Each year, the Nobel Prizes in the sciences highlight humanity’s most profound advances in understanding nature and ourselves. The 2025 laureates in medicine, physics, and chemistry have pushed the boundaries of knowledge in three realms—the living body, the quantum world, and the architecture of matter. Their discoveries reveal how life maintains harmony within, how quantum laws shape even macroscopic reality, and how we can design materials that defy chaos itself. Together, they tell a story of curiosity, creativity, and the enduring human quest to uncover order in complexity.

These explanations are written in a clear, narrative style that connects scientific detail with human curiosity. Each story follows the path from problem to discovery, showing not only what the scientists achieved, but also how their insights reshaped our understanding of nature. The goal is to make complex ideas accessible without oversimplifying their depth—to reveal the beauty of science through storytelling.

Peacemakers in Our Blood

The Story of the 2025 Nobel Prize in Physiology or Medicine for the Discovery of the Mechanisms of Immune Tolerance

The Nobel Prize in Physiology or Medicine for 2025 was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their groundbreaking discoveries explaining how our immune system, a powerful defender against infections, restrains itself from attacking the body’s own tissues. Their work revealed the existence and function of key cells that act as peacemakers within the body, as well as the gene that serves as their main control switch. These discoveries not only solved one of the central mysteries of immunology but also opened the door to entirely new ways of treating some of today’s most challenging diseases, from cancer to autoimmune disorders.

Our immune system is an evolutionary masterpiece that protects us daily from thousands of different microbes. Its astonishing ability lies in distinguishing foreign invaders from the body’s own healthy cells. This process, known as immune tolerance, begins largely in the thymus gland, where T cells—the key players in immune responses—are tested. Those that react too strongly to the body’s own proteins are destroyed in a process called central tolerance. Yet this safety check is not perfect, as some potentially dangerous self-reactive cells escape. This long puzzled scientists and suggested that an additional, peripheral control mechanism must exist within the body.

Shimon Sakaguchi approached the problem at a time when research on so-called suppressor T cells—thought to inhibit immune responses—had been largely abandoned due to misleading conclusions and a lack of solid evidence. Despite this, Sakaguchi persisted, inspired by earlier experiments showing that surgical removal of the thymus in three-day-old mice did not weaken their immune system but instead triggered a devastating attack on their own organs. He hypothesized that within mature T cells there exists a special population acting as a safeguard.

In a landmark study published in The Journal of Immunology in 1995, he used cellular markers to confirm his hypothesis. He isolated a subgroup of T cells (CD4+) and demonstrated that within it was a smaller subset expressing an additional surface marker, CD25. When he injected T cells lacking this CD4+CD25+ population into mice without a functioning immune system, the animals developed severe autoimmune diseases. However, when these cells were included, the mice remained healthy. This provided irrefutable evidence for the existence of regulatory T cells (Tregs), which actively maintain peace within the body.

Independently of the work taking place in Japan, Mary E. Brunkow and Fred Ramsdell in the United States were solving the puzzle from a different perspective. They came into possession of a strain of mice known as scurfy, which had accidentally appeared in the 1940s in a laboratory at Oak Ridge during radiation studies conducted as part of the Manhattan Project. Because of a spontaneous genetic mutation, these mice suffered from a fatal autoimmune disease that affected only males, indicating a defect on the X chromosome. In the 1990s, when the tools of molecular biology were still in their infancy, the two scientists set out to find a single incorrect letter in the sequence of 170 million base pairs that make up the mouse X chromosome.

After years of dedicated work, they managed to narrow the search down to about 500,000 base pairs containing twenty potential genes. It was only in the very last one—the twentieth gene—that they found the error: an insertion of two extra letters in the sequence of a previously unknown gene, which they named Foxp3. To confirm their discovery, they inserted a healthy copy of the gene into the genome of scurfy mice, which completely protected the animals from the disease. Soon afterward, in collaboration with pediatricians from around the world, they demonstrated that mutations in the human version of this gene, FOXP3, cause a rare but deadly autoimmune disorder in boys known as IPEX syndrome.

