House of COMMONS









Wednesday 30 November 2005


Evidence heard in Public Questions 1 - 102





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Oral Evidence

Taken before the Science and Technology Committee

on Wednesday 30 November 2005

Members present

Mr Phil Willis, in the Chair

Adam Afriyie

Dr Evan Harris

Dr Brian Iddon

Mr Brooks Newmark

Bob Spink


Examination of Witnesses


Witnesses: Professor Colin Blakemore, Chief Executive Officer, Medical Research Council (MRC), Dr Alan Hay, Director, WHO Influenza Reference Centre at MRC National Institute for Medical Research, Professor Andrew McMichael, Professor of Molecular Medicine MRC Human Immunology Unit, University of Oxford, Professor Anne Johnson, Deputy Chairman MRC Infections and Immunity Board (IIB), Department of Primary Care and Population Sciences, University College London, gave evidence.

Q1 Chairman: Good morning everyone. Could I thank our panel of experts for appearing before the Committee, and could I thank you very much indeed, Professor Blakemore, for sending in your paper which the Committee found useful in terms of the background to this one-off evidence session. We are grateful to you. Could I perhaps start with you, Professor Blakemore, and ask you what determined the timing of your visit to South East Asia and how you respond to the criticisms that this was just a knee-jerk reaction to the media, and that, rather then reassure the public, you created some panic.

Professor Blakemore: It would be a pretty fast reflex, Chairman, given that the publicity occurred a couple of days before an expert group went to visit Vietnam and China. I think the MRC would have to be congratulated for being able to organise something like that in two days. The plans for this visit had been evolving as part of our general strategy on the issue of emerging infectious disease, particularly flu, over really the course of a year. We first began to think about flu in the context of new and emerging infections about a year ago, with strategy discussions in the sub-committee of our Infections and Immunity Board, and, indeed, we made our first contact with the Chinese at that point, through discussions with Professor Chen Zhu, who is the Vice-President of the Chinese Academy of Sciences. Even those discussions included some talk of the possibility of collaboration with Chinese scientists in the area of infectious disease. In March this year, I wrote to a number of colleagues in Government departments and other agencies, spelling out our initial thoughts about MRC's contribution to work in the area of flu, proposing that we had an expert workshop and put forward the recommendations from that workshop, implementing them in MRC policy. That workshop will happen next week with experts from around the world, including from China and Vietnam, and the United States, and that will be the final step in developing our strategic approach to MRC's contribution. So this has been evolving for some time, Chairman.

Q2 Chairman: What was the main purpose then of going to South East Asia? Why did you have to go there? What did you do there that you could not have done back at base?

Professor Blakemore: The major infection amongst bird populations, both farm birds and wild birds, is in South East Asia.

Q3 Chairman: Not necessarily in China and Vietnam, but Cambodia, Indonesia and Thailand.

Professor Blakemore: That is true, Cambodia and Thailand and so on.

Q4 Chairman: And yet you chose not to go to those countries.

Professor Blakemore: We could not go everywhere and we already had contacts - and, again, some of those had been developing over a long period of time, partly with a visit from Dr Jeremy Farrar, an English researcher from Oxford who is based in Ho Chi Minh City in Vietnam. Those discussions informed and helped us to plan our trip. It is worth saying that the majority of cases of human infection have been in Vietnam and by far the largest number of birds that are infected are in China. Those seem to be the two natural places to concentrate our efforts.

Q5 Chairman: We understand there were two trips here in October: a mission taken by scientists led by Professor McMichael and a visit by yourself. However, the report that we received from you did not mention your activities at all. Have you fallen out with each other? Is there something we should know and in which the public should be interested?

Professor Blakemore: No, we are always the best of friends within the MRC community, Chairman.

Q6 Chairman: So I understand.

Professor Blakemore: I went to Beijing and Shanghai as part of a broader MRC delegation to China. Some 20 MRC scientists were in China during the two weeks of our activities there, of which the expert visit to Vietnam and South China was only a part. There is at the moment in China a week of activities, the UK-China Partners in Science Programme, and as the MRC's contribution to that we sponsored a workshop on cancer research in Beijing, with MRC scientists as well as Chinese scientists contributing to that. I attended that workshop, also spoke to senior colleagues in Chinese organisations, and signed memoranda of understanding with the Chinese Academy of Sciences and the National Natural Science Foundation of China as the underpinning of our future collaboration. I then met with the expert delegation in Beijing, after they had visited two or three of the locations, so that they were able to brief me on their activities so far.

Q7 Chairman: In your report to us you say that, as far as China is concerned, they have quite a sophisticated research base which is looking at bird flu pandemics. If you look at Indonesia and you look at Thailand, and particularly Cambodia, they have very, very small research bases - embryonic, to put it mildly - and yet you do not seem to have an interest in those countries. Why is that?

Professor Blakemore: I would like to hand over to my colleagues who are more expert than I am in those areas, but I will answer briefly. Clearly, in terms of progressing research activity it makes sense to us to build links with those countries in which there is already expertise and quite sophisticated, as you say, surveillance and laboratory work, as well as countries in which we have direct contacts. For instance, one of the institutes visited by the expert group was the Chinese Academy of Sciences Institute for Microbiology in Beijing, the director of which, Ninguo Gao, was a former student of Professor McMichael. It is those kinds of linkages clearly which are very valuable in building confidence and in building collaboration. Perhaps, Chairman, I could ask my colleagues to respond to the particular point.

Q8 Chairman: Of course. You have not fallen out, Professor McMichael.

Professor McMichael: Not in the least. No, we travelled down from Cambridge together last night. We went to Vietnam because, first of all, there have been more human cases there than any other country. We particularly wanted to meet clinicians who were treating cases and we had a very strong contact with Jeremy Farrar in Ho Chi Minh City who has seen about half the cases in Vietnam. We then moved into China. We have to recognise that China is very, very strong scientifically. They are building new institutes, recruiting researchers back from the United States and Europe, and they are building very rapidly and are building up their science base tremendously. This is a high technology country and we were very keen to talk to them about possible collaborations, about seeing where we might link both clinically and in the basic sciences. That is really why we chose those two countries. We only had a week. It would certainly be interesting to go to Indonesia and Cambodia but Vietnam and China seemed the most appropriate in the time we had.

Q9 Chairman: Professor Blakemore, we understand that the MRC Infections and Immunity Board is reviewing the Council's strategy for emerging infections and epidemic and pandemic control. Why are you doing that now?

Professor Blakemore: As I said, Chairman, that process began literally a year ago, in December last year, with the first discussions in the strategy sub-committee of that board. Professor McMichael is the chairman of the board and will be able to comment in more detail, but those discussions over the past year have been informing the development of strategy, and I use this opportunity to report to you that at our high level strategy committee meeting just yesterday we decided to recommend to the Council that we should make a new investment of up to 10 million.

Q10 Chairman: We will come on to cost in a minute. Are you saying that the current strategy is deficient?

Professor Blakemore: Strategy responds to circumstances. To the extent the circumstances are changing, clearly strategy has to change. I think we have clearly demonstrated that we have been very agile in responding to changing circumstances, Chairman.

Q11 Chairman: But it was last December when you began the strategy discussions.

Professor Blakemore: Yes.

Q12 Mr Newmark: Strategy is a longer-term thing but tactics is a short-term solution. Strategy is where you have a game plan and figure out what that game plan is. Tactics is where you respond to short-term changes in that game plan.

Professor Blakemore: I accept that, but of course strategy, like tactics, can change and should change in response to the broader term problems. Of course we are planning to do whatever we can on the shortest possible timescale, because we do not know when, if it happens, a pandemic will start, but equally we know flu is with us every year and, indeed, there will be other pandemics in the future, so we need to make longer term investments as well, and that is part of our plan.

Q13 Mr Newmark: Given the immediacy of the situation, given the resources that you seem to be putting into this, why is this review going to take until March 2006? I appreciate it is a relatively short amount of time, but ....

Professor Blakemore: There might be some misunderstanding here. The review will not be continued until March 2006, the process of receiving and assessing applications will. The review will essentially be completed - at least this stage of it - and the strategy changes, as I have said - at the end of next week, as we finish the workshop and we use that final information gathered from the workshop to define the precise nature of the call for proposals for work.

