Cancer’s Primeval Power and Murderous PurposeGeorge Johnson
Aug. 29 (Bloomberg) -- It was 2010 and I was driving through the badlands of northwest Colorado, far from the cool, green Rocky Mountains. This was the land where the oldest known example of cancer had been found: inside of a bone of a Jurassic Age dinosaur.
About 150 million years ago, the malignant growth had eaten away at the beast. It died and was buried under the layered debris of the ages. But a fragment of its petrified skeleton chanced to survive. It was discovered by an unknown rock hunter, cut and polished in a rock shop, and purchased by a man on vacation -- a doctor who knew bone cancer when he saw it.
We think of cancer as a modern scourge, but it was here long before people walked the Earth. Only very recently, in geological time, have creatures like us evolved who think there might be something they can do about it.
That evening, I thought about Nancy, the woman I had been married to. It had been almost seven years to the day since she was diagnosed with a metastatic cancer. I remembered the frantic search -- for the best doctor, the best treatment, the best hospital. The surgery, the chemotherapy, the radiation -- that was all behind us now, but the enigmatic nature of the disease still preyed on my mind.
The science, I knew, was deep and complex -- and I set out to learn everything I could. My goal, after two years of reading, studying and talking to scientists, was to reach a point where I, as an outsider, could hold the full sweep of the field in my head. I would never learn or understand every fine detail -- that would be impossible even for an expert. What I aimed for was a bird’s-eye view of the scientific terrain -- of what science does and does not know about cancer. I was in for a lot of surprises.
“Disease” began to seem too weak a word for this condition. It is a fundamental biological phenomenon. A single cell “decides” (for lack of a better word) to strike off on its own. Mutation by mutation, it evolves -- like a monster in the ecosystem of your body. Cancer is an occupying force with a will of its own.
For Nancy, the first sign was subtle at first: a swollen lymph node in her right inguinal area -- a symptom that can have many causes, often benign. (Cat scratch fever was our hopeful hypothesis.) The lump was biopsied, the cells were examined by a pathologist, and the diagnosis was made. I can still hear the doctor’s measured words: “I think we are looking at a carcinoma.”
Most cancers, by far, are carcinomas, which occur in the epithelial tissue that lines the exterior and the interior of the body. These cells are constantly being sloughed off and replaced, and every time new cells are born, they inevitably acquire mutations. That is the nature of life in an imperfect universe.
Mutations usually happen for no obvious reason -- the only identifiable cause is entropy, the natural tendency of all things complex to gradually succumb to the universe’s inherent randomness. Epithelial cells, forming the skin and lining the alimentary canal and digestive track, are vulnerable in another way. They are frequently exposed to substances in food and in the air that can damage DNA. Whatever the cause, the right combination of mutations can convert a normal cell into one that is cancerous.
In Nancy’s case, the lymph node was only a way station on what, unchecked, would be a mass migration through her body. The source, the doctors told us, could be the colon, the stomach, the ovaries, the uterus. The cancer could have come from almost anywhere.
“Metastatic carcinoma with an unknown primary.” A diagnosis doesn’t get much scarier than that. Somewhere in the recesses of her body, a cell had divided into two daughter cells, leaving one of them with a microscopic birth defect -- a mutation to its genome that caused it to divide a little faster than its neighbors.
Normally, that wouldn’t be a problem. The body is equipped with a phalanx of defenses. But as the aberrant cell divides, more mutations accumulate -- and some of these might be the very ones that disable the safeguards or enact mechanisms to work around them.
Freed from these constraints, the cell divides even faster. As one generation gives rise to another and another, more mutations occur, and the chances increase that a family of cells will develop the biochemical intelligence to outwit the rest of the body and grow into a malignant tumor.
What is happening is a sped-up version of Darwinian evolution, with the tumor becoming fitter and fitter, better equipped to dominate and thrive.
That was for me a jarring realization: What from the body’s point of view are dangerous mutations are, for the tumor, advantageous adaptations. As it fights off attacks from the immune system, it develops the ability to eat into the surrounding tissues and to nourish itself by growing its own blood vessels. It can learn to insinuate its way into the lymphatic system. Nancy’s cancer had reached that point, and it was only after weeks of tests that a positron emission tomography (PET) scan finally revealed the source of the trouble: the lining of her uterus, called the endometrium.
By the time the surgery was scheduled, the cancer had traveled across her body from the lymph node in her right leg to another in her left leg. Every day, it was getting smarter and more dangerous. You are not supposed to personify biological processes. But with cancer, even many scientists find it impossible to resist.
