DIY: Building brains from scratch
For obvious reasons, artificial intelligence makes headlines these days. No less extraordinary, but less known are the advances in making actual human and human-animal hybrid brains. Whether or not this will lead to a form of natural intelligence or consciousness in the future is certainly up for debate. But what you may not know is that scientists have been working for years towards developing brain systems that they can use to study the development of normal and different brains.
Last month, some scientists took the work to the next level by fusing a developing human minibrain with a rat brain. This is a huge milestone that deserves unpacking.
Part 1. Turning skin into brain cells
The story starts over a decade ago. Generally, once cells mature to form skin, brain, or lungs, for example, they don’t turn the clock back and turn into their precursor cells. The mature cells that are part of the muscle of your heart do not become neurons and that’s a good thing. But in 2006 and 2007, Shinya Yamanaka found that by engineering certain genes into adult skin cells he could reprogram them into becoming stem cells.
This took the scientific world by storm. Initially, Yamanaka’s discovery was met with disbelief. But today, these stem cells, known as induced pluripotent stem cells, are widely used in biomedical research. Because they’re immature cells, they can be nudged chemically to become different kinds of cells. And in 2012, Yamanaka won half of the Nobel Prize in Physiology or Medicine.
Stem cells can be coaxed into differentiating into different kinds of cells. They can then be grown in the lab into tissues that can be studied to see how diseases develop when something goes wrong. Because the tissues made of cells that come from stem cells are “young”, they also hold promise in regenerative medicine as replacements for ageing and diseased tissues.
Part 2. Growing human minibrains in the lab
But even if you can create a brain cell or neuron, you’re very far from getting an actual brain.
The brain truly is one of the last frontiers in science. It has around 100 billion brain cells or neurons which form around a hundred trillion connections. Small differences in early brain development can lead to neurological diseases, as well as the propensity for differences in thinking, mood, and behavior. There is a huge leap from creating single cells to complex 3D structure like the human brain.
As I mention in my recent column in Hindustan Times it’s almost as if we need to grow a brain from cells to be able to understand it. Which is exactly what some scientists thought of doing.
The next landmark in the study of brain development came in 2013. In a research article published in Nature, Madeline Lancaster successfully grew a 4-millimeter minibrain with all the hallmarks of a real growing human brain. Human skin cells were coaxed into becoming immature stem cells, which then were gently guided into becoming neurons. A scaffold supported the growth of the minibrain which showed features of tiny parts of a developing human brain.
Minibrains, known as brain organoids, are 3D blobs made up of thousands of communicating neurons. Neuroscientists around the world are now creating brain organoids to understand the formation of the human brain.
As Lancaster mentioned in a subsequent interview, the discovery of how to make these minibrains was accidental.
Brain organoid showing a brain-like structure with cells that give rise to neurons (reddish-purple) and neurons (green). Credit: Lancaster et al., 2013.
The process has been improved and replicated now by many lab and has resulted in many astonishing discoveries.
For example, last year, scientists led by Jay Gopalakrishnan grew brain organoids with eye-like formations, known as optic cups. The work, which was published in Cell Stem Cell, showed the integrated early development of precursors to eyes. At about 60 days of development, black eye-like optic cups were attached to the brain organoids. In photos, these brain organoids look like they actually have eyes on them.
Lab-grown brain organoids with optic cups that look like eyes. Credit: Elke Gabriel
Part 3. Frankenbrains: fusing a human brain with a rat brain
But as amazing as making minibrains in the lab is, brain organoids have their limitations. They never become fully formed “brains on a dish”.
Because they don’t receive nutrients from blood vessels in a dish or because they don’t receive electrical and chemical signals that a developing brain would under normal circumstances, brain organoids stop growing beyond a certain size. As a result, brain organoids lack the complexity of an actual brain.
As I write in my column —
This is where recently published work in Nature that has been described as the creation of a “Frankenbrain” in the popular press comes in. What researchers led by Sergiu Pasca did was both audacious and brilliant. To induce the fledgling human brain organoid to grow beyond the limits of the laboratory dish, they grafted it on to a developing young rat brain.
The human brain organoid was grafted on to the part of the developing rat brain that responds to rat whisker movement. Because the rat brain was still plastic and developing, it was able to make connections with the human brain organoid.
Researchers transplanted a human minibrain (shown in bright green) into the developing brain of a rat. In the process they created a hybrid brain .Credit: Stanford University
The brain organoid developed like a human brain cortex within the rat brain. As the brain organoid derived human part of the rat brain grew, it integrated signals from the rat. In other words, there was a functioning unit of a human brain plugged into a rat brain.
Make no mistake. The rat didn’t become outwardly human. It remained a rat. The researchers took pains to note that the animals didn’t suffer any observable neurological consequences like seizures or epilepsy as a result of the insertion of the human brain organoid. But a part of the rat brain developed characteristics of the human brain.
The approach could also be a model system for the study of human neurological and psychiatric illnesses. For example, hybrid brains that are derived from cells of patients with one developmental disorder were shown to have distinct characteristics from ones that didn’t.
There are ethical questions with research on the creation of brain organoids and hybrid brains. Some fear that the creation of complex brains might lead to human consciousness. But there is no clear definition of consciousness and what it entails. Lacking any sensory input, tiny brain organoids will not be able to develop complex thought. And if brain hybrids help to develop a better understanding of human diseases and their cures, then pursuing this line of research is warranted.
So how many steps do you actually need?
The answer may surprise you. ;-)
Here’s my thread on recently published work on the topic.
Other very interesting stuff.
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15% of US adults with a prior positive COVID-19 test reported current symptoms of Long COVID. This is a huge burden on the healthcare system.
A gene derived from an ancient virus might help the placenta defend a developing embryo against viral invaders.
“Ebola Is Back—and Vaccines Don’t Work Against It“ A timely story on the Sudan ebolavirus outbreak occurring in Uganda.
How long can a living thing survive? Spores of some bacteria have been revived from amber that is millions of years old. How then do these spores sense the time is right to “wake up” from a low power-mode? Here’s a Twitter thread from someone who found out.
A potent antifungal antibiotic dubbed solanimycin was found in rotten potatoes
This is an engaging talk on how the brain makes us see things that aren’t there.
And finally, this episode by Radiolab has got to be one of the best podcast episodes of the year.
