David Servan-Schreiber | November 2008 issue
I have cancer.
I was diagnosed with a brain tumor for the first time 15 years ago. After surgery and chemotherapy, I asked my oncologist for advice. What should I do to lead a healthy life and what precautions could I take to avoid a relapse? “There’s nothing special to do. Lead your life normally. We’ll do MRI scans at regular intervals and if your tumor comes back, we’ll detect it early,” replied this leading light of modern medicine.
“But aren’t there exercises I could do, a diet to follow or to avoid? Shouldn’t I be working on my mental outlook?” I asked. My colleague’s answer bewildered me. “In this domain, do what you like. It can’t do you any harm. But we don’t have any scientific evidence that any of these approaches can prevent a relapse.”
What my doctor meant was that oncology is an extraordinarily complex field that’s changing at breakneck speed. He was already hard-pressed to keep up with the most recent diagnostic and therapeutic procedures.
I know this problem as an academic physician. Each in our own specialty, we’re rarely aware of fundamental discoveries recently published in prestigious journals such as Science or Nature. Not until they’ve been the subject of large-scale human studies do we take note. Still, these breakthroughs may enable us to protect ourselves long before they’ve led to new drugs or protocols that will become mainstream treatments tomorrow.
When I found out I had a brain tumor, I was 31 years old, young and ambitious. I’d been out of my native France for more than 10 years, living in Pittsburgh, Pennsylvania. With a friend, I ran a laboratory of functional brain imaging funded by the National Institutes of Health. Our goal was to understand the mechanisms of thought by linking them to the workings of the brain. We had a new theory—on the role of the prefrontal cortex in schizophrenia—and were rising stars of American psychiatry.
I discovered overnight a world that looked familiar but, in fact, I knew little about—the world of the patient. I’d known casually the neurosurgeon to whom I was immediately referred. We’d had patients in common, and he was interested in my research. After my tumor was discovered, our conversations changed completely. No more allusions to my scientific experiments. I was asked to lay bare the intimate details of my life, describe my symptoms in full. We discussed my headaches, nausea, the chances I would have seizures. Stripped of my professional attributes, I joined the ranks of ordinary patients. I felt the ground giving way beneath me.
I clung as best I could to my status as a physician. Rather pitifully, I wore my white coat with my name and degrees embroidered in blue lettering to my appointments. In my hospital, where hierarchy was often pronounced, the nurses and orderlies who knew your status called you “doctor” respectfully. But when you were on a stretcher and no longer wearing your white coat, you became “Mr. So-and-so” or, more often, “honey.”
Like everyone else, you waited in the waiting room that as a doctor you’d breezed through, head high, avoiding eye contact with patients so as not to be waylaid. Like everyone else, you were taken to the examination room in a wheelchair. What did it matter if the rest of the time you moved around these same corridors on the run? “It’s hospital policy,” the orderly would say. You resigned yourself to being treated as someone who couldn’t be trusted to walk.
I entered a colorless world. It was a world where people were afforded no recognized qualifications, no profession. A world in which nobody was interested in what you did in life or what might be going through your mind. Often the only interesting thing about you was your latest scan. I began to feel frightened that I was among people defined primarily by their disease. I was afraid of becoming invisible. Afraid of no longer existing, even before dying. Perhaps I was going to die soon, but I still wanted to live fully up to the end.
I received conventional treatment, because it must be stated at the outset that to date, there’s no alternative approach to cancer that can cure the illness. It’s completely unreasonable to try to cure cancer without the best of conventional Western medicine: surgery, chemotherapy, radiotherapy, immunotherapy and soon, molecular genetics.
At the same time, it’s unreasonable to rely on this purely technical approach and neglect the natural capacity of our bodies to protect against tumors. We can take advantage of this natural protection to prevent the disease or enhance the benefits of treatment. (For more on the body’s ability to fend off tumors, read the interview with David Servan-Schreiber on page 50.)
The cancer went into remission, but I relapsed after that. Then I decided to learn everything I could to help my body defend against the illness. As a physician and established researcher, I had access to invaluable information about natural approaches to prevent or help treat cancer. I’ve kept cancer at bay for seven years now.
