There is incredible beauty in the way a human fetus develops from a tiny embryo in the womb to a newly born baby that many people aren’t aware of. This post shines a light on some of the things that unfold within that nine-month period, especially as it relates to two key challenges faced by the developing fetus. The first challenge is how to grow in an oxygen-poor environment. The second challenge is how a crucial organ (the brain) come into being such that at the time of birth, the baby is endowed with all the neurons a human being ever needs.

Anaerobic Metabolism

A typical human fetus develops in an environment with very little oxygen. The amount of oxygen in the blood of a fetus is comparable, in fact, to that of humans breathing without supplementary oxygen on the summit of Mount Everest! The developing placenta and specialized molecules create ingenious links to deliver some oxygen from the mother’s blood to the fetus, but the levels of oxygen in the embryo are still incredibly low.

So how does the fetus continue to develop until he or she enters the world? The answer lies in stem cells in the embryonic tissues. In 1931, the physiologist Otto Warburg won the Nobel Prize for his work on tumor metabolism, a totally different area of investigation than the study of fetus development. The problem that puzzled Warburg was that solid tumors begin to grow without their own blood supply. Of course, without a blood supply, the cells of a tumor have few nutrients to derive energy from. Yet, they manage to proliferate. Warburg wanted to know how they manage to do so. What he found was that cancer cells burn fuel in a different way from that of normal cells. Most of our cells metabolize glucose using oxygen, breaking it down to carbon dioxide and water in a way that produces energy stores for the cell. However, during sprinting or powerlifting, muscles burn fuel without oxygen (i.e. anaerobically), because the blood supply is insufficient to deliver all the oxygen that is needed to burn the fuel completely during such sudden bursts of work.

Warburg noted that cancer cells also burn fuel anaerobically, but they do so even when there is plenty of oxygen available. Out of the partially burned fuel, including intermediate waste such as lactic acid, the cancer cells can make new amino acids and nucleotides and so grow more efficiently than they would if they burned the fuel all the way down to carbon dioxide and water, “Warburg metabolism” as it is now called, not only helps cancer cells grow, but it also frees them from the need for a good supply of oxygen. And what works for cancer cells also works for a fetus growing in the oxygen-poor environment of the womb.

Stem Cells and Brain Development

Stem cells also play a crucial role in a fetus’s developing brain. During the first four weeks of gestation, the human embryo has a population of thousands of neural stem cells. The neural tube is packed with them, and they are rapidly multiplying. By the end of the first trimester of pregnancy, the fetal human brain is producing 15 million cells per hour.

In the second trimester, many neural stem cells change their mode of division to a more asymmetrical mode. That is, when one neural stem cell divides, it produces one daughter cell that remains a neural stem cell like its mother, but the other daughter is different; it either turns into a neuron (nerve cell) immediately or becomes a secondary progenitor that divides a very limited number of times before producing a small cluster of neurons. As more neural stem cells switch to this mode of division, the increase of cell members becomes less exponential and more linear. By the third trimester, the neural stem cells change their mode of division again. Now, they divide to produce two daughters that are both neurons, neither of which will ever divide again. Neuron production then begins to flatten out.

Once the last of the neural stem cells have finished dividing, neural proliferation is complete. By the time a baby is born, this process comes to a complete halt, and the baby’s brain at birth would have about 100 billion neurons! And each neuron would connect with one another like a hugely tangled spider web designed to allow a stupendous amount of information to be processed and acted on. Neurons in the baby’s hypothalamus will sense hunger, while neurons in his or her retina will see patterns in the richly visual world into which they are born. Amazingly, even though the head of every newborn baby is only about one third the size of adult human brains, the baby baby already contains almost all the neurons it will ever have!

Notes:

[1] This post is adapted from excerpts of a new book, Zero to Birth: How the Human Brain is Built (2022) by William A. Harris, a neuroscientist at Cambridge University.