Perspective
Catching Brains
When you ponder the brain, you look into the territory of the unverifiable.
By Elizabeth A. Reid Holter, M.D.
The second-year neurology residents referred to the pathology rotation at Massachusetts General Hospital as “brain-catching.” Our charges were the newly dead on their stainless steel tables in the morgue. We peeled scalps down, sawed off caps of skullbone, and removed brains with great care to avoid tearing their gossamer-like cranial nerves. Each brain went into its own white bucket of formaldehyde, suspended by strings to prevent deformity. There it hung for two weeks—until the fixative penetrated and solidified the gelatinous organ that had been a personality. (Only with proper steeping is a brain firm enough to be sliced like a loaf of bread and searched for anatomic correlates of the symptoms outlined in the patient’s chart.)
While the fresh brains fixed, we worked upstairs in the laboratory, where life was as slow-paced and civilized as E.P. Richardson, the neuropathologist in charge of our education. Amid microscopes, slides, and slices of brains, we stopped for afternoon tea. We sipped from porcelain cups with matching saucers and listened to his stories about the legendary investigator-physicians who worked out, through pathologic investigation, many basic neurologic concepts that we take for granted today. We knew these doctors as our clinical teachers, but he wanted us to appreciate them as the pioneers they were. Dr. Richardson had a schooner named Serenity, an Attorney General brother named Elliot, and a world-class understanding of the brain. Rumor had it that he worked for $1 per year, an arrangement we viewed as entirely possible given his devotion to neuropathology and to Mass General. But we did not speak of such things to him, and he did not speak of his famous brother to us—even though Richard Nixon’s Saturday Night Massacre was still news. (Elliot Richardson was one of the casualties of Watergate, forced to resign on October 23, 1973.)
During internal medicine training and the first year of neurology residency, I’d done my share of guessing at underlying pathology. Was that left hemiplegia caused by a hemorrhage or a thrombosis? If the latter, was it embolic or thrombotic? Was it housed in the internal capsule or in the brain stem? Was a seizure caused by a tumor or a scar from an old injury? Did the patient have metastatic tumors or progressive multifocal leukodystrophe? Angiograms, pnuemoencephalograms, EEGs, and spinal taps offered some data in those prescan days, but often we winged the diagnosis under the tutelage of physicians whose years of experience gave them a degree of assurance that we all aspired to.
I’d also been to Tuesday night “brain-cutting” sessions in the morgue’s conference room, where clinical cases were presented for literal and figurative dissection by our sages, the professors of the neurology department. The patient’s life was over, but his brain sat on a cutting board under a wet towel in the middle of an elegant conference table, while a nervous resident presented his story for consideration. After all opinions were voiced, the towel came off. Formaldehyde wafted through the room as the pathologist sliced the brain and revealed the answer—most of the time. But even if there was no identifiable gross pathology, microscopic analysis held the door open a little longer. Another couple of weeks of slide preparation and inspection had to pass before the book was closed on the patient’s life, with or without an explanatory coda.
In the 1970s, Massachusetts General was one of the last holdouts to require its clinical residents to learn so much pathology. Even then, imaging procedures were muscling their way into the business of final diagnosis. We had one of the first CT scanners, a hulking machine crammed into a submarine-like room, producing images of eight brains a day on a dot-matrix printer. Primitive as they were, the scans were a giant step in anatomic diagnosis, providing real-time, noninvasive glimpses of interior pathology. Well … not exactly. Images are real-time looks at mathematical derivatives of interior pathology. Real pathology is three-dimensional, with shape, texture, color, and smell.
I arrived for my year of pathology looking forward to a retreat from the messy and worrisome reality of the live patient—and to a strictly daytime call schedule. Autopsies could wait for sunrise. From what I’d seen of Tuesday night brain-cutting sessions, the uncertainty of the clinical world stopped at the morgue. I anticipated a period of learning that would endow me with some of the quiet assurance of “knowing” that the professors possessed.
