Staphylococcus aureus. You may have had it in connection with a wound infection. In most cases, it will pass without treatment, while severe cases may require antibiotics, which kills the bacteria. This is the case for the majority of the population. In fact, many of us — though we feel perfectly fine — carry staphylococci in the nose, a good, moist environment in which the bacteria thrive.
However, more and more staphylococci are becoming resistant to antibiotics (also known as multi resistant staphylococcus aureus or MRSA), and these infections can be difficult to treat.
“Antibiotics resistance is an increasing problem, especially on a global scale. And when you have this relatively simple infection which suddenly cannot be treated with antibiotics, the situation can turn serious, sometimes life-threatening,” says Professor Niels Ødum from the LEO Foundation Skin Immunology Research Center at the University of Copenhagen.
Therefore, all over the world, a lot of resources are being invested in fighting antibiotics resistance in staphylococcus aureus infections, and a new study among skin lymphoma patients has produced positive results. A new substance called endolysins has proven capable of killing both resistant and non-resistant staphylococcus aureus — without the need for antibiotics. But we will get back to that.
The discovery is good news to patients with a weak immune system to whom a staphylococcus aureus infection can be serious and, at worst, fatal. But it also adds to the knowledge we have of other forms of treatment.
“To people who are severely ill with e.g. skin lymphoma, staphylococci can be a huge, sometimes insoluble problem, as many are infected with a type of staphylococcus aureus that is resistant to antibiotics,” says Niels Ødum and adds:
“That is why we are careful not to give antibiotics to everyone, because we do not want to have to deal with more resistant bacteria. Therefore, it is important that we find new ways of treating — and not the least to prevent — these infections.”
New substance may be the answer
In some patients, a staphylococcus aureus will cause the cancer to worsen. And even though antibiotics appear to work in some cases, it is not without its problems.
“We can tell that giving high doses of antibiotics to patients with serious infections causes their health, skin and cancer symptoms to improve. But once we stop giving them antibiotics, the symptoms and staphylococci quickly return. Patients experience many adverse effects, and some risk getting resistant bacteria,” says Niels Ødum.
Therefore, treating staphylococcus aureus can be tricky. At worst, cancer patients may die of an infection which doctors are unable to treat.
And this is where endolysins enter the scene, as this new substance may be part of the solution to antibiotics resistance like MRSA.
“This particular endolysin is a brand new, artificially produced enzyme that has been improved several times and designed as a new drug,” explains Postdoc Emil Pallesen, who is first author of the study. He adds:
“The great thing about this enzyme is that it has been designed to penetrate the wall of staphylococcus aureus. This enables it to target and kill the harmful staphylococcus and leave harmless skin bacteria unharmed.”
And that is what made the researchers decide to test the new substance; they expected it to be able to kill both resistant and non-resistant staphylococcus bacteria.
“We have been testing the substance on skin samples from patients, and it does appear to kill staphylococcus aureus from patients. Endolysins do not care whether the bacterium is resistant to antibiotics or not, because it does not work in the same way as antibiotics,” says Niels Ødum and adds:
“The really good news is that our lab tests have showed that endolysins do not just eradicate staphylococcus aureus; they also inhibit their ability to promote cancer growth.”
Emil M.H. Pallesen, Maria Gluud, Chella K. Vadivel, Terkild B. Buus, Bob de Rooij, Ziao Zeng, Sana Ahmad, Andreas Willerslev-Olsen, Christian Röhrig, Maria R. Kamstrup, Lene Bay, Lise Lindahl, Thorbjørn Krejsgaard, Carsten Geisler, Charlotte M. Bonefeld, Lars Iversen, Anders Woetmann, Sergei B. Koralov, Thomas Bjarnsholt, Johan Frieling, Mathias Schmelcher, Niels Ødum. Endolysin inhibits skin colonization by patient-derived Staphylococcus aureus and malignant T cell activation in cutaneous T cell lymphoma. Journal of Investigative Dermatology, 2023; DOI: 10.1016/j.jid.2023.01.039
University of Copenhagen – The Faculty of Health and Medical Sciences
The viruses Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) have been linked to several cancers. For the first time, UNC School of Medicine scientists have discovered that these viruses use a human protein called barrier-to-autointegration factor 1, or BAF, to evade our innate immune response, allowing the viruses to spread and cause disease.
These findings, published in Nature Communications, suggest that BAF and related proteins could be therapeutic targets to prevent these viruses from spreading and leading to cancers, such as Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin lymphoma, multicentric Castleman disease, nasopharyngeal carcinoma, and gastric cancer.
