Professor Peter Openshaw discusses Respiratory Syncytial Virus Infection (RSV). RSV is a common respiratory virus that usually causes mild, cold-like symptoms in most adults but it is the leading cause of hospitalisation in babies Step into the world of groundbreaking medical research with the latest episode of our podcast as Sir Andrew Pollard engages in a riveting conversation with the esteemed Professor Peter Openshaw from Imperial University. Peter Openshaw is a respiratory physician and mucosal immunologist researcher, studying how the immune system both protects against viral infection but also causes disease. He has run studies of human experimental infection of volunteers since 2008 and is Director of the HIC-Vac consortium established to accelerate vaccine development for pathogens of high global impact.

Delving deep into the realm of Respiratory Syncytial Virus (RSV) infection, this episode unveils the complexities of a common respiratory virus that can escalate into a serious health concern. RSV is a common respiratory virus that usually causes mild, cold-like symptoms in most adults but it can become more severe and it is the leading cause of hospitalisation in babies.

In this illuminating dialogue, listeners are treated to a comprehensive exploration of RSV, from its seemingly innocuous cold-like symptoms to its potential for severe illness, particularly in vulnerable populations. The conversation navigates through Professor Openshaw's early investigations into immune responses, his fascination with inflammatory reactions, and the transformative advancements witnessed in RSV medical research over the years.

As the episode progresses, attention turns to the horizon of medical innovation, with a thoughtful examination of the challenges inherent in vaccine trials and the tantalising prospect of novel treatments for infectious diseases like RSV. Join Sir Andrew Pollard and Professor Peter Openshaw as they peer into the future, offering a glimpse of what lies ahead in the relentless pursuit of conquering respiratory ailments.

Sir Andrew Pollard talks to Sir Jeremy Farrar, Chief Scientist at the World Health Organisation and previously the director of The Wellcome Trust in the UK. Andrew Pollard's guest on this podcast is Sir Jeremy Farrar, who serves as the Chief Scientist at the World Health Organisation and held the position of director at the Wellcome Trust in the UK from 2013 to 2023.

Sir Farrar is a clinician-scientist who served for two terms at the Wellcome Trust. Besides overseeing a significant increase in the Trust's endowment and annual spending, he played a key role in the race to develop COVID-19 vaccines. Before joining Wellcome in 2013, Sir Farrar spent 17 years as the director of a clinical research unit at a hospital for tropical diseases in Vietnam, particularly focusing on emerging infectious diseases.

Jeremy discusses his early career training in Neurology and then his Ph.D. researching the immune disorder Myasthenia Gravis at Oxford University. This work led him to study infectious diseases primarily in Vietnam in the mid-1990s. A key transformative moment for Sir Farrar was the Nipah virus outbreak in Malaysia from September 1998 to May 1999. This outbreak resulted in 105 deaths and the near collapse of the key local pig-farming industry.

They then discuss the regional SARS-1 (Severe Acute Respiratory Syndrome) coronavirus outbreak of 2003 and the lessons learned from that outbreak. They also examine the impact of the H5N1 virus that followed shortly after SARS-CoV1. They talk through the risks posed in the future by a non-human influenza virus crossing the species barrier from birds, poultry, or animals and what needs to be done to monitor this risk in the future and what it means for future vaccine research.

In 2013, Sir Jeremy Farrar became the head of the Wellcome Trust in the UK. The Wellcome Trust, established in 1936 to fund research to improve human and animal health, is the largest funder of non-governmental funding for scientific research in the UK and one of the largest research providers globally. Sir Farrar talks about his task of steering this growth period for the Wellcome Trust and discusses the role of science communication and policy.

Turning to the events of 2020, Sir Farrar discloses how he initially was alerted to the pandemic outbreak in Wuhan by international colleagues and then the steps he took as an independent scientist to alert the scientific community and advise the UK government. The Wellcome Trust acted as a pivotal funder in 2020; it instigated and funded important vaccine and medical research work in the early period to underpin Covid-19 medical trials and studies.

Andrew Pollard and Jeremy Farrar finish their conversation by looking at the lessons learned from the pandemic and what needs to be done globally within science and wider society to prepare for any future infectious disease outbreak.

