruled the planet for at least 3.5 billion years, but only in the last century have we begun to appreciate their dominance. We now know that every environment has its own unseen community—its own microbiome. Microbes in the soil drive planetary cycles of important elements like carbon and nitrogen. Microbes in the oceans produce much of the oxygen we breathe. Microbes in our bodies build our organs, safeguard our health, and even steer our behavior.
Thanks to these revelations, microbes have become fashionable. They've attracted the attention of magazine editors, book writers, museum curators, and documentary makers. Now, they’ve even stormed the Oval Office.
In 2013, President Obama appointed Jo Handelsman, a pioneer of the modern age of microbiome science, as the associate director for science at the White House Office of Science and Technology Policy. Over the last year, Handelsman, with support from the Kavli Foundation, has facilitated three successive workshops—first with scientists, and later including funding agencies and industry representatives—to determine the big remaining mysteries of the microbiome and hash out ways of solving them.
The result is a proposal, penned by a group of leading microbiologists, for a Unified Microbiome Initiative (UMI)—a national coordinated effort to develop the tools we need to truly unlock the secrets of the microbial world. It will do for microbes what the BRAIN Initiative is doing for neuroscience.
“We’re trying to understand the central tenets of how bacteria, fungi, and viruses organize themselves, communicate, and deal with the world in any context, whether in the human body or in soil,” says Jack Gilbert from the University of Chicago. With that knowledge, microbiologists hope to better harness microbes to produce medical drugs and biofuels, stimulate the growth of crops, and treat everything from diabetes to allergies. “I’m super-pumped about this,” adds Gilbert.
The concept of the UMI is sensibly built upon the two big pillars—better technology, and more cooperation—that have driven progress in microbiology since its birth 340 years ago.
Let’s talk about the tools, first. In 1675, The Dutch draper Antoni van Leeuwenhoek became the first human to see bacteria after building, by hand, the best microscopes of his day. In the late 19th century, scientists developed laboratory techniques for growing microbes, including those from natural environments like soil and water—now, they could work with the bugs rather than just observing them. In the 1950s, Robert Hungate created a technique for growing bacteria that recoiled in the presence of oxygen, making it easier to study the multitudes in animal guts. In the 1980s, Norm Pace, Ed DeLong, and others developed techniques for identifying bacteria through their genes, without having to grow them at all.
Each of these innovations peeled back another layer of the microbial world—but many layers remain hidden. “We obtain huge collections of genes, but roughly 50 percent are unknown,” says Jeffrey Miller from the University of California, Los Angeles. Similarly, 98 percent of the chemicals that microbes produce are unknown. “We're trying to put together an extraordinarily complex puzzle with just a fraction of the pieces.”
We need better ways of “reading the microbiome better, faster, and cheaper,” says Rob Knight from the University of California, San Diego. These include techniques that can analyze the entire genomes of specific microbes, the genes they switch on, the proteins they make, and the molecules they produce. Gilbert also craves tools that can track molecules as they scurry and meander between microbes, or even within a single cell, in real-time.
New technology will also help to rectify the most common (and the most justified) complaint about microbiome research: that it’s mostly an imprecise exercise in cataloging. Scientists will typically list and compare the microbes in, say, healthy and diseased lungs, but they’ll be unable to say whether the microbes caused the disease, or vice versa, or neither. “It's all mostly correlative,” says Miller. “We lack causal, rigorous, hypothesis-falsifying science.”
That can change with more precise ways of manipulating the microbiome—of adding, removing, editing, stimulating, and blocking specific cells or species. Currently, such manipulations rely on blunt instruments like antibiotics. “They’re like nukes,” says Gilbert. “We want to get snipers. If I can take a human-gut sample and selectively kill off individual organisms or turn off individual metabolisms, that would help me enormously to work out what specific organisms, genes, or metabolites do.”
With these techniques in place, the UMI brain-trust anticipates that within a decade, microbiologists will be able to build computer models that accurately simulate communities of microbes, and predict how they will change over time. “Imagine a smart toothbrush that’ll tell you if you’ll get caries, or from a patch on your skin that’ll say if you'll get dermatitis,” says Knight. “Instead of telling you where your microbiome is right now, we could predict where it'll be in the future and how you can personally modify that.”
All of this will depend upon more cooperation between microbiome researchers—the second theme of the UMI. At the moment, the field is growing, but fragmented. At least 17 federal funding agencies are throwing money at microbiome projects, with little coordination between them. Similarly, hundreds of scientists have flocked to the field, many of whom are running small projects that work on the same problems.
This horde of enthusiastic researchers have also fenced themselves off into distinct silos. Those who study animal microbiomes go to different conferences than those who work on human microbiomes, who don't talk to soil or water people. These are artificial boundaries that reflect historical divides between zoology, medicine, ecology, and other scientific disciplines; from a microbe’s perspective, they’d make no sense. Humans, plants, rivers, and prairies are each just another ecosystem, in which the same rules of life apply. By dividing ourselves, we are missing those similarities.
The ways in which microbial communities assemble in a newborn baby have lessons to teach us about a scorched forest. Ocean microbes that bounce back after an oil spill can reflect the responses of mouth microbes to a vigorous bout of tooth-brushing. The cross-talk between luminous bacteria in a Hawaiian squid might tell us about the growing communities that cover human lungs, or industrial-waste pipes, or hospital catheters. If we understand the principles behind these processes—assembly, resilience, communication, and more—we could better care for premature babies who don’t start off with the right communities, or restore disrupted ecosystems like fallow prairies and antibiotic-assaulted guts, or develop ways of deliberately seeding our buildings and living spaces with beneficial microbes.
To do that, the people who study microbiomes need to unite in new ways. Again, history sets a precedent. We know that breast milk contains sugars that nourish a baby’s first microbes thanks to a collaboration between Richard Kuhn, a chemist, and Paul Gyorgy, a pediatrician. We know how the glowing bacterium Vibrio fischeri signs an exclusive contract with the adorable Hawaiian bobtail squid thanks to a partnership between Margaret McFall-Ngai, a zoologist, and Ned Ruby, a microbiologist. And Jeff Gordon, who studied the development of the mammalian gut, showed how microbes contribute to obesity after teaming up with colleagues like Rob Knight, a computer whiz, and Ruth Ley, a microbial ecologist.
These trends must continue. “We need to bring in engineers, physicists, mathematicians, and chemists to develop new methods,” says McFall-Ngai.
"What we’re trying to do is to coordinate ourselves in the same way that the physics community did several decades ago—think of lots of mini-CERNs,” says Gilbert. “We won’t just have one agency releasing a call for proposals and all of us scrambling to get a piece of the pie. We’re not going to have as many parallel reinventions of the wheel.”
The UMI would also set standards for gathering and analyzing data. “Without that, you just have a patchwork of conflicting studies with conflicting results,” says Knight. “We need a solid foundation rather than the quicksand we have at present.”
These ambitions aren’t limited to the U.S., either. In an accompanying call to arms, McFall-Ngai, along with colleagues in Germany and China, suggests that the UMI should be an IMI—an International Microbiome Initiative. “Microbes don't have borders,” she says. “These are issues that affect all continents. It’s something that we as humankind need to approach with a unified front.”
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