Cell Biochemistry Martinsried



Cytometry, a Biomedical Key Discipline

G.Valet


Discipline versus Methodological Science

Cytometry appears to many as a methodology or tool science similarly as e.g. HPLC, electrophoresis, PCR, ultracentrifugation or microscopy. High scientific efforts during the development phase followed by industry mediated dissemination and comparatively low scientific activities for improvement during the utilization phase are characteristic for such sciences. While this life cycle is typical for many tool sciences, obvious exceptions do exist when tool sciences transit into discipline sciences.

Microscopy is a wellknown example. Microscopes are used as tools e.g. for the magnification of microfilms or during product control while the appropriate staining of particular micromorphological structures as well as the interpretation of histo- and cytopathological slides requires the knowledge of an entire scientific discipline (Histo- & cytopathology). The development of laser microscopes with specific molecular stains has recently opened new disciplinary fields to biochemical morphology and cellular research in general.

Biomedical Key Discipline (Cellular Medicine)

It is frequently assumed that better knowledge on biomolecules and their function will be the most decisive precondition for the understanding of the complexity of multi-population cellular systems. Nevertheless, the problem remains that even very exhaustive knowledge on the chemical composition, structure and function of biomolecules will not explain the architecture and functionality of entire cells or cellular systems i.e. molecular knowledge constitutes a necessary but not sufficient requirement for understand the complex reactivity of cellular systems in disease.

Cytometry, in contrast, permits to determine biochemical features of living, diseased or healthy cells close to their in-vivo condition. By this feature it is possible to access predictive medicine which provides information on disease development in individual patients. This constitutes an important extension of current statistical disease prognosis evaluation in medicine which is, in general, insufficient for disease course prediction in individual patients or for the development of individualized therapy schemes.

Simultaneous multiparameter measurement of biochemical parameters in single cells of heterogeneous cellular systems represents therefore a potentiator for biochemical information collection, unparalleled by other methodologies. The inherent principle of representative statistical sampling close to the action of disease processes, the use of multiparametric molecular stains, permits new biochemical system approaches for the characterization of complex organ and tissue architectures.

The predictive aspects for medicine as well as the instrumental, cell staining and multidimensional result interpretation knowledge constitute jointly the features which will advance cytometry from a tool science to a key discipline in biomedicine. Altogether predictive medicine by cytometry represents evidence based medicine (EBM) at the cellular level.

System Cytometry (Cytomics), a New Research Strategy

Homogeneous, synchronized model cell systems are used in traditional biochemistry to overcome the interpretation problem of results from cellular assays which average over many thousands or millions of cells in different functional states. Model syztems are useful for the investigation of fundamental cellular functions like signalling cascades, cell cycle regulation, antibody production, oxido/reductive balance, enzyme pathways, energy supply a.o. Model cell systems suffer, however, from severe inherent limitations when interrelations and regulations amongst various cell populations like in the hemo- or immunopoiesis are to be explored. Concerns about the representativeness of results from model cell systems e.g. for the human organism or about the possibility for introducing artifacts by cell synchronization procedures are therefore as old as the entire model cell system approach.

The cytometric one cell is one biochemical cuvette concept, overcomes these limitations by combining the advantage of microscopic single cell observation with the advantage of multiparametric quantitative biochemical analysis of intact and fully functional cells. The multiparametric system cytometry approach will therefore significantly alter e.g. the strategy of medicine oriented cell research in many instances.

One of these changes concerns the explicit investigation of in-vivo cellular heterogeneity. As much biochemical information as possible is collected in a maximum of potentially related but nevertheless different cell populations of complex cellular systems (blood, bone marrow, transplant biopsies etc). The enormous amount of information is then efficiently extracted by Standardized Multiparameter Data Pattern Classification (SMDC). This allows the biochemical analysis of unperturbed cell systems close to the in-vivo state. System cytometry is therefore centrally characterized by the explicit molecular analysis of the utmost cellular complexity instead of the traditional cellular monosystems.

Cytometry, a Partially Virtual Discipline

Cytometry has been a multidisciplinary science from its very beginning on. The common interests of biologists, hematologists, pathologists and engineers generated initially the synchronized effort of a small fraction of scientists in each of the disciplines to set out for the fast measurements of cellular parameters. The basis for a pulsing new body of intellectual and experimental knowledge was generated by this effort.

The successful industrial implementation and dissemination of instrumentation in combination with the various developments of single cell structural and functional biochemical assays has substantially enlarged but also altered the body of cytometric knowledge over the years. Advanced electronic network communication (telecytometry has added a very important new facette to this synchronized multidisciplinary effort.

The consequences of this is that the cytometric discipline in all likelihood will not be organized like other biomedical disciplines e.g. cell biology, biochemistry, internal medicine, zoology, botany etc. Cytometry consists of a rapidly evolving multisciplinary knowledge pool, represented and supported by many thousands of scientists worldwide. This knowledge pool constitutes a virtual entity with high intellectual and innovative strength. The practical realization of this scientific discipline will vary according to local needs e.g. chairs in large research institutions or in biomedical university focus centers, self standing scientific or routine laboratories in hospitals or industry as well as research groups within university departments.




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© 2024 G.Valet
1965-2006: Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany
Last Update: Feb.22,2002