I am on the faculty of the University of
California at San Francisco in the
department of hematology and oncology
and I’m going to talk to you today about
what I study I study cancer and I study
cancer in many aspects of it and I
approach this as a software engineer
approaches difficult problems we need a
lot but spend a lot of time to
understand many interesting things but
this is my encore career I was the vice
president of software tools at Apple
Steve Jobs hired me to help with the
Intel transition to develop Xcode and
the beginnings of iOS and the many
wonderful platform technologies that
everybody uses today and I would struck
at the time when Steve developed cancer
that this was a tools problem this is a
problem that we lack the tools to
sufficiently understand but I didn’t
have the background yet to do it so I
returned to college and actually got my
PhD in bioinformatics and biomolecular
engineering at the age of 48 and so
[Applause]
thank you you can teach an old dog new
tricks Steve as any patient does suffers
has to make decisions through this maze
of interlocking problems are you going
to go for surgery are you going to have
chemotherapy will you try radiation
therapy if those don’t work do you go
for experimental therapies do you go
into a clinical trial or do you try
alternative therapies and the tools for
looking at these problems and choosing
which is the right choice for you is
very difficult and even physicians
really don’t have tremendous guidance on
this except in a few special cases
sometimes we really have to just study
and understand and hope for the best and
I feel like that’s a place where the
medical world needs to improve if we
actually look at these statistics of who
lives and how long they survive we find
that in fact one of the biggest issues
is how quickly you’re diagnosed with
cancer and how quickly are you treated
and there’s this enormous gap between
patients in their five-year survival
rate um if they get diagnosed early and
cancer is localized or they diagnosed
late and the cancer is spread throughout
their bodies and hat and suffer through
and this is not just in that matter of
the amount of cancer it is it is also
the complexity of cancer and going to
tell you about how cancer like other
things are mutations that follow
evolution nothing in biology makes any
sense unless you understand evolution
but if you think about it with through
evolution eyes in the lens of that of
that idea you find that in fact
everything makes sense so you begin life
with a few mutations a few alterations
in your genes that can cause cancer
sometimes this is enough to cause cancer
in a child but most of the time we have
3 billion a C’s T’s and G’s in our body
and we accumulate these mutations and
they’re mostly benign we get them from
radiation we get them from the foods we
drink we get them from viruses and other
things
and those mutations eventually catch one
that is we call a driver mutation it
drives the cancer propels it forward and
increases the growth rate dramatically
when those driving mutations happen
among the things that get broken or the
error checking code that checks the DNA
itself and that error checking process
then begins this radicals changes to the
DNA you can actually lose chromosomes
you can get multiple copies you can get
many many more mutations and what is
happening is you actually don’t have one
cancer you have many I have a whole
spectrum of them and your immune system
is working to kill them but over time it
overwhelms the immune system and of
course u sub K
the notion of metastasis of course is
cancer that has followed this fitness
curve and has found many niches in the
body to live in so you may start off
with one kind of camp cancer in one
location to the body but it has found
other places to call home cancer
essentially has all the source code for
every program your body has ever run
including the programs that will run
when you were a fetus and ran during
development and those programs is just
punching it randomly eventually finds
one that is able to overcome the body’s
natural defenses this problem feels to
me a lot like a software problem where
it is running amok and so one of the
great technologies that we’ve developed
in the last ten years is targeted
therapy and some treating some cancers
is a lot like debugging you find the bug
and you go after it
so for melanoma patients who have the
beer as v600 mutation we use a drug
called raffinate and it goes and finds
the cancer cells that have the specific
mutation and blocks it and helps the
immune system target that unfortunately
it’s not like debugging because the bugs
actually adapt that what happens along
the way is we haven’t couldn’t killed
all of the cancer cells sort of like
trying to kill all the mosquitoes with
DDT you’ll find that there are a few
naturally that are resistant to it and
those are the ones that grow in
now you’ve got a cancer that is
resistant to the drug that you used this
idea is that cancer can actually develop
these many mechanisms of drug resistance
that those drug that it can actually
avoid the plate the location where the
drug was targeting it can actually
become a supercell where it actually
kicks out the poison faster than it can
take it in it actually reduces the
intake of the poison and it can actually
one of the main mechanisms that we often
use to fight cancer is we target
damaging the DNA the course cancer cells
