Science, Innovation and Technology Committee
Oral evidence: Emerging diseases and learnings from covid-19, HC 1303
Wednesday 21 June 2023
Ordered by the House of Commons to be published on Wednesday 21 June 2023.
Members present: Greg Clark (Chair); Aaron Bell; Tracey Crouch; Katherine Fletcher; Rebecca Long Bailey; Stephen Metcalfe; Carol Monaghan; Graham Stringer.
Questions 62 - 196
Witnesses
I: Professor Ian Barr, Deputy Director, World Health Organisation collaborating influenza centre, Doherty Institute, Melbourne; and Professor Paul Digard, Chair of Virology, Roslin Institute, University of Edinburgh.
II: Richard Griffiths, Chief Executive, British Poultry Council; and Professor James Pearce-Higgins, Director of Science, British Trust for Ornithology.
III: Marc Lacey, Global Executive Director, Pandemic Response Solutions, CSL Seqirus; and Dr Meera Chand, consultant microbiologist, Deputy Director of TB, Acute Respiratory, Zoonotic and Emerging Infections, UK Health Security Agency.
Written evidence from witnesses:
Witnesses: Professor Ian Barr and Professor Paul Digard.
Q62 Chair: The Science, Innovation and Technology Committee is in session and we continue our inquiry into emerging diseases and learnings from covid-19. Today we are looking particularly at avian influenza. We are very pleased to have some expert and distinguished witnesses, and this morning we start with Professor Paul Digard, who is with us in person and is the chair of virology at the Roslin Institute in the University of Edinburgh. Professor Digard’s research focus is on the replication and pathogenesis of influenza viruses. Joining us from Perth in Western Australia is Professor Ian Barr, who is the deputy director of the WHO collaborating centre for reference and research on influenza in Melbourne. Thank you both very much indeed for joining us.
Perhaps I can start with a basic question to Professor Digard. What are the distinguishing characteristics of avian influenza, and how does it differ from other influenzas?
Professor Digard: Avian flu is influenza A virus. It is the same species as the flu A that causes seasonal flu in humans, but when we talk about avian flu we are talking about the source population of the virus. At heart, flu A is an avian virus, and there is far more diversity of the virus in the bird population than in mammals, or in humans in particular.
Q63 Chair: I think I am right in saying that H5N1 is the subtype that is circulating in birds worldwide at the moment. Is that correct?
Professor Digard: Yes.
Q64 Chair: Does that subtype have any particular characteristics that make it different from others?
Professor Digard: Yes, the primary characteristic of H5N1 is that in avian terms it is a high pathogenicity virus. It has a specific feature in its haemagglutinin, the receptor-binding protein, that means it is highly lethal in domestic poultry, but not necessarily in other species, including people, although it can be.
Q65 Chair: I read in the written evidence that in birds it has a nearly 100% mortality rate.
Professor Digard: It depends on the species of bird. For chickens, turkeys and quail, yes; but it is not necessarily so for other species. In ducks, with the right type of duck and the right strain of H5N1 there can be inconsequential infection. It is very variable.
Q66 Chair: Do we know what determines how lethal it is for different species?
Professor Digard: Partially, but not fully. It is a very complex interplay between the virus and the host, because the virus cannot replicate without the host, so it interacts with numerous components of the host species, which differ between species. So the outcome of infection can be very different, depending on the match.
Q67 Chair: Professor Barr, you obviously take a global view of this. How concerned are you, and how concerned is the WHO, about H5N1 in particular and avian influenza in more general terms?
Professor Barr: H5N1 has been with us now for 25 to 30 years, so it is not a new virus. What we have seen that is new, in the last few years, is a very extensive global spread of H5N1 through wild bird populations, for which, normally, these avian influenza viruses are quite inconsequential. This particular virus has spread through wildlife and now into poultry and a number of mammalian species, as a global situation. We have never really seen that before to the extent we see it now. That includes South America for the first time. The only continents that have not been impacted by H5N1 are Antarctica and Australia. That is a new development and many of the characteristics that we have seen before are amplified in the current virus, such that wild birds that were not affected by this H5N1 variety in the past are now affected, with spillover into mammalian species to an extent that we have not seen before. The saving grace is that currently there seems to be low transmission into humans. We have one positive note, and a number of negative notes.
Q68 Chair: Thank you. Do we have any knowledge of why wild birds have proved more susceptible to this strain, at this time, than in the past?
Professor Barr: Yes, we are starting to understand some of those factors. Clearly, the extent of the outbreak is unprecedented, so that will come into play. We are still learning about these viruses. Some of them are reassorting with other viruses that are in the wild bird populations, so it is not just H5 that is out there. We have another 15 different types of influenza A that are always around in wild birds. The viruses can mix and match and have bad consequences, at least for avian species. We have been able to detect some of this, but we are still learning about why some species that were not susceptible in the past seem to be more susceptible now. It will probably take quite a while to work that out. A lot of species are involved and there is a lot of carnage out there.
Q69 Chair: Thank you very much indeed. A final question from me, at this point, Professor Barr: are there any other subtypes in addition to H5N1 that we should be particularly concerned about from a global point of view?
Professor Barr: The H5N1 is the one that we are talking about, mostly, today. There is H5N6; there have been smouldering infections in China for the last eight years or so, and it has killed something like 40-odd humans. I am not sure of the exact number. It has a high case fatality rate, so that is one to keep an eye on. Not too many years ago, in 2017 and 2018, we had H7 high-path and low-path viruses, which caused death, and there may have been some limited transmission between humans. There are a number of viruses out there that we need to keep an eye on. Fortunately, the one that I just mentioned, the H7 outbreak in China, seems to have subsided in both humans and birds, but H5N6 is still smouldering and there are still cases and deaths being recorded in China right now. Possibly we need to focus on H5N1 for the moment, but there are other things happening out there that we need to keep an eye on as well.
Chair: Thank you very much. That is very clear. I will turn to my colleagues, starting with Katherine Fletcher.
Q70 Katherine Fletcher: Thank you very much, Chair, and professors. We are, in part, doing this inquiry because we are trying to understand in a post-covid world what risks there are out there. We hear a lot in the press and our reading about how the next pandemic is coming and there is an opportunity for viruses to cross into the human population. Professor Digard—and then I will come to you, Professor Barr—what is the likelihood that this suite of avian influenzas could cross over and become another covid-style pandemic? The 40-odd people killed by H5N6 sounds serious. A potential further mutation could cause us a big problem. Is that fair?
Professor Digard: What is the chance of it becoming an epidemic or pandemic? I cannot put a number on it. All that I can say is that it is not zero. It is a real risk, but to try to put a value on that would just be a guesstimate. I would put the current risk from H5N1 at the highest it has been for a decade or so. As Ian said, we have had it with us for the last 25-plus years, and for the first 15 or so years of that it was causing very severe infections in humans—but dead-end spillover events. It evolved away from that, and stopped causing so many human infections for a few years. Now it is perhaps threatening to come back but is looking less virulent. Does all that change its risk of going pandemic? It is very hard to say. But there is one point that I would add to what Ian said a moment ago. The thing that has changed about it, in the current epizootic, is that it is the first time we have seen it cause mammal to mammal transmission in natural infections. In previous forms, it has had to be pushed very hard in the laboratory setting to become transmissible between mammals, but now it seems to be doing it of its own accord.
Q71 Katherine Fletcher: I may come back to when it is being pushed in the lab to understand how far away it is from being able to jump. We do not have your expertise here, but could you basically describe the types of mutations and changes? Is it like one of those old-fashioned machines with the bells and the reel, where, at the moment, we have five bells, and you are waiting for the sixth one? Is it all about the receptor-binding protein mutation, or is it actually about its replication as well?
Professor Digard: No, it is multifactorial. A lot of it is to do with the receptor-binding protein. The virus would have to evolve the right receptor preference. It would also probably have to change the pH at which it triggers entry into the cell. You would have other changes that go along with that, potentially, in the other viral glycoprotein—the other antigenic protein, the neuraminidase—because the two work together and it has to be balanced. Then there is a suite of changes on the inside of the virus that let it replicate in a given host, some of which we understand and can predict, and some of which we cannot.
Q72 Katherine Fletcher: So it is the sheer scale of it.
Professor Digard: Well, yes. In terms of replication we know that one subunit of the polymerase is very important. There has to be a good match for a particular host species, but we also know it is very easy for the virus to change that specificity. A single nucleotide change will do it.
Q73 Katherine Fletcher: Because of how similar polymerases are across the whole of life.
Professor Digard: Yes. One amino acid change in the viral polymerase will usually get it to work with this key cellular protein of many species.
Q74 Katherine Fletcher: Understood. Thank you. Professor Barr, at the WHO you are obviously monitoring this kind of thing from Western Australia. What do you assess to be the likelihood that this could flip into a pandemic—affecting humans, to be clear?
Professor Barr: I think the chances are low, but rather than just giving my personal opinion I will refer to a couple of studies. One is done by a group of WHO experts, which I contribute to, and is called the TIPRA. Those are tools to look at potential outbreaks of pandemics. There is another one, run by the CDC, called the IRAT system. Both of those systems have looked at these viruses.
The TIPRA looked at this most recently, and it judged the likelihood of an emergence of this particular virus as 5.5. That sounds like a high number but it is a moderate scale. It is in a pack with many other viruses. When we did the study a couple of years ago the likelihood score was 4.5—so not much change there.
The CDC IRAT measure has not been run very recently, but it was run semi-recently. They did a study in 2021 and their score for the emergence likelihood was 4.6. They did a further study in 2022 and scored it as a 4.4. That is moderate in their scale, as well. Just to give some context, they also looked at H5N6, which I mentioned earlier—the virus that has been smouldering in China—and scored it as 5.3. That, again, is moderate, so on all scores to date by experts within the CDC and the WHO, emergence is scored as moderate—but that is not zero by any means.
Q75 Katherine Fletcher: Understood. Do you think that public health bodies and the Government, both in the UK and abroad, are perceiving these risks appropriately, especially in the post-covid context?
Professor Barr: It is very hard to get traction for another pandemic after SARS-CoV-2, so, while most Governments are aware of what is happening, especially in the northern hemisphere, and now in certain countries in the southern hemisphere, until something breaks on the human side of things I do not think it will be taken too seriously. On the veterinary side, things are taken much more seriously. A couple of weeks ago we saw that Brazil has now had outbreaks of H5N1 of this particular clade and I found out that it is the world’s biggest exporter of chicken meat, so it is making dramatic changes to try to control that. The food security side of the outbreak should not be ignored. While the human risk at this stage is low, the food security risk for many countries is often not discussed.
