a time to be born this is a familiar
phrase
most people it’s an ancient phrase comes
from the recognition by the ancients
that nature is psychical that animals
sheep horses other species of
domestication were born at certain times
of year so this recognition that time
plays a role in our lives from the
beginning is an ancient one but there
are other dimensions of time that relate
to birth especially for the human that
need to be considered the time course of
pregnancy being one of them normal
pregnancy runs as most people know nine
months more exact 38 to 40 weeks if the
pregnancy is interrupted before that
problems arise we talk about preterm
birth being a pregnancy that ends before
weeks 37 if it ends much earlier than
that the chances of the baby surviving
are very very poor technology has
advanced so far that a late preemie
after week 30 32 of pregnancy has a good
chance of survival but may still have a
life long series of disabilities from
neurological immunological and otherwise
the causes of preterm labor are diverse
many still unknown and there really
hasn’t been much advancement in this
field in the last 3040 years there are a
lot of drugs used which extend labor
from the point of preterm contractions
maybe a week and granted every day is
valuable
the longer the pregnancy lasts the more
likely the child will be to survive
but I’m interested in time as you might
have picked up so there’s another
dimension of time that everyone knows
about when it comes to labor you ask any
OBGYN when her baby’s born and they all
say well the night that’s why I’ve got
to work nights off but you ask them why
why does it happen tonight there’s no
answer just is well I’m a scientist I
don’t like answers like that so I wanted
to know why does it happen
why does labor typically in an eighty
eighty-five percent of the human
population begin at night now you can
answer this in different ways you can
say well there’s an advantage to babies
being born at night at least there used
to be say a million years ago the woman
was pregnant and would retreat to her
clan to her tribe in the caves or in the
huts she would be around her peers her
families and be safe likelihood of the
child being born in safety and security
is much improved interestingly in other
animals rodents that are active at night
are giving birth in the daytime
well those animals in the daytime are in
their burrows so it’s the same logic
that they’re with their mates and
protected and safe so that’s one answer
but it’s not the answer I’m looking for
when I see a trace like this I think of
clocks biological clocks we’re all
familiar with our sleep/wake cycles this
is known to be under the control of a
part of the brain known as our clock and
this circadian clock which times 24-hour
rhythms regulates all sorts of things
not just our sleep/wake cycles as you
can see on this graph it regulates when
our fastest reaction times are late
afternoon when our blood pressure rises
the most when we’re most alert when our
body temperature is the minimum
so on so I’ve over the last 15 years
tried to address the possibility that
the timing of labor shown here in pink
which is nighttime is somehow associated
with the brain’s clock via its main
hormonal signal melatonin
who here has not heard of melatonin I
think everyone’s heard of melatonin in
the context of sleep right most people
turns out it’s a major hormonal output
signal of the brain to the rest of the
body to tell us it’s nighttime certain
things should happen other things
shouldn’t happen a real interesting
feature of melatonin is the fact that it
is secreted by the brain in response to
signals from the clock but it also feeds
back and works on the talk this is why I
take it for example for jet lag
I can reset my clock so that when I land
in Paris I’m no longer in American time
zone I’m in European time so it’s a nice
little trick I learned along the way now
this is a study from over 20 years ago
showing the pattern of sleep and wake in
a blind child now blind people generally
have a lot of issues with keeping their
sleep wake cycles and sync with the
outside world on the left you can see
the red trace tracks the onset of sleep
those dark horizontal bars each row is a
different day and this child is doing
what we say freerunning that is to say
the clock doesn’t have a sense of winds
the right time to sleep and when’s the
right time to wake up and this is of
course very challenging for the child to
stay awake in the daytime for example
and for the parents quite obviously in
this study one of the earlier studies
it’s been replicated a million times
they gave melatonin at those green
points in the right graph and I think
everyone immediately senses what’s going
on the clock is now locked into that so
this melatonin signal serves as a
feedback signal to our clocks to
establish the proper day/night rhythms
so this was very tantalizing
to me in the context of the timing of
birth now as I mentioned a moment ago
rats
since their night active they tend to
give birth in the daytime in the study
by Takayama many years ago they showed
that in the normal case the blue little
mice there are rats will normally be
born during the daytime when melatonin
