Contemporary research in neuroscience is constantly adding to and refining our knowledge of how the brain works. One of the tenets of that knowledge during most of the 20th century—that our brains are supplied from birth with a finite number of neurons that only dwindles with age and disease—was finally refuted in the 1990s, thanks to the paradigm-shifting work of Fred Gage and colleagues. However, quantifying how many neurons were born throughout life in the different regions of the human brain remained impossible. That is, until Jonas Frisen, of the Karolinska Institute in Stockholm, Sweden, and his colleagues had a wildly brilliant idea: using the spike in the concentration of radioactive carbon in the Earth’s atmosphere as a result of above-ground nuclear testing between 1945 and 1963. In an essay recently published in PLOS Biology, Frisen and colleague Aurelie Ernst recently reviewed what this highly original approach has taught us.
Dating the birth of neurons in the human brain
As a consequence of nuclear explosions in the mid-20th century, the atmospheric concentration of the radioactive isotope of carbon C-14 increased massively, before decreasing rapidly following the ban of most above-ground nuclear testing in 1963. Proliferating cells (including neuronal precursors) integrate carbon atoms into their DNA, and as this carbon ultimately comes from our environment, the amount of C-14 incorporated into a new neuron depends on the atmospheric concentration of C-14 at the time of its birth. The rapid changes in that concentration caused by nuclear testing thus provide a time scale of sorts that allows dating quite precisely the birth of a new neuron (the principle has been beautifully illustrated in a Perspective published by Science).
In their well worth reading essay, Ernst and Frisen focus for the most part on what this new technique, along with others, has added to our understanding of how the human brain renews some of its neuronal populations throughout life. They highlight in particular the commonalities and the differences in the dynamics of neuronal renewal between humans and other mammals.
An interview with Jonas Frisen
Dr. Frisen kindly agreed to answer a few questions, starting with how that brilliant idea came to him.
How did the idea come to you that above-ground nuclear testing during the Cold War would create an “atomic clock” of sorts that would allow dating the birth of cells in the human brain?
The idea came out of frustration of not being able to study cell turnover in humans. In archeology they retrospectively birth date specimen by carbon dating. This builds on the radioactive decay of C-14. I started reading up about this, thinking that maybe we could carbon date cells in the same way. This proved to be a very naive thought, as the radioactive half-life of C-14 is almost 6000 years, which provides a miserable resolution for the life span of cells.
When I read a little more about C-14 I came across the huge increase created by the nuclear bomb tests, followed by a steep drop as C-14 diffused from the atmosphere. When I saw that, I knew that we had to try the strategy.
So, it is a pure coincidence that we use the same isotope, C-14, for birth dating cells as they use in archeology. Whereas in archeology they take advantage of the radioactive decay, we take advantage of the varying concentrations created by the Cold War.
The Cold War has created a “time window of opportunity” for the retrospective birth dating of neurons. How long is this window and when will it close? Could other events (e.g. the nuclear catastrophe in Chernobyl, or natural accidents such as volcanic eruptions) give rise to similar opportunities?
The window is closing gradually, and it is not possible to say with any precision when it will be closed. However, tissue collected in biobanks now or earlier will be available for analysis for a long time to come. I am afraid that we are not aware of any other source of a similar pulse-chase like the situation of a marker that integrates in DNA.
Birth dating of neurons is currently only possible retrospectively, i.e. after death. Do you foresee any technical developments that would allow measuring neuronal birth in vivo?
That would be extremely valuable. I do not see how to do it today, but I wouldn’t be surprised if it comes.
Adult neurogenesis in humans is now a given. Will we one day be able to influence this process for therapeutic purposes, or even to “improve” the functions of the healthy brain?
I am optimistic that there will be therapeutic strategies in the future that lead to some replacement of neurons lost in disease.