Redox Signaling — How do we get diabetes?

Diabetes is an insidious, degenerative disease causing gradual loss of organ and limb function, often resulting in rotting of tissue, ulcers, amputation, blindness and a miserable death. Throughout thousands of years of recorded history it has been relatively rare affecting less than 0.1% of the population, as far as we know. Since the late 1920’s however the prevalence of diabetes has climbed, in 1958 in the U.S.A. it was almost 1%, steadily growing to over 11% in 2014. At the current rate of growth, it will affect about 50% or more of the children being born this decade. How do we get diabetes? It is not infectious. It might be genetic, it seems to run in families. Genetic factors, however, do not account for the sharp increase over the last 50 years (2 generations). So the question remains open.

Advances in redox biochemistry, during the last 10 years, give us some great insight into the cause of diabetes on a cellular level. In the last post, we explored the analogy that sugar in the blood is like “gasoline” to the hundreds of mitochondrial furnaces that are burning inside every cell in our body. Putting too much sugar (glucose) in the blood is like throwing too much gasoline on these fires. They flare up, throwing off “smoke” (oxidants and free radicals) into the cells. The beta cells in the pancreas are a bit strange when compared to other cells, they have a great many glucose “windows” (receptors) wide open to bring in the glucose molecules, and yet they do not have very many of the antioxidant (smoke scrubber) molecules that get rid of the oxidants and free radicals (smoke) that are produced. So when an incoming flood of glucose flares up the fires inside these beta cells, there is a real crisis. Too much glucose gets in, the fires in the mitochondria flare up to dangerous levels and the oxidants and free radicals (smoke signals) quickly build up and start causing damage. As usual, the standard “smoke alarm” messengers are sent out to alert the beta-cell control centers in the genes. When beta cells in the pancreas receive the “smoke signal”, they start producing insulin. The beta cells are both sensitive and vulnerable to high levels of glucose in the blood; the bigger the oxidative stress (smoke build-up) crisis, the more insulin is produced.
The crisis workers inside the beta cells furiously manufacture and package insulin molecules, and must work in an environment choked with free radical smoke. All the workers in the beta cells are waiting and hoping for the fires to go down, for the smoke to clear up, and for the crisis to pass. Some beta cells will not make it through a bad crisis and will end up dying in the process. Recall also that high oxidative stress (smoke build-up) can cause the cell to shut itself down and kill itself. High oxidative stress also releases messengers that cause inflammation and call the immune system to combat possible infections. The immune system also tends to accidentally kill the poor beta cells on occasion when the smoke signals get too large. As you might imagine, getting the blood glucose levels down to normal is the first priority for the beta cells (as it is for the rest of the glucose-stressed, inflamed cells in the body).
Insulin is the messenger sent out to get rid of the sugar in the blood. It signals most of the tissues in the body to burn or convert the excess blood sugar into fat molecules and to store them away in our fat cells and muscles. In our modern diet, we eat easily digestible refined sugars and white breads, causing blood sugar levels to rise many times above the amount we are built to handle. The excess insulin produced in this “crisis”, in an hour or so, converts too much of the sugars to fats and causes blood sugar to drop well below healthy levels, leading to hunger pangs, loss of energy and consumption of more sugary foods. Thus causing us to repeat this destructive cycle. Imagine the poor pancreatic beta cells, working overtime, choked with smoke and when the sugar crisis is finally over, it starts all over again; literally exhausting.
Incidentally, the beta cells are not the only sugar sensitive cells like this in the body, there are glucose sensor cells found in the emotional center of the brain that react to glucose quite a bit like the stressed beta cells, except instead of producing insulin, they produce a cocktail of “feel good” hormones, including serotonin, that serve to put us in a better mood and unfortunately also reinforce our drive to eat sugar.
It often takes many thousands of years before organisms can successfully adapt to a new set of molecules found in a new environment (before they can effectively be converted and utilized as effective supplies or fuel sources). These evolutionary hypotheses have been well supported by evidence from over a century of scientific discovery. Consider this sobering fact: in just the past several decades, all of us in the world have drastically changed the types and quantities of molecules that we ingest. We instinctually go toward the easily digestible bleached grains and highly concentrated processed sugars that supply us with many times the glucose fuels that we need at any given time and are poor sources of the other nutrients. Perhaps we are programmed to crave these readily available sources of quick energy, and there is economic potential there, but we are not physiologically equipped to handle or process this amount or composition of molecules.
At the same time, we tend to avoid the less “sexy”, but most needed, nutrients in our diets, like those in broccoli. In the next few decades, we might be forced to realize that we simply do not have many millennia to adapt to the new types and quantities of molecules we have in our “modern” diet. Natural selection will play itself out. Diabetes will kill us off. All scientific evidence, so far, strongly points to the established fact that nutrition is by far the most important factor in restoring, sustaining and maintaining health. Those that eat healthy natural diets testify to this fact, they have excellent overall health; some food for thought.