are some of the most rapidly growing
cells in the body we often target that
but in fact cancer fights us on that in
some sense by improving and being better
at him at fixing the damage from DNA in
that infection cores even worse in the
condition so with all these problems how
do we understand what goes on I’m going
to talk to you now about a child named
Quincy who came to UCSF for treatment
and his mother noticed that just
something wasn’t right he was five
months old and was treated or admitted
with an unusual rash and difficulty
breathing had high temperature
he had discomfortable and had a very
elevated white blood cell count
usually the sign of an infection but it
can also be of course a sign of cancer
to pediatric oncologist that I work with
pinyon loan dr. Eliot Stieglitz worked
saw Quincy and him came up with and
mainly thought this might be leukemia
but the question is which leukemia and
how do you treat it and kids do very
well with leukemia treatment on the
whole but Quincy had Quincy’s cancer
didn’t respond over time he developed
its massive abdomen and the diagnosis
after some examination was that had you
know Milo monocytic leukemia a rare but
very usually fatal cancer um and the
usual therapy for these kinds of
leukemia is to ablate to destroy all the
bone marrow old blood producing cells in
the body can give us a cell transplant
from a relative or
close match but Quincy was much too sick
for that Quincy you know would not be
able to survive such a dramatic
treatment the chemotherapy’s were tried
we went through one after another and
they showed no progress we then we pull
out our next set of tools and that is to
look at the genes themselves so we
sequence genes
Quincy’s genes using a panel we
developed at UCSF called the UCSF 500
500 gene panel and it would we found was
that there was a gene fusion a
connection between one gene and another
that doesn’t belong there
that this gene fusion actually puts in
the middle this other gene right square
in the middle in this kind of alteration
typically not something we’re born with
but can happen randomly at any time
because they’re the the splicing of the
DNA can happen easily and that’s sort of
like the idea of you have a headset but
instead of plugging in the right place
in your stereo or your phone you’re
actually plugging into the power supply
you’re gonna get this tremendous boost
the signal that is just noise and causes
this rapid growth it’s the wrong thing
to happen in time to understand these
kinds of phenomenon we’re very fortunate
that the federal government has created
this Cancer Genome Atlas TCGA kind of a
play on the AGC and T’s that we use and
this is a project that was just finished
was a follow-on project to the human
genome sequencing project in that
process we’ve sequenced 15,000 patients
I did some of the analysis of this it
was really amazing because you get to
see these patterns that recur and
understand how cancer affects in
multiple parts of the body that will see
the same mutations occurring in
different locations but causing are very
almost the same cancer but very
different effect and so wonderfully
developed at UC Santa Cruz where I was
at the time was this tumor map a map
where we took literally the Google Maps
technology and instead of it presenting
the tiles of the jeep of
occasions of places on the planet we had
locations in this vast space of the
cancer and allows us to zoom in you can
google it and find it yourself
and what’s interesting about it is we
can then do an analysis of where an
individual patient is by seeing how they
correlate with all the patients on the
map and to see where do they fit best
and we found Quincy Quincy was between
blood cancer the leukemia and kidney
cancer and that of course gives us the
ideas that in fact that maybe therapies
for kidney cancer might actually help
treat Quincy so there is in fact drugs
that do that and one very famous and
important drug called suratha nib is
targeted specifically for foot 3 gene
fusions and it’s for treating very
advanced quitting kidney cancers early
enough it happened to be developed by
Professor Frank McCormick also at UC San
Francisco so we went and talked to him
and found out more about this um this
drug we also did a literature search to
see if it is this has ever been tried
before but in fact when it has been
tried before it hasn’t worked very much
experimental very much uh not
necessarily the standard of care now
we’re looking into individual ideas of
how to pursue things and in fact was
recommended not to try this on pediatric
cancer patients so with that in mind
though we really were out of options and
at that point in time we said we have to
try this if nothing you know to see if
it will work and so here’s what Quincy’s
white blood cell counts and it had
climbed from point in time that he
started being seen up to very seriously
dangerous ult’s and first administration
of Sarafina worked to dramatically
reduce we said okay let’s give him a
little bit more up to 200 milligrams and
even better results and finally at about
300 milligrams amazingly you know we saw
him returning to normal
feeling much better in fact will show a
little bit
know that your child could potentially
die from this process was just
gut-wrenching I mean I just would go
into the bathroom and pray and cry and
just please don’t take my baby
it was really an emotional emotional
time for us and this medication actually
