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>> Alex Weinert: Hi, and welcome to the Microsoft Research Speaker Series. I
was told to say that. I hope I said it okay. My name is Alex Weinert, and I'm
here to talk a little bit to introduce Dr. Michael Jensen, who is our speaker
today. That's me, and the person clinging on to me is my son, Owen, at about 9
years old, probably six months or so after he started treatment for acute
lymphoblastic leukemia at Seattle Children's. Just shortly after Dr. Jensen
joined the team at Seattle Children's, coming from -- I hope I get this
right -- City of Hope, and that was largely made possible by the Ben Town
Foundation, who did some amazing work to get him up here.
And I was going to give you a quick little tour of why this talk matters a lot
to me and try to put some context around it, because the science is amazing,
and the technology is amazing, but it's actually a very human story at the
bottom of it.
So this is very much my personal story. So I want to talk to you about a
period from 2009, December, to March of 2010, which I would talking from zero
to 60 in four seconds if you have a good car. This is from wonderful to freak
out in three months.
In December, I would say everything was just great. By the end of December,
there was some weird kind of frequency in the amount of colds and sinus
infections and things like that that Owen was getting, but otherwise pretty
well. To the point where in January, he did something -- we're into cycling in
my family, and there's a mountain bike ride called the stinky spoke, and he
came across the line and everybody was amazed, and he was the youngest kid to
ever do that ride. Very, very strong, very fit athletic kid.
Still pretty strong. He had wanted to ride a charity ride to raise money for
cancer, actually, which was a 50-mile ride, so he'd been training pretty ride
and he went into a ride called the Chilly Hilly which is 30 miles. But he was
very weak and kind of off his game, I would say, at that time.
And by March, we find out, and some of this is retroactive, that we'd learned
this, but he'd been staying in from recess. He'd stopped going to lunch. He
had stopped eating breakfast at home. He started losing weight. He was
getting pallid. On March 21, we went out for a fun day, but he slept all the
way to the park and he didn't do anything at the park and he slept all the way
home. And I got really, it was like lights started coming on.
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So I got out a grocery list piece of paper and I wrote down in pencil, and I
still have this piece of paper, all the symptoms that I could think of and what
I'd been seeing since about January.
As I wrote the list, I got more and more kind of centered on what was probably
happening. And I gave it to my wife and I said, he has to be seen tomorrow.
And she called and they couldn't see him because they didn't have any schedule
time. We're like, well, this has been months building up so we can go another
day. That day, he was sent home from school with a fever of 102 degrees. But
we had the doctor's appointment set up for the morning so we thought, well,
that's all right.
We went in. He slept through the night. Went in in the morning, still had the
fever. She saw the list. This is Ballard pediatrics, if anybody cares, she
saw the list and immediately sent him for blood tests.
So here's my day, I send them off to the doctor in the morning. I good to
work, and at 3:30, I think oh, I wonder how the doctor's appointment went. Are
we on antibiotics now? And I got a text message from Heather in reply to my
message which was no, we're still in the lab. This is 3:30. I'm going into an
exec review.
And I think I had this -- yeah, so I'm going into an exec review at 3:30. And
I get this text, I'm starting to wonder what's going on. And the exec review
ends at 5:00, and I got a schedule plus, and this is through a weirdness of the
way we were communicating and her inability to reach me by phone. But the
first word I got was a schedule plus saying we need to be at Hemonc at 8:00 the
next morning. So I look up Hemonc, and it's hematology oncology and it
basically means cancer and blood disorders. So that was how I found out.
So the next morning, Owen goes in, and I want you to look at this picture.
That's him healthy. That's January, late January. That's the day he was
getting the blood tests. That's the next day. So the next day, we went in,
and -- I'm sorry. I'm getting more emotional than I thought I would.
And he was admitted, and we started chemo. And from that day to this day, he's
been taking chemo. That picture on the bottom left is a picture of his weekly
pill load. The picture in the middle from IT methotrexate, he was being neuro
toxic, his brain was basically poisoned. He had to go in for MRIs to deal with
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measuring the damage and addressing it and fixing it.
to mitigate it.
Thankfully, we were able
The picture there is when he was, I believe he was hepatotoxic, which means his
liver was failing, because of the chemo he was getting. You know, it's hair
loss, you can see that. One of the pills I have to give him every single night
has that warning label on it. It's a biohazard warning label. Okay? It says
Mercaptopurine.
In my family, we're really lucky. Owen is a standard risk low. He has great,
what's called cytology, which means the particular mutation he got that gave
him leukemia is one of the easiest ones for us to cure. He's one of the
luckiest kids out there as far as pediatric cancers go. He has it really easy.
That doesn't make it easy.
So by the numbers, and I pulled this data, there's a cite called PAC-2. This
is mostly from the organization called decog, which is a cancer oncology group.
Is that right? Children's oncology group, which is I think 250 or so hospitals
that collaborate with research and sharing data and treatment.
And so this is relatively current data. About 13,500 kids a year are diagnosed
in the U.S. About 36 a day. Mortality is about seven children a day. This is
the state of treatment today. ALL is the most common by a fairly wide margin
of the pediatric cancers, and then comes brain cancer.
So I said, you know, this is an introduction talking about a cure, and cure
with an asterisk. And so what's with the asterisk? The issue with the
asterisk is when we say cure, we're talking about 80 percent of children, not
100 percent of children. Secondly, of the statistics, I won't read through
them, but they have very, very significant side effects to the treatment. Not
just the treatment that he went through, and the suffering that he's gone
through for the last three years, but his long-term prognosis.
Like 74 percent of children will have one or more serious side effects. The
graph on the right is one I really want to call attention to. The top two
lines are average mortality for children in the United States. The bottom two
lines for female and male are for children who have been treated for cancer,
who have made it through the first five years of treatment.
these are what we call survivors.
These are people that meet the 80 percent
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criteria. This is what happens to them afterwards. That's the mortality.
Those are side effects of treatment. Secondary cancers, chemo that gives you
cancer. Radiation that gives you cancer. Chemo that gives you heart disease,
all right. Chronic cognitive disorders. Chronic depression, chronic pain.
Very serious things.
I put a picture of a single round in a chamber there with an arrow to 0.84.
That's the same statistics as Russian Roulette. Your chances of making it 25
years past treatment are worse than your chances of surviving Russian Roulette
if you're a pediatric cancer survivor.
