3-parent IVF: Why isn't it available in the United States?

This week, the House of Lords voted 280 to 48 to approve ‘three-person in vitro fertilization’ (IVF), also known as mitochondrial replacement therapy, which combines the DNA from three adults. The US Food and Drug Administration met last year to deliberate over sanctioning the assisted reproductive technology but has yet to approve the procedure.

Families with mitochondrial diseases are few, but the impacts are often devastating. Some of the most commonly recognized mitochondrial disorders are neurological conditions, heart problems and muscular dystrophy. Women who carry the DNA mutation can suffer multiple miscarriages, and a child with the same genetic fault may suffer greatly. Many do not survive beyond early childhood.

So why isn’t three-person IVF available in the US?

Mitochondrial replacement therapy was first performed successfully in 1996, in the United States, but there remains vocal concern (and confusion) as to whether mitochondrial replacement IVF might lead to widespread genetic engineering. But it’s not clear how or why critics think this technology could lead to so-called ‘designer babies’.

Mitochondrial replacement IVF does one simple thing: replaced a single strand of the mother’s DNA with third-party mitochondria from a healthy egg donor, as mitochondrial DNA is passed down from the maternal line. Traits such as hair and eye colour, on the other hand, are controlled by DNA in the cell nucleus. Rather than ignite a eugenics epidemic, mitochondrial IVF could save thousands of lives and prevent serious suffering that comes in the form of muscular dystrophy, blindness and heart conditions.

According to the United Mitochondrial Disease Foundation in Pittsburgh, between 1,000 and 4,000 children are born with mitochondrial disorders in the US each year. The number of people affected by mitochondrial mutations is difficult to calculate, since resulting conditions are varied and have divergent symptoms. So-called ‘three-person IVF’ could alleviate the difficult decision for women carrying a mutation who are afraid to have their own biological children, either to prevent the children’s suffering or to avoid passing on the genetic defect.

In 2001, the FDA effectively banned an assisted reproduction procedure similar to mitochondrial replacement IVF, cytoplasmic transfer, in which donor egg cytoplasm is injected into an egg with mutated mitochondria. The agency cited concerns about chromosomal abnormalities with three people’s DNA in one embryo and a need for oversight when transferring genetic material outside of egg and sperm fertilization.

A recent FDA report explains that the agency was previously concerned about the inadvertent transfer of cellular constituents, such as chromosomes, to the offspring. They were concerned about the possibility of increasing the likelihood of children born with significant birth defects in certain cases.

While there are two research groups currently working on the technology in the United States, FDA spokesperson Tara Goodin notes that currently, “The FDA has not made any decision regarding clinical trials of mitochondrial manipulation technology”. The agency is unable to confirm or comment on any current or pending investigation into new drug applications.

The National Institute of Medicine is also currently running a 19-month study that began in September, investigating the ethical and social policy concerns related to novel techniques that could prevent maternal transmission of mitochondrial DNA.

Cytoplasmic transfer has been tested and was practiced until the FDA put a stop to it in 2001. It’s the same basic thing, and researching mitochondria or replacement therapy isn’t illegal or secret. There are just limitations on this one particular practice.

The phrase ‘three-person baby’ is a bit of a misnomer. Rather, mitochondrial replacement therapy, which combines DNA from three adults, will be used for in-vitro fertilization only in women who carry the mitochondrial mutation. A single strand of the mother’s DNA would be replaced with third-party mitochondria from a healthy egg donor, as mitochondrial DNA is passed down from the maternal line. The baby would otherwise be 99.8% genetically linked to its two birth parents.

The first attempt at mitochondrial replacement IVF could happen as early as this autumn, when clinics can apply for licences to use the technique, with the resulting baby born as early as 2016.

Nita Farahany, director of Duke University’s interdisciplinary Science and Society initiative and a member of President Barack Obama’s Presidential Commission for the Study of Bioethical Issues, has come out in favor of the technology. In a 2014 piece for the Washington Post, she detailed why - despite a certain amount of hysteria in the media - this technology would not lead to a sudden Gattaca-style epidemic of ‘designer babies’.

Farahany explained that the donor of the additional mitochondria is not really a parent, considering that “99.9% of [the resulting egg’s] coding DNA from the intending mother”. She also pointed out that the “mitochondria give energy but not the coding traits that make us who we are”.

In a debate about whether to prohibit genetically altered babies — that is, any genetic modification, including life-saving alterations like mitochondrial replacement IVF — Farahany argued against such a ban.

Lehigh University’s Dena Davis, a bioethics professor specializing in religion and law, notes that debates over mitochondrial replacement are often the result of confusion.

“This is only an ethical problem if one has the misguided idea that babies and children are created by only two parents,” Davis says. “But, babies created through the use of a gestational surrogate mother already have three parents, because nine months’ pregnancy surely leaves its mark on an infant. And babies who are wet nursed, which used to be a common practice, received important nurturing and nutrients from a third parent.”

IVF, an assistive technology now widespread and commonplace, was similarly controversial when it was introduced in the 1970s. The Vatican, for example, opposed it on the grounds that it also disapproves of birth control and other fertility interventions, as outlined in Pope Paul VI’s Humanae Vitae. IVF could also result in the disposal of embryos, which is disallowed by the Church.

As was the case with mitochondrial replacement IVF, the UK gave birth to traditional IVF well before the US embraced the technology. The first so-called test-tube baby, Louise Brown, was born in England in 1978. Sir Robert Edwards, the physician and reproductive medicine specialist who pioneered IVF in Britain, won the Nobel Prize in Physiology and Medicine in 2010.

Still, some critics of the procedure believe this sort of technology is a step too far. Travis Rieder, a Hecht-Levi Fellow at Johns Hopkins Berman Institute of Bioethics, suggests that affected families should just adopt. But much like assistive reproductive technologies, there are also high costs of both time and money associated with even the most seamless adoption process.

Appearing on the Brian Lehrer radio show several weeks ago, Dr. Farahany notes that IVF and other reproductive technologies are widely available in the UK, whereas in US, the access to this technology would not be available to people across socioeconomic class due to the high cost and what will probably be inconsistent coverage by insurance providers, at least at first.

Even though the technology would help eradicate incurable, devastating genetic conditions, there’s no indication that ‘three-person babies’ will be approved and legalized in the US any time soon. At least, not until the FDA is satisfied that any potential risk - known or unknown - is worth the trade-off.

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