Safeguarding Australia
Being prepared – from a diagnostic laboratory perspective
Tuesday 4 March 2008
Dr Martyn Jeggo
Director of Australian Animal Health Laboratory (AAHL)
CSIRO
Dr Martyn Jeggo is the Director of CSIRO's Australian Animal Health Laboratory (AAHL) and has headed AAHL since September 2002. From 1996-2002, Dr Jeggo was the Head of the Animal Production and Health Science Section of the Joint Food and Agricultural Organisation/ International Atomic Energy Agency (FAO/IAEA) Division of Agriculture, in Vienna, Austria. In that role, he managed a range of FAO/IAEA Coordinated Research Programs involving more than 200 research contracts relating to animal production and health. These were operational in some 130 countries. Among other international activities, Dr Jeggo also developed an international external quality-assurance program for veterinary laboratories.
Being prepared – from a diagnostic laboratory perspective
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Good evening, ladies and gentlemen. First of all can I thank the organisers of this Safeguarding Australia lectures initiative for inviting me to give this presentation. Can I also thank you for coming along to listen to me. I hope I don't disappoint.
I have chosen in this lecture to talk about being prepared from the laboratory perspective, and I think we are in a very good position to do that. Having just experienced a major outbreak of equine influenza across the country we have certainly learnt a few lessons. But I will be taking you back a long way before there, and looking at how we have reached where we have reached at this point in time.
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I would like to talk to you a little in the beginning about the actual disease risks that we face, and then look at what is the role of the diagnostic laboratory, within the framework of managing those risks from these diseases. I will then look at how we as a country have prepared, and I will cite a lot of what goes on at the Australian Animal Health Laboratory (AAHL) but I'll be talking in general about our national laboratory network. And then perhaps, maybe a little unfairly to some, I will talk about some of the things that maybe we can do better, and touch on some of the blue-sky horizons that are out there and perhaps offer us some more intriguing solutions to some of the problems we face.
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So what are we talking about here? We are primarily talking about exotic animal diseases arriving in Australia. We are also, of course, concerned with a new disease that might occur in Australia, or a disease that is emerging or changing in character – the obvious one here that we are all familiar with is avian influenza. Most of these agents invoke serious biosecurity and biosafety issues, and therefore managing these components of biosafety and biosecurity is essential to being properly prepared.
The Australian Animal Health Laboratory was built with that in mind: managing those biosecurity and biosafety issues that are created by exotic agents outside Australia.
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I want to cite you this quote, which has been cited on many occasions and I may not have the words entirely correct. It was made by the Chief Medical Officer in the USA, who said he recognised that 'the risks to man from infectious diseases have all but disappeared and we need to focus on those diseases such as cancer that are a consequence of our environment, what we do and what we eat'. That statement was made in 1986. Unfortunately for the Chief Medical Officer of the time, it was not proved to be the correct thing to say.
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What are these disease risks? Let's try to work through them in more or less chronological order. (We have already mentioned them to begin with.)
Mad cow disease [BSE, bovine spongiform encephalopathy] arrived, a completely new disease, unknown in animals, and whilst for a long time we didn't think it affected man, it has clearly been shown to have an effect on man as well. So that was a new disease.
In 2001 the UK experienced an 'old friend': foot-and-mouth came back in the UK in a most devastating manner, costing perhaps £16 billion to the UK economy and affecting things in a way we had never even expected foot-and-mouth to affect them – things like tourism, and access to the rural environment.
We then had another new disease emerge, SARS [severe acute respiratory syndrome]. This was striking in the way that it spread round the world. It came out of China into Hong Kong and spread rapidly into Canada, causing a global effect and certainly bringing a number of different industries to their knees. Interestingly enough, here it was the tourist industry and, related to that, the aircraft industry, that perhaps suffered as much as anybody. So here was another new effect of a new disease.
I have mentioned avian influenza, and we are still in its grip. The critical thing here is the risk that this might pose to man if the virus were to mutate with the same level of virulence and start infecting man, and so it has had a huge impact globally.
Bluetongue may not be a disease that is familiar to many of you but nevertheless is interesting now because it has started to invade areas of Europe where it has never been seen before, and without doubt global warming and climatic change has enabled the vector of this disease to invade Europe where it wasn't before, and so we are now seeing a brand-new disease in parts of Europe. It is a disease which, although it doesn't cause disease in Australia, exists here.
And of course we've had equine influenza ourselves, over the past few months. I will come back to that later.
I can't leave out by far the most important disease that has affected mankind in the last few years. That is HIV/AIDS.
