Emma palmer
b.s. in biochemistry,
currently a ph.d. student in neuroscience
What if I studied Neuroscience, but could never touch a brain?
I have dedicated 6+ years to studying neuroscience, but I have never touched a brain (kind of). I’ve touched plastinated brains, which are treated with a kind of plastic to make them turn waxy, but it isn’t the same. I’ve dissected fly brains under a microscope. I’ve never even gotten my hands on a human brain tissue sample (yet).
It seems kind of odd, but, like many neuroscientist predecessors, the work I want to do doesn’t require actual brains. Sure, they are useful. Mammalian models are really great tools to study neurological diseases, but they aren’t the only tool and they may not even be the most useful tool.
I want to study neurodegenerative diseases like Alzheimer’s, Parkinson’s, Huntington’s, and hereditary ataxias. There are many ways to study these disease without touching brains. There are the somewhat more obvious ones — brain imaging and clinical trials using real patients. But how do the drugs we use in clinical trials get discovered and developed? Before they are given to humans or even mice and monkeys, they are studied in things that aren’t brains. The drugs and disease can be studied in cell models. Yes. We can grow neurons in a dish. And we can mutate them to produce diseases. We can then add drugs to these dishes and monitor if they help the cells survive. We can create “brain” organoids by scaffolding these cultured cells into a three dimensional structure with multiple cell types. This is particularly useful for neurodegenerative diseases that seemed to have a vascular component like Alzheimer’s. We can study how the disease and drugs impact the connections and interactions between cells of the organoids.
It seems counterintuitive, but we can also study diseases abiotically. Without life. Chemistry and physic are critical to understand how the chemical structures of drugs interact with biochemical signaling molecules. These systems can be modeled outside of cells just in a solution.
I have had some experience with most of the methods I have described. These techniques have allowed me, and many others, to gain a deep understanding of the brain and neurological disease.
Tomorrow (October 22, 2024) I will get my hands on a live mouse brain for the first time, and I will deepen my understanding of how it works and how things go wrong.
Despite never touching a live human brain, I have seen them and seen their activity. I have performed dozens of EEGs on willing volunteers to study things like their attentional processes and visual memory. The first time I saw those brain waves was amazing and somewhat nostalgic. My curiosity about the brain began about 15 years ago when I had to get my neurologist gave me an EEG. I remember being so enthralled and confused by the fact that this doctor man could see things from inside my brain. Even now, I desperately want to understand myself further by visualizing the structures of my brain. I am currently taking neuroanatomy as part of my PhD program curriculum. I am learning about all of the structures and pathways that make being a living, breathing, feeling, thinking human possible. I’ve seen some fMRI images of Zoé’s brain. I feel as though just scrolling through the images (in an attempt to study for my exam) has helped me understand her cognition and personality on a fundamental level. I long for that same understanding of my own brain.
I don’t know if I will ever touch a real human brain. I’m not even quite sure I want to. My understanding of the brain feels very real but on a certain level I know it is extremely limited by my experience. Would I still want to study the brain if I couldn’t ever see or touch one? I think so, but I can’t really say for sure. If seeing brains was common, would I find neuroscience to be more trivial? Maybe. All I know is that I am deeply curious about how and why our brainsand cognition degrade as we age and that we are an amalgamation of everything we have ever experienced. That experience is evident on the molecular, cellular, synaptic, systems, and behavioral level. Neuroscience is the only way I know to understand that.”
🧠
(2025, May 19)Additional entry:
Prior to the Fall of 2024, I had never seen or touched a mammalian brain. I had studied neuroanatomy extensively, to the extent that I became intimately familiar with a friend’s MRI scan of their own brain. But, despite calling myself a neuroscientist, my hands had never held a brain, and my eyes had never laid on its delicate structures. During this time, in the before, I believed that I did not strictly need brains to do the research I wanted to do. I could culture cells that turned into neurons to observe their behavior and how it changes in response to different drugs that may treat neurodegeneration. Or I could use human imaging techniques to observe these changes in people. Or I could use a simple animal model like a fruit fly, which I had done for two years.
In the first year of my PhD work, I handled mouse brains and even some human brain samples frequently. I have dissected brains, examined them microscopically, and was even able to record electrical activity from a single neuron. So now, in the after, I no longer believe I could answer the questions I have about the human brain and neurological disease without touching a brain. Sure, tools like cell culture, neuroimaging, and invertebrate models are crucial to the discovery process. Many genes regulating neurodevelopment were first discovered in fruit flies, and the ability to create neurons in culture has revolutionized the drug discovery process. One could argue (like I previously did) that it is completely feasible to do the research I want to do without touching a brain, but, even if it was, my own work would rely upon hundreds of scientists who came before me that did the dirty work of examining brains and neurological disease like Jan Evangelista Purkinje (who first described Purkinje cells in the cerebellum), Santiago Ramón y Cajal (who unearthed the architecture of neurons), Alois Alzheimer (who was the first to describe amyloid plaques and tau tangles in Alzheimer’s disease and whom the disease is named after), and Fritz Heinrich Lewy (who discovered abnormal protein deposits in Parkinson’s patients).
I want to know exactly how neurodegenerative diseases like Alzheimer’s, Huntington’s, Parkinson’s, ALS, and the spinocerebellar ataxias begin, how and why they progress, how we can treat them, and ultimately, how we can prevent them. The answers to these questions cannot be answered without mammalian preclinical models of disease or without the donation of brains to science. Part of my dissertation research is based upon the work of others, who have established what neurodegenerative disease looks like at the cellular and molecular level in humans. In my own research, I use mouse models of disease. These “transgenic” mice possess human genes with disease mutations that have been inserted into their genome, which causes the mice to have similar symptoms and cell pathology to human patients. With these mice, I can test different drugs that may help prevent cell death and/or alleviate symptoms or I can examine different molecular pathways that may contribute towards disease progression. Even the generation of these mice would not be possible without the scientists before me that discovered the human genes that cause disease.
As technology continues to advance, the need for human or mammalian brain samples decreases. This often makes doing science cheaper and faster. However, I believe it is important to remember that if something is discovered in a cell, the natural next step is to validate that discovery in an animal model and to remember that a drug must be tested in mammals for safety and efficacy before it is given to people. So, I am deeply thankful to every person who has donated their body/brain to science and to every research animal that has been sacrificed for science. Without them, we would never discover critical disease processes or develop new therapeutics to help those suffering from disease.
(Side bar – I urge everyone to consider donating their brain to science even if you don’t have a neurological disease because we neuroscientists need healthy control samples to make comparisons to, and these samples are harder to find).
The gif:
These neurons express a genetically encoded calcium indicator called GCaMP which is made of a green fluorescent protein and a calcium binding protein. When intracellular calcium increases during an action potential, a firing cell will fluoresce. This allows us to visualize neuronal firing indirectly.
*The gif is from Emma’s neuroscience bootcamp when she learned more basic imaging techniques upon entering the grad program. I don’t claim this video as my own, and rights are reserved to University of Michigan and were used for training purposes.
These neurons express a genetically encoded calcium indicator called GCaMP which is made of a green fluorescent protein and a calcium binding protein. When intracellular calcium increases during an action potential, a firing cell will fluoresce. This allows us to visualize neuronal firing indirectly.
*The gif is from Emma’s neuroscience bootcamp when she learned more basic imaging techniques upon entering the grad program. I don’t claim this video as my own, and rights are reserved to University of Michigan and were used for training purposes.