How, the colleague asked, was Clarke sure the increase was due to the cholesterol and not the ethanol?
Back to the lab, where the researchers experimented with various concentrations of ethanol, with and without cholesterol. It turned out that the cholesterol wasn't what was making the difference. It was the ethanol. Booze, in today's vernacular.
"We saw that the life extension was entirely due to the ethanol," Clarke said. "That got us going. How could a typical solvent diluted 1,000-fold have this profound effect?
"Then we found that it would work at 20,000-fold dilution," or one part ethanol to 20,000 parts water, he added. "That level was basically nothing."
The worms, incidentally, apparently enjoyed the trip. Castro, who is the lead author of the study and is now in the doctoral bioengineering program at the University of California, Santa Cruz, described it this way in releasing the study:
"What is even more interesting is the fact that the worms are in a stressed developmental stage. At high magnifications under the microscope, it was amazing to see how the worms given a little ethanol looked significantly more robust than worms not given ethanol."
In nature, the worms live in the soil and dine on bacteria, mainly from the decay of vegetation. But during the first phase of their lives, there may not be enough bacteria to keep them from starving.
"They are in the soil, no one is making it nice for them, they've got to make it nice for themselves and find bacteria to survive," he said. But it turns out that if there isn't anything there to eat, they can "arrest their growth and just hang out and hope for better conditions," possibly for as long as 10 days.
However, ethanol is frequently present in the soil from the decay of organic material, suggesting that maybe the tiny amount used in Clarke's lab was just enough nourishment to kick-start their lives. Possible, but not likely, Clarke said.
The researches experimented with various amounts of ethanol, but the worms took up only a tiny amount. They didn't pig out on all that was there. Maybe they were like binge drinkers who know they've reached a point where they should stop.
The actual mechanism that extended their lives remains pretty much of a mystery, but one is left with the question: So what? Worms are worms. Will it help us?
Clarke sees a path toward an answer. But it will take years. First, the researchers need to understand exactly how it works in the worm. Then, perhaps, they can move up to a mouse, if there is reason to believe a mouse shares a similar mechanism to that found in the worm. And then, finally, maybe to humans. But that, Clarke emphasizes, is a long shot.
"One of the most dangerous things you can do is try to make extrapolations from one organism to another, especially over this evolutionary distance," he said. But he is haunted by the fact that numerous research projects have shown that a limited amount of alcohol is beneficial to the human cardiovascular system.
That's still under debate, and alcohol is a dangerous drug, so the benefits -- if they are real -- do not come without liabilities. But if the life-extending mechanism can be found, perhaps some other compound, with fewer liabilities, will also work.
"We are excited," Clarke said.