VOGUE
MYSTERIOUS REMISSION
Ten years ago, Alice Epstein was given three months to live. Then her cancer inexplicably disappeared. What happened? Chip Brown examines evidence for a link between the mind, the immune system, and disease.
March 1995

She had begun to feel tired the previous winter, cross-country skiing with her husband, Seymour Epstein, a professor of psychology at the University of Massachusetts. One of their favorite ski tours was the old trolley bed that ran along the western edge of their property. Their 45 acres of hardwood forest border a state park in the Holyoke range in western Massachusetts. They had cut trails and dammed a swampy stream to form a pond right out of a Currier & Ives lithograph. They'd built their own house, a decked, dark-shingled place perched on a knoll with handsome prospects.

Until that winter, Alice had never had any trouble keeping up with Sy on skis; now she found herself falling farther and farther behind. Her afternoon naps stretched to two and three hours. Her chronic headaches were getting worse. She thought she was just drained from the push to finish her doctorate. She had not done as well as she expected on her oral exams, and though she was awarded the degree, she felt let down and dissatisfied.

After the fatigue came the night sweats. The sheets under her neck were soaked when she awoke in the morning. In early February, up at their summer house in New Hampshire, she found blood in her urine. Willard Weeks, M.D., at the Amherst Medical Associates told her to come in when she got back. The next day the lower left side of her back was torqued by pain worse than the worst agonies she'd experienced in childbirth. Get back here right away, Weeks said. She lay in the front seat of the yellow Volvo while Sy raced down Interstate 91.

The doctors at Amherst thought she might have a kidney stone or sonic kind of infection. The initial tests were unrevealing. Strangely, the pain vanished, never to return. It wasn't until she went for X rays at Cooley Dickinson Hospital that her doctors arrived at a diagnosis. It was far more dire: A lemon-size tumor was growing on her left kidney -Stage II cancer. The kidney would have to come out, along with some lymph nodes.

The question was, had the cancer spread to her lungs? The first X rays were clear-no metastasis. But in March, as she was going in for the kidney operation, the latest X rays showed a single lesion on her right lung. A month after that there were two spots on her right lung and a developing lesion on her left, unmistakable evidence that the cancer had advanced to Stage IV. Her chances of surviving more than five years were very low. Assessing the rate of growth, the oncologist in nearby Florence gave her three months to live. I'll never see myself with gray hair, she thought.

Yet here she was at the door of her house ten years later, in a tweed skirt and ski sweater, a thin, birdy, green-eyed woman with a smiling, seamed face and all the gray she could ever want in her hair. While her contemporaries moan about birthdays, she revels in her age. Gray in excelsis! Her first grandson, Casey Robert Sedennan, was born last fall, October 16; by all rights she should never have lived to cradle him in her arms. She skis abreast of her husband, reads without headaches, and luxuriates in the commonplaces of daily life-lunch, holiday visits, and old episodes of Star Trek.

In the last ten years, about 100,000 people have died of kidney cancer. Alice Epstein wasn't one of them. Her story is condensed in the sheaf of X rays she keeps in an upstairs closet. Each year she gets an update; each year the new picture tells the same remarkable tale. Her body is free of cancer. Ten years and counting. How did it happen? What saved her life?

Cancers go into remission all the time, mostly after they are subjected to mainstream treatments such as radiation or chemotherapy. In roughly the time since the federal government launched its "war on cancer" in 1971, mortality rates of cancer patients have declined only a little. Twenty years ago, three in nine survived more than five years; now it's three in eight. Those numbers largely reflect advances in prevention and early detection of the disease. The odds that metastasized Stage IV kidney cancer will go into complete remission remain extremely long -about four in 1,000.

Other than the operation that removed the tumor on her left kidney, Alice Epstein had no surgery. There was no chemotherapy that could treat her metastasized hypernephroma. She'd had no radiation, nor any of the new immunotherapies. Her remission, to put it simply, cannot be explained by established medical theory. It's an example of what's called a spontaneous remission.

