In a series of three articles, BBSRC Innovator of the Year 2013 winners reveal the secrets behind their innovations.
In this, the third, Social Innovator winner Peter Mertens recalls how his group helped prevent the bluetongue disease of sheep becoming endemic in the UK, saving the British economy an estimated £480M in 2008 alone.
In the second, Overall Innovator winner Dr Ryan Donnelly explained how hydrogel-based microneedles might be the future of safe drug delivery, and how they could be used for non-invasive blood monitoring. In the first, Commercial Innovator winner Dr Anna Hine revealed the highs and lows of commercialising an elegant technique for building proteins from gene libraries.
How does it feel to win?
It's good! We obviously knew the relative importance of the whole group efforts and we have received many thanks for doing the work, but this is the first actual award.
As a first award is it a bit special?
Yes, very much so. It's nice that it's recognition for the team and their collective work to make a difference – over 45 people were involved in this success and while we couldn't list all of them; it was simpler to represent the team as the four group leaders. This is recognition that we did a good job which is lovely, but the great thing is that we stopped all those animals dying and I would see that as the prize.
What's your experience with bluetongue disease?
We'd been working on bluetongue for 30-40 years at The Pirbright Institute (formerly the Institute for Animal Health) and initially it was a semi-tropical disease that people said was unlikely to come to the UK. But we knew we had Culicoides midges here, which we thought would transmit the disease from sheep-to-sheep, and we knew we had susceptible animals, so we raised awareness of the risk.
What happened during the outbreak in northern Europe?
The first recorded outbreak of bluetongue in northern Europe started in the Netherlands during 2006. In that year spread was low level and only a few animals were affected. The virus was typed as Bluetongue virus type 8 (BTV-8) at Pirbright, using a new generation of diagnostic assays that we had just developed specifically for such an eventuality. The virus survived through the winter (when there are few midges about to transmit it), reappearing with massively increased intensity during 2007.It then spread further across Europe, shutting down animal movements and trade and killing many thousands of animals. Defra were very and assembled a 'Bluetongue Experts Group' so that we could meet with policy makers and officials on a regular basis. We were working with the MET office, where they have a big computer running a program called NAME (Numerical Atmospheric-dispersion Modelling Environment), which based on wind movements predicts where the air at a specific place will be or were in the next or last 24 hours. They told us that on 4 August 2007 there was a plume of air from the infected region in the Netherlands that travelled across East Anglia. It was the right wind speed, temperature and time of year with lots of midges about and almost a month later we got the first ever recorded cases of bluetongue in the UK, which is about right (for the incubation period of the virus). Based on experience from mainland Europe, this indicated that in the next spring/summer (2008) we could expect massive levels of fatal infections in sheep and widespread but less severe disease in cattle in the UK, resulting in restrictions on animal movements and trade.
And how was a major UK outbreak averted?
There was no suitable vaccine for BTV-8 available in 2007 when we got our first few cases in the UK. It was clear to the Bluetongue Experts Group that without some decisive action 2008 was going to be a disaster for the UK livestock industry.
Defra had discussions with the big vaccine manufacturers and Intervet (now Merck, Sharpe and Dome) agreed to make an inactivated and therefore safe vaccine against the northern European strain of BTV-8. The veterinary Medicines Directorate therefore gave a provisional license in early 2008.
Defra's 'Joint Action against Bluetongue' (JAB) vaccination campaign started in spring 2008 before the midges came back and all credit to farmers and veterinarians because they got the vaccine out into the field. The vaccination campaign was voluntary, so to get publicity we went out and talked to vets and farmers, we did a lot of radio and TV interviews on News at Ten, Sky, everything…
What were the impacts of the vaccination campaign?
Gordon Brown was PM at the time and in an Oxford debate he stated that the relatively small amount of money spent on research at Pirbright had saved the UK £480M during 2008 alone (ref 1).
What were your innovations during this time?
First, we developed the suite of new diagnostic tests by rtPCR (reverse transcriptase polymerase chain reaction, which amplifies and detects DNA from the viral RNA) that allowed us to characterise the virus genetically and to determine its serotype within hours rather than weeks, something that is essential for vaccine development.
We shared these tests with other labs across Europe. We also provided support working with entomologists to find out which insects were transmitting the virus. We worked with modellers to predict how the outbreak would spread, with the MET Office who provided information on winds likely to move the bluetongue-carrying insects. The culmination of all that is that we advised Defra: "you must vaccinate against this or it will be a disaster."
What was novel about your new diagnostic system?
A couple of biochemical and immunological methods are really important. First, the vaccines were frankly pretty crude, containing all of the different proteins that make up the bluetongue virus, so as a result the animal makes antibodies to all of the viral proteins, making it very difficult to distinguish an infected from a vaccinated animal (DIVA). So if you vaccinate with that sort of vaccine, it's easy to end up with no diagnosis, no surveillance because everything looks positive. Secondly, the old tests were based on isolating the virus and adapting it to grow in cell culture, which has a high failure and can take weeks. Alternatively you can get antibodies from an infected animal and see if they can neutralise the virus, but that can also more than a week to do.
We used rtPCR and by selecting specific primers and probes (strands of DNA/RNA that match and amplify the virus DNA/RNA) we can identify the virus serotype (virus strain) within 3-4 hours. There are 26 types of bluetongue virus and it's important to identify the right one quickly. The rtPCR test would detect the virus in a blood sample, but the vaccine doesn't give you a false positive signal, and in face of infection and widespread vaccination, we still had working diagnostics.
