Charles Graeber - The Breakthrough: Immunotherapy and the Race to Cure Cancer

The good physician treats the disease; the great physician treats the patient who has the disease.

S IR W ILLIAM O SLER , 18491919

U ntil very recently weve had three main methods for treating cancer. Weve had surgery for at least three thousand years. We added radiation therapy in 1896. Then in 1946, chemical warfare research led to the use of a mustard gas derivative to kill cancer cells. Those poisons were the foundation for chemotherapy.

These cut, burn, and poison techniques are currently estimated to be able to cure cancer in about half of the people who develop the disease. And thats remarkable, a true medical accomplishment. But that leaves the other half of cancer patients. Last year, in the United States alone, that translated to nearly six hundred thousand people who died of the disease.

The fight was never fair. Weve been pitting simple drugs against creative mutating versions of our own cells, trying to kill the bad ones while sparing the good ones and making ourselves sick in the process. And weve been doing that for a very long time.

But now we have added a new and very different approachone that doesnt act directly on cancer, but on the immune system.

Our immune system has evolved over 500 million years into a personalized and effective natural defense against disease. It is a complex biology with a seemingly simple mission: to find and destroy anything thats not supposed to be in our bodies. Cells of the immune system are on constant patrol, hundreds of millions of them circulating throughout the body, slipping in and out of organs, searching out and destroying invaders that make us sick and body cells that have become infected, mutated, or defectivecells like cancer.

Which raises the question: Why doesnt the immune system fight cancer already?

The answer is, it does, or tries to. But cancer uses tricks to hide from the immune system, shut down our defenses, and avoid the fight. We dont stand a chance, unless we change the rules.

Cancer immunotherapy is the approach that works to defeat the tricks, unmask cancer, unleash the immune system, and restart the battle. It differs fundamentally from the other approaches we have to cancer, because it does not act upon cancer at all, not directly. Instead it unlocks the killer cells in our own natural immune system and allows them to do the job they were made for.

Cancer is us. Its the mistake that works. Cells in the body regularly go rogue, their chromosomes knocked out by particles of sunlight or toxins, mutated by viruses or genetics, age, or sheer randomness. Most of these mutations are fatal to the cell, but a few survive and divide.

99.9999 percent of the time, the immune system successfully recognizes these mutant cells and kills them. The problem is that rogue 0.0001 percent cell, the one that the immune system doesnt

Cancer is different. It does not announce itself like the flu or any other disease, or even a splinter. It doesnt seem to sound an alarm in the house of the body, or provoke an immune response, or show symptoms of immune battle: no fever or inflammation or swollen lymph glands, not even a sniffle. Instead, the tumor is suddenly discovered, an unwelcome guest that has been growing and spreading out, sometimes for years. Often by then it is too late.

To many cancer researchers, this apparent lack of immune response to cancer meant that the goal of helping an immune response to cancer was futilebecause there was nothing to help. Cancer was assumed to be too much a part of our selves to be noticed as non-self. The very concept of cancer immunotherapy seemed fundamentally flawed.

But throughout history, physicians had recorded rare cases of patients whose cancers apparently cured themselves. In a prescientific age these spontaneous remissions were seen as the work of magic or miracle; in fact, they are the work of an awakened immune system. For more than a hundred years researchers tried and failed to replicate those miracles through medicine, to vaccinate or spark an immune response to cancer similar to those against other formerly devastating diseases like polio, smallpox, or the flu. There were glimmers of hope, but no reliable treatments. By the year 2000, cancer immunologists had cured cancer in mice hundreds of times, but could not consistently translate those results to people. Most scientists believed they never would.