Professor Sir Peter Barnes FRS FMedSci, from the National Heart and Lung Institute (NHLI), was made a Knight Bachelor in this year’s King’s Birthday Honours “for services to respiratory science.” Sir Peter is Professor of Thoracic Medicine at the NHLI and he was Head of Respiratory Medicine at Imperial until 2017. Here he writes about his reaction to his award and describes some of the current research projects in chronic obstructive pulmonary disease (COPD).
My wife opened the letter “On His Majesty’s Service” as she thought it was a tax demand – I was absolutely shocked to see I had been offered a knighthood. Of course, I was and am delighted with the award. It is very good for respiratory science and medicine, which generally receives little public attention. This is surprising as chronic lung diseases are amongst the most common in the UK, affecting one in seven people and the third ranked cause of death. I would like to dedicate this award to all the brilliant students, post-docs, research fellows, visiting scientists and colleagues that I have worked with at Imperial College London over many decades.
After a medical registrar rotation, at University College Hospital, I unsuccessfully applied for several senior registrar posts in various specialities, as I was determined to become a general physician. In 1978 I applied for such a post in respiratory medicine at Hammersmith Hospital but was again unsuccessful. However, the head of respiratory medicine at Hammersmith, Professor Neil Pride, phoned me to say that I needed to do some research to get a clinical senior registrar post. So, I reluctantly agreed to undertake research on the pharmacology of asthma with Sir Colin Dollery, who was Head of the Department of Clinical Pharmacology at Hammersmith. This led me to research on asthma, exploring its underling cellular and molecular mechanisms and trying to understand how existing anti-asthma treatments worked. I became totally enthralled with asthma research and later spent over a year working at the University of California in San Francisco, where I was able to learn several new techniques. I returned to Hammersmith as a Consultant Physician and set up a research lab, where we studied autonomic receptors and innervation of the airways, with a focus on human airways and combined with experimental medicine studies in asthma patients. In 1985 I moved to a newly established chair role in clinical pharmacology at the Cardiothoracic Institute, which became the National Heart and Lung Institute. In 1987, I succeeded Dame Margaret Turner-Warwick as Professor of Thoracic Medicine and Head of Respiratory Medicine at Imperial. I was lucky to attract some outstanding researchers to work with me and we bult up the largest respiratory department in Europe and became the most highly cited research group in the world due to our world.
We studied the inflammatory mechanisms involved in asthma and COPD and uncovered the way steroids work in asthma by switching off activated inflammatory genes in the airways, whereas in COPD the high levels of oxidative stress blocked this molecular mechanism making the patients steroid resistant. We also studied the role of nerves in the airways and the role of neuropeptides. We found that nitric oxide (NO) was the neurotransmitter of bronchodilator nerves but that this mechanism was disrupted in asthma. Nitric oxide is produced in large amounts by the cells lining the airways of asthma, which leads to an increased concentration of NO in the breath. We showed that measuring NO in the breath was a simple non-invasive way to measure airway inflammation in asthma and this is now used as a routine test to monitor patients with asthma. We also studied the first effective biological treatment for asthma, an antibody that blocks the cytokine interleukin-5, which is now used to treat patients with severe eosinophilic asthma, a rare type of asthma that usually starts in adulthood and does not respond to treatment with common asthma medicine
We are now looking at accelerated lung ageing and cellular senescence – the process by which a cell ages and stops multiplying but does not die – as a key mechanism driving COPD, as senescent cells accumulate in the lungs of COPD patients and release a whole array of inflammatory mediators that result in disease progression. Acceleration of lung ageing is associated with a reduction in anti-ageing molecules, such as sirtuins. A marked reduction in the levels of sirtuin-1 in the lung appear to be due to the effect of a small RNA regulator called microRNA-34a, which is increased in COPD cells through the signalling pathways that lead to cellular senescence. Specifically blocking this increase in microRNA-34a surprisingly reduces senescence, indicating that accelerated ageing might even be reversible. We have recently found that microRNA-34a is released from senescent airway cells in COPD within vesicles, which are taken up by normal cells that then become senescence. We see this as a mechanism for spreading senescence, resulting in disease progression and also for spread of senescence outside the lungs to cause comorbidities, such as cardiovascular and renal disease. We are also now looking at drugs that remove senescent cells (senolytics) that may be useful drugs to treat COPD and its comorbidities in the future.
Although I was very reluctant to do any research, by chance I ventured into respiratory research, which has been fascinating over almost 40 years at Imperial and has led to some exciting discoveries that have improved our understanding and led to improved management of asthma and COPD. I plan to continue my research as long as I can!
About Sir Peter Barnes
Peter Barnes is a Senior Research Investigator at the National Heart and Lung Institute and Honorary Consultant Physician at Royal Brompton Hospital, London. A portrait has recently been commissioned of him and will be hung in the Guy Scadding Building once framed. You can also watch a special lecture delivered by Sir Peter Barnes as part of the Faculty of Medicine’s 25th anniversary celebrations.