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The Babies at the Fringes of Fertility Tech

Beyond the reach of U.S. law, doctors are changing the way babies are made

Illustrations by Maria Chimishkyan

IIt’s 10:30 p.m. in Kyiv, Ukraine, and Dr. Valery Zukin is at the hospital with a patient who needs emergency surgery. The patient is 31 weeks pregnant and has intestinal obstruction — a rare complication that’s potentially fatal in pregnant women. Zukin says the situation is under control, but he’s exhausted, and the stakes are high.

Earlier that day, Zukin had been at a fertility conference in Barcelona, where his groundbreaking fertility treatments made him and his colleagues the stars of the show. Now he’s sitting in a pale-yellow room at the Leleka Maternity Hospital, where he is CEO. Zukin is conferring with a team of doctors about how to save the young woman’s life — and her baby’s.

Zukin is accustomed to this kind of emergency. He’s one of the first embryologists in Ukraine, and as a leader in assisted reproductive technology, he’s part of a small cadre of doctors specializing in a revolutionary fertility technology known as mitochondrial replacement techniques (MRT). It’s promise: to make healthy babies possible for couples who are infertile or carry debilitating genetic disorders.

Though tonight’s patient got pregnant the old-fashioned way, Zukin and his colleagues are breaking new ground in radical fertility tech what seems like every other month. No stranger to controversy, Dr. John Zhang, Zukin’s partner at the aptly named clinic Darwin Life-Nadiya, is the first-known scientist to help a woman give birth to a baby who has three genetic parents using one of these techniques. In the United States, where Zhang works, the technique is regulated by the Food and Drug Administration (FDA) and is illegal — so Zhang went to Mexico.

Using MRT, Zhang created the embryo in New York and then flew back to Mexico with the fertilized egg and implanted it in a patient there. The announcement of the baby’s birth in 2016 rattled the world, but the blowback hasn’t deterred them. Zukin and Zhang are already working on the next crop of so-called three-parent babies — they’re just doing it beyond the short arm of U.S. law, in places like Ukraine and Mexico.

Forty years after the birth of Louise Brown, the first “test-tube baby,” we are living in a golden age of fertility tech.

To date, at least five babies who have the DNA of three people have been born using MRT (and at least one is a girl, which means that her genome changes will be heritable). Experts don’t know if there other MRT babies are out there, but with ongoing regulated clinical trials of the techniques in the UK, there may soon be more.

Forty years after the birth of Louise Brown, the first “test-tube baby,” we are living in a golden age of fertility tech. Even its detractors agree that MRT is an astonishing development in medical science — human genetic engineering in action. And it’s just one among a rash of new fertility techniques that stand to fundamentally change how humans procreate: live-donor uterus transplants, preimplantation genetic testing and selection, egg freezing, hyperprecise in vitro fertilization (IVF), CRISPR genome editing, in vitro gametogenesis (which uses reverse-engineered stem cells to make eggs and sperm from men), and the list goes on.

The U.S. government has made it clear it has no interest in approving MRT anytime soon, stalling the industry stateside, but the international fertility industry is booming. Medical tourism is a global market valued at $68 billion, and experts say a growing portion of that business comes from people traveling overseas to get frontier fertility treatments that are illegal at their home base. There’s no data on how many women from the United States travel abroad for fertility treatments, but experts think medical tourism already explains why some countries, such as Denmark, Spain, and Israel, have double the rate of babies born from reproductive tech than the United States.

“Sometimes it’s the people with an unusual vision who change the world,” Zukin says.

MRT is controversial, no doubt. It’s unregulated in most parts of the world, and many contend that it’s unethical. But the babies are coming anyway.

EEmbryo research has been progressing swiftly since IVF became a household concept 20 years ago. Technology like preimplantation genetic diagnosis (PGD) has allowed doctors to make sure the embryos that are implanted after IVF are of high quality, which has been shown in limited studies to improve the outcome of a pregnancy.

“If you look at the success of fertility therapies in 2018 compared to 10 years ago and compared to 10 years prior to that, the success has been exponential,” says David Ryley, a pioneering fertility specialist in Boston, Massachusetts. According to some research, this technique has raised the IVF live birth rate to nearly 70 percent, compared to IVF without PGD.

Ryley’s clinic, Boston IVF, has been a leading fertility center for more than 30 years. The clinic claims to have been the first in New England to help a lesbian couple get pregnant; in 1998, it was the first clinic to help a gay male couple have a baby via surrogate. The clinic also achieved a number of other firsts, including the first donor egg pregnancy in New England and the first birth in Massachusetts to result from a frozen egg back in 2006.

“When I was in residency back in the ’80s, you’d be lucky if you had a live birth rate of 10 percent,” Ryley says. As for the more out-there techniques underway, he adds, “I don’t mean to sound like a typical American, but in my opinion, more well-controlled, well-regulated research needs to be done. But is it exciting, especially for these people who suffer from these terrible disorders? Absolutely it’s exciting.”

Still, barriers exist. Another form of mitochondrial replacement, known as cytoplasmic transfer (CT), was banned by the FDA in 2001 because of a worry that it may lead to chromosomal abnormalities, which could result in birth defects.

For infertile couples or women who have endured multiple miscarriages, MRT represents another chance at having a child to whom they’re genetically related.

