IncyteGenomics
Featured Scientist Series
Testing the Boundaries
Mina
J. Bissell, Ph.D.
Director,
Life Sciences Division
Lawrence
Berkeley National Laboratory
Mina J. Bissell,
Ph.D., likes taking risks. Whether moving to
the United States from
Iran when she was barely 18 or
broadening scientists' conceptions of cell
behavior and
gene regulation, she
has consistently tested the
boundaries of
science—and of life. Driven by her
exceptional intellect,
energy, and compassion, Bissell is a
progressive and
outspoken thinker whose ideas have had
a significant impact
on cellular research. Bissell currently
serves as director of
the Life Sciences Division at
Lawrence Berkeley
National Laboratory, where she has
been working since
1976.
Bissell has always
been interested in understanding the
essence and impact of the environment around her. As a
young girl, Bissell
was encouraged, and inclined, to ask
questions and pursue
their answers. As an adult,
intellectual curiosity
directed her first toward literature
and then chemistry as
an undergraduate at Bryn Mawr
College (where she
studied for two years) and Radcliffe
College, from which
she graduated cum laude. Bissell went
on to study bacterial
genetics at Harvard University for
her Ph.D., but began
focusing on the cells—and their
surroundings—of higher
organisms during her postdoctoral
work at the University
of California at Berkeley.
Bissell's willingness
to think outside the box—or, in this
case, the
cell—prompted her to ask questions about cell
morphology and behavior. Her research led to her
hypothesis that the
extracellular matrix (ECM) was much
more than simply
cellular scaffolding. Bissell, her research
group, and other
collaborators began working with breast
cells, demonstrating
that when normal and cancerous
breast cells are grown
in culture (in the absence of the
ECM), each type grows
at the same rate and looks like
the other. When the
ECM is added to the culture,
however, both kinds of
cells change behavior: The normal
cells organize
themselves, stop growing, and become
differentiated, while
the cancerous cells grow rapidly in a
tumorous mass.
Bissell's group later showed that by
manipulating signals
from the ECM, they could get cancer
cells to behave normally.
Bissell's
three-dimensional approach revealed a crucial
social interaction—or
"dynamic reciprocity"—between ECM
molecules and the
nucleus: The ECM affects the pattern
of gene expression,
and the nucleus affects the makeup
of the ECM. Thus,
Bissell found that the nature of tissue
and organ specificity
cannot be known unless the
microenvironments of
the proteins within the tissues are
understood.
Grateful for her
upbringing; the support of local, national,
and international colleagues;
and the role of national labs
in fostering
scientific and technological advances, Bissell's
integrity and
scientific insight have earned her many
honors and awards,
including the U.S. Department of
Energy's Ernest
Orlando Lawrence Memorial Award and
election to the
Institute of Medicine of the National
Academy of Sciences.
Bissell is a past president of the
American Society of
Cell Biology and the recipient of an
honorary doctorate
from Pierre & Marie Curie University,
Paris (2001).
Incyte Genomics is
proud to present an in-depth
conversation with Mina
Bissell as part of an ongoing series
of discussions with
the dedicated, passionate scientists
who are shaping the
world of genomics and the life
sciences.
Mina Bissell was
interviewed by Christopher Vaughan, a
writer who lives in
Menlo Park, California. Vaughan is the
author or coauthor of
three popular books on science:
How Life Begins (Dell
Publishing 1997); The Promise of
Sleep (with William C.
Dement, Delacorte Press 1999); and
The Prenatal
Prescription (with Peter Nathanielsz, July
2001).
Q: Many of your
concepts were at first considered
radical. Do you think
you're naturally inclined toward bold
ideas?
DR. BISSELL: Yes, and I think that it comes from the
way I was raised.
Trust me—I'm a great believer in
genetics. I, like
others, am a creature both of my genes
and of how I was born
and raised. I come from a very
educated family and
was encouraged to express myself
from an early age. I
don't have any brothers, and I was
kind of like the son
in the family. I am also the youngest.
Whether I would have
been the same person had I not
had the same genetic
material, I don't know. I do have a
sister and cousins;
half of them are as outspoken as I
am, and half are not.
I grew up having
political debates with my father, and I
performed on stage
early on. I was raised to question
things, and it always
fascinated me to ask, "Why?" When
I look back on my
career, I realize that I have always
gotten myself into a
bit of trouble by doing things that
aren't quite
predictable. It's not because I go looking for
those things. I
honestly don't. I'm given a problem and I
start asking
questions, like the kid asking about the
emperor's clothes. The
question is, Why do I do this more
than most? It could be
partly cultural, partly genetic, and
partly the way I was
raised.