Q76 Katherine Fletcher: That is a very interesting point. A final question, if that is okay, Chair. Professor Digard, is the genetic similarity of farmed chickens, turkeys and ducks part of why the virus is so deadly when it gets into a crop?
Professor Digard: No, I would not say that particularly. I think it is more just down to the overall genetics of chickens and the virus. Farm chickens are relatively inbred, but there is quite a bit of variation in them. You have the distinction between broilers and layers, and the virus behaves the same in both populations of birds, as far as I know.
Q77 Katherine Fletcher: And would you add anything about how Governments perceive risks, Professor Digard—whether we are doing it properly?
Professor Digard: From the UK perspective, I would say that the Government are aware, and are responding. The BBSRC and DEFRA have put money into founding a research consortium on avian flu, to try to come up with some quick mitigations and forward strategies for this, so, yes, the Government here have responded, in my experience.
Katherine Fletcher: Understood.
Q78 Graham Stringer: If I may, I would like to ask Katherine’s question the other way around and look at a couple of cases from history where I would be interested in your interpretation. One case is what happened in 1976 in the States when David Lewis died of H1N1 and there was huge panic and a disastrous vaccination programme. He was the only person who got H1N1. I just wondered how you interpret that. More recently, when there was an epidemic of swine flu in Mexico, they panicked in the United States and when the virus got there it had very little impact. People got poorly, but very few people died. What is your interpretation of those two cases? What does it mean for how you look at the original infections?
Professor Digard: I view those episodes slightly differently. As to my understanding of the 1976 swine flu outbreak in the US, and the way it was interpreted, there was more than one infection—there were some severe infections, and they were worried that it was going to be 1918 all over again. That was a terrible pandemic, so they put a crash vaccination in process. You could view it as highly successful because they managed to vaccinate a decent fraction of the population in fairly short order. The perceived problem, as I see it, is that the epidemic fizzled out. It went away of its own accord, so you could view the vaccination programme as wasted time and effort—and of course you get adverse effects that may or may not be directly attributable to the vaccine, which led to political fallout, lawsuits and the whole thing being viewed as a failure.
I would not view 2009 as a trivial episode at all. Yes, it caused the most benign infection spectrum that we have seen from a pandemic strain of human flu so far, but still the scale made it a global pandemic. My colleagues in clinical medicine in the UK were saying that their respiratory clinics were overwhelmed. If 1 billion people are infected, it does not need a very high fraction of them to have severe disease for it to be a problem. I do not view it as trivial.
Q79 Graham Stringer: I suppose what I was getting at was that the case fatality rate in the States was a lot lower than in Mexico and a lot lower than was expected, and I was interested in your interpretation of that.
Professor Digard: Okay. The epidemiological information at the start of 2009 was unclear. I think Ian will know more about this than I do. The initial reports from Mexico were high, for severe infections, but it is unclear, to me at least, where that came from. When the virus spread elsewhere it was of much lower severity. Where the discrepancy comes from, I do not know. Maybe Ian does.
Q80 Graham Stringer: Professor Barr, do you want to add anything?
Professor Barr: Yes, it was very hard to untangle things that were going on in Mexico. There were various reports going around. There were probably more susceptible populations mixed in there. It was clear once it got to the US that we were not dealing with a highly pathogenic virus, in this instance. In my opinion we dodged a bullet in 2009. It was a virus that the majority of the population had seen before. The people most affected were children, and they were not severely affected. If it had been another virus, that we had not been pre-exposed to, we could have had much worse outcomes. Going back to earlier pandemics or quasi-pandemics, I think that we have learned a lot from 1976. I do not think those things will be repeated.
When to push the button to go is always a dilemma. I think people underestimate seasonal influenza; it kills a lot of people. To make the call to change over to a pandemic virus is always a difficult thing to do, but we have mechanisms in place to do it and we have learned that we can roll out vaccines a heck of a lot quicker post SARS-CoV-2, compared with what we attempted to do in 2009.
Graham Stringer: Thank you.
Q81 Aaron Bell: You have both said that the risk of a crossover to humans is low but not zero. What can and should we, both in the UK and internationally—I will come to Professor Barr in a moment—do to mitigate those risks, in terms of both preventing it from happening and minimising the effects if it did happen?
Professor Digard: We cannot prevent a pandemic from happening somewhere else in the world, but within the UK we can tighten up biosecurity and the processes for dealing with outbreaks in poultry, which has probably the highest risk of spillover from animals to people, and we can put foundations in place to deal with it if it does take off. This includes seed vaccines, lining up the plant capacity and having a plan for making vaccine in large amounts in a rush, if needs be.
Q82 Aaron Bell: Do you think those measures you have just outlined are largely happening in the UK?
Professor Digard: There are things we could do better but, certainly, at least some of it is happening.
Q83 Aaron Bell: What could we do better?
Professor Digard: The ground rock of dealing with poultry outbreaks in the UK is a cull procedure. In the infected premises and those around it, the birds are killed. I could be wrong, but I am not certain that we are dealing with that process as best we could. In 2003, when there was a high-path avian flu outbreak in Holland, the people clearing up the infected premises were vaccinated against human flu and were given the opportunity for prophylactic antiviral treatment to try to stop somebody in contact with the infected birds being simultaneously infected with human and avian flu, and the reassortment coming out that triggers a pandemic. My understanding is that we do not do that in the UK.
Q84 Aaron Bell: We probably should.
Professor Digard: I think it would be useful.
Q85 Aaron Bell: Thank you. Professor Barr, as Professor Digard said, we cannot control what is going on in every country in the world, but from an international perspective, what can we do to mitigate the risks of crossover and its impact, if and when it happens?
Professor Barr: There are a number of measures that you can take, probably none of which will be highly successful, but we are obliged to try these things; maybe some of them will be beneficial and some will not. In terms of the outbreaks you have seen in the UK, the measures would be: proper follow-up studies of the people most highly exposed to the viruses—there are a lot of viruses around in some of these outbreaks; proper PPE; as Paul said, antivirals being available; proper clean-up procedures; and following up with serology studies. So far, we have not seen much spillover or evidence of these viruses infecting man, but serology would give us that extra idea to see whether there has been enough virus taken up by a person and exposed in them to create an immune response. That is a good measure of whether some of these viruses might be slowly adapting to man without showing any symptomatic responses.
The other thing that has been talked about in the EU is vaccinating poultry. It is very controversial because evidence of antibody to influenza viruses, whether H5 or other influenza viruses, can be a halt on exports, so the EU is dealing with that. I understand that France is strongly considering vaccinating its birds. Other countries that are also looking at that, such as Belgium and others, probably will not vaccinate their birds. That is something for the agricultural and poultry industries to get their heads around. Clearly, it will be much more difficult to vaccinate wild birds, but maybe zoos and so on could do that.
The other thing clearly on the minds of western countries is stockpiles. Australia has stockpiles of vaccines for H5 which are up to date, so while they could not roll that out for the whole country, they could maybe do some ring vaccinations if necessary, or vaccinate healthcare workers who are involved in any particular outbreak. As well as stockpiles of vaccines, there are large stockpiles of antivirals that are held by the Government and ready to be rolled out. I am sure the UK probably has something similar, but I am not aware of the actual amounts of either of those.
Q86 Aaron Bell: Thank you, Professor Barr. You have set out a lot of practical challenges for Governments around the world, for agriculture departments and so on. Within the scientific community, do you think there is sufficient collaboration going on across the world in terms of fully addressing all the challenges of avian influenza and further research into it?
Professor Barr: The scientific community is very aware of the attention that these viruses are getting. As always, there is some difficulty sharing these viruses around laboratories. Only high-containment laboratories can deal with them. There is the overriding issue of gain of function, which has been in the spotlight. There is some hesitation about what to do with some of these viruses in some of the laboratories, but in the major ones, where we have these viruses, we can study them safely. We have some initial data, but, given the breadth of these outbreaks and the reassortment going on, it is very hard to track all the potential viruses and their outcomes. Recent publications have shown that a few little changes in the genetic make-up of these viruses can make them much more deadly in mammalian species. We really need to understand whether these are isolated viruses or whether they are becoming more common around the globe. That will take some time to work out.
Q87 Aaron Bell: You mentioned gain-of-function research. Is that going on into the avian flu family or, indeed, all the flu families? If so, what gain of function are scientists looking at in order to combat potential future natural developments?
Professor Barr: Gain of function is a very testy phrase. Some people would consider culturing a virus in a test tube gain of function. I certainly would not: it is a necessary part of understanding the virus’s replication and evolution. Putting viruses into animals could be considered gain of function, but, again, to understand the pathogenicity and severity of these things, that is a very necessary element. I do not think people are setting out to change the natural composition of these viruses; they are more trying to understand what impact these changes, which are occurring naturally, are having on the virus and on the virus host. There is much less blue-sky research being done in that area now than there was 18 years ago.
Q88 Aaron Bell: Have the allegations of what happened at Wuhan changed the environment for people operating in this field? The suggestion about Wuhan is that a furin cleavage site was put into a SARS-covid-like virus. From what you just said, it does not sound like that has happened in an equivalent way in terms of genetically modifying the code of any flu virus. Is that presumably off the table now?
Professor Barr: Most countries would probably consider it off the table. The furin cleavage site in the Wuhan story has been vastly overplayed, so I do not think that is a clear signal of gain of function. These things happen naturally, so I would be very careful about interpreting those sorts of modest changes in viruses as a gain of function coming out of a laboratory and not occurring naturally.
Q89 Aaron Bell: Thank you. Professor Digard, you said in answer to Katherine Fletcher that we were pushing the virus hard in the lab. What does that mean? Is that gain of function?
Professor Digard: No. I did not say that we were pushing hard; I was referring to controversial research done a decade or so ago with an older version of H5, where labs in the US and the Netherlands tried very hard to get it to become mammalian-transmissible and succeeded. That was viewed in some quarters as the worst sort of gain-of-function research, because potentially, if there was an escape of that virus—
Q90 Aaron Bell: Was that done through selective breeding or genetic modification?
Professor Digard: It was done through a combination of genetic modification and serial passage to select for virus variants that have the desired characteristics.
Q91 Aaron Bell: Are you aware of any labs in the UK or worldwide that have taken that approach to the current H5N1—to push that and see where it might go?
Professor Digard: No, I am not. Things are aimed far more at loss-of-function studies. The current H5 already has a furin cleavage site. What we do is we take it out so that we can work with it in the laboratory more safely—or prepare vaccines for it, for that matter.
Q92 Aaron Bell: Thank you. What support or resources are needed from the UK Government and so on to support scientific collaboration? Do you think there is sufficient support for these?