There are other reasons frontier fertility research doesn’t happen much stateside. The first is known as the Dickey-Wicker Amendment, an appropriations rider that bans federal funding for research that involves destroying embryos (which happens in nearly all embryo-related research). The amendment is included in the annual federal budget and has been renewed every year since 1996. Bioconservatives, pro-lifers, and many prominent American bioethicists continue to stand by the Dickey-Wicker Amendment.

In 2016, another congressional rider was added to the budget that prohibits the FDA from even accepting research applications for embryo research that would include editing the human germline, a move Stanford bioethicist Hank Greely called “dumb” at the time. It is similarly illegal to create a genetically modified embryo, which the FDA considers MRT embryos to be. Meanwhile, public opinion on the topic is shifting, with the majority of U.S. adults saying they think gene editing that treats serious congenital diseases is appropriate.

The UK has seen its own political brouhaha around MRT, but the results have been different. In 2015, Parliament gave the green light to begin the process of setting up a regulatory framework for clinics to provide MRT for couples with mitochondrial disease, a model that has been adopted in Australia and Singapore. As a result, legal, regulated three-person British babies are expected to be born anytime now.

MMRT and techniques like it are the result of progress in other areas of fertility research — namely, what goes wrong, and when, in the development of a fetus. Mitochondrial diseases, which can vary in severity, are among the most lethal genetic diseases, because they are rare and there are no cures. They are also passed along the matrilineal line, through mitochondrial DNA. In the United States, fewer than 4,000 babies are born every year with mitochondrial diseases; the other fetuses simply don’t make it that far.

For infertile couples or women who have endured multiple miscarriages, MRT represents another chance at having a child to whom they’re genetically related.

“A deputy [in the government] asked me if anyone has confirmed MRT is safe for the baby. I said, ‘Nobody has confirmed it.’”

There are at least three ways to split an ovum, or human egg, to separate the mitochondria from the nucleus. Zhang used maternal spindle transfer for the baby born in Mexico, while Zukin specializes in something called pronuclear transfer. Both techniques are legal in the UK for experimental treatments.

Zukin’s particular arrangement in Ukraine is cloudier. There are no explicit laws permitting the procedures, so he’s operating under a kind of gentlemen’s agreement with the Ukrainian government rather than an official regulatory pass. “We received special permission for clinical trials,” Zukin says. “A deputy [in the government] asked me if anyone has confirmed MRT is safe for the baby. I said, ‘Nobody has confirmed it.’”

Zukin says the data from his clinical experiments will provide the basis for the parliamentary decision on whether it will officially sanction or prohibit MRT. “If we have any confirmation that [MRT] is risky for babies’ health, it will be prohibited. If it is safe for the babies, and the babies are healthy, we will allow it,” he says.

Zukin says he has assisted in the birth of four healthy babies, is working with three pregnant women, and is about to start working with four more. His patients declined to be interviewed for this article. Zukin’s clinic is private. He charges up to the U.S. equivalent of $15,000 per cycle.

Zukin’s work has fertility specialists and ethicists around the world anxious — but excited.

Sarah Chan, a prominent bioethicist at University of Edinburgh who has published several papers on MRT, says that although Zukin’s experiments raise a lot of red flags, “If we never did anything, we’d never do anything.”

InIn the international fertility industry, the private market rules, with clinics like Zukin’s operating in regulatory gray areas. While the UK, Singapore, and Australia have announced plans to begin regulating the procedures soon, the dearth of options still means that nearly everyone who wants to try MRT is left with one choice: to shell out for plane tickets to foreign countries and pay whatever those doctors charge for a chance at a baby.

This, of course, raises the thorny question of who gets to access these technologies in the first place.

Zukin claims patients from Brazil, Israel, Sweden, China, and the United States — but he refuses to treat gay people out of his personal beliefs. (A spokesperson for the Darwin Life-Nadiya Clinic said that Zukin’s refusal to treat gay people does not reflect the company’s policies. A rep for Zhang says he believes that everyone who wants to should be able to have a baby.)

The Nuffield Council for Bioethics, the UK’s unofficial national bioethics body, wrote a report on MRT in 2014 that suggested that lesbian and other same-sex couples with female reproductive organs could use MRT to create genetically related offspring in the future.

“I do think that going forward, who this technology is provided to, and who decides this, is a concern,” says Edinburgh bioethicist Chan. “In the UK, all cases would be regulated through the national regulators. It wouldn’t be up to the whims of a particular clinician to say, ‘Well, I’m going to treat you, but I’m not going to treat you.’ If we are concerned about equitable access without discrimination to developing health care technologies, then we do have a concern about who gets their hands on them and who is enabled to do them,” Chan says.

Experts like Chan, Ryley, and many others in the field, myself included, believe that in order for these technologies to be equitably distributed, any couple, regardless of their sexual orientation, health status, or income, must be able to access them safely.

“I am sure that sooner or later, the FDA will approve of this treatment, after we have confirmation of the healthy status of the babies,” Zukin says.

In the meantime, two facts remain: Regulators aren’t doing a good job of keeping up with the science, and people who want babies will do nearly anything to get them.

Update: An earlier version of this piece incorrectly identified where the first MRT embryo was created. It was created in New York, and implanted in Mexico. This piece has also been updated to reflect Zhang’s position on treating gay patients.

Reporter. Bioethicist. Publishing on the intersection of ethics and policy with emerging science and tech. Sorry for the recipes if you’re here for news.

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