The Longitude Prize’s Daniel Berman explains how the initiative hopes to tackle the challenge of antimicrobial resistance.
In an interview shortly after winning the Nobel Prize in 1945 for discovering penicillin, Sir Alexander Fleming said: “The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism.” Fleming had essentially predicted antimicrobial resistance (AMR), something which is now seen as one of the most serious global threats to human health as we witness bacteria’s resistance to antibiotics increasingly spreading from country to country.
In the UK, the Chief Medical Officer for England, Professor Dame Sally Davies, warned of ‘a post-antibiotic apocalypse’ in her book The Drugs Don’t Work: A Global Threat, and the threat of a post-antibiotic world have been echoed by many others, who speak of very real dangers facing the human race should we no longer have access to such medicines.
It is therefore good to see efforts taking place to address this worrying issue. In the UK, in 2014, the then UK Prime Minister launched the Longitude Prize. This was a revised version of the prizes offered in England in the 1700s for a practical method for the precise determination of a ship’s longitude at sea – ships were getting lost at sea because of the inability to track longitude.
The 2014 incarnation of this prize began in 2013 when the Longitude Committee led by Astronomer Royal Lord Martin Rees, convened a roundtable consultation with over 40 of the country’s leading scientists, engineers, and politicians where ideas around the following themes were discussed:
- Global development;
- Technology and robotics;
- Democratising access to communications; and
- Health and wellbeing.
Six challenges were later shortlisted and the UK public had the opportunity to vote for the one they thought should become the focus of Longitude Prize. AMR was chosen on 25 June 2013. The current Longitude Prize is an international competition designed to incentivise the development of a rapid diagnostic test that would reduce the unnecessary use of antibiotics and better steer their use moving forwards.
An increase in resistance
Daniel Berman, who leads the Global Health Team, including the Longitude Prize, at Nesta’s Challenge Prize Centre, explained to SciTech Europa Quarterly that developing new rapid diagnostics to steer antibiotic use is of fundamental importance, not least because new European research has demonstrated that, in the context of hospital based infections, there has been a significant increase in resistance, which, he said, means that “operations which are not normally considered to be dangerous, such as a caesarean section or a hip replacement, could become incredibly dangerous because without antibiotics an infection can have a serious risk of death.”
The Longitude Prize currently has 77 teams competing from 14 different countries competing for the £8m (~€9.09m) pay-out. Some of those teams are academics, while others are companies (Berman explained that there are three categories of companies: start-ups, medium size enterprises and multinational companies.).
Berman continued: “The teams are using different technologies to address the challenge set out in the Longitude Prize (microfluidics, flow technology, genetic tests, and so on). Some of the tests are for bloodstream infections, for instance, with the idea being that it could be possible to diagnose such infections a lot quicker and then go on to identify the right antibiotic for treatment.
There will, of course, only be one winner, and the tests they develop must meet certain criteria, including ensuring that their test can provide results in under 30 minutes, whilst also being very reliable.
A decline in patents
A new study carried out by IP firm Marks & Clerk and CPA Global for the Longitude Prize has revealed a decline in the number of new point-of-care technologies being created to diagnose infectious diseases and identify AMR. According to the report, there has been a year on year decline in patent filings in this space, with filings reaching their highest levels for the past decade in 2014, with 118 patents for point-of-care diagnostics for infectious disease filed globally.
But by 2015, this figure had dropped significantly to 94 patents. Berman told SEQ that Marks & Clerk have been a partner of the Longitude Prize since the beginning, and Nesta decided to embark on a research project with them. Here, Marks & Clerk worked with CPA Global to identify relevant patents for point-of-care diagnostics for bacterial infections on the World Health Organization’s list of antibiotic-resistant ‘priority pathogens’ – a catalogue of 12 families of bacteria that pose the greatest threat to human health.
“They then identified relevant technologies, devices, and types of pathogens before analysing the patent information and identifying key trends in major applicants. They conducted both quantitative and qualitative work because their expertise and knowledge of the landscape and market meant that they were able to draw conclusions as a part of their analysis.”
Looking at the patents which had been filed internationally, the research project outlined the fact that there had been a general increase in the number of patent filings related to point-of-care tests aimed at pathogens of infectious diseases over the last 10 years. However the research also showed that from 2013 to 2015 there was a downward trend as innovation in the diagnostic space for AMR waned.
Berman said: “There were less filings in the last couple of years, and that is worrying because patent filings are essentially a surrogate to show innovation in this space. As such, a lack of innovation to address the urgent public health need of antimicrobial resistance is a cause for concern.”
He also highlighted the fact that it is the USA which is dominating innovation in this space, at least in terms of patenting, with 60% of the patents that were identified for infectious disease point-of-care diagnostics being filed there. “The UK is the second largest at just 8%,” he added, “with Europe in third place with 6%, and then Japan (4%), Korea (3%), and China (2%).”
