Cell Biochemistry Martinsried

Cytometry, a Biomedical Key Discipline


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 interpretation of histo- and cytopathological slides as well as the appropriate staining of particular micromorphological structures requires the knowledge of an entire scientific discipline. The development of laser microscopes with specific stains has recently opened new disciplinary fields to biochemical morphology and cellular research.

Biomedical Key Discipline (Cellular Medicine)

While 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 cell systems, it becomes increasingly clear that molecular knowledge constitutes a necessary but not sufficient requirement for this purpose. Cytometry, with its potential of determining biochemical cell features ex-vivo i.e. close to in-vivo conditions, constitutes a key discipline for cellular medicine as an extension of molecular medicine.

Image and flow cytometry are precisely quantifying microscopic techniques for multiparameter measurements. Simultaneous multiparameter measurement of biochemical parameters in single cells of heterogeneous cellular systems represents an enormeous potentiator for biochemical information collection which is entirely unparalleled by other existing methodologies. The inherent principle of representative statistical sampling, the use of multiparametric cell function stains with each cell as a living, individual reaction cuvette, provides entirely new biochemical system approaches to the characterization of complex organ and tissue architectures. In addition, viable cells, organelles, nuclei or chromosomes can be preparatively sorted according to complex parameter combinations for biochemical analysis or recultivation.

The instrumental, cell staining and multidimensional result interpretation knowledge, jointly constitute the main features which advance cytometry from a tool science to a key discipline science in biomedicine.

System Cytometry, 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 are averaging over many thousands or millions of cells in different functional state. Such assays are useful for the investigation of discrete cellular functions like antibody production or cell cycle mechanisms. Model cell systems suffer, however, from severe inherent limitations when interrelations amongst different cell populations are to be explored. Concerns about the representativeness of the results from model cell systems e.g. for the human organism or about the possibility for introducing artifacts by cell synchronization procedures are 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 performing specific biochemical reactions or assays of specific biomolecules in intact cells. The multiparametric system cytometry approach will therefore entirely alter e.g. the strategy of medicine oriented cell research in many instances.

One of these changes concerns the on purpose investigation of in-vivo cellular heterogeneity by the system cytometry. 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 Classification (SMDC). This allows the biochemical analysis of unperturbed complex cell systems close to the in-vivo state. The analysis of the utmost cellular complexity instead of cellular monosystems constitutes the central feature of system cytometry.

Cytometry as 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 biochemical assays has substantially enlarged but also altered the body of cytometric knowledge over the years. Advanced electronic network communication 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. Its practical realization will vary according to local needs e.g. chairs in large research institutions or biomedical university focus centers, self standing scientific or routine laboratories in academia or industry as well as research groups within university departments.

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For problems or comments, please contact:
G.Valet E-mail: valet@biochem.mpg.de , Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany, Tel: +49/89/8578-2518, -2525, Fax: +49/89/8578-2563, INTERNET address: http://www.biochem.mpg.de/valet/cytorel.html
Last update: Jun.6, 1997