An Oncologist's Pulitzer-Winning Cancer Biography.

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An Oncologist's Pulitzer-Winning Cancer Biography

DAVE DAVIES, host:

This is FRESH AIR. I'm Dave Davies in for Terry Gross.

When the, quote, "War on Cancer" was launched in 1971, after President
Nixon signed the National Cancer Act, Congress authorized hundreds of
millions of dollars for cancer research. Some scientists thought cancer
could be curable within a few years.

There's been a lot of false hope and hype since then, no cure but a lot
of progress. Where are we now in the war on cancer, and is it winnable?
Those are among the questions that inspired the new book "The Emperor of
All Maladies: A Biography of Cancer" by our guest Siddhartha Mukherjee.

Earlier this week, the book was awarded the Pulitzer Prize for general
nonfiction. The Pulitzer Committee called an elegant inquiry, at once
clinical and personal and to the long history of an insidious disease
that, despite treatment breakthroughs, still bedevils medical science.

As an oncologist immersed in the daily care of patients, Dr. Mukherjee
wanted to pull back and research the history of cancer to better
understand the illness he was confronting and treating. Siddhartha
Mukherjee is an assistant professor of medicine at Columbia University
and a staff physician at Columbia University Medical Center. Terry spoke
to him in November of last year.

TERRY GROSS, host:

Dr. Mukherjee, welcome to FRESH AIR. What did you want to get out of
writing this book as an oncologist yourself? Why is it important for you
to have an understanding of the history of cancer, and why do you want
your patients to know that?

Dr. SIDDHARTHA MUKHERJEE (Physician; Assistant Professor of Medicine,
Columbia University): Well part of the reason is that, you know, I think
one of the themes in the book is that the past, particularly in medicine
and science, is always conversing with the future. There are ways in
which you don't know until you excavate the past of medicine why we're
here right now and what happens next. I mean, Terry, you know, the book
really grew out of a question that a patient had asked me, and she was a
woman with abdominal cancer, and I was treating her. And she had
relapsed and responded and relapsed and responded, and finally she said:
You know, I'm willing to go on, but before I go on I need to know what
it is that I'm battling.

And it was a very humbling moment for me because not only could I not
answer her question, I couldn't point her to a book or a resource that
would answer her question in the most fundamental sense. I mean, there
are 5,000 books in the world about cancer, you know, how, if you want to
eat carrots, you can cure this kind of cancer et cetera.

And I actually found those books vaguely insulting. And I also found
that there was no resource. There was no history. And so I wrote this
book really because it wasn't there, and it was an attempt to try to
write the history and to bring us up to the present such that we could
understand what happens in the future.

GROSS: Before we talk about the history of cancer treatments, let's talk
about some of the things you and your patients are up against and the
brutality of some of the treatments. You describe your work with a
patient named Carla. Would you describe the kind of cancer that she had
and the incredible regimen of chemo that she had to undergo with only a
30 percent of surviving after all that.

Dr. MUKHERJEE: So Carla has acute lymphoblastic leukemia. It's a very
aggressive form of cancer of the white blood cells. It usually presents
in young children, but it can - there's a variant of it that presents in
young adults, actually even in older men and women. And Carla happened
to have the older variant, obviously. She was diagnosed when she was in
her 30s.

And in children, this kind of cancer is highly curable, 80 percent
curable, 90 percent curable, depending on the circumstances. But in
adults, for reasons that we still don't understand, the cure rate sinks
down to in the 30s and 40-percent range, and Carla had that variant of
cancer.

The chemotherapy regimen for this cancer is extremely toxic. It is a
regimen in which we go on and on and on, almost without any break,
combining multiple drugs, seven or eight drugs, adding radiation in
certain instances and in fact so much so that we actually put in
chemotherapy into the spinal cord in order to prevent these white blood
cells from overgrowing out in the brain. And so that's how toxic and
complicated this chemo regimen is.

GROSS: So what do you tell a patient like Carla when you know that the
odds of her surviving are 30 percent and that you're about to administer
this incredibly toxic set of chemo drugs including injections into her
spine to prevent the cancer from spreading to her brain?

Dr. MUKHERJEE: The first job you have, I think, is to inspire confidence
in a patient, and you do that actually by being humble. This is a kind
of great irony of oncology is that the thing that really inspires
confidence in patients is by telling them exactly what is known and
exactly what is unknown and trying to lead them through that process.

And in Carla's case, you know, I was a fellow in training, one of the
things that I said to her is, here's what we know. Here's what we know
will happen, and then we'll sort of meet this blast of the unknown. We
won't know whether your counts respond. We won't know what happens, but
when we are there we will find a way to solve that problem, and we'll do
it together.

And I think that, for me at least, is very reassuring to say as a
doctor, and I think, I hope, for patients, is very reassuring to hear.

GROSS: And she survived?

Dr. MUKHERJEE: Absolutely, she survives today.

GROSS: So let me ask you an honest question here. When a patient has
such a serious and hard-to-treat form of cancer and finds a doctor like
you who is obviously really smart and probably very good with a bedside
manner but kind of inexperienced because you're still a fellow at this
point in the story, do they get nervous that the doctor is young and
inexperienced? Have you faced that a lot?

