Lab Acquired Infections

"On reading," by Simon Wain-Hobson, is a weekly discussion of scientific papers and news articles around gain of function research in virology.

Since January 2024, Dr. Wain-Hobson has written weekly essays for Biosafety Now discussing risky research in virology. You can read his entire series here.

Poppies, oil on canvas, Edouard Debat-Ponsan (1847-1913). His Massage at the Hammam is remarkable. He lost his bourgeois clientele after taking sides in the Dreyfus affair that rocked France from 1894 to 1906.

On reading Laboratory-acquired infections and pathogen escapes worldwide between 2000 and 2021: a scoping review by Stuart Blacksell and colleagues, The Lancet 2024; 5:e194

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There are two aspects to this paper, lab acquired infections (LAIs) which will be addressed here, and accidental pathogen escape from lab settings. LAIs are not new. An investigation into 50 laboratory-acquired typhoid fever cases dating back to 1885; six deaths were recorded, and the method of infection was known in 23 cases, of which 16 cases were caused by mouth pipetting. As Salmonella enterica typhimurium was first cultivated by Georg Gaffky in 1884 LAIs occurred from the outset. Another study published in 1951 identified 39 deaths among 1342 LAIs (2.9%), the majority concerned bacteria.

The present study comprises a literature search for the period 2000-2021, so topical. Of 309 LAIs identified, most were reported from North America (79%), aka the USA, with far fewer from Europe (9%) and Asia (7%). Among the broad range of microbes, bacteria dominated (70%), and once again S. Typhimurium came out top at 50% of LAIs. Procedural errors represented the leading cause of LAIs, accounting for 69.3% of cases. There were 8 fatalities (2.6%), particularly associated with the plague and meningitis bacteria.

As these essays focus on virology, lets look at the data for them. Of the 43 LAIs caused by viral pathogens, vaccinia virus (n=13), Zika virus (n=5), and dengue virus and SARS-CoV (n=4) were the most common. Fortunately, infections with some nasty viruses such as Ebola were few. The only fatality was for an Ebola infection. Overall, the fatality (1/43 or 2.3%) was comparable to the 2.9% and 2.6% numbers given above.

Since the beginning of microbiology, a small number of researchers have contracted LAIs and died. This is not widely known, but occasionally they hit the news, for example a smallpox death in Birmingham UK after the virus had been eradicated. It’s an occupational hazard much like being part of airline cabin crew. And in the airline industry, huge efforts are made to reduce loss of life. Indeed, air travel is the safest form of transportation.

So, you might have thought the same was true in infectious diseases. Certainly, in the US there is an effort to learn from mistakes. The American Society for Biological Safety with their network and annual conferences is a place where people can discuss and learn how best to protect microbiologists from the microbes they work with. On reading spoke at a session on GOF, oops DURC, research at their 2013 conference and listened to other talks. There is still much to be done by institutions.

There is the European BioSafety Association which did discuss DURC briefly, but it hasn’t been the issue in Europe as it has in the US.

This paper reveals far fewer cases of reported LAIs in Europe and Asia compared to the US. On reading suspects massive underreporting in Europe – there is no way the microbiology community is almost 9 times smaller than that in the US. On reading knows for a fact that there is underreporting in France, with his Pasteur Institute being a notable exception. Journalist Ian Sample of the Guardian has documented underreporting in the UK.

Why such a poor performance from Europe? Unclear, but there is a parallel with the DURC (ex-GOF) debate on avian influenza viruses. Not a public whisper in most European countries – the UK and Germany have been ahead of the others, the Netherlands with difficulty which may be because Dr. Fouchier is Dutch. France just recently but more than a decade late. Yet for the others, nothing. Europe has not even underperformed in the DURC (ex-GOF) space – hopeless is closer to the reality. Using the US as a benchmark, European nations have been negligent when it comes to LAIs.

Underreporting is more widespread than thought and there is a good reason for it. Rather than seeing LAIs as an occupational hazard - to err is to be human - they are viewed as professional failures. After all Procedural errors represented the leading cause of LAIs, accounting for 69.3% of cases. This leads to the blame game which is too easy to play and is gobbled up by the press and social media. And while no amount of training can totally prevent accidents, training lowers risk.

As Bill said, laugh and the world laugh with you, weep and you weep alone. Shakespeare that is. Institutions love the good news, the high-profile paper with an accompanying press release, prestigious awards and grants that can be talked up. But when it’s bad news, a LAI or a lab leak, the reflex is to baton down. Why? Maybe there was inadequate training or institutional oversight. Furthermore, it won’t look good if the story gets out.

