What’s With NASGOF2 and House Ferret?

NASGOF2IsComing

If you’ve been watching my Twitter account, you’ve undoubtedly seen my parody of Game of Thrones over the last week: NASGOF2 is Coming/NASEM. And if you’re a Game of Thrones fan who works in or around gain-of-function/dual-use research of concern, then you likely giggled and nodded and probably planned to if not be at today’s meeting, at least watch it live on the internets.

If you’re a dual use person who isn’t familiar with Game of Thrones, I can’t help you–I don’t watch the show, either. All I know are the memes from the first season’s “Winter is Coming” advertisements, and I happen to both have Photoshop and be married to a fan of the show who is also one of the dual use experts. So when he offered his suggestion (instead of what I was working on), I jumped.

What was this remarkably funny suggestion? The profile of a ferret, because ferrets are what started this all.[note]Ron Fouchier and Yoshi Kawaoka published a series of experiments passing H5N1 through ferrets, ultimately making it very, very transmissable and very, very deadly. While DURC/GOF studies have been going on for a long time–Ramshaw’s mousepox is probably the most famous–this whole brouhaha can really be traced back to 2011/2012. You can read the start of it here.[/note] And because we’re talking the flu, naturally, the ferret is licking it’s sniffly nose (a detail I added and I’m grateful at least one person noticed and laughed about–oddly, not the husband).

So today, the ferrets have come home to do whatever the ferret equivalence of “roost” is, and the summary of a lot of hard work, arguing, publications, and general debate will be presented in front of a divided group of people. And me. I’ll be there with my gifs and giggles, rolling my eyes at the entire process and wondering if it’d help if I just made everyone read All I Really Need to Know I Learned in Kindergarten.


An Ebolanoia Anniversary–Or, The Emperor’s [Lack of] Disclosures

It’s the Ebolanioa anniversary! Over at Slate, Tara C. Smith takes us through a quick walk down memory lane, and the utterly outsized reactions and political theatre America went through a year ago: quarantines and threats and Daesh-licking doorknob villains, oh my.

Hulk-hits-Thor-after-defeating-alienOne thing still sticks in my craw: the utterly ludicrous suggestion from respected epidemiologist Michael T. Osterholm that we were all just afraid to talk about Ebola becoming airborne, but it was a real threat. Even though multiple, well-respected virologists and Ebola experts immediately corrected Osterholm’s panic piece, the panic piece is what took life, with other news outlets repeating him word-for-word–and few people questioning why such a respected epidemiologist would even propose such an outlandish thing, let alone in the pages of a New York Times op-ed rather than in a respected, peer reviewed publication.

While it pains me to point this out, because Osterholm was quite complementary of my anthrax- and NSABB-related posts, someone has to play the fool and point out the emperor has no clothes. Or in this case, the emperor has a pretty glaring conflict of interest, neatly laid out for all to see if they just take a look:
CIDRAPOct62015

Do you see it?
CIDRAPOct62015-Highlighted

3M, a “leading underwriter” of CIDRAP, where Osterholm is (and has been) director, is also a leading manufacturer of N95 masks. The sort of mask used for personal protective equipment if you’re treating a patient with an airborne infectious disease. The sort of mask that is typically advocated by those who have more than a little paranoia when it comes to disease in general.1 The sort of mask all over this National Institute for Occupational Safety and Health website.

Look, I completely understand the need for funding journalism, and as a whole I really enjoy CIDRAP’s reporting.2 Having been in publishing and journalism for over a decade at this point, I understand the need for funding, and just about everyone knows I have no lost love for the University of Minnesotta in general. But when you accept funding from outside sources, you have to start thinking about how that funding influences what you think, support, advocate for and write about. We know that it doesn’t take much to subtly, subconsciously, or consciously influence opinions, and major funding from a source of masks that would block airborne Ebola? That’s a pretty big conflict of interest that should be disclosed in any “but what about mutations” panic discussions in the public sphere.3


Addendum
It’s been brought to my attention that Osterholm et al’s mBio opinion piece, which I didn’t directly refer to here but waved a whole bunch of shade at, was amended in April of this year to “address” perceptions of conflict of interest. Unfortunately for CIDRAP and Osterholm et al, this attempt at damage control is pretty piss-poor. Their objection to being called out on the 3M conflict of interest boils down to what we’ve heard in other situations: the money goes into a giant pot at the university and we don’t know what dollars from them affect us, and besides, it’s unrestricted and they have no say!

Well. Except that if, per CIDRAP’s donation page, only 2% of their funding comes from the University proper, and they know who gives what to such a specific degree that they can list The Benson Foundation as a principle underwriter and 3M as a leading underwriter, then you can’t really say that “it just all goes into a pot and we don’t know which particular dollars 3M touched.” Because what you do know is that if 3M hadn’t touched a significant chunk of the money in that pot, it wouldn’t be there.

You, as an individual, know if you have $30 or $100 in your wallet, and you definitely know if $70 of the $100 came from a particular place. Trying to claim that a business that requires their donated money to function has no operational knowledge of where the money comes from is insulting to basically everyone’s intelligence.

The mBio amendment also attempted to claim that since they don’t talk about respirators in the piece, certainly they can’t be relevant to a piece talking about fears of an airborne mutation. I leave this to the audience: Do you think respirators are relevant, at all, to protection from airborne disease, even if not directly mentioned in an opinion piece? Hmm.

