TWiV 396: Influenza viruses with Peter Palese

TWiVVincent speaks with Peter Palese about his illustrious career in virology, from early work on neuraminidases to universal influenza virus vaccines, on episode #396 of the science show This Week in Virology.

You can find TWiV #396 at, or listen below.

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Moving beyond metagenomics to find the next pandemic virus

I was asked to write a commentary for the Proceedings of the National Academy of Sciences to accompany an article entitled SARS-like WIV1-CoV poised for human emergence. I’d like to explain why I wrote it and why I spent the last five paragraphs railing against regulating gain-of-function experiments.

Towards the end of 2014 the US government announced a pause of gain-of-function research involving research on influenza virus, SARS virus, and MERS virus that “may be reasonably anticipated to confer attributes to influenza, MERS, or SARS viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route.”

From the start I have opposed the gain-of-function pause. It’s a bad idea fostered by individuals who continue to believe, among other things, that influenza H5N1 virus adapted to transmit by aerosol among ferrets can also infect humans by the same route. Instead of stopping important research, a debate on the merits and risks of gain-of-function experiments should have been conducted while experiments were allowed to proceed.

Towards the end of last year a paper was published a paper on the potential of SARS-virus-like bat coronaviruses to cause human disease. The paper reawakened the debate on the risks and benefits of engineering viruses. Opponents of gain-of-function research began to make incorrect statements about this work. Richard Ebright said that ‘The only impact of this work is the creation, in a lab, of a new, non-natural risk”. Simon Wain-Hobson wrote that a novel virus was created that “grows remarkably well” in human cells; “if the virus escaped, nobody could predict the trajectory”. I have written extensively about why these are other similar statements ignore the value of the work. In my opinion these critics either did not read the paper, or if they did, did not understand it.

Several months later I was asked to write the commentary on a second paper examining the potential of SARS like viruses in bats to cause human disease. I agreed to write it because the science is excellent, the conclusions are important, and it would provide me with another venue for criticizing the gain-of-function pause.

In the PNAS paper, Menachery et al. describe a platform comprising metagenomics data, synthetic virology, transgenic mouse models, and monoclonal antibody therapy to assess the ability of SARS-CoV–like viruses to infect human cells and cause disease in mouse models. The results indicate that a bat SARS-like virus, WIV1-CoV, can infect human cells but is attenuated in mice. Additional changes in the WIV1-CoV genome are likely required to increase the pathogenesis of the virus for mice. The same experimental approaches could be used to examine the potential to infect humans of other animal viruses identified by metagenomics surveys. Unfortunately my commentary is behind a paywall, so for those who cannot read it, I’d like to quote from my final paragraphs on the gain-of-function issue:

The current government pause on these gain-of-function experiments was brought about in part by several vocal critics who feel that the risks of this work outweigh potential benefits. On multiple occasions these individuals have indicated that some of the SARS-CoV work discussed in the Menachery et al. article is of no merit. … These findings provide clear experimental paths for developing monoclonal antibodies and vaccines that could be used should another CoV begin to infect humans. The critics of gain-of-function experiments frequently cite apocalyptic scenarios involving the release of altered viruses and subsequent catastrophic effects on humans. Such statements represent personal opinions that are simply meant to scare the public and push us toward unneeded regulation. Virologists have been manipulating viruses for years—this author was the first to produce, 35 y ago, an infectious DNA clone of an animal virus—and no altered virus has gone on to cause an epidemic in humans. Although there have been recent lapses in high-containment biological facilities, none have resulted in harm, and work has gone on for years in many other facilities without incident. I understand that none of these arguments tell us what will happen in the future, but these are the data that we have to calculate risk, and it appears to be very low. As shown by Menacherry et al. in PNAS, the benefits are considerable.

A major goal of life science research is to improve human health, and prohibiting experiments because they may have some risk is contrary to this goal. Being overly cautious is not without its own risks, as we may not develop the advances needed to not only identify future pandemic viruses and develop methods to prevent and control disease, but to develop a basic understand- ing of pathogenesis that guides prevention. These are just some of the beneficial outcomes that we can predict. There are many examples of how science has progressed in areas that were never anticipated, the so-called serendipity of science. Examples abound, including the discovery of restriction enzymes that helped fuel the biotechnology revolution, and the development of the powerful CRISPR/Cas9 gene-editing technology from its obscure origins as a bacterial defense system.

