Interview with Sir David Weatherall

Thursday, December 3rd, 2009 at 3:42 pm

December 3, 2009 – CAF speaks with Sir David Weatherall, one the world’s foremost thalassemia experts, about the global thalassemia issue.

Sir David Weatherall founded the Institute of Molecular Medicine at Oxford in 1989, which in 2000 was renamed the Weatherall Institute of Molecular Medicine in his honor. He has worked extensively in thalassemia, bridging its clinical aspects to its molecular basis and providing a wealth of information that has proved invaluable in understanding the disorder. In recent years, Sir David has spent a great deal of time studying hemoglobin E and its interactions with beta thalassemia, especially in Southeast Asia and particularly in Sri Lanka. At the recent 9^th Cooley’s Anemia Symposium Sir David gave a keynote lecture on “Thalassemia as a Global Health Problem: Recent Progress towards its Control in the Developing Countries.” CAF is grateful to Sir David for agreeing to an interview at that Symposium.

Sir David Weatherall: I think it’s well-recognized now that the inherited disorders of hemoglobin (thalassemia and sickle cell disease) are by far the commonest single gene disorders in human beings, and there are extensive data around the world to suggest that somewhere around 300,000 or more babies are born with these diseases each year. The problem is that the reason these diseases are common is that in the past, carriers have been more resistant to malaria and therefore they’ve tended to live a bit longer and have more children than those who are not carriers and so the disease increased very rapidly in malarial areas. The distribution of malaria in a country is very uneven; therefore the distribution of these diseases is quite uneven, so if you estimate them in one spot or at one hospital, you get a completely erroneous idea of the frequency. In recent years there have been one or two micro mappings where people have gone around and taken samples from many parts of the country and the figures are probably on the whole higher than we have been able to estimate before. So although we know the hemoglobin disorders are extremely common, we don’t really know how common they are.

If you look at west of the Indian subcontinent, you primarily find beta thalassemia major. If you go east, there’s a very common hemoglobin variant called hemoglobin E which occurs in massive frequencies, up to 70% in some populations. In that variant hemoglobin E is not produced very effectively. There’s also a lot of beta thalassemia in these populations, so you find a disease called hemoglobin E beta thalassemia, in which a person inherits a hemoglobin E gene from one parent, a beta thalassemia gene from the other. That disease is extraordinarily variable; in some cases it is as severe as people with thalassemia major, in others, the person can grow and develop reasonably normally with low hemoglobin levels.

The big problem in countries with e beta thalassemia is trying to find out why it is so variable, as well as how to recognize the milder forms earlier. As we found in our work in places like Sri Lanka, we also need to know when we can avoid transfusion in e beta thalassemia. I think there are probably hundreds of thousands of children in Asia who may be getting transfusions unnecessarily. And of course, the burden for those countries once beta thalassemia surfaces and develops is enormous.

I think the biggest challenge for poorer countries is how to develop the kind of services that are available to children in the richer countries and it’s a question the thalassemia field needs to, address: What is the most cost effective way of doing that?

The governments of these countries are overburdened with communicable disease. There is still malaria, HIV AIDS, tuberculosis. And as their nutrition, hygiene and public health services improve, they’re starting to see the big killers of western society now, such as heart disease. So they have a double burden and most of them are still completely ignoring things like thalassemia and other genetic diseases.

My own feeling, having worked in these countries for a long time now, is that we must make a start and there are two cost effective approaches. One is what we call North-South partnerships, in other words, countries with expertise will try to form links with countries in which there is no expertise, and that has worked extremely well actually in many Asian countries. Many of the centers of expertise in India and Sri Lanka are the result of those partnerships.

But the next step is what I call South-South partnerships; in other words, a country like India, where they have real expertise, should try to link up with a place like Bangladesh, where there is a huge problem but no expertise, no trained staff, no trained doctors, nurses, counselors. Thailand, where there’s real expertise, should link up with places like Cambodia. That’s the concept we’ve been trying to promote over the last few years.

It’s been accepted by the World Health Organization as a valuable way forward and given lots of encouragement, but there’s been no actual input. I think we have to get over the message to the international health agencies that these approaches are very cost effective and probably the only rapid way forward.

I think I’m the only person at this Symposium
who has attended every one since 1963. I was just looking at the first Symposium before I came here. That was an extraordinary meeting because it brought together basic scientists who knew nothing about patients with people who were just starting to look at thalassemia. It was the first meeting in the world where the first methods for transfusing thalassemic children were properly discussed and where the underlying cause of the disease, which was just starting to become apparent, was discussed. Starting then and continuing on, I think the CAF-NYAS meetings have been a major force in the development of the thalassemia field.

I think CAF has been critically important in the development and understanding of thalassemia because it brings together not just the medical fraternity but patients and families, and includes major input and interaction between them. It’s the only real connection between patients and families and the medical profession at a level that allows for a kind of real genuine discussion of their problems and how we may train doctors in the better management of the disease. I think it’s very unusual. I know people with genetic disease need lifelong support, but this kind of coming together just hasn’t happened in very other branches of medicine.

We want, of course, a radical cure for thalassemia, and while bone marrow transplantation provides that, it is still only available for a limited number of people. I think at this particular meeting, we have shown that the molecular approach (e.g., gene therapy) has actually, slowly been developing toward the possibility of correcting genetic disease, and I think people should take very strong hope for the future in that. It’s going to take time, it’s very complex, but at this meeting, I was very encouraged by the real progress that has been made over the last few years. It will take a while, but we must believe in the future of that approach, because ultimately I think it will cure the disease.

Of course, a gene therapy cure is still some time away and when it comes will be expensive; in the meantime, I believe that the richer countries should do all they can through developing partnerships with the poorer countries to try to help them establish some kind of services for the control and management of thalassemia.

: News
: interview