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Evan Shulman: There's no
guarantees ever with life or

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with having a child. There's a
lot of assumptions that, you

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know, you're going to have a kid
and they're going to be healthy,

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but there's a lot that needs to
go right for that to happen. And

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it doesn't always work out like
that.

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Lauren Arora Hutchinson: In the
last episode of playing god?, we

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heard Kristelle and Evan
Shulman's story, how they

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tragically lost their son, Noah,
to a fatal genetic disorder

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called mitochondrial disease.

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Kristelle Shulman: I need you to
rest now. I don't want you to

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suffer anymore. No one should
ever go through this.

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Lauren Arora Hutchinson: 
Mitochondria are

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energy-producing structures
inside our cells that carry

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their own DNA, which is passed
down only through the maternal

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line. That means Noah inherited
the disease from Kristelle. So,

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when the Shulmans learned about
Noah's diagnosis, they also

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learned that Kristelle carries
the same genetic mutation in

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some of her own mitochondria.
Noah's mutation load was a

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hundred percent, meaning all of
his mitochondrial DNA carried

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the mutation. Kristelle's, they
discovered, is around 70%.

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Doctors warned them that if they
tried to have another

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biologically related child, the
risk of the disease being passed

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on would simply be too high.

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Evan Shulman: You guys cannot
have healthy biologic children.

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Lauren Arora Hutchinson: But
after Noah's death, instead of

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stepping back as might be
expected, they found themselves

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moving forward. They wanted
something different, not just

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for their family, but for others
facing the same risk and

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uncertainty.

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Kristelle Shulman: After he
passed, I think we vowed that we

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need to help others, you know?

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Evan Shulman: Something good has
to come out of this, like Noah,

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Noah has to have, like, his mark
on the world, beyond, you know,

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making all these friends in the
ICU, and he has to have a mark

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on the world.

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Lauren Arora Hutchinson: That
search led them towards a new

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and controversial reproductive
technology, one that could

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maybe, just maybe, help them
have a healthy biologically

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related child, but along the way
they would encounter unexpected

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complications, shifting
possibilities, and ultimately a

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different path to growing their
family than one they had

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imagined.

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Kristelle Shulman: I'm getting
goosebumps talking about it.

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Lauren Arora Hutchinson: This is
part two of the Shulman’s story,

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a story about how far one family
would go to have a healthy,

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biologically related child.
About how much risk and

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uncertainty they were willing to
accept and what ethical

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boundaries they were willing to
test.
 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? Around

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the same time that Kristelle and
Evan lost Noah, federal

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legislators in the US were
taking a position on what's

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called mitochondrial replacement
technology, or MRT. This novel

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reproductive technology takes
the nucleus from the egg of a

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woman with mitochondrial disease
and transfers it into a donor

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egg with healthy mitochondria,
whose own nucleus has been

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removed. That reconstructed egg
is then fertilized through IVF.

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To the Shulmans, this sounded
like the answer they were

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looking for.

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Evan Shulman: We're like we have
to figure out a way to do MRT.

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Lauren Arora Hutchinson: The
nucleus of a cell contains the

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vast majority of the DNA we
inherit from our parents, the

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genetic code that shapes who we
are. So while the resulting

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embryo would be the biological
child of the mother and father,

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it would also carry some genetic
material from the third person,

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the egg donor, for its
mitochondrial DNA. That's the

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whole point. The problem is that
this genetic change could be

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passed down to future
generations. In 2016, Congress

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effectively blocked the US Food
and Drug Administration from

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even considering whether to
license the use of the

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technology because of those
concerns. Still, some

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experimental research on MRT
continued. About a year later,

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hoping the results might soon
change, Kristelle and Evan took

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a leap of faith.

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Evan Shulman: We enrolled in an
MRT trial in the US that did not

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have approval to implant
embryos, but they had approval

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to create embryos. So, she
underwent an IVF cycle,

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harvested eggs with the
intention of creating an embryo.

