This interview is with Dr John Barrett, the Editor in Chief of Immunotherapy Insights and Section Chief of Stem Cell Allotransplantation in the Hematology Branch of the National Heat Lung and Blood Institute at the US National Institutes of Health.

Tom: What would you say is the primary focus of your research effort (and how do you refer to your 'sub-area')?

Dr Barrett: The central component of my research has been the use of stem cell transplantation to treat human malignancies. This clinical activity has led me into the study of the alloimmune response, immune reconstitution and tumor immunology. Specifically I study the role of T cells and Natural Killer (“NK”) cells in anti-tumor responses and the application of cell and vaccine based immunological approaches to treating malignant diseases.

Tom: What do you consider to be the most significant developments arising from research in your area?

Dr Barrett: The identification of both T cell and NK cell mediated graft-versus-leukemia effects following stem cell transplantatin has stimulated a continuing effort to identify the immunological mechanmisms underlying these potent clinical effects and to then devise new strategies to improve the GVL effect and apply principles learned in allogeneic stem cell transplantation to a wider context of immunotherapy for malignant disease.

Tom: What do you consider to be the most significant open questions and research challenges in your area?

Dr Barrett: The main challenges in this area are firstly to define the antigens driving T cell responses to leukemia, characterize successful T cell-leukemia cell interactions and apply translational research to adapt these findings into clinical strategies – developemnt of leuikemia vaccines, adoptive transfer of T cells and so on. Secondly, in the field of NK cell research we need to better understant the rules of engagement between NK cells and their target, define the way in which NK cells can control malignancies and again develop translational approaches to using NK cells in clinical treatments. and then to translate, and identify the NK-target cell interactions that lead to successful immunotherapy with NK cell infusions or methods to boost NK numbers and function.

Tom: Tell us about your collaborative research. Who else do you directly work with and what are the aims of your collaboration?

Dr Barrett: I believe collaborative research is the most effective way of moving the field forward – not only in the lab where at NIH we are fortunate in having almost limitless opportunities to work with scientists with diverse and highly specialise skills, but also in clinical research. This is particularly the case with our leukemia vaccine trials, where we are faced with the need to test a wide variety of schedules and indications. At a single institute it would take years to find enough patients to fully explore the various treatment approaches. We have therefore formed a “vaccine consortium” of five centers in the USA Europe and Australia with a view to sharing in coordinated but diverse trial approaches the vaccines, the outcome measurements, and the results of the trials. Similarly, stem cell transplantation is always a collaborative effort, both within the hospital unit where a multidisciplinary team is needed to assure the safe outcome for the patient, but also in the wider arena of the transplant community where ideas and results are shared rapidly among the specialists in the field.

Tom: Is balancing all these activities challenging? How do you deal with it and what tools do you find useful in doing so?

Dr Barrett: Diversity of effort always brings the challenge of keeping all the balls in the air and not ignoring one component of the operation. As well as having weekly meetings I have divided the activities of my research group into three sections and I meet with each subgroup for an hour a week. Keeping up with progress in the field is easy to do with the number of planned meetings I attend or those to which I am invited to participate as a speaker. The risk here is being away too much, although it is always valuable to talk to colleagues from around the world on a regular basis.

Tom: When did you decide to be primarily involved in the field that you are now in?

Dr Barrett: Many years ago! In 1970 I participated in the management of a child with severe combined immunodeficiency disease and was excited and fascinated by the successful outcome of this patient (the first allogeneic stem cell transplant for SCID in the United Kingdom). I think the scientific and clinical challenge of applying stem cell transplantation to the treatment of otherwise incurable diseases has never left me.

Tom: What resources do you find indispensible for your research work?

Dr Barrett: It's the combination of having a clinical research program closely linked to strong immunologically-based laboratory research that matters to me. The clinical work continually provides therapeutic challenges that require laboratory investigation to understand at the cellular and molecular level, with a view to moving back through translational research to apply new therapies to our patients.

Tom: What do you think about the development of open access publishing and open access development? How has it changed your perspective on research or development practices?

Dr Barrett: Open access publication for me is still an experiment with consequences that are as yet unclear. However the widspread availability of web-based science means it is inevitably going to gain an increasingly widening importance and acceptance within the scientific community. My concerns are how to maintain quality. Peer-review will be a critical component to maintain quality.

Tom: What books or journals do you think should be required reading for researchers working in your area?

Dr Barrett: Many journals cover my area of interest – Blood, Journal of Immunology, Nature Medicine, Leukemia, Haematologica, Biology of Blood and Marrow Transplantation, Bone Marrow Transplantation, Journal of Immunotherapy, Cytotherapy to name the most important.

Tom: What books are current on your reading list?

Dr Barrett: To be honest I don't have time for reading textbooks – I have just published a textbook in collaboration with Jennifer Treleaven called "Hematopoietic Stem Cell Transplantation in Clinical Practice" (Amazon.com). Other wise I read history – I have just read "Austerity Britain" by David Kynaston – a vivid account of the early post war years of hardship for the country that I remember from childhood (Amazon.com).

Tom: Do you teach any courses? Is so, which ones?

Dr Barrett: At NIH we are primarliy a research institute but we do have a fellowship training program for hematology where I participate in lectures and informal training in clinical hematology and stem cell transplantation on a regular basis.

Tom: Which historical research figures do you think have most influenced you in how you think about research? Why are they significant?

Dr Barrett: In the field of stem cell transplantation, aside from our only Nobel Prize Winner E Donnal Thomas who set clinical stem cell transplantation on the map, the person who stands out most is Professor Georges Mathe with whom I was fortunate enough to train for a brief time at Villejuif, Paris. Mathe was brilliant. In the 1950s he had already grasped the significance of the graft-versus-leukemia effect and had pioneered clinical stem cell transplantation to treat leukemia and radiation injury.

Tom: Which meetings do you attend on a regular basis?

Dr Barrett: My meeting year starts with the American Society of Blood and Marrow Transplantation followed by the European Group for Bone Marrow Transplantation, the International Society of Cellular Therapy and lastly, in December, the American Society of Hematology.

Tom: If you could change something about how research in your area is conducted, used, perceived, or resourced, what would it be?

Dr Barrett: I have to admit I work in an extremely favoured environment where day to day funding comes without the need to apply for grants. Our clinical trials are supported fully by the NIH which lessens our dependency on pharmaceutical companies and allows us great independence in trial design. We have access to a campus of over 6000 scientists so it is rare that we cannot find an expert in any field of biological science to collaborate with. It is almost true that the only limitation to performing innovative research rests with the abilities of the investigator. That said – yes – I would always welcome the opportunity to double the size of my core research group of 12 investigators and increase the clinical throughput, in order to more rapidly reach our goals of improving the treatment of human malignant diseases through immunotherapy.

My thanks to Dr Barrett.