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Magnifying the MicroAmazon Searching for potential new medicines where biodiversity boils over

It’s 8:00 a.m., and the field thermometer already reads 98° F. And that temperature does not account for the steam rising around Rosa Vásquez as she crouches over the river to collect her next sample.

On this early-August morning in the Peruvian Amazon rainforest, Vásquez scrapes lichen off rocks and gathers cyanobacteria from the mud beneath the water, looking for genetic clues that explain how microorganisms can endure this environment — how they have evolved to survive in a river so hot, it boils.

“My grandmother grew up in a high-Andes town that had almost no access to western medicine, so she had to rely on traditional medicinal knowledge,” Vásquez says, recalling the roots of her current research.

Long after the family moved to Peru’s capital of Lima, where Vásquez was born and raised, her grandmother continued to share her knowledge of the plants, herbs and soils she used to make her specialty cures.

“And even in modern medicine, there are so many examples of medications that originated from plants, fungi and bacteria,” Vásquez says. “I just grew up wondering: How does nature make these powerful compounds?”

Vásquez has been exploring the Amazon rainforest in search of answers to this question since she was in high school. By then, she had already begun reading more about what scientists call natural products — compounds produced by bacteria, fungi and other organisms, often as defense mechanisms, that have bioactive properties.

“I realized, I’ve heard lots of people talking about the Amazonian plants and their medicinal properties, but nobody is talking about the microbes that are unique to the Amazon in terms of the natural products they generate,” Vásquez says.

Now, as a graduate student in the University of Michigan Program in Chemical Biology and a researcher in the lab of David Sherman, Ph.D., at the U-M Life Sciences Institute, she is studying microorganisms that make their home in the Peruvian Boiling River. She hopes to identify the physiological processes that shield these organisms from their scalding surroundings — and, ultimately, understand how the protective natural products they generate might be harnessed as potential new medicines.

“What can we learn from these extremophiles that might apply to human physiology?,” she asks.

About the River

The Peruvian Boiling River is unique among geothermal rivers. Generally, such rivers are heated from nearby volcanos. But the river that weaves through the Mayantuyacu community in the Amazon rainforest is more than 430 miles from the closest volcano.

Researchers are now trying to determine how such a large, fast-moving river reaches 99.1° Celsius (almost 210° F). While the river’s ancient name, Shanay-timpishka (translating roughly to “boiled with the heat of the sun”), hints at an early hypothesis to explain the extreme temperatures, the current leading theory is that the river’s source waters are seeping deep into the earth, where they are heated and then rapidly returned to the surface through geothermal vents.

The Boiling River lies more than 450 miles inland from Peru’s coastal capital city (and over 3,500 miles from Sherman’s lab at the University of Michigan). To reach the remote site from Ann Arbor, Vásquez and her fellow researchers first flew to Lima, then took a small propeller-plane to the city of Pucallpa, where they boarded 4x4 trucks that could handle the three-hour journey through the off-road jungle terrain to Mayantuyacu.

The Boiling River Project

Since 2011, National Geographic Explorer and Boiling River Project Director Andrés Ruzo has been leading annual field expeditions to this site — with the blessing of Maestro Juan Flores, the Asháninka sheripiari (healer) who oversees the Mayantuyacu healing center — to gather data that can both advance understanding of this unique site and contribute to its conservation and protection.

The 2019 field season was the largest to date, with six research teams representing 23 institutions across 7 countries.

“The Boiling River Project is all about gaining a holistic perspective,” Ruzo explains. “Breakthroughs occur when you attempt to learn from everyone and when you mix disciplines. We want to explore the infinite spaces between disciplines, and discover just how interconnected our world is.”

While some of the 40-plus researchers on site in 2019 sought new species of mantis insects, and others analyzed how the river’s elevated temperatures affect surrounding plant growth, Vásquez turned to the community’s tiniest inhabitants.

Her project, “MicroAmazon: The Hidden World of Amazonian Extremophiles,” (a 2019 National Geographic Early Career Grant recipient) is exploring the river’s ecosystem to learn more about microbes, including lichens and cyanobacteria, living there — some of which exist only in this small stretch of the Amazon rainforest.

“We want to uncover the mechanisms these microorganisms use to survive in such high temperatures and determine how we might be able to engineer or hack those processes in the lab,” Vásquez explains.

“Could this potentially lead to novel natural products? We want to find out — because right now, no one really even knows what we have in there.”

The 2019 Boiling River field season was the first time that National Geographic explorers from various organizations and disciplines came together to learn about the Peruvian Amazon through their different lenses.

This mission materialized on site, as researchers joined other teams’ expeditions to learn about their projects. For her part, that meant Vásquez had an opportunity to educate her fellow explorers about natural products and broaden their perspectives on the importance of studying bacteria.

Ruzo says that the success of this interdisciplinary experiment forever changed his approach to leading expeditions to the site.

“We need to see with both eyes, walk with both feet, work with both hands, listen with both ears — but work together as one body and share our discoveries of how special the Boiling River is with one unified voice,” he says.

“Diversity is an unbelievable strength, and each new perspective unveils a new level of richness in our understanding of the world.”

in the lab

Back in Sherman’s lab at the LSI, samples from the Boiling River are now propagating the only permitted collection of Peruvian Amazon microbes in the United States.

By extracting and sequencing the data from these microorganisms, the researchers can begin to mine their genomes for the genetic blueprints that encode novel enzymes. Because they can survive in near-boiling temperatures, they may offer clues for creating biocatalysts that can perform reactions under difficult conditions.

“Since no one has ever explored these organisms, we want to understand — at a high level — what exciting new information is held within their genomes and how their enzymes compare to those of other organisms that can’t exist at these temperatures,” says Sherman, who is also a professor of medicinal chemistry in the U-M College of Pharmacy and a professor of microbiology and immunology in the U-M Medical School. “And then we want to determine if they have unique abilities to make metabolites that protect them — and whether those could offer new avenues to developing antibiotics, antifungal agents or antivirals.”

Even before they returned to Michigan, Vásquez and Sherman began planning their next field season in Peru. They hope to eventually establish a “field lab” at the Boiling River, with equipment that will enable them to not only collect samples, but also isolate DNA on site and even begin some initial natural product profiling.

“In general, less than 1% bacteria are able to grow in lab conditions,” Vásquez explains.

“If we can access their genomes on-site, we have the potential to expand our view on the extraordinary chemical diversity they produce at unparalleled levels.”

Credits:

This research is funded in part by the National Geographic Society through a 2019 Early Career Grant Award to Rosa Vásquez and philanthropic support from University of Michigan alumni. Field site photos by Stephanie King, Lab photos by Leisa Thompson, Bacteria photos by Rajani Arora and Stephanie King.