Gawande Clusters MedDispatch by jolinmilioncherie



                                                                  MEDICAL DISPATCH

                                             THE CANCER--CLUSTER MYTH
                                                   When a dozen people in a neighborhood develop
                                                     tumors, it can’t be coincidence. Or can it?
                                                                  BY ATUL GA ANDE

                                       S  it something in the water? During      thing seriously wrong with the Western
                                         the past two decades, reports of        Area,” the artist, Tyler Mercier, told the
                                         cancer clusters—communities in          Times. “The neighborhood may be con-
                                    which there seems to be an unusual           taminated.” In fact, the Los Alamos
                                    number of cancers—have soared. The           National Laboratory, which was the
                                    place names and the suspects vary, but       birthplace of the atomic bomb, had
                                    the basic story is nearly always the         once dumped millions of gallons of ra-
                                    same. The Central Valley farming town        dioactive and toxic waste in the sur-
                                    of McFarland, California, came to na-        rounding desert, without providing any
                                    tional attention in the eighties after a     solid documentation about precisely
                                    woman whose child was found to have          what was dumped or where. In San Ra-
                                    cancer learned of four other children        mon, California, a cluster of brain can-
                                    with cancer in just a few blocks around      cers was discovered at a high-school
                                    her home. Soon doctors identified six         class reunion. On Long Island, federal,
                                    more cases in the town, which had a          state, and local officials are currently
                                    population of sixty-four hundred. The        spending twenty-one million dollars to
                                    childhood-cancer rate proved to be four      try to find out why towns like West
                                    times as high as expected. Suspicion fell    Islip and Levittown have elevated rates
                                    on groundwater wells that had been           of breast cancer.
                                    contaminated by pesticides, and law-             I myself live in a cancer cluster. A res-
                                    suits were filed against six chemical         ident in my town—Newton, Massachu-
                                    companies.                                   setts—became suspicious of a decades-
                                       In 1990, in Los Alamos, New Mex-          old dump next to an elementary school
                                    ico, a local artist learned of seven cases   after her son developed cancer. She
                                    of brain cancer among residents of a         went from door to door and turned
                                    small section of the town’s Western          up forty-two cases of cancer within a
                                    Area. How could seven cases of brain         few blocks of her home. The cluster is
                                                                                                                                 PETER TILL

                                    cancer in one neighborhood be merely         being investigated by the state health
                                    a coincidence? “I think there is some-       department.

