April 2022, ScientificAmerican.com 55called them, “whose beating of wings may one day reveal to us the
secrets of the mind.” He produced thousands of drawings of neu-
rons, as beautiful as they are complex, which are still printed in
neuroanatomy textbooks and exhibited in art museums. More
than 100 years after he received his Nobel Prize, we are indebted
to Cajal for our knowledge of what the nervous system looks like.
Some scientists even have Cajal’s drawings of neurons tattooed on
their bodies. “Only true artists are attracted to science,” he said.A NEW TRUTH
in Cajal’S day, the most advanced method for visualizing cells was
histology, an intricate and temperamental process of staining dis-
sected tissue with chemicals whose molecules clung to the subtle
architecture of the cells, rendering them miraculously visible
through a light microscope. With the primitive stains available,
researchers across Europe tried and failed to clarify the question of
what lies inside the brain, believed to be the organ of the mind. Then,
in 1873, in the kitchen of his apartment in Abbiategrasso, outside
Milan, Italian researcher Camillo Golgi, through some combination
of luck and skill, hit on a new technique that revolutionized neuro-
anatomy. “I have obtained magnificent results and hope to do even
better in the future,” Golgi wrote in a letter to a friend, touting his
method as so powerful that it could reveal the structure of nervous
tissue “even to the blind.” He called it the black reaction. One of Gol-
gi’s students recognized “the marvelous beauty of the black reac-
tion ... [which] allows even the layman to appreciate the images in
which the cell silhouette stands out as if it had been drawn by Leon-
ardo.” Cajal, who first saw the technique in the home of a colleague
who had recently returned from studying in Paris, was absolutely
smitten. “On the perfectly translucent yellow background,” Cajal
recalled, “sparse black filaments appeared that were smooth and
thin or thorny and thick, as well as black triangular stellate or fusi-
form bodies! One would have thought that they were designs in Chi-
nese ink on transparent Japanese paper ... Here everything was sim-
ple, clear, and unconfused ... The amazed eye could not be removed
from this contemplation. The dream technique is a reality!”
Although the black reaction dramatically reduced the num-
ber of nerve elements visible on a microscope slide, those ele-
ments were still so densely packed that their fibers appeared
inextricable from one another. Traditionally, researchers stud-
ied nervous tissue from adult humans who had died naturally
after a normal life span. The problem was that in the adult ner-
vous system, the fibers were already fully grown and therefore
extremely structurally complex. Looking for a solution to this
problem, Cajal turned to embryology—also known as ontogeny—
which he had first read about in a college textbook. “If we view
the natural sequence in reverse,” Cajal explained, “we should
hardly be surprised to find that many structural complexities of
the nervous system gradually disappear.” In the nervous systems
of younger specimens, cell bodies would in theory be simpler,
fibers shorter and less numerous, and the relationships among
them easier to discern. The nervous system was also well suited
to the embryological method because as axons grow, they develop
myelin sheaths—insulating layers of fat and protein—which repel
the silver microcrystals, preventing the enclosed fibers from
being stained. Younger axons without thick sheaths more fully
absorb the stain. In addition, mature axons, which sometimes
grow to be a few feet long, are more likely to get chopped off dur-
ing sectioning. “Since the full-grown forest turns out to be impen-