Geneticists in Germany have combined human stem cells with Neanderthal DNA to grow miniature brains that hopefully could reveal major differences between humans and Neanderthals.

The organoid experiment will examine the disparities of three genes that are integral in the development of human brains.

By using CRISPR gene editing technique, the scientists altered the human stem cells to make it more similar to Neanderthal genes. The miniature brains are being grown inside a laboratory in Germany.

Svante Pääbo, director of the genetics department at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, hopes that their experiment could identify precisely the biological basis as to how humans reproduced to millions of species, propagate across the world, and develop cultures as opposed to their Neanderthal relatives.

The team's success, if achieved, is going to be a first in the study of genetics.

Growing Miniature Brains

Pääbo and his team employ chemical triggers to stimulate the stem cells to develop into neurons, which grouped together on their own to form into structures similar to brains. These structures, measuring a few millimeters, are not completely developed miniature brains yet but are in the process of growing into fully formed ones. For the meantime, as the growing process continues for about nine months, they exist as separate blobs devoid of any sensory inputs. 

"You don't get a well-formed human brain at all, but you see multiple regions have kind of formed; you can study the synapses and electrical activity and early developmental differences," explains Gray Camp of the Max Planck Institute and who is at the helm of the Neanderthal organoid experiments.

The geneticists will observe how fast these genetically engineered Neanderthal organoids divide and evolved on their own to mimic three-dimensional brain structures. The team will also dissect how the brain cells are wired up differently. They will subsequently assess these results to how the same processes take place on fully developed human brains.

The team will also examine whether the Neanderthal genes common in the DNA of people with European and Asian ancestry could influence brain development. They would like to find out if they can re-grow the Neanderthal brain and afterward resurrect the functionality of those Neanderthal genes, Camp says. 

Neanderthals And Humans

Pääbo explains that Neanderthals are the closest species to humans, hence, they make the perfect basis for comparison.

As for their present study, they want to pinpoint what exactly set humans apart for them to be able to evolve while the Neanderthals went extinct. The miniature brain experiment will not delineate which of the species is smarter, but why humans evolved to be capable of planning, socializing, and using languages, he adds.

In April, a study published in Scientific Reports, co-authored by Naomichi Ogihara of the Keio University in Japan, constructed a virtual model of a Neanderthal brain. This team of scientists, who are not involved with the present experiment conducted by the German scientists, was able to identify that Neanderthals has a larger brain than the Homo sapiens.

Neanderthals, however, had smaller cerebellum which is the portion of the brain responsible for speech and learning. This difference may be the reason why there was a disparity in social and cognitive abilities between Neanderthals and the Homo sapiens.

"Although the difference could be subtle, such a subtle difference may become significant in terms of natural selection," Ogihara explained.

The team from Japan, however, did not arrive at a conclusion that the Neanderthal's small cerebellum is the major contributing factor why the species went extinct.

The Neanderthal Genome

In 2010, Pääbo and his team reconstructed code of the Neanderthal genome based on samples acquired from four females who were inhabitants of Europe some 10 thousand years ago. Based on the samples, they concluded that about a third of the Neanderthal genome survived and is to be found in the genes of some people today.

In previous experiments, Pääbo's team had also injected Neanderthal genes into mice to observe what takes place during craniofacial development.

The same team had also injected Neanderthal pain perception genes into frog's eggs to compare the amount of pain bearable to Neanderthals and humans.

Now that the team progressed into experimenting on the brain, they hoped they could ultimately define why humans appeared to have the highest cognitive skills among all species.