Uwe Marx (born 26 June 1964) is a German physician and biotechnologist, and one of the world’s leading researchers in the fields of organ-on-a-chip technology and antibody production.
Academic Education He gained his qualification as a medical doctor with a specialization in biochemistry in 1988 and his MD in 1991 at Charité – Universitätsmedizin Berlin (a joint medical faculty of the Humboldt University and Free University Berlin) with his thesis on Human Monoclonal Antibodies.
Professional Academic Positions Uwe Marx was the head of the Department of Immunobiotechnology at the Institute of Medical Immunology, Charite – Universitätsmedizin Berlin between 1991 and 1995. He was the head of the Department of Medical Biotechnology at the Institute of Immunology and Transfusion Medicine, University of Leipzig between 1995 and 2000. He was the head of the GO-Bio Multi-Organ Chip Program “Multi-organ-bioreactors for the predictive substance testing in chip format,” which was supported by the German Federal Ministry of Education and Research (BMBF), at the Institute of Biotechnology, Technische Universität Berlin between 2010 and 2019. This led to the establishment of a multi-organ chip technology capable of maintaining more than 15 miniature human organ equivalents, such as liver, brain, skin, intestine and pancreatic islets, at a homeostatic steady state over periods of at least four weeks. Uwe Marx was appointed an Honorary Professor of Medical Biotechnology at the Technische Universität Berlin in 2022.
Career Uwe Marx is a world-renowned German physician and biotechnologist, specializing in the fields of organ-on-a-chip technology and antibody production. He is a physician, biotechnologist, successful serial entrepreneur, author, and inventor of as many as 30 patent families, which have led to more than 140 patents granted. He has published more than 130 peer-reviewed scientific papers. He is the co-founder of the German biotech companies: VITA 34 A.G., ProBioGen A.G. and TissUse GmbH.He has extensive experience in human biology and medicine, and is currently one of the world’s leading researchers in the field of microphysiological systems (MPS) technology, pioneering the field of human multi-organ chips. He was an early innovator in employing relevant non-animal models to develop more predictive human data with a vision to define human risk better and make safe drugs available to the patients faster. When he began his career in the early 1990s, rodents and higher species were used, to a large extent, to test the effects of pharmaceutical products, cosmetic compounds and other chemicals. He quickly recognized that the results of animal testing may not guarantee the same responses in humans. Improving the relevance to humans and potentially replacing animal testing with a more accurate and controllable approach was an urgent need. In 1989, while studying for his MD, he planned to recreate human immune organsU. Marx, W. Merz, S. Koch, A. Nagel, M. Schläfke, P.M. Schlag, W. Liebrich, L. Lübbe, R. von Baehr. (1994). Cultivation of hybridomas, human cancer and human primary cells using the miniaturized hollow fibre bioreactor TECNOMOUSE®. In: T. Kobayashi, Y. Kitagawa, K. Okumura (eds.), Animal Cell Technology: Basic & Applied Aspects. The Sixth International Meeting of the Japanese Association for Animal Cell Technology JAACT’93, vol. 6. Springer, Dordrecht, 171–175. and mimic organ functions and interactions outside a living organism.
One of his first research projects in 1991 involved the “in vitro production of monoclonal antibodies (mAbs)” to replace the standard method to “culture […] hybridoma cells producing monoclonal antibodies in the ascites mouse.” He and his team developed a hollow-fiber culture system for culturing hybridoma cells, which produce mAbs.U. Marx, H. Tanzmann, V. Jaeger, S.T. Kiessig, R. von Baehr. (1992). Simultaneous cultivation of two hybridoma cell lines in a hollow fiber bioreactor. Animal Cell Technology 534–537. . He was, therefore, able to show that an in vivo method could replace the highly criticized ascites mouse method by applying advanced biotechnology to cell culture.U. Marx, M.J. Embleton, R. Fischer, F.P. Gruber, U. Hansson, J. Heuer, W.A. de Leeuw, T. Logtenberg, W. Mert, D. Portetelle, J.-L. Romette, D.W. Straughan. (1997). Monclonal antibody production. The report and recommendations of ECVAM Workshop 23. Alternatives to Laboratory Animals 25: 121–137. DOI: 10.1177/026119299702500205. In 1994, Uwe Marx was one of the founders of ProBioGen AG, in Berlin. He joined the company as Chief Scientific Officer in 2000. Within this biotech company, he developed, among other products, a Human Artificial Lymph Node (HuALN) modelC. Giese, A. Lubitz, C.D. Demmler, J. Reuschel, K. Bergner, U. Marx. (2010). Immunological substance testing on human lymphatic micro-organoids in vitro. Journal of Biotechnology 148(1): 38–45. DOI: 10.1016/j.jbiotec.2010.03.001 which enables the prediction of human immune responses triggered by drug candidates in vitro. Using primary cells, this three-dimensional matrix bioreactor technology emulates in vivo-like reactions of a human lymph node to analyze, for example, immunogenicity, immune functions and the immunotoxicity of substances. He was the CSO of ProBioGen AG until 2010. In 1997, Uwe Marx was one of the founders of VITA 34 AG, in Leipzig, where he established the GMP-compliant cryopreservation process for the umbilical cord blood samples. Between 1999 and 2003, he was one of the founders and a supervisory board member of Novoplant AG, in Gatersleben, which ceased trading in 2008. In 2007, while still at ProBioGen AG, Uwe Marx published his vision of the multi-organ-chip (MOC) concept for the first time in his book “Drug Testing In Vitro – Breakthroughs and Trends in Cell Culture Technology”.Marx, U. and Sandig, V., John Wiley & Sons/VCH Weinheim, 2007. He describes the concept of the “micro-organoids” on which the perfused human MOC is based, in Chapter 11 (p. 318), “How drug development of the 21st century could benefit from human micro-organoid in vitro technologies,” as follows:
Organs are built up by multiple, identical, functionally self-reliant structural micro-organoid units. Micro-organoids are evolutionarily conserved and subject to genetically encoded self-assembly.
