In Memoriam of Marian Kies
How a Quiet Scientist Unlocked a New Frontier in Brain Disease
In the grand narrative of neuroscience, we celebrate the discoverers of neurons and the mappers of brain regions. But what about the architects of the brain's very insulation? For decades, the story of Dr. Marian Kies was a quiet footnote, yet her work laid the foundation for our understanding of multiple sclerosis and autoimmune brain diseases. This is the story of the woman who proved our immune system could turn against our own brain, and in doing so, gave science one of its most powerful tools.
To understand the significance of Kies' work, we must first appreciate myelin. Imagine the nerve fibers in your brain and spinal cord as electrical wires.
This is the copper core of the wire, the long projection of a neuron that carries electrical signals.
This is the plastic insulation wrapped tightly around the axon. It's not a continuous tube but a series of segments, like sausages on a string.
This biological insulation is crucial. It prevents electrical signals from leaking out and, astonishingly, speeds up signal transmission through a process called "saltatory conduction." The signal literally jumps from one gap in the myelin to the next, allowing you to think, move, and feel with incredible speed and precision.
When this myelin sheath deteriorates, as in Multiple Sclerosis (MS), the electrical signals short-circuit. This leads to the wide-ranging symptoms of MS: numbness, paralysis, vision loss, and cognitive decline. In the 1950s, scientists knew MS involved demyelination, but a burning question remained: What causes the body to attack its own myelin?
In 1958, Marian Kies and her colleague at the National Institutes of Health (NIH), Dr. Eliot Sokol, designed a landmark experiment. Their goal was audacious: to prove that the immune system alone could cause demyelination, and to create a reliable laboratory model to study it. This model would later be known as Experimental Autoimmune Encephalomyelitis (EAE).
Kies' experiment was elegant in its simplicity and powerful in its implications. Here is how they conducted it:
They carefully extracted myelin and other brain tissue proteins from the spinal cords of healthy guinea pigs.
This brain tissue was then homogenized and mixed with a powerful adjuvant—a substance that supercharges the immune response. The adjuvant used was Freund's Complete Adjuvant, which contains killed tuberculosis bacteria.
This potent mixture—the brain tissue emulsion—was injected under the skin of a separate group of live, healthy guinea pigs.
The team then meticulously observed the injected animals for signs of neurological disease.
The results were striking. Within two to three weeks, the injected guinea pigs began to show severe neurological symptoms, including:
When Kies and Sokol examined the brain and spinal cord tissue of these sick animals, they found their answer: widespread inflammation and patches of demyelination that looked remarkably similar to the lesions found in the brains of human MS patients.
This was the breakthrough. They had demonstrated that provoking the immune system with central nervous system tissue could cause it to "turn traitor" and launch a destructive attack on the brain's own myelin. This proved that demyelination could be a purely autoimmune process. The EAE model was born, and it remains the primary animal model used worldwide for MS research today.
| Days Post-Injection | Observed Symptoms | Severity Grade (1-5) |
|---|---|---|
| 1-10 | No visible symptoms | 0 |
| 11-14 | Lethargy, slight weight loss | 1 |
| 15-18 | Loss of tail tone, mild hind limb weakness | 2 |
| 19-21 | Partial hind limb paralysis | 3 |
| 22-25 | Complete hind limb paralysis | 4 |
| 26+ | Forelimb paralysis, moribund state | 5 |
Caption: A simplified timeline of disease progression in the EAE model, based on Kies' original observations. The severity grading system allows researchers to quantitatively compare the course of the disease.
| Tissue Sample (Source) | Presence of Inflammation | Presence of Demyelination | Similarity to Human MS Lesions |
|---|---|---|---|
| Healthy Guinea Pig | None | None | None |
| Injected Guinea Pig | Extensive | Extensive, in multiple foci | High |
Caption: The comparison of tissue samples provided the physical proof that the neurological symptoms were caused by immune-mediated damage to the myelin sheath.
| Injection Components | Incidence of Disease (%) | Average Day of Onset |
|---|---|---|
| Saline (Control) | 0% | N/A |
| Brain Tissue Alone | < 10% | > 30 days |
| Brain Tissue + Adjuvant | > 90% | 14-21 days |
Caption: This data underscores a critical finding from Kies' work: the adjuvant is not just a passive carrier. It is essential for powerfully activating the immune system to break tolerance and trigger the autoimmune attack, making the model reproducible and reliable.
Kies' experiment relied on a specific set of research reagents. Here's a breakdown of the essential tools in her toolkit and those still used in immunology today.
This is the "antigen" – the substance that the immune system learns to recognize as a foreign invader. It contains myelin proteins like MBP (Myelin Basic Protein), which Kies would later help isolate.
This is the "danger signal." It contains killed bacteria that intensely stimulate the innate immune system, creating a local inflammatory environment that forces the immune system to pay strong attention to the co-injected CNS antigen.
The animal model of choice. Their immune response to myelin proteins is particularly robust, making them ideal for establishing the initial model.
Although purified later, MBP became a key reagent directly stemming from this work. It is one of the major proteins in myelin that the immune system targets.
Marian Kies' 1958 experiment was a cornerstone of modern neuroimmunology . It provided the first direct, reproducible evidence that an immune response could target the brain, fundamentally changing how scientists viewed diseases like MS . Her work did not stop there; she was among the first to isolate and characterize myelin basic protein (MBP), the very "bullseye" the immune system attacks .
1958
Year of the landmark experiment
90%
Disease incidence with adjuvant
60+
Years EAE model has been used
Despite her monumental contributions, Kies remained a humble and dedicated scientist, more comfortable in the lab than in the spotlight. Her legacy, however, is anything but quiet. Every time a researcher uses the EAE model to test a new potential therapy for MS, every time a new insight into autoimmunity is gleaned, they are standing on the foundation built by Marian Kies. She was the quiet architect who gave us the blueprint to understand one of medicine's most complex puzzles.