Checkered history of cancer

A Biography of Cancer

By Siddhartha Mukherjee

Scribner. 592 pp. $30

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Reviewed by Jim Higgins

Oncologist Siddhartha Mukherjee's impressive, sobering new history of cancer and its treatment brings to mind the bitter wisdom that Walt Kelly expressed in

Pogo

: "We have met the enemy and he is us."

In the course of The Emperor of All Maladies, Mukherjee recounts many moments of heroism and brilliance by doctors and scientists battling the scourge, and of courage and forbearance by patients, often terminally ill, who serve as sentient guinea pigs for new treatments. But he also records many fumbles, ego-driven conflicts, and refusals by acknowledged experts to let facts get in the way of their cherished ideas.

"The hierarchical practice of medicine, its internal culture, its rituals of practice . . . were ideally arranged to resist change and to perpetuate orthodoxy," Mukherjee writes.

One outcome of that hierarchical practice: Many women with breast cancer had invasive, disfiguring radical mastectomies simply because that operation had become the standard operating procedure of its time.

Mukherjee's book is subtitled A Biography of Cancer, but it's really a group biography, of many kinds of cancers, and a chief lesson it imparts is that cancer treatments must be specific, targeted, and based on intimate knowledge of how the cells operate.

Mukherjee quotes researcher Mel Greaves' pithy summary of hundreds of years of attempts to explain what causes cancer: "It's bad bile. It's bad habits. It's bad bosses. It's bad genes."

The advent of anesthesia and antisepsis in the mid-to-late 1800s led to surgery as the preferred treatment for many locally restricted cancers. But patients often relapsed. Surgeon William Halsted pioneered the radical mastectomy for breast cancer, removing larger and larger swaths of tissue and lymph nodes in the hope of rooting out stray cancer cells.

Meanwhile, radium had been discovered, and researchers noticed its ability to kill rapidly dividing cells, leading to radiation treatments for local cancers. Doctors would also learn, alas, that radiation could cause cancer, too.

While neither a doctor nor a scientist, Mary Lasker (1900-94), a successful businesswoman and socialite, is a pivotal figure in Mukherjee's story. She and her brilliant ad-man husband, Albert Lasker, turned their attention to cancer and sought to transform "the landscape of American medical research using political lobbying and fund-raising at an unprecedented scale." The Laskerites, as her people became known, wanted a "Manhattan Project for cancer." They transformed a small doctors' group into the powerful American Cancer Society and promulgated a public War on Cancer.

The Laskerites also had, in Mukherjee's words, an "emphatic, unshakable faith in the underlying singularity of cancer more than its pluralities." Oncologists of the '60s were on a quest for a universal cure. "That assumption - that a monolithic hammer would eventually demolish a monolithic disease - surcharged physicians, scientists, and cancer lobbyists with vitality and energy."

Unfortunately, the narrative (political and medical) of singularity and the search for a magic bullet would founder on the plurality and specificity of the many varieties of cancer.

Take breast cancer, the subject of some of the most sorrowful pages in this book.

"Medicine, once considered virtually infallible in its judgment, was turning out to have deep fallibilities - flaws that appeared to cluster pointedly around issues of women's health," Mukherjee writes.

By the late 1960s, some surgeons and many patients began to challenge the dominance of the radical mastectomy. By 1981, the results of a 10-year trial showed that rates of breast cancer recurrence, relapse, death, and distant cancer metastasis were statistically identical among randomized patient groups treated via radical mastectomy, simple mastectomy, and surgery followed by radiation. The radical mastectomy, Mukherjee notes, is rarely, if ever, performed by surgeons today.

Continued research has shown the value of "Know thine enemy," according to Mukherjee:

"[It is] essential to 'know' the cancer as intimately as possible before rushing to treat it. . . . Early-stage breast cancer could not be treated like late-stage breast cancer. The meticulous separation of ER-positive and ER-negative cancers was crucial. . . . If tamoxifen had indiscriminately been tested on ER-negative breast cancer, the drug could have been discarded as having no benefit."

As Mukherjee tells it, many surgeons and researchers seemed to forget the patient was more than the site of their activities. "The movement to restore sanity and sanctity to end-of-life care to cancer patients" emerged from Europe after World War II, led by Cecily Saunders, a nurse who had become a doctor.

Patients, too, began to assert themselves. Learning from the successes of AIDS activists, cancer patients pushed for experimental medicines before trials were completed. No one wanted to be in the trials, Mukherjee explains, because they didn't want to be assigned to the non-treatment control groups.

Mukherjee, who treats patients himself, includes a few stories from his career. In one, he and an attending physician have just finished explaining to a 76-year-old woman with advanced, metastasized pancreatic cancer that they have run out of treatment options for her. Mukherjee stares down at his feet. The patient shrugs her shoulders and says, "I know we have reached an end."

"We hung our heads, ashamed," Mukherjee writes. "It was, I suspected, not the first time that a patient had consoled a doctor about the ineffectuality of his discipline."

In praising one of his mentors, a lung-cancer doctor named Thomas Lynch, Mukherjee writes about the man's touch with a patient nearly catatonic with fear:

"I watched him resuscitate. He emphasized process over outcome and transmitted astonishing amounts of information with a touch so slight that you might not even feel it."

As an author, Mukherjee shares some of his mentor's bedside manner. He is a good explainer and paces the book well.

People who are facing cancer treatment - their own or a loved one's - with a must-know-everything approach may want to read it. Other patients and family members may not want to read about the painful trial-and-error history of chemotherapy on the days their own appointments are scheduled.

In the final segments of The Emperor of All Maladies, Mukherjee discusses advances in identifying oncogenes and anti-oncogenes (tumor-promoting and tumor-suppressing genes), and how this has led to specific treatments. These science-filled sections are among the most intellectually challenging reading in his book, but also some of its most hopeful pages. "Twenty-four novel drugs have been listed by the National Cancer Institute for cancer-targeted therapies. Dozens more are in development."

Many incremental advances have led to some good news for Americans. Between 1990 and 2005, "the cancer-specific death rate had dropped nearly 15 percent, a decline unprecedented in the history of the disease," he writes. A multitude of developments led to the drop: Prevention (through discouraging smoking) led to a drop in lung cancer; screening led to drops in the colon and cervical cancer death rates; advances in chemotherapy resulted in fewer deaths from leukemia, lymphoma, and testicular cancer.

"Perhaps most symbolically, the decline in breast cancer mortality epitomized the cumulative and collaborative nature of these victories - and the importance of attacking cancer using multiple independent prongs."

When statistician Donald Berry parsed the data to assess the effect of each intervention independently, he found "a satisfying tie: both cancer prevention and chemotherapy had diminished breast cancer mortality equally - 12 percent for mammography and 12 percent for chemotherapy. . . . 'No one,' as Berry said, paraphrasing the Bible, 'had labored in vain.' "