On Monday, 13 months after He Jiankui announced that he had created the world’s first gene-edited babies, the Chinese scientist was sentenced to three years in prison and fined $430,000.
Working with two embryologists, who were also sentenced to fines and imprisonment, and an “unsuspecting doctor,” He used in vitro fertilization to create single cell embryos, whose DNA he then altered with the gene editing tool CRISPR-Cas9 to carry a gene variant thought to confer resistance to HIV. Couples recruited for the experiment included HIV positive men, who, He reasoned, would understand the value of resistance to the virus.
Edited embryos were transferred to their intended mothers. Twin girls were born in October 2018 and, we learned yesterday, a baby girl was born in 2019.
He Jiankui was proud of his experiment, which he deemed a success even though one of the twin girls was born with a mix of edited and unedited genes. The scientist likened his achievement to the work of Dr. Robert G. Edwards, the British physician who won the 2010 Nobel Prize in Physiology or Medicine for the development of IVF.
The international scientific community didn’t see it that way. Its reaction was almost uniform condemnation. Scientific leaders called it “irresponsible” and “premature,” saying it “failed to conform with international norms.”
Whether the work was also a violation of Chinese law wasn’t immediately clear to the international community. Several months later, however, a task force of the Health Commission of China in Guangdong Province reported that He Jiankui had violated general clinical research laws and rules, such as using a fake ethical review certificate and misleading participants about the study’s risks, and also violated an ethics guidance from 2003 that barred the reproductive use of research embryos. At yesterday’s sentencing, those violations were bundled together under the crime of “illegal medical practice” — essentially practicing medicine without a license — which in China carries a maximum sentence of 10 years in prison.
If He Jiankui had been a U.S. scientist, his alleged misleading of research participants and forging an ethics approval would have been considered unethical, and he would likely have been subject to sanctions from his employer, loss of research funding, and disqualification from clinical research. But the work would also have been illegal, although in a somewhat circuitous and distinctly American way.
In the 1990s and 2000s, well before the latest gene editing tools were developed but following advances in reproductive technology and completion of the human genome project, many countries passed national laws prohibiting the reproductive use of genetically modified human embryos. In the United Kingdom, which since 1990 has had one of the most developed legal frameworks for reproductive technology, transferring a genetically modified human embryo for gestation carries a penalty of up to 10 years in prison.
No directly analogous laws were ever passed in the U.S. until December 2015, when Congress included a brief 101-word provision in a budget appropriations bill that effectively outlawed human germline editing in the U.S.
The provision is a budget rider — a condition of federal funding for the U.S. Food and Drug Administration. For the past four years, it has prohibited the FDA from considering any application to conduct research in which a human embryo is intentionally created or modified to include a heritable genetic modification.
The 101 words amount to a ban because the FDA has asserted jurisdiction over all clinical uses of genetically manipulated human cells. As a result, anyone planning to use gene-edited cells in humans must submit an investigational new drug (IND) application to the FDA.
If the application proposes transfusing gene-edited cells into adults with sickle cell disease or some other genetic condition — as certain ongoing and proposed studies do — then the FDA will consider whether to issue the application or a waiver. But if the IND application involves transferring a genetically modified human embryo for gestation — even if only in one patient or one research subject — the FDA is absolutely barred from even considering it.
Sanctions for proceeding without an IND application include administrative actions like disqualification by the FDA from ongoing and future research. But violations of the Federal Food, Drug and Cosmetics Act also carry criminal penalties, including fines of up to $250,000 and imprisonment for up to 10 years.
Budget riders, however, expire. Since 2015, Congress has a chance every year to alter the language in this defacto germline editing ban or remove the provision altogether and turn the question over to the FDA’s regular decision-making processes. But it hasn’t done this.
In the summer of 2019, the U.S. House of Representatives was urged to amend the rider to carve out from the general prohibition a procedure that aims to prevent transmission of mitochondrial disease. Although Congress ultimately left the rider unchanged, it was, apparently for the first time, openly discussed by the House Appropriations Committee. Several members called for a fuller debate of the issue, noting that the prospect of germline genome modification raises profound questions that go well beyond where the federal government should spend its money.
If and when that fuller debate occurs, American lawmakers and the American public will have a chance to engage with the scientific and ethical complexities of gene editing technologies and to consider together how best to police its use in humans.
Until then, researchers in the U.S., like He Jiankui in China, risk prison time if they attempt germline gene editing.