So you can see that that statement made in 1986 by the Chief Medical Officer of the USA was perhaps a little bit ill-conceived at the time. It has certainly not proved to be the basis on which to go forward.
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Why have we got these disease risks? Well, we know that the risk from infectious diseases to man, animals and plants continues to grow, and we have just seen some examples of that. We are also now aware – and there have been a number of papers on this – that although we can argue the percentage, something like 75 per cent of new diseases in man come from animals. As I have just clearly illustrated, a number of the old infectious diseases continue to emerge, such as foot-and-mouth disease, avian influenza and bluetongue. And new diseases keep arising, such as HIV, BSE, Hendra/Nipah virus and, more recently, SARS.
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What are some of the drivers that are causing that to happen? I am not here to present you a lecture on that subject, but some of them will be fairly familiar. One thing, however, is the causative agent itself, and here we look at the virus which has the ability to rapidly evolve and adapt.
Man continues to provide a new host and continues to invade the agent's environment, and that's one of the reasons that we're seeing some of these viruses come out of a nidus, a comfortable situation where they weren't seen to be disease associated.
But there are other, more major factors which mankind is responsible for. One concerns the climate: global warming is undoubtedly changing the distribution of disease, in terms not only of the survival of the causative agents but also of the vectors that transmit them. The movement of people, animals and products now is global, and therefore we must look at the risks that we have to deal with on a much more global basis – and China is not very far from Australia. There is no doubt that urbanisation and centralisation in general, and the intensification of the animal production systems, provide for the virus an ideal environment in which to find lots of susceptible hosts and to adapt and to change.
So these are some of the things that we are going to have to cope with in dealing with these risks from infectious diseases.
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But, as many of you would clearly be aware, we now have this new element of bioterrorism, and related to that a biosecurity element. The main driver of this was what followed on from September the 11th, with the anthrax scare. Emerging out of that was the concept in the United States of homeland security, and the idea that we have now to look at bugs in terms of what they can do as bioterrorist weapons, as opposed to what they can do in their natural environment.
The US created a select list of agents, and that nearly brought American science to its knees at one stage, with very draconian measures both on the laboratories and on the scientists working in this space. Fortunately, that has been stepped back from a little bit now, but still that concept of select agents and all that goes with it is very strong. And Australia has recently enacted a new set of regulations around this. We have not called ours select agents, but we have called them SSBAs, security-sensitive biological agents. These rules have just been put in place and will actually come into law next year, and many of us are being involved in working out how we can meet these regulations.
It is recognised that a number of the diseases we get do occur through escapes from laboratories, and so laboratory biosecurity becomes a major issue. So not only do we have to consider dealing with bioterrorism as part of our diagnostic repertoire, but we also, as a laboratory, have to consider issues around biosecurity and biosafety.
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So what do diagnostic laboratories do? What is their role within this risk management of infectious diseases?
I have cut this down to what I see as five key elements. I am only going to talk a little bit more to these, in terms of how we prepare in Australia for dealing with this.
The first thing we do is to confirm the initial field diagnosis. A veterinarian or an animal health worker or a farmer suspects something and usually calls the local vet in, and then samples are taken and sent to the laboratory, and our role is then to confirm that diagnosis and from that one would require vaccinations initiated.
But we have to go beyond that to isolate and characterise the causative agent. I will come back to that in a moment.
Then, if it is an agent which we are worried about and that can spread, there is obviously going to be an emergency response, and the laboratory is critically involved in assisting in that.
Not only that, but we have to provide advice and technical input so that we can consider a range of different control and possible eradication options.
If eradication is the name of the game, eventually as we move towards recovery, we have to demonstrate 'proof of freedom'. If any of you have been familiar with the recent equine influenza outbreak, you will see that we now reached stage 5. We have walked our way through all of these with our laboratory network in Australia.
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What are the characteristics of confirming that initial diagnosis, and therefore how can we best prepare at the laboratory level to make sure we can do that?
Of the three key elements, perhaps the most important thing is speed. It depends of course on how infectious the causative agent is, but with foot-and-mouth disease a delay of 24 hours can be absolutely crucial. It took 36 hours in Taiwan to confirm an outbreak there, which because of that delay has been estimated to have cost them $4 billion in lost production.
But it is also important to get it right – here I have used the word 'specific'. In our case. as the laboratory which is responsible for making an exotic disease diagnosis, it is absolutely crucial that we get it right, that we are certain it is that agent. If we made the call that it was foot-and-mouth disease, the impact on Australian trade would be immediate and devastating, so specificity is critical.