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They were looking for what's
called a haplotype match, which

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essentially was somebody from a
similar genetic background, so

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potentially from similar
ancestral roots.

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Lauren Arora Hutchinson: You can
think of a haplotype as a kind

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of genetic zip code, a pattern
in mitochondrial DNA that traces

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maternal ancestry. Kristelle is
originally from the Philippines,

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so the hope of the researchers
was that an egg donor with a

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similar background might help
give an embryo a better chance

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of success.

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Evan Shulman: We were just
waiting for quite some time.

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Lauren Arora Hutchinson: And
while they waited, the Shulmans

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kept learning about MRT and
about its risks.

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Evan Shulman: You know, I went
to talks from researchers who

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have done a lot of research on
MRT. I read every paper that

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would come out on it, and
reading all these opinions, and

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we started to hear more about
concerns about the long-term

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outcomes of MRT.

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Lauren Arora Hutchinson: Chief
among them is that when you

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extract the nucleus from the
mother's egg cell to put into

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the healthy donor egg...

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Jeffrey Kahn: It's impossible to
take all of the nucleus and not

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carry some of the cytoplasm, and
the cytoplasm is where the

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disease-causing mitochondria
are, and so you're bringing over

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some disease-causing
mitochondria when you, you do

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that movement.

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Lauren Arora Hutchinson: Our
resident bioethicist and

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director of the Johns Hopkins
Berman Institute of Bioethics,

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Jeffrey Kahn.

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Jeffrey Kahn: Now, of course,
you're, you're vastly reducing

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the number, but because of the
way mitochondrial biology works,

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those disease-causing
mitochondria will multiply up in

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the new environment, and the
question is, how much is enough

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to pose, I guess, real risk of
mitochondrial DNA disease, even

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after MRT?

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Lauren Arora Hutchinson: In the
end, Kristelle and Evan were

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unable to find a donor egg that
was a close enough haplotype

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match, so they didn't move
forward in the MRT research

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study, but these questions about
risk and uncertainty were

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quickly reignited as they pushed
forward to explore other

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options.

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Kristelle Shulman: We did
consult with other mitochondrial

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disease specialists, and then,
of course, finally we met with

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Dr. Falk.

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Marni Falk: I met Kristelle and
Evan when they were trying to

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figure out whether they could
have a healthy baby.

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Lauren Arora Hutchinson: Dr.
Marni Falk, director of the

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Mitochondrial Medicine Frontier
Program at the Children's

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Hospital of Philadelphia.

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Marni Falk: And, it was a very
difficult conversation, but it

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was clear that they were very
motivated and wanted to do

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everything they could to have a
biologically related child, and

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that's, that's how we got to
know each other.

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Lauren Arora Hutchinson: Central
to their conversation was a

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puzzling question: why
Kristelle, who carries the

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genetic mutation in more than
70% of her mitochondrial DNA,

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had never shown any symptoms...

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Kristelle Shulman: When Dr. Falk
said, "you know, you're so

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active, you're constantly
working out." And so, she says

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that this is probably what is
helping you. You know, you're

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compensating.

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Lauren Arora Hutchinson: And
they begin looking more closely

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at her extended family.

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Kristelle Shulman: You know,
like my family had no idea, like

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I was the third of four
children, so and on my mom's

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side, they had eight, you know,
it's like a big family, so they

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had no idea.

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Lauren Arora Hutchinson: Had
anyone else been affected by the

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disease, like Noah?

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Kristelle Shulman: So one of my
aunts, yeah. So, she had a girl,

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and I think 18 months, like, she
passed. So I'm from the

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Philippines, and back then in
probably like late 70s-80s,

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healthcare is not the same as in
the US. They diagnosed her with

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pneumonia. You know, there was
no test, diagnostic testings, in

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terms of, you know, genetic
stuff, so it's... it was

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unknown. So that was the only
one, I guess, young cousin that

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I had who passed, but other than
that, like we had... you know,

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everyone's relatively healthy.