But believe me, I get
myself into more trouble than I
need! [Laughs.] People
say to me, "Mina, you are so
direct. How did you
ever get to be a division director?"
Sometimes I wonder. I
think that it takes other people
around me who appreciate
directness, are not afraid of
challenges, and allow
me to lead. In that respect, I give a
lot of credit to some
of the men and women with whom I
have worked—people who
are able to tolerate this kind of
boldness. But I'm
afraid I take the same kind of position in
many other aspects of
my life. I am very interested in
human rights, and I'm
one of these people who get very
upset about injustice
in science and in society. I have
always had very strong
opinions. At times, therefore, I
can come across as
being self-righteous, which is not a
good thing!
The success I've had
in saying unconventional things and
moving those ideas
forward has to do with the context I
was in. Initially,
being in a national lab was a necessity
because I was not
doing mainstream science and had to
stay in the [San
Francisco] Bay Area. In the beginning, it
wasn't as if I had ten
job offers at universities. But it
allowed me to be bold
and to survive.
Q: Describe the process of
your early breast cancer and
cell work.
DR. BISSELL: I used
breast cells as a model for how
normal behavior of a tissue comes to pass. Breast is one
of the few tissues in
the body that changes during adult
life. After women go
through puberty, the breast
develops. When an
animal becomes pregnant, the breast
develops further and
produces milk. When you take the
babies away, the
breast involutes. It changes constantly
as a function of the
hormones and the microenvironment,
so it appeared to be a
good model.
One of my earliest
fellows, Joanne Emerman, brought the
technique of culturing
mouse breast cells to my
laboratory.
Interestingly, when you put breast cells in
tissue-culture
plastic, they change shape, won't make
milk, and completely
forget where they came from. We
realized that something
had to be missing. We gave the
cells hormones; we
gave them all the nutrients they
need. They grew but
did not differentiate. What could be
missing? It appeared
to be the material of the
extracellular matrix.
Up to that point, people had thought
that the ECM was just
like scaffolding, but I thought that
maybe this material
actually contained the important
information. When we isolated the right kind of
ECM for
breast cell—called
basement membrane—put it in a dish,
and put the cells on
the top, it was miraculous: The cells
came together and reorganized. Now we know
that ECM
molecules and this
gelatinous basement membrane have
information. The ECM
is involved in signaling in the liver,
prostate, breast—you
name it. The ECM is involved in
every single tissue of
the body, including the lymphatic
and blood tissues as
well as the cells in the brain.
In 1980 I wrote a
theoretical article with two of the
fellows in my
laboratory, Glenn Hall and Gordon Parry,
posing the question,
"How does the extracellular matrix
direct gene
expression?" I took the concept of "dynamic
reciprocity" (a
term that one of my colleagues had used
to address how a
receptor may interact with the interior
of the cell), and I
applied it to this broader concept. I
theorized that the ECM—which of course is the product
of the genes—can
itself influence the genes, once it gets
out and reorganizes.
Cells make three-dimensional
organizations that are
not necessarily specified by the
genome but by what is
surrounding them.
Next I said,
"These things have information. They must
have receptors so that
they can send the information."
At the time, the
receptors for the ECM molecules had not
really been discovered
or at least appreciated. I thought,
"How would this
receptor work? It would have to be
attached to the scaffolding cytoskeleton inside
the cell."
I theorized that it is
then attached indirectly to the
nuclear matrix, which
at that time people didn't even
believe existed. Then I postulated—again, by reading
some literature and
thinking in 3-D—that the chromatin,
the structures into
which DNA is packed, is probably
attached to the nuclear
matrix. If something from the
outside behaves like a
pulley and it is pushed and pulled,
it sends information
all the way to the nucleus. Some
people think that it
is either all biochemical or all
mechanical, but I
suggested that the control is both
mechanical and
biochemical. If you destroy this unit of
control at any given
point, then dynamic reciprocity is
lost and the cells
could go awry.
This made a lot of
sense to me and to some of my
colleagues. So we set
out to show, step by step, how it
happens and where the
process can go wrong in disease
and, specifically, in
cancer.
Q: How did the broader
scientific world respond to your
theory about the
extracellular matrix?
