
most of us when we think about decisions we have to make will go by averages
we have to make will go by averages
we have to make will go by averages right so I think you know when we when
right so I think you know when we when
right so I think you know when we when we hear the sound of hoofbeats what
we hear the sound of hoofbeats what
we hear the sound of hoofbeats what would you think of you would think of
would you think of you would think of
would you think of you would think of horses right but today we’re going to
horses right but today we’re going to
horses right but today we’re going to talk about situations where you think
talk about situations where you think
talk about situations where you think about zebras and not horses which is a
about zebras and not horses which is a
about zebras and not horses which is a much rarer phenomenon but you know it
much rarer phenomenon but you know it
much rarer phenomenon but you know it seems counterintuitive right it’s almost
seems counterintuitive right it’s almost
seems counterintuitive right it’s almost irrational to expect a miracle that
irrational to expect a miracle that
irrational to expect a miracle that you’ll hear hoofbeats and then suddenly
you’ll hear hoofbeats and then suddenly
you’ll hear hoofbeats and then suddenly a zebra shows up and not not horses
a zebra shows up and not not horses
a zebra shows up and not not horses right but let’s see why this is
right but let’s see why this is
right but let’s see why this is important
important
important the reason is we’re going to talk about
the reason is we’re going to talk about
the reason is we’re going to talk about cancer right now cancer is a of course a
cancer right now cancer is a of course a
cancer right now cancer is a of course a challenge today to humanity and many of
challenge today to humanity and many of
challenge today to humanity and many of us here in fact how many people in the
us here in fact how many people in the
us here in fact how many people in the audience actually have a family member
audience actually have a family member
audience actually have a family member or a friend or a friend’s parent or who
or a friend or a friend’s parent or who
or a friend or a friend’s parent or who have actually battled cancer have you so
have actually battled cancer have you so
have actually battled cancer have you so you see it’s I would say roughly about a
you see it’s I would say roughly about a
you see it’s I would say roughly about a third of the audience has has had that
third of the audience has has had that
third of the audience has has had that experience so it’s becoming really
experience so it’s becoming really
experience so it’s becoming really something that really affects everyone
something that really affects everyone
something that really affects everyone and now with cancer there are two
and now with cancer there are two
and now with cancer there are two aspects of technology that are that are
aspects of technology that are that are
aspects of technology that are that are actually starting to help us address
actually starting to help us address
actually starting to help us address cancer as an individual’s disease not
cancer as an individual’s disease not
cancer as an individual’s disease not necessarily only something that you use
necessarily only something that you use
necessarily only something that you use evidence-based or statistical decisions
evidence-based or statistical decisions
evidence-based or statistical decisions to treat right so so this is sometimes
to treat right so so this is sometimes
to treat right so so this is sometimes called the N of one phenomenon in
called the N of one phenomenon in
called the N of one phenomenon in medicine it’s also being called
medicine it’s also being called
medicine it’s also being called precision medicine and for cancer this
precision medicine and for cancer this
precision medicine and for cancer this is actually not that far away and so
is actually not that far away and so
is actually not that far away and so this is the idea
this is the idea
this is the idea want to converted it now what is
want to converted it now what is
want to converted it now what is actually causing this and I’m in an
actually causing this and I’m in an
actually causing this and I’m in an institute of technology and what I would
institute of technology and what I would
institute of technology and what I would like to point out is that the there are
like to point out is that the there are
like to point out is that the there are you are at a very interesting time right
you are at a very interesting time right
you are at a very interesting time right now because we have two technologies
now because we have two technologies
now because we have two technologies that have hit exponential scale right
that have hit exponential scale right
that have hit exponential scale right one is of course Moore’s law which which
one is of course Moore’s law which which
one is of course Moore’s law which which we know is you know an exponential law
we know is you know an exponential law
we know is you know an exponential law that has made electronics and computing
that has made electronics and computing
that has made electronics and computing and communications happen and the it’s
and communications happen and the it’s
and communications happen and the it’s shown here on a log linear scale so it’s
shown here on a log linear scale so it’s
shown here on a log linear scale so it’s actually an exponential law but it is
actually an exponential law but it is
actually an exponential law but it is what has driven in some ways the fourth
what has driven in some ways the fourth
what has driven in some ways the fourth Industrial Revolution right and we’re
Industrial Revolution right and we’re
