The Role of the Toxicologic Pathologist in the Post-Genomic Era^#

Abstract

An era can be defined as a period in time identified by distinctive character, events, or practices. We are now in the genomic era. The pre-genomic era: There was a pre-genomic era. It started many years ago with novel and seminal animal experiments, primarily directed at studying cancer. It is marked by the development of the two-year rodent cancer bioassay and the ultimate realization that alternative approaches and short-term animal models were needed to replace this resource-intensive and time-consuming method for predicting human health risk. Many alternatives approaches and short-term animal models were proposed and tried but, to date, none have completely replaced our dependence upon the two-year rodent bioassay. However, the alternative approaches and models themselves have made tangible contributions to basic research, clinical medicine and to our understanding of cancer and they remain useful tools to address hypothesis-driven research questions. The pre-genomic era was a time when toxicologic pathologists played a major role in drug development, evaluating the cancer bioassay and the associated dose-setting toxicity studies, and exploring the utility of proposed alternative animal models. It was a time when there was shortage of qualified toxicologic pathologists. The genomic era: We are in the genomic era. It is a time when the genetic underpinnings of normal biological and pathologic processes are being discovered and documented. It is a time for sequencing entire genomes and deliberately silencing relevant segments of the mouse genome to see what each segment controls and if that silencing leads to increased susceptibility to disease. What remains to be charted in this genomic era is the complex interaction of genes, gene segments, post-translational modifications of encoded proteins, and environmental factors that affect genomic expression. In this current genomic era, the toxicologic pathologist has had to make room for a growing population of molecular biologists. In this present era newly emerging DVM and MD scientists enter the work arena with a PhD in pathology often based on some aspect of molecular biology or molecular pathology research. In molecular biology, the almost daily technological advances require one’s complete dedication to remain at the cutting edge of the science. Similarly, the practice of toxicologic pathology, like other morphological disciplines, is based largely on experience and requires dedicated daily examination of pathology material to maintain a well-trained eye capable of distilling specific information from stained tissue slides - a dedicated effort that cannot be well done as an intermezzo between other tasks. It is a rare individual that has true expertise in both molecular biology and pathology. In this genomic era, the newly emerging DVM-PhD or MD-PhD pathologist enters a marketplace without many job opportunities in contrast to the pre-genomic era. Many face an identity crisis needing to decide to become a competent pathologist or, alternatively, to become a ...

Highly Variable Genomic Landscape of Endogenous Retroviruses in the C57BL/6J Inbred Strain, Depending on Individual Mouse, Gender, Organ Type, and Organ Location

“…It is critical to clearly define and confirm the genetic constancy of animals which are employed in a wide range of experimental models for studying gene function, toxicity of candidate compounds, diseases, and others [ 34 , 35 ]. The definition and degree of the genetic constancy of research animals are tunable depending on the specific aim(s) of individual studies.…”

Looking Forward: Cutting-Edge Technologies and Skills for Pathologists in the Future

“…Toxicologic pathology and toxicologic pathologists play a major role in advancement of human and animal health. [1][2][3] The role played by a toxicologic pathologist is ever changing with the advancement of our understanding on the mechanism of diseases and rapid progress in the technologies leading to development of new tools. The role of a pathologist has changed over the years from an emphasis on routine clinical pathology end points and morphological characterization of the gross and microscopic changes in the tissues to an era where there is increasing pressure to integrate the large amount of molecular pathology data with the traditional toxicologic pathology end points.…”

“…This has been well articulated in a publication by Dr Maronpot. 1 He emphasizes the importance of organizing continuing education (CE) courses to create awareness and train the toxicologic pathologists in the new and emerging fields, as most of the training programs are currently not designed to incorporate newer technologies and tools in their curriculum. Therefore, CE courses will let toxicologic pathologists to stay current and be part of and/or leaders of the multidisciplinary teams engaged in advancing human and animal health.…”