Sir Andrew Pollard talks to Sir Peter Horby, Professor of Emerging Infectious Diseases and Director of the Pandemic Sciences Institute at Oxford. He is Co-Chief investigator of the RECOVERY trial of drug treatments for COVID. Peter Horby talks about his early medical career working with HIV patients in hospitals. He talks about his background in infectious diseases and public health. His work in researching treatments for infectious diseases led to working abroad on tropical diseases and public health. He talks about being part of the outbreak response team in Vietnam for the SARS-1 virus outbreak which had a high mortality rate but relatively few deaths.  Peter then explains about his work in an international peer to peer network, ISARIC, for clinical researchers studying emerging infectious diseases and related work on clinical trials in this area.

Andrew asks Peter about his work as Co-Chief investigator with Martin Landray, on the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trials in March 2020 at the start of the pandemic. The RECOVERY trial was designed to investigate multiple potential therapies for COVID-19, differentiating itself from other global studies by its ambitious scope. In contrast to some studies elsewhere, the RECOVERY trial aimed to assess various interventions simultaneously. The trial commenced without a predetermined sample size, initially planning for up to 20,000 patients but ultimately enrolling more than double that number. The trial focused on repurposed drugs initially, selecting existing medications with known safety profiles and reasonable likelihood of effectiveness. The rationale was to quickly assess drugs readily available in hospital pharmacies, such as aspirin and steroids. As the trial progressed, novel drugs specifically developed for COVID-19 were introduced.

The trial focused on repurposed drugs initially, selecting existing medications with known safety profiles and reasonable likelihood of effectiveness. The rationale was to quickly assess drugs readily available in hospital pharmacies, such as aspirin and steroids. As the trial progressed, novel drugs specifically developed for COVID-19 were introduced.

Despite initial scepticism about using immunosuppressive drugs like steroids, the trial eventually revealed significant success with dexamethasone, a cheap and widely available steroid. This safe drug probably led to over a million lives being saved during the early years of the pandemic according to Peter Horby.  This unexpected outcome showcased the trial's ability to challenge assumptions and contribute vital information to treatment of COVID patients. The study has now provided positive results on 12 different drugs for treatment.

The conversation continues with Peter and Andrew discussing future challenges in the area of emerging infectious diseases, possible future outbreaks and the need for further research and clinical trials.

Sir Andrew Pollard talks to Uğur Şahin. Şahin is a German oncologist and immunologist. He is the co-founder and CEO of BioNTech, which developed one of the major COVID-19 vaccines. Sir Andrew Pollard talks to Uğur Şahin. Şahin is a German oncologist and immunologist. He is the co-founder and CEO of BioNTech, which developed with US company Pfizer the hugely successful Pfizer-BioNTech COVID-19 vaccine.

Uğur has been intimately involved in the development of RNA technology through his company BioNTech and then made a huge contribution to the development of the Pfizer-BioNTech COVID-19 Vaccine.

Uğur chats with Andrew about his early life in Germany, his love of mathematics and his experiences at Medical School. A formative period was training as an oncologist, that led him into an interest in cancer vaccines and cancer immunotherapy.

They discuss the basics of vaccines for cancer treatment in particular how RNA vaccines work. Ribonucleic acid (RNA) is a molecule that is present in the majority of living organisms and viruses. Unlike a normal vaccine, RNA vaccines work by introducing an mRNA sequence (the molecule which tells cells what to build) which is coded for a disease specific antigen, once produced within the body, the antigen is recognised by the immune system, preparing it to fight the real thing.

The two chat around the science of testing how to improve the potency of the mRNA, and hence make a better vaccine. They also discuss how this technology could in the future be used to treat cancer.

Uğur Şahin then talks about the work done in very early 2020 by his company to develop an mRNA-based vaccine against COVID-19. For its development, BioNTech collaborated with American company Pfizer to carry out clinical trials, logistics, and manufacturing. The hugely successful Pfizer-BioNTech COVID-19 vaccine was the result and Uğur states that there has now been over 4 billion doses produced, saving lives around the world.

The discussion ends with Andrew Pollard asking for Uğur Şahin's thoughts on the future for applying these vaccine techniques to cancer therapies and for tackling global infectious diseases.

