When people hear the word "immunity," many likely think of a "defense system to protect the body from pathogens and viruses." However, when reconsidered from a biological perspective, one realizes that it hides a more profound, almost philosophical theme: "What is the self (oneself)?"

For the immune system to function correctly, it must accurately determine whether something in the body is the "self to be protected" or a "foreign substance (non-self) to be excluded." If this becomes ambiguous, the system will either fail to function or attack itself. In other words, the boundary of the existence known as the "self" must first be established.

While this mechanism has been studied in detail in vertebrates, including humans, much of the system in "invertebrates," which make up the vast majority of species on Earth, remained shrouded in mystery for a long time.

By integrating insights from developmental biology and immunobiology, Associate Professor Furukawa has produced a series of groundbreaking discoveries that overturn textbook common sense by tracking the dynamic growth process (metamorphosis) of the Blue Bat Star, which lives widely in the waters around Japan, and the behavior of microscopic cells within its body. bat star

A prime example is the "drama of starfish self-establishment."

The Blue Bat Star changes its appearance dramatically throughout its life. A "larval (child)" starfish hatched from an egg drifts in the ocean in a form far removed from the star shape familiar to us. Later, it settles on rocky areas and undergoes a dramatic makeover called "metamorphosis," finally being reborn as a star-shaped "juvenile starfish."

Research by Associate Professor Furukawa and others has revealed that starfish in this larval stage have an extremely strange characteristic: they "do not reject cells from other individuals of the same species at all."

In our bodies, if cells or organs from another person are transplanted, the immune system recognizes them as "non-self" and triggers a violent rejection. However, the immune system of a starfish in its larval stage accepts all living cells of the same species as "self." This means that the "immunological self," which strictly distinguishes one individual from another, has not yet been established.

Associate Professor Furukawa views this recognition mode of "same species = self" as the possible "origin of immunity."

"I believe that immunity did not suddenly appear after multicellular organisms were born, but is based on abilities from when they were unicellular organisms. What is necessary for a unicellular organism to survive is to avoid cannibalism and engage in sexual reproduction. To do that, a system is needed to recognize others who are not oneself, and to identify and tolerate members of the same group. I believe that is the origin of immunity, and its remnants can be found in larval starfish."

So, when does a starfish recognize members of the same group as "non-self"? In 2022, after repeated experiments, Associate Professor Furukawa's group became the first in the world to determine that the "self" is established during the "juvenile starfish" stage, shortly after it takes on a star shape.

The fact that the self is established upon the completion of metamorphosis holds significant meaning when considering what the self is. This is because, in fact, "stimulation by non-self (bacteria) in the environment is essential for metamorphosis."

Wild Blue Bat Stars settle on rocky areas and begin metamorphosis as they end their larval stage. At this time, it is thought that they decide on a settling location based on the presence or absence of a biofilm created by specific bacteria. In experiments, starfish are made to settle on gravel spread in a tank, but if this gravel is pre-sterilized with high heat to completely exclude bacteria, the starfish become unable to metamorphose.

The fact that life cannot even become "itself" in a completely isolated environment evokes the process by which we form our own selves within society, transcending the framework of biology; it can be called a truly beautiful dynamism of life.

Associate Professor Furukawa says, "I keep thinking about what the self is in the first place, but it is actually something very ambiguous. Simply put, the immune system is a system that determines the boundary between self and other—that is, it defines the self. Therefore, a change in the immune system means a change in the definition of the self. However, for example, when you are infected with a pathogen or get a vaccine, new immune memories are added, so the immune system changes little by little, but you yourself do not change. It's mysterious that your existence as 'yourself' is maintained no matter how much the immunity inside your body changes. In other words, the self is not a fixed, universal thing, but the very act of continuing to change—a 'self as an act,' so to speak."

The brilliance of Associate Professor Furukawa's research does not stop at such philosophical reflections. He is also approaching the possibility that the starfish metamorphosis process proceeds through a mechanism similar to human neurodegenerative diseases faced by modern medical sciences, such as Alzheimer's and Parkinson's.

This emerged as a "new fact" while comprehensively investigating the genes involved in the process of a starfish metamorphosing from a larva to an adult. The research group was reportedly perplexed when, instead of the expected gene networks related to the formation of the immune system directly linked to the establishment of the self, gene networks related to human neurodegenerative diseases appeared one after another.

Therefore, Associate Professor Furukawa and his team formulated a bold hypothesis.

When a larval starfish metamorphoses into its star-shaped adult form, it dismantles and disposes of its larval-type neural network. On the other hand, human Alzheimer's disease is also a disease where neurons die and the brain atrophies, and the "process of neurons dying" in both cases is strikingly similar. In other words, could starfish metamorphosis and Alzheimer's disease proceed through very similar molecular mechanisms?

While chasing that mystery in 2023, a paper providing a hint was published in the journal "Nature." An American research group determined that starfish have no torso and that "most of the star-shaped body corresponds to the head (brain) of us vertebrates."