put quincy into remission even before
his transplant so it was basically a
miracle so this is quincy
well all credit belongs to its doctors I
mean where as a researcher I’m just
merely helping out this amazing process
so what’s exciting about this is that we
did have a curative treatment for Quincy
and these amazing targeted therapies
helped but we don’t have this for every
patient and so part of the idea is of
course that we need to figure out is how
do we take this kind of precision
medicine well we know an enormous amount
about individual patients and how to
treat them and give it for everybody how
do we scale up in Silicon Valley of
course this is a big part of this and so
one technology that I will talk about
just very briefly is essentially usage
see you to this idea of programming
immune cells and this is something which
we’ve begun to do we have
immunotherapies that externally tell the
immune cells to ignore the the signals
that cancer generates to say don’t eat
me and that’s an amazing thing we can
block the ways that cancer evolves to
avoid the immune system to better tackle
it but I believe that a better
technology is coming along we have seen
the first of these in actually putting
genes into patient’s immune cells and
someday perhaps even making a generic
immune cell that can be used for many
many patients and the idea of course is
that with this additional programming
the a researcher a doctor can and can
work to improve and to turn your immune
system to precisely focus and target
your cancer perhaps even going beyond
cancer into other diseases such as
Crohn’s disease and immuno other
autoimmune diseases so very exciting
idea in the meantime in the meantime
what should you do what life is of
course a risky business and it’s
extremely important that you avoid
things that increase those risks really
it’s just a probability game you should
avoid smoking of any kind um but if you
need to smoke smoke less oddly enough
obesity is very much a cancer agent and
we say a much worse outcomes with
patients who have who are obese there
are other pathogens in the environment
kinds of viruses unprotected sex can
transmit those things that can cause and
lead the cancer and then there’s a host
of other dietary factors and being
sedentary and other things that you have
heard about before extremely important
that you manage and you know your risks
so this gives you some idea about what’s
going on so what what’s the conclusion
to this number one avoid risky business
seek treatment early before cancer has
had a chance to spread and be lucky
enough to get a mutation that we
actually know how to fix and by the way
increase your luck by donating to cancer research thank you very much
California at San Francisco in the
department of hematology and oncology
and I’m going to talk to you today about
what I study I study cancer and I study
cancer in many aspects of it and I
approach this as a software engineer
approaches difficult problems we need a
lot but spend a lot of time to
understand many interesting things but
this is my encore career I was the vice
president of software tools at Apple
Steve Jobs hired me to help with the
Intel transition to develop Xcode and
the beginnings of iOS and the many
wonderful platform technologies that
everybody uses today and I would struck
at the time when Steve developed cancer
that this was a tools problem this is a
problem that we lack the tools to
sufficiently understand but I didn’t
have the background yet to do it so I
returned to college and actually got my
PhD in bioinformatics and biomolecular
engineering at the age of 48 and so
[Applause]
thank you you can teach an old dog new
tricks Steve as any patient does suffers
has to make decisions through this maze
of interlocking problems are you going
to go for surgery are you going to have
chemotherapy will you try radiation
therapy if those don’t work do you go
for experimental therapies do you go
into a clinical trial or do you try
alternative therapies and the tools for
looking at these problems and choosing
which is the right choice for you is
very difficult and even physicians
really don’t have tremendous guidance on
this except in a few special cases
sometimes we really have to just study
and understand and hope for the best and
I feel like that’s a place where the
medical world needs to improve if we
actually look at these statistics of who
lives and how long they survive we find
that in fact one of the biggest issues
is how quickly you’re diagnosed with
cancer and how quickly are you treated
and there’s this enormous gap between
patients in their five-year survival
rate um if they get diagnosed early and
cancer is localized or they diagnosed
late and the cancer is spread throughout
their bodies and hat and suffer through
and this is not just in that matter of
the amount of cancer it is it is also
the complexity of cancer and going to
tell you about how cancer like other
things are mutations that follow
evolution nothing in biology makes any
sense unless you understand evolution
but if you think about it with through
evolution eyes in the lens of that of
that idea you find that in fact
everything makes sense so you begin life
with a few mutations a few alterations
in your genes that can cause cancer
sometimes this is enough to cause cancer
in a child but most of the time we have
3 billion a C’s T’s and G’s in our body
and we accumulate these mutations and
