The curious case of tuberculosis (and more)

If you have confidence in incident reports filed with NIH, then you probably think that the vast majority of BSL-3 lab accidents are caused by tuberculosis researchers like this one. I have rather many doubts about that.

[Today includes discussion of a sewage spill at USDA’s Ames, Iowa lab, and an interesting incident of the biosafety staff at a major northeastern institution rebelling against an IBC reluctant to report problems.]

You’d be forgiven for thinking that this post is about a tuberculosis lab accident. It’s not. At least not exactly. It’s about many of them, and what they mean, and don’t mean, as best as I can determine at this point in time.

For the past several months I’ve had FOIA pending with NIH for reports of lab accidents. In some cases, I am also requesting such reports directly from the institutions themselves. At this point, neither process is complete, so my observations are based on incomplete data.

The “Good News”

First what is ostensibly good news. Compared to the situation years ago, there’s little question that NIH’s effort to ask labs to bother to report accidents has resulted in more accident reporting. That is, NIH begging them to actually follow the ‘rules’ has had some beneficial effect. Whereas in the early 2000s NIH might have received 10 or 20 reports of accidents per year, today that number is higher.

Recently I was getting pretty testy with an NIH FOIA officer for his slow response to my request for over two years of reports. I assumed that there were only a few dozen short responsive documents. It turns out that he had a lot more to deal with than I thought. To date, NIH’s reply now includes over 2700 pages. (At least one tranche of records is yet to be released, so the final tally is unclear.)

That’s certainly an improvement but there’s not as much there there as the page count would suggest. Many times there is an initial report and then another recapitulating the same events, and e-mail chains that incorporate previous replies that turn two or three pages of content into a dozen or more repeating pages. And accident reports, typically 5-7 pages, usually include one or two pages of instructions, and then use 4-6 pages to relate what, in most cases, could be done in about two.

Which is fine, there’s no requirement for report density. The point, however, is that 2700 pages are not 2700 reports, it’s more like about 250 reports (though I haven’t counted yet).

Still, let’s give credit where it’s due, and NIH’s effort to get more reporting has resulted in more reports being made.

Which naturally then leads to the question of what’s in them, what can be discerned about their quality, and how they are being used. This post starts to answer those questions with some observations.

Those sloppy tuberculosis researchers

One would expect most reports to relate to research at BSL-1 or BSL-2, since that’s where most research takes place. And that is the case. The reports released to date contain very very few incidents at BSL-3. Does this mean that there aren’t very many accidents at BSL-3, or is there under reporting? I don’t have all the reports yet, and it’s possible that NIH is holding back the more “sensitive” reports for the final tranche of records, so we’ll have to reserve judgement.

What is so far most remarkable about accidents reported at BSL-3 is that they almost entirely relate to tuberculosis research. And little else. Whereas I have perhaps 20 reports of exposures or other incidents at BSL-3 involving tuberculosis, there are less than a handful involving other pathogens. (And none involving BSL-4 research.)

This is extraordinarily strange. Why are there five or more times as many accidents in Tb labs than there are in all the other BSL-3 labs put together? Are Tb researchers an especially clumsy crowd? Is the scale of tuberculosis research so large that it dwarfs everything else? Do Tb researchers use recombinant DNA more than other scientists?

None of those “innocent” explanations is very likely. I’m unaware of any reason to consider Tb researchers more accident-prone than their peers conducting other research at BSL-3, nor does Tb work occur on a scale that would cause such skewed numbers. And I see no evidence that Tb researchers use more rDNA, especially in this era when so many viruses, whole pathogens and other constructs, that are handled at BSL-3 are generated using rDNA.

Of BSL-3 pathogens that are frequently studied, Tb is one of the few that nobody seriously suggests would be an effective biological weapons agent. The body fights off most infections, and post-exposure development of active Tb can take quite a long time, if it happens at all. Do the characteristics of Tb make it less unpalatable for labs to report Tb accidents? Certainly reporting a Tb accident doesn’t have the same frightening overtones, and is less likely to have public relations implications, then accidents with pathogens identified as having potential for use as weapons.

We’ll reserve judgement for the time being, but NIH’s reply to date suggests that despite the overall increase in the number of reported accidents that there are major shortcomings when it comes to reporting of accidents involving the most dangerous pathogens.

USDA’s “insignificant” sewage spill

Another thing that is clearly a problem relates to the word “significant” as it appears in the Guidelines in relation to accident reporting, the varying interpretation of that word, and the shenanigans that its interpretation can permit.

Section IV-B-1-j.  Report any significant problems, violations of the NIH Guidelines, or any significant research-related accidents and illnesses to NIH OSP within thirty days …

One could spend a long time batting around what “significant” means, but suffice it to say that some institutions use its appearance in the Guidelines to avoid reporting accidents that are not insignificant.

My suspicion is that many institutions are doing performative reporting of relatively inconsequential lab incidents and sometimes then ducking behind creative interpretations of the Guidelines to avoid reporting of others. Did an active infection develop despite the antibiotics? No? It wasn’t “significant” then… Or, like the University of Texas at Austin, institutions aren’t only not reporting smaller things, they are not reporting at all, perhaps reasoning away all incidents as “insignificant”.