Redox Signaling — Smoke Signals from Metabolic Fires



As we sit inside our cozy homes, in front of the fireplace that brings us warmth and energy, we feel the benefits and all seems well. What happens if smoke from the fire started billowing out into the room? We are immediately alerted, smoke alarms go off, we are moved to immediate action. We realize that besides providing energy, fires can be dangerous. Fire produces smoke, free radicals, carbon monoxide, sparks and ash, fires can get out of control. In order to harness the ample benefits of fire, we have made special places in our homes where the fires can be controlled. We have devices that control the fire, harvest the energy, and alert us if the smoke builds up. This scenario provides us a great analogy of what is happening inside our trillions of cells. Inside every one of our cells, fuels are delivered, like oils and gasoline (fatty acids and sugars), that burn with the provided oxygen inside an average of 200 controlled furnaces (called mitochondria) in every cell, this fire produces smoke (ROS) that is eliminated by scrubbers (antioxidants) and detected by smoke detectors (thioredoxin semaphores, Nf-kappaB). All of these devices must be in place inside our cells to harness the energy of these metabolic fires.

At the junctions inside the cells where the oxygen pathways and fuel pathways merge, the fire of life provides energy. Even on a molecular level, nothing happens without energy. The major reason that we search for food and take in oxygen is to provide the fuel molecules and oxygen molecules maintain these vital fires of life inside our cells. Within this fire of life, the universal energy molecule, ATP, is forged. ATP powers all of the molecular machines, players, instruments, everything that requires energy in our cells. Every time you blink an eye, think a thought, twitch a muscle or feel a breeze, trillions of ATP molecules are spent to fuel the action. If the fire of life were to go out, in seconds the cell would run out of its supply of ATP energy molecules and the concert of life in the cell would quickly come to an end. There is nothing more important to a cell than to keep these fires burning.

The “smoke” that comes out of these cellular fires, reactive oxygen species (ROS), composed mostly of superoxide free radicals (O2*-) and hydrogen peroxide (H2O2), increases when the fires of life flare up inside the mitochondrial furnaces. These ROS (smoke) molecules affect the semaphore molecules (smoke detectors) that, in turn, change “color” and redirect molecules along the pathways. In other words, these smoke detectors are intelligent and are wired to make changes inside the cell. This is at the essence of redox signaling. The ROS superoxide free radicals (O2*-) and hydrogen peroxide molecules (H2O2), just like smoke, are highly energetic and reactive, and can also damage certain sensitive structures in the cell (like the DNA). Thus plant and animal cells have adapted to produce various types of antioxidant enzymes (smoke scrubbers), such as glutathione and SOD that can eliminate ROS “smoke” and keep it out of sensitive areas. As might be expected, these antioxidant enzymes are tightly regulated and controlled by redox signaling networks. For example, too much hydrogen peroxide in the cell will activate the redox signaling semaphores along pathways that turn down the metabolic fires and increase the production of antioxidants (smoke scrubbers) needed to eliminate the ROS (smoke).

