3-person IVF and Infertility: What Kind of Slippery Slope is This?

Reacting to two breaking news stories about 3-person in vitro fertilization (IVF) in less than two weeks, Paul Knoepfler, professor and stem cell researcher at UC Davis, recently tweeted:

Right before our eyes real sllippery slope on 3-person IVF? Doc using pronuclear transfer to "treat infertility" https://t.co/0ekDpCV16M

— Paul Knoepfler (@pknoepfler) October 11, 2016

On September, 27, 2016, news broke that NYC-based fertility doctor John Zhang and his team had delivered a baby the previous April that they created using a controversial mitochondrial manipulation technique, also known as 3-person IVF, that results in an embryo with DNA from three people. The baby was born in Mexico in order to avoid US regulation, as Zhang explicitly admitted. Despite the multiple violations of medical ethics involved, the media craze that followed largely heroized Zhang, depicting him as a doctor altruistically seeking to prevent the transmission of mitochondrial disease.

The prevention of mitochondrial disease has been the core justification cited all along for permitting these controversial, high-risk techniques that represent a form of inheritable genetic engineering, also known as human germline modification.

On October 10, news broke that Valery Zukin, a fertility doctor at the Nadiya Clinic in Kiev, Ukraine, had used 3-person IVF not to lower the risk of mitochondrial disease, but as a treatment for infertility.

The media in this case was surprisingly quiet, perhaps because Zukin had supplied no published evidence of his claim, although the BBC did publish a somewhat critical piece entitled “3 person baby ‘race’ dangerous.”

On October 19 Nature News reported a claim that yet another baby conceived using some kind of mitochondrial manipulation technique has been born, this time in China. A paper is said to be under review at another journal.

What kind of slippery slope is this? It’s been clear from the beginning of the controversy surrounding 3-person IVF that it would be difficult to control its commercial uses beyond disease prevention. This is especially true when it comes to introducing  these genetic manipulation techniques into the multi-billion-dollar global fertility industry, a venture that could be extremely lucrative for all involved. 

To what extent has anticipation of this possibility been part of the story from the start? While we can’t know for sure, here are several points that might help make this connection:

• In the late 1990s and early 2000s, a precursor to 3-person IVF known as ooplasmic transfer was developed for age-related infertility and put into use without clinical trials. In 2001, the U.S. FDA stopped the procedure after at least two dozen babies had been born, citing lack of evidence of safety and efficacy. No such evidence was produced at the time. On October 24, 2016, Reproductive BioMedicine Online published the first follow-up study of these children. Despite the inconclusive nature of the study, which the authors admit is based on limited, subjective survey data from only 75% of the children’s parents, and with zero follow-up testing of the children themselves, they conclude that the procedure has not produced any long-term effects.

• In February 2012, Shoukhrat Mitalipov, professor at the Oregon Health and Science University, filed a patent for maternal spindle transfer (MST) as a technique for providing prenatal treatment for mitochondrial disease in humans. In November 2012, he founded MitoGenome Therapeutics to reportedly commercialize his work.

• On February 25 and 26, 2014, the FDA held a public meeting to discuss using 3-person IVF techniques for “the prevention of  transmission of mitochondrial disease or treatment of infertility.” Although the FDA does not make information from its applications public, this strongly suggests that someone applied for permission to conduct clinical trials towards both of these aims.

• In January 2015, Mitalipov and MitoGenome Therapeutics teamed up with Chinese stem cell banking company Boyalife and the Korean company H-Bion, led by disgraced cloning researcher turned dog-clone entrepreneur Hwang Woo-suk, to start a lab in China. In a Nature News article, Mitalipov described the collaboration as a way to move his 3-person IVF research forward, stating, “Fertility and mitochondrial disease are a big clinical opportunity.”

• In February 2015, Mitalipov confirmed that he had requested permission from the FDA to conduct two clinical trials using 3-person IVF techniques in the United States, the first to treat mitochondrial disease and the second to treat age-related infertility.

• In February 2016, John Zhang of New York City-based New Hope Fertility Center released a video in which he lauded the technique’s usefulness as a fertility treatment, only briefly mentioning its potential use in the prevention of mitochondrial disease (see video at 3:05). This video was released only a few months before Zhang and his team delivered the aforementioned baby in Mexico for a Jordanian couple at risk of transmitting Leigh Syndrome.

• In September 2016, Norbert Gleicher, a fertility specialist at the Center for Human Reproduction in New York City, says he sought a meeting with the FDA to discuss 3-person IVF for US patients, including as a treatment for infertility.

CGS and others have criticized moving forward with 3-person IVF, even to prevent the transmission of mitochondrial disease, because of the unknown health consequences for resulting children and future generations, because safer options for forming families are already available, and because permitting mitochondrial manipulation in humans could open the door to other forms of human inheritable genetic modification. Throughout the policy considerations in the US and the UK about these techniques, the notion that they would be taken up as a treatment for infertility has been downplayed as unlikely or even fanciful. Yet here we are. When fame and fortune come into play, the slide can become very slippery indeed.

Previously on Biopolitical Times:

• 3-Person IVF Breaking News: Where Are the Advocates for the Public Interest?
• Dangers of an Unscientific Policy Process: Why the UK's legalization of "three-person babies" should not be the model for CRISPR
• The Case Against Public Investment in Reproductive Genetic Modification
• Scientists Warn Against "3-Parent IVF" Experiment
• Eight Misconceptions about “Three-Parent Babies”
• Key Questions About the Social and Ethical Implications of Nuclear Genome Transfer or “3-Person IVF” Techniques
• Litany of Unknowns Surface at FDA Meeting on Germline Mitochondrial Techniques

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