Dr. James Allison doesn't look the part. The
diehard Willie Nelson fan has an unruly head of gray hair and
plays harmonica with his blues band. He's been described in the
press as a "carousing Texan." He's also a Nobel laureate, a man
whose unwavering faith in and curiosity about the human immune
system led to one of the most revolutionary developments in
cancer research in over a century. Oh, and he saved my life.
Eight years ago, after a diagnosis Stage 4 melanoma, I became
one of the first human subjects in a combination clinical trial
Allison was heading up at Memorial Sloan Kettering Hospital. The
trail would take a unique approach, stimulating my T-cells to
recognize and destroy my rapidly running amok tumors. Twelve
weeks later, I was cancer free.
There have been plenty more encouraging successes like mine over
the past several years, thanks to clinical trials and FDA
approvals for innovative, immune system-based approaches to
cancer. And Dr. Allison is now the subject of a new documentary
from director Bill Haney, narrated by Lone Star State native
Woody Harrelson and carrying the appropriately simple name,
"Breakthrough." It's a deep dive into the fascinating science of
immunotherapy, and a portrait of an iconoclast who always
believed there was another way to treat cancer beyond the
traditional — and unreliable — trifecta of chemo, radiation and
surgery.
The last time I saw Jim Allison was a year ago, when he was in
New York to receive the Dr. Paul Janssen Award for Biomedical
Research. There was a lot of buzz in the room that evening that
this award might be a prelude to the Nobel. Sure enough, a few
weeks later, Allison did indeed find himself standing on a stage
with the king of Sweden. "Breakthrough" captures the electricity
of that moment, and then goes back and shows you just how much
frustration and heartbreak and failure and hustle and tenacity
and collaboration led up to it. I spoke to Allison via phone
recently about the new era in cancer, and the long journey from
Alice to Stockholm.
This conversation has been edited and condensed for clarity.
I know so much about you and your story, but I'm curious about
how this movie came about, and its timing in relation to the
Nobel Prize announcements.
Bill emailed me about two years ago. I got an introduction from
a mutual friend of ours, the cancer biologist Tyler Jacks from
MIT. Bill was searching for something, a unifying topic. He
thought about cancer drugs, so Tyler suggested me. We started
talking way before anything with the prizes. He came to Houston.
He spent a lot of time filming, getting to know me and talking
in various locations. Filming had actually ended when the
announcement about the Nobel was made. Everything else had been
shot, but it made a suitable end to the movie, I guess.
This is an intimate exploration of your life, your family, your
losses, your marriages. Did you have any hesitation about doing
something like this? You are also a man of medicine. People
expect, I think, a certain degree of detachment from people in
the medical world. This is very personal. This is very raw and
unguarded, you holding a beer and playing with Willie Nelson.
One of the things that Bill wanted us to do, and I actually
agree with, was to try to have an accurate portrayal of what
scientists and what doing science are like. I'm not going to say
my way of doing it or my experience is generalizable to
everybody, but the point is, you can do science and have fun.
[But] you've certainly got to be detached in weighing evidence
and weighing data when you're making a diagnosis for a patient.
The same is true when doing research. We do believe there's such
things as facts, and you have to get the facts right. Your views
don't matter. It's, the data, the data.
And then there's the human side. This movie is about the passion
and the personal drive of not just you, but everyone in this
story. You were out there in the trenches when very few people
believed in the power of immunotherapy. You had to lobby for
financial support and for research support. What does it feel
like now? Does it feel maybe it could've happened faster if we'd
had more people who had more faith?
When we were doing the early work, it was all basic science.
Nobody could criticize that. We were trying to understand how
T-cells work. When you'd get up to the point of saying, "Well,
we're going to do immunotherapy," that's when skepticism started
coming out from cancer biologists and oncologists.
In time, I tried to flip it around. Instead of saying, "Hey,
we're looking for a cure for cancer," I said, "Here. Look at
this mechanism we've discovered. Look what we can do with it."
That flipped it on its head, both in our approach to doing the
science and also the approach of trying to get it to people.
I didn't want to start off saying, "I'm going to show you how
we're going to cure cancer." I'd expect people immediately to
say, "Oh, yeah, right. Here we go again, some more of this
immunology junk." So, "Okay, let me show you something here.
This is a really cool thing about how T-cells are regulated.
There's this little bitty place here where we've got a system
built in to stop a response. If we can figure out how to let
that loose, let the immune system rip, the cancer part will take
care of itself. Imagine that."
Can you explain why is it that immunotherapy only seems to work
right now on certain cancers, and why it only seems to work
right now on certain people? We're not yet at the point where
this is the magic bullet. It was magic for me, but that's still
unusual.
