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:

Do you see it?

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

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.

Teens Think Up Ethically Questionable STI Detection Method

Because there’s nothing the media likes more than a good look at all these teeny genius stories (except maybe catching a politician with their pants down, figuratively or literally), the primary non-Supreme-Court-ruling-on-Obamacare story making the rounds right now is the S.T.EYE condom, developed by three teenage boys from the Isaac Newton Academy in London. The S.T.EYE changes colour* when it comes in contact with a sexually transmitted infection (hence the name), which is being heralded as ground-breaking, revolutionary, disruptive technology–of course, since this was a TeenTech entry and winner. One of the young inventors, Daanyaal Ali, 14, says that they created the S.T.EYE because they wanted “to make something that made detecting harmful STIs safer than ever before, so that people can take immediate action in the privacy of their own homes without the often-scary procedures at the doctors.” (And as an aside, I find it fascinating that the teenagers want to reduce the embarrassment of going to clinics and emphasize “the privacy of your own home” line so frequently used by DTC advocates without stopping to consider the major hurdle of: duckie-pretty-pink--large-msg-131051452728if you’re putting the condom on to have sex with someone(s) else, then you’re not alone and we’re right back to the embarrassment-only this time it’s in the privacy of your own home while you’re naked in front of someone you want to have sex with. Which kind of sounds like it should be the beginning of an 80s movie starring Jon Cryer.)

This is an ambitious goal, and it’s laudable that teenagers are behind the idea; a validated, direct-to-consumer, at-home STI test that is inexpensive and accurate would be a great addition to public health. I’m not sure anyone can disagrees with that. The problem here is in implementation: the teens envision their test being wrapped up in a condom, which means that at least one person’s STI test will be revealed after-the-act, rather than before. While you may think “great, post-exposure notice,” it’s not that simple. What happens, for example, to informed consent? You’re talking about revealing whether or not someone has an STI to not just themselves but their partner(s)-at-the-moment; is there something that clearly identifies these as S.T.EYE condoms? Will it be impossible to miss that this condom your partner is providing (or that you provide a partner) will glow in the presence of an STI, regardless of who is infected? Will all parties need to sign a contract honoring the privacy of all participants before opening the condom? Will it come with a EULA-disguised-as-informed-consent? Remember, informed consent can’t be coercive-is right before having sex the bestest time in the world to assure non-coerced consent?

And other difficulties: how do you know who “triggered” the glow? Presumably it glows the same “uh-oh” colour regardless of which side of the condom the exposure occurred on. What if there are multiple partners? Are they considering impregnating dental dams with the same technology to include lesbians, or is this only for penis-based sex? Will the antibodies in the condom react to antigens in saliva? Can you still use lube? But, with exception of exactly who this condom is being created for, those issues are largely technical issues, and they’ve been well-deconstructed elsewhere.

Autonomy to make decisions, ability to consent after given full information, privacy of medical information; these are all pretty basic medical ethics 101 concepts, and they’ve been ignored here. I certainly don’t fault a trio of teenagers for that-but I can and do fault the teachers who encouraged them to pursue this line of thought, as well as the people who awarded it as innovative (not to mention the non-critical journalists breathlessly reporting it).

Innovation is the lifeblood of the technology industry; I understand that. My father had his own technology business when I was a kid. I was part of the technology innovation industry for a decade, and played a role in disruptive medical technologies.1 I was raised in Silicon Valley before it was Silicon Valley; I do understand, and I have no real interest or desire to stifle creativity, innovation, or even disruption. The problem is that in the pursuit of “can” at all costs, “should” is being left in the dust. Should we develop condoms that glow on exposure to STIs? Maybe not. Why? Well, how about the scenario where someone is killed for exposing someone to an STI? How about the person who is too embarrassed or ashamed to get help and kills themselves? What about the person who is shamed across their community, online, for having an STI, with a glowing condom as “proof”? And why do I even have to reach for such dramatic examples of “maybe we shouldn’t do this,” when “how do you manage consent” is such a present and problematic issue?

Of course, this isn’t just about innovation-it’s also about disruption. And the disruption here isn’t the idea of color-changing-upon-STI-detection condoms, but who is having the idea: teenagers. These teens are envisioning medical devices that are conveying diagnostic information, and they’re doing so outside of the normal channel that we expect medical devices to be developed in. That means the typical standards that are in place for medical device development (specificity, standards, quality control, labeling requirements, documented risks, etc) haven’t been addressed (or likely even thought about). To quote Nick, “In the world of distributed technology, these things are increasingly up to the individual, and we need to start adopting an “ethics of design” into our disruptive tech scene.” In other words, this project shouldn’t have made it to a technology competition without serious consideration given to plausibly, specificity, testing standards, and the other things that, presumably, the condom manufacturing company that has partnered with these teen boys will now take on.