Viruses are in a constant battle with the cellular immune system, which includes the protein cyclic GMP-AMP synthase, or cGAS, which binds to viral DNA and sounds the alarm to trigger immune responses and fight the viral invaders. We’ve discovered that KSHV and EBV use a different host cell protein, BAF, to prevent cGAS from sounding the alarm.”
Blossom Damania, PhD, Senior Author, the Boshamer Distinguished Professor of Microbiology and Immunology and member of the Lineberger Comprehensive Cancer Center
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Viruses have evolved with humans for millions of years, so it’s no surprise they’ve evolved tricks to evade our natural, or innate, immune responses. Finding out precisely how viruses do this is the basis for creating vaccines and therapeutics to overcome their tricks.
In the case of KSHV and EBV, the expression of BAF is increased upon infection, suggesting that these viruses take advantage of this host protein to blunt the immune response to infection. In a series of experiments, Damania’s lab found that BAF contributes to the degradation of the cGAS DNA sensor. With less cGAS protein available in the infected cell to detect DNA, the cells mount weaker immune responses, which allows these two viruses to replicate and spread more efficiently.
“BAF enables EBV and KSHV to reactivate from latency, replicate, and make more of themselves,” said first author Grant Broussard, a graduate student in the Genetics and Molecular Biology Curriculum at UNC Lineberger. “Our study highlights the prominent role that DNA detection pathways like the cGAS pathway play in controlling viral infection.”
He stressed that disrupting BAF activity with targeted therapies could reduce its immunosuppressive effects, thus restricting replication of these viruses to prevent the spread of disease.
Damania, who is a Leukemia and Lymphoma Society Scholar and a Burroughs Wellcome Fund Investigator in Infectious Diseases, added, “Preventing lytic replication will prevent transmission of these viruses and also reduce the global cancer burden associated with these two viruses.”
Thought LeadersMatthew DunneDirector for Drug DiscoveryMicreos Pharamceuticals
For World Antimicrobial Awareness Week 2022, we speak to Matthew Dunne, Director for Drug Discovery at Micreos Pharmaceuticals, about the importance of creating new targeted antibacterial products.
Please can you introduce yourself and tell us about your role at Micreos?
My name is Matthew Dunne, and I am a Director for Drug Discovery at Micreos Pharmaceuticals in Switzerland. I provide strategic and technical leadership for R&D and preclinical activities within our newly established Division of Antimicrobial Vector Innovation. I joined Micreos in May of 2022 from the Swiss Federal Institute of Technology Zurich (ETH Zurich) at the same time as Dr. Samuel Kilcher, who sits alongside me as co-Director within the new division, which is developing a new class of medicines we have coined Antimicrobial Vectors.
In my capacity as Director, I work from Micreos’ state-of-the-art research facility in Switzerland, where I analyze data together with our growing team of genetic engineers and biologists. In addition to providing leadership of this new, highly innovative drug discovery division, I provide assistance with developing our regulatory affairs strategy, the management of external innovation development projects with industry partners and academia, as well as dealing with a variety of diverse tasks that are typical for a fast-growing biotech company.
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You are currently a Director of Drug Discovery at Micreos, a company working to develop the world’s first targeted antibacterial products. Can you tell us more about Micreos’ vision and the importance of finding alternatives to antibiotics?
Micreos is working towards providing innovative therapeutic solutions that deliver a profound and transformational impact to improve the standard of care for people living with devastating illnesses.
Antimicrobial resistance, or AMR is a naturally occurring process that cannot be eliminated; it can only be controlled. Unfortunately, decades of overprescribing antibiotics in combination with the use of antibiotics in agriculture and farming, such as growth factors for livestock (that has been banned in the EU since 2006), has driven the spread of antimicrobial resistance genes among bacterial pathogens. AMR is estimated to have caused 1.27 million deaths in 2019, with this number expected to keep on growing. Nevertheless, we are fighting back.
At Micreos, we are developing two classes of antimicrobials: Endolysins and Antimicrobial Vectors. Both have different modes of action compared to antibiotics, making them capable of killing all AMR bacteria. Both technologies provide other important advantages, too, such as their ability to precisely kill a specific pathogenic species while leaving commensal or “good” bacteria unaffected. Also, due to their alternative mechanisms of action, they are able to circumvent some of the harmful side effects of antibiotic use.
The drug discovery sector has seen considerable advances in the last decade, thanks largely to technology and increased collaboration. How do you feel this sector has changed in recent years and what has personally been the most exciting development that you have seen?
Global healthcare is rapidly transitioning towards precision medicine. Personally, I think the most impressive advancements over the last decade have been realized with nucleic acids. For example, antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) that modulate gene expression are being designed for large indications, rare diseases, and even patients with ultrarare, “n-of-1” diseases.
