The Emperor of All Maladies: A Biography of Cancer (18 page)

Just a few hundred miles south of Yale, at the Burroughs Wellcome laboratory in New York, the biochemist
George Hitchings had also
turned to Ehrlich’s method to find molecules with a specific ability to kill cancer cells. Inspired by Yella Subbarao’s anti-folates, Hitchings focused on synthesizing decoy molecules that when taken up by cells killed them. His first targets were precursors of DNA and RNA. Hitchings’s approach was broadly disdained by academic scientists as a “fishing expedition.” “
Scientists in academia stood disdainfully
apart from this kind of activity,” a colleague of Hitchings’s recalled. “[They] argued that it would be premature to attempt chemotherapy without sufficient basic knowledge about biochemistry, physiology, and pharmacology. In truth, the field had been sterile for thirty-five years or so since Ehrlich’s work.”

By 1944, Hitchings’s fishing expedition had yet to yield a single chemical fish. Mounds of bacterial plates had grown around him like a molding, decrepit garden with still no sign of a promised drug. Almost on instinct, he hired a young assistant named Gertrude Elion, whose future seemed even more precarious than Hitchings’s. The daughter of Lithuanian immigrants, born with a precocious scientific intellect and a thirst for chemical knowledge, Elion had completed a master’s degree in chemistry from New York University in 1941 while teaching high school science during the day and performing her research for her thesis at night and on weekends. Although highly qualified, talented, and driven, she had been unable to find a job in an academic laboratory. Frustrated by repeated rejections, she had found a position as a supermarket product supervisor. When Hitchings found Trudy Elion, who would soon become one of the most innovative synthetic chemists of her generation (and a future Nobel laureate), she was working for a food lab in New York, testing the acidity of pickles and the color of egg yolk going into mayonnaise.

Rescued from a life of pickles and mayonnaise, Gertrude Elion leapt into synthetic chemistry. Like Hitchings, she started off by hunting for chemicals that could block bacterial growth by inhibiting DNA—but then added her own strategic twist.
Instead of sifting through mounds
of unknown chemicals at random, Elion focused on one class of compounds,
called purines. Purines were ringlike molecules with a central core of six carbon atoms that were known to be involved in the building of DNA. She thought she would add various chemical side chains to each of the six carbon atoms, producing dozens of new variants of purine.

Elion’s collection of new molecules was a strange merry-go-round of beasts. One molecule—2,6-diaminopurine—was too toxic at even low doses to give the drug to animals. Another molecule smelled like garlic purified a thousand times. Many were unstable, or useless, or both. But in 1951, Elion found a variant molecule called 6-mercaptopurine, or 6-MP.

6-MP failed some preliminary toxicological tests on animals (the drug is strangely toxic to dogs), and was nearly abandoned. But the success of mustard gas in killing cancer cells had boosted the confidence of early chemotherapists. In 1948, Cornelius “Dusty” Rhoads, a former army officer, left his position as chief of the army’s Chemical Warfare Unit to become the director of the Memorial Hospital (and its attached research institute), thus sealing the connection between the chemical warfare of the battlefields and chemical warfare in the body. Intrigued by the cancer-killing properties of poisonous chemicals, Rhoads actively pursued a collaboration between Hitchings and Elion’s lab at Burroughs Wellcome and Memorial Hospital. Within months of having been tested on cells in a petri dish, 6-MP was packaged off to be tested in human patients.

Predictably, the first target was acute lymphoblastic leukemia—the rare tumor that now occupied the limelight of oncology.
In the early 1950s, two physician-scientists
, Joseph Burchenal and Mary Lois Murphy, launched a clinical trial at Memorial to use 6-MP on children with ALL.

Burchenal and Murphy were astonished by the speedy remissions produced by 6-MP. Leukemia cells flickered and vanished in the bone marrow and the blood, often within a few days of treatment. But, like the remissions in Boston, these were disappointingly temporary, lasting only a few weeks. As with Farber’s anti-folates, there was only a fleeting glimpse of a cure.

The name “Jimmy” is a household word in New England
. . . a nickname for the boy next door.

—
The House That “Jimmy” Built

I’ve made a long voyage
and been to a strange country, and I’ve seen the dark man very close.

—Thomas Wolfe

Flickering and feeble, the leukemia remissions in Boston and New York nevertheless mesmerized Farber. If lymphoblastic leukemia, one of the most lethal forms of cancer, could be thwarted by two distinct chemicals (even if only for a month or two), then perhaps a deeper principle was at stake. Perhaps a series of such poisons was hidden in the chemical world, perfectly designed to obliterate cancer cells but spare normal cells. The fingerling of that idea kept knocking in his mind as he paced up and down the wards every evening, writing notes and examining smears late into the night. Perhaps he had stumbled upon an even more provocative principle—that cancer could be cured by chemicals alone.

But how might he jump-start the discovery of these incredible chemicals? His operation in Boston was clearly far too small. How might he create a more powerful platform to propel him toward the cure for childhood leukemia—and then for cancer at large?