Look, it’s a common misunderstanding that noting a conflict of interest is akin to admitting guilt or bribery or corruption. It doesn’t have to be like this, and this perception exists in large part because so many people try to pass off their COI as no big deal. But the literature has shown, time and again, that it is a big deal, and that no one is immune from the influence that things as little as pens or as big as unrestricted checks can have on perceptions. If you-the-scientist want us-the-reader to give weight to your opinion paper that, say, Ebola might mutate to become airborne and ZOMG, then perhaps you-the-scientist should give weight to the multiple peer-reviewed papers that say your center funding presents a conflict of interest that requires a necessary disclosure.


June: National Ship Live Anthrax Month!

ff_anthrax_fbi4_fOkay, I know we’re a bit ahead of June, but we’re within shipping for June, right? And at this point, a rather concerning pattern of “shipping live anthrax” is developing.

Yep! It’s that time again! Er, yet another mishap involving a lab sending a viable select agent to someone who shouldn’t have it. Er, someones. In this case, an unknown number of private commercial labs in nine states. NINE! And that would be alarming in and of itself, without that whole one year ago gift that keeps on giving. Or the previous Oakland Children’s Hospital incident in 2004.

Well. I guess in defense of the CDC, who owns the previous mishaps, this was a Department of Defense lab “mishap.”

Skeptical Scully

Very seriously, it appears there’s an issue here beyond “oh oops, culture of carelessness” – we have three clear and separate incidents of live anthrax being shipped out to people who should not have live anthrax:

    2004 – Oakland Children’s Hospital (should have received inactivated anthrax from the CDC; never did figure out what they were doing with anthrax)
    2014 – Three in-house CDC labs (should have received inactivated anthrax)
    2015 – Unknown number of private, commercial labs (should have received inactivated anthrax for “field-based testing to identify biological threats in the environment”)

Can we perhaps maybe finally agree that we have a massive problem with research laboratories, select agents, and oh, I dunno, what’s the word I want? Culture? Accountability?

Oh right!

Safety.


Last night, after I was entirely too tired to edit this post, it came out that not only were multiple labs in nine U.S. states–California, Delaware, Maryland, New Jersey, New York, Tennessee, Texas, Virginia and Wisconsin–and South Korea. Osan Air Base, which is an American military base, but still. A statement from the base says up to 22 people in a training laboratory were exposed: Five active duty Air Force members, 10 active duty Army members, three civilian officials and four contractors, all of whom are now receiving prophylactic treatment. -KH, 28 May 2015

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.”4 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.[foonote]See my forthcoming post on the Asilomyth of Asilomar.[/footnote] 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 creations3 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,4 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!5

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.


Paternalism, Procedure, Precedent: The Ethics of Using Unproven Therapies in an Ebola Outbreak

The WHO medical ethics panel convened Monday to discuss the ethics of using experimental treatments for Ebola in West African nations affected by the disease. I am relieved to note that this morning they released their unanimous recommendation: “it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects, as potential treatment or prevention.” WHOsOnFirstThere are, of course, the common caveats about ethical criteria guiding the interventions, but ultimately the recommendation has saved me from a tortured “WHO’s on first”-style commentary.[note]For other commentary on the committee composition, see Udo Schuklenk’s short, sweet, and to the point commentary; you can also read his reaction to their statement here.[/note] I’m sure we all appreciate that.

But just because the WHO recommendation follows what I’ve been arguing for the last 10-odd days doesn’t mean that the argument is actually over. In fact, as far as I can tell, it’s just getting worse, where worse should be interpreted to mean “even more people coming out of the woodwork to argue about ethics when they don’t have any familiarity with ethics.” Granted, Twitter is full of sample bias, but still. It is for this reason that I think it’s still important to post this statement on the ethics of providing unproven interventions that my husband (a real life bioethicist) and I worked on last week. We were side-tracked by needing to actually verify the science behind ZMapp, as well as the additional hands-throwing-up of hearing that ZMapp was provided for a Spanish priest after various US public officials stated there was none left to give.[note]After it was confirmed that the Spanish priest received ZMapp, also discussions about disparate treatment of people from the Developed vs Developing World.[note]Again, to clarify: This was finished on Saturday afternoon. Obviously, in that time frame, we have learned that a third Westerner was given ZMapp, it was released to two West African doctors, and WHO’s medical ethicspanel convened and–pleasantly–reached the same conclusion we did. This is merely a more detailed argument for the release of unproven interventions.[/note] [Cross-posted at The Broken Spoke.]


Paternalism, Procedure, Precedent
The Ethics of Using Unproven Therapies in an Ebola Outbreak

A “secret serum.” A vaccine. A cure. A miracle. With the announcement of the use of ZMapp to treat two Americans sick with the Ebola virus with apparently no ill effect, the hum and buzz on social media, commentary websites, and even the 24/7 news cycle, has become one of “should the serum be given to Africa? Will it?” The question has dominated for more than a week, and become something that the World Health Organization feels it needs to address by convening a panel of medical ethics experts to offer an analysis of what should be done.

And the general question about untested cures/vaccines in the event of a disease pandemic is an important one; there are already guidelines for what kind of treatments can and will be made available during a flu pandemic, and it seems quite sensible that a guideline be developed for all potential pandemic pathogens. However, it isn’t a question that is relevant in the current context, because we are already past that.

While people may be stating “should the serum be made available?” that’s not the question being asked.
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