The Emperor of All Maladies: A Biography of Cancer (44 page)

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Authors: Siddhartha Mukherjee

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BOOK: The Emperor of All Maladies: A Biography of Cancer
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In principle, this might have been correct. As the ’85 survey suggested, many doctors were indeed underdosing chemotherapy—at least by the standards advocated by most oncologists, or even by the NCI. But the obverse idea—that
maximizing
chemotherapy would maximize gains in survival—was also untested. For some forms of cancer (some subtypes of breast cancer, for instance) increasing the intensity of dosage would eventually result in increasing efficacy. But for a vast majority of cancers, more intensive regimens of standard chemotherapeutic drugs did not necessarily mean more survival. “Hit hard and hit early,” a dogma borrowed from the NCI’s experience with childhood leukemia, was not going to be a general solution to all forms of cancer.

A more nuanced critique of Bailar and Smith came, unsurprisingly, from Lester Breslow, the UCLA epidemiologist. Breslow reasoned that while age-adjusted mortality was one method of appraising the War on Cancer, it was by no means the only measure of progress or failure. In fact, by highlighting only one measure, Bailar and Smith had created a fallacy of their own: they had oversimplified the measure of progress. “
The problem with reliance on a single measure
of progress,” Breslow wrote, “is that the impression conveyed can vary dramatically when the measure is changed.”

To illustrate his point, Breslow proposed an alternative metric. If chemotherapy cured a five-year-old child of ALL, he argued, then it saved
a full sixty-five years of potential life (given an overall life expectancy of about seventy). In contrast, the chemotherapeutic cure in a sixty-five-year-old man contributed only five additional years given a life expectancy of seventy. But Bailar and Smith’s chosen metric—age-adjusted mortality—could not detect any difference in the two cases. A young woman cured of lymphoma, with fifty additional years of life, was judged by the same metric as an elderly woman cured of breast cancer, who might succumb to some other cause of death in the next year. If “years of life saved” was used as a measure of progress on cancer, then the numbers turned far more palatable. Now, instead of losing the War on Cancer, it appeared that we were winning it.

Breslow, pointedly, wasn’t recommending one form of calculus over another; his point was to show that measurement itself was subjective. “
Our purpose in making these calculations
,” he wrote, “is to indicate how sensitive one’s conclusions are to the choice of measure. In 1980, cancer was responsible for 1.824 million lost years of potential life in the United States to age 65. If, however, the cancer mortality rates of 1950 had prevailed, 2.093 million years of potential life would have been lost.”

The measurement of illness, Breslow was arguing, is an inherently subjective activity: it inevitably ends up being a measure of ourselves. Objective decisions come to rest on normative ones. Cairns or Bailar could tell us how many absolute lives were being saved or lost by cancer therapeutics. But to decide whether the investment in cancer research was “worth it,” one needed to start by questioning the notion of “worth” itself: was the life extension of a five-year-old “worth” more than the life extension of a sixty-year-old? Even Bailar and Smith’s “most fundamental measure of clinical outcome”—death—was far from fundamental. Death (or at least the social meaning of death) could be counted and recounted with other gauges, often resulting in vastly different conclusions. The appraisal of diseases depends, Breslow argued, on our
self
-appraisal. Society and illness often encounter each other in parallel mirrors, each holding up a Rorschach test for the other.

Bailar might have been willing to concede these philosophical points, but he had a more pragmatic agenda. He was using the numbers to prove a
principle. As Cairns had already pointed out, the only intervention ever known to reduce the aggregate mortality for a disease—
any
disease—at a population level was prevention. Even if other measures were chosen to evaluate our progress against cancer, Bailar argued that it was indubitably true that prevention, as a strategy, had been neglected by the NCI in its ever-manic pursuit of cures.

A vast majority of the institute’s grants, 80 percent, were directed toward treatment strategies for cancer;
prevention research received
about 20 percent. (
By 1992, this number had increased
to 30 percent; of the NCI’s $2 billion research budget, $600 million was being spent on prevention research.)
In 1974, describing to Mary Lasker
the comprehensive activities of the NCI, the director, Frank Rauscher, wrote effusively about its three-pronged approach to cancer: “Treatment, Rehabilitation and Continuing Care.” That there was no mention of either prevention or early detection was symptomatic: the institute did not even consider cancer prevention a core strength.

A similarly lopsided bias existed in private research institutions.
At Memorial Sloan-Kettering in New York
, for instance, only one laboratory out of nearly a hundred identified itself as having a prevention research program in the 1970s. When one researcher surveyed a large cohort of doctors in the early 1960s, he was surprised to learn that “not one” was able to suggest an “idea, lead or theory on cancer prevention.”
Prevention, he noted drily
, was being carried out “on a part-time basis.”
*

This skew of priorities, Bailar argued, was the calculated by-product of 1950s-era science; of books, such as Garb’s
Cure for Cancer
, that had forecast impossibly lofty goals; of the Laskerites’ near-hypnotic conviction that cancer could be cured within the decade; of the steely, insistent enthusiasm of researchers such as Farber. The vision could be traced back to Ehrlich, ensconced in the semiotic sorcery of his favorite phrase: “magic bullet.” Progressive, optimistic, and rationalistic, this vision—of magic bullets and miracle cures—had admittedly swept aside the pessimism around cancer and radically transformed the history of oncology. But the notion of the “cure” as the singular solution to cancer had degenerated into a sclerotic dogma. Bailar and Smith noted, “
A shift in research emphasis
, from research on treatment to research on prevention, seems necessary if substantial progress against cancer is to be forthcoming. . . . Past disappointments must be dealt with in an objective, straightforward and comprehensive manner before we go much further in pursuit of a cure that always seems just out of reach.”