How was your new test used during the outbreak?
Our reference lab ended up testing approximately 100,000 samples during the 2007-2008 outbreak so animals could be moved safely, and to prevent importation of more virus-infected animals.
Surveillance was really important to help show where we should vaccinate. It also helped us to monitor and if need be prevent importation of any more infected animals, particularly as by this time BTV-1 had also been detected in Normandy. Finally, it was needed to show that after the vaccination campaign, we were again 'disease free'. EU legislation means that we were obliged to accept animals from northern Europe, but now that the whole of northern Europe is disease free – vaccination has stopped and we've gone back to peace time as it were.
Who else has benefitted from the new tests?
In effect the new system includes group specific assays that will detect any bluetongue strain, as well as 26 individual tests (for the 26 bluetongue serotypes). Although the old assays still work these new tests have become the standard diagnosis system for bluetongue all around world. We've shared the tests with labs in America, Australia, most of Europe, India, Korea, parts of Africa and Russia. Beyond that we've work with a company (LSI) to commercialise the diagnostic tests, so you can now buy them off the shelf.
We've also developed similar tests for African horse sickness virus, for epizootic haemorrhagic disease virus and equine encephalosis virus… all viruses that are related to bluetongue. The Pirbright Laboratory is also a Community Reference Laboratory for bluetongue in Europe.
We're now setting up networks of labs in Brazil and India, particularly, to get a wider picture of what's going on globally. We have just got a grant awarded in Brazil, and there's other applications pending to work with more international partners.
We are currently working towards cross-reactive vaccines that will protect against and prevent transmission of any bluetongue strain. If successful this would allow a more rapid response to future incursions of novel bluetongue types into Europe. The recent successes and rapid eradication of BTV-1 and 8 in northern Europe, after the inactivated vaccine campaigns, suggests that a fully cross-reactive vaccine could potentially also lead the way to global control of BTV and even an eradication campaign.
What is the bluetongue threat to the UK?
Although the type 8 has gone away, there are a lot of strains still in circulating southern Europe, and type 14 in Russia, Poland and countries immediately to the east of Europe. We're waiting to see if it spreads further into Europe this summer.
We've stopped vaccinating as there isn't a current problem, and there is roughly a 20% turnover in animals in the UK each year, so in 4-5 years we're back to having a fully naive and susceptible population. Particularly if we have a warm summer it could all kick off again as we still have the animals and the vectors.
Did you always want to be a scientist?
I always knew I wanted to be a scientist from the age of about eight. Originally I was interested more in plants and botany, growing orchids and cacti – things which I still enjoy. I got into all that at school, and then did 'A' level biology, physics, mathematics, and chemistry. I went onto a degree in Microbiology and Virology at Warwick University, and then an opportunity appeared for a post-graduate degree working on viruses of insects in the Forestry Department at Oxford. After my doctorate I moved to Canada as a post-doctoral Fellow at the University of Guelph in Ontario, working on viruses of salmon and trout. These viruses all have genomes composed of separate segments of double-stranded RNA. I came back to the UK in 1981, 32 years ago, and have worked on bluetongue mostly to the present day. Is it really as long as that?!
Is such a success story the pinnacle of your career?
It's certainly one of them. About 10 years ago with Dave Stuart's group at Oxford University we solved the atomic structure of the bluetongue virus core – it's composed of 1000 separate protein molecules which I think is still the largest atomic structure ever solved – and that got onto the front page on Nature. Scientifically that was a real high spot.
This is a high spot in a different way. This is one of the major recent successes for veterinary medicine. If you look at what happened in Germany, France, Holland and Belgium, they lost hundreds of thousands of animals directly killed by the disease. In UK we had 300 infected animals, of which probably less than 50 died with no culling at all because the virus is insect-transmitted and we currently have no effective way of controlling the midges.
The UK has perhaps the richest history of scientific innovation of any country in the world, and the Royal Society report The Scientific Century: securing our future prosperity shows that innovation and commercialisation are flourishing in Britain.
For example, from 2006-10 university spinout companies have floated on the stock market or been taken over for a combined total of £3.5Bn and employ 14,000 people in the UK. Furthermore, between 2000 and 2008, patents granted to UK universities increased by 136% and university spin outs had a turnover of £1.1Bn in 2007/08 (ref 2).
The perception that the UK is not successful when it comes to commercialising science, or as some have put it: "Britain invents; the world profits" is therefore clearly outdated, and that strategies to harness and increase innovation are working.
In addition to the benefits it brings, it is argued that present £7.5Bn science budget pays for itself many times over as technology is developed and then taxed as it is sold. The Medical Research Council estimates every pound it spends brings a 39p return each year (ref 3). Moreover, independent studies have shown that for maximum market sector productivity and impact, government innovation policy should focus on direct spending on research councils (ref 4).
Finally, the UK produces more publications and citations for the money it spends on research than any other G8 nation. Specifically, the UK produces 7.9% of the world's publications, receives 11.8% of citations, and 14.4% of citations with the highest impact, even though the UK consists of only 1% of the world's population (ref 2).
- The economic and social impact of the Institute for Animal Health's work on Bluetongue disease (BTV-8) (PDF)
- The Scientific Century: securing our future prosperity
- Medical Research: What's it worth? (PDF)
- Public support for innovation, intangible investment and productivity growth in the UK market sector (PDF)