It’s fantastic that there are challenges like TeenTech to encourage teenagers to pursue STEM-related careers. However, we need to make sure that we are setting the foundations to good research by teaching all aspects of research and development, including ethics, and make sure that our enthusiasm for encouragement doesn’t overshadow the necessity of ethical oversight.

*26 June 2015: Just a quick clarification, based in Maggie’s nice comment below: I want to stress that the idea the teens presented at TeenTech are conceptual ideas, not actual prototypes or working models. I do think that this stage is definitely where the “ethics of design” needs to be built in, but presumably–hopefully–that dialog will continue happening as the teenagers partner with a company to see what happens in science after you have that initial “oh hey” idea.

Apple Updates HealthKit’s Ethics Requirements–But Don’t Celebrate Just Yet

In the on-going drama of Apple’s ResearchKit and its lack of conforming to modern expectations regarding human subjects research, Apple has updated the guidelines for apps “using the HealthKit framework or conducting human subject research for health purposes, such as through the use of ResearchKit,”1 requiring “approval from an independent ethics review board.” At first blush, this seems great–one of the bigger problems raised when Apple debuted Health/ResearchKit in March was that there didn’t appear to be any nod to or concession towards the necessity of ethical oversight of human subjects research, a conversation that’s been growing louder over the years, especially as Silicon Valley has become more interested in the potential “killer app” money behind health care products.

Unfortunately, a closer read of the actual guidelines shows that there’s still a lot to be desired, and Apple really needs to actually bring in someone familiar with medical ethics and health policy to help them not only with the language of their guidelines for apps, but also to review any app that wants to utilize the HealthKit framework or use ResearchKit for health-related research.

ResearchKit-HSR-April302015The revised guidelines can be read here; a snapshot of section 27, HealthKit and Human Subject Research, taken on April 30, 2015, can be seen to the right (click to embiggen). The particular language regarding ethics review boards is at the very end:

27.10 Apps conducting health-related human subject research must secure approval from an independent ethics review board. Proof of such approval must be provided upon request.

Obviously, the first and largest problem here is that proof of ethics board approval isn’t required, it merely needs to be available upon request, but a tumble of questions spill forth from that:

  • Who will have the capability to request to see this paperwork?
  • Can end users say “I want to see the ethics board approval?”
  • What is going to trigger Apple wanting to see this paperwork?
  • Who’s going to make sure that there was actually approval, rather than just submission? It’s not like it’s unusual for companies to try to fly under regulatory radar and sell products or services that haven’t been approved for their specific use (see: 23andMe, LuSys Labs).
  • Who at Apple is qualified to know that the ethics approval was granted by a legitimate, registered institutional review board (IRB)? (Does Apple even know how to check this information?)
  • Is Apple’s use of “independent ethics review board” an acknowledgement of outside-the-US names (where “Research Ethics Committee” or “Independent Ethics Committee” are more frequently used), or is this a way to dodge the requirement of use of an IRB, which does have specific and legal meaning within the USA?
  • What level of paperwork is Apple expecting app submitters to have for IRB approval? (Will they need to show the full paperwork filed? Will Apple be policing that paperwork to make sure it was what was necessary for the app’s purpose? Will they require meeting minutes? A one-page sign-off from an IRB?)
  • Precisely what qualifies an ethics review board as “indepdenent”?
  • Uh, what is “health-related” research, anyhow?
  • If the ethics review board says “this isn’t something that needs our approval, so here’s a waiver,” will Apple accept that as “approval”? (Because technically, that’s not approval.)

And of course, separate from this is the fact that currently, research (at least within America) only requires IRB oversight if money for that research is coming from the federal government. While yes, it’s true that all legitimate academic journals will require that the research was approved by an IRB and followed the conventions of the Declaration of Helsinki, not everyone is doing research with an eye towards publication within a peer-reviewed journal. This means that anyone doing HealthKit or ResearchKit work who is not embedded within an academic institution that has access to an on-site IRB will have to pay a for-profit IRB to review the app design and research goals – will Apple be looking for proof of payment? (And of course, that assumes that Apple will consider a university IRB “independent.” ResearchKitHealthKitAppleI’m relatively sure Carl Elliott would have some choice words about that particular assumption.)

All in all, this-the entirety of section 27, to be frank-reads as Apple scrambling, post-debut, to mollify the science journalists and media-savvy ethicists who have been honest and critical about Apple’s failures to understand even the most basic aspects of protecting the subject in human subjects research. It doesn’t actually seem to indicate Apple understands what is actually required from those doing human subjects research, only that Apple lawyers seem to be aware that there is a serious potential for a lawsuit here, and thus are trying to figure out how to best cover their corporate asses.

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.

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?”


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,…

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.”

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,…


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.