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Paula Hammond: A new superweapon in the fight against cancer

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Cancer is a very clever, adaptable disease. To defeat it, says medical researcher and educator Paula Hammond, we need a new and powerful mode of attack. With her colleagues at MIT, Hammond engineered a nanoparticle one-hundredth the size of a human hair that can treat the most aggressive, drug-resistant cancers. Learn more about this molecular superweapon and join Hammond's quest to fight a disease that affects us all.

- Medical researcher and educator
Paula Hammond, head of MIT's Department of Chemical Engineering, is developing new technologies to kill cancer cells. Full bio

Cancer affects all of us --
00:12
especially the ones that come
back over and over again,
00:14
the highly invasive
and drug-resistant ones,
00:18
the ones that defy medical treatment,
00:21
even when we throw our best drugs at them.
00:23
Engineering at the molecular level,
00:27
working at the smallest of scales,
00:30
can provide exciting new ways
00:32
to fight the most aggressive
forms of cancer.
00:35
Cancer is a very clever disease.
00:39
There are some forms of cancer,
00:42
which, fortunately, we've learned
how to address relatively well
00:43
with known and established
drugs and surgery.
00:48
But there are some forms of cancer
00:52
that don't respond to these approaches,
00:54
and the tumor survives or comes back,
00:56
even after an onslaught of drugs.
00:59
We can think of these
very aggressive forms of cancer
01:01
as kind of supervillains in a comic book.
01:05
They're clever, they're adaptable,
01:09
and they're very good at staying alive.
01:12
And, like most supervillains these days,
01:15
their superpowers come
from a genetic mutation.
01:18
The genes that are modified
inside these tumor cells
01:24
can enable and encode for new
and unimagined modes of survival,
01:27
allowing the cancer cell to live through
01:32
even our best chemotherapy treatments.
01:35
One example is a trick
in which a gene allows a cell,
01:38
even as the drug approaches the cell,
01:43
to push the drug out,
01:46
before the drug can have any effect.
01:49
Imagine -- the cell effectively
spits out the drug.
01:51
This is just one example
of the many genetic tricks
01:56
in the bag of our supervillain, cancer.
01:59
All due to mutant genes.
02:01
So, we have a supervillain
with incredible superpowers.
02:04
And we need a new and powerful
mode of attack.
02:09
Actually, we can turn off a gene.
02:13
The key is a set of molecules
known as siRNA.
02:17
siRNA are short sequences of genetic code
02:20
that guide a cell to block a certain gene.
02:25
Each siRNA molecule
can turn off a specific gene
02:28
inside the cell.
02:32
For many years since its discovery,
02:35
scientists have been very excited
02:37
about how we can apply
these gene blockers in medicine.
02:39
But, there is a problem.
02:43
siRNA works well inside the cell.
02:44
But if it gets exposed to the enzymes
02:47
that reside in our bloodstream
or our tissues,
02:50
it degrades within seconds.
02:53
It has to be packaged, protected
through its journey through the body
02:55
on its way to the final target
inside the cancer cell.
02:59
So, here's our strategy.
03:03
First, we'll dose the cancer cell
with siRNA, the gene blocker,
03:06
and silence those survival genes,
03:10
and then we'll whop it with a chemo drug.
03:11
But how do we carry that out?
03:14
Using molecular engineering,
03:16
we can actually design a superweapon
03:19
that can travel through the bloodstream.
03:23
It has to be tiny enough
to get through the bloodstream,
03:25
it's got to be small enough
to penetrate the tumor tissue,
03:28
and it's got to be tiny enough
to be taken up inside the cancer cell.
03:32
To do this job well,
03:36
it has to be about one one-hundredth
the size of a human hair.
03:38
Let's take a closer look
at how we can build this nanoparticle.
03:44
First, let's start
with the nanoparticle core.
03:48
It's a tiny capsule that contains
the chemotherapy drug.
03:51
This is the poison that will
actually end the tumor cell's life.
03:55
Around this core, we'll wrap a very thin,
03:59
nanometers-thin blanket of siRNA.
04:03
This is our gene blocker.
04:06
Because siRNA is strongly
negatively charged,
04:08
we can protect it
04:12
with a nice, protective layer
of positively charged polymer.
04:14
The two oppositely charged
molecules stick together
04:19
through charge attraction,
04:22
and that provides us
with a protective layer
04:24
that prevents the siRNA
from degrading in the bloodstream.
04:26
We're almost done.
04:29
(Laughter)
04:31
But there is one more big obstacle
we have to think about.
04:32
In fact, it may be the biggest
obstacle of all.
04:36
How do we deploy this superweapon?
04:39
I mean, every good weapon
needs to be targeted,
04:41
we have to target this superweapon
to the supervillain cells
04:43
that reside in the tumor.
04:47
But our bodies have a natural
immune-defense system:
