The in-vitro fertilization (IVF) technique involves the donation of mitochondria, which provide energy for cells and contain their own DNA.
Most of a cell's genetic material, or DNA, is contained within the nucleus but a small amount (less than 1%) is found in the mitochondria, which is passed, intact, from mother to child through her egg.
If a mother's mitochondrial DNA is faulty, it is possible that she may pass on a number of rare, but very serious, mitochondrial diseases, including muscle weakness, diabetes, heart problems, epilepsy and stroke-like episodes.
In serious cases, these diseases can lead to death. According to a study by the Children's Hospital of Philadelphia
, mitochondrial disease-causing mutations occur in at least 1 in 4,300 Americans.
The spindle nuclear transfer technique allows faulty mitochondria in the mother's egg to be replaced with the healthy mitochondria of another woman, before the father's sperm is used to fertilize the egg to create an embryo.
Zhang used the technique last year in an attempt to prevent Leigh syndrome
, a severe neurological condition that affects at least one in 40,000 newborns. The mother he treated had previously miscarried four times and given birth to two children, one of whom survived less than a year and another lived for only 6 years, both due to the syndrome.
On April 6, 2016, the mother gave birth to a reportedly healthy baby boy. "Transfer of the [normal] embryo resulted in an uneventful pregnancy with delivery of a healthy boy at 37 weeks of gestation," wrote Zhang and his co-authors in the published study.
Zhang's team of doctors went to Mexico to perform the procedure, as it had not been approved for use in the US by the FDA but was unregulated in Mexico.
In its letter, the FDA said Zhang's article stated the genetically modified embryo had been created in the United States but implanted over the border.
CNN reached out to Zhang's office for comment on Monday but received no immediate response.
Mary A. Malarkey, the director of the FDA's Office of Compliance and Biologics Quality at the agency's Center for Biologics Evaluation and Research, said Zhang had submitted a written request dated April 22, 2016, "asking for a pre-investigational new drug (IND) meeting for a clinical investigation of a 'spindle transfer for assisted pregnancy in patients with mitochondrial disease.'
She wrote in Friday's letter that the FDA declined the request in line with Congress's prohibition on the use of funds to accept IND submissions for clinical investigations that involve a human embryo being "intentionally created or modified to include a heritable genetic modification."
She wrote: "Your April 2016 letter further informed FDA that "until an effective IND is in place, and a clinical trial is authorized by FDA, Darwin [L]life will not use its spindle transfer technology again within the United States to support ex-US studies or procedures."
But Malarkey then highlighted that Zhang had not been honoring that commitment. "You continue to market MRT (mitochondrial replacement technology) to prevent the transmission of mitochondrial disease and to treat infertility," she wrote.
Malarkey said the embryo Zhang's team created in 2016 did not meet federal regulations with respect to human cells, tissues, or cellular or tissue based products and was also subject to regulations regarding drugs and biological products that barred it from being exported.
"This letter is not intended to be an all-inclusive list of violations. It is your responsibility to ensure full compliance with the FD&C Act (Federal Food Drug and Cosmetic Act
) and the PHS Act (Public Health Service Act
) and their implementing regulations," she wrote.
Malarkey then requested Zhang to notify the FDA, in writing, of the steps he has taken or will take to address the violation and to prevent its recurrence.
Other 3-parent IVF babies
Though the baby born in Mexico in 2016 was billed by Zhang as a "first ever," a different version of this same technique had been used by fertility clinics in the past, said Professor Hank Greely
of Stanford University after Zhang's study was published last year.
"About a dozen such babies were born in the US in the late 1990s/early 2000s before the FDA -- pushed, I think, by cloning concerns -- decided that this procedure needed FDA approval," said Greely.
The clinics who did this before have since stopped performing the procedure, he added.
In February 2015, UK lawmakers voted in favor of a law
that would allow another form of the pioneering technique, known as pronuclear transfer, by doctors in Newcastle. This method involves fertilizing both the mother's and donor's eggs with the father's sperm, then transferring the nucleus from the mother's fertilized egg into the fertilized donor egg.
But the UK's Human Fertilization and Embryology Authority did not give the green light to the treatment until December 2016
, after further safety tests.
Lori P. Knowles, adjunct assistant professor at the University of Alberta School of Public Health, said the fact that the technique had been used to produce a girl was significant.
The reason the experimental method was cause for concern -- and was vigorously debated in the UK before approval -- is the genetic modifications produced in a girl baby could be passed onto her children, Knowles said.
"We know for sure that she will be passing on her mitochondrial DNA through her maternal line," said Knowles. If in the future this baby girl has genetic children, they will inherit her genetic modifications "and that's always been a really bright line," said Knowles -- a line not to be crossed until rigorous scientific testing proves it is safe.
Dr. Valery Zukin, director of the Nadiya Clinic for Reproductive Medicine, where the controversial pronuclear transfer technique was performed, said there were no regulations concerning the procedure in Ukraine.