While we are in the underwater world of living cells inside us, it becomes obvious that there is quite a bit of construction going on all around us.  Communities of billions of cells houses are being taken down and rebuilt every day;  equivalent in scope to the demolition and rebuilding of every building on earth, every day.  What does our body need to build and rebuild our cells?

Building Materials — Micronutrients (vitamins and minerals, molecules taken from our food), fuel (sugars and fats), amino acids (the building blocks for proteins).  All of these molecular materials are found in plants, you can build an elephant from just the materials found in plants.

Water and electrolytes [salts] — A nice high water table helps everything work smoother, a low water table slows everything down.

Oxygen — This hardly needs mentioning.  Let’s point out, however, that oxygen is only one of the many oxidants that are essential to the function of our cells.

Building Plans — The building plans for the cell are found in the DNA.  In the DNA there is a repository of all the plans needed to build the micro machines, workers, and structures in the cell.

Messengers — These are the signaling molecules that run back and forth delivering messages to the workers.  They read the DNA plans, push the genetic buttons that create the workers and machines, and deliver the messages that tell the workers what to do.

Is there anything else needed?  I think we have listed everything we need to build a cell.  Out of these components, which one do you find most interesting?

In the last 15 years almost all of the groundbreaking work in cellular microbiology has been done on the messenger components of the cell, affording the scientists several Nobel Prizes.  Redox signaling messengers (made from the most abundant elements in nature) are perhaps the most fundamental of all the messengers in the cell.  They pass the messages needed to build and maintain all the types of cells that exist in nature.  There is no doubt that understanding the messenger systems of the cell will bring us the next greatest discoveries in life sciences.

We are finally descending into the heart of redox signaling country, we come to a place where there are many different pathways branching off in many different directions.  And it looks like we are going to get wet.  All of these redox signaling pathways are going directly into a huge ocean of salt water.  We put on our scuba gear and tread in.  There is no other way.  All molecular activities in all forms of life on earth take place in salt water, it is the vital fluid of all life.  All our cells and tissues are submersed in this ocean of fluids.

Under the salt water we find great currents of vital elements moving past in living rivers coursing throughout the extensive communities of living cells.  Each cell is like a submerged house in this vast ocean, all of the cells are stacked in neighborhoods closely surrounded by these flowing rivers of currents; like houses along streets.  These communities of cells are connected and fed by the currents that flow past them. Every living cell is alongside these moving rivers of life; each cell is connected by it.

Now imagine, if you can, this underwater community extends to fill all the oceans on earth, some 70 trillion houses; equivalent to every man, woman and child on earth today, each building 10,000 houses along these river currents.  This represents the vast extent of the community of cells that exists inside just one living human being.

Of course, the rivers of life are mostly the networks of blood vessels–literally miles of them–feeding all the cells in our body.  Our heart pumps this river of life though this vast network of blood vessels that connects and supplies our cells with all of the elements of life that they need.  This river travels in only one direction, nothing much travels upstream.  Along with oxygen, all of the fuel, building materials, chemical signals–everything needed to sustain life–travel along these rivers.  The things that cannot be transported directly through the plasma fluid in the veins (for whatever reason) have little specialized “submarines” built for them to transport them down this river of life.

The cells have access to these currents of life through the receptor windows, chimneys, vents and doors.  We can imagine the little molecular inhabitants of these cell houses floating in these fluids, swimming around inside their houses and between their houses under the water.  The fluid that exists inside and around our cells in our body is somewhat similar to the seawater that is in our oceans.  Blood plasma contains 0.9% salt, with a mixture of minerals; the ocean contains 1.9% salt, with similar types of minerals.  We are now getting a better idea of what it really must be like to live in a community of cells.

With this picture in mind, it is easy to see that the fluid pathways that exist in, around and between our cells (individually and collectively) allow the molecules that are needed to sustain life (fuel, material, supplies or signals) to be available to all of our cells.  It is also important to know that each living cell controls access to the “doors” and “windows”, and will not allow entry to just any molecule that happens to be floating by.  In our cell communities, the doors and windows are called receptors and co-receptors and they selectively allow in only the fuels, materials supplies, and signals that are needed and used by the cells at any particular moment. Very few things can “seep through the cracks”.  In this way, the cells have control over what is allowed to come in and what is allowed to go out.  This selective behavior of the cells makes sense as we consider the complex logistics necessary for sharing resources among the trillions of cells in this thriving underwater community.  Collectively, all of the fluid pathways constitute a vital one-way river of life that connects, surrounds, and passes through all of the cells, tissues, organs and systems of our body.

