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0:00On April 6th, 2016, a baby boy was born in Mexico.
0:03That’s not surprising; babies are
born every day all over the world.
0:07But this kid was special.
0:08A lot of us have two parents
to thank for our existence.
0:11But this boy was co-authored
by a whole team of scientists,
0:14and had three genetic parents.
0:16And he’s not the only one!
Despite the ethical debates
0:19and complex lab techniques involved,
0:21more three-parent babies
have been born since then.
0:24There are some excellent reasons
0:25why you’d need a bonus genetic parent.
0:27But as I’ll explain, there’s still a lot we
0:30need to learn about the science underlying it—
0:32especially as those babies grow up.
0:37Let’s start with the basics.
0:39To make a two-parent baby,
you need sperm and an egg.
0:42These two cells collide, fuse,
0:44and combine their DNA to make a full genome.
0:46Most of that DNA is nuclear DNA,
0:49which is contained in a cell’s nucleus.
0:50It codes for things like eye
color, hair color, and height—
0:54plus lots of invisible processes
that keep your body running.
0:57But that isn’t the only kind of DNA you have.
0:59You’ve probably heard of the mitochondria
1:01as the powerhouse of the cell.
1:02Cue flashbacks to high school biology.
1:04But powerhouses would be more accurate,
1:07since each of your cells contains
1:09hundreds to thousands of mitochondria.
1:11They help break down glucose and create ATP,
1:13which are energy packets that
your cells use for everything
1:16from muscle contractions to chemical reactions.
1:19But mitochondria also have their own unique DNA,
1:22called you guessed it mitochondrial DNA.
1:25Scientists aren’t positive how mitochondria
1:27ended up with this genetic contraband.
1:29But one of the most popular hypotheses is
1:31that some time over a billion years ago,
1:33a bacterial cell and a more complex
1:36host cell loved each other very much,
1:38so the bacterial cell moved into the host cell,
1:41helping it metabolize better, and
eventually became a part of it.
1:44Fast forward to today, and
that love story left you
1:47with 37 extra genes, all
related to cellular energy.
1:50So going back to that two-parent baby,
1:53both the sperm and the egg come to the party
1:55with nuclear DNA and mitochondrial DNA.
1:57But, soon after fertilization, the hundred or so
2:00paternal mitochondria are
destroyed, meaning that only the
2:04mitochondria from the egg
cell get passed to the baby.
2:06And it’s probably a good thing the paternal
2:08mitochondria don’t make the party’s guest list,
2:11because sperm are super bad at
proofreading their mitochondrial DNA,
2:15leading to boatloads of mutations.
2:17Mutations in DNA aren’t inherently
bad, but having more of them
2:21generally means that you have a
higher chance of harmful mutations.
2:24So all the mitochondria— and mitochondrial DNA—
2:27a baby gets came from the egg,
making it a gift from mom to you.
2:31But if that egg happens to have
2:33mitochondria with harmful DNA mutations,
2:36those mutations can lead
to mitochondrial diseases.
2:39That’s not something any parent
wants to give their child.
2:41To make matters more complicated,
2:43a parent might have a mix of healthy and
2:45mutated mitochondrial DNA throughout their cells,
2:48which is called heteroplasmy.
2:50And even if the parent has so few
mutated mitochondria that they
2:54don’t have disease symptoms, their
eggs can tell a different story.
2:57Some of their eggs might have a ton of the mutated
3:00mitochondrial DNA, while others might have almost
3:03exclusively healthy mitochondria.
It’s really luck of the draw.
3:06Then there’s the people who
only have mutated mitochondria,
3:09which is called homoplasmy.
3:11That pretty much guarantees that their eggs will
3:13have mutated mitochondrial DNA and their
3:16offspring will develop a
related mitochondrial disease.
3:19Unless, of course, you get a fertility lab
3:21involved in your baby making. And a third parent.
3:24Using mitochondrial
replacement techniques, or MRT,
3:27scientists can keep the original
two parents’ nuclear DNA
3:31but swap in a donor’s mitochondrial DNA.
3:33That means all the obvious
stuff we usually associate with
3:36genetic inheritance, like hair
or eye color, is coming from
3:40the two parents who contributed nuclear DNA.
3:42And the donor mitochondrial
DNA contributes to critical
3:45behind-the-scenes things like
cellular energy production.
3:48There are different kinds of MRT being explored,
3:51but two techniques are most
popular. And just for simplicity,
3:54I’ll use “mom,” “dad,” and “donor” to refer to the
3:57three sources of DNA involved in these procedures—
4:00though fertility clinics
help all kinds of families.
