CONCLUDING OUR TOUR OF CELLULAR CONVERSATIONS

WHAT CONCLUSIONS CAN BE DRAWN from this tour of cellular conversations? Although cells are considered the most basic characteristic that defines life, it is actually the conversations among cells, and also the conversations that take place inside them, that determine biological activity and produce the essence of life. The science of cell communication allows new ways to understand health and disease. It also has implications for understanding evolution as well as consciousness.

While elaborate signals among neurons have been observed for years, why hasn’t signaling among all other cells been obvious before now? It has been hidden from general view because of impenetrable jargon in scientific journals. Arcane terminologies of signals, receptors, genes, and cell subtypes aren’t generally known, even across various research areas. Professional articles and books on molecular signaling are complex and don’t provide this overarching synthesis. They are hard to understand, even for clinicians and scientists who don’t actively work in a particular field. Also, most of this information has been discovered in the past several years, and biology dogmas die hard.

The synthesis of scientific data in this book makes it easy to see why communication among cells has wide-ranging significance. Descriptions of cellular conversations help demystify the latest research on immunity, digestion, cancer, neuroscience, pain, and other topics. This overview—not available anywhere else in one place—is particularly important for those who are ill and trying to follow advanced treatments.

UNDERSTANDING NATURAL CONVERSATIONS

Perhaps most surprising is that all types of cells from completely different evolutionary lineages—bacteria, archaea, fungus, worms, plants, and human cells—naturally talk with each other using similar signals. This simple fact allows readers to see how biology works. For example, everyone has heard that microbes have great influence in human lives. But it’s not clear how this occurs without understanding that microbes speak with all human cells in the same language that human cells use to converse with each other. The influence of microbes on human cells is the result of these natural conversations between them, in which one clearly understands the language of the other.

There are multiple other examples. Understanding the natural conversations that occur among cancer cells, microbes, and immune cells generates the latest medical treatments in which microbes and T cells can be used to attack cancer. Other examples include the multiple ways that brain and immune systems talk with each other, related to chronic pain syndromes and stress. It is also the daily natural conversations of gut lining cells with immune cells that allow us to gain a better understanding of food allergies. Also, natural conversations of gut lining cells and microbes determine what microbes become dangerous, enabling us to provide avenues for exploring new treatments for infections.

SURPRISING NEW PHYSIOLOGY

New science shows that physiological functions, dependent on multiple various simultaneous conversations, can be more complex than previously thought. No one suspected until now that events in one organ could be based on wide-ranging conversations with tissue cells, blood vessel cells, neurons, microbes, immune cells, and even cells in distant organs.

Signaling in the Brain

Signals among neurons are considered the gold standard for understanding brain function. But, in fact, we are learning from new research that neurons cannot function without elaborate signaling among glia cells, blood vessel cells, immune cells, and lining cells. Also, neurons commonly use multiple simultaneous types of communication, such as neurotransmitters, immune signals, electrical synapses, brain waves, and sacs filled with information molecules. Conversations related to pain use entirely different types of large complex synapses that incorporate signals from multiple types of cells at the same time.

New types of conversations have also been found in the brain. No one knew, for example, that myelin patterns are so complex; myelin had always been considered to be just simple insulation. Now, research shows myelin-producing cells are part of wide-ranging conversations that determine changing patterns to accommodate various travel speeds required for circuits throughout the brain. Researchers discovered that these conversations are enabled by a newly found type of synapse between the neuron’s axon and the nearby myelin sheath.

Researchers were also surprised to find elaborate conversations between multiple guardian cells that are now known to determine what is allowed to enter the brain. Via signals circulating in cerebrospinal fluid, lining cells are able to call for precise types of immune cells to provide help at exact locations in the brain. Also, it was never clear before why there were so few ordinary immune cells in the brain. Now, newly discovered conversations between resident brain immune cells and immune cells outside the brain are found to be vital for preventing adverse mental states, autoimmune diseases, and degenerative brain diseases.

