German nonsense
"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 Safety-relevant research in virology from the German Society for Virology, March 13, 2025. Quotations are from their English translation.
The German Society for Virology (GFV) has fallen into the US laid trap brought about by replacing DURC by GOF which, as readers know, has a long history in biology. Just look at the opening statement: Gain-of-function (GoF) is an important part of virology research / In most cases GoF does not lead to increased pathogenicity / GoF is strictly regulated by the Genetic Engineering Act / GoF projects are safety assessed at many levels / GoF is essential for antiviral drug research and vaccine development.
The first sentence (S1) refers to GOF 1.0, its historical sense. S2 acknowledges that most GOF 1.0 research does not lead to increased pathogenicity but clearly implies that some can. We call it GOF 2.0 which is synonymous with the dangerous GOF research as per White House Executive Order. S3 and 4 say that everything is under control. S5 says that as GOF 1.0 helps with antiviral drug research and vaccine development there is nothing to discuss. We’ve seen this before from the NIH who have rolled out the drug and vaccine development argument to shut down discussion of GOF 2.0.
The GFV doesn’t, or doesn’t want to understand that in 2025, after a harrowing pandemic the public wants to be informed, not necessarily participate actively in, certainly not control, but be aware of what works and doesn’t. And why not via journalists? This isn’t a big ask, especially as the public finances the virologists.
The GFV’s opinion is divided up into 8 sections some of which we’ll look at. The first is a Call for a rational discourse on the risks and opportunities of gain-of-function research in virology
We are told that "gain-of-function" is often used in an undifferentiated way, giving the false impression that this method is mainly used by researchers to increase the pathogenicity of pathogens. We’ve known that for a while. Only GOF 2.0 is of concern. They do not resolve this ambiguity. As no rational discourse is evident, don’t waste people’s time.
What does GoF research mean in virology and why is it necessary? One example is the insertion of genes for fluorescent proteins into a virus genome using genetic engineering, which makes it easier to identify infected cells in laboratory experiments. This does not increase pathogenicity. Of course it doesn’t increase pathogenesis, no molecular biologist would ever claim such a thing. It is of great use in the lab, but unhelpful to this discussion.
This type of research is important in order to understand how viruses can adapt to the human immune response or develop resistance to antiviral therapies and what measures can protect against them. Let’s take this at face value. The virus escapes, hence a new vaccine or drugs are needed. A no brainer. …we would not be able to assess the pandemic potential of viruses that are already circulating in nature. GOF 2.0 can’t assess the pandemic potential of viruses out there. Kawaoka has said recently that bird flu H5N1 is not a risk to humans, and he was one of the biggest proponents of GOF 2.0 back in 2012. The GFV is behind the curve.
Then there is a sharp turn. If changes are introduced that could possibly increase the risk potential of a pathogen due to altered transmissibility, reduced sensitivity to drugs or increased pathogenicity potential, this research falls into the area of additionally regulated "safety-relevant research" and is also referred to as GoF research of concern (GoFRoC). So, the focus of the document is the anemic and vague term safety related research is GOF 2.0. Talk about putting fluorescent proteins into viruses was irrelevant, just to fill space. They don’t seem to know that the ephemeral term GoFRoC is no longer used.
In the next section entitled GoF in virological research we learn that this research is also crucial in the international preparation for future pandemics ("pandemic preparedness"). Nonsense. Not even the NIH believe this when you dig into what they say. (Following the science).
However, the amplification or addition of properties (gain) is often at the expense of the viral ability to multiply, so that these modified viruses have a lower risk potential than the original viruses. The insertion of a furin cleavage site in a coronavirus Spike or flu hemagglutinin protein more often than not increases pathogenesis. It is trivial to engineer. For influenza this has been done by many groups including one in Germany – engineering resulted in four novel viruses that were lethal for chickens. Moreover, the H2, H4, and H8 reassortants were transmitted to some contact chickens. If you were a chicken this is definitely dangerous GOF 2.0.
Dear reader, please understand that if the virologist sets their mind on getting a virus with greater pathogenesis or transmission, they will probably get there. (Observer bias). Just remember what man has done with dog breading without knowing a thing about Mendelian genetics. Or Russian silver foxes in just 50 years. Utter nonsense.