Banning certain types of potentially risky experiments is short sighted and impedes the potential of science to improve human health. Rather than banning experiments, such as those described by Menachery et al., measures should be put in place to allow their safe conduct. In this way science’s full benefits for society can be realized, unfettered by artificial boundaries.

TWiV 363: Eat flu and dyad

On episode #363 of the science show This Week in Virology, The TWiVers reveal influenza virus replication in the ferret mammary gland and spread to a nursing infant, and selection of transmissible influenza viruses in the soft palate.

You can find TWiV #363 at

1977 H1N1 influenza virus is not relevant to the gain of function debate

The individuals who believe that certain types of gain-of-function experiments should not be done because they are too dangerous (including Lipsitch, Osterholm, Wain-Hobson,) cite the 1977 influenza virus H1N1 strain as an example of a laboratory accident that has led to a global epidemic. A new analysis shows that the reappearance of the 1997 H1N1 virus has little relevance to the gain-of-function debate.

Human influenza viruses of the H3N2 subtype were circulating in May of 1977 when H1N1 viruses were identified in China and then Russia. These viruses spread globally and continue to circulate to this day. The results of serological tests and genetic analysis indicated that these viruses were very similar to viruses of the same subtype which circulated in 1950 (I was in the Palese laboratory in 1977 when these finding emerged). Three hypotheses were suggested to explain the re-emergence of the H1N1 virus: a laboratory accident, deliberate release, or a vaccine trial.

Rozo and Gronvall have re-examined the available evidence for the origin of the 1977 H1N1 virus. While there is ample documentation of the extensive work done during the 1970s in the Soviet Union on biological weapons, there is no evidence that Biopreparat had attempted to weaponize influenza virus. The release of the 1977 H1N1 virus from a biological weapons program is therefore considered unlikely.

It is more likely that the 1977 H1N1 virus was released during testing of influenza virus vaccines. Many such trials were ongoing in the USSR and China during the 1960s-70s. C.M. Chu, a Chinese virologist, told Peter Palese that the H1N1 strain was in fact used in challenge studies of thousands of military recruits, an event which could have initiated the outbreak.

The hypothesis that the 1977 H1N1 virus accidentally escaped from a research laboratory is formally possible, but there are even less data to support this contention. Shortly after this virus emerged, WHO discounted the possibility of a laboratory accident, based on investigations of Soviet and Chinese laboratories. Furthermore, the H1N1 virus was isolated at nearly the same time in three distant areas of China, making release from a single laboratory unlikely.

It is of interest that with the onset of the gain-of-function debate, which began in 2011 with the adaptation of influenza H5N1 virus to aerosol transmission among ferrets, the ‘laboratory accident’ scenario for the emergence of the 1977 strain has been increasingly used as an example of why certain types of experiments are ‘too dangerous’ to be done (See graph, upper left). For example, Wain-Hobson says that ‘1977 H1N1 represented an accidental reintroduction of an old vaccine strain pre-1957, probably from a Russian research lab’. Furmanski writes that ‘The virus may have escaped from a lab attempting to prepare an attenuated H1N1 vaccine’. In the debate on gain-of-function experiments, the laboratory escape hypothesis is prominently featured in public presentations.

The use of an unproven hypothesis to support the view that some research is too dangerous to do is another example of how those opposed to gain-of-function research bend the truth to advance their position. I have previously explained how Lipsitch incorrectly represented the results of the H5N1 ferret transmission studies. We should not be surprised at this tactic. After all, Lipsitch originally called for a debate on the gain-of-function issue, then shortly thereafter declared that the moratorium should be permanent.

Rozo and Gronvall conclude that the use of the 1977 influenza epidemic as a cautionary tale is wrong, because it is more likely that it was the result of a vaccine trial and not a single laboratory accident:

While the events that led to the 1977 influenza epidemic cannot preclude a future consequential accident stemming from the laboratory, it remains likely that to this date, there has been no real-world example of a laboratory accident that has led to a global epidemic.

TWiV 321: aTRIP and a pause

On episode #321 of the science show This Week in Virology, Paul Duprex joins the TWiV team to discuss the current moratorium on viral research to alter transmission, range and resistance, infectivity and immunity, and pathogenesis.

You can find TWiV #321 at

The value of influenza aerosol transmission experiments

ferretA Harvard epidemiologist has been on a crusade to curtail aerosol transmission experiments on avian influenza H5N1 virus because he believes that they are too dangerous and of little value. Recently he has taken his arguments to the Op-Ed pages of the New York Times. While Dr. Lipsitch is certainly entitled to his opinion, his arguments do not support his conclusions.