There's a couple things I want to sign off with. One is a couple of good
pictures. One of them was inpatient last Christmas. So we made the doctors
who were rounding come in and put on reindeer. We wouldn't let them in unless
they put on reindeer heads. And the person on the left, closest to us, is
Dr. Rebecca Gardner, and Dr. Gardner is working with Dr. Jensen to begin the
phase one trials for the work he's going to talk about to you today.
And the other thing is if there's anybody who is paying attention online or in
the room would like to learn how to help, one of the things we do, and I can
give you lots of ideas, but one of them is that we have a cycling team, and we
raised about 50,000 through Microsoft last year for this research.
And then finally, if you're interested, you could go look at the link. It
might be sensitive, so I'm just going to say there exists a [indiscernible],
but it points, I think, very directly to the profound need to fund research.
And then I'm going to sign off with something that Owen was insistent we did
last night.
>>: Hello, I'm Owen Weinert. I'm an 11-year-old cancer patient in treatment
for acute lymphocytic leukemia. I was diagnosed in March of 2010 when I was
just 8 years old, and I've been taking chemo orally through injections or
through spinal tap ever since.
Dr. Michael Jensen's research is a new way to program the T cells to fight back
against cancer cells called blasts in the body. It's like adding a feature on
the body's own defense system. And so without further ado, Dr. Michael Jensen.
>> Dr. Mike Jensen: Okay. Thank you all for coming. This is a real privilege
to be able to come here and tell you about our research at Seattle Children's
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Research Institute. If I'm successful, I will hopefully open some doors for
you in to the type of work and the way we think about doing our research at the
institute, and also I think through this, you'll see some fairly startling
parallels to maybe some of the research you do here at Microsoft, and there's
potential synergies that may flow from that.
I want to also begin by thanking you, Microsoft employees, because over the
years through your employee giving programs, Seattle Children's has, I think,
benefits as one of the top five charitable organizations to receive your help,
and it's gone a long way. And we have a lot more work to do.
Also, I want to point out that we have a research institute at Seattle
Children's Hospital, Seattle Children's Research Institute, and this really
came from the recognition by the hospital about seven or eight years ago that
if we are to fully capitalize on the future well-being and health of our
children and children around the world, that Seattle Children's Hospital had to
engage in biomedical research to find the cures and the treatments to help kids
either prevent serious illness from occurring and to safeguard their futures.
So we are located, actually, in downtown Seattle. We're one of the top five
NIH funded pediatric research institutes in the country. And a lot of people
in the Seattle region don't know that we exist yet, and so I'm trying to spread
the word. We are a serious operation in terms of biomedical research, and I'm
here to tell you a little bit about our cancer research program.
So I think Owen gave you a very vivid snapshot, and his father, Alex, thank you
for that. And I think most people, if I were to say what is cancer in a child
look like, an image just like this would come up in your minds. I think for
most of you, that would be true and there's probably very few of you, and
wherever you are watching this, that hasn't seen cancer play out in a loved
one, whether it's a parent, grandparent, a friend, a child.
This image is a lot like the image of a child with leukemia if that child were
diagnosed in 1963. It hasn't changed a lot. And that's because in large part,
we are still relegated to dealing with cancer with the same basic armamentarium
that we've been using over decades now. Chemotherapy, radiation, surgery. Cut
it out, burn it out or poison it out of the body. A lot of chemotherapy
actually evolved from poisons that were developed in World War One and World
War II that we learned how to give just enough to not kill the patient with the
goal of killing rapidly proliferating cancer cells.
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With kids, we have, I guess, an opportunity as pediatric cancer specialists,
because kids have generally good hearts and they have good lungs, they have
healthy bodies, we can give more chemotherapy in higher doses to a child than
an adult could ever survive. And that's what has allowed us over the last
couple of decades to move the bar such that in 2013, about 75 to 80 percent of
kids can be what we call cured. That means the tumor doesn't come back within
five years. And you heard about some of being cured is not -- doesn't mean
that you're going to be able to have a long and uncomplicated life ahead of
you.
So we have a lot of work to do and when I talk about those cure rates in the
'70s and '80s, that's in large part because acute lymphoblastic leukemia is
very curable and that's the most common. But if you look at cure rates of the
common solid tumors that we see in kids, things like neuroblastoma and brain
tumors and rabdos, we're well below the 50 percent mark in 2013 with the most
aggressive therapies a human body can tolerate. We have to do better.
So why is it crucial for us at Seattle Children's Research Institute and other
cancer research programs around the country and around the world to try to help
create solutions through research for kids with cancer? One part of the story
is I don't think we can rely on big pharma and the industrial complex of
medical research to come to the rescue of children. That's in large part
because of the numbers you saw Alex give. You add up all the kids with cancer,
it's still called an orphan disease. And from a business perspective, it's a
business orphan disease in terms of how many of your pills you'll be able to
sell to that population.
Kids' cancer is fundamentally different than adult cancers and doesn't respond
the same. Nor do we do studies that test the potency or side effects in kids.
When we get to use a drug that's been developed for breast cancer in a child,
it's not because we know how much to give and what the side effects will be.
As pediatric oncologists, we have to do that on our own.
And the third component is there's a lot of emphasis now in pharmaceuticals to
think of cancer as -- make cancer a chronic disease. Develop pills that a
person can take every day from the time they're diagnosed to the time they pass
away that will slow the tempo, put a lid on it. And that might be great if
you're in your 70s and you can get another ten years of high quality life. But
if you're a 3-year-old with a brain tumor and the only drugs that exist are
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drugs that will give you another five, eight, ten years, that's an empty -that's an empty victory. So we have to do better. We have to do research
that's really drilling down to try to cure the disease.
And if we can do that for kids, and translate that to the common adult cancers,
everybody wins. So cancer is the number one cause of death from disease in the
United States in children. Of the toxicities, you've heard about, but they can
be life-threatening at the time, and they can cause life-long disabilities that
take away a child's future for a healthy and fulfilled life.
And the treatment of cancers, you heard, greatly increases your chances of
getting cancer 30 years later. Colon cancer rates in kids that were cured of
pediatric cancer skyrocket. So because of the therapies that we use, we doom a
lot of childhood survivors to be back in an oncology clinic again as an adult
with something like colon cancer, breast cancer, kidney cancer.
So our vision at Ben Towne Center For Childhood Cancer Research at Seattle
Children's Research Institute is to really accelerate the timetable to do
innovative translational research where all children can be cured, and we cure
them with therapies that are specific enough that it doesn't harm the body
along the way.