It took me months of research to begin to understand how I could help my body protect itself from cancer. I participated in conferences in the U.S. and Europe that brought together researchers exploring treatments that work with the “terrain” as they address the disease. I scoured medical databases and combed scientific publications. I soon perceived that the available information was often incomplete and widely dispersed. It only took on its full meaning when it was combined.
Taken as a whole, the mass of scientific data reveals an essential role for our natural defenses in the battle against cancer. Thanks to key encounters with other physicians and practitioners already working in this field, I managed to put all this information into practice along with my treatment.
This is what I learned: If we all have a potential cancer lying dormant in us, each of us also has a body designed to fight the process of tumor development. Something about our way of life weakens our defenses against this disease. It’s up to each of us to use our body’s natural defenses.
In cancer’s grip, the whole body is at war. Cancer cells act like armed bandits, roving outside the law. They’re unhindered by any of the restraints a healthy body respects. With their abnormal genes, they escape the mechanisms controlling normal, healthy tissues. For example, they lose the obligation to die after a certain number of divisions. They become “immortal.” They ignore signals from surrounding tissues—alarmed by the overcrowding—that tell them to stop multiplying. Still worse, they poison these tissues with the substances they secrete. These poisons create a local inflammation that stimulates the cancerous expansion even more, at the expense of neighboring territories. Finally, like an army on the march seeking fresh supplies, they requisition nearby blood vessels. They force them to proliferate and furnish the oxygen and nutrients needed for the growth of what will soon become a tumor.
Under certain circumstances, these savage bands are disrupted and lose their virulence: when the immune system mobilizes against them; when the body refuses to create the inflammation without which they can neither grow nor invade new territories; or when blood vessels refuse to reproduce and provide the supplies the cells need to grow.
These are the mechanisms that can be reinforced to prevent the disease from taking hold. Once a tumor is installed, none of these natural defenses replace chemotherapy or radiotherapy. But they can be exploited, accompanying conventional treatments, to mobilize the body’s resistance to cancer.
Of all the strains of cancer cells researchers use, the most virulent are the S180—for “sarcoma 180”—cells. Stemming from one specific mouse in a Swiss laboratory, they’re bred on a large scale. Throughout the world, they’re used to study cancer under identical conditions. They’re particularly abnormal, containing an unusual number of chromosomes. They secrete great quantities of cytokines, toxic substances that destroy the envelopes of cells with which they come in contact.
Once S180 cells are injected into a mouse, they reproduce so fast the tumor mass doubles every 10 hours. They invade the surrounding tissues and destroy everything they find along the way. Inside the abdominal cavity, their growth rapidly overwhelms the drainage capacity of the lymphatic system. Fluids, called ascites, build up in the abdomen, as in a clogged bathtub. These light-colored fluids provide an ideal environment for S180 cells to grow. They go on reproducing dangerously until a vital organ breaks down or a major blood vessel bursts, leading to death.
In his laboratory at Wake Forest University in North Carolina, Zheng Cui, professor of biology, didn’t study cancer, but the metabolism of fats. Antibodies were needed for his experiments, and to obtain them, the famous S180 cells were injected into mice. The injected cells provoked the production of ascites, so the antibodies could easily be extracted. None of the mice injected with several thousand S180 cells would survive more than a month, so this standard procedure required a continual renewal of “livestock.” Until the day when a strange event took place.
A young researcher, Liya Qin, had injected 200,000 S180 cells into a group of mice. It was the usual dose for this common procedure. But one of them, Mouse No. 6, had resisted the injection. It kept a resolutely flat abdomen. Liya repeated the shot unsuccessfully. On the advice of Zheng, who was supervising her research, she doubled the dose, still to no effect. She then injected 10 times the dose: 2 million cells. To her amazement, there was still neither cancer nor ascites in the recalcitrant mouse. Zheng began to doubt his assistant’s competence. He decided to give the injection himself. For good measure, he injected 20 million cells and made sure the liquid had penetrated the abdomen. Two weeks later, still nothing. He then tried 200 million cells—1,000 times the usual dose—to no avail.
