Interviews With Experts
Claas Kirchhelle: Institut National de la Santé et de la Recherche Médicale
To better understand the history of AMR development and antimicrobial research we talked to Claas Kirchhelle who is a well-known historian of ‘drugs and bugs’. Currently an Associate Research Professor at INSERM, Claas has a special focus on the history of antimicrobial resistance, vaccination policies, and environmental health. His interdisciplinary approach brings together historical analysis with insights from microbiology, policy, and ethics, offering a unique perspective on the challenges of modern healthcare. Discussing the current state of antimicrobial research with Claas made us wonder how one can contribute to combating the AMR crisis in the real world. Especially his take on big pharma companies lacking interest in novel antimicrobials despite constant flow of innovations. This is because antimicrobials don’t fit the established commercial scheme and struggle to compete with “blockbuster drugs” such as Ozempic and Keytruda or even conventional antibiotics. Also, Claas highlighted that the AMR crisis is a complex global problem and cannot be simply solved through the efforts of few countries, as long as the largest consumers of antibiotics do not put appropriate regulations in place because AMR bacteria would still be able to rapidly spread in the globalised world of flights and international trade. Finally, we found it inspiring to discuss the future of antimicrobial research with Claas. He argued that the next generation of antimicrobials is more likely to come out of independent research projects and start-ups rather than from large pharmaceutical companies, offering hope for more innovative solutions in the fight against AMR.
Kevin Foster: Sir William Dunn School of Pathology
As a chair of Microbiology at the Sir William School of Pathology at the University of Oxford, Kevin Foster had a lot to say about the prospects of our technology in the context of natural microbiomes. He drew our attention to the difference that we should expect between the laboratory conditions and naturally occurring biofilms. For instance, he pointed out that the efficiency of plasmid transfer may depend on the composition of a given microbiome, and these differences should be experimentally assessed. Also, he suggested we test our plasmid with cells that grow at different speed, as in gut microbiomes it is often the case that bacteria grow at significantly slower rate. Kevin concluded that, provided we can achieve strain specificity on the sequence level with Cas12a, the biggest challenge for our systems will be to sustain high enough rates of conjugation to outstrip pathogen growth, and so whether there will be enough cell-cell contact to reach all of the pathogen cells.
Katharina Ramshorn: Oxford Science Enterprises
Katharina is a Live Sciences Investment Associate at the Oxford Science Enterprises. We had an opportunity to pitch our project to Katherina in search of feedback regarding how we should present it and potentially make it more commercialisable. We discussed market availability and competition and came to the conclusion that the livestock market might be the most attractive for our project. Meeting Katherina inspired us to conduct thoughtful market analysis to see in which sector OneRing might be best suited.
Professor Nicole Stoesser: Oxford University Hospitals NHS Foundation Trust
As our project progressed, in order to fully grasp the long term impact our project could have on the healthcare sector, we met with Nicole Stoesser. As a Consultant in Infection for the Oxford University Hospitals NHS Foundation Trust, an NIHR Oxford Senior Research Fellow, and an Associate Professor in Infectious Diseases at the University of Oxford, Nicole was able to provide us with a full picture of the current state of AMR affairs both in the UK and globally. Understanding the current policies that regulate the prescription of antibiotics, especially last-resort antibiotics, helped us to realise the policy hurdles that may lie ahead for our project. Hearing Nicole’s opinions on the crisis of innovation in antimicrobial research was particularly telling, as was hearing about new government policy schemes that aim to incentivise pharmaceutical companies to develop antimicrobials. From a clinical perspective, we also appreciated Nicole’s ideas of potential use cases for OneRing, such as to prevent infection from urinary catheters, ventilators, and prothestic joints. Hearing Nicole’s concerns regarding the potential immune response that might be elicited from our OneRing solution led us to a key inflexion point: looking ahead, we now hope to carry out further research on the effects of stripping our host E.Coli of any surface proteins that could lead to an immune response.
Professor Craig MacLean: University of Oxford, Department of Biology
Interested in understanding how efficacious OneRing might be in a biological system, we met with Craig MacLean, a professor of evolution and microbiology at the University of Oxford. Throughout our conversation, we began to see the many challenges that our system will face in the microbiome. Not only might our plasmid face anti-cas systems after successful conjugation, but there was also the chance recipient bacteria might expel our plasmid. Craig also pointed out that, due to the high copy number plasmid we had designed, the RP4 conjugation system, and the strong promoter, our host E. Coli would likely suffer from major fitness costs. Reaching a reflection point, we began to think about ways of mitigating these potential issues. One solution we decided upon was artificially upregulating glycolysis in our host E. Coli to mitigate fitness costs. Our conversation soon turned to the use of antibiotics in farming, and their many effects. During our interview, we began to understand pro-antibiotic use arguments, as Craig explained the use of growth-promoting antibiotics in the livestock industry can lead to a significant increase in meat yield from the same number of animals. Perhaps it was time to hone in on the issues of antibiotic use in the livestock industry…
Laura Higham: Food Animal Initiative Farms
In order to gain a better understanding of antimicrobial stewardship, and more broadly the use of antibiotics in the livestock industry, we met with Laura Higham, a Programme Manager & Veterinary Consultant for FAI Farms. Working with industry-leading companies such as KFC, M&S, MacDonalds, Nestle, and IKEA, FAI Farms helps to deliver positive change to animal-based production systems, especially in the context of reducing antibiotic use in global supply chains. Meeting with Laura thus exposed us to the urgent need to further decrease antibiotic use in the livestock industry, and the challenges farmers often face in doing so. During our meeting, we were able to delve into the economic costs of reducing antibiotic use, the effects antibiotic reduction can have on animal health, and current novel antimicrobials being used by farmers today. One of the main takeaways we enjoyed was the increasing role veterinarians play in the livestock industry, as farms continue to make the shift from routine antibiotic administration to targeted, veterinarian prescribed, antibiotic use.
