Translator: Tanya Cushman Reviewer: Peter van de Ven
Have you ever been in a hedge maze?
If you don't know what I'm talking about,
these are mazes made of tall hedges, so tall you can't see over them.
Inside, the paths twist and turn;
there's lots of dead ends and false starts and blind alleys.
The goal of the maze is to get to the center,
where there's a prize waiting for you.
Imagine some wondrous hidden treasure.
With the really big ones, you can get stuck inside for hours,
but you know that there's got to be a way in.
If you keep on trying, you'll get to that treasure.
I sometimes think that I live in a hedge maze.
My days are filled with twists and turns and dead ends and blind alleys.
I almost find myself right back where I started,
having gone in circles for a while.
I know there's something really important at the end of my journey,
but I sometimes question whether I'll ever get there,
and yet I keep on trying.
You see, I'm in the midst of a 34-year battle with cancer.
No, it's not what you're thinking - I'm not a cancer survivor,
but I've been studying the disease for more than half my life.
I think about cancer every day.
And having been in this particular maze for so long,
I've learned a few things about how to stick with it
when the answer always seems one step away.
Today, I direct the Koch Institute at MIT,
directly across the street from where we're speaking.
And in this role,
I support the work of hundreds of cancer scientists and cancer-oriented engineers
who are working across disciplines
trying to develop novel situations to the long-standing problems of cancer.
Each day we make progress, and each day we experience failure.
Some experiments provide brilliant new insights;
most experiments provide nothing.
It's a classic case of two steps forward, one step back.
But when you're trying to do something for the first time -
and that's what all good science is -
there are no turn-by-turn directions.
One discovery enables the next experiment.
Ultimately, the results hang together,
and the landscape begins to look more familiar.
Little by little, we make progress.
Little by little, we unlock the mysteries of cancer.
It's a painstaking process,
incredibly rewarding on some days,
infuriating on others.
I'm guessing you've had these days in your life pursuits as well.
I'm not the only one in this room who's been stuck in a maze.
So, why do we keep going?
Why do we press on?
As a cancer researcher, I'd suggest there are three important factors.
The first is passion.
A passion to do something bigger than yourself -
for your family, for your community or maybe even for humanity.
The second is history;
history guiding us to the best path forward.
And the third is progress,
making progress towards your goal,
knowing that you're going to get there,
maybe not today, but someday.
For the cancer researcher, there's actually a confluence of passions.
On the one hand, every cancer researcher I know
is driven to develop a world without cancer.
In academic labs and government labs and industry labs,
individuals who have chosen this profession want to do their part,
even if it's a small part,
to address a major human health problem.
And we can all agree that cancer is that.
Human beings have been developing cancer
for as long as there have been human beings.
It's an inevitable risk of multicellular organisms like us
who live a long time.
And we can accelerate that risk by various self-inflicted insults,
like cigarette smoking, that causes damage to our DNA
and mutations in the genes that regulate normal cellular growth.
Some researchers are motivated by the enormity of the problem.
In the next year, 1.6 million Americans will be diagnosed with cancer,
and that doesn't include another million
who are diagnosed with non-melanoma skin cancer.
600,000 people will die from the disease.
That's more than 1,500 per day.
Worldwide, more than 8 million people will die from cancer this year.
That's more than AIDS, malaria and tuberculosis combined.
Clearly, although we are making progress, cancer remains a major health problem.
But I find that the cancer researcher
is motivated more so by the individual cases:
the family member, the friend, the patient
or perhaps somebody you've never met who was lost to cancer.
Joining the struggle to understand cancer and doing something about it
addresses an inherent instinct we all have
in trying to help our fellow human being.
Believe me, these motivations are stronger than the big, scary statistics;
it's personal and deeply emotional.
The other passion that drives cancer researchers
is the discovery process itself.
Scientists are, at heart, explorers, trying to understand the unknown.
When you're in the midst of that maze, even with all the challenges,
it's exhilarating.
It allows you to distill your knowledge and your creativity
into that perfect experiment.
And the result of that experiment
might hold the key to unlock one of the secrets of cancer.
And in that moment of discovery,
when it's just you and that key experimental result,
you realize that you're seeing something important
that no one has ever seen before.
That's a truly awesome moment.
For me, the decision to become a cancer researcher
came early and quite suddenly.
I was a college student,
and I heard a lecture by an MIT professor named Bob Weinberg.
I'd never heard of him before.
He told us about his research related to specific mutations in cancers,
alterations in normal genes that turn them into a cancer-causing form.
I was captivated.
I was hooked.
Because the implications of this were that if all cancers were different
by specific characteristic mutations
that explained and directed their abnormal behavior,
perhaps we could find new medicines that would counteract those effects,
that would be more effective, more selective anti-cancer agents.
This is what I wanted to do.
After college, I went off to graduate school at UCSF
and had the privilege of working with Harold Varmus,
who went on to win the Nobel Prize for his work in cancer genetics.
Convinced that cancer genetics was the way forward,
for my post-doctoral studies, I decided to join the lab of Bob Weinberg,
whose lecture had inspired me to enter the field years before.
My project was to use new methods in genetic engineering
to create better, more powerful preclinical models of cancer.
I arrived in Bob's lab with gusto, brimming with overconfidence.
(Laughter)
And then I spent the next four years failing.
Everything I tried didn't work.
Techniques failed and failed again and again.
Weeks went by, months, years without a single significant result.
When they finally did work,
the preclinical models that we developed had unexpected and disappointing outcomes.
