KOPYA NG SALIN 🔗
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Kristelle Shulman: My name is
Kristelle Shulman. I am a nurse
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practitioner for about almost 20
years,
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Evan Shulman: and I'm Evan
Shulman, and I've been a PA, or
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physician assistant, for 20
years.
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Kristelle Shulman: That's
actually how we met. In the
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hospital.
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Evan Shulman: Yep, that was it.
She said hello to me in the
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elevator, and we had both looked
at each other, I guess, for a
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while, but at the time Kristelle
was working in the recovery
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area, and I never had an excuse
to talk to her, and the elevator
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was, was it one day.
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Lauren Arora Hutchinson: In many
ways, Evan and Kristelle are an
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ordinary couple, two working
people with busy lives. They're
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now married. They live in New
York City. They love to
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exercise. And shortly after
getting married in 2015, they
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did what many couples do. They
decided to start a family.
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Kristelle Shulman: We had a
normal pregnancy, as well as
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delivery. Noah was born on
December 29th, 2016 It was the
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best feeling in the world.
Inexplicable, I would say.
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Evan Shulman: He was born
relatively healthy, initially
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had some low glucose levels. He
was checked multiple times by
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the pediatric team, by the NICU.
They assured us everything was
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fine, and he was right from the
beginning pretty difficult to
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feed.
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Lauren Arora Hutchinson: Noah
struggled to breastfeed. While
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this was troubling to Evan and
Kristelle, the hospital staff
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reassured them there was nothing
to worry about.
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Evan Shulman: In the hospital,
we were assured that he's, you
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know, newborn, and he'll get it.
He just needs time to get it. By
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the time we were discharged
home, Kristelle had actually met
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with a lactation consultant, in
addition to the pediatric team,
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the NICU team. Everybody met
with us and reassured that
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everything's normal, so we went
home…
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Lauren Arora Hutchinson: Unfortunately,
the feeding troubles continued.
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Evan Shulman: And this went on.
This went on for almost 10-11
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days, and every night was
difficult, because we'd wake up
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to feed him. Feeds were taking
half hour, 45 minutes, an hour,
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sometimes. Sometimes an hour and
a half, just to get him to take
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down 15 or 20 mls of milk. So he
was, he was expending so much
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energy to feed that he was
falling asleep during the feed,
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and we said something is clearly
wrong. Like this is… this cannot
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be normal. We addressed these
concerns with our pediatrician
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in the office. At one point, he
kind of played it off as, oh,
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you're both medical
professionals and probably a
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little hyper sensitive, and
don't worry, just go home, he's
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going to feed. So, anyway, we
said something is definitely not
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right, and we called the
pediatrician's office, and the
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pediatrician, who we usually see
was not in, and we saw a much
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more junior pediatrician in the
office who spent, I would say, a
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good 30 minutes with Noah, held
him, tried to feed him, didn't
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just listen to our story and
send us out. He devoted a
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significant amount of time, and
then told us he was concerned,
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said he wasn't quite sure what
he's concerned about, and he
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said, “Go home if he's not
feeding in the next hour or two,
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then you need to take him to the
pediatric ER.” We went home, got
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a bag, and then went straight to
the ER, and that was really when
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everything started to unfold.
Um, sorry.
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Lauren Arora Hutchinson: What
happened next would change their
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lives and turn them into
accidental pioneers of genetic
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medicine. Over the next two
episodes, we're bringing you the
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story of Evan and Kristelle.
We'll retrace the steps of their
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heartbreaking journey, and hear
how they navigated a series of
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scientific and ethical
quandaries with no obvious
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answers. Along the way, their
story takes unexpected turns and
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ventures into new scientific
territory, more than we could
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cover in a single episode.
Perhaps unsurprisingly, their
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story deals with some difficult
themes and challenging moments.
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Please take care while
listening. I'm Lauren Arora
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Hutchinson, director of the
iDeas Lab at the Johns Hopkins
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Berman Institute of Bioethics,
and this is playing god?
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Evan Shulman: So, when we got
there, he was pretty lethargic,
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and immediately they said that
they were concerned and started
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doing a full panel of labs on
him. We waited out through the
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night, we just stayed by his
side, and then I think the next
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day was when the metabolic team
came and saw him and they
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started to mention, for the
first time, concern for
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mitochondrial disease.
