Announcement: Precision Medicine and the Reinvention of Human Disease

In January, 2018, Academic Press is publishing my latest book, Precision Medicine and the Reinvention of Human Disease

Here is the book description, from the back cover:

Despite what you may have read in the popular press and in social media, Precision Medicine is not devoted to finding unique treatments for individuals, based on analyzing their DNA. To the contrary, the goal of Precision Medicine is to find general treatments that are highly effective for large numbers of individuals who fall into precisely diagnosed groups.

We now know that every disease develops over time, through a sequence of defined biological steps, and that these steps may differ among individuals, based on genetic and environmental conditions. We are currently developing rational therapies and preventive measures, based on our precise understanding of the steps leading to the clinical expression of diseases.

Precision Medicine and the Reinvention of Human Disease explains the scientific breakthroughs that have changed the way that we understand diseases, and reveals how medical scientists are using this new knowledge to launch a medical revolution.

Key Features

• Clarifies the foundational concepts of Precision Medicine, distinguishing this field from its predecessors such as genomics, pharmacogenetics, and personalized medicine.
• Gathers the chief conceptual advances in the fields of genetics, pathology, and bioinformatics, and synthesizes a coherent narrative for the field of Precision Medicine.
• Delivers its message in plain language, and in a relaxed, conversational writing style, making it easy to understand the complex subject matter.
• Guides the reader through a coherent and logical narrative, gradually providing expertise and skills along the way.
• Covers the importance of data sharing in Precision Medicine, and the many data-related challenges that confront this fragile new field.

Table of Contents

Preface.                                                                 

Chapter 1. Introduction: Seriously, What is Precision Medicine?                     
  Glossary
  References


Chapter 2. Redefining Disease Causality                                            
  Section 2.1 Causality and Its Paradoxes                              
  Section 2.2 Why We Are Confident that Diseases Develop in Steps                  
  Section 2.3 Cause of Death                                           
  Section 2.4 What Is a Disease Pathway?                                              
  Section 2.5 Does Single Event Pathogenesis Ever Happen?      
  Glossary
  References


Chapter 3. Genetics: Clues, Not Answers, to the Mysteries of Precision Medicine         
  Section 3.1 Inscrutable Genes                                               
  Section 3.2 Inscrutable Diseases                                            
  Section 3.3 Recursive Epigenomic/Genomic Diseases                                              
  Section 3.4 Why a Gene-based Disease Classification Is a Bad Idea           
  Glossary
  References


Chapter 4. Disease Convergence
  Section 4.1 Mechanisms of Convergence                                       
  Section 4.2 Phenocopy Diseases: Convergence Without Mutation        
  Section 4.3 The Autoantibody Phenocopies                                      
  Section 4.4 Pathway-Directed Treatments for Convergent Diseases             
  Glossary
  References


Chapter 5. The Precision of the Rare Diseases                                          
  Section 5.1 The Biological Differences Between Rare Diseases and Common Diseases   
  Section 5.2 Precision Medicine's First Benefit: Cures for Rare Diseases            
  Section 5.3 What the Rare Diseases Tell Us About the Common Diseases               
  Section 5.4 Treatments for Rare Diseases are Effective Against the Common Diseases 
  Glossary
  References


Chapter 6. Precision Organisms                                                        
  Section 6.1 Modern Taxonomy of Infectious Diseases                                    
  Section 6.2 Our Genome Is a Book Titled "The History of Human Infections"           
  Section 6.3 Inflammatory Diseases: Collateral Damage in the War on Human Infection    
  Section 6.4 Revising Koch's Postulates in the Era of Precision Diagnostics      
  Section 6.5 Diseases-in-waiting                                              
  Section 6.6 Precision Taxonomy                                               
  Glossary
  References


Chapter 7. Reinventing Diagnosis                                                  
  Section 7.1 The Principles of Classification               
  Section 7.2 Superclasses                                                     
  Section 7.3 Classifications Cannot Be Based on Similarities                       
  Section 7.4 The Horrible Consequences of Class Blending                
  Section 7.5 What Is Precision Diagnosis?                                   
  Glossary
  References


Chapter 8. Precision Data                                                              
  Section 8.1 What Are the Minimal Necessary Properties of Good Data?              
  Section 8.2 Data Identification and Data Deidentification                      
  Section 8.3 What Do We Do With Non-quantitative, Descriptive Data?    
  Section 8.4 Incredibly Simple Methods to Understand Precision Medicine Data         
  Section 8.5 Data Reanalysis: More important than the Original Data Analysis      
  Section 8.6 What Is Data Sharing, and Why Don't We Do More of It?              
  Glossary
  References


Chapter 9. The Alternate Futures of Precision Medicine                               
  Section 9.1 Hypersurveillance                           
  Section 9.2 Do It Yourself Medicine                                   
  Section 9.3 Eugenics                                          
  Section 9.4 Public Health                                                
  Section 9.5 The Data Analyst of Tomorrow                           
  Section 9.6 Fast, Cheap, Precise Clinical Trials              
  Section 9.7 Animal Experimentation                 
  Glossary
  References

Causality: Single Gene Disorders Can be Biologically Complex

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

One of the points discussed in the book is disease causation, and how we often fool ourselves into thinking that we understand how a disease develops, simply because we can name the gene or agent that precipitates the disease.

