Virologist Ron Fouchier: 'If you stop this research, you will surrender to the next pandemic'
Virology The fierce debate that arose when Ron Fouchier announced the results of an experiment in which he created a potential pandemic flu still haunts him.
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He feels "super honored", Ron Fouchier (56). On Friday 10 March, the Rotterdam virologist received the prestigious M.W. Beijerinck Virology Prize from the Royal Netherlands Academy of Arts and Sciences (KNAW) for his leading research on respiratory viruses. "To be on the same list as all those big names who have received the award is a great honor. The last time a Dutchman got it was 25 years ago – that was Ab Osterhaus." He involuntarily got a lump in his throat during the ceremony, he said after the ceremony.
The prize is perhaps even more special for Fouchier than for his predecessors. Because long before virologists were seriously threatened by corona opponents, he was already acquainted with such resistance.
A few days before the ceremony, the tall virologist sat down for a conversation at a table in his office on the seventeenth floor of Erasmus MC, where the Viroscience department is located. He likes to talk about his research, but keeps his arms folded reservedly. Because inevitably we come to an important pivot of his studies: the so-calledgain-of-functionresearch, in which you make viruses potentially more dangerous and research them in a high-security lab to learn from them, and to be able to develop medicines and vaccines.
Such research has been under heavy fire again since the corona pandemic in 2020, because discussion arose about a possible lab leak in Wuhan. It is the third time in nine years that gain-of-function research in the US has largely come to a standstill. The first time, in 2011, Fouchier was in the middle of the storm.Also read:The laboratory in Wuhan where corona started – or not
Fouchier has specialized in respiratory viruses, including the human flu virus, for the past 25 years. How do they develop, how do they escape the immune system? With these insights, scientists can develop medicines and vaccines. He discovered three previously undescribed viruses, including the human metapneumovirus and MERS in 2012, and characterized new viruses such as SARS in 2003.
And he filled a gaping hole in the textbooks for virologists with his research into zoonoses – animal viruses that can infect humans, and that may unleash pandemics. Very topical, now that a very pathogenic bird flu has been circulating continuously among wild birds worldwide since 2021. Thanks to his gain-of-function research, virologists know exactly which mutations the bird flu virus H5N1 needs to become transmissible between two mammals, such as between two humans.
The bird flu virus multiplies in the intestines of birds. Fouchier introduced known mutations of three previous pandemic flu viruses into the bird flu virus H5N1. He then allowed that virus to evolve further in ferrets, in his high-security lab. In this way, he discovered which mutations are needed for the bird flu virus to thrive in the much cooler respiratory tract of humans. There are only five.
There were the wildest stories going around, and we were not allowed to refute them
You just closed a video meeting with the RIVM. Are you worried about bird flu?
"Our research in 2011 showed that the bird flu virus H5N1 can become transmissible between mammals as a respiratory virus. That gives a warning. Since then, outbreaks have been culled rapidly, we sometimes already see two out of five mutations. And investments are being made in vaccine development. Hopefully, this will prevent a pandemic. The World Health Organization, the WHO, can put vaccine prototypes against H5N1 into production at the push of a button.Also read:Bird flu is always around. So why are virologists holding their breath now?
"Fortunately, the bird flu virus that is now circulating does not make many people sick, unlike the variants until 2012. Then there were hundreds of known infections, half of the people died from them. But it does transfer worryingly easily to mammals. Thirty different species have already been infected, from all kinds of bears to foxes, martens, otters, and seals, also here in the Netherlands. Often there are serious neurological symptoms, those animals can no longer stand on their feet. And you see some of the same mutations in the virus in these animals as in the ferrets in our lab at the time. Five years ago, we would have done the same research again a long time ago, with the virus that is now circulating. To assess the risk to people. But that's not possible now."
This type of research was also stopped in 2011, after you had submitted your manuscript to the scientific journalScience. Why did the US government stop the publication?
"The research was high on the priority list of the WHO, the European Union and the US National Institutes of Health, they had also funded it. Dozens of labs had been working on this for years. We happened to be the best. But the American government was afraid that our knowledge could be misused by terrorists. Big nonsense. Terrorists can get much more dangerous viruses in much simpler ways."
As a result, you were threatened.
"The American government forbade publication, and forbade us to communicate about it. The most wild stories circulated in the press, and we were not allowed to refute them. Then you come under fire. We got police protection."
A nasty development. Did you feel supported?
"Absolutely, by colleagues and Erasmus MC. But the Dutch government turned away from us. That certainly doesn't help. According to Henk Bleeker, then State Secretary for Economic Affairs, we should have applied for an export license. He invoked a European regulation fordual use: For example, if you design stealth technology, you can't just export it. Nonsense, the same regulation states that scientific research is not covered. But if we were to send it again without a permit, we would be locked up, including the entire board of directors of the Erasmus MC. It was absurd. Three months earlier, I had already told 500 virologists about the research at a conference in Malta. People had just written down those mutations there. For that reason alone, such a publication ban is an illusion."
