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Hattar 1

Winter Trophy @ Greenway High


Congressional Research - December 2016

Legislation Label: 8/“Mitochondrial” Researcher Name: Yousef Hattar

Pro:
I. There are many risks if we leave this issue unattended

Source: Steril, Fertil. "Three-Parent IVF: Gene Replacement for the Prevention of Inherited Mitochondrial Diseases." National
Center for Biotechnology Information Search Database. NCBI, Jan. 2014. Web. 1 Dec. 2016.

However, it is estimated that about 1 in 4,000 children


The true prevalence of mtDNA disease is unknown.
are born in the U.S. with an inherited with mitochondrial disease. (2) Mitochondrial
disease often affects high energy requiring tissues such as brain, muscle, liver, heart,
kidney, and the CNS. These diseases are clinically heterogeneous but symptoms may
include deafness, blindness, diabetes, muscle weakness, heart, kidney, and liver failure.
There are a number of well-defined clinical syndromes. But, many patients do not fall into easily defined clinical groups.

II. Real World Examples (Good for an Intro)

Source: Toynbee, Polly. "This Isn't about Three-parent Babies. It's about Saving Families Needless Misery | Polly Toynbee."
Opinion. Guardian News and Media, 03 Feb. 2015. Web. 01 Dec. 2016.

Alison Maguire lost her four-year-old daughter Niamh to mitochondrial disease, which
prompted her to help set up the Lily Foundation to campaign for this new treatment. “Almost all her life Niamh was in pain,” she said.
Suffering from extreme epileptic cramps, her mother says: “She screamed and
screamed, and it was awful for everyone to watch her. Then her sight failed too.”

III. The Mitochondrial Process is Safe

Source: Saul, Heather. "Three-parent Babies: Main Arguments for and against Ahead of Crucial MPs Vote." The Independent.
Independent Digital News and Media, 3 Feb. 2015. Web. 01 Dec. 2016.

Dr Gillian Lockwood, a reproductive ethicist, told the BBC that despite being widely
referred to as 'three-parent babies', "in fact it is 2.001-parent IVF".

"Less than a tenth of one per cent of the genome is actually going to be affected. It is not
part of what makes us genetically who we are," she said.

"It doesn't affect height, eye colour, intelligence, musicality. It simply allows the batteries
to work properly."

IV. This Procedure has been Tested to be Safe

Source: Walsh, Fergus. "Three-person Babies IVF Technique ‘safe’." BBC News. BBC, 08 June 2016. Web. 01 Dec. 2016.
Hattar 2
Winter Trophy @ Greenway High
Congressional Research - December 2016

Legislation Label: 8/“Mitochondrial” Researcher Name: Yousef Hattar

Scientists at Newcastle University are trying to help women who are at risk of passing on serious genetic disorders to have a healthy
child.

Last year the UK approved laws to permit the procedure, which involves using donor DNA from a second woman.

The study in Nature found the technique will lead to normal pregnancies.

The process, known as "early pronuclear transfer" involves removing the parents' key genetic material from an embryo within hours
of fertilisation, leaving behind the woman's faulty mitochondria.

The parental DNA, which contains all the key genes responsible for character and appearance, is then transferred into a donor
woman's embryo, which has its nucleus removed but contains healthy mitochondria.

Last year the UK became the first country to approve laws to permit the procedure.

A study involving more than 500 eggs from 64 donor women found that the new
procedure did not adversely affect embryo development and significantly reduced the
amount of faulty mitochondria being passed on.

Prof Doug Turnbull, director of the Wellcome Trust Centre for Mitochondrial Disease at Newcastle University and a co-author of the
study, said: "This study using normal human eggs is a major advance in our work towards
preventing transmission of mitochondrial DNA disease."

Prof Mary Herbert, also from the centre, added: "We are optimistic that the technique we have developed will offer affected women
the possibility of reducing the risk of transmitting mitochondrial DNA to their children" .

But the studies showed the technique was not always successful. The amount of faulty
mitochondrial DNA transferred during the procedure was less than 2%.

However, one in five of the stem cell lines created from the embryos showed an increase in carryover of defective DNA from the
original embryo.

Prof Turnbull said: "Our studies on stem cells does express a cautionary note that it might not be 100% efficient in preventing
transmission, but for many women who carry these mutations the risk is far less than conceiving naturally."

V. Sharing DNA isn’t New/ Doesn’t Change Much about the Child

Source: Feltman, Rachel. "The UK Voted Yes on ‘three-parent Babies’ Today. Here’s How One Baby Can Have Three People’s
DNA." The Washington Post. The Washington Post, 3 Feb. 2015. Web. 1 Dec. 2016.

