living cell (5)

We have covered two of the most important, and most ancient, processes within a cell, protein synthesis and DNA replication.  But these are hardly the only complex, mysterious processes that take place in a cell. 

Consider the figure below [13-20] and note the caption indicates that this represents, “a small fraction of the reactions that occur in a cell.”

The text goes on to say:

For all these pathways to work together smoothly as is required to allow the cell to survive and to respond to its environment, the choice of which pathway each metabolite will follow must be carefully regulated at every branch point. [p. 447]

We haven’t any explanation as to how each pathway is “carefully regulated at every branch point.”  Nor is it likely that lifeless biochemical reactions are solely responsible.  The text goes on to elaborate:

…depending on conditions, a cell must decide whether to route key metabolites into anabolic or catabolic pathways – in other words, whether to use them to build other molecules or burn them to provide immediate energy. [p. 447]

How does the cell ‘decide’?  Does some rational process, one that weighs various inputs, take place that favors to build some molecules and burn others?  To make things more interesting…

All the reactions shown in Figure 13-20 occur in a cell that is less than 0.1 mm in diameter, and each step requires a different enzyme.  To add to the complexity, the same substrate is often a part of many different pathways. [p. 447]

This fact alone makes it clear that something other than biochemistry occurs within a living cell, because under non-living conditions, the same reactions would occur without distinction or priority.  In other words, they would be missing the timing, coordination and selection we discern in living reactions.  Non-living reactions lack control:

To balance the activities of these interrelated reactions – and to allow organisms to adapt swiftly to changes in food availability or energy expenditure – an elaborate network of control mechanisms regulates and coordinates the activity of the enzymes that catalyze the myriad metabolic reactions that go on in a cell. [emphasis original]  [p. 447]

In order to accomplish much of the coordination and communication within a cell, an elaborate set of signaling pathways exist.  According to the text:

Individual cells, like multicellular organisms, need to sense and respond to their environment.  A free-living cell – even the most humble bacterium – must be able to track down nutrients, tell the difference between light and dark, and avoid poisons and predators.

 In a multicellular organism, things are much more complicated.  Cells must interpret the multitude of signals they receive from other cells to help coordinate their behavior.  During animal development, for example, cells in the embryo exchange signals to determine which specialized role each cell will adopt, what position it will occupy in the animal, and whether it will survive, divide, or die.  Later in life, a large variety of signals coordinates the animals growth and its day-to-day physiology and behavior. [p. 533]

This is simply fantastic, that such systems exist in a living cell, yet in some ways unsurprising: how else would a cell, or an organism, survive?  

Whether part of a plant or an animal, a cell receives messages from many sources, and it must integrate this information to generate an appropriate response: to live or die; to divide, to differentiate, to change shape, to move, to send out a chemical message of its own, and so on. [p. 567]

This integration is made possible by connections and interaction that occur between different signaling pathways.  Such cross-talk allows the cell to bring together multiple streams of information and react to a rich combination of signals. [p. 568]

For a more detailed look, consider figure 16-9 below.

The text speaks to the complexity of the signaling pathways:

As dauntingly complex as such pathways may seem, the complexity of cell signaling is actually much greater still.  First, we have not discussed all of the intracellular signaling pathways that operate in cells. Second, although we depict these signaling pathways as being relatively linear and self-contained, they do not operate entirely independently. [p. 562]

For instance, let’s take a closer look at the RTKs (Receptor Tyrosine Kinases) below in figure 16-29:

The text explains that 

As long as they remain together, the signaling protein complexes assembled on the cytosolic tails of the RTKs can transmit a signal along several routes simultaneously to many destinations in the cell, thus activating and coordinating the numerous biochemical changes that are required to trigger a complex response such as cell proliferation or differentiation.  To help terminate the response, the tyrosine phosphorylations are reversed by tyrosine phosphatases, which remove the phosphates that were added to the tyrosine’s of both the RTKs and other intracellular signaling proteins in response to the extracellular signal.  In some cases activated RTKs (as well as some GPCRs) are inactivated in a more brutal way: they are dragged into the interior of the cell by endocytosis and then destroyed by digestion in lysosomes. [p. 559]

Scientists have discovered local and tactical explanations, identifying signaling molecules and how they interact with others, without determining how the entire network functions:

Information received from different intra-cellular signaling pathways can converge on [protein kinase], which then convert a multicomponent input to a single outgoing signal.  These integrating proteins, in turn, can deliver a signal to many downstream targets.  In this way, the intracellular signaling system may act like a network of nerve cells in the brain – or like a collection of microprocessors in a computer – interpreting complex information and generating complex responses. [p. 568]

To provide some sense of scale to the signaling network within a living cell, consider the following table, one that lists examples of signal molecules [table 16-1]: 

The text ends on this topic by acknowledging our fundamental ignorance as to how all of this comes together in a coordinated and functioning manner:

Our understanding of these intricate networks is still evolving: we are still discovering new links in the chains, new signaling partners, new connections, and even new pathways…Yet even if we could identify every single component in the elaborate network of signaling pathways, it will remain a major challenge to figure out exactly how they all work together to allow cells – and organisms – to integrate the diverse array of information that inundates them constantly and to respond in a way that enhances their ability to adapt and survive.  [my emphasis] [p. 569]

The last sentence above encapsulates perfectly my intent.  It is this ‘major challenge’ that I propose to emphasize in the Vicarian Domain.