A gene may code for a single protein, but complex genetic and epigenetic conditions will effect the individual's response to a specific gene defect. Hence, different individuals, each with their own unique genome and epigenome, will respond differently to the same genetic aberration. Here is an excerpt from Chapter 9:

If an aberration of a single gene were the only cause of a disease, then all of the consequences of the genetic aberration would be identical in every affected person. The is seldom the case, but sickle cell disease is a rare exception to the rule (i.e., sickle cell disease has a remarkably uniform clinical phenotype in affected individuals).

What would happen if a genetic aberration, known to produce disease in humans, were recapitulated in a mouse? If the mouse homologue served the same purpose as the human gene, and if the gene were the sole cause of the disease, then you might expect the disease to be the same in man and mouse.

Lesch–Nyhan disease is a rare syndrome caused by a deficiency of HGPRT (hypoxanthine-guanine phosphoribosyl transferase), an enzyme involved in purine metabolism. In humans, HGPRT deficiency results in high levels of uric acid, with resultant renal disease and gout. A vast array of neurologic and psychologic signs accompanies the syndrome, including self-mutilation. Neurologic features tend to increase as the affected child ages. The same HGPRT deficiency of humans can be produced in mice. Mice with HGPRT deficiency do not have disease. As far as anyone can tell, mice with HGPRT deficiency are totally normal [18]. How can this be?

A single gene cannot cause a disease all by itself. Every monogenic disease is expressed in a complex system wherein the defective gene is a participant in various pathways that eventually lead to a disease. The mouse, evidently, has a set of pathways that compensates for the deficiency in HGPRT.

Diabetes is usually a common polygenic disease. There are rare subtypes of type 2 diabetes that have a monogenic origin. As you would expect, these rare subtypes arise in children, and have a Mendelian pattern of inheritance. One such monogenic form of diabetes is MODY-8 (maturity-onset diabetes of the young), caused by a mutation in the carboxyl-ester lipase gene. This same mutation was delivered to a transgenic mouse, intended as an animal model for MODY (see Glossary item, Transgenic). Mice carrying the same altered gene as the human failed to develop any signs of diabetes, or pancreatic damage, or any dysfunction caused by the mutated gene [19].

I urge you to read more about my 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. tags: rare disease, common disease, orphan disease, orphan drugs, monogenic disease, complex disease, causality, disease causation, cause of disease, pathogenesis

Causality versus Pathogenesis

In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

One of the points discussed in the book is disease causation, and how we often fool ourselves into thinking that we understand how a disease develops, simply because we can name the gene or agent that precipitates the disease.

Here is an excerpt from Chapter 8 [Note: Pathogenesis is the sequence of cellular events that eventually leads to the clinical expression of a disease]:

In the field of medicine, we often cannot assign a specific cause to a particular disease without seriously misleading ourselves. For example, what is the cause of rheumatic fever? Rheumatic fever is an autoimmune process that targets the heart. Rheumatic fever occurs in people who have been infected with a Group A strain of Streptococcus pyogenes. The infection, which usually presents as a pharyngitis, elicits an immune response against a bacterial antigen. The antibody species that target the bacterial antigen happen to cross-react with proteins in normal heart and vessels. These cross-reacting antibodies damage the heart and vessels to produce rheumatic fever.

Rheumatic fever is one of the most thoroughly studied and best understood diseases known to man. Knowing all that we know about the pathogenesis, pathology, and clinical features of rheumatic fever, it should be easy to specify the cause of the disease. Alas, this is not the case. For example, we cannot assert that rheumatic fever is caused by Streptococcus pyogenes because not all cases of infection lead to rheumatic fever, and because the clinical features of the disease are not actually caused by the infection. Likewise, we cannot assert that rheumatic fever is an autoimmune disease because it does not result from a defect in the autoimmune response. Basically, rheumatic fever involves a normal immune response to a foreign antigen (i.e., a protein of Streptococcus pyogenes bacteria) that happens to cross-react with the heart proteins. Furthermore, we cannot claim that rheumatic fever is caused by a heart defect; the heart is an innocent bystander in a process that evolved over time in tissues other than the heart (i.e., the pharynx and other tissues in which immunocytes reside). The more we know about the pathogenesis of rheumatic fever, the more difficult it becomes to specify its cause.

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. tags: rare disease, common disease, orphan disease, orphan drugs, rheumatic fever, rheumatic heart disease, heart disease, immune disease, strep infection, causality, disease causation, cause of disease, pathogenesis