Many of the redox regulatory processes are aimed at maintaining proper homeostatic balance of redox potentials in all the fluids in the various parts of the cells and tissues. Shifts in the redox potential (smoke signals) of vital fluids in and around the cells will generally activate redox signaling pathways that are designed to ultimately return the redox state to “normal” again. In the past decade, we have learned that it is dangerous to try to force the elimination of all superoxide free radicals or hydrogen peroxide in our body. In fact, the body will try to counterbalance any efforts to change the established natural balance by producing more of the lacking species to compensate. In order to maintain life processes, we require well-balanced control of these types ROS in our body. There are a variety of redox signaling pathways that naturally maintain normal redox balances and potentials throughout all the fluids in our body. Without both the oxidants and the antioxidants inside these vital fluids, this homeostatic balance would quickly be destroyed, and we would surely die. ROS is an essential signaling molecule.

If we were to completely eliminate the smoke from the fires inside our cells, the smoke detector semaphores would not be activated when the fires flare up and get out of control. ROS smoke is required to make the whole system work. Without ROS smoke, the damage detection mechanisms are shut down. In the vast majority of cancer cells, for example, the redox signaling system has been shut down, the mitochondrial furnaces have been shut down, the redox detection semaphores (smoke detectors) are not able to work. Without the aid of this redox signaling system, these damaged cells cannot be effectively detected, repaired or destroyed; they become immortal and remain broken. Smoldering fires are not extinguished, damage is propagated. Life is threatened.

As we contemplate these concepts, we realize that life is preserved by those devices inside our cells that maintain proper redox balance. It creates that cozy space inside our cells, where all is well; the fires are burning at their proper level, the smoke is being handled and the energy efficiently harnessed. When fires flare up, smoke billows out, alarms go off, smoke detectors are activated that will push the genes that will bring it all back into control. That is one description of redox signaling.