In order to overcome the limited predictive power of preclinical testing in animal models, which has been the main dilemma of drug development, Uwe Marx proposed developing the perfused MOC using human cells, tissues and organoids. He is internationally recognized as one of the inventors of the perfused MOC technology.F. Sonntag, N. Schilling, K. Mader, M. Gruchow, U. Klotzbach, G. Lindner, R. Horland, I. Wagner, R. Lauster, S. Howitz, S. Hoffmann, U. Marx. (2010). Design and prototyping of a chip-based multi-micro-organoid culture system for substance testing, predictive to human (substance) exposure. Journal of Biotechnology 148(1): 70–75. DOI: 10.1016/j.jbiotec.2010.02.001 Since 2009, Uwe Marx has been working together with other scientists to reproduce the human organism on a microfluidic chip at a scale of 1:100,000.U. Marx, H. Walles, S. Hoffmann, G. Lindner, R. Horland, F. Sonntag, U. Klotzbach, D. Sakharov, A. Tonevitsky, R. Lauster. (2012). ‘Human-on-a-chip’ developments: a translational cutting-edge alternative to systemic safety assessment and efficiency evaluation of substance in laboratory animal and man? Alternatives to Laboratory Animals 40(5): 235–257. DOI: 10.1177/026119291204000504 The aim is to shorten the entire drug development process and reduce animal experiments and drug testing in humans during clinical trials.
In 2010, Uwe Marx founded TissUse GmbH, the first MOC company worldwide, as a spin-off biotech company of the Department of Medical Biotechnology of the Technische Universität Berlin (chair: Prof. Roland Lauster), which has been at the forefront of “pioneering human-on-a-chip developments.” He was CEO of the company from 2010 until 2020, when he became CSO. In 2013, TissUse GmbH published the proof of concept of the perfused human two-tissue MOC, “A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture.”I. Wagner, E.-M. Materne, S. Brincker, U. Süssbier, C. Frädrich, M. Busek, F. Sonntag, D.A. Sakharov, E.V. Truchkin, A.G. Tonevitsky, R. Lauster. (2013). A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. Lab on a Chip. 13(18): 3538–3547. DOI: 10.1039/c3lc50234a. The final aim is to combine different “organoids” to generate a human-on-a-chip, which allows studies of complex physiological organs interactions. The inclusion of human organ equivalents for liver, intestine, kidney and skin for ADME and toxicity (ADMET) testing was developed in a four-organ chip. The system is being developed for disease models for preclinical efficacy and toxicity testing of new drugs. An example is the human microfluidic two-organ chip model which maintained a functional circulation between pancreatic islet micro-tissues and liver spheroids in an insulin-free medium;S. Bauer, C. Wennberg Huldt, K.P. Kanebratt, I. Durieux, D. Gunne, S. Andersson, L. Ewart, W.G. Haynes, I. Maschmeyer, A. Winter, C. Ämmälä, U. Marx, T.B. Andersson. (2017). Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model. Scientific Reports 7(1): 14620. DOI: 10.1038/s41598-017-14815-w. this is a promising simulation of human type 2 diabetes mellitus. Uwe Marx’s team at TissUse GmbH has also succeeded in generating different human organoids for induced pluripotent stem cells (hiPSC) lines from donors, which were generated by reprogramming peripheral blood mononuclear cells with episomal vectors.A.P. Ramme, L. Koenig, T. Hasenberg, C. Schwenk, C. Magauer, D. Faust, A.K. Lorenz, A.-C. Krebs, C. Drewell, K. Schirrmann, A. Vladetic, G.-C. Lin, S. Pabinger W. Neuhaus, F. Bois, R. Lauster, U. Marx, E.-M. Dehne. Autologous induced pluripotent stem cell-derived four-organ-chip. Future Science OA 5(8): FSO413. This technology allows one to study drug effects in MOCs on individuals with different genetic backgrounds, for example, human disease models. Meanwhile, Tissue has developed a wide range of fit-for-purpose MOCS for the drug industry and four of these assays are used for internal portfolio decision-making in drug development: the bone marrow model and three of the two-organ models – the liver-pancreas, the liver-thyroid and the skin-tumor model. These four commercial assays have entered industrial decision-making at six sites of international drug companies, such as AstraZeneca, Roche and Bayer.