4:03One method is the pronuclear transfer.
4:05For this, two eggs are
fertilized by the dad’s sperm.
4:08One egg is the mom’s and the other is the donor’s.
4:11After fertilization, the nuclear
material gets scooped out of both eggs,
4:14and the stuff from the mom’s
egg is put into the donor’s.
4:17That creates an embryo that has the mom’s
4:19nuclear DNA but the donor’s mitochondrial DNA.
4:22If everything looks a-okay, then the embryo can
4:25be transferred into a uterus to get growing!
4:26But that whole destroying
a nucleus thing does mean
4:30one fertilized egg is sort
of destroyed in the process,
4:33and that can be a bit
uncomfortable for some people.
4:36Another method is the maternal spindle transfer.
4:38Here, the eggs’ nuclear material
are swapped before fertilization.
4:42That creates an egg with
the mom’s spindle apparatus,
4:44which are the bits that move chromosomes around,
4:47and the donor’s mitochondria, which is then
4:49fertilized with the dad’s sperm.
4:50Then, the same rules apply.
If it passes inspection,
4:53it can be delivered to a uterus for growing
4:55This was the method used for
the three-parent baby in 2016,
4:58since it avoids the ethical concerns around
5:01discarding already fertilized human eggs.
5:03So that covers the how of someone getting a bonus
5:06genetic parent. An egg-stra parent, if you will.
5:09And while mitochondrial replacement
techniques open the door for
5:12certain groups of three to
have children genetically
5:14related to all of them, the main use
so far has been to help two-parent
5:18couples avoid passing down
severe mitochondrial diseases.
5:21That was the case for that MRT
baby born in Mexico in 2016.
5:25His chromosomal mother was a heteroplasmic
5:27carrier for something called Leigh syndrome.
5:29Leigh syndrome, also called Leigh’s disease,
5:31is a heritable mitochondrial disease that causes
5:34nerve cell death and is usually
fatal to children by 3 years old.
5:37Unfortunately, this mother had
already lost two children to
5:40Leigh’s disease, in addition
to having four miscarriages.
5:43And when the researchers sampled
mitochondrial DNA from her eggs,
5:46nearly 100% carried the mutation
that causes Leigh’s syndrome.
5:50So MRT was pretty much her only
option to avoid passing down
5:54the condition while maintaining a
genetic relationship to her child.
5:57And the spindle transfer procedure
5:59led to the birth of a healthy baby boy.
6:01He was the first MRT baby, but
he certainly wasn’t the last.
6:04At the time we filmed this video,
8 MRT babies had been born in
6:08the UK after their mothers were
confirmed to have pathogenic
6:11mitochondrial DNA and went through
these fertility treatments.
6:14But mitochondrial diseases aren’t the only reason
6:16scientists are working with
families to create MRT babies.
6:19They’re also researching more
general causes of infertility.
6:22But before we get to that,
here’s a quick ad break.
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7:11Some researchers think that in
cases where the cause of infertility
7:14isn’t clear, the problem could be
hiding in the cytoplasm of the egg.
7:18Since MRT plops one egg’s nucleus
into a donor egg, that fresh egg
7:22and cytoplasm might have what’s
needed to support pregnancy.
7:25To test that hypothesis, a 2023 paper published
7:28in the journal of Fertility and
Sterility investigated whether
7:32MRT using the spindle
transfer method could benefit
7:3525 couples who struggled
with infertility in Greece.
7:38Over the course of the study,
19 three-parent embryos
7:41were transferred. In the end, 6 babies were born.
7:44/Maybe/ that means MRT can
help with mystery infertility.
7:48But considering this was a
small pilot study and 19 hopeful
7:51couples were still left childless,
it’s definitely not the only answer.
7:55Plus, that was one of several studies
to reveal a major flaw in MRT:
7:59the chromosomal mother’s
mitochondria can be stubborn as heck.
8:02Because these embryologists are
working with tiny single egg cells,
8:06some mutated mitochondria can
hitchhike into the donor’s egg
8:09when the mom’s nucleus is transferred, and then
8:12out-replicate the donor’s
healthy mitochondria over time.
8:15One of those 6 babies born to
couples in Greece had less than
8:181% maternal mitochondrial DNA
when it was a wee blastocyst,
8:22but that spiked up to around 30 to 50% at birth
8:25based on samples of cells from different tissues.