*
Although this line of questioning may be intrinsically flawed since it does not recognize the interrelatedness of preventive and therapeutic research.

PART FOUR
 
PREVENTION IS
THE CURE

It should first be noted
, however, that the 1960s and 1970s did not witness so much a difficult
birth
of approaches to prevention that focused on environmental and lifestyle causes of cancer, as a difficult reinvention of an older tradition of interest in these possible causes.

—David Cantor

The idea of preventive medicine
is faintly un-American. It means, first, recognizing that the enemy is us.


Chicago Tribune
, 1975

The same correlation could be drawn
to the intake of milk. . . . No kind of interviewing [can] get satisfactory results from patients. . . . Since nothing had been proved there exists no reason why experimental work should be conducted along this line.

—U.S. surgeon general
Leonard Scheele on the link
between smoking and cancer

“Coffins of black”

When my mother died I was very young
,

And my father sold me while yet my tongue,

Could scarcely cry weep weep weep weep,

So your chimneys I sweep & in soot I sleep . . .

And so he was quiet, & that very night.

As Tom was a sleeping he had such a sight

That thousands of sweepers Dick, Joe, Ned, & Jack

Were all of them lock’d up in coffins of black

—William Blake

In 1775, more than a century before Ehrlich fantasized about chemotherapy or Virchow espoused his theory of cancer cells, a surgeon at St. Bartholomew’s Hospital named Percivall Pott noticed a marked rise in cases of scrotal cancer in his clinic. Pott was a methodical, compulsive, reclusive man, and his first impulse, predictably, had been to try to devise an elegant operation to excise the tumors. But as cases streamed into his London clinic, he noticed a larger trend. His patients were almost invariably chimney sweeps or “climbing-boys”—poor, indentured orphans apprenticed to sweeps and sent up into chimneys to clean the flues of ash, often nearly naked and swathed in oil. The correlation startled Pott.
It is a disease, he wrote
, “peculiar to a certain set of people . . .; I mean the chimney-sweepers’ cancer. It is a disease which always makes its first attack on . . . the inferior part of the scrotum; where it produces a superficial, painful, ragged, ill-looking sore, with hard and rising edges. . . . I never saw it under the age of puberty, which is, I suppose, one reason why it is generally taken, both by patient and surgeon, for venereal; and being treated with mercurials, is thereby soon and much exasperated.”

Pott might easily have accepted this throwaway explanation. In Georgian England, sweeps and climbing-boys were regarded as general cesspools of disease—dirty, consumptive, syphilitic, pox-ridden—and a “ragged, ill-looking sore,” easily attributed to some sexually transmitted illness, was usually treated with a toxic mercury-based chemical and otherwise shrugged off. (“
Syphilis,” as the saying ran
, “was one night with Venus, followed by a thousand nights with mercury.”) But Pott was searching for a deeper, more systematic explanation. If the illness was venereal, he asked, why, of all things, the predilection for only one trade? If a sexual “sore,” then why would it get “exasperated” by standard emollient drugs?

Frustrated, Pott transformed into a reluctant epidemiologist. Rather than devise new methods to operate on these scrotal tumors, he began to hunt for the cause of this unusual disease. He noted that sweeps spent hours in bodily contact with grime and ash. He recorded that minute, invisible particles of soot could be found lodged under their skin for days, and that scrotal cancer typically burst out of a superficial skin wound that tradesmen called a soot wart. Sifting through these observations, Pott eventually pinned his suspicion on chimney soot lodged chronically in the skin as the most likely cause of scrotal cancer.

Pott’s observation extended the work of the Paduan physician Bernardino Ramazzini.
In 1713, Ramazzini had published
a monumental work—
De Morbis Artificum Diatriba—
that had documented dozens of diseases that clustered around particular occupations. Ramazzini called these diseases
morbis artificum
—man-made diseases. Soot cancer, Pott claimed, was one such
morbis artificum—
only in this case, a man-made disease for which the inciting agent could be identified. Although Pott lacked the vocabulary to describe it as such, he had discovered a carcinogen.
*

The implication of Pott’s work was far-reaching. If soot, and not some mystical, numinous humor (à la Galen), caused scrotal cancer, then two facts had to be true. First, external agents, rather than imbalances of internal fluids, had to lie at the root of carcinogenesis—a theory so radical for its time that even Pott hesitated to believe it. “All this makes
it (at first) a very different case
from a cancer which appears in an elderly man, whose fluids are become acrimonious from time,” he wrote (paying sly homage to Galen, while undermining Galenic theory).

Second, if a foreign substance was truly the cause, then cancer was
potentially preventable. There was no need to purge the body of fluids. Since the illness was man-made, its solution could also be man-made. Remove the carcinogen—and cancer would stop appearing.

But the simplest means of removing the carcinogen was perhaps the most difficult to achieve.
Eighteenth-century England
was a land of factories, coal, and chimneys—and by extension, of child labor and chimney sweeps servicing these factories and chimneys. Chimney sweeping, though still a relatively rare occupation for children—by 1851, Britain had about eleven hundred sweeps under the age of fifteen—was emblematic of an economy deeply dependent on children’s labor. Orphans, often as young as four and five years old, were “apprenticed” to master sweeps for a small price. (“
I wants a ’prentis
, and I am ready to take him,” says Mr. Gamfield, the dark, malevolent chimney sweep in Dickens’s
Oliver Twist
. By an odd stroke of luck, Oliver is spared from being sold to Gamfield, who has already sent two previous apprentices to their deaths by asphyxiation in chimneys.)

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