With these findings, two key pillars were established—soon united by science into a coherent whole. Sakaguchi’s team quickly discovered that the Foxp3 gene is expressed almost exclusively in the regulatory T cells he had identified. Moreover, they showed that by artificially introducing Foxp3 into ordinary T cells, these could be converted into fully functional regulatory T cells. It thus became clear that Foxp3 was not just another gene among many, but a “master switch” or transcription factor directing the entire development and activity of these vital peacemakers of the immune system. The absence of a single type of cell, controlled by a single gene, is enough to unleash a devastating autoimmune response.

The work of this year’s laureates has provided science with molecular tools to finely tune the immune system, opening the way to new, targeted therapies. In cancer treatment, the aim is to suppress or eliminate regulatory T cells in the tumor microenvironment, since cancer cells often exploit them for self-protection. In autoimmune diseases and organ transplantation, the goal is the opposite: to increase the number or enhance the function of regulatory T cells to calm unwanted immune reactions. Various strategies are already being tested in clinical trials—from administering substances that stimulate the growth of these cells to genetic engineering approaches that equip them with an “address” so they can find and protect a specific organ.

Shimon Sakaguchi, born in 1951, is a professor at Osaka University in Japan. Mary E. Brunkow, born in 1961, is a senior program manager at the Institute for Systems Biology in Seattle, USA. Fred Ramsdell, born in 1960, serves as a scientific advisor at Sonoma Biotherapeutics in San Francisco, USA.

For younger readers, here’s a simple explanation of the 2025 Nobel Prize in Physiology or Medicine:

Imagine your body as a big city. Inside it lives an army of tiny guards. This army is called the immune system. Their job is to protect you all the time and chase away invaders like viruses and bacteria.

But sometimes, some guards get too eager. They want so badly to defend the body that they might accidentally attack its own healthy parts. This can cause problems and make you sick.

Scientists discovered that among these guards are also special supervisors. These are cells with a very specific job—to watch over the other guards and make sure they behave properly.

When they see a guard about to attack something that belongs to the body, they stop it and prevent the attack. In this way, they make sure the immune system works correctly and doesn’t cause harm.

But for these supervisors to exist, they need a special construction plan. This plan is written inside our bodies, in something called the Foxp3 gene. It’s the instruction that tells how an ordinary guard can become an effective supervisor. If there’s a mistake in this plan, the supervisors can’t develop properly, and the guards might start causing damage.

Three scientists—Mary, Fred, and Shimon—discovered these supervisors and their special blueprint. Their discovery is very important because it helps doctors find new ways to treat diseases. Now they can try to increase the number of supervisors to calm down an overactive immune system, or turn them off so the guards can fight harder against serious illnesses like cancer.

Jumping Through a Wall

The 2025 Nobel Prize in Physics for the Discovery of Macroscopic Quantum Tunneling and Energy Quantization in an Electric Circuit

Imagine throwing a ball at a wall. Naturally, you expect it to bounce back every time. That’s the world as we know it—the realm of “ordinary” classical physics that governs our everyday experience. Now imagine that, every once in a while, the ball would simply vanish on one side of the wall and appear on the other, without ever breaking through it. It sounds like science fiction, yet phenomena exactly like this occur in the microscopic world and are described by quantum mechanics. This strange effect is called tunneling.

The Nobel Prize in Physics for 2025 was awarded to a trio of scientists—John Clarke, Michel Devoret, and John Martinis—who demonstrated that this peculiar quantum “leap through a wall” can occur not just with a single particle, but with billions of them simultaneously, in a system large enough to hold in your hands.

It was a feat achieved in the mid-1980s at the University of California, Berkeley, by a team consisting of Professor John Clarke, postdoctoral researcher Michel Devoret, and doctoral student John Martinis. They built a special electrical circuit whose core was a so-called Josephson junction—two superconductors separated by an extremely thin insulating barrier. In superconductors, electrons pair up into what are known as Cooper pairs and begin to move in perfect synchrony, like a flawlessly coordinated dance troupe. Because of this, billions of pairs behave as a single, enormous “super-particle,” described by one wave function.