Sir Andrew Pollard talks to Sir Pascal Soriot, the CEO of AstraZeneca about their pandemic partnership to develop the AstraZeneca/Oxford vaccine. Over three billion vaccines have been delivered, saving six and a half million lives. It’s a reunion in this episode of the Oxford Colloquy, as Sir Andrew Pollard talks to Sir Pascal Soriot, the CEO of AstraZeneca (AZ), about their pandemic partnership to develop the AstraZeneca/Oxford vaccine. Although, as you’ll discover, they have more than vaccines in common.

From his early childhood in a relatively poor suburb of Paris, that included a love of horses, Sir Pascal talks about his first career, as a vet. But a desire to explore the world led him to the pharmaceutical industry, human health, and eventually to the top job at AZ.

With AZ now one of the fastest growing global pharmaceutical companies, Sir Pascal spends much of his time travelling. With a workstation at every site, and a ‘water cooler’ style of leadership, he keeps his ear to the ground and across vast operations.

Sir Pascal puts this period of rapid growth down to a combination of following the science, putting patients at the heart of drug development, and a well-defined focus on cancer, cardio-vascular disease, respiratory disease and more recently, rare disease.

It was early on in the pandemic that Sir Pascal realised that COVID-19 was likely to be a very big problem. He describes AZ’s very modest start – supplying masks and looking at repurposing existing drugs for treatment. But he was then introduced to Oxford’s vaccine scientists by Regius Professor of Medicine, Sir John Bell, and work together began.

Sir Pascal describes the AZ/Oxford partnership as very successful – a marriage of scientific expertise, with large-scale manufacturing and distribution skills. Both Sir Andrew and Sir Pascal note the sense of pride felt among all those involved at delivering three billion vaccines that have saved over six and a half million lives around the world.

Professor Eddie Holmes, who co-authored the publication of the genome sequence of SARS-CoV-2 through work with colleagues in Wuhan, China speaks to Professor Andrew Pollard about his scientific career and this pivotal pandemic work. An interview between Prof Sir Andrew Pollard and Prof Eddie Holmes, an evolutionary biologist, fellow of the Academy of Sciences in Australia and the Royal Society. The discussion delves into the evolution of coronaviruses, with a particular focus on the origins of COVID-19 in Wuhan, China.  The interview begins by exploring Eddie's academic journey, from a background in social anthropology to his transition into the field of viruses and evolutionary genetics. The conversation highlights the rapid mutation rates of viruses, particularly viruses like HIV, which mutate daily in infected individuals. The episode develops further, discussing how Eddie found himself at the forefront of pandemic research, thanks to his previous work and collaborations in China. He explains the sequence of events leading to his involvement, from collaborating with researchers in Wuhan and Shanghai to the critical role in identifying the virus responsible for the outbreak and sharing this information internationally.

 

The conversation then explores the role of mutation tracking in determining the cross-species transmission of viruses, such as COVID-19, which allows scientists to trace the origins of a virus and determine potential reservoir species. Eddie provides insights into the origins of SARS-CoV-2 through natural mutation between species, and highlights the challenges and criticisms faced by scientists involved in the investigation.

 

The discussion also explores how the environment, which includes factors like drugs, vaccines, and the host's immune response, influences the mutations in viruses. Eddie explains that the environment acts as a selective sieve, allowing certain mutations to survive and shaping the evolution of the virus. Regarding the long-term control of highly mutable viruses, such as HIV and SARS-CoV-2, Eddie suggests that while predicting and targeting the right mutations is challenging, it is not impossible. He discusses the potential for AI to improve prediction and intervention strategies. However, the ongoing evolution of viruses and the need to adapt drugs and vaccines to new variants remain challenges to be addressed. The podcast provides valuable insights into the fascinating world of viral evolution, offering a glimpse into the complexities of viruses and their impact on human health.

Andrew Pollard talks to Professor Maheshi Ramasamy about her pandemic work as a hospital consultant treating extremely sick patients in intensive care. They also discuss her research career in vaccines and infectious diseases. Professor Maheshi Ramasamy is a consultant physician at the John Radcliffe Hospital in Oxford and also a clinician scientist at the Oxford Vaccine Group.

