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October 13, 2024 50 mins
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Episode Transcript

Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:12):
So here's your babies in four day and as we
can see, they're identical.

Speaker 2 (00:22):
Twins are as close as nature gets to human cloning.
Their identical genetic makeup is one of the wonders of
human reproduction. The close similarities can astound even identicals separated
at birth often lead to strikingly similar lives with the

(00:46):
same jobs, tastes, and hobbies, but identicals can also confound expectation.
Advance in genetic science are revealing that identical twins are
not as identical as we thought. Through state of the

(01:12):
Art in the womb, four D ultrasound scans, scientifically accurate
visual effects, and specially shot microscopy footage, we will reveal
the hidden world of twin fetal development in a world

(01:48):
where most of us are individual. Identical twins capture the imagination,
but for scientists it's not their similarities that prove most fascinating,
but their differences. They may not look it, but these
boys are identical twins born with dramatically different birth weights.

(02:17):
Twins like these with major physiological differences present an enormous
opportunity to reveal truths about human identity, from fingerprints and
intelligence to disease and even sexual orientation. Like everyone, identical

(02:50):
twins begin life as a single cell a fertilized egg
called a zygote. This cell contains twenty three pairs of chromosomes,
tightly packed strings of genes, one set from the mother's

(03:10):
egg and one from the father's sperm. Together, they make
up the entire genetic blueprint for a new human life.
A few hours after fertilization, the cell, with its cargo

(03:33):
of chromosomes, embarks on a remarkable journey. It travels along
the Filipian tube towards the womb. The single cell now
starts to divide, first two, then four, then eight, each
cell an identical replica of the other. This rapidly multiplying

(03:58):
collection of cells is called a blaster, and it's here
that nature's most remarkable reproductive anomaly can sometimes occur. Very occasionally,
there is an event so mysterious that until recently it's
never been witnessed. Several days after conception, the blastocyst spontaneously

(04:26):
splits into two. Each new blastocyst is composed of cells
with the same identical set of chromosomes, carrying the same
arrangement of genes along their length. The two blastocysts now
have the potential to develop into identical twins. Exactly how

(04:56):
and why the blasticism splits is one of reeper ductive
sciences greatest mysteries. But in two thousand and seven, during
a laboratory study of twenty six embryos, embryologists witness this
event for the first time. The blastocyst's outer membrane is

(05:17):
called the zona pellucida, the lining inside is called the trophoblast.
Just one cell layer thick, the trophoblast will eventually develop
into the precenter. Within lies the inner cell mass embryonic
stem cells that will eventually become the fetus. Over the

(05:42):
course of four days, the embryologists noticed that a junction
between a cell and the trophoblast membrane would regularly weaken,
letting liquid leak out and causing the trothoblast to collapse
like a balloon full of water. Then it would repair itself.

(06:05):
But in two of the eggs, the embryologists spotted something
no one had ever seen before. After the membrane collapsed,
the inner cell mass divided in two, each clump sticking
to a different side of the trough of blast as
it reinflated. If these clumps were to develop in uterol,

(06:30):
they would eventually grow into identical twins born from the
same single fertilized egg. It's not surprising that most identicals
retain a similar physical appearance as they grow up. Influence
of genes reaches beyond how we look. Genes also affect

(06:53):
personality and taste, making us flamboyant rather than shy, with
the tape for coffee instead of tea, and a love
of routine or desire for experimentation. Similarities between twins are
often more than skin deep. Dennis and David Herrera of

(07:17):
fifty three year old identicals from California. After high school,
both became officers for the Los Angeles Police Department. Because
they were raised together and went to the same school
and had the same friends, it's impossible to say whether
their career choice was influenced by their genes or their upbringing.