TNY—2/8/98—PAGE 34   LIVE OPI N40548 4C,133LS

    No doubt, one reason for the verita-    such investigations, epidemiologists
ble cluster of cancer clusters in recent    tend to be skeptical about their worth.
years is the widespread attention that
cases like those in McFarland and Los
Alamos received, and the ensuing in-
crease in public awareness and concern.
                                            W      HEN     public-health investigators
                                                     fail to turn up any explanation
                                            for the appearance of a cancer clus-
Another reason, though, is the way in       ter, communities can find it frustrating,
which states have responded to that         even suspicious. After all, these investi-
concern: they’ve made available to the      gators are highly efficient in tracking
public data on potential toxic sites,       down the causes of other kinds of dis-
along with information from “cancer         ease clusters. “Outbreak” stories usually
registries” about local cancer rates. The   start the same way: someone has an in-
result has been to make it easier for       tuition that there are just too many peo-
people to find worrisome patterns, and,      ple coming down with some illness and
more and more, they’ve done so. In          asks the health department to investi-
the late eighties, public-health depart-    gate. With outbreaks, though, such in-
ments were receiving between thirteen       tuitions are vindicated in case after case.
hundred and sixteen hundred reports         Consider the cluster of American Le-
of feared cancer clusters, or “cluster      gionnaires who came down with an un-
alarms,” each year. Last year, in Massa-    usual lung disease in Philadelphia in
chusetts alone, the state health depart-    1976; the startling number of limb
ment responded to between three thou-       deformities among children born to Jap-
sand and four thousand cluster alarms.      anese women in the sixties; and the ap-
Under public pressure, state and fed-       pearance of rare Pneumocystis carinii
eral agencies throughout the country        pneumonia in five young homosexual
are engaging in “cancer mapping”            men in Los Angeles in 1981. All these
to find clusters that nobody has yet         clusters prompted what are called “hot-
reported.                                   pursuit investigations” by public-health
    A community that is afflicted with       authorities, and all resulted in the defin-
an unusual number of cancers quite          itive identification of a cause: namely,
naturally looks for a cause in the envi-    Legionella pneumonitis, or Legionnaires’
ronment—in the ground, the water,           disease; mercury poisoning from contam-
the air. And correlations are sometimes     inated fish; and H.I.V. infection. In fact,
found: the cluster may arise after, say,    successful hot-pursuit investigations of
contamination of the water supply by        disease clusters take place almost every
a possible carcinogen. The problem is       day. A typical recent issue of the Cen-
that when scientists have tried to con-     ters for Disease Control’s Morbidity and
firm such causes, they haven’t been able     Mortality Weekly Report described a
to. Raymond Richard Neutra, Califor-        cluster of six patients who developed
nia’s chief environmental health inves-     muscle pain after eating fried fish. In-
tigator and an expert on cancer clus-       vestigation by health authorities iden-
ters, points out that among hundreds        tified the condition as Haff disease,
of exhaustive, published investigations     which is caused by a toxin sometimes
of residential clusters in the United       present in buffalo fish. Four of the cases
States, not one has convincingly iden-      were traced to a single Louisiana whole-
tified an underlying environmental           saler, whose suppliers fished the same
cause. Abroad, in only a handful of         tributaries of the Mississippi River.
cases has a neighborhood cancer clus-           What’s more, for centuries scientists
ter been shown to arise from an en-         have succeeded in tracking down the
vironmental cause. And only one of          causes of clusters of cancer that aren’t
these cases ended with the discovery of     residential. In 1775, the surgeon Perci-
an unrecognized carcinogen. It was in       vall Pott discovered a cluster of scrotal-
a Turkish village called Karain, where      cancer cases among London chimney
twenty-five cases of mesothelioma, a         sweeps. It was common practice then
rare form of lung cancer, cropped up        for young boys to do their job naked,
among fewer than eight hundred vil-         the better to slither down chimneys,
lagers. (Scientists traced the cancer       and so high concentrations of carcino-
to a mineral called erionite, which         genic coal dust would accumulate in the
is abundant in the soil there.) Given       ridges of their scrota. Pott’s chimney
the exceedingly poor success rate of        sweeps proved to be a classic example of

TNY—2/8/99—PAGE 35
36                                                                                          THE NEW YORKER, FEBRUARY 8, 1999