Dr. MUKHERJEE: I did. I continue to face that. I mean, as it turns out,
when you're being treated at an academic medical center, the fellow is
not the only person who is taking care of you. The fellow is overseen by
attendings. There's a whole team of doctors and nurses and a whole
variety of people come to allow you to go through this, so the fellow is
one part of this.

But that said, I think the fellow is a very major part of it because
it's the person whose learning curve is the most exponential. And in a
sense, I always say this, you know, to my own family, it's the person
who is right at the frontlines who actually knows the most about
medicine.

When I was training in internal medicine we sometimes used to perform a
procedure in which we would put a catheter, a centralized catheter into
the heart. And I would say to myself, you know, if I ever had to have it
done for myself or a loved one, the person I would choose is not the
senior attending, not the junior person in training but the fellow who
has just come out of training because they know exactly what the risks
and benefits are.

They've sort of been at the frontline. They're like the soldier who has
been there, who knows trench warfare. And so in some ways I think, of
course, there is a whole team of experienced professionals who weigh in
on the care but the fellow's experience is the most acute.

GROSS: If you're just joining us, my guest is Dr. Siddhartha Mukherjee.
He's an oncologist who has written a new book called, "The Emperor of
All Maladies" and it's a history of cancer.

Can you explain for us laypeople what the current understanding is of
what causes a cell to become cancerous?

Dr. MUKHERJEE: We've begun to get a glimpse of this, of this event. And
what we know about it is the following: There are - in cells, there are
genes that are present whose normal function is to regulate the growth
of the metabolism and the cell division of cells.

And corruptions of these genes, mutations of these genes essentially
activate or inactivate critical processes that act like accelerators and
brakes. So to rephrase this: You can imagine the cell as a molecular
machine, and cell division is one of the activities it performs, and
there are accelerators and brakes on cell division.

Now if you, by mutating genes, if you jam the accelerators, or if you
mess up the brakes, then the cell doesn't know how to stop dividing, and
it begins to divide incessantly. And part of that division also creates
even more mutations.

Sometimes there are genes that can be mutated, which can accelerate the
mutations of other genes. And this process goes on and on until you've
found a cell which is now capable of infinite cell division and does not
know when to stop dividing, and that's what unleashes a cancer cell.

But that said, I think that's just the beginning of an understanding.
Obviously cancer is not just a dividing cell. It's a complex disease. It
invades, it metastasizes, it evades the immune system. And so there are
many, many other features of cancer which are still in their infancy in
terms of our understanding.

GROSS: Can you tell us about another feature of cancer that has recently
been discovered?

Dr. MUKHERJEE: Well actually, one of the most amazing - I just recently
went to a seminar, an academic seminar at Columbia, in which the
scientist was trying to find out: How is it that cancer evades the
immune system?

So he has been obsessed with this idea for several years and has finally
invented a mechanism by which he can reactivate the host's immune system
and potentially attack the cancer.

And this is not just a kind of a fantasy, but in fact one of the first
such drugs recently was put into a clinical trial in metastatic melanoma
and was surprisingly effective at increasing the survival of patients
with metastatic melanoma.

And he reminded me that, in fact, there has been no drug, no known drug
in the past, which has increased survival of patients with metastatic
melanoma, and yet activation of the host's immune system seems to
increase survival. So that just tells us how little we know about sort
of the global qualities of cancer, about these new qualities that we're
discovering.

GROSS: We're in an era where there are now some targeted drugs, drugs
targeted to specific forms of cancer, and there are many more drugs in
the works. I guess the two best-known targeted drugs are Herceptin and
Gleevec. I'd like you to choose one of those two drugs that's easier to
describe and tell us how it works as a targeted drug.

Dr. MUKHERJEE: So Gleevec is an excellent example of how one can target
cancer therapy. Essentially, the cells that Gleevec attacks are a form
of a particular leukemia. It's called chronic myelogenous leukemia, or
CML - I'll call it CML.

CML cells have an activated gene, and that gene is what drives them to
proliferate pathologically, to keep dividing pathologically. And that
gene was discovered in the 1980s and it's called BCR-ABL.

And essentially what Gleevec does is that that gene makes a protein
called BCR-ABL and Gleevec essentially goes in and lodges itself into
the heart of this protein, this pathological driver of cell division,
and inactivates it.

There's a lovely phrase that someone used about this. A chemist said:
Gleevec is like an arrow directed at BCR-ABL's heart. And that phrase is
really memorable because essentially this little molecule goes and jams
itself inside the heart of this driver protein and essentially
inactivates it, and that's how it makes it possible to kill these
pathologically proliferating white cells, and that's what makes it a
targeted therapy.

GROSS: So how toxic is Gleevec compared to the kind of chemo that most
people are familiar with where you lose your hair and you get nauseous
and...

Dr. MUKHERJEE: It is absolutely not toxic at all. I mean, you know,
there are minor side effects of Gleevec, but it's not toxic. It's
amazing. If you see a patient on - who is taking Gleevec for CML, the
idea that they were going through chemotherapy may or may not even occur
to you. I mean, there are side effects of any medicine, but really the
non-toxicity to the rest of the body is absolutely shocking.

GROSS: And what's amazing too, isn't this form of leukemia a very deadly
form of leukemia?