In the section Safety-relevant research on viruses is closely regulated we learn that A laboratory for safety-relevant research must meet structural and safety requirements that are monitored by the authorities and must be approved by the supervisory authorities for safety levels 3 and 4. Finally we learn what safety-relevant research is. Yet it is unhelpful and imprecise. Work on Ebola virus is allowed only in a level 4 lab. Nobody in their right mind would be doing GOF 2.0 research on the Ebola virus. An earlier essay reported on coronavirus work that was performed in a level 2 lab when it merited level 3. This goes under the GFV’s radar.
Society needs researchers to work on Ebola and Marburg viruses to name but two. The public wouldn’t understand if we didn’t. By contrast, we don’t need GOF 2.0 research on microbes that does not yield any useful information that can be exploited by people working in public health – just take a look at numerous essays on this site.
We then read that In these laboratories, the safety standards are so high that unintentional escape of pathogens is reliably prevented if handled properly. The nasty little secret is in the words if handled properly. As scientists the GFV know that a perfect system doesn’t exist. Just look at the state of the world. As virologists they know that the leak of foot and mouth disease virus from the UK’s top BSL-4 facility at Pirbright was due to something prosaic like a bunged up waste pipe.
As they must know about the risks of handling biological agents they should know about black swan events, the disproportionate role of high-profile, hard-to-predict, and rare events that are beyond the realm of normal expectations in history, science, finance, and technology.
A recent example of the totally unexpected occurred in a NIH run BSL-4 lab at Fort Detrick. Speaking anonymously, an HHS source revealed that one of the researchers poked a hole in the other's protective equipment during a vicious 'lovers' spat'.
Four things:
• Researchers systematically overestimate the benefits of their work and underestimate the risks.
• Researchers occasionally get infected with the viruses and bacteria they study. Sometimes they die (Lab acquired infections).
• Microbes rarely get into nature but the data show that they do. Virology has had its Chernobyl moment.
This sentence should be rewritten thus: In these laboratories, the safety standards are so high that unintentional escape of pathogens is reliably prevented until something unexpected or stupid happens and then we’re not sure.
It is precisely for this reason that safety relevant research in virology should be reserved for natural virus that need our attention. The small but non-zero risks associated with GOF 2.0 virus research, for which there are no benefits, make the decision not to perform it easy to make.
The final section is entitled The safety regulations for risk research have proven their worth which is as should be, but which is valid until some black swan event comes along. Part of risk culture as in the nuclear environment is to reduce the number of risky labs. Society understands that. So why not come out clearly and say that experiments that have the potential for catastrophic risk, such as a pandemic, and no benefits to society, like the Fouchier and Kawaoka experiments, aka GOF 2.0, should be shelved? As the US has recently done.
As said before, the public is shouldering the risk while only the scientists benefit from another paper to add to their CV.
We’re told that This risk analysis is always reviewed by the ZKBS from security level 3. This is the Central Commission for Biological Safety (ZKBS): Yet only this year a paper on a novel coronavirus was criticized in the NY Times because it was performed at a biosecurity level 2 (Coronavirus biosafety levels). There are a surprising number of papers where groups are adapting animal viruses to growth on human cells that are performed in biosecurity level 2 labs. For example, canine distemper virus performed by groups in Wurzburg, Germany and Bern Switzerland (More GOOfing). More examples will be given in a forthcoming essay.
The GfV does not consider a tightening of the guidelines for the regulation and evaluation of safety-relevant research to be expedient. That has the merit of being clear. However, they go a step too far: The GFV recognizes the danger of a disproportionate regulation and slowing down of necessary translational and basic research in virology, which aims to protect and maintain human and animal health, also in international comparison. This is pushback, preserving the status quo by hiding behind regulations and committees.
The impact of bureaucracy on the UK’s government’s handling of COVID was… Get to the point. Read just one terrible conclusion from the UK independent enquiry; Across the UK, systems had grown to be overly bureaucratic. Instead of focusing on skills, technology and infrastructure, they were focused on creating groups, sub-groups and documents. Frightening, depressing.
On reading is at odds with the GFV and considers that experiments making novel human viruses from animal viruses should not be performed.
