CRISPR and the Amoral Othering of Chinese Researchers

I’ve been under a rock for the last week or so, first at a conference in San Diego, and then fighting off a nasty combination of strep throat, laryngitis, and double ear infections. (So when I say “under a rock,” I mean hiding under the blankets in my bed, spending most of my time sleeping.) So while bits and pieces of the “CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes” paper published in Protein & Cell by researchers from Sun Yat-sen University in Guangzhou, China, made its way to me, it wasn’t until today I felt well enough to say anything about it–mostly because I don’t expect what I have to say will be very popular. So without further adieu, a few unpopular thoughts on Zhou, Huang, et al’s paper.

Claim
The paper was rejected by Nature, Science, other top journals, for being unethical.

Hah. Ahem. Look, if Nature, Science, et al, want to make that sort of “it’s unethical we can’t publish it” claim, they might want to do so when the ethics-inclined folks who’ve been around a while are, I don’t know, busy, off tilting at other windmills, at a conference in Bermuda, or something. Because history here isn’t really kind to the so-called “top journals” when it comes to publishing unethical material; see, for just a really short course on it, the Fouchier and Kawaoka H5N1 gain-of-function debacle. “Top journals” were burned by the response to the H5N1 enhancement debacle, and were flat-out caught unaware that such a thing as “bioethics” had enough of a voice to be heard. They don’t want to be caught again, so they’re walking away from anything possibly controversial right now, and the debate over CRISPR/Cas9 has already been going up in the flames of controversy.

In short, any time any “Top Journal” says “we’re concerned about the ethics” you should actually read “we don’t want to be involved in any mainstream media controversy.”1 They learned this with H5N1 GOF issue to the point that these days, any debate over GOF/dual-use research of concern/potential pandemic pathogen research is met with a chorus of “la la la can’t hear you publish what?”

Claim
OH MY GOD THE CHINESE ARE MAKING GENETICALLY MODIFIED HUMAN BEINGS!

Fu_ManchuReally? Is it time for the great Bondsian bad guy freak-out? Do you suppose the folks who are making this claim picture Zhou, Huang, et al, twirling Fu-Manchu moustaches while wearing Zhongshan suit-inspired lab coats as they look upon an army of genetically modified super humans being incubated in chained women who were discarded as babies for being female? How many tropes do you suppose are shoved into this image of evil?

Again, take it from an old-timer: “we have to do it before the Chinese” has been a rallying cry for an awful lot of the science that falls at the intersection of bioethics and transhumanism. Why? Because “the Chinese” stands for “people who don’t have our values and belief systems-they’re DIFFERENT.” We’ve heard it with cloning humans, dual-use research of concern, with just about everything, and now we’re hearing it with CRISPR/Cas9: “we” have to do it before the big scary Not Western people do it!

Except some researchers from China do it and what–it’s suddenly “not ethical” because they’re Chinese? Pundits, scientists and otherwise, are freaking out not because “omg someone edited embryos with CRIPSR!” but because “the Chinese” have. (And do you note how most folks are just saying “the Chinese” as if the paper has no authors? See: creating a big bad menace in your mind.) And unfortunately, this excuse isn’t limited to Top Journals rejecting the paper for claims of it being unethical. The concern shows up in Paul Knoepfler’s blog, as well:

It is worth noting that the current study had institutional ethical approval according to a statement in the paper:

“This study conformed to ethical standards of Helsinki Declaration and national legislation and was approved by the Medical Ethical Committee of the First Affiliated Hospital, Sun Yat-sen University. The patients donated their tripronuclear (3PN) zygotes for research and signed informed consent forms.”

Would an institutional review board in another country such as the US have given the green light to making GM human embryos? I don’t know.

The emphasis there is mine, and it’s one I dislike making,2 since I do consider Paul a friend. But what this shows is just how pervasive the idea that “the Chinese aren’t moral like us” is: Zhou, Huang, et al, swore to the study conforming by ethical standards required by the Helsinki Declaration as well as their own national legislation, noted it was approved by a MEC–and people are still questioning whether it was ethical enough, because they’re Not Western.

Which ties into the third issue people seem to be having,…

Claim
OMG the Chinese did CRISPR/Cas9 editing this is so worrying aren’t you bothered YOU SHOULD BE BOTHERED!