Redox Pathways Interconnect the Body

These last few weeks, much has happened in the world of Redox Signaling. James Watson, who co-discovered the 3-D helical structure of DNA, has stepped forward with an article in the prestigious Lancet journal to champion this field of science, stating that he considers his work in this field to be his greatest accomplishment since DNA. You can type “Watson Redox ROS” into any search engine to explore this. The formal research on redox signaling has to do with how reactive oxygen species (ROS, examples: H2O2, O2*-,ClO-,etc.), reactive nitrogen species (RNS example: NO) and reactive sulfur species (RSS example: H2S) interact with the molecular semaphores in the vast ocean of fluids inside us. These molecular semaphores are proteins (like thioredoxin) that change conformation and state when they come into contact with these reactive molecules and redirect molecular traffic in our cells. Imagine the implications.
Amazing as these molecular processes of life inside our cells may seem to us, possibly even more amazing is that trillions of individual cells combine to form the complex tissues and organs that pump our blood, think our thoughts and move our muscles. The enormity and complexity of any one of these machines is mind-boggling. Take a moment and ponder the importance of the proper function the cells, with all of the molecular machinery inside them, to the vital functionality of the whole organism. These tiny molecular machines are all seemingly unaware of the crucial role they play in the big picture as they complete their tasks with incredible precision and speed. And yet they cannot be completely oblivious to everything that is happening even trillions of cells away. The tiny molecules that move our muscles, for example, must react to signals from our brain originating from relatively vast distances away, they are sensitive to these signals and know exactly what to do when they come. In fact, it would be wrong to say that all of these tiny molecular machines act independently of each other, even if they are separated from each other by truly astronomical distances on the atomic scale. In a very real sense, they all are connected by the signals that they send to each other.
Single-cell organisms do not have to be connected to anything beyond what is happening in their immediate environment. Signals from the outside mostly help the single-cell organism to find food or light and help it avoid dangers. In a sense, single-cell organisms are selfish, their biological mechanisms are tuned mostly to their own individual survival, their molecular machinery is focused on sustaining proper internal function and they do not need the complex, elaborate external messaging systems that exist in multi-cellular organisms. This gives single-cell organisms, like bacteria, a disadvantage when compared with multi-cellular organisms. We will see, later on, that our immune system is able to detect and kill bacteria with the help of a combination of reactive oxygen species (ROS) that rips apart bacteria and simultaneously activates redox signaling networks in and between our cells. Over hundreds of millions of years, bacteria and primitive single-cell organisms have not been able to adapt to dominate multi-cellular life. In principle, our immune system is universally effective.
It might be interesting to contemplate, for a moment, what the fundamental differences are between single-cell and multi-cellular organisms. Cooperation, almost by its definition, seems to be the key to success in multi-cellular organisms; cooperation that is mediated by the connections made between the cells. If we are working on the scale of the molecular machinery inside each of the individual cells, then being connected means that cells can send messages between each other that will alter the way these tiny molecular machines conduct business in each of the connected cells. It may even mean that individual cells can be asked to sacrifice themselves and shut down for the good of the whole organism. The individual cells are programmed to obey the directives that are sent through their connections. These connections become absolutely essential for the survival of the organism.
Suppose, for example, that a single cell in your body cuts off the connections it has to all the other cells. This rogue cell can no longer receive the messages and directives from the rest of your cells and starts to act in a way as to preserve its own survival, similar to a single-cell organism. It becomes a cancerous cell. If it is successful in its struggle to survive and duplicate itself, then the whole organism will eventually die. In a very real sense, it is the connections made between cells that allow them to cooperate and to fulfill their own appointed role. Through these connections, billions of your cells every day realize that they are damaged and are called upon to selflessly sacrifice themselves, to die and to be replaced by the division of neighboring healthy cells, in order to help preserve the health of the organism as a whole.
On the most fundamental level, the molecular machines in your cells react, shift and change based on the messages that come into them through the connections that exist between your cells. They all work to fulfill their appointed roles, precisely and faithfully. There are literally thousands of different types of messages that are sent between cells, both chemical and electrical, that influence the way these tiny molecular machines function. In a very real sense, all of the 50 to 100 trillion cells in your body are all intricately connected and unified to provide you with the precious gift of life that you now possess.