Let's step back, since we are not doing anything whatsoever to
directly engage the cancer but rather manipulate the immune
system. In the real world, cancer is not just cancer. It's many
different diseases. Some, like melanoma, have already attracted
the attention of the immune system. They're robustly infiltrated
with immune cells but just can't get the job done. Melanoma and
other kinds of cancers, particularly those caused by carcinogens
such as tobacco or ultraviolet radiation, have many, many many
mutations in the cells. The fact that some of these cancers have
so many mutations is what makes them largely resistant to
therapy by more conventional means. The immune system really
thrives on diversity and heterogeneity. Some of the cancers that
have fewer mutations don't have so many target antigens
probably. That's one reason that they don't respond quite as
well.
Prostate cancer, for example, although we're getting responses
for prostate now. It's early days. In other tumors like
glioblastoma and pancreatic cancer, which are notoriously
difficult, there are a lot of individual aspects that would make
them difficult targets. They've got their own defense mechanisms
which help protect them. This is a harder nut to crack, but
we're studying it. Where we're at now, it's not just melanoma on
the approvals, by the way. It's melanoma, non-small-cell, small
cell lung cancer, kidney cancer, bladder cancer, Hodgkins
lymphoma, head and neck cancer, Merkel cell carcinoma. The list
goes on and on.
A few years ago, the kind of diagnoses that people like me had,
it was just a death sentence. I certainly as a patient didn't
understand immunotherapy, because the common parlance of cancer
previously was, "Everybody does chemo, everybody does
radiation." Do you think that that is changing? Do you think
that patients are becoming more sophisticated?
I think they are, and also I think we are becoming more
sophisticated. Oncologists for example. They'll call us to get
biopsies of tumors and start dissecting them, in terms of how
cellular and molecular things are going on and how they change
when they hit it with immunotherapy. We are beginning to learn
how to go from a 30% to 40% response, like we're seeing in
kidney cancer now. We are learning carefully how to start
building on that to get it up. Maybe we can get melanoma close
to 100%, Maybe we can get some of the other cancers up higher by
studying what's going on. In the movie, the question was "Will
this work?" Now the question is how do we get in to work in more
kinds of cancer at higher frequencies.
What we're doing now is sort of a reverse translation approach.
Before, we'd look at what happened to the mouse in the
laboratory and then take it to the people. Now we're looking and
seeing what's going on to the people. We're going back to the
bench with human tissues and seeing what changes, and maybe we
can model that in some cases in the animals to see, "Does this
work in this situation?" We're constantly in process from the
lab to the clinic, from the clinic back to the lab and to the
lab back to the clinic again. We're trying to accelerate that
cycle as fast as we can. It is disappointing that we're not at
100% for the more kinds of cancer, even 50%. We can be, I think.
There's something that I learned from [pioneering immunotherapy
researcher] Lloyd Old. He always said, "You should learn
something from every patient." So that's what we're at now. It's
not just treating patients, looking for clinical signal or not,
and moving on. It's rather, "What happened? What are the
molecules that changed? What are the cells that changed? Which
ones are good? Which ones are bad? How do we stay on top of
this?" It's an exciting time, and I'm really optimistic about
these combinations to improve things.
Saved my life. Saved my life when the outlook was not good. It
was very moving to me near the end of the film when you were
reading that letter from a woman whose husband was treated. You
still take this very personally. I saw it when you were at the
Janssen Awards, you were teary and moved. This is still a person
to person experience for you.
Absolutely. I've gotten to know [early clinical trial success
story] Sharon Belvin very well. Just saying, "Wow, here she is,
many years later with a family and everything, after she had
nothing to look forward to," that's what it's all about.
This is a movie that shows a lot of disappointment and a lot of
failure. The story of of medicine is often, "We have these
expensive drugs and these protocols and the pharmaceutical
industry, they're the big bads." What is rarely understood is
the amount of failure and the amount of time that goes into a
scientific breakthrough like this one. Was that a priority for
you in telling the story?
It usually is. What I try to say is, "You can't just walk in and
prove something. How science works is you try to disprove
something and if you can't, maybe it's right." You are wrong
most of the time and you have to get used to that, but you learn
from the mistakes.
The movie does a great job of capturing some of the major
frustrating moments along the way. There were many side routes
we started to take, and they didn't work out so we pulled back,
regrouped, started again. That's just the way it works. If
you're really doing cutting edge stuff, you don't know what the
right answers are when you ask the question. Otherwise it'd be
easy to show. So you just have to persist. People say, "When did
you start this work?" I think the first paper that I published
which relevant to this was in 1982.
What is the end goal? When will you rest, Jim Allison?
I don't know. Right now the goal is to keep building on what
we've got try to bring it to more people. I guess I'll rest when
I don't have enough energy to do it, or the brains to keep
making contributions.
# # #
"Breakthrough" opens in theaters across the country on September
27. |