So in my world, I'm trained as a molecular immunologist, and I think about how
the immune system works. And in your vernacular, in some ways, immune system
uses -- the immune system uses devices to get the job done, and the device I
want to talk about today is a device of a white blood cell called a lymphocyte
and, in particular, the T lymphocyte. The T lymphocyte is really the master
regulator of the immune system.
If you develop a sore throat and your lymph nodes and your throat get swollen
and tender, that's because millions and millions of these T cells are going
into that area to rid that area of the virus that's trying to get into your
body.
T cells move throughout the body, and they have sensors, they have programs and
sensors that allow them to make decisions. And if a T cell that is roaming
your body encounters a virus that it has a sensor for, then it can do
something, a fairly typical program that it executes that goes something like
this.
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Here's a C cell. It's encountered a cell with influenza virus on the inside,
the T cell is now getting signals through its sensors that activate a program
that tell that T cell, drill holes in the membrane of the virally infected
cell, insert packets of proteins that make the virally infected cell dissolve
into a dead bit of cellular mush, if you will, and do that repetitively.
Right now, the virally infected cell has been destroyed. The virus can't come
out. The infection won't be propagated, and there are vacuum cleaner like
cells of the immune system that come by, call macrophages, that clean up the
mess.
These T cells that encounter a virus when you're six years old will be in your
body when you're 70 years old, waiting there to protect you if that virus were
to try to come in again. If you had a polio vaccine, those same T cells are in
your body protecting you from polio decades later because part of the program
for the T cells to differentiate and become a memory cell that sits back and
says, I've seen it before, I know what to do when I encounter it again.
So how do T cells make this decision? When that T cell bumps up against a
virally infected cell, it has to make a critical decision. Turn on the
program, destroy that cell or back off and say that cell is a healthy cell. I
don't want to do that. You think about it, the immune system and T cells have
to make critical decisions every day. If the T cells are too fired up and they
are not having discretion, then you get things like ought to immunity,
rheumatoid arthritis, diabetes, MS.
If the T cells are too wound down, they may come up against a fairly abnormal
cancer cell and say, well, it's not -- that cancer cell is not really like a
virally infected cell, I'm not getting all the signals that say to trigger, I'm
just going to back off and leave it alone. And that's this tight rope walk
that the immune system has to walk every day.
So let's drill down a little bit more into the molecules that are involved in
this -- you see it here, the trellis reaching out with kind of cellular hands
and fingers and probes, and basically going over the surface of another cell to
say are you okay? Are you a normal cell, or are you abnormal? And really
what's happening there on the inside of that is a number of molecules that
start to engage from the surface of the T cell to the surface of either the
virally infected cell, the cancer cell or the stimulatory cell of the immune
system.
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This is a lot like the central nervous system forming synapses. In the central
nervous system, the synapses are fairly stable over time, but in a T cell, this
T cell is roaming around the body and doing it basically on an as-needed basis.
If there is an antigen from a virus, for instance, it's going to be sitting up
in this cleft here and the T cell sensors, when that triggers, will trigger the
T cell to what I showed you, destroy the virally infected cell.
So that's the natural biology that's been integrated into T cells over the
course of evolution.
>>:
Can I ask one question?
What are APC cells?
>> Dr. Mike Jensen: APC stands for antigen presenting cells. So that's the
cell that's designed to present new things to T cells when you get a vaccine or
when you see a virus for the first time. So the immune system has evolved over
millions of years. Cancers, when they occur in the body, come from a cell that
essentially, the break is broken and the gas pedal is stuck on. The cancer
cell, within the life cycle of its existence in your body, is evolving as well.
And it's evolving and selecting against an immune system that wants to get rid
of it.
We know that if you're born with a genetic syndrome in which your immune system
doesn't form naturally, you get a lot higher cancer rates than if you're
otherwise healthy. So the immune system gets rid of most all the cancers that
are generated in our body over time, but it's that cancer cell that makes a few
extra evolutionary steps because its genome is unstable that could subvert the
immune system and basically become invisible to the immune system.
Then you have the diagnosis of cancer when you walk into the doctor's office,
but your immune system isn't globally impaired. You can still fight
infections. It's not like you have HIV virus and your immune system has been
destroyed. Because tumors use very specific mechanisms in order to thwart the
ability of the immune system to either know it's there or to be able to do
anything about it when it encounters it.
This is the problem of cancer when we, I as a doctor, see it in the clinic.
The cat's kind of out of the bag. The tumor's already had a chance over the
years that it has been quietly in the body developing to basically evade the
immune response.
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So what can we do about that? In your world and in the world of technology,
we're in a logarithmic increases in knowledge and technology and the ability to
do things, and I would say that in biomedical research, we lag behind
technologies that you probably take for granted that you see the pace of in
large part because we have difficulty accessing it in realtime.
But having said that, can we think about a T cell as a device? It's a mobile
device. And can we create apps for T cells to allow them to do something that
the cancer never expected. Basically create an orthogonal immune response that
the cancer never sees coming, because we are now reprogramming T cells,
creating artificial intelligence for T cells when we isolate them out of the
body so they can go back into the body and hunt down cancer in a way that the
immune system and the rest of the body cannot do.
So that's the concept. In many ways, I think about a T cell in ways in which
there are similar structures and functions as a personal computer. The nucleus
is essentially the hard drive. Chromosomes are depositories of large amounts
of data bits. There are programs that turn on and off, based on
transcriptional factors that go in and turn on gene expression. Messenger RNAs
made in proteins come out that is basically the functional units. So what
we're talking about is going in and putting Apps into the hard drive of T
cells, into the nucleus, into the chromosomes to create new functions.
You might get a little squirmish now.
Amy?
>>:
[indiscernible].
>> Dr. Mike Jensen:
>>:
Yes, we have a question in the back.
Could I do that at the end?
Absolutely.
>> Dr. Mike Jensen: That would be great. Remind me of that, okay. So for
those of you who have taken some molecular biology, there is something you
learned, I'm sure you remember about it and you think about it every day called
the central dogma. Which is DNA begets RNA, messenger RNA, which codes for
proteins and proteins do something. That's our grandparents' central dogma.
Boy, that's changed, because RNA and DNA and proteins can do a whole lot more
than that central dogma.
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But for us, the issue is can we create apps that are encoded by DNA that create
artificial mRNAs, that create artificial proteins and have those apps installed
in T cells so those artificial proteins can allow the T cell to attack the
cancer. So we're working along this line of thought.