DR. BISSELL: The theory was supported by a small
minority in the United
States who were thinking along the
same lines. But it had
enthusiastic support from a few
prominent scientists
in Russia and Eastern European
countries. I think
that's partly because back then those
people had very few
technological gadgets but a good
deal of intelligence
and time to think. I used to get
wonderful letters from
people in the Soviet Union and a
few other countries
saying, "Wow, this is so exciting. We
believe that this is
true." But in the United States,
scientists basically didn't take the idea
seriously.
Molecular biology and
gene-cloning were very
exciting—there was not
much enthusiasm for complexity!
Q: What might be the
advantages of having cell behavior
regulated partly by
something outside the cell?
DR. BISSELL: Once
again it relates to the fact that the
information inside
every cell's genome is the same. If you
have everything
regulated from the inside, how do you
bring about local and
rapid regulation of gene expression
in a way that is
tissue specific? It's a very difficult thing
to do. On the other
hand, if you have a marriage, if you
will, between the
outside and the inside, the outside
factors could very
quickly and locally change the
regulation of the gene inside, and vice
versa. They could
create a
microenvironment that would allow tissue
specificity of cell
behavior. It's difficult to think that you
could always start with a fixed genome and have each
cell respond from
within in so many different
ways—imagine all these
organs, let alone memory, vision,
and smell. Over the
years, we as well as others have
shown that the
extracellular matrix is an important player
in regulating tissue
or organ specificity. It seems to be
one of the central
regulators.
Q: What constitutes
the designer microenvironments that
you talk about in your
research? Has that idea changed
over the years?
DR. BISSELL: When you
put the cells in a
microenvironment that
is malleable and permissive to a
certain tissue, the
cells have a memory of organization
and
three-dimensionality. They recognize it, and they
start behaving the way they're supposed to behave.
They begin laying down
their own ECM—basement
membrane—which is now
tissue-specific. In a sense, cells
make their own
designer microenvironments if you allow
them to.
In the case of the
breast, we use materials such as
basement membrane
isolated from an interesting mouse
tumor or gels made of
rat-tail collagen. We have defined
what is around the
breast cells in vivo, but this material is
hard to isolate and
gets denatured during the process of
isolation. When we put
cells together with these
gelatinous substrata
in three dimensions, the cells
remember what they are
supposed to do and they now
make their correct
ECM.
But my real ambition in the next five years or so—in
collaboration with my
colleague in Denmark, Olé
Petersen—is to make an
honest-to-goodness model of
the breast in 3-D.
That would require not only breast
epithelial cells but
also the other cell types that are
around the breast in
vivo. These cell types all talk to one
another, and they each
do different things. We have
already nearly
succeeded in making a replica of breast
tumors in 3-D and have
made recent advances with
putting epithelial and
myoepithelial cells of the breast
together in 3-D.
We have limited
ourselves to the study of the breast
because we don't have
the time to develop yet another
designer model. But
more and more, researchers are
creating different
models. I think that each tissue or
organ will require a
specific designer microenvironment,
probably developed
from different materials than we have
used.
Q: You're suggesting
that the extracellular matrix tells the
cell that it exists in
a social environment with other cells?
DR. BISSELL: Correct.
There is a social interaction
between the cells and
also in relation to the nucleus. The
outside tells the
nucleus what to do, and the nucleus
tells the outside what
to do. The signals go back and
forth and change very rapidly and
dynamically. That's
why I refer to the
concept as "dynamic reciprocity."
We need to understand
this interaction in relation to
every organ and tissue in the body. My
colleagues and I
know just a little
about that interaction in the breast.
Some people know a bit
about skin, and others know a bit
about brain, but
really we all know very little. There is so
much to learn, and the
sequencing of the genome is just
the very beginning.
Q: What other
disorders may be tied to change in the
extracellular matrix?
DR. BISSELL:
Generally, people think about the ECM in
relation to cancer
because it's easier to see how
disorganization leads
to cancer. But I believe that many
kinds of disorders and
diseases may be tied to
misregulation of the
ECM. There is, for example, a skin
problem called
epidermolysis bullosa. One type of this
disease results from a mutation in one of the
three genes
for laminin, which is
an important basement membrane
component in various
tissues. Mutation in these ECM
genes can wreak havoc
in different kinds of tissues and
cause a variety of
diseases.
Q: Might that make the
extracellular matrix a more
advantageous target
for cancer therapies?