Q14 Mr Newmark: Given we are pretty close to that date, are you able to say what the recommendations are likely to be?

Professor Blakemore: The recommendations to Council, as I have already said, are that the MRC should make an investment of 10 million, probably in two stages, one very rapidly and the other allowing proposals to come in that cannot be delivered immediately. What should be covered in that area - although, as I say, this will be followed by the results of the workshop - would be new approaches to the development of antiviral therapy, new approaches to vaccines, immunotherapy, clinical observations, rapid diagnosis. There are many areas in which we think there could be quick developments, innovative developments, as well as longer-term research to inform the future.

Chairman: I want to keep the cost issue separate and return to that.

Q15 Mr Newmark: I would like to change direction slightly. My next question is to Professor McMichael. The press notice emphasises the trip was intended to identify opportunities for research collaboration. What plans for collaboration have emerged? How will collaboration work in practice?

Professor McMichael: We looked for opportunities at each place we visited. The best opportunities I think come from, first of all, Ho Chi Minh City where Jeremy Farrar is. He has substantial funding from the Lottery Trust and some funding, increasing probably, from the National Institute of Health in the USA. But there are still parts of his programme he would like to put forward to the MRC and we discussed that. It is also a place where we could sponsor young scientists, both clinical and non-clinical, to go and work and we could receive scientists from them in MRC-sponsored universities and institutes in the UK. In North Vietnam - and Professor Johnson could probably speak more about this - there are opportunities for epidemiological research with WHO there in Hanoi. In China, there are two clinical centres we visited, one in Gwangzhou and the other in Beijing, where there are existing collaborations on SARS, and the UN hospital in Beijing has been designated the Beijing centre for clinical cases of avian flu. Should they transmit into humans on a large scale, that will be the centre. There are existing collaborations and we could build on that, and we explored those opportunities there. In the basic sciences, in the Chinese Academy of Sciences' Institute of Microbiology and Biophysics, there are well established UK collaborations already. The heads of those two institutes have worked in the UK in recent years and there are opportunities for bliateral exchanges there. Finally, in Harbin and Hong Kong: in Hong Kong there is already great potential for collaborations with Dr Malik Peries, who has also worked in the UK; and in Harbin - and perhaps Alan Hay could say more about it - that is the centre in China for the infection in birds, and Sir John Skehel is very enthused about possible collaborations there.

Q16 Mr Newmark: Just to get a little more granularity in your answer, when I view collaboration there are three forms I would look at. One is shared information, shared research, shared intelligence. The other form is people contributing on either side, on our side as well as theirs. And I guess the third form is money. Would you say that is balanced all the way through in China and in Vietnam, on all three of those criteria I have identified?

Professor McMichael: I think so. The first thing is the people. We need to identify potential people who will collaborate with each other and then it is possible for them to come to the MRC to look for funds. There may be matching funds from the host country, particularly from China. Then research programmes can be built up around that.

Q17 Chairman: Before I leave this line of questioning, Professor Blakemore, could I say there is an impression - and perhaps you will say we are hopelessly wrong on this - of some sort of panic within the MRC in terms of dealing with the threat of avian flu. Back in 1997 the first cases of H5N1 were discovered in Hong Kong with six fatalities. We seem to have a long lead-in time to this and yet there is a huge amount of activity over the last few months. Why is that? Is it your job to look ahead?

Professor Blakemore: I think it is both unfortunate and unfair if you think the MRC's response to this situation is one of panic. Certainly panic amongst the public two or three weeks ago was being fuelled by a lot of media interest - which you notice has passed, like the Indian summer. I have tried to reassure you that the MRC, outside the blaze of publicity, has been planning and developing its strategy and changing its tactics in response to the situation over at least the past year. Could I point out - and perhaps my colleague, Dr Alan Hay, who is the Director of the Worth Health Organisation Coordinating Centre at Mill Hill, should comment most on this - the MRC has been centrally involved in research on flu, in monitoring flu, in responding to changes in strains of flu and helping the development of vaccines ever since the flu virus was discovered at the National Institute of Medical Research in the 1930s.

Q18 Chairman: We are going to come on to Dr Hay and I think that point does need to be made. Could I turn to you, Professor McMichael. Did you cover all you wanted to on your visit? What is there left to do? Did your visit uncover new problems which you clearly now have to work on? Or did it confirm what you already knew?

Professor McMichael: I think it did both. It confirmed some of the things that we expected. We were looking for areas where research was needed. I think we identified those in clinical management, in epidemiology, in the issue of the virus in birds and in the potential for future work of the clinical trial nature, of how to treat this infection and the kinds of things that might be possible.

Q19 Chairman: In terms of unexpected problems, there was nothing that surprised you.

Professor McMichael: I do not think so. My colleague Anne Johnson can probably comment. I think probably not.

Professor Johnson: No. We were able to speak to a lot of people firsthand - and that was of tremendous benefit, to speak to people who had managed the cases, to understand the situation in the area. We obviously were able to get more detail and more firsthand information, but we did not, I do not think, come across anything that particularly surprised us.

Q20 Chairman: Okay. Professor Blakemore, we understand you signed a memorandum of understanding with your Chinese counterparts in the Academy of Sciences. What was the significance of that? What does it actually mean in practice?

Professor Blakemore: There are more memoranda of understanding than there are -----

Q21 Chairman: There seem to be a lot of them about.

Professor Blakemore: Exactly. I was making exactly that point, Chairman. A memorandum of understanding does not guarantee research collaboration but it is usually a necessary condition for such collaboration. It is an expression of intent and I think you can see from Professor McMichael's comments that the intent is certainly there in the case of China, with several plans which are rapidly evolving. We have already made a commitment that part of the new funding will be used specifically for an exchange programme with China. Could I add, Chairman, that we hope to increase our collaboration with Chinese scientists, not only in the area of emerging infectious disease but other areas too. So the memoranda of understanding - there were two of them - will underpin those wider collaborations.

Q22 Chairman: Given that this is an issue which affects the whole of Europe as well, were there similar moves from European research councils going out to China and Vietnam as well at the same time?

Professor Blakemore: I turn to my colleagues, in case they know of them. I am not sure. I think we can be confident that every research active government around the world and agency around the world is thinking about interactions. I should mention that the Pasteur Institute, based in Paris, France, has already established a research facility, a Pasteur Institute in China, in Shanghai, and presumably that is the basis of their interest in emerging and infectious disease in China. But there could be other collaborations that I do not know about. I could perhaps mention the United States -----

Q23 Chairman: Just trying to follow my line, are we simply continuing to duplicate across the whole of Europe, given that we have now seen cases in Romania in terms of avian activity there, diseased birds.

Professor Blakemore: There are, I think, more opportunities for joining up the reactions of agencies. But we would all be criticised if we had not acted as quickly as we could and I think we need to move towards joining up internationally what we do. Could I point out that I will be going to China again in three weeks time for a meting of a committee of heads of international biomedical research organisations, and of course infectious disease, and especially flu, is a large element of the agenda for that meeting. The heads of agencies from all around the world, from Europe, Australia, North America, China will be able to compare notes and strategies on their approach to avian flu.

Chairman: We will return to this in a second.

Q24 Mr Newmark: Did you take the opportunity to gather information about surveillance and avian flu in China? How reliable are the statistics relating to avian flu that we have from China?

Professor McMichael: The surveillance in birds comes mostly from Harbin. Alan Hay knows a lot more about that than I do, because I was not on the Harbin branch of the visit. Surveillance in humans, Anne may be able to comment on. While we were there, there were two possible cases identified or reported in the media. Indeed, we could not meet the Chinese National Institute of Epidemiology because they had all gone out to look at those. Subsequently, there were three cases confirmed in China as human cases - the first three.

Q25 Mr Newmark: Are you concerned that the Chinese authorities seem to have performed a u-turn regarding recent human cases of avian influenza in the Hunan province?

Professor McMichael: We do not know it was a u-turn. Those are the cases I was referring to. They were cautious initially, but they subsequently agreed. One of them, the girl, was cremated, and there was no scientific data. On her brother, that was confirmed as a positive case.

