Dr Ali Taher, MD, PhD, FRCP, has spent more than three decades shaping the understanding and treatment of thalassemia. As Associate VP for Academic Centers at the American University of Beirut (AUB) and Director of the Naef K. Basile Cancer Institute, he has integrated high-level research with clinical excellence. Trained in Beirut and London, he returned to Lebanon to help establish the Chronic Care Center’s Thalassemia Department, a distinct entity that has become an internationally recognizsd clinical research unit. Beyond his leadership at AUB – where he also founded the Faculty of Medicine’s Fellowship and Residents Research Program – his work remains focused on expanding access to care in a context of ongoing instability.
You have been at the centre of thalassemia research and treatment for more than three decades. Taking yourself back to the beginning – what first drew you to this field?
After completing my training at the American University of Beirut, I went to London to continue at the Royal Free Hospital, where I trained primarily in benign haematology – thalassemia, sickle cell disease, thrombosis, and bleeding disorders. My mentor there was Victor Hoffbrand, one of the genuine authorities on iron and thalassemia, and a steady stream of Arab patients would come to London seeking second opinions on their conditions. That gave me an early and formative exposure to the disease and to the very particular challenges facing patients from our region.
The decisive moment, however, came later – when Lebanon’s First Lady at the time wanted to establish a dedicated thalassemia centre in the country. She came to meet me, and that conversation brought into sharp focus something I had been circling: the scale of what was not being done, the inadequacy of how these patients were being managed, and the genuine opportunity to build something that would matter. When I returned to Lebanon in the early 1990s, I was the driving force behind setting up the Thalassemia Centre, and my involvement in both the treatment and prevention of the disease has been unbroken ever since. There is a personal dimension to this commitment as well – I have always believed in finding a field through which one can genuinely grow over a lifetime, and thalassemia has given me exactly that.
How has the understanding and management of thalassemia evolved since those early years, and where do the most important gaps remain?
For a long time, the dominant focus in haemoglobin disorders was molecular – identifying mutations, characterising the genetics. The clinical picture was comparatively underexplored. When I began working with Professor Cappellini in Milan and the late Professor David Weatherall, we set out to investigate the clinical and physiological dimensions more rigorously, moving from observation to hypothesis to clinical trial. From that work came a much clearer understanding of the importance of haemoglobin levels, of the meaningful clinical distinction between transfusion-dependent and non-transfusion-dependent thalassemia, and of the fact that this is fundamentally a multidisciplinary disease – one that implicates cardiology, hepatology, endocrinology, and numerous other specialties alongside haematology. That recognition has shaped how comprehensive care is now structured around the world.
From there the field moved progressively toward novel therapies – first optimisation of transfusion and chelation, and more recently disease-modifying and potentially curative treatments, including gene therapy. In parallel, prevention has been essential, and I would argue it represents the most significant success story in this field. The ability to reduce the birth rate of affected children through awareness campaigns, premarital screening, and prenatal diagnosis has been transformative in countries like Lebanon, where we have brought the number of new cases from fifty or sixty per year down to two or three.
But there is a dimension of this evolution that I feel compelled to address directly, because I think the field does not always engage with it honestly. We spend a great deal of time discussing gene therapy and the most sophisticated novel agents – conversations that matter, and in which I am actively involved. Yet approximately 80 percent of thalassemia patients globally live in low- and middle-income countries where access to even the most basic treatment – safe transfusions and effective iron chelation – cannot be taken for granted. I am not proud of a situation in which we celebrate the frontier of science while the majority of our patients are excluded from its benefits. That tension is something I have written about, and it is something the field needs to hold consistently in view.
The therapeutic landscape has expanded considerably in recent years. Could you walk us through where treatment options stand today, and what is approaching?
The foundation of management for transfusion-dependent patients has always been regular blood transfusion – every three to four weeks – accompanied by iron chelation to manage the iron overload that inevitably results. Chelation therapy itself evolved significantly with the introduction of oral agents, which replaced earlier subcutaneous and intravenous regimens and made a meaningful difference to patients’ quality of life and long-term adherence.
The genuine breakthrough has come with the novel disease-modifying therapies. Luspatercept, a subcutaneous injection administered every three weeks, works by promoting red blood cell maturation and has demonstrated clinically meaningful reductions in transfusion burden – it was the first of these agents to reach approval. The second, mitapivat, is an oral agent that reduces ineffective red cell production and increases haemoglobin in non-transfusion-dependent patients, while also reducing transfusion requirements in transfusion-dependent patients. It has just received FDA approval, and we are awaiting registration in the Gulf region, beginning with Saudi Arabia, before it becomes more broadly available – including eventually in Lebanon. A third agent, currently entering Phase III, is one I would refer you to Novo Nordisk to discuss further.
Beyond these, gene therapy is a genuine clinical reality for a subset of patients. But as I have said, my concern is always for the broader population. If the resources required for a single gene therapy case in a resource-limited country could instead provide years of safe, high-quality transfusion and chelation care to many patients – supporting their growth, their education, their capacity to build a life – that is a question of allocation that the field and its funders are obliged to engage with seriously.
You have made the point that access needs to be embedded in clinical trial design from the outset rather than treated as an afterthought. Could you expand on that?
