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Prof Sir Peter J. Ratcliffe, of the Francis Crick Institute and the University of Oxford, along with William G. Kaelin Jr. and Gregg L. Semenza from the US, have won the Nobel Prize in Physiology or Medicine for their discoveries of how cells sense and adapt to oxygen availability.
Prof Nick Lane, Professor of Evolutionary Biochemistry, UCL, said:
“All truly complex life on our planet needs oxygen. If oxygen levels change, the behaviour of our cells has to change too – and fast! Small shifts in oxygen levels can switch on hundreds of genes though a protein called hypoxia-inducible factor. This protein has shaped life’s adaptations to different environments and now turns out to be central to how cells live or die in cancer, heart disease and many other conditions, even sculpting our normal growth. Peter Ratcliffe and his colleagues have mapped out how cells react within a matter of minutes to tiny changes in oxygen levels. Few discoveries in modern biology have as long a reach, because nothing else is as central to being alive as oxygen, heart-beat by heart-beat.”
Prof John Iredale, Pro Vice-Chancellor Health and Life Sciences, University of Bristol, said:
“This is wonderful news. Peter is an outstanding scientist and it is immensely gratifying to see his ground breaking work recognised through the prize. Peter is also an extraordinary advocate for both UK and international science, a generous mentor and collaborator and a strong supporter of young scientific talent.”
Prof Sir Robert Lechler PMedSci, President of The Academy of Medical Sciences, said:
“I am thrilled to hear the great news that our Fellow Peter Ratcliffe has jointly won this year’s Nobel Prize in Physiology or Medicine.
“Peter’s ground-breaking work has unlocked one of human biology’s big mysteries: how our cells adapt to help us cope with changing oxygen levels. This mechanism is fundamental for human life and its discovery is already impacting on treatment of disease – supporting the development of promising experimental anaemia drugs and having the potential to better treat other diseases such as cancer.
“This win is a shining example of how the international collaboration of skilled and inquisitive minds can lead to major discoveries within the field of fundamental science. The UK punches above its weight on science, and this shows how high quality basic science can have incredible benefits for patients.”
Prof Kim Barrett, Editor-in-Chief of The Journal of Physiology, and Distinguished Professor of Medicine, UC San Diego, said:
“It’s exciting to see the 2019 Nobel Prize in Physiology or Medicine awarded for such important work in physiology. Oxygen is vital to life but can be toxic in excess, so it is not surprising that cells and organisms have designed exquisitely elegant systems to sense and respond to inappropriate oxygen availability.
“The Nobel Prize reflects the detailed insights into those systems generated by Ratcliffe, Semenza and Kaelin. We are proud at The Journal of Physiology to have published numerous related papers from two of these honorees (Ratcliffe and Semenza). The prize also illustrates that scientists working in seemingly disparate fields can often come together to generate truly foundational insights.”
Prof Mike Tipton MBE FPhysiol, Professor of Human & Applied Physiology, Extreme Environments Laboratory, University of Portsmouth, said:
“Oxygen is essential for human life, it is used in respiration as part of the process that converts food into energy to enable metabolism and thereby sustain life. But oxygen has to be managed well within the body; too much oxygen (such as could occur in hyperbaric environments or when breathing 100% for clinical purposes) is toxic, and too little (as could occur in disease states, trauma or at altitude) results in death. The body can, within reason, adapt to lower partial pressures of oxygen than those normally experienced: such adaptation is crucial to physiological function at altitude and in some disease states. So research that investigates how cells sense, control and adapt to different oxygen levels is fundamental to humans life.”
Dr Mark Downs CSci FRSB, Chief Executive of the Royal Society of Biology, said:
“It is fantastic to see UK science gain such high profile recognition again for our continuing role in ground breaking biological discovery research. It is a wonderful example of how the fundamental understanding of biological processes can inspire, inform and lead to real-world impact.
“The award to Sir Peter Radcliffe and his two co-awardees in the USA is not only extremely well deserved, but serves to highlight the international endeavour of science and the inherent complexity and inter-connectedness of biology: the science of life.”
Prof Christopher Garland, Professor of Vascular Pharmacology, University of Oxford, said:
“Oxygen is essential for cell and tissue metabolism and therefore life, so changes in oxygen must to be monitored so cells can adapt and survive.