04:49
cells that reside in the bloodstream
04:53
and pick out things that don't belong,
04:55
so that it can destroy or eliminate them.
04:58
And guess what? Our nanoparticle
is considered a foreign object.
05:00
We have to sneak our nanoparticle
past the tumor defense system.
05:05
We have to get it past this mechanism
of getting rid of the foreign object
05:09
by disguising it.
05:15
So we add one more
negatively charged layer
05:17
around this nanoparticle,
05:21
which serves two purposes.
05:23
First, this outer layer is one
of the naturally charged,
05:24
highly hydrated polysaccharides
that resides in our body.
05:28
It creates a cloud of water molecules
around the nanoparticle
05:33
that gives us an invisibility
cloaking effect.
05:38
This invisibility cloak allows
the nanoparticle
05:42
to travel through the bloodstream
05:44
long and far enough to reach the tumor,
05:46
without getting eliminated by the body.
05:49
Second, this layer contains molecules
05:51
which bind specifically to our tumor cell.
05:56
Once bound, the cancer cell
takes up the nanoparticle,
06:00
and now we have our nanoparticle
inside the cancer cell
06:04
and ready to deploy.
06:08
Alright! I feel the same way. Let's go!
06:11
(Applause)
06:13
The siRNA is deployed first.
06:19
It acts for hours,
06:24
giving enough time to silence
and block those survival genes.
06:25
We have now disabled
those genetic superpowers.
06:31
What remains is a cancer cell
with no special defenses.
06:35
Then, the chemotherapy drug
comes out of the core
06:38
and destroys the tumor cell
cleanly and efficiently.
06:41
With sufficient gene blockers,
06:46
we can address many
different kinds of mutations,
06:48
allowing the chance to sweep out tumors,
06:51
without leaving behind any bad guys.
06:54
So, how does our strategy work?
06:56
We've tested these nanostructure
particles in animals
07:01
using a highly aggressive form
of triple-negative breast cancer.
07:05
This triple-negative breast cancer
exhibits the gene
07:08
that spits out cancer drug
as soon as it is delivered.
07:11
Usually, doxorubicin -- let's call
it "dox" -- is the cancer drug
07:15
that is the first line of treatment
for breast cancer.
07:20
So, we first treated our animals
with a dox core, dox only.
07:23
The tumor slowed their rate of growth,
07:30
but they still grew rapidly,
07:32
doubling in size
over a period of two weeks.
07:34
Then, we tried
our combination superweapon.
07:37
A nanolayer particle with siRNA
against the chemo pump,
07:41
plus, we have the dox in the core.
07:45
And look -- we found that not only
did the tumors stop growing,
07:48
they actually decreased in size
07:53
and were eliminated in some cases.
07:55
The tumors were actually regressing.
07:58
(Applause)
08:01
What's great about this approach
is that it can be personalized.
08:09
We can add many different layers of siRNA
08:13
to address different mutations
and tumor defense mechanisms.
08:16
And we can put different drugs
into the nanoparticle core.
08:19
As doctors learn how to test patients
08:23
and understand certain
tumor genetic types,
08:26
they can help us determine which patients
can benefit from this strategy
08:30
and which gene blockers we can use.
08:34
Ovarian cancer strikes
a special chord with me.
08:38
It is a very aggressive cancer,
08:41
in part because it's discovered
at very late stages,
08:43
when it's highly advanced
08:46
and there are a number
of genetic mutations.
08:47
After the first round of chemotherapy,
08:50
this cancer comes back
for 75 percent of patients.
08:53
And it usually comes back
in a drug-resistant form.
08:58
High-grade ovarian cancer
09:02
is one of the biggest
supervillains out there.
09:03
And we're now directing our superweapon
09:05
toward its defeat.
09:07
As a researcher,
09:11
I usually don't get to work with patients.
09:12
But I recently met a mother
09:15
who is an ovarian cancer survivor,
Mimi, and her daughter, Paige.
09:18
I was deeply inspired
by the optimism and strength
09:24
that both mother and daughter displayed
09:28
and by their story of courage and support.
09:31
At this event, we spoke
about the different technologies
09:34
directed at cancer.
09:38
And Mimi was in tears
09:40
as she explained how learning
about these efforts
09:41
gives her hope for future generations,
09:44
including her own daughter.
09:46
This really touched me.
09:49
It's not just about building
really elegant science.
09:51
It's about changing people's lives.
09:54
It's about understanding
the power of engineering
09:58
on the scale of molecules.
10:01
I know that as students like Paige
move forward in their careers,
10:03
they'll open new possibilities
10:07
in addressing some of the big
health problems in the world --
10:08
including ovarian cancer, neurological
disorders, infectious disease --
10:12
just as chemical engineering has
found a way to open doors for me,
10:17
and has provided a way of engineering
10:22
on the tiniest scale,
that of molecules,
10:24
to heal on the human scale.
10:28
Thank you.
10:31
(Applause)
10:32

