He identified DNA from Egyptian mummies. He opened Denisovskoe people, an extinct species of ancient man, sekvenirovanie DNA from the tiny bone fragment. He led a large study on the recovery of the genome of Neanderthal man and found traces of their genes are still hiding in some of us today. Now, Swedish geneticist Dr. Svante Paabo wants to turn the paleontology upside down — this time he plans to grow stem cells Neanderthals in a tiny organelles of the brain in vitro.
In his plans there is no full recovery of the Neanderthal brain in a VAT — rather, he wants to use gene editing to give the human stem cells of multiple gene variants, found in Neanderthals. These edited stem cells are then placed in a small cell of the brain, simulating brain development in the fetus, complete with their own blood vessels, neural networks and functioning synapses.
Comparing the growth neandertalian mini-brain with a human brain, Paabo hopes to isolate the genetic factors that make us so special.
“Neanderthals were intelligent as other mammals. They did not go into the ocean, if you have not seen the other shore,” says Paabo. “But for me, the biggest question in the history of mankind is: why do we become so desperate?”.
Paleontologists have long wondered how evolution made our amazing brains. Comparing our genetics with the genetics of our closest relatives-apes, geneticists have painstakingly identified a handful of different critical genes. For example, small mutations in the FOXP2, appears to underlie our ability to form phonemes and words. Some even believe that the FOXP2 is a key biological advantage, which gives us our rich, rich language.
Unfortunately, the comparison of the genomes can only identify genes that differ between humans and apes — but how those genes have shaped our brain development, this question remains unanswered.
“Before, we were just limited to viewing the data in the sequencing and cataloging of differences among other primates,” laments neurogenetic Simon Fisher, the governing Institute for psycholinguistics max Planck in Nijmegen, the Netherlands. “We are slightly disappointed, working for many years with traditional tools.”
Now, thanks to the amazing technology of DNA, everything must change.
About thirty years ago, Paabo began seriously to consider a radical idea: is it possible to extract DNA from dead tissue? Although DNA is relatively stable compared to other biomolecule, such as protein, it begins to disintegrate quickly after death. The famous double helix, thoroughly winded by nature in a compact structure, with time split into shorter fragments. To assemble these pieces back into a single structure is extremely challenging, but in 1985, using the remains of a 2400-year old mummy, Paabo has convincingly shown that it can be done.
This discovery opened wide the doors of paleontology. Scientists have ceased to be bound by traditional DNA of modern, living species; they have a powerful tool that allows you to go back in time and study the DNA that was lost in history.
Blinded by this initial success, Paabo appealed to the Neanderthals, the mysterious branches of a people extinct for over 30,000 years ago. In 2016, he published the first complete genome of a Neanderthal, shocking scientists and the public an intriguing result: 1 to 6 percent of the genes of Neanderthals were present in people from Europe, the Middle East and the Far East. In other words, at some point in ancient history, our ancestors danced the horizontal tango with their Neanderthal cousins, and we are the direct heritage of these dances.
“Neanderthals left imprint in the DNA of people alive. It’s very cool. Neanderthals are not extinct,” said Svante Paabo at the time.
His discovery led to the broader question: to what extent Neanderthals we related? As modern humans, these hominids with a wide jaw and prominent brow arch lived in caves and painted on walls, created hats and decorated their bodies with flowers long before the foot of modern humans have set foot on Europe. However, they died out, and people reached a billion in number and scattered around the globe.
Comparing our genomes, the Paabo group has identified several regions containing variations of DNA changes, which could help people to adapt. Among them, the genomic region that play a role in cognitive development.
Although our wildly different fates may not be entirely related to differences in cognition, Paabo believes that this place would be a good start. And thanks to the organelles of the brain now he can test his ideas.
The organelles of the brain called the cerebral spheres, mini-brain, cerebral organelles. First coined in 2013, these fancy balls or drops of the brain look very creepy. But as their growth reflects the development of human embryonic brain, these beads quickly became a favorite toy of neuroscientists.
Recipes brain organelles are very different, but usually they are made from human stem cells. Under close supervision cells slowly develop in deformed chunks of brain tissue with chemical soup. Like the real human brain, the majority of drops contain a structure similar to the cerebral cortex, the wrinkled outer layer of the brain, which organizes cognitive functions of the highest level, such as attention, language and thought.
After sufficient time, the neurons inside the brain grow bulbs electrical activity and are connected to neural networks, some connections stretch across organoid. These brain drops are not “mini-brains” in the sense that it can think or feel, no. But a careful analysis of their cellular composition and gene expression showed a set of functional neural types in the aggregate which resembles the fetal brain in the second trimester.
In other words, the brain balls are the ideal candidates for the study of brain development. Since its inception, they were used to simulate autism, schizophrenia and the effect of the Zeke virus in the brain of the fetus.
And now, thanks to Paabo, they will find application in paleontology.
The revival of the Neanderthal
To recover the entire Neanderthal genome, scientists would have to change a million genes. This ambitious target is currently not possible even with the use of sophisticated tools for genome editing such as CRISPR.
Is a rough edit of all the Neanderthal variants in human stem cells, Paabo uses a more subtle approach: introduces just three key genes that differ between humans and Neanderthals, and then monitors the impact of these genes on brain development.
This is a proven method.
A few years ago, working with the Wieland Hatteras, a neuroscientist of the Institute of molecular cell biology and genetics max Planck, the team has grown a brain organelles, using leukocytes of man and other primates. Drops brain has evolved a few weeks, allowing scientists to compare and contrast how different the growth of cells in different species. Using live microscopy, the scientists discovered that human cells be a half times longer than monkeys to line up their chromosomes, before separation of daughter cells. And this elongation somehow AIDS people to generate a lot more neural stem cells than our closest relatives among primates.
Paabo hopes to find more similar striking differences from Neanderthal mini-brains, because they could explain why modern humans are defeated as a species.
“The best result would be that genetic changes lead to longer or more branched growth in neurons,” he says. “You could say that it’s a biological basis for why our brain is functioning differently.”
In the end, this is only the beginning of the study of human uniqueness, which became possible only now.