Rinderpest
"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.
On reading Ten reasons for NOT maintaining or storing rinderpest virus
Rinderpest was mainly a disease of cattle caused by a measles like virus. The word is German for cattle plague. A massive vaccination program in the late 20 century drove the virus to extinction. The last case was reported in 2001 and the disease declared eradicated a decade later.
It is only the second microbe to be eradicated, the first being the smallpox agent, variola virus. Some readers will know that the virus is only kept in one two labs in the world, although the odd vial unexpectedly shows up. Rinderpest virus (RPV) still exists in lab freezers around the world while its genome sequence is on the cloud.
Once rinderpest had been declared eradicated there was a joint call in 2014 by the Food and Agriculture Organization and the World Organization for Animal Health to reduce the number of RPV stocks and material containing the virus. Most of the material was attenuated vaccine virus, field strains as well as frozen infected animal tissue.
Why the call? It’s a truism to say that no system is perfect and accidents with microbes happen. Scientists and technicians occasionally get infected by some really nasty microbes. The call starts with some implacable logic The best way to protect a country from an outbreak of rinderpest virus infection is to not have the virus in the country in the first place. Yep.
The first reason not to maintain RPV is The country hosting the facility from which the rinderpest virus escaped would lose its rinderpest free status once a case is confirmed; even in one animal. Even one animal, severe indeed. It is followed by This would undermine decades of international effort and investment to eradicate the disease leading to immense embarrassment and a huge loss of credibility for the country responsible for the release.
The harsh reality is clear from reason 2: Economic losses through trade restrictions may push some of the population, dependent on agriculture for an income, further into poverty.
Followed by part of reason 3: As a result of production losses, food security for millions of families in affected developing countries will come under threat. This may result in starvation, malnutrition and social unrest.
Then this from reason 4: Animal-based food industries within and outside the country would be paralyzed.
The remaining reasons are in a similar vein. People would suffer greatly if rinderpest returned. There are clearly some adults in the room. Yet that was then; how successful was the call?
A 2023 paper entitled ‘Risk of rinderpest virus re-introduction 10-years post-eradication’ addresses precisely this point. In 2011 there were 44 labs holding RPV stocks/material mainly in BSL-3 and -4 labs but with some in BSL-2 labs as well. By 2021 the number was down to 14. BSL = biosafety level 1 to 4; the higher the level the more dangerous the virus. So down, but not out.
This article went on to quantitate various sorts of risk and a number of scenarios including biological warfare. Overall, the accidental use of laboratory virus stocks and deliberate use of vaccine stocks were the main contributors to the overall risk variability in the 2012 study, whereas the anti-animal biological warfare pathway had the most influence on the 2022 risk estimate. If this pathway is excluded from the model, the median overall risk estimate reduced from “Low” to “Very Low”.
The paper discusses the need to reduce further the number of labs holding material containing RPV. Yet there is a rider: rinderpest viruses could be re-created using publicly available genetic sequences. There are around 130 rinderpest virus genomes available on the web. This brings us back to the malevolent mind.
It closes by noting that the risk of rinderpest re-introduction could be further reduced by continuing the efforts to relocate and destroy virus stocks, to limit their use, and to restrict the production and storage of vaccine stocks. However, even with such measures, the maximum risk is unlikely to become negligible, so ensuring commensurate response preparedness remains important.
The adults are saying that even 20 years after the eradication of rinderpest, more effort is necessary to eliminate frozen RPV just to reduce the risk of an accident.
Now circle back to the DURC research on H5N1 avian flu viruses and the resurrection of 1918 Spanish flu. It seems that nobody is using the DURC H5N1 strains today which makes sense as they are of unfathomable use to public health. Almost 19 years after the resurrection of Spanish flu, virologists have probably scoped out the big brush strokes, even though that work is debatable (1918 and all that). Sure, Spanish flu can be used as a reference for assessing novel flu viruses, which are of unfathomable use to public health… (Spanish lookalikes).
Can we simply destroy the stocks of 1918 flu and the DURC engineered H5N1 flu viruses to reduce accidents? To make the world just a little safer. If the veterinary world is advocating destroying rinderpest virus material to protect animals and humans, then it should be a no brainer to do so for these flu viruses.
Furthermore, The cost of safely maintaining rinderpest virus in a laboratory may be significant and the burden of responsibility in ensuring safe storage will be high. Not only was DURC H5N1 work incapable of ever delivering something of use to public health agencies, but there are also finite risks associated with storing them.
To err is to be human. A cliché but true, nonetheless. Note that even if these DURC flu viruses were destroyed, they could always be resurrected by reverse genetics using the genome sequences accessed from public data bases. But then the same could be done by the malevolent mind that everyone mentions in the context of dual use research of concern… and then promptly forgets.
On the one hand virology has eradicated the smallpox and rinderpest agents which was widely applauded. On the other hand, it has generated novel viruses of pandemic potential no less, which was considered good science before there had been a chance to discuss it among virologists (Chilled virology). More than ten years down the line the fallacious claim that DURC research could help with the making of vaccines still surfaces.
We can make the world a slightly less dangerous place by destroying stocks of these viruses. For once, this is tangible and quickly done.
Aside 1
Reverse genetics allows the recovery of a flu virus using circular DNA molecules called plasmids. You could envision destroying the virus stocks while keeping the plasmids. Accordingly, recovery of virus would be a matter of days to two weeks. Everyone is agreed that these plasmids are not intrinsically harmful and do not require sophisticated or expensive storage. By contrast, they should be stored in a secure repository. A simple case of derisking.
Aside 2
The capital letters in the title are the authors emphasis.
Aside 3
With the new May 7 policy from USG, the term GOF is kaput. Accordingly, DURC is used from now on.
