Alana Saarinen loves playing golf and the
piano, listening to music and hanging out with
friends. In those respects, she's like many
teenagers around the world. Except she's not,
because every cell in Alana's body isn't like
mine and yours - Alana is one of a few people
in the world who have DNA from three
people.
"A lot of people say I have facial features from
my mum, my eyes look like my dad… I have
some traits from them and my personality is the
same too," says Alana.
"I also have DNA from a third lady. But I
wouldn't consider her a third parent, I just have
some of her mitochondria."
Mitochondria are often called the cell's factories.
They are the bits that create the energy all of
our cells need to work, and keep the body
functioning. But they also contain a little bit of
DNA.
Alana Saarinen is one of only 30 to 50 people in
the world who have some mitochondria, and
therefore a bit of DNA, from a third person. She
was conceived through a pioneering infertility
treatment in the USA which was later banned.
But soon there could be more people like Alana,
with three genetic parents, because the UK is
looking to legalise a new, similar technique
which would use a donor's mitochondria to try
to eliminate debilitating genetic diseases. It is
called mitochondrial replacement and if
Parliament votes to let this happen, the UK
would become the only country in the world to
allow children with three people's DNA to be
born.
The structure of a cell
Nucleus: Where the majority of our DNA is held
- this determines how we look and our
personality
Mitochondria: Often described as the cell's
factories, these create the energy to make the
cell function
Cytoplasm: The jelly like substance that
contains the nucleus and mitochondria
Alana was born through an infertility treatment
called cytoplasmic transfer.
Her mum, Sharon Saarinen, had been trying to
have a baby for 10 years through numerous IVF
procedures.
"I felt worthless. I felt guilty that I couldn't give
my husband a child. When you want a biological
child but you can't have one, you're distraught.
You can't sleep, it's 24-7, constantly on your
mind," she says.
Cytoplasmic transfer was pioneered in the late
1990s by a clinical embryologist Dr Jacques
Cohen and his team at the St Barnabus Institute
in New Jersey, US.
"We felt that there was a chance that there was
some element, some structure in the cytoplasm
that didn't function optimally. One of the major
candidates that could have been involved here
are structures called mitochondria," he says.
Cohen transferred a bit of a donor woman's
cytoplasm, containing mitochondria, to Sharon
Saarinen's egg. It was then fertilised with her
husband's sperm. As a little bit of mitochondria
was transferred, some DNA from the donor was
in the embryo.
Seventeen babies were born at Cohen's clinic,
as a result of cytoplasmic transfer, who could
have had DNA from three people.
But there was concern about some of the
babies.
"There was one early miscarriage, considering
there were twelve pregnancies that is an
expected number," says Cohen.
He and his team believed that miscarriage
occurred because the foetus was missing an X
chromosome.
"Then there was another twin pregnancy, where
one [of the twins] was considered entirely
normal and the other had a missing X chromosome.
"So that's two out of the small group of
foetuses that was obtained from this procedure.
This did worry us and we reported that in the
literature and in our ethical and review board
that oversees these procedures," he says.
At the time of birth, the other babies were all
fine. A year or two later, another of the children
was found to have "early signs of pervasive
early developmental disorder which is a range
of cognitive diseases which also includes
autism." Cohen told me.
He says it's difficult to know if the abnormalities
happened by chance or because of the
procedure.
Other clinics copied the technique and Cohen
estimates that around 30 to 50 children
worldwide were born who could have DNA from
three people as a result.
But in 2002 the American regulator, the FDA
(Food and Drug Administration) asked clinics to
stop doing cytoplasmic transfer due to safety
and ethical concerns. All of them did.
"There was a reaction from scientists, ethicists,
the public at large, I think most of it was
supportive, some of it was critical - I think this is
normal, every time an experiment is done in
medicine there is a reaction - what are the risks
here?" says Cohen.
At the time, some were concerned because they
felt this was germ line genetic modification.
What "germ line" means is that a child like
Alana would pass her unusual genetic code
down to her children. And their children, would
pass it to their children and so on.
Because we inherit our mitochondria only from
our mothers, only female children would pass
their unusual genetic code on. Crossing the
germ line as it is known has never been done
before so very little is known about what the
outcome could be.
Due to a lack of funding, Cohen says, it hasn't
been possible to find out about how any of the
children like Alana who were born from
cytoplasmic transfer are doing. But the St
Barnabus Institute is now starting a follow up
study to check their progress.