DR. BISSELL: I wouldn't say that it makes it a
more
advantageous target,
but I think that it is a very good
additional way to
attack cancer.
The ECM is not just one
molecule; it is a collection of
molecules that talk to
their receptors, and the receptors
in turn talk to the
cytoskeleton and the nucleus to
change the cell. Any
of those molecules involved in signal
transduction by the
ECM are every bit as good a target
for a therapy. In the
past we have paid tremendous
attention to growth
factors and growth regulation, but
we need to pay equal attention to those genes
that
determine organ
specificity and structural specificity. The
ECM is one part of
cell regulation, and thinking about how
the ECM can be part of therapy is very good. We now
know that many growth
factors need ECM signaling to
function, so we must
understand both kinds of signaling.
Let me make an additional
point: We concentrate too
much on the cancer
cell itself. Often it's what is outside
these cells that leads
to genomic instability and mutation.
For example, when your
cells have the BRCA 1 and BRCA
2 mutations, why do
you get only breast cancer and
ovarian cancer? Why
don't you get cancer of the skin?
Why don't you get
cancer of the gut? These mutations
are in every one of
your cells but cause only very specific
types of cancer. Even
with the breast cancer genes, not
everybody who has a
BRCA 1 or 2 mutation gets breast
cancer. And even if you do get breast cancer, you get it
in only a few cells.
What happens to the
rest of the breast cells that are just
sitting there? The
breast cells, I think, are all poised to
become cancerous
sooner or later. Even if you don't have
a primary mutation
like BRCA 1 or 2, a drastic change in
microenvironment can
lead to mutation in the epithelial
cells. In
collaboration with Zena Werb at the University of
California at San
Francisco, we made transgenic mice
that overexpress
metalloproteinases in the breast to
destroy the ECM. Those mice eventually got breast
cancer.
Remember that there is
a significant correlation between
cancer and aging.
Aging is an organismic-level
phenomenon. As you get older, one of the most
important
things in your body
that changes is the ECM's and cells'
microenvironment. We
get wrinkles because the ECM that
is normally supple and allows correct
signaling starts to
dissolve. Matrix
metalloproteinases, which dissolve the
ECM, get up-regulated
as you age. They disrupt dynamic
reciprocity and create
a situation in which the epithelial
cells are poised to
become unstable.
I argue that we should
also be directing cancer therapy
toward the field
outside the cell. Is there a way to
change the
whole-field-effect of a tissue? Could we
change the
microenvironment so that another tumor
doesn't develop? In
terms of gene therapy, I think these
are additional challenges. We have shown that we can
revert malignant
breast cells by manipulating ECM
receptors on the
surface of the cells.
Q: Is there something
fundamental about the role of the
ECM, like the p53
gene, in causing cancer?
DR. BISSELL: I would
say that the extracellular matrix
and its interaction
with its receptor could regulate genes
like p53; in fact,
there is some evidence for this from
other labs. I think
that everything is absolutely
interconnected. When
we do 2-D studies (on plastic) as
opposed to 3-D, we find that a lot of genes
get changed.
The cells in 2-D
express some genes that are not
expressed in 3-D, and
vice versa. We also find that many
genes are modified when
cells are grown in 3-D as
opposed to 2-D. We
have data to show that the ECM and
its receptor affect
cell-cell interaction—which in turn
impacts the ECM and
its receptor. Both of these things
affect important genes
within the nucleus, such as p53.
They all work in
concert.
I believe that cancer
may be caused by a mutation of
classical tumor
suppressors, by a disorganization of the
cytoskeleton, and/or
by messing up the extracellular
matrix. The result is
similar, but the pathways by which
someone gets cancer
are different.
Q: In other words,
once a person gets cancer, the
extracellular matrix
may be tied to metastasis by allowing
cancer cells to exist
in microenvironments that differ from
those in which they originated?
DR. BISSELL: Exactly.
But I am saying more than that.
Cancer can start by
messing up the ECM and structure,
but loss or change of
the ECM is also involved in
metastasis. For these
cells to get out of their tissue,
they have to travel
out of their ECM, so extracellular
matrix-degrading
enzymes get produced. They eat up the
ECM, and then the
cells are able to move. This doesn't
mean that tumor cells
can't make extracellular matrix.
Sometimes they make
gobs of it, but they don't assemble
it correctly. They make piles of it, but it doesn't
know
how to get organized.
