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Tuesday, January 24, 2012
Through the Lens of Molecular Medicine: John Donne, Illness, and Cancer

BY MATTHEW KATZ, MD

 

Cancer is an illness of transformation. Biologically, it represents a change in growth and homeostasis. Metaphorically, a cancer diagnosis can transform how you see yourself and the way you experience life afterward.  Even after successful treatment, patients live with continual uncertainty, leaving them in a limbo called NED because confirming cure is difficult.

 

Over the past few decades, we have lessened the taboo of cancer primarily with war analogies. While helpful to some, the metaphor of the body at war with itself can create its own anxieties. It also colors how we treat our patients: testing new “weapons”; evaluating outcomes as victory or defeat; “survivors.” Even well-fought wars weaken and injure non-combatants, and the metaphor has the power to transform our patients into casualties.  We can do better.

 

Because suffering is universal, sometimes looking at it through a different lens provides new perspective. John Donne, metaphysical poet and priest, wrote on death and illness in many works before dying of stomach cancer in 1631. One of his most beautiful works, Meditation XVII, remains powerful to this day and I believe is an excellent source to reframe how we look at the cancer experience. 

 

By reflecting on Donne’s words through the lens of molecular medicine, perhaps we can see cancer and illness in a different way.

 

Metaphysics and Molecular Medicine: Reflections upon Death and Illness

Perchance the cell for whom caspases toll may be so ill that he knows not it tolls for him; and perchance I may think myself much better than I am, as those who are about me and see my state may have caused it to toll for me, and I know not that. Homeostasis is diffuse, universal, so are all her actions; all that she does belongs to all.

 

When she creates a stem cell, that action concerns me; for that stem cell is thereby connected to that head which is my head too, and engrafted into the body whereof I am a member. And when she engulfs an apoptotic cell, that action concerns me: all cells are one genetic code and is one volume; when one cell dies, one chapter is not torn out of the book, but translated into a better language; and every chapter must be so translated.

 

Life employs many signaling pathways; some by senescence, some by dysregulation, some by cytotoxic agents, some by immunogenic response; but life's hand is in every pathway and binds up all our scattered apoptotic fragments again in that library where every antigen and epitope shall lie open to one another. As therefore the ligand that initiates apoptosis may call upon both the stem cell and its daughter cells to come, so this signal calls us all; but how much more me, who am brought so near the threshold by this state.

 

Disruption within the microenvironment (in which antigens and membrane proteins, cytokines, and reactive oxygen species all mingle) may affect which cells should apoptose first; and it was determined that those that divided first should be called earliest.

 

If we understand aright the dignity of the molecule that signals mitochondrial uncoupling, we would be glad to make it ours by dividing early, to make it ours as well as his whose indeed it is.  Apoptosis tolls for her that thinks it doth; and though it signals again, yet from the instant of cytochrome-c release she remains united to life. Who casts not up her receptors to growth factors when they stimulate hyperplasia? but who shuts off his receptors from cytokines when infection breaks out? Who bends not her kinases to any molecular switch which upon any occasion signals? but who can remove it from calcium ions which transmit a piece of himself out of this world?

 

No cell is an island, entire of itself; every cell is a piece of the organ, a part of the main. If a mutant clonogen be washed away by phagocytes, this body is the less, as well as if a normal gland were, as well as if an organelle of thy friend's or of thine own were. Any cell's death diminishes me, because I am involved in life; and therefore never send to know for whom apoptosis tolls; it tolls for thee.

 

Neither can we call this a begging or a borrowing of misery, as though we are not miserable enough ourselves but must fetch in more from the next cell, in taking upon us the misery of our neighbors. Truly it were an excusable covetousness if we did; for injury is a treasure, and scarce any cell hath enough of it. No cell hath stressors enough that is not matured and ripened by it, and made more fit for life by that affliction.

 

If a cell promulgates transcription in genes, or in excess ATP, and have none transmitted into paracrine factors, his stress response will not sustain him as he migrates. Tribulation is treasure in the nature of it, but it is not physiologic unless it brings us nearer to homeostasis and to our neighbors. Another cell may be sick too, and sick to death, and this affliction may lie in his cytoplasm as unused ATP and be of no use to him; but this signal that tells me of his affliction digs out and applies that stimulus to me, if by consideration of another's dangers, I take mine own into contemplation and so secure myself by renewing my commitment to life, who is our only security.

 

 

MATTHEW KATZ, MD (@subatomicdoc), is a radiation oncologist and partner at Radiation Oncology Associates, PA.  He currently serves as Communications Chair for the American Society of Radiation Oncology (ASTRO) and on the external advisory board for Mayo Clinic Center for Social Media.

 

 

 

 

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