Sharon Saarinen says her daughter Alana is a
healthy, typical teenager
"I couldn't ask for a better child. She is an
intelligent, beautiful girl inside and out, she
loves math and science … she does really well in
school. She helps me around the house… when
she's not texting!"
"She has always been healthy. Never anything
more than a basic cold, or a flu every now and
then. No health problems at all."
The health of the children, like Alana, born from
cytoplasmic transfer is under scrutiny now
because of the UK's decision to consider
legalising mitochondrial replacement, where the
mitochondria of a donor woman will be used to
create a child.
It would not be available for people with fertility
problems but for those who carry diseases of
the mitochondria and would otherwise pass
down these genetic abnormalities to their
children.
Exactly how it is done still needs to be
determined as there are two ways of doing the
procedure, depending on when the eggs are
fertilised.
Eggs from a mother with unhealthy
mitochondria and a donor with healthy
mitochondria are collected
The nucleus, containing the majority of the
genetic material, is removed from both
eggs. The donor nucleus is destroyed
The mother's nucleus is inserted into the
donor egg - it now has healthy
mitochondria. The egg is then fertilised by
the father's sperm
Both the mother's and donor's eggs are
fertilised with the father's sperm to create
two embryos
The pronuclei, the nuclei during the process
of fertilisation, contain the majority of the
genetic material. They are removed from
both embryos. The donor's is destroyed
A healthy embryo is created by putting the
parents' pronuclei into the donor embryo
"Mitochondrial diseases tend to involve tissues
or organs which are heavily dependent on
energy," says Prof Doug Turnbull from The
University of Newcastle. He has treated people
with mitochondrial disease for decades and is
one of those who has developed these new
techniques to try to cure these debilitating
diseases.
"The conditions can therefore involve the heart,
the brain or sometimes the skeletal muscle," he
says.
"People can have very bad heart problems
which can cause the heart to fail eventually,
they can be very weak and require respirators
or be in a wheelchair. With the brain, they can
get epilepsy, strokes and eventually severe
dementia."
Turnbull estimates that around 1 in 3000-5000
people in the UK have a mitochondrial disease.
"We can treat the symptoms. We can improve
the quality and length of peoples' lives but we
can't cure them."
The mitochondria carry some DNA, around 13
"important genes" says Turnbull.
That compares to the "23,000 important genes"
in the nucleus where most of our DNA is held.
This is the DNA that determines our traits and
personality.
"We're not trying to create some characteristic
that makes this person a stronger person or
[someone who] will have blonde hair. We're
trying to prevent disease and I think that is the
only justification for doing this," he says.
Sharon Bernardi, from Sunderland in the North
of England, is someone who mitochondrial
replacement could have helped.
Bernardi has lost seven children to
mitochondrial disease .
"I have babies in three different cemeteries,"
she told us in her sitting room, surrounded by
photographs of all her children.
"That is not the way you plan your life when
you're trying to have a family. I have lovely
photos and lovely memories but obviously that's
all I have got now."
The doctors didn't know why Bernardi's babies
kept passing away only hours after they were
born. So that's why she kept trying, hoping she
would have a healthy child.
With her fourth child, Edward, at first everything
seemed different. He was healthy until he was
about four and a half. But it was then that he
was diagnosed with Leigh's disease, a type of
mitochondrial disease, and his health
deteriorated throughout the years.
"From the age of 20 Edward [found] getting
around more difficult. He started to get new
symptoms - spasms. He'd start screaming...
four, five, six hours at a time. His muscles used
to tense up, his hands, his face. It was like
dystonic spasms - a really bad spasm. [For]
eight hours he'd be in pain, screaming. His face
would twist up and his hands would get really
stiff. It was hard to see."
Edward Bernardi passed away three years ago,
when he was 21.
"My life was totally for Edward. Even now
sometimes if I have gone to sleep, I still wake
up, and think, 'It's very quiet.' I have to slip
back into reality and think, 'Don't be silly,
Edward's not there. He's not in his room'."
"Without a heartbeat I would have gone for this
[mitochondrial replacement]. I hope this is a
new option. I hope people take it seriously and
it's approved.
"I don't want my son to have just died for
nothing. I want him to have made a difference."
"His life was robbed at 21. We're trying to stop
this. People have to understand this is a life
disease. We're trying not to pass it on to
children and make it better for future families."