No mouse had lived more than two months in this lab after being injected with the S180 cells. Mouse No. 6 was in its eighth month, despite the astronomical doses of cancer cells injected directly into its abdomen, where they typically reproduce the fastest. Zheng began to suspect they might have encountered the impossible—a mouse that was naturally resistant to cancer.
The growth of cancer is counteracted by poorly understood mechanisms. Over the last 10 years, some of these mechanisms have been brought to light and examined in the laboratory. Zheng’s Mouse No. 6 shed light on the first one: the power of the immune system when it’s totally mobilized.
Once convinced that the famous rodent—known as Mighty Mouse—was resistant to cancer, Zheng turned to a new concern. There was only one Mighty Mouse, and a mouse lives two years at most. Once it was dead, how could his extraordinary resistance be examined? And what if it caught a virus or pneumonia? Zheng thought about preserving his DNA or cloning him. The first successful mouse clones had just been announced. Then one of his colleagues asked, “Have you thought about breeding him?”
Not only did Mighty Mouse go on to have a family—with a normal, nonresistant female—but half its grandchildren inherited its resistance to S180 cells. Like their grandfather, these mice could take in and perfectly resist 2 million S180 cells, a dose that became fairly ordinary in the laboratory. They even tolerated 2 billion S180 cells, 10 percent of their total weight. This is the equivalent, in a human being, of injecting a 12- to 17-pound mass of an ultra-virulent tumor.
At one point, Zheng was away from the lab on sabbatical for several months. When he returned and resumed his experiments with the resistant mice, a serious disappointment was awaiting. Two weeks after the usual injection, the mice all developed cancerous ascites. What had happened? How had they lost their resistance during his absence?
For days he thought constantly about this setback and wondered what mistake he might have made. As most of his colleagues had suggested, perhaps the “discovery” was too good to be true. He was so disappointed he stopped going to see the mice. They were probably all dying, four weeks after the injections. When he eventually returned to the laboratory, heavy-hearted, he raised the cover of their cage and froze: The mice were unquestionably alive, and the swelling induced by the ascites had disappeared.
After several days of feverish experiments, the explanation emerged. At a certain age—six months for a mouse, the equivalent of 50 years for a human—the mechanism of resistance is weakened. At first, the cancer started to develop, which explained the abdomens swollen with ascites. But about two weeks later (one to two years on a human scale), the tumors’ presence eventually activated the mice’s resistance. The tumors melted away by the minute and vanished in less than 24 hours (one to two months on a human scale). The mice returned to their customary activities, including highly active sex lives. For the first time, science had an experimental model, reproducible on demand, of the spontaneous regression of cancer.
However, the mechanisms underlying this mysterious reabsorption still needed to be explained. It was Zheng’s colleague Mark Miller, a specialist in the development of cancer cells, who penetrated the mystery. In examining samples of S180 cells taken from the abdomens of the miraculous mice, Miller discovered a real battlefield. Instead of the usual cancer cells—rounded, hairy and aggressive—he saw cells that were smooth, dented, full of holes. These cells were locked in combat with white blood cells of the immune system, including the famous “natural killer,” or “NK,” cells. Miller was even able to film the white blood cells’ attack on the S180 cells by video microscopy. He’d found the explanation for the enigma: The resistant mice were able to mount a powerful defense, thanks to their immune systems, even after cancer had taken hold.
Natural killer cells are special agents of the immune system. Like all white blood cells, they patrol the organism continually in search of bacteria, viruses or new cancer cells. But while the other cells need previous exposure to disease agents to recognize and combat them, NK cells don’t need prior introduction to an antigen to mobilize. As soon as they detect an enemy, they gather around the intruder, seeking membrane-to-membrane contact. Once they make contact, NK cells aim their internal equipment at their targets, like tank turrets. This equipment carries vesicles—sacs—filled with poisons.