Orchestrating the Pathways of Life — Redox Signaling Semaphores

These first few posts are helpful to bring our minds into the framework that will allow us to understand what life looks like on the molecular scale, all with the end to help conceptualize what the signaling networks that define life and connect all of the molecular players might look like on the molecular scale inside our body. On the molecular scale, everything is immense; there are a trillion billion water molecules in just one small drop of water, almost an unfathomable amount; in reality even the smallest drop of water contains a vast ocean of water molecules, stretching off into infinity in all directions in the molecular perspective. Even a single cell in this perspective, contains an enormous pool of molecules surrounded by an undulating membrane containing “windows” and “doors” (receptors) that allow molecules to pass through from the outside to the inside of our cells. Each cell can be thought of as a submerged “house” that protects the processes of life taking place inside. The molecular materials and supplies that the cell needs comes in through selective “windows” and “doors” (oxygen, nutrients, building materials, etc.); very few molecules can “seep in” through the cracks.
The pushing and pulling action of the constantly jostling sea of water molecules mark the pathways that molecules follow as they navigate through this ocean of water molecules inside your body. As molecules travel through this sea of water molecules, it can be somewhat like watching a huge “pinball” game. The traveling molecules will be bounced, pushed and pulled along through an array of “bumpers” and “magnets” until they finally arrive at their destination. Every once in a while, there will be a “bumper” or “magnet” in this sea of molecules that will push or pull them in the desired direction. It is amazing how much control can be exerted over seemingly random processes by a few well-placed “bumpers” or “magnets” in this huge molecular pinball game of life. The “signal beacons” that mark the pathways are often well-placed molecules that simply help nudge the ocean travelers in the desired direction. The “windows”, “doors” and “mailboxes” outside and inside the cells are full of specialized “signaling beacon” molecules that are specially designed to attract or repel only specific kinds of molecules out of the sea of passing molecules, making for a well-marked and designated pathway for certain kinds of molecules. Due to the combined efforts of all these types of well-placed signaling beacon molecules, all the molecules of life are able to successfully navigate the pathways of life in the ocean inside us and arrive safely at their intended destinations, even over what might seem to be astronomical distances on the molecular scale. The true glory and intelligence of the cell lies in how it controls this molecular signaling beacons and the traffic they direct. Five Nobel prizes have been awarded in as many years for work in understanding cell signaling, the implications are incredible.
What are the factors that determine the action of these “signaling beacons” that guide the molecules of life along the myriad pathways traversing the ocean inside us? We find that the real factors that determine these pathways lead us to examine the details of what happens in the local molecular environment surrounding the signaling beacons that mark the pathways. And what happens in the local environment around these signaling beacons is intimately connected to what is happening in the sea of constantly moving water molecules, and islands of charged clusters, surrounding these signaling beacons. So if we want to know the answer, it all comes back around to what happens in the salt-water environment that transmits signals to the surrounding molecules. Again we realize that the critical clues to life are found in what happens in the world of the all-encompassing water molecules. So, how are signals transmitted through this sea of water molecules?
Changing the redox potential or pH in the neighborhood of a “signaling beacon” can change the nature of its signal and thus shift the associated pathway. For a simple analogy, think of a signaling beacon as a “semaphore” floating on a buoy in the middle of the ocean. Changing the redox potential in the water surrounding the signaling beacon can change the “color” of the semaphore, say from green to red. This change of state shifts the “traffic patterns” of the molecules that are directed by this signaling beacon and thus shifts the pathway of millions of the molecules traveling through our internal ocean. This kind of signaling is referred to as redox signaling, it changes the nature of the signaling beacons and redirects the molecular pathways through the ocean of life inside us. There are molecular pathways that control literally every aspect of our existence. Pathways in our brain allow us to store our memories, think our thoughts, feel our feelings, and be aware of everything happening in our body and environment; joining with pathways in our body that beat our heart, breath our air, move our muscles, digest our food, control our metabolism and process billions of signals from every part of our body. We have seen that these pathways allow us to move the molecular materials and supplies needed throughout all of our cell communities. These pathways allow us to deliver the messages between the molecular players in our cells, tissues, organs and systems needed to operate our genes, sustain and maintain cooperation and homeostatic balance between all of our trillions of cells throughout all of our cellular communities.
We have come to an understanding that these life-sustaining pathways must allow molecules and electrical fields to pass through the vast fluid ocean of life that exists inside, outside and between all of our cellular communities and that connects all of the molecular players inside them. Finally we have come to a realization that all of the molecular traffic traversing these pathways through this vast sea of life are controlled by signaling beacons, much like “semaphores”, that determine what happens to the molecular travelers at the trillions of critical junctions or intersections all along the various pathways. We know how insulin and glucagon modify the glucose pathways in the body, for example. We ponder the question “Who controls these signaling beacons?” and find that, beside philosophical considerations, many of these signaling beacons are controlled by signaling molecules that exist in the sea of water molecules that surround them. These signaling molecules modify the state of the various signaling beacons (semaphores) that direct traffic along the molecular pathways. We will consider a special set of these molecules, redox signaling molecules, that are the most fundamental of all of these signaling molecules, composed of the very molecules that form the vast ocean inside us. We have quite a journey ahead of us.


The Harmonious Orchestration of Life


     It is no surprise then, when we consider all of the incredible complexities of life that everything comes down to how the molecules are formed and put together and how they interact inside the living cells and tissues.  The basic fundamental secrets of life, we might suppose, are found in how the molecules themselves are formed, how they interact with other molecules in their environment and how they shift and change over the course of their existence.  It seems a bit strange, at first, to fathom how all life can be composed of molecules, a bunch of whirling particles following a set of physical laws and fields, and how this can lead to sentient, conscious beings that are self-aware, can act for themselves and have learned enough to discover and ponder the very principles that allow themselves to exist.  This might be an open question, yet there is no denying that on the most fundamental level we are composed of molecules and yet we hold within ourselves the breath of life.