Industrial Revolution right and we’re all affected by it we carry around a
all affected by it we carry around a
all affected by it we carry around a smartphone today which has pretty much a
smartphone today which has pretty much a
smartphone today which has pretty much a very powerful computer in it and that’s
very powerful computer in it and that’s
very powerful computer in it and that’s all possible because of Moore’s law well
all possible because of Moore’s law well
all possible because of Moore’s law well it turns out that there’s another law
it turns out that there’s another law
it turns out that there’s another law it’s that is also accelerating and that
it’s that is also accelerating and that
it’s that is also accelerating and that is called flat Lee’s law and flat leaves
is called flat Lee’s law and flat leaves
is called flat Lee’s law and flat leaves law is about being able to read DNA
law is about being able to read DNA
law is about being able to read DNA sequences in great detail and at
sequences in great detail and at
sequences in great detail and at reasonable cost right and if you see the
reasonable cost right and if you see the
reasonable cost right and if you see the curve there actually flattens law is
curve there actually flattens law is
curve there actually flattens law is drawing propping faster than Moore’s Law
drawing propping faster than Moore’s Law
drawing propping faster than Moore’s Law in the last maybe ten years and this is
in the last maybe ten years and this is
in the last maybe ten years and this is called next-generation sequencing and
called next-generation sequencing and
called next-generation sequencing and it’s actually moving roughly at the
it’s actually moving roughly at the
it’s actually moving roughly at the square of Moore’s law you see the
square of Moore’s law you see the
square of Moore’s law you see the timeline during which information
timeline during which information
timeline during which information technology has taken off is roughly the
technology has taken off is roughly the
technology has taken off is roughly the timeline during which the field of
timeline during which the field of
timeline during which the field of genomics has also developed so around
genomics has also developed so around
genomics has also developed so around the time that the first computers were
the time that the first computers were
the time that the first computers were being conceived you also had that the
being conceived you also had that the
being conceived you also had that the double helix structure of DNA solved by
double helix structure of DNA solved by
double helix structure of DNA solved by Watson and Crick and then you know
Watson and Crick and then you know
Watson and Crick and then you know industrialization in information
industrialization in information
industrialization in information technology have
technology have
technology have a little bit earlier but by about the
a little bit earlier but by about the
a little bit earlier but by about the mid-80s instruments for being able to
mid-80s instruments for being able to
mid-80s instruments for being able to sequence and read off genome data
sequence and read off genome data
sequence and read off genome data started becoming available if you look
started becoming available if you look
started becoming available if you look at the progress in in electronics in you
at the progress in in electronics in you
at the progress in in electronics in you know 1958 I guess the the first company
know 1958 I guess the the first company
know 1958 I guess the the first company that that made semiconductors was set up
that that made semiconductors was set up
that that made semiconductors was set up similarly for genomics it started in
similarly for genomics it started in
similarly for genomics it started in 1985 or so so it’s not a genomic started
1985 or so so it’s not a genomic started
1985 or so so it’s not a genomic started off a little bit later but by about 2006
off a little bit later but by about 2006
off a little bit later but by about 2006 you know we had reached what we call the
you know we had reached what we call the
you know we had reached what we call the second half of the chessboard you know
second half of the chessboard you know
second half of the chessboard you know the story about the chessboard right put
the story about the chessboard right put
the story about the chessboard right put one grain of rice on the first square
one grain of rice on the first square
one grain of rice on the first square double it on the second doublet again on
double it on the second doublet again on
double it on the second doublet again on the third and so forth so when you get
the third and so forth so when you get
the third and so forth so when you get halfway through the chessboard you reach
halfway through the chessboard you reach
halfway through the chessboard you reach about four billion now that means that
about four billion now that means that
about four billion now that means that the technology has improved four billion
the technology has improved four billion
the technology has improved four billion times right and that’s very substantial
times right and that’s very substantial
times right and that’s very substantial so once you get past that into that
so once you get past that into that
so once you get past that into that second half of the chessboard you see
second half of the chessboard you see
second half of the chessboard you see really miraculous use of technology and
really miraculous use of technology and
really miraculous use of technology and that’s what we’re experiencing today
that’s what we’re experiencing today
that’s what we’re experiencing today whether it’s autonomous vehicles or
whether it’s autonomous vehicles or