(07:46):
To really test the extent to which our genes influence
our life choices, scientists study identicals who have been separated
at birth and raised in different environments. Daphne and Barbara
were separated as babies and had no contact with each
other for forty years. They were raised in very different families,

(08:13):
one by a scientist, the other by a municipal gardener.
But the similarities between them are striking and perhaps beyond coincidence.
They both left school at fourteen. At sixteen, they both
fell in love. In their early twenties, they each married

(08:36):
their childhood sweethearts. They both suffered miscarriages at the same age,
but went on to have children in their early twenties.
Both have an irrational fear of blood and of falling down.
When they met for the first time on a train platform,

(08:58):
they wore almost identical clothing. The similarities are remarkable. They
suggest that genes play a powerful role in shaping many
aspects of our lives and personalities. But as we will see,

(09:18):
it's the differences between identicals that could offer science the
greatest opportunity, the chance to solve the age old debate
of nature versus nurture. When these twins were born in
two thousand and six, Jake weighed a healthy two and
a half kilos. His twin Tom weighed just over half

(09:40):
a chillo. Since they're identicals, this dramatic difference was a
mystery for answers. Doctors look to the one environment the
boys shared before birth. The womb. By day five, the

(10:07):
two identical blastocysts have reached the womb. Now they face
one of the most critical events in their nine month odyssey,
one that could dramatically affect their fortunes in the womb
and beyond. When they were born, Jake weighed two and
a half kilos and his brother Tom half a chuilo,

(10:32):
and yet they're identical, born just minutes apart. How could
twins with the same genes look so different. The answer
may lie not in their DNA, but in events that
occurred in the environment they shared the womb, and the

(10:58):
first most critical events is implantation. Around day six, the
blastocyst must implant in the wall of the womb, securing
its position for the next two hundred and fifty days growth,

(11:20):
but timing is everything. Each twin will rely on a
placenter to supply it with oxygen and nutrients, but the
placenta only starts to develop after implantation, So blastocysts that
split early before they implant each get their own placenter,

(11:41):
but those that split late after implantation must share one.
A shared placenter may mean one twin receives less nourishment
than the other as a result, it grows much more slowly,
a condition called selective intra uterine growth restriction. There are

(12:12):
even rare instances when identical twins have their own presenters
and yet developed this condition. Identicals Jake and Tom are
one such case. Their different weights are the result of
events that occurred long before they're born, but their effects

(12:34):
may last a lifetime. In fact, the later the egg splits,
the more critical the situation can become. This is Lakshmi,
a three year old girl from northern India. Amazingly, only
a few months ago, she had an additional set of

(12:54):
arms and legs, and X rays revealed an extra pelvis.
Strictly speaking, these don't belong to Lakshmi, but to her headless,
inverted and undeveloped twin, called a parasitic twin. And yet

(13:15):
the difference between a parasitic twin and a healthy twin
is just a matter of days. In most cases, identical
twins are created during a twelve to thirteen day window
following fertilization. After this time, the basic embryo starts to

(13:37):
organize itself into the first stages of the crude embryonic body.
It may be that if the embryo splits during this organization,
separation is never fully completed, and the two embryos remain fused.
This rare reproductive accident occurs once in every two hundred

(13:58):
thousand berths and usually results in conjoined twins. Identical twins
joined at the head or body. Parasitic twins are in
essence conjoined twins, except one twin is totally dependent on
the other fully functional one. In Lakshmi's case, her headless
twin relied entirely on her for survival. In November two

(14:24):
thousand seven, Lakshmi underwent a delicate, twenty seven hour operation
to remove the malformed twins, unwonted arms and legs, and
to reconstruct her pelvis. Without this, she would most likely
have died in her teens. The operation was a success

(14:45):
and the doctor's hope she will walk unaided once implantation
has occurred. Embryonic development is surprisingly rapid. By the end

(15:07):
of the third week, a rudimentary body shape is already emerging.
The embryo already resembles the beginnings of a body totally
unprotected by skin and bone. On one edge, stem cells

(15:28):
flow over and are assigned their fate by the organizer.
One of the first organs to form is the heart,
until now just a clump of muscle cells. Then, around
day twenty two, a single cell in this dormant clump
of muscle cells spontaneously contracts. It sets off a chain reaction,

(16:00):
One after the other. Neighboring cells begin to contract until
the entire vessel is pulsating. Two tiny hearts about the

(16:23):
size of two pin heads beating together. Our twin embryos

(16:45):
have approximately the same number of cells, the same DNA,
and yet incredibly they may already be different, and those
differences will become deeper and more profound as they develop,