The third, linked element is lines of reporting. It is absolutely crucial that the right person is making the right call. It might be possible – it is possible technically now – to provide farmers with pen-side tests to make that call on a foot-and-mouth diagnosis in the field. But if their line of reporting is directly to the local newspaper, we could certainly see that trade could be impacted on negatively very rapidly indeed. We need to have quite clear and concise lines of reporting.
So how have we prepared for that? The first thing we have done is to identify a list of key diseases and prioritise it: what are our most important ones, which ones represent the largest risk?
Australia has been very diligent in preparing plans for all of these diseases, the so-called AUSVET plans. These are prepared for all the major diseases, and with them is linked what samples you take and how you submit them to the laboratory. It is all documented, and that proved crucial in mounting an effective and rapid response to equine influenza.
It is also pretty important that we have validated assays ready developed – or that at the least, if we are not certain of the disease and we may not have the tests, we know how to go about developing those in an effective and rapid manner.
So in the Animal Health Laboratory we have prioritised all these major diseases, we have worked with livestock owners, we have worked with the Department of Agriculture, Fisheries and Forestry (DAFF) to determine that prioritised list, and made sure that for the major diseases we do have validated assays.
We have started to develop a new range of rapid and specific tests. A lot of these are built round the PCR (polymerase chain reaction), and this is a test that is very exquisite, very specific – it is also very sensitive, so it has to be very carefully controlled. It is proving incredibly valuable in the arsenal of weapons that we can use against these diseases, in diagnosing them rapidly.
We have got very clear lines of reporting, very clear lines between us and state laboratories about how we go about reporting these diseases to ensure that it goes through the right channels.
Part of that suite is making sure that the veterinarian in the field rapidly can assess, 'Maybe this is foot-and-mouth disease.' And so we run training courses, in conjunction with many others, to ensure that our field personnel are well trained in rapid disease recognition.
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The next element is to isolate and characterise the causative agent. That is important for a number of reasons.
Obviously, speed again is important here, but also important is trace back: where did it come from? With equine influenza it was important to find out which particular strain it was, where that strain occurred elsewhere in the world, and so what was the possible source of it.
Equally, we want to select a vaccine. for some diseases, like rindepest, there is no problem: there is only one vaccine available in the world, and it works against all the rindepest viruses we know of. But in the case of equine influenza there were many different vaccines – and in foot-and-mouth disease it was exactly the same. So it is important that we can characterise that virus for vaccine selection, if that is going to be the option we use.
So we have to very quickly get on and isolate and characterise the causative agent. For this we have to maintain a whole range of isolation techniques, putting it into animals, growing it in tissues, and using molecular techniques, such as PCR.
More and more we are using these molecular techniques. When AAHL was opened in 1985, the primary way of isolation was to put it in animals. Now our primary approach is to try and replicate up the genome of the causative agent, and so we have started to introduce high throughput systems that enable us to grow it up rapidly and sequence it.
One of the things we want to be able to do is to predict what might be the outcome, through so-called bio-modelling. A drawback that was recognised in the UK was that that capability didn't exist at the Pirbright Laboratory, which was responsible for foot-and-mouth disease in the UK, and so a number of modellers from different parts of the UK started to make decisions on what was the right way forward. It is absolutely critical that the laboratory do the biological experiments involved in that. That was a gap in the UK, and it is one we intend to close.
It is important with all of this data to make sure that we manage it, that we bring it together and that we use it, and so we have developed a range of different data transfer systems. I have mentioned two of them on this slide, LIMS [Laboratory Information Management System] and STARS [Sample Tracking and Reporting System]. This enables us to manage our bio-informatics information more effectively, to more rapidly make the sorts of decisions we need to make in terms of, for example, vaccine selection.
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Obviously, we will be assisting in the emergency response: looking at samples that come in from new premises that might be infected with the disease, monitoring what has happened where the disease is, being involved in movement control and so on. So we have to have a 'surge' capacity.
We are going to get a rapidly increased number of samples coming in – that is exactly what happened here in Australia with the equine influenza outbreak – and that has with it again high data throughput, and again lines of reporting are essential and that has to be worked out.
But as you ramp up the testing, and as more and more samples come in, it is easier to make errors. So it is absolutely crucial, as we do that, that we have effective quality assurance (QA) systems in place that make sure that the tests we are using are still working effectively and we are reporting the right results.
