This fertility doctor is pushing the boundaries of human reproduction, with little regulation

This fertility doctor is pushing the boundaries of human reproduction, with little regulation

By Ariana Eunjung Cha May 14 at 7:00 AM

NEW YORK — When future historians look back on the 21st century, one of the most iconic photos may be of a smiling, dark-haired man in blue scrubs protectively holding a newborn — the world’s first commercially produced “three-parent” baby.

This is John Zhang, the Chinese-born, British-educated founder and medical director of a Manhattan fertility center that is blowing up the way humans reproduce.

In 2009, Zhang helped a 49-year-old patient become the world’s oldest known woman to carry her own child. In the not-too-distant future, he says, 60-year-old women will be able to do the same.

In 2015, Zhang stunned his scientific peers by transferring a genetically “abnormal” embryo to the womb of a woman who had run out of other options. Abnormal embryos — which appear to have the wrong number of chromosomes — are almost universally considered nonviable and discarded by other fertility doctors. The woman gave birth to a healthy baby girl, prompting clinics around the world to reevaluate their policies.

But it was the three-parent baby that really put Zhang on the map. Working with a Jordanian couple who had lost six babies — two in infancy, four in miscarriages — to Leigh syndrome, a heritable neurological disorder, Zhang put to practical use a procedure that others had dared to try only on animals.

He extracted the woman’s nuclear DNA, which carries the biological material responsible for such things as physical appearance and other major traits, but not the ones that lead to Leigh disease. Then he inserted the DNA into a healthy donor egg and fertilized it with sperm from the woman’s husband. The child, a boy born in 2016, appears to be free from the disease.

“If there is a gene which causes a problem, it would be washed out through natural evolution. Eventually, these kind of babies are not going to be born. That is how nature selects,” Zhang said in a recent interview. “But if we can alter the gene, why can’t we alter it?”

For some, the “three-parent baby” was a joyous miracle of 21st-century medicine. In a feature about 10 people who matter in science, the journal Nature dubbed Zhang a “fertility rebel.” For others — including U.S. regulators — the baby’s birth marked an unnerving step down the slippery slope of tinkering with human life in ways that are not fully understood.

In the countless news reports and opinion pieces that followed, writers made comparisons to the dystopian worlds of “Gattaca” — a movie in which babies conceived the natural way are believed to be inferior to those who are genetically manipulated in a lab for intellect and athletic ability — and “Orphan Black” — a TV show that raises the specter of genetically designed clones.

It didn’t help that Zhang’s company soon began to market the technology through his two companies, New Hope Fertility Clinic and Darwin Life, a biotech start-up. They offered to take DNA from older women and put it into donor eggs from younger women so that women of almost any age could bear their genetic children. The idea caused a sensation at a time when many women are delaying childbirth and then having trouble bearing children after the age of 40.

The proposed service landed him in the crosshairs of the Food and Drug Administration, which for decades has had a mostly hands-off policy when it comes to the fertility industry. Last August, the FDA ordered Zhang to stop marketing the technology, effectively shutting down the program.

In a warning letter, FDA officials said Congress had effectively prohibited the genetic editing of heritable traits in human embryos in 2015 and that Zhang did not have approval to proceed with his research. Zhang had created the three-parent embryo in the United States and transferred it to the mother’s uterus in Mexico. But, the FDA warned, “such human subject research cannot legally be performed in the United States. Nor is exportation permitted.”

In response, New Hope and Darwin Life overhauled their marketing materials and pledged not to offer the service. An FDA spokeswoman confirmed that the matter had been resolved. Geoffrey Hawes, a spokesman for Zhang’s companies, said that they had “worked closely with and will continue to work within the FDA guidelines.”

In the meantime, he said, use of the procedure has been allowed in Britain, Ukraine and China. And the companies are encouraging other researchers to seek similar approvals in other nations “to allow further research in this field.”

Zhang himself declined to discuss regulatory matters. But, he said, “my personal opinion is very simple: Any technology will eventually benefit mankind and should be allowed. Look at history: People were against antibiotics, general anesthesia, vaccines” — scientific developments that wound up saving millions of lives.

While that may be true, regulators and ethicists have nonetheless been unsettled by what seemed a race by Zhang to profit from a procedure with profound moral and religious implications.

Marcy Darnovsky, executive director of the Center for Genetics and Society, rolled her eyes at the characterization of Zhang as a sort of “heroic rebel” who helped a couple who were otherwise without hope. New Scientist, which was the first to publish a story on the birth of the three-parent child in September 2016, quoted Zhang’s scientific peers calling the achievement “great news,” “exciting” and “revolutionary.”

“Come on. He clearly saw himself as in a position to begin a commercial enterprise — perhaps a very lucrative one at that — for an indication for which absolutely no one is saying it’s okay,” Darnovsky said.

“There is a fairly quick move from development to marketing,” added Leigh Turner, a bioethicist at the University of Minnesota, “and that is a cause for concern.”

