Curt Civin ’70 shares a moment with a young patient named Megan, who has
acute myeloid leukemia. |
New Blood
By Tom Nugent
One summer morning in 1981, a 32-year-old
assistant professor at The Johns Hopkins University School of Medicine sat
at his kitchen table, doodling on a yellow legal pad. Between sips of coffee,
the physician scribbled a series of phrases and images on the paper in front
of him. Among the many words he wrote were three that would one day make him
a legend in the world of cancer research: marrow stem cells. And among the many
images he drew were a grinning fish and a dangling hook.
Curt Civin ’70 is a pediatric oncologist, and
his doodling that day reflected his preoccupation with what was then the most
challenging problem in his field: 80 percent of young leukemia patients were
dying, even with bone-marrow transplants, because of marrow rejection and re-infection
from cancer-tainted blood. Like many pediatric oncologists, Civin was looking
for a way to give patients new blood that would be cancer-free and safe for their
immune systems. For Civin the quest had a special meaning.
A biology major at Amherst, Civin had always been keenly interested
in medical research. Then, during his senior year, his mother died after a long
fight with breast cancer. “All of a sudden," he recalls today, “instead
of looking vaguely at science and medicine on my horizon, I was looking specifically
at cancer. The [medical] treatment my mother received was so primitive—so
toxic and ineffective—that it made me realize how much we didn’t
know about cancer. Month after month I watched her suffering terribly, and there
was nothing I could do about it. I vowed that I would spend my career working
on cancer."
After graduating from Amherst, he attended Harvard Medical School and completed
his residency in pediatrics at the Boston Children’s Hospital Medical Center.
After additional training in immunology research and pediatric oncology at the
National Institutes of Health, he signed on as a faculty physician-scientist
in pediatric oncology at Johns Hopkins in 1979. Only two years later, while caring
for dozens of young cancer patients each day, Civin began the long series of
experiments and observations that eventually led to his breakthrough.
The problem that Civin was trying to solve was enormously difficult at the molecular
level, but the clinical issues were nonetheless clear. Even with compatible donors,
a patient’s immune system would often reject transplanted bone marrow.
To avoid that problem, doctors would sometimes turn to the patient’s own
marrow. If it appeared that the patient’s marrow was cancer-free, doctors
would remove and store it in a sophisticated freezer, give the patient high levels
of chemotherapy (and sometimes radiotherapy) in an attempt to kill the cancer,
and then reintroduce the stored marrow to make new blood. But too often the patient’s
marrow contained one or two cancerous cells that would cause the cancer to grow
back, along with the needed normal cells.
Civin wondered if there were an immunological way to isolate the marrow’s “master
cells" (also known as “hematopoietic stem cells") that give
birth to the new blood cells, and then inject those back into the patient, where
they could begin building the new ingredients (white and red blood cells, along
with platelets) required to repair the ravaged body’s blood and immune
systems. If he could isolate these stem cells, he could use them to boost healthy
blood production, while reducing the risk of introducing cancer cells that contaminated
the bone marrow.
Unfortunately for Civin and his fellow cancer researchers, only about 1 percent
of the cells in human bone marrow belong to the stem-cell variety that can build
different kinds of blood and immune cells from scratch. In 1981, there was no
way to pull out these rare stem cells. Without a stem-cell-specific tool, the
researchers had little hope of being able to isolate and then harvest the cells.
Until that summer morning in 1981, the sheer complexity of this needle-in-a-haystack
chemistry problem had defeated researchers.
Enter the fishhook and the nibbling fish.
Remembering that moment of insight during a recent interview in his lab at The
Johns Hopkins University School of Medicine, Civin lit up with the fiery enthusiasm
of a born researcher. “As I struggled with the problem," he recalled, “I
gradually began to think of isolating the stem cell as catching a fish. And so
I asked myself: ‘What hook can I use to catch it?’ I soon realized
that if I could make a monoclonal antibody targeted to a specific antigen on
the stem cell, that antibody would provide a hook to go in and ‘catch’ the
1 percent of bone-marrow blood cells that are actually stem cells."
Translation: What Civin wanted to do was build an antibody, a foreign-cell-attacking
protein, that would recognize and then bind to an “antigen"—a
signature protein molecule that would be found only on the stem cell.
Continued >>
Photo: Frank Ward
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