Thursday, July 10, 2014

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