By MIKE MAGEE
With the announcement of the 2025 Nobel Prize in Physiology or Medicine last week, the American Association of Immunologists (AAI) took an understandable victory lap, stating: “This Nobel Prize demonstrates how immunology is central to medicine and human health. The ability to harness, modulate, or restrain immune responses holds promise across a vast range of diseases — from autoimmune conditions to cancer, allergies, infectious disease, and beyond.”
This year’s award went to Mary E. Brunkow, Fred Ramsdell and Dr. Shimon Sakaguchi, and it couldn’t have come at a better time as our nation’s scientific community and their governmental, academic and corporate science leaders push back against vaccine skeptic RFK Jr.
As the AAI proudly exclaims, “Since 1901, Nobel Prizes have been awarded to 27 AAI members for their innovation and achievements in immunology and related disciplines.” Make that 28 with the addition of Dr. Sakaguchi, a Distinguished Fellow of AAI.
The field of Immunology and the Nobel Prize in Physiology or Medicine have grown side by side over the past century.
Immunity has Latin roots from the word immunitas which in Roman times was offered to denote exemption from the burden of taxation to worthy citizens by their Emperor. Protection from disease is a bit more complicated than that and offers our White Blood Cells (WBCs) a starring role. These cells are produced in the bone marrow, then bivouacked to the fetal thymus for instruction on how to attack only invaders, but spare our own healthy cells.
WBC’s are organized in specialized divisions. WBC neutrophils engulf bacterial, fungi, and fungi as immediate first responders. Monocyte macrophages are an additional first line of defense, literally gobbling and digesting bacteria and damaged cells through a process called “phagocytosis.” B-cells produce specific proteins called antibodies, designed to learn and remember specific invaders chemical make-up or “antigen.” They can ID offenders quickly and neutralize target bacteria, toxins, and viruses. And T-cells are specially designed to go after viruses hidden within the human cells themselves.
The first ever Nobel Prize in Physiology or Medicine went to German scientist, Emil von Behring, eleven years after he demonstrated “passive immunity.” He was able to isolate poisons or toxins derived from tetanus and diphtheria microorganisms, inject them into lab animals, and subsequently prove that the animals were now “protected” from tetanus and diphtheria infection. These antitoxins, liberally employed in New York City, where diphtheria was the major killer of infants, quickly ended that sad epidemic.
The body’s inner defense system began to reveal its mysteries in the early 1900s. Brussel scientist Jules Bordet, while studying the bacteria Anthrax, was able to not only identified protein antibodies in response to anthrax infection, but also a series of companion proteins. This cascade of proteins linked to the antibodies enhanced their bacterial killing power. In 1919 Bordet received his Nobel Prize for the discovery of a series of “complement” proteins, which when activated help antibodies “drill holes” through bacterial cell walls and destroy them.
Victories against certain pathogens were hard fought. In the case of poliovirus, which had a predilection to invade motor neurons, especially in children, and cause paralysis, it required a remarkable collaboration between government, academic medical researchers and local community based doctors and nurses to ultimately succeed. The effort involved simultaneous testing in children of two very different vaccines.
Current vaccine skeptics like RFK Jr. argue against historic facts.
One need only to examine graphs of annual case loads for diseases like diphtheria and polio, before and after the introduction of vaccines, to appreciate the dramatic preservation of life that resulted from intentional but safe exposure to killed or attenuated vaccines.
In this same era, scientific theorists like UK scientist Nils Jerne. were proven right. But it took three decades for the scientific community to agree. His 1984 Nobel Prize read, “He asserted that all kinds of antibodies already have developed during the fetus stage and that the immune system functions through selection. In 1971, he proved that lymphocytes teach themselves to recognize the body’s own substances in the thymus gland… An immunological reaction arises when an antigen disturbs the system’s equilibrium.”
By then, those Jerne’s WBCs had been termed “B lymphocytes” by an Australian scientist named Macfarlane Burnet, a 1960 Nobel laureate, who also saw antibodies already established in the fetus. These individuals were part of a long tradition of medical science imagineers. For example, Robert Koch’s main assistant was Paul Ehrlich, who imagined the inner workings of the cell this way, “In his eyes, cells were surrounded by tiny spike-like molecular structures, or ‘side-chains’, as he called them, and that these were responsible for trapping nutrients and other chemicals, and for drawing them inside the cell.”
The “side chains” were in fact antibodies, large protein molecules made up of two long and two short chains. It was later proven that roughly 80% of the four chains are identical in all antibodies. The remaining 20% varies, forming unique antigen bonding sites for each and every antigen. Almost immediately scientists began to wonder whether they could reconfigure these large proteins to create “monoclonal antibodies” to fight cancers like melanoma.
Imagination has occasionally carried the day. But more often direct problem solving uncovers answers. That was the case when French scientist, Jean Dausset described an “HLA (human leucocyte antigen) fingerprint.” One question always leads to another. In this case, “Why do HLAs exist?” What was eventually uncovered was that certain microorganisms (viruses) take up residence inside human cells gaining protected status.
To deal with the problem, humans possess a specialized WBC – termed “T-cell.” But for the T-cell to destroy an intracellular virus, it must “recognize and respond” to two messaging signals. First, the virus’s antigen. Second, a permissive signal that informs that the virus is housed in a host cell that deserves preservation. The fingerprint HLA is that signal.
Which brings us back to the most recent Nobel award last week for discoveries that the committee labeled as “fundamental.” How so? In the 1980’s Dr. Shimon Sakaguchi proved that humans have a backup system to prevent errant self-attacks – specialized “regulatory T cells” that develop in the thymus after birth in the first few weeks of life. It then took two more decades (in 2001) for Dr. Brunkow and Dr. Ramsdell to identify the gene (FOXP3) responsible for creating “regulatory T-cells.” No gene – no regulatory T-cells.
Why is this important? Two reasons:
- Turns out, cancers have a nasty habit of surrounding themselves with regulatory T-cells that protect them from an immune system that would otherwise eliminate them. New drugs may be able to selectively turn off the FOXP3 gene and allow appropriate destruction of these cancer cells by the bodies regular T-cells.
- On the flip side, autoimmune diseases (where the body turns on itself) appear to be fueled by the absence of effective FOXP3 gene enabled “regulatory T-cells. New drugs geared to turn on the gene and its critical cells may shut down the self-destructive process.
Immunology is a mysterious, complex, and constantly evolving field of study. Host and predators (including everything from a microorganism invader to a rogue cancer cell, to a wooden splinter left unaddressed) could be fatal. But to respond the host must first identify the threat, and activate a specific and effective response, without inadvertently injuring the host itself. As our understanding has grown, harnessing the immune system to chase down metastatic cancer cells, or suppress a deadly rejection of a transplanted organ, or self-modify to avoid auto-immune destruction are clearly within our grasp in the not too distant future.
So to sum it all up, science is a process and RFK Jr. is ill-equipped to referee it.
Mike Magee MD is a Medical Historian and regular contributor to THCB. He is the author of CODE BLUE: Inside America’s Medical Industrial Complex. (Grove/2020)
