They’ll do this by observing the thin ring of starlight around an exoplanet while it is positioned in front of its parent star. Gases in the exoplanet’s atmosphere will absorb certain frequencies of the starlight, leaving telltale dips in the spectrum.

As Domagal-Goldman, then a researcher at the University of Washington’s Virtual Planetary Laboratory (VPL), well knew, the gold standard in biosignature gases is oxygen. Not only is oxygen produced in abundance by Earth’s flora—and thus, possibly, other planets’—but 50 years of conventional wisdom held that it could not be produced at detectable levels by geology or photochemistry alone, making it a forgery-proof signature of life. Oxygen filled the sky on Domagal-Goldman’s simulated world, however, not as a result of biological activity there, but because extreme solar radiation was stripping oxygen atoms off carbon-dioxide molecules in the air faster than they could recombine. This biosignature could be forged after all.

The search for biosignature gases around faraway exoplanets “is an inherently messy problem,” said Victoria Meadows, an Australian powerhouse who heads VPL. In the years since Domagal-Goldman’s discovery, Meadows has charged her team of 75 with identifying the major “oxygen false positives” that can arise on exoplanets, as well as ways to distinguish these false alarms from true oxygenic signs of biological activity. Meadows still thinks oxygen is the best biosignature gas. But, she said, “If I’m going to look for this, I want to make sure that when I see it, I know what I’m seeing.”

Meanwhile, Sara Seager, a dogged hunter of “twin Earths” at the Massachusetts Institute of Technology who is widely credited with inventing the spectral technique for analyzing exoplanet atmospheres, is pushing research on biosignature gases in a different direction. Seager acknowledges that oxygen is promising, but she urges the astrobiology community to be less terra-centric in its view of how alien life might operate—to think beyond Earth’s geochemistry and the particular air we breathe. “My view is that we do not want to leave a single stone unturned; we need to consider everything,” she said.

As future telescopes widen the survey of Earth-like worlds, it’s only a matter of time before a potential biosignature gas is detected in a faraway sky. It will look like the discovery of all time: evidence that we are not alone. But how will we know for sure?

Scientists must quickly hone their models and address the caveats if they are to select the best exoplanets to target with the James Webb telescope. Because of the hundreds of hours it will take to examine the spectrum for each planetary atmosphere and the many competing demands on its time, the telescope will likely only observe between one and three earthlike worlds in the habitable “Goldilocks” zones of nearby stars. In choosing from a growing list of known exoplanets, the scientists want to avoid planetary circumstances in which oxygen false positives arise. “We’re looking at maybe putting our eggs, if not all in one basket, at least in only a couple of baskets,” Meadows said, “so it’s important to try and figure out what we should be looking for there. And in particular, how we might get fooled.”