Having finished reading The Emperor of All Maladies, I am required by my conscience to put this out into the ether:

Thank you, Dr. Siddhartha Mukherjee.  Thank you.

If I repeat that thank-you daily for a few decades, I might be able to encompass what that book has meant for and to me, and for my family. I pray God they find the courage to plow through it, too.

It explains so much.

And not just in the nuts-and-bolts sense of explaining what the disease is and how it works. That by itself is a tremendous gift for patients like me who require as much information as possible in order to feel mentally healthy. I don’t want to read about cancer. I’d rather remain blithely ignorant, thank you. But when I’m feeling overwhelmed by a problem much larger than myself, I want to plow through facts, to sort them in my head and let an understanding assemble itself, even if that understanding is grim. My greatest weapon is my mind; when something frightens me, I attack it with my mind until that terror is encompassed and my opponent is dead, dead, dead. To do anything less feels like a willful misuse of my abilities.

But with OM, there simply isn’t any information out there; everything I’ve found can be summed up in a couple pages. Maladies didn’t give me information about OM–the word “melanoma” appears precisely twice in the whole 460+ page book–but it gave me great peace nonetheless. It allowed me to experience profound compassion, reading about the millions of people who have suffered this beast before. But it also did something far more important for me personally: it explained why. And it explained how. 

“Why and how of what?” you ask.

Nothing less than everything to do with cancer. And it does this by explaining oncology itself.

Anyone who reads that line and has no idea what I’m talking about has never experienced the profound disconnect of discussing cancer with an oncologist.

In absence of facts for my disease, the “why” and “how” become everything.

***

Why

Without having met my grandfather or even having glanced at his medical file, Dr. Mukherjee explained why my grandfather’s death in 1984 of a brain tumor was so. Fucking. Horrific.  Why it destroyed my grandmother’s retirement, her sense of safety, her trust in the medical profession, and her ability to speak about her own husband’s memory without her face twisting in anguish. Dr. Mukherjee explained why, to this day, my mother twitches when she hears a loved one moving around the house at night.

Without having met my husband’s grandmother or even having glanced at her medical file, Dr. Mukherjee explained why her death of a brain tumor in 2008 was such a different experience.  Why she passed humanely, with as little pain as possible, and with as many of her faculties (and as much of her dignity) intact as possible for as long as possible. Why, to this day, my father-in-law can talk about his mother and smile, even though her death is twenty years fresher.

Dr. Mukherjee explained what the difference between those two experiences was, and it had little to do with the better palliative care treatments developed over the last quarter century, or with the rise of hospice care–though both those things are critical needs.

Oncology itself had to come of age.

His description of the mid-1980s as “oncology’s darkest hour” was a revelation for me. It was the height of surgical intervention for cancer; the height of radiation use; the peak use of the biggest, most cytotoxic chemotherapy cocktails. In short, it was the single most awful time to be a cancer patient. The prevailing thought process in oncology was that, if all these tools had been developed, why not use them? And if just one process was good, what if more was better? And if these processes worked for some cancers, why not all cancers–even the ones that seemingly have no hope?

I was ten years old at the time. When I saw my grandfather–six feet tall, over 200 pounds, with hands like steel–break down sobbing in terror in my tiny grandmother’s arms the night before his surgery, I thought maybe they shouldn’t go through with it. I had no idea how to tell him that, though. I thought I shouldn’t say anything about my gut instinct. I thought maybe the grownups in the room really did know what they were doing.

Turns out, I was probably the clearest-thinking human being in the room that day. The cancer killed him anyway–it just took more than a year to do it, instead of a few months. In that year he wasn’t my grandfather; he wasn’t even a human being. He was a barely-animate radioactive corpse with chemo-puke on his shirt. All the things that had made him my mother’s father were left on the operating table on Christmas Eve morning, 1982.

When they wheeled what was left of him out to see us, the nurse accidentally knocked his little hospital cap askew, treating us all to the sight of inches of black caterpillar stitches up the center of his forehead. The young buck who cut the tumor out of my grandfather’s skull grinned as he talked about the techniques he’d used. Ten-year-old-me thought, Jesus, what’s wrong with this doctor? Even the nurse looked horrified as she bobbled the cap back into place.

That was oncology in the 1980’s.

