Summary & Study Guide - The Emperor of All Maladies (eBook)

Chapter 1

Black Bile in Tumors

In the laboratory buried in the basement of the Children's Hospital in Boston on a December morning in 1947, a man named Sidney Farber waited for the parcel from New York to arrive. There were no patients in the lab here, just the bodies and tissues of patients brought down for autopsies and examinations.

Farber was the chief of pathology at Children's. For Farber, pathology was a discipline more preoccupied with the dead than the living. Now felt impatient watching illness from its sidelines, Farber would try to treat patients in the clinic upstairs. He would try to use the knowledge from his pathological specimens to devise new therapies for diseases. The parcel from New York contained a few vials of chemical called aminopterin which he hoped might stop the growth of leukemia in children.

A SUPPURATION OF BLOOD

IF FARBER HAD asked any doctors in the clinic upstairs about the likelihood of developing an anti-leukemic drug, they would have told him not to bother. Childhood leukemia had confused and frustrated doctors ever since its discovery on March 19, 1845 by a Scottish physician named John Bennett. The patient was a 28-year-old man with a mysterious swelling in his spleen. In the course of a few weeks, the patient had spiraled from symptom to symptom - fevers, flashes of bleeding, sudden abdominal pain, swollen tumors spouting in his armpits, and his neck. Bennett treated him with leeches and purging, but to no avail. At the autopsy, Bennett concluded that his patient had succumbed to an infection because his blood was full of white blood cells. He called his case "a suppuration of blood."

Four months later, a young German professor at the University of Wurzburg named Rudolf Virchow published a similar case. The patient's blood was overgrown with white blood cells, forming dense and pulpy pools in her spleen. At autopsy, Virchow found layers of white blood floating above the red. He called the disease "weisses Blut" - white blood. In 1847, he changed the name to "leukemia" - from "leukos", the Greek word for "white".

Virchow was a pathologist in training. He believed all living things were made of cells. And that cells could grow in only two ways: either by increasing its number, or by increasing its size. He called these two modes hyperplasia and hypertrophy. Examining cancerous growths through his microscope, Virchow concluded that cancer was hyperplasia in its extreme form.

By the time Virchow died in 1902, a new theory of cancer had come together out of these observations. Cancer is an aberrant, and uncontrolled cell division creating "tumors" that would attack and destroy organs and normal tissues. These tumors could also spread (or metastasize) to other parts of the body, such as the lungs and the brain.

Leukemia is a malignant overgrown of white cells in the blood. It comes in several forms. It could be chronic and indolent, or acute and violent. The second version comes in further types, based on the type of white blood cells involved. Cancers of the myeloid cells are called acute myeloid leukemias (AML); cancers of the lymphoid cells are called lymphomas; and cancers of immature lymphoid cells are called acute lymphoblastic leukemias (ALL). The most common leukemia in children is ALL.

SIDNEY FABER, THE third of fourteen children, was born in Buffalo, New York, in 1903. His father, Simon Farber, had immigrated to America from Poland in the late 19th century and worked in an insurance agency. Having completed his advanced training in pathology in the late 1920s, Farber became the first full-time pathologist at the Children's Hospital in Boston. His specialty was pediatric pathology, the study of children's diseases.

Yet Farber was driven by the hunger to treat patients. Sitting in his basement laboratory one day in the summer of 1947, he was inspired to focus his attention to the oldest and most hopeless variants of leukemia - childhood leukemia. The disease had been analyzed, and classified meticulously, but with no therapeutic or practical advances.

The package from New York was waiting in the laboratory that December morning. As he pulled out the vials of chemicals from the package, he was throwing open a new way of thinking about cancer.

A MONSTER MORE INSATIABLE THAN THE GUILLOTINE

SYDNEY FARBER'S PACKAGE of chemicals arrived at a pivotal moment in the history of medicine. In the first quarter of the 20th century, cancer had overtaken the three common deadly diseases - typhoid fever, smallpox, and tuberculosis - to become the second most common killer, just behind heart diseases. Although new miracle drugs appeared at an astonishing rate after World War II in the late 1940s, no effective drugs had been found for cancer. To cure a cancer, doctors had only two options: incising it with surgery, or incinerating it with radiation.

