Trying to connect the dots on CRISPR baby story paints a dark, cloudy picture

connect the dots

When I was a little kid I played this game called “connect the dots” or “dot-to-dot”, where you draw a line from dot-to-dot in numerical order and at some point a picture starts to emerge. I think kids and even some adults still play this today. They even come in extreme versions with hundreds or thousands of dots now (see image of books). I always tried to guess what the picture would be as soon as possible and sometimes even before starting to draw the lines.connect the dots

A lion? A fire engine? A tree house? A baby?

In the last two days, some of us effectively have been playing a science version of “connect the dots” related to all the elements of the reported CRISPR gene editing of embryos to make actual genetically modified humans. What exactly happened? What’s the back story? How bad is this for the very promising CRISPR research field more generally?

How the story began

The bombshell news just broke Sunday night (here and here) that scientist Dr. Jiankui He of China claims he has produced twin CRISPR’d babies. He even put out glossy YouTube videos about how great it all is. He says specific mutations were introduced via CRISPR in the wildtype CCR5 gene in embryos then used to make the twin babies. The rationale was that the mutations could make the babies less susceptible to HIV infection. In my view this is a very weak rationale, especially since HIV prevention can already be achieved without gene editing anybody, which is extremely risky.

Ethics?

More broadly, as I wrote yesterday I view what Dr. He has done, assuming he actually did CRISPR human embryos and make babies from them, as unethical and risky.  I can see that He feels passionately about his work from his videos even if I disagree with his logic and question both the ethics of what he did and to some degree his motivations. Interestingly, according to a new STAT News piece, it seems He informally discussed human embryo research more broadly (not producing CRISPR babies) and ethics with some bioethicists in the last year or two. Did he really listen and learn from his discussions with father-son bioethicists William Hurlbut and Benjamin Hurlbut?

The two Hurlbuts don’t approve of what he’s done, but their quotes portray He as a “good guy” and not a rogue. Others haven’t been so kind. Well-known Stanford law professor Hank Greely responded to the work by He without pulling any punches:

“This is criminally reckless and I unequivocally condemn the experiment,” said Hank Greely, director of the center for law and the biosciences at Stanford University. “I was shocked and upset last night when I read the news.”

The dots

There seems to be much more to this story (what I’m calling “the dots”) that could use a good dose of sunlight and transparency. The dot of Dr. He’s announcement of the CRISPR’d twins was curiously timed with other “dots” including his YouTube videos. This same week he published an odd paper supposedly providing guidance to others on the ethical use of CRISPR in humans. Reportedly the second author on this paper seems to be not a scientist, but instead is a public relations guy. Weird, huh? Also, one could argue that practically speaking He violated some of the principles in his own paper.

In addition, this week the U.S. National Academies as well as other international scientific and policy makers are holding an international meeting on “genome editing” that includes quite a bit of emphasis on human embryo gene editing. Although Dr. He is not a high-profile CRISPR researcher, somehow he is speaking not once but twice at this meeting of big wigs. Another dot.

For background in 2015, scientists and policy makers gathered in Washington D.C. for the first of these “human gene editing” meetings. It was focused in part on potential future use of CRISPR to make heritable genetic changes in embryos that then could be used to make babies. I attended that meeting and found it very helpful in thinking about key issues. It broadened my understanding of this arena. However, I was concerned to see the organizers release a statement at the end that I felt wasn’t strong enough and didn’t call for a moratorium on using CRISPR to make genetically modified babies.

Fast forwarding three years back to present day 2018, not only is Dr. He a speaker at this year’s meeting, but also after the news broke of his CRISPR baby production, yesterday the organizers of the genome editing meeting issued a fairly bland statement in response that said nothing specific in reaction to what he did. It seems they will allow He to go ahead and speak at the meeting. This decision (which still could change) likely will be helpful for transparency but does it kind of condone what he did even if indirectly?

I asked people on Twitter about this kind of dilemma and if He should be allowed to speak and from the 190+ votes so far, there is roughly an equal split (below).

Separate from the meeting, it was reassuring at least to see one of the pioneers of CRISPR gene editing, Feng Zhang, say he supports a clear moratorium on CRISPR use in human reproduction now.

Where do all these “dots” leave us today? Can we connect them?

We need much more information to get a clear picture, but in my view they paint a partial picture that isn’t pretty. The dots suggest to me that He orchestrated events this week for maximum publicity for himself and his unethical work. He also wasn’t up front about his intentions and where things stood with his research, and there remain uncertainties and concerns over whether he got needed ethics approvals and conducted proper consent with trial participants.

In addition, the dots may be reflective of some messy behind-the-scenes science politics as this story continues to evolve. They also raise more questions like who funded He’s work. I also wonder about the range of reactions amongst the organizers of the big genome editing meeting this week to the news. Do some support or are at least OK with what He did?

What happens next?

I expect there will be more dots and they will be easier to connect in coming days. It most likely won’t be a happy picture that emerges. More broadly, I can’t imagine how this story helps the CRISPR field and all the exciting, ethical research that is ongoing and planned including gene therapy clinical trials.

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