Another experience in this underwater world becomes very real to us.  We cannot communicate with each other except by finding a way to send messages through the salt water that surrounds us.  Since we have eyes, it may be easier for us to use lights or hand signals; but the molecular inhabitants of this world must have different, more interesting ways of communicating among themselves.  In order to send a signal through water, the inhabitants have a limited number of options. If they have excess electrons or protons, they can use “email” and send electrical signals along the cables that connect the cells (neuronal material).  If not, molecules can physically move with the currents between houses and travel like mail carriers to deliver the messages personally to the intended recipients (like hormones).  Or, more interestingly, they can modify the molecules in the surrounding water (by reducing or oxidizing them) to and send ripple-like messaging to other nearby molecules through the surrounding salt-water medium.

Let us try to understand how this last form of communication works.  How can life’s molecules modify the salt water molecules that surrounds them?  We discover that as with all molecules, salt-water molecules can be reduced and oxidized (redox’d) through exchanges of electrons.  Some biological molecules, like NADPH complexes, physically modify salt-water molecules (Na⁺, Cl^–, H₂O) and reorganize them into other molecules such as hydrogen peroxide (H₂O₂), super oxides (O₂^*-,HO₂), hyperchlorites (OCl-, HOCl, NaOCl), captured gasses (O₂, H₂), ions (H⁺,OH^–), and a variety of other molecules, ions and free radicals.  These molecules are part of the class of redox signaling molecules that can send messages through the salt water.  If you are curious to find a complete list, you can google Reactive Oxygen Species (ROS) and find all in this class of molecules.  ROS are part of the fundamental class of redox signaling molecules found in all living organisms.  There are other types of redox signaling molecules.  If you add nitrogen (N₂), which comprises 80% of the air we breathe, then nitric oxide (NO) can be formed, this is part of a class called Reactive Nitrogen Species (RNS).  Then adding sulfur, very abundant in sea water, we also get Reactive Sulfur Species (RSS).  ROS, RNS, and RSS comprise the class of redox signaling molecules that we are exploring.  Each one of these redox signaling molecules can carry clear messages through the salt-water medium inside us.  We simply could not live without them.

We have now become formally introduced to some of the ways that molecules can communicate among each other.  Redox signaling may be by far the most interesting way of them all.

Welcome to redox signaling country!

This week as I have been traveling, I will include the preface to my new book (to be published soon) before we get further into the concepts and science of redox signaling:

Preface – The Journey

I have always enjoyed exploring nature.  I grew up near the Rocky Mountains.  In my young years, whenever we had a chance, my brother and I would take off in any direction into the mountain trails and off-trails to explore the unknown.  These excursions into the unknown carry some of the most memorable experiences of my life.  There was the constant intense exertion of a tough climb followed by the thrill of a new discovery.  There are certain things that we soon learned along the way.  Following unexplored paths is difficult and often ends in the disappointment.  More times than not, we ran into insurmountable barriers, thick brush, loose sliding shale, sheer cliff faces, steep ravines, and so forth that forced us to back up and find another way around.  However, from time to time during our journey, the path opened up into a breathtaking panoramic view. We paused (and sometimes hooted and hollered) to enjoy the majesty of it all.  From these vantage points, we could see where we were, how far we had come, and where we were going, along with all of the incredible expansive terrain that we had yet to explore.  Along with this drive for discovery also came the realization that the true joy in exploration comes in discovering truths that already exist in nature but have not been seen before.  I remember being on a remote winding trail in virgin wilderness and finding a candy bar wrapper and felt let down that someone had been there before us.

