Volume 35, Issue 5

The Human Genetic Examination Act (Genetic Diagnosis Act – GenDG) entered into force on 1 February, 2010. This act applies to genetic examinations and analyses for medical purposes, for those determining descent as well as in the insurance and employment sectors. The act regulates the duty to inform patients prior to genetic analysis and to obtain their informed consent, as well as the legal conditions of reporting the results of genetic examinations and analyses and handling of genetic data and genetic samples obtained thereby.

The Human Genetic Examination Act (Genetic Diagnosis Act – GenDG) entered into force on 1 February 2010. This act applies to genetic examinations and analyses for medical purposes, for those determining descent as well as in the insurance and employment sectors. The act regulates the duty to inform patients prior to genetic analysis and to obtain their informed consent, as well as the legal conditions of reporting the results of genetic examinations and analyses and handling of genetic data and genetic samples obtained thereby.

The German Genetic Diagnostics Act (GenDG) in its current version, effective since Feburary 2010, has far-reaching consequences for all physicians and also for many patients. After more than one year of experience working with the GenDG, much of the previously criticized wording has proved to be inadequate. From the beginning, experts critisised that besides the direct analysis of germline DNA, gene products should not be included in the scope of the act – potentially having a very broad impact on the entire in vitro diagnostics field. Problems with applying the act range from the impossibility to distinguish between genetic and non-genetic examinations to enormous bureaucratic hurdles which in some areas interfere with an efficient, state-of-the-art patient care (i.e., newborn screening, treatment with blood products). The rapid progress in technology, which is currently revolutionizing genetic diagnostics worldwide, has been set narrow boundaries by the German GenDG, while at the same time “personalized medicine” applying exactly the same technologies is being funded by government research grants. From the viewpoint of the concerned physicians and patients, there is an urgent need to amend the act itself and efficient action to take by the committee on genetic diagnostics (GEKO) which was appointed to define guidelines for the practical use of the GenDG.

The German Genetic Diagnostics Act (GenDG) in its current version, effective since February 2010, has far-reaching consequences for all physicians and also for many patients. After more than 1 year of experience working with the GenDG, much of the previous criticism has proved to be inadequate. From the beginning, experts complained that besides the direct analysis of germline DNA, gene products should not be included in the scope of the act – potentially having a very broad impact on the entire in vitro diagnostics field. Problems with applying the act range from the impossibility of distinguishing between genetic and non-genetic examinations to enormous bureaucratic hurdles, which in some areas interfere with an efficient, state-of-the-art patient care (i.e., newborn screening, treatment with blood products). The rapid progress in technology, which is currently revolutionizing genetic diagnostics worldwide, has been set with narrow boundaries by the German GenDG, while at the same time “personalised medicine”, applying exactly the same technologies, is being funded by government research grants. From the viewpoints of the concerned physicians and patients, there is an urgent need to amend the act itself, and efficient action should be taken by the committee on genetic diagnostics (GEKO), which was appointed to define guidelines for the practical use of the GenDG.

Few EU countries have passed legislations regulating medical genetic testing. In 2010, the German “Law on Genetic Testing in Humans” (GenDG) became active. It regulates laboratory diagnostic procedures in a comprehensive way to avert discrimination of citizens on the basis of genetic data. Specifically, its definition of a genetic test encompasses – next to the number and structure of chromosomes – any other class of biomolecule, i.e., sequence and concentration of nucleic acids and their modified derivatives, proteins and in the case of metabolic diseases also the intermediary or final end products of biochemical pathways. This reflects the will of the legislator to uncouple the genetic question in medical diagnostics from the biomaterial substrate needed to be analyzed. To deal with the ramifications of this broad approach in everyday clinical medicine, §23 of the GenDG establishes the installation of the German Gene Diagnostics Commission (GEKO) to issue guidelines for the laboratory and clinical diagnostician. The GEKO is an interdisciplinary committee consisting of medical professionals as well as representatives from ethics and patients interest organizations. Furthermore, the German counties and professional healthcare organizations can send delegates as invited guests to GEKO plenary and working group meetings. This paper describes the set-up and operative work of the German GEKO commissioned to support medical genetic testing in compliance with current German legislation.

The following recommendations for the differentiation of lymphatic cells in the blood film of adults have been developed by the working group for laboratory diagnostics of the German Society of Haematology and Oncology on behalf of the German and Austrian haematological societies. The nomenclature of lymphatic cells should be harmonised in Germany and Europe and should provide a practical approach on how to differentiate lymphatic cells. The basis of the new nomenclature is the upfront classification into inconspicuous or conspicuous lymphatic cells. In a second step, the conspicuous cells are further assigned to “atypical cells, suspect reactive” or “atypical cells, suspect neoplastic”. The percentages of the resulting three-way division are integrated into the differential white count. If this assignment of conspicuous cells is impossible, they are called “atypical cells, uncertain nature” in a fourth category of “diverse cells”. This category of “diverse cells” also contains cells which are only rarely or never present in the normal blood film or unclear cells. The assignment to the category “diverse” essentially requires a comment in the report describing these cells and a subsequent clarification of such findings.