Dr. MUKHERJEE: It used to be.

GROSS: Right, right.

Dr. MUKHERJEE: It used to be. There is a very interesting quote in the
book, you know, one of the people who I interviewed in the book is Brian
Druker, who of course invented Gleevec along with a couple of other
chemists at Novartis.

And Brian Druker said to me at the end of his interview, he said, you
know, he's achieved the perfect inversion of everything that an
oncologist wants now because, because patients on Gleevec are living
longer and longer and longer, the prevalence of CML is increasing.

So in other words people are living so long that you can now begin to
see people alive with CML in the world, sort of taking Gleevec because
you take it chronically, and so Brian says he's achieved the perfect
inversion of the goals of an oncologist. He's increased the prevalence
of cancer in the world.

GROSS: Right, right because people aren't dying.

Dr. MUKHERJEE: People aren't dying, exactly.

GROSS: Yeah.

Dr. MUKHERJEE: They're living with cancer, as opposed to dying of
cancer.

GROSS: So what are the implications of Gleevec for the future of cancer
treatment?

Dr. MUKHERJEE: Well the, one of the implications is that number one as
Bruce Chabner, again, who I interviewed for the book, is that, you know,
Gleevec is a little bit like, it's a little bit like the four-minute
mile.

So, you know, when Roger Bannister ran the four-minute mile, before he
ran the four-minute mile, people had all these theories about, you know,
you can never run a four-minute mile because your lungs can just not
breathe fast enough or your legs or your muscles are not designed -
there's an intrinsic barrier to being able to run the four-minute mile.

And of course Bannister showed that that was not true. And since then,
now I don't know what the latest number is, but it's something like
three minutes and few seconds.

And so what that means to us, what Gleevec means to us, is much like the
four-minute mile: There's no intrinsic barrier to designing specific
therapies. Such therapies in proof could exist. We just have to find
them.

And so Gleevec essentially opens an approach to running what people are
calling oncology's four-minute mile, which is finding specific therapies
for every form of cancer.

GROSS: And this is a kind of therapy that, unlike most chemo, doesn't
kill most cells.

Dr. MUKHERJEE: Normal cells, that's right. So it has - and, you know,
we'll go back to the history - but it has what would be called exquisite
specificity: the idea that you would be able to kill the cancer cells
while sparing normal cells.

You'd find what are called Achilles' heels of cancer cells, find exactly
those things that make cancer cells dependent on certain conditions for
their growth, and you'd be able to target those specifically such that
you now would be able to kill cancer cells and spare normal cells.

DAVIES: Dr. Siddhartha Mukherjee, speaking with Terry Gross. More after
a break. This is FRESH AIR.

(Soundbite of music)

DAVIES: We're listening to Terry's interview recorded last year with Dr.
Siddhartha Mukherjee, author of "The Emperor of All Maladies: A
Biography of Cancer." The book has been awarded the Pulitzer Prize.

GROSS: You write in the book that when a chemo drug or the immune system
attacks cancer that then mutant clones can resist the attack and start
to grow. And then the fittest cancer cells survive, and they start
reproducing. Is it similar to the way bacteria can become resistant to
antibiotics?

Dr. MUKHERJEE: That's exactly right. That's the exact analogy. In fact,
that's exactly how cancer cells mutate, and every round unleashes - you
know, it's sort of like, I sometimes say it's like the Galapagos trapped
inside your body. Every round unleashes yet another set of resistant
cells and so forth until you've finally got the next evolving clone of
cells.

GROSS: So that must make cancer much harder to treat because you become
resistant to the treatment, no?

Dr. MUKHERJEE: That's exactly right. So you have to find the treatment
that will reach that perfect balance between eliminating all cancer
cells such that you ultimately are left with none. That is the ultimate
cure. But sometimes you don't - again, sometimes you don't need to do
that.

Again if you come back to Gleevec; Gleevec doesn't really eliminate
cancer from your body. What it does is it sends the cancer cells into a
kind of state of deep hibernation. It kills all the actively
proliferating ones.

But interestingly, when you stop taking Gleevec, you can relapse with
cancer cells that are somehow hidden somewhere in your body. It's a
process we don't understand fully.

GROSS: Why is it that breast cancer cells are different than leukemia
cells, and they're different than colon cancer cells? Now, as you point
out in the book, the original idea for the War on Cancer was that cancer
cells are cancer cells: We'll figure out a way to kill all the cancer
cells and therefore we will vanquish cancer. But it turned out to not be
that simple because all the cancers have different cells.

Dr. MUKHERJEE: That's correct. I mean, this is a very common question,
you know, why is it that breast cancer cells are different from leukemia
cells? The simplest answer to that question of course is that it's
partly because breast cells are different from blood cells.

Our body has evolved exquisitely detailed instructions that allow a nose
cell to become a nose and that allow a blood cell to become blood and a
breast cell to become a breast cell, and they are all performing
functions that are requisite for the survival of a multi-cellular
organism called a human being.

Now that's part of the reason, of course, then that is that when a
breast cell becomes a breast cancer cell, it evolves along a particular
pathway, but it still retains some of the characteristics of its
original precursor or ancestral breast cell.

And therefore every single tissue, every single tissue that bears cells
that divide, therefore there's a diversity of cancers that is produced.