whether it’s autonomous vehicles or artificial intelligence systems and all
artificial intelligence systems and all
artificial intelligence systems and all kinds of impact of you know the the
kinds of impact of you know the the
kinds of impact of you know the the second half of the Moore’s Law impact in
second half of the Moore’s Law impact in
second half of the Moore’s Law impact in in technology now what what has happened
in technology now what what has happened
in technology now what what has happened in genomics is that it went along with
in genomics is that it went along with
in genomics is that it went along with Moore’s law for a while but then it
Moore’s law for a while but then it
Moore’s law for a while but then it accelerated even faster
accelerated even faster
accelerated even faster so it so happens that this year in 2017
so it so happens that this year in 2017
so it so happens that this year in 2017 we have entered the second half of
we have entered the second half of
we have entered the second half of genomics as well so what does this
genomics as well so what does this
genomics as well so what does this actually mean this means that it’s
actually mean this means that it’s
actually mean this means that it’s getting cheaper faster and better to be
getting cheaper faster and better to be
getting cheaper faster and better to be able to read the DNA of of an individual
able to read the DNA of of an individual
able to read the DNA of of an individual and be able to make certain decisions
and be able to make certain decisions
and be able to make certain decisions based on that and that’s what
based on that and that’s what
based on that and that’s what this whole thing with precision medicine
this whole thing with precision medicine
this whole thing with precision medicine and cancer is about right so ah there we
and cancer is about right so ah there we
and cancer is about right so ah there we go so what is this DNA this DNA is
go so what is this DNA this DNA is
go so what is this DNA this DNA is essentially a book that we have
essentially a book that we have
essentially a book that we have trillions of copies of right and it’s in
trillions of copies of right and it’s in
trillions of copies of right and it’s in the DNA of that you’re born with and
the DNA of that you’re born with and
the DNA of that you’re born with and that’s actually a book which is written
that’s actually a book which is written
that’s actually a book which is written in an alphabet of just four letters ACGT
in an alphabet of just four letters ACGT
in an alphabet of just four letters ACGT and it it’s a fairly long book in the
and it it’s a fairly long book in the
and it it’s a fairly long book in the sense that it’s three billion letters
sense that it’s three billion letters
sense that it’s three billion letters long right and we all have this it’s you
long right and we all have this it’s you
long right and we all have this it’s you know I think most of you have had some
know I think most of you have had some
know I think most of you have had some introductory biology so I won’t belabor
introductory biology so I won’t belabor
introductory biology so I won’t belabor this now what did the human genome
this now what did the human genome
this now what did the human genome project achieve it gave us the first
project achieve it gave us the first
project achieve it gave us the first reference genome of of a human being now
reference genome of of a human being now
reference genome of of a human being now so if the black band there is the
so if the black band there is the
so if the black band there is the reference genome now when I take an
reference genome now when I take an
reference genome now when I take an individual patients DNA and start
individual patients DNA and start
individual patients DNA and start sequencing it I’ll sequence it in small
sequencing it I’ll sequence it in small
sequencing it I’ll sequence it in small bits right and those are called reads
bits right and those are called reads
bits right and those are called reads now I can do a string matching and put
now I can do a string matching and put
now I can do a string matching and put that read against the reference genome
that read against the reference genome
that read against the reference genome and I know where it where it actually
and I know where it where it actually
and I know where it where it actually fits right but if you just do one copy
fits right but if you just do one copy
fits right but if you just do one copy of the DNA you’re likely to make errors
of the DNA you’re likely to make errors
of the DNA you’re likely to make errors so what we do is actually put many many
so what we do is actually put many many
so what we do is actually put many many copies of DNA cut it up into B’s pieces
copies of DNA cut it up into B’s pieces
copies of DNA cut it up into B’s pieces sequence those pieces and then assemble
sequence those pieces and then assemble
sequence those pieces and then assemble them so that’s a big computational
them so that’s a big computational
them so that’s a big computational challenge but it can be done right and
challenge but it can be done right and
challenge but it can be done right and so for cancer patients for example you
so for cancer patients for example you
so for cancer patients for example you take about a thousand copies of the DNA
take about a thousand copies of the DNA
take about a thousand copies of the DNA from the tumor and you will actually
from the tumor and you will actually
from the tumor and you will actually sequence those and put those thousand
sequence those and put those thousand
sequence those and put those thousand copies in fragments in reads as as you
copies in fragments in reads as as you
copies in fragments in reads as as you see in the picture there now you can
