In this blog post, we will look at how the concepts of antibodies and immunity were established, from Pasteur to Bordet.

The evolution of life sciences through the history and experiments of early immunology

Immunity, the ability of the human body to defend itself against external pathogens, is a biological concept that everyone is familiar with today. However, the principles behind the physiological phenomenon of immunity and the discovery of its mechanisms were established through a process that was more complex and lengthy than one might imagine. The
concept of immunity has existed since ancient times. For example, it had long been observed that people who nursed patients with infectious diseases or handled their bodies were less susceptible to those diseases, suggesting that some form of “resistance” developed. However, no scientific explanation for why and how this phenomenon occurs was properly presented until the mid-19th century. The main reason for this was that at the time, there was a lack of understanding about the causative agents (pathogens) of diseases, and the experimental techniques to deal with them were inadequate.

The discovery of pathogens and the beginning of immunity experiments

At the end of the 19th century, with the development of microscope technology, pathogenic strains began to be isolated and cultured in laboratories, and immunology rapidly advanced. The most notable figure at this time was Louis Pasteur. In the course of his research on microorganisms that cause infectious diseases, he discovered that weakening pathogens and injecting them into living organisms could induce immunity to the disease.
A representative example is his experiment on avian cholera. Pasteur injected chickens with cholera bacteria that had been left at room temperature for a long time to weaken their pathogenicity. Although the chickens became ill, most of them recovered without dying. When these chickens were injected with highly pathogenic cholera bacteria again, they did not become ill at all. In other words, the first infection served as a kind of “training” that enabled the chickens to acquire immunity to the pathogen.
This experiment was the first experimental proof that immunity is induced by exposure to pathogens. However, this result only showed that the “phenomenon of immunity” actually occurs, and did not explain its internal working principles or mechanisms at the cellular level.

The discovery of antibodies and antitoxins: Behring’s contribution

Emil von Behring took up Pasteur’s question and explored the specific mechanisms of the immune phenomenon. While studying bacterial infectious diseases such as diphtheria and tetanus, he discovered that specific substances are produced to neutralize the toxins secreted by these pathogens in the body. He named these substances “antitoxins,” which correspond to the early concept of immune proteins that we now call “antibodies.”
Furthermore, Behring proved that these antitoxins could be transferred from one individual to another. In other words, if serum from an immunized animal was extracted and injected into another animal, that animal would also become immune to the disease. This discovery gave birth to the concept of passive immunity, and based on this, anti-diphtheria serum began to be used in the treatment of diphtheria patients at the end of the 19th century.
Bering’s research was an important milestone in revealing that immunity is not simply “resistance,” but the result of the action of specific substances produced within the body.

Immunity can kill not only toxins but also pathogens themselves

However, immunity cannot be explained solely by the neutralization of toxins. Richard Pfeiffer’s experiments revealed that there is also an immune response to pathogens themselves, even in the absence of toxins.
Pfeiffer immunized mice by inoculating them with weakened cholera bacteria, and then injected strong cholera bacteria into the abdominal cavity of the mice.
The bacteria were completely destroyed. Interestingly, when the same bacteria were injected into mice that had not been immunized, they died, but when the serum from the immunized mice was also injected, the bacteria were killed and the mice survived.
Piper thus demonstrated that antibodies not only neutralize toxins, but also have the ability to directly kill the actual pathogen itself. He named these antibodies that directly dissolve and kill bacteria “lymphocyte antibodies” and the immune response caused by them “lymphocyte immunity.”
However, his experiments had limitations. Although the lytic reaction occurred in living organisms, it did not occur in an in vitro environment such as a test tube. This raised the possibility that antibodies work in cooperation with other biological factors.

Bordet completes the puzzle of immunity: the identity of complement

Based on Piper’s research, Jules Bordet was the one who identified the hidden helper of the immune response. In the course of repeating experiments similar to those of Piper, he discovered one important difference.
When fresh serum from immunized animals was exposed to cholera bacteria outside the body, the bacteria were killed. However, when the serum was heated or stored for a long time, its ability to kill bacteria disappeared. Surprisingly, when a small amount of fresh serum from normal animals without immunity was added to the inactivated serum, its bactericidal activity was restored.
This experiment confirmed that there was another component in the immune response besides antibodies. Borde classified these into two substances.
First, antibodies are produced in immunized animals and are heat-resistant substances.
Second, another substance that plays a supporting role is easily destroyed by heat or long-term storage and is inherently different from antibodies in that it is naturally present in the serum of all animals.
The second substance discovered by Borda is what is now known as “complement,” which is central to immunology today. Complement works with antibodies to effectively eliminate pathogens and is now considered an important factor at the intersection of innate and acquired immunity.

Immunology: From Past Experiments to Today’s Medicine

Vaccines, serum therapy, and antibody-based drugs, which we now take for granted, are all based on the experimental discoveries described above. Immunity is not simply an instinctive defense mechanism that prevents disease, but a sophisticated biological response achieved through the cooperative action of complex biochemical substances such as antibodies and complement.
Pasteur’s “immunity through experience,” Behring’s discovery of antibodies, Piper’s demonstration of the mechanism of pathogen destruction, and Bordet’s completion of the complement system—all of these processes laid the foundation for immunology to become a core field of life sciences today.
It is no mere coincidence that we have strong immunity to certain diseases. It is the result of countless scientists’ persistent observation, experimentation, analysis, and accumulated failures, and it is thanks to this history that we are able to enjoy healthier and safer lives.