Trials and Transplantations

How did you become interested in pathology?

When I was a teenager, I dreamed of becoming a doctor. It was a difficult time; my life had changed suddenly with the death of my father and I had to work at many different jobs to support my family. I ended up falling in love with medicine and eventually I graduated from the Universidad Autonoma de Mexico (UNAM) and specialized in internal medicine. Then my life changed again – I was accepted at Harvard University for my clinical training, received a World Health Organization fellowship and spent four years studying immunogenetics at the Dana Farber Cancer Institute. But the changes didn’t stop there; my next move was to London, where I researched human leukocyte antigen polymorphisms and trained at Imperial College London and University College London, and then I moved to California to undertake a postdoctoral position at Stanford. It was in 1993 that I accepted the position of Scientific Research Director at the Anthony Nolan Trust, a post that has served me in good stead for the past 23 years, and has allowed me to contribute substantially to the area of hematopoietic stem cell transplantation (HSCT). What have I learned from studying pathology around the world? That medicine is a universal subject with one common goal: to help patients survive and improve their quality of life. Resources may make a difference to the quality of medical care, but we all just want the opportunity to cure every patient in need of treatment.

What are you most proud of in your career?

The Anthony Nolan Trust was established in 1974 by Shirley Nolan, whose son Anthony had been diagnosed with Wiskott-Aldrich Syndrome. At that time, there were no other registries and the concept of being an unrelated donor did not exist. Shirley Nolan changed the world, and thanks to her brilliant initiative, there are now over 28 million registered donors worldwide and over one million transplants have been performed. I am very proud to have established the Anthony Nolan Research Institute (ANRI), which has published over 1,200 scientific papers with over 12,000 citations. We’ve also become a center for education, training over 160 scientists, and have helped communities abroad to establish and develop their own registries. The ANRI has collaborated on a global scale to improve the outcome of HSCT and this has been a great satisfaction to me.

I feel strongly that my involvement in teaching and training is one of my greatest achievements. We owe a responsibility to the younger generation – to give them a varied education and to help them progress in their careers. I feel that dedicating our time to opening new ways of thinking, providing new opportunities, and leading our students down the road to knowledge pays us back enormously in many different ways.

What are the most interesting projects you’ve worked on?

I led the “AlloStem” Consortium, which brought together clinical and research groups from across the European Union and beyond. Over 100 scientists and 24 biomedical research teams joined our Associate Membership program, and five small- and medium-sized enterprises worked on developing immunotherapeutic strategies to treat hematological and neoplastic diseases. The results from the project were very impressive – with over 288 papers published, 17 patent applications, and four new databases created, I think the work will generate important contributions to the field of stem cell transplantation for many years to come. Currently, I co-coordinate a follow-on project: “T-Control,” a consortium of six leading European groups that use immunotherapeutic strategies to generate cell therapies for graft-versus-host disease, leukemia and post-transplant infection complications. We are already initiating clinical trials and are enthusiastic that, with the development of new cell therapy weapons, we may be able to control most of the complications that affect the outcome of HSCT.

And your hopes for the future?

I hope that we’ll be able to control or even cure cancers without the need for HSCT and that we’ll be able to generate alternative treatments. We are already seeing pioneering steps being taken, such as chimeric antigen receptor T cells, PD-1 antagonists and targeted drugs. I’m optimistic that the stem cells can be applied to other conditions, too. In the shorter term, with over 28 million donors registered and new developments in transplantation all the time, I want every patient in need of HSCT to be able to find a donor.

Over the next few years, my research group plans to use third-generation sequencing and other new technologies for genotyping, with the goal of demystifying the role of immunogenetic differences in HSCT outcomes. We also want to develop new cell therapy strategies using cord blood cell products, such as natural killer cells, regulatory T cells and cord plasma to fight relapse, infection and graft-versus-host disease. We’re hoping to coordinate clinical trials in these areas very soon!

What advice would you give to a young Alejandro Madrigal?

To always work with passion in the hope that you can make a difference – however small – to the lives of patients, as this would be a wonderful contribution to improving the health of as many people as possible around the world. I think that all pathologists should do their jobs with passion, because the ultimate goal is to change and improve clinical practice, save lives, and make the world a better place.