Nature Science Cell
How did this happen?
In animal models, it is very easy to label stem cells and trace what happens to them over time based on where they migrate and what kind of mature cells they become. Lineage-tracing studies can be accomplished by injections of chemical compounds that label a dividing cell or by genetically engineering the animal to label stem cell populations with fluorescent proteins.
The same studies that are done in animals are very difficult to perform in humans. Due to obvious ethical reasons, we cannot genetically engineer humans. In the past, a chemical compound known as Bromodeoxyuridine (BrdU) was injected into human cancer patients to study tumor cell proliferation. Given that BrdU also labels stem cells and all the resulting daughter cells, postmortem brain tissues from these cancer patients were collected and used to study human neural stem cell. This study was published in Nature Medicine during the late 1990s and provided the first-ever proof that the human adult brain can make new neurons.
However, due to safety concerns, BrdU is no longer injected into humans. Thus, we are left with very limited tools to trace the lineage stem cells and follow what happens to these stem cells over time in humans.
This is where the nuclear bombs come in.
When nuclear bombs were tested during the Cold War era, high amounts of carbon isotope 14 (14C) were released into the atmosphere. 14C reacts with oxygen to form carbon dioxide, which is taken up by plants. By eating the plants directly or consuming animals that live off the plants, humans who live around the nuclear bomb test sites ingest 14C.
As a result, when a cell divides, 14C is incorporated into a person’s genome. In the same way that archaeologists use 14C to determine the age of fossil samples, 14C concentrations here can be used to determine the age of the cell, and therefore reveal cell replacement dynamics in humans from postmortem samples.
The first study to utilize this nuclear bomb-derived 14C dating approach, which was published in Cell in 2005, showed that new neurons are not added to the human cortex after birth.
The study came from the Jonas Frisén lab of the Karolinska Institutet, whose group is still continuing to employ the approach today. Expanding their initial studies, the Frisén lab utilized the same approach to later on show that approximately 700 new neurons are added to the human hippocampus each day.
The 14C dating approach is not restricted to the brain. The Frisén lab extended their first reports in the human brain to the heart, providing evidence that the mature human heart may actually generate new muscle cells.
It is not unreasonable to expect that the 14C dating approach due to atomic bomb testing will be applied to other organ systems to investigate the dynamics of cell generation. So far, the brain and heart have been studied, but there are many other areas, from the intestines to the olfactory epithelium, that are known to regenerate cells. In an unexpected twist of fate, nuclear bomb explosions have actually uncovered a scientific pot of gold for researchers better to understand cell generation in humans.