is low that blue arrow however if you
remove the source of melatonin which is
the brains pineal gland that rhythm is
lost
these animals are giving birth across 24
hours pretty randomly however if you
restore melatonin to the mother rat in a
manner that replicates the normal
nighttime pattern you get back to the
normal timing of births so this was very
strong evidence for me that there is a
connection between melatonin and the
timing of birth at least in the rat now
I can’t go taking the pineal gland out
of women who are pregnant to study this
right so I had to approach this whole
question in a different manner
my hypothesis graphically shown here is
that labor leading to birth is occurring
during the night time and as I’ve
indicated the largest majority of women
do enter labor at nighttime these
contractions here shown in pink get
higher and higher during the course of
night correlated with that is this rise
of melatonin in the bloodstream so the
hypothesis I developed about 10 years
ago is that the timing of human labor is
a circadian event a 24-hour pattern that
is mediated by the action of melatonin
melatonin in pregnancy was not very well
studied I was one of the fearless
scientists who would attack this
question we know what signals night
phase we were the first group to show
that the receptors the the antenna for
melatonin proteins in the uterus are
present we showed in a series of studies
that these
chapters when melatonin is present
causes contractions of the uterus this
is very similar to oxytocin many people
know oxytocin as a labor inducing drug
interesting and very important for our
thinking is that the receptors in the
uterus are not there throughout most of
pregnancy but appear at the end of
pregnancy when labor begins very
analogous to the oxytocin receptors so
there rose the question well if you’re
saying it might be linked to preterm but
there’s no receptors in the uterus
during most of pregnancy how can that be
so we had to make a very Herculean
effort to find women who would give us
biopsy material when they went into
preterm labor this was not easy but we
managed to get five samples and all five
of these women have melatonin receptors
so this really excited us that the
hypothesis could be true our working
hypothesis then out of all this data was
that melatonin underlies contractions
leading to labor well if we impede if we
somehow interfere with that signal we
should be able to lower contractions
well how does one do that like I say I’m
not going to take the pineal gland out
at these women there are drugs which we
use in the laboratory can block the
receptors they’ve never been clinically
tested there are drugs which can block
the synthesis in the brain again too
many side effects so we landed upon a
unique approach and yet one that’s not
unfamiliar you’ve probably heard or read
somewhere along the way about photo
therapy yeah photo therapy is used to
treat seasonal affective disorder which
is a circadian disorder by the way
winter depression right and it involves
using a lamp a photo therapy monitor
that the person looks at in the morning
to lower their depressive state well I
have friends in this field as you might
imagine
and so I said hey can I borrow your
phototherapy lab for a few years it’s in
a few years maybe a few months but I
managed to compromise on a year and we
set up a study involving pregnant women
undergoing contractions now these
weren’t preterm contractions cuz there’s
no way to know are you gonna go preterm
next week
we can’t know this right so we had to go
with women late in pregnancy who were
starting to contract needless to say
this was somewhat risky because in a few
cases they had their babies before they
came to the study we had to wait till
the very end of pregnancy to see those
contractions appearing the hypothesis
the prediction shown here is that that
melatonin rise the blue line here which
is the normal pattern by inhibiting it
with light which is known to work should
suppress contractions right
if melatonin underlies those
contractions if we suppress not don’t
should suppress the contractions people
thought I was crazy
said what you’re gonna show a light
pregnant women and stop the contractions
that’s nuts nuts but it worked it worked
every woman responded to light we gave
them one hour of light exposure shown
here the white bar at 11 p.m. at night
you see the contractions earlier rising
as night precedes that one hour of light
suppressed every woman not entirely some
were suppressed by 50% others by 60% now
there’s a hundred percent remarkably
when we turned the light off they
remained suppressed in most cases for
many hours so there was a bit of a lag
phase thereafter suppression and then
there is a bit of a rebound here are
four examples and you see there’s some
variability you know people aren’t rats
they very divergent in the responses to
things but in every case we lowered
contractions and generally suppress them
for hours when I told the office of
intellectual property about this they
said get a patent
you got to get a patent so we did and
that led to kinderman
we formed this company three years ago
with the goal of using lights as a drug
if you will light to suppress