It comes down to what clinical research is ultimately for. If we develop a therapy that cannot reach the people who need it, the science serves a very limited purpose. From the earliest stages of trial design, we have an obligation to ask how the therapy being studied will eventually become accessible – not only in high-income markets but across the full range of populations that carry the burden of the disease.
Part of the answer lies in better patient stratification. Rather than applying a high-cost therapy universally when only a proportion of patients will respond optimally, we should be identifying the clinical and molecular variables that predict response and directing resources accordingly. This is personalised medicine in its truest sense – not simply deploying the most sophisticated available tool, but matching the right intervention to the right patient, and ensuring that those who do not require the most expensive option receive excellent, appropriately targeted care instead. A therapy that benefits 60 percent of recipients while the remaining 40 percent receive it unnecessarily, at substantial cost, is not a model that serves public health. Those considerations need to be embedded in how we design trials and how we define success.
You have continued to run clinical trials in Lebanon through repeated periods of conflict. How have you maintained those operations, and what lessons have you taken from the experience?
Lebanon’s resilience is something I have come to understand at a very practical level. We have lived through multiple conflicts, and what I have consistently observed is that within 72 hours of any cessation of hostilities, we are able to resume operations – a recovery capacity that would be very difficult to replicate in countries without that accumulated experience of functioning under adversity.
The key has been building a genuinely self-sufficient team. I have developed a group of pharmacists, young physicians, and regulatory specialists who are themselves Lebanese and who remain in the country. I established a 24-hour patient contact line so that no patient on an active trial loses connection with the system, and for those who cannot physically reach the centre, we go to them or manage remotely where clinically appropriate. Lebanon’s geography actually helps here – most patients can reach us within a manageable time when conditions allow. What holds the system together when external conditions are most difficult is the quality of the relationship between our patients and their physicians: a trust built over years, through consistency and honesty, that does not fracture easily. Patient advocacy has been critical throughout – giving patients a clear and honest picture of how they are progressing and what we are doing to support them has maintained engagement even in the most challenging periods. I wrote about this in The Lancet Haematology, in a paper specifically on running clinical trials during wartime, because the lessons are transferable and deserve to be shared.
Retaining talent in Lebanon is an obvious challenge. What has been your strategy for building the next generation of doctors?
Lebanon has seven or eight medical schools, and the American University of Beirut alone graduates 110 medical students per year, of whom roughly 90 go on to train in the United States. If even 10 to 15 percent of those return, that is a meaningful and sustained influx of highly trained people. I have seen that happen, and I have been part of making it happen. I could have remained in London – I was a consultant there and the path was open to me. I chose to come back because I believed in what could be built here, and because I wanted to make a difference from within rather than from a comfortable distance. That decision, thirty years ago, has shaped everything that followed.
What sustains this model is offering genuine career development: structured mentorship, involvement in internationally recognised research, and the opportunity to build a reputation that extends well beyond Lebanon. The international networks matter enormously in this regard. Our connections with institutions such as MD Anderson, Memorial Sloan Kettering, and the Royal College of Physicians in London keep ideas and people flowing in both directions – a researcher can be physically in Beirut and intellectually at the centre of the global conversation, which is increasingly what the best young clinicians want. I would also note that the current environment in the United States has prompted some Lebanese physicians who had built careers there to reconsider. The stability they assumed was permanent has proved less certain, and that recalibration is quietly bringing people back. If you want to grow your country, at some point you need to be in it.
What advice would you give to colleagues in other specialties or other countries who are trying to build comparable depth of expertise in a rare disease?
Three things, which I offer to everyone who asks. The first is passion – you must be genuinely drawn to the field you choose, because the depth of commitment required to make a real contribution to a rare disease over a career is not sustainable without it. The second is focus. If you are serious about a rare disease, commit to it fully. Your patient volume will be lower, and your income may reflect that, but the distinctiveness of your academic contribution will be of a different order than if you had chosen a condition present everywhere. The third is networking. My connections with colleagues in London, Milan, and the United States have been as important to everything I have built as anything I have done within Lebanon itself. Passion, focus, and a well-cultivated international network – if you have those three things, the trajectory that follows will surprise you.
I would add one structural point: one of the most underappreciated gaps in rare disease medicine globally – and I have discussed this extensively with colleagues across the Gulf – is the absence of robust patient registries across large parts of the world. Without a registry, you cannot characterise your patient population, cannot conduct meaningful epidemiological research, and cannot attract the clinical trials that bring new therapies to local patients. Building that infrastructure is unglamorous, painstaking work. It is also foundational.
Looking ahead, what are you most focused on in the next phase of your work?
The clinical trial with Novo Nordisk is a clear near-term priority, and gene therapy remains an area I follow closely. I am also increasingly engaged with bleeding disorders alongside thalassemia, which has brought new dimensions to my research.
But if I am candid about where my energy is moving, it is toward a different kind of contribution. I am at a stage where I want to spend more time relaying ideas, shaping thinking, and opening career paths for others. That means writing – I am working on a book focused on access, treatment systems, and health policy rather than on molecular science – and it means investing more deliberately in the development of younger colleagues so that they can carry this work forward and develop their own vision for the field. Classical haematology – the benign haematology that has been my life’s work – is not drawing the interest from the next generation that it deserves, and keeping that interest alive is perhaps the most important thing I can contribute at this point in my career.
