Thursday, June 5, 2014

New Book Explains the Importance of Rare Disease Research

This week, my latest book entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. This book builds the case that the best way to advance our understanding of the common diseases is to focus our attention on the rare diseases.

The following text is excerpted from the book's Preface.

In biology, there are no outliers; no circumstances that are rare enough to be ignored. Every disease, no matter how rare, operates under the same biological principles that pertain to common diseases. In 1657, William Harvey, the noted physiologist, wrote: "Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows tracings of her workings apart from the beaten paths; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature, by careful investigation of cases of rarer forms of disease.

We shall see that the rare diseases are much simpler, genetically, than the common diseases. The rare disease can be conceived as controlled experiments of nature, in which everything is identical in the diseased and the normal organisms, except for one single factor that is the root cause of the ensuing disease. By studying the rare diseases, we can begin to piece together the more complex parts of common diseases.

The book has five large themes that emerge, in one form or another, in every chapter.

1. In the past two decades, there have been enormous advances in the diagnosis and treatment of the rare diseases. In the same period, progress in the common diseases has stagnated. Advances in the rare diseases have profoundly influenced the theory and the practice of modern medicine.

2. The molecular pathways that are operative in the rare diseases contribute to the pathogenesis of the common diseases. Hence, the rare diseases are not the exceptions to the general rules that apply to common diseases; the rare diseases are the exceptions upon which the general rules of common diseases are based.

3. Research into the genetics of common diseases indicates that these diseases are much more complex than we had anticipated. Many rare diseases have simple genetics, wherein a mutation in a single gene accounts for a clinical outcome. The same simple pathways found in the rare diseases serve as components of the common diseases. If the common diseases are the puzzles that modern medical researchers are mandated to solve, then the rare diseases are the pieces of the puzzles.

4. If we fail to study the rare diseases in a comprehensive way, we lose the opportunity to see the important biological relationships among diseases consigned to non-overlapping sub-disciplines of medicine.

5. Every scientific field must have a set of fundamental principles that describes, explains, or predicts its own operation. Rare diseases operate under a set of principles, and these principles can be inferred from well-documented pathologic, clinical, and epidemiologic observations.

Today, there is no recognized field of medicine devoted to the study of rare diseases; but there should be.

Content and Organization of the Book

There are three parts to the book. In Part I (Understanding the Problem), we discuss the differences between the rare and the common diseases, and why it is crucial to understand these differences. To stir your interest, here are just a few of the most striking differences: 1) Most of the rare diseases occur in early childhood, while most of the common diseases occur in adulthood; 2) The genetic determinants of most rare diseases have a simple Mendelian pattern, dependent on whether the disease trait occurs in the father, or mother, or both. Genetic influences in the common diseases seldom display Mendelian inheritance; 3) Rare diseases often occur as syndromes involving multiple organs through seemingly unrelated pathological processes. Common diseases usually involve a single organ or involve multiple organs involved by a common pathologic process.

The most common pathological conditions of humans are aging, metabolic diseases (including diabetes, hypertension, and obesity), diseases of the heart and vessels, infectious diseases, and cancer. Each of these disorders is characterized by pathologic processes that bear some relation to the processes that operate in rare diseases. In Part II (Rare lessons for Common Diseases), we discuss the rare diseases that have helped us understand of the common diseases. Emphasis is placed on the enormous value of rare disease research. We begin to ask and answer some of the fundamental questions raised in Part I. Specifically, how is it possible for two diseases to share the same pathologic mechanisms without sharing similar genetic alterations? Why are the common diseases often caused, in no small part, by environmental (i.e., non-genetic) influences, while the rare disease counterparts are driven by single genetic flaws? Why are the rare diseases often syndromic (i.e. involving multiple organs with multiple types of abnormalities and dysfunctions), while the so-called complex common diseases often manifest in a single pathological process? In Part II, we will discuss a variety of pathologic mechanisms that apply to classes of rare diseases. We will also see how these same mechanisms operate in the common diseases. We will explore the relationship between genotype and phenotype, and we will address one of the most important questions in modern disease biology: "How is it possible that complex and variable disease genotypes operating in unique individuals will converge to produce one disease with the same biological features from individual to individual?"

In Part III (Fundamental Relationships Between Rare and Common Diseases), we answer the as-yet unanswered questions from Part I, plus the new questions raised in Part II. The reasons why rare diseases are different from common diseases are explained. The convergence of pathologic mechanisms and clinical outcome observed in rare diseases and common diseases, as it relates to the prevention, diagnosis, and treatment of both types of diseases, is described in detail.

I urge you to read more about this book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.

- Jules J. Berman, Ph.D., M.D.