The Breakthrough

For over 100 years, scientists struggled to find a way to help our natural human immune system fight cancer. Most considered it impossible. But that all changed with The Breakthrough. Do we finally understand cancer well enough to cure it? New York Times bestselling author Charles Graeber writes about his latest research.

When I started working on my book, The Breakthrough, I didn’t know that it would take four years to write.

And I certainly didn’t know that, four years later, the people I was speaking to, and the discoveries they made, would be awarded the Nobel Prize in medicine.

But what I did know, what was immediately obvious, was that the topic was important, but the material wasn’t easy to explain. So, how was I supposed to make a clear, thrilling story out of this complex stuff? The crossroads of two incredibly complex and incompletely understood biological systems, and a field grasped, until recently, by only a handful of MD/PhDs around the world?

But I got lucky. Inside this seemingly complicated story are a host of fascinating, inspiring and often hilarious people. There also turned out to be a thrilling detective story. And, of course, I also discovered a lot of heroes, and an especially terrible villain.


The villain, of course, is cancer. It’s a living disease, it changes and mutates and escapes.

The problem is that, unfortunately, the usual cancer drugs do none of those things. They can not mutate or evolve. Cancer dances; cancer drugs just stand there.

As a result, no drug, no poison or other such medical “solution” was ever going to “cure” the hundreds of diseases of mutation that we refer to collectively as cancer. We might poison it for a while, but if even a single cell of that cancer survives, eventually cancer mutates and comes back. It dances away. But until recently, we didn’t realize it.

But new discoveries have changed all this. Finally, we have learned how to dance.

We now have new, mutating solutions to our mutating problem. It’s called immunotherapy. These new class of cancer therapies take advantage of our built in, natural personal defense system, the 500 million year old biological technology we know as the immune system. This system is complex and and highly adaptive. It dances. It’s perfectly designed to identify and adapt to invaders to the body and kill them.

And now we’ve discovered the key to unleash this system to fight cancer too.

And that’s The Breakthrough.


Cancer is confounding and difficult. And that is because it turns out to be very different from other diseases.

We all know when we have a cold or a flu. It’s obvious, because there are symptoms. You’re aware that your body is trying to “fight something off”- to combat some invader to your body, some pathogen in your bloodstream. Your body becomes a battleground for that fight, and your symptoms are the smoke and noise of the battle.

But cancer is different. It’s not obvious, not at first. There’s no fever, not even a sniffle Usually, you need a test to even realize that you have the disease. It’s one of the most deadly of diseases, and yet, it seems, one against which our bodies don’t even seem to fight back against. And why is that?

Four years ago, I started working on understanding this question, and laying out the answer in a fast—paced story that non-scientists like me could understand as well. My motivation wasn’t just that this is quite possibly the most significant scientific breakthrough of our generation, a fascinating story that, somehow, most people have never heard of. It was also more personal. Nearly everyone has been touched by this disease in some way- certainly I have, in the form of friends and family both. And nearly 40% of us will be diagnosed with cancer in our lifetimes.

Until very recently, we’ve had three basic treatments for the disease, all of them pretty nasty.

The oldest is just to cut out the cancer, we’ve been doing that for thousands of years. Then the discovery of radium in 1896 led to radiation therapy to kill tumors. Then in 1946, research from the U.S. Army’s Department of Chemical Warfare led to the practice of poisoning cancer cells, i.e. “chemotherapy”. More recently, we also added drugs that attempt to starve tumors of their nutrients or blood supply.

These traditional “cut, burn and poison” techniques do cure cancer in about half of all cases. That’s great, but of little use for the other half of patients. That translated to approximately 9,055,027 cancer deaths worldwide in 2018.

But for most diseases, we don’t use knives or poisons or nukes. In fact, for most disease we don’t rely on medicine at all. Our body does the job for us, without us even thinking about it.

This of course is the immune system. This is a complex ecosystem of killers and helpers, spies and reporters that does an excellent job of sorting out what doesn’t belong in the body and getting rid of it. We’ve learned to take further advantage of that system with vaccines, which prepares our immune armies for a disease by showing it some dead or weakened examples to practice on.