Professor Digard: You will never ask a scientist what is needed and not get the answer, “More money, please.”
Aaron Bell: Yes.
Professor Digard: The research support is there, and, yes, we would like more. On the collaboration side in the UK, BBSRC and DEFRA funded the flu map consortium, and we are currently negotiating with UKRI for a bigger and broader extension. What would also help is legislative flexibility over handling the pathogen. Ian said it is only workable within high-containment laboratories. The UK has a very specific system where it has dual classification for animal and human pathogens that are not quite the same. They overlap and partially map on to each other, but they are not identical. For H5N1, that means there are only two laboratories in the UK that can work on it and handle it for diagnostic and surveillance purposes. That is a hindrance, which could be looked at without leading to any higher risk from a laboratory perspective.
Q93 Aaron Bell: I have one final, more generic question for you both. Does the fact that we are aware that this virus is circulating give us an advantage in preventing the next pandemic, whatever that might be, or is it more likely that the next pandemic will come from an unexpected, previously unknown source?
Professor Digard: I cannot give a hard answer to that question, but, of course, knowing what is out there and what is a risk is a huge advantage. The story is that H7N9 was causing huge problems in China five or six years ago, and then it stopped. From the outside world, the epidemiological spillover into humans disappeared, and that coincided with the aftermath of the Chinese instituting a mandatory vaccination policy in poultry, which took away the source of human infection. They would not have done that if they had not known about the virus and had not been looking at the sequence of it, thinking, “This is looking more and more like a mammal-transmissible virus.”
Q94 Aaron Bell: Professor Barr, I put the same question to you. Following on from what Professor Digard said, obviously we get an advantage from knowing what is out there, but is it the case that we are focusing too much on what we know about and not enough on what we do not know about, to use a Donald Rumsfeld-type phrase?
Professor Barr: Yes, Donald put it very well. What we do not know, we do not know, so what are we left with? We can deal with what we can deal with. We know that H5 is a problem and that H7 is too. The WHO and a number of laboratories involved in the WHO network have generated seed vaccines to those viruses. Not many of them have gone into humans, so one area we could definitely look at is doing some human clinical trials to understand how these avian viruses behave and how our immune responses to the viruses are generated.
There are plenty of things we can do. I would be very reluctant to give odds on what the next pandemic virus will be. It is a very difficult task and we can only prepare for what we know about and hope that it will stand us in good stead to react to anything that comes down the line, whether it is avian influenza, swine influenza or something that is not even an influenza virus, as we have seen with SARS-CoV-2. We have learned a lot from the current pandemic, and I hope that that will add to what we currently know about the influenza situation globally.
Aaron Bell: Thank you, professor.
Q95 Chair: Professor Digard, could you say something more about what you said to Aaron about gain-of-function research, in particular pushing viruses into mammalian transmission? I think you said that that happened in the 1970s, and that people have drawn back from doing it.
Professor Digard: The controversial work on H5N1 was done in the early 2010s, but yes, people have drawn back from that.
Q96 Chair: I am interested in the governance of that, as it were. Is that a set of individual decisions, or is there an international protocol that has restricted that?
Professor Digard: It is handled at a national level but also by consensus among the research community, and the funders also influence it.
Q97 Chair: Are there structured dialogues to align policies on that internationally?
Professor Digard: We talk about it. I do not know whether there is anything formal at the moment.
Q98 Chair: I am interested because it has applications for other things, such as the governance of AI, for example. When one recognises something that one should not do, what are the governance arrangements that can stop it? There is an interesting case study. What has stopped this push into mammalian transmission? Professor Barr, do you have a perspective on that?
Professor Barr: Most Governments have relooked at this. In the US, they have put a stop on all of what they consider gain of function—and it is a very conservative definition—for a number of years while they address those questions. In Australia, we did not put a stop on that type of work with legislation, but there was an informal stop on any of that sort of work being considered. What has come out of it is that, clearly, there is a more responsible attitude from the institutional biosafety committees that currently have to approve any of this type of work in Australia, and that is reviewed by other committees in the federal system. There is a check and balance system in place in Australia, and I am sure that that is the case now in many countries around the world.
Q99 Chair: What about countries like China and Russia, which in many respects do not operate according to the same like-minded rules and understandings?
Professor Barr: I am not really in a position to comment on that. I know for a fact that, following SARS-CoV-1, some 20-odd years ago, they closed a lot of their laboratories and tightened up a lot of their handling of pathogenic organisms, but I would not like to comment on their procedural actions for dealing with scientific research.
Q100 Chair: Thank you. Professor Digard?
Professor Digard: My Chinese collaborators operate under very similar guidance to what we have here in the UK. It is overseen at the national level through a series of risk assessments and permissions.
Chair: Thank you very much indeed; that is very interesting.
Q101 Tracey Crouch: Following on from that, and your response to Aaron about legislative flexibility for pathogen handling, is there a country of best practice that you would like us to look at?
Professor Digard: The specific thing I am referring to is the difficulty of doing surveillance for H5N1 in the UK at the moment. The SAPO legislation means that we cannot take a sample from an infected animal or wild bird and deal with that sample for PCR analysis anywhere except at the APHA or the Pirbright Institute, whereas you can make the argument that, if you collect the sample in a way that means the virus is then activated at the point of contact, it comes out of the SAPO legislation. We are talking to HSA about that. It has held surveillance back over the recent epizootic so far.
Q102 Tracey Crouch: Which countries do it better?
Professor Digard: My colleagues in the US and China tell me that they have one framework that treats pathogens the same, whether they are animal or human. That is simpler.
Q103 Tracey Crouch: How do we ensure that the HSA, the Animal and Plant Health Agency and other public bodies are able to provide accurate guidance regarding avian influenza, especially in the light of some of the answers that both of you have given this morning already to some of our questions?
Professor Digard: Committee systems work towards that. For instance, DEFRA has a science advisory committee that brings in experts on the subject area to advise. Does that answer your question?
Q104 Tracey Crouch: Sort of. Do you think that the guidance issued so far has been good enough, or could it be improved?
Professor Digard: Things can always be improved. I would not say that the guidance so far has been poor; it has been okay. I have helped write some of it.
Q105 Tracey Crouch: So it is excellent. Professor Barr, with a global oversight, do you have any comments about how we can ensure that we have accurate guidance regarding avian influenza?
Professor Barr: Most countries have these silos between agricultural and human health, and the One Health concept has tried to break that down a bit. I would encourage the UK and other countries to embrace the One Health concept more. It is important to have capability at all your laboratories to detect these viruses so that, if something unusual turns up, at least there is diagnostic capacity to test those viruses. You do not need to do anything more than test them. That is a very low-risk operation, so most labs are capable of dealing with these clinical samples without any risk to the person testing them or people around them. Having good diagnostic capacity at your key laboratories is important, and trying to break down the barriers with One Health and in any legislation that might be limiting work in the human or agricultural space.
Tracey Crouch: Thank you.
Q106 Graham Stringer: Professor Barr, I have a question that has been at the back of my mind for a long time. When the northern hemisphere decides what vaccines to develop for the winter, we look at what has happened in the southern hemisphere—in Australia, New Zealand and so on. When Australia develops vaccines, how do you decide what to put in yours?
Professor Barr: There is a bit of navel-gazing. The north looks south, and the south looks north. Sometimes you can see patterns that viruses track around, but sometimes they do not. We take a much more global view of viruses, collecting them throughout the globe. These are WHO decisions, which are usually replicated in Australia. For the southern hemisphere vaccines, which are usually given in March or April, we have a meeting in the prior September with the WHO, and we look at all the data around the world. That includes tropical regions, where viruses circulate all year round; we do not just look at particular temperate zones.
We try to do things six to 12 months in advance of when these viruses will be circulating, and we give it our best guess. Sometimes we do not get it completely right, but often we do not get it too far wrong, either. We certainly get criticised if the match is not a very high match. It is a little bit of a gamble. We use modelling, AI and all the things we have talked about this morning to try to give us a better insight into matching of the virus, until we can develop virus vaccines that are more broadly reactive and last for a longer period. Influenza is a tricky beast, even at the seasonal level.
Q107 Graham Stringer: About five years ago, when the northern hemisphere got it wrong with the vaccine it was using, on this Committee we did not know much about it at the time, so we got experts in and asked them about the development of a vaccine. We asked them whether there was a prospect of a universal flu vaccine. If I remember correctly, their answer was possibly in 10 years. Is there a time horizon for the development of a universal flu vaccine?
Professor Barr: It is very challenging. Let us put another 10 years down on the table.
Graham Stringer: I thought that might be the answer.
Professor Barr: We have been talking about this for 50 years and we have made little progress. We cannot even make a highly efficacious seasonal vaccine when we are putting only four components in it—much less covering all types of influenza A and influenza B.
Q108 Graham Stringer: Generally, are any countries approaching the threat and risk of avian flu better than others? Where would we look for the best exemplars?
Professor Barr: From my point of view, you would not focus on any one country. Paul has already given the example of China, which has shown the effectiveness of vaccinating poultry to reduce the risk of human spillover. Other countries probably have very good biosecurity approaches to raising poultry and other species that might be at risk. I would not focus on a single country but maybe do a bit of a broad sweep and see how countries are reacting to this current wave. I am sure that there are things that could be learned from many countries, rather than a single country.
Q109 Graham Stringer: The World Health Organisation, and Governments, are considering amendments to the international health regulations that would give the World Health Organisation more control over individual countries’ responses to the threat of not just avian flu but other potential epidemics and pandemics. What is your view of that? Will we lose something if we hand over that control to the World Health Organisation?
Professor Barr: Updating the IHR is under discussion and another piece of legislation is also circling around: the pandemic treaty. It is a little unclear in my mind how those two will pan out and interplay. The Nagoya protocol is also impacting these outcomes. In my mind, we are still in a little bit of a state of flux about how these will work and interplay with the various Governments’ own decisions.
Q110 Graham Stringer: To ask a previous question in a different way, is it possible to guess or work out the chances of where a serious outbreak of avian flu will take place? Is it more likely in one country than another? If so, which country?
Professor Barr: I have never played roulette and I do not intend to start now. You are asking a very difficult question. Clearly, countries that have more susceptible populations of either swine or poultry are at higher risk from a spillover event that might then end up as an epidemic or a pandemic. The role of the animal-human interface is something we do not understand well, and a super-spreader event might be the cause of the next pandemic, rather than something occurring in a particular country.
Q111 Graham Stringer: My last question, Professor Barr, is double-barrelled. Do you think we will be better prepared because of lessons learned, or not learned, from the covid epidemic, if human-to-human transmission of avian flu is detected outside the UK—in Australia, in your case? What response do you think the UK or Australian Government should make, and will it include lessons learned from covid?