contractions now you can’t really
envision a woman at risk of preterm
labor using a photo therapy lamp every
night to blast her partner you know
that’s not gonna work right so we
decided we needed to develop a an
individual light emitting device better
known as a mask and more importantly we
wanted to fine-tune it turns out that
the suppression of melatonin by white
light is entirely due to one wavelength
and that’s blue light now isn’t that
interesting
blue light where do we normally see a
lot of blue light in our world the sky
hey don’t tell me iPhones the sky the
sky is blue we evolved under this world
with blue light was daytime and so our
eyes have developed a specific sensor
for blue light and it’s that wavelength
of light that is the most effective at
suppressing melatonin now it is present
in iPhones and TV screens and all these
other things and that’s why you should
use the filter evenings to prevent that
interference with your clock more
importantly blue light goes through the
skin which means in a mask if the
woman’s eyes are closed it’ll go through
the closed eyelids
she doesn’t have to stand there staring
at this light
all night long right so we thought that
was a clear advantage so kinder med has
developed a mask which I actually
happened to have on me yeah
now with the bright lights on the stage
you probably can’t see this but this
shines well as always it doesn’t work
when I want it to this is the mask small
blue lights behind it they come on
automatically suppress melatonin the
woman doesn’t have to worry about
anything other than sleeping there are
very few side effects
certainly fewer than drugs it’s
comfortable it’s convenient and it’s
very inexpensive drug therapy for
preterm labor can run into the tens
fifty thousand dollars per treatment so
this is definitely an advance we think
our goal ultimately of course is to
treat preterm labor this is a huge
problem as I said it hasn’t changed in
the world in 30 years still about 10% of
all pregnancies end in preterm labor
the emotional costs the family costs the
healthcare costs are huge talking thirty
forty billion dollars in this country
alone annually in the world fifteen
million babies are born preterm and many
of them don’t survive it’s time to try
something new even if it appears science
fiction we think our blue light mask
will make great strides in reducing
preterm labor and we’re working with
Harvard right now on some testing of the
masks and other groups around the
country my hope is that within a year we
can start saving millions of babies
lives around the world thank you very
much
[Applause]
you
phrase
most people it’s an ancient phrase comes
from the recognition by the ancients
that nature is psychical that animals
sheep horses other species of
domestication were born at certain times
of year so this recognition that time
plays a role in our lives from the
beginning is an ancient one but there
are other dimensions of time that relate
to birth especially for the human that
need to be considered the time course of
pregnancy being one of them normal
pregnancy runs as most people know nine
months more exact 38 to 40 weeks if the
pregnancy is interrupted before that
problems arise we talk about preterm
birth being a pregnancy that ends before
weeks 37 if it ends much earlier than
that the chances of the baby surviving
are very very poor technology has
advanced so far that a late preemie
after week 30 32 of pregnancy has a good
chance of survival but may still have a
life long series of disabilities from
neurological immunological and otherwise
the causes of preterm labor are diverse
many still unknown and there really
hasn’t been much advancement in this
field in the last 3040 years there are a
lot of drugs used which extend labor
from the point of preterm contractions
maybe a week and granted every day is
valuable
the longer the pregnancy lasts the more
likely the child will be to survive
but I’m interested in time as you might
have picked up so there’s another
dimension of time that everyone knows
about when it comes to labor you ask any
OBGYN when her baby’s born and they all
say well the night that’s why I’ve got
to work nights off but you ask them why
why does it happen tonight there’s no
answer just is well I’m a scientist I
don’t like answers like that so I wanted
to know why does it happen
why does labor typically in an eighty
eighty-five percent of the human
population begin at night now you can
answer this in different ways you can
say well there’s an advantage to babies
being born at night at least there used
to be say a million years ago the woman
was pregnant and would retreat to her
clan to her tribe in the caves or in the
huts she would be around her peers her
families and be safe likelihood of the
child being born in safety and security
is much improved interestingly in other
animals rodents that are active at night
are giving birth in the daytime
well those animals in the daytime are in
their burrows so it’s the same logic
that they’re with their mates and
protected and safe so that’s one answer
but it’s not the answer I’m looking for
when I see a trace like this I think of
clocks biological clocks we’re all
familiar with our sleep/wake cycles this