     On the most fundamental level, all life brings into itself the elements that it needs to sustain life processes and releases the waste products that are generated.  For humans these basic elements of life are water, nutrition, oxygen, fuel and waste.  Deprive us of any of these elements and we cannot exist.  This is universally true, right down to the cellular level.  After all, it is within the aqueous interior of our cells that oxygen is combined with fuel to create energy, where nutrients are used to build tissues, organs and systems and where waste is created.  Our lungs supply oxygen to our cells, our digestive system provides nutrients and fuels to our cells, our skin, mouths, stomachs and blood vessels absorb the water our cells need.  In short, all of the activities we do to sustain our life involves the necessary processes that bring the elements of life to our cells.  And then it is within the chambers of our cells that these molecular elements are processed into the molecules that are needed and where the energy is released that is needed to sustain the whole process and where waste products are generated and eliminated.  The processes of life are largely performed by self-sustaining, self-actuating molecular engines inside our cells, and the mystery of how this all works and sustains itself resides inside living cells, where the molecular mechanisms of life reside.

      The molecular orchestrations of life in our body are performed in perfect rhythm and harmony, every day, all working together to give us this incredible gift of life.  In an orchestra there are various types of players each trained to play their instruments with precision and mastery.  These players and their instruments can be compared to the masterful, beautifully crafted tiny molecular machines inside our cells.  The players in an orchestra gather together with their instruments, poised to perform their parts; the molecular machines in our cells are gathered together, organized and positioned precisely, ready to perform their part.  The musical score is then copied and passed out to the various players in the orchestra, similar to the way that the instructions within the DNA of our genes are copied into RNA and passed around to the players in our cells.  In the cell, the written music in the score represents the genetic instructions distributed to be performed by the molecular players.  Before the conductor steps onto the platform, the players warm up and practice their individual parts, the result is a dissonant jumble of individual musical lines, each conveying some part of a message, disjoint, confusing; there is no unity, order or sense to it.

     The conductor then steps up and taps his stand.  All the players with their instruments stand at attention and silent anticipation ensues.  All attention is on the conductor as he starts the beat and the instruments begin to play their individual parts at the programmed time.  Something interesting happens at that point.  All of the individual parts come together and start to convey a unified message; instead of individual parts, a harmonious orchestration ensues, each individual instrument now works together with the others to create a much richer and powerful message than would ever be possible with one instrument alone.  The individual parts then “make sense” as they are heard along with the other parts.  All of the instruments interplay in wonderful synchronization toward a singular purpose.

     If an orchestration is successful, a feeling described as “electricity” propagates as instruments, players, orchestra and audience link in to the same beat, the same message, the same emotional response.  There is an almost transcendent feeling unifying hundreds of people that are sharing a single message all conveyed by the vibrating air that surrounds them.  Most all of us have had this experience at one time or another, regardless of the type of music. This feeling may have more to it than it seems.  It appears to be programmed by life itself, it resonates with the harmonious orchestration of life that takes place inside your cells, tissues, organs and systems, trillions of tiny molecular orchestras performing together in remarkable harmony and rhythm, programmed by the “musical score” that is written inside the DNA.  The music is passed around inside the cells by messengers, generating and organizing the players and instruments.  The music is performed by these molecular orchestras performing the program of life inside the cells.  And just like in the orchestra, the real magic happens when a “beat” signal is established and all of these molecular instruments, cells, tissues and systems start listening to each other and acting in harmony, responding to the parts that are being played by the other instruments, each playing their part at the proper time.  Isn’t it interesting that this idea of harmonious orchestration even works on the molecular level, in fact on every level, inside your cells, tissues, organs and systems.  These harmonious molecular orchestrations inside us allow us to live.