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Lauren Arora Hutchinson: Maybe,
they thought, this was a reason

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for hope.

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Evan Shulman: We suggested that
everybody in the family get

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tested, and it turns out that
there was quite a wide range of

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mutation load in them. So,
anywhere from 28 percent to

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Kristelle being the highest of
70 something percent. So, then

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we took a step back and we said,
well, if Kristelle's mother was

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able to produce children with a
wide spread of heteroplasmy,

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then maybe Kristelle has eggs
with the same wide spread.

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Lauren Arora Hutchinson: The
realization changed their

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options. If some of Kristelle's
eggs carried lower levels of the

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mutation, maybe they could have
a healthy child, without needing

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to do MRT. They reached back out
to Newcastle University, a

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pioneer of new techniques to
address mitochondrial disease.

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Evan Shulman: We gave them all
the results that we got here,

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and they said, "Okay, we're
going to present it at our

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multidisciplinary conference,
and we'll get back to you." And

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then, within a week or two, they
got back to us, and they said,

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"we think you'd be excellent
candidates for genetic

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diagnostic testing of our own
embryos."

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Lauren Arora Hutchinson: This
approach would be a cutting-edge

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new version of what's called
pre-implantation genetic

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testing, or PGT.

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Marni Falk: PGT is a very
standard used every day all

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across the United States of
America in the setting of in

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vitro fertilization.

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Lauren Arora Hutchinson: Dr.
Marni Falk, again.

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Marni Falk: When you have an
embryo and you take a sample on

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day five for most nuclear genes,
and you ask the question, is the

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mutation that's known to run in
this family present in this

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embryo. That's preimplantation
genetic testing, and that's

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being used for any nuclear gene
disorder. What hasn't been

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available until recently is
preimplantation genetic testing

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for errors in the mitochondrial
DNA.

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Lauren Arora Hutchinson: The
Shulmans decided to become

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pioneers of this new approach.
It's an extremely delicate

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process.

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Marni Falk: You have to be
really precise to know that the

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result you're giving doesn't
just find the mutation, but

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tells you the percentage of that
mutation in that cell, and then

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the other question that people
weren't certain of is, how

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likely is that level that you
find on day three after an

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embryo has been created relate
to trillions of cells dividing

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over time by the time that
baby's born to know what the

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level would be in their organs,
their brain, their heart, their

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kidney, or their blood. Could it
become 30% or 50% or 80% in

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certain organs of the actual
baby? Those answers still aren't

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known.

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Lauren Arora Hutchinson: The
uncertainty remained profound,

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but the Shulmans remained
certain they wanted to push

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ahead. They began planning to go
to Newcastle for tests, which

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was the only place in the world
where PGT for mitochondrial DNA

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was available.

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Evan Shulman: It was a lot of
work. We had to spend about a

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year and a half doing a lot of
legwork here. Kristelle

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underwent another IVF cycle.
There was a lot of red tape, a

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lot of barriers, a lot of lab
work back and forth, and at the

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time they were not comfortable
receiving genetic material from

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here, and just essentially just
shipping it over there. They

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wanted us present with our eggs
or embryos, and they wanted to

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do the embryo transfer in real
time with Kristelle there.

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Kristelle Shulman: We also
found, like, I mean, on top of

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those barriers I think
financially too was a big one,

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so luckily, like I wasn't, you
know, a nurse practitioner at

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Mount Sinai, and it was
unionized. So, the IVF, the

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fertility, was covered, but it,
you know, of course, it wasn't

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enough, so there was some things
that we had to, you know, we had

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savings, so it's, it's a lot too
financially.

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Lauren Arora Hutchinson: After
18 months of preparation,

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Kristelle and Evan were finally
ready to fly to Newcastle.

