Cave worms could hold the secrets to a better life
The wriggling residents of the darkest, wettest, and most toxic places on Earth may be beneficial to us all.
THE AIR INSIDE SULPHUR CAVE in Steamboat Springs, Colorado, is full of poisonous hydrogen sulfide and lethal levels of carbon dioxide. The cavern, blocked off with a three-board fence, has hosted few visitors. Old editions of the Steamboat Pilot newspaper detail the few earlier expeditions, like when 1930s spelunkers wearing gas masks could manage going inside only in four-minute spurts. Or when a 1960s speleologist with an oxygen supply thrust himself, convulsing, back toward the entrance and had to be dragged into fresh air.
David Steinmann wasn’t intimidated, though. “The most deadly gas is actually what bubbles out of soda,” he says, smiling. Steinmann, an environmental consultant and research associate in the zoology department of the Denver Museum of Nature & Science, is also a volunteer firefighter and plenty used to inhospitable spaces.
Putting on the requisite protective gear for any trip underground felt similar to donning a breathing apparatus to fight flames. It was 2007, and a Colorado group from the National Speleological Society had organized an expedition to the cave, enlisting 10 experts to study the strange space’s geology, biology, history, and water chemistry. Steinmann was there to sniff out new species. It’s kind of his deal. He’s discovered more than 100 previously unidentified organisms. And that day 14 years ago, Sulphur Cave was about to turn up another.
Steinmann recalls the other scientists letting him go first, before they crawled on stuff or otherwise disturbed anything. Kitted out, he scooted into the entrance—about the size of a hot tub and flush with the ground. It was mucky, then wet, slippery, and gross, ultimately descending 25 feet under the surface and measuring around 180 feet long. His favorite. Unpleasant places, he knew, are where novel beings make nice lives for themselves.
As Steinmann continued, he recognized colonies of microbes hanging from the ceiling, dripping mucus-like acid that could burn a hole through a shirt and give the skin what he jokingly calls “a little sunburn.” Named snottites (cavers have a sense of humor), these organisms survive toxic-to-us sulfur compounds.
When Steinmann slunk farther in, he soon saw a spring collecting into a couple of pools—each about 5 feet across and more toxic with hydrogen sulfide than volcanic vents at the bottom of the ocean. And in the pools, worms. Tens of thousands of tiny, red, wriggling tubes, clustered together in the hundreds. An inch or two long and only as wide as pencil graphite, they looked, in the aggregate, almost like sea anemones, or overly starched angel-hair pasta. “I’d never seen anything like that before in my life,” he says. “It was a very unusual environment. And I just thought, These have to be something new.”
Steinmann was right: After years of analysis, he and a team of researchers were able to announce that these blood-colored creatures, now called Limnodrilus sulphurensis, were a brand-new species, so far found only in this cave and one nearby hot spring.
But more than being simply new, the worms might be utilitarian. L. sulphurensis are part of a class of organisms called extremophiles, a term for beings that thrive in the far-flung fringes where humans generally do not. Some love salt. Others embrace frigidity. Still more bask in radioactivity, metallicity, acidity, heat, dryness, darkness. It turns out they often produce chemicals that humans can use to make our comparably tame existence even cushier.
The fruits of extremophiles’ quiet, evolutionary labor now go into everything from detergent to medicine. But exotic wrigglers in particular seem to be promising sources of antibiotics, ones that might even work against drug-resistant pathogens. Having lived with colonies of bacteria that they both need and need to fight, the critters may have developed biochemical coping mechanisms that could find their way into pills you buy at the pharmacy.
Learning how extremophiles might help modern society requires that someone discover them, investigate their potential utility, then reproduce their natural habits in an industrial setting. None of those are small tasks, or ones that can be completed in short order, which is why, 14 years after the Sulphur Cave discovery, the process of figuring out if or how L. sulphurensis might prove useful continues. The initial step in that process is often a slippery, smelly, messy one—into the places on Earth people were least meant to be. In these spots, biological innovation lurks, living as it has for eons. “There’s still a lot to be discovered,” says Steinmann, “and a lot of unknowns.”