(17:05):
shedding light on some of the deepest mysteries of human identity.
Is personality innate or learnt over time? Why do some
of us succumb to disease while others remain immune? And

(17:28):
from where do we get our skin color? What makes
one person gay another straight? The answers are not as
simple as we once thought. Remi and Kiran are fraternal twins,

(17:50):
the result of two separate sperm fertilizing two separate eggs.
The girl's parents are of mixed ancestry. This usually means
the children will also look mixed race, but not always

(18:11):
Being mixed ancestry means carrying a mixed set of genes
for both lighter and darker skin. In Remi's case, a
sperm with a set of genes that produce darker skinned
children fertilized an egg with similar characteristics. In Kian's case,

(18:32):
a sperm with genes that create lighter skin children fertilized
a similar egg too. The result twins, but twins who
look very different. Remi and Kian show us that twins
can often confound expectation, but they are not the only ones.

(18:58):
In two thousand and one, a pair of twins were
born who at first appeared to be a boy and
a girl. On closer inspection, it became clear that one
had signs of both male and female genitalia. The twin
was a hermaphrodite. Scientists believe that this happened because a
single egg was fertilized by two sperm, one with a

(19:22):
female sex chromosome and one with a male sex chromosome.
The egg developed into a blastocyst with both male and
female cells. The egg then divided, and each of the
two new cells she had an extra chromosome. Resulting in
a blastocyst composed of both male and female cells. That

(19:52):
blastocyst then split to create twins. By chance. One had
more cells with the male sex chrome and developed into
a boy, while the other had similar numbers of cells
with male and female sex chromosomes, resulting in a child
with male and female genitalia. It was a startling discovery.

(20:16):
Twins who are halfway between identical and fraternal, the only
known case of semi identicals in the world. The simple
classifications were used to are breaking down and will come
to inform much of our newer understanding about how twins,
and by extension, all of us develop. At five weeks,

(20:44):
our identical twin embryos are beginning to take shape. Now
curved into a C shape, their heads and tails can
be distincts, as can hearts, spinal columns, and the beginnings

(21:09):
of tiny limbuds. At this stage, the embryo looks almost
indistinguishable to any vertebrate in the animal kingdom. These fragile creatures,
just one and a half millimeters long, are about to

(21:30):
embark on a critical period of brain development. This five
week milestone could be another stage where identicals develop key
differences before they're even born. Salsau and Jesus are identical twins.

(21:57):
They were raised together. As they grew up, they remained
physically similar, but their tastes and interests began to diverge.
Celso became interested in dance and academia, while Jazeus preferred sports.

(22:17):
The most surprising difference between the two brothers is that
Celso here wearing black, is gay. The differing sexual orientation
of identical twins is an opportunity to investigate one of
science's most controversial questions. Are people born gay? As Celsou

(22:44):
and Jazeus were raised by the same parents in the
same household, they inevitably shared the same environment at a
crucial time in their personal development. In the general population,
the chance of someone being gay is less than five
percent unless you have a gay twin. Here, the chances

(23:09):
are much higher. If you're fraternal, sharing half your genes,
there's nearly a twenty five percent chance that you will
also be gay. If you're identical, sharing all your genes,
there's roughly a fifty percent chance that you will also

(23:29):
be gay. This suggests that there must be some genetic
component to our sexuality. However, it can't be all down
to genes. Otherwise all identicals would be either both gay

(23:52):
or both straight. Some other factor must be at play.
In their first few weeks, all fetuses develop along similar lines.
If nothing changed, we would all be born. Female. Fetuses

(24:18):
with the male Y chromosome will form testes at about
week six that begin to produce the hormone testosterone, but
at about the eighth week, testosterone is released and may
affect early brain development. This hormone masculinizes the body. Testosterone

(24:40):
also masculinizes the brain, including a part called the hypothalamus,
part of the network which controls who we find sexually attractive.
Some scientists believe that the more the hypothalamus is exposed
to testosterone, the more it sets the stage for a
sexual inclination towards women. Occasionally, a male fetus may not

(25:09):
produce sufficient testosterone or its brain does not absorb enough
to shape it along heterosexual nines. If this theory is right,
then it may be that Celso the gay brother, absorbed
enough testosterone to masculinize his body, but not enough to
fully differentiate his brain. As a result, he was left

(25:31):
with a desire for men. Although there are still many
mysteries twins like these are playing a crucial role in
informing scientists about how and when we all develop our sexuality.

