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 by stating: “This Nobel Prize demonstrates how immunology is fundamental to medicine and human health. The ability to harness, modulate or restrict immune responses holds promise in a wide range of diseases, from autoimmune conditions to cancer, allergies, infectious diseases and more.”
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 its government, academic, and corporate scientific leaders grapple with Vaccine skeptic RFK Jr.
Ash the AAI proudly exclaims, “Since 1901, 27 AAI members have been awarded Nobel Prizes for their innovation and achievements in immunology and related disciplines.” I reached 28 with the addition of Dr. Sakaguchi, a distinguished member of the AAI.
The field of Immunology and the Nobel Prize in Physiology or Medicine have grown together over the last century.
Immunity has Latin roots of the word. immunities which in Roman times was offered to denote the exemption from the burden of taxes to worthy citizens by their Emperor. Protection against disease is a little more complicated than that and gives our white blood cells (WBC) a starring role. These cells are produced in the bone marrow and then bivouacked in the fetal thymus for instructions on how to attack only the invaders, but respecting our own healthy cells.
The WBCs are organized into specialized divisions. WBC neutrophils engulf bacteria, fungi, and fungi as immediate first responders. Monocyte macrophages are an additional first line of defense, literally devouring and digesting bacteria and damaged cells through a process called “phagocytosis.” B cells produce specific proteins called antibodies, designed to learn and remember the chemical composition or “antigen” of specific invaders. They can identify offenders quickly and neutralize target bacteria, toxins and viruses. And T cells are specially designed to go after viruses hidden inside human cells themselves.
The first Nobel Prize in Physiology or Medicine went to the 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 laboratory animals, and subsequently demonstrate that the animals were now “protected” from tetanus and diphtheria infection. These antitoxins, used liberally in New York City, where diphtheria was the main cause of death among children, it quickly put an end to that sad epidemic.
The body’s internal defense system began to reveal its mysteries at the beginning of the 20th century. Brussels scientist Julio BordetWhile studying the Anthrax bacteria, he was able to not only identify protein antibodies in response to anthrax infection, but also a number of accompanying proteins. This cascade of proteins linked to the antibodies improved their bacteria-destroying power. In 1919, Bordet received his Nobel Prize for the discovery of a series of “complementary” proteins that, when activated, help antibodies “punch holes” through the walls of bacterial cells and destroy them.
Victories against certain pathogens were very close. In the case of polio virus, which had a predilection for invading motor neurons, especially in children, and causing paralysis, required a remarkable collaboration between the government, academic medical researchers, and local community doctors and nurses to finally succeed. The effort involved simultaneous testing in children of two very different vaccines.
Today’s vaccine skeptics, like RFK Jr., argue against historical facts.
It is only necessary examine charts of annual cases of diseases such as 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.
At this same time, scientific theorists such as scientists in the United Kingdom Nils Jerne. They were proven right. But it took three decades for the scientific community to agree. His 1984 Nobel Prize stated: “He stated that during the fetal stage all types of antibodies have already been developed and that the immune system works by selection. In 1971, he demonstrated that lymphocytes learn by themselves to recognize the body’s own substances in the thymus gland… An immunological reaction arises when an antigen alters the balance of the system.”
By then, Jerne’s white blood cells had been named “B lymphocytes” by an Australian scientist named Burnet MacfarlaneNobel Prize winner of 1960, which also saw antibodies already established in the fetus. These individuals were part of a long tradition of imagineers of medical science. For example, Robert Koch was senior assistant Pablo Ehrlich, who imagined the inner workings of the cell this way: “In his view, cells were surrounded by small spike-like molecular structures, or ‘side chains,’ as he called them, and that these were responsible for trapping nutrients and other chemicals and drawing them into the cell.”
The “side chains” were actually antibodies, large protein molecules made up of two long and two short chains. It was later shown that approximately 80% of the four chains are identical in all antibodies. The remaining 20% vary, forming antigen binding sites unique to each and every antigen. Almost immediately, scientists began to wonder if they could reconfigure these large proteins to create “monoclonal antibodies” to combat cancers such as melanoma.
Sometimes imagination has triumphed. But more often than not, direct problem solving uncovers answers. This was the case when the French scientist, Jean Dausset described an “HLA (human leukocyte antigen) fingerprint.” One question always leads to another. In this case, “Why do HLAs exist?” What was finally discovered was that certain microorganisms (viruses) settle inside human cells and obtain a protected state.
To address the problem, humans have a specialized white blood cell, called a “T cell.” But for the T cell to destroy an intracellular virus, it must “recognize and respond” to two messaging signals. First, the virus antigen. Second, a permissive signal that informs that the virus is hosted in a host cell that deserves conservation. The HLA fingerprint is that signal.
Which brings us back to last week’s most recent Nobel Prize for discoveries the committee called “fundamental.” How is that? In the 1980s Dr. Shimon Sakaguchi showed 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 weeks of life. Then it took two more decades (in 2001) to Dr. Brunkov and Dr. Ramsdell to identify the gene (FOXP3) responsible for creating “regulatory T cells.” No genes, no regulatory T cells.
Why is this important? Two reasons:
- It turns out that 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 can selectively disable the FOXP3 gene and allow proper destruction of these cancer cells by the body’s normal T cells.
- On the other hand, autoimmune diseases (in which the body turns against itself) appear to be fueled by the absence of FOXP3 gene-enabled regulatory T cells. New drugs designed to activate the gene and its critical cells may stop the self-destructive process.
Immunology is a mysterious, complex and constantly evolving field of study. The host and predators (including everything from an invading microorganism to a rogue cancer cell to an unaddressed splinter of wood) could be fatal. But to respond, the host must first identify the threat and activate a specific, effective response, without inadvertently harming the host itself. As our knowledge has grown, harnessing the immune system to pursue metastatic cancer cells, or suppress fatal rejection of a transplanted organ, or self-modify to avoid autoimmune destruction is clearly within our reach in the not-too-distant future.
So, to summarize, science is a process and RFK Jr. is not prepared to arbitrate 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. (Greet/2020)
