By Edwin L. Cooperh, PhD
I Grew up in Houston, Texas, a humid, subtropical environment where the advent of spring brought myriad pleasures to excite the imagination of a curious and budding zoologist. My neighborhood came alive with returning insects — butterflies and mosquitoes filled the air, and cockroaches and spiders busied themselves with various survival strategies on the ground. April showers would replenish streams and ponds for tadpoles, and flowers burst with dusty pollen for voracious honeybees.
This menagerie nourished my curiosity and, without my knowing it, encouraged my future course as a scientist — specifically, a zoologist with a particular interest in studying the evolution of the immune system.
Later, my interest in the field of immunology began to exert itself. Clearly, studying immune response was not nearly as esoteric as decoding the evolution of the immune system; after all, what could analyses of the evolution of the immune system have to do with immunizing humans against diseases?
I did not yet have an understanding of the underlying scientific basis of animal existence, of which the immune system is, of course, an essential component. What I did see, always with awe, was the behavior of animals, their sexuality, communication, potential agricultural importance and, just maybe, the role that they play in our world today.
Much later, I came to understand essential elements that distinguish individuality of species and what undergirds the basis for immunologic responses — the capacity of all living things, both plants and animals, to recognize self from not-self.
This capacity is essential for the survival of all species, irrespective of their position in the living world. All organisms, beginning with protozoans, survive due to the precise function of self/not-self recognition. I vividly remember the first time this came into sharp focus for me. I spent hours watching ants traversing well-worn trails — formicidae superhighways, as it were — in two directions. Ants that were obviously from one colony would politely greet each other with an appropriate antennal embrace, an ant kiss, and then move on in their opposite directions along the path. On the other hand, when ants from different colonies would encounter one another along the path, they would attack and destroy each other.
Could there be a clearer demonstration that clarifies the necessity of recognizing self from not-self? Any disturbance of this refined, sensitive recognition of similarities or differences between natives and outsiders would interrupt the well-worn path; this forms the fundamental core of the essence of immune recognition and response.
Dr. Edwin L. Cooper has taught for 57 years at UCLA, where he is Distinguished Professor of Laboratory and Comparative Immunology. He is founding editor-in-chief of the journals Developmental & Comparative Immunology and Evidence-Based Complementary and Alternative Medicine and the author of Advances in Comparative Immunology (Springer, 2019, 1,092 pages).
It was, for me, a Eureka moment: Self/not-self is an essential feature of all living creatures, no matter the level of animal organization. It is central to their being and is that which enables them to remain undisturbed by aggression and to survive.
This is what I learned from ants. Now let us think about humans and the immune responses that take place within our bodies. Our white cells behave like ants traveling along the well-worn paths of our blood vessels; when they encounter a foreign ant from another colony, they attack and destroy it, demonstrating, again, the basic necessity of recognizing the difference between self and not-self.
Thus the analogy: If foreign components — bacteria, for example — gain entrance to the blood of a human, immune cells in the bloodstream will be ant-like and recognize the bacteria as foreign. The germs will be attacked and eliminated in a healthy human. Analogous processes also must be occurring in non-human animals, most of which have inhabited Earth much longer than have humans.
Studies of such processes have constituted much of my career. Little did I know as an adolescent wrapped in the humid warmth of a Texas spring that I would one day cobble together this understanding that transcends all organisms. At that time, I had not yet seen a microscope. I associated my understanding with that which ensures life’s preservation as the components of innate immunity.
Ant behavior is ubiquitous and diverse, but it is not unique. Even one-celled animals like paramecia and amoebae are equipped to ensure their own viability by recognizing not-self as a potential threat. Thus, the analogy of ant behavior exists in many forms throughout the living world. We still have so much more to learn from them about the living world.