see in the picture there now you can
see in the picture there now you can actually look down a specific position
actually look down a specific position
actually look down a specific position in there
in there
in there friends genome and see if the same
friends genome and see if the same
friends genome and see if the same pattern is in all the reads and you see
pattern is in all the reads and you see
pattern is in all the reads and you see here there is there is a I think it’s an
here there is there is a I think it’s an
here there is there is a I think it’s an a which is replaced by a T right that’s
a which is replaced by a T right that’s
a which is replaced by a T right that’s called a single nucleotide polymorphism
called a single nucleotide polymorphism
called a single nucleotide polymorphism so it’s actually something so the the
so it’s actually something so the the
so it’s actually something so the the the easier way to call it is a snip it’s
the easier way to call it is a snip it’s
the easier way to call it is a snip it’s a snip right and these the snip actually
a snip right and these the snip actually
a snip right and these the snip actually is such that it is from in some sense
is such that it is from in some sense
is such that it is from in some sense from the the both copies of the of the
from the the both copies of the of the
from the the both copies of the of the DNA which means that it came from both
DNA which means that it came from both
DNA which means that it came from both parents right you can also have snips
parents right you can also have snips
parents right you can also have snips which are heterozygous that is it comes
which are heterozygous that is it comes
which are heterozygous that is it comes from only one parent right if it comes
from only one parent right if it comes
from only one parent right if it comes from both friends you call it homozygous
from both friends you call it homozygous
from both friends you call it homozygous if it’s from only one parent equal it
if it’s from only one parent equal it
if it’s from only one parent equal it heterozygous right and then you can
heterozygous right and then you can
heterozygous right and then you can start collecting and looking at all of
start collecting and looking at all of
start collecting and looking at all of these snips right now for each human
these snips right now for each human
these snips right now for each human being there are you know lots and lots
being there are you know lots and lots
being there are you know lots and lots of snips that that arise in the genome
of snips that that arise in the genome
of snips that that arise in the genome but only one of them or maybe a few of
but only one of them or maybe a few of
but only one of them or maybe a few of them together are causing problems
them together are causing problems
them together are causing problems causing a disease or some so you have to
causing a disease or some so you have to
causing a disease or some so you have to be able to sort it all out so we won’t
be able to sort it all out so we won’t
be able to sort it all out so we won’t get into the details of how you sort it
get into the details of how you sort it
get into the details of how you sort it all that but but let’s let’s look about
all that but but let’s let’s look about
all that but but let’s let’s look about look at how this is starting to help
look at how this is starting to help
look at how this is starting to help people right and so this is the famous
people right and so this is the famous
people right and so this is the famous story of a Ling young boy called
story of a Ling young boy called
story of a Ling young boy called Nicholas Volker who was in some sense
Nicholas Volker who was in some sense
Nicholas Volker who was in some sense the poster you know child of genomic
the poster you know child of genomic
the poster you know child of genomic medicine because you know he was having
medicine because you know he was having
medicine because you know he was having lots of problems with essentially with
lots of problems with essentially with
lots of problems with essentially with digestion and I had to have many many
digestion and I had to have many many
digestion and I had to have many many surgeries and at some point the doctors
surgeries and at some point the doctors
surgeries and at some point the doctors suspected that there was some problem
suspected that there was some problem
suspected that there was some problem with his immune system but to confirm it
with his immune system but to confirm it
with his immune system but to confirm it they sequenced his DNA and they actually
they sequenced his DNA and they actually
they sequenced his DNA and they actually found the culprit gene
found the culprit gene
found the culprit gene and they found that mutations which had
and they found that mutations which had
and they found that mutations which had caused the immunodeficiency at which
caused the immunodeficiency at which
caused the immunodeficiency at which point they were able to get him a bone
point they were able to get him a bone
point they were able to get him a bone marrow transplant and and this was about
marrow transplant and and this was about
marrow transplant and and this was about maybe eight years ago so so this boy is
maybe eight years ago so so this boy is
maybe eight years ago so so this boy is now healthy he is going to school then
now healthy he is going to school then
now healthy he is going to school then and so on so so they you know the the
and so on so so they you know the the
and so on so so they you know the the story of how this boy was you know
story of how this boy was you know
story of how this boy was you know diagnosed and then recovered is was
diagnosed and then recovered is was
