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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, 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 include Alexis Carrel, (1912) who pioneered vascular suturing techniques , 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, Edward C. Kendall, (1950) who, with Reichstein and Hench, studied the hormones of the adrenal cortex, their structure and biological effects which helped develop cortisone as a therapeutic agent, 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, Peter C. Doherty and Rolf M. Zinkernagel, (1996), who discovered cell mediated immune defense, J. Robin Warren, (2005) who with Barry J. Marshall, recognized that gastritis and gastric cancer are caused by infections with Helicobacter pylori, and Harald zur Hausen (2008) for his discovery that human papilloma viruses cause cervical cancer.