Innovators 2012 part three – Jim Murray
9 May 2012
In a series of three articles, BBSRC Innovator of the Year 2012 winners reveal the secrets behind their innovations.
In this, the third, Professor Jim Murray of the University of Cardiff describes how new DNA detection technology using light could improve on-the-spot medical and food diagnostics. In the first, Professor George Lomonossoff of the John Innes Centre explains how a safe and accessible way to make proteins in plants could revolutionise vaccine screening and yield novel metabolites. In the second, Professor Russell Foster explains how discovering an entirely new class of photoreceptor in the eye transformed our understanding of how body clocks regulate healthy ageing.
In 2009 BBSRC established the annual Innovator of the Year competition to celebrate scientists who delivered science with high economic and social impact. See 'The money of all invention' for details on how innovation powers the technological treadmill that can solve both local and global problems, drive economic growth, and make our lives longer, easier and happier.
How does it feel to win?
It's really exciting – I felt very honoured. It reflects a tremendous amount of effort put in by a number of people, and particularly my co-applicant, Dr Laurence Tisi, who really has brought this whole project from initial concept to commercial reality.
Everyone is delighted to get recognition for an exciting new concept that could make a lot of difference to people worldwide in delivering the benefits of diagnostics in a whole range of applications from healthcare to environmental safety.
Describe your innovation in your own words...
I like to characterise it as 'DNA-into-light' technology. The BART [Bioluminescent Assay in Real-Time] technology means we can detect any chosen DNA sequence and produce a light signal. And because it's based around copying the DNA many times so we can detect it, it means it's also incredibly sensitive.
The spin-out company Laurence and I founded called Lumora has developed a prototype device that you can pick up in one hand; the present version is roughly the size of an old-fashioned telephone. This means the test has simplicity of operation, it's low cost, it's portable and it can be used almost anywhere.
It's based on light detection of DNA, not chemical?
Yes. The conventional method for detecting pathogens by DNA sequence is to use real-time PCR [polymerase chain reaction], which is usually a complex lab-based technique. In this, the temperature must cycle up and down and the detection system is based on detecting fluorescence from the copied DNA itself.
How is the BART system different?
We detect a byproduct of that DNA copying process. A chemical is made when you synthesize DNA called pyrophosphate. This can be converted using an enzyme into ATP [adenosine triphosphate], the universal energy currency of life. Then we measure ATP using a temperature stable form of the enzyme that makes fireflies glow, luciferase, which we've been working on for a number of years. This is called bioluminescence – the production of light by an enzyme, and is totally different from fluorescence, which is when you have to shine light of one wavelength onto something to excite emission of a different colour light.
So luciferase reacts with ATP, which is measured as a proxy for the DNA?
That's right. The neat thing about the whole system is that it's run in one tube and all the ingredients are there from the start. So you just add your sample, heat it so that the DNA is copied by a constant temperature DNA amplification mechanism, and the light signal rises to a peak and then switches off in proportion to the amount of target material that was originally present. So we can tell whether a target organism is there and how much is there.
And the DNA is specific to what you are looking for?
When the DNA is copied we are only copying a small piece of DNA we choose to be unique to that particular organism. So for example in a HIV-specific test it will only give a signal when HIV is detected. And you can test for any DNA sequence from any organism.
What kinds of tests?
A stated focus of the company is currently in HIV tests, which is important in two particular areas. One, viral load testing – monitoring the amount of virus in a patient to ensure that treatment with anti-retroviral drugs is effective which enables clinicians to modulate treatment. And secondly, testing newly born infants to see if they have picked up the virus from their mothers.
Why medical diagnostics?
A reason why the technology is exciting is that it will be sensitive and accurate enough for the developed world, and low cost enough to be used in low resource settings in the developing world, particularly in sub-Saharan Africa where there is a desperate need to test people for infection.
There are several million Africans receiving anti-retroviral therapy but very little testing to monitor if that treatment is working – there's only a handful of laboratory sites with real-time PCR to give a quantitative measure of the amount of virus present in a person. The prize-winning technology can be run in a mobile clinic, and be operated by a relatively untrained person like a nurse.
How has the company developed?
When the company was first set up it was to develop tests to detect sexually transmitted diseases, particularly Chlamydia. But in 2006 the company changed direction to develop tests for food following funding from the venture capital group, Tate and Lyle Ventures, which has a focus on food technologies and nutrition. More recently, in 2011 Lumora announced a joint development and licensing agreement with 3M for tests based on the BART technology.