And so for us, you know, state of the art phone here, point that out. How do
we do this? We make our app from recombinant DNA models that we create. We
download the app into the T cell, and one of our first areas of synthetic
biology is the app codes for a protein that's like a molecular velcro that's
designed to be a lock and key so when now this T cell bumps up against the
cancer cell, instead of the T cell saying, you're not normal, but you're not so
abnormal that I'm going to trigger you, the velcro molecules look on to
structures on the tumor sell, and on the inside of the velcro molecules, the
whole alarm system that the T cell uses, when it's triggered by a virally
infected cell. So we're creating now synthetic biology by creating artificial
velcro-like receptors to express in T cells.
I'm very happy to see that you have an app lab in your institution. I would
recommend, this is just my bias that your app lab employees wear white, long
white lab coats. It's much more impressive. Yes, sir?
>>: I'm just wondering, do the T cell successful in detecting a cancer cell be
consumed in the process?
>> Dr. Mike Jensen: No. So just like T cells that fight infections, we know
this from our lymph nodes in our neck, massive increases of a very few cells to
millions or billions of cells over the course of a day or week or two, the
infection and gone, and the evolutionary program for the trellis let's have 99
percent of those billion cells go die off. If we didn't do that, by the time
we were 21 years old, we'd weigh about 500 pounds and about 350 pounds would be
T cells, because we're always seeing infections. Our T cells are grow, they
die back. And that one percent that's left over are those memory cells that
will stay for the rest of your life and give you immunity.
It's a very good question. So I'm going to show you the app and how it works
first and then I'm going to show you under the hood how we made the app.
So this is human neuroblastoma. It's one of the most lethal forms of pediatric
cancer. These are living, human neuroblastoma cells. They're growing on a
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plastic petri dish and we're imaging them through a video camera attached to a
microscope. These cells will rapidly grow and take over the petri dish in a
matter of 24 to 48 hours. What I'm about to do is add in human T cells that
we've genetically engineered to have an app that codes for a velcro for a
neuroblastoma.
And to orient you right now, these little guys here, these are all the T cells
that have been added. There's about one T cell for every cancer cell in the
entire dish. And what I want you to notice first is how mobile these -- my
kids call these the pack man cells or angry bees. You get a sense, they're
swarming. They're going over the entire dish, but now something happens where
now they're seeing the tumor cells, and you see that there's far fewer of these
T cells that are just floating around where there's no cancer cells. They're
actually coalescing around the tumor cells, even within this short part of the
video, you see probably 80 percent of the cancer cells have been wiped clean
off the petri dish.
And you see how this plays out. The other thing I want you to see is now
there's clusters of T cells. These are not tumor cells. These are now
clusters of T cells. The number of T cells in the petri dish are starting to
grow massively, because the T cells, through the velcro molecule, have seen the
cancer cells. If we put T cells in this dish that had no velcro, there would
be a few T cells that would float around, and they would die off in 12 to 24
hours.
So as. A biologist and researcher, I'm like okay, how fast do these cells
move? How many times can one cell kill a number of tumor cells. How many
cells will come from one cell and divide and become clusters of cells. That's
one part of my mind.
And then the other part of my mind, I get this kind of Al Pacino voice that
comes on, and it goes something like, you know, hey, neuroblastoma, let me show
you my little friend, the T cells. And that's not right. I shouldn't do that.
That's not a plug for the Scarface movie, but, you know, this is pretty
exciting for us to see this.
And now we're probably about six hours after adding the T cells. I want to
point out one cell here. Your heart goes out to this guy. This is the
neuroblastoma. I think it's one of the last ones in the dish. It's like I
don't know what happened to those other guys, but I made it. I'm going to hang
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out here and I'm going to grow back and take over this dish when the T cells
are gone. It's a very ill advised perspective for that cell, and there you go.
There are no more tumor cells. This is about six hours. Radiation and
chemotherapy can't work this fast. Look at these T cells grow.
So this is a very dynamic, living therapy. We're talking about taking a tube
of blood from a patient, bringing it into a manufacturing environment, putting
the app into the T cells, growing up several million or billion of these T
cells outside the body for a week or two and then infusing that back into the
patient where those living T cells that came from the patient go back in with
this new program.
Now, you saw how rapidly these cells start to grow, and that's a good thing,
because there's a lot of tumor in the body when we treat most of our patients.
There's millions, if not trillions of tumor cells.
One app that I won't talk a lot about, but I think it's very important for this
kind of work, because this is gene therapy or genetic engineering, is we put
another app in with the velcro molecule called a suicide gene. What that means
is that if we want these T cells to go away because they're getting over active
or they've been around too long, we can give the patient a pill that activates
the suicide gene and kills just the genetically engineered cells in the body
and not the other T cells.
And that's a safety feature that we put into the system.
>>: Can you [indiscernible] sort of balances out only on the ones that we're
working?
>> Dr. Mike Jensen: That's exactly where we're going. About three slides from
now, I want to show share that with you. So what's under the hood? How did we
make this app happen? And what we did is conceptually, let's create what we
call orthogonal function of the immune system through engineering. And the way
we make these velcro molecules is we choose protein domains from monoclonal
antibodies. You probably heard of Herceptin for breast cancer, or Rituxan for
lymphoma therapy. There's a whole array of monoclonal antibody therapies.
Most of those antibodies came genetically from mice. Now we have genetic
libraries where we can make whole human libraries of antibodies and monoclonals
that come from the human genome, but it's all made artificially. We cloned the
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DNA from the antigen binding domain and we cloned the DNA from the T cell
sensor, what's natively in the T cell and we fused these molecules so it looks
like an antibody on the outside and it's a T cell receptor on the inside. And
the tumor has no idea that this is coming, because there's no parallel in the
natural immune system for this to happen.
Of course, Reese's figured this out a long time ago.
things and making something even better.
It's bringing two great
So not to alarm anyone, but in my world, in my laboratory, we work with chain
reactions and HIV and all these things, and I want to put some perspective.
Because in the media, when we talk about this research, the media says, oh, you
work with a crippled HIV virus and it scares the bejeebers out of most people.
I want to put some perspective.
So we make this recombinant DNA technology possible through instruments that
look the size of a toaster now. And the lab techs can put in the ingredients
for making DNA and a template molecule to start with. They press a button,
they go to Starbucks and have a latte. And about 90 minutes later, they come
back with two to the fifth perfect copies of that DNA.
