Visual Analogy

The story through image

Bone Builders

The aging of the population diverts our sometimes-relutant attention toward those disorders of age that may not be lethal but that diminish the quality of remaining life. Osteoporosis qualifies as one of those disorders.

In recent years the ability to treat osteoporosis underwent a major advance with discovery of bisphosphonates, a class of drug that interferes with the bone-remodeling process, a process that may become unbalanced in certain bone disorders and with the decline of steroid hormones that occurs with age.

The adult skeleton is not a static entity.  Bone is constructed by osteoblasts and broken down by osteoclasts in a constant process of remodeling.  When breakdown of bone exceeds production, the skeleton becomes fragile and prone to fracture.

The class of drug known as bisphosphonates helps to restore the remodeling balance by inhibiting the breakdown of bone.  

Tree bones

Imagination is the one weapon in the war against reality.
Jules de Gaultier

P-Glycoprotein Pump 
(or how cancer cells adapt to chemotherapy)

Researchers were confounded by the fact that initial success in chemotherapy was often followed by failure, despite use of chemically dissimilar chemotherapeutic agents.  Somehow, cancer cells exposed to chemotherapeutic drugs "learned" to recognize and extrude the drugs before they did their damage.  It turned out that the explanation for this ability lay in an early mammalian adaptation.  

One of the reasons mammals survived as a species was the p-glycoprotein pump, a membrane-bound molecule that developed early in the evolutionary process.  When toxins entered the cell on which this pump was located, it ejected them before they damaged the cell.  As mammals diversified and developed, the pump diversified along with them.  In time it branched into a family of genes capable of protecting against various toxins, even those containing different chemical substrates.  Contained in the genes of many cells, the pump can be expressed upon exposure to toxic agents to commence its protective traits.  When cancer cells are exposed to but not killed by chemotherapeutic agents, many of which are derived from such natural toxins as snake and spider venom, the stage is set for expression of the p-glycoprotein pump.  Thus, the value of the pump and its purpose hinges on one's perspective.  

Pictured is the hydrophobic-and-hydrophilic pump, which disparate (water-loving, water-avoiding) nature I felt was contained in the form of the mermaid.  She is associated with a channel or pore through which toxins are extruded from the cell's interior.  Entering the cell behind her left shoulder and not yet detected by her is the unlovely visage of an agent toxic to the cell.  


The pIXY 321 Molecule
(or healing survivors of chemotherapy)

Chemotherapy works by killing rapidly dividing cells.  In adults, whose growth has stopped, rapidly dividing cells can be caused by cancer.  

But stem cells split quickly as well, and are thus inadvertent victims of chemotherapy.  Stem cells reside in bone marrow, where they produce eventual blood cells and assist the immune system.  In this illustration stem cells are shown as spheres.

Bacterial invasion of the body stimulates its inflammatory defense in this way:  When challenged by foreign invaders, macrophages and other protective blood cells in the host exude growth factors called cytokines.  These cytokines affect stem cells, causing them to divide and produce other types of blood cells in a defensive inflammatory response.  The new blood cells diminish the adverse effects of chemotherapy, as well as fight infection, in the host.

Cytokines are not created equal, and come in a variety of forms; the two types shown here are synthetic.  Cytokines of any stripe attach by way of "keys" to receptors, shown as "locks," on stem cells.  Each unique cytokine key fits its unique cytokine receptor on the stem cell.  Sometimes the different receptors to which different cytokines attach happen to be adjacent on the stem cells.  When they are adjacent, and are simultaneously stimulated by their respective cytokines, the stem cell proliferates, producing a much greater quantity of protective blood cells.  Thus, it would be beneficial for defending stem cells to have adjacent receptors for the cytokines IL-3 and GM-CSF simultaneously engaged.

Because chemotherapy kills stem cells, we assist those remaining with synthetic IL-3 and GM-CSF growth factors.  The two depicted here are IL-3 (green seahorses) and GM-CSF (blue-gray dragon).  Although these synthetic drugs have keys that fit the proper stem-cell receptor, they also have unwanted side effects,  designated by the fantastic shapes attached to the synthetic keys.

A recombinant process has produced yet another synthetic growth factor (with yet another unlikely name).  pIXY 321, as it is called, incorporates the useful parts of synthetic IL-3 and GM-CSF while avoiding most side effects.  Also, because it is a single molecule, it increases the chance of simultaneous binding to stem-cell receptors.  It is depicted as the key chain incorporating both dissimilar types of growth-factor keys.

More production from the stem cells remaining after chemotherapy assists the immune system of the host in fighting infection; other lymphocytes made by stem cells produce their own natural-killer cells that directly fight cancer.  Soon, of course, barring calamity, we will be able directly to attack cancer cells, bypassing the damage we now inflict on cancer's host. 

Bird branch

The Clock is Ticking           

even in Boulder!