Q26 Mr Newmark: My next question is to Dr Hay. Given that you said in December 1997 that "... surveillance in China is a real problem. We have to think of beefing up monitoring there ..." do you think this visit was a case of too little too late?

Dr Hay: I think it is important to recognise that the MRC has had a long-term commitment to international collaboration in influenza via the World Influenza Centre that was established in 1948. We have continued to collaborate since then. The WHO global influenza programme now comprises four international collaborating centres, of which we are one, and some 120 national influenza centres in countries scattered around the world, including an influenza centre in Beijing and a recently established national influenza centre in Hanoi. The response in 1997 was much more low-key than it has been recently, for obvious reasons - well, not so obvious - but we dealt with it in the same way then as we do now, as a response to an emergency which is coordinated by the WHO, and we play a full part in this. The research which we do at the National Institute for Medical Research relates to much of our interests in the WHO influenza centre.

Q27 Chairman: Are you satisfied, in answer to Brooks' question, that the surveillance in China is now of an appropriate order? Because that is not the impression you gave, Dr Hay.

Dr Hay: The interaction could clearly be better in terms of information transfer. The WHO, together with ourselves, established an animal influenza network - around 2002, I think it was - in relation to an international project which included Hong Kong, in fact, and this helped to spark the establishment of this particular network which was focused on avian human influenza in South East Asia. This small network included the Harbin laboratory, which is the national centre for avian influenza in China. So we were able to learn the extent of this network, and that in fact the surveillance in birds in China is really quite good; it is just: How much do we learn about what is going on? Clearly the information we get is less than we would like. Certainly, in terms of the human cases in China, this is also an issue, but, as you know, recently the Chinese authorities have invited the WHO to send a team into work together with Chinese medical scientists to evaluate the suspected cases of H5N1 and to evaluate whether there is more extensive infection within China.

Q28 Dr Iddon: We are dealing with three difficult problems here. First of all, the World Health only announced laboratory confirmed cases of this disease.

Dr Hay: Certainly.

Q29 Dr Iddon: Secondly, we are dealing in South Eastern Asia with some very important areas. Thirdly, of course you have already implied that there may also be some political difficulties, in that countries like China, for example, might not want to announce the real truth. My real question is: Do you really have an accurate picture of avian flu in that part of the world because of those three difficulties?

Dr Hay: We really rely very heavily on the WHO to coordinate the activities and acquire as much information as we can. This is why, in confirming cases, it is important that we have really accurate information on that. There has been a considerable concern, particularly in Vietnam, that there would be much more widespread people, even at a sub-clinical level. A lot of the people involved are working flat out all the time, but there has been probably a difficulty in getting specimens, in terms of doing sero-surveillance, for example, to evaluate accurately the extent of the possible spread. But the information that is available to date, which has been acquired with the assistance of WHO and shared with the group that is involved in monitoring H5N1 viruses, which includes our own laboratory, is that there is no evidence of extensive infections, very extensive infections. But much of this information we have, of course, is not necessarily published.

Q30 Mr Newmark: Reading between the lines - and I am not trying to put words into your mouth - notwithstanding the series of facts that we have set out as to surveillance, what is happening there and how you are beefing up monitoring, the reality is that the Chinese are the gatekeepers of the flow of much of the information, which means we are very reliant on what they choose to give us. And, while there has been some improvement towards an independent monitoring of what is happening there, it is still relatively poor.

Dr Hay: Yes, we are reliant on the goodwill of people to provide information about issues in which we are interested. This pertains not simply to countries of Eastern Asia but also to European countries. It is very important to remember that the crisis at the moment is a crisis in poultry. We are dealing with an avian virus that has caused widespread outbreaks in poultry in these regions which has been devastating for various reasons, whether for commercial reasons or more at the family level in terms of people's livelihoods, and this is an agricultural-veterinary problem. On the human cases - there have been relatively few, as you know, sporadic human cases - we want to know as much as possible. But getting information on what is happening in the poultry populations in other countries, in Russia, Romania, et cetera, all takes time as well. We again are dependent on people providing that information. We cannot go in and demand it.

Q31 Bob Spink: Is it not a fact that once you get the mutation, so that you get a true human-to-human pandemic developing, it will be so infectious and virulent that we will find out pretty damn quick, because, given air travel, people will start to go down around the world? There is no way they are going to be able to hide when this virus mutates, if that is what it does. Is that not so?

Dr Hay: That is true. That is why there is tremendous effort going into analysing as many viruses as possible, from birds and from people, to detect as early as we can any changes that appear to be occurring which might influence the ability of the virus to infect and transmit between people. A lot of information is being collected. As I say, it s not widely publicised. There is a group of H5 reference labs, coordinated by the WHO, and we are collecting as much information as we can and sharing that information. Based on the information we have, WHO continues at time to make available relevant conclusions regarding the information. So we have quite a lot of information on bird viruses and a lot of information on the human viruses and the interrelationship between these. Of course we would like to have more information.

Q32 Chairman: You have given an extra 0.5 million to WHO in terms of surveillance. That seems to be a drop in the ocean, if you do not mind me saying so. Do we need to spend more in that area? You have not mentioned surveillance, for instance, in places like Cambodia and Indonesia, where it is even less sophisticated than in significant parts of China.

Dr Hay: That is right. The surveillance in those parts of the world has been relatively poor compared with in many other parts. There are other parts of the world, such as India also where surveillance has been very poor. So there are many black holes in the WHO network. The WHO has been aware of this and has been trying to increase surveillance in these areas over the past few years with a global agenda which it established some years ago. The United States certainly has put a lot of money into improving surveillance in South East Asian countries, and, as you say, the Department of Health has made a contribution also in this respect. So a lot is being done and WHO tries to take a coordinating role and a proactive role in stimulating increased surveillance and increased interaction.

Chairman: Thank you, Dr Hay. We are going to move on now to risk.

Q33 Dr Iddon: I am wondering if there is any real way of estimating the current risk of avian flu on the worldwide population but more importantly to our own citizens in this country.

Dr Hay: That is very difficult. Really we do not know what it will take for this virus to become established in the human population. We are also keeping our eye on other viruses. The focus on H5N1 is because it is a very nasty virus, a very virulent virus for people as well as for birds. The contrast, to some extent, was when there was the outbreak in the Netherlands in 2003 which caused some 90-odd cases of conjunctivitis and we did not take a lot of notice until there was one that nearly died of the infection. A lot of the interest is because of the virulence of this virus and the morality associated with it, but there are other viruses out there that have caused human infections that we know about and which actually have some characteristics which suggest they may be more likely than H5N1 to cause the next pandemic. We are keeping an eye on all these aspects. There is quite a lot of work going on in the background with regard to the development of strains of virus that it would be appropriate for making a vaccine against, not only H5 but some of these other viruses, should it prove necessary.

Q34 Dr Iddon: When the virus was isolated in Turkey and Romania, did that cause a greater level of risk with our own population in Britain, do you think?

Dr Hay: I do not think so, not directly, because I think the risk still is certainly very much focused in South East Asia. However, it does expand the area, increasing the number of outbreaks in poultry, and of course there is a greater risk of infection to the local population and in particular those who are culling poultry. But the risk in terms of the virus changing to a human virus is still focused in South East Asia. I think also the implications of the spread of the viruses to Europe and the potential spread to Africa raise real concerns.

Dr Iddon: When does the level of risk start to ring real alarm bells in the Department of Health and the world? Is it when we see the first case of avian-to-human transmitted disease? Will we start to get very excited by that, or would we wait until human-to-human transmission became a real possibility?

Q35 Chairman: Specifically in the UK.

Dr Hay: It is very difficult to look specifically at the UK. Flu is an international disease. The MRC treats it as such. That is our perspective. In terms of the UK, having plans in place to deal with the pandemic goes back quite some way, to a time when they were one of very few countries that had such a plan. They have been increasing the detailed aspects of this plan over recent years and are well recognised to have one of the best developed plans, and much of what is done in this country by the Department of Health through the HPA is recognised as an example of how other European countries should be developing plans and other countries around the world. But, once again, the WHO has developed key plans, provides assistance to anyone who wishes to develop plans, and has had many meeting on these subjects over the last couple of years and even more. The whole thing was stimulated in 1997. It was not simply that we had a resurgence of interest in 2004: the interest in developing, being more prepared to combat a pandemic, has really been going on since 1997.