In Sulphur Cave, Steinmann stooped to scoop up samples of the worms and unbury them from their horrible-to-us habitat. Someone else collected data on the chamber’s microbiology, its bacterial soup—the very mélange the creatures had had to develop defenses to live within. Nearby, a veteran deep-cave explorer and mapper went into a crack and reappeared empty-handed, red-faced, and barely able to breathe, covered in goo.
TODAY, CHEMICALS FROM extremophiles go into lactose-free milk, insecticides, laundry soaps, pigments, biofuels. But people have turned to them for help for thousands of years. “Halophiles are technically mentioned in the Bible,” says James Coker, director of Johns Hopkins University’s Center for Biotechnology Education, referring to salt-loving organisms. The Old Testament scribes didn’t mention halophiles by name, of course. The word germ hadn’t yet been uttered in any language. But peep the talk about salt harvesting, says Coker: Those long-ago humans knew it was mining time when the crystals turned red—a shift caused by microorganisms whose pigment protects them from the sun. Some halophiles can live happily in water 10 times more saline than the ocean; other -philes occupy similarly extra niches, like the cooling pools of nuclear reactors. “For them, of course, it’s not extreme,” says Coker. “It’s where they live. It’s like asking us, ‘How can you live in 75 degrees?’”
People who go out looking for such beasts are sometimes called bio-prospectors. They trek the globe to find organisms that live in extremis. “They dig around in the dirt, take samples of ice down in Antarctica, go into the weird lakes of Australia and Yellowstone, and just collect things, then come back to the lab and try to figure out if it’s new or not,” says Coker.
After Steinmann emerged from Sulphur Cave, he got in touch with a worm expert at the United States Geological Survey, who brought together an international team to identify and characterize the eyeless crimson noodles. Based at six universities from Boulder, Colorado, to Rostock, Germany, they were biologists, zoologists, molecular physiologists, geologists, worm specialists. Steinmann and the Colorado contingent went back to the source three more times to gather additional samples and do environmental studies.
After a 2009 expedition, Steinmann packaged up worms preserved in ethyl alcohol and sent them to Europe for DNA analysis. He also shipped a batch of live specimens in an aerated container full of cave water and algae. They took to it. “That’s easy living, in this aquarium with oxygen and food,” he says, “compared to that crazy cave.”
Nutrients, in those dark and cold spaces, are hard to come by, Steinmann explains, sitting in a Colorado food court surrounded by easy calories. In the caves pocking the mountains just west of him, most organisms skim their energy from the poop of larger animals that venture underground—pack rats, marmots, hikers—or from the occasional decaying log that falls through the entrance. That waste, though, can stick feet-thick to the floor, locked in both time and space like rock strata.
Steinmann wasn’t always attuned to the extreme life of caves. The bug for such exploration bit him in the 1990s, when a speleology convention came to Colorado, bringing with it cave biologist David Hubbard, who had dived beneath the surface throughout the state. “In a week, he found like 10 new species,” says Steinmann.
At the time, he was working as a stream biologist, collecting and analyzing invertebrates and water bugs. Running a company called Professional Wetlands Consulting, he’s done projects for the US Forest Service, golf courses, ski resorts, housing developments, and school systems, all of which need maps of wetland boundaries, environmental analysis, and inventories of species to understand the impact construction or expansion will have on the aqueous areas. Scrambling and sliding underground was simply his occasional hobby, which he’d dabbled in since high school. But like a rockfall, an idea fell on him: He could combine work and play. “I just started looking for life,” he recalls. Now, as a research associate with the Denver Museum of Nature & Science, Steinmann has revealed dozens of previously unknown organisms underground in Colorado. He’s an expert in new-thing discovery, but he leaves the deep lab investigation on the potential applications to others. He’s more of a bio-peeper than a bio-prospector.
Across the pond, researcher Christer Erséus of the University of Gothenburg in Sweden was tasked with doing genetic analysis on the L. sulphurensis worms. The team studied the creatures’ network of vessels that easily absorb scant oxygen. Their vital fluids have high oxygen binding capabilities. “I’m always joking that certain athletes would love to have worm blood,” says Steinmann. But the squigglers were thin as lace and long, making the draw tricky.
