Many mysteries remain. For one, what role do innexins—the proteins that shuffle calcium from one cell to the next—play? To identify the calcium pathway, Coburn worked with worms that had a gene mutation that switched off innexin production. No innexins meant no calcium propagation and no death wave. But did the absence of innexins since birth introduce any side effects? “I’m not so sure whether or not having these genes during development could be a problem,” Hansen says. The ideal experiment would leave the innexins intact as the worms mature and then switch them off later in life.
Remarkably, biologists can do this. By feeding the worms a special blend of their favorite food—genetically modified bacteria—researchers can introduce a genetic “off-switch” anytime they like. The technique won Andrew Fire and Craig Mello the Nobel Prize in Physiology or Medicine in 2006.
Researchers would also like to know what starts the calcium wave. “That's the big question,” Gems says. He wonders whether it begins in the same way as rigor mortis, the stiffening of muscles after death. In rigor mortis the inhibition of ATP, the basic unit of energy within a cell, triggers a release of calcium into the muscles. That is, without ATP the cell can’t keep out the calcium ions. Hansen also speculates about what role other tissues play: “It would be cool to ask if it starts in the neurons or muscle,” which could reveal insights into human death.
Both Gems and Coburn are at a loss to explain why the death wave only propagates from front to back. Coburn suggests it might have something to do with a bundle of nerve cells sitting next to the beginning of the intestine. The researchers also think there must be some undiscovered organization in the intestine that differentiates front from back. The intestine is the worm’s only major organ and so has to simultaneously function as a liver and stomach as well. “It’s just a long tube of cells,” Hansen explains, “but there may actually be different compartments, just like our intestinal tube…, that is compelling to us.”
For the moment they have no clear answers but they remain enthralled with the phenomenon. “People are fascinated by seeing this spectral glow of death in an organism,” Gems remarks. “I think that’s important. You don’t get much wonder in C. elegans.”