Paola Arlotta: Brain Development from Stem Cell to Organoid

Lex Fridman introduces Paola Arlotta as a professor of stem cell and regenerative biology at Harvard University who studies the molecular laws governing the birth, differentiation and assembly of the human cerebral cortex, exploring the brain's complexity by studying and engineering elements of its development. After the standard show sign-off, he thanks Patreon supporter Amy Jeffress, an artist.

Fridman opens with an out-of-the-box question about how likely intelligent life with a brain like ours is elsewhere in the universe and how hard the brain is to build through evolution. Arlotta notes that it has happened once, on this planet, which shows it could happen again elsewhere; it is only a matter of probability.

She says making the human brain is pretty difficult and, above all, little is known about how the process happens. Most knowledge of mammalian brain development comes from other brains, such as the mouse, whose brain looks nothing like the human brain when the two are put side by side. Studying the mouse has huge value, but there is a limit to what it can reveal about how the human brain is made.

Asked how much she knows and how often she is in awe, Arlotta says awe is constant. At the very beginning of embryogenesis, by means not fully understood, the neural tube literally self-assembles, in an embryo and also from stem cells in a dish. Stem cells within it then give rise to thousands of cell types in the brain over time. The time needed is species time: nearly nine months of gestation for humans plus about 20 years of postnatal learning, against about 20 days for a mouse embryo.

This holds in a dish too: a mouse brain organoid forms faster than one from human stem cells. Fridman concludes that the speed is controlled by the species and so is not accidental. Arlotta says it is very important for getting the brain humans have, and speculates that it reflects how long humans need after birth to learn what an adult brain requires, from infancy through puberty.

She describes the beginning in the embryo. As the embryo builds muscle, heart and blood, it also builds the brain from a simple neural tube of cells running from head to tail. Over many months of gestation in humans, the tube's stem cell-like cells produce the many building blocks, the many different cell types that will form specific brain structures, so embryonic development is the time of making the building blocks.