Little by little, though, reality crept into my idealized projection. Autopsies sometimes happened at night. There were cases that didn’t have solutions, and cases whose answers weren’t what the clinical picture suggested. The mental images I’d constructed while dealing with live patients didn’t match what I saw under my scalpel or microscope. For instance, I’d pictured neurosurgeons excising my patients’ brain tumors along clearly demarcated lines between normal and abnormal tissue. But under the microscope, abnormal cells were undisciplined, popping up millimeters, even centimeters away from the tumor, intruders in otherwise normal tissue. Tumor cells sometimes looked almost normal. Normal cells sometimes looked almost like tumor cells. How could the surgeon find edges when normal and abnormal faded in and out of each other’s territories? Strokes of comparable size in different brains produced different degrees of deficit. And although we classified degenerative disorders according to which cells dropped out, which abnormal structures appeared, and what stains they took up, our meticulous descriptions said nothing about the causes of these devastating malfunctions.
These uncertainties were small change compared with the big questions posed by the fixed brains of ex-people. Lined up in their buckets, all brains were monotonously similar. Sliced, sectioned, stained, and viewed under a high-power microscope, they had identical features. There were no markers anywhere for sex or race, IQ or EQ, educational level, social skills, hobbies, interests, or loves. There was no way to tell whether the brain belonged to a left-handed major league pitcher, a right-handed mathematician, or an ambidextrous serial killer. Brains differed in size and harbored varied abnormalities, but overall, the most striking feature was their sameness.
In short, the brains in the buckets and under the microscope gave up no clues as to how and why we are what we are as human beings. For our mundane purposes, though, this was immaterial. We were in the lab to learn the nature and course of diseases that afflicted live patients—to have a three-dimensional, hands-on, direct experience. It is one thing to see a stroke or tumor in the flat plane of a scan. It is quite another to trace the contours with your finger, feeling the alien firmness of a tumor or the cheesy softness of an abscess, marveling all the while at the capacity of the ugly tissue to wreak havoc in the life of the patient.
Marveling at one thing leads to wondering about another, though, and the tug of the big questions was sometimes irresistible. When you ponder the brain, you look into the territory of the unverifiable, where the sages are philosophers, writers, and, lately, physicists. Sometimes, as we sipped our afternoon tea, we ventured into that void and played with ideas about consciousness, will, spirit, and individuality. It was entertaining but of no practical use in the world of medicine. So along with our teacups, we put those conversations away and turned back to patients and disease, where answers were at least possible, if not always forthcoming.
Today we look at functional MRIs and see which parts of the brain light up with which tasks; we identify different neurotransmitters rising and falling like tides washing in and out. A Nobel Prize goes to the man who figures out how the nerve cells of a slug store things slugs learn because it is a step toward figuring out our own memories. Eminent neuroscientists teach us that the precious selves we identify with are mere projections of electrochemical impulses zipping around the brain. The more we learn, the less the brain appears to be the seat of a soul or the essence of a man, and the more it becomes just another organ. A very specialized organ, to be sure. Maybe something like a radio—a receiver, processor, and transmitter that conjures up its own operator—but just an organ nevertheless.
The trouble with this strictly mechanistic picture comes once you love someone. The dispassionate neurology resident may accept the idea of a personality having been nothing more than an ephemeral cloud of electrons spinning through the synaptic clefts now frozen in formaldehyde on the slide under the microscope. The families who cherished that personality would probably find the notion ludicrous—or at least repellent. Too bad, say the scientists. That’s all there is. Get used to it.
I just can’t be that certain. I know what a brain looks like inside and out, and what parts make what things work. I know that nothing visible in there disappears when the patient dies. Technology takes the deconstruction deeper, using mathematical derivatives and statistical analyses to peer inside cells and break down the blueprint in the genome. Someday, maybe, we will have it all figured out. But I have suspicion that once we get down to the smallest parts—the quarks and neutrinos that build not only us but the rest of the universe—we will be holding the pieces of the most marvelous instrument we will ever know and still wondering where and what the timeless “watcher” of our dreams is. We will be staring out at the void again, at the edge of the known world where science works. We will sigh, put our teacups away, and go back to work. But in our spare time we might want to look up the sages of that unverifiable world. There is wisdom beyond science, and it is open for exploration. MM
Elizabeth Reid Holter is a neurologist and writer in Edina.