2023-10-13 11:50:12
Mistakes can also happen in safety laboratories – with potentially serious consequences. (picture alliance / dpa / Jan Woitas)
In the laboratory, viruses can be genetically manipulated to make them more dangerous. This is how researchers recognize which mutations pose a danger: the natural development of pathogens should be anticipated in order to stop them. In the case of the bird flu virus H5N1, for example, a targeted search is being carried out for mutations that would allow the virus to spread among humans at a similar rate as among birds.
But how useful is this so-called gain-of-function research really when it comes to preventing a pandemic? What would happen if a dangerous virus escaped the laboratory? Should the experiments be banned? Or regulate them more strictly? What alternatives are there?
The English name gain of function refers to the result of the research: the virus can do more followingwards than before. The more dangerous the pathogens, the higher the demands on laboratory safety. In an S2 laboratory (protection level 2), employees are allowed to examine relatively harmless pathogens, such as the flu viruses that cause sore throats, runny noses and fevers in Germany every winter.
For more dangerous germs, a higher biological protection level is required: S3 is the second highest. Four biolaboratories in Germany meet the highest safety level: these are the so-called BSL-4 laboratories. Experiments are primarily carried out here with filoviruses: Ebola and Marburg viruses, which cause severe, often fatal fevers with internal bleeding. BSL-4 laboratories only exist in 27 countries worldwide.
Martin Schwemmle from the Institute of Virology at the University Hospital of Freiburg primarily focuses on viruses that come from the animal kingdom. For example, influenza viruses, which primarily infect bats or birds, but sometimes also spread to people – with fatal consequences. “We have H5N1 viruses from Indonesia,” reports the researcher: “They were isolated from a child who died from it. And of course they are highly pathogenic. If you get infected with it, you might actually become so seriously ill that you can’t save the person.”
In safety laboratories, it is possible to specifically modify pathogens and give them new properties. Influenza viruses, for example, can be tailor-made in cell cultures – according to a modular principle. These viruses then have new properties that they did not have before. “Actually, each of these experiments is a gain-of-function experiment – depending on how you define gain of function,” says Schwemmle.
The main purpose of gain-of-function research is to be better prepared for a potential pandemic, says influenza researcher Martin Schwemmle. The viruses in nature are constantly mutating. With regard to the H5N1 bird flu, Schwemmle is worried – because H5N1 is currently eating its way through the global bird population as a pandemic.
“It is important to know how these viruses can change,” says the scientist. “These circulating influenza viruses on H5N1: If they have infected a mammal and unfortunately come back into the bird world and multiply there once more, it might be that “There are mammalian signatures in the virus that make it easier to then infect humans.”
The goal of gain-of-function experiments is not only to detect dangerous changes in a pathogen at an early stage. It’s also regarding understanding the pathogen itself – how it works, how it reproduces. With this knowledge, vaccines or effective antiviral drugs can be developed.
One scenario is that the virus does not make the jump by chance in nature, but in the laboratory through gain-of-function research: in other words, through the very measure that was actually intended to prevent a pandemic. This scenario is called “Lab Leak”: the catastrophe from the laboratory.
A flu virus that has killed at least 500,000 people may have escaped from a vaccine lab. The first cases were reported in Russia in 1977. The pathogen’s genome showed a striking number of similarities to an influenza virus that had been prevalent twenty years earlier. It therefore seems likely that it survived all these years in a laboratory.
But please note: none of the flu viruses were created through gain-of-function research. This suspicion was only expressed in connection with SARS-CoV-2.
The corona pandemic has reignited the debate regarding gain-of-function research. Some critics are calling for it to be banned. One of them is Günter Theißen, a geneticist at the Friedrich Schiller University in Jena. The risk is too great, he argues, of a sharpened virus escaping the laboratory.
Theißen points out “how dangerous it actually is when viruses that are already pathogenic for humans are made even more dangerous for research purposes.” Another point of criticism from Theißen: It is “unclear whether these experiments would even catch the things that occur in nature at some point.”
Critics also see the danger that the research results will be misused. For example, bioterrorists might take advantage of the results and methods published by researchers in specialist journals.
In 2009, an incident occurred in a German BSL-4 laboratory at the Bernhard Nocht Institute: an employee sustained minimal injuries with a needle through three pairs of gloves. The cannula was empty, but it had previously contained Ebola viruses. But the woman did not become infected.
Regarding the discussion regarding Corona and gain-of-function research, Stephan Becker from the Institute of Virology at the Philipps University of Marburg says: “Let’s assume that this Sars-CoV-2 pathogen did not come from the laboratory. but was actually transmitted to humans through an animal. Then one would say that it would have been irresponsible not to work with the SARS-CoV-1 pathogen in the laboratory and to understand how this virus is transmitted, which proteins in this virus are the targets for a vaccine, and what options there are to develop antiviral drugs. If we hadn’t known all of this, the development of the vaccines, which were created in a sensationally quick time, would have been carried out in a much more reduced manner. We certainly would have needed much longer. In this respect, I think the need to work on such viruses is actually obvious.”
So not doing research also has risks. Becker comes to the conclusion that the “H5N1 virus, for example, needs to be monitored very closely. And what we are seeing now is the largest spread of H5N1 worldwide.”
It is the dilemma of gain-of-function research: without it, we are blind to the danger of a pandemic. However, with it we increase the risk that it will break out.
In Germany there are a lot of laws and regulations for experiments with viruses and bacteria. In addition, the German Research Foundation and the Leopoldina have set up their own committee: the Joint Committee on Dealing with Security-Related Research.
In addition, so-called commissions for ethics in research (KEF) were set up. There are now KEFs at almost every university in Germany. They serve as a contact point for researchers who are planning a potentially risky project and are not sure whether it should be carried out for ethical reasons or not.
In Europe, only a small group of scientists are calling for a ban on gain-of-function research. In the USA, social attitudes towards the targeted viruses have always fluctuated. At the moment, following the pandemic, the signs point to a restrictive approach once more. According to the Global BioLabs Report, numerous laboratories with the highest security level are being planned.
One possibility would be to change our own behavior, because the greatest risk is ourselves. Virologist Stephan Becker: “I think it has something to do with how we humans interact with our environment. We have a way of exploiting our environment – and also exploiting animals through factory farming, through fur farms – which overall contributes to the fact that the danger of such pandemic spreads of viruses that jump from animals to humans has become very great .”
Dangerous virus variants can arise particularly well when different species come together in a small space in an animal breeding operation. Pigs or minks can serve as mixing vessels if, for example, they are infected with human flu viruses and bird flu viruses at the same time. The virus strains are then able to exchange genes and thus expand their host range.
In October 2022, there was a large outbreak of H5N1 at a fur farm in Spain. And since mid-July 2023, countless fur farms in western Finland have been affected. A mutation has been found that facilitates infection between minks.
The new mutant has not yet managed to spread to humans, but there is a risk that mixtures will be created in the minks that will then be as easily transmissible in the population as human influenza viruses – and as deadly as bird flu viruses.
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