Well, no, I’m not bothered by the paper. I am bothered that Protein & Cell did such a rapid turn-around on peer review for the paper, but I have that concern whenever any journal does such “rapid turn-around” (and you’re kidding yourself if you think this is an isolated event-it’s very much not). Nor am I bothered that “the Chinese” did this particular CRISPR/Cas9 experiment, just like I’m not bothered by human embryonic stem cell research. The researchers (and again, let’s think for a minute about the alienating and Othering going on by insisting on referring to the folks behind this research as “The Chinese”) answered some pretty important questions about the immediate applicable functionality of CRISPR/Cas9 editing–which is especially important given the recent moral panic going on about the technology as a whole.3 In short, they learned two major pieces of information that have direct implications for any conversation about future use in humans–and bans on the technology.

  1. CRISPR isn’t 100% accurate, and sometimes “missed,” inserting DNA in the wrong place. This is problematic, because instead of offering a cure for $Whatever, it can actually create a new problem. So, not a benign “oops.”
  2. Even the embryos that were edited correctly by CRISPR ended up as mosaics-in other words, it wasn’t a universal fix. This, as Carl Zimmer explains, means that it’s a lot harder to take a single cell from an embryo and “verify” that it’s been fixed, and it’s hard to know whether or not the fix will manifest, pass down in the germline, etc.

In other words, as Zhou, Huang, et al say themselves: their “study underscores the challenges facing clinical applications of CRISPR/Cas9.”

Claim
But what about the embryos?!

Zhou, Huang, et al used tripronuclear (3PN) zygotes for their research. These zygotes occur in upwards of 5% of IVF attempts, and are discarded because, while they might develop into blastocysts in vitro, they absolutely do not develop further in vivo. In other words, these are non-viable creations4 with a built-in suicide switch: they’re never going to develop into bouncing babies, Chinese or otherwise. In fact, it was because of the very specific concerns over CRISPR/Cas9-mediated gene editing in normal embryos that Zhou, Huang, et al used 3PN zygotes: it says so, right there in the paper. (So what was that about ethical concerns, again? You can’t really say they weren’t thinking about it when they put it right there in the paper. Repeatedly.)

If I were to be moved by the creation of these 3PN CRISPR creations as somehow unethical, then wouldn’t I also be obligated to find human embryonic stem cells unethical? I don’t,5 so in practicing a policy of consistency,…

Conclusion

Look, the panic over the CRISPR paper comes down to this: people somehow believe that there’s “moral control” if Westerners do this research. To which all I can really say is, DURC folks? Maybe y’all missed the boat on how to get traction on this issue, and should have run around all a-panic, OMG THE JAPANESE!6

More seriously, the history of science and medicine should underscore and emphasize the fact that “like us” does not mean “moral and ethical.”

As I was pointing out to Razib Khan and others on Twitter, I was around during the OMG DOLLY NOW WE’RE GOING TO CLONE HUMANS AND THE END IS NEAR panic, which as Khan noted, hasn’t happened–or at least, the Raelians haven’t made us believe. Will the same happen to CRISPR/Cas9-mediated gene editing?Gattaca It’s hard to say, because the technology is so new, and whether or not we’ll be able to overcome random DNA insertions and mosaic, chimeric embryos is down the line enough that it’s speculative.

But whether we’re on our way to a GATTACA-esque future or not, one thing is certain: the first step to any dialog over CRISPR/Cas9-mediated gene editing isn’t going to be an Asilomar-like conference. It’s going to be to stop demonizing “The Chinese” as being a-moral, immoral scientists.


Edited to add: BTW, this was originally a stream-of-conscious Twitter rant that I was goaded to turning into a full blog post. You can read the original, see comments, etc, starting here.


Angelina Jolie & Frank Talk About Women’s Health & Personal Choices

Angelie Jolie has written another NYTimes Op-Ed, this one on her double mastectomy and subsequent bilateral salpingo-oophorectomy (removal of both ovaries and fallopean tubes). It appears she took note of the concern that her first op-ed (on her mastectomy choice) possibly having undue influence on other women with BRCA mutations, because she says, clearly:

I did not do this solely because I carry the BRCA1 gene mutation, and I want other women to hear this. A positive BRCA test does not mean a leap to surgery. I have spoken to many doctors, surgeons and naturopaths. There are other options. Some women take birth control pills or rely on alternative medicines combined with frequent checks. There is more than one way to deal with any health issue. The most important thing is to learn about the options and choose what is right for you personally.