So several billion copies over 30 cycles. And it's all replicas of artificial
sequences that we can now make in hours. And back when I was a post-doc in the
laboratory, we didn't have these machines. We had a hot water bath and a cold
water bath and a stop watch and we used to do it by hand. Now these things are
multiplex and they're controlled by servers and computers that will control
arrays of these devices to create the building blocks.
The way we get the app into the T cell is we use a remnant of the HIV virus.
HIV evolved to be really effective at getting into T cells and delivering its
genetic load. Yes, it's a crippled HIV virus, but it's been so -- we have so
torn it apart genetically that the only thing about HIV that's left to this
virus is the ability to get into the T cell and to deliver a recombinant DNA
molecules into the cell hard drive by integrating into the chromosome.
These viral vectors have no ability to make virus again. It's a one-way trip.
Put our app into the chromosome. There's nothing left and now the T cell can
go on with the only ramification of having seen that viral vector is now it has
a new genome, the new app that's working.
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So let me give you an example of how technology is changing our lives. We used
to do cancer experiments in mice where the only thing we can do is measure how
long a mouse lived or with calipers measure tumors under the skin. And that
meant that doing mouse experiments usually took months and you had to do
hundreds of mice to get the data, because you had only one outcome.
Using PCR, some bright folks decided, hey, let's clone out from the firefly,
the gene in the firefly tail that makes light. So it's a biological living
cell that can make light. And let's PCR that up so that we can express it.
Here it's expressed in bacteria. If you add in a substrate, the chemical
reaction creates photons. And now living cells can make photons of light. And
then some other engineer said let's take Hubble telescope liquid cooled CCD
cameras instead of looking at galaxies, let's look at animals.
What you get now is the ability to image in a living animal that has some
sleeping medicine light coming from the tumor. And there are different enzymes
now that can make different lights based on different chemical inputs. So you
can input the T cells by giving the mouse one medicine and couple hours later
come back, give the mouse the other medicine and image the tumor cell. This
allows us to do animal experiments with just a couple mice and because we can
recursively, in the same mouse, test and see what's going on over time, it's
very powerful, and it speeds our work up enormously.
So reprogrammed T cells can be tested in mice that have no mouse immune system.
There's no rejection going on. And I told you that T cells are mobile devices.
Here's an example of this technology. We've infused human T cells that have
the firefly gene in a mouse that has a tumor over here. The T cells go in
through the vein. They go up to the heart, and they hang out in the lung for
an hour or two before they go to the rest of the body.
And what we found was this is a natural aspect of T cell biology is that
they'll spread out throughout the body. This is 24, 48, and about 72 hours,
this is what T cells do. They home to the tumor.
What we've learned is that T cells have the equivalent of a chemical nose.
They can smell things. And tumors make smells that are like three day old
garbage and the T cell says I've got to go to where the smell is the strongest
because I have to take out the garbage. That's my goal.
So it's based on the activity of a type of protein and peptide called a
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chemokine in which cells have evolved to go either towards the highest amount
of that or to the lowest amount of that. And T cells happen to respond to
tumor chemokines very, very robustly.
So the other thing we can do is we can test our model systems. This is where
we put the firefly gene into the tumor cell. And here we're imaging human
glioblastoma, the most lethal form of brain cancer that is not curable today.
And here, if we put those tumor cells that make light into the mouse brain and
then we come and we treat the mice, and if we treat the mice with a T cell that
has a velcro that we've developed for acute lymphoblastic leukemia, the T cell
interaction with the tumor is so specific because of the reprogramming, it's
expected that we see this. It's as if we gave no treatment and all the tumors
grow.
We've designed a velcro molecule for targeting T cells to human glioblastoma,
and if we give one dose of those T cells to a cohort of animals, this is about
72 hours after the T cells were given. Day 11 afterwards and for the natural
life span of the mice, the tumors don't come back. And when we look at the
brain, there's very little pathology. There's just a little bit of a reaction
of cells in the brain to that, and the mice were functionally and behaviorally,
for what mice do. You know, they run around and chase each other's tails.
They were doing all of that perfectly well.
So getting back to your question, we have many different apps that we're
working on. So this is an app for velcro molecules so the T cell can see the
tumor cells. We're making apps for T cells that allows them to grow and
proliferate when they see a tumor in a place where T cells don't normally grow,
such as in the brain.
We're making apps for the T cells to become a biologic factory in and of itself
and start secreting recombinant proteins into the tumor micro environment when
they get there. And we're creating apps here, this is called an riboswitch,
which is part of the mRNA of the central dogma, where you can create secondary
structures such that this becomes a little sensor for a drug that the doctor
gives.
And if the doctor gives the drug, it will turn on the transgene and allow the
cells to do their thing. And if the doctor says, well, I think you're done
now, why don't you stop taking the pills, call me in the morning and we'll see
if we have to turn it on or off again the next day. So we're starting to work
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now with these technologies. And I think the potential strength of this -each one could have a role. But the potential real, I think, breakthrough
strength is this idea, can we create circuitry. Can we have the different apps
start organizing and making decisions based on what the other app is doing.
So we're getting very interested in creating networks or synthetic biology to
import into T cells for cancer therapy. And I think, you know, I'm talking
about cancer therapy to you in this talk, but this could be equally true for T
cells of the immune system that are the cells that say, hey, don't do anything.
Those are called regulatory T cells. So for autoimmune diseases, we have the
potential of engineering those T regulatory cells in patients with autoimmune
disease for patients to go back in the body and turn off an autoimmune response
such as one that causes MS or diabetes.
So this is all happening in the labs at Ben Towne Center For Childhood Cancer
Research. It's very easy to get really engrossed in this technology. I'm
sure -- you know, there will be times when my wife says hello! I'm here and
you have to now focus on dinner and getting the kids to sleep.
But really, we are a biomedical research institute that has a very, very
defined focus on bringing this to therapies that will help kids with cancer.
And this is the classic conundrum for the academic researcher.
You can do your mouse work and get grants and write papers and be pretty happy,
or you can go off this cliff and say, how do I take this work that you've seen
and turn it into a clinical trial that's supported adequately that will be
approved by the FDA and you can go through all the regulatory hurdles. By the
way, with absolutely zero budget, no project management, not even a secretary
to answer the phones. It's a real hard job.
I think Seattle Children's Research Institute has said we can't have this be
the paradigm where the researcher heads back to the mice. We have to go
forward and they've been very, very creative.
