Spotlight: Dr. Francesco Marincola
Ilene Raymond Rush
Editor
September 2008
Francesco M. Marincola, M.D., chief of the Infectious Disease and Immunogenetics Section (IDIS) at the Clinical Center, National Institutes of Health in Bethesda, Maryland, graduated from the University of Milan, Italy, in 1978. After a year in the Italian military, he moved to Stanford, California, where he completed his surgical training as well as research training in transplant and cancer immunology. In 1990 he moved to the National Cancer Institute (part of the National Institutes of Health, USA) where he continued his research in tumor immunology by developing strategies for studying tumor/host interactions in the context of human genetic polymorphism and cancer heterogeneity. He has since broadened the scope of his research to include other fields of human immunology in which genetic polymorphism is the hallmark of human disease. His continuous efforts in developing strategies for studying diseases directly in humans, rather than relying on often misleading animal models, fostered his interest in starting the Journal of Translational Medicine in 2003.
Can you define translational medicine?
The goal of translational medicine is to test novel therapeutic strategies developed through experimentation in humans. I see translational medicine as a two-way road: from bench to bedside and bedside to bench. The idea is that ex vivo human observation may help researchers to see patterns of disease and to decide what might be useful to investigate.
Translational medicine can help to validate the clinical potential of novel discoveries, identify novel concepts relevant to human disease, increase the efficiency in which new therapeutic strategies can be tested on human subjects, profile feedback to researchers about the effects of treatment, and develop reagents for the characterization of the disease processes.
What generated your interest in the bedside to bench approach offered by translational research?
One reason is that our understanding of human disease remains limited and pre-clinical models have shown a discouraging propensity of failure when only mechanistic approaches towards understanding diseases and developing a hypothesis are employed.
It makes sense why so much research has gone in the direction of bench to bedside: genetic issues, for example, are much more difficult to control in humans. But given the decline in new medicines, we need to have a wider range of approaches to developing what areas are most important to investigate when it comes to human disease. We need to have a better lever to study humans and areas of commonality.
What roadblocks prevent this two-way approach?
In part, it has to do with the nature of disease: the genetic variety of our species, the extreme and evolving heterogeneity of some diseases (such as cancer or viral diseases) and external ethical and practical considerations. Animal models are sometimes easier to work with. The problem is that animal models do not represent the essence of human diseases but an attempt to put the bull’s eye in the trajectory of the projectile rather than designing a response to moving targets.
How might you rethink current research models?
I would urge researchers to think about using human observation when drawing up their pre-clinical hypotheses. The problem is that some pre-clinical models that don’t consider patients can lead to hypotheses that aren’t very useful in eventually treating or curing the disease. You need to go to the humans and identify relevant questions.
Can you give an example?
Sure. In a recent conference I watched as five speakers presented back to back talks in which each researcher provided convincing evidence that his or her protein was the ‘orchestrator’ of melanoma and therefore, the preferred target of future therapies. Nobody noted the contradiction of these claims of five different sources.
Is translational medicine a radical concept?
No, it’s not. Sir Francis Bacon agreed that the quality of hypotheses depend on the quality and relevance of the facts on which is its based. The scientific revolution has been driven by induction that draws on knowledge from the natural world through experimentation, observation, and testing of hypotheses. It’s absolutely true that facts must be confirmed by experimentation that can be reproduced and tested, but this does not mean that facts should simply validate the foundation on which the experimentation is based. Experiment and observation should lead to an accurate description of the facts upon which we could base a relevant hypothesis.
Journal of Translational Medicine 2007, 5:21doi:10.1186/1479-5876-5-21
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