I really appreciate her matter-of-factly discussing health issues that are “the domain of women,” discussing her treatment choices, her uterus, her IUD, and so on. It’s frank talk women don’t hear often enough when medicine discusses our bodies.

I also think that her emphasis on feeling feminine, even though she’s had a double mastectomy and salpingo-oophorectomy, is really important. Women too often receive the message that their femininity is through their breasts or their ability to reproduce, which can be especially harmful and self-destroying in the face of cancer. Being feminine isn’t contained within breasts, ovaries, or fallopean tubes, and the more open discussion we have about how you can feel and be feminine regardless of primary or secondary sex characteristics, the better.

Primum Non Nocere and the Hippocratic Oath

HippocraticOathUnless you’ve been under a rock or on a boat in the middle of the oceanTrue story: I’ve known of major news stories that have happened while people were on a research cave trip and while on a no-internet-except-for-work research cruise in the middle of the ocean, so apparently this happens more than you’d think., you’re aware that the United States is in the middle of a measles outbreak that has, so far, infected over 100 people, and was traced back to December Disneyland visits.

There’s been a lot of chatter lately over encouraging adherence to vaccines, lawsuits,I highly recommend Dorit Rubinstein Reiss’s paper on this, and am endebted to J.H. for pointing me to it. and so on-and in the ways of the world, in the last 24 hours, people have suddenly shifted to what the Hippocratic Oath says and whether primum non nocere (“do no harm”) is part of the Oath, and what that means for doctors who peddle anti-vaccine beliefs (and in particular, charming Arizona cardiologist and vaccine refuser Jack Wolfson).

As I mentioned on Twitter this morning, this would be a really convenient time to have someone with a piece of paper saying they have a degree in medical history around. (Hi.) So, a quick summary and expansion of this morning’s question and answer:

Is “primum non nocere” part of the Hippocratic Oath?

No, not in the original versions of the Oath that we have. This isn’t to say that the idea of what we would now call the principle of non-maleficence isn’t written in to even the earliest examples of the Oath, merely that the particular phrasing doesn’t show up. What does occur in the early versions of the Oath are phrases like “abstain from harm” – which is pretty close. The phrase “do good and do no harm” does occur in another part of the Hippocratic Collection, the Epidemics.

So what’s the origin of the phrase primum non nocere?

Good question–one that many people have made dissertations and other research projects out of. The last I was reading about this (which admittedly was a few years ago), the general consensus seemed to be that the specific phrase first enters American medical lexicon in the mid-1800s in reference to an earlier medical textbook.

What’s important here, though, at least in terms of talking about contemporary non-maleficence and beneficence, is that the concept behind “do no harm” (regardless of phrasing) has been a part of medicine for a very long time. This is one of the reasons the concept of “not cutting for stone” is in the Hippocratic Oath: removal of kidney stones (the stone being cut) in men used to be a rather brutal, bloody, and deadly procedure, and thus was left to the barber-surgeons, rather than the more refined doctors.

That said, I’d also say it’s equally important to not place a lot of emphasis on the Hippocratic Oath. While it is an incredibly important piece of medical history, it also banned surgery (not just removing kidney stones), providing abortions, and providing deadly medications. Those trained in medicine were expected to train their own sons in medicine, as well as the sons of their teacher – and tuition? Not a thing. Oh, and don’t forget swearing fealty to Apollo. (I wouldn’t want anyone who is anti-choice or anti-euthanasia for religious reasons to get too excited here.)

And of course, all of this ties in to the last, and common, question about the Oath: is the Hippocratic Oath actually a legally binding oath? At least in America, no.

What the Hippocratic Oath is, in many ways, is another living document that is frequently revised to reflect contemporary views–which is why the bits about leaving surgery to the professionals has been taken out–and still contains elements that have been considered essential to the art/techne of medicine for roughly 2500 years. It is a wonderful part of the history and lineage of medicine, connecting what was to what is. What it is not is a place to look for legalistic or even moral answers for contemporary medico-social issues.