(25:56):
By the eighth week, our identical twins have finished their
embryonic stage of development and are now known as fetuses
from the Latin meaning offspring. The twins, now secure in
their own sex but sharing a percenter, have approximately two
hundred days left until birth. Now their growth accelerates. By

(26:26):
thirteen weeks, they're beginning to look more human. The eyes
have moved together and the head is in better proportion
to the rest of the body. It's also the end

(26:48):
of the first trimester, the time most pregnant women will
have their initial ultrasound scan. The ultrasound sonographer checks for
basic signs of normal development.

Speaker 1 (27:06):
So here's your babies in four D. And as we
can see the identical.

Speaker 2 (27:17):
The sonographer sees a single placenta, a sure sign that
the twins are identical.

Speaker 1 (27:23):
We can see here a single percenter like a T section,
in which proves that you're having identical twins. So when
would you see them start interacting or reacting against each other.
We can see them almost sort of moving.

Speaker 2 (27:40):
From now on, the mother will be monitored closely twin
pregnancies are more at risk of premature births. Immature development
of lungs and organs can lead to complications. These complications
make natural childbirth more dangerous. As a result, twins are

(28:02):
around fifty percent more likely to be borne by cesarean
section than Singleton's. The timing of the scan also marks
the start of the second trimester. The second trimester, from

(28:22):
twelve to twenty four weeks, will see not only dramatic growth,
but massive development in everything from the structure of the
brain to the refinement of facial features. By the end
of this stage, the fetuses will be small but almost
perfectly formed. They look very similar, but newer search reveals

(28:52):
that even at this early stage, identical twins may already
be less identical. Subtle changes are under way that will
become greater throughout their lives, and the mechanism responsible is
one of the most complex yet fascinating processes in the

(29:14):
whole of human development. Fifteen weeks into their journey from
conception to birth, our identical twins begin to move for

(29:36):
the first time. They start to interact, exploring their environment
with their hands and feet, touching and even appearing to
kiss their mother. In later pregnancy will feel the same case.

(30:00):
Each twin feels in muteroe. At times they appear aggressive,
at others almost caring. They look identical, but unseen influences
may already be taking effect, ones that could subtly alter
the expression of genes in their growing body identicals. Jake

(30:31):
and Tom are now aged seventeen months. Jake is eight
centimeters taller than Tom and four kilos heavier When they
were born in two thousand and six, doctors attributed these
discrepancies in size and weight to restricted nutrition or blood

(30:54):
flow in the womb. They expected Tom to catch up,
but after a year and a half, they're investigating whether
Tom may be suffering from a genetic condition called Russell's
Silver syndrome, a growth disorder. One of the causes of
this syndrome may be a problem with a growth gene

(31:15):
on chromosome eleven. Scientists are puzzling over why Tom and
his brother do not both have a syndrome. Identical twins,
after all, have identical genes. Genetic puzzles like these are

(31:39):
opening up a little known world at the outer reaches
of science, epigenetics. This growing field of biology may help
explain the differences between twins like Tom and Jake. Epigenetic

(32:00):
reveals that while their DNA code may be the same,
the way it functions can differ. The human genome contains
around twenty five thousand genes, each with its own specific function,
such as producing energy or directing cell division. Now geneticists

(32:21):
are investigating a previously unknown aspect of the genome called
the epigenome. There is a series of chemicals that act
as switches capable of activating or deactivating individual genes. One
of these switches works by a process called DNA methylation.

(32:43):
This causes enzymes insider cell to attach a minuscule molecular
compound a methyl group, to a gene. This compound can
deactivate or at times activate the gene, but the gene
remains the cell's DNA profile is unchaeed changed. This could

(33:06):
explain the difference between identical twins Jake and Tom. Some
as yet unidentified environmental factor in early cell development has
caused a methyl group to attach itself to a gene
on one of Tom's chromosomes, a gene associated with growth.

