The Emperor of All Maladies: A Biography of Cancer

In 1951, Albert Lasker received a colon cancer diagnosis. He became “one in four” (116) people who would contend with cancer, a victim of the disease he had worked to defeat. After he died in 1952, Mary became even more urgent in her efforts. She wanted not only to raise funds but to lead the campaign, starting with a reorganization of the National Cancer Institute (NCI).

Farber also developed what was probably ulcerative colitis, which predisposes people toward cancer in the colon and bile duct. He had surgery at a small hospital, trying to keep his disease secret from his colleagues, and it is likely that he was contending with cancer, not just precancer. As a result, he wore a colostomy bag hidden under his clothing.

Vannevar Bush, who had served as the head of the Office of Scientific Research and Development (OSRD) during World War II, directed the new approach to scientific research in the post-war period. Although his agency had produced the atomic bomb and sought scientists who pursued practical rather than basic research, he began to advocate the advancement of basic research to push science forward. The National Science Foundation, founded in 1950, was built on this premise.

However, the “Laskerites,” as the allies of the Laskers were known, wanted “a Manhattan Project for cancer” (121). They wanted to solve the cancer problem, not just conduct open-ended research. After all, Farber had tried out aminopterin without understanding in advance how it actually worked. The first step was to create a unit for the discovery of anti-cancer drugs. In 1954, after the Laskerites’ lobbying efforts, the Senate granted the NCI the right to build a program, called the Cancer Chemotherapy National Service Center (CCNSC), to find chemotherapeutic drugs.

Farber continued to try to find his own drugs, trying out a chemical called actinomycin D, which microbiologist Selman Waksman had found as an antibiotic. It had promising results in cases of Wilms’ tumor, a rare kind of kidney cancer, and Farber’s assistants found the drug had a synergistic effect with X-rays. Wilms’ tumor was the first kind of metastatic cancer to respond to drug treatment.

Farber’s hospital, where suffering children were able to go about on carts with their IV tubes, swung between optimism and despair. Although many children in the hospital met with sad deaths, Farber waged on, convinced that combinations of medicines would work.

Mukherjee describes his treatment of Carla Reed, who wonders at her 30% survival rate. He will treat her with three rounds of chemotherapy: induction, intensification, and maintenance. After the first round, her white blood cell count would fall quickly so that she would have no immune system. Her treatment would then intensify if she didn’t go into remission. If she did, she would still need two years of maintenance. Doctors would have to inject chemicals into her spinal fluid to enter her brain. 

At the National Cancer Institute (NCI) in Bethesda, Maryland, a hot-tempered, flamboyant doctor named Emil Freireich, who was a fellow of Farber’s chemotherapy regimen, paired up with Emil Frei, a composed man of few words. Gordon Zubrod, the director of NCI’s Clinical Center, was a consummate delegator, referred to as the “Eisenhower of cancer research” (130), and he brought the two Emils to Bethesda to be on the front lines of the hospital. The two Emils balanced each other out and worked in a synergistic way.

Zubrod made sure that the researchers worked together collaboratively in different cities and that they did not compete. Farber called the first group meeting, which was successful, and the researchers now had a professional community. Scientists used randomized trials (with a placebo and control group) to test streptomycin for tuberculosis, and Zubrod built upon this methodology to test anti-cancer drugs.

Zubrod, Frei, and Freireich also studied the way in which bacteria developed resistance to drugs meant to treat them, as well as the way in which several types of antibacterial drugs worked together. NCI, Roswell Park, and Children’s Hospital in Buffalo, New York, launched Protocol I to test three antileukemia drugs together. Although the children still died by the end of one year, the intense treatment was more effective. This marked a successful experimental collaboration among all the medical teams. In the second experiment, some patients received one drug, while others received two. Those who received two had a remission rate of 45%, compared to 15-20% for the other group. In the third experiment, patients received two drugs, and one group received follow-up drugs while the other received a placebo. The patients who received a more aggressive regimen fared better. The team creeped toward giving four drugs together, knowing that resistance to the ways of the “butcher shop,” what others at NCI called the leukemia ward, would be strong.

Frei and Freireich received news about the discoveries of Min Chiu Li and Roy Hertz at the NCI. Li was born in China and worked with Hertz on choriocarcinoma, the cancer of the placenta, to escape involvement in the Korean War. A patient who was bleeding profusely from tumors that had spread into her lungs received antifolates. As a result, to the researchers’ surprise, the woman’s tumors totally vanished. Li found that a hormone the cancer produced was still present in the patient’s blood, so he kept giving her the drugs until the level reached zero.

The institutional review board at the NCI objected to Li’s decision, citing his actions as dangerous, and fired him. However, scientists discovered over time that the patients who stopped receiving the drug relapsed, while those who continued to receive it were free of the disease. Li had discovered a fundamental truth in treating cancer: The disease had to be treated until every trace of it was eradicated. Although Li lost his job, he had produced the first cure of cancer in adults using chemotherapy.

