Jul 23, 2021
Could Algae Help Uncover the Meaning of Life?
How often does your brain think about itself?
Right now, the network in my brain is managing countless signals to help me think of the next word.
Your brain is coordinating your vision and interpreting the message.
All while regulating our heartbeats, temperature, breathing, and more.
It should be no surprise that the brain is a magnificent and complex part of our bodies. Although extensive research has been conducted on the functioning of our brains, there are still many mysteries to be unlocked.
These mysteries are especially concerning, as according to the WHO, up to 1 billion people currently live with a mental disorder.
That could be about to change. All by turning on a light.
Recent breakthroughs in neuroscience could allow us to understand precisely how our brain works. Next, we could begin to make targeted cures for brain disorders. After that? We could start to assess what makes us human.
Before we get there, let’s recap some of what we do know about our brains. Our brains are composed of billions of cells, an important category we’ll focus on are called neurons. Neurons fire in certain patterns and combinations to control our thoughts and behaviours. They chat with each other through neural connections, or synapses.
But what language are they speaking?
In the 1700s the Italian scientist Luigi Galvani was walking through a market during a lightning storm and noticed some frog legs that appeared to be twitching from the electricity in the storm. Using electrodes in his lab he determined that our neurons use electrical signals to pass information.
Today, we know that neurons contain ion channel receptors, or “gates” to the cell membranes that are opened using a key — such as a neurotransmitter like serotonin. Charged ions flow into the cell, depolarizing the neuron, and causing it to “fire.” This is called an action potential.
Once we figured out what language neurons spoke, we could start influencing the messages they sent to each other.
In the 1930s researchers began to use electrical stimulation (electrodes) on human brains. Deep brain stimulation is still used today to treat brain disorders such as Parkinson’s disease.
The problem is that this therapy lacks precision and comes with side effects. Instead of targeting one neural pathway, the electricity activates huge sections of brain tissue at once. It’s been described as using an excavator when a shovel could do the job.
There must be a better way!
BIG HELP FROM A LITTLE FRIEND
It turns out the big breakthrough in neuroscience was hiding in the ponds in our backyards.
Common single-celled algae called Chlamydomonas contain an “eyespot” that detects light. When light is sensed, the alga uses its cute little tail to swim closer to the source. This is quite like how my eyes detect taco trucks resulting in my legs running towards them. The proteins within the eyespot that are light-sensitive are an opsin called channelrhodopsins or ChR2.
ChR2 proteins act as a gate. The key that opens this gate is blue light.
Hey, that reminds me of something. We just learned about how our neurons also have a gate that is unlocked by neurotransmitters. I see an opportunity here…
So did Karl Deisseroth and his team in 2005. Scientists were initially able to clone the gene that produces ChR2 and insert it into the neurons that control the movement of rats. At this point, the cells were still in a petri dish.
By 2007, scientists could attach the gene containing the blue light “gate” protein to a friendly, benign virus and inject that (friendly) virus into the brains of living mice. These viruses can be programmed to target certain neurons and not their neighbours, giving us the ultra-precision that we’ve been seeking.
At this point, scientists have genetically engineered mice with neural action potentials that fire when exposed to blue light. The next step is to attach small fiberoptic cables that emit blue light into the brains of the mice. By firing these lights at certain frequencies, we can directly affect the animal’s behaviour.
OPTOGENETICS: COMBINING LIGHT AND GENETICS TO CONTROL THE ACTIVITY OF CELLS
Thus, optogenetics was born. Instead of using neurotransmitters, the “key” to the genetically modified “gates” is now blue light.
Here’s why this idea is so illuminating.
We’re not dealing with an excavator anymore. Not even a shovel. Now we can dig into the brain’s circuits with laser-like precision.
If you moved into a new house with an unlabeled circuit breaker, you would start by flipping each switch on or off to see what part of the house it affects. Optogenetics has similarly allowed us to map neural functions in animals such as mice, fish, and worms.
Once we know what individual neurons control, we can begin to treat disorders and further alter behaviour.
Pretty exciting right? At this point your brain is probably overflowing with adrenaline neurotransmitters.
SO HOW IS OPTOGENETICS BEING USED?
We know our neurons are constantly communicating with each other…but what happens when they stop chatting? When neurons get shy it results in many of the brain disorders which affect so many of us.
Anxiety disorders are the most common mental illness in the U.S., affecting over 18% of the population every year. Studies have shown that anxiety and emotion are largely controlled by a part of our brain called the amygdala. There are also antianxiety neurons in this region.
Scientists bred a group of extremely anxious mice and attached ChR2 proteins to their antianxiety neurons. When exposed to blue light these mice left their dark and safe corners and began to explore more open areas, demonstrating a reduction in their anxiety levels.
In 2011, a team led by Ed Boyden studied a group of three blind mice. Or maybe a few more.