The researchers trapped this system in a state with no electrical voltage, as if it were stuck in a valley from which, according to the laws of classical physics, it could not escape. Then the impossible happened: the entire system, as a whole, “jumped” or tunneled through the energy barrier and produced a measurable voltage on the other side. This was the first clear evidence of macroscopic quantum tunneling.

But that wasn’t all. The team also showed that the system absorbed energy only in specific, discrete packets—or quanta—much like an atom does. The discovery was groundbreaking because it blurred the boundary between the microscopic world of atoms and our everyday, macroscopic reality. The experiment was even compared to the famous Schrödinger’s cat, since it created a large system that could be fully described by a single quantum equation.

The significance of this work extends far beyond a deeper understanding of nature. By demonstrating that quantum states can be controlled in a macroscopic circuit, the researchers opened the door to a new technological era. Josephson junctions became the building blocks of qubits—the fundamental units used in today’s quantum computers. The work of Clarke, Devoret, and Martinis not only unveiled one of the deepest mysteries of physics but also laid the foundation for a technological revolution whose full impact we have yet to see.

Hotels for Molecules

The 2025 Nobel Prize in Chemistry for the Development of Metal–Organic Frameworks and a New Era of Material Design

In nature, a fundamental law prevails: entropy—everything tends toward disorder. Molecules do not like to arrange themselves into perfect patterns; they prefer to intertwine into tangled, amorphous masses. That is why the idea of forcing them, through the strongest chemical bonds, to build ordered, crystalline structures was long considered unimaginable—almost heretical—by most chemists. They believed it simply couldn’t be done. Yet it was precisely this struggle against nature’s basic tendency that Omar Yaghi chose to take on, igniting a revolution that, together with Susumu Kitagawa and Richard Robson, earned him the 2025 Nobel Prize in Chemistry.

Yaghi rejected the traditional approach, which he mockingly called “shake and bake”—a kind of chemistry done without a clear recipe. He dreamed instead of becoming a molecular architect, constructing with atoms as if they were LEGO bricks. After years of experimentation, he finally discovered how to outsmart entropy. He found the precise balance of temperature, pressure, and time that allowed molecules, as they formed, to settle and align into an ordered structure—without sacrificing the strength of the bonds holding them together. The result was metal–organic frameworks (MOFs), materials with astonishing properties. His groundbreaking creation, known as MOF-5, possessed such an enormous internal surface area that a single handful of it could cover an entire football field.

This victory over chaos was not Yaghi’s alone. It was built on the work of two other pioneers. Richard Robson was the first to even imagine such a structure when, back in 1989, he created the first—albeit fragile—framework. Susumu Kitagawa then breathed life into these frameworks. He developed the first truly stable versions and discovered that they could even be flexible—that they could “breathe” and dynamically respond to the molecules entering them.

Today, these materials are already helping to solve some of humanity’s greatest challenges. In arid regions of the world, such as California’s Death Valley, they are being used to harvest clean drinking water directly from the air, with some devices requiring nothing more than sunlight to operate. On an industrial scale, hundreds of tons of these materials are used in cement plants to capture carbon dioxide from smokestacks, preventing it from entering the atmosphere. Other variants purify water of harmful chemicals such as PFAS, store hydrogen as a fuel, and even deliver medicines directly to cancer cells.

But the revolution is far from over. Yaghi now leads an institute where he combines the power of artificial intelligence with molecular architecture to accelerate the discovery of new materials for combating climate change. His ultimate goal is to create materials that operate according to a predefined code—something akin to a DNA sequence. He dreams of a material that could be “programmed” with instructions to convert captured carbon dioxide into fuel or other useful substances.

The story of MOFs is, in essence, a story of how understanding and mastering the fundamental laws of nature has given humanity the tools to build a better future.

Translated from the Slovene original, available here: kvarkadabra.net.

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THE ANATOMY OF KNOWLEDGE

Explaining the 2025 Nobel Prizes