they’re mostly benign we get them from
radiation we get them from the foods we
drink we get them from viruses and other
things
and those mutations eventually catch one
that is we call a driver mutation it
drives the cancer propels it forward and
increases the growth rate dramatically
when those driving mutations happen
among the things that get broken or the
error checking code that checks the DNA
itself and that error checking process
then begins this radicals changes to the
DNA you can actually lose chromosomes
you can get multiple copies you can get
many many more mutations and what is
happening is you actually don’t have one
cancer you have many I have a whole
spectrum of them and your immune system
is working to kill them but over time it
overwhelms the immune system and of
course u sub K
the notion of metastasis of course is
cancer that has followed this fitness
curve and has found many niches in the
body to live in so you may start off
with one kind of camp cancer in one
location to the body but it has found
other places to call home cancer
essentially has all the source code for
every program your body has ever run
including the programs that will run
when you were a fetus and ran during
development and those programs is just
punching it randomly eventually finds
one that is able to overcome the body’s
natural defenses this problem feels to
me a lot like a software problem where
it is running amok and so one of the
great technologies that we’ve developed
in the last ten years is targeted
therapy and some treating some cancers
is a lot like debugging you find the bug
and you go after it
so for melanoma patients who have the
beer as v600 mutation we use a drug
called raffinate and it goes and finds
the cancer cells that have the specific
mutation and blocks it and helps the
immune system target that unfortunately
it’s not like debugging because the bugs
actually adapt that what happens along
the way is we haven’t couldn’t killed
all of the cancer cells sort of like
trying to kill all the mosquitoes with
DDT you’ll find that there are a few
naturally that are resistant to it and
those are the ones that grow in
now you’ve got a cancer that is
resistant to the drug that you used this
idea is that cancer can actually develop
these many mechanisms of drug resistance
that those drug that it can actually
avoid the plate the location where the
drug was targeting it can actually
become a supercell where it actually
kicks out the poison faster than it can
take it in it actually reduces the
intake of the poison and it can actually
one of the main mechanisms that we often
use to fight cancer is we target
damaging the DNA the course cancer cells
are some of the most rapidly growing
cells in the body we often target that
but in fact cancer fights us on that in
some sense by improving and being better
at him at fixing the damage from DNA in
that infection cores even worse in the
condition so with all these problems how
do we understand what goes on I’m going
to talk to you now about a child named
Quincy who came to UCSF for treatment
and his mother noticed that just
something wasn’t right he was five
months old and was treated or admitted
with an unusual rash and difficulty
breathing had high temperature
he had discomfortable and had a very
elevated white blood cell count
usually the sign of an infection but it
can also be of course a sign of cancer
to pediatric oncologist that I work with
pinyon loan dr. Eliot Stieglitz worked
saw Quincy and him came up with and
mainly thought this might be leukemia
but the question is which leukemia and
how do you treat it and kids do very
well with leukemia treatment on the
whole but Quincy had Quincy’s cancer
didn’t respond over time he developed
its massive abdomen and the diagnosis
after some examination was that had you
know Milo monocytic leukemia a rare but
very usually fatal cancer um and the
usual therapy for these kinds of
leukemia is to ablate to destroy all the
bone marrow old blood producing cells in
the body can give us a cell transplant
from a relative or
close match but Quincy was much too sick
for that Quincy you know would not be
able to survive such a dramatic
treatment the chemotherapy’s were tried
we went through one after another and
they showed no progress we then we pull
out our next set of tools and that is to
look at the genes themselves so we
sequence genes
Quincy’s genes using a panel we
developed at UCSF called the UCSF 500
500 gene panel and it would we found was
that there was a gene fusion a
connection between one gene and another
that doesn’t belong there
that this gene fusion actually puts in
the middle this other gene right square
in the middle in this kind of alteration
typically not something we’re born with
but can happen randomly at any time
because they’re the the splicing of the
DNA can happen easily and that’s sort of
like the idea of you have a headset but
instead of plugging in the right place
in your stereo or your phone you’re
actually plugging into the power supply
you’re gonna get this tremendous boost
the signal that is just noise and causes
this rapid growth it’s the wrong thing
to happen in time to understand these
kinds of phenomenon we’re very fortunate
that the federal government has created
this Cancer Genome Atlas TCGA kind of a
play on the AGC and T’s that we use and
this is a project that was just finished
was a follow-on project to the human
genome sequencing project in that