Now that said, there are commonalities, as well, and one of the most
amazing things about modern or contemporary cancer genetics is that it
is reorganizing the universe of cancer in terms of peculiar and
unexpected organizations.

I'll give you a good example of that. We talked a little bit about this
kind of leukemia called chronic myelogenous leukemia, or CML, and we
said that there's a mutation in a particular gene, which drives this
leukemia. This gene happens to be called BCR-ABL. They're actually two
genes fused together, BCR and ABL, which create this mutant gene, BCR-
ABL.

Now, it turns out that there is a cousin gene, which is active in a
completely different kind of cancer, a solid tumor that grows typically
in the abdomen called a gastrointestinal sarcoma, or a GIST.

You would say: Well there's no relationship between a leukemia, which
grows in the blood and chokes the spleen, and a solid tumor that grows
in the abdomen and doesn't resemble it anatomically or physiologically
at all. But it turns out if you lift up the covers, there are common
genes. There are cousin genes that drive both of them.

Now if you hadn't uncovered the underlying genetics and reorganized the
world of cancer, you'd never imagined that these are connected. And this
is what's happening overall in oncology. So in other words, a breast
cancer might turn out to have a very close resemblance with a gastric
cancer but not every breast cancer. And this kind of reorganization of
cancer in terms of its internal genetic anatomy has really changed the
way we treat and approach cancer in general.

GROSS: Is our genetic system programmed to get cancer?

Dr. MUKHERJEE: Well, you know, it's always hard to answer questions
which are, which speculate about evolution. But this much is for sure:
The very genes that allow cells to proliferate, to survive, to move, to
adapt to circumstances, to resist poisons, those very genes, when they
become corrupted, are genes that are co-opted by cancer cells to become
cancer.

So there is, of course, a deep link, and as the book suggests, if
there's a seminal discovery in oncology in the last 20 years, it's
exactly that, it's the idea that cancer genes are often, this is not
always true, but are often mutated versions of normal genes.

And that moment, the arrival of that moment, really chilled the world of
cancer biology. The book describes that moment. It really sent a kind of
a chill down the spine of cancer biology because here we were hoping
that cancer would turn out to be some exogenous event, a virus or
something that could be then removed from our environment or removed
from our bodies and therefore we would be rid of it.

But the idea that cancer genes are sitting inside each and every one of
our chromosomes, just waiting to be corrupted or inactivated and thereby
unleashing cancer is of course one of the seminal ideas of oncology.

But it also, it's a - as you can imagine - a deep philosophical idea
about what it means to be a human being and how sort of the seeds of
cancer are sort of already inlaid into our chromosomes.

DAVIES: Dr. Siddhartha Mukherjee is the author of "The Emperor of All
Maladies: A Biography of Cancer." It was awarded the Pulitzer Prize for
nonfiction earlier this week. Dr. Mukherjee will be back in the second
half of the show.

I'm Dave Davies, and this is FRESH AIR.

(Soundbite of music)

DAVIES: This is FRESH AIR. I'm Dave Davies, in for Terry Gross. We're
listening to Terry's interview recorded last November with Dr.
Siddhartha Mukherjee, author of the book "The Emperor of All Maladies: A
Biography of Cancer." Earlier this week, the book was awarded the
Pulitzer Prize for non-fiction. Dr. Mukherjee is an assistant professor
of medicine at Columbia University and a staff physician at Columbia
University Medical Center.

GROSS: You write about how horrible cancer treatment was in the '70s and
how difficult cancer wards were and the intensity of nausea caused by
the chemo drugs. Why is it that chemo drugs - many chemo drugs don't
produce that intensity of nausea any longer?

Dr. MUKHERJEE: Well, to some extent it's because the drugs themselves
have changed and we've found ways to create variants - chemical variants
of those that don't cause that much nausea. But really, really the real
secret is that we found better, newer anti-nausea medicines. The kind of
anti-nausea medicines that are deployed in the wards today are
fundamentally different from the ones that were available.

And you know, one of the things that gets ignored in the history of
cancer is the enormous role that taking care of symptoms, that
palliative care has had in this disease. Anti-nausea drugs, anti-pain
medicines, psychological and psychiatric help; antidepressants have
played an enormous role in taking care of the cancer patient, not as
kind of a site of a single disease, but as a human being in totality.

And I actually wanted to return to that history in this book and I paid
a separate tribute to Cicely Saunders, this nurse from England, who sort
of launched the palliative care movement. And Cicely Saunders had
something very evocative to say about it. She said two things. One thing
is she says - well, first of all, I want to emphasize the fact that
palliation is not the negative of treatment. It's not the antimatter of
chemotherapy.

It's essentially part of the same problem-solving. You can't take care -
even if patients who have a treatable or curable form of cancer, you
can't take care of them without paying attention to the palliative
aspects of their care. And the second thing she said, and it's not soft
medicine. This is medicine as hard-edged, as real, as central to the
care of patients.

So I think again, to come back to your question, anti-nausea medicines
are just one of several different ways that we've learned to take care
of patients who are undergoing chemotherapy.