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Lauren Arora Hutchinson:
Mitochondria are like many
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little power plants in each of
our cells. Throughout our body,
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they take nutrients and convert
them into energy that cells use
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to multiply, divide, and
regulate. The doctors worried
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that something might be wrong
with these tiny power plants,
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that Noah could have been born
with a small error in the DNA of
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his mitochondria, that this
mutation could be the cause of
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Noah's problems, and that if it
was, the prognosis could be
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dire. Receiving this news, they
decided to transfer Noah to
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Mount Sinai in Manhattan, a
hospital better equipped to help
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him.
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Evan Shulman: We got there
probably around midnight. I
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mean, it was like… we had the
biggest greeting by this huge
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team, like Noah was really
swarmed by people, and we stayed
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with him there through the
night, and they said it looks
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like for sure this is going to
be a mitochondrial disease, and
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we need to wait for genetic
testing.
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Lauren Arora Hutchinson: You
might remember from biology
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class that most of your DNA is
held in the nucleus of each
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cell. That's the genetic code
that shapes our bodies and many
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of our traits, but all of your
mitochondria also carry their
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own separate bits of DNA. That
mitochondrial DNA isn’t the same
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as the rest of our DNA. It
doesn’t determine or shape most
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of who we are, but it is
essential for how our cells
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produce energy. And so when
there’s a mutation in
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mitochondrial DNA, it can cause
mitochondrial disease. That's
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what the doctors at Mount Sinai
were testing. Noah stayed in the
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hospital for days, then weeks,
as his parents waited for the
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results.
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Evan Shulman: He had a lot of
difficulties. He had seizures.
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He ended up getting intubated.
He had respiratory distress.
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Kristelle Shulman: Evan and I
would sit right by his room,
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just alone, and like, how did we
get here? What happened? You
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know, we'd come back to his room
and just make sure that we, you
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know, wipe our tears and make
sure that we, that he hears us,
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and he and I, and when we know
that he knows we're there, it's
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just like that room was
surrounded by his like essence,
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you know.
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Evan Shulman: It took about 30
days from the date of admission
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to get back the mitochondrial
panel, and the team sat down
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with us and told us that Noah
has mitochondrial disease
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confirmed, and that he has 100%
mutation load, which also known
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as homoplasmy, meaning all his
cells are affected by it.
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Lauren Arora Hutchinson: Not
everyone with mitochondrial
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disease is affected in the same
way. The human body is made up
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of trillions of cells, and every
cell contains hundreds,
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sometimes thousands of
mitochondria, each with its own
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genetic code. Some people have a
mix of healthy and mutated
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mitochondrial DNA. That's called
heteroplasmy, but Noah's test
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showed homoplasmy. 100% of his
mitochondria carried the
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mutation. Doctors refer to this
percentage as mutation load, and
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Noah's was the highest it could
possibly be.
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Kristelle Shulman: You know,
sitting in that family room, and
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just, you know, we were
surrounded by fellows and
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doctors and attendings, just the
two of us sitting like this, and
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you know, holding each other's
hands.
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Lauren Arora Hutchinson: People
meet devastating news in
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different ways. Some turn
inward. Some lean on family.
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Some focus on simply getting
through each hour. For Kristelle
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and Evan, even in the midst of
their shock, there was a sense
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of purpose, an instinct to do
everything they could for Noah.
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Evan Shulman: So, while Noah was
sick in the hospital, Kristelle
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and I sort of took on different
roles. She was obviously Noah's
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mom and was there for, you know,
the best compassion that she
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could ever give her son, and my
role was figuring out how are we
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gonna make sure that Noah's
getting the best care possible
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at the same time. So, I did a
PubMed search, which searches
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all medical journals, and I
searched for the specific
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mutation that Noah has, and I
emailed every author on every
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paper that I could get a hold
of… had a tremendous response,
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almost everybody wrote back to
me whether they had any
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information to provide or not.
And in particular, Newcastle
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University in England wrote
back, and it turns out Newcastle
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had a family with the exact same
mutation that they've been
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following. They, they asked us
what they were doing for Noah.
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We told them, and sadly the only
treatment was supportive care,
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and they assured us that, you
know, what was being done is the
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best that can be done.
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Lauren Arora Hutchinson: For
Evan and Kristelle, it was
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confirmation that Noah's life
couldn't be saved, only made
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more comfortable.
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Kristelle Shulman: Having our
son just, you know, laying in
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that incubator, sorry, like
really just holding on to his
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dear life, you know, and I
wasn't ready to let him go. You
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know, we weren't ready to let
him go.
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Evan Shulman: Noah spent more
than two months in the NICU,
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like that became his home, and
we were very fortunate. The team
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taking care of him, and the
nurses, they were
his family,
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the things that they saw him go
through, and we saw him go
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through. I mean, how do you, how
do you, why would this happen to
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a baby? There's really no
explanation.
