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An Interview with Sir Magdi Yacoub

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An Interview with Sir Magdi Yacoub Disease Models & Mechanisms 2, 433-435 (2009) doi:10.1242/dmm.004176 Published by The Company of Biologists 2009 A MODEL FOR LIFE Taking translational research to heart: an interview with Sir Magdi Yacoub Sir Magdi Yacoub is a founding editor of DMM, whose work as a cardiac surgeon and researcher has devised new operations for congenital and acquired heart disease, and has advanced heart and heart- lung transplantation techniques. He and his collaborators have studied the sophisticated functions of living heart valves and are using stem cells to produce a tissue-engineered valve that can reproduce their functions. Here, he discusses with fellow DMM founding editor Nadia Rosenthal, how his career evolved and why he hopes research will put heart surgeons like himself out of business. ir Magdi Yacoub is quite arguably As a doctor, you chose to work on the the world’s leading heart and lung heart; how did you start? transplant surgeon. He has been a My dad was a surgeon and I was fascinated part of numerous firsts in cardio- with the profession of being a doctor and DMM thoracic surgery: the UK’s first looking after people. Then something hap- Sheart transplant and first live lobe lung pened when I was 4 to 5 years old; my dad’s transplant, as well as the first ever domino sister died of heart disease while she was operation, in which a patient with failing only in her twenties. She was his younger lungs receives a new heart and lungs, and a beloved sister and he went into a state of de- second patient receives the first patient’s pression. He kept saying that this should fully functioning heart. have been prevented. It was all due to a Sir Yacoub has performed more trans- narrow heart valve, and some people plants than any other surgeon in the around the world in those days were start- world. However, his contributions to ing to open these valves. This specialty of healthcare don’t end in the clinic. He de- heart surgery was starting to save lives and veloped transplantation technique guide- so I declared to him ‘I am going to be a heart lines for the United States’ National Heart surgeon!’ He said, ‘Oh, don’t be ridiculous!’ Lung and Blood Institute, and led the but at that very young age it inspired me to Harefield Hospital to become the UK’s follow that line and to see what was being of the world, how do you feel that this ex- leading transplant center. Additionally, his done to help heart patients. I targeted perience has influenced your life as a re- Disease Models & Mechanisms research on cardiac disease and cardiac certain individuals around the world who searcher? What aspects of your experi- therapies holds great promise for the happened to be in Sweden, Denmark and ence in the operating room dealing with future. For instance, Sir Yacoub and col- Britain. One person who patients come back to leagues produced the first human heart inspired me most was What really absorbs my influence you when valve from stem cells. [cardiac surgery attention now is the working with your re- In this Model for Life article, Sir Magdi pioneer] Mr Brock, who search assistants and spoke with fellow DMM founding editor later became Lord Brock massive divide in the fellows? and leading researcher Dr Nadia Rosenthal, of Wimbledon. As a world between those who I spent the early part of Head of the European Molecular Biology youngster I really have and those who have my career trying to learn Laboratory (EMBL) in Italy. He reflects on wanted to work for him, more about the heart his journey into cardiology and organ trans- and to learn from him, not, and the great and how to deal with plant research and surgery, discusses new and eventually I became differences in life structural problems. I projects to help address disparities in his Senior Registrar. The expectancy in different became really fascinated human healthcare, and prognosticates on rest is history since this with the function of the the contribution of model organism work to started me on my path. parts of the world heart, just watching it. I translational research and medicine. came to understand that That’s a poignant story, because narrow it’s a lot more than a contracting organ and valve syndrome actually relates to your it is the result of a very sophisticated system Sir Magdi Yacoub is Professor of Cardiothoracic Surgery at Imperial College London current research. Now that you have of tissues, cells and molecules coordinated (e-mail: [email protected]) become one of the great heart surgeons to perfection. I wanted to know more about Disease Models & Mechanisms 433 A MODEL FOR LIFE Sir Magdi Yacoub this organ. I spent a lot of my time and is due solely to hypertrophy. There are af- conditions but arguably even more impor- career – hours, days, years – focused on the fected patients who present without hyper- tantly, surgery generates human tissue for heart because I wanted to know more about trophy, for example. In addition, hypertro- examination. That is the advantage of trans- its workings. phy itself is not as simple as the name lational research: we then come to someone Then it dawned on me that it’s one thing implies. It is accompanied by an increase in like you, Nadia, to ask for help to create the to save people who are in trouble, ‘pulling specific types of fibrous tissues that affect necessary model organisms. them out of the river’, if you like, and it’s the cardiac system, conduction, the mitral another to try and stop them falling into the valve and possibly other parts of the heart. Great, I am ready! Now let’s talk about river in the first place. I heard about many This may underlie the arrhythmias we see some of the less conventional ways you preventive measures but they were rela- in this disease. have married clinical experience with re- tively primitive because they didn’t address If we turn to developmental biology and search. The left ventricular assist device the fundamental mechanisms underlying consider where each part of the heart orig- (LAVD) was originally used to support a the disease process. Initially, I wanted to inates, we see that the cells responsible for weak heart until a donor heart could be know the fundamental mechanisms of the different affected parts of the heart have a identified. In the last decade your work normally functioning heart. When I started common lineage, which provides an indi- has transformed LVAD use from a my academic research career, which was cation of how the phenotype has occurred. bridge-to-transplant into a bridge-to- after I had significant experience as a heart This promotes a unifying hypothesis for hy- recovery procedure using a combination surgeon, I dedicated a lot of my time, effort pertrophic cardiomyopathies based on of surgery and pharmacology. Many pa- and funding to build a Department of lineage, and is very exciting. But generating tients no longer need transplants. This Surgery at Imperial College that was dedi- a hypothesis is one thing, validating it is breakthrough treatment came from your cated to molecular and cellular biology another. That’s where joining forces with unconventional way of looking at the rather than surgery. Some people would say, somebody with expertise in animal models problem. How would you advise young DMM ‘Well, that sounds really odd because you like yourself, Nadia, would be so exciting, people to step outside of mainstream ap- are researching things that will prevent the because we can then start to validate the proaches to become a little more adven- need for cardiac surgery, which is your spe- components of our hypothesis. By using turous? cialty’ and I respond, ‘That would be the animal models with conditional expression Having worked with the heart for so long, happiest day of my life, to stop this cruel of certain molecules and mutations at dif- I was intrigued by its biology and sophisti- type of surgery!’ I am not going to give up ferent stages of development, we can test cated functions, and this convinced me surgery because it still saves people. But it whether this is the case. These studies could that, to emulate some of these functions, I would be so much better to understand have massive implications for understand- needed to think outside the box. I was ini- how to treat the disease without actually ing the disease and for treating the people tially attracted to transplantation and trans- cutting people and that’s why I am fasci- who have incomplete phenotypes. Without plantation immunology. However, so many nated with this science. engaging the appropriate model organisms, heart failure patients need a transplant but we will continue to speculate and offer non- are not going to get one owing to the In the next 5 to 10 years, what do you en- specific treatment. It’s less than optimal. massive shortage of donor organs. So, I in- vision as the forward advances in mod- There is also power in mixing informa- vestigated the use of assist devices, which eling cardiac function using animals, tion from models and clinical data. With my take over much of the heart’s pumping tissues or cells? Where do you see the big Florentine colleagues Franco Cecchi and function. Although they are not a real sub- Disease Models & Mechanisms breakthroughs coming through at this Iacopo Olivotto, we have successfully begun stitute for a human heart, these devices point, for the field or for your own re- exploring the evolving theory that gene ex- could have a niche in patient treatment search? pression dynamics are altered in hyper- since they can keep a patient alive for a I think that developing models, whether trophic cardiomyopathy.
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