The FDA sent a stern letter today to Dr. John Zhang, PhD, MD, the physician who last year created a genetically modified human embryo in the U.S. and then exported it to Mexico where he self-reported creating a genetically modified baby boy.
While the genetically modified baby created in Mexico was reportedly seemingly OK, it’s not clear what kind of health issues he might face in the future and I haven’t seen much data on him. I believe his parents subsequently declined to have him participate in future research so that will be an issue in terms of knowing outcomes.
I’ve blogged before about Zhang and his cross-border effort and I’ve hosted a guest post with a Mexican perspective on that as well. According to the new FDA untitled letter (why not a warning letter considering the letter seems full of what seem like “warnings”?), Zhang made the genetically modified embryo in the U.S. without approval (which the FDA can’t legally give but in theory would be required) from the agency plus he exported it to Mexico also without the required approval.
To be clear, what Zhang did has nothing to do with CRISPR or directly with the big news this week on Shoukhrat Mitalipov having CRISPR’d human embryos. I don’t believe that the FDA would have any oversight over what Mitalipov did research-wise with CRISPR’ing human embryos in his Nature paper and it wasn’t federally funded. However, Mitalipov did create genetically modified human embryos as well, but via CRISPR. Also, Mitalipov is reportedly interested in genetic and reproductive technologies to potentially prevent mitochondrial disease in humans, but his Nature paper wasn’t on that and again Zhang didn’t use CRISPR.
Instead what Zhang did is a technique that has been variously called 3-person IVF, 3-parent baby technology (not a name I like), mitochondrial replacement therapy, nuclear DNA transfer, etc. It is technically called, ““spindle transfer for assisted pregnancy in patients with mitochondrial disease.”
The goal with this 3-person IVF technology is to combine the germinal material of two parents-to-be with the enucleated egg of a donor to avoid diseased mitochondria carried in the egg of the mother-to-be. This is all done with the hope of avoiding the transfer of mitochondrial disease to an offspring.
A very similar 3-person IVF approach is technically permitted now in the UK with proper licensure and approval, but not in the U.S. It’s unclear what rules are currently in place in Mexico on this. It’s a very good overall goal to work toward preventing horrible mitochondrial diseases, but I see 3-person IVF as a super risky procedure in its various forms and it could easily do more harm than good.
The FDA letter to Zhang includes a mention of marketing of the human genetic modification approach via his company Darwin Life, Inc. In addition, the FDA says of Zhang’s procedure:
“Moreover, as noted above, FDA cannot accept an IND for a clinical investigation involving your HCT/P, and such human subject research cannot legally be performed in the United States. Nor is exportation permitted unless it meets the requirements of an applicable export exemption.”
Strong words. The FDA also says, “We request that you notify this office, in writing, of the steps you have taken or will take to address the violation noted above and to prevent recurrence.”
I asked Bioethicist Leigh Turner of the University of Minnesota for his take on the letter:
“The FDA letter identifies several key issues. It mentions specific marketing claims while indicating that such claims can only be made after obtaining a valid biologics license. It notes that substantial evidence must be provided to obtain a BLA, and the way to generate such evidence is by having an Investigational New Drug application in effect. It also states that the company had no such IND in effect and had agreed not to use its spindle technology transfer program in the U.S. until an IND is in effect. But of course there is a catch: the FDA cannot and will not consider such an IND application. This bind appears to have prompted an end run around federal regulations by exporting genetically modified embryos to Mexico. (The letter doesn’t mention how many embryos have been shipped from the U.S. to Mexico.) Challenging this apparent effort to engage in regulatory arbitrage, the FDA letter states that Zhang and his companies do not have permission to export genetically modified embryos and the embryos do not fall within regulatory exemptions. Translation: Zhang cannot circumnavigate federal regulations by shipping genetically modified embryos to a clinic in Mexico. In short, several noncompliant practices are identified, with the usual reminder that such FDA letters are not all-inclusive and the burden is on the company to comply in all respects with federal regulations. Bottom line: Zhang needs to stop making marketing claims about offering a “cure” for mitochondrial disease and he cannot ship genetically modified embryos out of the U.S. to jurisdictions with less stringent regulations.”
What happens next?
Does the agency actually take some kind of practical action on this? Does Zhang proceed but just make the genetically modified human embryos in Mexico or somewhere else outside the U.S.? What happens with the marketing and the company Darwin Life?
Big HT to Leigh Turner for finding the FDA letter.