Ethics Council consults experts on the future of genetic diagnosis

There has been significant progress in molecular genetics research in recent years, and as a result genetic analyses have increasingly become an integral part of clinical practice. Experts from the fields of scientific and technological development and practical application informed the Ethics Council on the latest developments.

The first speaker was Karl J. Lackner, Director of the Institute of Clinical Chemistry and Laboratory Medicine of Mainz University, who introduced the high-throughput procedures of molecular diagnostics (rapid, automated procedures to analyse a large number of samples) and the development of sequencing technology in the last thirty years. He reported that the efficiency of such procedures is constantly rising, while at the same time the sequencing costs are constantly falling. At present, the limits of these procedures lie predominantly in the margin of error and the amount and interpretation of the data produced.

Bernd Timmermann, Head of the Sequencing Core Facility at the Max Planck Institute for Molecular Genetics in Berlin, gave information on technical details of several approaches in next generation sequencing and their application. Projects based on these procedures, such as 1000 Genomes or Onco-Track, have the objective of identifying variations in the genome and biomarkers for illnesses and of collecting data for later simulations of cell physiology. The crucial factor for the quality of sequencing, he said, is the depth of sequencing. However, it is a problem that even on repeated analysis a large number of false positives may be found.

Representing the pharmaceutical research company Qiagen GmbH, Tobias Ruckes, Senior Director, Head of Marketing Molecular Diagnostics EMEA in Hamburg, presented current developments in personalized medicine as part of biomarker diagnosis to select the suitable therapy. He reported that in some cases this diagnosis is already in use. In order to optimize this procedure, it is necessary to obtain further information on the interaction of various biomarkers in order that the present detection of individual markers can be replaced by multiple testing.

Linking to this, Christian Meisel, Head of Oncology and Translational Medicine for Roche Pharma Research and Early Development in Penzberg, emphasized that pharmaceutical research is becoming increasingly complex, since detecting biomarkers and – building on this – the development of valid diagnostic tests is a lengthy and difficult process.

Karsten R. Held, Medical Director of the Centre for Human Genetics in Hamburg, reported that the application of genetic diagnosis is only acceptable on the principle of “advice – diagnosis – advice”. For with the increasing technical sensitivity of the tests, the probability of misdiagnosis and the creation of data that are difficult to interpret increases. According to Professor Held, the interpretation of a genetic finding can only be made in conjunction with the clinical examination. In future, the increase of knowledge of epigenetic processes will be decisive for the interpretability of data and thus for genetic diagnosis.

Carsten Bergmann, Head of the Centre for Human Genetics of Bioscientia in Ingelheim, chose the example of cilia diseases to show that there may be several causes for the same disease, with transitions that may be overlapping or fluid. This means that there is often no convincing correlation between the genetic findings and the manifestation of the disease, which makes it difficult to make a definite diagnosis in clinical practice.

Wera Hofmann, Medical Director of LifeCodexx AG in Konstanz, addressed the current development of a procedure for non-invasive molecular-genetic prenatal diagnosis (PD). Based on the examination of cell-free foetal DNA from maternal blood, this procedure has already been successfully tested for the early diagnosis of trisomy 13, 18 and 21. Dr. Hofmann pointed out that the primary value of the test is to supplement prenatal diagnosis in risk pregnancies and to reduce the stress of invasive procedures on pregnant women. Dr. Hofmann did not exclude the possibility that further applications for this procedure may be found in future.

Anja Victor, a biometrician at Merck KGaA in Darmstadt, spoke on the statistical analysis and problems in genetic association studies and multiple test procedures. Because the data are often presented selectively, the clinical significance of statistical results is usually overrated, and therefore a validation and replication of the results is essential.

In the two panel discussions, the members of the Ethics Council were particularly interested in questions of quality assurance, susceptibility of the data to errors and the costs of the procedures. They also questioned the manner of dealing with surplus data and the handling of the duty of information and the provision of advice.

Audio recordings of the contributions to the hearing may be accessed here.