Will we avoid the next pandemic or risk causing it by hunting for viruses?

Will we avoid the next pandemic or risk causing it by hunting for viruses?

Covid-19 caught us off guard. And to prevent this from happening again, part of the scientific community is pressing to multiply efforts aimed at predicting which viruses could cause the next pandemic. Studying animal viruses before they make the famous leap of species, so as to be ready in case of need; going to find them in nature, and perhaps manipulating them in the laboratory to verify their zoonotic potential, and the risks they would entail once adapted to our species. However, not everyone agrees: in the US there is a heated debate on the advisability of stricter rules for these researches, defined as "gain of function", which provide for the creation of new potentially lethal pathogens in test tubes. The risk, according to skeptics, is that by playing too much with viruses that currently do not represent a danger to humans, efforts to prevent the next pandemic will paradoxically end up provoking it.

The debate in America The debate on gain of function studies gained global attention in 2011, when two research groups, one Dutch and one Japanese-American, announced that they had modified the virus of avian flu H5N1, making it capable of effectively infecting ferrets by air. At the time, many called the new virus the most dangerous pathogen in the world, and for a very good reason: avian flu is an extremely infectious (at least in birds) and dramatically lethal disease, with a mortality that in humans it is around 60% of the infected. The only thing that has prevented this virus from causing a catastrophic pandemic to date is the fact that transmission between human beings is almost impossible. In fact, all known cases date back to infections contracted from contact with sick birds, and even so the transmissibility of the virus to our species is extremely low. An H5N1 virus capable of infecting ferrets, however, is quite another thing: the step for infection between man and man is much shorter, indeed, practically taken for granted.

The objective of the researchers, of course , was to study more thoroughly the pandemic risks of avian and the mechanisms of infection of the virus, to move forward in the development of vaccines or therapies. According to many other scientists, however, the risks of the virus escaping from the laboratories in which it was kept (or worse, that some ill-intentioned entity could exploit the research to transform it into a biological weapon), far outweighed the potential benefits. In the wake of a debate that split the scientific community (and not only), two incidents in 2014 in American maximum security laboratories, in which personnel risked being exposed to anthrax and avian flu virus, the United States decided to order a temporary halt to gain of function research, blocking state funding in this area for three years.

The moratorium expired in 2017, with the approval of new guidelines for research funding gain of function which provides for an ad hoc evaluation of each project. The new rules should have allayed the doubts of skeptics, but just two years after their application, the National Institute of Health (Nih) approved the funding of two research aimed, again, to modify the avian virus to make it more dangerous for the human beings. The controversy has resumed, and the Nih has decided to open a public consultation on the issue. The first session took place on April 27, and as reported by an article in Nature, saw the participation of a large group of experts in virology and biosecurity, who asked for the tightening of the rules governing research in which pathogens are made more lethal or more transmissible, and the extension of the rules even outside the National Institute of Health, to reach all federal agencies, and even private entities such as pharmaceutical companies and philanthropic institutions.

The danger is real? The danger of gain-of-function research is linked to the risk of an accident causing dangerous viruses and bacteria to escape from the laboratories. And unfortunately, such cases have not been lacking even in recent years. In 2014, Usa Today reported, for example, that it obtained from the Centers for Disease Control and Prevention a series of documents that proved more than 1,100 accidents in American laboratories between 2008 and 2012, in which personnel had been exposed to viruses, bacteria or potentially dangerous toxins. In 2016, the first official report on the safety of American laboratories revealed as many as 199 accidents that occurred in 2015 alone. In one case, the laboratory staff was infected with the bacterium Coxiella burnetii, the causative agent of Q fever, a disease that reaches a lethality of 38% in the case of symptomatic disease, and which was studied and developed as a biological weapon up to the years 1960s by the US Army.

An accident, of course, does not necessarily translate into contagion or an epidemic. A 2012 CDC report, however, helps us to understand how often the risk has arisen in recent years. In fact, between 2004 and 2011 in America there were 11 confirmed cases of infections contracted during a laboratory accident, of which 4 occurred in laboratories with biosecurity level 3, just below those with biosecurity level 4 in which they are managed. pathogens with proven pandemic capabilities, such as Ebola or the Marburg virus. And even in these forts of science there is no shortage of problems. This is confirmed by a document of the Government accountability office: 21 confirmed cases of pathogens not neutralized correctly (and therefore in contact with personnel without the necessary safety devices) in American laboratories, several of which occurred in laboratories with biosafety level 4, which involved Ebola and the Marburg virus.