is known to be under the control of a
part of the brain known as our clock and
this circadian clock which times 24-hour
rhythms regulates all sorts of things
not just our sleep/wake cycles as you
can see on this graph it regulates when
our fastest reaction times are late
afternoon when our blood pressure rises
the most when we’re most alert when our
body temperature is the minimum
so on so I’ve over the last 15 years
tried to address the possibility that
the timing of labor shown here in pink
which is nighttime is somehow associated
with the brain’s clock via its main
hormonal signal melatonin
who here has not heard of melatonin I
think everyone’s heard of melatonin in
the context of sleep right most people
turns out it’s a major hormonal output
signal of the brain to the rest of the
body to tell us it’s nighttime certain
things should happen other things
shouldn’t happen a real interesting
feature of melatonin is the fact that it
is secreted by the brain in response to
signals from the clock but it also feeds
back and works on the talk this is why I
take it for example for jet lag
I can reset my clock so that when I land
in Paris I’m no longer in American time
zone I’m in European time so it’s a nice
little trick I learned along the way now
this is a study from over 20 years ago
showing the pattern of sleep and wake in
a blind child now blind people generally
have a lot of issues with keeping their
sleep wake cycles and sync with the
outside world on the left you can see
the red trace tracks the onset of sleep
those dark horizontal bars each row is a
different day and this child is doing
what we say freerunning that is to say
the clock doesn’t have a sense of winds
the right time to sleep and when’s the
right time to wake up and this is of
course very challenging for the child to
stay awake in the daytime for example
and for the parents quite obviously in
this study one of the earlier studies
it’s been replicated a million times
they gave melatonin at those green
points in the right graph and I think
everyone immediately senses what’s going
on the clock is now locked into that so
this melatonin signal serves as a
feedback signal to our clocks to
establish the proper day/night rhythms
so this was very tantalizing
to me in the context of the timing of
birth now as I mentioned a moment ago
rats
since their night active they tend to
give birth in the daytime in the study
by Takayama many years ago they showed
that in the normal case the blue little
mice there are rats will normally be
born during the daytime when melatonin
is low that blue arrow however if you
remove the source of melatonin which is
the brains pineal gland that rhythm is
lost
these animals are giving birth across 24
hours pretty randomly however if you
restore melatonin to the mother rat in a
manner that replicates the normal
nighttime pattern you get back to the
normal timing of births so this was very
strong evidence for me that there is a
connection between melatonin and the
timing of birth at least in the rat now
I can’t go taking the pineal gland out
of women who are pregnant to study this
right so I had to approach this whole
question in a different manner
my hypothesis graphically shown here is
that labor leading to birth is occurring
during the night time and as I’ve
indicated the largest majority of women
do enter labor at nighttime these
contractions here shown in pink get
higher and higher during the course of
night correlated with that is this rise
of melatonin in the bloodstream so the
hypothesis I developed about 10 years
ago is that the timing of human labor is
a circadian event a 24-hour pattern that
is mediated by the action of melatonin
melatonin in pregnancy was not very well
studied I was one of the fearless
scientists who would attack this
question we know what signals night
phase we were the first group to show
that the receptors the the antenna for
melatonin proteins in the uterus are
present we showed in a series of studies
that these
chapters when melatonin is present
causes contractions of the uterus this
is very similar to oxytocin many people
know oxytocin as a labor inducing drug
interesting and very important for our
thinking is that the receptors in the
uterus are not there throughout most of
pregnancy but appear at the end of
pregnancy when labor begins very
analogous to the oxytocin receptors so
there rose the question well if you’re
saying it might be linked to preterm but
there’s no receptors in the uterus
during most of pregnancy how can that be
so we had to make a very Herculean
effort to find women who would give us
biopsy material when they went into
preterm labor this was not easy but we
managed to get five samples and all five
of these women have melatonin receptors
so this really excited us that the
hypothesis could be true our working
hypothesis then out of all this data was
that melatonin underlies contractions
leading to labor well if we impede if we
somehow interfere with that signal we
should be able to lower contractions
well how does one do that like I say I’m
not going to take the pineal gland out
at these women there are drugs which we
use in the laboratory can block the
receptors they’ve never been clinically