In the last two years, we all witnessed another form of nucleic acid therapy, mRNA. In less than a year, scientists went from sequencing the SARS-CoV-2 virus to designing different mRNA vaccines for global distribution. I am sure there are going to be many more exciting developments within this space in the near future. I am especially interested to see how the mRNA field progresses with regard to gene therapy, where mRNA can be administered to compensate for a faulty gene or protein.
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Micreos has recently launched a new world-class antimicrobial vector engineering team to ramp up the fight against antimicrobial resistance (AMR). Can you tell us more about why this team was created and the work you are carrying out?
Bacteriophages are natural predators of bacteria that, for over 100 years, have sat on the sidelines of modern medicine. They have mostly been applied as an experimental treatment, reserved for patients suffering from chronic infections that are untreatable with conventional antibiotics. As the threat of AMR intensifies, there is a significant demand for developing and enhancing the capabilities of alternative therapeutics to treat bacterial infections, among many other chronic and rare diseases.
At Micreos Pharmaceuticals, we are heavily invested in harnessing the power of genetic information. In the Division of Antimicrobial Vectors, we use the genomes of bacterial viruses or bacteriophages as “blueprints” for engineering using CRISPR-Cas technology as well as various synthetic approaches. First, we isolate and sequence bacteriophages from different environments that are predisposed to target and kill certain pathogenic species. Next, the fun starts, as the team and I get to apply our knowledge and expertise in bacteriophages, biochemistry, and structural biology to reprogram these genetic “blueprints” to generate Antimicrobial Vector libraries.
We can engineer structural genes for improved stability, introduce heterologous payloads for improved potency, remove unneeded elements for better efficiency and safety, and reprogram their targeting capabilities to reach bacteria in niche locations, such as intracellular reservoirs or biofilms. The resulting libraries of Antimicrobial Vectors provide unique and therapeutically important functions when used against bacterial infections.
This new team combines individuals with a variety of knowledge across various sectors, including molecular microbiology, genetic engineering, and phage therapy. Why is having a multidisciplinary team vital when developing new ways to tackle infectious diseases?
We are fortunate to have assembled a multidisciplinary team of experts proficient in all aspects of the Antimicrobial Vector R&D process, from selecting and testing environmental bacteriophages, to designing genetic scaffolds for reprogramming, to early-stage production, efficacy assessment, manufacturing optimization, and preclinical testing.
Our team also works very closely with experts in clinical trial design and regulatory affairs. This not only makes for interesting coffee breaks, where ideas and alternative perspectives are thrown around, but it ensures that we have a drug development pipeline that runs as efficiently as possible. It is important to have frequent input regarding aspects of safety, translatability, and efficacy to ensure our medicines will translate as quickly as possible from bench to bedside.
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How can the technology developed at Micreos help to tackle AMR through the creation of precision antimicrobials?
We are seeing more and more biologics and recombinant protein-based therapies in development to accompany small-molecule antibiotics in the fight against AMR. Micreos has already established itself as the global experts in engineering of endolysins, which has led to an array of precision protein-based antimicrobials capable of targeted killing of harmful S. aureus pathogen while leaving beneficial bacteria intact and without triggering resistance development.
During my PhD studies at EMBL Hamburg, I solved the atomic structures of these cell wall degrading enzymes and witnessed firsthand how miniscule amounts of endolysin could eradicate entire monocultures of specific bacteria in minutes with no off-target effects against “good” bacteria, such as those found on our skin or in our guts. Unlike the development of AMR against antibiotics, scientists do not expect to see similar resistance mechanisms emerge for endolysins due to their targeting of essential cell wall components that are extremely difficult for bacteria to modify.
Currently, our pharmaceutical grade endolysins are being developed for atopic dermatitis, diabetic foot ulcers, cutaneous T-cell lymphoma (based on excessive skin colonization by S. aureus) and bloodstream infections.
At the right time, and following extensive preclinical testing, we are all excited to witness our Antimicrobial Vector technology follow in the footsteps of our endolysins as it translates from discovery to clinical trials and onto improving the standard of care for people suffering from infections and many other devastating disorders.
Every year, the world celebrates World Antimicrobial Awareness Week (WAAW), dedicated to spreading awareness about AMR. The theme for 2022 is ‘Preventing Antimicrobial Resistance Together‘. What does this message mean to you, and how can international collaboration help to tackle this global health threat?
In 2019, nearly 5 million people died from illnesses involving AMR bacteria. Based on the current trajectory, these numbers are only going to keep rising – and at quicker and quicker rates – with predictions estimating AMR will cause 10 million deaths by the year 2050. The solution to controlling antimicrobial resistance is to work together internationally to implement more effective governance surrounding antimicrobials, improve public awareness surrounding antibiotics, and fund the development of new classes of antimicrobials to bolster our arsenal of available medicines.