Q36 Dr Iddon: How do you see the media having handled the topic of avian influenza? Do you think they have panicked the general population? Do you think they have overdone the risk of a pandemic or not?

Dr Hay: I think in terms of the media it is difficult, whether it is the media that does it or people's response to it. If you focus on the fact that there have been 130-odd cases confirmed and half of those have been fatal, this is something which some people would find extremely worrying and concerning. Others may view it that this is largely an avian disease: there have been a few, sporadic human cases and the chance of it spreading within the human population is probably remote. This is the difficulty of taking a very objective view of what the risk really is. I think it is understandable that some people will get very concerned; other people probably will not take much notice. Certainly it has been unfortunate that people have identified the normal annual flu vaccine to protect people against flu this winter to be of any use against this H5 virus and that people would go and get vaccinated for that purpose. I think that sort of message is very unfortunate.

Professor Johnson: If I could add a comment about media coverage. I think this is a classical example of the divergence of practice in the media. We are all aware of the screaming sensationalism of some of the front page headlines about risk which certainly generated some panic and irrational behaviour. On the other hand, as is so often the case, if you were to turn to the science pages you would find informative and very valuable coverage of the nature of flu and pandemics and historical experience - which I do think will have helped to raise public awareness. This is a more general issue, but I think the media in this country is paradoxical, in the sense that they have some of the best science journalists in the world and, frankly, some of the worst news-desk coverage of issues that involve science. I think the public is certainly more informed about the issue now. That has generated some difficulties in behaviour - particularly the run on seasonal flu vaccinations and private sources of Tamiflu (the antiviral) and so on - but actually in the long-run I think we will see that the little episode of media coverage will have helped to keep the public informed.

Q37 Bob Spink: Do you think the Chief Scientist's intervention in this was helpful? Do you think he was accurate in saying that this virus is likely to mutate human-to-human; that that is highly likely to happen at some stage; and that when that happens we will be looking at 55,000 deaths in this country as a result of that? Do you think that was helpful? Do you think the media acted responsibly reporting that? Do you think that helped to cause a shortage of the current flu vaccine for those who are frail and vulnerable, who need that vaccine now and are being denied that vaccine?

Professor Johnson: Perhaps I could respond first to that, Chairman. I think you are referring to Sir Liam, the Chief Medical Officer.

Q38 Bob Spink: Yes, I am.

Professor Johnson: I think you have accurately reported what he said and I do not think one can fault what he said, that there is a probability of this virus mutating or recombining in a way that could cause a pandemic, that if there were a pandemic then we would have to be predicting considerable fatality, given the case fatality for the present infections of H5N1 at approximately 50 per cent (given the historical record of case fatalities for the 1918 pandemic, which was a very similar virus according to the analysis done at the National Institute of Medical Research). So we have to be prepared. This is all guesswork at this stage, but certainly it is not unreasonable to think in terms of thousands or tens of thousands of people dying. 250,000 I think died in the 1918 outbreak in this country. I think the Chief Medical Officer would have been criticised for being complacent if we faced this year - and let us hope it is not this year, next, or in the future - a pandemic with high case fatality if he had not pointed out that possibility.

Chairman: Could we ask Dr Hay and Professor Johnston to comment on that question as well, please.

Mr Newmark: Maybe as something to think about while they are answering, Chairman: my colleague referred to the frail and vulnerable as the people that we should be caring about, but actually, it is more likely the robust and healthy, like my colleague here and I ,who are more likely, as I understand, to be affected by this than either very young people or very old people. Is that true or not true?

Q39 Bob Spink: Perhaps I might explain that I was referring to the frail and vulnerable in respect of the current flu risk, not H5N1.

Professor Johnson: This is an interesting point, Mr Newmark, and perhaps Professor Johnston could comment. I think you are probably referring to the pattern of infection in the 1918 outbreak.

Q40 Mr Newmark: Yes, I am.

Professor Johnson: Clearly the pattern of infection in the 1918 outbreak was that of affecting young people, with less of the infection occurring in the elderly - or there was a different pattern of infection. There are a number of theories about why that might have been the case, due to viral exposure or to the state of the population at the end of the First World War. There is also information about population movements at that time, and some of that has been highlighted in historical data that has been looked at around the 1918 epidemic. So the emergence of epidemics is, as always, an interaction between the biology of viruses and the behaviour of populations. One of the things that I think has been going on is the very difficult problem of communicating risk to the population in a situation where there is uncertainty. That is where we find ourselves. Some of you may have heard Lord May on the Today programme this morning talking about the problems of communicating uncertainty. In the field of public health, I think it is essential to communicate uncertainty. We had to do this in my own area in the context of the AIDS epidemic in the early 1980s. In that field this country achieved a great deal by its public education efforts, in achieving one of the lowest rates of HIV in the world and in achieving quite remarkable changes in behaviour. You could say that is perhaps not relevant, but the relevance or the translation of that is communicating risk to the population. That is what I think is going on. The preparedness for pandemic flu lies of course in the hands of the Department of Health and with the Chief Medical Officer and that aspect of pandemic planning is not directly of concern to the Medical Research Council. The concern of the MRC is to ensure that we can contribute by the kind of underpinning research which could help that. In the field of epidemiology, we were impressed on our visit to Vietnam and to China at the efforts that were going on to account for cases, to investigate them, but there is nevertheless a need to underpin that general surveillance with a good research programme that understands some of the questions you are asking. With H5N1 human influenza, there are just over 130 cases worldwide. That is a very small - thank goodness - human experience, but it is essential that the world responds to this in such a way that we understand the clinical cause of the disease, the people it is affecting, and that we go a little bit further in the outbreak investigations, to use active epidemiological techniques - sometimes called "shoe leather epidemiology" - which is to get out into the field and look at these outbreaks in greater detail. That may be very difficult - and when I say "in greater detail" one has the cases and one finds the individual cases, but it is the kind of work Dr Hay has been discussing, where one might look around an outbreak in greater detail, at what is going on in the human population and the avian population, looking at: Are we missing milder cases? and so on. Some of that work has been going on but it could be done in a more systematic way with more research investment. I think that is really the arena in which the MRC can contribute.

Q41 Chairman: Do you agree with the 50,000 figure that Sir Liam Donaldson put forward?

Professor Johnson: These figures have been based on the best estimates from mathematical models and from an understanding of what went on in the 1918 epidemic. I must return to this question of uncertainty. If or when - because pandemics of influenza have occurred throughout history - the next big flu problem arises - and it may not be H5N1, it may be another virus - when this transmits between humans, we cannot be certain about what the clinical course will be, and we cannot be certain that the high mortality associated with the current avian-to-human transmissions will be maintained - and I think Dr Hay will be better able to comment. Precise statements of exact number might be the excess mortality - and remember that we are talking about excess mortality here - is liable to vary according to those parameters, as we have seen from different epidemics: the case fatality in the 1918 epidemic was much higher than it was in the subsequent epidemics in the 1960s and so on. So there are uncertainties, but those are the best estimates that have been given to Sir Liam by those who have looked at this in great detail.

Q42 Chairman: Would you like to comment, Dr Hay, before we move on?

Dr Hay: I do not have much to add. I think it was very important that Sir Liam did stress the seriousness of the situation and what could possibly happen. The 50,000 quote is the lower estimate and is based really on what happened in the Hong Kong pandemic of 1968.

Q43 Bob Spink: If 55,000 (I think it was) is the lower estimate, what would be the highest?

Dr Hay: We really do not know. As Anne has indicated, the course of infection in these patients, which has been studied in Vietnam and other countries, is different from the short, acute infection that we normally have from human flu. Of course the age range affected differs from those that are non-vulnerable in our community. So there is a lot we do not know of what would happen and what will happen when the next pandemic strikes.

Chairman: Moving on now to scientific advice.