We also have to have an ability to develop new tests. For example, in Australia we decided to use a vaccine in the equine influenza outbreak, and we then needed a test that would separate vaccinated from naturally infected animals, and I am sure you can all see that that is a crucial tool in the armoury in trying to manage the outbreak. So we have to rapidly develop new tests.
Also, if we are working with several other laboratories, there is an issue of having a sufficient number of reagents and sufficient equipment available.
The first key area of preparedness is to make sure we have got trained staff available. One of the fortunate aspects of AAHL is that we have a very large research program, and we have a cadre, a pool of staff who are experienced in working right across these areas. So we do have an available surge capacity in staff.
We introduced robotics some four years ago, paid for by the Department of Agriculture, and we now have a high throughput capability built around that robotics.
I have mentioned the Laboratory Information Management System that has improved our data handling, and I have mentioned QA. We are fully accredited and we maintain that, and we make sure that we have internal quality control – IQC is a daily operational activity – and that all our tests are validated. It is interesting to note that in the UK the tests were not validated, and the EU were very reluctant to pay the UK a lot of money at the end of the day because they had not used validated tests. We have validated tests.
And we retain emergency stocks of crucial reagents, and we actually talk all the time to manufacturers in terms of needing extra equipment in case of major outbreaks such as, for example, PCR equipment.
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One of the key elements we would have to do is to talk to those decision makers and policy makers who are trying to manage the outbreak, and that is where it is important that we have experience of diseases, we know what the risks are from a disease, how much virus is shed, which particular species might be shedding it. And this comes from having an effective science and research program underpinning it. So one of the things that AAHL does is to maintain an extensive and vibrant underpinning research program, and that is crucial to us in delivering this outcome. I will come back to that in a moment.
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As we move to recovery and proof of freedom testing there is a large number of animals, invariably, that have to be tested. So again we want high throughput testing capability and again a strong QA environment. In this case, not only do we want to know that results can be believed; it may well be that so do our trading partners or those overseas. We have to be able to show to them that our tests are giving reliable results and that they can be convinced that Australia has genuinely eradicated whatever disease it is saying it has eradicated. And clearly we have to understand the regulatory environment of a test that might be used at an international level.
We achieve that again by having a surge capacity, and by being accredited – we maintain our QA – but we are also very familiar with the regulatory environment by being an international reference laboratory for a whole range of different diseases, and that means that we are in that international regulatory environment and we know what has got to be done for Australia to demonstrate that it is genuinely clear of these diseases.
We do focus on continually improving and monitoring our tests. I use here the word DIVA [differentiate infected from vaccinated animals], which is the name of the test that separates vaccinated from naturally infected animals. Increasingly it is becoming the order of the day to use vaccines in dealing with these major epizootics, and so these types of tests are crucial. We continually assess and develop these in our own laboratory.
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Here I have listed some additional activities, just to give you a feel for a few more things that we do. Like all good emergency response personnel we have to have plans, and over the last three or four years, learning from many of the other groups in Australia, we have developed emergency response plans for these exotic diseases. And we do practise them. In the last two or three years we have had major laboratory exercises in foot-and-mouth disease and avian influenza, but I have to say there is nothing like the real thing and equine influenza was probably the best 'simulation exercise' we could have had.
We have a duty roster: we have to have people on duty 24 hours a day. And I have mentioned to you that we have many of our research scientists who are continually being introduced and working in the diagnostic area so that they can transfer in response to a major outbreak.
I have put 'overseas activities' here. That hides a plethora of work that we do, in two different ways. First, it is clearly advantageous to Australia if the countries around Australia have an effective management system, diagnostic system, response system. That will reduce the risk to Australia. So we do work closely with those countries around Australia to ensure that they are as best prepared as we can help them be. Secondly, by working in those countries we better understand the risks that they pose to Australia. We get first-hand experience with many of the diseases that don't occur in Australia. So these overseas activities are crucial in our preparedness portfolio.
Training is critical. We train staff from state diagnostic laboratories in Australia, so that they will be prepared. But, as I mentioned, we also bring in veterinarians and demonstrate to them these diseases and the samples that we need, to ensure that in general everybody is prepared and able to respond to a major outbreak.
I have already mentioned some of the quality assurance activities, but AAHL has a huge focus in this area to ensure that what we do we know can be relied on as correct.
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I mentioned previously that underpinning research program, and to me that is key to the role of AAHL.