GROSS: One of the forms of chemotherapy is the mega dose form, where you
harvest your own stem cells from your bone marrow and once those stem
cells are out of your system and aren't in danger of being killed by the
chemo, you administer massive doses of chemo in the hopes of killing the
cancer cells. And then when the mega doses of chemo were done, you
reintroduce the person's stem cells and, you know, hope for the best.
What's the status of that treatment now? Is that still being used a lot?
What kind of cancers is it considered most effective for?

Dr. MUKHERJEE: The major trials were run in breast cancer and then the
trials were negative. And this was a - it's a very sad episode in
oncology. You know, this episode actually is a recapitulation of the
past in some ways. And it goes back to this old theory which is that if
something is good then more of that something must be better.

And so the idea was that especially in the 1980s, the idea was that for
breast cancer we just weren't trying hard enough. If we could increase
the doses of chemotherapy, if we could muscle them up even further then
we would finally eliminate breast cancer from the body. And, of course,
the reason we couldn't do that so simply was essentially, the bone
marrow of patients would give way and the patients would die of bone
marrow failure.

And so the idea that grew out of that was, well, what if we just took
the bone marrow out, froze it, gave maximum dose of chemotherapy to
breast cancer patients and then reintroduce the bone marrow back. Well,
now we have a perfect solution. We can maximize chemotherapy and we can
now also protect the bone marrow.

Unfortunately, of course, it didn't work and that story is told in the
book. And it's a tragic, tragic story because there was a point of time
when women and doctors were so convinced that this would work that they
almost wouldn't participate in clinical trials. They said, well, how can
we possibly run a trial on something that we know has got to work? This
story carries the memory of the kind of optimism that very quickly tips
into hubris, which is so much part of the story of cancer.

GROSS: Now, you write about the infighting that was taking place in the
'70s between therapists using radiation and chemotherapists. What was
the fight about?

Dr. MUKHERJEE: The fight about - was what - you know, everyone was
trying to find the best solution to cancer. And the surgeons, the
chemotherapists and the radiotherapists all thought they had the right
answer. Now as it turned out, none of them had the right answer, and
also as it turns out, all of them needed to collaborate with each other
to treat cancer.

Or to give you an example, today breast cancer, particularly, is treated
with every single one of those modes. You have surgery followed by
radiation followed by chemotherapy followed by targeted therapy. And
that's what has allowed breast cancer to change from a very lethal
disease to, in some cases, a chronic disease, which is much less lethal
than it was 50 or 100 years ago. But it depends on an incredible
collaboration between every single sub discipline within oncology.

GROSS: Speaking of breast cancer, there was a period when radical
mastectomies had become the preferred method of treatment. And I want
you to describe like what a super-radical mastectomy was like in, would
this be the '70s or the '80s?

Dr. MUKHERJEE: A little bit before that, super-radical mastectomies were
beginning to be performed. So radical mastectomy is yet another theory
of cancer in which, again, follows the dictum of if something is good,
then more must be better. Radical mastectomy was invented by several
people, most notably William Halsted, on the theory that we weren't
cutting enough. That somehow or the other, little minute remnants of
tissue were being left behind, and that if we cut more, we would cure
more. And so Halsted began to excavate deeper and deeper into the
breast, to cut large amounts of the breast and the associated lymph
nodes out.

And this edged further and further until you reached the super-radical,
the ultra-radical mastectomy in which not only the breast but parts of,
you know, parts of the collarbone or parts of the tissue under the arm
would all be excised. It was like a macabre race to take out as much of
the cancerous body as possible so as to cure women.

GROSS: And why was that discontinued?

Dr. MUKHERJEE: Well, it was discontinued because ultimately, trials
showed that it didn't really help. In fact, as it turned out, even small
tumors could metastasize elsewhere in the body and therefore, cutting
more locally didn't save any extra lives. And it took 90 years before
surgeons and chemotherapists and oncologists could collaborate with each
other to launch the kind of trials that finally showed that radical
mastectomies didn't improve survival by a month, compared to a
lumpectomy plus radiation or a local mastectomy.

DAVIES: Dr. Siddhartha Mukherjee speaking with Terry Gross. More after a
break. This is Fresh Air.

(Soundbite of music)

DAVIES: We're listening to Terry's interview recorded last year with Dr.
Siddhartha Mukherjee, author of "The Emperor of All Maladies: A
Biography of Cancer." The book has been awarded the Pulitzer Prize.

GROSS: Now breast cancer is one of the cancers that we know there's a
gene, the BRCA gene. Actually, there's a couple of BRCA genes, right?

Dr. MUKHERJEE: That's correct.

GROSS: So how does that advance the possibility of treating breast
cancer?

Dr. MUKHERJEE: Well, it advances in several different ways. But before
we go into the advancements, you have to recognize an important fact
that if you take all the known genes that we've identified, which are
responsible for breast cancer, we don't even get to 50 percent of
familial breast cancer. In other words, if you take every known gene
that's been identified as a risk factor for breast cancer, we are only
scratching the surface of the number of genes that are involved in
breast cancer. So BRCA1 and BRCA2 are just the beginnings of a story.

GROSS: Right. And is it helping to treat breast cancer?