In a month, the DNA results came back. The worms were like nothing anyone had ever seen before. But even with that genetic certainty, gathering enough information to announce and characterize a new species is a trial. It took the group—all of whom were also working on other projects—nine years to establish the species’s taxonomic place and to publish papers in Zootaxa and Hydrobiologia detailing its existence, anatomical characteristics, and home: the most unpleasant spot in Steamboat Springs.
NOT LONG AFTER publication in 2016, Steinmann connected with a French researcher named Aurélie Tasiemski, who specializes in the antibiotic potential of extreme worms.
L. sulphurensis isn’t like the critters Tasiemski normally works with. A biologist and associate professor at the Center for Infection & Immunity of Lille, Institut Pasteur of Lille in northern France, she focuses on tinier ones, usually from marine environments. But this American variety captured her thoughts because of its sulfury homestead. “From my experience, worms inhabiting such extreme habitats are interesting sources of novel antibiotics,” says Tasiemski, who was the first scientist to investigate exotic worms’ antimicrobial potential, publishing her initial paper about regular leeches’ antibiotic prowess in 2004 and her first article on a weird sea worm in 2014.
Steinmann offered to send her some L. sulphurensis to study and from which to perhaps extract antimicrobial peptides—compounds made of amino acids that can take down bacteria. But doing so called for fresh, live specimens, and collecting them required planning another expedition, getting permits from Steamboat Springs, gathering a team, taking the precautions that keep one alive in Sulphur Cave, and then successfully shipping the worms to Europe. With Steinmann’s full-time job and other spelunking expeditions, along with pandemic complications, the new harvest is taking a while. But he plans to send worms across the Atlantic in 2022.
Once the wrigglers arrive, Tasiemski will know exactly what to do. She’s been studying unusual worms since early in her career, starting with leeches around 2000, then moving on to squirmers from oceanic hydrothermal vents in the 2010s. “I was very interested by the biology of not-typical organisms,” she says. “I think it’s because everyone doesn’t care about them.” She likes an underwater underdog, and she wanted to understand how worms could have adapted to live in what she calls “such crazy physical environments.”
The answer, which she discovered and first published in 2014, is that they can coexist with bacteria that help them—as our microbiome helps us—and zap the bacteria that would hinder them. They have specific immunity, able to produce peptides that target only the bad guys. She discovered such compounds (which humans also possess) in Alvinella pompejana, also called the Pompeii worm, that could work as antibiotics for particularly gnarly pathogens. After two collecting cruises in the East Pacific Rise, a tectonic plate boundary, in 2010 and 2012, it took her three months to find and purify their peptides. She patented both ideas right away.
Tasiemski and her colleagues—including former graduate student Renato Bruno—have spent years venturing into the ocean in search of additional specimens. “The problem is that for like 1,000 worms, you have to spend weeks and weeks of sampling,” says Bruno. After they acquire the animals, they have to freeze them immediately on the boat and keep them cold until they get back to the lab. (Sometimes other bio-prospectors bring back live creatures to their labs, where they foster their growth and reproduction and see in real time what compounds they produce.)
Tasiemski’s team sorts the wrigglers from the grains of sea sand, whose size isn’t dissimilar to theirs. Separated, the worms then need to be ground into a sort of paste, an action Tasiemski mimes with a motion like that of crushing herbs with a mortar and pestle.
The paste contains everything the creature has to offer, and her team wants only the antimicrobial peptides. Luckily, these have a specific, small dimension. A specialized piece of lab equipment called a high-performance liquid chromatograph analyzes each component by sifting for precise molecules. The researchers mix the sample with a liquid solvent, which the machine pumps through a solid material. The solid snatches particles of different sizes and compositions in different ways, separating them like a high-tech sieve.
Isolated pure peptides land in bacteria-laden petri dishes. After a day or two, if the compound worked, the dish shows a germy outer ring and a blank disk in the middle where the defense vanquished the bacteria.
