|
Discovering
How Taxol Works
By Karen Young Kreeger
Susan
Band Horwitz ’58 recalls a story about L. Joe
Berry, one of her former biology professors at
Bryn Mawr. About four years after she graduated,
Horwitz and her husband dropped in at Bryn Mawr
on their way back to the Boston area from a camping
trip in the Appalachians. "As we were walking
down the corridor talking, Dr. Berry yelled out
from his office, 'Gee, that sounds like Susan
Band.' My husband was shocked. He had been at
Harvard where there were big classes and no one
would ever do that."
To
Horwitz, this encounter exemplifies the kind of
close relationships she cultivated during her
undergraduate studies at Bryn Mawr. Over four
decades later, Horwitz is now the Falkenstein
Professor of Cancer Research at Albert Einstein
College of Medicine in New York and co-chair of
its department of molecular pharmacology.
Researching
Anti-Tumor Drugs
One
of Horwitz's most outstanding scientific achievements
was determining how the anti-cancer drug Taxol
slows tumor growth. This effort encouraged the
National Cancer Institute to pursue Taxol as an
antitumor drug and eventually led to the approval
by the Food and Drug Administration of Taxol in
the treatment of ovarian, breast and lung cancers.
Horwitz
started her research on Taxol in 1976, about the
same time she became interested in small molecules,
particularly those of natural origin, and their
use in treating disease. Taxol had been isolated
from the bark of the yew tree and its structure
determined. The fact that it had lengthened the
lifespans of mice with some experimental cancers
encouraged the NCI to look at Taxol as a potential
anticancer agent. In 1976, NCI wrote to Horwitz,
asking if she would look at Taxol's mechanism
of action.
"The
chemical structure of Taxol is unique and it looked
extremely interesting to me, so I said yes, please
send me 10 milligrams," she recalls. "Within a
month we knew that we had a very interesting molecule
that was doing something to cells, which no one
else had seen occur with a small molecule. It
was very exciting."
Specifically
what Horwitz and colleagues found was that Taxol
binds to microtubules, which are part of the cytoskeleton
of all cells. Microtubules are important to cell
division, and when Taxol binds to these structures,
it paralyzes them, slowing dramatically the ability
of the cell to divide.
A
Bit of Serendipity
Horwitz’s
work with Taxol unexpectedly renewed her ties
to Bryn Mawr. She has collaborated on the drug's
synthesis with a faculty member, Charles Swindell,
a former chair of the Chemistry Department. "I
happened to be glancing through the Bryn Mawr
Alumnae Bulletin and I stopped at the word
Taxol, seeing that Swindell received a grant to
work on the synthesis of Taxol," she says. "I
gave him a call and of course he didn't know that
I had graduated from Bryn Mawr, but after a bit
of introduction we became very good friends."
They published many papers together, some co-authored
with Nancy Krauss '91, a doctoral student who
was studying with Swindell.
For
the past three decades Horwitz’s lab —
which by her count currently numbers more than
10 people, from Ph.D. students to postdocs and
visiting scientists — has been researching
not only Taxol and other potentially important
anticancer drugs but also how tumors become resistant
to drugs. "We're looking for new drugs that would
demonstrate efficacy in different tumors from
those treated by Taxol that would also be active
in Taxol-resistant tumors."
Horwitz
is also very active in the Albert Einstein Cancer
Center, where she is the associate director for
therapeutics. In addition, she was just elected
president of the American Association for Cancer
Research, a large nonprofit professional organization
with 17,000 members. "This is a new activity for
me and I'm looking forward to it," she says.
Balancing
Professional and Family Life
After
graduating from Bryn Mawr, Horwitz went on to
Brandeis University, where she was in the first
class of the newly formed graduate department
of biochemistry. She received her Ph.D. there
in 1963 for work on dehydrogenases, enzymes that
modify sugar alcohols in microorganisms.
Of
her graduate-school years, she says, "Lots of
things happened to me besides getting my Ph.D."
She married, and she delivered twin boys five
days after defending her dissertation. From there
she took a number of part-time postdoc positions
before her children entered grade school —
at Tufts University Medical School, Emory University
and the Albert Einstein College of Medicine, where
she has been since the late 1960s.
"After
I worked part-time for a couple of years, I realized
that I had to make a decision because my children
were going into the first grade," she remembers.
"Working part-time, I was paid miserably and it
was clearly not going to get me anywhere. So I
said to myself, ‘it's now or never —
either come back full-time or be part-time forever.’"
She immediately accepted a full-time position
and hasn't regretted her decision one bit.
Horwitz
is refreshingly open about how she melded her
career in science with raising a family: "There's
no single way to do it. Each of us has to find
whatever way we're comfortable with, and follow
the track that makes us happy and productive."
She attributes part of this attitude and confidence
to her days at Bryn Mawr: "I think the feeling
that women can be productive and be successful
is imbued in you at Bryn Mawr."
About the Author
Karen Young Kreeger is a science
journalist who writes on biomedical and women’s
health topics, as well as careers in science.
Her most recent work has appeared in Bioscience,
Genome Technology, Muse and The
Scientist
|
