I'm Sorry, Steve. I Wish We Had Done Better

Article excerpt

Byline: Siddhartha Mukherjee

We are failing to treat and prevent cancer even as the promise of life-saving remedies awaits us. On the anniversary of Steve Jobs's death, leading oncologist and the author of 'The Emperor of All Maladies' explains how we failed to save an icon and why we will lose so many more lives if we do not give cancer research the funding it deserves.

In Oct. 5, the night that Steve Jobs died, I ascended 30,000 feet into the thin air above New York on a flight to California. On my lap was a stash of scientific papers. I was reading and taking notes--where else?--on an iPad.

Jobs's death--like a generational Rorschach test--had provoked complex reactions within each of us. There was grief in abundance, of course, admixed with a sense of loss, with desolation and nostalgia. Outside the Apple store in SoHo, New York, that evening, there were bouquets of white gerberas and red roses. Someone had left a bushel of apples by the doorstep and a sign that read "I-miss ..."

I missed Jobs, too--but I also felt a personal embarrassment in his death. I am an oncologist and a cancer researcher. I felt as if my profession, my discipline, and my generation had let him down. Steve Jobs had promised--and then delivered--life-altering technologies. Had we, in all honesty, given him any such life-altering technologies back?

I ask the question in all earnestness. Jobs's life ended because of a form of pancreatic cancer called pancreatic neuroendocrine tumor, or PNET. These tumors are fleetingly rare: about five in every million men and women are diagnosed with PNETs each year. Deciphering the biology of rare cancers is often challenging. But the past five years have revealed extraordinary insights into the biology of some rare cancers--and PNETs, coincidentally enough, have led part of that charge. By comparing several such tumors, scientists are beginning to understand the biology of these peculiar tumors.

But understanding biology is an abstract activity. Steve Jobs needed more than "biology." He needed medicines. And despite our efforts, we were unable to transform our knowledge about PNETs into medical realities during his lifetime. The question is, are we ready to achieve this transformation sometime in the near future?

Let's take PNETs as a case in point. In 2008 a team of scientists from Johns Hopkins University set out to document all the gene mutations in PNETs--creating a systematic genetic "anatomy" of these tumors. Cancer, of course, is ultimately a disease of mutations in genes. Human cells possess about 23,000 genes in total. In cancer cells some of these genes are changed--mutated--and begin to function abnormally.

Many of the genes that are mutated in various cancers, predictably, control cellular growth. Genes regulate the growth of cells like invisible puppeteers tugging and pushing opposing strings behind curtains. There are genes that command a cell to grow and those that tell a cell to stop growing. Cancer occurs when these growth-control genes are mutated, resulting in the dysregulated growth of a cell.

But the genes most frequently mutated in PNETs are odd. They don't seem to control growth directly; rather they seem to affect the way cells regulate genes. Take a moment to understand this by considering normal development. A cell in the retina possesses the same 23,000 genes as a cell in the skin, yet these two cells barely resemble each other in shape, size, or behavior. How does a cell, then, "know" how to become a retinal cell versus a skin cell? How can the same set of 23,000 genes be used to specify such radically diverse behaviors, functions, and forms?

Part of the answer lies in the way genes are controlled, or regulated. Although a skin cell and a retinal cell inherit the same set of 23,000 genes, a skin cell activates or suppresses a unique subset of the total--say 5,000 of the 23,000--while a retinal cell activates another subset. …