A team of scientists from Stanford University (USA) has transplanted human neurons into the brains of newborn rats and has managed to integrate this implanted brain tissue and influence the behavior of animals. The breakthrough opens a new window to study psychiatric illness, but raises thorny bioethical questions, such as what is the moral status of these rats with human neurons.
Romanian doctor Sergiu Pasca, 40, has led the experiments. His group specializes in producing “brain organoids”: little balls a few millimeters in diameter with a few million cells, which are used to study the functioning of a real, much more complex organ in the laboratory. A human brain weighs one and a half kilos and has about 86,000 million neurons.
Human brain organoids produced in the laboratory of Sergiu Pasca. Stanford University
Pasca’s group takes cells from a person’s skin and rewinds them using a chemical cocktail to their embryonic state, a stage in which they are capable of becoming any organ in the body: liver, muscle, kidney, brain. Scientists then guide those ancient skin cells to transform into brain cells. The researchers have now gone a step further and have transplanted these balls – similar to the human cerebral cortex – to the brain of rats about three days old, genetically modified so that they lack an immune system and avoid rejection. The grafted neurons have successfully integrated: touching the animal’s whiskers activates the human cells. They are involved in the senses of rats.
Pasca doesn’t think his animals have developed anything resembling a human consciousness, given the type of cells involved and their imperfect integration. “To understand psychiatric disorders we need better models. And, the more human these models are, the more we will have to address these ethical issues”, argues the doctor, who advises against using this strategy in monkeys or apes. “We need to strike a balance between the potential benefits of avoiding some of the suffering caused by these devastating brain disorders and the risks of generating models that are too human-like,” he reasons.
His study is published this Wednesday in the journal Nature, spearhead of the best world science. The authors also include the American neuroscientist Karl Deisseroth, father of optogenetics, a revolutionary technique that allows neurons to be activated or deactivated by laser bursts, thanks to the prior introduction of light-sensitive algae genes. Researchers have used this tool on rats trained to lick a tube if they want to get water. When their human neurons are activated by light, the rodents come to lick the device, so the scientists deduce that their transplanted cerebral cortex participates in the learning processes.
Doctor Sergiu Pasca, from Stanford University, in the United States. Stanford University
Sergiu Pasca believes that the main application of his rodents will be in disease research. His team has already started with Timothy syndrome, an extremely rare disorder that causes serious neurological and cardiac problems in children. Scientists have transplanted cells from three patients into the brains of rats and have detected hitherto unknown neuronal defects. The Stanford lab is also researching two dozen other brain disorders, including autism and schizophrenia. “Now we can test new drugs in animals and study their effects on transplanted human neurons,” celebrates Pasca.
Neuroscientist Raül Andero, from the Autonomous University of Barcelona, has pioneered the study of memory in mice using optogenetics. Andero snorts at the “spectacularity” of the new job, in which he has not participated. “It’s fantastic, it opens up a new field, I’m completely blown away. It has absolutely incredible implications for researching neuropsychiatric and neurodegenerative diseases”, he opines. “I think that not even the authors have had time to think about all the applications. We are going to spend years discovering new applications of this”, applauds Andero, who urges not to cross red lines. “You have to be very careful. In neuroscience, what is almost happening in the driverless car sector, where the debates are more ethical than technological”, he warns.
The pioneering work of the Spanish biochemist Ira Espuny-Camacho, then at the Free University of Brussels, already showed a decade ago that human neurons can be integrated into the brain circuits of a mouse. The Stanford team has now gone further, showing that these foreign neurons can play a role in rodent behavior. Sergiu Pasca points out that his group transplants brain organoids into newborn rats whose human cells self-organize, making it easier for them to grow, mature and feed through blood vessels. Neuroscience now enters uncharted territory, the ever-moving frontiers of bioethics.