Describing Life — Atoms are Everything

Image     Let there be no mistake, this journey of discovery gets quite interesting as we look at what is really happening inside these incredible bodies that we possess.  Things are even more interesting when you are looking at things on the atomic or molecular level.  Be prepared to take the red pill and enter the rabbit hole…the path that leads to the reality that awaits.

      In my college career, I learned that atoms are governed by a set of quantum mechanical laws and symmetries that determine how atoms are built and can fit together to make molecules.  Predictive models can be built, mathematically, to describe how single atoms interact with surrounding atoms.  These models make use of the concept of “fields”, like electric fields, magnetic fields, gravitational fields, etc. that describe how atoms interact with each other and the fields that exist around them.  The behavior of each particle characterized and influenced by the fields that the particle itself generates and the fields that surround it.  In a sense, we can experience this concept by playing with common refrigerator magnets.  We notice that if we orient magnets a certain way they will attract each other, by some sort of invisible “field” and yet in other ways they will repel each other, and so there are only a limited number of configurations that allow them to stick together to form structures.  Electric fields we observe, by rubbing balloons on cloth, for example, also follow physical laws.  These observable but invisible fields are formed from the alignment of trillions of trillions of fields from the individual atoms that make up the objects, each atom possessing its own fields and following similar types of laws.

     There are only four types of fields we know of in nature. The “gravitational” field is so weak that you need objects the size of a planet before you can really feel it, but it is far-reaching and stretches across the entire universe.  In sharp contrast, the “strong” field only acts over a distance the size of a proton, but is a trillion trillion trillion times stronger than the gravitational field.  The strong field sticks the protons together when they get close enough to each other, otherwise the clusters of protons in a nucleus would fly apart.  The “weak” field binds electrons and protons together to make neutrons.  But the king of the fields, of course, is the “electromagnetic” field that causes the electrons to be attracted to the protons, electrons to repel electrons, and protons to repel protons.  The electromagnetic field causes the electrons to move in and buzz around the clusters of protons in the nucleus (that are bound together by the strong fields).  The electrons spread themselves out around these clusters of protons to form atoms.  All of this amounts to atomic field theory.  The combined fields from all these particles inside the atoms also serve to attract and repel the neighboring atoms, and cause the atoms to arrange themselves and “stick” together into structures called molecules.

     If we were somehow to look at matter on its most fundamental level, we would see that everything we sense, experience and know to be real is composed of trillions of trillions of fundamental particles that are simply following the governing laws of what is known as field theory.  Everything is made of tiny particles floating around in space like electrons, protons and neutrons that are spinning and rotating around each other at blazing speeds.  All of these tiny sub-atomic particles cannot be modeled as individual solid objects, they do not have solid boundaries, but are best characterized by the fields that they create and how they interact with each other.  What we perceive as being a solid surface is formed because these particles have organized themselves into structures that “stick” together, much like stacking a bunch of charged floating magnets together to form a floating surface of magnets, where the motion of each magnet is restricted by the fields generated by the neighboring magnets.

          If we place our hand on a table, or surface, for example, we sense pressure when the electromagnetic fields from the array of atoms in our hands push against the fields from the array of atoms on the surface.  As the atoms of the surface are pushed by the fields of the atoms in your hand, the atoms of the surface will slightly flex out of place and push back on the atoms in your hand.  Your hand will not be able to go through the surface without breaking the bonds that hold the surface atoms together.  If we could somehow magically turn off the electromagnetic fields, there would be more than enough space to allow the atoms in your hand to pass through the atoms of the table.  The electromagnetic field prevents this from happening, it both holds atoms together by attractive forces and keeps atoms spaced apart by repulsive forces as well; it acts over relatively large distances on the atomic scale, these fields are sort of like fields from super-charged refrigerator magnets floating in space, strong enough to attract or repel each other even when they are several lengths away from each other.