(33:27):
The growth gene is still there, but it's been switched off.
By investigating the mystery of twins like Tom and Jake,
Geneticists are finally beginning to find clues to some of
the great mysteries of the human genome. This is a

(33:54):
map of chromosomes belonging to identical twins from age three
on the left to twins aged fifteen on the right.
The red markings are an indication of the increase in
the methylation that has occurred to their chromosomes over half
a century. We know that factors like smoking, diet, and
chemical exposure can, over a lifetime, wreak havoc with how

(34:16):
genes operate. What's astounding is that there are different environmental
influences in not only our lifetime, but also in utero. Hormones, space,
quality of nutrition can all affect identical embryos differently, even
those sharing a placenta. The activation and deactivation of genes

(34:41):
during early development could explain many of the twists of
fate that affect us all why one person is struck
by disease while another spared. Epigenetics may also play a
significant role in determining sexuality. If sexual preference is associated
with an asthet unidentified gene, it may be that the

(35:03):
epigenetic suppression or activation of this gene dictates sexual preference.
These genetic switches may be the answer to why one
twin absorbs more testosterone than the other, resulting in one
being gay and the other straight. It's becoming clear that

(35:25):
our health, personality, tastes, and even appearance are not the
product of either our genes or our environment, but that
nature and nurture are inextricably bound, with epigenetics the tangible
biological link between the two, and most surprisingly of all,

(35:46):
new research claims these subtle changes to a gene's expression
can be passed on down through the generations without affecting
the underlying DNA. Studying a register of births and deaths
in a remote region of northern Sweden, researchers noticed a
peculiar phenomenon. A generation of boys who experienced a famine

(36:11):
had grandchildren who led longer lives. On the other hand,
descendants of those boys who enjoyed plentiful food as children
experienced an increased risk of diabetes, cardiovascular disease, and higher
mortality rates. The effect of famine was especially strong if

(36:38):
the boy was at the age when he was just
about to start producing reproductive cells his sperm. It seems
the genetic makeup of these reproductive cells were directly but
subtly altered by the famine or feast. Through their sperm,
they passed on a nutritional legacy to future generations. The

(37:03):
more we explore the hidden world of epigenetics, the more
it seems we are not simply a product of our genes.
We may even have the power to steer our genetic
destiny and perhaps that of our descendants, through lifestyle choices
such as smoking, diet, and exercise. What makes identicals unique

(37:27):
and useful to genetics is that their genome is one
hundred percent match, or at least that's what we thought. Now,
powerful new DNA techniques are revealing a different story, one
that is only just unfolding. As the second trimester draws

(37:52):
to a close, the twins will have a second scan.
The development of external features such as limbs and eyes
will be checked, and the major organs will be examined
for signs of defects. The twins are about twenty centimeters long,
small enough to cradle in the palm of the hand.

(38:21):
The twenty week scan is the time when most mothers
will discover whether they're having a boy or a girl.
Gender identification can be done as early as eleven to
twelve weeks, but is more certain at the four months scan.
The scan reveals our twins are boys. Our twins are

(38:50):
twenty four weeks into development. Their mother can now feel
them kick inside the wound. A battle for space is raging.

(39:10):
A scan reveals this struggle and perhaps even a glimpse
of emerging personalities. Ultrasound studies combined with observations of twins
after birth, show very early forms of shy or extrovert behavior.

(39:31):
In one study of fraternal twins, the shire twin would
occasionally hang onto his umbilical cord and even appear to
lick it, while his sister would seek to grab, kick,
and push him. Intriguingly, this pattern continued after birth. At

(39:51):
four years of age, the shy twin still exhibited retiring behavior,
while his more extrovert sister would try to grab and
play with him. It seems our personalities may well begin
to form in the womb. From week twenty nine onwards,

(40:22):
the fetuses are beginning to resemble newborn babies. Their body
fat rapidly increases, bones are fully developed but still soft
and pliable. Head hair grows thicker, and fingernails reach the fingertips. Already,

(40:50):
our twins' fingerprints are different. Epigenetic changes have already impacted
the genes that control the pattern of the fingertips. These
fingerprint differences will become more pronounced as the fingertips develop.
They receive blood from the veins. This makes them swell,

