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.