In 1676, when amateur scientist Antonie van Leeuwenhoek peered through a microscope of his own design and became the first person to see bacteria, it forever changed our view of the world.

Until that moment, life on earth was assumed to end with the smallest organisms visible to the naked eye (e.g., lice). But van Leeuwenhoek’s discovery of a previously unseen world teeming with microbes ultimately led to the germ theory of disease—and to advances like pasteurization and vaccination that changed the course of human history.

And now a similar revolution is taking place. A new tool allows scientists to probe even deeper into our surroundings. And it has revealed yet another layer of previously unknown organisms thriving around us.

This new category is called dark life, and nobody knew it was there.

How scientists missed it

“Dark life is those organisms that are not visible to the human eye and cannot be successfully cultured,” says biochemist Mark Miller, of the University of California San Diego (UCSD). “And until we had these very sophisticated DNA techniques available to us, we also could not detect it.”

Traditionally, the way scientists study microorganisms is to culture them. They take bacteria from the environment, streak it onto a plate, and let it grow until a single cell forming colony develops. They can then study and analyze those colonies.

“The things we know well are the ones that appear when we try to culture them in the media that we choose,” says Miller. “Microbiologists have a huge panoply of possible media, but the potential for a requirement is almost infinite. It excludes anything where the nutritional requirement is extreme.”

But now, new techniques in DNA analysis combined with advanced computing power, aka ‘the computational microscope,' mean that work can be done on a single cell. Scientists no longer need a colony or a culture—they can just use the one piece they already have.

Researchers like Laura Hug, a microbiologist at the University of Waterloo, are taking advantage of this innovation to revise and expand ‘the tree of life’, one of the most important organizing principles in biology.

Hug does this through genomic sampling of unusual places around the world, like deep sea vents and the inside of dolphin’s mouths – places where the conditions are extreme and only those organisms with unusual requirements might survive and thrive.

Her analyses so far have resulted in the identification of over 1,000 previously unknown or little-known organisms.

“It’s kind of mind-blowing,” says Miller. “There are whole metabolic pathways that I, as a classically-trained biochemist, think are essential for life that seem to be missing from these new organisms.”

Choking on data

But as scientists add more and more species to the tree of life, the time that it takes to do the necessary calculations increases exponentially. And pretty soon, researchers max out their computer resources.

“This is an interesting time because DNA sequencing is cheap: you can get all the data you want,” says Miller. “But you get so much data you choke on it.”

One answer to that problem is the CIPRES (CyberInfrastructure for Phylogenetic RESearch) science gateway. Supported by the National Science Foundation (NSF) and National Institutes of Health (NIH), CIPRES allows scientists around the world to analyze large data sets on supercomputers such as San Diego Supercomputer Center’s Comet.

“If you know what analysis you want to run, you can just click boxes,” says Miller. “You don’t have to know how to use a scheduler on a supercomputer. All that stuff is done behind the scenes by us.”

And that ease of use can dramatically speed up the pace of research and discovery.

“The idea is, you can run your data, and we’ll run the analysis for you in a very efficient way,” says Miller. “If you’re running ten jobs a week on your laptop, you can instead run all ten at CIPRES and have publication-quality results overnight.”

New frontiers

What’s really fascinating about dark life is the questions it raises about what constitutes life: What are the requirements for life? What defines life? If we change the definition of alive, then who knows what might meet the requirements.

Just as van Leeuwenhoek’s discovery of bacteria ultimately created a chain reaction of advances in science and medicine, there’s no telling what other revelations the discovery of dark life might yet lead to—on this world or others.

“We have a very chauvinistic view of what life is,” Miller says. “As scientists, we tend to get a little rigid in our thinking about what we feel comfortable with and what we understand—which is normal and natural and appropriate. But I’d be so tickled to think that there is something out there reproducing with something other than DNA.”