It is important that drug developers, researchers, health authorities, and academics all play a part, no matter how big (e.g., establishing initiatives and investment funds) or small (e.g., tweets, chats among friends in the pub), to help raise public awareness surrounding AMR. Events such as those taking place during WAAW and their ability to disseminate information about AMR and its threat to our everyday lives are incredibly important. The public needs to know that AMR could impact our normal way of life. We risk reversing nearly a century of progress in public health if we allow normally innocuous infections to again become untreatable.
In addition to WAAW, we are seeing an expansion in other AMR initiatives, the introduction of innovation funds, and a growing number of collaborative organizations providing much-needed platforms for engagement and collaboration between industry, researchers, non-profit organizations, charities, and governments around the world.
Micreos has always focused on forging strong collaborations with other industry partners, clinicians, and academia to help advance the development of our precision antimicrobials. For instance, our proprietary endolysin technology was created together with ETH Zurich, which remains an important partner to us moving forwards with our Antimicrobial Vector technology.
Image Credit: The World Health Organization
Despite AMR being described as one of the top 10 threats to humanity, many people still do not understand its wide-reaching effects. Why is this, and why is it therefore so critical to continue to raise awareness?
I believe this is due to poor public communication and education regarding what antibiotics are, how they work, and what AMR really means. In 2015, when the WHO asked 10,000 people from 12 different countries about antibiotics, 76% of respondents believed that antibiotic resistance happens when the body becomes resistant to antibiotics – rather than bacteria becoming resistant to the antibiotics. Moreover, 44% of people believed they are not at risk of antibiotic-resistant infections if they simply take antibiotics as prescribed and of course, that is not correct.
Governments, academics, drug developers, and health professionals must do better at communicating a clearer message about what antibiotics are and – most importantly – why they are a precious resource that we cannot continue to take for granted.
What do you believe the future of antimicrobials to look like? Is it possible to one day see a world without resistance?
Another imminent threat to human existence is climate change, which shares many similarities, such as urgency, severity, and global effects, as we are seeing with the spread of AMR. What gives me hope for the future of antimicrobials and tackling AMR is witnessing the growth in public conversation and awareness surrounding climate change; the same will happen with AMR.
Improving awareness for AMR is about educating and mobilizing audiences so they are driven to take their own actions and make their own decisions toward confronting this growing crisis. I am hopeful that everyone will play a part through communication, the sharing of novel solutions, and advocating for change that will be shaped by our different experiences, cultures, and underlying values.
Originally from Macclesfield in the Northwest of England, Matthew studied Biochemistry at the University of Birmingham before obtaining a Ph.D. in Biochemistry and Structural Biology from the European Molecular Biology Laboratory (EMBL) in Hamburg and the University College Cork, Ireland, where he characterized the atomic structure and function of endolysins.
For the last eight years, Matthew has worked as a Postdoc and then Senior Scientist at the Swiss Institute of Technology in Zurich (ETH Zurich), where he investigated the molecular-level interactions of bacteriophages against a wide variety of foodborne and clinical pathogens, produced novel bacterial diagnostics, and developed genetic engineering tools that have been used to produce different types of bacteriophage-based therapeutics and diagnostic elements. Matthew maintains a research group within the lab of Prof. Martin Loessner at ETH Zurich, where he is actively involved in using genetic engineering to further explore how bacteriophages interact with their hosts, as well as lead a team of researchers developing bacteriophages to treat urinary tract infections for assessment in future clinical trials.
Matthew lives in Zurich with his wife, Alyssa Hill, also a Senior Scientist in Pharmaceutical Chemistry at ETH Zurich. In his free time, you will find Matthew swimming in the lakes and rivers dotted around the city, coaching and playing field hockey for the Red Sox HC, or skiing, hiking, and exploring Switzerland with Alyssa.
Eichenseher F, Herpers BL, Badoux P, Leyva-Castillo JM, Geha RS, van der Zwart M, McKellar J, Janssen F, de Rooij B, Selvakumar L, Röhrig C, Frieling J, Offerhaus M, Loessner MJ, Schmelcher M. Linker-Improved Chimeric Endolysin Selectively Kills Staphylococcus aureus In Vitro, on Reconstituted Human Epidermis, and in a Murine Model of Skin Infection. Antimicrob Agents Chemother. 2022 May 17;66(5):e0227321. doi: 10.1128/aac.02273-21. Epub 2022 Apr 13. PMID: 35416713; PMCID: PMC9112974.
Immune checkpoint inhibitors such as Keytruda and Opdivo work by unleashing the immune system’s T cells to attack tumor cells. Their introduction a decade ago marked a major advance in cancer therapy, but only 10% to 30% of treated patients experience long-term improvement. In a paper published online today in The Journal of Clinical Investigation (JCI), scientists at Albert Einstein College of Medicine describe findings that could bolster the effectiveness of immune-checkpoint therapy.