                                                                                           be exposed to seventy per cent of the
                                                                                           maximum tolerated dose in the course
                                                                                           of a full year, or the equivalent. “This
                                                                                           kind of exposure is credible as part of
                                                                                           chemotherapy or in some work settings,”
                                                                                           he wrote in a 1990 paper, “but it must
                                                                                           be very rare for most neighborhood and
                                                                                           school settings.” For that reason, investi-
                                                                                           gations of occupational cancer clusters
                                                                                           have been vastly more successful than in-
                                                                                           vestigations of residential cancer clusters.
                                                                                              Matters are further complicated by the
                                                                                           fact that cancer isn’t one disease. What
                                                                                           turns a breast cell into breast cancer isn’t
                                                                                           what turns a white blood cell into leu-
                                                                                           kemia: the precise combination of hits
                                                                                           varies. Yet some clusters lump together
                                                                                           people with tumors that have entirely
                                                                                           different biologies and are unlikely to
                                                                                           have the same cause. The cluster in
                                                                                           McFarland, for example, involved eleven
                 “Sometimes it’s important to stop whatever break                          children with nine kinds of cancer. Some
                       you’re taking and just do the work.”                                of the brain-cancer cases in the Los
                                                                                           Alamos cluster were really cancers of
                                      •          •                                         other organs which had metastasized to
                                                                                           the brain.
an “occupational” cluster. Scientists have    chance combination of successive muta-
also been successful in investigating so-
called “medical” clusters. In the late
nineteen-sixties, for example, the pathol-
                                              tions in these genes—multiple “hits,” as
                                              cancer biologists put it—to make a cell
                                              cancerous rather than simply killing it. A
                                                                                           I F true neighborhood clusters—that is,
                                                                                                local clusters arising from a common
                                                                                           environmental cause—are so rare, why
ogist Arthur Herbst was surprised to          carcinogen provides one hit. Other hits      do we see so many? In a sense, we’re
come across eight women between the           may come from a genetic defect, a fur-       programmed to: nearly all of them are
ages of fifteen and twenty-two who had         ther environmental exposure, a sponta-       the result of almost irresistible errors in
clear-cell adenocarcinoma, a type of cer-     neous mutation. Even when people have        perception. In a pioneering article pub-
vical cancer that had never been seen in      been subjected to a heavy dose of a car-     lished in 1971, the cognitive psycholo-
women so young. In 1971, he published         cinogen and many cells have been dam-        gists Daniel Kahneman and Amos Tver-
a study linking the cases to an anti-         aged, they will not all get cancer. (For     sky identified a systematic error in human
miscarriage drug called diethylstilbe-        example, DES causes clear-cell adeno-        judgment which they called the Belief
strol, or DES, which the mothers of           carcinoma in only one out of a thou-         in the Law of Small Numbers. People
these women had taken during preg-            sand women exposed to it in utero.) As       assume that the pattern of a large popu-
nancy. Subsequent studies confirmed            a rule, it takes a long time before a cell   lation will be replicated in all its subsets.
the link with DES, which was taken by         receives enough hits to produce the can-     But clusters will occur simply through
some five million pregnant women be-           cer, and so, unlike infections or acute      chance. After seeing a long sequence of
tween 1938 and 1971. The investiga-           toxic reactions, the effect of a carcino-    red on the roulette wheel, people find
tion of medical and occupational cancer       gen in a community won’t be seen for         it hard to resist the idea that black is
clusters has led to the discovery of dozens   years. Besides, in a mobile society like     “due”—or else they start to wonder
of carcinogens, including asbestos, vinyl     ours, cancer victims who seem to be          whether the wheel is rigged. We assume
chloride, and certain artificial dyes.         clustered may not all have lived in an       that a sequence of R-R-R-R-R-R is
    So why don’t hot-pursuit investiga-       area long enough for their cancers to        somehow less random than, say, R-R-
tions of neighborhood cancer clusters         have a common cause.                         B-R-B-B. But the two sequences are
yield such successes? For one thing, many        To produce a cancer cluster, a carcino-   equally likely. (Casinos make a lot of
clusters fall apart simply because they       gen has to hit a great many cells in a       money from the Belief in the Law of
violate basic rules of cancer behavior.       great many people. A brief, low-level        Small Numbers.) Truly random patterns
Cancer develops when a cell starts mul-       exposure to a carcinogen is unlikely to do   often don’t appear random to us. The
tiplying out of control, and the process      the job. Raymond Richard Neutra has          statistician William Feller studied one
by which this happens isn’t straight-         calculated that for a carcinogen to pro-     classic example. During the Germans’
forward. A carcinogen doesn’t just flip        duce a sevenfold increase in the occur-      intensive bombing of South London in
some cancer switch to “on.” Cells have a      rence of a cancer (a rate of increase not    the Second World War, a few areas
variety of genes that keep them func-         considered particularly high by epide-       were hit several times and others were
tioning normally, and it takes an almost      miologists) a population would have to       not hit at all. The places that were not

MEDICAL DISPATCH                                                                                                                    37

