Cell Biochemistry Martinsried

Cytomics, a Biomedical Key Discipline


from: Purdue CD-ROM Vol.8   2004   ISBN 1-890423-C6-5

1. 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 represent tools e.g. for the magnification of microfilms or during product control while the specific staining of particular micromorphological structures or molecules in tissue sections or smears as well as the interpretation of the resulting images requires the knowledge of the entire scientific histo- & cytopathology discipline.

The development of confocal laser or laser scanning microscopes together with the use of molecule specific fluorescence stains has opened new disciplinary fields to biochemical morphology and cellular research in general with their very specific staining and interpretation knowledge.

2. Cytomics, a Biomedical Key Discipline

It is frequently assumed that the genome sequence in conjunction with better knowledge on biomolecules and their function will be the most decisive precondition for the understanding of the complexity of multi-population cellular systems. This is, however, unlikely considering the problems encountered when predicting protein 3D-structures from their amino acid sequences which involve only 27 amino acids as compared to the possible complexity of biomolecular arrangements resulting from the 20.000-30.000 gene products Molecular knowledge constitutes therefore a necessary but not sufficient condition for the understanding of the complex molecular architecture and reactivity of cellular systems in health and disease.

Cytomics as molecular cell and cell systems oriented research access a multiplicity of biochemical features within the full heterogeneity of cell systems close to their in-vivo condition with the potential for predictive medicine by cytomics providing information on the future disease development in the individual patient. The individulized view constitutes an important extension of current statistical disease prognosis evaluation in medicine (e.g. Kaplan-Meier or hierarchical clustering) which is, in general, insufficient for individualized therapy schemes. As a consequence patients are over- oder undertreated and costly double blind trials are usually necessary for therapy improvement.

The simultaneous multiparameter measurement of biochemical parameters in single cells of heterogeneous cellular systems potentiates the degree of molecular knowledge collection. Representative statistical sampling in the full heterogeneity of cellular systems (cytomes) at the very level of molecular action of disease processes will permit new molecular system approaches for the characterization of complex organ and tissue architectures.

The predictive aspects for medicine, the instrumental, the cell staining and the multidimensional result interpretation knowledge constitute jointly the features which advances cytomics (system cytometry) to a key discipline in the biomedical sciences. Altogether predictive medicine by cytomics represents evidence based medicine (EBM) at the cellular level.

3. 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 systems are useful for the investigation of fundamental cellular functions like signalling cascades, cell cycle regulation, cell death, antibody production, oxido/reductive balance, enzyme pathways, energy supply a.o. Model cell systems suffer, however, from inherent limitations. Interrelations and regulations amongst various cell populations like in the hemo- or immunopoiesis model systems may not be representative for the human situation or artifacts may be introduced e.g. by cell synchronization procedures.

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 functional cells. The multiparametric cytomics approach will therefore significantly alter e.g. the strategy of medicine oriented cell research in many instances (medical cytomics, clinical cytomics).

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) in patients. 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. Using the systemic approach from cells to patients, a relational system like a kind of periodic system of cells for the objective molecular description of normal and abnormal cells states in health and disease can be elaborated in a human cytome project.

4. Cytomics, a Partially Virtual Discipline

The cytometric science field 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 in cytometers. 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. New microscopic, chip and bead array based technologies in combination with advanced electronic network (telepathology, telecytometry) communication have added important new facettes to this multidisciplinary effort.

The consequences of this is that the cytomics discipline so far is not organized like many other biomedical disciplines. The rapidly evolving multisciplinary knowledge pool is represented and supported by many thousands of scientists worldwide working in quite different scientific areas. This entire knowledge pool constitutes a virtual entity with high intellectual and innovative strength. The practical implementation of this scientific discipline will therefore vary according to local needs e.g. departments 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 or industry departments.

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1965-2006: Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany
Last update: Apr 10,2004
First display: Feb 14,1997