When the European Space Agency last week asked scientists to come up with ideas for instruments that can detect life on Mars, it was thinking about life-as-we-know-it. The instruments will be the payload on the agency's ExoMars mission, scheduled for 2009 launch, which will land a rover on the Red Planet. "Its first important goal will be to detect organic molecules on Mars, and to clearly establish their biological origin (or otherwise)," said ExoMars study scientist Jorge Vago.

Mars is believed to possess liquid water. Vago thinks there's a good chance that meteorites from Earth transported our native chemistry to Mars, and maybe even our native bacteria. "We know that conditions for life on early Mars were much more hospitable than they are today. Hence, there is a high probability that 'our life' made a foothold on Mars some billions of years ago. This, however, is an hypothesis which we would like to address." So the ExoMars rover's instruments will look for life that is based on water and carbon chemistry.

But some carbon-based life forms at the US National Research Council (NRC) are wondering whether limiting the hunt to organic molecules and water is enough. The Committee on the Origins and Evolution of Life (COEL), a subcommittee of the NRC's Space Studies Board, notes that lab experiments suggest life might be based on molecular structures quite different from those we already know. If life originated independently, even within our own solar system, it might not be detectable by space missions carrying instruments designed to look for Earthlike biomolecules or their products.

The committee would like to examine the prospects for what it is calling "weird life." Members want to evaluate the possibility that non-standard chemistry may support life-as-we-don't-know-it, both in the known solar system and in conceivable extrasolar environments. They would also like to help funding agencies figure out sensible ways of expanding this knowledge. The project has been approved at the NRC and is now seeking support from NASA and the National Science Foundation.

Possibilities for weird life were explored at a COEL workshop last year. "We also looked at artificial life and digital life. There are many possibilities. Some have some anchor to reality and others are mainly speculation," David Smith told The Scientist. "We agreed that we should do something, but that it was best to make a small initial foray. We plan to look at small deviations, basically retaining the same biochemistry as Earth's, but asking what would happen if the solvent wasn't water, like on Titan," said Smith, who is on the Space Studies Board staff.

Titan is one of Saturn's moons. As it happens, the Cassini mission to Saturn that was launched in 1997 will be delivering a probe into Titan's atmosphere in January 2005. The probe and the robotic laboratory it will parachute to Titan's surface are not designed to search for life. They will collect information on Titan's environment and chemistry, and scientists hope they will reveal something about what prebiotic conditions might have been like on Earth. "This might give us a hint what to look for," Smith said. "This is a place that has existed for 4.5 billion years with a solvent other than water."

On future planetary missions, the challenge will be to persuade NASA — in the face of competing demands for payload space — that weird life might exist, according to COEL member Steven Benner, chemistry professor at the University of Florida. "Then you have to make a plausible case that there is an experiment that you can do, robotically usually, that will establish in a yes/no, up/down way, with no ambiguity, whether or not that life exists there," said Benner.

What's been missing, he argues, is a sense of how creatures that are made from organic molecules might look for creatures that aren't. Benner and his colleagues, of course, have some thoughts about potential biosignatures for weird life. One telltale sign might be molecules with repeating electrical charges.

Each phosphate on the backbone of DNA carries a negative charge. Repeating charges are, Benner noted, the reason DNA can evolve. Normally, changing the structure of a molecule even a little bit can change its physical properties dramatically. That's a potential disaster for a replicating molecule, because structural change can wreck its ability to copy itself. "This repeating charge is really what allows DNA to support evolution," he said. "But the minute you change the repeating negative charges on the phosphates, all of this nice tidy rule-based molecular recognition — A pairs with T and G pairs with C — that all goes away."

Electrical charges are always the most important characteristic of a molecule, according to Benner. "That's a chemical principle. If you have a repeating charge, you can change the sequence of bases in the coding region of the DNA while changing the physical properties of the molecule hardly at all," explained.

Benner and his colleagues have synthesized malfunctioning DNA analogs that do not have repeating charges. They have also synthesized variants of natural DNA that have bases other than A, T, G, and C. "It turns out that you can change the bases at will. We've invented an alphabet with 12 letters instead of the four found our natural genetic systems, and it works perfectly fine."

So the Florida team have argued that repeating charges — which could just as well be positive as negative — are a universal signature for genetic molecules. "You might not have ribose like you have on DNA, and you might not have the same bases like you have on DNA, but you will have that repeating charge. It turns out that you can build instruments relatively inexpensively that look for repeating charges on a molecule regardless of the detailed chemical structure of the molecule that bears those charges."

For now, Benner's repeating-charge detector is strictly hypothetical. ESA's Vago noted that, although ExoMars will focus on organic molecules, he hopes the 2009 mission will include several kinds of sensors — for example, a life marker chip, a microarray that will permit direct exploration for a few thousand molecules found in life-as-we-know-it. He also points out that two venerable instruments are always useful: the microscope and the camera. "As a species, humans rely a lot on visual information to derive conclusions. Regardless of what other instruments say, I am sure in the end we will want to see what it is that produces the interesting data we are observing."