Scientists often study the past as obsessively as historians because few other professions depend so acutely on it. Every experiment is a conversation with a prior experiment, every new theory a refutation of the old. Farber, too, studied the past compulsively—and the episode that pivotally fascinated him was the story of the national polio campaign. As a student at Harvard in the 1920s, Farber had witnessed polio epidemics sweeping through the city, leaving waves of paralyzed children in their wake. In the acute phase of polio, the virus can paralyze the diaphragm,
making it nearly impossible to breathe. Even a decade later, in the mid-1930s, the only treatment available for this paralysis was an
artificial respirator known as the iron lung
. As Farber had rounded on the wards of Children’s Hospital as a resident, iron lungs had continuously huffed in the background, with children suspended within these dreaded contraptions often for weeks on end. The suspension of patients inside these iron lungs symbolized the limbolike, paralytic state of polio research. Little was known about the nature of the virus or the biology of the infection, and campaigns to control the spread of polio were poorly advertised and generally ignored by the public.

Polio research was shaken out of its torpor
by Franklin Roosevelt in 1937. A victim of a prior epidemic, paralyzed from the waist down, Roosevelt had launched a polio hospital and research center, called the Warm Springs Foundation, in Georgia in 1927. At first, his political advisers tried to distance his image from the disease. (A paralyzed president trying to march a nation out of a depression was considered a disastrous image; Roosevelt’s public appearances were thus elaborately orchestrated to show him only from the waist up.) But reelected by a staggering margin in 1936, a defiant and resurgent Roosevelt returned to his original cause and launched the National Foundation for Infantile Paralysis, an advocacy group to advance research on and publicize polio.

The foundation, the largest disease-focused association in American history, galvanized polio research. Within one year of its launch, the actor Eddie Cantor created the March of Dimes campaign for the foundation—a massive and highly coordinated national fund-raising effort that asked every citizen to send Roosevelt a dime to support polio education and research. Hollywood celebrities, Broadway stars, and radio personalities soon joined the bandwagon, and the response was dazzling.
Within a few weeks, 2,680,000 dimes
had poured into the White House. Posters were widely circulated, and money and public attention flooded into polio research. By the late 1940s, funded in part by these campaigns, John Enders had nearly succeeded in culturing poliovirus in his lab, and Sabin and Salk, building on Enders’s work, were well on their way to preparing the first polio vaccines.

Farber fantasized about a similar campaign for leukemia, perhaps for cancer in general. He envisioned a foundation for children’s cancer that would spearhead the effort. But he needed an ally to help launch the foundation, preferably an ally outside the hospital, where he had few allies.

Farber did not need to look far. In early May 1947, while Farber was still in the middle of his aminopterin trial, a group of men from the Variety Club of New England, led by Bill Koster, toured his laboratory.

Founded in 1927 in Philadelphia by a group of men in show business—producers, directors, actors, entertainers, and film-theater owners—the Variety Club had initially been modeled after the dining clubs of New York and London. But in 1928, just a year after its inception, the club had unwittingly acquired a more active social agenda. In the winter of 1928, with the city teetering on the abyss of the Depression, a woman had abandoned her child at the doorstep of the Sheridan Square Film Theater. A note pinned on the child read:

Please take care of my baby. Her name is Catherine
. I can no longer take care of her. I have eight others. My husband is out of work. She was born on Thanksgiving Day. I have always heard of the goodness of show business and I pray to God that you will look out for her.

The cinematic melodrama of the episode, and the heartfelt appeal to the “goodness of show business,” made a deep impression on the members of the fledgling club. Adopting the orphan girl, the club paid for her upbringing and education. She was given the name Catherine Variety Sheridan—her middle name for the club and her last name for the theater outside which she had been found.

The Catherine Sheridan story was widely reported in the press and brought more media exposure to the club than its members had ever envisioned. Thrust into the public eye as a philanthropic organization, the club now made children’s welfare its project. In the late 1940s, as the boom in postwar moviemaking brought even more money into the club’s coffers, new chapters of the club sprouted in cities throughout the nation. Catherine Sheridan’s story and her photograph were printed and publicized in club offices throughout the nation. Sheridan became the club’s unofficial mascot.

The influx of money and public attention also brought a search for other children’s charity projects. Koster’s visit to the Children’s Hospital in Boston was a scouting mission to find another such project. He was escorted around the hospital to the labs and clinics of prominent doctors. When Koster asked the chief of hematology at Children’s for suggestions
for donations to the hospital, the chief was characteristically cautious: “
Well, I need a new microscope
,” he said.

In contrast, when Koster stopped by Farber’s office, he found an excitable, articulate scientist with a larger-than-life vision—a messiah in a box. Farber didn’t want a microscope; he had an audacious telescopic plan that captivated Koster. Farber asked the club to help him create a new fund to build a massive research hospital dedicated to children’s cancer.

Farber and Koster got started immediately. In early 1948, they launched an organization called the Children’s Cancer Research Fund to jump-start research and advocacy around children’s cancers. In March 1948, they organized a raffle to raise
money and netted
$45,456—an impressive amount to start, but still short of what Farber and Koster hoped for. Cancer research, they felt, needed a more effective message, a strategy to catapult it into public fame. Sometime that spring, Koster, remembering the success with Sheridan, had the inspired idea of finding a “mascot” for Farber’s research fund—a Catherine Sheridan for cancer. Koster and Farber searched Children’s wards and Farber’s clinic for a poster child to pitch the fund to the public.