diagnosed and then recovered is was written up as a book and it won the
written up as a book and it won the
written up as a book and it won the Pulitzer Prize
Pulitzer Prize
Pulitzer Prize the next story of course many of you are
the next story of course many of you are
the next story of course many of you are familiar with because this happened just
familiar with because this happened just
familiar with because this happened just a couple of years ago Angelina Jolie
a couple of years ago Angelina Jolie
a couple of years ago Angelina Jolie actually discovered that she has
actually discovered that she has
actually discovered that she has inherited some terrible genetic factors
inherited some terrible genetic factors
inherited some terrible genetic factors for breast and ovarian cancer from her
for breast and ovarian cancer from her
for breast and ovarian cancer from her mother and and she had two family
mother and and she had two family
mother and and she had two family members a mother and her aunt affected
members a mother and her aunt affected
members a mother and her aunt affected and and therefore took some bold
and and therefore took some bold
and and therefore took some bold decisions on elective surgeries to
decisions on elective surgeries to
decisions on elective surgeries to improve her chances of not getting
improve her chances of not getting
improve her chances of not getting cancer went in later age right so it’s
cancer went in later age right so it’s
cancer went in later age right so it’s an example of again you know where
an example of again you know where
an example of again you know where individualized medicine or you know I
individualized medicine or you know I
individualized medicine or you know I said the zebra right comes into play
said the zebra right comes into play
said the zebra right comes into play because in her case she had ovarian
because in her case she had ovarian
because in her case she had ovarian cancer which then later on there was a
cancer which then later on there was a
cancer which then later on there was a relapse in breast cancer and and then we
relapse in breast cancer and and then we
relapse in breast cancer and and then we analyzed her DNA a tumor DNA and we know
analyzed her DNA a tumor DNA and we know
analyzed her DNA a tumor DNA and we know not a tumor DNA but her the germline DNA
not a tumor DNA but her the germline DNA
not a tumor DNA but her the germline DNA the DNA she was born with and found that
the DNA she was born with and found that
the DNA she was born with and found that there was an inherited factor which
there was an inherited factor which
there was an inherited factor which which then led to treatment all of this
which then led to treatment all of this
which then led to treatment all of this type of diagnosis today is possible in
type of diagnosis today is possible in
type of diagnosis today is possible in India it’s done by this company called
India it’s done by this company called
India it’s done by this company called strand which which a bunch of us started
strand which which a bunch of us started
strand which which a bunch of us started and we have a platform called strand
and we have a platform called strand
and we have a platform called strand Ramanujan that actually helps with with
Ramanujan that actually helps with with
Ramanujan that actually helps with with this diagnosis if you want to read about
this diagnosis if you want to read about
this diagnosis if you want to read about more zebras stories there’s a book
more zebras stories there’s a book
more zebras stories there’s a book called genomic quirks that remain Sharan
called genomic quirks that remain Sharan
called genomic quirks that remain Sharan my co-founder has written which is
my co-founder has written which is
my co-founder has written which is available on Amazon and which can will
available on Amazon and which can will
available on Amazon and which can will also shortly be issued by the Indian
also shortly be issued by the Indian
also shortly be issued by the Indian Institute of Science Press so
Institute of Science Press so
Institute of Science Press so essentially we are entering an era of
essentially we are entering an era of
essentially we are entering an era of precision medicine based on I think the
precision medicine based on I think the
precision medicine based on I think the first impact we are seeing is in cancer
first impact we are seeing is in cancer
first impact we are seeing is in cancer or as in the case of Nicolas Volker in
or as in the case of Nicolas Volker in
or as in the case of Nicolas Volker in rare disorders
rare disorders
rare disorders you know immunodeficiency ease and
you know immunodeficiency ease and
you know immunodeficiency ease and lysosomal storage disorders and so on
lysosomal storage disorders and so on
lysosomal storage disorders and so on where you are able to to actually treat
where you are able to to actually treat
where you are able to to actually treat the patient on the specifics of what the
the patient on the specifics of what the
the patient on the specifics of what the patient’s inherited DNA is and what is
patient’s inherited DNA is and what is
patient’s inherited DNA is and what is causing the disease and and so I think
causing the disease and and so I think
causing the disease and and so I think in some sense this is transforming the
in some sense this is transforming the
in some sense this is transforming the way in which medicine is being practiced
way in which medicine is being practiced
way in which medicine is being practiced and that’s the idea that I wanted to
and that’s the idea that I wanted to
and that’s the idea that I wanted to convey today thank you
convey today thank you
convey today thank you [Applause]
”
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