The results were subtle;
the biology was complex.
With each setback,
I found it harder and harder to drag my sorry ass back into the lab.
What was the point?
Perhaps I should just fold my cards and go off and become a lawyer.
I was helplessly stuck in the maze.
But convinced that it should work and the project was still worth doing,
we carried on.
And with contributions from many labs around the world,
we eventually did succeed.
In the process, we figured out how to make those techniques work better.
We can now perform them with ease.
The preclinical models that we developed have been highly useful for my lab;
they formed the foundation of my research for more than 20 years,
and they've become a mainstay of cancer researchers the world over.
I've been faced with this problem many times in my research career:
kill the project and move on or persevere?
Sometimes it makes sense to stop;
the techniques are just not mature enough to succeed,
or we just don't know enough to tell us what the results are explaining to us.
But when you decide to go on,
the stories from the past, of success, provide guidance and motivation.
As an example, let me tell you that the very first clue
that cancer is different from normal cells by specific genetic alterations
happened in 1960.
It happens to be the year of my birth, and that was not that long ago.
(Laughter)
Researchers in Philadelphia discovered that for a particular type of leukemia,
there was a characteristic chromosomal alteration,
which has now become known as the "Philadelphia chromosome."
Over the next two decades,
many researchers then characterized the nature of the genes
that were altered in that chromosome,
and still other researchers, in industry and academia,
then developed medicines that could counteract the effects of those mutations.
Patients with this form of leukemia, which used to be uniformly fatal,
now take these medicines with their orange juice in the morning
with little or no side effects.
And this keeps their cancers at bay.
The first of these medicines, Gleevec,
was approved by the Food and Drug Administration in 2001,
41 years after the Philadelphia chromosome was first observed.
There were many twists and turns in this story, lots of blind alleys,
and there actually are some still today,
but this example provides an important lesson in staying the course,
ultimately to arrive at a critical milestone
for cancer patients and for the field of cancer research.
What took 41 years in the development of Gleevec is happening much faster now.
Technologies are improving; timelines are shrinking.
New methods to stimulate the immune system to fight cancer
are showing great promise.
Developments in DNA sequencing technology are allowing more and more cancer patients
to get the genomes of their cancer sequence
to find actionable mutations,
mutations that might make them susceptible to a specific type of anti-cancer agent.
Oncologists are now armed with an array of such agents,
and there are more to come.
We've entered a new era of precision cancer medicine.
This is benefiting a tremendous number of cancer patients today.
For example, let me tell you the case of Stacey Ray,
a woman I never met but for whom I feel a close kinship.
In February of 2009, at the age of 48,
Stacey was diagnosed with metastatic lung cancer,
which had already spread to her limbs and to her brain.
This was a devastating diagnosis, to be sure,
and also completely unexpected because Stacey had never smoked.
So advanced was Stacey's disease
that her doctors told her that she probably just had a few months to live.
They prescribed conventional chemotherapy and told her to get her affairs in order.
These are not the words a cancer patient wants to hear.
I learned about Stacey's situation from my sister,
who called me to ask if there were any research developments
that might benefit her.
In fact, in the recent past,
two mutations had been identified in a subset of lung cancers,
and for these particular lung cancers
there were medicines directed at those mutations.
On my urging, Stacey's DNA was sequenced and found to have one of those mutations,
which, amazingly enough, had just been discovered just two years before
by a researcher in Tokyo, Japan.
With the help of Alice Shaw, an oncologist,
Stacey was enrolled in a clinical trial for this medicine,
and almost immediately, her tumors shrank dramatically.
Thanks to a basic science discovery made two years before
and the diligence efforts of industry scientists and clinical investigators,
Stacey was given a reprieve of her death sentence.
She returned to work; she returned to her life.
Thanks to a basic science discovery made by a researcher half a world away,
Stacey was given the precious gift of time.
This is what progress looks like.
Unfortunately, this story does not have a happy ending.
It's the maze at its most frustrating.
Stacey's cancer evolved mechanisms to evade the drug's action,
and in the spring of 2011, she passed away.
Two steps forward, one step back.
It's now time for researchers to get back to the lab,
figure out how that resistant mechanism occurred.
In time, oncologists will be armed with countermeasures
to overcome the evasive action that Stacey's cancer took,
and the outcome for future patients will be better.
Two more steps forward.
As a naive 20 year old,
I thought the path from cancer science to cancer solutions
would be straight and easy to navigate.
In fact, the maze that is cancer is incredibly complex.
The solutions that we have developed
have come from the dedicated efforts of a legion of researchers
who are committing to find those solutions
no matter how hard it is,
no matter how long it takes.
We stay in life's mazes because we have a passion,
a passion to succeed.
It's what drives us in our darkest moments;
it's the wind in our sails.
We use history to help illuminate the path forward,
and we notice the progress that we make
and those who are in our maze with us make
to give us momentum and confidence that we will reach our goals.
And we cancer researchers, we will prevail.
We'll develop techniques that prevent certain cancers from occurring.
We'll intercept certain cancers
before they develop too far and they can be more easily managed.
And I predict that in my lifetime,
using the tools that science and technology have provided us,
for those cancers that are now all too often lethal -
pancreas cancer, glioblastoma, advanced forms of lung cancer and more -
we will be able to effectively control these diseases
and, in increasing numbers, cure them.
I'm looking forward to getting a look at that hidden treasure;
I'm sure we all are.
Thanks very much.
(Applause)