Freireich grew increasingly frustrated with the slow pace of research in clinical trials, and he had to face parents whose children had died. Researchers introduced a new anticancer drug called vincristine into the clinical trials—a poisonous plant-alkaloid from the Madagascar periwinkle. The researchers had to fold this into their four-drug regimen in a way that was not toxic to a child with leukemia. However, testing this regimen of drugs would take a great deal of time.

A scientist from Alabama named Howard Skipper, who called himself “the mouse doctor” (140), found a way around this problem. He used a mouse cell line called L-1210, which was a kind of lymphoid leukemia that could be grown in a petri dish, and injected it into mice, where it would rapidly multiply. Skipper figured out two important things: Chemotherapy drugs killed a fixed percentage of cancer cells, and this number was unique to each drug. The findings indicated that administering drugs had to be an iterative, or repetitive process. By adding drugs together, he could get a synergistic effect. More drugs were better than fewer.

From these findings, Frei and Freireich concluded that doctors would have to give children with leukemia several drugs in dose after dose, though such treatments would test the patients’ limits. They planned to try a regime of four drugs: vincristine, amethopterin, mercaptopurine, and prednisone, together known as VAMP.

The idea of administering four drugs, which were essentially poisons, together stunned Zubrod. When Frei and Freireich announced their findings at a national meeting about blood cancers, the audience revolted. As a result, Frei had to agree to conduct the trial of VAMP without the cooperative research group, Acute Leukemia Group B (ALGB).

The first trial, started in 1961, seemed catastrophic at first. The patients hovered near death, and the doctors just tried to make them comfortable. However, after about three weeks, the patients’ cancers were in complete remission. Over time, as patients survived several rounds of chemotherapy, skeptics turned to endorsing the VAMP regimen.

However, then patients began returning to the clinic with headaches, which suggested to the doctors that leukemia was present in the brain. Spinal taps confirmed this. While the treatment had wiped leukemia out of their bone marrow, the children’s brains were infected with it. Morale declined, and Frei and Freireich left for the MD Anderson Cancer Center in Houston.

Leukemia didn’t infect the central nervous systems of about 5% of patients, who survived. Mukherjee tracked one of the survivors down, a 56-year-old woman in Maine whom he calls “Ella.” Treated in Boston as an 11-year-old in 1964, the regimen she endured was horrific—it was so painful that she became addicted to morphine and had to quit it through force of will. Nonetheless, she felt spared: “I feel as if I slipped through” (149). Farber brought cases such as hers to Congress, where he was ready to launch a campaign to get more money for research. He was also ready to win the war against adult cancers.

To Mukherjee, cancer seems too simple a term for the vast taxonomy of diseases within it, although the Laskerites presented it as a monolith. Farber and Lasker sought a universal cure for a disease that scientists assumed to be medically consolidated. Mukherjee presents two of his cases as an example, demonstrating that treating cancer yields various results. At the Dana-Farber Cancer Institute, Mukherjee treats Bea Sorenson, a diminutive but forceful 76-year-old with pancreatic cancer. She tried various chemotherapy drugs, to no avail, and Mukherjee must tell her there is nothing left to try. The author also tells the story of a 24-year-old athlete named Ben Orman who discovered a lump in his neck in 2004. Doctors diagnosed him with Hodgkin’s lymphoma and gave him an 85% chance of recovery. Whereas Sorenson’s pancreatic cancer will inevitably kill her, Orman will likely survive Hodgkin’s lymphoma.

Thomas Hodgkin discovered Hodgkin’s lymphoma. Hodgkin was a 19th century English anatomist who became a librarian of disease and pathology, organizing diseases by organs rather than date. He found cadavers with enlargement of the lymph nodes and believed he had found a new disease. He also noted that, unlike other cancers, the disease spread predictably from one lymph node to the one adjacent to it.

Henry Kaplan, a Stanford professor of radiology, heard about the construction of a linear accelerator, which fires electrons at a single target. He needed a localized cancer on which to turn this new form of treatment, and he chose Hodgkin’s lymphoma. In 1962, he set out to prove that extended field radiation could cure early forms of the disease. In his first trial, he found that extended field radiation decreased the relapse rate of the disease. Careful to choose patients only with localized types of the disease, he found that higher doses of radiation resulted in decreased relapse rates, and some patients survived five years. By being careful about the patients in his study, he increased his success rate. He was also successful because he picked a disease that was “a regional illness” (161) and not capricious in its spread in the body. The idea that the treatment had to fit the disease became central to cancer treatment, over time.

Frei began to experiment on whether using cellular poisons from various sources could eliminate advanced cancers. Researchers like George Canellos, Vincent DeVita, and Zubrod, began to use these drugs on Hodgkin’s disease. DeVita developed a cocktail called MOMP, composed of methotrexate, vincristine, nitrogen mustard, and prednisone. Scientists confined patients to isolation chambers to prevent infection. DeVita then tried a more potent cocktail called MOPP, in which the more potent procarbazine replaced methotrexate.

The patients in the trials suffered horrible nausea, along with sterility in men and some women, and a rare form of pneumonia (which was later part of the HIV epidemic). Some patients, cured of Hodgkin’s, would later present with drug-resistant leukemia. But the results were amazing—of the 43 patients, 35 achieved complete remission.