‘Funders won’t like it.’ Yes, On reading has come across this phrase in this context. Put bluntly, funders and philanthropists are daft to defy the laws of thermodynamics - perfect systems don’t exist. LAIs have been part of microbiology since the beginning.

To push lab accidents of all shades and forms under the carpet, aka underreporting, self-censorship, active discouragement, or lost in administrative layers, is to fail those whose jobs are to work on these nasty microbes. Help the scientists to reduce the number of LAIs as much as possible.

Post COVID we’ve heard zillions of times that we need to learn about the origins of the pandemic to better prepare ourselves for the next one. For the record, this was said after the big Ebola outbreak of 2014, the flu pandemic of 2009 and AIDS before that, so we need substance not words.

Learning from errors has led to many great scientific discoveries but when it comes to LAIs there doesn’t seem to be much learning, particularly in Europe and Asia.

This feeds into the bigger institutional picture. In the previous essay, Sounds of Silence, we learnt that We cannot expect people to call attention to problems when it is not safe for them to do so. At present, it is unsafe in too many research settings. Those who question the status quo can be ostracized and labelled as troublemakers. Note that most of the researchers doing bench work are those lower down the ladder. They don’t have a chance if the blame game is played.

If institute directors cannot create an environment where microbiologists can learn from LAIs, then something is badly wrong. As we have seen on US university campuses this spring, if the physical safety of students cannot be guaranteed, then how can they learn?

Then there is professional pride. Virologists have mixed up isolates before which is another occupational hazard they live with. Many scientists have contaminated cell lines by the aggressive human cervical carcinoma cell line, HeLa, which is driven by the oncogenic human papillomavirus, HPV18. Another occupational hazard which can be limited, especially today, but experience shows that it still occurs. Yet the gent who first published rampant HeLa contamination of cell lines was badly treated and vilified when all he was doing was a service to the community.

That was then, but history shows the messenger is often badly treated. Scientists with their PhDs and titles, laws and logic pride themselves on their rationality. Yet pride is getting in the way leading to irrationality and silly cover ups.

All this means that science doesn’t self-correct at all easily and that some, invariably those at the coal face, pay an unfair price for speaking out or getting infected.

There appears to be a blindness not just in science although we’ll remain focused on virology. Open criticism is too hard to take and elicits an anaphylactic response - pushback by virologists to the NSABB report (Going places) on risky virus work; the calamitously lightweight early opinions on COVID origins; or the profound reticence to discuss the genesis of novel human viruses for over a decade, which, if made by the military, would have been slammed as dangerous biological weapons research. Journalists wake up!

Yet it is worse. Malicious minds are being provided do-it-yourself manuals on the web free of charge and paid for by the US taxpayer. Dual Use Research of Concern is a concept but no more. Lip service is paid, a committee nods it on, yet no dog barks. And now we suspect massive underreporting of LAIs in Europe and no doubt elsewhere.

If administrators can’t even protect those they administer, how can they protect the public?

Dear reader, when it comes to scientists getting accidentally infected, don’t ask for accountability for that will freeze everything. Suspend this understandable desire and demand openness so that we can learn about the procedural errors and other quirks that occasionally lead to scientists getting infected. That would help the very scientists who are on the long and winding road to beating the hell out of viruses.

Support infectious disease research but go hard on the pursuit of DURC (ex-GOF) virology that cannot answer questions, that makes the world a more dangerous place.

Go hard on the funders, public and private, as well as the universities and institutions who support what is the equivalent to biological warfare research, who allow it to be published openly, who pull in overheads for such work.

Without realizing how financially exposed they are. A class action could hobble their mission.

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Aside 1

A commentary on this article was published in The Bulletin of the Atomic Scientists.

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Aside 2

A very recent news report in the September 7, 2024 issue of Science closes with a summary of poliovirus leaks and infections. Work from the Pasteur Institute was part of eradicating old stocks of poliovirus in research labs. In the essay Rinderpest the raison d’être for eradication of extinct viruses was discussed. On reading repeats the need to eradicate the stocks of 1916 Spanish flu for the same reasons and the Fouchier and Kawaoka stocks of, presumably human transmissible, GOF enhanced H5N1 bird flu viruses.

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Simon Wain-Hobson is an emeritus professor at the Institute Pasteur, Paris, from which he retired in 2021. He and his colleagues were the first to sequence the genome of HIV, and Wain-Hobson has published more than 230 papers on virology and cancer.