Most of the diseases that we work with don't occur in Australia, and there isn't first-hand experience of them. If we weren't doing that research, we would have a great problem in providing a proper risk assessment of those diseases and ensuring that we have the right tests and providing information and technical advice to the policy makers and government, whether state or Commonwealth. So it is important that that works. It maintains the vibrancy of our diagnostic programs if these people are diagnosing diseases through a research problem that may not be in the samples coming in from an outbreak.
One of the tricks in doing this is to maintain a balance between diagnostic and research activities, and it is not an easy balance to maintain. Diagnostic work might seem quite an exciting place to be at the moment, but for a lot of the time it doesn't have the excitement of the research program, so many of the diagnosticians would rather be doing research. But getting the balance is absolutely crucial, and in fact there was a very sorry lesson learnt with the foot-and-mouth outbreak in the UK, when the Pirbright probably didn't have that balance right. So when it came to the UK responding to that foot-and-mouth outbreak, it didn't have robotics in place, it didn't have an effective QA system in place, it didn't have data management in place, it didn't have validated tests. But it had a great research program. So it is very important that we maintain a balance as part of being prepared.
I have mentioned here, briefly, some of the research areas that we work in. They are not particularly difficult to come to grips with, because they do make sense.
First of all, we have to be working with the disease, we have to understand the disease. So we work with the pathogenesis of it. We need all the time to have new test development, so that forms another cornerstone of our research program. We certainly want to look at innovative control options, and one of the ones we are looking at at the moment is developing chickens that might be resistant to avian influenza. But there is a whole range of other options that we look at as part of our research program. And I mentioned previously the area of predictive bio-modelling, which we see as an important and increasing area of our research portfolio.
So you can see that those four areas really cover the whole span needed to underpin our diagnostic program.
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But is all this enough? I don't want to give a detailed account of what was learnt from the equine influenza, because (a) this is not the right forum, and (b) we haven't yet finished the job. But I will touch on a few lessons that we have already learnt, that are in fact giving us some of the clues to go forward.
One thing is for certain. It does take an awfully long time to get samples to AAHL from some parts of the country, and perhaps this is too long. Therefore, we may need to look at other ways of doing field diagnosis prior to samples getting to AAHL and having confirmation. What is critical is not knowing absolutely what it is but, if you think it is 90 per cent certain, taking corrective action which can be undone later in the day if it is proved not to be correct.
An obvious one here is movement restrictions. In the equine influenza outbreak, what saved the day for Victoria, without a doubt, was the call made by New South Wales that they thought they had got equine influenza. The borders were immediately shut and horses could not cross them. It was actually two days later that samples arrived in AAHL. That call was made by a state laboratory, quite correctly – actually, breaking the rules that were in place at the time, but nevertheless a highly effective call, and that is what needs to be done more quickly.
There are now many tests that can be used and can be used in a biosecure environment, and can be used in state laboratories which won't have the same level of biosecurity as AAHL or even can be used in the field. I will touch on that in a moment.
In reality, the diagnostic response isn't just given by AAHL. An enormous amount of excellent work has been done by the state laboratory in New South Wales and the state laboratories in Queensland. In fact, the vast majority of testing has been done in those laboratories. The New South Wales lab tested something like 120,000 samples. It is a team approach that we need to have.
But we still have problems with information exchange. We still don't have in place full systems for moving data around.
Transparency of reporting still remains a problem.
Quality assurance of tests becomes even more crucial when you have got a network approach, and when people are testing in many centres, and we certainly have been working on that area.
We are not alone in this – which is quite an interesting point to make. More recently, in talking to colleagues in the USA and Canada, I find that they have the same situation that we have in Australia: they are very large, and they have a federated system. They have a number of states and they have a Commonwealth, in our case, and a national government, both in Canada and in the United States. And they have an identical system to ours. And so they have started to look at, 'How do we manage this environment with infectious disease risks within a federated environment and a large land mass?'
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One of the solutions is to create a devolved emergency response laboratory network, and to look at it that disease things are national. We have this national animal health laboratory system developing to provide a national approach, and we are looking at some tests that could be devolved to the field or state laboratory system that are biosecure and are biosafe. That would naturally build surge capacity into the system, because it wouldn't just be AAHL, it would be a number of laboratories that would be involved in any response.
Clearly we would have to ensure transparency of reporting, and we would have to make quality assurance a central element of it. And that is exactly what is going on in the USA and Canada right now, in those areas.
Fundamentally, we can approach this problem more nationally and recognise that these diseases are trans-boundary. They are known as trans-boundary diseases at an international level, and they are within the Australian context.