After a year of wrangling, permit applications and lawsuits, Fouchier was allowed to publish. "The WHO stood firm. They did share the concern that it could be repeated in labs that are not as secure as ours. The WHO has drawn up recommendations and guidelines for this. Then the US changed tack."
Such research is done in labs with the highest levels of biosecurity. How are escape risks covered there?
"In a lab with the highest biosafety level, BSL-4, the researcher walks in a completely dense moon suit. These labs work on very dangerous and deadly viruses, such as Ebola, Nipah or Hendra. Up to 80 percent of infected people die from it. In a BSL-3 lab, one works with slightly less dangerous viruses, such as SARS, MERS or SARS-CoV-2. The researcher wears protective clothing and works in biosafety cabinets.
"Here in Rotterdam, we have built our BSL-3 lab specifically for respiratory viruses. We don't pack the employee but the experiment. This is completely shielded from the researcher: he can only work in the biosafety cabinet via large built-in fixed gloves. Samples go in and out through disinfection sluices. The steel cabinets are continuously monitored for leaks, and thanks to negative pressure, the air is always sucked in. It could also be qualified BSL-4, but that is not necessary for the viruses we work with."
And now you can't continue with this research again?
"No, it doesn't. Part of my research is funded by the US government, and it is temporarily banned there. There is a strong lobby against this kind of research, by people who are afraid that these kinds of viruses will escape from a lab."
Is that fear also unjustified? Surely viruses sometimes escape, such as SARS twice in Beijing in 2004?
"The number of virus escapes from a lab with serious consequences is zero. It happens sporadically that someone becomes infected in a lab, usually through a bite from a laboratory animal, or a broken glove. The lab worker then immediately goes into quarantine and is treated so that such a virus does not spread further. Here too we have quarantine rooms, but we have never needed them. In that BSL-3 lab in Beijing, a student had been eating, in an overcrowded lab, against all the rules. Such a lab is also immediately shut down in China. Worldwide, there have been two or three lab infections with Ebola, some with HIV, with needlestick incidents. So those escapes do happen, but they never created lab pandemics."
The number of virus escapes from a lab with severe consequences is zero
Not everyone thinks so.
"We all have the same doubts about the Wuhan Institute of Virology lab. But for SARS-CoV-2, there is no evidence yet that it comes from a lab. And there is certainly evidence that these types of viruses exist in the wild. So until proven otherwise, I assume that it has a natural origin.
"There is one incident that is sometimes mentioned: the return of the H1N1 flu virus in 1977. But that wasn't a lab incident, that was a study in which people were vaccinated with weakened virus in China or Russia – they keep that in the middle. That became a problem worldwide."Also read:Where did Covid-19 come from? Even American intelligence services do not agree on this among themselves
Is there also supervision of those recommendations that WHO made in 2012 for this type of research?
"There is no international regime of control of BLS-3 labs. But from the BSL-4 labs, they check each other, including the labs in China and Russia. The virology lab in Wuhan has been inspected by American BSL-4 experts. And our Rotterdam lab is also checked by the American and Dutch governments.
"Much creepier are the military BSL-4 labs. It is forbidden worldwide to make biological weapons. But you can defend yourself against it, for example against anthrax attacks or Ebola attacks, and do tests for that. So the American, Chinese and Russian governments have such labs, and the research that happens there is secret.
"So in the U.S., gain-of-function research is now prohibited if it's funded by the National Institutes of Health, but not if it's funded by the Department of Defense or by Homeland Security. While that is scarier. That should just be transparent."
Why is gain-of-function research allowed in Europe?
"Because the safety rules here are much stricter than in the US. We have strict rules for working with genetically modified organisms and ethical rules. The risk must be negligible for people and the environment.
"In the US there are less strict rules, and if your research is funded with private money, those rules don't apply. Then in principle you can just make such organisms in your garage."
"Was the Kafkaesque thing in 2011 also the reason that you stayed in the background during the corona pandemic?"
"We have two excellent coronavirus experts in Rotterdam, Bart Haagmans and Marion Koopmans, they have picked that up. I am indeed tired of this kind of nonsense, I prefer to stay in the background. Because the accusations stick to you anyway. My colleague in the US has never received a large grant again, I sometimes notice it in comments from reviewers on manuscripts and grants."
Then the recognition of this prize is extra special.
"Certainly. Virologists appreciate my research, it is often people from other fields who have difficulty with it. I am convinced that with this kind of research we can prevent a pandemic every now and then. And, if that doesn't work, be better prepared for it. If you stop this research, you will surrender to the next pandemic."
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Ron Fouchier (Tilburg, 1966) is professor of molecular virologyat the ErasmusMC in Rotterdam. He is also affiliated with the National Influenza Centre, which monitors the annual flu viruses and chooses the most appropriate vaccines.
He obtained his doctorate in 1995on HIV research. Three years later, he switched to research on respiratory viruses in Rotterdam. Among other things, he launched a Dutch surveillance network for bird flu.
He likes to spend his free time cooking or camping, or with his two daughters in De Kuip – he was their football coach for years, they go to all Feyenoord's home games. Fouchier lives in Rotterdam with his wife, who is also a colleague.
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