Accounts of spontaneous remission are the inspiring ring, all-but-impossible success stories that underscore the tension between personal experience and remorseless statistics. They have drawn new interest in recent years, not simply because they epitomize the mystery of the body's ability to heal itself, but because they raise intriguing questions about whether emotions, attitudes, and the sundry other attributes of mental life might help the body heal.

Remission stories have been reported for centuries, often in religious terms when recoveries were considered miraculous evidence of the power of faith and prayer. One of the most famous dates from the latter half of the thirteenth century, when Peregrine Laziosi, a young priest in the order of the Servites, was suffering from cancer of the foot. The night before he was scheduled to have the foot amputated, he prayed for many hours, then fell into a light sleep, during which he dreamed that the tumor had vanished. When he awoke, his doctors could not find any trace of the disease. He lived to 80 years of age. He is remembered today as Saint Peregrine, the patron saint of people with cancer.

Anecdotal accounts of spontaneous-remission cases prove nothing by themselves, but it's virtually impossible to study the phenomenon clinically since the remissions can't be predicted or controlled. Historically they have been viewed as artifacts of a faulty diagnosis. For most of the nineteenth century it was difficult to accurately identify cancer -now diagnosed via the microscopic study of tissue- so many patients who were said to have recovered "miraculously" may indeed not have had the disease in the first place.

Over the years the phenomenon of spontaneous remission has received scant attention. There is no epidemiology of inexplicable remissions, no national registry of remission cases, no journal in which reports can be reviewed and compared. Nobody knows even how frequently spontaneous remissions occur. One estimate in 1979 put the number of reported cases at around 20 a year but suggested there might be more, including those remissions credited to such unproven treatments as shark cartilage or regimens of carrot juice drinks and coffee enemas.

The first significant survey of spontaneous remissions was conducted by G.L. Rohdenburg in 1918. He looked at 302 cases, mostly cancers of the breast and uterus. Rohdenburg noted that remissions had sometimes occurred after surgery in which only part of the tumor had been removed. He also noted that fever seemed to be associated with remissions, a link that had been noted in medical reports since the 1700s.

Nearly half a century passed before the next thorough attempt to unravel the mystery of inexplicable recoveries. In 1966, Tilden C. Everson and Warren H. Cole published a monograph in which they made an exhaustive analysis of 176 cases of "spontaneous regression. " The authors were surgeons at the University of Illinois College of Medicine; Cole had served as president of the American Cancer Society. One pattern the doctors noted was that 68 percent of the remissions occurred in six kinds of cancer; the most common was the hypernephroma that would afflict Alice Epstein 20 years later. Cole and Everson couldn't explain why remissions were more prevalent in certain kinds of cancers, let alone the process by which remission occurred. They speculated about the influence of hormones and the endocrine system, high fever, or an allergic or immune reaction. Perhaps something interfered with the blood supply to the tumor; perhaps the patient was unusually sensitive to the therapy. Cole would eventually write that he believed most cases of spontaneous remission were triggered by some sort of immunological response.

That the immune system played some role in cancer was clear from studies in the late 1940s. Research showed that animals could produce antibodies capable of fighting chemically induced tumors. Further work over the next 30 years would show that human cancer patients also produced tumor-fighting antibodies; cancers were worse in patients whose immune systems didn't make the antibodies. The field of organ transplants produced evidence of the impressive response immune systems could mount against tumors. There was, for instance, the case of a man who had received a transplanted kidney that contained latent cancerous tissue. Tumors spread through the patient's body until the immune-suppressing drugs he'd been taking were stopped. Then the tumors dramatically disappeared.

The first and only national conference on spontaneous remission was held in 1974 at Johns Hopkins University School of Medicine. The purpose, as Edward Lewison, M.D., put it, was to help doctors listen more closely to those "whispers of nature" whereby patients were healed without apparent cause.