Signals to Fight Infection

Discovering signals related to infections has also been surprising. No one expected that capillaries provide travel directions for blood cells and instructions for stem cells about organ repair. Or that blood cells receive instructions from a variety of cells, including immune cells, tissue cells, neurons, and even platelets. Recent observations show that these signals direct traveling white blood cells as to where they should exit blood vessels at exact locations and where they should squeeze through difficult spaces in tissue. Signals give instructions for travel in difficult terrain, using such techniques as moving against blood flow and altering shapes and metabolism.

Researchers were also surprised to learn how platelets converse with immune cells, blood cells, and capillary cells as first responders for infections. With no nucleus to direct them, they still are able to communicate with signals built in before their birth from mother cells. Platelets direct actions against microbe infections and trauma until T cells can arrive. Based on signals, platelets change shapes for multiple activities, including organizing blood flow and helping to rebuild tissue while diminishing scar tissue growth.

Cancer Cell Behavior

Behavior of cancer cells is particularly fascinating. Cancer cells communicate among their own comrades for all group activities, as well as with microbes, immune cells, and neighboring local tissue cells. Cancer colonies entice local tissue cells and blood vessels to help them grow. Cancer cells intercept and manipulate signals to evade attacks from immune cells and microbes. Even more surprising is that these cells communicate with distant regions to create pleasant environments for metastatic colonies. Because sacs are cancer’s favorite communication vehicle, blood tests now monitor sacs in the blood to determine whether cancer is present.

Microbe Extensive Communication Ability

Microbes have the ability to communicate with all types of creatures. New findings show that virulence in human illness is not just based on the characteristics or amount of specific microbes but rather on the conversations among multiple species, even in highly structured bio-films. Researchers are learning more about how conversations among microbes and immune cells influence outcomes of infection. Also, signals from microbes in the gut affect digestion, metabolism, anxiety, and obesity. In addition, microbe signals can help or hurt cancer cells.

In the plant world, trees and other plants communicate with each other through microscopic wires made of long, thin fungal cells, and this can take place through an entire forest. Signals provide mutual protection, with warnings about specific dangers, as well as a way to share nutrients.

Organelle Conversations

The new science of signaling has also shed light on the surprising ways organelles participate in cell function. Wide-ranging conversations among various organelles respond to cell stress and provide quality control for mitochondria, membranes, and production of proteins. Elaborate signaling inside neurons provides precise transport of materials along the axon and allows complex decision making to take place among multiple compartments in dendrites. We are also learning about how the primary cilium might function as a cell’s central control center, as sort of the “brain” of a cell, with its tubular structure used as an antenna for signaling.

SEARCHING FOR ANSWERS IN MODERN MEDICINE

When looking for new treatments, a paradigm shift needs to take place to explore completely new avenues never considered before. Now, instead of reducing proposed mechanisms to one cell or one organ, research must investigate widespread collaboration and competition among multiple cells throughout the body. Examples include conversations among immune cells and brain cells for various functions never thought to involve both. Who would have suspected that mental states can be directly altered by signals from T cells that are not even in brain tissue?

As medical science becomes increasingly complex, most people find it more challenging than ever to comprehend what maintains health and what causes disease. It is difficult to follow advanced medical treatments for cancer, infectious diseases, immune diseases, chronic pain, food allergies, and brain disease. Cellular conversations allow understanding of how immunology, neuroscience, microbiology, and cancer research fit together. They allow understanding of what future treatments might be, such as finding new microbial products in the gut that affect obesity, bowel disease, or anxiety. Since conversations between immune cells and brain cells are implicated in stress, depression, pain syndromes, cancer, and brain trauma, cell signaling in all aspects and all places of the body is where research must be pursued in the search for more effective treatments.

ORIGINS OF EVOLUTION AND INTELLIGENCE

Cell conversations are also important when considering mechanisms of evolution and the origins of intelligence in nature. Are cells intelligent? Could cellular language of signaling be related to intelligence in creatures? Unfortunately, it is not possible to answer these questions because there is no confirmed definition of intelligence. Nor are there serviceable definitions of awareness or consciousness; we say that cells are alive, but our definition of life is inadequate. For example, many researchers don’t consider viruses to be living entities, yet viruses have very elaborate lifestyles, with the ability to specifically counter actions of large complex cells through signaling and other processes.