Rather than rally T cells against cancer, the Einstein research team used different human immune cells known as natural killer (NK) cells-;with dramatic results.
We believe the novel immunotherapy we’ve developed has great potential to move into clinical trials involving various types of cancer.”
Xingxing Zang, M.Med., Ph.D., Study Leader
Xingxing Zang is the the Louis Goldstein Swan Chair in Cancer Research and professor of microbiology & immunology, of oncology, of urology, and of medicine at Einstein and a member of the Cancer Therapeutics Program of the Montefiore Einstein Cancer Center.
Telling friend from foe
The surfaces of immune cells are studded with receptors known as “checkpoint” proteins, which prevent immune cells from straying beyond their usual targets (pathogen-infected cells and cancer cells). When checkpoint receptors on immune cells bind with proteins expressed by the body’s own normal cells, the interaction puts the brakes on a possible immune-cell attack. Diabolically, most types of cancer cells express proteins that bind with checkpoint proteins, tricking immune cells into standing down and not attacking the tumor.
Immune checkpoint inhibitors are monoclonal antibodies designed to short-circuit immune-cell/cancer-cell interactions by blocking either the tumor proteins or the immune-cell receptors that bind with tumor proteins. With no brakes to impede them, immune cells can attack and destroy cancer cells.
New focus on natural killer cells
The limited effectiveness of checkpoint inhibitors prompted Dr. Zang and other scientists to look at checkpoint pathways involving NK cells, which-;like T cells-;play major roles in eliminating unwanted cells. A cancer-cell protein called PVR soon captured their attention. “We realized that PVR may be a very important protein that human cancers use to hobble the immune system’s attack,” said Dr. Zang.
PVR protein is usually absent or very scarce in normal tissues but is found in abundance in many types of tumors including colorectal, ovarian, lung, esophageal, head and neck, stomach, and pancreatic cancer as well as myeloid leukemia and melanoma. Moreover, PVRs appeared to inhibit T cell and NK cell activity by binding to a checkpoint protein called TIGIT-;prompting efforts to interrupt the TIGIT/PVR pathway by using monoclonal antibodies made against TIGIT. More than 100 clinical trials targeting TIGIT are now in progress worldwide. However, several clinical studies including two large phase 3 clinical trials have recently failed to improve cancer outcomes.
Recognizing the role of a new receptor
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Meanwhile, the cancer-cell protein PVR was found to have another “binding partner” on NK cells: KIR2DL5. “We hypothesized that PVR suppresses NK cell activity not by binding with TIGIT but by binding with the recently recognized KIR2DL5,” said Dr. Zang. To find out, he and his colleagues synthesized a monoclonal antibody targeting KIR2DL5 and carried out in vitro and in vivo experiments using the antibody.
In their JCI paper, Dr. Zang and colleagues demonstrated that KIR2DL5 is a commonly occurring checkpoint receptor on the surface of human NK cells, which PVR cancer proteins use to suppress immune attack. In studies involving humanized animal models of several types of human cancers, the researchers showed that their monoclonal antibody against KIR2DL5-;by blocking the KIR2DL5/PVR pathway-;allowed NK cells to vigorously attack and shrink human tumors and prolong animal survival (see accompanying illustration). “These preclinical findings raise our hopes that targeting the KIR2DL5/PVR pathway was a good idea and that the monoclonal antibody we’ve developed may be an effective immunotherapy,” said Dr. Zang.
Einstein has filed a patent application for KIR2DL5/PVR immune checkpoint including antibody drugs and is interested in a partnership to further develop and commercialize the technology.
Dr. Zang has previously developed and patented more than 10 immune checkpoint inhibitors. One of those inhibitors is now being tested in China in phase 2 clinical trials involving several hundred patients with advanced solid cancers (non-small cell lung cancer, small cell lung cancer, nasopharyngeal cancer, head and neck cancer, melanoma, lymphoma) or recurrent/refractory blood cancers (acute myeloid leukemia, myelodysplastic syndromes). Another of Dr. Zang’s immune checkpoint inhibitors will be evaluated starting next year in cancer clinical trials in the United States.
Ren, X., et al. (2022) Blockade of the immunosuppressive KIR2DL5/PVR pathway elicits potent human NK cell-mediated antitumor immunity. Journal of Clinical Investigation.doi.org/10.1172/JCI163620.
Thought LeadersProfessor Roberto La RagioneChair of TrusteesHumanimal Trust
In this interview, News-Medical speaks to Professor Roberto La Ragione, Chair of Trustees at Humanimal Trust, about the concept of One Medicine and how human and veterinary medicine can collaborate, share knowledge, and initiate research for the benefit of both humans and animals.