The babies that result from this technique can only attribute around .1% of their DNA to the third party, so "parent" is a bit of a strong
word. The donor provides only their mitochondria. Often called the "power plants" of the cell, the mitochondria converts energy from
food into energy that can power a cell. When someone's mitochondria don't function properly, it's bad news indeed.
Mitochondrial diseases can cause a whole host of life threatening problems, and it's
estimated that as many as 4,000 children are born with such conditions in the United
States each year.

The technique up for vote, which was developed by British researchers, takes a mitochondria from a healthy female donor and
combines it with the DNA of two parents in an in-vitro fertilization. This can be accomplished at either the egg stage or the embryo
stage: In one method, two eggs are fertilized with the father's sperm -- one from the donor, and one from the mother -- and the
parents' genetic information is inserted into the donor's embryo, which has had everything but the mitochondria cleared out. In
another, the nucleus of a mother's egg cell is placed directly into a donor egg, replacing the original nucleus there.
Hattar 3
Winter Trophy @ Greenway High
Congressional Research - December 2016

Legislation Label: 8/“Mitochondrial” Researcher Name: Yousef Hattar

"The biggest problem is that this has been described as three-parent IVF. In fact it is
2.001-parent IVF," Gillian Lockwood, a reproductive ethicist, told the BBC. "Less than a
tenth of one per cent of the genome is actually going to be affected. It is not part of what
makes us genetically who we are.It doesn't affect height, eye color, intelligence,
musicality. It simply allows the batteries to work properly." There are already people out three with
2.001 parents. A similar technique was pioneered in the U.S. during the 90s, but was banned after less than 100 babies were born.

In fact, having a stranger's DNA in your body permanently isn't a novel idea at all.
"Think about bone marrow transplants,"Peter Braude, emeritus professor of obstetrics
and gynecology at Kings College London, told the BBC. "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."

VI. There are many Mitochondrial Diseases

Source: Fox, Maggie. "Three-Parent Babies Are OK, Experts Say." NBCNews.com. NBCUniversal News Group, 03 Feb. 2016.
Web. 01 Dec. 2016.

Damaged mitochondria are responsible for more than 200 different diseases.They
include Alpers disease, which causes seizures, dementia and blindness, and Leigh's
disease, a progressive disorder in which brain cells gradually die off, causing a range of
symptoms.

There's no cure for any of these conditions.

"MRT, if effective, could satisfy the desire of women to have a genetically related child without incurring the risk of passing on
mitochondrial disease," the panel wrote.

Con:
I. This Procedure can Affect Future Generations for the Worse

Source: Knapton, Sarah. "Three-parent Babies: The Arguments for and against." The Telegraph. Telegraph Media Group, 3
Feb. 2015. Web. 01 Dec. 2016.

However experts have warned that three-parent babies could be at greater risk of cancer
and premature ageing, and would need to be monitored all their lives.
They have warned that MPs would be making an ‘historic mistake’ by passing new laws.
Hattar 4
Winter Trophy @ Greenway High
Congressional Research - December 2016

Legislation Label: 8/“Mitochondrial” Researcher Name: Yousef Hattar

Dr Trevor Stammers Programme Director in Bioethics and Medical Law at St Mary's


University, said: “Even if these babies are born they will have to be monitored all their
lives, and their children will have to be as well. “We do not yet know the interaction between the mitochondrial
and nuclear DNA. To say that it is the same as changing a battery is facile. It’s an extremely complex thing.”

Dr Paul Knoepfler, associate professor at the University of California, Davis, said: “Since this is uncharted territory and the
children born from this technology would have heritable genetic changes, there are also
significant unknown risks to future generations.

“There are numerous serious risks associated with this technology. These include most
notably the possibility that developmentally disabled or deceased babies will be
produced.

“Aberrations could lead to developmental defects in babies or also manifest in later life
as increased rates of ageing of cancer.”

II. This Procedure is Faulty

Source: Weintraub, Karen. ""Three-Parent Baby" Procedure Faces New Hurdle." Scientific American. Scientific American, 30
Nov. 2016. Web. 01 Dec. 2016.

A promising technique to prevent mothers from passing on devastating mitochondrial diseases


was thrown a biological curve ball this week: A paper published Wednesday in Nature shows
that such diseases can come back to sicken a child, even when 99 percent of the
mother’s own mitochondria are eliminated.

Mitochondria are the tiny power plants that provide the energy every cell needs to function. When a large percentage of these
organelles malfunction, cells cannot do their jobs—and everything from weakness to death can result. Mothers with certain
conditions may have such low levels of faulty mitochondria that they have no symptoms, but their kids can inherit a higher burden of
these defective mitochondria, leading to devastating illness.

In attempt to combat this problem, researchers have essentially been—as one doctor described it—taking the “yellow part” of a
mother’s egg and inserting it into the “white” of a donor’s egg. Because the child ends up with DNA from its mother, father and a
donor, this mitochondrial replacement therapy has been nicknamed the “three-parent baby” technique. An apparently healthy boy
was born using the approach in April in Mexico. He carries about 1 percent of his mother’s mitochondria, which if allowed to pass to
him in full might have caused Leigh syndrome, a severe neurological disorder that is generally fatal in early childhood. His parents
had two previous children who died of the disease, one at age 6 and one at 8 months, New Scientist
reported.