Q44 Adam Afriyie: I must first declare a personal interest, in that I have a cold virus today, but I am not going to submit my body to medical research! I am interested in examining the scientific advice and the process by which the Government gets that advice and whether or not they use that advice. My first question is to Professor Blakemore. What role has the MRC played in advising Government on a strategy in avian flu?

Professor Blakemore: The Government has a mechanism for soliciting scientific advice. MRC is not a central part of that mechanism. The mechanism is managed by the Chief Scientific Advisor, Sir David King, and there are equivalent Chief Scientific Advisors in many government departments. They coordinate their activities and their patterns of advice to Government. They will consult as widely as they need to gain expert information and we are certainly consulted from time to time. But, for instance, Sir David King, who is about to leave for China, has asked the MRC for a briefing on the outcome of our visit there and we are regularly in contact with Sir David, feeding into the advisory process.

Q45 Adam Afriyie: Let us say in the last year, have you as Chief Executive of MRC fed any information or advice directly to ministers or civil servants or has it all been via Sir David King?

Professor Blakemore: There have been discussions with, for instance, colleagues in the Department of Health, Sir Liam Donaldson and Dr David Harper, who is leading the Department of Health flu preparedness programme. I have, as you have implied, spoken to Sir David King, and certainly with a wide range of other colleagues. Not with ministers - but I am quite sure that the information is being coordinated at a civil servant and ministerial level.

Q46 Chairman: You are quite sure?

Professor Blakemore: Yes, I am actually. I attended, for instance, a briefing dinner, organised by Sir Liam, with full representation of government agencies and very comprehensive discussion and coverage about flu preparedness, which raised my confidence in the degree of coordination of both advice and planning across government departments.

Q47 Adam Afriyie: That leads me to my key question: Has there been a case in the last year or two years where you feel that the scientific advice that you have given and the strategic advice that you have given, via whichever route to government, has not been listened to in full or not been taken on board in full? If so, what was the situation?

Professor Blakemore: No, I can think of no such situation. We have been developing our own plans, as I think I made clear earlier, over the past year, and so have other government departments. I think it is quite understandable that the degree of coordination across government should have been continuously improving during that period of time. One could not have expected a response to an unusual and unpredictable situation to have been perfectly planned from the very start, but I think you can be assured that we are very well joined up now.

Q48 Adam Afriyie: In summary, you are satisfied that what the MRC have been advising has been fully taken on board by government in a way that which you think is appropriate and reasonable.

Professor Blakemore: We have not been giving advice to government directly. That is not our role in this case. The sort of advice about which presumably government is most concerned would be coming from the Department of Health and it would be contingency planning for things like surveillance, quarantine, restriction of travel, how to deal with schools, plans in hospitals, distribution of therapeutics and so on. That is not MRC territory, so there has not been either an avenue or a need for the MRC to be feeding specific advice into government. We have been doing our own thing - and, I hope you will agree, doing it well - and we are well coordinated with all those other activities across government.

Q49 Chairman: In terms of the research evidence, your advice must underpin what advice Sir Liam Donaldson gives. It must underpin the way in which the government goes about, for instance, issues of buying vaccines and what-have-you. From this line of questioning, we are trying to get at how joined up the whole process is. You have not given me, if I am honest, Professor Blakemore, a reassurance that ministers have a direct track into the evidence which you provide government.

Professor Blakemore: Then I ----

Q50 Chairman: Is that another unfair comment?

Professor Blakemore: Chairman, I have obviously failed to convey to you my own confidence in that process. I can only emphasise that it is not the principal responsibility of the MRC to be advising government on its flu strategy. Of course, our research will inform that process. I should point out that the workshop which we are holding next week will be attended by representations from the Department of Health, from the Health Protection Agency, from the other research councils and so on. The outcome of that discussion will therefore be feeding into the general process of advice. I have also mentioned that I participated in the comprehensive dinner discussion organised by Sir Liam Donaldson, where again there was promulgation of option and advice. But, of course, advice depends on evidence. While we have a core of evidence, a bedrock of evidence - and Alan Hay is a good example of MRC's contribution of that - this is, as we all know, a changed and evolving situation, so the evidence will be developing, and the MRC is playing its part in making sure that we have the evidence that will be necessary in the future. We have information about the clinical pattern of this disease and the epidemiological spread of the disease; the identification of new viral strains; and appropriate - possibly new - ways to approach development of antiviral drugs and vaccines.

Q51 Dr Iddon: Dr Hay, you have been saying for a long time that a flu pandemic is an ever present threat, based on the work you have been doing and the scientific evidence that you have been collecting. Do you think the Government has been listening? Or have you felt there has been an uphill battle to get people to listen in Government circles?

Dr Hay: From my perspective, this country has always had this major commitment in terms of doing its bit in monitoring influenza and the changes that occur in the viruses in terms of a necessity to update vaccines, for example, and in terms of monitoring for the emergence of another pandemic. Who should be doing what? If we go back to 1997, far less people were involved in the question of whether that particular H5N1 might emerge as a pandemic and the communication was much more on a personal level and we transmitted information and the Chief Medical Officer called appropriate meetings, etcetera. Now, of course, we are dealing with a situation which has been around for almost two years now, where people have become more and more concerned gradually, a lot more people have become involved and governments have made comments about it. What has happened over the past few years is that clearly more and more people have realised that this threat really might just be round the corner. I do not think it is so surprising that this has been a gradual learning process for most people.

Q52 Dr Iddon: The media attention on this particular virus must have helped your cause.

Dr Hay: I think the media attention really is important, as in any situation of common interest, to make people aware of what is going on and to stimulate interest and action in particular and to get more resources to focus on the problem at hand, which again is finding out as much as we can within the region, in South-East Asia, where this is happening, to put more resources into the WHO in terms of their coordinating activities and to get more resources as well within various countries in terms of being prepared to deal with a pandemic when that should strike.

Q53 Dr Iddon: As Head of the World Influenza Centre, you must have a special ability to see what is happening in every leading country which is doing scientific research in this field. I am particularly interested in the way that governments use the scientific advice available from people like you in policy making. Where do you think Britain fits on the scale? Are we one of the best, are we in the middle or could we be doing more?

Dr Hay: I think we have been doing quite well. It is very difficult to plan for something that you really do not know the characteristics of and people have realised that this is a difficult task and have put a lot of effort in to that in many countries and in particular in this country.

Q54 Dr Iddon: You feed information into the World Health Organisation as well as into our own Government circles. Is there any difference in the way that you talk to these two bodies?

Dr Hay: I am probably tied in closer with the World Health Organisation, the international network, than within the national networks since that clearly is our prime role. I think it is important to realise that the WHO plays an extremely important role in collating information and providing advice. This was evident at the time of the SARS emergency. It was the existence of the WHO influenza network that actually made it possible to monitor the development and spread of that particular infection. As you will recall, it was the WHO that was providing mainly information and recommendations regarding travel, etcetera. It is really wrong not to realise the impact of the international recommendations and information from the WHO. It is crucial in terms of how the Government would respond to what was happening.

Q55 Dr Iddon: Are you saying that perhaps the World Health Organisation in advising our Government has more clout than if you have advised them directly?

Dr Hay: Certainly. The advice from the WHO is usually made on the basis of communal consultation which I am very often part of.

Q56 Dr Iddon: Could you ever see a situation where the World Health Organisation and our own Government would reach a disagreement, and what do you think should happen if they did?

Dr Hay: I guess our Government has to decide what it wants to do.

Chairman: That is a very diplomatic answer.

Q57 Bob Spink: I wanted to address the area of what we do if we get a pandemic, how we approach that and so on, focusing on vaccine development and manufacture and distribution if vaccines are scarce. First of all, we understand from Dr John Wood of the NIBSC and his evidence to the House of Lords Select Committee that the Government has got a stockpile of the H5N1 vaccine. Is that just a placebo, a PR exercise or could it be genuinely useful?

Dr Hay: I think it certainly could be genuinely useful in terms of vaccinating key workers who are at the frontline and most likely to be infected in an initial exposure of this country to a pandemic.

Q58 Bob Spink: What is the probability that that vaccine would reduce mortality and morbidity? Can you put a figure on that?

