The incredible record of the Nobel Prize in immunology – The Health Care Blog

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, declaring: “This Nobel Prize demonstrates how essential immunology is to medicine and human health. The ability to harness, modulate or constrain immune responses shows promise in a wide range of diseases, from diseases from autoimmune disorders to cancer, allergies, infectious diseases and beyond.”

This year’s prize 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 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 it 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 developed side by side over the past century.

Immunity has Latin roots from the word immunitas which, in Roman times, was proposed to denote the exemption of deserving citizens from the tax burden by their emperor. Protection against disease is a little more complicated than that and gives our white blood cells (WBC) a leading role. These cells are produced in the bone marrow, then bivouacked to the fetal thymus to receive instructions on how to attack only invaders, while sparing our own healthy cells.

The WBCs are organized into specialized divisions. WBC neutrophils engulf bacteria, fungi, and fungi as immediate first responders. Monocyte macrophages provide an additional first line of defense, literally engulfing and digesting damaged bacteria and cells through a process called “phagocytosis.” B cells produce specific proteins called antibodies, designed to learn and remember the specific chemical composition of invaders or “antigens.” They can quickly identify offenders and neutralize target bacteria, toxins and viruses. And T cells are specially designed to attack viruses hidden within human cells themselves.

The first-ever Nobel Prize in physiology or medicine was awarded 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 laboratory animals, and subsequently prove that the animals were now “protected” against tetanus and diphtheria infection. These antitoxins, generously used in New York, where diphtheria was the main cause of mortality among infants, quickly put an end to this sad epidemic.

The body’s internal defense system began to reveal its mysteries in the early 1900s. Brussels scientist Jules Bordet, studying anthrax bacteria, was able to identify not only protein antibodies in response to anthrax infection, but also a series of companion proteins. This cascade of proteins linked to antibodies reinforced their bacterial killing power. In 1919, Bordet received his Nobel Prize for discovering a series of “complementary” proteins that, when activated, help antibodies “punch holes” in bacterial cell walls and destroy them.

Victories against certain pathogens have been hard-won. In the case of poliovirus, which had a predilection to invade motor neurons, particularly in children, and cause paralysis, it took a remarkable collaboration between the government, university medical researchers, and local community doctors and nurses to ultimately succeed. The effort involved simultaneous testing in children of two very different vaccines.

Today’s vaccine skeptics, like RFK Jr., object to historical facts.

One need only look at graphs of the annual number of cases of diseases like diphtheria and polio, before and after the introduction of vaccines, to appreciate the dramatic preservation of life resulting from intentional but safe exposure to killed or attenuated vaccines.

At the same time, scientific theorists like the British scientist Nils Jerne. were right. But it took three decades for the scientific community to agree. His 1984 Nobel Prize said: “He claimed that all kinds of antibodies are already developed during the fetal stage and that the immune system works by selection. In 1971 he proved that lymphocytes learn themselves to recognize the body’s own substances in the thymus… An immunological reaction occurs when an antigen disrupts the balance of the system.”

At that time, these Jerne leukocytes had been called “B lymphocytes” by an Australian scientist named Macfarlane Burnet, a Nobel Prize winner in 1960, who had also observed antibodies already established in the fetus. These individuals were part of a long tradition of imagineers of medical science. For example, Robert Koch’s chief assistant was Paul Ehrlich, who imagined the inner workings of the cell this way: “In his view, cells were surrounded by tiny spike-like molecular structures, or “side chains,” as he called them, and these were responsible for trapping nutrients and other chemicals and drawing them inside the cell.

The “side chains” were actually antibodies, large protein molecules made up of two long chains and two short chains. It was later proven that about 80% of the four chains are identical in all antibodies. The remaining 20% ​​varies, forming unique antigen binding sites for each antigen. Almost immediately, scientists began wondering if they could reconfigure these large proteins to create “monoclonal antibodies” to fight cancers like melanoma.

Imagination sometimes took over. But more often than not, direct problem solving uncovers answers. This was the case when 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 is that certain microorganisms (viruses) settle inside human cells and obtain a protected status there.

To solve this problem, humans have a specialized WBC, called a “T cell.” But for T cells to destroy an intracellular virus, they 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 worth preserving. The HLA fingerprint is that signal.

Which brings us back to the latest Nobel Prize awarded last week for discoveries the committee called “fundamental.” How so? In the 1980s, 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, during the first weeks of life. It then took another two decades (in 2001) for Drs Brunkow and Ramsdell to identify the gene (FOXP3) responsible for the creation of “regulatory T cells”. No gene – no regulatory T cells.

Why is this important? Two reasons:

1. 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 could selectively deactivate the FOXP3 gene and allow proper destruction of these cancer cells by the body’s regular T cells.
2. On the other hand, autoimmune diseases (in which the body turns in on itself) appear to be fueled by the absence of “effective regulatory T cells activated by the FOXP3 gene.” New drugs to activate the gene and its critical cells could stop the self-destructive process.

Immunology is a mysterious, complex and constantly evolving field of study. Both the host and predators (including anything from an invading microorganism to a malicious cancer cell to an unanswered splinter of wood) could be deadly. But to respond, the host must first identify the threat and activate a specific and effective response, without inadvertently harming the host itself. As our understanding has grown, harnessing the immune system to hunt metastatic cancer cells, suppress lethal 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 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)