The Pathologist in Research
 Chief Pathologist Dr.
Elizabeth Unger, CDC, reviews a microarray image of gene expression data
with postdoctoral fellow
Martin Steinau, Ph.D.
The pathologist-investigator seeks new
understanding of the basic nature of disease as a first step toward devising
better ways to identify, control and prevent it. In many cases, the normal
must be understood in order to define the abnormal. Pathologists have a
unique advantage in biomedical research because of their close ties to
clinical medicine, their familiarity with laboratory technology, and their
recognition of and insight into the significance of diseased tissue changes.
Pathologists engaged in research use the sophisticated technologies of
modern molecular biology, biochemistry, immunology, cell biology and tissue
pathology. These tools and methods include cell culture, biochemical
analysis, electron microscopy, immunological and molecular genetic
techniques, computer modeling, and use of animal models. Understanding at
the molecular level is particularly critical in defining normal biological
mechanisms, so that the defects that lead to disease can be recognized.
Pathologists are uniquely prepared to investigate the causes and mechanisms
of disease because of their experience in recognition of disease
manifestations. Some examples of the range of problems under study have
included tracing a newly recognized disease to its origin, or improving
diagnostic approaches to well-known diseases, or identifying the genetic
basis for response (or failure of response) to treatment.
Pathologists figured prominently in recognition of pulmonary disease among
smokers, miners, asbestos and textile workers; of liver cancer from
prolonged contact with vinyl chloride and aflatoxin; of nerve disorders and
sterility from exposure to certain pesticides and toxic wastes.
The pathologist plays a key role in improving diagnoses through identifying
new pathogenic bacteria, discovery of new infectious agents such as Hanta
virus, and better application of modern methods of diagnosis; some recent
examples include the unraveling of the role of retroviruses in AIDS, the
application of DNA hybridization for rapid and precise identification of
atypical forms of mycobacteria that cause infections closely related to
tuberculosis, and the identification of the virus that causes SARS.
Pathologists have recognized new diseases produced by medications used to
treat various illnesses.
They have identified genes that are amplified in certain kinds of cancer and
devised methods to test for gene amplification. Using such methods, it has
been demonstrated that amplification of an oncogene in the childhood tumor,
neuroblastoma, is an indicator of poor prognosis. Other amplified genes seem
to confer drug resistance.
Other important pathology research led to the recognition that smoking and
obesity are associated with the early onset of atherosclerosis in young
Americans as well as the relationship between elevated levels of
homocysteine and heart disease.
Pathologists who used their
understanding of pathologic processes to make significant contributions to
medicine have garnered Nobel Prizes. For example, Nobel Laureate
pathologists in the US have included Karl Landsteiner, (1930) the discoverer
of the A, B, O blood groups, George Whipple, (1934) who, with Minot and
Murphy, recognized that liver contained a substance necessary to prevent
pernicious anemia, Thomas Weller, (1954) who developed methods for the
growth of polio virus in tissue culture, Peyton Rous, (1966) the discoverer
of tumor-inducing viruses, Baruj Benacerraf, (1980) who identified
genetically determined structures on the cell surface that regulate
immunological reactions, and J. Robin Warren, (2005) who with Barry J.
Marshall, recognized that gastritis and gastric cancer are caused by
infections with Helicobacter pylori. |