By the time my husband’s grandmother received a similar diagnosis in 2008, even her GP had an answer for her, though the oncologist concurred. That answer was, Margaret, I’m sorry, but there simply isn’t anything we can do except make you as comfortable as possible. They explained what had been done to a generation of cancer patients like her–what had been done to my grandfather and others like him in the 1980’s–and what the results had been, and why that was simply not a treatment at all. She agreed, they made her comfortable, she passed quietly.

For that to happen, oncology itself had to grow up. That young buck had emotionally beaten my grandfather, my grandmother, and my mother into accepting his prescribed treatments. He acted as if accepting the inevitable was weakness and cowardice of the highest order. After years of acting like a teenager with the keys to both Dad’s sports car and the liquor cabinet, oncology learned to weigh risk and benefit and decide when there simply wasn’t a good call to make. To hear an oncologist admit it healed a wound I hadn’t realized I was still carrying.

It gives me a measure of peace to know that, if the worst happens for me, I probably won’t be treated as somebody’s personal career-making guinea pig. I have a chance at passing with something of myself, and my family’s hearts, intact.

And that’s just the why part of The Emperor of All Maladies. I haven’t even gotten to the how yet.

***

How

You’ve probably heard the story of the five blind men and the elephant. One grabs the tail and says an elephant is like a rope. One feels the leg and says no, an elephant is like a tree. The man who touches the trunk recoils and cries no, an elephant is like a huge, powerful snake! The man touching the ear says no, you fools, an elephant is as thin as paper and soft, while the man touching the elephant’s side insists that the animal is no different than a wall.

Dr. Mukherjee uses exactly that analogy to address the history of how oncologists have diagnosed and treated cancer. How astonishing, to see an Ivy League Rhodes Scholar oncologist refer to himself and his colleagues as blind. Because that’s what it feels like to me as a cancer patient, dealing with my own oncologist. She’s not a bad one at all–in fact, she’s really damn good. But asking her questions is an enterprise fraught with peril. If I ask the exact same question with even slightly different phrasing, I get a completely different answer. How goddamn frustrating that is! What is she, fucking blind? How can I ask the same question and get two opposite answers?

Therefore how humbling it is, to read The Emperor of All Maladies and discover how that can really be. The answer is that cancer is so wildly complex that the elephant analogy isn’t even fractionally big enough to contain it. My ignorance is not as good as my oncologist’s knowledge. When I ask a question and I think I’ve phrased it the same way, I quite possibly haven’t…and the different answers lie in the details about cancer that I’ve failed to grasp. Instead of viewing those different answers with paranoia–feeling like my oncologist is lying to me, withholding treatment from me, hiding something from me–Maladies allowed me to realize that I really am out of my depth with this thing, and that my oncologist is, too. There really are no good answers for OM yet. When my oncologist gives me an apologetic look and says, “I don’t know. No one does,” she means it.

And this is not for lack of trying.

I’ll give you another analogy that’s helped me a lot lately. You’ve no doubt heard the phrase, “I’m just a dwarf standing on the shoulders of giants.” The idea being conveyed is that the person getting all the credit has only made one tiny addition to the corpus of knowledge–that it was the work of giants in the field who got him or her to the point where that last addition was enough to unlock the secrets, to get the clear view of the problem and thus answer it.

With oncology, there have never been any giants. It’s dwarves all the way down.

I take one pill a day at bedtime. That pill is the best guess anybody’s got at a treatment that will prevent the metastasis of OM.

To arrive at this pill, oncology had to invent entire branches of medical and biological science out of whole cloth. And it often had to actively disprove entire branches of medical and biological “knowledge” first before it could get on with the new stuff.

Regardez, as a friend of mine used to say. (And believe me when I say, this is the shortest way I could sum this knowledge up!)

First, oncologists had to prove what cancer was and what it wasn’t.  If you think that’s easy, you’ve never had to patiently explain to someone that there is no such thing as the “stomach flu.” (“Hell yeah there is,” that person says angrily. “My whole family had it last week!” To which I sigh and say, “Influenza is an upper respiratory tract virus. The stomach virus you had is called ‘noro.’ The two virii have utterly different infection load requirements, and though their infection vectors often overlap, they aren’t necessarily the same. The treatments are different, too. The disinfection protocols are also not the same.” And dear reader, even after all that, people have argued with me. SMH.)

Second, oncologists had to prove that a cancer particular to chickens (I kid you not!) could be passed along by a virus. It’s called the Rous Sarcoma Virus, or RSV.