“Sir Peter Ratcliffe and colleagues discovered an enzyme (a prolyl-hydroxylase) that is activated by oxygen (it is a co-substrate) within cells. With normal levels of oxygen the enzyme destroys a transcription factor called hypoxia inducible factor, or HIF-1, that cells make all the time. When oxygen levels in the cell drop, called hypoxia, the enzyme does not destroy HIF-1 so well and cells change activity to improve oxygen delivery, such as by making more red blood cells and new blood vessels.
“The research that attracted the 2019 Nobel Prize in Physiology or Medicine was carried out in Oxford, where Peter Ratcliffe is a Fellow of Magdalen College and the tenth Fellow of Magdalen to win a Nobel Prize.”
Prof Jeremy Farrar, Director, Wellcome, said:
“We’re delighted that today’s Nobel Prize recognises Peter Ratcliffe’s research into how our cells cope with varying amounts of oxygen, which has been supported by Wellcome since the early 1990s. Peter and his colleagues’ work on the fundamental processes taking place in our cells is now leading to new treatments for a range of disorders such as anaemia, cardiovascular disease, macular degeneration and cancer.
“As a clinical researcher myself, I’m really pleased that the long journey between laboratory research and improving the treatment of patients is being celebrated.
“These discoveries are only possible thanks to researchers working together and collaborating. A Nobel Prize can only honour the efforts of three individuals, but research is built on the efforts of teams of researchers. I know Peter cares deeply about those he works with, and many of those he has supported have gone on to achieve amazing things in their own careers.”
Prof Jeremy Ward, Emeritus Professor of Respiratory Cell Physiology, King’s College London, said:
“As a scientist working in the field of oxygen sensing myself, I am overjoyed that Peter Ratcliffe, Gregg Semenza and William Kaelin have been rightly recognised by award of the Nobel prize for their meticulous and ground-breaking studies which elucidated the hypoxia-inducible factor (HIF) pathway. This pathway is fundamental to the way the body works in health and disease. As a key example, it provides the mechanism by which the number of red cells which carry oxygen in the blood is regulated to match the requirement of the tissues for oxygen with its availability. This is why some athletes train at altitude, because the low oxygen levels stimulate an increase in red cells which then gives them an advantage at sea level by improving oxygen delivery to the muscles during strenuous exercise.
“The HIF pathway is also critical to growth of certain tumours – where oxygen levels in the tumour are low – to development of new blood vessels in poorly perfused tissues, and to detrimental changes in the lungs and elsewhere in people with chronic hypoxic lung disease.
The outstanding work of Ratcliffe, Semenza and Kaelin has identified a fundamental cellular process that is vital to life, yet can also contribute to disease. This has huge potential for the development of novel treatments for serious and currently difficult to treat conditions.”
Prof Douglas Higgs, Director, MRC Weatherall Institute of Molecular Medicine, University of Oxford, said:
“The 2019 Nobel Prize in Physiology or Medicine yet again illustrates how breakthroughs in clinical medicine most often come from curiosity driven science. Much of Peter Ratcliffe’s key work in understanding how cells sense and adapt to the availability of Oxygen (1989 – 1998) was carried out in the MRC Weatherall Institute of Molecular Medicine (University of Oxford) where exactly this approach to solving major questions in Biomedicine have been fostered since its inception.”
Prof Moira Whyte, Vice Principal and Head of the College of Medicine and Veterinary Medicine, University of Edinburgh, said:
“I am personally thrilled by this. In addition to his outstanding science Peter has inspired and encouraged many younger and older researchers across the UK and beyond to work on the relevance of oxygen-sensing pathways in a wide variety of organ systems and disease processes. He is very generous with his time and support.”
Prof Sir Mark Walport, UK Research and Innovation Chief Executive, said:
“Very many congratulations to Sir Peter Ratcliffe for the award of the Nobel Prize for his part in the discovery of the mechanisms for sensing oxygen levels in tissues in the human body – a medically important discovery that amply deserves this recognition.”
Prof Venki Ramakrishnan, President of the Royal Society said:
“I am delighted to hear that Royal Society Fellow Sir Peter Ratcliffe has been jointly awarded the Nobel Prize in physiology and medicine this year. We offer our congratulations to him and to Professors Kaelin and Semenza, who share the prize.
