Mitochondrial DNA Replacement Gains Acceptance in the UK

E. Scott Sills, MD PhD
Center for Advanced Genetics
The IVF Clinic San Diego County
+1 949-899-5686

Scientist processing DNA sample in laboratory

What does it all mean, and what’s next?

As a fertility specialist, I get questions every day about various treatments used to help patients grow (or start) their families.

This week, big news about a fertility treatment overseas has resulted in more than the usual number of contacts. Why?

The reason for all the fuss is that Britain is now set to be the world’s first country to allow something called mitochondrial transfer (MT) therapy.

MT is a special type of procedure done during IVF that takes out a tiny amount of abnormal or diseased DNA in a mother’s egg, and replaces it with healthy DNA from a second (usually younger) woman. That “improved” egg is then fertilized to make a healthier embryo.

It also means that the resulting baby would get genetic material from two “mothers” plus one father.

Under the original UK law this technique was prohibited, because such genetically altered human embryos could never be implanted into a woman. But this week, the House of Commons took a major step and voted to change that law.

What medical problem does mitochondrial transfer with IVF fix?

As background, mitochondria are the “powerhouses” (energy factories) for all our cells, so they do important work. Mitochondria exist outside the cell nucleus—they keep their own set of 37 genes distinct from the thousands of genes located in the nuclear control room.

In mitochondrial disease, body parts with high energy demands are affected most: brain, liver, muscles, and heart. Such disorders as Alpers’ disease, Barth syndrome, Leigh’s disease, and Pearson syndrome are all types of mitochondrial disease.

But recent studies have suggested that faulty mitochondria may also be linked to diabetes, Parkinson’s, deafness, poor eyesight, and seizure conditions.

Each year, about 1 in 200 babies is born with defects in their mitochondrial DNA. Many of these will have only mild symptoms, or problems that emerge later in life.

However, about one in 6,500 babies will have a crippling illness that cuts their lives short. Sadly, there are no cures for mitochondrial disorders.

Here in the U.S. some 4,000 babies are affected by this annually. Such genetic error usually causes serious impairment, strikes in early childhood, and is often fatal well before adulthood.

Okay, so what is the controversy about MT?

Because MT passes on genetic changes from one generation to another, any unexpected problems caused by the procedure could impact somebody who is not even born yet. We do not fully understand how mitochondria and the DNA they contain might affect a patient’s characteristics in unknown ways. Accordingly, some experts believe we should wait to learn more about mitochondria and then legalize the technique.

Sometimes MT is said to result in ‘three-parent’ babies…is that accurate?

Not really. As the ethicist Arthur Caplan from NYU wrote recently, even though donor mitochondria come from another woman, it’s hard to see how that alone gives the donor the same status as a parent. Prof. Caplan uses a car example to prove the point: If you give the battery from your car to a friend whose own car battery has died, does that now make you an owner of her car?

Other experts have also reminded MT opponents that existing treatments like sperm donation, egg donation, and embryo donation, surrogacy—even adoption—have all been available for many years and the family unit has survived pretty well.

Will MT be available in the United States?

MT was actually done in America first by two famous IVF doctors, Jacques Cohen and Jamie Grifo, but the FDA quickly shut down all work on the experimental project. Maybe the file can now be reopened. The feasibility of offering MT again in the US is gaining interest. Last week, meetings at the Institute of Medicine on this topic were called at the request of the FDA.

With a new law in place, how will MT work in the UK?

The new British law will state that women donating their mitochondria would stay anonymous and have no rights over any offspring conceived from IVF and mitochondrial transfer. At a genetic level, 100% of the approximately 20,000 genes in the baby’s 23 pairs of chromosomes will still come from the mother and father. The donor supplies only the mitochondria, which accounts for less than 0.2% of the total DNA of each cell.

Will this change in U.K. law make ‘designer’ babies a possibility?