Professor Barr: One of the big lessons that we learned from the pandemic, at least for seasonal influenza, was that you can stop influenza in its tracks by doing all the things that we did for covid. That was pre-vaccine. Stopping international travel, halting personal movement and introducing mask-wearing are all non-pharmaceutical interventions that will, for sure, work for influenza, whether it is a new pandemic strain or something that we might have seen before. Those things will work, and we are now in a much better position in terms of making vaccines quickly. We have the mRNA platform, which we never had before, so we are in a much better position there, too.
We have learned a few lessons: how to make vaccines quickly; stop transmission, at least to some extent; and ameliorate transmission events in both the community and hospitals. We have learned quite a bit, and the UK has contributed a lot to our understanding and to our quick response to new pandemics in the way in which you have set up clinical trials and incorporated research studies into these sorts of events. That has been very beneficial to the rest of the world as well.
Graham Stringer: Thank you very much.
Chair: Thank you, Graham. I thank both of our witnesses for a fascinating set of insights this morning. Professor Paul Digard and Professor Ian Barr, thank you very much indeed for your evidence today.
Witnesses: Richard Griffiths and Professor James Pearce-Higgins.
Q112 Chair: I am going to invite our next pair of witnesses to join us at the table. As they come up I will introduce them. Professor James Pearce‑Higgins is director of science at the British Trust for Ornithology. He is also a member of the BTO’s steering group for avian influenza. Thank you very much indeed for joining us. With him is Richard Griffiths, chief executive of the British Poultry Council and also a director of the International Poultry Council. We are very pleased to have both of them here today.
Perhaps I can start with a question to Professor Pearce‑Higgins. What is the current situation in terms of the spread of the virus of avian flu among wild birds, and how has this changed in the past few months?
Professor Pearce-Higgins: Thank you very much for the invitation to come and speak to you today. You will be very much aware of the unprecedented nature of the outbreak in wild birds last year, particularly how it impacted large numbers of our breeding seabirds. We are in a different situation this breeding season. We are not seeing so much of an impact on those coastal seabird colonies. Numbers are very much down, particularly for some species, compared with previous years. I will perhaps talk a little bit about that further down the line, but we are seeing very high levels of mortality in black-headed gulls and common terns, so the virus has shifted its behaviour and we are now seeing it impacting much more on inland seabird colonies.
Q113 Chair: From what? It has gone to black-headed gulls and terns. Which species were affected before?
Professor Pearce-Higgins: Last year we saw very high levels of mortality among a lot of coastal and seabird species, including great skuas, gannets, a number of tern species, guillemots and kittiwakes, which are very much coastal and cliff-nesting species. Some of those are species of which we hold internationally important numbers. For example, 60% of the world’s great skuas and gannets are in this country. Those impacts will have had significant population level consequences. There is survey work happening at the moment to understand the magnitude of the impacts on those populations. Now we are seeing that change to affect black-headed gulls and, probably by association because they share breeding sites, common terns. We estimate that over the past three months or so probably as a minimum figure 5% of our black-headed gulls will have succumbed to the virus.
One of the things that has changed in our capacity to understand what has happened since last year is that we have been very proactive. We have developed our BirdTrack app, which is a web portal and phone app where people can submit sightings of birds. We have made it easy for people also to submit sightings of dead birds. We are getting records from the general public—birdwatchers—to enable us to track those mortalities around the country almost in real time, coupled with professional conservationists and the statutory nature conservation bodies—RSPB and so on—encouraging their site staff to submit sightings to a system called Epicollect. We have been collating those to track those mortalities week on week and reporting it back, so we are in a much better situation in understanding the wild bird context than we were this time last year.
Q114 Tracey Crouch: To follow that up, I read that puffins, curiously, have been left relatively unscathed by this. Is there any particular reason why that might be?
Professor Pearce-Higgins: There is variability in the species being affected, even between colonies of the same species. Last year lots of sandwich terns in England and the Netherlands had very high mortalities in colonies, whereas some of the Scottish sandwich tern populations were relatively unaffected. There are some real vagaries in terms of the virus that we do not fully understand. As we heard in the previous session, those species-specific differences can be very difficult to understand. Currently, we are doing some analyses of those cases over the past couple of years to try to give us a better handle on what the potential risks and vulnerabilities for different species are.
I understand that at least part of the change this year is perhaps down to changes in the virus. We are now seeing a more gull-adapted version of the virus, which is perhaps why it is sweeping through our black-headed gulls. We started to get signs of black-headed gull mortality in southern Europe, in France, in the winter. That is where a proportion of our birds spend the winter, so probably on migration back to the UK they would have transferred it to us. It is now spreading through the breeding colonies and is also impacting black-headed gulls right across Europe in terms of current large-scale mortalities. I suspect the virus is evolving, and there are also vagaries and chance in the susceptibility of different species and colonies.
Q115 Tracey Crouch: Am I right in thinking that certain birds of prey have also become vulnerable?
Professor Pearce-Higgins: Yes. One of the real challenges with this has been understanding the routes of transmission. We might come on to that and think about the poultry sector as well. We think seabirds are highly vulnerable once it gets into a particular colony because they are packed together at a high density and there are lots of interactions, even perhaps directly with dead birds as well. We also think that some of the scavenging species, like birds of prey—white-tailed eagles or buzzards—could well be predating on infected carcases. That forms another route of transmission. One potential reason why great skuas are so susceptible—as I said, we hold about 60% of the world’s population, and we estimate a minimum of 2,500 were killed last year out of a population of perhaps 18,000 or 19,000 individuals—is that they are widely known as avian predators and scavengers and so would have been predating on the infected carcases of their neighbours, as it were, and circulating the virus much more.
Q116 Tracey Crouch: Are you concerned about any spread to common garden birds, which at the moment are very low risk?
Professor Pearce-Higgins: We and others classically regard some of the songbirds as generally being at lower risk. We have not seen any evidence of large-scale mortalities or instances of those. We have not seen any evidence in our large-scale population surveillance data that those populations are declining, but it is worth noting that generally you do not see small garden birds dying in large numbers, even in cold winters. So the detectability of carcases of infected individuals would be much less than perhaps seeing a load of dead geese or dead seabirds washed up on the beach. There are detectability challenges there.
One thing perhaps worth reflecting on is that we do not have good viral surveillance of what is happening in wild bird populations above and beyond when we see large numbers of dead birds. The Dutch have a system that uses volunteer bird ringers. They have about 180 trade bird ringers to undertake some viral sampling as part of their wider network of disease surveillance. Over recent years that has picked up both Usutu virus and West Nile virus in wild birds in the Netherlands. We have had discussions in a UK context about whether that is possible. As we heard in the previous session, there are real challenges around viral capacity to deal potentially with large numbers of samples that would have a low probability of having virus in them, and there are also potential issues with the legislation about how we would do that sampling safely.
Q117 Tracey Crouch: Could you briefly explain why we should, for want of a better expression, care about this? I am going to ask you questions about how we can mitigate the spread, but why should we mitigate the spread of avian flu?
Professor Pearce-Higgins: There are several components. Obviously, we have international responsibilities. I will take the conservation of these species argument first. The impact on some of these species will potentially alter their extinction risk, so there is a conservation imperative. What we are seeing at the moment is pretty unprecedented.
These are also species of birds that are impacted by a number of other threats and pressures. The virus has the potential to multiply with some of those other threats to cause those extinction risks, but, as I think we heard previously, understanding what is happening in the wild bird context is also very important from a One Health perspective in terms of the potential risk of spillover either into the agricultural context or even the human health context. If you have large numbers of wild species or individuals with a virus that has that potential, you need to understand what is happening.
There is much more join-up that we can have between wild bird surveillance and the work we do, which is very much coupled with bringing in professionals and our volunteer birdwatchers, citizen science and bird ringers. A partnership between professionals and the public delivers a lot for the public sector in terms of our understanding of what is happening in the natural world. That is a paradigm we operate and work very well in that conservation setting, but has a lot more potential to deliver for some of these wider issues, such as thinking about zoonotic spillover.
Q118 Tracey Crouch: Obviously, some of the most affected seabirds are ones that are already under threat from other factors such as climate and species change anyway. How can we mitigate the spread in wild birds?
Professor Pearce-Higgins: It is very difficult. We ran an expert workshop jointly with JNCC in the autumn. The main thing potentially considered as worth trialling—there are trials happening this year on the back of this and some evidence from last year—where you have high levels of mortality is intensive carcase removal to try to break the likelihood of scavenging as a mechanism for infection. There is weak evidence, I would say, from the Netherlands that that could reduce infection rates in sandwich terns. We need to improve that evidence base. That will be about dampening the magnitude of any mortalities in a particular instance; that will not be changing the spread of the virus.
For those sorts of questions you are dealing with much wider issues, because we are talking particularly about migratory birds as well. The risks in a UK context are not just down to what is happening in the UK; they are potentially down to thinking about issues of biosecurity globally or along migratory pathways. As I have said, the pathways are the mechanisms by which the virus can get into birds and then how that can be transmitted onwards. We are looking to break those. It may well be that there are issues over biosecurity that are worth considering and potentially tightening up. I have talked about the surveillance side of things, which I think can be improved as well. As we heard in the previous session, trying to think about things from a One Health perspective and be much more joined up would be really helpful.
Q119 Tracey Crouch: Finally, Professor Pearce-Higgins, do you think that you and other relevant actors are getting enough support from the Government but also other Governments in trying to mitigate the spread?
Professor Pearce-Higgins: I think we are making good progress. We work well with the JNCC and the statutory nature conservation bodies, but that is one sector. A lot of the work we do has been in that sphere. One of the challenges has been to consider the value of what we are doing for other sectors, like agriculture or public health, which I think is beginning to change. A key evidence gap for us at the moment, for example, is to understand the abundance of gulls in winter. We think they are a key vector and bridging species, but we are reliant on population estimates from 2003 to 2005. We are in the process of trying to secure funding for surveys for next winter, but despite the urgency of the situation, as we see it, and the importance of those as a species, only about 40% of that funding has been committed.
Q120 Tracey Crouch: Funding from whom?
Professor Pearce-Higgins: This would be from Government, the statutory nature conservation bodies and so on. That is a multi-year survey. It is difficult to get that funding confirmed over multiple years. We are almost having to operate at risk to set up something. It would be a citizen science project using our expertise as well, so obviously lots of positive ways of engaging with the public to help tackle the issue in understanding where these birds are, their numbers and so on.