“Oxygen is the vital ingredient for the survival of every cell in our bodies, too little – or too much – can spell disaster. Understanding how evolution has equipped cells to detect and respond to fluctuating oxygen levels helps answer fundamental questions about how animal life emerged. But as Dr Ratcliffe’s work at the University of Oxford and the Francis Crick Institute shows us, it also gives insights into the way these processes continue to shape our health and wellbeing, and suggests new ways to treat conditions like heart disease and cancer.
“It is a richly deserved honour for each of the researchers recognised today, and underscores the depth of talent in the UK as well as the fact that advancing scientific understanding is so often an international endeavour.”
Sir Paul Nurse, Director, The Francis Crick Institute, said:
“Many congratulations to Peter Ratcliffe for his well-deserved award of the 2019 Nobel Prize in Physiology or Medicine, awarded jointly with William Kaelin of Harvard and Gregg Semenza of Johns Hopkins for ‘discoveries of how cells sense and adapt to oxygen availability’. Peter’s work has led to unexpected discoveries, revealing a universal mechanism for detecting and responding to oxygen levels in all our cells. These discoveries are based on innovative experiments, highly imaginative mechanisms, and a total dedication to absolute rigour. Peter is an exemplary clinician scientist. We are proud to have him at the Crick as our Director of Clinical Research.”
Prof Bridget Lumb, President of The Physiological Society, said:
“This year’s Nobel Prize puts physiology front and centre. It shines a light on the vital research carried out by physiologists.
“Cutting edge physiological research such as this is improving our understanding of how our bodies work and thereby helping keep us healthy.
“Thanks to this research we know much more about how different levels of oxygen impact on physiological processes in our bodies. This has huge implications for everything from recovery from injury and protection from disease, through to improving exercise performance.”
Prof Cormac Taylor, University College Dublin’s Conway Institute, said:
“The 2019 Nobel Prize for Peter, Bill and Gregg is a very well deserved recognition of their immense contribution to our understanding of how, cells, tissues and organisms adapt to oxygen deprivation. This discovery has opened up a new field of biology and provided a new therapeutic target for diseases ranging from anemia to cancer and inflammatory disease.
“Our evolution has depended on our ability to use oxygen to make energy and to adapt when oxygen levels are low.
“Humans require a constant supply of oxygen to live, but we often encounter situations where the amount of oxygen we have is low. This is the case for extreme situations, such as mountain climbers, but is also faced by people with diseases such as cancer or anaemia.
“The discovery of the HIF pathway answered the question about how our cells adapt to low oxygen and allow cells, tissues and whole bodies to adapt. This is a key and vital piece of understanding the physiology of how our bodies work.
“Targeting the pathways identified by this research opens up new treatment options for people with diseases such as anaemia or cancer.”
Dr Andrew Murray, Department of Physiology, Development and Neuroscience, University of Cambridge, said:
“Oxygen is fundamental to animal life, allowing our mitochondria to extract energy from the food we eat. The work of Kaelin, Ratcliffe and Semenza revealed the elegant mechanisms by which our cells sense oxygen levels and respond to fluctuations, enhancing the delivery of oxygen to the tissues of the body and altering our metabolism.
“Since the first reports of the hypoxia inducible factors appeared in the early 1990s, we have come to realise the vital role they play in our everyday physiology, in allowing humans to live at high altitude and in countless biomedical scenarios. Hypoxia (a low tissue oxygen content) is a feature of many diseases including heart failure, chronic lung disease and many cancers.
“The work of these three scientists and their teams has paved the way to a greater understanding of these common, life-threatening conditions and new strategies to treat them. Congratulations to the three new Nobel Laureates, this is richly deserved!”
Prof Fiona Watt, Executive Chair, Medical Research Council (MRC), said:
“Many congratulations to Peter Ratcliffe – this is a well deserved honour. I look forward to continuing to work with Peter in his role as director of clinical research at the Francis Crick Institute.”
Prof Sir Colin Blakemore, Professor of Neuroscience, City University of Hong Kong; Emeritus Professor of Neuroscience, University of Oxford; and Honorary Professorial Fellow, School of Advanced Study, University of London, said:
“This is simply brilliant news. Another Nobel for the UK, for Oxford, for Magdalen College, and for the Crick. At last British science has something to celebrate, despite the impending disaster of Brexit.”
https://www.nobelprize.org/prizes/medicine/2019/press-release/
Declared interests
The nature of this story means everyone quoted above could be perceived to have a stake in it. So our policy is not to ask for interests to be declared, instead they are implicit in each person’s affiliation.