In an unprecedented experiment, Stanford scientists achieved a feat of biology that simultaneously dazzles us with its novelty and triggers a sense of ethical unease. They implanted human brain cells into a rat, blurring the line between species, sparking a flurry of questions on the potential implications of such an act.
"If you want to study complex brain processes and how they go wrong and how they affect Behavior, you can't model those with an in vitro organoid you gotta grow them in Vivo attached to a living organism"
The object of this unique experiment was to determine if the human neurons could merge with the rat's brain enough to control its behavior and respond when they tickled its whiskers. The rationale for such a venture, while challenging our preconceived notions of biology, is grounded in a profound aspiration: a better understanding of brain disorders.
Human Cerebral Organoids: A New Hope in Understanding Brain Disorders
Human cerebral organoids or mini-brains, grown in labs, usually from reprogrammed skin cells, are a crucial tool to study brain disorders. These organoids self-organize into biological neural networks with electrical communication, similar to a developing brain. The challenge, however, lies in their growth. Outside of a living organism, these organoids can only grow up to a few millimeters wide due to the lack of blood supply and chemical signals they would receive in a real brain.
Enter the rat's brain. By transplanting these organoids into rats, scientists managed to create a more realistic model, with the organoids growing up to nine times their original size in three months. The rat's brain provided not only the needed blood supply but also allowed for a unique interaction between human and rat cells.
Genetic Expression and The Curious Case of the OSTN Gene
Transplanting the organoids led to changes in their gene expression. One particular gene that drew scientists' attention was the ostn gene, which is unique to primate brains. Intriguingly, the organoids expressed more of this gene, even though they were grown in a rat's brain.
"In primates, ostn was repurposed to regulate the growth of dendrites in their increasingly complex brains"
The expression patterns of both the in vivo and in vitro organoids were found to be similar to a human fetus of about the same age. However, it is important to note that this does not equate to the organoids having the mind of a fetus.
The Promise of In Vivo Organoids and the Whisker Tickle Test
By developing an organoid model of a rare and deadly genetic disorder called Timothy syndrome, the researchers found unusual patterns of dendrite branching that could only be detected in transplanted organoids. But how integrated were these human cells within the rat's brain?
"If you tickle this whisker, you'll get a response there on S1 so if you want to activate an organoid on top of S1, the scientific approach is whisker tickles"
As it turns out, the organoid showed electrical response not only when the rat's S1 region (responsible for sensory input) was stimulated but also when the rat's whiskers were tickled.
Human Cells Integration: A Deep Dive into the Rat's Brain
The extent of this integration didn't stop there. The human cells from the organoid had managed to permeate deeply into the rat's brain, reaching as far as the thalamus. The rat neurons made their way into the organoid, and conversely, the human neurons traveled far within the rat's brain.
"They found human cells marked with rabies in the rats S1 and in the thalamus. So the human cells were deeply integrated into the rat's brain."
With the use of a lentivirus, human neural projections were found throughout the rat's brain - the motor cortex, auditory prefrontal, and hippocampus. This level of integration went even further, as the organoid could be triggered to send signals to the rat's brain using optogenetics. A blue light would trigger an electrical response not only in the organoid but also in the rat cortex.
Can the Organoid Control the Rat? The Reality of 'Rat Mind Control'
But could this electrical communication lead to the human mini brain controlling the rat's behavior? The researchers trained the rats to associate the activation of the organoid (indicated by a blue light) with getting water as a reward. After a couple of weeks, the rats responded significantly more when their organoid was activated.
"So the researchers activated rat neurons to drive reward-seeking behaviors, which you can think of as rat mind control."
The researchers, however, didn't notice significant differences in the transplanted rats' memory, motor activity, or fear learning as compared to normal rats. While one might hastily equate this to 'rat mind control', it's important to understand that this experiment aligns more with classical conditioning (like Pavlov's dog) but with an added layer of genetic modification.
The Ethical Dilemma: Where Do We Draw the Line?
While the potential benefits of this research are huge, especially in treating neurodevelopmental disorders, the ethical implications cannot be overlooked.
"How do you weigh that against the possibility of creating a self-aware rat or a conscious organoid?"
As we forge ahead with advances in brain research, we are also tasked with difficult questions. How do we balance the need for scientific advancement with the moral obligation to respect the integrity of all sentient beings? And, what measures do we have to ensure that such research does not pave the way for unregulated and ethically dubious experiments in the future?
The experiment at Stanford marks a significant milestone in our understanding of brain disorders, but it also opens up a pandora's box of ethical queries that we must address responsibly. As we continue to marvel at our scientific progress, we must also maintain a vigilant watch over the ethical boundaries we tread. Our curiosity should drive us to explore, but our wisdom should dictate the path we choose.
This experiment isn't just a step towards understanding brain disorders better; it's a leap into the unknown, challenging us to redefine the limits of science while ensuring we don't lose sight of our ethical compass.