At that time, a provocative link between the immune system and the mind was coming to light. It was the year that psychologist Robert Ader made a serendipitous discovery at the University of Rochester School of Medicine and Dentistry. Ader had been conditioning rats to associate the taste of saccharin water with stomachaches. He would give them some sweet water and then a shot of the drug cyclophosphamide. He found that a lot of his young and healthy rats were dying prematurely. The drug was a strong immunosuppressant and was lowering the rats' T-cell counts, making them more vulnerable to infections. What Ader himself could hardly believe, until he enlisted an immunologist and set out to test the idea, was that the drug was not required to lower the T-cell counts. The rats learned that when they drank sweet water, they got sick. After a while, a taste of the water alone -without cyclophosphamide- was enough to suppress their immune systems. One sip, and their T-cell counts declined as if they'd been given the drug.

It was a surprising discovery. Researchers had assumed that the immune system functioned independently of the nervous system; textbooks on immunology didn't mention the brain. Ader's work opened a new world of previously unknown chemical interactions between the immune and nervous systems, and marked the beginning of a new discipline called psychoneuroimmunology, or PNI. Despite the early skepticism and even hostility of many people in the medical world, research in PNI has exploded in the last fifteen years. Studies have found that biochemicals released by nerves, which are in charge of such things as making people feel happy or thirsty, can also affect white blood cells, stalwarts of the body's defense system. Receptors for these biochemicals exist in the brain, the spleen, the lymph nodes, and throughout the body. Experiments on the way stress affects immunity have indicated how these biochemical mechanisms are manifest. For example, the stress of exams has been shown to alter medical students' T-cell counts and immune-system activity. Accountants suffer similar immunosuppression during the tax crush.

The PNI field is still controversial, in part for the extravagant claims made in its name. (Citing PNI research, for example, one company promises that its "biomagnetic" bracelets can build immunity.) But as scientists learn more about the links between the immune and endocrine and nervous systems, it does become harder to say what is body and what is mind. For the most part, medical reports of inexplicable remissions religiously avoid discussing the mental states of the lucky patients, but PNI research offers a new lens with which to focus on the relationship between the subjective experience of healing and its physiological expression.

In 1983, prompted in part by PNI research, the Fetzer Institute and the Institute of Noetic Sciences launched a ten-year program to study the body's healing abilities. As part of the program, the California-based noetic sciences institute, a 45,000-member research organization founded by Apollo 14 astronaut Edgar Mitchell in 1973 to study the mind, undertook a massive review of the literature of spontaneous remission. Research director Brendan O'Regan had always wondered why more attention had not been paid to survivors. Why did medicine take its gospel only from the casualties of terminal illnesses?

With Caryle Hirshberg, a biochemist, O'Regan began combing computer data banks and medical libraries for all spontaneous-remission reports published in world medical literature back to the last century. At the time there were only two books on the subject, and both were out of print. Hirshberg and O'Regan looked through more than 800 medical journals in 20 languages. They unearthed more than 1,000 reports of spontaneous remissions of cancer and hundreds more examples of inexplicable remissions of other illnesses. The annotated bibliography of reports that O'Regan and Hirshberg came up with is the foundation of a new book that Hirshberg has cowritten with Marc Ian Barasch called Remarkable Recovery (Riverhead Books), due out this month. Unfortunately O'Regan did not live long enough to see it, or even the bibliography, in print; he died, of cancer, August 16, 1992.

Hirshberg and O'Regan divided the reports of spontaneous remissions into four categories. In some cases, patients got better than the therapy was supposed to make them. In others, patients made remarkable recoveries without any medical treatment at all. A third class included those reports in which patients credited their healings to faith and the intercession of a divine force, such as the 65 cases carefully documented by the medical commission at the French Catholic shrine of Lourdes. Lastly, there were remissions that seemed to demonstrate the power of the placebo effect: Patients recovered using unproven alternative treatments or, in some cases, treatments that were shown later not to be effective at all.