So this is where my center exists on the corner of Olive and Bourne. I invite
you all if you have a chance to come and have a tour. There's nothing like
seeing the facility from the inside and seeing what's going on. I'm trying to
create this academic research institute with a very strong flavor of biotech
infrastructure so I actually have a preclinical development team that is to
take the research from the laboratories and fast track it and do what's
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necessary to get it to the point where the FDA can look at it and authorize a
clinical trial.
We also have in this building, because it was biotech company in its former
life, called targeted genetics, we have clean room facilities for manufacturing
cells that are at a level of purity, potency and safety that the FDA will allow
us to take cells that we manufacture here and give them back to patients at
Seattle Children's Hospital and FDA supervised clinical trials. So we have
this and we're up and running. We built this and got it running in about 18
months.
And what we're doing now is we've created now, it's one thing to make enough
cells to treat a mouse. It's a whole different things to make enough cells to
treat a human. It's a scalar difference and all the methodologies that are
good for making a million cells fall apart when you try to make a billion at a
time. So we've had to do what biotech companies do is do process development.
How do we go from a tube of blood into the clean rooms to make enough cells
that it will be a dose for a child on a clinical trial.
And as of this August, we received the FDA's approval to move forward with our
first clinical trial to treat children with acute lymphoblastic leukemia. The
type of leukemia Owen has if the tumor relapses. And those are children who
have very poor prognoses.
Here's an example of some of the work that I did before coming back to
Children's Hospital in Seattle, back at City of Hope. We were doing studies
for glioblastoma multiformae, using the same app that I showed you in the mice,
which patients with relapsed, unresectable tumors that have failed radiation
and chemotherapy come into the trial, we give T cell doses, starting with a
small dose up to higher doses and here's an example of a patient with a near
complete regression of a highly refractory tumor.
I think if we can start doing this in glioblastoma multiformae, things like
leukemia and then neuroblastoma and sarcomas are going to be pretty
straightforward.
So we have a hit list. I'm about doing this to better children's outcomes in
cancer. So relapsed leukemia, neuroblastoma, brain tumors, sarcomas. This
causes about 80 percent of all cancer death in children. And then once we lick
these, we'll get into the rare tumors.
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I think the important part of this is what our velcro molecules target on a
pediatric cancer are fairly unique, because cancer in kids evolves genetically
in a very different way from adults. Adults, it's because of all your skin,
your intestines, everything that interacts with planet earth on life, you're
accumulating small hits, small hits, small hits.
For kids, it's really more dramatic genetic changes that occur during
development of the body, where you have to go from one cell to become a liver
or muscle or brain, and you have to step on the gas and take off of the brake,
and that's when there's a vulnerability.
But having said that, that velcro molecule that we developed for neuroblastoma,
if I showed you the same experiment in the petri dish with ovarian cancer, the
same thing would have happened. So we're creating molecules and applications
that could help in very common adult carcinomas, such as colon carcinoma,
breast, prostate. And we're here to help our peers.
Our process for doing, to give you the big picture, it's probably a lot like
when you do with software development. It's an iterative process. So we
discover in the laboratory, we take those discoveries forward to make them
ready for an application. Here it would be a clinical trial. We do the
clinical trial, and then we study the patients very carefully. What worked and
what didn't work.
Because our recombinant DNA is just like software. We can go back and adjust
the code to tweak the app to do better where it needs to, or if it's too strong
in another Ware, we can tune it down and then we can take it through, and take
it through this iterative process to really try to evolve the therapeutic to
its safest and most reliable iteration.
So I think to get back to the beginning, this is where we are in 2013. I'm
cautiously optimistic if we're able to push this forward that in the
not-to-distant future, maybe being cured of cancer as a child may look like
this, where a diagnosis happens on Wednesday. You give your blood sample on
Friday, and next week, you come back for your T cells for an overnight infusion
and the likes of chemotherapy and radiation are relegated to the medical
history books.
None of this would have been possible working in a vacuum.
And here in Seattle
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we have this incredible collaborative environment with scientists and
researchers at the UW and the Fred Hutch helping us. We help them. We have an
incredible support basis through Ben Towne foundation. I encourage you to go
to their website and check them out. Crush Kids Cancer has come through for us
and is really helping us with our leukemia trials.
So it's going to take a village to get this done. I think what keeps me up at
night, the hardest thing about all of this is that this is what you need in
terms of financial input to cure mice of cancer and this is what you need to
cure kids of cancer. The NIH, the federal government only funds this much.
That's all they're going to do. Only three cents on every dollar, cancer
research dollar from the NIH goes to pediatric cancer research. It's very
underserved. And as you know, because of our economic situation nationally,
that NIH budget, that 3 percent is getting smaller and smaller very rapidly.
So that's what keeps me up at night. I want to thank you for your time and
attention. And I could take questions either here or remotely as well, right,
Amy?
>>: Once the therapy that you're working on is under way, what is the
difference in cost -- or what you would imagine the difference in cost between
your therapy and traditional chemo and radiation.
>> Dr. Mike Jensen: That's a good question. So right now, in the beginning,
at its small scale, it's at its most expensive phase. To do our clinical
trials, it's about 30 to 35 thousand dollars per product per kid. That sounds
expensive. I will point out that there are a lot of drugs now on the market
that you have to take every day to keep the -- that won't cure you. That will
give you a couple extra years or maybe sometimes only a couple extra months.
Some of those pills can cost $60,000 a year to take, and you have take it year
in and year out.
A bone marrow transplant costs a quarter of a million dollars. If everything
goes smoothly. The lifetime cost to deal with the side effects can be millions
of dollars. So this can -- if this can be a therapy that's highly effective
with minimal toxicity, it will more than pay for itself. It sounds exotic and
expensive now, but I think that's, you know, that's a new technology coming
into an early application phenomenon.
>>:
[indiscernible] paid out over $2 million.
I mean, $35,000 is chump
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change.
>> Dr. Mike Jensen: Leukemia therapy is pretty cheap compared to the other
forms of therapy. Yeah?
>>: I don't know anything about the field, really.
source of funding for this research?
Are insurance companies a
>> Dr. Mike Jensen: No, no. So no, insurance companies don't fund the
research, and for phase one studies, which we have to go through, insurance
companies won't even pay the hospital bill for a bag of IV solution that's
given to a patient while they're there to get the experimental therapy.
We have to bootstrap this. And one of the things that, for instance, Ben Towne
foundation has started is let's think about fund-raising. If we have to do a
trial that the FDA says is 50 patients, let's start raising funds and say okay,
we have enough for three patients, five, ten. How do we make that happen.
