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