Many health experts worldwide believe mitochondrial donation could be an effective preventive strategy for mitochondrial diseases like muscular dystrophy.
Mitochondrial diseases are caused by genetic mutations in mitochondria - energy-producing membranes that are present in almost all cells of the body. These mutations stop the mitochondria from converting food and oxygen into energy, negatively affecting the heart, brain, muscles, lungs and other parts of the body.
While mitochondrial mutations can be triggered by environmental factors, they are most commonly passed from mother to child. Some children who inherit these mutations may show signs of disease at birth, while others may have later onset.
There is currently no cure for mitochondrial diseases. But many health experts worldwide believe mitochondrial donation, also referred to as mitochondrial DNA transfer or "three-parent" in vitro fertilization (IVF), could be an effective preventive strategy.
What is mitochondrial donation?
Mitochondrial donation is a form of assisted reproductive technology. It involves replacing the faulty mitochondria in a mother's egg with healthy mitochondria from the egg of a female donor.
There are two ways in which mitochondrial donation can be carried out. The first is maternal spindle transfer, which involves removing nuclear DNA - containing 99.9% of all DNA in a cell - from the donor egg. This means that only the part of the cell containing the healthy mitochondria remains. The healthy egg is then fertilized and placed in the mother's uterus.
The second mitochondrial donation method is pronuclear transfer. This involves the mother's egg and donor egg being fertilized first, so two embryos are created. The nuclear DNA is removed from the donor egg, and the nuclear DNA from the mother's egg is transferred to the donor egg, which contains the healthy mitochondria.
To date, neither method has been tested in humans. However, the maternal spindle transfer technique has proved successful in monkeys, resulting in the birth of healthy offspring, while pronuclear transfer has proved effective in halting mitochondrial disease development in mice with mitochondrial mutations.
In addition, maternal spindle transfer has been tested on human eggs, while pronuclear transfer has been tested on human fertilized eggs. Both methods led to the development of blastocysts - thin, hollow structures containing a cluster of cells that develop in early embryonic development. Researchers say this indicates that mitochondrial donation would result in normal embryonic development in humans.
According to the Wellcome Trust Centre for Mitochondrial Research in the UK, there is no evidence to suggest the technique will cause harm to a mother or child.
The potential benefits of mitochondrial donation
"The benefit [of mitochondrial donation] is clear," Dr. Sarah Rappaport, policy officer at the Wellcome Trust, told Medical News Today. "It will give families affected by serious mitochondrial disease a chance of having healthy children free of a devastating and often life-limiting disease."
Last month, the results of a study published in The New England Journal of Medicine - conducted by Prof. Doug Turnbull of Newcastle University and director of the Wellcome Trust Centre for Mitochondrial Research in the UK, who pioneered mitochondrial donation - estimated that the technique could reduce the risk of mitochondrial disease transmission for around 2,500 women in the UK, potentially saving 150 babies from such diseases each year.
Research suggests mitochondrial donation could prevent more than 12,400 women in the US from transmitting mitochondrial diseases, meaning at least 770 babies could be saved from these diseases annually.
And the benefits could be even greater in the US. The study suggests mitochondrial donation could prevent more than 12,400 women in the US from transmitting mitochondrial diseases, meaning at least 770 babies could be saved from these diseases annually.
It is understandable that the procedure has gathered monumental support, not only from members of parliament (MPs), but from families who have been severely affected by mitochondrial disease.
In 2012, BBC News reported on a mother from the UK - Sharon Bernadi - who had lost all of her seven children to mitochondrial disease. As such, Bernadi strongly supports mitochondrial donation and, in a more recent story from BBC News, said she was "overwhelmed" by the support the procedure has received from UK Parliament.
The technique has also received strong support from health organizations and charities worldwide - one of which is UK charity Muscular Dystrophy Campaign.
"There are currently no means to treat devastating mitochondrial diseases, which can cause muscle wastage, loss of vision, stroke-like episodes and a premature death," says Robert Meadowcroft, chief executive of the charity. "Preventing inheritance, where possible, remains our only option, and that is why we have invested in and wholly support this pioneering technique."
Next month, the House of Lords will vote on whether mitochondrial donation should pass into UK law under the Human Fertilisation and Embryology Act. Because of the overwhelming support in the House of Commons from MPs - who voted 328 to 128 in favor of the technique - it is expected to pass.
Prof. Turnbull and colleagues say they are ready to start trialing mitochondrial donation in humans in October this year, meaning the first baby from the procedure could be born in 2016.
But while there is overwhelming support for the method, some people believe legalizing mitochondrial donation in the UK could open a can of worms on a global scale.
Will legalizing mitochondrial donation pave the way for 'designer babies'?
A major concern surrounding the legalization of mitochondrial donation is that it could make "designer babies" - embryos that are genetically engineered to have preferred characteristics - widely acceptable.
In November 2014, Prof. Paul Knoepfler, of the University of California-Davis School of Medicine, wrote an open letter to the UK parliament urging them to vote against the legalization of mitochondrial donation, and the issue of designer babies was one of the concerns raised.
