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Felix B. Engel, PhD

Research Fellow, Department of Cardiology, Children's Hospital, Department of Cell Biology, Harvard Medical School

REVIEW

Thank you very much for the opportunity to read and review the book by Hanan Polansky. As a trained biotechnologist, I am used to the approach to establish mathematical models for biological processes and believe it is very important for our deeper understanding of molecular mechanisms of diseases.

It was a pleasure to start reading the book. The preface especially caught my attention. It is clearly written and prepares oneself for the following rather complicated technical part due to the large number of mathematical equations. Fortunately, Hanan Polansky provides many examples to clarify the mathematical functions he is carefully introducing in each chapter. In my opinion it is very interesting to read the book, and it is intellectually satisfying. However, the book is very challenging as it covers a wide range of topics such as cell motility, atherosclerosis, autoimmune diseases, cellular signaling, and cancer. Thus, it is very tiring. The organization of the book is also sometimes confusing and maybe too many examples are given.

To my knowledge, Hanan Polansky used a unique, novel approach to further stimulate our understanding of the origin and establishment of chronic diseases. I hope that more attempts will follow to model other important molecular mechanisms. The theory described is very interesting, and the amazing correlation between theoretical predictions and observed in vivo effects seems to validate it. However, it is important to demonstrate that this theory can be used to predict so far not performed experiments and helps to develop novel therapeutics for human diseases.

I am working in the field of heart regeneration, and thus I am familiar with atherosclerosis, obesity and cell cycle studies (cancer). Moreover, I am very interested in understanding cell signaling regarding heart regeneration. Personally, I am also interested in chronic diseases. To be honest, I was surprised to realize by reading the book that all the described diseases might be based on a common cause. It is amazing how Hanan Polansky was able to establish a model describing how chronic diseases are based on the modulation of endogenous regulatory networks by a foreign genome that enters the host in the form of viral infection.

I believe every scientist working with biological systems should read the book to become aware of how important mathematical descriptions of systems are. Moreover, the book demonstrates in a very elegant way how important it is to see the big picture and not to be focused on isolated systems. I find the book very challenging as it covers a wide range of topics such as cell motility, atherosclerosis, autoimmune diseases, cellular signaling, and cancer. Therefore, to fully comprehend the underlying common mechanism(s), although explained well, one needs to have reasonable background knowledge in such diverse subjects. From my own perspective, the idea behind the book certainly seems to be a stimulator for young students. However, I believe the book is too complex as a medical textbook because it is lacking too much basic information needed to understand it.

The book has the potential to impact medical research and drug discovery and time will show. Although the theory was demonstrated very convincingly it might be oversimplifying the problems underlying chronic diseases. Nevertheless, I am convinced that the work of Hanan Polansky will contribute to a deeper understanding of the mechanism of chronic diseases and this brings the field a big step forward.

BIOGRAPHY

Dr. Felix B. Engel studied biotechnology at the Technical University in Berlin, Germany. During this time, he worked on the characterization of replication origins in Schizosaccharomycespompe and developed during his diploma thesis, a selection system for ribozymes that are able to catalyze bimolecular reactions. Afterwards, he became interested in regenerative medicine. At the Max Delbrueck Center for Molecular Medicine, he established during his PhD thesis, a mammalian myocardial cell-free system demonstrating that the mammalian heart is, in principle, able to regenerate. Finally, Dr. Engel joined Mark T. Keating's group at Harvard Medical School/Children's Hospital. At the moment, he works on the induction of dedifferentiation and proliferation of mammalian cardiomyocytes as a fundamental mechanism of heart regeneration as Mark Keating's group has shown previously in zebrafish.

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