Q121 Tracey Crouch: Am I allowed to ask how much funding you are seeking?
Professor Pearce-Higgins: From memory, it is of the order of £200,000 to £250,000 over a couple of years. I cannot remember the exact figure.
Q122 Tracey Crouch: That is a lot of money.
Professor Pearce-Higgins: It is partly down to the magnitude of the budgets and the priorities of these things from a conservation perspective relative to the potential that we see for those data also answering some of the wider questions. What we then find difficult perhaps is being able to have the right conversations with the right people who have the right sources of funding. I think it comes back to a kind of underlying message rather than just talking about the specific. There is perhaps a need for more join-up and cross-sectoral working to help us.
Q123 Chair: The Farne islands off the Northumberland coast are an important seabird haven. They have been closed to visitors for much of the spring. I think they still are. Why is that? What is the advantage of stopping people going to places where there is a worry about avian flu?
Professor Pearce-Higgins: As I understand it, that has been very much a decision from the National Trust perspective, working with some of the local boat companies and so on to provide confidence in an experience that can be offered to visitors in terms of their being able to visit the islands by boat and remotely, without the risks of trying to set up something that might have to stop as the situation progresses.
Q124 Chair: It is not about the transmission of the infection.
Professor Pearce-Higgins: Part of the risk around that could be that, if you have a vulnerable population, there can be concerns over disturbance causing stress to the birds or interactions with the virus. The general consensus when we have talked about this previously is that that is probably a relatively low-magnitude contributing factor to the overall spread of the virus, but there may be certain circumstances where, because of the particular site, the nature of the birds and visitor pressure—somewhere like the Farne islands potentially has very large numbers of visitors—it may be prudent to restrict visitor presence.
Q125 Chair: Is there any evidence that boat traffic or humans setting foot on an island contribute to further deaths from avian influenza?
Professor Pearce-Higgins: There will not be that specific evidence. There are a number of different pathways that organisations will be looking potentially to break. One is the direct accidental transmission of the virus on footwear or whatever from a site that could be infected to somewhere else. Obviously, you can potentially deal with that with good disinfectant and biosecurity. Another is the potential stress consequences for the birds, or the potential for the birds then to interact differently in their setting in response to that disturbance, but it is probably a relatively low risk in general. The magnitude of that risk is very hard to quantify. There is a lot of stochasticity and randomness, as we heard in the previous session, as to what magnitude of effect you get on a particular site.
Q126 Chair: One of the things we are trying to do in this inquiry is learn some of the lessons of covid-19. One reflection we have made is that a lot of restrictions on people’s movements and suchlike turned out to have little or no foundation in scientific fact. It is very important for confidence in science that when people’s behaviour is restricted, purportedly on scientific grounds, they actually exist. I am interested in this example, given that what we have heard so far is that avian-to-human transmission does not seem to exist to any appreciable extent, but there has been quite a draconian response to cut off the Farne islands to visitors. Potentially, in future this might apply to other places, and there are lots of people who want to watch birds. I do not understand the scientific justification for that.
Professor Pearce-Higgins: To be clear, I cannot speak for the National Trust.
Chair: But you are a professor in this area.
Professor Pearce-Higgins: Yes. What is going on in those circumstances, and with other landowners, is that the landowner has that proviso and ability to make those restrictions for access permission or not, subject to various reasons for doing that.
Q127 Chair: What if they just find that convenient? Going back to covid, one of the concerns was that things we had enjoyed doing were overridden as required in a way by exaggerated science. It is very important, not least for confidence in science, that when scientific reasons are advanced or intimated they should be rigorous. We cannot just deploy scientific reasons when actually they do not exist.
Professor Pearce-Higgins: I agree with you. One of the things we did as an organisation for the past year or so, as soon as this avian influenza outbreak hit our radar, was to organise weekly and then fortnightly meetings with conservation bodies from across the UK and some of the NGOs specifically to look at some of these issues, particularly the risks that changes in access could have, as we found out with covid, to our ability to monitor what was happening with the virus and what was happening with bird populations. Those meetings have continued fortnightly until now and have been very helpful in managing that risk exactly in the way you are saying.
I think that initially there was a more precautionary approach to concerns over disturbance and restrictions around even some of the scientific activities. For example, the work NatureScot has led with its framework decision making, with others in the sector, has been trying to balance, exactly as you say, the potential but relatively small risks that could occur through those sorts of disturbance interventions with the benefits, particularly if you are talking about scientific data collection and people undertaking surveys.
Q128 Chair: The RSPB has lots of bird reserves across the country. Is it restricting access to any sites on the grounds of avian flu?
Professor Pearce-Higgins: My understanding is that it closed its reserve in Belfast fairly recently, in the past week or so, in response to black-headed gull mortalities, but that has been largely because if you go there you will see lots of dead and dying individuals and it is not a very positive visitor experience, rather than necessarily doing it to try to manage the consequences for birds.
In summary, I would agree with your presumptions in terms of the questioning. What we are trying to do as a science-based organisation is make the right kinds of decisions based on our evidence.
Q129 Chair: I will turn to Stephen Metcalfe in a moment. We will also have some questions for Mr Griffiths about the poultry industry. You talked about funding for observation and the counting of birds over seasons. It is obvious that that is useful information, but does that help in the management or eradication of avian influenza? It is interesting to know, but does that have any material impact on our prospect of reducing the spread?
Professor Pearce-Higgins: There are several ways in which it can. First, I think that understanding the size and distribution of bird species, looking particularly at some of the species that have been affected and what is left after those impacts, is very important in informing future conservation action, protection and appropriate management, almost aside from the virus.
Secondly, understanding where the birds are is really important and valuable, because one then understands what that wider infection pressure on other sectors potentially looks like. I talked about gulls earlier. One of the real reasons for wanting to understand much better the abundance, distributions and movements of those and some of the other groups is to understand what that risk potentially looks like for other settings, whether it is the poultry sector or, for example, large numbers of gulls flocking in areas with free-range pigs. There is potential there for virally infected birds to be interacting with livestock in other settings. One of the things that could be done better moving forward is to consider how best to use the bird surveillance data that we oversee to inform these other sectors.
Q130 Chair: I can see that you can use the incidence of black-headed gull mortality, perhaps, to make a decision as to whether pigs should be kept indoors or whatever, but you cannot control the movement of black-headed gulls, so it is one way. Sadly and unfortunately, having that information does not equip you with any tools to manage the pandemic in the wild bird population. Is that right?
Professor Pearce-Higgins: It is very difficult to do anything large scale.
Q131 Chair: We are just observing it; we really cannot do anything about it.
Professor Pearce-Higgins: I have talked about carcase removal, which may be something that can dampen the spread under certain circumstances. Also, if you have species that are particularly threatened and at risk, there is a question as to the extent to which vaccination may play a part. I know that the North Americans are considering this with respect to the Californian condor at the moment and are undertaking some trials. As was shared previously, there are some real practical challenges about how you would do that in a wild bird context, but potentially if you have individuals that are in a captive setting, or you are able perhaps to get individuals in the nest, that may be a last-ditch resort you might want to employ for particularly threatened species, but probably only in those limited circumstances.
Q132 Stephen Metcalfe: I will return to vaccination in a minute. Before I do that, can we talk a little bit about the management of infection in poultry farms? There have been some biosecurity measures in place recently. How effective do you think those measures have been?
Richard Griffiths: Considering that, across the country since October, we have had 185 incidents of HPAI, the science of biosecurity is well understood. It is about the application of it. We are in a position where we are talking about something not theoretical but practical. We are living with AI. These measures are things like barriers, changing clothes when going into and out of houses, maintaining cleanliness and maintenance of infrastructure. That has to be applied 24/7. It has failed in instances and we need to learn the lessons from that and improve it, but there is no 100% guarantee with biosecurity. That is why we need a selection of tools in the toolbox. It always has to be the first line of defence. We need to keep improving it, but we need to look in other areas as well. One of them is vaccination, which has been mentioned.
Q133 Stephen Metcalfe: You said it has failed. Has it failed wholescale or in part, and is that because the measures were too onerous to adhere to?
Richard Griffiths: It will vary from incident to incident because the means by which AI gets into poultry sheds can vary.
Q134 Stephen Metcalfe: Just for clarification, we are doing an inquiry into AI, as in artificial intelligence, but this is avian influenza.
Richard Griffiths: Yes. It could be carried in on a person’s footwear; it could be carried in by rodents, if there is a hole somewhere in the shed; theoretically, it could be dust, or any aspect. I think you can say that biosecurity as a whole is broadly good and understood and is probably well applied, but there are instances where obviously it has not been effective.
Q135 Stephen Metcalfe: There are commercial keepers and private backyard keepers. How important is it that these measures are applied equally in both environments?
Richard Griffiths: On the commercial side, it is absolutely essential; it is absolutely fundamental. For small-scale backyard flocks, when the risk is low—maybe there is influenza in the country—their need for biosecurity is very low because there is very little contact between them. When the risk is higher and there is a need to bring outdoor birds indoors, whether that is backyard flocks or free range, the same measures cannot be applied, but the separation of kept birds from wild birds is fundamental. It is about distance: keep them away from bodies of water; keep them separated. The same principle applies, but different measures might be applied.
Q136 Stephen Metcalfe: One of the measures was mandatory housing of domesticated birds. I believe that was lifted in part on 18 April. What impact do you think that will have on the spread of the disease?
Richard Griffiths: The housing measures are always science-based and guided by DEFRA.
Q137 Stephen Metcalfe: Is that on a by-site basis?
Richard Griffiths: No, on a national basis. That will be judged. England, Scotland, Wales and Northern Ireland will decide separately but they will co‑ordinate. That is always a science-based assessment made by DEFRA. It is applied at a time when the risk to poultry has increased, so removing the housing order—again a science-based and risk-based decision—should not have an effect on the spread of the disease.
Q138 Stephen Metcalfe: Is that among both domesticated and wild birds?
Richard Griffiths: Wild birds are different. All we can do as the poultry sector is apply the strongest possible measures to our birds. As has been said, control within wild birds would be incredibly difficult. Sometimes we have to take quite extreme measures in the control and management of the disease within our flocks. For example, any flock that gets avian influenza is culled. Stamping out the disease is essential.
Q139 Stephen Metcalfe: Thank you. I want to move on to vaccination and immunity, because one can lead to the other. What are the chances of birds, either domestic or wild, developing natural immunity to H5N1?