The process messes up the
balance that
determines tissue and organ specificity.
Q: How does genomic
science affect the work that you
do?
DR. BISSELL: I use all
the tools that genomic researchers
are developing. All of
the genes that are expressed by
the mammary gland need to be cloned, need to be
known. I didn't
discover the metalloproteinases—other
people discovered (and
continue to discover) them and
have cloned and
sequenced them—but I use them as
markers and tools.
As far as the study of
the genome goes, I think of a
lovely slide that I
usually show at the end of my talks. It
says, "Science is
built of facts, as a house is built with
stones. But a
collection of facts is no more science than
a heap of stones is a
house." I say that a collection of
genes doesn't define a
particular tissue or organ, in the
same way that a lot of
bricks do not define a house.
Clearly, we need those
collections of genes; we need to
understand the
proteins that are being expressed and the
regulatory sequences
that make those proteins carry out
their function. My
work is just another facet of the
biology we need to do.
The reason I've been perhaps a
little too loud in the
last 15 years is that 98 percent of
the researchers are
working to understand genes, and
maybe 2 percent are
trying to understand the
extracellular regulation of cells. It needs to be 50-50
because both sides are
important. We ought to be
working together to
understand the whole complexity of
tissue specificity.
The imbalance is
somewhat understandable because
science, by its
nature, needs to simplify. I do argue,
though, that some of
the ideas my laboratory is putting
forward are not as complicated as they
sound. If you
isolate genes and then
study them in isolation or under
unnatural conditions,
you make life a lot more complicated
because isolated cells
can give you misleading
information. But if
you put them in the right context, they
give you the
information that you want to know: how
those genes and cells
may behave when they are in your
body. But, of course,
in the final analysis you also want
to study these
regulations in vivo.
Q: Are you worried
about the ethical implications of
human genome research? For example, once we have the
power to test for the
presence of genes like BRCA 1 and
BRCA 2, how do you
advise whether or not to be tested?
DR. BISSELL: At the
same time that I'm a great
advocate for human
rights, I'm also a great advocate for
freedom to seek
information. No one should muzzle
science. Knowledge is
a one-way process, and you can't
stop it. If people do
decide they want genetic tests, then
they should have
genetic tests. If they don't want to
have them, they
shouldn't. As scientists, we need to
educate as we discover. It's the same way I feel
about
abortion issues or
fetal research. If we're not doing
anything that
infringes on the basic rights of another
human being, we ought
to be able to do it.
On the other hand, I
do think that we need certain laws
and regulations to
prevent powerful people from taking
advantage of this
information. We also need to educate
people about the pros
and cons of genetic testing. Do
you want to know
whether you have a BRCA 1 or 2
mutation? If I had a
mother and a grandmother and/or a
sister who had breast cancer, I would get
tested.
Admittedly, the test
is not always accurate. I would
remind everyone that a
number of people who have BRCA
1 or 2 do not get
breast cancer—and even if you do get
it, you can take care
of it if you find out early.
I'm all for genetic
engineering, but we need to make sure
that it doesn't harm
the environment. I'm all for finding
out what kind of genes
people have but at the same time
educating them about
what this information means. I'm
also all for
diversity. In other words, I think it's very
important for people
to realize that the implications of
these things are not
simple. We must preserve our
creativity, diversity,
and three-dimensional way of
thinking.
Q: Can laws to control
the use of genetic information be
effective?
DR. BISSELL: I don't
see why not. If laws are created in
consultation with
scientists and the scientific societies,
they could make sense
and could work. If we end up with
politicians telling
scientists and society what to do, it's
not good.
I'm not saying that scientists should run
amok. They are
like anybody else:
They need to police themselves, and
they need to exercise
a certain degree of control.
Science, like all other professions, has its
portion of
crooks, yet I don't
think that scientists are unscrupulous.
A lot of scientists
are arrogant, and we are susceptible to
the same kinds of
problems as anyone else. It's just that
if you're a scientist,
in the same way as if you're a
doctor, you have an
additional obligation to try to uphold
the truth, whatever
that may be.
Q: How does the
funding system for a national laboratory
impact your research?
DR. BISSELL: The way
that biology is funded in national
labs is different from
how scientists get funded at the
National Institutes of
Health [NIH] in-house laboratories.
The latter have their
funding and salaries provided. This
was never the case in
national labs for biology. People
don't understand that
all of our funding, including the
scientists' salaries,
are on "soft money," so we have to
constantly compete.