Talking to MNT, Prof. Knoepfler said:
"I do believe that legalizing and using this technology in humans, which clearly would produce genetically modified humans, is a step closer to designer babies.
That is not the intention of the proponents of this technology and they well even oppose anyone using their methods and techniques for such more extreme efforts, but once the line has been crossed and the technology is out there, who can control it? Who decides what is an appropriate or inappropriate use?"
But according to Dr. Rappaport, mitochondrial donation and designer babies are "scientifically and legally worlds apart and one will not lead to the other."
"Mitochondrial donation is not, and cannot be used for, deliberately modifying physical traits," she told us. "The only difference is that children will be born free of mitochondrial disease. Genetic modification of the DNA in the cell nucleus will remain illegal, there is no intention to change this and no legal precedent will be set."
Could the technique influence a child's personality?
Concerns have also been raised about whether mitochondrial donation may influence a child's personality and affect their mental health. "Some animal studies suggested that this kind of procedure can lead to neurological changes," said Prof. Knoepfler. "It is a concern and the risks for humans conceived via this process include neurological problems."
However, Prof. Dame Sally Davis, chief medical officer for England, notes that mitochondrial DNA represents less than 0.054% of the total DNA, and is not part of the nuclear DNA that influences personality and other characteristics.
"There is no evidence that mitochondrial DNA influences a child's personality," Dr. Rappaport told MNT. "Put simply, nuclear DNA makes us who we are and determines appearance and personality, and the main function of mitochondrial DNA is to generate energy - the 'battery pack.'"
However, Dr. Trevor Stammers, program director in bioethics and medical law at St. Mary's University in Twickenham, UK, says the medical field does not know enough about the connection between nuclear and mitochondrial DNA to reach this conclusion.
Dr. Ted Morrow, evolutionary biologist at the UK's University of Sussex, adds:
"There are a number of published studies that indicate genetic variation in the mitochondrial DNA influences an individual's personality. So swapping out the mitochondrial DNA from one person and replacing it with another will undoubtedly influence many different characteristics of an individual."
In addition, some experts say mitochondrial donation could even increase a child's risk of disease. In an article from The Telegraph, Dr. Rhiannon Lloyd, of the Zoological Society in London, UK, notes that in more than 50% of animal studies investigating mitochondrial donation, faulty mitochondrial DNA was transferred.
"Risks to the children who would be produced by this technique are many and include developmental disability, increased cancer risk and even death," Prof. Knoepfler told us. "The few previous experiences in humans in the US and China with related attempts at such technology led to not only a few healthy children, but also disastrous outcomes such as chromosomal damage and developmental problems."
As such, Prof. Knoepfler and many other opposers of mitochondrial donation say the procedure needs to undergo much more research before it is legalized for human use. "Furthermore comprehensive primate and other animal studies are needed to have a better grasp of all that this technology might bring both positively and negatively," adds Prof. Knoepfler.
What is the US standpoint on mitochondrial donation?
While the UK looks set to legalize mitochondrial donation, the US is not moving quite so fast.
In February 2014, the Cellular, Tissue and Gene Therapies Advisory Committee of the US Food and Drug Administration (FDA) held a meeting to discuss the issue.
The briefing document from the meeting reveals that the FDA require further studies on the technique before they can consider it for human use.
A spokesperson from the FDA told MNT:
"The FDA have not made any decision regarding clinical trials of mitochondrial manipulation technology. However, it is also important to note that the FDA cannot confirm the existence of or comment on any current/pending IND [investigational new drug] applications.
The FDA's primary concern, as we consider clinical trials using these technologies, will be the safety of the women participating in these studies and any children born as a result of these studies."
The FDA's reluctance to support mitochondrial donation as strongly as the UK is perhaps unsurprising. In the early 2000s, the use of a similar technique called cytoplasmic transfer - in which a cytoplasm from a donor egg is placed inside an egg with faulty mitochondria - was banned by the organization due to safety and ethical concerns.
Prof. Knoepfler said he supports the FDA's decision in requesting more research into mitochondrial donation and believes the UK should be adopting the same approach.
"With all due sensitivity and respect to the families facing mitochondrial diseases, I would ask why the UK seems to be rushing to approve this extreme approach when, from a rational scientific and medical perspective, this sense of urgency does not seem prudent," he told us. "It could easily do more harm than good if implemented so soon."
However, it seems many US researchers - including some linked to the FDA - believe the UK is right to move forward with mitochondrial donation.
In an open letter to The Guardian last month, Prof. John Gearhart, a member of the FDA advisory committee, and other researchers urged UK MPs to vote in favor of the technique, claiming it will encourage its use in other countries.
"A positive vote would not only allow affected families to choose to use this new procedure under the care of the globally respected Newcastle team, with proper advice and safeguards," they wrote, "it would also be an international demonstration of how good regulation helps medical science to advance in step with wider society."