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Evan Shulman: The first time we
actually treated it like a

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vacation, we had a whole
itinerary planned out. I mean,

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we, we love to travel together.
We had embryos created here in

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the US, they were frozen on day
one of development, and those

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embryos were taken, hand
delivered by courrier to the UK,

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and we met them there, and the
team at Newcastle, who we had

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been speaking with for a year
and a half, was, of course,

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great. They were so welcoming
and warm and positive.

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Lauren Arora Hutchinson: The
embryos were thawed, allowed to

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grow, and then tested.

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Evan Shulman: And then I would
say, I think it was like the

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next day, I forget where we
were. I think we were at a beach

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or something. We were, we were
walking around, and we got a

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call from the embryologist with
our results, and we were like

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ecstatic. She told us we had one
embryo that was as low as 10%

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mutation load, and on the flip
side, we had several that were

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like 98-99% which essentially is
basically what Noah had, and

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again it was one of those like
bittersweet moments where we're

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like, wow, like hearing 10% we
know there's a chance for a

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healthy child in there, and also
hearing 99 is scary, because if

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we just blindly went into this
again and had children again, it

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could have landed on that, and
we'd be in the exact same place

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again.

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Lauren Arora Hutchinson: With
high hopes, they tried

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implanting the embryo with that
10% mutation load, but

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unfortunately, as often happens
with IVF, it didn't lead to a

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pregnancy. Once again, they were
left asking themselves, what

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level of risk is low enough?

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Jeffrey Kahn: What's the
threshold? That's the question

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that the Shulmans and others at
the sort of early stage of these

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kinds of technologies have to
wrestle with.

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Lauren Arora Hutchinson: Jeffrey
Kahn, again.

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Jeffrey Kahn: And so, you have
to be comfortable with this

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level of risk and uncertainty,
and decide whether or not to go

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forward. You know, put yourself
in a position like that... what

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would you do? They weren't being
offered the option to make the

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risk go away altogether, and so
they had to decide how

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comfortable they would be with
some level of risk.

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Lauren Arora Hutchinson: That
was a decision only the Shulmans

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could make.

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Evan Shulman: In Newcastle, they
said they were comfortable in

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the 35 to 40% range, and they
even said, honestly, 50% is

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probably okay.

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Kristelle Shulman: And I think
it's also because they saw that

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I had 70 to 80% and that I was
able to pretty much live a

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normal life, thank God. So it
was definitely individualized.

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Evan Shulman: As far as like
what level of risk to accept, we

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kind of started thinking like
there's no, there's no guarantee

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every pregnancy is a risk, and
if, if you had cancer that ran

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in the family, would you not
have a child, or if you had

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heart disease running in the
family, would you not have a

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child? If you knew that there
was a reasonable chance that

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they could avoid it later on?
And that was kind of the

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approach that we took. We tried
to take a step back, and while

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mitochondrial disease is very
serious, most often it's not,

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it's not terminal with a low
threshold, you can live a

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perfectly healthy life.

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Kristelle Shulman: Or even a
high threshold,

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Evan Shulman: or even a high
threshold. Yeah, yeah.

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Kristelle Shulman: So it's,
yeah.

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Lauren Arora Hutchinson: Over
the next four years, they went

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through multiple rounds of IVF,
six embryo transfers, and three

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trips across the Atlantic. There
were setbacks, failed

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implantations, and early
pregnancy losses. It was

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exhausting and heartbreaking at
times. They weren't sure they

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could keep going.

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Kristelle Shulman: Oh my
goodness, we just didn't think

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it was possible, but we were
still hopeful. We wanted to keep

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going, I wasn't going to stop,
and I think it's also Noah

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pushing me to it, because I knew
once I held him, I knew once I

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had him, like... it's just
something that I don't want to

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miss out on.

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Lauren Arora Hutchinson: But
then, in late 2020, using an

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embryo with a low enough
mutation load, Kristelle finally

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got pregnant.