No. Physical traits like eye color, hair color, height etc are all governed by nuclear DNA, not mitochondrial DNA. Remember, MT does not change the nuclear DNA. The ban on altering nuclear DNA remains in place in the UK.

What do we know about the science of how mitochondrial disorders are passed on to babies?

Even though everybody has mitochondria in their cells, babies only receive mitochondria from their mothers. Some women might have abnormal mitochondria and not be aware of it. This could happen when the female has so few faulty mitochondria that she herself has almost no symptoms.

However, her eggs will harbor various amounts of faulty mitochondria so she can still pass on defective mitochondria to any embryo made from her own eggs.

What are ways to prevent mitochondrial disease here currently?

A good reproductive endocrinologist should discuss several treatment options for affected women who want to have children. At present, they can adopt or they can use donor egg IVF (which uses eggs donated from another woman).

In these approaches, there is no increased risk for mitochondrial disease since the children have none of the mother’s own DNA.

For women who insist on having their own ‘genetically related’ children, adoption and egg donor IVF will not really be acceptable. For these patients, they can do IVF using ‘native gametes’ (i.e., their own egg & sperm) and then test the embryos for mitochondrial mutations using a technique called PGS (pre-implantation screening). This is what my unit has the most experience with, and it has the added advantage of reducing the risk of miscarriage—since genetic error in embryos is a leading cause of IVF failure.

For additional questions about infertility or mitochondrial conditions, contact Dr. Sills at drsills@cox.net. Click here For further reading.


LSO version ESS DUBLIN sepiaEric Scott Sills is a native of east Tennessee. He is an internationally recognized physician, lecturer, administrator, and editor with a background in reproductive endocrinology, biotechnology, and medical regulation. Dr Sills received his undergraduate degree from Vanderbilt University and holds a PhD (molecular biology) from London’s University of Westminster. His MD was awarded by the University Of Tennessee in 1992. Dr Sills’ clinical training in gynecology was obtained at NYU Downtown Hospital. He completed his sub-specialty fellowship in reproductive endocrinology & infertility at New York Presbyterian Hospital-Cornell Medical Center, working under fertility pioneers Gianpiero Palermo and Zev Rosenwaks. Dr Sills is Board Certified by the American Board of Obstetrics & Gynecology, and is a Fellow of the American College Of Obstetricians & Gynecologists, American College Of Surgeons, Royal College Of Physicians (Ireland), and Society Of Biology (UK). He is registered and/or licensed for medicine in California, New York, and the United Kingdom.

Before returning to the United States, Dr Sills was Director for Research Programs at one of Europe’s most successful reproductive biology units, Sims Institute (2008-2011). In Dublin, he led the Institute’s subspecialty academic output to a level exceeding all five Irish medical schools combined. Having directed investigative teams in Europe and the United States, Dr. Sills has discovered three human gene mutations since 2001.

In the arena Of E.U. public health policy, Dr. Sills’ 2009 analysis of the status of non-transferred embryos correctly anticipated a Supreme Court decision with major implications for clinical fertility practice in Ireland. Dr. Sills was also the first to publish successful outcomes from surrogacy and IVF in Ireland (2008), the first to describe Irish births from dual anonymous gamete donation (2010), the first to report IVF births in premature ovarian failure using oocytes donated from a twin sister (2010), and the first to report Irish deliveries after frozen surgically-retrieved sperm (2011). Previously, Dr Sills chaired a research initiative among Arab and Israeli fertility centres across 13 Countries—the first multinational collaboration of its kind in the Middle East (2007). The following year he accepted a Board of Regents nomination to the New York State Board for Medicine, one of the busiest state medical licensure bodies in the United States.

Dr Sills is among a select group of IVF experts with works published in each of the world’s top four medical journals—The Lancet, JAMA, The New England Journal of Medicine, and BMJ. Having authored more than 100 peer-reviewed publications, Dr Sills has refereed manuscripts for numerous scholarly journals of global scope.