In early 2013 Lipsitch was the subject of a piece in Harvard Magazine about avian influenza H5N1 virus entitled The Deadliest Virus.  I have previously criticized this article  in which Lipsitch calls for more stringent H5N1 policies. More recently Lipsitch published an opinion in PLoS Medicine in which he called for alternatives to experiments with potential pandemic pathogens. We discussed this piece thoroughly on This Week in Virology #287.  The arguments he uses in both cases are similar to those in the OpEd.

The Times OpEd is entitled Anthrax? That’s not the real worry. The title is a reference to the possible exposure to anthrax bacteria of workers at the Centers for Disease Control. Even worse than anthrax, argues Lipsitch, would be accidental exposure to a pathogen that could transmit readily among humans. He then argues that such a pathogen is being created in laboratories that study avian influenza H5N1 transmission.

Lipsitch tells us ‘These experiments use flu strains like H5N1, which kills up to 60 percent of humans who catch it from birds.’ As an epidemiologist Lipsitch knows that this statement is wrong. The case fatality ratio for avian H5N1 influenza virus in humans is 60% – the number of deaths divided by the cases of human infections that are diagnosed according to WHO criteria. The mortality rate is quite different: it is the number of fatalities divided by the total number of H5N1 infections of humans. For a number of reasons the H5N1 mortality ratio in humans has been a difficult number to determine.

Next Lipsitch incorrectly states that the goal of experiments in which avian influenza H5N1 viruses are given the ability to transmit by aerosol among ferrets is ‘to see what gives a flu virus the potential to create a pandemic.’ The goal of these experiments is to identify mechanistically what is needed to make an avian influenza virus transmit among mammals. Transmission of a virus is required for a pandemic, but by no means does it assure one. I do hope that Lipsitch knows better, and is simply trying to scare the readers.

He then turns to the experiments of Kawaoka and colleagues who recently reconstructed a 1918-like avian influenza virus and provided it with the ability to transmit by aerosol among ferrets. These experiments are inaccurately described. Lipsitch writes that the reconstructed virus was ‘both contagious and comparably deadly to the 1918 flu that killed tens of millions of people worldwide’. In fact the reconstructed virus is less virulent in ferrets than the 1918 H1N1 virus that infected humans. In the same sentence Lipsitch mixes virulence in ferrets with virulence in humans – something even my virology students know is wrong. Then he writes that ‘Unlike experiments with anthrax, creating such flu strains in the lab presents a danger that affects us all, because once it is out, such a strain would be extremely hard to control.’ This is not true for the 1918-like avian influenza virus assembled by the Kawaoka lab: it was shown that antibodies to the 2009 pandemic H1N1 influenza virus can block its replication. The current influenza virus vaccine contains a 2009 H1N1 component that would protect against the 1918-like avian influenza virus.

The crux of the problem seems to be that Lipsitch does not understand the purpose of influenza virus transmission experiments. He writes that ‘The virologists conducting these experiments say that by learning about how flu transmits in ferrets, we will be able to develop better vaccines and spot dangerous strains in birds before they become pandemic threats.’ This justification for the work is wrong.

Both Kawaoka and Fouchier have suggested that identifying mutations that improve aerosol transmission of avian influenza viruses in ferrets might help to detect strains with transmission potential, and help vaccine manufacture. I think it was an error to focus on these potential benefits because it detracted from the real value of the work, to provide mechanistic information on what allows aerosol transmission of influenza viruses among mammals.

In the Kawaoka and Fouchier studies, it was found that adaptation of H5N1 influenza virus from avian to mammalian receptors lead to a decrease in the stability of the viral HA glycoprotein. This property had to be reversed in order for these viruses to transmit by aerosol among ferrets. Similar stabilization of the HA protein was observed when the reconstructed 1918-like avian influenza virus was adapted to aerosol transmission among ferrets. It is not simply coincidence when three independent studies come up with the same outcome: clearly HA stability is important for aerosol transmission among mammals. This is one property to look for in circulating H5N1 strains, not simply amino acid changes.

Lipsitch mentions nothing about the mechanism of transmission; he focuses on identifying mutations for surveillance and vaccine development. He ignores the fundamental importance of this work. In this context, the work has tremendous value.

The remainder of the Times OpEd reminds us how often accidents occur in high security biological labortories. There are problems with these arguments. Lipsitch cites the emergence of an H1N1 influenza virus in 1977 as ‘escaped from a lab in China or the Soviet Union’. While is seems clear that the 1977 H1N1 virus probably came from a laboratory, there is zero evidence that it was a laboratory accident. It is equally likely that the virus was part of a clinical trial in which it was deliberately administered to humans.

