History tells us to be more skeptical of He Jiankui’s CRISPR baby story

Could He Jiankui have faked part or all of his CRISPR babies story? If so, how? Why?

Or to put it another way, almost everyone seems to be assuming the story is real, but should we be more skeptical? Should we flip things around and assume the story isn’t entirely kosher until proven otherwise?

I once said that the CRISPR field feels like it moves in dog years (very fast!) Consistent with that warp speed, the last 2 weeks have felt more like months.

In case you missed it, He Jiankui claims that he made twin CRISPR’d babies with mutations (see here why I don’t think we should call them “gene edit”) in the CCR5 gene that amongst other things when intact confers significant susceptibility to HIV infection. Note that there are established non-genetic ways to prevent HIV transmission.

He gave a talk at the 2nd international genome editing meeting showing some data in a blur of slides to try to back up his claim. However, the data he presented really proved close to nothing. There’s no way for any of us to know where his sequencing data (shown and not shown) came from biologically. Did the data in fact come from fetal-derived materials and from actual babies as claimed? Or instead did the data come from CRISPR’d stem cells? From embryos that were never implanted?

Unless the Chinese government intervenes with an aggressive investigation that includes direct sampling of the twin’s and parents’ DNA followed by independent sequencing, we may never know the truth. If the family doesn’t consent, such government action would be almost certainly be ethically impermissible in my view and I’m not advocating they do it, but without such direct evidence there’s probably no way to be sure what happened.

Perhaps the family will consent?

Another scenario (less severe and unfortunately also less elucidating) moving things toward greater clarity that is being discussed is that He Jiankui may send (or already have sent) his raw sequencing data to an independent lab for analysis. However, I don’t see how that other lab could be sure of the biological source of the sequencing data. Maybe there’s some clever way to achieve this, but I don’t see how.

If hypothetically for the moment we say He Jiankui faked some or all of this story, why’d he do it?

There are many possible reasons. We’ve seen other examples of researchers engaging in misconduct in this general sphere of research over the past 10-20 years. For the last two weeks my overall gut feeling has been that He Jiankui did not fake his CRISPR babies, but as I’ve thought about it in a historical perspective the last few days, I’m less sure.

Remember Woo Suk Hwang and his fake cloning of human embryonic stem cells? Haruko Obokata and colleagues and their fake STAP cells? You may not remember Hisashi Moriguchi, but he seems to have faked doing IPS cell transplants into patients.

Further back there were the Raelians’ claims to have cloned human babies, which most of us think was not true but at the time made global headlines (see image of news headline above). More recently there is the Piero Anversa situation.

It seems in these kinds of cases that the primary motive was often to be viewed globally as a star, pioneering scientist.

The other thing to consider is that reports suggest that He Jiankui was secretive or potentially even dishonest with others about what he was doing. For instance, his university may have been kept in the dark. The physicians who helped with the IVF/embryo production may not have known or even been lied to on some things. The equivalent of the Chinese IRB provider suggested there may have been forged signatures. Given this context, why should we just trust He about his story, especially with no publication to back it up? Even if he somehow can publish this work despite potential ethical lapses that in theory might make publishing nearly impossible (in practice some journal editor will almost certainly give in to temptation), we still won’t know if we can trust what the paper claims.

On the other hand, common sense points out that it wouldn’t have been much more work for He Jiankui to try to do the real CRISPR baby experiment than to have faked it. By contrast, other scientists who have faked things in the past did so at last in part because the actual work was extremely challenging or impossible at the time. Also, if He faked this, wouldn’t he have made his data look better and less messy?

So did He fake it or not?

My best guess right now is that the whole story isn’t a fraud and that he actually did do this experiment, but that the reported outcomes aren’t entirely accurate and are more negative than He has indicated.

But really, who knows? For all these reasons, it might be wise to occasionally remind ourselves as I’ve tried to do in my blog posts on this situation that we don’t have rigorous, verified data on any of this CRISPR baby story. As scientists we should be more skeptical in such circumstances, especially given the history mentioned above.