Janna Levin, an American Astrophysicist, once remarked:
Science without story telling collapses to a set of equations or a ledger full of data.”
The story below is part real, part theoretical. It’s a fascinating journey of how a cell might transcend from “normal” to the unbridled growth that we know as cancer.
By the early 1990’s, cancer biologists could begin to model the genesis of cancer in terms of molecular changes in genes. To understand the model, let us begin with a normal cell, say a lung cell that resides in the left lung of a forty-year-old fire-safety-equipment installer. One morning in 1968 a minute sliver of asbestos from his equipment wafts through the air and lodges in the vicinity of that cell. His body reacts to the sliver with an inflammation. The cells around the sliver begin to divide furiously, like a minuscule wound trying to heal, and a small clump of cells derived from the original cell arises at the site.
In one cell in that clump an accidental mutation occurs in the ras gene. The mutation creates an activated version of ras. The cell containing the mutant gene is driven to grow more swiftly than its neighbors and creates a clump within the original clump of cells. It is not yet a cancer cell, but a cell in which uncontrolled cell division has partly been unleashed- cancer’s primordial ancestor.
A decade passes. The small collection of ras-mutant cells (ras is a gene that signals to cells to proliferate and divide – a mutant ras gene causes uncontrolled growth and hence is a precursor to cancer) continues to proliferate, unnoticed, in the far periphery of the lung. The man smokes cigarettes, and a carcinogenic chemical in tar reaches the periphery of the lung and collides with the clump of ras-mutated cells. A cell in this clump acquires a second mutation in its genes, activating a second oncogene.
Another decade passes. Yet another cell in that secondary mass of cells is caught in the path of an errant X-ray and acquires yet another mutation, this time inactivating a tumor suppressor gene. This mutation has little effect since the cell possesses a second copy of that gene. But in the next year, another mutation inactivates the second copy of the tumor suppressor gene, creating a cell that possesses two activated oncogenes and an inactive tumor suppressor gene.
Now a fatal march is on, an unraveling begins. The cells, now with four mutations, begin to outgrow their brethren. As the cells grow, they acquire additional mutations and they activate pathways, resulting in cells even further adapted for growth and survival. One mutation in the tumor allows it to incite blood vessels to grow; another mutation within this blood-nourished tumor allows the tumor to survive even in areas of the body with low oxygen.
Mutant cells beget cells beget cells. A gene that increases the mobility of the cells is activated in a cell. This cell, having acquired motility, can migrated through the lung tissue and enter the bloodstream. A descendant of this mobile cancer cell acquires the capacity to survive in the bone. This cell, having migrated through the blood, reaches the outer edge of the pelvis, where it begins yet another cycle of survival, selection and colonization. It represents the first metastasis of a tumor that originated in the lung.
The man is occasionally short of breath. He feels a tingle of pain in the periphery of his lung. Occasionally, he senses something moving under his rib cage when he walks. Another year passes, and the sensations accelerate. The man visits a physician and a CT scan is performed, revealing a rind-like mass wrapped around a bronchus in the lung. A biopsy reveals lung cancer. A surgeon examines the man and the CT scan of the chest and deems the cancer inoperable. Three weeks after that visit, the man returns to the medical clinic complaining of pain in his ribs and his hips. A bone scan reveals metastasis to the pelvis and the ribs.
Intravenous chemotherapy is initiated. The cells in the lung tumor respond. The man soldiers through a punishing regimen of multiple cell-killing drugs. But during the treatment, one cell in the tumor acquires yet another mutation that makes it resistant to the drug used to treat the cancer. Seven months after his initial diagnosis, the tumor relapses all over the body- in the lungs, the bones, the liver. On the morning of October 17, 2004, deeply narcotized on opiates in a hospital bed in Boston and surrounded by his wife and his children, the man dies of metastatic lung cancer, a sliver of asbestos still lodged in the periphery of his lung. He is seventy-six years old.
I began this as a hypothetical story of cancer. The genes, carcinogens, and the sequence of mutations in this story are all certainly hypothetical. But the body at its center is real. This man was the first patient to die in my care during my fellowship in cancer medicine at Massachusetts General Hospital.
Medicine, I said, begins with storytelling. Patients tell stories to describe illness; doctors tell stories to understand it. Science tells its own story to explain diseases. This story of one cancer’s genesis-of carcinogens causing mutations in internal genes, unleashing cascading pathways in cells that then cycle through mutation, selection, and survival-represents the most cogent outline we have of cancer’s birth.
–From The Emperor of All Maladies by Siddhartha Mukherjee
The Pulitzer Prize winning book, The Emperor of All Maladies, is one of my favorite books on medicine. It chronicles the history of cancer over several centuries. The book is loaded with intriguing stories of courageous patients, doctors and the fight against one of the most gruesome diseases. Some of the stories, such as Barbara Bradford’s (see issue one of In Sickness and Wealth), are encouraging and filled with hope. Others are tragic and end in death. Up until the 1970s, the progress made in cancer treatments was slow. Despite surgical advances, chemotherapeutic advances and radiation, etc., survival rates hardly moved. In breast cancer, women would undergo mutilating surgical procedures followed by gruesome and toxic chemotherapy and/or radiation. Yet most still succumbed because, despite all the advances in other diseases, the causes of unbridled growth among our normal cells evaded scientific explanation.
But in recent decades, great strides have been made in cancer. We live in exciting times as novel drugs and therapies help our immune system in the fight against cancer. Just this week, Duke University announced a breakthrough in the treatment of Glioblastoma, one of the worst cancers you can have. Glioblastoma is brain cancer and it is virulent and up until now, all known chemotherapy agents have been absolutely helpless against this disease. Duke University was able to use a modified polio virus to attack Glioblastoma. While much work needs to be done, the war rages on. And life by life, we are advancing. Survival rates are expanding. The toxic side effects are becoming more well-managed and novel approaches to chemo delivery, like nanotechnology, show great promise. Lives are being changed.
We started In Sickness and Wealth to shed light on companies doing just that, and to enlighten readers with a balance of science and business. Sometimes a company fails to deliver better healthcare, not because a treatment doesn’t exist or science can’t develop one, but because it can’t survive the logistics of access, delivery, and sustainability. Join us for a front row seat to explore companies that allow us the privilege of ownership in innovation that delivers value. So grab a seat. This is a fight you don’t want to miss, for millions of lives will be impacted, as we witness the eventual victory against cancer and other maladies – so that one day, the story we tell won’t be a 76-year old man fearing death due to lung cancer, but rather of him looking his grand-daughter in the eye as they dance at her wedding.