Researchers are growing human, ape and monkey brain tissue in the lab in order to understand what makes us different. Human brains are clearly unique in some way, given that we’re the only animal that can make and post memes online and fly into space. But questions still surround why we’re different from our close relatives, the other great apes, and it’s difficult to access the brain tissue needed to study these differences. One team of scientists hopes to explore the subject in a way that only humans can: with the help of genetic sequencing and organoids, miniature organs grown from stem cells in petri dishes.
“By studying the development of not just our own species but our closest living relatives, you can start to understand the mechanisms that lead to how our cells and tissues are different,” J. Grey Camp, one of the study’s corresponding authors and a group leader at the Institute of Molecular and Clinical Ophthalmology in Basel, Switzerland, told Gizmodo. “Now we have the tools to do that: induced pluripotent stem cells, CRISPR, organoids, and single cell genomics.”
Stem cells are a kind of base cell that can turn into other kinds of more specialised cells, while induced pluripotent stem cells, iPSCs, are stem cells that scientists have created from other cells. Here, researchers led by Sabina Kanton, Michael James Boyle, and Zhisong He at the Max Planck Institute for Evolutionary Anthropology created iPSCs from white blood cells taken from zoo animal and human blood samples. Then, using various ingredients, they can coax these cells to progress through the stages of early brain development, similar to what developing embryos undergo, until they begin specialising and become three-dimensional lumps of brain tissue.
The researchers observed for four months as the human, macaque, and chimpanzee brain organoids grew and the cells began to take on rolls. They took samples to profile the RNA in the individual cells — essentially, which parts of the DNA the cell is actually using to make proteins, and how that differs between cells. Using this data, they created an “atlas” of the human-specific genes and the genetic mechanisms that altered the cells’ appearances during development. The researchers also compared their organoids to tissue taken from dead humans, chimps, a bonobo and a macaque, recording which specific changes occur in both adult and developing brains and which occur only in adults.
This study didn’t dive into specific differences in how the genes affected the larger-scale structure of the organoid itself, Camp explained. However, they observed that the human organoids seemed less developed during the same amount of time than the chimp and macaque brains did, perhaps evidence of slower maturation times seen in past studies, according to the paper published today in Nature.
One researcher not involved in the study, Alex Pollen, assistant professor at the University of California, San Francisco, told Gizmodo that this study was an important step forward in the field for the way it recapitulated the differences between monkey, ape, and human brain development. He was especially excited with the way the researchers saw differences in the brains that carried all the way through to differences in real brain tissue. However, he said it will take “real work” before this experimental model can truly model mature brain cells.
Another researcher not involved in the study, Gül Dölen, assistant professor of neuroscience at Johns Hopkins University, cautioned that there are complexities to brain development that organoids can’t capture and that lots of brain development occurs long after we’re born. Plus, she said, there’s more than just genetics to the story; it’s also about the wiring between brain cells.
And yes, I asked Camp if he ever thought about the fact that he was working with mini brains and whether the brains liked to be experimented on. He said that these organoids lack much of the machinery that real brains have and have minimal electrical activity.
Still, the researchers behind the new paper hope that they’ve produced a resource that others can use to further explain what makes us human. Perhaps scientists can perform similar efforts using organoids to understand other differences, like in our respiratory or digestive systems. Camp said he’s just happy to see the experiment come to fruition: “It’s amazing that this is even possible.”