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Kristelle Shulman: I remember
looking at the pregnancy, you

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know, stick, and we're like,
what, like, like, you know, we

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just... it was surreal. It was
almost like, this can't be real,

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this is, this is impossible, and
you know I'm getting goosebumps

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talking about it.

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Evan Shulman: There was jumping
involved, I think.

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Kristelle Shulman: Lots of
jumping and screaming and...

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Evan Shulman:  Kristelle and I
both still remember our

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expressions.

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Kristelle Shulman: So throughout
the pregnancy, you know, of

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course, we were worried.

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Evan Shulman: But, she had a
completely normal pregnancy for

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nine months, and then 2021, Nora
was born.

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Kristelle Shulman: Delivering
Nora was not without

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complications, and I said, 'Oh
my god, Nora, you came into this

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world like loud, like just you
just made sure that you are

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here, like, and she's still like
that. She's just Nora. I can't

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describe her. Can you describe
her, right? She's... Evan said

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that she's a tank, and that's
true. She is a tank.

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Lauren Arora Hutchinson: Nora
was one of the first babies born

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in the US to have been screened
for mitochondrial disease risk

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using PGT, and most
importantly...

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Kristelle Shulman: You know,
she's healthy. Thank God, she's

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so healthy, and I hope she
can... I pray that she continues

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to be healthy. So it was, it was
nice, it was a good feeling,

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just knowing that it worked, you
know?

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Lauren Arora Hutchinson: After
Nora was born, doctors measured

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her mutation level again.

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Evan Shulman: Her heteroplasmy
matched exactly what they

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predicted when she was an
embryo. She goes once a year to

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see Dr. Falk and make sure that
she stays on track with

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everything, but she was always
ahead of the curve with her

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growth, with speaking, with all
her milestones, and now next

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year she's going to be starting
kindergarten.
 She's turning

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five this summer already, and
yeah, she makes us very happy.

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And then last year we added to
that with our second baby girl,

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Hannah, who was born November
2024, and she's now walking and

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babbling and also hitting all
her milestones.

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Marni Falk: When you hear the
voice you know of the laughing

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child who's been born from this
and you hear the stories of the

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families... we are all very much
indebted to the Shulmans,

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because they really did have to
go through an awful lot. Many,

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many cycles, many, many trips,
many, many conversations, a lot

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of stress, a lot of hope, a lot
of failure, and they're, they're

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on the side now of having two
healthy children.

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Jeffrey Kahn: The people who are
first are... I think it's always

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00:22:53,805 --> 00:22:56,955
right to talk about them in
some, some sense as a pioneer,

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so they're, they're breaking new
ground here. And, and it's so

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novel that, that it's hard to
say well, we know from

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experience that because there
isn't any experience yet. The

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Shulmans were really at the
forefront of this. At some point

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that technology will be shared
and developed, and it will be

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more available in more parts of
the world. So, it's pioneering

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00:23:17,820 --> 00:23:20,070
on the part of the Shulmans,
it's pioneering on the part of

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00:23:20,070 --> 00:23:22,935
the laboratories, pioneering on
the part of the physicians who

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are helping, but that's how
that's how medicine advances.

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Lauren Arora Hutchinson: Since
the Shulmans’ early

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conversations with Newcastle,
the science has continued to

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evolve. The technique they used,
mitochondrial PGT, which allows

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00:23:42,620 --> 00:23:46,070
the lab to screen embryos for
mitochondrial disease before

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pregnancy, is still only offered
in a few places in the world.

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The approach that the Shulman’s
first considered, mitochondrial

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replacement technology or MRT,
aims to prevent disease by

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replacing faulty mitochondria in
the egg itself, prior to

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00:24:07,475 --> 00:24:14,810
fertilization. MRT still isn’t
permitted in the United States

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and is tightly regulated in the
few places it is allowed. But in

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2025, doctors in the UK reported
what many are calling a medical

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00:24:28,430 --> 00:24:36,155
breakthrough: the births of at
least eight babies using MRT. So

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far, all appear to be healthy.

