In the coming decades, new rovers will roam the sands of Mars. An orbiter will sample the seas of Jupiter's moon Europa. A drone will grace the skies of Saturn's moon Titan. Mission planners dream of equipping these mechanical scouts with instruments capable of scouring the unknown environments for signs of life, but the technology required to do so is deceptively complex.
Explorers seeking alien life must first grapple with questions of fundamental biology. What does it mean to be alive? What traits must all organisms share — even those that might inhabit methane lakes or ice-locked oceans? The burgeoning field of astrobiology seeks answers in the form of "biosignatures"— surefire signs of life that a simple experiment could identify, such as DNA or proteins.
DNA is like a toolkit that stores and transmits vital information passed from a living organism to its offspring. The molecule's ingredients, called nucleotides, are four components coiled in a double helix called adenine, cytosine, guanine and thymine.
But as researchers debate which molecules to look for, recent work suggests casting a broader net. In 2019, for instance, a team of synthetic biologists showed that the four-molecule genetic code that describes all known life on Earth isn't the only group of molecules that could support evolution.
"You set these grand challenges to make a new Darwinian system," says Steven Benner, founder of the Foundation for Applied Molecular Evolution at the University of Florida and leader of the group. "That drags scientists kicking and screaming across uncharted terrain."
The recent research, which was published in the journal Science, covered new ground regarding genetic information storage. Netflix represents digital movies as long strings of 0's and 1's, and all known Earth organisms follow a similar strategy. They store instructions for producing copies of themselves in their DNA — another long string, but one assembled from four molecules rather than two numbers. This system enables evolution by being reliable enough to safeguard those instructions between generations while maintaining the flexibility for occasional revisions.
But does the alphabet of life have to contain four letters? Some have argued yes — four elements strike the perfect balance between fitting in more information and a lower risk of typos. Up to 12 letters are possible on paper, though, and Benner has spent three decades (during two of which he received NASA funding totaling nearly $5 million) realizing some of them in the lab. In the new research, his group announced the construction of an eight-molecule system capable of storing, copying and editing information. They dubbed it hachimoji DNA, meaning "eight letters" in Japanese.
The minor molecular tweak has major consequences for biotechnology. When it comes to manipulating biomolecules and microbes, modern techniques rely on a suite of tools that work only with the traditional four elements of DNA. For even the simplest tasks with hachimoji molecules, Benner's group had to reinvent new biological equivalents of the wheel. "Everything that you take for granted in modern biotechnology, you have to do yourself," he says. "You're basically back to doing 1960s molecular biology."
And hachimoji molecules represent just minor riffs on standard DNA, with a few oxygen and nitrogen atoms shuffled around here and there. Biologists would really struggle to get a handle on a truly alien system. Letting his imagination run wild, Benner speculates about exotic DNA molecules forming a flat sheet, as opposed to a linear strand. Good luck trying to fit that square peg into a round detector.
In a recent proposal currently under review for funding by NASA, Benner's team advocates for taking a more universal approach. They hope to build a device that searches for molecules with traits that are theoretically essential for any genetic molecule: traits determined by decades of experimentation with alternatives like hachimoji.
First, the molecule should be long. Short molecules can't hold enough information to do anything useful. Second, the molecule should be complex enough that it isn't mirror symmetric, for similar reasons. Third, its frame should feature repeating charges, either positive or negative. DNA keeps its stiff double helix shape because it has negatively charged edges that repel each other. Otherwise it could fold and get tangled. Alien DNA, the thinking goes, should fit this general archetype.
The group has designed a lunchbox-size "universal life detection" instrument that would take in water from Europa's global ocean or Martian ice, attract long positively charged molecules to one plate and negatively charged ones to another, and use beams of light to gauge the complexity of the molecules.
This test should detect any life in the area, microbial or otherwise, as long as it has some sort of biological genetic code akin to DNA. "If you ran seawater through it, you could find DNA from shrimp," says Nathan Bramall, CEO of Leiden Measurement Technology, the company that would build the prototype, "but not [computerized life like Apple's assistant] Siri."
And the lunchbox is just one of the life-detection projects aiming to catch a ride to another world. In 2018 NASA awarded Pennsylvania-based nanotechnology start-up Goeppert a $125,000 grant to develop a device that can analyze the size and shape of potential biomolecules as they pass through a nanometer-size pore. This type of "nanopore" experiment could complement Benner's universal life-detection machine, according to Kathryn Bywaters, a SETI scientist working at NASA Ames. "I don't think any one life-detection instrument will be the end all be all," she says. "It's going to be a suite of instruments looking for multiple different smoking guns."
Development of any single device may stall, but these two projects represent small bets in NASA's growing astrobiology portfolio, as the agency prepares for more ambitious missions to Mars and distant moons. And both Bywaters and Bramall feel optimistic about their devices, expecting that they'll be ready to fly before the end of the decade.
Other researchers involved in the astrobiology community, however, wonder if even these out-of-the-box approaches don't go far enough. Buried in Benner's criteria for a genetic molecule lies an implicit definition of life: a structure that evolves. But Carol Cleland, a philosopher and the director of the Center for the Study of Origins at the University of Colorado Boulder, worries that any search based on checking rigid boxes is doomed to have blind spots. Must all life be Darwinian life?
She praises Benner's work targeting long, charged molecules as a great starting point but urges an even more open-minded approach that focuses on more general anomalies — phenomena that resist simple physical or biological characterization. She points to the conflicting Viking experiments on Mars in the 1970s, when a lander found some support for metabolizing microbes but no evidence for organic molecules, as a prime example. Most researchers deemed the result negative because it failed to fit the prevailing definition of life, but Cleland suggests that such perplexing edge cases may be the most fruitful directions for discovering totally new biology.
Asking whether we are alone in the solar system may be simple, but teasing out the answer will take time and effort, she suggests, no matter what instruments NASA ends up sending to far-off worlds. "I don't think you're going to discover truly alien life in one mission," she says. "You're going to discover stuff that is provocative."