Because we are on our own, and, you know, used to be before the recession hit,
it used to be that you could get grants and make it work through grants. But
now, without philanthropy, we're just going to cure mice.
>>: You had mentioned high rates of evolution of cancer cells.
if the cancer cell outpaces the [indiscernible]?
What happens
>> Dr. Mike Jensen: It's a good question. I think part of it is strategically
to target the velcro to molecules that are drivers of the cancer. So there's
oncogenic protein, such as receptors that sit on the surface that signal to the
cancer cells, always grow, always grow. So if we can -- and there's evidence
that tumors can become addicted to those oncogenic drivers. So if you hit the
tumor at its Achilles heel, with a velcro, that's a good step.
The other aspect of what we're working on is I showed you mono-specific velcro
molecules, we're now building these so there's more than one specificity. So
we could have one T cell through one molecule start seeing two to three
different antigens and then the chance of a mutation occurring to have one
antigen loss and a second antigen loss, it's a multiplication factor. And so
that becomes much more rare.
So that's a major issue for any targeted therapy for cancer, whether it's drug
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or immunotherapy. But I think this technology platform has abilities to really
address it in a meaningful way.
>>:
You can always update your app, right?
>> Dr. Mike Jensen: Yeah, so we could have -- for individual cancers, we're
probably going to have a small library of apps. Because what I see the future
being is that the way cancer drugs are developed now, you develop a drug, and
you give it to a thousand patients whether the drug's going to help them or
not, and you ask, well, it caused the tumor to shrink in 20 percent. That's a
winner.
What I -- this technology is so targeted that what I see is you're going to
have a biopsy of your tumor. Its genome is going to be sequenced. You going
to know what's expressed and what's not expressed, and we're going to have
basically a Chinese menu list of these velcro molecules. And if we have 20
different velcro molecules and your tumor has four, we're going to make your T
cell product for you with those four that match the tumor that's inside your
border.
This kind of personalized matching up the therapy with really what's important
for you to be cured of cancer, not a population of patients.
>>:
And you can test that, right?
>> Dr. Mike Jensen:
Yes.
>>: So would the modified T cells or these customized T cells, is there
recurrence of cancer? Because I know that's a problem with leukemia,
recurrence or another occurrence of cancer. Would that then reduce that,
eliminate that risk?
>> Dr. Mike Jensen: Well, that's the goal that certainly one of the goals -I'm not developing this therapy and my team's not developing this therapy to
just palliate, to give you a couple extra years. We want this therapy to
eradicate every cancer cell that's in the body.
We know from animal studies and some early clinical trials that these cells,
once infused in the body, appear potentially never to go away. So they could
be sitting there and if the target is absolutely tumor-specific, why not have
23
them for the rest of your life just in case.
There are some targets that we might say, it's a good target to get rid of
leukemia, but it will also get rid of the normal B cells, and that's the most
effective form of this therapy right now. And you can do without B cells
probably for months or a year or two, but without B cells in your immune
system, that's going to be a problem later on, and that's where we have this
concept that we'll use the suicide gene.
Let's say a patient goes into remission and they're in remission three weeks or
three months or three years later, then we'll say, we'll have a discussion,
we're going to get rid of those cells now. We're going to let the B cells come
back. But we have another vial of the T cells that we made for you in the
freezer, because these cells can be put into suspended animation for decades,
if not a lifetime.
There is a potential, I think, if you look really forward, it's like, you know,
we toss out cord blood. That's your most healthy, resilient part of your
immune system when you're born. There's a lot of it in the cord blood that
gets put in the trash can. Why not, you know, some day thinking big, it's just
standard to have your immune cells frozen back for you from that cord blood,
because the immune system does wear down. When you get your 70s, 80s and 90s,
one of the major causes of end of life physiologically is the immune system
basically exhausting itself and you die of an infection.
And so this idea of replenishing the immune system or having it there for you,
if you get cancer when you're 60, 70 or 80, which is when the cancer rates
really start going up in the latter part of life. I think that should be on
the table. Yeah?
>>: Do you have the app to adapt this therapy from pediatric cancer to
geriatric cancer and everything in between? Or is there something about
pediatric cancer that makes this effective?
>> Dr. Mike Jensen: No. So like at the hutch, I'm working with scientists and
faculty there. And as I'm launching the leukemia trial, they're launching the
adult version of it. There's a lot of back and forth, back and forth, back and
forth. Some of the velcro molecules that I need to generate for pediatric
cancer will never work in anything but a pediatric neuroblastoma, for instance.
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Every now and then I'll
cancer. I give the app
this happen for ovarian
say, oh, that does work
back and forth.
have a hit, neuroblastoma. Oh, it also gets ovarian
to the folks at the U, I say go with it, please. Make
cancer. Sometimes they'll have molecules that would
for pediatric, and we're sharing it back and forth,
>>: How many patients do you think have to go through your clinical trials
before the FDA will approve your process?
>> Dr. Mike Jensen: So typically, the very first trial of a new therapeutic is
called a phase one study. A phase one study is statistically geared to show
that the therapy is safe. And to determine what's called the maximal tolerated
dose. Now, for a T cell, there may be no maximal tolerated dose, because it
doesn't work like chemotherapy, in which we'd stop at the maximal
manufacturable dose.
We do those studies in cohorts. First three patients get this many cells or
this much drug, higher, higher, until we start seeing side effects. Typically,
that's a clinical trial. That's about 25 patients or so, just to give you a
ballpark.
The next type of study is a phase two study that shows, okay, in what
percentage of patients at that safe dose do you get tumor responses. How
effective is it?
Usually, what will happen is if you have positive phase two data that, at that
point, based on statutes and law, an insurance company then would be obligated
to pay for the cost of us making the T cells in our facility. We can't make a
profit, but the actual cost. That's a big deal. That's only happened a couple
times, but that would be the paradigm.
You know, Seattle's been a real driving force in curative cancer therapeutics
for decades now. Bone marrow transplant was founded in Seattle and is now a
life saving procedure all around the world. This would be potentially could be
a similar type of deployment where centers of excellence that have these
facilities, manufacturing facilities, can start making products for patients
and patients come in and receive that therapy.
We're also doing developments where we freeze the cells so we can FedEx them
back to where the patient is. So we can become a hub and be able to supply
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products around the country and eventually all around the world.