What can be said is that biology is based on information transfer. Ubiquitous transfer of information among cells somehow leads to actions of much larger and more complex organs and a multitude of organisms, which include animals and plants. In current biology, information transfer begins with chemical reactions, DNA codes, RNA codes, and the exact shapes of proteins, lipids, and sugars. Cellular communication uses these information codes as signals.

Information codes also exist at every level of biology across six orders of magnitude—from molecules to humans. At the molecular scale, information is in the form of chemical signals; at the scale of human societies, information is encoded in mathematics and language. It is not known how this flow of information is directed and organized at either of these levels.

A CENTRAL CONTROL CENTER FOR INFORMATION DISTRIBUTION—DOES ONE EXIST?

Efforts to understand how human brains use information have not yet been successful: no clear source of direction for the widespread information flow in brain circuits, for instance, has been found. Attempts have failed to detect a central control module in the brain, such as a seat of consciousness and subjective experience. Instead, brain activity seems to be distributed widely among diverse cell clusters using signals that change frequently in milliseconds. During neuroplasticity from learning, multiple circuits throughout the brain alter themselves in different ways simultaneously, without an obvious central commanding post to direct these processes.

Comparing various animal brains with diverse and unusual capacities, the same types of questions remain. Information flow in nonhuman animal brains uses similar cellular molecular signals, but in different ways. The very capable octopus brain distributes its neurons between the center and its arms, somewhat the same way that the human brain distributes some of its power to the large semiautonomous gut nervous system.

Small brains of lizards and birds show surprisingly advanced abilities. As brains get even smaller, various types of signals produce remarkable abilities, such as in insects. An example is bees, which have tiny brain structures quite different from humans’ but are able to utilize symbolic language, abstract concepts, advanced learning, mathematical abilities, and kaleidoscopic visual memory.

One issue facing scientists is the fact that we don’t know if all the types of signals have been discovered yet. As well as chemical and electrical signals, there could be other types, such as electromagnetic fields, photons, and quantum states, which might be directing information flow. While cells are powered by DNA and RNA information codes, it is mysterious how regulation of genes also includes three-dimensional shapes of DNA and tags placed on both DNA and its protective molecules.

Three-dimensional shapes of proteins, known to produce their precise actions, are so complex that modern supercomputers cannot yet compute how proteins fold into these shapes based on sequences of amino acids. But at the same time, individual cells are able to manufacture new sequences of codes to build new precisely shaped attack proteins.

We don’t understand how human cells by themselves can show such surprisingly advanced levels of activity based on information transfer, without a clear source of direction. Cells self-edit their own DNA in elaborate multistep methods—fixing DNA errors and producing unique antibodies and T cell receptors.

Another example of advanced information transfer without obvious direction is the way cells are able to edit messenger RNAs. This complex editing can produce up to five hundred different proteins by cutting up and sewing together RNA pieces produced from a strand of DNA that used to be considered one gene. It is also not clear how immune cells can stay in close communication with the stable wires of the nervous system while traveling without obvious direction.

LIFE AND INFORMATION TRANSFER

While we don’t know what life is, we do know it involves information transfer based on signaling of viruses and bacteria, signaling among human cells, signaling in complex circuits of brain cells, and signaling among human beings in society using language and mathematics. But we also don’t know exactly what information is or how it is directed in nature at these various levels.

While information exists in each human brain, how does it exist outside individual brains in the annals of collected memories of individuals that form scientific knowledge and culture? The same question can be asked about how information exists in individuals and among groups at all other levels. Where does the direction come from when cells are able to talk with each other in surprising ways that influence the entire organism? How can ants and bees demonstrate elaborate individual behavior, but the superorganism performance is greater than each individual’s capacity?

As matter and energy interact at all scales of the universe, could information transfer be another fundamental aspect of physical nature? Are particular types of information transfer the definition of life?

Thus far, physics postulates three divergent laws for very different sizes—quantum laws at the infinitesimal subatomic scale, Newtonian laws at the scale of humans, and general relativity at the great size of the universe.

Are the rules of information and life different at these three scales? Humans lie somewhere near the middle of this vast number of orders of magnitude, with information transfers at each level. As more is discovered about cellular conversations, perhaps we’ll be able to begin to answer some of these questions.