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Archive: A groundbreaking IVF
technique involving three people

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has resulted in the births of
eight babies free from what can

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be devastating diseases.
Scientists in Newcastle have

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pioneered the technique to stop
mothers passing down a mutation

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in their DNA that can cause
mitochondrial disease, which

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commonly impacts major organs,
such as the heart and the brain.

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Evan Shulman: The beginning of
our mission was to help other

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00:25:23,740 --> 00:25:27,100
families and hopefully prevent
other people from going through

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00:25:27,100 --> 00:25:31,885
this, and we've had a number of
families reach out to us, and

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00:25:31,885 --> 00:25:36,115
one family reached out to us,
who we, we ultimately ended up

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getting them in the hands of
Newcastle, and they had a son

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who was born about a year after
Nora.
 They named him Noah,

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which is pretty touching for us
to hear, and they actually

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brought him to our daughter's
first birthday party at our

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house, and we got to meet the
family and meet their son, and

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it was sort of surreal to see a
baby that was born healthy from

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a technique that was, I want to
say, almost nobody in the US

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00:26:20,695 --> 00:26:26,665
knew was even available, and no
one was supporting. And now here

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we are, we have two babies
sitting together who were born

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from the same technique,
healthy, happy. There's these

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days when we look at each other,
and we're like, how did we get

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00:26:40,600 --> 00:26:46,780
here? Like, how did we turn
things around for us, and end up

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00:26:46,780 --> 00:26:52,270
with two beautiful girls in
front of us... the family that

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we always wanted.

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Lauren Arora Hutchinson: Next
time on playing god?

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00:27:21,925 --> 00:27:25,810
Rebecca Morrison: I mean, I'm
just a person that is trying to

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00:27:25,810 --> 00:27:30,850
determine something for my own
health. What is the responsible

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00:27:30,850 --> 00:27:36,130
thing to do as a human being, as
a woman, as a mother, as a wife,

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00:27:36,130 --> 00:27:43,210
as a daughter, as a person.
Should I do it? Do I need to do

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00:27:43,210 --> 00:27:45,685
it? Do I have to do it?

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Lauren Arora Hutchinson: Many
thanks, again, to Kristelle and

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00:27:50,520 --> 00:27:54,600
Evan Shulman for sharing their
story with us, and to Jeffrey

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00:27:54,600 --> 00:28:00,060
Kahn and Marni Falk.
 
 playing
god? is a production of the

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00:28:00,060 --> 00:28:03,810
Dracopoulos-Bloomberg iDeas Lab
at the Johns Hopkins Berman

404
00:28:03,810 --> 00:28:08,415
Institute of Bioethics, made in
association with Sea Salt and

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00:28:08,415 --> 00:28:12,825
Mango Productions.
 
 This
episode was produced by Redzi

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00:28:12,825 --> 00:28:17,865
Bernard, with help from Brian
Ricker and Lyric Bowditch.
 
 

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00:28:17,775 --> 00:28:22,245
Our Executive Editor is Tony
Phillips.
 Music and sound

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00:28:22,245 --> 00:28:27,645
design by Alexander Overington.
iDeas Lab Producer, Lyric

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00:28:27,645 --> 00:28:33,870
Bowditch.
 Researcher, Brian
Ricker.
 Story Editor, Simon

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00:28:33,870 --> 00:28:39,780
Adler.
 Show art by Barry
Pousman and Shawn Carney.
 Our

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00:28:39,780 --> 00:28:44,460
Production Coordinators are Leah
Lord and Susan Snead.
 Our

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00:28:44,460 --> 00:28:49,710
Executive Producers are Jeffrey
Kahn and Anna Mastroianni.
 
 

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00:28:49,620 --> 00:28:55,065
I’m Lauren Arora Hutchinson,
host and Managing Editor.
 Come

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00:28:55,065 --> 00:28:58,665
back next week for more playing
god?