Also, most people don't realize that researchers
supported by the
Department of Energy [DOE] have
contributed
tremendously to some of the boldest ideas in
biology in the United
States. They are the ones who
started the Human
Genome Project. They are the ones
who supported the
first studies on DNA repair, which now
has become a huge
field. They are the ones who
supported Bruce Ames
when he developed the Ames
Test. At the time, he
couldn't get money from the NIH.
In addition, the DOE
has developed a huge amount of
technology that has come out of national labs. It has
allowed individual
scientists a degree of freedom to do
what they like. I was
fortunate enough to have run into a
few men in the DOE who
appreciated that I was
passionate about what
I was doing, and they felt that I
was an original
thinker. They gave me enough freedom to
move a little in other
directions. I am totally indebted to
the Office of
Biological and Environmental Research and
to the DOE. I think
the NIH is a magnificent and well-run
system, but people
don't appreciate how important it is in
science to have
multiple sources of funding. Without
funding for bold
research, creativity really gets stifled.
Scientists and artists
have a lot in common: Good
scientists have an artistic streak, and requiring them
to
accept the
conventional wisdom would stifle their
creativity. Scientists
should be encouraged to push the
envelope.
Funding organizations
ought to allow scientists some
freedom to be able to
explore things that are not
fashionable. One of
the worries I have about how
biotechnology and
biology get developed these days is
that we kind of clone
ourselves: You go to a study
section and they say,
"Oh, but you don't have the
background," or
"Your ideas don't agree with what's
published. How could
your ideas be true?" That's one of
the reasons we should
support the NIH as well as the
National Science
Foundation [NSF]. We should support
the DOE's Office of Biological and
Environmental Science,
but also NASA's
biological office. It's crucial in a free
society that we don't
rely on just one giant organization,
even when it works so very well. I'm a passionate
advocate of multiple
funding sources. It's important for
originality, and I'm
delighted to see that the NIH now
includes originality
as a criterion for supporting research.
Also, it is wonderful
that people as prominent as Harold
Varmus—the very
successful and brilliant past director of
the NIH—are now calling
for doubling the funding also for
the NSF and for the
Office of Science of the DOE.
Q: Let's turn to your
own "developmental matrix." How did
growing up in Iran
shape your perspective about your
career?
DR. BISSELL: People
often ask me how a woman from
the Middle East has
been able to come to this country,
go to Harvard, and be
successful in creating and directing
a huge division. I
remind them that hundreds of
thousands of women are
out there who have done the
most amazing things.
The United States is full of such
immigrants, but I
think I have done what I have done
precisely because I
come from Iran.
When I was growing up,
Iran was a class-divided society,
very much like the old
England. In fact, class was more
important than gender.
I was fortunate enough to come
from a well-to-do and
educated family and to have a
stable background.
Basically, I grew up telling people
what to do and was
encouraged to express myself. I was
encouraged by my
mother especially, although my father
also expected us to
have higher education and to
achieve. Women of my family's class did
exactly as they
pleased because they
had a "room of their own"! Women
had children, but they
also had servants, so they were
more free to pursue careers and their own interests.
My sister does not buy
this explanation. She says, "But
you also were the top
high school student in the country.
You were number one in
most or all subjects." But I think
that thousands of kids
out there could be top students if
they had the same
opportunities.
It didn't occur to me
that I—or anyone—couldn't do what
I did. I came to the
United States all by myself, when I
was barely 18. I had
won a big scholarship and landed in
New York. I went to
college, got married, and had a child
the first year of graduate school. This was
35 years ago,
when only 3 of the 200
students at Harvard Medical
School were women.
Everybody immediately assumed I
would quit. Maybe I
was being naive, because I didn't
realize how difficult
things could be: I didn't have
servants; I didn't
have my mother next door; we were
living on student
salaries. But it didn't occur to me even
once to quit.
People would say,
"Of course you are quitting. What is
your mother going to
say?" You know what my mother
said? She called from
Iran and said, "You're not quitting,
are you?" and she
came to help for a few months. Now
how many American
mothers, 35 years ago, would say
this to their
daughters? They would make you feel
guilty—they would say,
"You have to stay home and take
care of your
kid." I'm not saying that people shouldn't do
that. People should
stay home and take care of their kids
full-time, if they
want to. But with my energy level when
I was that young, if
somebody had forced me to stay
home I probably would
have jumped off the roof. I
probably would have driven my kids crazy. (I'm sure
they
thought I drove them
crazy anyway!) I have a wonderful
daughter and a
wonderful son. Both are well educated
and in good shape.