There are two important things that are moving this forward. One is that there is a laboratory network system called SCAHLS [named for the DAFF Sub-Committee on Animal Health Laboratory Standards], where all the veterinary bodies meet together. In fact, there is a meeting next week at the Australian Animal Health Laboratory, where we will have a workshop on this approach. And I and some of my state colleagues, and indeed my colleagues from DAFF, will be visiting Canada to discuss how they have devolved their system, and look at whether we can learn lessons from them.
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I want to take you now on a little bit of a ride, a little bit of an adventure to look at one or two things on the horizon that might help us in moving forward.
Biosensors are something that was promised four or five years ago, when we really got excited about them. The idea is that we would implant a device in a sentinel animal – a sheep, a chicken, a cow – and that that would be able to detect a disease agent or something occurring in the animal that gave us information that it was infected, and that could be transmitted remotely to a central laboratory. Now, that may sound somewhat futuristic but in reality it already occurs. (I will come onto that in a moment.) Clearly there would be an enormous decrease in the delay; it would be real-time. These tests that we are talking about usually have enhanced sensitivity, and are detecting down to very low numbers of molecules. They are usually very simple assays, and are deployed on site – they can be used anywhere in the field. They don't have a dependency on skilled operators, and so they obviously would work well in poor laboratory environments.
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Do such systems exist? Well, there is one that works quite effectively, and that is one that measures glucose. The device itself, the sensor, is implanted under the skin and transmits to a receiver, which actually is worn on the wrist and gives a continual readout of glucose levels. That is available now, and has been for some time. When this first came out, everybody got very excited and felt, 'This is the way forward.'
And I certainly was involved in a biosecurity research centre where this was one of the cornerstones of what we intended to develop.
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Unfortunately, life is never meant to be simple, and it isn't in this case. What we found is that biofouling – that is, the creation of the body's response around these sensors under the skin or elsewhere – is highly restrictive in many situations, and so far we haven't cracked that problem. And so, whilst we actually do have the technology to detect the organism, and we have certainly got the technology to transmit the information, the body is still pretty good at dealing with us, and so it manages to put a fog around the issues that aren't working.
So it something for tomorrow, but it is certain that in some way we will see one answer to many of the problems we face.
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But what have we got today? I have mentioned already a little bit about this to date, but I want to just take you a little bit further with it.
I mentioned to you the PCR tests. These PCR assays now are becoming very easy to use, they are becoming very small – and you can see at the top left on this slide a tiny machine, whereas the picture at the bottom left shows a much larger device. These are now commercially available. At a meeting in Melbourne last November we were shown these devices working. They are biosecure, the operator merely puts the sample in them, following straightforward instructions, and the machine does everything else. There is nothing else to do.
Even more exciting, these machines are connected to a satellite phone (it is inbuilt in them) and the information is transmitted in real time to, let's say, the Australian Animal Health Laboratory. We can actually see the test results coming off. They usually come off in anywhere between 40 minutes and an hour, and we would actually see that test run in the field in real time, and be able to draw the conclusion at the central lab of whether that sample put in there in the field was positive or negative, to a very high degree of specificity and sensitivity. These are available now; they are commercially available. They cost about $20,000 a go at the moment, which makes it a bit prohibitive to stick one on every farm in Australia, but nevertheless they give you a good clue to where we might be going.
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I will just mention one or two other gaps. These are much broader issues that I see, before I come to a summary.
In relation to financial resources, one of the problems with the world we live in is that we are basically an insurance policy. We're there in case something happens. And as with all good insurance policies, when times get hard, the first thing you do is to start reducing your insurance policy and say, 'Well, perhaps we'll have to do without that, because maybe it won't happen.' And that is the threat that we live under all the time. In many ways, in 1986 when that statement was made, we saw a considerable reduction in the input into veterinary laboratories and, I suspect, medical laboratories around the world, certainly in Australia. There was a genuine belief that you didn't need to invest in that area, and so the insurance policy was reduced. We are to some extent paying the price for that now, and we need to rethink about those insurance policies.
Investment doesn't just involve the infrastructure but it also involves the people. And so for quite a number of years very few people went into laboratory work, very few people went into infectious disease research or diagnosis, and now we are paying the price for that also. We have very few young people coming through the system, and that gives us a gap that we have to make up. A lot of work is being done in that area, and there is a lot of activity right now, but that is a gap.