It's a very interesting time in this field in terms of biotechnology. Ten
years ago, when I talked about this stuff, folks in biotech and pharma, their
eyes would glaze over. What do you mean a patient-specific product. You mean
you're going to make something for each patient? Yeah, yeah. Dendrion kind of
broke that glass ceiling in a way.
We could talk about maybe offline their technologies and, you know, what
challenges they have. But it could be that same type of phenomenon where
companies can create these hubs and be able to FedEx in cells and then FedEx
out products back to patients.
>>: For the mice cancer cells that you worked on, what percentage -- what was
your success rate of killing it, but in addition it killed the mice?
>> Dr. Mike Jensen: My general philosophy is if you're working with something
that can't cure 100 percent of the mice, it's not good enough for a human
trial. It's a little bit of an artificial situation, because we create models
that help us read out something. So they're nowhere close to being like real
world. This is the same as a patient when they come in with a diagnosis of
acute lymphoblastic leukemia. We rig the system in ways that we try to parse
it so we ask a specific question of the model that gives us an insight into the
biology of the system or different aspects of it. But it's never -- the models
are never good enough to say this replicates the clinical situation. You
really have to move quickly into that phase one trial.
>>:
So they're a little optimistic, but how good is optimistic right now?
>> Dr. Mike Jensen: Well, the velcro technology, you know, I've been in this
for 16 years. There's a couple other institutions in the country that have
been working on this. We all collaborate and share information. But the
Children's Hospital of Philadelphia was the first to treat the first three or
four children, and there were children of that very first cohort that got one
dose of cells in which their leukemia was most of their bone marrow that
everything had failed, and about three weeks later, they go into remission.
And without any chemotherapy. And some of the first kids treated are now eight
months out in remission with these T cells floating around.
So the ability of this therapy to cure a human, I think, is becoming quite
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clear. How do we make this address all cancers in different patient
populations become usable is a big challenge.
>>: What I was getting at is I was wondering for the mice that you can freely
test, if you had 90 percent success rate, once you can kill them in the dish,
you can kill them in the mouse. Is it 50 percent? Because it seems like it's
the same thing with the human cells without any approval, you can just test it
in the dish. If you're effective there ->> Dr. Mike Jensen: The dish, if it's not effective in the dish, it won't cure
a mouse. If it's effective in the dish, you can probably create a mouse model
where it's 100 percent effective by how many tumor cells you put in and what
the timing is.
There have been situations where it looks good in the petri dish and it's a
complete failure in the mouse, and that's an end of story for that version of
the app. We usually go back and say, okay, we need to advance it more in the
molecular side before we go back.
So there's a lot of ping-pong back and forth.
>>:
So it's hard to say?
>> Dr. Mike Jensen: Yeah. It's very empiric right now. We'd love to have
molecular models based on crystal structures of these molecules and
comprehensive readouts of signaling pathways that are predictive, and that's
part of what I hope to do in the next year or two is what works in the petri
dish, what works in the model. Give me the type of readout called mass spec,
and tell me about all the signaling molecules that get turned on for the one
that works, compared to the one that doesn't work. And can we then kind of
high through-put the velcro molecules based on a signature that's predictive of
18 months of laboratory work. That would be a nice place to get to.
I know there's a urinary biomarker question. I know so little about urinary
biomarkers, that I'm -- I think I should defer.
>>: There's another question about [indiscernible].
opportunities [inaudible].
>> Dr. Mike Jensen:
Oh, who is that person?
One was about volunteer
Name the names.
I think
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that's ->>:
[indiscernible].
>> Dr. Mike Jensen: It's a really good question, and we were talking about
this a little bit. I think we, in biomedical -- in academic biomedical
research, you would be horrified by the lack of sophistication and access to
tools, even computational tools and ability to communicate and share data sets
between individuals down the hall or between SCRI, where I am, and the UW and
the Hutch and across the country.
It's woefully under developed and under supported, and I think, you know, we
are now getting into Big Data. The genomeics efforts I was saying that I'm
part of a grant that seeks to link genomeics data, which is sequencing the
genomes of hundreds of cancer cell lines and patient genomes and link it with
what can we pull out of that computationally that will identify the target for
the velcro.
And I'm trying to -- we're trying to put together this organization that will
span seven or eight institutions in the United States and a couple in Canada.
And we're in a vacuum. So I think there's -- it's a great conversation that I
would love to have with any of you offline and talk about. I think an
organization like Microsoft could have incredible impact in helping academic
researchers and non-for-profits be able to work faster and more efficiently.
I'm a clinical oncologist by training, pediatric oncologist, and I will tell
you that the main thing that families think about is time. And you walk
through the waiting room, and they look up at you and say when is that
breakthrough coming to save my child's life or to make it so my child doesn't
need to have radiation to their brain. It's all about time and it's all about
acceleration. And any assets we can bring from any, any sectors in industry or
otherwise to help accelerate the process are most welcome.
>>: I'll give my unsolicited pitch here. I'm part of the cancer advocacy
network field. I work in research. And we support Seattle Children's
Hospital, specifically Dr. Michael Jensen's work. But there are about 13
cancer research guilds that support Seattle Children's Hospital and my guild
pulls them all together and has a website where you can find all kinds of
activities, events, ways to volunteer, ways to donate. You've got the Ben
Towne Foundation, which funds Mike Jensen as well, and then Alex here has his
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Crush Kids Cancer, which is part of the ->> Alex Weinert:
It's part of the guild.
>>: So there's all kinds of ways that people can help, and we believe that the
cure is in the research.
>> Alex Weinert: As Dr. Jensen said, the hope is in the research. The thing
that anybody in my situation up here more than anything is relapse. Owen goes
off treatment in May and he's got a higher probability of relapse right after
he goes off treatment. If that were to happen, those are the trials that can
save Owen's life. So that hope, and I know parents who have seen that window
come and go.
Certainly, I'd be willing to volunteer Lisa or myself, if you want to know more
about how to volunteer to help, we would be happy to be a liaison for
Microsoft. So my name is on the first set of slides. Just send me an email.
>>: And I'm in research. I'm Lisa Clausen. Just to mention, if anybody
actually wants to come in and see Mike's lab and see the facilities, we do
tours. There's contact information on some flyers that are outside as well.
You can get my card as well and I can set something up for you.
>> Dr. Mike Jensen: So thank you all for coming to this lecture and all of you
out there in cyberspace too. It was really great to have this chance to come
and tell you about our work. Thank you.