“We have met the enemy and he is us.” Walt Kelly, Pogo comics
I have been writing about resistance to toxic chemicals. And though I have plenty of posts on other stuff, I have shied away from cancer, even though one of the biggest problems with treating cancer is resistance. Yet it is difficult to write about. Why more so than antibiotic resistance, or deadly viruses, I am not sure. Maybe because rationally or irrationally there is such fear of the cancer that it is unnerving to write about. Or maybe because it is a heavy topic that resonates with far too many people. But cancer is natural. The cancerous cell is the renegade cell that has become free from life’s rules of order. It is rapid evolution at its best and worst. Its origins are as old if not older than the first “true animals” and it is, by most accounts, a greater threat to the human population today than at any other point in our modern history.
At its most basic, cancer is a disease of multicellular life. Whatever the driving force leading to multicellular life, whether population genetics, energetics, oxygen toxicity, or some combination of all of the above, the increased complexity of the gene and cellular architecture allowed for new features laying the groundwork for a new kind of social organization, a society of cells. My body is a highly functional social network. An improved facility for cell-to-cell communication and coordination, adherence between cells and, counter-intuitively the capacity for a cell to die on “command” all are important components of the multicellular toolkit; tools which may have allowed single eukaryotes to build multicellular homes for themselves. And which also laid the groundwork for the inevitability of the cancerous cell. As with any social organization there are collaborators, independents, and renegades.
As I ponder the tens of trillions of somatic cells in my body, the tens of thousands of genes per cell, and the numerous opportunities for mutation I wonder if and when cancer might strike. With good fortune and good genes, maybe it never will. Or perhaps it already has, and I am unaware. Given the opportunity, it is a wonder that cancerous growths are not more pervasive. How complex life avoided this fate may reside in the mechanics of cancer, the body’s defenses, and the fact that all genes do not contribute equally to the evolution of cancer. Recent efforts to characterize the genomes of cancer cells are continually providing insight into the specific genes which when mutated are most likely to contribute to cancerous changes in humans. Currently the proportion of genes associated with somatic cancer (and the great majority of cancer occurs in somatic as opposed to germ cells) represent just 1.6% of the human genome, a small proportion, although a figure which is likely to increase with increased sequencing efforts. While genomics holds great promise, cancer is incredibly complex and a wily beast. When it comes to resisting toxic chemicals, cancerous cells are more than up to the task. In many cases cancerous cells are resistant before treatment begins. But more about that next blog.
For an excellent book about cancer’s history, biology and treatment read Siddhartha Mukherjee’s The Emperor of Maladies: a biography of cancer. Or, if you aren’t into reading (though you would be missing out on a great book) watch the Ken Burns mini-series beginning tonight, March 30.