The team inserted the gene containing ChR2 into the mice’s retinas. The light-sensitive gates were able to replace the damaged retinal cells. There are currently two clinical trials being conducted using a similar technique in humans. Optogenetics could be a solution to restoring vision in the over one hundred thousand Americans who have lost their vision to retinitis pigmentosa.
This is a photo of a dragonfly wearing an (adorable) mind control backpack. It is part of the organization Draper’s DragonflEye project where they have used optogenetics to guide the flight of dragonflies. This is in part achievable by attaching opsins to the “steering” motor neurons in the insect.
In clinical trials on animals, optogenetics has shown promise in treating or better identifying the circuits causing Alzheimer’s, Parkinson’s, PTSD, and more. Researchers at Tufts University are even experimenting with using optogenetics to revert cells to non-dividing states to cure cancer.
All right. That should be enough to sell you on optogenetics. You’re probably saying, “get those algae in me!” So, what’s holding optogenetics back from application in humans?
1) The first barrier is the genetic engineering required to code the ChR2 protein into our bodies. The introduction of nonhuman DNA comes with its own risks and potential unintended side effects. Perhaps public sentiment will change with increased exposure to the safety and science behind mRNA vaccines?
2) Not to brag, but another problem is that our brains are very large and complicated. Mapping individual neuron pathways will take time. Initial studies show that these roadblocks are not necessarily permanent, so we should start thinking about where this technology could take us.
WHAT COMES NEXT FOR OPTOGENETICS?
Instead of focusing on one neuron, we can start to think about the opportunities of using light to target a matrix of neurons with their own independent light sources. This would allow us to control more complex mechanisms in the brain.
For example, globally more than 264 million people suffer from depression.
We currently use antidepressants like Prozac and Zoloft to enhance signaling between our neurons. One issue with these drugs is that the affected serotonin molecules are located throughout the brain. Psychiatric disorders are instead believed to result from inefficiencies in specific circuits.
David Anderson, a biology professor at the California Institute of Technology said regarding drug treatments, “If you dump a gallon of oil over your car’s engine, some of it will dribble into the right place, but a lot of it will end up doing more harm than good.”
Optogenetics could allow us to more accurately identify the circuit that regulates depression and help reduce its effects without adverse consequences.
This leads to an interesting dilemma. In another optogenetics experiment, a mouse was rewarded with dopamine, or pleasure, when it touched a button within a box. It touched the button hundreds of times. Sure, we also can get that dopamine hit by watching dog videos on our phones. But if you had the same button, would you ever stop pressing it?
Thus, this little alga leads me to the ultimate question of what it means to be human. Is the purpose to experience joy? If so, then we should maximize our dopamine and endorphin exposure and live in endless ecstasy.
But maybe there is something more to both life and joy. Maybe a warm hug or fresh bread or hearing laughter elicits something that simply cannot be replicated artificially.
Still with me? Let’s go one step further.
So far, we have focused only on using blue light which triggers ChR2.
But ChR2 is not the only type of opsin.
Halorhodopsins exist in a bacterium located in salt flats. When exposed to yellow light this protein closes the ion gate and silences the neuron. Attaching these to our neurons could allow us to temporarily shut off overactive brain activity to stop seizures or epilepsies from occurring.
What if we added both blue and yellow reactive opsins to our neural network?
We could essentially create an on/off switch for the components of our brain. Theoretically, our brain functions could eventually be modeled in a string of 1s and 0s, just like a computer. That raises a few questions for me:
o Would that allow us to experience all sensations remotely?
o Could we stop experiencing pain?
o Could we simulate a physical response to touch in prosthetics?
o Could we download our memories?
o Would we even need our physical bodies to experience life?
The inner workings of the brain and the source of the mind have been a mystery to us for centuries. The form surrounding Michelangelo’s God bears an uncanny resemblance to the cross-section of a brain. Perhaps the great artist was sending the message that a divine power is responsible for life as well as our intellect and consciousness. That leads me to the question: if we conquer the brain, do we become deities ourselves?
THINGS ARE ABOUT TO CHANGE
As optogenetics approaches human use, I think it’s crucial that we use our current non-algae-infused brains to ask some questions in preparation. These include:
o If we could create “superhumans” with extended memory or increased brain capacity, would the transformation process be expensive? Would this create a financial-based divide between enhanced and original brains?
o Is creativity able to be programmed? Could the arts one day be consumed by science?
o Could we be creating our own Brave New World with no adversity? Would we still appreciate joy if we did not know its absence?
I don’t have the answers to all these questions. However, I believe it is imperative that we continue to ask them.
I believe that we could use optogenetics to cure our ailments and make our lives more meaningful. But we must be wary of going too far and losing all meaning that we once had.
We are going to see some profound developments in optogenetics during our lifetimes. One thing I know for sure is that I’ll never look at an old green pond full of algae the same way again.