Please can you introduce yourself, tell us about your professional background, and your role at Humanimal Trust?
I am Professor Roberto La Ragione, Chair of Trustees at Humanimal Trust.
I graduated in 1995 and then studied for a postgraduate degree in veterinary microbiology at the Royal Veterinary College (University of London). In 1996, I moved to the government’s Veterinary Laboratories Agency (VLA) to undertake a Ph.D. on the pathogenesis of E. coli in poultry. Upon completing my Ph.D. studies, I commenced a post-doctoral position at Royal Holloway, University of London, studying E. coli virulence factors and vaccine development.
Since 2001, my work has focused largely on understanding the pathogenesis of zoonotic bacterial pathogens to develop control strategies. I have led several commercial, Defra, research councils (BBSRC, MRC, EPSRC, AHRC, Innovate) and EU projects in this area.
My current research interests focus on the pathogenesis of food-borne pathogens with a particular interest in Antimicrobial Resistance (AMR) and the development of intervention strategies, including vaccines, rapid diagnostic, pre, and probiotics. I have published over 190 papers in the area of host-microbe interaction, with a particular emphasis on E. coli,Salmonella, vaccines, probiotics, and AMR.
In 2005, I was appointed Head of Pathogenesis and Control at the AHVLA, and in 2010, I was appointed Professor of Veterinary Microbiology and Pathology at the University of Surrey. I gained the FRCPath in 2010, and in 2012, I was appointed the Associate Dean for Veterinary Strategy in the new School of Veterinary Medicine at the University of Surrey. In 2014, I was appointed to the position of Head of the Department of Pathology and Infectious Diseases and Director of the Veterinary Pathology Centre. In 2019 I was appointed Deputy Head of the School of Veterinary Medicine at the University of Surrey, and then in 2021, I was appointed Head of the School of Biosciences and Medicine.
I am the past president of the Med-Vet-Net Association and the Veterinary Research Club, the current Chair of Humanimal Trust, a member of the FSA ACMSF AMR sub-committee, a Trustee of the Houghton Trust, a member of the APHA Science Advisory Board and Chair of the Royal College of Pathologists Veterinary Pathology SAC. I am an Associate member of the European College of Veterinary Microbiology, and in 2020, I was awarded an Honorary Associateship of the Royal College of Veterinary Surgeons.
Humanimal Trust is a unique organization. Please could you tell us about the organization’s origin, purpose, and values?
Humanimal Trust is the only organization in the UK with the sole and specific purpose of progressing One Medicine.
It was founded in May 2014 by world-renowned orthopedic-neuro veterinary surgeon Professor Noel Fitzpatrick – otherwise known as the TV Supervet. As a vet, Noel Fitzpatrick experienced personally the deep divide between human and animal medicine and saw how unfair this was.
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Frustrated by the lack of opportunities to share what he was learning from veterinary practice or to benefit from relevant learning from human medicine, he decided to create the platform himself. This laid the foundations for the work Humanimal Trust does today, removing barriers and seeking to close the divide between human and animal medicine.
Our five areas of work spell out I-CARE, which sums up the way we feel, our supporters feel, and we hope everybody will one day feel about One Medicine:
Influence – we care about bringing together everyone who cares about One Medicine to create a road map for change in public policy, education, and at the clinical coalface.
Collaboration – we care about creating opportunities for human and veterinary professionals and students to learn from one another (in person and virtually) by demonstrating One Medicine at work.
Awareness – we care that people should know and understand the benefits of One Medicine for humans and animals, about non-animal alternatives to laboratory models, and how much human and animal medicine can learn from one another’s clinical practice – saving time, money, and lives.
Research – we care about research – funding it, facilitating it, shouting about it – that could benefit humans and animals without using laboratory animal models.
Education – we care about learning – every child learning about the connections between humans and animals; veterinary and human medical students learning with and from one another; practitioners learning continuously from their peers.
Humanimal Trust advocates for One Medicine. What is One Medicine, when did this concept originate, and how has the understanding of it evolved in recent years?
The origins of One Medicine date back to the nineteenth century when Rudolf Virchow linked human and animal health. Sir William Osler, Dr. Calvin Schwabe, Lord Lawson Soulsby, and others have since continued to expand the One Medicine concept, identifying the connections, commonalities, and synergies between human and veterinary medicine.
It was whilst studying the history of medicine that Professor Fitzpatrick came upon a term used to describe human and veterinary medicine working with one another: One Medicine. The third edition of Dr. Calvin Schwabe’s seminal publication in 1984 of ‘Veterinary Medicine and Human Health’ which spoke of One Medicine, laid the foundation for what we now know as One Health, but in considering this text, Fitzpatrick identified a need to move away from a public health agenda to a common health agenda focusing on infectious and non-infectious diseases.
