Cell Fate and the Brain in the Dish: What Organoids Reveal About Autism

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Growing brains on petri dishes may sound like an idea straight out of science fiction, but in fact this concept is practiced in research all around the world today. Scientists call them organoids, and these artificial organs have been developed to study many organ systems, not just the brain. The process can take weeks to even a full year, but the general steps go something like this; First, a patient whom scientists would like to study has their blood drawn. Using the blood, scientists can create stem cells that reflect each and every individual they are derived from. Using different formulations of nutrients and growing environments, they can be coaxed to become whatever kind of cell the scientists want them to be, whether its neurons are heart cells or skin cells. When more mature cell types like these are grown together, they naturally start to aggregate into a clump that can mimic the basic structure of organs, like the brain. It’s essentially like hitting “rewind,” skipping to what you’re interested in, and then hitting “play” on someone’s cells in a petri dish.

As I walked through the rows upon rows of lab benches in the basement of the Altman Clinical and Translational Research Institute (ACTRI) at UC San Diego, I couldn’t help but think about what discoveries were waiting behind each door. The shelves were jam-packed with lab equipment, some of which looked decades old, others which were large and shiny. There were glass fridges filled with vials and dishes of various colors, shining iridescently with mysterious labels. That day, I visited one of the many labs which call ACTRI home, the Campbell Lab. 

The Campbell Lab researches neural cell fate. It sounds cryptic, but the concept gets at the foundation of what makes us who we are. All humans start as embryos. Depending on how early-stage you’re looking at, we’re essentially a clump of stem cells. So what determines what our cells eventually become… part of our heart? Part of our eye? Or part of our brains? The answer can be very complicated, and much is still left to be discovered. However, what is known is that a combination of both genetics and the environment determine when certain parts of the genome are activated or deactivated, leading to the process of differentiation. Cell fate is foundational to the process of neurodevelopment and is a huge area of interest in the scientific community. Many neurodivergent conditions, such as autism, aren't linked to just one gene. Not everyone with autism carries autism risk genes, yet autism presents similarly in many on the spectrum. There’s actually a term for autism cases with unknown causes, called “idiopathic” autism, and it accounts for an estimated 85% of all diagnoses. What is known is that autism is a neurodevelopmental condition, and that it most likely is a result of dysfunction somewhere along the incredibly complex cell fate pathway.

Vani Taluja is a neuroscience PhD student at the Campbell Lab who has long been on a mission to better understand conditions like autism. She was inspired to pursue research in this area because of a friend whose neurodevelopmental condition went undiagnosed for many years. “For her family, not really knowing what was going on, it was hard to find other people that have gone through a similar thing,” she recalls. But when they received the diagnosis, an entire community of help and resources became accessible. Vani works to study how the brain develops prenatally so cases like her friend’s can be identified and addressed earlier. And she does this using brain organoids.

“I’m looking at neurodevelopment prenatally in autism,” she explains. “We use stem cells that are reprogrammed (converted) from blood cells from kids [with autism] that we see in the clinic. We are able to grow organoids, which are like tiny brains in a dish, to try and understand how their brains were growing before they were born,” Vani continues. “Then we’re also looking at their behavior and their brain growth at two years of age, to see if we can find any connections between prenatal brain growth, two-year-old brain development, and how their behaviors are at two years-old.”

What Vani and her collaborators are attempting is actually a huge effort that fundamentally is trying to break the wall between research in cells grown in a lab environment and research in living, breathing humans. Autism is a complex condition, and by taking it apart from both a cellular and behavioral perspective, researchers like Vani can get a better understanding of the bigger picture. What they’ve found so far lines up with other findings researchers have noticed about autism, which is a promising direction for their work as a reliable model for autism and possibly a future tool for diagnosis. 

“The biggest thing we found is that organoids developed from these kids with autism are bigger than those from typical controls,” Vani explains. About 20 years ago, her collaborators also discovered a similar pattern amongst two year-olds with autism in which their brains were bigger in overall cortex size. In fact, they had about 67% more neurons in the prefrontal cortex. While the cause of this is still a mystery, Vani and her team have been working hard to uncover possible reasons. 

She attributes much of the day-to-day research to analysis integrated with coding and artificial intelligence (AI) programs. Growing organoids doesn’t always go as planned. In fact, they’re known to be on the more difficult end of the spectrum in terms of maintenance and nurturing to a healthy state. Many organoid researchers like Vani need to give their organoids fresh nutrients every few days to keep them alive. It’s a labor-intensive process, but well-worth the time, especially when integrated with technology.

“I developed an AI pipeline that’s able to identify what’s an organoid and what’s not, and to measure them for me,” Vani said. Not only is it less biased, but it also makes it possible for Vani to count and measure the size of hundreds of organoids at every stage of growth. 

Getting an autism diagnosis today can be a challenging ordeal and, for many, unaffordable. With tests consisting of hours of qualitative behavioral exercises and a cost of about $5,000, many families are unable to go through with it even when their child needs it. There’s also an age barrier, where behavioral tests for autism diagnosis are not considered reliable until babies are at least two years old. The average age of autism diagnosis in the U.S. is even later, at five years. With what Vani and her team have found, it’s possible any child in the future may be able to be tested for autism with just their blood, no matter how young they are. Continuing to develop their AI algorithm could lead to diagnoses with less human bias and no need for an age limit, lowering barriers and encouraging early intervention for the autism community. In the future, they hope that no one should have to wait until early adulthood to find help. †

Written by Editor and Staff Writer Eleanor Jung (eljung@ucsd.edu)

Works Cited:

Autism Speaks. (2023). Autism statistics and facts. Retrieved from Autism Speaks website: https://www.autismspeaks.org/autism-statistics-asd

Casanova, M. F., Casanova, E. L., Frye, R. E., Baeza-Velasco, C., LaSalle, J. M., Hagerman, R. J., … Natowicz, M. R. (2020). Editorial: Secondary vs. Idiopathic Autism. Frontiers in Psychiatry, 11. https://doi.org/10.3389/fpsyt.2020.00297

CDC. (2024, May 8). Screening for Autism Spectrum Disorder. Retrieved from Autism Spectrum Disorder (ASD) website: https://www.cdc.gov/autism/diagnosis/index.html

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