(41:11):
forming distinctive fingerprint patterns. If blood flow from the percenter
in one twin is restricted, blood may be directed away
from the fingers and other extremities, leaving this twin with
more wells on their fingerprints than the other. Our fingerprint
patterns can help to indicate how unhealthy our heart will

(41:32):
be in adult life. The more wells, the greater the
chance of later heart problems. From the moment a fertilized
egg divides in two, various influences on the genetic code

(41:52):
conspire to create differences between identical twins, differences that can
become more pronounced over time. Yet it's always been assumed
that identical twins share identical DNA until a discovery in
two thousand and seven surprised the scientific world. Researchers set

(42:19):
out to investigate one of the most puzzling anomalies in
the life of twins, why one succumbs to a genetically
inherited disease while the other is unaffected. They chose Parkinson's
because it's more likely to be caused by a spontaneous

(42:41):
genetic cause than be inherited. So the scientists examined the
genes of nineteen pairs of identical twins, including nine pairs
in which only one twin showed signs of the genetic disorder.

(43:02):
They wanted to challenge the common perception that identicals are
genetically identical. Indeed, their analysis showed that there were differences
between the number of genes each twin had. Genes usually
occur in two copies, one inherited from each parent, but

(43:23):
this study has revealed it's possible to have just one copy,
or to have three or more copies of the same gene.
This phenomenon, called copy number variation, can fundamentally alter the
genes function and may induce the disease in one twin
and not the other. It's a major breakthrough in our

(43:58):
understanding of disease and in the study of twins, because
the discovery means that identicals are not a one hundred
percent genetic match. The very definition of identical twins needs
to be revised, as advances in technology can prove that
small but significant changes are present in all identical twins.

(44:24):
Our identical twin boys are approaching full urn already. There
will be subtle genetic differences between them that may shape
very different futures. But first they must face the most
dangerous stage of their long journey in the womb, the birth.

(44:47):
It's thirty five weeks. The twins are now fully developed.
They have hair, eyelashes, nails, and can open and close
their eyes and mouths. Conditions in the womb are becoming cramped,

(45:15):
but around two kilos each weighs about a third less
than the average singleton baby, but combined they put tremendous
pressure on the womb. Premature deliveries for twins before full

(45:35):
term at thirty seven weeks are common. Our twins will
be borne at week thirty five by cesarean section. About
half of twins are delivered this way due to the
difficulties and dangers of giving birth to two babies naturally.

(46:03):
To ensure safety, there is a larger than normal delivery
team on hand. The obstetrician swiftly cuts the first membrane
and then the second Caesareans are always performed quickly to

(46:29):
reduce the risks of complications. He plunges his hand into
the womb and takes the first baby out. The baby
takes his first breath and emits a healthy screen. The

(46:52):
cord to the placenta, his lifeline for the last thirty
five weeks is finally cut. Working briskly, the surgeon looks

(47:13):
for his twin. With his twin brother out of the way,
he follows quickly, also paid first. Following birth. It's not
always obvious to the obstetrician whether the twins are identical

(47:36):
or fraternal. Our twins have a shared placenter, the clearest
indication that they are identical. If the identicals have separate percenters,
as happens occasionally, DNA analysis is the only sure method
of identification. After an extraordinary journey, our two reproductive marvels

(48:10):
have made it safely into the world. They may look alike,
but we now know they are already different. Two hundred
and forty five days ago, a fertilized egg divided, creating
two identical embryos. From that moment onwards, their paths began

(48:36):
to diverge. Inequalities in nutrition or space, differing exposure to hormones,
small alterations in their epigenetic profiling, even minute differences in
the underlying genome, all combined to create subtle, yet significant differences.

(49:00):
Now the twins are about to embark on the next
stage of their journey. As they grow, facing diverse experiences
and influences, the differences between them will become ever greater.
These differences bring us closer to answering some of humanity's

(49:22):
most profound questions. The study of identical twins has shed
new light on the complex mix of genetics and environment,
nature and nurture that makes each of us unique. It
has profound and far reaching implications for how we all
lead our lives.
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