Moreover, when reviewing the three Rs (refinement, reduction, and replacement) in relation to animal use in research, it became clear that a fourth R was missing from the 3Rs principle – the principle of reciprocity so that not only do medical practitioners and allied researchers benefit, but also patients, regardless of their species.
By considering the contribution that animals can make to research by studying their lives and their responses to naturally occurring, spontaneous diseases rather than using experimental animal models in research, the use of animals in research can be significantly reduced.
One Medicine and the ‘Biology of the Future’ (Biology Week 2020)
Why is it currently the case that human and veterinary medicine are kept separate, and why would it be beneficial to change this?
Although the practice of bringing veterinary and human medical and research professionals together is thought to stimulate new and innovative research, historically, this has been challenging. A number of studies have investigated why this could be, and different levels of awareness and priorities may be one reason. A 2020 study, which surveyed vets and GPs in Australia, found that vets generally had more awareness and felt more confident in engaging in zoonoses management compared to GPs, and were also more likely to initiate cross-professional referrals.
The Trust believes that education is key to One Medicine. Only by learning about the similarities between humans and animals from the earliest stage to collaboration in the most advanced science and clinical practice will we promote change. Therefore, we must ensure that the best research, clinical practice and learning, benefiting both humans and animals, are accessible, funded, encouraged, and promoted.
A study published in 2017 by a group of scientists in The Netherlands noted that having a clear common goal (like One Medicine) can help to stimulate collaboration. The study also suggested that professional organizations could be important facilitators of collaboration in this area.
With this in mind, in 2020, the Trust launched the Humanimal Hub, a free online platform for all human and animal medical and veterinary professionals to meet, collaborate, share knowledge, and initiate research for the benefit of both humans and animals.
While still in its infancy, the Hub already has over 250 members. It provides a much-needed virtual space for connections to be made and conversations to be initiated, which the Trust actively seeks to nurture. For example, Anna Radford, a Consultant in Paediatric Surgery at Hull University NHS Trust and Leeds Children’s Hospital, was looking to collaborate with an individual or group in veterinary medicine with a specialty in problems with urinary tract or kidneys and/or antimicrobial resistance. Through the Hub, we were able to identify a suitable professional, and as a result, an interdisciplinary group has been set up to identify common urological conditions affecting both humans and companion animals.
Anna was also introduced to a diagnostics company working in the animal medical care field at the Trust’s inaugural global ‘One Medicine Symposium: Stronger Together’ in May 2021. Through them, Anna has set up a new collaboration to determine whether this diagnostic technology developed with companion animal medicine in mind could potentially also be useful to help diagnose urinary, joint, and cerebrospinal fluid infections in a busy NHS hospital setting.
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These are just two examples of how we know that great things can happen when animal and human health professionals and scientists come together.
Which areas of medicine do you currently focus on, and what benefits does One Medicine provide to this particular area?
I believe One Medicine has transformative potential across all areas of medicine where physiological and genetic similarities exist between humans and animals. There are five main pillars of research that the Trust currently seeks to fund, namely infection control and antimicrobial resistance; cancer; bone and joint disease; brain and spinal disease; and regenerative medicine.
In line with this, the Trust began an important collaboration with the children’s charity Action Medical Research in 2020 to help support two child-focused medical research projects. The first study, led by Professor Hall-Scraggs at University College London, focuses on juvenile idiopathic arthritis (JIA). Patients with JIA have a disease that causes inflammation of their joints. This leads to pain, joint deformity, disability, and reduced quality of life. There are newer drugs now available that suppress joint inflammation, but these are expensive and can have side effects, the most serious being life-threatening infection. Magnetic resonance imaging (MRI) scans can show inflammation of joints. By measuring inflammation in patients with juvenile idiopathic arthritis, the study could help optimize their treatment by showing how much inflammation is present and whether it changes with treatment.
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The second study, which is ongoing, is investigating infection prevention and its impact on antimicrobial resistance in critically ill children, led by Dr. Nazima Pathan, Lecturer in Paediatric Intensive Care at the University of Cambridge. The transferable data from both studies has real potential to help improve the lives of humans and animals with similar conditions.
Another example of research the Trust has funded concerns liquid biopsies for canine patients. This research was undertaken by Professor Joanna Morris and Dr. Tomoko Iwata at the University of Glasgow and is a great example of reciprocity whereby human and animal bladder cancer patients may benefit from this research.
Are there any particular examples of where either human or veterinary medicine has led to advances in the other?