Dr Hay: We really cannot. If it is an H5N1 virus, we do not know the characteristics of that virus yet. We know, for example, that the viruses which have infected people in Indonesia are distinguishable from the viruses that have been infecting most of the people in Vietnam. The experimental lots of vaccines that have been produced to date are based on the Vietnamese virus, so we do not know how effective that vaccine would be against the Indonesian virus, but we can be sure that it would provide some reasonable level of protection, probably at least to minimise the death rate. It is very important to have at least something in your arsenal to use in the event of a spread to this country.

Q59 Bob Spink: I would like to look at the timescales now. There are two stages. The first one is identifying the strain and developing a vaccine once a pandemic starts and then there is manufacturing that vaccine. Based on the evidence given to the House of Lords Select Committee, it seems that identifying the strain and the development of the vaccine stage would take about ten or 11 weeks and that the manufacture stage would take about five or six months. Does that seem reasonable to you? Is that achievable?

Dr Hay: Yes. The timelines vary somewhat depending on who one is talking to. Clearly in five or six months' time the manufacturer might be able to make the first lots of vaccine in less time than that. All we can say is it will be done as quickly as possible, but a vaccine will not be produced in any significant amounts ahead of the actual pandemic being initiated and us knowing what the characteristics of the viruses are.

Q60 Bob Spink: Is there anything that the Government could be doing now, irrespective of cost, to shorten that timescale?

Dr Hay: In the immediate term what we have to focus on is the vaccines that we can use at the present time. In the longer timescale this fits in with the MRC's support for further work on different types of vaccines which may well shorten the lead time in terms of manufacturing a vaccine.

Q61 Adam Afriyie: Is there anything that you would like to ask the Government to do now that would assist you in that process? Is there any barrier to anything you would like to do from a scientific point of view?

Dr Hay: What people want to do at the moment is to do clinical trials with the vaccines that have been prepared, to determine the most appropriate formulations of that vaccine and to get a suitable immune response such that we know that when it is used it will be effective. This involves investigating the use of different adjuvant, for example, to increase the potency of the vaccine such that we can use as little as possible of the actual vaccine in one particular immunization.

Q62 Bob Spink: Is it any use getting stuck into the general antivirals, will they help to reduce morbidity and mortality rates? Should I be looking for an antiviral?

Dr Hay: Until we have the vaccines the antivirals are all we have really got. The focus has been on one single antiviral, Tamiflu, although there is another drug licensed but it is not currently available.

Chairman: We will come on to this later.

Q63 Dr Harris: The question is not what we would like to do in terms of trials. The question that Dr Spink asked was what should the Government be doing now that would enable us to have the right capacity and to shorten the time? Everyone knows we want to do clinical trials to get the right adjuvants and all that. We are seeking to scrutinise Government. Is there anything out there? I can suggest some things and you can say yes or no, but I thought you might have some off the top of your head that should be being done now.

Dr Hay: As far as I know the Department of Health has already been in discussions with manufacturing companies to agree the production of sufficient vaccines for the whole population.

Q64 Dr Harris: What about building up capacity? Vaccine manufacturers have said that they need to have more contracts for the seasonal flu vaccine in order that they do not build factories which are just not feasible for them economically. Even if the cost-effectiveness is not as it should be, should we not be increasing the amount of seasonal vaccine we supply in Europe and in this country?

Dr Hay: That is correct. That is the logical situation to have, it makes common sense. The companies are not going to increase their manufacturing capability over and above that which they use to manufacture the vaccine they sell.

Q65 Dr Harris: So there is something that the Government should be doing. Your advice would be that in this country and across Europe we should be ordering more seasonal flu vaccine to build up capacity.

Dr Hay: Certainly encouraging the use of the vaccine would help us in the event of a pandemic.

Q66 Bob Spink: Should we also be developing a 'library' of vaccine strains? Would that help?

Dr Hay: There has been a certain amount done on this in terms of choosing those viruses that are most likely to cause a pandemic and a number of strains have been prepared and this is on-going work, some of it being coordinated by the WHO and some of it being initiated by the European Union.

Q67 Bob Spink: The UK is known to be a world leader in the development of influenza virus vaccines and so on. Is our expertise being provided to the rest of the world? Is it being properly harnessed and used?

Dr Hay: The efforts in terms of the preparation of vaccine seeds and the information for those vaccine seeds is a role which the NIBSC play along with ourselves at the international level together with the WHO and the viruses chosen are agreed by the WHO group.

Q68 Bob Spink: What about the methods of vaccine production? We are still stuck in the old steam age using eggs. Should we be moving to DNA or to cell culture technologies?

Dr Hay: DNA is a different type of vaccine. To move to cell culture is a move which has been gathering momentum over the last few years. There was reluctance by manufacturers to invest the amount of money required, but more and more are doing so and this is quite a logical progression.

Q69 Chairman: What research is the MRC doing in this area?

Dr Hay: This is more an issue for the manufacturing companies themselves.

Chairman: Why?

Q70 Dr Harris: Is there not a role for Government - because there is not a market at the moment - to really push on this? I am not hugely keen on research being driven by Government, but a pandemic seems to be a reasonable excuse compared to some other things. Should they not be pushing much more investment, offering incentives for industry and partnerships for research into alternative vaccine methods of manufacture?

Dr Hay: There have been a number of coordinated meetings ---

Q71 Dr Harris: I would like a yes or no answer. Should the Government be doing more than it is doing at the moment?

Dr Hay: It is necessary for governments to collaborate with the manufacturing industry in improving the potential to provide a flu vaccine.

Q72 Dr Harris: Is the Government doing what you have just suggested needs to be done sufficiently at the moment, yes or no?

Dr Hay: I do not know enough of the detail to judge on one particular government. There is quite a lot of effort between governments and the manufacturing industry in this area. It is considered to be a very serious situation.

Q73 Chairman: We would like to get an answer from you and the panel to that specific question.

Professor Blakemore: I am not in a position to comment on exactly that point. I do not have facts about how much interaction there is specifically between Government and industry on cell based culture. What I can say is that cell based culture techniques will certainly be one of the areas that will be highlighted in the call for research proposals in the MRC scheme. I would not want to give the impression that this country is lagging behind the entire world in thinking about cell based culture. I had a meeting with Elias Zerhouni, who is the Director of NIH in Washington, just three weeks ago and it is very much at the top of his mind because he feels that it needs to be pushed and developed, and it will be on the agenda for that meeting that I mentioned in Beijing in three weeks' time for heads of international research organisations. It has the potential to replace egg based techniques for vaccine production. Egg based techniques, although it sounds terribly antiquated, have stood the test of time and served us very well. They are the best means available at the moment for developing vaccines.

Q74 Bob Spink: The egg based technique may be justifiable, but we are talking about avian flu and eggs may become in shorter supply than they are now. We are looking at perhaps the Government's order of 120 million doses and you need one egg for every dose. Should we not be looking at different technologies?

Professor Blakemore: I think perhaps Andrew is the best person to answer this question.

Professor McMichael: We want to keep it out of the chickens in this country and that may not threaten the supply of eggs in the short term. I think in the meeting we are having next week this very issue will come up. Where the MRC is putting more funds into research this will enable us to look at proposals like this that are not the kind of 'sexy' proposals that we would normally look at that are very high quality, exciting science. This is an important issue that to some extent is a bit boring, but it is incredibly important and this might be something that, if suitable proposals come in, the MRC would look at and fund.

Q75 Dr Harris: On vaccines, given the problems of getting enough capacity - and that is relying on industry to feel there is a current market, but it is less worried than the Government is about a pandemic flu - is there a role for the Government to set up a publicly funded manufacturing facility that is there and available even if there is no commercial business case for it and that can be used when necessary?

Dr Hay: I think they are unlikely to do that.

Q76 Bob Spink: Would you like them to?

Dr Hay: I think we have quite a clear understanding of the relative roles of the public health services and the manufacturing ---

Q77 Chairman: With respect, we do not get that impression at all. We get the impression, if I am honest, that it is being left to the market and that if there was a pandemic there would be a real problem in terms of getting vaccines quickly enough to people because there is no capacity, you have no intentions of investing in research and the Government is just basically going to have a wait and see policy.