USDA’s Sewage Problem

For example, the USDA National Animal Disease Center in Ames, Iowa had a sewage problem in the fall of 2019. Researchers there had infected cattle with genetically engineered paratuberculosis strains. Also called Johne’s Disease, paratuberculosis is geographically widespread. It effects different ruminant species differently, but seldom kills cattle. Nevertheless, the disease – and the need to maintain vigilance for it – is a drag on production in North America and elsewhere.

The sewer line of the paratuberculosis lab is tied into that of several other ABSL-2 labs that feed into the same processing tanks and overflow system. According to USDA, solid effluent from another lab in the system caused the common sewer line to do what sewer lines eventually do, clog. The unlucky souls on duty that day in the maintenance department had to open the sewer line outside of containment in order to clear the clog, resulting in spilled sewage and, well, obviously they had to handle the pipes and equipment to clear the clog. (The sewage usually flows into large tanks, is heat treated, and then released into the Ames municipal system.)

USDA initially contacted NIH following the incident, but then backtracked and asked to withdraw its report. That was because USDA’s Institutional Biosafety Committee reviewed the incident and decided that it was not “significant”. USDA reasoned that since the sewer pipe was opened in what it calls a “controlled area” (i.e. in the building but outside of lab containment) that was vertically above the entry point of the line from the rDNA lab, and because the maintenance workers wore PPE, that it did not “result in environmental release or exposures of animals or laboratory workers.”

While USDA’s reasoning is clearly self-serving …

– a spill of over two gallons of sewage occurred outside of containment;

– PPE worn outside of the lab is not the same thing as ABSL2 containment; and,

– the maintenance workers augered down into the line to clear the clog,

… NIH replied without any comment on the incident, and by inviting USDA to “reach out directly … in the future if you have any questions about incident reporting“.

Incident bureaucratically eliminated.

Ten out of ten large animal wranglers working at ABSL-2 agreed that sewer backups are not a good thing.

A biosafety office rebels

Normally I don’t hesitate to name names. In this case, I’m making a temporary exception. The institution I refer to here is a northeastern university with major biomedical research programs. A parvenu in this region of big old names, this institution has detractors and is frequently a bit of a lightning rod. Because I want to focus on the systemic aspects of this case, and not the institution itself, I’m not naming it here and now.

This 2018 incident or, in the view of the IBC, non-incident was a researcher working with genetically engineered strains of Burholderia cenocepacia without IBC approval. (Unapproved rDNA experiments are a very common occurrence to be discussed in the future.) B. cenopacia strains are frequently resistant to common antibiotics, are an opportunistic pathogen of humans, and are a particular problem in persons with cystic fibrosis.

The scientist was informed that his protocol was expiring and that he needed to update and renew his approval. The researcher did not do so, yet he continued to operate, during which time he generated new genetically engineered strains not reviewed by the IBC at all. Confronted by the biosafety office, the researcher offered innocent explanations about being confused by a new computer system and a newly placed “submit” button.

Once discovered by others, the researcher accepted responsibility, but one of the subtexts of the correspondence that was subsequently generated seems to be that the biosafety officers weren’t wholly comfortable with his explanations, and that they may have suspected conscious violation. The scientist would have known, after all, that he had not received the requisite renewal.

Conducting rDNA research without IBC approval is a clearly reportable incident under the NIH Guidelines. But when IBC met, it decided that the professor’s failure to renew his protocol despite the biosafety office’s reminders was not “significant”. Therefore, the IBC decided not to report it to NIH.

The IBC’s motivation? According to the biosafety office, which went over the head of the IBC and filed its own report with NIH, members of the IBC feared that the researcher’s access to federal grants might be impaired if his noncompliance was reported.

The incident is quite notable because the biosafety staff was bold enough to report it despite the decision of the IBC not to. This is a highly unusual reversal of the typical power dynamic between professors and biosafety staff. As a frustrated former Ivy League biosafety officer recently told me in private conversation, at his vaunted institution his experience was that the principal investigators were “answerable only to God,” and definitely not the biosafety office.

And by the way, Darren Sledjeski, you’re the relevant NIH program officer if you’re reading this.*

But Darren, who manages* the professor’s grants, probably hasn’t heard anything about the incident. NIH replied to the biosafety office by confirming that it was correct to report it, but reassured the IBC not to worry about any consequences. It wrote that “for the vast majority of the reports that we receive, if the institutional response is found to be appropriate, no further action is taken.” Meaning that the IBC needn’t fret about
Sledjeski finding out.

Of course what the “institutional response” was in this case is difficult to define. Was it the IBC’s decision to not report or the biosafety office’s move to do so anyway? NIH is apparently ignoring the IBC’s misstep and going with the unusual move by the biosafety officers as the official response.

I think, though, that IBC monkey business about “significant” happens way too much and and in too many places. There is more evidence of this to come.

NIH’s response to the biosafety office notes that in “egregious” cases, “NIH OSP may work with the NIH Office of Extramural Research [i.e the money handlers] to address such situations.”

So I’ve filed a new FOIA. And that is for every accident report received by NIH OSP in which it has “worked with the NIH Office of Extramural Research” over a period of a number of years. I’m betting the number where any significant such interaction took place is zero.

* Ooops, looks like Darren has moved on. No idea who his replacement is.


Sign up for notification of new posts

All information submitted is confidential. It will not be shared with anyone. Please note that you MUST reply to a confirmation e-mail in order for your subscription to take effect.

Leave a Reply

Your email address will not be published. Required fields are marked *