Cancer research is perhaps the area for which One Medicine is most well-known. For example, dogs, long considered our best friends, don’t just share our lives but also risk factors for certain diseases. Many diseases also share genetic similarities between humans and dogs. Canine lymphoma, the second most common cancer in dogs, has relatively similar characteristics to human non-Hodgkin lymphoma. Around 1 in 8 golden retrievers will develop canine lymphoma, and CRUK estimates that 1 in 39 males and 1 in 51 females are at risk of being diagnosed with non-Hodgkin lymphoma. Both species need better, more effective ways to treat the disease, and clinical trials with canine veterinary patients have been helping to fast-track the development of new treatments in this area for several years.
Image Credit: Varvara Serebrova/Shutterstock.com
The US-based DISCO initiative recognizes the value of aligning veterinary and human drug development projects and explains why it can be worthwhile to include veterinary patients at an early stage in cancer drug development trials. From shortening drug development times to encouraging cross-collaboration between the disciplines for the benefit of both human and veterinary patients, the potential advantages of this approach are clearly laid out in a landmark 2019 paper, which came about from a workshop of the World Small Animal Veterinary Association’s One Health committee.
What is the one thing you wish people knew about One Medicine?
One Medicine is about human and animal healthcare advancing hand in hand, in an equitable and sustainable way, and not at the expense of an animal’s life.
How can people, both medical professionals and the general public, get involved with Humanimal Trust and support the One Medicine cause?
Human and animal medical professionals, students, and researchers can join the Humanimal Hub for free and use it as an opportunity to collaborate, share knowledge, and initiate research with other like-minded individuals. The Trust also holds an annual One Medicine Day event that brings together researchers, doctors, vets, allied healthcare professionals, and students from around the world to discuss practical ways forward for One Medicine. The year’s ‘One Medicine Day Seminar: One Medicine in Action’ talks can be found here.
There are also opportunities to join our team as a volunteer Ambassador, write articles for us, present at events or act as a moderator for the Hub.
There are many ways that members of the public interested in One Medicine can get involved too, from signing The Humanimal Pledge or organizing a Paws for a Picnic fundraiser with family and friends to leaving a gift in your will or becoming a volunteer speaker in your local community.
What is next for yourself and Humanimal Trust?
We recognize the need to present One Medicine consistently through an education lens. Our absolute priority is to improve understanding at every level – from pre-school to professional training (veterinary and medical undergraduates) and development – of the relationship between human and animal health and the need for collaboration and reciprocity of benefit to humans and animals.
With this in mind, our focus for the next twelve months is on four key areas of activity:
Focused awareness building among key audiences
Developing partnerships, networks, and collaborations
Education
Research funding, engagement, and influencing activity
To help drive this, we have appointed a new CEO, Joe Bailey, who will be joining us in November from RSPCA Assured, together with a new Trustee, Anna Radford, whom I referred to earlier. I have no doubt that their understanding of and passion for our purpose will help take Humanimal Trust to the next level.
We are expanding our Science Committee, which will strengthen our ability to draw on the best available expertise to make better-informed decisions about which research activities we prioritize for funding or support. In addition, to support the strategic development of our educational program, we have created a new role – Schools Education Manager – which will enable us to initiate the long-term development of a One Medicine curriculum.
We will soon launch our new Podcast series, which I’m very excited about. This will follow the Trust’s previous series, Humanimal Connection, but with a very different feel to it, so watch this space.
About Professor Roberto La Ragione, BSc (Hons) MSc Ph.D. FRSB CBiol FIBMS CSci AECVM FRCPath HonAssocRCVS
I am a Professor of Veterinary Microbiology and Pathology in the School of Veterinary Medicine and the Head of the School of Biosciences and Medicine at the University of Surrey. My role includes delivering and overseeing teaching and research in the School and running my own research group, which consists of vets, doctors, and scientists. My current research interests focus on Antimicrobial Resistance (AMR) and understanding the pathogenesis of zoonotic bacterial pathogens (those that can be transmitted from animals to humans and, in some cases, from humans to animals). I also have a particular interest in developing control and intervention strategies, including rapid diagnostics, vaccines and probiotics for controlling bacterial pathogens in companion and food-producing animals. I have published over 190 peer-reviewed papers in the area of microbiology and pathology.
My role includes delivering and overseeing teaching and research in the School and running my own research group, which consists of vets, doctors, and scientists. My current research interests focus on Antimicrobial Resistance (AMR) and understanding the pathogenesis of zoonotic bacterial pathogens (those that can be transmitted from animals to humans and, in some cases, from humans to animals). I also have a particular interest in developing control and intervention strategies, including rapid diagnostics, vaccines and probiotics for controlling bacterial pathogens in companion and food-producing animals. I have published over 190 peer-reviewed papers in the area of microbiology and pathology.