But some people believe this technique could
set us on a slippery slope towards genetically
modified humans.
"These regulations would authorise the crossing
of a rubicon for the first time. It would
authorise germ line therapy... to alter the genes
of an individual. This is something defined by
the EU Charter of Fundamental Rights as
effectively constituting eugenics," says British
MP Fiona Bruce who chairs the All Party
Parliamentary Pro-Life Group.
"We will have approved a technique and what
that technique could be used for in the future
who knows. We're opening a Pandora's box."
The regulator in the UK, the HFEA or Human
Fertilisation and Embryology Authority, has held
three independent reviews to scrutinise the
safety of this technique. The conclusions were
that mitochondrial replacement is "not unsafe".
That means "it would be reasonable, with some
additional experiments, to take it into clinical
practice if all circumstances are fulfilled" says
Peter Braude, emeritus professor of obstetrics
and gynaecology at Kings College London. He sat
on all three HFEA scientific reviews.
"In any move from science to clinical practice
there is a leap of faith - it has to be done," he
says.
He adds that many of the concerns being raised
now about this are the same as the ones cited
in the early days of IVF. The UK has for decades
been a leader in assisted reproduction science
and is where the world's first test tube baby,
Louise Brown, was born in 1978.
"The headlines then were 'playing God' and
'genetically modified humans'," says Braude.
"There have been few episodes I'm aware of in
the history of assisted reproduction that have
had to be stopped because of hazard. It's all
gone pretty swimmingly as far as I'm aware."
Braude says that mitochondrial replacement has
gone through much more scrutiny than previous,
now well established, assisted reproduction
techniques did, such as IVF.
"Whereas the original techniques were used
with only [experiments from] mice, rabbits, lab
animals... the big difference here is we also
have issue of human embryos and this work has
been tested in macaque monkeys in primates.
All those were very useful, reassuring… hence
why we came to the conclusion that this is not
unsafe."
The experiments done on macaque monkeys
were done in Oregon, US and the monkeys are
now five years old and seem to be healthy.
Braude also points out that having a third
person's DNA in your system is "nothing
particularly new".
"Think about bone marrow transplants, let's say
unfortunately you have leukaemia and you have
to have your bone marrow radiated for the
cancer to be killed and then it is replaced by
bone marrow from someone else - say me.
Effectively from that time onwards, you will
have circulating in your body DNA from me. You
won't be related to me, you may be grateful to
me, but you will have DNA from a third person
circulating in your body."
What is different, say critics, about
mitochondrial replacement, is that DNA from the
donor will be passed down future generations.
Dr Ted Morrow, an evolutionary biologist from
the University of Sussex, and colleagues have
carried out mitochondrial replacement
experiments on other animals. He raised safety
concerns about mitochondrial replacement to
the scientific reviews.
"For mice, there were changes in cognitive
ability... to learn and do things using their brain.
In fruit flies and seed beetles there were
changes in male fertility, changes in ageing, a
range of different traits were effected in various
experiments," he says.
The HFEA's scientific reviews dismissed
Morrow's findings as not relevant to humans
because they were done on inbred animals.
Morrow stands by his research and says the
scientific panels should not have dismissed his
findings so quickly.
It is Morrow's evidence that critics such as Fiona
Bruce cite when saying this technique is not safe
enough.
She has called a debate in the House of
Commons today to discuss mitochondrial
replacement. She does not believe there has
been enough debate about what the UK is
proposing to do. "The technique itself could
allow the child to inherit untried untested
medical complications," she says.
Morrow says that all the coverage of his
research has been "a rather odd experience".
"In the press it's sometimes portrayed that the
scientists think this, and the pro-life group this.
I'm a scientist but I'm not a pro-lifer. I think
this is a genuine safety concern - that's it."
Alana and Sharon Saarinen have been watching
the debate in the UK with interest.
"I wish I could meet her, the donor, to tell her I
am so grateful for what she did for us. How can
you thank someone for giving you a life? That's
impossible," says Sharon.
Alana agrees with her mum. "I think it would be
nice to thank her. But I wouldn't want to have
a relationship or connection with her. The DNA I
have of her is just so small."
"I know she might have another person's
mitochondria, [but] look what a great person
she turned out to be, and healthy. Just because
she'll pass it on to her children it won't bother
me in the least. I know it was the right thing to
do. I have the living proof every day to see how
great it turned out."
Credit: BBC