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Kristelle Shulman: He had like
these two episodes of like
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cardiac arrest, and like the
first one I like yelled out from
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outside, and I said, I'm not
ready to let you go yet. Don't
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go, and he didn't go, and then I
think that the last time, the
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last one, we were actually able
to say goodbye, like I felt like
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I was able to say I need you to
rest now. I don't want you to
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suffer anymore. No one, babies,
any humans, any one should ever
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go through this.
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Evan Shulman: Noah passed away
at just shy of three months old.
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Lauren Arora Hutchinson: It was
a terrible end to a
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heartbreaking three month
ordeal, but it was also the
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start of a much longer odyssey,
because when Noah was tested and
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diagnosed with mitochondrial
disease, the doctors also tested
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Kristelle, and the results there
weren't good news either.
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Kristelle Shulman: I had about
75% of the dysfunction, the
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mitochondrial dysfunction, and
so I had to also worry about my
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health as well.
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Evan Shulman: And, sort of in
the same breath, they said you
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guys cannot have healthy
biologic children.
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Lauren Arora Hutchinson: You
see, while the nuclear DNA that
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shapes who we are is inherited
from both parents...
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Marni Falk: All of our
mitochondria comes through our
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mother through the egg.
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Lauren Arora Hutchinson: This is
Dr. Marni Falk, a clinical
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geneticist and pediatrician. She
runs the mitochondrial medicine
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frontier program at the
Children's Hospital of
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Philadelphia.
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Marni Falk: When somebody's a
carrier of a mitochondrial DNA
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mutation, the question becomes:
do all of her eggs have this?
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Will every child get this? If
you had jelly beans in a jar,
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like some were red and some were
green, and you put your hand in,
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how many red would you pull out?
Well, it's very hard to predict,
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right? And you'd probably pull
out a different percentage each
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time, and that's what happens
with these mutations.
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Evan Shulman: And...
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Kristelle Shulman: Yeah, that
was um... sorry.
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Evan Shulman: Kristelle -
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Kristelle Shulman: Do you mind?
It's, you know, it was
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heartbreaking because we had a
vision, you know, like of our
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family and of a big family. And
so, you know, when we heard
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that, we thought that was like a
death sentence. We were told
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that that was it, you know, we
could either do adoption or egg
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donation, but… so that was a
really tough thing to swallow.
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It was hard.
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Lauren Arora Hutchinson: But
they weren't ready to give up on
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their dream of having
biologically related children,
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and so the Shulmans wrote back
to the people in Newcastle.
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Evan Shulman: I emailed them
back, and I said, what are...
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what other options would we have
in the future for other children
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when we first heard about
mitochondrial replacement
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therapy, or MRT.
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Lauren Arora Hutchinson: MRT is
a fascinating science fiction
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sounding technology.
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Marni Falk: Colloquially, people
refer to it as a three parent
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baby, but the proper term is
mitochondrial replacement
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technology.
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Jeffrey Kahn: You're combining
genetic material from two women
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to make one egg, which is then
fertilized by one sperm.
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Lauren Arora Hutchinson: Jeffrey
Kahn, our resident bioethicist
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and director of the Johns
Hopkins Berman Institute of
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Bioethics. And he says a
technology like this could work
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well in cases like the Shulmans,
because of how our cells are
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structured and how mitochondrial
DNA is passed from mothers to
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their children.
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Jeffrey Kahn: Mitochondria are
in the cytoplasm of a cell, so
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think
of that as the white part
of a chicken egg. If you don't
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want that white part to be
passed on, you need to figure
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out how to get the yolk part,
where the nucleus is, where the
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DNA that makes us who we are
resides out of the egg of a
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woman who we know carries
mitochondrial DNA disease. So,
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think of it as plucking out the
yellow and putting it into the
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white part of a chicken egg that
has had its yellow part removed.
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Marni Falk: And you basically do
a swap. You take out the nucleus
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from the intended parents, and
you put it into the cell that
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has healthy mitochondria from
the donor.
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Jeffrey Kahn: MRT seems to offer
a way to eliminate the risk of
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mitochondrial DNA disease, and
it certainly holds out the
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prospect of that in a way that
other options at that time
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certainly did not.
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Lauren Arora Hutchinson: The
science behind MRT first began
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to take shape in the early
2000s. Over the next decade,
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researchers showed that these
techniques could work, first in
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animals and then in human
embryos, raising the possibility
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of preventing mitochondrial
disease. But MRT would also
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raise profound ethical questions
about altering the genetics of
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children who might be born this
way.