Screening vs Diagnostic – Differentiating Difficulties Lead to Tragedies

I’ve been a relatively vocal critic of unregulated over-the-counter and direct-to-consumer screening kits for years, and moreso in the last few, as 23andMe flirted with the DTC genetic screening market. I felt (and still believe) that yanking the 23andMe kits was necessary because they’d not been validated and had no overight or FDA approval. Perhaps not surprisingly, the most common pushback I received on thisWell, possibly second-most. I did receive a lot of “it’s my DNA and I’ll do what I want with it” retorts, too. was that no one would actually use an OTC, DTC, or otherwise unregulated test to make decisions.

This Boston Globe story, by Beth Daley at the New England Center for Investigative Reporting, helps to prove my point: people do make life-changing decisions based on the results of screenings and unregulated (or non-regulated) tests, instead of diagnostic tests. Aside from being a very big problem, this can often be incredibly tragic:

Now, evidence is building that some women are terminating pregnancies based on the screening tests alone. A recent study … found that 6.2 percent of women who received test results showing their fetus at high risk for a chromosomal condition terminated pregnancies without getting a diagnostic test such as an amniocentesis.

And at Stanford University, there have been at least three cases of women aborting healthy fetuses that had received a high-risk screen result. …

In one of the three Stanford cases, the woman actually obtained a confirmatory test and was told the fetus was fine, but aborted anyway because of her faith in the screening company’s accuracy claims. “She felt it couldn’t be wrong.”

And no, these screening kits aren’t subject to regulation, because yay, loopholes. Expect them to be closed in oh, nine years, give or take.

It’s always nice to have another point of data to support an argument.

And yes, possibly I’m humming a revised version of a song from West Side Story, as I idly think about sending this link to people who told me there was just no way people’d make life-changing choices without doctor feedback/approval. I feel petty, oh so petty, I feel petty and witty and bright,...

OutbreakChat: A Livetweet of a Movie That Gives People Nightmares,…

Outbreak-ForBlog…and probably not for the reason you think. Outbreak is one of those movies people seem to either love or hate (or possibly love to hate); almost everyone I know who has anything to do with public health, infectious diseases, or virology tends to swear up a blue storm when the movie comes up.

So naturally, a group of us are going to watch it in real-time tonight, drinking and live-tweeting our thoughts on Twitter. This will include fact-checks, snark, and almost certainly questions and answers from the crowd-at-large. Who is doing this? Well, you might remember David Shiffman (@whysharksmatter) from my Virtually Speaking Science interview a few months ago; while he might seem like an odd choice to organize this, remember he has significant experience with pop culture/movie portrayals of sharks, mermaids, and other scientifically incorrect portrayals of the ocean.

Tara Haelle (@tarahaelle) is a freelance journalist probably best known for her excellent article that debunks flu myths. She’s written extensively on science and the need for accuracy in media imagery and discussion.

Nicholas Evans (@neva9257) is a post-doctoral bioethicist at the University of Pennsylvania’s Department of Medical Ethics and Health Policy, based in the Perelman School of Medicine. He specializes in biosecurity, bioterrorism, and the ethics of pandemic preparedness, and recently wrote a piece for Slate explaining why Ebola is not a bioweapon, despite media myths. (He’s also my husband.)

And what am I (@rocza) doing involved in this? Well, aside from spending much of the last couple of months educating Twitter about Ebola, blogging extensively about Ebola, and doing Justice Putnam’s “The Morning After” radio show to talk about the ethics of science journalism and Ebola coverage, I once upon a time was pursuing a PhD in bioethics and philosophy, looking at how popular media portrayals of medical issues affects our medical-decision-making (a continuation of my undergraduate thesis on autonomy and medical ethics). I’ve taught courses through pop culture (Stargate and Applied Ethics), and one of my most popular and invited lectures was on why we watch reality TV. I also have a weird affinity for Ebola; I once intended to become a virus hunter, and I’ve been studying Ebola, outbreaks, and the research for going on 20 years.

We are, of course, hoping more people will join in the viewing party-both experts and lay people alike. So pop up some popcorn, grab your favourite beverage of choice, and join us at 8pm ET tonight (#OutbreakChat) to see firsthand what set the foundations for the Ebolanoia that has raced through the world these past few months.

Edited to add: Bingo cards are available on Twitter.