Evan Shulman: There's no guarantees ever with life or
with having a child. There's a lot of assumptions that, you
know, you're going to have a kid and they're going to be healthy,
but there's a lot that needs to go right for that to happen. And
it doesn't always work out like that.
Lauren Arora Hutchinson: In the last episode of playing god?, we
heard Kristelle and Evan Shulman's story, how they
tragically lost their son, Noah, to a fatal genetic disorder
called mitochondrial disease.
Kristelle Shulman: I need you to rest now. I don't want you to
suffer anymore. No one should ever go through this.
Lauren Arora Hutchinson: Mitochondria are
energy-producing structures inside our cells that carry
their own DNA, which is passed down only through the maternal
line. That means Noah inherited the disease from Kristelle. So,
when the Shulmans learned about Noah's diagnosis, they also
learned that Kristelle carries the same genetic mutation in
some of her own mitochondria. Noah's mutation load was a
hundred percent, meaning all of his mitochondrial DNA carried
the mutation. Kristelle's, they discovered, is around 70%.
Doctors warned them that if they tried to have another
biologically related child, the risk of the disease being passed
on would simply be too high.
Evan Shulman: You guys cannot have healthy biologic children.
Lauren Arora Hutchinson: But after Noah's death, instead of
stepping back as might be expected, they found themselves
moving forward. They wanted something different, not just
for their family, but for others facing the same risk and
uncertainty.
Kristelle Shulman: After he passed, I think we vowed that we
need to help others, you know?
Evan Shulman: Something good has to come out of this, like Noah,
Noah has to have, like, his mark on the world, beyond, you know,
making all these friends in the ICU, and he has to have a mark
on the world.
Lauren Arora Hutchinson: That search led them towards a new
and controversial reproductive technology, one that could
maybe, just maybe, help them have a healthy biologically
related child, but along the way they would encounter unexpected
complications, shifting possibilities, and ultimately a
different path to growing their family than one they had
imagined.
Kristelle Shulman: I'm getting goosebumps talking about it.
Lauren Arora Hutchinson: This is part two of the Shulman’s story,
a story about how far one family would go to have a healthy,
biologically related child. About how much risk and
uncertainty they were willing to accept and what ethical
boundaries they were willing to test. I'm Lauren Arora
Hutchinson, Director of the iDeas Lab at the Johns Hopkins
Berman Institute of Bioethics, and this is playing god? Around
the same time that Kristelle and Evan lost Noah, federal
legislators in the US were taking a position on what's
called mitochondrial replacement technology, or MRT. This novel
reproductive technology takes the nucleus from the egg of a
woman with mitochondrial disease and transfers it into a donor
egg with healthy mitochondria, whose own nucleus has been
removed. That reconstructed egg is then fertilized through IVF.
To the Shulmans, this sounded like the answer they were
looking for.
Evan Shulman: We're like we have to figure out a way to do MRT.
Lauren Arora Hutchinson: The nucleus of a cell contains the
vast majority of the DNA we inherit from our parents, the
genetic code that shapes who we are. So while the resulting
embryo would be the biological child of the mother and father,
it would also carry some genetic material from the third person,
the egg donor, for its mitochondrial DNA. That's the
whole point. The problem is that this genetic change could be
passed down to future generations. In 2016, Congress
effectively blocked the US Food and Drug Administration from
even considering whether to license the use of the
technology because of those concerns. Still, some
experimental research on MRT continued. About a year later,
hoping the results might soon change, Kristelle and Evan took
a leap of faith.
Evan Shulman: We enrolled in an MRT trial in the US that did not
have approval to implant embryos, but they had approval
to create embryos. So, she underwent an IVF cycle,
harvested eggs with the intention of creating an embryo.
They were looking for what's called a haplotype match, which
essentially was somebody from a similar genetic background, so
potentially from similar ancestral roots.
Lauren Arora Hutchinson: You can think of a haplotype as a kind
of genetic zip code, a pattern in mitochondrial DNA that traces
maternal ancestry. Kristelle is originally from the Philippines,
so the hope of the researchers was that an egg donor with a
similar background might help give an embryo a better chance
of success.
Evan Shulman: We were just waiting for quite some time.
Lauren Arora Hutchinson: And while they waited, the Shulmans
kept learning about MRT and about its risks.
Evan Shulman: You know, I went to talks from researchers who
have done a lot of research on MRT. I read every paper that
would come out on it, and reading all these opinions, and
we started to hear more about concerns about the long-term
outcomes of MRT.
Lauren Arora Hutchinson: Chief among them is that when you
extract the nucleus from the mother's egg cell to put into
the healthy donor egg...
Jeffrey Kahn: It's impossible to take all of the nucleus and not
carry some of the cytoplasm, and the cytoplasm is where the
disease-causing mitochondria are, and so you're bringing over
some disease-causing mitochondria when you, you do
that movement.