The immune system works remarkably well. Except in the case of cancer. It’s not just that it fails to win- it’s that it doesn’t even seem to show up for the fight. But why?

For most of the history of modern medicine, the explanation for that failure was that cancer is us- and if our immune system attacked us, we’d die.

Cancer is a normal body cell. It’s mutated and reproduces out of control, but, the assumption was, not foreign enough for the immune system to see as “foreign”. The conclusion: trying to help the immune system fight cancer was pointless. The only way to beat cancer, according to science, was cut poison and burn. Most research money, time and talent went into finding better poisons.

The small handful of scientists who stubbornly believed that the immune system could recognize and kill cancer - the cancer immunotherapists who - were the laughing stock of the scientific community.

But they had good reasons to believe the immune system could kill cancer. They looked back to history, and the occasional report of patients whose bodies seemed to somehow, miraculously, cure cancer spontaneously, usually after some sort of other infection. Once these “spontaneous remissions” were considered magic or miracle. They believed it was in fact the work of an awakened immune system.

They looked to the late 19th century, when an audacious young New York City doctor named William Coley attempted his own mad scientist experiments to recreate these “spontaneous remissions” through a home-made brew of toxic bacteria.

For 100 years Coley’s ideas were ridiculed, then largely forgotten. But a handful of scientists continued to attempt to recreate the “miracle”. In order to do that, they had to answer the question. If the immune system could see and kill cancer, then why didn’t it?

For most of a century, the work was pretty hopeless. And by the 1990’s, cancer immunotherapy as a legitimate scientific research field was nearly extinct.

The breakthrough discovery came from an unlikely place, in the form of a hard living harmonica playing Texan named Jim Allison. It was his discovery, along with that of Japanese scientist Tasuku Honjo, that would eventually be awarded the 2018 Nobel Prize.

Allison and Honjo discovered that the immune system can recognize and kill cancer. But cancer takes advantage of safety mechanisms built into our killer immune cells (called T cells). Allison and Honjo found two- in fact, there may be hundreds, or even thousands. These safety mechanisms are like brakes designed to keep T cells from hurting normal cells. They’re like a secret handshake your body can give your killer cells, telling it, I’m one of you, don’t attack me.

Cancer had learned to take advantage of these safety mechanisms. It gave T cells the secret handshake, telling it not to attack.

But now that we realize this, we can do something about it. We can block the secret handshakes, and let T cells kill cancer like the common cold.

This is our penicillin moment against cancer. Cancer immunotherapy was once seen as a sad joke; now it’s regarded as the answer. Nearly every cancer researcher and pharmaceutical company in the world has joined the hunt, buoyed by billions of dollars and a growing army of skilled scientists and thinkers from every discipline. And it’s only the beginning. The few cancer immunotherapy drugs that we have developed have already dramatically changed outcomes for tens of thousands of patients, and thousands more new drugs are in the development pipeline. These treatments we have now don’t yet work on all cancers or all patients. But for those who do respond, especially in melanoma, lung and kidney cancers, the results are measured not in extra weeks or months of life, but in lifetimes. And we’ve effectively cured some cancers, such as forms of childhood leukemias. The work is not finished, but the point is that we’ve finally begun on the only track that can cure cancer. We’ve found the mutating solution to the mutating problem. Now the work is to better the science, continue the research, and grow the circle of responders. And this is the breakthrough.

Incredibly, many patients are still unaware that we have fundamentally changed the odds in the war against cancer. And even many doctors, especially those who were trained specifically to believe that cancer immunotherapy was impossible, are still unable or unwilling to suggest such options to their patients. The Breakthrough is meaningless if we can’t take advantage of it. And to do that, we need to hear about it, and understand it. For me, there could be no better reason to write a book.

The Breakthrough: Immunotherapy and the Race to Cure Cancer


CHARLES GRAEBER is a contributor to ink and paper publications including The New Yorker, Elk, New York Magazine, GQ, Outside, Bloomberg Businessweek, The New York Times, National Geographic Adventure and many more. His work has been honored with An Overseas Press Club award for Outstanding International Journalism, a 2012 New York Press Club prize, an American Poet's Prize (2nd). His non-fiction book, The Good Nurse, is a New York Times bestseller.

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