In short, the dangers seem unfortunately inevitable. And they grow as the number of labs handling dangerous viruses grows. In many cases, it is a risk that you cannot do without: to develop a vaccine, a drug or an antidote it is necessary to study viruses, bacteria and lethal toxins, and the risk of accidents (however extremely low) is counterbalanced. from the importance of this research to tackle diseases that represent a concrete risk for humanity. When we go to modify a virus otherwise harmless to our species, things change: the risk of unleashing it on humanity begins to have a very different weight in the balance with the entirely theoretical benefits that we could derive from it.

Also because it is not always easy to establish what should be considered as gain of function research. It is not enough for a virus to be modified (which is done all too often): the operation must make it more dangerous for our species, and obviously we can have very different opinions about it. This is demonstrated by the controversy that still surrounds the coronavirus research carried out at the Wuhan Institute of Virology with the support of the National Institute of Allergy and Infectious Diseases (Niaid). The funding, in fact, also arrived during the period in which the American moratorium was active, and after repeated parliamentary questions the story has now turned into a political case (Fauci, director of Niaid, is accused of having lied to the congress by denying having funded prohibited research), which revolves precisely around what to consider, and what not, as gain of function.

What about virus hunting? At this point the time has probably come to face the elephant in the room: the hypothesis of the lab leak, that is, that the current Covid-19 pandemic began right in the laboratories of the Wuhan institute of virology. There are no certainties about it. But in the last year convincing evidence has emerged that shows that in the laboratories of the Chinese city, located a few kilometers from the market where the first outbreak of Covid-19 is believed to have taken place, research was actually carried out that aimed to modify the Sars like coronaviruses. (those of which Sars and Sars-Cov-2 are part) to study the pandemic risks.

Whether it was during these experiments that Sars-Cov-2 originated it is impossible to say (the majority of experts currently denies that the virus has characteristics attributable to an artificial origin). Just as it is impossible to establish whether it was a laboratory accident that spread it in the nearby market, starting the pandemic. What is certain is that the fact that the facility was located so close to the epicenter of the pandemic, and that its biosecurity level 4 laboratory (where the SARS virus was studied) had opened just two years earlier, is at least curious. This, combined with the reluctance to reveal the research carried out by the institute demonstrated by the Chinese government, should be a wake-up call. Especially as regards the future.

It is in laboratories such as the one in Wuhan, in fact, that the new viruses discovered in bats, pangolins and other potential animal reservoirs are collected. And all it takes is a little bad luck, an accident that puts the staff in contact with a sample contaminated by a virus capable of making the leap of species, to set the tone for a pandemic, even without the need for dangerous gain of function experiments. Prior to the arrival of Covid, the EcoHealth Alliance research institute (of which Peter Daszak is the president) had collaborated with the Wuhan virology institute for years, within programs such as the Predict project (funded with 200 million dollars from the US government), accumulating over 15,000 biological samples of wild bats, and discovering about 400 new animal viruses, of which about fifty belong to the SARS family.

The idea behind this research is that a sufficiently complete mapping of viruses present in nature and ready for a leap of species would allow us to predict which pathogens pose the greatest risks, and to equip ourselves to prevent any problems. In the wake of the emergency of the last two years, the US government now seems intent on increasing efforts in this field. In October, it announced the launch of a new program, called Discovery & Exploration of Emerging Pathogens - Viral Zoonoses (Deep-Vzn), which will invest $ 125 million over the next five years to fund the collection and study of potentially dangerous animal viruses. . Similar is also the goal of the Centers for Research in Emerging Infectious Diseases (Creid), a network of institutes and laboratories (which will once again include EcoHealth alliance) dedicated to the mapping of viruses with zoonotic potential, and funded starting from 2020 from the National Institute of Allergy and Infectious Diseases with about $ 17 million a year.

“They look for the viruses that seem most dangerous, bring them to the laboratory, and experiment with us to determine which ones pose a risk pandemic, ”Kevin Esvelt, a biologist at MIT with expertise in gene drive and bioethics, told Vox. "The moment you take them to the laboratory and start working on them, you are running the risk of accidentally triggering a pandemic."

With the multiplication of laboratories working on animal viruses with high pandemic potential, the risks of errors and accidents will only increase. And even then, the potential benefits don't seem to outweigh the danger. The research and study of animal viruses has been going on for decades, and concrete results in terms of prevention or new therapies and vaccines are struggling to arrive. A great opponent of this strategy is (or was at least until a few years ago) the virologist Kristian Andersen, of the Scripp Research Institute (in 2020 his laboratory became part of the Creid network). In a comment published in 2018 in Nature together with colleagues Edward Holmes and Andrew Rambaut, he expressed himself in this way about the research that wants to predict the next zoonotic pandemics: "Large-scale genomic mappings of animal viruses will certainly increase our knowledge about diversity and the evolution of viruses. But in our opinion, understanding how diseases arise and how to prevent them will be extremely limited ".

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