One dramatic example of this last type is a case first published in 1957. Doctors had given up on a patient named Mr. Wright, who had tumors the size of oranges in his neck, groin, chest, and abdomen. It was thought he had two weeks to live. But Mr. Wright hoped that Krebiozen, a faddish wonder drug of the time, could cure him. At the hospital where experimental tests of Krebiozen were being conducted, he begged the doctors to let him participate in the studies. He got his first shot on a Friday. Bruno Klopfer, M.D., thought his patient might well be dead by Monday, but when he returned, he found Mr. Wright's tumors had "melted like snowballs on a hot stove." In only a few days they had regressed to half their size. The patient could breathe without oxygen and move around the ward. Within ten days he was discharged, "all signs of the disease having vanished in this short time." He was even able to take his airplane up to 12,000 feet. Eight weeks later reports emerged that questioned the efficacy of Krebiozen, and Mr. Wright, who was "reasonably logical and scientific in his thinking," was disturbed. Now it was his hope that began to melt, and his tumors returned. Klopfer decided to perform an experiment that the standards of informed consent would probably disallow today. He lied to his patient. He told Mr. Wright that a new double-strength batch of Krebiozen was arriving. This time he injected his patient with fresh water. He was astonished to see that Mr. Wright's tumors shrank even more dramatically than the first time. The power of water and faith dried up the fluid in Mr. Wright's chest, and again he could walk around easily and take his plane for a spin. He was symptom-free for two months. But then he read the news that clinical tests had conclusively demonstrated that the wonder drug was worthless. He was readmitted to the hospital. "His faith was now gone," Klopfer reported, "his last hope vanished, and he succumbed in less than two days."

So much for life on the information highway. What Hirshberg and O'Regan found when they began talking to people who had had spontaneous remissions was that many of them did not believe they had gotten better "spontaneously." They thought they had worked like hell to get better, and that this was crucial to their recoveries. That is to say that psychological factors -their moods, their emotions, their beliefs- made the vital difference.

Although the medical evidence of a link between the mind and the immune system is new, the idea that emotion not only influences the course of an existing cancer but can actually engender it has been around for thousands of years. The Greek physician Galen, in the second century A.D., believed cancer was linked to melancholy. Depression -despite extensive evidence to the contrary- has long been associated in popular belief with cancer. In the 1950s, psychologists began to develop the still-controversial concept of the type C personality to describe people whose tendency to repress emotion seemed to be correlated to cancer. Contemporary bestselling medical popularizers like Bernard Siegel have gone so far as to invite cancer patients to ask themselves why they need their illness -a request that in the eyes of the medical community not only flies in the face of accepted scientific fact but imposes an unwarranted burden of guilt on cancer patients who aren't able to cure themselves.

Still, medical science clearly recognizes the value of therapy and support to help cancer patients deal with the emotional stress of the disease. Psychiatrists and psychologists are routinely included in a cancer patient's medical team. The field of psychosocial oncology is dedicated to exploring the influence of mental factors on the disease.

In a landmark study, Stanford University psychiatrist David Spiegel showed that group therapy doubled the time of survival of women with metastatic breast cancer. Spiegel's study was all the more remarkable because he had set out to prove the opposite -that psychological factors had no influence on how long cancer patients might survive. Nevertheless, the stay of execution among Spiegel's breast cancer patients amounted to an extra eighteen months or so, a far cry from the apparently openended endowment of years Alice Epstein's remission has bestowed.

While there is now compelling evidence that psychological factors can prolong the survival of cancer patients, no evidence supports the conclusion that emotions cause, or can do away with, cancer. It bears repeating. As Barrie Cassileth writes in Everyone's Guide to Cancer Therapy (Somerville House Books): "Advocates ... claim that happiness, positive attitudes, a strong will, meditation, mental imagery, and other psychological or mental efforts can cause cancer to regress or disappear. These claims are groundless. Emotions do not influence cancer outcome (nor is there any evidence that they play a role in the development of cancer in the first place). Attitude, meditation, and so on can enhance the quality of life -an important goal in itself- but they do not cure cancer."