Professor Pearce-Higgins: I am not a virologist, but my understanding is that that is happening. For a proportion of some of the seabirds we have talked about—gannets are a good example—we see them coming back with different eye colour. There is work happening at the moment to test those to see whether those species have been exposed to the virus in part and whether that is a consequence or sign of them having immunity. I think that is likely. There is evidence among other species, for some of the water birds, of potential immunity. One of the features of the outbreak last year was that there was some evidence that particularly younger individuals and chicks were perhaps more susceptible than some of our longer-lived birds and adults. Again, because of immunity to, say, low-path avian influenza, they may be incurring some benefit in relation to H5N1, but my understanding is that that is still very much an emerging field. That is my sense of where the evidence lies at the moment.
Q140 Stephen Metcalfe: Is the impact of birds having immunity pretty obvious, in that it would reduce the spread, or are there other issues we should be aware of?
Professor Pearce-Higgins: This might be just a personal limitation, but I do not know the extent to which having immunity affects the ability of those individuals to shed the virus and pass it on. There are clearly two important elements. As for the impact that the virus has on the survival of a particular individual, that is where immunity does play a part. It may also dampen shedding, but I do not know that.
Q141 Stephen Metcalfe: At the moment is the Government’s health advice, such as washing hands after feeding wild birds, sufficient to mitigate the risk to the general public if they are shedding this virus? What advice would you give someone?
Professor Pearce-Higgins: I think the advice, particularly in the context of garden feeding, as was mentioned earlier, is that it is very low. The sense is that there is not a lot of avian influenza circulating among garden birds at the moment. If there was, those are the sorts of individuals that would be likely to die very quickly. The likelihood of those birds interacting with garden feeders is very low.
Probably the greatest risk for the public is more about when they come across carcases of dead birds that could be infected. There is very clear guidance out there about how you should handle those, double-bagging them and so on. The key thing is that we have been encouraging people to report those dead birds to us but also importantly to DEFRA or, in Northern Ireland, the DAERA helpline so that, if appropriate, those can be tested. That is a key part of surveillance.
We are talking about avian influenza. That is not the only wildlife disease or bird disease that is circulating at the moment. The hygiene questions are also relevant to some of those around garden feeding. We have seen very big impacts from a protozoan disease called trichomoniasis in some of our finches, greenfinches, chaffinches and so on, that is causing long-term population decline. There, the message is that hygiene around garden feeders is really important. These are partly symptomatic of the challenges there are for these birds in the wider environment. They are having to concentrate at these sites, potentially increasing infection risk, because naturally the seed-rich habitats are no longer there in the farmed landscape.
Q142 Stephen Metcalfe: Recognising what you said about the limited amount of infection potentially in wild birds in gardens and so on, in terms of advice to the general public about the best possible measures to protect themselves, is it as simple as washing hands? Are there any other measures—for example, masks?
Professor Pearce-Higgins: It is just washing hands as good practical hygiene, and also cleaning feeders on a regular basis with the use of mild detergent.
Q143 Stephen Metcalfe: I said I would return to vaccination. We have two different sets of birds: the wild ones and the domesticated ones. What are the benefits and limitations of deploying a vaccine programme first in domesticated birds? Presumably, that is more practical. Is it at all possible in wild birds?
Richard Griffiths: Vaccination is a hot topic at the moment. Our industry and DEFRA have a vaccination taskforce. One of the issues is that we are trying to get enough information to make an informed decision. We believe that vaccination is an important tool. It is not a panacea; it will not solve it. It has to be used in conjunction with biosecurity, but there are challenges to overcome with vaccination. The viability of a vaccine is for the drug companies. There is public perception because we are coming at it from a food production perspective. There is the impact on trade. Some countries will or will not accept meat from vaccinated birds, or countries that vaccinate. Then there is the actual cost of surveillance. If you are going to vaccinate, you need to have a surveillance plan in place to be able to track the virus. As we have all learned a little bit from covid, a vaccine will not stop birds getting the virus. It will make them a little more resistant to getting it and it will reduce the risk of shedding it, but even vaccinated birds could get avian influenza. We need those measures and controls in place before we ever actually vaccinate.
Poultry is one of those areas where you probably would not vaccinate all the birds; you would perhaps vaccinate the longer-lived birds, maybe breeders. Christmas turkeys are brought up time and again, but that is a really good example of where a vaccine could help a sector. We are not at that point yet. It might in the end be cost-prohibitive; the vaccines might not be viable, so there are challenges, but we are working on it. I think it is really important.
Q144 Stephen Metcalfe: Okay, thank you. You said that there are issues around vaccination, particularly in the countries that may refuse to take poultry that has been vaccinated. Is there any evidence as to why that would be the case—as to what the issue with the vaccine would be?
Richard Griffiths: To be brutally honest, I think it is more about the trade barriers and control of trade than about the disease itself. We are in a position where we would have to move on a global scale on vaccination in order to eliminate the use of vaccination or non-vaccination as a trade barrier. Part of this process is deciding whether the tail wags the dog. Does trade policy guide disease control policy, or—as I think should be the case—is disease control policy more important, and should that guide trade policy? Those two need to work together very closely if we are to come to a conclusion.
Brazil is an example. In all these years, it has never had a case of avian influenza in domestic poultry. It has only just recently had cases in wild birds. It is perhaps understandably very reticent about vaccination, whereas we and Europe are much more enthusiastic about getting it in the toolbox.
Q145 Stephen Metcalfe: Is the example you have given from Brazil actually accurate—I am not denigrating their system—or is it to do with better surveillance more recently?
Richard Griffiths: I could not comment on Brazil’s policies. I know it has very good equivalent surveillance policies in place.
Q146 Stephen Metcalfe: Okay. You have explained that there must be a difference between vaccinating the human population and bird population just in the nature of how you can track its progress. Maybe you do want to comment on that. Finally, is there any way of introducing vaccines into wild birds at all?
Professor Pearce-Higgins: As I said earlier, there are real practical difficulties. The most likely way of doing it would probably be in instances where you are dealing with individuals that you are handling for a time, whether it is through captive breeding in the context of a rare species—and that is the context of the Californian condor example I mentioned earlier. Perhaps if you are head-starting or handling young birds, it is probably best done if you want to vaccinate a significant proportion of the species. You are most likely to do that for generally rarer species, and then it would be possible to do that. I just do not see how you could practically deploy a vaccine at scale for more common and widespread species.
Stephen Metcalfe: Okay, thank you very much.
Q147 Chair: Mr Griffiths, you mentioned Christmas turkeys and that there is regularly a panic as to whether there are going to be supplies of them. If it were the case that turkeys were vaccinated, could we be sure that there was no risk to human health from eating vaccinated meat? Is that rigorously—
Richard Griffiths: Yes. That is not a concern at all because of the surveillance that would need to go alongside the vaccination. A lot of this is about gathering more and more information as we progress to improve the tools that we have.
Q148 Chair: I am just thinking about the chemistry of it. Have there been rigorous studies that have established that eating vaccinated meat has no consequential health effects for a human?
Richard Griffiths: That is a question for the drug companies rather than me. That is outside my skillset. It is a fair question. Residue testing is a fundamental part of food production.
Chair: We will address that with the food companies. As there are no further questions, thank you, Professor Pearce-Higgins and Mr Griffiths, for your evidence today.
Witnesses: Marc Lacey and Dr Meera Chand.
Q149 Chair: We will now invite our final panel of witnesses to join us at the table. I will introduce them as they take their seats. Dr Meera Chand is a consultant microbiologist and deputy director of TB, acute respiratory, zoonotic and emerging infections at the UK Health Security Agency, UKHSA. Dr Chand previously worked as a consultant at Public Heath England’s national infection service. Thank you very much for coming, Dr Chand. Marc Lacey is the global executive director for pandemic response solutions at CSL Seqirus, which manufactures vaccines in this country. Thank you very much for coming.
Perhaps I can start with a question to Dr Chand. Could you give the Committee an update on where we stand in this country on the threat of avian influenza and what your agency’s response is to that as we speak?
Dr Chand: We agree with the WHO that the risk to the general population is very low from the current virus. The virus that we have in birds in the UK, which you have already discussed earlier in the session, is H5N1, a particular clade, 2.3.4.4b, which has been around for the past two to three years. This virus is not showing signs of being good at infecting humans, and no evidence has been detected that it can transmit between humans.
You can get a sense of that from the fact that, despite the enormous avian outbreak that we have discussed and likely many thousands of human exposures, we have only had detections of 10 human cases globally. We have to accept the limitations of who is tested and what surveillance is undertaken, but only five of those were symptomatic human cases and five of them were asymptomatic detections found through enhanced surveillance. There have been no detected onwards transmission events in any of those cases.
In the UK, we have some detections in humans, but that is because we are running enhanced surveillance; we are testing asymptomatic poultry workers to have closer surveillance and an understanding of the risk at the avian-human interface. I can talk a bit more about that in a moment.
Today I can report the last published data as of our briefing of 2 June. We have had three human detections in the UK in total. One was in December 2021, which was part of a pilot study that we were undertaking of enhanced surveillance at that time. In March, after consultation with expert partners, we initiated a field surveillance study. We now deploy our rapid investigation team to infected premises to enrol poultry workers and to ask them to undertake serial swabbing after their exposure so that we can get the most detailed view of whether we are seeing any subclinical infections. Through that, we have had two additional detections, at that time, of only 85 who were recruited.
Q150 Chair: That brings it up to five detected cases.
Dr Chand: No, sorry, that is three in total in the UK: one in 2021 and two now.
Chair: That is within the three. There is one previous one, and then the two makes three. I see.
Dr Chand: We published those data through a technical briefing series that are all available online. All of those detections remained asymptomatic. We have not had anyone unwell presenting to healthcare detected as having H5N1 in this country. We also take very seriously the risk of the virus changing to become more human transmissible. That has already been discussed this morning.
Q151 Chair: Before we go on to that, let me just ask a couple of questions. The three people who were discovered to have the infection are all poultry workers—people who were working with birds—are they?
Dr Chand: No, not all of them are, actually. In the pilot surveillance study, it was wider recruitment, and that was an individual with exposure to a backyard flock.
Chair: To a what?
Dr Chand: To a backyard flock—not a professional poultry worker—whereas the other two have been employed in various settings in poultry work.
Q152 Chair: I see. All three were asymptomatic.
Dr Chand: Asymptomatic, yes.
Q153 Chair: In terms of the surveillance, you said you ask workers to be swabbed. Is that in every place where there is a confirmed outbreak?
Dr Chand: No, there is a process around this. It is a study that we run in very close collaboration with APHA. When an infected premises is notified, the study team has a discussion with them about the suitability of the premises for the study, which means that there has to be a safe area where the workers can be met and recruited and so on, and there may be other issues for which APHA would suggest we would not use that premises. A risk assessment is undertaken there. If APHA is in agreement, we will deploy our field team to that site. They attend outside the biosecurity zone, and they will take informed consent from people to participate. It is quite important that it is informed consent because, clearly, it has consequences for you as an individual if we have a positive detection and you then have to isolate and your contacts are traced. It is important that people understand what it is that they are enrolling for.