     The field properties that make these atoms align and stick to each other describe and determine all the properties of matter.  For example, if the electromagnetic fields from the atoms on the surface of the table were aligned so that they would attract the atoms in your hand, the surface would be considered “sticky” and you might have a little difficulty removing your hand from the table.  It is the configuration of atoms bound together in these molecules that gives them their characteristics how they interact with all of the other molecules in their local environment.  The way the molecules interact, in turn, determines the properties of all matter and explains on the most fundamental level what all things are and how all things work.

     As we have attempted to visualize what things might look like if we were the size of an atom, it may be helpful to realize that the electrons are moving at several million miles per hour on the average, the atoms on a surface are interacting with each other over a million million times a second and a typical inch of surface is tens of millions of atoms long.  Anything large enough to see, like a speck of dust in the sunlight, consists of many trillions of atoms and anything large enough to feel, like a salt crystal, consists of a billion billion atoms.  You need to realize that everything is extremely small and extremely fast on the atomic scale.  The surface of your table on an atomic scale would look like a vast system of mountains and valleys made of vibrating molecules stretching off into infinity in all directions.

      This visualization will help us understand the true nature of the molecular forms of life in our cells as we dive into the inner workings of life and the signaling networks that hold it all together.  Let there be no mistake, this journey of discovery gets quite interesting as we look at what is really happening inside these incredible bodies that we possess.  Things are even more interesting when you are looking at things on the atomic or molecular level.  Be prepared to take the red pill and enter the rabbit hole…the path that leads to the reality awaits.


The Breath of Life


The complexity and beauty of life are transformative.  Just a moment’s contemplation of your own hand, observing the complex structure and functionality, the blood vessels, the hair, skin, skeletal  structure, joints, the ability to make it respond to your every command, can invoke a sense of the wonder of how it all works.  If you take the time to look closer, with a magnifying glass or microscope, you will see things you might never knew existed: vast fractured landscapes, hills and valleys.  You may see things that make this supposedly familiar part of you seem foreign: strange, moist valleys, dry wastelands, tiny creatures moving about.  In truth, you would have to spend about a month of exploration just getting to know the back of your own hand, and that is only the top layer of the skin, saying of nothing of the wonders that exist beneath the skin.

Certainly, this concept applies to more than just your hand, the same could be said of all life.  In all honesty, a true understanding of how life works requires a much closer view inside the structure of living things, past the tissues, down into the cells, past the living cell structures and past the bustling activity of thousands of different cellular components, down to the smallest elements of the working internal machinery.  It is here where the secret of life resides and where we might find our answers to how all life works.  Most scientific investigation of things on this small of a scale is relatively recent.  When my father was born, simple, basic cell structure was first being investigated.  When I was born, DNA and its function were first being explored.

During my lifetime, knowledge has grown exponentially to the point where we have mapped the whole human genome and now know almost 1% of the internal workings of a cell.  The acquisition of knowledge is a noble and worthy pursuit, embodying the greatest accomplishments of this century.  Discoveries are being made daily.  My children will possibly live in a day where the majority of fundamental cellular microbiological mechanisms will be known and much of the secret of life revealed.

How and where will the secret of life be found?  In my youth I was taught that an atom was the smallest fundamental unit of all matter.  In my young mind, I reasoned that the mysteries of how all things work must be found in the atom.  I was so enamored by this concept that I ended up studying atomic physics in college and later went on to earn my Ph.D. in that field.  The answers to the universe, I thought, must be found in how the atoms work.  After all, there only exist a grand total of less than 100 stable types of atoms.  Out of those there are only 20 or so necessary for life processes and the vast majority of the molecules of life are combinations of Carbon, Hydrogen, Oxygen, Nitrogen, Phosphorous and Sulfur, only 6 of them.  In the innocence of youth, I reasoned, it should not be too hard to figure out how everything works, it’s like putting together tinker toys or Legos where only a few different types of Legos exist.  I may have underestimated just a bit how many different things you can build with just this limited set of “Legos”.