Then they had to prove that cancer had other causes, too–not just virii.  It’s taken hundreds of years to disprove the idea that there is a single cause of cancer. Cancer is a constellation of diseases, each with a particular cause; whether aggravated or triggered by viral, environmental, or other factors, the only unifying issue behind all cancers is that they arise from altered gene pathways. More (much more) on this in a minute.

Next, oncologists had to discover a little thing called transcription…oh, and DNA, RNA, chromosomes, and the entire branch of science known as genetics. Why is transcription important? Because it explains how DNA copies itself. And why is that important? Because that’s how cancer copies itself.

Then they had to turn the dogma of “DNA to RNA goes only one direction and not the other.” Whaaaaaat? What does this mean? It means they had to figure out the existence of retroviruses! Transcription is real, but so is reverse transcription (RNA can change DNA). Some virii can alter the DNA of their host cells by being RNA themselves! That’s what the “retro” part in “retrovirus” means–backward. Retroviruses work the DNA-copying process backward. The virus copies itself into the host’s DNA and changes it.

The next step was identifying which human genes these virii like RSV could glom onto. The first one they found is called “src,” or SARC. Here’s the kicker: the src in RSV is an exact viral copy of the src that already exists in our chromosomal DNA. In short, cancer is no different than life itself. It is us.

Take a minute. Let that sink in. We are cancer. Cancer is us. It’s just us in a “distorted” state.

It took another long while for oncologists to figure out the next step, which is that there’s only one difference between viral src and chromosomal src. In the viral copy, the switch that turns cell growth on and off has been switched permanently “on.” How that switch gets flipped is a process called phosphorylation. An enzyme called a kinase gives that switch a little phosphate tag, and that’s what starts the cell reproducing. If it’s a cancer cell, well, that cell’s going to grow without stopping. And if there are enough of those cells growing…

Oh, and did I mention that oncologists then had to figure out which kinases drive which pathways in and out of the cell? And which kinase it is that drives each individual cancer had to be addressed, and how to specifically inhibit each kinase and not inhibit others, and to do it enough to stop the cancer but not harm other kinase processes in the body (oh, those pesky side effects!)…

For the record, my cancer isn’t viral (they don’t think), and it’s not chromosomal src they’re targeting but c-met inside the tumor itself…but without those damn chickens my medicine wouldn’t exist. It’s taken a century of crossing disciplines to get here.

And to give you a sense of scale: Over 100 oncogenes (and counting) have been identified. And there are about 100 known kinases, too. So there are in theory over 100×100 different targeted therapy drugs still to be invented–because you can bet that for every oncogene and pathway combination, there’s a cancer.

And that’s just the invention path that leads to my nightly pill. There are just as many more invention paths out there as there are parts to the elephant. I’m sure that, if a unifying cause and cure is ever discovered, everybody out there will say, “Of course, you idiots, it was an elephant the whole time!” But that’s negating the generations of thankless work that went into that discovery.

Oh yeah, baby. I see it now. It’s dwarves all the way down.

***

So my oncologist can be forgiven when I ask her if I have to be chemotherapy naive to participate in her immunotherapy trial later on and she says yes and then I say, “Well I guess that kills the idea of participating in this other clinical trial right now” and she gives me a blank look. “Why would you say that?” she says. And I’m thinking, is she deaf, I just told her that other trial is chemotherapy. “Because it’s chemotherapy,” I repeat, feeling like I may have made a bad call in hiring her as my oncologist. Then the sound of gears shifting in her head is audible. “This drug here is not a cytotoxic chemotherapy,” she replies. “It’s a targeted therapy, a tyrosine kinase inhibitor. Yes, it’s called chemotherapy, but it means totally different things when it comes to chemotherapy naievete. You can totally participate in this trial right now–which I highly recommend–and still participate in mine later.”

Thanks, Dr. Mukherjee. You speak oncologist. You also speak patient. And now that I’ve read your book, I have the words to understand when my oncologist brings an entire discipline of science to bear on a problem that I can’t even see…and I have the humility to understand that if I’m confused, I have a right to be. I also have the right to ask her questions until I get good answers…and she has the right to be honest if there are no answers, without experiencing anger from me. 

Such delicate negotiations are to be expected. We are, of course, just commoners dealing with an emperor.