There is a curious twist to this document published on March 13, 2025. The day before two German newspapers, Die Zeit and Sueddeutsche Zeitung, published stories reporting that the German intelligence service believed it 80-90% likely that the COVID virus emerged from the Wuhan Institute of Virology.
This is hardly a coincidence, although the relationship is unclear. Whatever, it is pushback and could have been written by the staunchly pro-dangerous GOF research American Society for Microbiology that has been the subject of several essays with just two mentioned here (Deconstructing the portrait, Electroplated nickel silver).
The GFV don’t even seem to know that Dr Kawaoka, architect of GOF 2.0 research on the bird flu H5N1 virus has changed his mind. Our findings indicate that dissemination of viruses at these levels is unlikely and offers an explanation as to why, despite significant numbers of human infections, a mammalian transmissible H5N1 has not yet emerged.
The GFV’s position is dangerous and could impact the entire world.
Conclusion
Do not support GOF 2.0 research on viruses because it is dangerous and has nothing of benefit for public health.
Aside
There is a 2025 paper from a Chinese group showing adaptation of Canine Distemper Virus to human cells. …we conducted gain-of -function (GOF) experiments via serial passaging of the CDV 5804PeH strain in vitro in cells expressing human SLAM (Vero-hSLAM). This virus strain was designated 5804PeH-VhS. Emphasis added.
It required just one mutation (D540G) which was the same as that reported 12 years ago (CDV). See the essay More GOOFing. The virus grew well in human blood cells. Nothing was said as to the biosafety level, although presumably it was BSL-2 which is insufficient.
Very good points here Simon.
Germany, like many places, still has a long way to go with understanding the risks of dangerous biological science experiments...beginning with their own history.
Here you mentioned the Chernobyl of Virology;
The problem is that risk systems that place reward with laboratory scientists and risk with the population of our shared globe...well even in identifying Lab Leak events the scientists involved simultaneously identify why those risks are no longer relevant and thus their work should go on uninterrupted. As with this JHU paper in the lead up to COVID outbreak:
<<The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently gained popularity in discussions about the biosafety risks of gain-of-function (GOF) influenza virus research, as an argument for why this research should not be performed. There is now a moratorium in the United States on funding GOF research while the benefits and risks, including the potential for accident, are analyzed. Given the importance of this historical epidemic to ongoing policy debates, we revisit the evidence that the 1977 epidemic was not natural and examine three potential origins: a laboratory accident, a live-vaccine trial escape, or deliberate release as a biological weapon. Based on available evidence, the 1977 strain was indeed too closely matched to decades-old strains to likely be a natural occurrence. While the origin of the outbreak cannot be conclusively determined without additional evidence, there are very plausible alternatives to the laboratory accident hypothesis, diminishing the relevance of the 1977 experience to the modern GOF debate.>>
https://journals.asm.org/doi/10.1128/mbio.01013-15
So in this instance I am glad you mentioned Marburg Virus...so named as it leaked from a lab in Germany.
<<Marburg virus disease (MVD) is a severe disease with a fatality ratio of up to 88%. This rate can be lower with good and early patient care.
MVD was initially detected in 1967 after two simultaneous outbreaks in Marburg and Frankfurt in Germany, and in Belgrade, Serbia. The outbreak was associated with laboratory work using African green monkeys (Cercopithecus aethiops) imported from Uganda.>>
The denial of the dangers of virology, including DURC and GOF, by German scientists is not surprising.
https://www.who.int/health-topics/marburg-virus-disease#tab=tab_1
No doubt the irony of GOF experiments on Marburg Virus and similar viruses in Germany will be lost on the GFV who will no doubt claim that this history is irrelevant...the stupidity here is at Fawlty Towers level...Don't Mention the War...
https://www.youtube.com/watch?v=Tms0yk9kqVM
The main concern here is that Democratic and Independent processes are not yet strong enough to regulate Global Virology and other forms of Dangerous Biological research in any case.
The outcome may well be that due to a lovers argument in a lab anywhere in the world where scientists are people... we all will soon glow with fluorescent proteins...or worse.
Gives another sense to Lover's Glow.
Thank you and I agree:
<<On reading is at odds with the GFV and considers that experiments making novel human viruses from animal viruses should not be performed.>>