In my career as a scientist, I have experienced the same pain and joy of exploration that I felt in those early days on mountain trails.  To the subject at hand, when I first started to explore the possibilities of redox signaling, my expectations were very small that it would lead to anywhere interesting.  After all, salt water is abundant and has been explored extensively already.  I went up this off-trail just wondering where it might lead.  As more and more opened to view, I became cautiously optimistic.  The data from credible studies was showing me that, despite having some of the most reactive molecules in nature, this composition was perfectly safe for many types of cells and tissues.  More data showed that this composition is very similar to the “bullets” used by the immune system to kill all types of microbes.  Further studies have shown that it is potently antimicrobial itself, killing many different types of resistant microbes on contact.  Perfectly safe and antimicrobial…could this be true?  If so, there could be many applications, including that of a nearly perfect disinfectant.  The first glimmers of possibility were starting to open to my view.

In our modern world, it has come to a point where our very survival depends on the ability to utilize these newly discovered technologies for our benefit. We rely on them more and more in order to continue to thrive.  We rely on the transportation technologies that carry supplies, as in the plastics and new materials used to build our cars, containers and houses, the semi-conductor technologies that run our computers, cars, phones, TV’s etc.  We also rely on the energy, electricity, oil, nuclear, solar, etc. that is needed to carry on all the activities of life every day.  Along with the incredible benefits these technologies bring, there are also some liabilities. With solemn realization, we are finding that misuse of these same technologies can also serve toward our destruction.  In our pursuit of dominance, we have developed nuclear bombs that can destroy even our most modern and advanced cities in the blink of an eye.

In every sense, our journey of discovery is a human journey, embodying the principles of the human equation that we are learning along the way: human struggle and striving, the indomitable human spirit, mixed in with greed, strife and suffering.  As our knowledge increases, seemingly without bound, in true exponential fashion, in conjunction with the power it provides us to change our environment, there is a real concomitant need to master the human equation, for with great power comes great responsibility and the stakes are getting much too high to ignore.  With the knowledge that we presently have in agricultural sciences, for example, it is within the realm of possibility, given what we have on hand today, to adequately grow and distribute sufficient food to feed all of the people in the world.  If it is not lack of technology that prevents us from doing so, then what is it?  As knowledge increases past the point where we are able to understand the very nature of life itself, then the really difficult questions  begin to surface.  I yearn, with all that is human within me, to believe that we will be ready and willing to face our own humanity as we travel along the journey of life into a promising future.

We truly live in exciting times where the mysteries of the ages are finally being peeled back and revealed.  At present, the acquisition of knowledge is dizzying, quickly outdistancing our ability to assimilate it and apply it to real-world problems.  From 1650 through 1750, there was only one scientific journal published.  Ever since about 1785, about 10 generations ago, the number of scientific journals started doubling every 22.5 years consistently [ref: 21].  In the early 1900’s, there were only 250 journals with about 7,000 articles published per year, including articles by Albert Einstein and Max Plank that have changed the very world in which we live.  In 2009, there were over 12,000 journals and over 1 million articles.  Every month, over 100,000 scientific articles are being published, each representing months of laboratory work, amounting to millions of months of scientific work that is published and available to us each and every month.

In the upcoming century, one of the most worthy pursuits, almost to the point of being revered as sacred, is to unravel the mystery of what makes us live.  Can we really understand the physical principles upon which life is based well enough to grasp the very nature of life?  We are already on the pathway and, barring global calamity, we will amass enough knowledge in the next 50 years to get a good picture of the nature of our own being on a physical level.  What advantage is this knowledge going to give us?  When we have half of the picture, to what end will we use this knowledge?  Will it be utilized, even unknowingly, to promote destructive efforts?

I take some comfort in that the fact that the evolution of knowledge is based on principles that require constructive efforts, and that misery and destruction are based on ignorance.  Scientists must spend years acquiring the knowledge, which requires development of the strikingly human characteristics; the hunger to know the truth and more importantly, the dedication to study and research in unveiling the truth.  These same human elements that enable scientific development are those that will help us overcome differences and move toward a bright future.  The possession of such a desire leads to knowledge and self-actualization, whereas the lack of such proves self-destructive and must ultimately diminish.  These are the very principles and laws that allow for our existence, that allow us to adapt and live, the physical laws that govern how our body works and how we thrive.  As we discover these principles, let us not think that we are greater than them; let us not think that we can govern them; rather, let us reverence them and search for greater understanding; let us discover and conform to true principles and enjoy the life that has been given us and that which exists in such great harmony and abundance around us.