…it remains a mystery how different cell types in the same animal grow to be so different in size. [p. 645]

As far as we currently know, all developmental intelligence/design/planning resides within individual cells, and more specifically, within the cell’s DNA:

Three fundamental processes largely determine organ and body size: cell growth, cell division, and cell death.  Each of these processes, in turn, depends on programs intrinsic to the individual cell, regulated by signals from other cells in the body. [p. 639]

The text lays out the basic challenge:

Cells are the building blocks of multicellular organisms.  Although this seems a relatively simple statement, it raises deep questions.  Cells are not like bricks: they are small and squishy and enclosed in a flimsy membrane less than a hundred-thousandth of a millimeter thick.  How, then, can cells be joined together robustly to construct a giraffe’s neck, a redwood tree, or muscles that can support an elephant’s weight?  How are all the different cell types in a plant or an animal produced, and how do they assemble so that each is in its proper place?  Most mysterious of all, if cells are the building blocks, where is the builder and where are the architect’s plans? [p. 691]

In other words, how is it possible that developmental decisions reside exclusively within cell(s)?  The text reflects our basic ignorance:

What adjustment of cell behavior explains the length of an elephant’s trunk, or the size of its brain or liver?  These questions are largely unanswered. [p. 639]

The text points to regulatory DNA as driving the specific development program within an organism:

All these species [humans, chimps…dogs, cats and mice] contain essentially the same protein coding genes…What makes these creatures so different…?

 The instructions needed to produce a multicellular animal from a fertilized egg are provided, in large part, by the regulatory DNA sequence associated with each gene…Regulatory DNA sequences ultimately dictate each organisms developmental program – the rules its cells follow as they proliferate, assess their positions in the embryo, and specialize by switching on and off specific genes at the right time and place.  [p. 326]

Cell differentiation is both the key to this mystery, and then another mystery:

All cells must be able to turn genes on and off in response to signals in their environment.  But the cells of multicellular organisms have taken this type of transcriptional control to an extreme, using it in highly specialized ways to form organized arrays of differentiated cell types.  Such decisions present a special challenge: once a cell in a multicellular organism becomes committed to differentiate into a specific cell type the choice of fate is generally maintained through subsequent cell divisions.  This means that the changes in gene expression, which are often triggered by a transient signal, must be remembered by the cell.  Such cell memory is a prerequisite for the creation of organized tissues and for the maintenance of stably differentiated cell types. [p. 278]

Throughout this chapter I have referred to complexity again and again.  As a reminder, recall that we identified two kinds of complexity: ‘disorganized complexity’ and ‘organized complexity.’  

The non-living world swarms with disorganized complexity, as it relates to a system with many millions of parts that interact randomly and as a system can be characterized though probabilities and other statistical methods.  The example given is gas in a container with the individual parts being the molecules of gas.  While it would be exceedingly complex to map the motion and predict future motion of particular molecules, the system as a whole will consistently exert the same internal pressure given the same physical circumstances.

This is not the kind of complexity we have been reviewing.  In fact, the distinction between the two is fundamental to this book.  ‘Organized complexity’ describes a system with a number of parts that interact non-randomly or in a correlated way.  Unlike disorganized complexity, a system of organized complexity doesn’t require a large number of parts for the system to display emergent properties, or for that system to interact non-randomly with other systems.  

The complexity we have witnessed in living cells is enormously well organized.  In fact, outside the living world, and more recently the human one, organized complexity simply doesn’t exist.

One property above all makes living things seem almost miraculously different form nonliving matter: they create and maintain order in a universe that is tending always toward greater disorder.  To accomplish this remarkable feat, the cells in a living organism must continuously carry out a never-ending stream of chemical reactions to maintain their structure, meet metabolic needs, and stave off unrelenting chemical decay. [p. 81]

The organized complexity we have encountered several times in this chapter indicate that something other than known physical and chemical properties is involved.  Something profound, intentional, and coordinated.

Biomolecular Scientists have done an amazing job.  The explanations they have provided for molecular activities are incredible, given the scale, the complexity, and the general inaccessibility of their subject.  The questions I pose wouldn’t be possible without the progress they have made in recent decades.

But I am posing a specific question: do we expect to continue drilling down into these molecular processes and limit explanations to what we have already discovered?  In other words, do we expect more of the same, with increased fidelity to local, tactical explanations of how one molecular event occurs, or another?  Are the scientists confident that ultimate explanations will consist of known chemical and physical properties?  

I am suggesting that the answer to these questions is a firm no.  Within the Vicarian Domain, that is, the bio-molecular world, I expect new natural forces, entities, or conditions to be discovered that will provide the explanation for the planning, coordination, communication, intention and focus we witness in these biological transactions.  Some form of agency currently unknown.

And we can be perfectly confident that the new explanations that resolve these biological mysteries will reside within the natural world.  This confidence arises from the fact that humans have been blaming one natural mystery after another on god and/or his minions since humans have existed, and time after time science has effectively debunked these supernatural explanations and replaced them with scientific ones.   I expect the same will hold when we discover the secrets of the Vicarian Domain.

Even if scientists can answer a particular question posed in this chapter with a local, tactical explanation, each new answer will pose new questions, in the same way explaining how the gas/air mixture in the firing chamber of an internal combustion engine is the correct mixture by pointing to the function of the carburetor doesn’t fully explain how a car gets from one place to another.  There exists an ultimate, natural explanation as to why and how a living cell operates, how organisms grow into one kind of organism and not another, how the development of the brain includes instinctive instructions to the living organism, how one organism evolves into another, and how life originated in the first place.