Dr Hay: That is not true. We interact with the vaccine manufacturers twice a year when the WHO makes recommendations. There is dialogue between the manufacturers in terms of vaccine production, with our side in terms of the strains and just how this process works and problems that occur on both sides, so there is an ongoing dialogue regarding this. In terms of the provision of vaccine for this country in the event of a pandemic, I thought the Department of Health already was securing the availability of the 120 million doses so why would it need to build its own plant for that?

Dr Iddon: The previous Committee looked at chemical and biological warfare both with a visit to America and to places like Porton Down and others in this country. We came to the conclusion that if there was a serious risk from biological warfare in this country we ought to have a public capacity and that that public capacity may be based at Porton Down so that we could step up production when industry were lacking in filling the gap. That is a comment rather than a question.

Q78 Dr Harris: Dr Hay, you are saying that the Government has got a sleeping order for 125 million doses assuming that it is efficacious at one dose per injection and you do not need to increase the amount in there and that we will not suddenly find that we are outbid by another country that does this or we can sue while we are all not getting our vaccine. What I have not had an answer to, Professor Blakemore, is this question of whether you think the Government should be putting more money in to research into alternative vaccine approaches and manufacturing capacity.

Professor Blakemore: I would always be very happy for the Government to put more money into research and the MRC could certainly use more. As we have shown in the plan to invest 10 million, which is a significant amount of money, within existing resources we do have the capacity to respond to new scientific situations even within present capacity. I would like to comment on the proposal that Government ought to be establishing a public facility for vaccine production. If we had some massive enterprise, presumably a large investment of public funds ---

Chairman: We are not suggesting that. The question was whether you think that there should be.

Q79 Mr Newmark: Is the Government doing enough given that we are facing a potential pandemic?

Professor Blakemore: I think one could rehearse exactly the same arguments for pharmaceuticals production. The pharmaceuticals industry, despite some of the criticisms of it, has actually served us very well in producing drugs. I think industry is responding responsibly to the present circumstances. We know that there have been discussions going on between governments and international agencies, with vaccine producers and indeed with pharmaceutical companies that produce antivirals about how they can gear up their production, divert productivity, subcontract it to other generic producers and so on. I think this is a rather good example of governments working with industry in a potentially world threatening situation.

Mr Newmark: We are facing a potential pandemic. We do not necessarily want to rely totally on the market because the market rarely delivers what is needed in a pandemic. Given that situation, does Professor Blakemore believe that the Government is genuinely doing enough?

Q80 Chairman: Is the answer yes or no?

Professor Blakemore: I really believe that the Government is doing all that it can reasonably be expected to do at this stage and international comparisons show that, if anywhere, we are at the top of the league. Interestingly, you will have seen from the announcement by President Bush very recently that America is catching up in terms of its strategy for vaccine purchase, antiviral purchase and indeed investment in research for the underdevelopment of new technologies.

Q81 Dr Harris: If you were trying to control a pandemic, would it not be sensible to give the human influenza vaccine to people in Vietnam because that reduces the likelihood and therefore it is projected to delay the onset of re-combination occurring? Why are we spending such huge amounts of money on stockpiling, which is arguably less effective and likely to be resisted by the virus antivirals, instead of vaccinating the Vietnamese and some of the Chinese against human flu to prevent the re-combination? Have I missed something?

Professor Blakemore: The correct approach to any innovative suggestion like that is to ask yourself how you would defend such a decision if circumstances in the future when a pandemic happened showed that you were wrong. For instance, what if the essential mutation happens in Turkey or in Greece and we have given all of our seasonal flu vaccine to Vietnam, assuming that would be where it starts?

Q82 Dr Harris: I have already said that we need to build up capacity and I think that was agreed with. According to your Dr Farra, it is far more likely to happen in these places where humans are in very close contact with large numbers of chickens and pigs. On the basis of a risk approach, would that not be a sensible thing to do and would it not be the ethical thing it do?

Professor Blakemore: We do have limited resources and it is a matter of arriving at the most sensible use of the resources that we have. There is a need now in this country for seasonal flu vaccination. Thousands of people die each year from regular seasonal flu. The present strategy is designed to protect them. I would not like to see the limited resources we have diverted on the basis of a very interesting scientific epidemiological speculation.

Professor McMichael: I think the other approach would be to try and do something about the infection in the birds and/or in the chickens and ducks where it is transferring into humans. In Hong Kong they killed all the chickens after the original outbreak and that stopped it. In Thailand they culled their chickens. In Vietnam they are trying to vaccinate all the chicken. They have three vaccines, two from China and one from the Netherlands. In China they have a ring culling and a ring vaccination strategy developing. I do not know what they are doing in Cambodia or Indonesia, Alan may know. This may be an alternative way of approaching the problem out there.

Dr Harris: Is it an either or? Presumably, Colin, people die of flu in Vietnam and China as well as in Britain and indeed they may be more likely to die because perhaps their health service is not as good at providing the access and the treatments. Just looking at it globally on an ethical basis and one life and the fact that it is more likely to be cost effective in those countries, even on that basis would you not agree that the WHO ought to be concentrating on human seasonal flu vaccination in those areas as well as doing these other things as a priority, to save lives from flu and to reduce the chance of re-combination and a pandemic emerging in those high risk countries?

Bob Spink: And to increase capacity.

Q83 Dr Harris: It is a triple win.

Professor Blakemore: China has probably the biggest vaccine production capacity in the world and has a fantastic track record in the production of bird flu vaccines. One of the interesting possibilities is that that huge capacity for animal vaccine production might, in extremes, be diverted to human vaccine production. The facility that Sir John Scale visited, I think I am right in saying, produces literally millions of doses per day of bird flu vaccine. This is not a situation where China needs that much help in terms of vaccine capacity production from us; they might be able to help us.

Q84 Bob Spink: Could I ask what the timescale would be in converting the animal to human flu vaccine capacity given that there was the political will do it?

Professor Blakemore: I think it is a matter of the facilities themselves and the regulatory framework, the nature of the facilities where they are up to GMP standards and so on; those would be the principal problems. Diverting production to a different vaccine, whether human or a different animal strain is relatively trivial. What matters is the nature of the facilities and the regulatory framework for the transfer to human production in animal facilities.

Q85 Bob Spink: Is any investigation going on to check the preparedness of this if it did become extremely necessary?

Professor Blakemore: This certainly is an area of discussion amongst the WHO representatives in Beijing that I spoke to and I understand they are in contact with the Chinese authorities to discuss that possibility.

Q86 Dr Harris: I want to turn to antivirals which we trickled into earlier. We have already heard from Dr Hay that they are not enormously effective and we know that there is a danger and indeed reports already of resistance, of natural selection and evolution taking place with regard to one. Is it sensible in your view that the UK Government and other governments that have done this are putting all their eggs in one basket in respect of buying Tamiflu and not looking for a mixture of that and Relenza?

Dr Hay: I did not mean to imply that the Tamiflu was not effective.

Q87 Dr Harris: We do not know.

Dr Hay: At the present time, as I have already indicated, the actual characteristics of the infection differ from a normal human infection in the case of the H5N1 and we do not really know the best way to manage those infections in terms of reducing the infection and saving lives, so there is a lot of research needed to learn more about this. There is evidence, for example, that whereas the current recommendation is that the drug will only be effective if taken within 48 hours of onset, with the longer infection and replication of the virus in the case of H5N1 it has been shown that giving the drug at a later time has reduced the virus infection and that people have survived. We have to learn about that. The issue of resistance is also of major concern and really what characteristics are leading to the emergence of resistance. The critical nature of these people at the time when they are administered the drug can seriously affect the potential effectiveness of the drug in different cases. There is a lot we need to learn about that on the Tamiflu side. We know, as you imply, that these resistant viruses are still sensitive to the Relenza drug. Relenza has not been available to any significant extent and has not been the drug of choice because of the way in which it has to be administered. You can pop a pill for Tamiflu but you have to use an inhaler for Relenza. In these critical cases it is not clear that administration would be very easy or very successful. There are suggestions that research should be done on an injectable formulation of Relenza as one way of making that drug more useful. The emphasis really is that a lot of research has to be done. In terms of the combinations of drugs that one might use, there has been essentially no work done at the clinical level in the human, the studies to date have all been done in animals.