And that led to the opportunity to explore other areas?
Yes, and in 2011 £1.5M investment was raised in a round led by Catapult Venture Mangers to accelerate progress into clinical molecular diagnostics. And you can test for any disease where there is an infectious agent to test for.
Medical molecular diagnostics is based on DNA or RNA testing – and BART can be easily used to test for either – is a US$6Bn global market.
What are the origins of this technology?
It all started back in the 1990s when there were concerns that biological warfare agents might be used in the Gulf conflict. We were asked if we could develop a form of luciferase that was more stable to high temperature conditions, because you can use it to detect microorganisms non-specifically based on the fact that all organisms contain ATP. That's the basis of commercial cleanliness tests today that monitor whether surfaces have been cleaned properly.
So we developed more stable forms of luciferase capable of surviving the temperatures you would meet in the desert. The normal firefly enzyme is very sensitive to temperature and activity drops off very quickly even at 37C. This heat stable luciferase was later critical in the development of the BART test that needs to run at quite a high temperature.
And this was where BBSRC funding comes in?
This luciferase work started in my lab at the University of Cambridge with a postdoc, Dr Peter White, and was originally funded through Porton Down and DSTL. Then Dr Tisi took charge of the project in the lab and carried on with a three-year project grant from BBSRC to further improve luciferase for various applications. During that period of BBSRC-funded research that we came up with a predecessor technology to the one we are using now.
How significant was this predecessor technology?
This did give a bioluminescent (light) readout of the presence of a specific organism but it involved adding regents after a normal PCR DNA amplification, and we realised eventually that this technology was probably not commercially viable because it would create a big contamination issue. So we were brainstorming how we could get around this – as I recall it was sitting in the pub one evening with a glass of beer with Laurence – and we had the idea of doing it all in one tube in real time.
Your 'Eureka!' moment was in the pub!?
That was the moment of truth – after a couple of pints – when we realised that if we could do it all in one tube we would have something really powerful.
Not The Eagle pub where Francis Crick announced the discovery of DNA's structure?
Actually I think it was The Spread Eagle – another Cambridge pub well known for science academics – although it's been gentrified under another name now.
And after that Lumora took off?
Yes, that opened up the possibility for Lumora's first fund-raising round. And for this we had to get it to work. Olga Gandelman, another former postdoc in my lab, also played a significant role in the early stages of developing the technology, as did Vicki Church.
Then there was the very long road of development to making it a reality. Although we're getting better at recognising academic success in innovation activities, a tremendous amount of innovative work goes on with scientists in companies to actually make things really work – and I think that often that's not fully recognised and the fantastic team of scientists at Lumora led by Laurence have done a brilliant job in making it all work and bringing it to reality.
What was BBSRC's funding role then?
It would not have happened without BBSRC funding. BBSRC didn't fund the final work leading to the invention, but it created the conditions so it could happen because BBSRC had been funding Laurence's luciferase work when we were first thinking about detecting specific DNA sequences with luciferase. If he hadn't been able to work on the luciferase project and had the freedom to explore new ideas, it wouldn't have come about.
I think this shows an important point – often key innovations don't arise specifically because of grant applications that directly fund them, they arise because BBSRC is funding good people to do other things and good innovative people will come up with interesting ideas. So it's all to do with enabling the environment and BBSRC plays such an important role in supporting that.
BBSRC continue to support the work mainly through CASE Studentships, and we have one now with Lumora to continue to develop aspects of the technology.
The technology can be used anywhere, so there are applications in clinical diagnosis, environmental monitoring, bioterrorism, hygiene and public safety, water quality – really anywhere where you need to test for specific organisms. Particularly relevant are applications where at the moment testing isn't done using DNA tests because they are too expensive, so there are whole areas where they haven't been used. Environmental monitoring, food, and medical diagnostics in the developing world, are all good examples. The portability of the assay also opens up new areas such as veterinary tests; the ability to test for diseases on farms would of course be tremendously helpful in the event of major disease outbreaks.
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 1).
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 2). 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 3).
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 1).
- The Scientific Century: securing our future prosperity
- Medical Research: Whats it worth?
- Public support for innovation, intangible investment and productivity growth in the UK market sector