Cassileth, a professor of medicine at the University of North Carolina, acknowledges that "there is some scientific experimental evidence showing that the immune system plays a role in the body's defenses against cancer," but she cautions that there is very little evidence that suggests the immune system "is helpful against metastatic disease once cancer has developed."

Despite the lack of clear proof that the mind can work through the immune system to reverse the course of cancer, however, the possibility remains intriguing -not only because some evidence hints at such a process but also because there is no other good way to explain why some people's cancer can miraculously disappear. At the least, it is possible to understand why Alice Epstein believes that she owes her life precisely to the link that Cassileth dismisses. More specifically, she believes she owes her life to six weeks of intense psychological work in which she spent hours in meditation and therapy, essentially rebuilding her psychic house from the ground up. She can't prove that's what cured her. She can't show that she wouldn't have gotten better if she had gone shopping for six weeks instead. She acknowledges that hers is only one case. But "I believe in the psychological aspect of cancer," she says, sitting in her dining room on a matchless fall day. "It's not for everybody, but in my case, it was almost classical. The way I was in the world set me up for the cancer."


221U-007-007
Cancer patient Alice Epstein points out the lesions on her lung in an X ray taken ten years ago. They have since disappeared.

Of course she didn't know this until she was looking at the world through the veil of her imminent demise. A few days after the devastating news, she went walking in the woods with Sy. She had been walking in new snow and she began to weep because she thought it was the last snow she'd ever see. Sy put his arm around her. In the midst of her misery she cried out suddenly, "I am not going to die! I will fight it. I will fight it with everything I have, and I will defeat it." Her husband was thrilled by the iron in his wife's voice. However, it was one thing not to want to die, another to know why you wanted life. Why did she want to live? he asked. Alice cast about for reasons and, finding none, despaired. Maybe the family would be better off if she were dead, she said. He was shocked. How could Alice not feel the love he had for her, the love their children and their friends had?

It seemed Alice would die before there were answers to these questions. Sy Epstein's life's work was the mechanics of the mind. He had proposed a new theory of the unconscious and won research awards from the National Institute of Mental Health. It was obvious to him that if he was going to be of help to Alice, he would have to face facts: He forced himself to accept that Alice was going to die; he imagined her funeral and himself going back to the house alone.

And then with the energy that would have otherwise gone to denying the reality of his wife's condition or feeling sorry for himself, he called the National Cancer Institute and requested everything written about metastasized kidney cancer. He learned that Alice had less than a 4 percent chance of surviving beyond two years. But as he began to examine the research, he was surprised to discover the extent of the scientific literature that linked psychological factors to the biochemistry of the endocrine and immune systems.

Might Alice's immune system be enhanced by psychological factors? "I was skeptical at first," Sy Epstein recalls. "The idea that your psychological state could influence something like cancer seems far-out. There are so many people with weird ideas who make extravagant claims for things like laetrile or magical cures. But moods affect the immune system, and the immune system affects cancer, and so the inference that moods can affect cancer is high."

Moreover, he had been struck by the similarity between Alice and the controversial descriptions of the "cancer prone" personality. He knew that lots of people who don't meet the criteria for a cancer-prone personality get cancer. The important factor in a number of cancers is genetic predisposition. Still, for the subset of people who fit the cancer-prone personality, perhaps psychological factors might have some effect. As he put it in the introduction to Mind, Fantasy and Healing (Del acorte Press), the book his wife wrote four years later: "On the surface Alice was cheerful, helpful to others, highly competent, and much loved by people in and out of the family. The only one who did not love her was herself. She could do things for others, but she could not do things for herself, nor could she accept favors from others, nor, apparently, could she even accept the fact that others loved her. Her manifest enthusiasm and cheerfulness masked an underlying depression. It seemed to me that, if in her case personality had played an important role in the etiology of the cancer, then changing her personality could contribute to her recovery."

