My first cut is longitudinal along the crevice that separates the brain’s two hemispheres. I then slice into the left hemisphere, from front to back, creating uniform slices about half an inch thick. After a while, I feel the brain becoming mushy as it warms. Instead of falling neatly onto the cutting board, the slices fold over and crumple. I continue, though, getting better with each cut.
I pick up and examine each slice, and Dr. Herman points to its folds and creases and the borders marked by different tones of pinkish gray or white. These delineate subregions of the brain, the gray, neuron-rich areas and the white connecting fibers that run between them. Depending on where a given slice is, a particular specimen may include parts of the hippocampus, the amygdala, or some other structures inside the brain.
We quickly place each slice on a glass plate and immerse it in a mixture of dry ice and a volatile chemical called isopentane—a slurry with a very low temperature of minus 86°C. The semiliquid mixture steams and bubbles violently as we slide the tissue into it, and the slice freezes instantly, turning in seconds from bloody pink to frosted white. This procedure preserves the anatomy of the slice, preventing cell membranes from bursting open as they would during a slower freezing process. We promptly fish it out with forceps and place it in a plastic bag that we seal shut and label with a printed barcode. The preservation process is now complete.
If this brain initially resembled an ordinary piece of meat, it now looks like a stack of cold cuts in a grocery store’s deli case. As if to reinforce that impression, white-coated technicians arrive to ferry the cut-up samples to our laboratory’s deep freezer. There the specimens will sit, cold and silent, until they can be employed in our endless quest to discover the brain’s secrets.
Human brains are exquisitely complex, but we can learn a great deal about them by studying creatures with brains vastly simpler than our own, as I found out early in my scientific career.
Thirty years before I became the leader of the brain bank at NIMH, I was a young research scientist at the Institute of Psychiatry and Neurology in Warsaw with a master’s degree in chemistry and a PhD in medical sciences with a focus on the brain and nervous system. In the mid-1980s, I was working on clinical trials of drugs manufactured by Western companies to treat schizophrenia and living in a small apartment in Warsaw with Mirek, my then boyfriend, and my two young children from my first marriage.
In August of 1988, our lives were upended. That month, at the invitation of a German pharmaceutical company, I attended the International Congress of Neuropsychopharmacology in Munich. I was to present a poster on certain antipsychotic drugs designed to reduce the severity of hallucinations and psychosis, the most distressing symptoms of schizophrenia. I had no way of knowing that my focus was soon to shift from treating this terrible disease to hunting for its underlying causes.
I arrived in Munich with no more than twenty dollars in my pocket—an entire month’s salary—and was immediately dazzled by the opulence of West Germany. But my culture shock paled in comparison to the thrill I experienced when, at the conference, I was approached by Dr. Daniel R. Weinberger, an NIMH psychiatrist who was world-renowned for his studies on schizophrenia. No sooner had we met than Dr. Weinberger offhandedly suggested I come work as a postdoc in his lab.
I could hardly believe my luck. NIH was the most prestigious medical institution in the world, and its mental-health division was at the forefront of global research on the very illnesses that I’d devoted my career to studying. I’d never dared to dream that I might someday end up at NIMH myself.
A few days later, I returned to Poland and proudly announced to Mirek and my children that we were going to America! They were just as excited as I was. Poland at the time was looking bleaker and more unstable than ever, and many of its unhappy citizens dreamed of the freedom that the West offered. And everyone knew that American society was the freest of them all.
I arrived in the United States ahead of my family, in the spring of 1989, just as Poland was tipping toward democracy and threatening to bring the rest of the Soviet bloc down. The day after my arrival, Dr. Weinberger—who would be my boss for the next twenty-three years—drove me to the NIH campus and introduced me to Dr. George Jaskiw, a psychiatry fellow from Canada. Dr. Jaskiw became an enthusiastic mentor to me, and together we began to explore the mysteries of the same disease—schizophrenia—that I had studied in drug trials in Warsaw.
Dr. Jaskiw and I worked on rats because their brains are similar to human brains in their structure, although not nearly as sophisticated, and because rats display complex behaviors, such as working memory, cognition, and social behaviors, that are useful in understanding humans. We first focused on creating slight defects in the hippocampi of living rats because robust research data at that time suggested that the hippocampi in humans with schizophrenia were structurally abnormal and therefore did not function correctly. To disrupt the connections between the hippocampus and the prefrontal cortex in the brains of newborn rats, we injected minute amounts of neurotoxins into the hippocampus. In this way, we created brains with faulty wiring between these two areas critical in schizophrenia. We wanted to see how different our neurologically altered rats would be from normal animals and, especially, how they would behave when they grew up.
I’d never sliced into any creature, living or dead, but I was delighted to be part of this work. We threw ourselves into the experiments with the crazed abandon of knowledge-hungry scientists. Once, when I needed a quiet area to conduct our rat-behavior experiments, I placed my rats in their testing cages on the floor