According to Berman, it is also interesting to note that the lion’s share of patents are in the private sector, and that within the academic sector only one of the top 10 universities in terms of filing for point-of-care diagnostics was outside of the USA – that being the University of Edinburgh in Scotland, which has a very active diagnostic programme within their medical school.
However, while patent filings for infectious disease have decreased in the last five years, the percentage relating specifically to the detection of bacteria has actually increased during the same period, and so the news is not all bad. Nevertheless, whether the WHO’s list of priority pathogens, which was only published in 2017, will have an impact on future patent filings in this space remains to be seen.
Market and the policy issues
One of the reasons for this waning of patent filings in recent years may, Berman said, be due to a lack of market pull. He also told SciTech Europa that there appears to be a strong consensus on the part of test developers that “there is a huge need for pull funding and market creation. Activity in product development is waning because companies and venture capitalists are not convinced that the market is strong or lucrative enough, and that needs to change.
There has been significant investment into antibiotic development in recent years and much of this has been targeted at supporting organisations to conduct preclinical work – to identify and develop targets. On the other hand, big pharma companies continue to exit the antibiotic development market – most recently Novartis. This means that there are real concerns that promising antibiotics will not be carried into Phase II and Phase III trials.
In terms of diagnostics, Berman said, the 77 teams involved in the Longitude Prize – as well as others – often find that investors are not convinced that these products will find a ready market. As such, Berman said that he and others in the field are calling for the creation of a fund that would feed this market.
He told SEQ: “This could be similar to that which we see with regard to vaccines for developing countries: Gavi, the Vaccine Alliance, consolidates the market and guarantees payments. In the case of AMR, such a mechanism could be for both developed and developing countries. The creation of this type of fund could change the dynamic for investors and make this market more attractive.”
A further issue highlighted by Berman with regard to financing was that the grants which have been made available to Longitude Prize teams have been relatively small (up to £25,000), “and what is needed now is grants on the level of £100,000-500,000, either via venture capitalists or grant schemes.”
Mobile phone-led technology
The new report also revealed that there has been a recent increase in filings for mobile phone-led technology and hand-held devices, 44% of which have been filed within the past five years. This is, of course, a positive development, and Berman explained that the growth being seen here may be the result of several factors. For instance, smart phone-type technologies are widely accessible, and so if this technology can be used then there is no need to buy another device.
“They are easy to use,” Berman added. “And while they would not be used in a lab, they could be used in environments such as a GP surgery or at the bedside in a hospital. In this space we are also seeing some technologies begin to merge. For instance, there is perhaps the potential to develop a system which used a smart phone-like device to record a patient’s answers to questions, the results of which would recommend which test should be run.
“This is a kind of fusion between decision support and biological tests, and it has even gotten to the point now where you can plug a cartridge into a smart phone device which will actually conduct the test, with the smart phone acting as the computer.”
A further example would be the potential to test for bacteria, and once the specific bacteria has been identified, a database of resistance contained within the smart phone-like device would inform the doctor of which antibiotic to prescribe based on the resistance in that region.
Berman also explained that it is important to point out that, from a regulatory perspective, the authorities are unlikely to approve a smart phone as a medical device because every time the operating system is updated it will need to be considered as a new device. As such, the idea is rather for the technology (such as Android, for example) to be used but for it to be offline and locked down so that no software updates are received.
While, with the advent and subsequent evolution of smart phone technology and mobile communications more generally there has been a deluge of health- and medical-related apps available for the general public to freely download, there is no risk that the type of technology being developed by the Longitude Prize teams to become lost amongst them – many of which actually have little or no impact. That is due to the fact that in the medical area, Berman explained, the ‘tool’ needs to be recommended in guidelines or approved for use.
This is crucial, he added, because “if you misdiagnose an infection it can potentially become life-threatening, and so there is a clear need for the technologies being used to be effective and dependable, and this can only be achieved through a regulated marketplace.”
One Health, an approach which takes an holistic view of human, animal, and environmental health, is widely held as being key to solving the AMR challenge moving forwards – antibiotics are widely used in the agriculture sector, for instance, and can pass into the food chain or leach into the environment.
While the Longitude Prize is designed for human health, Berman did suggest that some of the technologies that will emerge from this endeavour could be very relevant for animal health as well. He added: “It is also important to point out that progress is being made elsewhere when it comes to One Health and animal health. That is, in agriculture – particularly in areas such as using antibiotics as a growth stimulator for poultry, for example – there are now strict rules in place in Europe, and there are positive signs in places like the USA.
“However, unfortunately in developing countries we are also seeing a huge increase of this use of antibiotics as growth promoters in livestock.”
The Longitude Prize
The Longitude Prize is thus making headway. Given that the WHO estimates that antibiotics treatments add an average of 20 years to all of our lives it is imperative that the AMR challenge is addressed – and addressed soon. As such, the Longitude Prize will continue to judge entries every four months until December 2019. Updates can be found here: www.longitudeprize.org.
Global Health Team, Challenge Prize Centre
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