Lipsitch also cites the numerous incidents that occur in American laboratories involving select agents. I suggest the reader listen to Ron Fouchier explain on TWiV #291 how a computer crash must be recorded as an incident in high biosecurity laboratories, but does not lead to the release of infectious agents.

Lipsitch clearly feels that the benefits of aerosol transmission research do not justify the risks involved. I agree that the experiments do have some risk, but it is not as clear cut as Lipsitch would suggest. Although ferrets are a good model for influenza virus pathogenesis, like any animal model, they are not predictive of what occurs in humans. An influenza virus that transmits by aerosol among ferrets cannot be assumed to transmit in the same way among humans. This is the assumption made by Lipsitch, and it is wrong.

I agree that transmission work on avian H5N1 influenza virus must be done under the proper containment. Before these experiments can be done they are subject to extensive review of the proposed containment and mitigation procedures. There is no justification for the additional regulation proposed by Lipsitch.

In my opinion aerosol transmission experiments on avian influenza viruses are well worth the risk. We know nothing about what controls aerosol transmission of viruses. The way to obtain this information is to take a virus that does not transmit by aerosol, derive a transmissible version, and determine why the virus has this new property. To conclude that such experiments are not worth the risk not only ignores the importance of understanding transmission, but also fails to acknowledge the unpredictable nature of science. Often the best experimental results are those which were never anticipated.

Lipsitch ends by saying that ‘There are dozens of safe research strategies to understand, prevent and treat pandemic flu. Only one strategy — creating virulent, contagious strains — risks inciting such a pandemic.’ Creating a virulent strain is not part of the strategy. Lipsitch conveniently ignores the fact that Fouchier’s H5N1 strain that transmits by aerosol among ferrets is not virulent when transmitted by that route. And of course we do not know if these strains would be transmissible in humans.

I am very disappointed that the Times chose to publish this OpEd without checking Lipsitch’s statements. He is certainly entitled to his own opinion, but he is not entitled to his own facts.

TWiV 291: Ft. Collins abuzz with virologists

Vincent, Rich, and Kathy and their guests Clodagh and Ron recorded episode #291 of the science show This Week in Virology at the 33rd annual meeting of the American Society for Virology at Colorado State University in Ft. Collins, Colorado.

You can find TWiV #291 at

Reconstruction of 1918-like avian influenza virus stirs concern over gain of function experiments

ferretThe gain of function experiments in which avian influenza H5N1 virus was provided the ability to transmit by aerosol among ferrets were met with substantial outrage from both the press and even some scientists; scenarios of lethal viruses escaping from the laboratory and killing millions proliferated (see examples here and here). The recent publication of new influenza virus gain of function studies from the laboratories of Kawaoka and Perez have unleashed another barrage of criticism. What exactly was done and what does it mean?

According to critics, virologists should not be entrusted to carry out gain of function studies with influenza virus; they are dangerous and of no scientific value. The headline of a Guardian article is “Scientists condemn ‘crazy, dangerous’ creation of deadly airborne flu virus” (the headline is at best misleading because the influenza virus that was reconstructed by Kawaoka and colleagues is not deadly when transmitted by aerosol). The main opponents of the work appear to be Lord May*, former President of the Royal Society; Harvard epidemiologist Mark Lipsitch; and virologist Simon Wain Hobson. They all have nasty things to say about the work and the people doing it. To his credit, author of the Guardian article Ian Sample (who likely did not write the headline) does present both sides of the study, and attempts to explain what was done. He even quotes Kawaoka on the value of the work. But much is left unsaid, and without a detailed analysis of the study, its importance is not readily apparent.

The work by Kawaoka and colleagues attempts to answer the question of whether an influenza virus similar to that which killed 50 million people in 1918 could emerge today. First they identified in the avian influenza virus sequence database individual RNA segments that encode proteins that are very similar to the 1918 viral proteins.

Next, an infectious influenza virus was produced with 8 RNA segments that encode proteins highly related to those of the 1918 virus. Each RNA segment originates from a different avian influenza virus, and differs by 8 (PB2), 6 (PB1), 20 (PB1-F2), 9 (PA), 7 (NP), 33 (HA), 31 (NA), 1 (M1), 5 (M2), 4 (NS1), and 0 (NS2) amino acids from the 1918 virus.

