Could Immunotherapy Offer a Cure for Cancer?


If someone were to give cancer a human face, it would probably be that of an archvillain in a comic book series — a master of evil who can adapt at will to any attack, lurking lethally in the shadows, shifting its shape and location, resistant to almost any weaponry humans devise. At least, that has been the story until very recently; the new book by Charles Graeber, “The Breakthrough: Immunotherapy and the Race to Cure Cancer,” artfully traces the history of old and new developments that may have — finally — resulted in an actual cure for the most dreaded of all diseases. If you or a loved one has recently received a cancer diagnosis, or has been living with it as a chronic, if terrifying, condition, this book and the advances it describes offer far more than the usual glimmer of hope.

Immunotherapy essentially involves training the body’s own immune system to fight the disease. It’s an idea that scientists have been exploring since the end of the 19th century, when a Harvard-trained surgeon named William Coley met a vivacious young woman with a painful lump on her hand, swollen to half the size of an olive. Coley found and cut out a mass, but it grew back. Eventually it was found to be a sarcoma, a form of cancer that was already racing through his young patient’s body. She died at 17.

Disturbed by her death and determined to find another way to treat cancer, Coley began searching through his hospital’s medical records. He soon came upon the case of a sad sack German immigrant named Fred Stein. Stein had been hospitalized in 1885 with an egg-size mass bulging from his left cheek; every time he was operated on — five times in the next three years — it came back stronger until it was, in Graeber’s words, “as big as a man’s fist.” Like many patients who endured frequent hospitalizations, Stein also contracted streptococcus pyogenes, which caused high fever, chills, inflammation and, far too often, death. (Its old name, dating back to the Middle Ages, was St. Anthony’s Fire.)

Stein appeared to be yet another doomed patient, but his doctors noted an interesting coincidence: Each time he developed a high fever, his tumors began to shrink. “Four and a half months later both the infection and the cancer were gone, and Stein walked out of the hospital,” Graeber writes.

In what could have been an episode of “The Knick,” Coley roamed the poverty-ridden Lower East Side until he tracked down Stein, “a tall, gaunt man with the glandular severity of an Old Testament hermit.” Now Coley had a question: Why had Stein lived while his patient died, when both had, in his mind, experienced the same disease and the same treatment? Coley determined the difference was that Stein’s fever had somehow enlisted his immune system as a cure.

That moment could have signaled the beginning of the field of immunotherapy and, perhaps, the beginning of a new way to fight cancer — but no one else in the medical field bought it. Instead, as Graeber points out, Coley was relegated to quackdom, and the conventional, respectable treatments for cancer remained those of surgery, chemotherapy and radiation — “cut, burn and poison” in the words of the author and the medical establishment he writes about. It is simplistic but probably accurate to say that most cancer research went in the wrong direction early and stayed there: The conventional wisdom held that it was best to attack the disease instead of looking for ways to help the body heal itself.

Graeber, then, tells an untold story that runs parallel to Siddhartha Mukherjee’s erudite 2011 cancer history, “The Emperor of All Maladies.” Immunotherapy — teaching the immune system to attack cancer — was barely even acknowledged when that book was published. In highlighting it now, “The Breakthrough” relates an unfolding and very frustrating mystery. Researchers have come tantalizingly close to beating the disease — even creating miraculous cures in mice and the occasional human — only to come up against another harrowing complexity in the body they hadn’t imagined or anticipated. Over the years, these scientists became like a platoon that could get itself behind enemy lines, only to find itself without weapons. Returning with weapons, they would find they had no bullets. Returning with bullets, they would discover they had the wrong kind, and so on. “The Breakthrough” is the story of this desperate war waged on a cellular level.

Like many medical stories, it isn’t an easy one to tell, thanks to an unlimited supply of jargon and scientific terms that can cause a migraine in the average reader. (“PD-LI seemed to be involved in a different type of T cell inhibition. It wasn’t the activation phase. PD-I/PD-LI seemed to stop T cell attack long after they had been activated.”) Graeber does a good job of hacking through it all, interspersing the medical research with interesting accounts of patients and their determined physicians. One of the most fascinating stories involves the eccentric and highly confident James P. Allison, once an outsider from the small Texas town of Alice, who went on to discover how T cells could be programmed to fight cancerous tumors. Graeber describes him as looking like a cross “between Jerry Garcia and Ben Franklin … a basic science researcher happy to be wrong 99 times to be right once.”

Graeber also thoughtfully provides the reader with a two-page glossary in the front and extensive notes in back, including a Cliffs Notes-type section called “The Breakthrough, in Brief” and a jaunty one after it entitled “A Brief Anecdotal History of Disease, Humans, and the Quest for Immunity.” A discerning reader might wish for a better-crafted book, with much of this information woven into the text itself, but it’s a debatable point; you wouldn’t want it to get in the way of the story, and it probably would.

Graeber is cautious when writing about modern-day patients who have experienced miraculous recoveries — new treatments that leave them cancer free after all other conventional attempts have failed. He points out that immunotherapy doesn’t work on everyone, and that time and far more research will be replete with as many failures as successes. However, the fact that Allison won the Nobel Prize in Physiology or Medicine this past October assures immunotherapy its rightful place in the fight against cancer. It might just be the killer kryptonite we desperately need.