On contact with the cancer cell’s surface, the vesicles are released and the chemical weapons of the NK cells—perforin and granzymes—penetrate the membrane. The molecules of perforin take the shape of tiny rings. They’re assembled in the shape of a tube, forming a passage for the granzymes through the cancer cell’s membrane. At the core of the cancer cell, the granzymes then activate the mechanisms of programmed self-destruction. It’s as though they give the cancer cell an order to commit suicide, one it has no choice but to obey. In response to this message, the cell’s nucleus crumbles, leading to its collapse. The deflated remains of the cell are then ready to be digested by macrophages, the garbage collectors of the immune system, which are found in the wake of NK cells.
Like the immune cells of Zheng’s resistant mice, human NK cells can kill different types of cancer cells, in particular sarcoma cells and those of breast, prostate, lung and colon cancer. An investigation of 77 women with breast cancer studied over a 12-year period suggested how important these cells may be for recovery.
First, samples of each woman’s tumor taken at the time of diagnosis were cultivated with her own NK cells. Certain patients’ NK cells didn’t react, as though their natural vitality had been mysteriously sapped. The NKs of other patients, in contrast, went about a serious cleanup, indicating an active immune system. Twelve years later, at the end of the study, almost half (47 percent) of the patients whose NKs hadn’t reacted in the laboratory had died. On the other hand, 95 percent of those whose immune systems had been active under the microscope were still alive.
Other studies delivered similar conclusions: The less active the NK and other white blood cells were under the microscope, the more rapid the cancer’s progress, the more it spread throughout the body in the form of metastases, and the lower the chances of survival 11 years later. Lively immune cells thus seem essential to countering the growth and spread of cancer.
In a cruel way, Mary-Ann, a Scottish woman who wasn’t suffering from cancer, learned how crucial the immune system is in preventing tumors from taking hold. She suffered from renal failure, a serious disease of the kidneys that makes them incapable of filtering blood. This leads to the accumulation of toxins in the body. To avoid the dialysis she had to undergo at the hospital several times a week, she had a kidney transplant.
For a year and a half, Mary-Ann was able to live almost normally. The only constraint was a daily intake of immune-suppressing drugs. Their purpose, as their name suggests, was to weaken her immune system to prevent it from rejecting the transplant that was keeping her alive.
At that point, though, a gnawing pain developed at the site of the transplanted kidney and an abnormal nodule was identified on her left breast during a routine mammogram. A biopsy revealed the appearance of a double metastasis of melanoma—a serious skin cancer. However, they found no primary melanoma that might have been the source of these metastases.
Called in by the surgeons, dermatologist Rona MacKie was no better able to explain this mysterious case of phantom melanoma. Everything was done to save Mary-Ann. The immunosuppressants were stopped. But it was too late. Six months later, she died of the general invasion of a melanoma, the original site of which could never be found.
Shortly afterward, George, a second patient who’d had a kidney transplant in the same hospital, developed a metastatic melanoma with no original tumor. This time, MacKie could no longer believe in coincidence or blame the impenetrable mysteries of medicine. Thanks to a register of transplanted organs, she traced the kidneys back to the donor. The donor’s general health had met all the usual requirements: no hepatitis, no HIV and, of course, no cancer.
But MacKie persevered, and finally discovered the donor’s name in a Scottish database of patients with melanoma. Eighteen years earlier, the donor had been operated on for a tiny, quarter-centimeter (one-tenth of an inch) skin tumor. The woman had received care for 15 years at a melanoma clinic. Finally, she had been declared “completely cured” a year before her accidental death, unrelated to this old, extinct cancer.
In this patient, for all intents and purposes “cured” of cancer, organs healthy in appearance still carried microtumors her immune system kept in check. These were transplanted into new bodies—George’s and Mary-Ann’s—whose immune systems had been weakened on purpose to prevent rejection of the transplanted kidneys. In the absence of a normal immune system, the microtumors rapidly went back to their chaotic, invasive ways.
Thanks to her detective work, MacKie convinced her colleagues in the department of renal transplants to stop the second patient’s daily immunosuppressants. Instead, they gave him an aggressive immunostimulant, so he’d reject the melanoma-bearing transplant as quickly as possible. A few weeks later, they were able to remove the kidney. Even though he had to go back to dialysis, two years later George was still alive and showed no signs of melanoma. Once it had recovered its natural power, his immune system fulfilled its mission and expelled the tumors.
