This Controversial Doctor Wants To Use ‘Three-Parent’ Embryos To Treat Infertility

This Controversial Doctor Wants To Use ‘Three-Parent’ Embryos To Treat Infertility

Last spring, John Zhang made headlines after his fertility clinic announced that for the first time a baby had been born using a new technique requiring three genetic parents. The baby’s mother carried the genes for a fatal nervous system disorder called Leigh syndrome, but Zhang had been able to keep the disease from being inherited by her son by swapping in a donor’s mitochondrial DNA, the teeny bit of DNA where Leigh syndrome is housed. Since the technique is illegal in the US, the baby had been born in Mexico, where, as Zhang explained in a comment he might live to regret, “there are no rules.”

Image: Shutterstoc

Now Zhang is taking his so-called “three-parent baby” technique commercial, and targeting a different market altogether: The booming, multi-billion dollar fertility market. Instead of focusing on women who risk passing on mitochondrial diseases to their offspring, he hopes to use the technique as a cure for infertility.

As the website for the company, Darwin Life, puts it, it’s a “revolutionary technology designed to reverse the effects of age on human oocytes and repair certain cellular defects.”

The company is already in the process of screening women between the ages of 42 to 47 who have undergone multiple failed IVF procedures to be the company’s potential first clients. The procedure will cost as much as $US100,000 ($131,176).

But Zhang has many critics who argue that his technique is not well-studied enough to begin with, let alone ready to be sold to women for a six-figure sum for a condition it was not originally pioneered to treat.

“There’s no decent evidence that mitochondrial transfer will help age-related infertility. We’re in a mitochondrial fad right now where it is being blamed, or credited, with everything,” Stanford bioethicist Hank Greely told Gizmodo. “It offends me deeply when someone charges three arms and four legs for a procedure that has next to no evidence for efficacy and very little evidence for safety.”

The idea of using genetic material from a donor to help fix problematic egg cells isn’t exactly new. In the 1990s several babies were born with genetic material from three “parents” using a different technique, but some of them eventually developed genetic disorders and the technology was never approved. Then, as in now, the primary purpose was solving the problem of mitochondrial disease. Mitochondrial DNA is made up of just 37 genes and generally speaking can only be passed on to a child by its mother. Replace that teeny slice of code through IVF, the thinking goes, and you can save a child from a deadly disorder they will otherwise definitely inherit.

Recent developments, such as Zhang’s technique, have again garnered interest into research using donor mitochondrial DNA to create an embryo. But so far, it has only been legally approved in the UK, under very strict guidelines. In March, the UK issued the first licence for a clinic to perform the procedure. Zhang’s first procedure, meanwhile, exploited legal grey areas, designing an embryo in the US and inserting it into the mother in Mexico. For future procedures, the eggs will be made in the US, and implanted somewhere outside the country.

Many have criticised the US for its obstruction of the technology, arguing that it could help eliminate rare diseases. Still, Zhang’s methodology has come under fire. In April, at the urging of fellow scientists, Zhang published a report describing the technique and his first success in greater detail. In publishing the report, the the journal Reproductive BioMedicine Online ran a note alongside it citing “weaknesses and limitations in a number of areas”, including questions of the full risks of the procedure and whether the child would be healthy long term. The embryo implanted, for example, still had about a five per cent load of the defective DNA, and the long-term effects of that DNA in the child are still unclear. (New Hope Fertility Clinic said the baby, which is now over a year old, is still doing just fine.)

“The best way to see what will happen in the future is to examine what has transpired in the past,” Zhang told Gizmodo. “We look at the first heart transplant in South Africa, and people thought it was an abomination, that doctors were putting one person’s soul into another body. Now this procedure is commonplace and has saved millions of people. IVF was, in 1978, feared and rejected by the general population. That, too, is now commonplace.”

But the bigger fear, perhaps, is that Zhang’s company will simply be taking advantage of emotionally vulnerable patients with a still unproven cure.

“We really don’t know what is going on in this technique, or that the baby is going to grow up normally, or, most importantly whether this is even going to work,” UCSF molecular biologist Patrick O’Farrell told Gizmodo. “In my mind, the most disturbing thing about all of this is there are hopeful parents who want to have kids and there is a fertility industry that takes advantage of them. It’s free enterprise gone crazy.”

Zhang’s work cites research that suggests bad mitochondria may be the reason older women have a tougher time producing viable eggs.

“Globally we have seen success from our own work and our colleagues in mouse, cow and rabbit models,” Zhang said. “That research shows that nuclear transfer can restore meiotic errors that are age-related.”

But the true cause of age-related infertility is still an unknown. In a paper Zhang published last year about a 30-year-old woman who had failed IVF twice and became pregnant via his technique, he argues it was a success even though she did not make it to term.

Both Greely and O’Farrell said that only in the cases where women suffer from diseases that could be passed on to their children are the risks of the procedure justifiable.

“Beyond that, even careful clinical trials aren’t justified, let alone uncontrolled clinical use,” Greely said. “I hope Mexico (or wherever else he goes) shuts him down.”

In January, a child was born to a previously infertile couple in Ukraine using the genetic material from three parents faced similar blowback.

Zhang refutes this point. After all, IVF is already a taxing, uncertain procedure that many women endure multiple times, costing into the tens of thousands of dollars each time. The majority of those fail to produce a successful pregnancy. And all those failed IVF contribute to a global fertility services market that is expected to exceed $US21 billion ($27.6 billion) by 2020, according to market research firm Technavio’s 2016 report.

“I don’t think that we should discriminate between who benefits, a patient with infertility versus a patient who has an inheritable genetic disease,” he said. “Their desires to have a healthy, happy family are the same.”

Eventually, he says, he sees the technique being used for everything from cancer treatments, to reversing ageing and eventually, yes, creating designer babies free of “undesirable” genes.

“It is a moral imperative to help people if it is our power,” he said.

[MIT Technology Review]