hit seemed to have been deliberately          holes, we tend to notice cases first—          and water. Thousands, sometimes mil-
spared, and, Kahneman says, people be-        four cancer patients on one street—and        lions, of dollars are spent. And, with all
came convinced that those places were         then define the population base around         those tests, correlations inevitably turn
where the Germans had their spies.            them. With rare conditions, such as           up. Yet, years later, in case after case,
When Feller analyzed the statistics of the    Haff disease or mercury poisoning, even       nothing definite is confirmed.
bomb hits, however, he found that the         a small clutch of cases really would rep-
distribution matched a random pattern.
    Daniel Kahneman himself was in-
volved in a similar case. “During the
                                              resent a dramatic excess, no matter how
                                              much Texas sharpshooting we did. But
                                              most cancers are common enough that
                                                                                            “    HE    reality is that they’re an abso-
                                                                                                    lute, total, and complete waste of
                                                                                            taxpayer dollars,” says Alan Bender, an
Yom Kippur War, in 1973, I was ap-            noticeable residential clusters are bound     epidemiologist with the Minnesota De-
proached by people in the Israeli Air         to occur. Raymond Richard Neutra              partment of Health, which investigated
Force,” he told me. “They had two             points out that, given a typical registry     more than a thousand cancer clusters
squads that had left base, and when the       of eighty different cancers, you could        in the state between 1984 and 1995.
squads came back one had lost four            expect twenty-seven hundred and fifty          The problem of perception and poli-
planes and the other had lost none.           of California’s five thousand census           tics, however, remains. If you’re a pub-
They wanted to investigate for all kinds      tracts to have statistically significant but   lic health official, try explaining why
of differences between the squadrons,         perfectly random elevations of cancer.        a dozen children with cancer in one
like whether pilots in one squadron had       So if you check to see whether your           neighborhood doesn’t warrant investi-
seen their wives more than in the other.      neighborhood has an elevated rate of a        gation. According to a national study,
I told them to stop wasting their time.”      specific cancer, chances are better than       health departments have been able to
A difference of four lost planes could eas-   even that it does—and it almost cer-          reassure people by education in more
ily have occurred by chance. Yet Kahne-       tainly won’t mean a thing. Even when          than seventy per cent of cluster alarms.
man knew that if Air Force officials in-       you’ve established a correlation between      Somewhere between one and three per
vestigated they would inevitably find          a specific cancer and a potential car-         cent of alarms, however, result in ex-
some measurable differences between           cinogen, scientists have hardly any way       pensive on-site investigations. And the
the squadrons and feel compelled to act       to distinguish the “true” cancer cluster      cases that are investigated aren’t even
on them.                                      that’s worth investigating from the crowd     the best-grounded ones: they are the
    Human beings evidently have a deep-       of cluster impostors.                         cases pushed by the media, enraged cit-
seated tendency to see meaning in the             One helpful tip-off is an extraordi-      izens, or politicians. “Look, you can’t
ordinary variations that are bound to         narily high cancer rate. In Karain, Tur-      just kiss people off,” Bender says. In
appear in small samples. For example,         key, the incidence of mesothelioma was        fact, Minnesota has built such an effec-
most basketball players and fans believe      more than seven thousand times as high as     tive public-response apparatus that it
that players have hot and cold streaks        expected. In even the most serious clus-      has not needed to conduct a formal
in shooting. In a paper entitled “The         ter alarms that public-health departments     cluster investigation in three years.
Hot Hand in Basketball,” Tversky and          have received, however, the cancer rate has       Public-health departments aren’t
two colleagues painstakingly analyzed         been nowhere near that high. (The law-        lavishly funded, and scientists are re-
the shooting of individual players in         yer Jan Schlichtmann, of “Civil Action”       luctant to see money spent on some-
more than eighty games played by the          fame, is now representing victims of a        thing that has proved to be as un-
Philadelphia 76ers, the New Jersey            cancer cluster in Dover Town-                           productive as neighborhood
Nets, and the New York Knicks during          ship, New Jersey, where the                             cluster alarms or cancer map-
the 1980-81 season. It turned out that        childhood-cancer rate is thirty                         ping. Still, public confidence
basketball players—even notorious “streak     per cent higher than expected.)                         is poorly served by officials
shooters”—have no more runs of hits or            This isn’t to say that car-                         who respond to inquiries with
misses than would be expected by chance.      cinogens in the local environ-                          a scientific brushoff and a layer
Because of the human tendency to per-         ment can’t raise cancer rates;                          of bureaucracy. To be part of a
ceive clusters in random sequences, how-      it’s just that such increases dis-                      cancer cluster is a frightening
ever, Tversky and his colleagues found        appear in all the background variation        thing, and it magnifies our ordinary re-
that “no amount of exposure to such se-       that occurs in small populations. In          sponse when cancer strikes: we want to
quences will convince the player, the         larger populations, it’s a different story.   hold something or someone responsi-
coach, or the fan that the sequences are      The 1986 Chernobyl disaster exposed           ble, even allocate blame. Health offi-
in fact random. The more basketball           hundreds of thousands of people to            cials who understand the fear and anger
one watches and plays, the more oppor-        radiation; scientists were able to estab-     can have impressive success, as the ones
tunities one has to observe what appears      lish that it caused a more than one-          in Minnesota have shown. But there
to be streak shooting.”                       hundred-fold increase in thyroid cancer       are times when you cannot maintain
    In epidemiology, the tendency to          among children years later. By contrast,      public trust without acting on public
isolate clusters from their context is        investigating an isolated neighborhood        concerns. Science alone won’t put to
known as the Texas-sharpshooter fal-          cancer cluster is almost always a futile      rest questions like the one a McFar-
lacy. Like a Texas sharpshooter who           exercise. Investigators knock on doors,       land mother posed to the Los Angeles
shoots at the side of a barn and then         track down former residents, and check        Times: “How many more of our children
draws a bull’s-eye around the bullet          medical records. They sample air, soil,       must die before something is done?” o


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