Andrew Pollard talks to Professor Ramasamy about her hospital work at the John Radcliffe Hospital as a consultant at the start of the pandemic. She discusses as a researcher the alerts she received of a new virus and as a consultant the early stages of preparing the hospital for the influx of COVID-19 patients and being on the ward for the first arrivals of patients. She talks very movingly about the first few months of working with extremely sick patients in intensive work and the increasing surge of unwell patients on the ward. She reflects on this difficult period and how she personally coped with the intense work pressure and also how she and medical colleagues dealt with the stress and the need to protect their families from the spread of the virus. They also reflect on the later waves of COVID-19 in December 2020 after the initial lockdown that again meant hospitals reached capacity with sick patients and how the knowledge of new treatments from research such as the Recovery trials and the vaccine programme affected patient outcomes.

They start the conversation by discussing her early childhood interest in medicine and how that led to her long distinguished research career in vaccines and infectious diseases.

Professor Maheshi Ramasamy is a consultant physician at the John Radcliffe Hospital in Oxford and also a clinician scientist at the Oxford Vaccine Group. Mahesh is a fellow at Magdalen College, Oxford, and Deputy Director of graduate medicine at Oxford University.

Shabir Madhi Professor of Vaccinology at the University of the Witwatersrand,Johannesburg, South Africa discusses the effect of the global pandemic on Africa and his work on COVID-19 vaccines. In this episode, Andrew Pollard speaks to Professor Shabir Madhi about his life working in medicine in South Africa and his work on the epidemiology of childhood infectious diseases including HIV. Shabir Madhi is Professor of Vaccinology at the University of the Witwatersrand, Johannesburg, South Africa; and co-founder and co-Director of the African Leadership Initiative for Vaccinology Expertise (ALIVE). His research has focused on the epidemiology, and clinical development of lifesaving vaccines against pneumonia and diarrheal disease. He is leading the first two COVID-19 vaccine studies being undertaken in Africa.

Sir Andrew and Professor Adam Finn discuss his work as paediatrician specialising in infectious diseases. They discuss the pandemic as it affected children and the different responses to the disease in adults and children. Professor Adam Finn, Professor of paediatrics at the University of Bristol and head of the Bristol Children's Vaccine Centre talks to Sir Andrew Pollard about his experience of the pandemic. Professor Finn is a paediatrician specialising in infectious diseases, and has been running vaccine trials for about 25 years with a fascination for the immune responses in the nose and throat. They discuss his experience of the pandemic as a paediatrician and how the immune response to the COVID-19 disease differed between adults and younger children.

Sir Andrew Pollard & Sir Patrick Vallance discuss the COVID-19 pandemic. He shares insights into his medical career and vital work during the pandemic as Chief Scientific Adviser to the UK government. Sir Patrick Vallance FRS FMedSci FRCP HonFREng was UK Government Chief Scientific Adviser (GCSA) from April 2018 to April 2023.Previous to that role he was President of Research and Development at Glaxo Smith Kline and before that Professor of Medicine at UCLA, California.

He took on a crucial role in the UK response to the COVID-19 pandemic. In this podcast episode he discusses with Andrew Pollard how he was aware of the emerging news about the virus at the end of 2019 and the steps he took to prepare the government for the potential impact.

Before discussing the pandemic, they step back to look at his medical career, his very broad experience as a clinician, as an academic and then working as a scientist in the pharmaceutical industry. This experience led to a deep understanding of the whole process that underpins drug development and the complexities around regulation.

They discuss policy decisions and policy design in his role of Chief Scientific adviser - "It isn't just the linear process from scientific evidence, it involves economics. It involves social considerations, ethical, moral, political, legal, and all of those things need to be taken into account by ministers when they make decisions".

They move on to discuss the activities around the pandemic response with Sir Patrick's key role as chief scientific advisor - from initially hearing news of an outbreak in China to the early response, the plans for lockdown to support the NHS and the strategies involved in the development of vaccines and their rollout. Finally, they discuss how to deal with stress on a personal level and the benefit of having trusted close colleagues to rely on and the need for sharing information between a network of science advisors in other countries.