Associate Professor Furukawa describes his surprise at that time: "If most of the body is a head, then the process of metamorphosis becomes exactly a 'model of brain development.' It's like the brain is being built when it goes from larva to adult. Since development and pathology are two sides of the same coin, I thought they were connected."

If the details of these mechanisms are elucidated, it could potentially be useful for research such as the treatment of neurodegenerative diseases in the future.

The momentum of Associate Professor Furukawa's group shows no signs of stopping. In 2025, they announced the discovery of the "ancestor of platelets," which once again rewrote life science textbooks and garnered significant attention.

Platelets, which clot blood, are fragments of cells that do not have a nucleus, and until now, they were considered a "privilege of mammals only (a highly evolved system)." The global common sense until now was that an invertebrate like a starfish could not possibly have such a thing.

However, Associate Professor Furukawa's group discovered cells considered to be the ancestors of those "platelets" inside the body of a starfish. They revealed that "platelets without a nucleus," previously thought to be unique to mammals, also exist in starfish and contribute to immunity and hemostasis. He said they thoroughly questioned and investigated a phenomenon that initially appeared to be a "failure" by a student in the lab.

The 19th-century naturalist Louis Agassiz left the words, "Study nature, not books." Associate Professor Furukawa cherishes these words, which are displayed in the library of the Woods Hole Oceanographic Institution in the U.S., as he continues his research with his students.

"I think Agassiz's words mean not to believe in and follow authority unconditionally. Studying is important, but what is written in books is not always correct, and the development of science is a history of rewriting textbooks."

Associate Professor Furukawa considers the starfish his "partner," but choosing it as a research subject was accidental.

As a child, he vaguely aspired to be a researcher. Keio University, the only university he was accepted to, did not have a department of biology at the time. He lost motivation, devoted himself to band activities with the aim of becoming a professional, and repeatedly failed to advance to the next grade.

However, that turned out to be a blessing, as it opened the path to the newly established Department of Biosciences and Informatics. Thinking he couldn't win if he competed normally against his talented peers, Associate Professor Furukawa went around asking them what their "least favorite theme" was and chose the then-unpopular starfish as his research subject.

A year after starting his research, he learned that Ilya Mechnikov, a Russian zoologist who won the Nobel Prize in Physiology or Medicine in 1908, first discovered phagocytes (immune cells) through research using starfish. To Associate Professor Furukawa's eyes, starfish—which almost no one in the world had touched since Mechnikov—appeared as a "treasure trove" with no competitors.

He still vividly remembers the moment during his student days, after spending over a year, when he first identified part of a gene involved in immunity. "I'm the only one in the world who knows this sequence. Thinking that gave me goosebumps. I kept it to myself for a whole night without telling anyone. Once you taste that addictive joy, you can't stop being a researcher."

Given how deeply he has delved into biology, one might think he loves living things, but in fact, it's not that he loves the creatures themselves. What attracted him was the mechanism.

"I originally liked plastic models and miniatures, and among them, there are things that move like living creatures, right? But even if they move like living creatures, they aren't alive. Where is the difference between something that is alive and something that isn't? I've been very interested in that for a long time."

Where is the difference between living and non-living things, and where is the difference between self and non-self? This exploration, which transcends the framework of biology, is developing into a joint project involving philosophy researchers. Furthermore, Associate Professor Furukawa is considering applications in social science fields such as psychology and social media networks.

"The phenomenon of being able or unable to become friends in social media clusters can also be called a problem of self and non-self in a group. The boundaries of the 'self' seen from living creatures are surprisingly ambiguous, yet they continue to exist while maintaining harmony. Continuing to be a self that stays the same while changing every day. I think it would be interesting if I could expand that kind of ambiguity, as it is, into the realm of social sciences."

As for future prospects in biological research, Associate Professor Furukawa hopes for an increase in researchers who target a wider variety of organisms.

"Currently, it is said that there are about tens of millions to hundreds of millions of species of living things on Earth. Among them, fewer than 3 million species have names. Current knowledge in life sciences is likely nothing more than what has been obtained from about 20 species of 'model organisms.' I believe treasure troves lie dormant in organisms that have not yet been researched."

In today's society, which emphasizes efficiency, cost-performance, and time-performance, what Associate Professor Furukawa most wants to convey to his students is "the importance of loving waste and redundancy."

"Biological systems are extremely redundant and have a lot of waste. If you seek efficiency too much, the system becomes rigid; rather, it is because there is waste (redundancy) that living things can remain flexible and robust. Students these days tend to prioritize cost-performance and time-performance, but embracing a lot of waste should actually make them stronger in the future. That's why I'm sending the message that not just studying, but also 'waste' like playing, is important."

Composition: Toru Tamakawa, Editor-in-Chief of Asahi Shimbun GLOBE+

Interview/Text: Kaori Sawaki

Photography: Hiromi Shinada