One of earth’s most primitive civilizations isn’t hidden in the depths of a tropical rain forest or sequestered on a remote island. It has no artifacts to analyze, no traditions to document, no exotic rituals to preserve. It lives in pond scum, and its name is Volvox.
Under the microscope, magnified fortyfold, Volvox cartieri (its full name) resembles an olive-colored golf ball, stamped with a handful of dark green spots. At higher magnifications, its dappled “skin” resolves into a mosaic of cells, embedded in a sphere of translucent jelly, the spots into clusters of daughter cells clinging like soap bubbles to the inner wall of the sphere. Trees and grasses are anchored by their roots, but V. cartieri can swim and spin, propelled through the water by whiplike projections, or flagella, that sprout from each of its cells.
The family Volvocacae—the tribe of green algae that includes V. cartieri—are a sociable lot. In contrast to the independent lifestyles of unicellular organisms that biologists call “protists,” many volvocacaens prefer to live in groups, ranging in size from tiny Gonium with a dozen-odd cells to Volvox species containing as many
as 50,000—a veritable city of an organism. But a crowd is not necessarily a community. The cells that comprise Gonium, for example, are no more than guests in the same motel. Anonymous, transient, and opportunistic, each can decide at any time to quit the group and start its own colony. V. cartieri, on the other hand, has adopted a social contract similar to that honored by plants and animals. Its cells have relinquished their autonomy and pledged lifelong commitment to each other. No longer capable of living alone, they die if separated from one another.
V. cartieri is indivisible because it has opted for a division of labor. One type of cell, designated “somatic,” is responsible for infrastructure and transportation. These cells keep a roof over everyone’s head, as well as build and operate the flagella that power the colony around the pond. Others, known as “gonidia,” have no flagella. Confined to the southern hemisphere of the cellular globe, they specialize in reproduction; the daughter colonies are their handiwork. But their most celebrated reproductive skill is sex. Come midsummer, they undergo a primitive sort of puberty in which some—indistinguishable from their colleagues on the outside, genetically male on the inside—differentiate into sperm cells, while the others, secretly female, produce eggs. At maturity these germ cells abandon the soon-to-die somatic cells and mate, giving rise to a resilient zygote able to weather summer’s heat and winter’s drought by taking refuge in the silt at the bottom of the pond, where it lies dormant until next year’s spring rains.
Gonium is a coalition. Volvox, on the other hand, is a collaboration, tens of thousands of cells forged into a “whole functioning interdependently”—the Oxford Dictionary definition of a society. Such teamwork is possible only because the members of Volvox have evolved one additional, priceless faculty: language.
By pooling resources and dividing the work, a human society can accomplish things that would be impossible for a single individual:
construct a city, feed the masses, maintain an army, build an empire. Cooperation and specialization also allow a cellular society—even one as simple as Volvox—to exploit natural resources and cope with emergencies in ways that are simply beyond the reach of a single cell. For example, because it has mastered the art of synchronized swimming, Volvox can glide quickly and efficiently to the choicest spot in the pond. And should the pond threaten to dry up in the summer heat, Volvox’s discovery of sex and the marriage of specialized germ cells provide for the survival of the next generation (and for the family genes the young inherit from their parents), even if every last somatic cell dies. In more advanced multicellular organisms, like humans, an even greater degree of specialization and organization coordinates the action of millions of cells to form the cellular equivalent of states—highly stratified, complex societies that have not only adapted to the challenges of environments as diverse as the rain forest and the desert, the open sea, and a backyard pond but have also helped shape those environments.
Cooperation requires conversation. As biologist John Tyler Bonner puts it, all biological societies have in common the need for “some coordination, some integration or communication between its members.” Humans speak to one another. Sounds, scents, and postures connect members of animal societies. Volvox cannot talk, hiss, growl, trill, or show its teeth, but even the members of this simple cellular society have found a way to communicate. Strands of cytoplasm connecting its constituent cells transmit chemical substances that coordinate the beating of the flagella, while the somatic cells, unable to participate in sex, say the word that initiates it. Sensorium and sibyl as well as transport coordinator, they read the signs—rising temperatures, less room to move, a subtle brackishness of the water—and predict the future. Before dehydration overtakes them, they warn their fecund sisters, producing and secreting a protein that diffuses into the surrounding water and triggers the sexual differentiation of the gonidia, the reproductive cells.
The language of all cellular societies is similarly based, not on sounds or gestures but on chemistry. Using molecules where we would use words, constructing sentences from chains of proteins, the cells that make up the bodies of multicellular organisms inform, wheedle, command, exhort, reassure, nurture, criticize, and instruct each other. Their conversations direct every physiological function, report every newsworthy event, record every memory, heal every wound. Like our spoken and written language, which can be used to describe both the past and the present, or fact as well as fantasy, this chemical language is versatile, as useful for orchestrating the development of tissues and organs as issuing a request for more food. Like our language, it is flexible, permitting molecular “words” to be combined in more than one way, as well as accommodating, open to the addition of new words. Our language—aided by the postal service, the telephone, the fax machine, and the Internet—enables correspondents separated by long distances to communicate with one another. Similarly, diffusible chemical signals, relayed from sender to recipient via the bloodstream or directed over long distances by cellular structures that are the equivalent of telecommunications networks, permit even distant cells to share information, so that a biological society, regardless of its size or complexity, can coordinate the activities and regulate the social behavior of its many members. Just as many social scientists consider language to be one of the seminal accomplishments of human society, biologists rank chemical communication as one of the most important advances in cellular societies, a skill essential to the evolution of the multicellular lifestyle.