Q88 Dr Harris: So you do not have a problem with having just one antiviral stockpiled, which is Tamiflu?

Dr Hay: Certainly there is more need to consider the usefulness of having Relenza as well and this would take the burden off the production of a single antiviral, but this is a decision for countries to make in terms of which drugs they want. Some countries have ordered a stockpile of Relenza as well as Tamiflu.

Q89 Dr Harris: France, for example. Given what you have said about the need to do more clinical research, do you think there is a role for Government to instigate that clinical research into the areas that you indicated in your last answer but one?

Dr Hay: I think more support is needed from the Government via the MRC, for example, to support this research and I think that these would be items which the delegation to South-East Asia have considered very seriously.

Q90 Dr Harris: Colin said that he thought the pharmaceutical companies had behaved very well in these areas. Sir John Sulston argues that we need to find a way of decoupling R&D from manufacture to enable the manufacturer of Tamiflu, for example, not to be limited by the decisions of a company, however well behaved that company is in respect of licensing out to large scale manufacturing facilities elsewhere. Do you think there is a case for that or is Sir John hopelessly idealistic?

Dr Hay: I do not think there is a case for that and I think there have been appropriate discussions. My understanding is that Roche have been in discussions with companies in a number of countries about licensing the production of Tamiflu.

Q91 Dr Iddon: Is there not a major bottleneck which is almost impossible to overcome with Tamiflu in that one of the starting materials for the manufacture of Tamiflu is shikimic acid, which is a natural product and you cannot force the manufacture of that? That is the real bottleneck in Tamiflu manufacture, is it not?

Dr Hay: You can make it from bacteria. That is not the bottleneck, as I understand from Roche, that some perceive.

Chairman: Our final line of questioning is going to be on costs.

Q92 Mr Newmark: I am directing my questioning to Professor Blakemore again. I am not talking about the 10 million extra; this is an annual sum I am talking about now. The MRC has been investing approximately 1.6 million per annum on flu research. Given the flu pandemic could kill 50,000 or so, is this enough money on an annual basis?

Professor Blakemore: You have to set that question in the context of all the other demands in terms of health burden that the MRC has a responsibility to tackle. You could quote similar figures for pulmonary disease, Alzheimer's, HIV and so on. In all of those areas we have activity and we would always like to do more. The important thing is to show that we are responsive when the need increases and we have done exactly that in the case of flu. At Mill Hill we maintain not only the World Health Organisation centre but a very strong research division working on flu and others that work on other infectious diseases and that is part of the MRC's commitment to virology, infectious disease and immunology.

Q93 Mr Newmark: Given limited resources, you would love to spend more but this is enough that can deal with on-going flu challenges in the future.

Professor Blakemore: Within the portfolio of MRC activities I think we are doing our best in the area of flu. The question is whether there is more capacity out there in the community of a very high quality that is worthy of support. I am sure Professor McMichael, who is Chairman of the Infections and Immunity Board, would be very happy to tell you about all the wonderful work that he would love to fund if his board had more money.

Chairman: That is for another occasion.

Mr Newmark: Let us deal with the bigger number now. The MRC report that was written for us on Friday stated that the MRC would be committing at least 2 million for research on a potentially pandemic flu. Yesterday and today we have been informed that the MRC is committing 10 million. Where did you find the 8 million extra over the last weekend?

Q94 Chairman: Could it be from the 52 underspends?

Professor Blakemore: We have a plan for using a fraction of our underspend this year. We prefer to call it carry forward rather than underspend, but that would be an issue for another of your hearings. The MRC maintains a strategic fund which it deploys in response to more pressing need than the plans that we can draw up at the beginning of each year. We devolve most of our expenditure in the extra-mural programme in research grants to our boards to administer directly and we retain a strategic fund which we can deploy in special circumstances. We have decided to recommend - this is only a recommendation at the moment and the decision was made yesterday - to council not simply the 2 million that we have already made a preliminary decision about but a total of up to 10 million for work on flu.

Q95 Mr Newmark: Is this not really a knee-jerk reaction that is going to end up depriving funding elsewhere or is this extra money that is now coming in?

Professor Blakemore: If it is money from a central pot being used for this purpose, it could have been used for other purposes if we had not used it this way. That is exactly what strategy and tactics are all about, making sensible decisions about how to deploy limited resources.

Q96 Chairman: Was part of the tactics that you were appearing here this morning and it was important to have a good announcement on the Today programme?

Professor Blakemore: I would not want to deflate the ego of the Committee, but it is not appearances here which determine the strategy of the MRC.

Q97 Chairman: We are glad to hear it.

Professor Blakemore: I tried to unpack the background to the decisions that we have been making over the past few days and will be making next week as a result of the workshop and I hope I convinced you that they were not a reflex reaction to present interesting circumstances but were well conceived over the course of a year or more of thinking against a background of a long-term investment in flu research in the MRC.

Q98 Mr Newmark: Over what timescale do you see this 10 million being spent?

Professor Blakemore: That is a very interesting question. We have yet to work up the details of the call which will be illuminated by the outcome of the meeting next week. We envisage three forms of potential support. The first is conventional research grants which might last anything from three years to five years but with an emphasis on rapid delivery in the present circumstances. We also want to consider applications from researchers who have plans for work that could commence only when a pandemic starts, in other words when viral samples are available. I think this is a genuinely innovative move to agree to fund research projects even in advance of there being the material on which to base the subjects and we can snap into action as soon as the virus emerges. Thirdly, we would like to give the potential for existing MRC supported researchers, whether in our own units or in the university sector, to divert their research effort into issues of flu either before or after the beginning of a pandemic, with a guarantee that they could have the additional money at the end of that period to continue their original project. These are all things that we are mulling over at the moment as part of the call to give the maximum flexibility of response.

Q99 Adam Afriyie: Have you had any representations at all that have caused you to make this decision over the weekend? Has something changed out there or was this always planned?

Professor Blakemore: I think the crucial event was the meeting of our Strategy, Corporate Policy and Evaluation committees over the last two days in which the results of the visit to Vietnam and China and the deliberation within Andrew McMichael's board and discussions elsewhere have influenced the recommendations that have come out of the meeting of that strategy committee.

Q100 Mr Newmark: How are these readiness protocols going to work in practice? In the event of an epidemic, could the MRC end up overspending its budget?

Professor McMichael: I think we could respond with the first year of that funding from existing board budget, but we do refer back to council at regular intervals three times a year, whereas if we were running into trouble then we would go to council to look at the strategy budget and I think we could respond within that at least for the first year.

Q101 Chairman: Professor Blakemore, Alan Hay said earlier that other viruses might be showing characteristics that make them more likely candidates for causing pandemics than in fact the one that is being looked at at the moment. Do you feel that the current predominance in terms of avian influenza is diverting attention from those other possibilities? Which other infections would in fact cause you the greatest concern that we perhaps are not spending enough attention on?

Professor Blakemore: Certainly Alan could comment on that and on the continuous programme of work in NIMR and elsewhere around the world to monitor the appearance of new strains and to advise WHO on which are thought to be the most dangerous and concerning strains with the development of seasonal flu vaccines in particular. As Alan said earlier, the reason for special concern about H5 is the very high case fatality rate associated with human infection at the moment and the similarity of that virus to the 1918 virus which caused a very serious pandemic. I think it is quite right to be concentrating considerable attention on H5N1 but not diverting the regular surveillance that goes on for all other viral strains.

Q102 Chairman: Do you agree with that?

Dr Hay: Let me correct one thing. All the different viruses we are looking at are avian viruses, that is the source of these different subtypes of influenza A which are the potential candidates for a pandemic. The only exception to that would be the potential re-emergence of the human H2N2 virus which has not been circulating since 1968 in many of the population and it is the younger section of the population who are vulnerable to infection by that, so that is something which people are keeping their eye on also.

Chairman: Thank you all very much indeed for your attendance this morning.