Lauren Arora Hutchinson: Our resident bioethicist and
director of the Johns Hopkins Berman Institute of Bioethics,
Jeffrey Kahn.
Jeffrey Kahn: Now, of course, you're, you're vastly reducing
the number, but because of the way mitochondrial biology works,
those disease-causing mitochondria will multiply up in
the new environment, and the question is, how much is enough
to pose, I guess, real risk of mitochondrial DNA disease, even
after MRT?
Lauren Arora Hutchinson: In the end, Kristelle and Evan were
unable to find a donor egg that was a close enough haplotype
match, so they didn't move forward in the MRT research
study, but these questions about risk and uncertainty were
quickly reignited as they pushed forward to explore other
options.
Kristelle Shulman: We did consult with other mitochondrial
disease specialists, and then, of course, finally we met with
Dr. Falk.
Marni Falk: I met Kristelle and Evan when they were trying to
figure out whether they could have a healthy baby.
Lauren Arora Hutchinson: Dr. Marni Falk, director of the
Mitochondrial Medicine Frontier Program at the Children's
Hospital of Philadelphia.
Marni Falk: And, it was a very difficult conversation, but it
was clear that they were very motivated and wanted to do
everything they could to have a biologically related child, and
that's, that's how we got to know each other.
Lauren Arora Hutchinson: Central to their conversation was a
puzzling question: why Kristelle, who carries the
genetic mutation in more than 70% of her mitochondrial DNA,
had never shown any symptoms...
Kristelle Shulman: When Dr. Falk said, "you know, you're so
active, you're constantly working out." And so, she says
that this is probably what is helping you. You know, you're
compensating.
Lauren Arora Hutchinson: And they begin looking more closely
at her extended family.
Kristelle Shulman: You know, like my family had no idea, like
I was the third of four children, so and on my mom's
side, they had eight, you know, it's like a big family, so they
had no idea.
Lauren Arora Hutchinson: Had anyone else been affected by the
disease, like Noah?
Kristelle Shulman: So one of my aunts, yeah. So, she had a girl,
and I think 18 months, like, she passed. So I'm from the
Philippines, and back then in probably like late 70s-80s,
healthcare is not the same as in the US. They diagnosed her with
pneumonia. You know, there was no test, diagnostic testings, in
terms of, you know, genetic stuff, so it's... it was
unknown. So that was the only one, I guess, young cousin that
I had who passed, but other than that, like we had... you know,
everyone's relatively healthy.
Lauren Arora Hutchinson: Maybe, they thought, this was a reason
for hope.
Evan Shulman: We suggested that everybody in the family get
tested, and it turns out that there was quite a wide range of
mutation load in them. So, anywhere from 28 percent to
Kristelle being the highest of 70 something percent. So, then
we took a step back and we said, well, if Kristelle's mother was
able to produce children with a wide spread of heteroplasmy,
then maybe Kristelle has eggs with the same wide spread.
Lauren Arora Hutchinson: The realization changed their
options. If some of Kristelle's eggs carried lower levels of the
mutation, maybe they could have a healthy child, without needing
to do MRT. They reached back out to Newcastle University, a
pioneer of new techniques to address mitochondrial disease.
Evan Shulman: We gave them all the results that we got here,
and they said, "Okay, we're going to present it at our
multidisciplinary conference, and we'll get back to you." And
then, within a week or two, they got back to us, and they said,
"we think you'd be excellent candidates for genetic
diagnostic testing of our own embryos."
Lauren Arora Hutchinson: This approach would be a cutting-edge
new version of what's called pre-implantation genetic
testing, or PGT.
Marni Falk: PGT is a very standard used every day all
across the United States of America in the setting of in
vitro fertilization.
Lauren Arora Hutchinson: Dr. Marni Falk, again.
Marni Falk: When you have an embryo and you take a sample on
day five for most nuclear genes, and you ask the question, is the
mutation that's known to run in this family present in this
embryo. That's preimplantation genetic testing, and that's
being used for any nuclear gene disorder. What hasn't been
available until recently is preimplantation genetic testing
for errors in the mitochondrial DNA.
Lauren Arora Hutchinson: The Shulmans decided to become
pioneers of this new approach. It's an extremely delicate
process.
Marni Falk: You have to be really precise to know that the
result you're giving doesn't just find the mutation, but
tells you the percentage of that mutation in that cell, and then
the other question that people weren't certain of is, how
likely is that level that you find on day three after an
embryo has been created relate to trillions of cells dividing
over time by the time that baby's born to know what the
level would be in their organs, their brain, their heart, their
kidney, or their blood. Could it become 30% or 50% or 80% in
certain organs of the actual baby? Those answers still aren't
known.