The molecular biologists who worked for over a decade to sequence the human genome have sometimes referred to that sequence as “the book of life.” But even they acknowledge that our DNA alone actually tells us little about the way our bodies operate. To our cells, the book of life is no more than a reference manual; it’s the proteins encoded in the genes, not the genes themselves, that actually build and maintain the molecular machinery essential to life,
including the network of signaling pathways that allow our 60 trillion cells to function as a single organism. Genes conserve, but only living cells can converse; from the words written in their genes over billions of years of evolution, they construct a language—the language of life.
Cells had barely been discovered when scientists peering into primitive microscopes first began to examine the architecture and activities of their civilization. In 1682—only two decades after the first published description of plant cells—Anton van Leeuwenhoek (the Dutch lens grinder and amateur microscopist famous for his descriptions of one-celled “animalcules”) wrote a letter to the Royal Society documenting his observations of a structure known today as the cell nucleus. In the 1820s a French physician, Francois-Vincent Raspail, incinerated cells on a platinum spoon and analyzed the residue to discern their chemical makeup. By the end of the nineteenth century, cell biologists had discovered dyes and staining techniques that revealed new aspects of the cell’s internal structure; within a few more decades, they’d learned how to deconstruct cells and separate their constituent components by spinning the slurry in a centrifuge. By the end of the twentieth century, the electron microscope, advances in protein chemistry, radioactive tracers and fluorescent markers, and the techniques of molecular biology had described the structure, physiology, and genetic makeup of cells with exquisite detail.
The excavations carried out by anatomists, biochemists, and molecular biologists yielded precious artifacts: the tools used by cells to make a living, the features of their personalities, the machinery that furnishes their interiors. And they also revealed molecular words and protein phrases, fragments of the most ancient language on earth.
These discoveries, as important to biology as the discovery of the Rosetta stone was to history and linguistics, have added to the story
of life the direct testimony of cells themselves. Just as scholars who deciphered the hieroglyphics of ancient Egypt, the cuneiform symbols of Mesopotamia, and the Linear B script of Mycenaean Greece enriched our understanding of these extraordinary civilizations, biologists struggling to decipher the chemical language of cells have opened another window on the civilization of multicellular organisms. In the conversations between cells, they have discerned the details of everyday life in cellular society. In addition, they have observed firsthand how miscommunication between cells can precipitate a catastrophe. Too much or too little of a signaling molecule, a gene mutation that compromises a cell’s hearing, a defect that blocks the free flow of information within the cell, outside interference from foreign chemicals can all lead to confusion instead of communication. Cellular language researchers now know that such pathological misunderstandings lie at the heart of some of our most intractable diseases: cancer, diabetes, obesity, addiction, autoimmune disorders. Slowly, haltingly at first, and then with increasing confidence, their understanding has enabled them to speak to cells as well, fashioning drugs to talk sense to our bodies when degeneration and disease create confusion or misunderstanding.
For nearly a century these researchers have eavesdropped on the conversations between cells, hoping to master the basics of their language. This book is the story of their discoveries as well as an anthology of the tales they’ve heard cells tell. It describes how cell-to-cell communication shapes a fertilized egg into a body, maintains tissues, regulates the distribution of resources, records memories, and builds a firewall against invaders. It explains how the disruption of signaling pathways can precipitate communication breakdowns that result in well-known medical conditions. Finally, it reveals how farsighted researchers are beginning to apply what’s been learned about cellular communication to the solution of biology’s ultimate problem: how the processes that sustain life emerge from the collaborations between inanimate molecules. In doing so they hope to lead the way
out of reductionism toward an integrated biology that acknowledges the complexity of living organisms.
Children master languages with ease, but for adults, learning to speak any new language is difficult. The words are strange and may be hard to pronounce. The rules of grammar are unfamiliar. The culture itself, its idioms and customs, baffle and conspire to embarrass. Until a student has acquired a rudimentary vocabulary and learned the correct way to join those words into sentences, even a simple conversation can be a struggle. The language spoken by cells is no different. Though I have endeavored to make the unknown less formidable by streamlining sentences and reducing the use of acronyms and abbreviations, you may feel at first as if you’re back in high school, trying to conjugate foreign verbs. Be patient; practice makes perfect.
The language of cells is the language of modern biology. Because a working knowledge of cellular signaling mechanisms “is essential to our understanding of the control of virtually all biological processes,” according to the editors of the journal Science, cell communication has become one of the hottest topics in biomedical research. Over the past several decades, the number of scientific papers published on cellular communication has skyrocketed, not only in journals read by cell biologists but also in those devoted to neuroscience, immunology, pharmacology, physiology, developmental biology, infectious diseases, and molecular biology as well as clinical research journals. What I present here is, by necessity, only an overview of this vast literature. I apologize to any in the scientific community who feel I have omitted or glossed over their favorite topics and offer in my defense the hope that readers will be left wanting to know more and will have acquired the language skills they need to satisfy this curiosity.