Dr. MUKHERJEE: Absolutely, in two or three different ways. Number one is
that if you happen to have BRCA1 or BRCA2, your siblings and your
children can also be found out whether they carry this risk factor, this
mutation or not, and they can be screened more intensively for the
possible development of breast cancer. Or, in more extreme
circumstances, women have chosen to undergo prophylactic mastectomies or
prophylactic ovarian removals to prevent breast cancer. And both - all
those strategies work.

The final piece of it is that for the first time, we're beginning to see
targeted therapies that particularly attack breast cancers that are
mutated in the BRCA genes. So this is - this takes advantage of the fact
that if you have a mutation in the BRCA gene, then your breast cancer
has certain proclivities that normal cells don't. And, in fact, there
have been therapies that are directed against those proclivities, such
that they now exploit the biology of the BRCA gene.

GROSS: You've just completed a biography of cancer looking at the
history of cancer. I'm going to ask you to look ahead now. What are some
of the strategies or medicines that you are most hopeful about?

Dr. MUKHERJEE: The few things that I'm extremely hopeful about is that I
think the wealth of information that's coming out of the human genome
and the cancer genome will eventually lead to a whole new host of new
medicines. That's already started. I talked a little bit about Gleevec,
for instance, and so forth. I think those are where the treatment is
going.

Now that said, I think there's an equally important role of prevention
and the book talks about this. I think even in prevention, we are moving
in a direction in which we are integrating the insights of the genome
into prevention. And by that, I mean, instead of looking for carcinogens
just in the environment using large epidemiological studies, we're
beginning to look using more innovative ways to find carcinogens in the
world.

How do various chemicals affect genes? You can essentially ask this
question: Do these chemicals mutate genes that are important in the
development of cancer? And you can make more sophisticated variations of
this. You can say well, okay, even if they don't mutate genes, do they
activate certain genes? And you can do this in a petri dish before this
chemical gets released into the real world.

So this kind of questioning, I think, can be - is really beneficial
because you could then potentially prevent putative carcinogens from
appearing in the world.

GROSS: What kind of cancer breakthrough would you most like to see in
your lifetime?

Dr. MUKHERJEE: Well, I'd like to see important breakthroughs in cancers
that are tough to treat: pancreatic cancer, esophageal cancer, some
variants of brain cancers. Those are, you know, if you think about
cancer as a march of progress, as a kind of the Pied Piper, as sort of
leading out into Hamelin, there are many cancers that have been left
behind in that march.

They're sort of frozen in time and metastatic pancreatic cancer,
metastatic melanoma, some brain cancers are those. So I'd love to see
those - at least something happen in those directions.

GROSS: You describe a scene that I found so interesting. You know, you
talk about how your patients live in cancer world, but you kind of live
in cancer world, too, because you're so obsessed with treating your
patients and with understanding how the treatments work, with learning
the history of cancer for your book. So there you are with your wife in
the delivery room. She's delivering her first baby, you're asked to like
cut the umbilical cord. And what goes through your mind?

Dr. MUKHERJEE: Well, I'm trying to cut the umbilical cord, and here I am
in sort of the most glorious moment of my life, the birth of my child.
And on one side of my brain I'm saying to myself, I have got to harvest
her umbilical cord blood cells because these cells are useful in
transplantations for kids who have leukemia.

GROSS: Now what happens typically to the umbilical cord blood cells?

Dr. MUKHERJEE: You know, it's often, and this is the tragedy of it, it's
often flushed down the sink and often not collected all. I think, you
know, we absolutely need to have better centralized banking facilities
free of charge which allow us to bank these cells because kids with
leukemia can benefit from cord blood transplantation and they need these
- these are very precious cells.

GROSS: Why are they so precious?

Dr. MUKHERJEE: Well, because they contain blood-forming stem cells that
can go into the blood and create new blood. And they are so precious
because they can be transplanted into another child and give rise to the
blood system of the child and you can therefore eliminate the leukemia.
And if you eliminate leukemia you can often eliminate the normal - the
child's blood stem cells and you can replace it with the cord blood from
another child, and that's why they're incredibly precious.

GROSS: So were you able to harvest the blood stem cells from the
umbilical cord of your baby?

Dr. MUKHERJEE: I was able to harvest the cord blood cells. But I was
also able, thankfully, at the end of it all to enjoy the moment of
childbirth.

GROSS: Thank you so much for talking with us.

Dr. MUKHERJEE: Thank you so much. It's a real pleasure.

DAVIES: Dr. Siddhartha Mukherjee is the author of "The Emperor of All
Maladies: A Biography of Cancer." It was awarded the Pulitzer Prize for
non-fiction earlier this week. Dr. Mukherjee spoke with Terry Gross last
November.
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A Heartbreaking Work Of Staggering Horror

DAVE DAVIES, host:

"Incendies," the title translates as scorched, is a French-Canadian film
that was nominated for a 2010 Academy Award. The movie tells the story
of a woman from the Middle East who survived her country's civil war.
After her death, her grown children try to reconstruct the events of her
life. Film critic David Edelstein has this review.

DAVID EDELSTEIN: In the overture to "Incendies," a group of small boys
have most of their hair shaved off by soldiers. The boys are bloodied
and bruised. Some sort of attack has plainly just happened. The music
underscoring this is Radiohead's sad, slurred, "You and Whose Army?"

One boy, who has three vertical dots tattooed on the back of his foot,
stares into the camera with a look of monstrous hate, a stare that eats
into the mind.

