At the turn of the 20th century, people didn’t have a clear understanding of immunity. While it was clear that individuals could acquire resistance to disease, the biological processes responsible for this protection were deeply contested. Mechnikov and Ehrlich approached this problem from different directions, advancing theories that were initially seen as opposing.
Mechnikov argued that specialised cells actively eliminated invading organisms, while Ehrlich showed that immunity also depended on specific substances circulating in the blood. Their joint Nobel recognition reflected the eventual understanding that both mechanisms were essential components of a unified immune system.
Early scientific formation
Ilya Ilyich Mechnikov (also spelled Élie Metchnikoff) was born on May 15, 1845, near Kharkov in the Russian Empire, in what is now Ukraine. Trained initially as a zoologist and embryologist, he was interested in fundamental biological processes more than clinical medicine. His early work focused on invertebrates and developmental biology, an approach that later shaped his thinking about immunity as an evolutionarily conserved phenomenon. After periods of academic work across Europe, he joined the Pasteur Institute in Paris, where he conducted much of the research that would define his scientific legacy.
Paul Ehrlich was born on March 14, 1854, in Strehlen, then part of Prussia. He trained as a physician but was equally grounded in chemistry and microscopy. From early in his career, Ehrlich showed an interest in how dyes selectively stained tissues and cells, a curiosity that evolved into a broader investigation of chemical specificity in biological systems. His research career combined laboratory science with an explicit focus on therapeutic application, reflecting his belief that biological mechanisms could be harnessed to treat disease in targeted ways.
Mechnikov and cellular immunity
In the early 1880s, Mechnikov noticed something striking while studying starfish larvae and other simple organisms. When a foreign object entered the body, certain mobile cells quickly moved towards it and swallowed it. He suggested that this process later called phagocytosis was one of the body’s main ways of fighting infection.
Mechnikov then showed that the same thing happens in more complex animals, including humans. White blood cells, he argued, actively seek out and destroy bacteria, rather than simply reacting after damage has already occurred. This went against the popular belief at the time that immunity depended mostly on substances floating in the blood.
By putting these cells at the centre of the body’s defence, Mechnikov changed how scientists understood infection and inflammation. He showed that inflammation is not just a sign of harm, but a protective response, and that the body has an inbuilt, organised defence system from the very start — what we now call innate immunity.
He also looked at immunity from an evolutionary point of view, noting that these defence mechanisms exist across many species. This helped establish immunity as a basic function of life itself, laying the groundwork for later research at the molecular and genetic level.
Ehrlich and humoral immunity
Ehrlich’s work addressed a different aspect of immune defence. Through studies of toxins, antitoxins and blood components, he proposed that cells possessed specific molecular structures, described in his side-chain theory — that could bind selectively to foreign substances. When these structures interacted with toxins or microbes, the cell responded by producing excess copies, which were released into the bloodstream as antibodies.
Although later refined, this theory introduced the central concept of specificity, explaining how immune responses could distinguish between different pathogens and retain memory of prior exposure. Ehrlich’s ideas clarified why immunity could be both targeted and durable, providing a mechanistic explanation for vaccination and passive immunisation.
Ehrlich also translated theory into clinical innovation. His development of Salvarsan — the first effective ‘magic bullet’ chemotherapy for syphilis and other infections like trypanosomiasis– represented the first systematic attempt to design a drug that selectively targeted a pathogen while minimising harm to the host. This work established the principles of chemotherapy and introduced the idea of targeted therapy, which remains central to modern pharmacology and oncology.
Nobel recognition
The Nobel Committee awarded the 1908 Prize jointly “for their work on immunity,” recognising that cellular and humoral mechanisms were not mutually exclusive but complementary. At the time, Mechnikov’s and Ehrlich’s theories had divided the scientific community. Subsequent research demonstrated that innate cellular responses and adaptive antibody-mediated responses operate together, forming an integrated immune system.
This synthesis reshaped medicine. It allowed infectious diseases to be understood as dynamic interactions between pathogens and host defences, rather than as isolated microbial events. It also provided the conceptual foundation for immunisation strategies that engage both early cellular responses and long-term immune memory.
Impact on medicine and public health
Their ideas continue to influence how we treat disease today, far beyond infections. Many modern cancer treatments are built on Ehrlich’s belief that medicines can be designed to target illness precisely, without harming the rest of the body. At the same time, Mechnikov’s work on inflammation and the body’s first line of defence has shaped how doctors understand long-term inflammatory and immune-related conditions.
On a larger scale, public health systems across the world, from routine vaccination programmes to how countries prepare for and track pandemics are rooted in these early discoveries about immunity. Health organisations still depend on these basic principles when making policies, planning interventions and assessing risks to populations.
Enduring legacy
Mechnikov is widely regarded as a founder of innate immunology, recognised for demonstrating that specialised cells play an active and organised role in host defence. His later work also explored ageing and the relationship between intestinal microbes and health, anticipating areas of research that have gained prominence in recent decades.
Ehrlich’s influence extends across immunology, pharmacology and therapeutic science. Concepts such as antibodies, receptors and targeted treatment form part of the core language of modern medicine and remain central to drug development and clinical research.
Together, Mechnikov and Ehrlich transformed the understanding of immunity from a collection of observations into a coherent scientific framework. More than a century later, immunology remains a cornerstone of medicine and public health, built on foundations they helped define.
Published – December 14, 2025 06:47 pm IST