Researchers were able to show that the white blood cells of Professor Zheng Cui’s mice could eliminate as many as 2 billion cancer cells in a few weeks. Barely six hours after the injection of cancer cells, the abdomens of these special mice are invaded by 160 million white blood cells. In the face of this onslaught, 20 million cancer cells vanish in half a day.
Prior to these experiments on Mighty Mouse and its descendants, no one would have dared hope the immune system was capable of mobilizing to such an extent— not to the point of coming to terms with a cancer that was 10 percent of the body’s weight. No one would have imagined it possible, the immunologists least of all.
The reigning consensus on the limits of the immune system would probably have prevented a conventional immunologist from paying attention to the phenomenal health of Mouse No. 6. That’s what Lloyd Old, professor of cancer immunology at Memorial Sloan-Kettering Cancer Center in New York City, thought. To Zheng—who didn’t know anything about immunology before coming across Mouse No. 6—he wrote, “We can be thankful that you are not an immunologist. Otherwise, you would have definitely thrown away this mouse without hesitation.” To which Zheng replied, “We should just be grateful that Nature never read our textbooks.”
The body’s resources and its potential for dealing with disease are still too-often underestimated by modern science. Of course, in the case of Mighty Mouse, this extraordinary resistance is related to the rodent’s genes. But what about all the people, perhaps like you and me, who aren’t endowed with these exceptional genes? To what extent can we expect an “ordinary” immune system to perform extraordinary feats?
The answer resides in the fighting spirit of our immune cells, crucial participants in our readiness to foil cancer. We can arouse their vitality or, at the very least, stop slowing them down. The supermice succeed better than anyone else, but each of us can “urge on” our white blood cells so they give their all in their confrontation with cancer. Several studies show that, like soldiers, human immune cells fight harder when they’re treated with respect (i.e., when they’re well fed and protected from toxins) and their commanding officer keeps a cool head (he or she deals with his or her emotions and acts with poise).
Studies on the activity of immune cells (including NK cells) show they’re at their best when our diets are healthy, our environment is “clean” and our physical activity involves the entire body, not just our brains and hands. Immune cells are also sensitive to our emotions. They react positively to states in which joy and feelings of connection with those around us predominate. It’s as though our immune cells mobilize better in the service of a life objectively worth living. (For more on natural ways to boost your immune system, see the box on page 53.)
Cancer is a fascinating and perverse phenomenon. It borrows its disturbing intelligence from our vital functions to corrupt them and finally turn them against themselves. Recent studies have revealed how this corruption operates. Whether it’s generating inflammation or fabricating blood vessels, cancer imitates our basic aptitude for regeneration, while aiming for the opposite outcome. It’s the reverse of health, the negative of our vitality.
But that doesn’t necessarily mean that it’s invulnerable. In fact, it’s vulnerable in ways our immune system knows naturally how to exploit. At the outposts of our defense system, our immune cells—including our NK cells—represent a powerful chemical armada that constantly nips cancers in the bud.
All the facts bear out this conclusion; Everything that strengthens our precious immune cells impedes the growth of cancers. All in all, by stimulating our immune cells, fighting inflammation (with nutrition, physical exercise and emotional balance) and opposing angiogenesis—the development of new blood vessels—we undercut cancer’s spread. Acting in tandem with strictly conventional medical approaches, we can enhance our body’s resources. The “price” to pay is to lead a more fully conscious, more balanced and—in the end—more beautiful life.
From a scientist and researcher, ignorant of the body’s natural defenses, I became a physician who relies above all on these natural mechanisms. My cancer helped me make that irreversible change.
I’ve been celebrating the anniversary of my cancer diagnosis for 14 years. I think about what happened to me, the pain, the fear, the crisis. I give thanks because I was transformed, because I’m a much happier man since that second birth.
David Servan-Schreiber is a French psychiatrist and neurologist, and a columnist for Ode. This is an edited excerpt from his book, Anticancer: A New Way of Life