8:28Scientists call that bounceback reversion.
8:30And while it wasn’t a huge concern
for this infertility study,
8:33since the parents all had
healthy mitochondrial DNA,
8:36it’s a major concern when MRT is being
8:38used to prevent mitochondrial diseases.
8:40Reversion even happened with that
first MRT baby born in Mexico.
8:44At birth, some of his samples contained over
8:479% of his mom’s mutated mitochondrial DNA.
8:50But, luckily, it seems like 9% isn’t enough
8:53for someone to get symptoms of Leigh syndrome.
8:55The mix of two parents’
mitochondrial DNA in one cell has
8:58actually been a concern since
experiments in the 1990s.
9:01Back then, scientists were
considering whether a technique
9:03called cytoplasmic transfer
might help with infertility.
9:06In cytoplasmic transfer, the cytoplasm
9:09and all the stuff inside—including mitochondria—
9:11from a healthy donor egg is added
to the intended parent’s egg.
9:15The idea was that some fresh cytoplasm might
9:17cancel out whatever was
going wrong fertility-wise.
9:20If we’re being nitpicky, these were
9:20technically the first three-parent babies.
9:23But it seems like having a mix
of two types of mitochondrial DNA
9:26might be dangerous, even if there
aren’t pathogenic mutations.
9:30We don’t have exact records
of how many babies were
9:33born from this research, but
we think it’s about 30 or so.
9:36And we know that at least two or
three of those children ended up
9:39with serious complications with
their chromosomes or development.
9:43Because of those cases, the
scientific community now
9:45seems to agree that cytoplasmic
transfer isn’t safe in humans.
9:48Plus, studies involving mice
also suggest that even mixing
9:52two healthy mitochondrial DNA sources can cause
9:55cognitive impairment and behavioral abnormalities.
9:58Regulatory bodies across the
world have struggled with how to
10:01balance the potential benefits of
MRT against these kinds of safety
10:04concerns from tinkering with
reproductive genetics in the lab.
10:07In 2015, the United Kingdom became
the first country to explicitly
10:11legalize MRT while addressing the
challenge of scientific oversight.
10:15They have a regulatory authority that grants
10:17clinics licenses to perform the procedure and
10:20reviews each potential patient
on a case-by-case basis.
10:23And only one fertility
clinic currently can use MRT.
10:26Essentially, the country decided that highly
10:28regulating the procedure was the best way forward.
10:31In stark contrast is the United States.
10:33After those cytoplasmic transfer safety concerns,
10:36the FDA decided in 2001 that any future egg
10:39experimentation would require their approval.
10:41And Congress also practically banned the clinical
10:44trials necessary for that FDA approval.
10:46So while MRT isn’t technically banned in the US,
10:50there isn’t a clear path forward either.
10:52The majority of countries around the world are
10:54taking a “wait and see” approach, like Singapore.
10:57Or they haven’t really considered regulating MRT
10:59beyond some murky laws, like Mexico and Ukraine.
11:02Because of this lack of
standardization, it’s hard to say
11:05exactly how many three-parent
babies have been born in total.
11:08We mentioned those 8 MRT births in the UK,
11:10and the fertility study in
Greece that led to 6 babies.
11:13At least 7 babies have been
born using mitochondrial
11:16replacement techniques in Ukraine, and let’s not
11:18forget that first MRT baby who was born in Mexico.
11:21That’s around 22 babies. And if
you want to include the 30 or so
11:25that were conceived from cytoplasmic
transfer back in the 90s, then
11:29you’ve maybe got 50 humans walking
around with three people’s DNA.
11:33But again, nobody’s really
tallying—aside from us, just now,
11:37with incomplete information!
So it’s hard to know for sure.
11:40The science of making a three-parent
baby is still in its infancy.
11:44And even with the challenges of
keeping track of these babies and
11:47the risk of reversion, scientists
are hopeful about the future of MRT.
11:51At the time the paper came out,
in July of 2025, those 8 babies
11:55born in the UK were between
5 months and 2 years old.
11:58None of them had any major
or permanent health concerns—
12:01even though one of them had around
12:0316% mutated mitochondrial DNA at birth.
12:06The first ever MRT baby, who was born in Mexico,
12:09is only nine years old now, so it
will be a while before scientists
12:12can accurately assess the long-term
safety of these techniques.
12:15But since the future of MRT could
involve addressing infertility,
12:18helping non-traditional
families grow, or avoiding fatal
12:21mitochondrial diseases, it’s
probably worth the wait.