Nancy’s operation was successful. But after the cancerous tissues and lymph nodes were removed and examined, the diagnosis only got worse. This was not the most common type of endometrial cancer -- one that can have a very high survival rate. It was a rare, extraordinarily aggressive kind called uterine papillary serous carcinoma, or UPSC. According to a paper published around that time, the five-year chance of survival for Stage 4 UPSC -- this is what the doctors said she had -- was as low as 5 percent.
For so aggressive a cancer in someone so young (she was in her early 40s), the only tools at the oncologist’s disposal were a triple cocktail of corrosive chemotherapy drugs followed by an intense course of radiation. The therapy had to be as brutal as the cancer. I didn’t know this then: The first chemotherapy drugs were derived from mustard gas. And they are still in use. A drug called mustargen, or nitrogen mustard, which is used to treat some cancers, is banned under the 1993 Chemical Weapons Convention -- unless the enemy consists of cancer cells.
We had briefly hoped that Nancy could be treated with one of the gentler “targeted therapies” -- the so-called magic bullets reputed to zero in only on the cancerous cells while avoiding the healthy ones. But none of them had the power to attack this kind of cancer. The only remedy was an old-fashioned blunderbuss assault with chemical toxins -- cisplatin, doxorubicin, paclitaxel -- and finishing up with X-rays.
All of these poisons kill healthy cells along with the cancerous ones. Since the cancer cells are dividing at a faster rate and are often less able to repair themselves, they are killed in greater numbers. That is the idea, anyway. But while the treatment is in progress, the errant cells continue to evolve. They can become immune to the poisons or more resistant to radiation.
It has been almost 10 years since those brutal months. But the treatment would hardly be different for someone diagnosed with the cancer today -- or for almost any metastatic cancer, particularly those in advanced stages. The news is filled with reports of the latest targeted therapies such as “super Herceptin,” described as “a heat-seeking missile” that delivers the poison directly to the errant cancer cells. Or the newest immunotherapies, in which a patient’s own immune cells are removed and reprogrammed to destroy the cancer. But none of these turn out to be as effective as they sound. For an advanced metastatic cancer, the best that can usually be offered is a few extra months of misery.
Nancy was lucky. The treatment worked, and she is healthier than ever. But such a close brush with death changes a person in other ways. Though we survived her cancer, our marriage did not.
As our life together was unwinding, I kept up the chase, learning everything I could about what scientists are learning about this attack from within.
It is eerie enough to think of a cancer evolving like a quasi-creature in the ecosystem of your body -- acquiring through random mutation and selection the powers to thrive. But the malignant cells don’t have to develop all of their tools from scratch. They can take advantage of mechanisms already built into the cell -- including those a fertilized egg uses as it divides and develops in the womb. These genes, which are switched off after a baby has been fully formed, can be switched back on by the cancer cell. Susan Sontag called cancer “a demonic pregnancy,” “a fetus with its own will.” That is more than an arresting metaphor.
Just as remarkable is the way an aggressive tumor is capable not only of destroying healthy cells -- but also of recruiting them to aid in the attack. The tumor not only learns to evade the immune system, but it also turns it into an ally. That is one of the paradoxes of cancer. The various devices normally used to heal a wound -- destroying diseased tissue and replacing it with healthy new growth -- are used to promote the development of the cancer.
The complexity of this all -- the biological brilliance -- is enthralling. And appalling. As I explored this new world, I found myself torn between seeing cancer as it was for Nancy -- a terrifying, debilitating illness -- and cancer as an intellectual puzzle. When I felt myself straying too high into the stratosphere of abstraction, I had her story to pull me back to the ground.
Then, just as I was almost done writing, came the next, bigger blow. Joe, my youngest brother, was diagnosed with what the oncologists called squamous cell carcinoma of the head and neck -- usually a very survivable cancer. He had none of the recognized risk factors. The only thing that could be called a cause was a deadly series of random, microscopic blows.
As he went through the gamut -- surgery, radiation, chemo, and then chemo again -- I tried to encourage him with what I had learned about the science of cancer. I think I even tried to put things in perspective with that story about the dinosaur. For all science has discovered about the intricacies of the cancer cell, there was nothing to help him. Less than a year after the diagnosis, he had died.
(George Johnson is a science journalist and author. This article was adapted from his latest book, “The Cancer Chronicles: Unlocking Medicine’s Deepest Mystery,” published by Alfred A. Knopf.)
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