It's not until the end of the film that you understand the full
implications of that stare, what led up to it, and what happened
afterward. When you do, it hits you like a blow. "Incendies" is a
detective story, a tantalizing puzzle movie. It's set in Quebec and in
an unnamed Middle Eastern country that's pretty clearly Lebanon. A pair
of twins in their 20s - Jeanne and her strangely hostile brother, Simon
- attend the reading of their late mother's will, which instructs them
to locate a father they thought had died decades earlier and a brother
they never knew existed.

And as they embark on what amounts to a grim scavenger hunt, there are
flashbacks of their mother, Nawal, a Christian woman who's disgraced
when she falls in love with a Muslim refugee, whom her brothers promptly
murder. She has a baby that is taken away, and then her grandmother
sends her off to a university in a distant city. But civil war breaks
out, and Nawal careens from bloody horror to bloody horror, as right-
wing Christian militias massacre Muslims, and Muslims massacre
Christians right back.

Because Simon found his mother distant and unreliable, it's the
daughter, Jeanne, a graduate student who teaches, quote, "pure
mathematics" in Montreal, who travels to the Middle East and learns
about the mother she only thought she knew. There is one thunderous
revelation after another, a snarl of atrocities and assassinations.

You'd never guess "Incendies" is based on a play by Quebec writer Wajdi
Mouawad, who fled a war-ravaged Lebanon for France when he was eight.
Director Denis Villeneuve has made it breathe onscreen, so that you feel
as if you're moving with the characters through a maze - sometimes
literally, as when Simon finally comes to the Mideast and visits a
makeshift refugee village in search of the Muslim warlord who can
provide the final piece of the puzzle.

As the mother, Nawal, the actress Lubna Azabal is riveting. You see her
bludgeoned over and over, literally and figuratively, until she has wept
all she can weep and tries to force herself to show nothing - a doomed
enterprise.

The film is full of terrible incidents, including the murders of
children. But Villeneuve's handling isn't cheap or exploitive. I could
never watch certain sequences again, but I understood as I watched why I
needed to see them.

Without giving anything away, I'll tell you that the final revelation,
which comes in the last 10 minutes, is preposterous. It's where you do
see "Incendies'" theatrical origins. It's not stagebound, but it's
heavily symbolic, and what has seemed until now a fairly realistic movie
becomes a myth - a lament for a culture in which families are perverted
by what one character calls the merciless logic of reprisals.

The first two hours of "Incendies" don't quite gel with the last 10
minutes, but this remains an extraordinary piece of storytelling, a
diagram of the chain of human suffering with a hellish sting in its
tail.

DAVIES: David Edelstein is film critic for New York magazine. He
reviewed the French-Canadian film "Incendies."

Coming up, TV critic David Bianculli on three offerings from HBO.

This is FRESH AIR.
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This Weekend, HBO Has Something For Everyone

DAVE DAVIES, host:

Last weekend, HBO premiered the "Game of Thrones" a new fantasy series
that drew enough interest and viewers to earn a second season renewal
after one telecast.

This weekend, HBO continues its rollout of fresh April programming by
presenting three different types of TV shows in as many days. A new
comedy special, a new dramatic telemovie, and the return of a continuing
HBO drama series.

TV critic David Bianculli has seen all three.

DAVID BIANCULLI: Coupled with last week's "Game of Thrones" premiere,
this weekend's HBO lineup really demonstrates the wide range of
programming this premium TV service is capable of providing. On Friday,
there's a new special called "Talking Funny," in which four top comics
spend an hour sitting around, talking comedy.

On Saturday, there's a new made-for-TV movie called "Cinema Verite,"
which recreates the making of the landmark 1973 PBS documentary series,
"An American Family," which essentially marked the birth of reality
television.

And on Sunday, there's the second-season premiere of the ambitious,
evocative, very musical drama series "Treme," about life in New Orleans
after Hurricane Katrina. Three types of programming, and all are done
very well, indeed.

"Talking Funny," the comedy special premiering Friday, is like shows
done earlier for other networks by David Steinberg and Paul Provenza.
It's nothing more and nothing less than comedians talking casually about
their art, their senses of humor, their inspirations and their lives.
One difference with "Talking Funny" is that it's done without a studio
audience, so the comics are playing to no one but each other. And
there's no moderator, just a conversation.

The other difference - the one that makes this special so strong - is
the all-star caliber of its four guests, all of whom share the spotlight
for the entire, entertaining hour. Jerry Seinfeld, Chris Rock, Louis
C.K., Ricky Gervais. Need I say more? I didn't think so.

Saturday's telemovie, "Cinema Verite," is a very interesting animal.
It's a dramatic re-creation of the filming of what is widely considered
television's first reality series: a PBS experiment in which a camera
crew filmed the daily lives of California's Bill and Pat Loud and their
children, and turned it into a national TV series.

Tim Robbins and Diane Lane play Bill and Pat, whose marital problems
eventually are revealed during filming, and Thomas Dekker plays Lance,
their openly, proudly gay son, whose appearance on TV in the early '70s
was groundbreaking and controversial in and of itself.

The filmmaker behind the project, Craig Gilbert, is played by James
Gandolfini, distancing himself completely from his iconic HBO role as
Tony Soprano.