I have mentioned IT, I have mentioned information exchange, but it is crucial. In our modern world, our machines generate an awful lot of data, and unless we can manage that data and make sense of it, there is little point in generating it. And so bioinformatics and managing data are a crucial area. In Australia we are seeing right now some serious investment in that. I don't know how many of you in the audience are familiar with the NCRIS (National Collaborative Research Infrastructure Strategy) investment. What it means is that the Commonwealth science organisations are investing around $500 million in creating an IT structure throughout Australia that will ensure that our research information can be moved around. The diagnostic laboratories have plugged in to that through their own programs. This slide contains a few acronyms, but what it is showing you is that there is software being developed, larger pipes to send the data down are being developed, it is being addressed. So we are not naïve to it, but it will take time and we do have some exposure right now.
Finally – and this is perhaps the biggest single message I need to leave you with – there is the left-field concept, that most of what comes at us, we did not expect to come at us. Whether it is the equine influenza, or foot-and-mouth disease in the UK, or SARS, or BSE, none of them were predictable. In fact, Europe did a wonderful exercise in the year 2000, looking really carefully at where foot-and-mouth would come into Europe, and they recognised that it would come across the border into Austria and into Germany. They got it seriously wrong.
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We come to the bottom line. The risks continue to grow, and we will get outbreaks. It is not going to go away. The risks are continuing, and I think I have given you enough demonstration of that.
We will need to continually evolve and improve, and I have demonstrated, I hope, in my talk that we are thinking that through, not only in terms of technology but also in terms of the systems and policies and strategies that we have got in place.
And we always need to be ready to learn. There will be new technologies, there will be new approaches, and we need to be up with the ball in picking this up.
As I mentioned, we do need to keep up continual assessment of technologies. There are some great things around the corner. The question is how to choose the right ones and get them into the area and operating effectively for us to manage those risks.
And I think we need to continue to think outside the box. The concept of the devolved network is not something, I think, that was particularly openly thought about until very recently, but somebody has come up with the idea and now we can see it as presenting a way forward, and one we can explore.
So the bottom line is: yes, we are prepared – at least as well as we can be, given the unknowns.
Thank you very much.
Discussion
Kurt Lambeck: Thank you very much, Martyn, for a very informative lecture. I am very glad to know that you are here to protect us from these emerging diseases, and I am particularly glad that you are here to give good advice to our policy makers. So thank you very much.
Question: How many laboratories are in the network around Australia?
Martyn Jeggo: We have seven state laboratories. We have a number of university laboratories and we have a number of private laboratories, and potentially all of them can be in the network. I indicated to you that this is a new idea, and we have got a long way to go in taking this forward. But we are not excluding any laboratory, in terms of whether it is university, whether it is a state veterinary laboratory or whether it is a private laboratory. As I said to you, that will be the starting point of the meeting next week, where we will start to explore how this might work. It is potentially quite a number of laboratories.
Question (Adrian Gibbs): Firstly getting back to the idea, which I am very interested by, of the need to know exactly what an exotic entry is so you can advise on vaccines. The equine influenza, certainly, led to the importation of a vaccine which wasn't just equine influenza; it was in fact a haemagglutinin gene of equine influenza and canarypox. So instead of having one disease to look out for, you really had two diseases, because canarypox had not been, as far as I know, tested for in Australia and there is some preliminary evidence that it would infect marsupials but had never been tested.
So were you entirely happy with the choice of that particular vaccine?
Martyn Jeggo: As you would well know, there is a regulator in Australia, the OGTR [Office of the Gene Technology Regulator], whose function is to look at the risks associated with importation of these types of genes and gene products. And of course before permission was given for AQIS [Australian Quarantine and Inspection Service] to import the vaccine – and you are right, it was a pox vaccine recombinant – that had to go to OGTR and they did a full assessment of it.
Now, there were caveats and rules to that importation, which meant that it is restricted in use to this disease emergency. So they did not give an open licence for it to come in, but nevertheless that assessment was done by our best experts and it was their opinion that it was safe to use in this emergency situation.
Question (cont.) (Adrian Gibbs): This is a supplementary question. Is anybody following up whether it has escaped into wild birds and marsupials?
Martyn Jeggo: I don't know that anyone has specifically followed up at this stage. I think the risk is extremely low. I think you are right, there is a possibility, but as far as I know nothing has been done in that area at this moment in time.
Question (cont.) (Adrian Gibbs): One of the ghosts in this building is that of the late Bede Morris. One of his passions towards the end of his life was over the business of importing exotic pathogens in order for people like yourself to keep up with the latest needs and requirements, rather than going overseas and studying them there. He ran a very long campaign opposing the importation of foot-and-mouth disease virus, and I wonder whether we can reassure his ghost that exotic pathogens are not now imported. There must be some sorts of rules about it. What are the rules?