Q154 Chair: How long is the isolation for?
Dr Chand: Given the state of knowledge that we have about the virus in humans, which obviously is very limited with the limited number of cases, at the moment we will retest people to check that they are negative.
Q155 Chair: They have to be isolated until they test negative.
Dr Chand: Usually what has happened is that, yes, we would have them assessed. If we had a positive detection, we would have them assessed in a high-consequence infectious diseases centre and re-swabbed.
Q156 Chair: Of these three, or perhaps the most recent two, how long did it take before they tested negative?
Dr Chand: They were negative by the next time that we saw them.
Q157 Chair: Which was how long?
Dr Chand: I am sorry, I do not have all the facts of the days. I am also a little bit hesitant about the clinical confidentiality of the cases. The way that the study works is that we ask them to post in samples, so by the time we do the test there is already a small amount of delay.
Q158 Chair: Is it days, weeks or months?
Dr Chand: Days.
Q159 Chair: I see. So, they tested positive, and then they were negative again within days.
Dr Chand: Yes.
Q160 Chair: As you know, part of this inquiry is lessons learned from covid, of which contact tracing and testing was a subject of intense interest. What is the protocol for contact tracing of those people?
Dr Chand: H5N1 is classified for us as a high-consequence infectious disease, and that means we deploy a standardised high-consequence infection response, which is the highest-stringency approach that we use for something that is a novel pathogen. An experienced health protection consultant, for example, would interview the patient. We would identify all contacts. We would attempt to contact them and have them tested. They may be asked to isolate. It is a situational assessment. Many of the times, a lot of these people’s contacts are the other people who work on the farm anyway, so they will be enrolled in our study and we will already be monitoring and testing them. Generally, the approach is high-consequence infection, high stringency.
Q161 Chair: Of the people who were infected and whose contacts were traced, did any of their contacts test positive?
Dr Chand: No, we have not detected any positivity among contacts, and we have undertaken testing.
Q162 Chair: How many contacts have been tested?
Dr Chand: It is in the 20s. One of the cases had many contacts enrolled in the study. Twenty contacts were identified, 15 contacts were tested, and they were all negative.
Q163 Chair: In terms of the statutory powers, during the pandemic obviously contact tracing was considered to be very important. Is both the testing aspect and the contact tracing compulsory?
Dr Chand: No.
Q164 Chair: What has been your experience of voluntary participation in this? Has everyone you have asked to be tested been willing to be tested?
Dr Chand: Generally, I think there has been a relatively good response.
Q165 Chair: “Generally” and “relatively”. Can you be a bit more precise?
Dr Chand: Yes, I think there has been a good response.
Q166 Chair: What is a good response? Has everyone whom you have asked to be tested said yes?
Dr Chand: Those whom we have been able to contact. These workers are a group of people who move from farm to farm and can sometimes be difficult to contact. They may have moved location since they were in contact with the index case. There have been some difficulties in reaching everybody.
Q167 Chair: That is in terms of the contacts. I am sorry to be pedantic about this, but as to the primary cases, everyone whom you have asked has been tested.
Dr Chand: Seventy per cent of people within the biosecurity zones have agreed to participate. Different reasons may contribute to those who do not participate. For example, the study team may judge that there is a sufficient language barrier that they are not able to give informed consent. It is not just people refusing. There may be other reasons.
Q168 Chair: How does that compare to the regime for covid in testing?
Dr Chand: This is a different situation because we are not undertaking clinical testing here; we are asking people to enrol in a surveillance study. We are asking them to voluntarily participate, looking for an infection that is asymptomatic. It is not an issue for their own health.
Q169 Chair: God forbid that this were to develop in a way that it transmitted to humans and we had to stand up precautions and measures such as we did in the early days of covid, do you have the powers to require people to be tested and to disclose their contacts? Is one of the learnings or lessons from covid that those powers are clear and available to you? Are they in place?
Dr Chand: No, my understanding is that those powers were pandemic-specific. This is not an area that I work on directly, but I do not believe we have those powers for avian influenza at the moment.
Q170 Chair: You would need an equivalent of the Coronavirus Act to give them. I see.
In terms of the overall level of surveillance in the country, these tests have been done on poultry workers or people associated with that work. Is there and should there be more general surveillance across the country, such as there has been for covid run by the ONS, for avian influenza?
Dr Chand: We want to build on the respiratory surveillance systems that are already in place and look at their fitness for detecting emerging respiratory infections as well as monitoring seasonal infections. We have done some work on this, which was published earlier this year, on the different times to detection that it might take for different types of surveillance approaches to identify different sizes of outbreaks.
When we think of where we can look for this type of infection, we can look in hospital, and a number of surveillance systems run already on hospitalised respiratory infections; we can look in the community; and then we can target high-risk populations, potentially; and in this case we look at the poultry workers.
When you think about an emerging infection event, a lot of where you will detect it depends on the severity of the disease. If this is a virus that causes very severe infection in humans, it will be detected quickly in intensive care units. We have already asked the NHS to continue influenza A testing in intensive care units even out of season for severe respiratory infections, and to ensure that they are subtyped or sent to us for subtyping so that we would detect if we were seeing severe infections caused by an unusual subtype of influenza as a response.
The community infection surveillance is more challenging because in order to detect an outbreak early you would need to be testing a very large number of people all the time. What we need to think about—and this is a very active area of design for us at the moment—is how we can optimise efficiencies using samples that have already been taken or tests that are already under way for clinical reasons to have a composite view of what is happening in the country.
Q171 Chair: You will remember that at the beginning of covid one of the big areas of public policy interest was people coming from outside the UK being infected with covid and then spreading it. Were it to be the case that there was avian-to-human transmission in another country, are you confident that we could detect that at our borders or our airports with people coming through them to stop it transmitting in the way that covid did, or is that impossible, as seemed to be the case with covid?
Dr Chand: The area of preparedness for operational capability at the borders is not one that I work on directly. It is part of the work of the Centre for Pandemic Preparedness, which is a new part of UKHSA that looks at those capabilities in advance. I can reflect on two sets of discussions that were had last year.
One is when we had the peak of covid in China and covid testing was stood up for travellers from China. That was possible and, importantly, people voluntarily participated in it. There were important learnings from that.
The second is that we continuously review what might be possible in the way of operational stand-up at the border when we see outbreaks of other high-consequence infections elsewhere in the world, of which there were many last year. Those options were reviewed and continuously revisited during that time. Generally, that area of preparedness work sits with CPP, and we could submit further evidence on that if that is of interest.
Q172 Chair: Okay, thank you. Finally, Mr Lacey, your company manufactures vaccines. Is there enough preparedness for a potential event that involves transmission that has consequences for humans? I assume you are involved in discussions with the Government on preparedness. Can you reflect on how adequate they are?
Marc Lacey: Let me go globally first. We have agreements with about 30 Governments for pandemic reservation and also pre-pandemic vaccine. We also have research collaborations and studies on pandemic strains ongoing. If we are talking about the contemporary H5 clade, the 2.3.4.4b that has been discussed by my colleagues, we have the seed for that virus at each of our three manufacturing sites, including our site at Liverpool. We have the largest end-to-end vaccine facility in the UK.
In the last year, we have manufactured for four countries to supply H5 vaccines of that higher clade, and we have demand from about another 11 more. We are in dialogue in the UK. The UK has put out an expression of interest to which we have responded, and we await that procurement process to respond. Importantly, we are making sure that we have the seeds at site, and we are trying to make some early preparatory stages in advance of that procurement process. However, we would encourage the completion of that process if that is what the UK wishes to do.
You asked me about general preparedness. From a global perspective, there are Governments that have a more active and diverse approach on pre-pandemic vaccines for humans—small quantities for at-risk or critical worker populations—but it is always subject to advice. I know JCVI has recently relooked at the advice that it gave in 2018 and thought about whether we should be doing a little bit more in this area.
Q173 Chair: Which countries have these more tactical stocks available?
Marc Lacey: There are a number that do. The United States, Australia and Singapore would be leading figures. The US probably has the most proactive and diverse approach, and it gets into a cadence each year. These are vaccines that are made in the gap between the southern and northern hemisphere. There is a limited space for them, but they tend to be more proactive in that space.
Let me give you an example. The US last year procured H5N8 vaccines, a novel H5 clade; and H2N3, which is a re-emergence risk, a swine virus and an H2N3. They are relatively small volumes, but it is trying to make sure that the first part of the process of getting a vaccine ready is there and in place.
Q174 Chair: What volumes would the US have?
Marc Lacey: The US looks at different levels of populations. You are probably talking about only one or two bulk batches, up to five per year.
Q175 Chair: How many is in a bulk?
Marc Lacey: It depends on the yield of the batch. Typically, it would be looking at populations somewhere between 2% and 8%, that kind of scale, in bulk.
Q176 Chair: Between 2% and 8% of what?
Marc Lacey: The population.
Q177 Chair: So vaccines for 2% to 8% of the US population.
Marc Lacey: Unformulated vaccines. Those bulks are held in large biocontainers and can be stored for longer than filled product. Most prepared countries tend to have a larger bulk stockpile, and then they have filled product that is used either in clinical research or in consideration of outbreak populations. Most of it is stockpiled. We are probably at the moment now where Governments are thinking about how it should be used in populations. Does that give you a sense of it?
Q178 Chair: Obviously, there is a critical choice here. You can spend money, and money is tight, on things that you do not expect to use and hope not to use—and there have been examples in which procurements have had to be scrapped—versus the preparedness that comes from that. We will obviously speak to the Minister in due course, but is there a view behind the Government’s policy on this that you can have a just-in-time response—if not literally then within a short period of time you can stand it up—so that you do not need to have those stockpiles? Is that part of their analysis from the discussions you have had with them?
Marc Lacey: I think they see the things as complementary. The primary measure is a pandemic strain-specific vaccine and a reservation probably for the whole population, and then the vulnerable period between an outbreak and a potential move towards a pandemic, with one of the mitigants being a pre-pandemic vaccine. As has been raised here, it is difficult to guess which risk you might see emerge. The focus that we talk about normally is not about stockpile for stockpile’s sake but stockpile so that you are developing the vaccine, you have gone through the early stage of development, and you run faster with it.
Chair: Thank you very much. I am going to turn to my colleagues. Rebecca Long Bailey has some questions.