The 1918-like avian influenza virus was less pathogenic in mice and ferrets compared with the 1918 virus, and more pathogenic than a duck influenza virus isolated in 1976. Virulence in ferrets increased when the HA or PB2 genes of the 1918-like avian influenza virus were substituted with those from the 1918 virus.

Aerosol transmission among ferrets was determined for the 1918-like avian influenza virus, and reassortants containing 1918 viral genes (these experiments are done by housing infected and uninfected ferrets in neighboring cages). The 1918 influenza virus was transmitted to 2 of 3 ferrets. Neither the 1918-like avian influenza virus, nor the 1976 duck influenza virus transmitted among ferrets. Aerosol transmission among ferrets was observed after infection with two different reassortant viruses of the 1918-avian like influenza virus: one which possesses the 1918 virus PB2, HA, and NA RNAs (1918 PB2:HA:NA/Avian), and one which possesses the 1918 virus PA, PB1, PB2, NP, and HA genes (1918(3P+NP):HA/Avian).

It is known from previous work that amino acid changes in the viral HA and PB2 proteins are important in allowing avian influenza viruses to infect humans. Changes in the viral HA glycoprotein (HA190D/225D) shift receptor specificity from avian to human sialic acids, while a change at amino acid 627 of the PB2 protein to a lysine (627K) allows avian influenza viruses to efficiently replicate in mammalian cells, and at the lower temperatures of the human upper respiratory tract.

These changes were introduced into the genome of the 1918-like avian influenza virus. One of three contact ferrets was infected with 1918-like avian PB2-627K:HA-89ED/190D/225D virus (a mixture of glutamic acid and aspartic acid at amino acid 89 was introduced during propagation of the virus in cell culture). Virus recovered from this animal had three additional mutations: its genotype is 1918-like avian PB2-627K/684D:HA-89ED/113SN/190D/225D/265DV:PA-253M (there are mixtures of amino acids at HA89, 113, and 265). This virus was more virulent in ferrets and transmitted by aerosol more efficiently than the 1918-like avian influenza virus. The virus recovered from contact ferrets contained yet another amino acid change, a T-to-I mutation at position 232 of NP. Therefore ten amino acid changes are associated with allowing the 1918-like avian influenza virus to transmit by aerosol among ferrets. Aerosol transmission of these viruses is not associated with lethal disease in ferrets.

Previous studies have shown that changes in the HA needed for binding to human sialic acid receptors reduced the stability of the HA protein. Adaptation of these viruses to aerosol transmission among ferrets required amino acid changes in the HA that restore its stability. Similar results were obtained in this study of the 1918-like avian influenza virus, namely, that changes that allow binding to human receptors (HA-190D/225D) destabilize the HA protein, and changes associated with aerosol transmission (HA-89D and HA- 89D/113N) restore stability.

The ability of current influenza virus vaccines and antivirals to block replication with ferret transmissible versions of the 1918-like avian influenza virus was determined. Sera from humans immunized with the 2009 pandemic H1N1 strain poorly neutralized the virus, indicating that this vaccine would likely not be protective if a similar virus were to emerge. However replication of the ferret transmissible 1918-like avian influenza virus is inhibited by the antiviral drug oseltamivir.

Examination of influenza virus sequence databases reveals that avian viruses encoding PB2, PB1, NP, M, and NS genes of closest similarity to those of the 1918-like avian virus have circulated largely in North America and Europe. The PB2-627K change is present in 168 of 4,293 avian PB2 genes (4%), and the HA-190D change is in 9 of 266 avian H1 HA sequences (3%), and one also had HA-225D.

Most of the viral sequences used in this work were obtained quite recently, indicating that influenza viruses encoding 1918-like proteins continue to circulate 95 years after the pandemic.  Now that we have discussed the work, we can summarize why it is important:

  • An infectious 1918-like avian virus can be assembled from RNA segments from circulating viruses that is of intermediate virulence in ferrets. Ten amino acid changes are sufficient to allow this virus to transmit by aerosol among ferrets.
  • Confirmation that transmissibility of influenza virus among ferrets depends on a stable HA glycoprotein. This result was a surprising outcome of the initial studies on aerosol transmission of H5N1 avian influenza viruses among ferrets, and provided mechanistic information about what is important for transmission. Experiments can now be designed to determine if HA stability is also important for influenza virus transmission in humans.
  • We understand little about why some viruses transmit well by aerosol while others do not. Transmission should be a selectable trait – the virus with a random mutation can reach another host by aerosol, where it replicates and can transmit further. Why types of mutation allow better transmission? Why don’t avian influenza viruses become transmissible among humans more frequently? Are there fitness tradeoffs to becoming transmissible? These and similar questions about transmission can be answered with sutdies of the types discussed here. The list is not confined to influenza virus: aerosol transmission of measles virus, rhinovirus, adenovirus, and many others, is poorly understood. This work shows what can be done and will surely inspire similar work with other viruses.