Quantitative measurement of free light chains in serum has become an important parameter in the diagnostic assessment of plasma cell dyscrasias. Being part of the initial diagnostic approach as well as in monitoring and evaluation of remission, the test provides crucial contributions to disease assessment. Thus, measurement of free light chains has been included in international guidelines for the diagnosis and monitoring of plasma cell dyscrasias and has become a routine part of paraprotein detection. The recently introduced quantitative measurement of immunoglobulin heavy/light chain pairs will probably be of similar value; however, the method has yet to be validated in larger studies.

Laboratories are highly complex facilities that are characterized by interdisciplinary work. This requires that employees have a high level of competence in every single step of a process. In this article, some basic elements and methods of knowledge management are introduced. In addition, important factors of success are discussed and it is demonstrated how knowledge management, if introduced correctly, can improve business processes in a company.

Diagnostic pathways in the field of laboratory medicine could contribute economically to integrate modern „disease management“ from the perspective of healthcare policy into a complex development with limited resources. The objective is to bridge the gap between medical and economic demand. Diagnostic pathways could be an innovative way to optimize processes in medicine with the objective of transparency of costs, results and performance, especially if technical prerequisites for web-based communication (i.e., order entry, digitized laboratory analyzed findings) are given. The precondition is that laboratory diagnostics must be appreciated as a core procedure of a hospital. Furthermore, diagnostic pathways provide the opportunity to define processes concerning disease severity and rate of resource usage. The pathways support the physician by finding the probable or medically worthwhile primary and secondary diagnosis for coding the DRG (Diagnoses Related Groups). This results in guaranteeing revenues and an increase in the quality of therapy. The very visualization of medical decisions by diagnostic pathways results in the reduction of ill-conceived activities and consequently in an improvement of health economics.

Diagnostic pathways in the field of laboratory medicine could contribute economically to integrate modern “disease management” from the perspective of healthcare policy into a complex development with limited resources. The objective is to bridge the gap between medical and economic demand. Diagnostic pathways could be an innovative way to optimise processes in medicine with the objective of transparency of costs, results and performance, especially if technical prerequisites for web-based communication (i.e., order entry, digitised laboratory analysed findings) are given. The precondition is that laboratory diagnostics must be appreciated as a core procedure of a hospital. Furthermore, diagnostic pathways provide the opportunity to define processes concerning disease severity and rate of resource usage. The pathways support the physician by finding the probable or medically worthwhile primary and secondary diagnosis for coding the DRG (Diagnoses Related Groups). This results in guaranteeing revenues and an increase in the quality of therapy. The very visualisation of medical decisions by diagnostic pathways results in the reduction of ill-conceived activities and consequently in an improvement of health economics.

Laboratory medicine has two equally important fundamental roots – chemistry and medical diagnostics. Dating back to the 19 th century, the groundwork for laboratory medicine was laid by an influential chemist, Justus von Liebig. In the early 20 th century significant discoveries in the field were also made by German scientists, such as Robert Koch, Emil von Behring and Paul Ehrlich. Since this time chemistry has gained more influence in medical diagnostics enabling a better understand­ing of the pathobiochemistry of human beings. The history of the Institute for Clinical Chemistry in Mannheim began in 1909 when the physician, Franz Volhard, applied for an independent hospital laboratory. Ernst Josef Lesser, physiologist and the discoverer of insulin (called by him „Glukopausin“), was appointed the institute's first director in 1910. In 1928 his successor was the physician and pharmacologist, Walter Siegfried Loewe, who first described the analysis of estrogen. An unpleasant interim characterized the time between 1933 and 1948. In 1948, Hans Jürgen Staudinger, a very successful chemist in the field of suprarenal steroids, took over the head of the formerly famous institute. Through his scientific achievements during 11 consecutive years, he reinstalled the outstanding reputation of the Mannheim laboratory. He was succeeded by the physician and chemist, Volker Klingmüller, whose credit was the future-orientated laboratory automation. Reinhard Kattermann, a highly recommended lipid scientist, followed in 1975 but died unexpectedly in 1996. The gap was temporarily filled by the physician and chemist, Hermann Wisser, who headed the institute for the next 4 years. It is to his credit that an academic chair was installed in Mannheim and in 2002 the physician, Michael Neumaier, was appointed as full professor. Since then the main emphasis on molecular diagnostics and genome analytics have expanded the wide field of laboratory medicine in Mannheim.

In May 2011, the Molecular Diagnostics Section of the German Society of Clinical Chemistry and Laboratory Medicine comprising the working groups Genomics, Proteomics, Bioinformatics and Biobanking held its 10th anniversary meeting in the Protestant Academy in Tutzing near Munich. During these 10 years, this meeting has developed into an important forum for scientific discussion in the German-speaking world. Up to a few years ago, the main challenges in molecular diagnostics were of a technical nature. With the increasing use of these methods in routine diagnostics, clinical issues are now becoming more important. Several of these were discussed this year in Tutzing, with particular emphasis on cancer diagnostics. Is it possible, for example, to define molecular cancer diagnostics? Which molecular signatures are useful in this regard? What is the importance of newer biomarkers such as microRNA? What bioinformatic methods must we use to identify novel candidate genes? How can we exploit these to develop new biomarkers? How should samples for these studies be stored in biobanks? At present, definitive answers to these questions do not exist, but we hope this report will at least help the reader to assess the current state of the scientific debate in these fields.