Alice recovered quickly from the kidney surgery but remained in limbo while doctors monitored the lesion on her right lung. If the condition of the lung did not change for a month, they would operate. If it got worse, surgery would be pointless. She was spending a good part of her days meditating, using a technique she'd learned a year earlier when she attended a Buddhist meditation workshop at the behest of her daughter Marty. Alice also had been imagining her white blood cells eating the slimy black cancer cells, following exercises in Getting Well Again (Bantam), by O. Carl Simonton and Stephanie Matthews-Simonton. She was not in any pain. All things considered, she felt pretty good.

When in mid-April 1985 Dr. Weeks came out to the house to report on her latest X rays, she knew the news was bad. There were two lesions on her right lung, he said, and one developing on her left. On April 23, oncologist George R. Bowers fleshed out the grim details, gave her three months to live, and recommended a gamma interferon program in Boston. He scoffed at the suggestion that there was anything to be gained by psychological work. "He didn't leave us with any hope," Alice recalls. "His attitude was 'Let's face it, you have three months to live, and I'm a busy guy.' " They looked into the Boston interferon program, and another one in New Haven. The side effects were sobering -life-threatening infections, heart disturbances, nausea, hair loss.

Alice was resolved to try interferon. But in the meantime ... maybe there was more they could do psychologically. Maybe she couldn't realistically hope to cure her cancer, but she could find out why she felt so empty and unloved. And maybe that would help. So she went into therapy, and soon forgot she was sick.

"I didn't know if therapy would have a physical effect. The outcome I wanted was psychological wholeness," she says. The results came quickly, so fast that her therapist, Dorothy Firman, regarded her with awe. She could feel changes in her mental state within three weeks. She felt more powerful, more lovable.

She decided it was finally time to enroll in the interferon program in New Haven. She drove down with Sy in June, but new chest X rays revealed a stunning turn of events. A technician stuck the new picture on a screen. Marc S. Ernstoff, M.D., came in with X rays that had been taken six weeks earlier. Alice and Sy, the technician, and the doctor stared up at the images. One of the spots on her right lung was significantly smaller than it had been in April. "And then," Alice wrote later, as my eyes focused on the place he was pointing out, I heard Sy and myself saying in unison, 'But where is the second one?'"

The doctor said that he could see where the spot had been, but it had almost completely vanished. Ernstoff said he thought he could see what might be another lesion developing on the left lung, but Alice was so excited it hardly mattered. She asked for a two-week postponement of her start in the interferon program.

When Alice came back for another chest X ray, Ernstoff insisted that there was no change, but the Epsteins had gotten pretty sharp at reading X rays. (Alice had taken to ducking into the women's room on the trip from the radiology lab to the oncology department to preview the film.) It was obvious to them that the spot was shrinking. She called her therapist and her daughters. She had a new lease on the future.

At the end of the year, Weeks said she had a chance to survive. She continued to get monthly X rays, and the reports would come back marked NO CHANGE. For more than two years, the radiologists looked at the X rays and said, "No change." But Alice and Sy could see there was change. It was as if the doctors were incapable of perceiving a fact without a context in which it could be explained.

What happened? Was some latent healing system activated by the hours of meditation, the breakthroughs of self-understanding, and the burgeoning sense of connection to a spiritual identity? Or was she lucky enough to get a break-have a balky gene switch on, or some lazy protein wake up at the last moment and preserve her life for a while? Or both? She is emblematic of spontaneous remissions only in that a remission occurred.

But to Sy Epstein, it is significant that in the summer of 1985, when Alice was distracted by the planning for Marty's wedding, she temporarily stopped her strict regimen of self-exploration. And her tumors accordingly stopped shrinking. She was overtired. She didn't have time to pursue her meditation as diligently. When she resumed the regimen, the tumors again began to diminish. This, in her husband's view, was suggestive evidence of the efficacy of the psychological approach: The condition was improved with the introduction of a variable. The improvement halted when the variable was withdrawn and resumed when the variable was reintroduced.

Alice now gets phone calls from people who have cancer; they just want to talk to her, like she's a good-luck charm. She tells them amazing things are possible. And so the days go by. She reads at night. She watches Star Trek. She walks in the woods with her husband. In the winter, she turns her face to the snow..

END