tested there are drugs which can block
the synthesis in the brain again too
many side effects so we landed upon a
unique approach and yet one that’s not
unfamiliar you’ve probably heard or read
somewhere along the way about photo
therapy yeah photo therapy is used to
treat seasonal affective disorder which
is a circadian disorder by the way
winter depression right and it involves
using a lamp a photo therapy monitor
that the person looks at in the morning
to lower their depressive state well I
have friends in this field as you might
imagine
and so I said hey can I borrow your
phototherapy lab for a few years it’s in
a few years maybe a few months but I
managed to compromise on a year and we
set up a study involving pregnant women
undergoing contractions now these
weren’t preterm contractions cuz there’s
no way to know are you gonna go preterm
next week
we can’t know this right so we had to go
with women late in pregnancy who were
starting to contract needless to say
this was somewhat risky because in a few
cases they had their babies before they
came to the study we had to wait till
the very end of pregnancy to see those
contractions appearing the hypothesis
the prediction shown here is that that
melatonin rise the blue line here which
is the normal pattern by inhibiting it
with light which is known to work should
suppress contractions right
if melatonin underlies those
contractions if we suppress not don’t
should suppress the contractions people
thought I was crazy
said what you’re gonna show a light
pregnant women and stop the contractions
that’s nuts nuts but it worked it worked
every woman responded to light we gave
them one hour of light exposure shown
here the white bar at 11 p.m. at night
you see the contractions earlier rising
as night precedes that one hour of light
suppressed every woman not entirely some
were suppressed by 50% others by 60% now
there’s a hundred percent remarkably
when we turned the light off they
remained suppressed in most cases for
many hours so there was a bit of a lag
phase thereafter suppression and then
there is a bit of a rebound here are
four examples and you see there’s some
variability you know people aren’t rats
they very divergent in the responses to
things but in every case we lowered
contractions and generally suppress them
for hours when I told the office of
intellectual property about this they
said get a patent
you got to get a patent so we did and
that led to kinderman
we formed this company three years ago
with the goal of using lights as a drug
if you will light to suppress
contractions now you can’t really
envision a woman at risk of preterm
labor using a photo therapy lamp every
night to blast her partner you know
that’s not gonna work right so we
decided we needed to develop a an
individual light emitting device better
known as a mask and more importantly we
wanted to fine-tune it turns out that
the suppression of melatonin by white
light is entirely due to one wavelength
and that’s blue light now isn’t that
interesting
blue light where do we normally see a
lot of blue light in our world the sky
hey don’t tell me iPhones the sky the
sky is blue we evolved under this world
with blue light was daytime and so our
eyes have developed a specific sensor
for blue light and it’s that wavelength
of light that is the most effective at
suppressing melatonin now it is present
in iPhones and TV screens and all these
other things and that’s why you should
use the filter evenings to prevent that
interference with your clock more
importantly blue light goes through the
skin which means in a mask if the
woman’s eyes are closed it’ll go through
the closed eyelids
she doesn’t have to stand there staring
at this light
all night long right so we thought that
was a clear advantage so kinder med has
developed a mask which I actually
happened to have on me yeah
now with the bright lights on the stage
you probably can’t see this but this
shines well as always it doesn’t work
when I want it to this is the mask small
blue lights behind it they come on
automatically suppress melatonin the
woman doesn’t have to worry about
anything other than sleeping there are
very few side effects
certainly fewer than drugs it’s
comfortable it’s convenient and it’s
very inexpensive drug therapy for
preterm labor can run into the tens
fifty thousand dollars per treatment so
this is definitely an advance we think
our goal ultimately of course is to
treat preterm labor this is a huge
problem as I said it hasn’t changed in
the world in 30 years still about 10% of
all pregnancies end in preterm labor
the emotional costs the family costs the
healthcare costs are huge talking thirty
forty billion dollars in this country
alone annually in the world fifteen
million babies are born preterm and many
of them don’t survive it’s time to try
something new even if it appears science
fiction we think our blue light mask
will make great strides in reducing
preterm labor and we’re working with
Harvard right now on some testing of the
masks and other groups around the
country my hope is that within a year we
can start saving millions of babies
lives around the world thank you very
much
[Applause]
you
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