The Emperor of All Maladies: A Biography of Cancer

The chemotherapy units of cancer wards continued to be grim places. Oncologists had new weapons at their disposal, including the 1976 drug cisplatin. Biophysicist Barnett Rosenberg discovered cisplatin while trying to conduct an experiment with electrical currents and bacteria. John Cleland was a 22-year-old veterinary student in Indiana in 1973 when doctors diagnosed him with metastatic testicular cancer. After using other drugs that failed to produce an effect, he received cisplatin. He became the first patient who used a cocktail called BVP, consisting of bleomycin, vinblastine, and cisplatin. Ten days later, the tumors in his lungs disappeared. Einhorn, his doctor, had cured a solid cancer with chemotherapy.

Although the drug produced horrible nausea and there were fewer antiemetic drugs, cisplatin became the new en vogue drug, one that pushed patients toward death to save them. At the NCI, scientists tested cytotoxins with abandon. Although the medical community still did not understand cancer well, oncologists believed that these medicines would cure cancer. In the mid-1970s, a cocktail of seven drugs, including a chemical cousin of nitrogen mustard, cured Burkitt’s lymphoma.

As doctors opposed to fighting in Vietnam flooded into the NCI, there were 22 Comprehensive Cancer Centers spread across the country. They conducted trial and error on a broad scale to find cures. However, patients felt that the drugs “smiling oncologists” (209) gave them flattened them. Some of the trials ended in the patients’ deaths and without any meaningful response to chemotherapy.

Opponents to aggressive cytotoxic therapy emerged. They argued that poisonous drugs could not be the only way to attack cancer and that scientists needed to understand the biology of each cancer cell before developing drugs. A urologist named Charles Huggins became the unlikely proponent of this idea. Huggins found that cancer cells in the prostate needed testosterone to survive, and cancer cells were more like normal cells than previously thought.

Huggins decided to inject DES and Premarin, synthetic forms of estrogen, into men with prostate cancer to carry out what he called “chemical castration” (213). The result was remission, although this did not cure the prostate cancer. However, it proved that doctors did not always need to use cytotoxins to bring about remissions.

The next step was to use hormonal deprivation to cure breast cancer. In the 1880s, a Scottish surgeon named George Beatson heard from shepherds that removing the ovaries of cows changed their udders and ability to lactate. However, the reason this occurred was not clear until the discovery of estrogen decades later. Huggins, working with a chemist named Elwood Jensen, found that some breast cancer cells were receptive to estrogen (or ER-positive) while some were not (ER-negative).

They searched for an anti-estrogen medicine in vain to test on both ER-positive and ER-negative women. British chemists named Arthur Walpole and Dora Richardson led a team that eventually developed a chemical called tamoxifen in 1962. An oncologist named Mary Cole at the Christie Hospital in Manchester, England, launched a trial in which many patients underwent remission from breast cancer, though they later relapsed. Later, in 1973, V. Craig Jordan, working at a lab in Shrewsbury, Massachusetts, found that cancer cells with the estrogen receptor were highly responsive to tamoxifen, while those that lacked it were not: “For the first time in the history of cancer, a drug, its target, and a cancer cell had been conjoined by a core molecular logic” (217). 

Cole began to wonder what would happen if doctors used tamoxifen to treat women with earlier-stage cancers. At the NCI, a researcher named Paul Carbone carried out a trial to test whether adding chemotherapy after surgery reduced the rate of relapse. He used the phrase “adjuvant therapy,” coming from the Latin phrase “to help” (219). However, most surgeons regarded chemotherapists as their foes, so Carbone could not recruit enough patients into his study.

The Italian oncologist Gianni Bonadonna then agreed to conduct a trial in Milan. In his trial, half of the women received no treatment and half received a chemotherapeutic cocktail called CMF. In 1975, he reported his results: Nearly half the women who had not received therapy after surgery relapsed, while only a third of the women who received the adjuvant therapy did so.

Bernie Fisher tested the effect of tamoxifen on women with ER-positive tumors starting in 1977. Treatment with tamoxifen reduced cancer relapse by almost 50%, especially among women over 50. Tamoxifen had few significant side effects. Therefore, by the early 1980s, new paradigms of treatment had arisen. Adjuvant therapy and hormonal therapy did not cure cancer, but they prolonged remissions that could last for years or even decades.

These cures highlighted principles of cancer biology and treatment, including the idea that cancer was heterogeneous and that doctors had to understand the cancer before treating it. Doctors could divide breast cancer into early and late stages and into ER receptive and ER negative types. The idea that there was a single cure for cancer, which scientists furthered in the 1970s, was now outdated.

However, the author continued to experience from patients the idea, in the words of one patient’s daughter, that “more is more” (223). This patient was elderly and weak, and her kidney and liver were barely functioning, but her daughter, a physician, wanted the most aggressive treatment possible.

In the 1980s, the field of palliative care began to develop. Cicely Saunders, a nurse in England, first developed this methodology with the goal to help patients die peacefully—with less pain and more dignity. Although doctors were reluctant to embrace palliative care, as it meant resignation and defeat to them, scientists developed antinausea and anti-pain medicines, and hospice care spread across the US. 

In 1985, a Harvard biologist named John Cairns embarked on a plan to measure the success in the war against cancer using state-by-state records of cancer deaths. He found that despite advances, “less than one in twenty patients diagnosed with cancer […] had benefited” (228) from the new therapies developed since the 1950s.

In 1986, two Harvard researchers named John Bailar and Elaine Smith produced a report in the New England Journal of Medicine that used age-adjusted scales to report mortality rates from cancer. They found that rather than decreasing, cancer rates had actually increased from 1962 to 1965, largely as a result of increased smoking rates. They called the approach that focused only on a treatment a “qualified failure” (231), a barbed criticism of the NCI. A UCLA epidemiologist named Lester Barlow disagreed with Bailar and Smith’s methods, arguing that it judged a child cured of cancer who went on to live for 60 more years the same way it did an older person whose treatment added five years to his or her life. However, Bailar and Smith’s point was a larger one—that cancer needed prevention as well as treatment. At the NCI and other hospitals, far more money was devoted to treatment than prevention, following Ehrlich’s idea of finding a “magic bullet” (234). Instead, scientists needed to focus more on prevention.