Here in an early scene, he presents his sales pitch for the series to
skeptical New York TV executives, using a giant projection of the family
Christmas card portrait as a visual aid.

(Soundbite of movie, "Cinema Verite")

Mr. JAMES GANDOLFINI (Actor): (as Craig Gilbert) Gentlemen, meet the
Louds. You had some hardworking, Nixon-supporting dad, a smart and
sultry mom. She's a little too late for women's lib, but too young to be
a discarded housewife. A 16-year-old daughter, who is experiencing her
first, serious boyfriend. The little one, who's in love with her horse.
And two boys, who will think they're the next Rolling Stones. And the
other (unintelligible) moved to Manhattan to make it. I have yet to meet
him. Why no applause, here, gentlemen?

Unidentified Man: For what? Five hours of pass the salt? I don't get the
point.

Mr. GANDOLFINI: (as Craig Gilbert) The point is we've gone to the moon
and beyond, but we have yet to get past the American front door. And
when we get past that door, what do you think we're going to find? The
smiling faces on the Christmas cards? The cute little jokes with the
laugh tracks? No. Now, no one has ever done this before. So if anyone
should be asking what the point is, it should be me, of having to beg to
finance what could be the most groundbreaking 10 hours of TV ever put on
the air.

BRANCULLI: As dramatized by writer David Seltzer and directors Shari
Springer Berman and Robert Pulcini, even this early experiment in
reality TV had all the hallmarks and drawbacks of the genre. Its
subjects jockeyed for screen time and acted out for the camera. Its
producer manipulated results not only by clever editing, but by setting
up confrontations while filming. Lane and Robbins, as the often-feuding
couple, succeed in making you care for their characters, even as they're
shown making one poor decision after another.

But the most powerful moments in "Cinema Verite" come near the end, when
play-acting gives way to the real thing. And the telemovie includes
vintage clips of the real Loud family, being interviewed on "The Dick
Cavett Show" and elsewhere, talking about their time in the TV
spotlight.

Oh, and don't change channels early. The updates at the very end,
filling us in on what happened to the drama's various real-life
characters, are well worth the wait.

Finally, there's Sunday's "Treme," the second-season return of the show
about post-Katrina New Orleans. It's by David Simon and Eric Overmyer
from "The Wire," so it's not a simple snapshot. In fact, in this new
season, which begins 14 months after Katrina, the focus is broader.
Janette, the talented cook played by Kim Dickens from "Deadwood," is now
working for a dictatorial chef in New York, and she's not the only
central character who has fled to another city.

But some have stayed, determined to rebuild the city and their own
lives. Horn player Antoine Batiste, played with such seeming ease by
Wendell Pierce, continues to slide from gig to gig, but has dreams of
starting his own band. So does DJ Davis McAlary, played by Steve Zahn.

And perhaps the most emotional story line as this second season begins
is that of Toni Bernette, played by Melissa Leo, who won an Oscar
between seasons for her supporting role in "The Fighter."

In last season's finale, her professor husband, played by John Goodman,
committed suicide, but their daughter Sophia still thinks his death by
drowning was an accident. The mother knows better, but has other
problems to confront, like the concerns of people she represents as a
lawyer, trying to make sense of all the red tape, missing records and
overworked police force.

David Morse, as police lieutenant Terry Colson, represents all three, as
in this scene, when he meets Melissa Leo's Toni for a quick meal at a
local diner. At first, it's all business. But before long, it's all
personal.

(Soundbite of TV show, "Treme")

Ms. MELISSA LEO: (as Toni Bernette) When are you going to stop harassing
me on (unintelligible) on Jackson Square?

Mr. DAVID MORSE: (as Terry Colson) Oh, are we going to fight about that,
too? How's Sophia?

Ms. LEO: (as Toni Bernette) Depressed, angry, anxious. Aren't we all?

Mr. MORSE: (as Terry Colson) Everybody is out of their minds.

MS. LEO: (as Toni Bernette) How are yours?

Mr. MORSE: (as Terry Colson) Fine. I guess. (unintelligible) as you get
them on the phone, it's always monosyllables and, you know,
multitasking. I can always tell. Yeah, oh. Sure, dad. What?

Ms. LEO: (as Toni Bernette) Sounds familiar.

(Soundbite of laughter)

Mr. MORSE: (as Terry Colson) It's been six months.

Ms. LEO: (as Toni Bernette) Seven.

Mr. MORSE: (as Terry Colson) Things getting any better?

Ms. LEO: (as Toni Bernette) (unintelligible)

Mr. MORSE: (as Terry Colson) Talk about it.

Ms. LEO: (as Toni Bernette) It was an accident. She knows.

BRANCULLI: I love that scene, in part because it pairs two of my
favorite actors from two of my favorite series: Leo from "Homicide: Life
on the Street" and Morse from "St. Elsewhere." But it's also because, as
with everyone else in "Treme," I believe these characters. I root for
them. I worry about them. And boy, do I love the music they play.
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Transcripts are created on a rush deadline, and accuracy and availability may vary. This text may not be in its final form and may be updated or revised in the future. Please be aware that the authoritative record of Fresh Air interviews and reviews are the audio recordings of each segment.