Do these experiments constitute an unacceptable risk to humans? Whether or not the 1918-like avian influenza virus, or its transmissible derivatives, would replicate, transmit, and cause disease in humans is unknown. While ferrets are a good model for influenza virus pathogenesis, they cannot be used to predict what will occur in humans. Nevertheless it is prudent to work with these avian influenza viruses under appropriate containment, and that is how this work was done. The risk is worth taking, not only because understanding transmission is fundamentally important, but also because of unanticipated results which often substantially advance the field.

The Guardian quotes Lipsitch as saying that “Scientists should not take such risks without strong evidence that the work could save lives, which this paper does not provide”. The value of science cannot only be judged in terms of helping human health, no matter what the risk. If we only did work to improve human health, we would not have most of the advances in science that we have today. One example is the biotechnology industry, and the recombinant DNA revolution, which emerged from the crucial discovery of restriction enzymes in bacteria – work that was not propelled by an interest in saving lives.

The results obtained from the study of the reconstruction of a 1918-like avian influenza virus are important experiments whose value is clear. They are not without risk, but the risk can be mitigated. It serves no useful purpose to rail against influenza virus gain of function experiments, especially without discussing the work and its significance. I urge detractors of this type of work to carefully review the experiments and what they mean in the larger context of influenza virus pathogenesis. I understand that the papers are complex and might not be easily understood by those without scientific training, and that is why I have tried to explain these experiments as they are published (examples here and here).

In the next post, I’ll explain the gain of function experiments recently published by the Perez laboratory.

*May’s objection is that the scientists carrying out the work are ‘grossly ambitious people’. All scientists are ambitious, but that is not what drives Kawaoka and Perez to do this work. I suggest that Lord May read the papers and base his criticism on the science.

TWiV 287: A potentially pandemic podcast

On episode #287 of the science show This Week in Virology, Matt Frieman updates the TWiV team on MERS-coronavirus, and joins in a discussion of whether we should further regulate research on potentially pandemic pathogens.

You can find TWiV #287 at

Fouchier vs the Dutch government on influenza H5N1 research

ferretFrom Martin Enserink at ScienceInsider:

Virologist Ron Fouchier has suffered a loss in a legal battle with the Dutch government over the publication of his controversial H5N1 influenza research. On Friday, a Dutch district court ruled that the government was right to ask Fouchier to obtain an export license before sending two hotly debated papers out for publication.

Readers of this blog will remember the furor sparked by Fouchier’s experiments in 2011 in which he developed an avian influenza H5N1 isolate that could transmit among ferrets by aerosol. When Fouchier was ready to publish the results, the Dutch government required that Fouchier apply for an export license. In so doing they were applying EU regulations that are designed to prevent the spread of biological weapons.

Fouchier applied for and was granted an export license on 27 April 2012. Fouchier’s employer, Erasmus Medical Center, appealed the decision to require an export license for this type of work. It is this appeal that was recently denied by a Dutch district court.

Fouchier rightfully claims that such EU regulations put him at a disadvantage compared with other groups. For example, Kawaoka’s findings on aerosol-transmitted avian influenza H5N1 virus in ferrets were not subject to EU export rules and were published ahead of Fouchier’s paper. I can understand Fouchier’s position; science is very competitive and being the first to publish is a coveted position. I am not sure that this is an issue worth bringing to the courts: even though Fouchier published after Kawaoka, most virologists credit the observations to both laboratories. The Dutch government should recognize that its scientists must be internationally competitive and expedite such future requests.

In my view, there is a larger issue at stake here: what constitutes research that requires an export license? I would argue that the avian influenza H5N1 virus that Fouchier produced is not a biological weapon. Remember that while this virus could transmit among caged ferrets by aerosol, it was markedly attenuated. In other words, gaining the ability to transmit by aerosol came at a fitness cost that reduced the virulence of the virus in ferrets. Such a virus is not a biological weapon, and should not have been subject to EU export requirements.

I do not know who in the Dutch government reviews such export license requests, but hopefully the next time Fouchier or any other virologist applies, there will be knowledgeable virologists involved in making the correct decision.