But the new laboratory study shows that the mother’s mitochondria can sometimes
replicate faster than the donor’s and come to dominate again, potentially bringing
disease with it. Still, that effect is likely to be rare, says Shoukhrat Mitalipov, the developmental biologist who led the
research and has used the technique on mice and monkeys, reportedly without seeing any health problems. Mitalipov and Paula
Amato, a reproductive endocrinologist also at Oregon Health & Science University in Portland, said at a news conference that they
think mitochondrial replacement therapy should be tested in a clinical trial—despite concerns about the mother’s defective
mitochondrial DNA making a comeback. “Because these diseases are so debilitating and often fatal and there are no cures, we
think it’s still worth trying to move this research forward to prevent those diseases if we can,” Amato says. Congress currently bans
such three-parent procedures for clinical use in the United States, but the United Kingdom has approved a similar technique that
would allow even more of the mother’s mitochondria to be passed on to the child and a trial could likely be conducted there,
Mitalipov says.

Although mitochondrial diseases are fairly rare, affecting about one in 5,000 children, Mitalipov and Amato say the three-parent
technique could theoretically also be used to treat infertility and help with some stem cell treatments. Mitochondria (which have their
own DNA, separate from the DNA in a cell’s nucleus) are inherited solely from the mother. Some consider the three-parent
Hattar 5
Winter Trophy @ Greenway High
Congressional Research - December 2016

Legislation Label: 8/“Mitochondrial” Researcher Name: Yousef Hattar

procedure controversial because of this mix of DNA, and because scientists worldwide have agreed to avoid making changes to
human genetic inheritance.

III. This Procedure Doesn’t Necessarily Stop the Problem


Source: Knapton, Sarah. "'Three Parent Baby' Technique Could Still Pass on Mutated DNA, Study Shows." The Telegraph.
Telegraph Media Group, 8 June 2016. Web. 01 Dec. 2016.

On Wednesday, scientists at Newcastle University, said they had succeeded in carrying out the technique on fertilised human
embryos which were shown to develop well.

However they warned that in some instances up to four per cent of mutated DNA had
carried-over into the embryos and said they could not guarantee disease prevention.
Although the embryos were only kept alive for six days, cells taken from the embryos were cultured for longer to check that healthy
development continued. Worryingly in one instance mutated DNA which had carried-over was
found to increase over time until it reached disease-causing levels.

The scientists said it was 'inevitable' that some mutated DNA would be carried over and
said that maternal screening should be considered in pregnancy to check that the baby
was free of disease following the technique.

IV. There is Opposition from Other Groups of People

Source: Sample, Ian. "'Three-parent' Babies Explained: What Are the Concerns and Are They Justified?" The Guardian.
Guardian News and Media, 02 Feb. 2015. Web. 01 Dec. 2016.

What objections do people have to the procedure?


Mitochondrial transfer passes on genetic changes from one generation to another. That raises ethical concerns because any
unexpected problems caused by the procedure could affect people who are not yet born, and so cannot give their consent to have
the treatment. Mitochondria
are not completely understood, and the DNA they hold might
affect people’s traits in unknown ways. For that reason, some scientists believe
mitochondria should be better understood before the procedures are legalised. The
Church of England says it is not opposed in principle, but wants to see more scientific
research and debate on the ethics, safety and efficacy before the law is changed.

Are there other religious objections?


The Catholic church opposes one form of mitochondrial transfer, called pronuclear
transfer, because a fertilised egg from the mother is destroyed in the process. Catholic
ethicists have also complained that mitochondrial transfer introduces a “rupture”
between mother and father and “dilutes parenthood”.

V. This Procedure Could Lead to Future Legal Ones

Source: Toynbee, Polly. "This Isn't about Three-parent Babies. It's about Saving Families Needless Misery | Polly Toynbee."
Opinion. Guardian News and Media, 03 Feb. 2015. Web. 01 Dec. 2016.
Hattar 6
Winter Trophy @ Greenway High
Congressional Research - December 2016

Legislation Label: 8/“Mitochondrial” Researcher Name: Yousef Hattar

But tampering with any human DNA is illegal, and requires parliament to agree new
regulations. Inevitably it has led to warnings of “genetically modified humans”, “GM
babies” and even “designer babies”. Some ask whether children should have a right to
contact this “third parent”, although the donor contributes nothing to the child’s nature.
The good news is that once faulty mitochondria are replaced, children never pass on the disease. But that alarms some: once genes
Nothing can be 100%, but
are changed – even mere battery cells – that child’s germ line is altered forever. Is it safe?
an impressive array of Nobel prizewinners say the research has been as thorough as it
can be, with more results to come.

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