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"Living Downstream"
by Sandra Steingraber, Ph.D.
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Bathed in a brilliant yellow-green light, they look like
bats floating in a perfectly round pond. I have seen many
micrographs of cancerous tissue-reproduced neatly in atlases
of human tumor cell lines or on the shiny pages of medical
journals-but never before have I stared at living cancer cells.
Alive, they look to me like bats.
"Now compare that one to this one."
The first petri dish is removed and replaced by another,
and I look again through the microscope. In this second watery
landscape, they look more like fallen leaves-some drift together
in large masses, others in smaller clusters.
"Okay, here's dish number three."
Now they are everywhere. A mosaic of islands and jutting
peninsulas. Pieces of a crazy quilt tossed into a lake.
A raft of vines tangled with shards of crockery. There is
no one way to describe them. Collectively or alone, cancer
cells are more chaotically arranged than the shy, scurrying
animals from which the disease-as well as the zodiac constellation-derives
its name. Cancer, carcinogen, carcinoma, from the Greek karkinos,
"the crab."
The three petri dishes I have been asked to compare contain
estrogen-sensitive breast cancer cells derived from a human
cell line called MCF-7. The first dish is the control. Its
culture medium, the broth that nourishes the growing cells,
contains no estrogen. The third dish is a control of the opposite
sort. Its medium was innoculated with the most potent known
form of human estrogen, which is called estradiol. It's also
the dish with the most luxuriant growth. By definition, estrogen-sensitive
breast tumors grow faster in the presence of estrogen, and
MCF-7 cells are well-known exemplifiers of this principle.
It is the second dish, the one with the intermediate growth
rate, that reveals the significant finding. Its culture medium
has been laced with trace amounts of endosulfan, an organochlorine
pesticide. These three dishes are part of a series of experiments
showing that endosulfan-introduced in 1954 and now widely
used on salad crops-is estrogenic. Like the hormone it mimics,
endosulfan stimulates breast cancer cells to divide and multiply.
In this ability, endosulfan is much less effective than a
woman's own estradiol. However, studies similar to this one
have shown that endosulfan can act in concert with other xenoestrogens,
that is, chemicals foreign to the body that, directly or indirectly,
act like estrogens. For example, when ten different synthetic
chemicals, all estrogen mimics, are added to the culture medium
at one-tenth the minimal dose required for proliferation of
MCF-7 cells, proliferation ensues. Like raindrops eroding
a boulder, quantities of weakly estrogenic chemicals too small
to exert observable effects on their own have a significant
impact when combined. Furthermore, some xenoestrogens may
have the ability to interact with naturally occurring estrogens
and amplify their effect. If confirmed, such results imply
that "safe" levels of exposure to individual estrogen-mimicking
chemicals may not exist. (The actual cellular pathways followed
by xenoestrogens are described in Chapter Eleven.)
The discovery that xenoestrogens can work additively was
made by the cell biologists Ana Soto and Carlos Sonnenschein,
whose laboratory in downtown Boston I am visiting. Since their
1991 discovery that nonylphenol stimulates the growth of MCF-7
cells, they have continued to probe the phenomenon of estrogen
mimicry and its implications for breast cancer. In addition
to plastic additives, Soto and Sonnenschein have identified
estrogenic activity in a variety of pesticides. Some, like
endosulfan, are still in use. Others, such as dieldrin and
toxaphene, are now banned.
That toxaphene-fat soluble and stubbornly persistent-should
prove estrogenic is particularly frightening. Identified as
an animal carcinogen in 1979 and banned in 1982, toxaphene
was not so long ago the most heavily used insecticide in the
United States. It was the chemical weapon of choice against
boll weevils in cotton fields, where it was used in extraordinary
quantities. In 1950, northern Alabama cotton fields received
an average of sixty-three pounds per acre. Rachel Carson herself
denounced toxaphene as an indiscriminate killer of fish, and
in Silent Spring she described in detail the die-offs of crappies,
bass, and sunfish in southern streams and farm ponds. Ironically,
it rose to even greater popularity after pesticides like DDT
fell into disfavor.
Toxaphene's continuing effects on wildlife are what led Soto
and Sonnenschein to become concerned about its possible relationship
to breast cancer. When field researchers linked toxaphene
to reproductive damage in seals and documented its ongoing
accumulation in the muscle fat of Arctic and Baltic salmon,
these two laboratory researchers decided to test its effects
on breast cancer cells. Not only does toxaphene cause MCF-7
cells to proliferate, the pair discovered, but it does so
at levels well within the range of concentrations now found
in the flesh of some salmon.
