The First Gene-Edited Babies
By: Fsi Stanford
Tags: Law, Fsi Scholars, Genetics, Health, CRISPR

Q&A with Hank Greely, the Deane F. and Kate Edelman Johnson Professor of Law at Stanford Law School and an affiliate of FSI’s Stanford Health Policy. Written by Sharon Driscoll. This article was originally published by the Stanford Law School.

Last month, He Jiankui, a Chinese researcher, announced the birth of the world’s first gene-edited babies, whose DNA had been edited to reduce the risk of HIV infection. While the claim has not yet been verified, Chinese authorities have launched an investigation and ordered this researcher’s work to stop. In the discussion that follows, Stanford Law Professor Hank Greely, an expert in the ethical, legal, and social implications of new biomedical technologies, discusses the legal and ethical questions surrounding the new world of gene-editing.

First, can you explain what the Chinese researcher, He Jiankui, did?

I’ll try but, first, we don’t know whether He Jiankui did anything except make YouTube videos and give a talk. There has been no independent verification that these babies exist, let alone that he edited their genes. It would be a very bold fraud, but bold frauds have been carried out before in bioscience, including, notably, Hwang Woo-Suk’s false claim in 2004–05 that he had successfully cloned human embryos.

Assuming He Jiankui did what he said he did, he used a fantastic new DNA editing tool called CRISPR (“Clustered Regularly Interspaced Short Palindromic Repeats”) in human embryos very shortly after the eggs were fertilized. His goal was to change a gene called CCR5. This gene makes a protein that sits on the outside of some our white blood cells, crucial to the immune system, called T cells. There is good evidence that T cells that lack CCR5 cannot be (or cannot easily be) infected with HIV; about 1% of Northern Europeans (and a smaller percentage of people elsewhere) have a particular change in their CCR5 gene that deleted 32 base pairs (“letters”) in the DNA sequence and they do not seem to get HIV infections. So, his stated goal was to provide these embryos (and the babies, teenagers, and adults they turn into) with immunity from HIV infection. The data he released, however, shows that one of the twins only had half of her cells modified. If half of her T cells have CCR5, she could still be HIV infected. The other twin had all of her cells changed but not in the way He Jiankui intended, and not in the way found in people. We have no idea whether she will be immune, wholly or partially, from HIV infection.

Is it legal in the US — or anywhere? If not, why?

It is not legal in the US. The FDA takes the position, which I think courts would most likely uphold, that genetically altered human embryos are either drugs or biological products (or both) and so under its jurisdiction. It is illegal — a federal crime — to distribute a new drug without FDA approval. The FDA has not approved genome editing for embryos for clinical use. For research uses only, you can get FDA permission more easily. You need to submit an application to the FDA for what’s called an Investigation New Drug (IND) exemption. You need to show the FDA that there is good reason, based on non-human research, that this will not be too risky for the research participants and that there is a reasonable chance it will be effective. His work would not satisfy either side of this and so would not get an IND.

But that’s not relevant right now because since December 2015 Congress has regularly added an amendment to the FDA’s funding bill, prohibiting it from even considering any application, of any kind, for human germline editing. So, if you did this in the US now, you’d be doing it without FDA approval, which would make your use an illegal distribution of a new drug.

In many other countries, particularly in Europe, any germline human genome editing is illegal by specific statute (which it is not in the US). In most countries there is no law on this — many poor countries have other things to worry about — so it is legal (at least, not specifically illegal) in most countries.

What are the dangers? What are the potential benefits?

One danger to the children is that CRISPR might have caused damage to other parts of their DNA. These so-called off-target effects are fairly common when CRISPR is used. In addition to changes in other parts of the genome, we know that He Jiankui did not accurately make the changes he aimed for in the CCR5 gene; it’s possible that the He Jiankui-modified gene would not only be ineffective at preventing HIV but affirmatively harmful.

A second danger is that life without a working CCR5 gene may have its own problems. The Northern Europeans without it include adults and appear healthy but they haven’t been closely followed to see if they are at higher risk for other problems. There is some early evidence, for example, that they might be more susceptible to West Nile Virus and influenza.

The potential benefit to the babies is HIV immunity but it is of very little weight. One twin cannot be immune because half of her cells have CCR5. The other may not be immune. And both are “saved” from the possibility, probably small, that they would become infected after being exposed to HIV (probably several decades in the future). HIV is already a manageable disease (though certainly not fun); we have no idea how easily preventable or treatable it may be in 20 years.

The potential benefit to science/medicine is showing that CRISPR’d babies can be born but if that is worth establishing, it could and should be done in a different setting, with an embryo with a very serious disease for which no good alternative exists.

When might it become legal?

It could become legal any time Congress lets the appropriations rider lapse (next fall) and FDA decided there was enough safety information to allow it to proceed. I expect that neither of those will happen anytime soon.

When/if it does, would it be governed or overseen by an international organization? How might it be regulated?

Highly unlikely. In the US it will be overseen by FDA and local IRBs. Not perfect but not terrible.

What are the ethical challenges we’ll face when it does become legal?

For me, really not much. The safety issues for the kids are key. Apart from that, based on our current knowledge of human genetics, there are very few situations where gene editing in embryos will be better than embryo selection. We don’t know enough to make super babies and are unlikely to anytime soon. For some people doing any genetic editing that could pass down to future generations is itself a major ethical issue, a “line in the sand” we should not pass. As I have written elsewhere, I don’t think that’s right. See https://leapsmag.com/much-ado-about-nothing-much-crispr-for-human-embryo-editing/.

What legal issues do you anticipate?

If this is tried before it is legal, I would expect federal criminal charges against the clinics/scientists. That might raise the question of whether a gene-modified human embryo really is a drug or biological device for purposes of FDA law. If this is tried after it is legal and it goes wrong, big malpractice suits. If it gets used under appropriate regulation, not much.

* He Jiankui was a postdoctoral scholar at Stanford in the laboratory of Prof. Stephen Quake from January 2011 to January 2012. His work in the Quake lab focused on computational analysis and was in no way related to gene-editing.