Proposals to launch a national response against cancer had ebbed and flowed in America since the early 1900s. In May 1937, cancer was magnified in the public eye again thanks to cancer articles appearing in the Fortune, the Life, and the Time magazines. The U.S. government held a joint Senate-House conference in June to draft legislation to address the issue. On August 5, President Roosevelt signed the National Cancer Act of 1937, creating a new entity called the National Cancer Institute (NCI) to coordinate cancer education and research.

But World War II had shifted the nation's priority from cancer research to the war. The promised funds from Congress never materialized, and the NCI languished in neglect. The social outcry about cancer also drifted into silence.

IF A CURE for leukemia could be found, Farber reasoned, it would be found within hematology—the study of normal blood. In 1928, a young English physician named Lucy Wills discovered that folic acid, a vitamin-like substance found in fruits and vegetables, could restore the normal genesis of blood in nutrient-deprived patients. Farber wondered whether folic acid could restore the normalcy of blood in children with leukemia. But as he injected synthetic folic acid into a cohort of leukemia children, Farber found that folic acid sped up the growth of leukemia rather than stopping it. He stopped the experiment in a hurry.

But Farber was intrigued by the response of the leukemia cells to folic acid. What if he could find a drug to suppress folic acid - an antifolate?

Farber's supply of folic acid had come from the laboratory of an old friend - a chemist called Yellapragada Subbarao or Yella. Yella was a physician turned cellular physiologist. Having finished his medical training in India, Yella could not practice medicine in America because he had no license. He started as a night porter at a hospital, switched to a day job as a biochemist, and then joined the Lederle Lab in 1940.

With a slight alteration of the recipe, Yella created multiple variants of folic acid, some of which behaved like antagonists to folic acid. In the late summer of 1947, Yella sent the first package of antifolates to Farber.

FARBER'S GAUNTLET

ON AUGUST 16, 1947, in the town of Dorchester in New England, a two-year-old boy named Robert Sandler was brought to Children's Hospital in Boston. He had been ill with a wax and wane fever for over two weeks. The condition had worsened. His spleen was enlarged, and his blood sample had thousands of immature lymphoid leukemic blasts. His twin brother, Elliot, was in perfect health.

Farber had received the first package of antifolates from Yella a few weeks before Sandler's arrival. On September 6, 1947, Farber injected Sandler with pteroylaspartic acid or PAA, the first of Yella's antifolates. But PAA had little effect. On December 28, Farber received a new version of antifolate - aminopterin. He injected the boy with it. The response was remarkable. The white cell count stopped its astronomical ascent, hovered at a plateau, and then dropped. And the leukemic blasts gradually flickered out in the blood and then disappeared. By New Year's Eve, the count had dropped to one-sixth of its peak value, bottoming out at a near normal level. The cancer hadn't vanished, but it had temporarily abated.

Sandler's remission was unprecedented in the history of leukemia. Farber started to treat the slow train of children with childhood leukemia arriving at his clinic. An incredible pattern emerged: antifolates could destroy leukemia cells and make them disappear for a while.

But the cancer relapsed after a few months of remission, refusing to respond to even the most potent of Yella's drugs. Robert Sandler died in 1948.

In June 1948, Farber published his study in the New England Journal of Medicine. The paper was received with skepticism, disbelief and outrage. The obliteration of an aggressive cancer using a chemical drug was unprecedented in the history of cancer.

A PRIVATE PLAGUE

WE TEND TO assume that cancers in humans are diseases caused by industrialization and modern lifestyles, but studies showed these diseases occurred thousands of years before modern industrial societies existed.

The world's first medical description of cancer was discovered in Egypt and dates back to about 2500...