The VAMP trials, in the meantime, hit a low point as many patients succumbed to brain cancer. A Farber protégé named Donald Pinkel was recruited to start a cancer program at St. Jude’s hospital in Memphis. Pinkel believed that as many as 8 combinations of chemotherapy drug combinations had to be used, along with injecting the drugs into the spinal fluid to prevent the spread of cancer to the brain. He also thought that radiation had to be part of the treatment and that patients had to receive chemotherapy for months or even years. As fellows, the author and his colleagues called it “total hell” (168), and his patient, Carla, showed the effects of this type of treatment. She retreated into herself, shuffling around the hospital like a zombie, after many blood tests, spinal taps, and bone marrow biopsies.

Pinkel’s original cohort, in spite of the hell they endured, did well. By 1979, 80% of the patients had remained disease free. The idea that doctors could only treat leukemia patients with palliative care was over.

By 1968, the success of the trials in Bethesda and Memphis marked a seismic shift in the quest to treat cancer, as DeVita described: “A revolution [has been] set in motion” (171). A cure seemed imminent, and Farber threw a party in Boston to celebrate Jimmy’s 21st birthday. The real Jimmy, 32-year-old Einar Gustafson, was alive and living on a Maine farm with his wife and three children but was absent from the event; Farber preferred to regard Jimmy as more of an abstraction than an actual person. Researchers and the political campaign around cancer obsessed over a chemical cure for all cancers: Cancer was as a monolith, one enemy to defeat.

Scientists believed that there was not only one cure for cancer but one cause: viruses. This theory went back to the work of a chicken virologist named Peyton Rous at the Rockefeller Institute in New York City. At this time, scientists believed the somatic mutation theory of cancer, which suggested that environmental carcinogens such as soot changed the structure of the cell and caused cancer. Rous, however, was able to transplant sarcomas, a kind of cancer, from one chicken to the next, and even the filter of the cancerous cells, without the cells themselves, resulted in cancer. What was responsible for causing cancer, he believed, was a particle within the cell, a virus which he named Rous sarcoma virus, or RSV.

In 1958, an Irish surgeon named Denis Burkitt found an aggressive form of lymphoma that occurred among children in the malaria belt of sub-Saharan Africa. He found a human virus in the cancer cells and called it Epstein-Barr virus (or EBV). The idea of a virus spreading cancer spread caused hysteria among people wondering if they could be infected. However, monkeys inoculated with human tumors did not develop a single cancer virus.

Rous won the Nobel Prize for medicine and physiology in 1966. In his speech, he admitted that the virus theory needed more research but criticized the somatic theory. Therefore, two theories became hastily stitched together: Viruses cause cancer, and combinations of poisonous drugs, or cytotoxins, would cure cancer.

The fact that scientists could not connect the cure and cause of cancer led some to claim that they were putting the cart before the horse, but Farber and the Laskerites were eager to strike while the political iron was hot and launch an all-out war on cancer. At the same time, a professor at the University of Missouri named Solomon Garb rose to national prominence in 1968 with his book Cure for Cancer: A National Goal.

After the Apollo mission to the moon in 1969, the Laskerites began to model their campaign on the propulsion the rocket achieved through a long campaign to get to the moon. Mary Lasker referred to conquering “inner space” and launched a “moon shot” for cancer (179).

In 1969, an ad appeared in the Washington Post (and later the New York Times) imploring President Nixon to do something to help those with cancer and to honor the 318,000 Americans who died of cancer the year before. The full-fledged public campaign against cancer had begun. Cancer spoke to the psychological neuroses of the age. People no longer feared outside threats, as they had during the height of the Cold War. Instead, they feared contagion from within, as movies such as The Exorcist showed. In people’s fears, the “Big Bomb” was replaced by the “Big C” (182), or cancer. The Laskerites benefited from this approach, in which society linked cancer to the destruction of the American dream.

Lasker proposed the formation of a committee called the Commission on the Conquest of Cancer. Mainly composed of her friends, including Farber, it met an ally in the form of Richard Nixon, who wanted an aggressive, practical approach to scientific problems. The panel issued a report in 1970 that suggested creating “a NASA for cancer” (184). Its budget was to reach $1 billion by the mid-1970s. At the same time, Senators Ted Kennedy and Jacob Javits launched a bill to create a National Cancer Authority in 1971. Lasker asked her friend, advice column Ann Landers, to publicize the bill in her column. The public response was overwhelming, as truckloads of mail arrived on Capitol Hill, and the bill sailed through the Senate with the vote 79-1. The bill stalled in the House, where the Laskerites had fewer allies, until Nixon, facing re-election and needing the victory that Vietnam could not give him, put his weight behind the bill. A modified bill passed the House, and Nixon signed the National Cancer Act into law in December of 1971.

While the act dedicated a great deal of money to cancer research, Farber and Lasker sustained political harm. Farber returned to Boston and Lasker to New York, where she turned to urban beautification projects. Even scientists at the NIH felt that they didn’t get what they wanted. In 1973, Farber died of cardiac arrest in his office at the Dana-Farber Cancer Institute. From an office near where Farber had died, Mukherjee called Carla Reed on a warm morning in August of 2005 to tell her that her cancer was in remission.