Lauren Arora Hutchinson: The uncertainty remained profound,
but the Shulmans remained certain they wanted to push
ahead. They began planning to go to Newcastle for tests, which
was the only place in the world where PGT for mitochondrial DNA
was available.
Evan Shulman: It was a lot of work. We had to spend about a
year and a half doing a lot of legwork here. Kristelle
underwent another IVF cycle. There was a lot of red tape, a
lot of barriers, a lot of lab work back and forth, and at the
time they were not comfortable receiving genetic material from
here, and just essentially just shipping it over there. They
wanted us present with our eggs or embryos, and they wanted to
do the embryo transfer in real time with Kristelle there.
Kristelle Shulman: We also found, like, I mean, on top of
those barriers I think financially too was a big one,
so luckily, like I wasn't, you know, a nurse practitioner at
Mount Sinai, and it was unionized. So, the IVF, the
fertility, was covered, but it, you know, of course, it wasn't
enough, so there was some things that we had to, you know, we had
savings, so it's, it's a lot too financially.
Lauren Arora Hutchinson: After 18 months of preparation,
Kristelle and Evan were finally ready to fly to Newcastle.
Evan Shulman: The first time we actually treated it like a
vacation, we had a whole itinerary planned out. I mean,
we, we love to travel together. We had embryos created here in
the US, they were frozen on day one of development, and those
embryos were taken, hand delivered by courrier to the UK,
and we met them there, and the team at Newcastle, who we had
been speaking with for a year and a half, was, of course,
great. They were so welcoming and warm and positive.
Lauren Arora Hutchinson: The embryos were thawed, allowed to
grow, and then tested.
Evan Shulman: And then I would say, I think it was like the
next day, I forget where we were. I think we were at a beach
or something. We were, we were walking around, and we got a
call from the embryologist with our results, and we were like
ecstatic. She told us we had one embryo that was as low as 10%
mutation load, and on the flip side, we had several that were
like 98-99% which essentially is basically what Noah had, and
again it was one of those like bittersweet moments where we're
like, wow, like hearing 10% we know there's a chance for a
healthy child in there, and also hearing 99 is scary, because if
we just blindly went into this again and had children again, it
could have landed on that, and we'd be in the exact same place
again.
Lauren Arora Hutchinson: With high hopes, they tried
implanting the embryo with that 10% mutation load, but
unfortunately, as often happens with IVF, it didn't lead to a
pregnancy. Once again, they were left asking themselves, what
level of risk is low enough?
Jeffrey Kahn: What's the threshold? That's the question
that the Shulmans and others at the sort of early stage of these
kinds of technologies have to wrestle with.
Lauren Arora Hutchinson: Jeffrey Kahn, again.
Jeffrey Kahn: And so, you have to be comfortable with this
level of risk and uncertainty, and decide whether or not to go
forward. You know, put yourself in a position like that... what
would you do? They weren't being offered the option to make the
risk go away altogether, and so they had to decide how
comfortable they would be with some level of risk.
Lauren Arora Hutchinson: That was a decision only the Shulmans
could make.
Evan Shulman: In Newcastle, they said they were comfortable in
the 35 to 40% range, and they even said, honestly, 50% is
probably okay.
Kristelle Shulman: And I think it's also because they saw that
I had 70 to 80% and that I was able to pretty much live a
normal life, thank God. So it was definitely individualized.
Evan Shulman: As far as like what level of risk to accept, we
kind of started thinking like there's no, there's no guarantee
every pregnancy is a risk, and if, if you had cancer that ran
in the family, would you not have a child, or if you had
heart disease running in the family, would you not have a
child? If you knew that there was a reasonable chance that
they could avoid it later on? And that was kind of the
approach that we took. We tried to take a step back, and while
mitochondrial disease is very serious, most often it's not,
it's not terminal with a low threshold, you can live a
perfectly healthy life.
Kristelle Shulman: Or even a high threshold,
Evan Shulman: or even a high threshold. Yeah, yeah.
Kristelle Shulman: So it's, yeah.
Lauren Arora Hutchinson: Over the next four years, they went
through multiple rounds of IVF, six embryo transfers, and three
trips across the Atlantic. There were setbacks, failed
implantations, and early pregnancy losses. It was
exhausting and heartbreaking at times. They weren't sure they
could keep going.
Kristelle Shulman: Oh my goodness, we just didn't think
it was possible, but we were still hopeful. We wanted to keep
going, I wasn't going to stop, and I think it's also Noah
pushing me to it, because 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: But then, in late 2020, using an
embryo with a low enough mutation load, Kristelle finally
got pregnant.