process we’ve sequenced 15,000 patients
I did some of the analysis of this it
was really amazing because you get to
see these patterns that recur and
understand how cancer affects in
multiple parts of the body that will see
the same mutations occurring in
different locations but causing are very
almost the same cancer but very
different effect and so wonderfully
developed at UC Santa Cruz where I was
at the time was this tumor map a map
where we took literally the Google Maps
technology and instead of it presenting
the tiles of the jeep of
occasions of places on the planet we had
locations in this vast space of the
cancer and allows us to zoom in you can
google it and find it yourself
and what’s interesting about it is we
can then do an analysis of where an
individual patient is by seeing how they
correlate with all the patients on the
map and to see where do they fit best
and we found Quincy Quincy was between
blood cancer the leukemia and kidney
cancer and that of course gives us the
ideas that in fact that maybe therapies
for kidney cancer might actually help
treat Quincy so there is in fact drugs
that do that and one very famous and
important drug called suratha nib is
targeted specifically for foot 3 gene
fusions and it’s for treating very
advanced quitting kidney cancers early
enough it happened to be developed by
Professor Frank McCormick also at UC San
Francisco so we went and talked to him
and found out more about this um this
drug we also did a literature search to
see if it is this has ever been tried
before but in fact when it has been
tried before it hasn’t worked very much
experimental very much uh not
necessarily the standard of care now
we’re looking into individual ideas of
how to pursue things and in fact was
recommended not to try this on pediatric
cancer patients so with that in mind
though we really were out of options and
at that point in time we said we have to
try this if nothing you know to see if
it will work and so here’s what Quincy’s
white blood cell counts and it had
climbed from point in time that he
started being seen up to very seriously
dangerous ult’s and first administration
of Sarafina worked to dramatically
reduce we said okay let’s give him a
little bit more up to 200 milligrams and
even better results and finally at about
300 milligrams amazingly you know we saw
him returning to normal
feeling much better in fact will show a
little bit
know that your child could potentially
die from this process was just
gut-wrenching I mean I just would go
into the bathroom and pray and cry and
just please don’t take my baby
it was really an emotional emotional
time for us and this medication actually
put quincy into remission even before
his transplant so it was basically a
miracle so this is quincy
well all credit belongs to its doctors I
mean where as a researcher I’m just
merely helping out this amazing process
so what’s exciting about this is that we
did have a curative treatment for Quincy
and these amazing targeted therapies
helped but we don’t have this for every
patient and so part of the idea is of
course that we need to figure out is how
do we take this kind of precision
medicine well we know an enormous amount
about individual patients and how to
treat them and give it for everybody how
do we scale up in Silicon Valley of
course this is a big part of this and so
one technology that I will talk about
just very briefly is essentially usage
see you to this idea of programming
immune cells and this is something which
we’ve begun to do we have
immunotherapies that externally tell the
immune cells to ignore the the signals
that cancer generates to say don’t eat
me and that’s an amazing thing we can
block the ways that cancer evolves to
avoid the immune system to better tackle
it but I believe that a better
technology is coming along we have seen
the first of these in actually putting
genes into patient’s immune cells and
someday perhaps even making a generic
immune cell that can be used for many
many patients and the idea of course is
that with this additional programming
the a researcher a doctor can and can
work to improve and to turn your immune
system to precisely focus and target
your cancer perhaps even going beyond
cancer into other diseases such as
Crohn’s disease and immuno other
autoimmune diseases so very exciting
idea in the meantime in the meantime
what should you do what life is of
course a risky business and it’s
extremely important that you avoid
things that increase those risks really
it’s just a probability game you should
avoid smoking of any kind um but if you
need to smoke smoke less oddly enough
obesity is very much a cancer agent and
we say a much worse outcomes with
patients who have who are obese there
are other pathogens in the environment
kinds of viruses unprotected sex can
transmit those things that can cause and
lead the cancer and then there’s a host
of other dietary factors and being
sedentary and other things that you have
heard about before extremely important
that you manage and you know your risks
so this gives you some idea about what’s
going on so what what’s the conclusion
to this number one avoid risky business
seek treatment early before cancer has
had a chance to spread and be lucky
enough to get a mutation that we
actually know how to fix and by the way
increase your luck by donating to cancer research thank you very much
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