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Jeffrey Kahn: You're changing
the genetic makeup of the
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mitochondria in that individual.
It's a heritable genetic change.
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Lauren Arora Hutchinson:
Heritable, meaning the genetic
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changes created through MRT can
be passed down to future
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generations. This creates an
ethical conundrum. How should we
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think about the risks and
consequences, not only for the
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baby born through this process,
but that baby's future children,
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or their children's children?
Around the world, policymakers
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began grappling with MRT. In the
United Kingdom, the government
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launched a formal process,
including public consultation,
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to consider whether, and how, to
allow the procedure on a case by
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case basis. In the United
States, federal agencies were
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also beginning to weigh the
scientific and ethical questions
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raised by MRT. The U.S. Food and
Drug Administration, or FDA,
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asked the U.S. National Academy
of Medicine to convene an expert
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committee in 2015, chaired by
our very own, Jeffrey Kahn.
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Jeffrey Kahn: And so the first
question we wrestled with is, is
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it ethically acceptable to
create that kind of heritable
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genetic change which would be
passed on to future generations?
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Lauren Arora Hutchinson: The
expert committee spent a year
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reviewing the latest science and
debating the ethics of such a
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novel reproductive technology.
They heard testimony from
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scientists, physicians, and,
importantly, affected families.
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In the end, they issued a report
with recommendations to the FDA
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about how to move forward.
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Jeffrey Kahn: In the case of
mitochondria, that passage only
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happens through the maternal
line from mothers to their
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offspring, and so if a daughter
were created this way, then she
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would pass on that mitochondrial
DNA change to her offspring, but
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if a male, a boy was born, he
would not. So, if you don't
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implant female embryos, there's
no way of passing on the
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heritable genetic change to
future offspring. So, that was
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one way for us to avoid the
concerns about heritable genetic
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change through generations has
its own ethics concerns when
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you're talking about sex
selection, but we thought that
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was a reasonable trade off,
certainly for the purpose of FDA
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review in a clinical trial.
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Lauren Arora Hutchinson: But in
the end, the agency’s hands were
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tied. The U.S. government took a
different position.
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Archive: If there is no further
debate, the member from Alabama,
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Lauren Arora Hutchinson: while
Jeffrey Kahn and the other
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committee members were in the
meeting room to deliver their
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recommendations to the FDA.
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Archive: Thank you, Madam Chair.
The bottom line is the science
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and the bioethics need to catch
up with potential disasters that
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could occur.
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Jeffrey Kahn: We were told that
the budget bill, the last budget
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bill in the Obama administration
included a rider restricting the
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FDA from receiving any
applications for licensure of a
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technology that modified a human
embryo genetically or led to any
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heritable genetic change.
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Archive: Question is on the
amendment offered by the member
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from Alabama, all those in favor
say aye. Aye. Those opposed, say
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no. No. In the opinion of the
chair, the ayes have it, and the
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amendment is adopted.
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Jeffrey Kahn: And therefore, it
would mean they would be
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prohibited from receiving
license applications to do MRT.
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Lauren Arora Hutchinson: Next
time on playing god?
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Evan Shulman: We have to figure
out a way to do MRT.
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Kristelle Shulman: I wanted to
keep going. I wasn't going to
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stop. I knew once I held him, I
knew once I had him, like it's
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just something that I don't want
to miss out on.
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Lauren Arora Hutchinson: Many
thanks to our guests in this
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episode. To Kristelle and Evan
Shulman for sharing their story
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with us, and to Jeffrey Kahn and
Marni Falk.
playing god? is a
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production of the
Dracopoulos-Bloomberg iDeas Lab
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at the Johns Hopkins Berman
Institute of Bioethics, made in
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association with Sea Salt and
Mango Productions.
This
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00:24:13,845 --> 00:24:17,730
episode was produced by Redzi
Bernard, with help from Brian
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00:24:17,730 --> 00:24:22,800
Ricker and Lyric Bowditch.
Our Executive Editor is Tony
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Phillips.
Music and sound
design by Alexander Overington.
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iDeas Lab Producer, Lyric
Bowditch.
Researcher, Brian
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Ricker.
Story Editor, Simon
Adler.
Show art by Barry
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Pousman and Shawn Carney.
Our
Production Coordinators are Leah
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Lord and Susan Snead.
Our
Executive Producers are Jeffrey
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Kahn and Anna Mastroianni.
I’m Lauren Arora Hutchinson,
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host and Managing Editor.
Come back next week for more
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playing god?