Tasiemski’s lab analyzes the structures and the bacteria-killing properties of promising peptides. This lets them identify the molecular compositions that help them to keep their antibiotic effect in salty, acidic, hot, cold, or high-pressure conditions. “We found a correlation between the structure of the molecule and the environment in which the worm is found,” says Bruno. Certain constructions evolved to work in specific conditions—and all these adaptations could, potentially, be harnessed for human hardiness. Antimicrobial peptides seem to work particularly well against so-called ESKAPE pathogens, six supervirulent germs that are also resistant to antibiotics.
Scientists have known about the natural world’s antimicrobial peptides, and their applications for human immunity, since the early 1980s, and have since discovered more than 3,000 of them. Only a couple of dozen of those compounds, though, have come from worms.
The biochemical adaptations of wrigglers hold promise in part because they live in places where they never come into contact with bacteria that hurt humans. Their properties are novel, then, to the germs that make us sick. “The bacteria doesn’t know how to escape,” Tasiemski says. Plus, worms’ peptides, usually produced by their skin, can stand up to the extreme temperatures of the outside environment, meaning they don’t need ultrarefrigeration like many such medicinal ingredients. “You can keep them on the table,” she says. It also means that future antibiotics won’t be harmed by the temperature of a fevered human body, as some drugs are.
Once her lab has isolated and characterized the peptides, Tasiemski doesn’t have to grow worms to get more of their chemicals. They can be synthesized.
Today, Tasiemski is testing her patented peptides on mice, which will take about two years. If they do well in the rodent world, the trials will eventually move on to humans. That direct-patient work will fall to someone else, and will, if it succeeds, require partnerships with pharmaceutical makers, for both testing and large-scale production. “For the moment, we don’t need to be associated with a big company,” she says. “But we’re going to need to.”
Tasiemski is hopeful that investigation into the sulfur-loving Steamboat Springs worm will prove similarly fruitful. But she loves the thrill of discovery more than finding applications. “Wow, I’m the first to see these,” she recalls thinking of her own finds, like novel hydrothermal vents in the Pacific Ocean. It was strange, bobbing in the water, to think that no human had ever laid eyeballs on these spots before. And it was strange to think that in understanding organisms’ survival there, she could help us with our own.
TO DATE, the FDA has approved just seven of the more than 3,000 known antimicrobial peptides for use in pharmaceuticals, like the over-the-counter ointment Neosporin. All came either from nonextreme bacteria or derivatives of other such peptides and spent around 15 years or more in development between discovery and approval. Though scientists have studied others, those inquiries stalled out before clinical trials. Sometimes the peptides weren’t as effective in the lab as they had seemed in their natural environment. Sometimes they had effects likely to be toxic on human biochemistry. Sometimes they were unstable.
Getting to the clinical stage at all represents its own hurdle: Researchers like Tasiemski need to pass the task to researchers with connections to, if not Big Pharma, at least small pharma. Explorers like Steinmann, academics like Tasiemski, and the industrialists who could bring their work to a wider audience occupy different niches. It takes a long time, when it happens at all. But on the scale of the evolution of extremophile animals, it is, one supposes, the blink of an annelid eye.
But the extremophiles-for-capitalism movement will coalesce, Johns Hopkins’ Coker maintains. “This is going to happen,” he says. There is too much potential lurking in vents and caves, and too much money to be made, for nature’s secrets to remain shrouded. And Coker is thinking even further afield, about how things could turn out when humans go to Mars and look for life in a place that has Earth’s extremes of cold dryness.
Steinmann, though, remains firmly grounded on—and also deep inside—this planet, and he hopes to find even more beings who’ve carved out ecological caverns for themselves. “Much is unknown right here in our own backyard in America,” he says, gazing across the food court. “I found new species in my woodpile.”
Spotting those surprises just requires getting dirty, and looking more closely, to see that the world isn’t as nailed-down as it seems, that there is potential bubbling in puddles and cracks: Life, living in its own ideal conditions, whose hardships may help us. “We can steal all their secrets,” says Steinmann.