Successors to the departed Cassini spacecraft, visualized above, could one day carry DNA sequencers through Enceladus’s plume.


Want to discover truly alien life? Pack a genome sequencer

THE WOODLANDS, TEXAS—What if aliens aren’t like us? For a long time, that’s been a confounding problem in the search for life beyond Earth: If alien life looks nothing like it does on our planet, if it abjures DNA and RNA for building blocks utterly strange, how could robotic explorers even know that they’ve discovered it?

With scientists eyeing the potentially habitable waters of Jupiter’s moon Europa and Saturn’s moon Enceladus, this question has only grown more pressing. It’s fine to think any life on Mars could have shared ancestry with Earth—the planets are close and have shared a lot of grist over billions of years—but DNA-based life at Saturn? That would be a stretch.

Still, the hunt for nonterran life could be accomplished with a tool familiar in any biology lab, scientists suggested here yesterday at the Lunar and Planetary Science Conference and in a paper in press at Astrobiology. If you want to have the broadest possible search for life, both terran and nonterran, they say, pack a genome sequencer. “You could have a completely different biochemistry,” says Sarah Stewart Johnson, an astrobiologist at Georgetown University in Washington, D.C., who led the work. “But you could still see a signal.”

The technique as proposed would work because nucleic acids like DNA are promiscuous. Take a strand 30 to 80 nucleotides long and it will naturally form secondary and tertiary structures that will bind with a host of materials and shapes: biologicals like peptides and proteins, sure, but also to organic molecules, minerals, and even metals.

Johnson’s team borrowed a technique from cancer biology, called the systematic evolution of ligands by exponential enrichment (SELEX), which creates a huge library of random, short chains of nucleotides, called aptamers, and then incubates them with a target of choice, such a specific breast cancer cell. SELEX is typically repeated multiple times, with scientists filtering out the aptamers that are not specific to their target.

“The idea here would be to flip that around,” Johnson says. Their sensor would expose samples to all those random aptamers, garnering information from each hit. “Analyze the whole binding pattern, anything that binds,” she says. These patterns could then be amplified and sequenced, revealing a pattern of chemical complexity that Johnson calls a fingerprint.

Such a fingerprint would not be as clear as catching DNA in a sequencer. But if a sample is exposed to such an aptamer library, a complex molecule is going to bind with a lot more sequences than a simple one. And complexity, especially if captured in a very small sample, is likely a hallmark of life. "It might not be as definitive as your DNA sequencer, but it could be, if not a biosignature, a really strong bioprint,”Johnson says.

This is not the only approach to agnostic life detection, as the nascent field is called, most of which require trading definitiveness for inclusivity. Johnson has worked with other scientists who have shown how a mass spectrometer, a tool common on NASA robotic missions right now, could be twinned with algorithms designed to evaluate a molecule’s complexity, not just its weight. Other techniques could gauge signs of mobility or energy use to flag nonterran life, Johnson adds, though those are not as technologically ready.

In recent years, genome sequencers have dramatically shrunk in size; Oxford Nanopore’s MinION, for example, weighs only 85 grams and fits in your hand. Although no NASA mission currently has plans to take a sequencer into space, the agency is supporting several efforts to get the technology ready for exploration.

Johnson’s proposal seems innovative and could complement other efforts at life detection, says Christopher Carr, an astrobiologist at the Massachusetts Institute of Technology in Cambridge who is not involved in the work. Carr is leading one of the NASA sequencing efforts, and Johnson’s technique could increase such a tool’s usefulness. “It will have a high likelihood to produce data for any given sample, whether or not it contains life,” he says. But the approach also carries the risk of providing confusing data, especially from unknown materials. Careful preparation and instruments that provide context for the sample could help overcome such hurdles, he adds.

Johnson, for one, is eager to get going with the hunt for life. She wants sequencers everywhere—not just on the outer planets, but also for samples of the Mars subsurface or Saturn’s moon Titan, dipped in frozen methane. “I want to go to Titan where everything is crazy and different,” she says. “I just want to go. I want to go everywhere.”