Frustration was the mother of invention for Jonas Fris¿n of the Medical Nobel Institute in Stockholm, when he set out to map the ages of various body parts in living people. As a neuroscientist working toward regenerating brain tissue, he would have found it handy to know whether some or all of the human brain ever regenerates naturally and, if so, how often. "I was pretty annoyed," Fris¿n says, because the question was unanswerable for humans: the techniques used to tag cells and watch their life cycles in animals employ toxic chemicals that could not ethically be used on people.
Then Fris¿n learned of a natural tag unique to people born after 1955, when aboveground testing of nuclear weapons increased substantially. The explosions, which stopped after the 1963 Limited Test Ban Treaty, threw enormous amounts of carbon 14 isotope into the atmosphere that quickly diffused around the globe. Plants incorporated the carbon 14 into their cells, animals ate the plants, and people ate both, absorbing the isotope into their own cells and creating a trail Fris¿n could follow.
He teamed up with Bruce A. Buchholz of Lawrence Livermore National Laboratory, who had already used atomic-era carbon 14 traces to determine the age of plaques in brain tissue samples from Alzheimer's victims. Fris¿n's project was much more complex, however, because cells are chock-full of proteins that are continually being produced and degraded. To learn the true age of a cell, Fris¿n needed something that is formed at the moment of the cell's birth and remains stable throughout its life, which meant he needed to isolate and date its DNA.
By measuring the amount of carbon 14 incorporated into the DNA molecule at its creation, then correlating it with atmospheric carbon 14 levels, Fris¿n finally had a test that could give him answers. As it turns out, the team reported in the journal Cell this past summer, many parts of our bodies are much younger than the whole. Jejunum cells from the gut tissue of subjects in their mid-30s were less than 16 years old. Skeletal muscle from two subjects in their late 30s was just over 15 years old.
But the big surprises were in the brain, where Fris¿n tested cells from the cerebellum and occipital cortex. Neurons in both tissues dated to a period at or near the subjects' birth, indicating that those parts of the brain are formed at the beginning of life and do not normally turn over.
Fris¿n thinks it is too soon to know whether his finding means less hope for therapeutic approaches to regenerating damaged brain tissue. "I wouldn't say so. Perhaps a little less hope than if there was ongoing vigorous regeneration," he admits. But he is eager to do follow-up studies on brain tissue from stroke victims, for example, to see if those neurons do regenerate after injury. He also plans to study heart muscle and the insulin-producing beta cells of the pancreas, both tissues whose regenerative capacity is hotly debated and both of great therapeutic interest. Fris¿n hopes other researchers will employ the technique as well to study their favorite organs.
Bomb-era carbon 14 levels started dropping rapidly after 1965, sloping downward by 50 percent every 11 years. After 1990, according to Buchholz, the signal left in human cells is faint. Scientists can use this technique indefinitely to date stored tissue samples from the period, Fris¿n notes. And Buchholz is now employing the method for forensic work. Given the "huge segment of the population" born during the relevant era, Buchholz--a baby boomer himself--says, "the technique will certainly be very useful for the rest of my career."