Author: Mike Magee
With the announcement last week of the 2025 Nobel Prize in Physiology or Medicine, the American Association of Immunologists (AAI) was understandably victorious, saying: “This Nobel Prize demonstrates the central role of immunology to medicine and human health. The ability to harness, modulate, or suppress immune responses holds promise for diseases ranging from autoimmune diseases to cancer, allergies, infectious diseases, and more.”
This year’s award, presented to Mary E. Brunkow, Fred Ramsdell, and Dr. Shimon Sakaguchi, could not 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 declares, “Since 1901, the Nobel Prize has been awarded to 27 AAI members for their innovations and achievements in immunology and related disciplines.” The addition of AAI Distinguished Fellow Dr. Sakaguchi brings this number to 28.
Over the past century, the field of immunology has grown side by side with the Nobel Prize in Physiology or Medicine.
The Latin root of immunity is “immunitas,” which in Roman times meant an emperor's exemption from the burden of taxation on worthy citizens. Preventing disease is a little more complicated than that, and white blood cells (WBCs) play an important role. These cells are produced in the bone marrow and then camp out in the fetal thymus, receiving instructions on how to attack only invaders but leave our own healthy cells unharmed.
The WBC is made up of specialized departments. White blood cells neutrophils act as first responders to phagocytose bacteria, fungi, and fungi. Mononuclear macrophages are an additional first line of defense, engulfing 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 makeup, or “antigen,” of a specific invader. They quickly identify culprits and neutralize target bacteria, toxins and viruses. T cells are specifically designed to track down viruses hidden within human cells.
German scientist Emil von Behring won the first Nobel Prize in Physiology or Medicine eleven years after he demonstrated “passive immunity.” He was able to isolate poisons, or toxins, from the tetanus and diphtheria microorganisms, inject them into experimental animals, and subsequently demonstrated that the animals were now “protected” from tetanus and diphtheria infection. These antitoxins were used in large quantities in New York City, where diphtheria was a major killer of infants, quickly ending the tragic epidemic.
The body's internal defense system began to unravel its mysteries in the early 1900s. While studying anthrax bacteria, Brussels scientist Jules Bordet was able to identify not only protein antibodies against anthrax infection, but also a series of companion proteins. This cascade of proteins linked to the antibodies enhances their bacteria-killing abilities. Beaudet won the Nobel Prize in 1919 for his discovery of a series of “complement” proteins that, when activated, help antibodies “drill holes” in bacterial cell walls and destroy them.
Victory against some pathogens will be hard-fought. In the case of poliovirus, which tends to invade motor neurons, especially in children, and cause paralysis, ultimate success will require close collaboration between governments, academic medical researchers, and local community doctors and nurses. The work involves testing two very different vaccines in children simultaneously.
Currently, vaccine skeptics like RFK Jr. argue against historical facts.
One need only examine charts of annual case numbers for diseases such as diphtheria and polio before and after the introduction of vaccines to see the remarkable saving of life resulting from intentional but safe exposure to inactivated or attenuated vaccines.
During the same era, scientific theorists such as the British scientist Nils Jerne. Proven correct. But it took the scientific community three decades to reach a consensus. When he won the Nobel Prize in 1984, he wrote: “He asserted that various antibodies are formed in the fetal stage and that the immune system acts through selection. In 1971, he demonstrated that lymphocytes are able to self-recognize the body's own substances in the thymus… An immune response occurs when an antigen disturbs the balance of the system.”
At that time, these white blood cells in Jayne were called “B lymphocytes” by the Australian scientist Macfarlane Burnet (1960 Nobel Prize winner), who also discovered that antibodies had been built up in the fetus. These men were part of a long tradition of medical scientific imagineers. For example, Robert Koch's chief assistant Paul Ehrlich imagined the inner workings of cells this way: “He saw cells as surrounded by tiny, spike-like molecular structures (which he called 'side chains') that were responsible for trapping nutrients and other chemicals and drawing them into the cell.”
The “side chains” are actually antibodies, large protein molecules made up of two long chains and two short chains. It was later shown that approximately 80% of the four chains in all antibodies are identical. The remaining 20% are distinct, forming unique antigen-binding sites for each antigen. Almost immediately, scientists began to wonder whether they could reconfigure these large proteins to make “monoclonal antibodies” to fight cancers such as melanoma.
Imagination sometimes gets the better of you. But more often than not, the answer can be found by directly addressing the problem. This is the case with the “HLA (human leukocyte antigen) fingerprint” described by French scientist Jean Dausset. One question always leads to another. In this case, the question “Why do HLAs exist?” It was ultimately discovered that certain microorganisms (viruses) reside within human cells and acquire a protected status.
To solve this problem, humans have a special type of white blood cells called “T cells.” But for a T cell to eliminate intracellular viruses, it must “recognize and respond” to two information signals. First, the antigens of the virus. Second, a permissive signal informing the virus that it is in a host cell worthy of preservation. Fingerprint HLA is this signal.
Which brings us back to last week's latest Nobel Prize ceremony, which was awarded to discoveries that the committee labeled “fundamental.” how so? In the 1980s, Dr. Shimon Sakaguchi demonstrated that humans have a backup system to protect against errant self-attacks: specialized “regulatory T cells” that develop in the thymus during the first few weeks of life. It then took Dr. Brunkow and Dr. Ramsdell another twenty years (2001) to identify the gene responsible for generating “regulatory T cells” (FOXP3). No genes – no regulatory T cells.
Why is this important? Two reasons:
- It turns out that cancer has a nasty habit of surrounding itself with regulatory T cells to protect them from the immune system, which would otherwise destroy them. New drugs may be able to selectively turn off the FOXP3 gene and allow the body's regular T cells to properly destroy these cancer cells.
- On the other hand, autoimmune diseases (which the body starts on its own) appear to be exacerbated by a lack of effective “regulatory T cells” enabled by the FOXP3 gene. New drugs designed to turn on this gene and its key cells may shut down the self-destructive process.
Immunology is a mysterious, complex, and ever-evolving field of study. Hosts and predators, ranging from microbial invaders to rogue cancer cells to untreated wood debris, can be deadly. But to respond, the host must first identify the threat and initiate a specific and effective response without inadvertently harming the host itself. As our understanding continues to deepen, it is clear that in the not-too-distant future, it will be within our grasp to harness the immune system to hunt down metastatic cancer cells, or suppress fatal rejection of transplanted organs, or modify itself to avoid autoimmune destruction.
All in all, science is a process, and Robert F. Kennedy Jr. was not in a position to judge it.
Mike Magee, MD, is a medical historian and regular contributor to THCB. He is the author of “Code Blue: Inside the American Medical-Industrial Complex.” (Grove/2020)