Q179 Rebecca Long Bailey: Thank you. Dr Chand, what lessons have been learned from the covid-19 pandemic or other outbreaks regarding surveillance methods or technologies that were used in response to this most recent avian flu outbreak?
Dr Chand: There are several different areas of work that I would like to highlight. First, the definitive lessons learned will be from the inquiry, and what we are doing now is already being implemented based on our experience but will also continue to evolve according to those lessons.
The first thing to highlight is that a piece of work is co-ordinated as part of an enhanced preparedness activity by the Centre for Pandemic Preparedness in UKHSA around the design of what surveillance should look like as a human outbreak initiates and expands. It takes into account the thinking about what were the parameters that we needed to know for decision making during covid, how we would now generate those parameters most effectively, the systems we would need to do that, how we would operationalise and so on, flowing back from what we need for decision making. That is quite a first-principles refresh on thinking about surveillance for an outbreak or a pandemic. That is one area.
The second area, which is the area that I work on directly, is more about the technical risk assessment, and two important things have come through there. We have mentioned a lot about One Health this morning. One of the things that has changed is the understanding that we do not want to wait for the first human cases to be seeing risk, so we now work in a much more seamless way with APHA. We have free data-sharing arrangements between us. We bring all our data into a single place. We analyse jointly and we risk-assess jointly. That allows us to be looking at risks at an early point with a joint human and animal health understanding feeding in. That has been a really important change for us.
The second thing that is already implemented is the inset use of pathogen genomics. That was really important in covid. We could detect variants, we could characterise them, and then we could understand why the pandemic changed its behaviour as it did. We used genomics as a completely inset dataset as well as epidemiology for the risk assessment and horizon scanning of emerging influenzas. It is both the data that is generated in the UK and, very importantly, all the data generated globally. There is that really good surveillance feed, in that it is not just epidemiology waiting for cases, but also looking at what the virus is doing first.
Those are some areas that have already developed in advance. As the lessons come through from the inquiry, we will be able to build on those as well.
Q180 Rebecca Long Bailey: Thank you. Mr Lacey, have any advances in regulatory procedure or vaccine technology been co-opted for the avian influenza response, from your perspective?
Marc Lacey: In vaccine technology, there are probably two things. One is an earlier technology that we used broadly in seasonal but we now use in our pandemic or our pre-pandemic vaccines, and those are adjuvants. Adjuvants have a priming effect and spread, and they can allow coverage between more strains.
The second part is the mRNA technology that has come to prevalence with covid. We have two studies, one in H2N3 and one in H5N1, looking at next-generation mRNA—self-amplifying mRNA. It is really early for that data. We have egg, we have cell, we have recombinant, and we have self-amplifying mRNA as platforms across our business globally. We would say that the cell and egg are the proven platforms that have demonstrated this. In 2009, we delivered the first vaccine from declaration to administration in 97 days, and in Europe and the UK we delivered that in 111 days.
mRNA looks really interesting. The early data is really early, and we have to pursue that science vigorously. Certainly, at the moment, when we are standing ready to respond, we are doing it out of proven and authorised platforms.
Q181 Rebecca Long Bailey: In your view more generally, what are the benefits and limitations of vaccinating poultry workers or those who are at risk of exposure to avian influenza?
Marc Lacey: As I mentioned in my previous answer, the majority of pre-pandemic vaccines stockpiled at small quantities have been held within that, and they have only been used in research formats with poultry workers and in laboratories. There is fairly little evidence there yet. I would encourage the JCVI to look at that and consider the evidence, and we could present the evidence that we have as our products and take from others. Certainly, I have never seen a level of avian spread that we currently have and 11,000 mammalian deaths. That is an environment where JCVI could positively consider that again. I am probably not the expert to make that judgment, but you have the experts there to do that.
Q182 Rebecca Long Bailey: Dr Chand, what is your view?
Dr Chand: I do not think I am expert to comment on that, I am afraid.
Q183 Rebecca Long Bailey: Okay. How much further do you think this current incident needs to escalate before discussion should be had about vaccine programmes and whether manufacturing and stockpiling need to be taking place, or are those conversations that are already happening?
Marc Lacey: Those conversations are already happening. Going back to Greg’s comments earlier, it is about how you have a reasoned response and a diversity so that what you are doing is setting up your manufacturing system to be able to respond fast. We all know economically where we are as a country, and we have to make reasoned, prioritised choices. The mammalian spillover we have seen has already moved us into that zone.
Q184 Rebecca Long Bailey: Dr Chand.
Dr Chand: I agree with all of that. Certainly, those discussions are already ongoing. There is an important science question at the heart of this as well, for which there is some evidence but maybe not all the evidence yet. By definition, we do not currently have the virus that would be the human virus. It will be a different virus from any of the ones that we are seeing in the avian or animal populations. What we would be looking at if we had any vaccines that were prepared for an early outbreak would be a mismatched vaccine, to some extent.
An important science question is to understand the potential benefits of a mismatched vaccine on severe disease or death as opposed to an infection and, therefore, what the right strategy is for using such a vaccine. That is a very important discussion about the very beginning of an outbreak where you may need all the advantages that you can get before you have the manufacturing swing into place for the actual matched pandemic vaccine.
Q185 Rebecca Long Bailey: Just for clarity, is there an effective vaccine for the current H5N1 strain?
Dr Chand: In humans?
Rebecca Long Bailey: For human use, yes.
Dr Chand: Again, that is not my area of expertise.
Marc Lacey: We have an approved vaccine for H5N1 in Europe and the UK. We are strain-changing that vaccine with this contemporary strain as we speak. We have manufactured bulk antigen at all three of our sites now. That is the first stage of the manufacturing process. Do we have an approved vaccine for the 2.3.4.4b clade now? No, we do not, but we are going through the process with the regulators, MHRA and EMA, to do that.
Rebecca Long Bailey: Thank you.
Q186 Graham Stringer: Is the vaccine you have and are developing an mRNA vaccine?
Marc Lacey: We have developed in cell, in egg, and we have early development programmes in self-amplifying mRNA. They are at phase 1, which is the first stage. If there was an outbreak now, we would be leveraging our egg factory in Liverpool on our cell process that we have separately.
Q187 Graham Stringer: Are there any particular risks associated with using eggs?
Marc Lacey: Eggs are the most broadly used form. Normally, the risks that are flagged are of biosecurity and containment of the egg supply chain. As we heard from our previous experts, the facilities we have are both diversified and sealed facilities. That is one. The variability that we are probably more concerned about is the variability in yield that we see. When we look at some of the more novel technologies like cell, we see stronger yields, and we have seen that in H5N1 and been manufacturing for some time.
Q188 Graham Stringer: This may be a question without any real meaning if you are an expert, which I am not, in this area. Are there any particular risks associated with eggs and avian influenza?
Marc Lacey: I do not believe there are any more risks than there are in a seasonal setting. The capacity remains in egg, and the capacity is the thing that you will need to drive speed. We are not still building egg factories, if that gives you a signal. We think that the future is different. We think it is cell and we think it is second-generation mRNA, but that is more of a future-looking comment.
Q189 Graham Stringer: That partly answers my next question about whether or not there is a hierarchy of effectiveness between the different vaccine technologies. If there is, what is the hierarchy?
Marc Lacey: That would depend on pathogen and strain. The burden of evidence and proof currently sits in egg, cell and recombinant to show how well those vaccines perform. The newer technologies are still developing that but at a quite early stage. It is a little bit of an apples and oranges comparison.
Q190 Graham Stringer: Is there a real difference between how we are approaching being ready for an avian influenza outbreak and other countries?
Marc Lacey: The surveillance approach we have is similar. The step in front that I see from some countries is a prioritisation and manufacture of those early bulk stages of the process, and then some into filled product. We have heard from our colleagues in the UK Government that there is an intent to do that.
Q191 Graham Stringer: In the life sciences sector, which the Government regularly tell us is an area in which we are world-leading, we seem to have dropped behind as a percentage of world capacity since the covid outbreak. Will that be a problem in terms of responding to an outbreak? In particular, is the capacity of the large vaccine manufacturing facility that was being prepared in Oxfordshire, which appears to be in trouble, going to be a problem?
Marc Lacey: Do you mean the VMIC centre in Harwell?
Graham Stringer: Yes.
Marc Lacey: Let me talk from our perspective. Industrial investment is key. We have a corporate entity here. We export to 12 countries seasonally and 24 countries from a pandemic perspective. What do we need as an environment to thrive in? We need the academic and research investment, and we need the diverse platforms investment with the UK Government. We see good indication that that is intent going forward.
The Harwell facility is looking at some of the mRNA and how that might play out. You need to look at the data. Clearly, in coronavirus, it has had some positive effect. The RSV data also looks pretty encouraging. Some of the early flu data is not as strong, and there is more we need to do as scientists to understand if it will be better than what we currently have.
Graham Stringer: Thank you.
Q192 Chair: Thank you very much indeed. Mr Lacey, when I was a Minister I visited your facility in Liverpool, and I seem to remember from that time that you were the largest consumer, not just purchaser, of eggs in the UK. Have I remembered that correctly?
Marc Lacey: Yes, you are correct.
Q193 Chair: That is still the case, is it?
Marc Lacey: It is still the case.
Q194 Chair: How many eggs a year do you use?
Marc Lacey: Crikey, that is a very good question. The statistic I am aware of is up to 400,000 a week when we are in the period of preparing for a seasonal vaccination campaign.
Q195 Chair: Graham asked about future technologies such as mRNA and all the rest of it, but, at the moment, you use eggs for a lot of your vaccines. What is the resilience to a widespread outbreak of avian influenza that causes the national flock to have to be slaughtered, which then paradoxically stops the vaccines being manufactured to guard against it spreading to humans and other birds?
Marc Lacey: We manufacture in two platforms; one is a cell-based medium and one is egg-based. The UK facility that you visited is egg-based. The way that we mitigate that is by having flocks in sealed units and by having a diversification of flocks should there be an event, so if one gets closed down we could use another. That has been a mechanism that has worked for a number of years. We think the next stage is probably more of a migration into cell or mRNA in the future.
Q196 Chair: But just at the moment, if there were to be a widespread outbreak that caused flocks to be slaughtered, would you then be in a position of not being able to manufacture the vaccines that are required?
Marc Lacey: Only if the virus got into the sealed units where our eggs are manufactured. We think that there is both diversity in that supply and biocontainment that addresses that.
Chair: If there are no further questions from my colleagues, can I thank Mr Lacey and Dr Chand very much for their evidence? I thank all our witnesses this morning. That concludes this meeting of the Committee, but not the inquiry; we will continue taking evidence for a few more sessions.