The parents Zhang has helped have a different view. Monica Halem, who is in her late 40s, suffered six miscarriages before giving birth to a healthy baby after Zhang implanted an “abnormal” embryo in her womb. Without scientists such as Zhang, she said, progress in the field would have stalled long ago.

“He’s way out there in terms of research,” Halem said. “He’s not afraid to try certain things, and that’s what we need in fertility right now.”

Zhang doesn’t like to talk much about himself or his background. He’ll say he was born the youngest of three children in the lakeside city of Hangzhou in China, the home of Alibaba founder Jack Ma. Zhang’s father was a cardiologist, his mother a reproductive health specialist. Both his sisters are doctors, too. The rest of what he’ll reveal is what’s already on his résumé: He went to the Zhejiang University School of Medicine in China, got his PhD at the University of Cambridge, and did his obstetrics and gynecology residency at the New York University School of Medicine.

Zhang’s PhD adviser at Cambridge, W.R. “Twink” Allen, describes how “he first came to us in strange and funny circumstances.”

It was 1983 and Allen was a professor with the university’s prestigious research group working on fertility in various species of large mammals — sheep, cattle, horses. Allen ran the equine unit. Zhang had no experience with (or interest in) the animals. But Cambridge at the time was a lively place for someone interested in the field, and it is where many of the modern breeding techniques — from cloning to splitting embryos to make twins — would eventually be developed.

Zhang, who had recently left China, literally walked into Allen’s office off the street, responding to an ad for someone to help with research on the horses. Allen recalled that the young man, small and slim, was a “cheeky chap” who had none of the qualifications for the position.

But, Allen recalls, “he was just full of ideas. It bubbled out of him.”

Zhang not only got the job, he also got his doctorate in a speedy three years and was off to America. He started at Virginia’s busy Dominion Fertility and then moved to New York to found New Hope Fertility, where he now serves as chief executive and a practicing physician.

The clinic has grown into one of the most recognizable names in the industry, attracting celebrities, royalty and wealthy people from China, Russia and other parts of the globe who come to Zhang specifically for his willingness to push boundaries.

At 55, Zhang said he has become increasingly philosophical and spiritual. The father of three children, he joked that he now works only six days a week. He also does charitable work, using reproductive technologies to save endangered species including the king rhino and the cheetah.

On a recent weekday during a break between patients, he spoke rapidly about his vision for the future, including his hope that his biotech start-up, Darwin Life, a spinoff of his clinical practice, will bring the breakthroughs of the fertility industry to other arenas.

Maybe an “Uber-like” service could bring fertility kits to women at the appropriate time of each month, he said. Or maybe a woman’s fertility could be extended so that humans could colonize Mars, and the universe beyond, as billionaire Elon Musk imagines. Until humans can travel faster than light, Zhang calculates, passengers on spaceships would have to remain fertile into their 80s to make the trip, set up a colony and then procreate.

He believes the key to many of the world’s great unsolved problems — including hunger and aging — lies in nuclear DNA transfer, the technique he used with the three-parent baby, and gene editing, which permits the modification of certain heritable traits, theoretically in anyone of any age.

Take food, for example. “What would you say if I told you this technique could make artificial meat? This is just an example. You could use nuclear transfer of special types of cells to get a piece of a cow instead of raising a whole cow and then getting a filet mignon,” he said.

Zhang predicted that the ability to edit genes and transfer DNA will transform the world as quickly and dramatically as the tech revolution, that shift from computers that occupied entire rooms to smartphones that fit in everyone’s hip pocket. He noted that, initially, one smartphone GPS service erroneously depicted the Brooklyn Bridge with a sharp, roller-coaster-like plunge.

“In the beginning, if mass technology misleads us, it is totally normal,” he said. “That doesn’t mean this technology is useless. You just have to know how to use it.”

When asked about technological glitches in the making of human babies — when a mistake could mean the difference between life and death or a good life and one of suffering — he became thoughtful.

“You have to discuss with the patient what are the risks, what is the worst things that could happen.” He looked sad as he described the darkest scenarios. “The worst thing that could happen is to have a baby that is abnormal. The least worst is to have a miscarriage.”

Still, he said he believes doctors should “not be gatekeepers, but educators and counselors.”

“Too often, we think we are big doctors and we know everything. Too many times we talk about ‘expert opinions,’ ” Zhang said. “But very often I have found when we discuss everything we have not thought enough about what the patient really wants.”

Zhang argued that gene editing of babies one day will be as safe and common as mobile phones. He expressed frustration about the controversy over his work.

“It is morally and ethically acceptable that people go see the plastic surgeon to do a breast job or change part of their body. It is absolutely fine for people to wear blue contact lenses and color their hair,” he said. So why, he asked, is there such argument over designer babies and other alterations to our physical future?

He pounded his fist on the table once. Nobody disputes the value of intrauterine fetal surgery, which involves cutting a woman to repair a defect in the unborn child. So why is the alternative — editing genes while the baby is still a clump of cells — controversial?

“There needs to be some serious debating,” he said.


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