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About the Speaker:

Paula Hammond - Medical researcher and educator
Paula Hammond, head of MIT's Department of Chemical Engineering, is developing new technologies to kill cancer cells.

Why you should listen

Professor Paula T. Hammond is the Head of the Department of Chemical Engineering and David H. Koch Chair Professor in Engineering at the Massachusetts Institute of Technology (MIT). She is a member of MIT's Koch Institute for Integrative Cancer Research, the MIT Energy Initiative and a founding member of the MIT Institute for Soldier Nanotechnology. She has recently been named the new head of the Department of Chemical Engineering (ChemE). She is the first woman and the first person of color appointed to the post. She also served as the Executive Officer (Associate Chair) of the Chemical Engineering Department (2008-2011).

Professor Hammond was elected into the 2013 Class of the American Academy of Arts and Sciences. She is also the recipient of the 2013 AIChE Charles M. A. Stine Award, which is bestowed annually to a leading researcher in recognition of outstanding contributions to the field of materials science and engineering, and the 2014 Alpha Chi Sigma Award for Chemical Engineering Research. She was also selected to receive the Department of Defense Ovarian Cancer Teal Innovator Award in 2013. She has been listed in the prestigious Highly Cited Researchers 2014 list, published by Thomson Reuters in the Materials Science category. This list contains the world's most influential researchers across 21 scientific disciplines based on highly cited papers in the 2002-2012 period. She is also included in the report: The World's Most Influential Scientific Minds 2014.

Professor Hammond serves as an Associate Editor of the American Chemical Society journal, ACS Nano. She has published over 250 scientific papers and holds over 20 patents based on her research at MIT. She was named a Fellow of the American Physical Society, the American Institute of Biological and Medical Engineers, and the American Chemical Society Polymer Division. In 2010, she was named the Scientist of the Year by the Harvard Foundation.

Professor Hammond received her B.S. in Chemical Engineering from MIT in 1984, and her M.S. from Georgia Tech in 1988 and earned her Ph.D. in 1993 from MIT.