Kristelle Shulman: I remember looking at the pregnancy, you
know, stick, and we're like, what, like, like, you know, we
just... it was surreal. It was almost like, this can't be real,
this is, this is impossible, and you know I'm getting goosebumps
talking about it.
Evan Shulman: There was jumping involved, I think.
Kristelle Shulman: Lots of jumping and screaming and...
Evan Shulman: Kristelle and I both still remember our
expressions.
Kristelle Shulman: So throughout the pregnancy, you know, of
course, we were worried.
Evan Shulman: But, she had a completely normal pregnancy for
nine months, and then 2021, Nora was born.
Kristelle Shulman: Delivering Nora was not without
complications, and I said, 'Oh my god, Nora, you came into this
world like loud, like just you just made sure that you are
here, like, and she's still like that. She's just Nora. I can't
describe her. Can you describe her, right? She's... Evan said
that she's a tank, and that's true. She is a tank.
Lauren Arora Hutchinson: Nora was one of the first babies born
in the US to have been screened for mitochondrial disease risk
using PGT, and most importantly...
Kristelle Shulman: You know, she's healthy. Thank God, she's
so healthy, and I hope she can... I pray that she continues
to be healthy. So it was, it was nice, it was a good feeling,
just knowing that it worked, you know?
Lauren Arora Hutchinson: After Nora was born, doctors measured
her mutation level again.
Evan Shulman: Her heteroplasmy matched exactly what they
predicted when she was an embryo. She goes once a year to
see Dr. Falk and make sure that she stays on track with
everything, but she was always ahead of the curve with her
growth, with speaking, with all her milestones, and now next
year she's going to be starting kindergarten. She's turning
five this summer already, and yeah, she makes us very happy.
And then last year we added to that with our second baby girl,
Hannah, who was born November 2024, and she's now walking and
babbling and also hitting all her milestones.
Marni Falk: When you hear the voice you know of the laughing
child who's been born from this and you hear the stories of the
families... we are all very much indebted to the Shulmans,
because they really did have to go through an awful lot. Many,
many cycles, many, many trips, many, many conversations, a lot
of stress, a lot of hope, a lot of failure, and they're, they're
on the side now of having two healthy children.
Jeffrey Kahn: The people who are first are... I think it's always
right to talk about them in some, some sense as a pioneer,
so they're, they're breaking new ground here. And, and it's so
novel that, that it's hard to say well, we know from
experience that because there isn't any experience yet. The
Shulmans were really at the forefront of this. At some point
that technology will be shared and developed, and it will be
more available in more parts of the world. So, it's pioneering
on the part of the Shulmans, it's pioneering on the part of
the laboratories, pioneering on the part of the physicians who
are helping, but that's how that's how medicine advances.
Lauren Arora Hutchinson: Since the Shulmans’ early
conversations with Newcastle, the science has continued to
evolve. The technique they used, mitochondrial PGT, which allows
the lab to screen embryos for mitochondrial disease before
pregnancy, is still only offered in a few places in the world.
The approach that the Shulman’s first considered, mitochondrial
replacement technology or MRT, aims to prevent disease by
replacing faulty mitochondria in the egg itself, prior to
fertilization. MRT still isn’t permitted in the United States
and is tightly regulated in the few places it is allowed. But in
2025, doctors in the UK reported what many are calling a medical
breakthrough: the births of at least eight babies using MRT. So
far, all appear to be healthy.
Archive: A groundbreaking IVF technique involving three people
has resulted in the births of eight babies free from what can
be devastating diseases. Scientists in Newcastle have
pioneered the technique to stop mothers passing down a mutation
in their DNA that can cause mitochondrial disease, which
commonly impacts major organs, such as the heart and the brain.
Evan Shulman: The beginning of our mission was to help other
families and hopefully prevent other people from going through
this, and we've had a number of families reach out to us, and
one family reached out to us, who we, we ultimately ended up
getting them in the hands of Newcastle, and they had a son
who was born about a year after Nora. They named him Noah,
which is pretty touching for us to hear, and they actually
brought him to our daughter's first birthday party at our
house, and we got to meet the family and meet their son, and
it was sort of surreal to see a baby that was born healthy from
a technique that was, I want to say, almost nobody in the US
knew was even available, and no one was supporting. And now here
we are, we have two babies sitting together who were born
from the same technique, healthy, happy. There's these
days when we look at each other, and we're like, how did we get
here? Like, how did we turn things around for us, and end up
with two beautiful girls in front of us... the family that
we always wanted.
Lauren Arora Hutchinson: Next time on playing god?
Rebecca Morrison: I mean, I'm just a person that is trying to
determine something for my own health. What is the responsible
thing to do as a human being, as a woman, as a mother, as a wife,
as a daughter, as a person. Should I do it? Do I need to do
it? Do I have to do it?
Lauren Arora Hutchinson: Many thanks, again, 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?