Soto and Sonnenschein's work thus depends on a collaboration
between cell biology, which peers through magnifying lenses
at the smallest units of life, and wildlife biology, which
monitors the world's animals. In this way, changes in the
growth rate of breast cancer cells in a Boston laboratory
help elucidate the reasons for reproductive failures among
sea mammals living thousands of miles away-and vice versa.
The evidence from animals, in turn, provides reasons for rising
cancer rates among humans, as well as our routes of exposure
to cancer-promoting agents.
But let's go back for a moment to the microscope and look
once more at the cells named MCF-7. Whose breasts did they
come from, and what was her fate?
Finding answers to such questions isn't easy. Medical researchers
maintain a comfortable distance between themselves and the
cancer patients who provide the human tissues used in their
experiments. The results of research involving MCF-7 cells
are reported in numerous published articles. Even as the cells'
various properties are described in depth, these papers mention
almost nothing about their human origins.
Here is what I do know. All successfully established cancer
cell lines, including MCF-7, are immortal, meaning that they
will reproduce endlessly in covered dishes so long as they
are provided with the proper nutrients. Under such conditions,
most human cells-even most cancer cells-tend to die out after
a finite number of cell divisions. No one knows why some cancer
cells can attain immortality while others cannot. Because
they can be shipped all over the world, immortal cell lines
allow many laboratories to conduct research on cells from
the same tumor over long periods of time. Immortal cells are
to cancer researchers what sourdough starter is to bread bakers.
BT-20, VHB-1, MDA-MB-241, CAL-18B, T47D: these are the names
of other famous breast cancer cell lines. MCF-7 is among the
oldest and is also considered the most reliable-the coin of
the realm, according to one researcher. Its name reveals a
few interesting clues. MCF stands for Michigan Cancer Foundation,
the Detroit institution that makes this cell line available
to laboratories around the world. The trailing seven refers
to the number of attempts that were required to establish
a self-perpetuating stock of cells from the body of the particular
woman patient who consented to this effort. Immortality was
finally achieved on the seventh try.
"Does this mean cancerous cells were withdrawn multiple
times?" I ask into the phone, trying to imagine the procedure,
wondering if it was painful, wondering how many attempts she
was willing to submit to.
"Yes, that's right," says Joe Michaels of the Michigan
Cancer Foundation.
I learn that her birth name was Frances Mallon. At the time
of her diagnosis, she was a nun-Sister Catherine Frances-at
the Immaculate Heart of Mary Convent in Monroe, Michigan,
a small town midway between Detroit and Toledo on the west
bank of Lake Erie. Strangely enough, I have been there.
The Immaculate Heart of Mary, which has a long history of
involvement with social issues, was the setting for a conference
I attended in 1992 concerning organochlorine contamination
of the Great Lakes. So, not only have I looked at the cells
of her breasts, but I have walked through the corridors of
her home and eaten in her dining room.
Sister Catherine Frances died of her disease in 1970. An
old newspaper clipping reports that "she was a slightly
built woman of medium height, with auburn hair, gray eyes
and hands that were remarkable for their delicate beauty."
Before entering Immaculate Heart in 1945, she had worked for
twenty-five years as a stenographer at the Mueller Brass Company
in Port Huron. Both her mother and sister had died of cancer
before her. Her father had died of tuberculosis. The cancer
cells that ultimately begat the MCF-7 line were extracted
from fluid trapped in her chest cavity. This is all I know.
In 1995, at a national breast cancer meeting, I am introduced
to a well-known researcher whose work I admire. Over dinner
we discuss his current experiments, and I ask which cell line
he uses.
"MCF-7. It's a very well-described line."
"Did you know that she was a nun?"
There is a long pause. I watch him grope toward this unexpected
bit of information. He blinks several times and takes a few
swallows from his glass of ice water.
"Then, MCF is her name, her initials?" His voice
is low and gentle.
"Actually, no . . ."
Now, as I'm writing, I propose a rechristening of MCF-7.
Let them be called IBFM-7: the Immortal Breasts of Frances
Mallon, attempt number seven. Let them be known as a sacrament:
This is my body, which is broken for you. This do in remembrance
of me.
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