Martyn Jeggo: Before any exotic pathogen can be brought into Australia, it has to be evaluated fully by AQIS, and if it is one that OGTR is interested in, it has to go through OGTR as well. So there is a very formal process before any pathogen can come in, and that process has to be fully gone through before we make any attempt to bring it in. It is not an open door, we can't just bring pathogens that are exotic to Australia into Australia without doing these full risk assessments first of all. It is under very, very clear regulatory control.
As you are probably aware and as I mentioned in my talk, there is now going to be an increase in these regulations – based more around the biosecurity aspects and the security-sensitive biological agents, but it will see an increase in regulation around that area. I don't think it is quite clear yet who the regulator might be. It may well be something that OGTR has added to its portfolio of things it has to do, but nevertheless there will be a continual assessment of that. Throughout the presentation I mentioned biosecurity and biosafety issues as paramount, and I would fully endorse the concerns that Bede Morris had at that time and we still have today.
Question (Jim Peacock): What are we doing about the difficulty of bringing young researchers into the country to help fill the people gap that you mentioned?
Martyn Jeggo: There are a number of things being done. First of all we recognise the problem, and that is a very good starting point. And there have been a number of surveys conducted, certainly around the veterinary area. For example, Andrew Turner, who is CVO [Chief Veterinary Officer] of Victoria, has conducted a survey of veterinary laboratory needs. Animal Health Australia is at the moment looking at that area very closely and working with industry to consider ways of providing training fellowships and the like to improve that. We at AAHL have recently received extra funding from the Commonwealth government to recruit people, and we are recruiting with very much a younger age group in mind and bringing in people who can be part of the succession planning process. We are looking not just within Australia but globally, not only trying to attract Australians back to Australia – and there are some very, very good Australians overseas – but also bringing in some new blood to try and enhance that capability.
So, in general, we are aware of the problem, there are more resources being put in that area, but we have still got a long way to go.
Question: One of the important quarantine issues when investigating exotic diseases is the biosecurity risk in handling and transporting confirmatory material containing an infective agent. I am just wondering how much of a priority it is for AAHL to investigate not just expensive in-field tests but more the issues of being able to do tests within AAHL on samples that are themselves not really infective. I am referring to the idea of, say, having a simple blood drop on filter paper and being able to do extensive pathotyping on that, rather than needing to have actual agents on a swab and large blood samples and things, because the current system substantially slows down transport et cetera.
Martyn Jeggo: I guess you are asking around the question of what we would call pen-side tests.
Question (cont.): Not really pen-side tests. It is more actually relying on AAHL to give a complementary diagnosis with the extra facility, but the fact that you can actually deliver to AAHL something extremely rapidly because it is not such a risk. Rather than a swab that actually contained agent upon it, or a large serum sample, you might actually have taken a very inactivated sample. I don't know the science of it, but there are certain technologies being investigated in the world where you can really come up with a confirmatory diagnosis on the basis of your genetic testing.
Martyn Jeggo: Really, I think I referred to that in the talk quite a few times. I talked about PCR technology, and that is basically looking for bits of the plant rather than the whole plant, and most of these gene-based technologies do rely on specimens that can be treated quite roughly. Small amounts of DNA will survive in the environment extremely well.
Certainly that is where most diagnosis has gone these days, to looking at that genetic material. Mostly from that material you couldn't actually grow the organism, but you can make some very rapid and exquisite tentative specific diagnoses. So yes, of course we are working in that area. That is really mostly what I was talking about in terms of those PCR tests that are around that area, and that means we can give you a diagnosis in a matter of hours, as opposed to before, when it might take us two to three days to get a confirmation.
Question (cont.): My question is relating to whether those technologies are heading towards being test in their own right, and not requiring other tests.
Martyn Jeggo: They are, yes. What you really want is more than one test, and it doesn't really matter what it is – you don't have to grow the organism up but if you've got two or three tests all saying the same thing, you have a great deal more confidence in confirming that diagnosis. So yes, they are being used in that manner. I can give you a very clear example.
We had two different PCR tests for equine influenza that the labs were able to run. The first test was on one particular part of the gene, and if that was positive then they would run another test on another part of the gene to confirm that it actually was equine influenza. That was two of those PCR tests, run one after the other, the second one being the confirmation test.
Kurt Lambeck: Thank you again very much, Martyn, for a very interesting talk. Thank you again to the audience for coming this evening. It is always gratifying to see a good audience on a Tuesday evening in Canberra.
