A New Horrific State of Consciousness

The end is nigh! Scientists are growing brains in jars confined to a horrific existence: fully aware, but unable to move, to breathe, to experience, stripped of their ability to even cry out in despair. 

Well, not exactly. This experiment, which went viral on the internet for conjuring a very I Have No Mouth and I Must Scream flavor of terror, isn't as terrifying as you might glean from the tweet about it above. These little brains aren't conscious, have rudimentary structure, and are only the size of peas. Even so, growing brains and eyes from scratch gives us valuable information about how these organs develop in embryos, and how changes to that development leads to disease.

These tiny blobs are called brain organoids, and are made by manipulating and growing stem cells. A stem cell, broadly speaking, is an undifferentiated cell, meaning it has the potential to turn into any other type of cell, being it bone, brain, or blood. When you were an embryo (in case you can't remember), you were made up of only stem cells, which divided and changed into all the different organs in your body. Scientists can use cultured stem cells in the same way, adding specific proteins that changes them into miniature livers, hearts, or, in this case, brains with light-sensitive eyes. They're basically blobs of brain tissue, incapable of thoughts or emotions, which makes them useful when employing real brains would be expensive, or at the least very ethically dubious.

The brain organoids grew symmetrical eye-like structures, which are those black blobs stuck to their bodies.

Like other organoids, growing miniature eyes in the lab has been done before, but not like this. Using stem cells, other researchers managed to create optic cups, the structures which go on to form almost the entire globe of the eye. However, in this experiment, researchers wanted to grow eye structures together with brain tissue to see how the two interacted as they developed together.

The results of the experiment are not unlike something out of science fiction. After adding retinol acetate, or vitamin A, to neural stem cells, eye cups developed within 30 days, and the visible, symmetrical eye structures we can see came in at about 50 days, mirroring the timeline of eye development in embryos. And, though they look like just black blobs, the rudimentary eyes contained different retinal cell types as well as lens and corneal tissue. They also formed connections to the rest of the neural tissue, and were sensitive to light, producing electrical impulses when exposed to it.

How a brain organoid develops eyes.

Being able to grow tiny brains with eyes isn't just cool and a bit frightening, though. Watching eyes as they develop can help us figure out what causes blindness at birth, or to analyze how different growth conditions might impact eye development and cause disease. They could even be cultured from a specific person's cells to create personalized transplants. Though these brain organoids can't think for themselves, they are giving us a lot to think about as far as the future of healing our eyes.

Mitochondria: Powerhouse of the Eyes?

Mitochondria are the powerhouse of the cell, as any fifth-grade biology student could tell you. (Mitochondria is plural, one of them is called a mitochondrion). These tiny organelles turn the food, water, and air you consume into energy that can power your whole body. They also might be helping you see color more clearly.

Mitochondria are present in every cell, but not every cell gets the same amount. Generally, the more energy a cell needs, the more mitochondria it has. Your hardworking heart muscle cells, for example, are rich with them, having about 5,000 per cell! Your skin cells, by comparison, have just a few hundred.

Another cell type with a plenitude of mitochondria: your eyes. Specifically, inside your retinas, the light-sensitive tissue in the back of your eyeballs, exists a specialized type of cells called cone cells that allow us to see color. Cone cells are broadly organized into an outer segment, which picks up light, and an inner segment, which handles the rest of the cell's functions. It is in the inner segment that mitochondria cluster into a long bundle in inner segment of the cell.

Diagram of a cone cell

Initially, it was thought that this glut of mitochondria produced energy for the cone cells. That, like heart muscle cells, they were using up a lot of energy. But researchers found that most of the energy produced in the cone cells came from glycolysis, a separate process that doesn't involve the mitochondria at all.

Evolutionarily, though, this doesn't make sense. There'd be no reason to pack so many mitochondria into cone cells if they were just sitting there. But if they weren't making energy, what were they doing?

The answer to this riddle came as a result of a rather morbid experiment. Scientists chose 13-lined ground squirrels as their model organism, since they're diurnal (coming out during the day and sleeping at night), and so have lots of cone cells for sensing color. The squirrels were raised in captivity for 5 months, fed cat chow and given some bedding and a PVC pipe for enrichment. On their day of reckoning they were gassed and decapitated by guillotine. (I am not making this up, it's in the "Methods" section of the research article. And I am still thinking about their little squirrel heads rolling)

They gave their lives for science.

Their eyes were dissected, with the retinas cut into tiny pieces which were then fixed to microscope slides. Layers were peeled away until only the light-detecting cone cells remained, then a light was shined onto the live cells, mimicking the passage of light through the eyes. While those bundles of mitochondria might be expected to scatter the light, they instead focused it on the light-sensing outer segment of the cone cells. The oily membrane of the mitochondria had special reflective properties that made them "microlenses" for incoming light, creating a higher-resolution image.

While the study was carried out on squirrels, it has several implications for humans' eyes as well. For example, it helps explain the Stiles-Crawford effect, a phenomenon where color is perceived differently when seen through the pupil versus the edge of the eye. Through experiments and computer modeling, researchers saw that the mitochondrial interaction with light lined up with the Stiles-Crawford effect. In humans, this could be a useful way to diagnose eye disease, since many eye diseases cause mitochondrial dysfunction.

Here's a helpful explanation in the form of a video.

A Feeling in the Pit of Your Stomach

Do you think your brain is a rational actor? That is, do you think with your "head" and not your "heart" or your "gut"? (This blog is going to become Jonathan Frakes Asks You Things, isn't it?) We have a tendency to attribute different parts of our cognition to parts of the body - the heart is emotional, the gut instinctive, the eyes superficial, the brain logical. However, these are merely metaphors, and as we all know, only the brain is responsible for processing information and making decisions. Is it really, though?

The digestive tract has its own nervous system, known as the enteric nervous system. The enteric nervous system is a division of the autonomic nervous system, which consists of those nerves that transmit information to and from the internal organs. Some other functions of the autonomic nervous system include regulating your heart rate and breathing, all unconscious processes, meaning they happen without you needing to manually control them. Imagine having to think about contracting your heart every second, and you'll be thankful you have this nervous system.

The enteric nervous system consists of all the nerves that control digestive functions, including peristalsis (the contraction of the intestines to move food along). Lining your digestive tract are over 200 million neurons, at least as many as in the spinal cord. Like your heartbeat or breathing, its functions are automatic, not consciously controlled. They even have the capacity to continue without the brain telling them to do so. When the vagus nerve, the main messenger from the brain to the autonomic nervous system, is severed, digestive functions were found to still continue.

There's a lot of layers going on here. Basically, nerves hide out between the muscles and the inner surface of the digestive tract.

There is some evidence and much speculation that the enteric nervous system could have an effect on cognitive processes, such as emotions and decision-making. While the enteric nervous system on a basic level creates the sensations of nausea and bloating, much of the information it sends is processed subconsciously, and can possibly determine mood. The enteric nervous system may also relay information from the pounds of microorganisms living in the gut, which can impact emotion and behavior. So your "gut feeling" could be a feeling from your gut after all.

Who is really holding the reins, then? New discoveries about the enteric nervous system challenge our brain-centric perception of behavior and mood. They can also change the way we diagnose, research, and treat certain neurological disorders, such as Autism Spectrum Disorder, Parkinson's, and ALS. Digestive dysfunctions are common along with the neurological symptoms of these disorders. With autism, a certain gene that is associated with the disorder is also associated with poor motility in the gut. These studies are developing, and mostly done on mice, but it remains to be seen how much of what we think of as brain dysfunction is closely linked to the gut.