They're now both married, and I'm a
grandmother.
I had my daughter
during my first year of graduate
school, and my son the
second year of postdoc, and I
just continued to work. I never stopped. Now I look back
and realize how
difficult it was. I keep thinking, "How on
earth did I do
it?" But in the end it was worth it.
Q: Even with all your
energy, it must have been
challenging to raise a
family, earn your degree, and work
all at the same time.
How did you manage to give
appropriate time and
energy to each commitment?
DR. BISSELL: It was
even harder because I was doing
very unconventional
science. That didn't help. I didn't
have a regular mentor;
I didn't have a club to which I
belonged. At the time, I didn't know that what I
was
doing was so hard; I
just didn't see it that way. Again,
that's part of this
whole background situation. People
don't realize how much
our background shapes us. Some
very powerful men in
science think I'm a little too
outspoken, or that I
say inappropriate things. Sometimes
I wish I wouldn't say
certain things to my colleagues, but
it comes from my
background. I was never punished for
speaking my mind; I
was encouraged. If I had been
punished, I probably
would have gotten so depressed
that I would not have
developed the same way. But
cultural backgrounds
play a big role in how people
behave.
Q: How has being a
woman scientist in the United States
affected you? Has it
been a detriment?
DR. BISSELL: Oh, it
has. In my generation, being a
woman really was a
handicap in science. But believe it or
not, I didn't recognize that until after graduate school.
After my postdoc I got
my first job here at Berkeley. I
realized when I
started the job that a male colleague of
mine—who was younger,
had fewer publications, and
hadn't done half as
much as I—had been hired into a
better position with a
much higher salary: He was my
boss. I wasn't used to
that kind of discrimination. I
couldn't understand
it, and the injustice of it really
affected me. I looked
at the situation and thought,
"Huh?" Of
course it made me angry and caused problems,
because I can't be as creative when I'm dealing
with
anger. Nevertheless, I
managed to move on. As I moved
higher and higher up,
things became more and more
difficult. In
retrospect, it could have been partly my
fault—I may have
appeared to feel entitled, which isn't
right. But part of it
was simply frustration.
But I think I lucked
out in many different ways, partly
because of sheer force
of energy. Now I feel very
grateful, and I'm sure
I could have done things differently
had I realized the
cultural differences. I'm grateful to
many people, including
my current director at the
Lawrence Berkeley
National Laboratory, Chuck Shank; the
people in the
Department of Energy's Office of Biological
and Environmental Research; and a few other colleagues
across the United
States who have been very supportive.
Unfortunately, even
though younger women may not
have as much trouble,
I do think that a lot of
discrimination still
goes on, even though people think it
has been eliminated.
I'm pleased to see how
many gains women have made in
science, but I still see the difference between being a
man and being a woman
in the field. Very often, I'm the
only woman in the
room. In a lot of cases, I'm the only
one who speaks up. And
often, when I speak up too
much, it causes
trouble. Of course, men can also get
themselves in trouble
if they speak up, yet there is still a
big difference.
Q: Do you think that any of the relatively new areas
of
genomic research are
"friendlier" to women?
DR. BISSELL: Yes and
no. People say, for example, "We
have enough women in
biology because it is the study of
nature and is
intuitive for women. We don't have enough
women in physics
because women don't think that way." I
was surprised to
notice years ago that some of the best
physicists in this
country are women of Italian origin, and
I always wondered why
so many brilliant female physicists
come from Italy. Then
I found out that in Italy, physics is
considered a fine art.
Men go into politics and finance,
and women are
encouraged to do math and physics along
with painting and
music!
I think our family's
expectations as we are growing up
have a lot to do with
the career we end up in. It is my
hope that the genomic
sciences will remain more open to
women. Diversity and
different points of view are good for
science. It's not just
because 50 percent of this society
is made up of women—I
think that women do bring
different insights to
science.
Q: You've said that you had difficulty choosing
between
pursuing chemistry or
literature. Do you feel that you
made the right
decision?
DR. BISSELL: I think I
did, although literature—and
having taken what I
believe was one of the best English
classes this country
had to offer, at Bryn Mawr
College—has stood me
in terrific stead. I still read a
tremendous amount of
literature. Colleagues ask where I
find the time, but I
read just before I go to bed. I love
good writing. It's
such a pleasure.
I eventually chose
chemistry because I figured that I can
read on my own but I
can't study chemistry on my own.
I'm glad I did
science. I absolutely love what I do. My
enthusiasm and love of
science is what has carried me
through all these
years. It is like doing jigsaw puzzles and
getting paid for it!
Q: Is it important for
scientists to study literature and
take other courses not related to science?
DR. BISSELL:
Absolutely; I think so. Scientists are not
being taught enough
social sciences or enough literature.
These are very
important subjects, and I think that a
liberal-arts education
is a very good background for
scientists. Too many
people are being trained to be
straight-A premed
students. They cram, but they don't
become full human
beings.
From time to time, we
have scientific geniuses who are
really weird and are
social misfits. What we also want are
creative scientists
who can also be nice human beings
and interact with
society. This is one of the problems
that scientists have:
Often, they are not articulate
enough to express
themselves or speak to the public, or
they don't care to do
so. I'm delighted to see scientists
involved in politics.
Bruce Alberts, who is the president of
the National Academy
of Sciences and an inspiration in
many areas, including
science education, recently
returned from Iran
with the other two National Academy
presidents. They went
to Isfahan, where 6 out of the 12
members of the city council apparently were
medical
doctors. He said that
this would never happen in the
United States.
In societies like
Iran's, scientists are revered. This year,
even under the Islamic
regime, Iranian women make up 60
percent of the medical
school class, and the figures are
similar in science,
engineering, and architecture. We need
more of that in this
country. We need a marriage
between politics and
science, and we need multifaceted
scientists. Fine arts,
literature, and the rest of the
liberal-arts curriculum should be introduced into science.
It would help shape
scientists' ways of thinking and allow
us to better
understand biology. The reverse is also true:
Society needs scientific education. We must
encourage
our children not to be
afraid of science.
Q: Has your
liberal-arts background made you more open
to an
"environmental" view of cells and their regulation?
DR. BISSELL:
Absolutely. But at the same time, it's
important not to be
afraid of physics, math, and
computers. It's
crucial that we educate minorities and
women in those areas,
because it's easy to be scared of
math, science, and
physics. People need to overcome
their fear of these
subjects. But they need teachers who
encourage them. I had wonderful math and physics
teachers in high
school, and some were bright and
inspiring women.
Ultimately, society
needs to create multifaceted
individuals to think in multifaceted ways. But, we
have to
study science to
understand the complexity of what we
face in the new
millennium.
Q: The existing
intense collaboration between industry
and academia
represents a huge change in the research
environment since the
early 1970s. Has the change been
good for biology?
DR. BISSELL: In
general, it's been good. In any case, we
can't stop it. The
part that worries me is what worries
everybody else—that
patent laws and secrecy affect
researchers' ability to
talk about their work. A lot of
scientists say,
"I won't talk about it until I can patent it,"
and they aren't as
willing to share their research material.
It's difficult to get
information from companies. These
attitudes can be
harmful.
The good news, of
course, is that [industrial-academic
collaboration] has
brought a lot of very intelligent and
capable people into research. They realize they don't
have to go to the
stock market to make money: They
can go into biology to
make money! [Chuckles.] It also
has created a bigger
job market for biologists. We need
to watch for the
dangers and increase the benefits.
Cooperation and
interaction with industry is good, as long
as it doesn't muzzle
us too much.
Q: Looking to the
future, what areas of biology and
genomic research
should researchers be focusing on?
DR. BISSELL: Opinions
vary, and some areas are rather
obvious, but something I really would like to see
emphasized more in
biology—and in combination with
genomics—is the
science of imaging. It's important for
people to really think
about where genes are expressed. I
want to see companies
and universities paying a lot more
attention to imaging
because we will not understand the
nature of tissue and
organ specificity unless we know
exactly the
microenvironments of these proteins within
the cells and tissues.
I would like to see a combination of
genomics and imaging
being developed. That's another
reason I'm in a
national lab—it allows a multifacetedness
that until recently
didn't exist in universities.
I'd also like to see
larger and more equal teams of people
collaborating and bringing different disciplines
together.
At the national
laboratories, biologists are working next to
informatics experts,
engineers, and physicists. We
encourage multiteam
investigations. This is the way of
the future in biology.
