Pioneering method for stem cell diagnosis:

Frankfurt. Our blood is constantly renewing itself. Every second, millions of new cells are added to the bloodstream to replace dying blood cells. They arise from hematopoietic (blood-forming) stem cells in the bone marrow and then gradually mature in several stages. A distinction is traditionally made between four main growth pathways: the first pathway produces red blood cells that transport oxygen, and the second supplies platelets, or platelets, that stop bleeding and allow wounds to heal. In the third pathway, white blood cells develop, giving us our innate immune defense, like granulocytes, for example, and in the fourth pathway, B and T cells develop, which form the basis of our acquired immune defense in the event of infection. However, as research progressed, distinguishing between these pathways became more and more difficult.

Hematopoietic stem cells were discovered in 1961. This discovery enabled the introduction of bone marrow transplants in the 1970s to treat certain types of leukemia. Observing the behavior of transplanted cells in the recipient organism has led to several new insights into hematopoiesis. However, the fact that these insights were obtained under artificial conditions limited their informational value. After all, previously transplanted stem cells were taken from their natural context. But with the help of genetic markers, it has been possible since the 1980s to study the development of blood cells in their natural context. This method, called lineage tracing, was applied more accurately over the following decades—but only in animal experiments because, as it turns out, introducing artificial genetic markers into humans is out of the question.

In human blood, lineage can only be traced by observing normal DNA mutations that occur after cell division in one daughter cell but not in the other, and thus spread only in specific cell families (clones). In 2010, researchers attempted to track such mutations throughout the genome of blood cells. However, given the over three billion ‘letters’ (base pairs) in our genome and despite state-of-the-art methods, this is extremely expensive and error-prone. For this reason, Leif Ludwig focused on proving natural mutations in the mitochondria of blood cells. These cellular powerhouses have their own much smaller genome of about 16,600 base pairs. Leif Ludwig combined their analysis with the latest single-cell sequencing technology (single-cell omics), enabling him to make statements about the actual health status of the cells under examination at the same time. In the meantime, he and his team have improved their method in such a way that they can analyze tens of thousands of cells in bone marrow and blood samples from a patient.

It has long been assumed that hematopoietic stem cells are not a uniform source but form a heterogeneous population, from which different developmental pathways develop and branch in many directions during the ongoing formation of new blood. For example, one stem cell may produce only platelets, or platelets, and another from all types of blood cells. So the relationships in our blood are very blurred. Leif Ludwig’s analytical method now makes it possible to separate them more easily in order to determine, for example, at what point a leukemia cell develops or a degenerative change occurs. It opens the way for human medicine to conduct such studies in the future for the first time in daily clinical practice and derive therapeutic interventions from them.

From 2003 onwards, Dr. Leif C. Hoon-Ludwig studied Biochemistry at the Free University of Berlin, and then Human Medicine at the Charité-Universität Berlin. As a PhD candidate in biochemistry, he did research at the Whitehead Institute for Biomedical Research from 2011 to 2015 and a postdoctoral researcher at the Broad Institute at MIT and Harvard University from 2016 to 2020, both in Cambridge/USA. He has chaired the Emmy Noether Small Research Group at the Berlin Institute of Health in Charite and the Berlin Institute for Medical Systems Biology (Max Delbrück-Center) since November 2020.

The prize will be awarded – together with the main prize for 2023 – by the Chairman of the Scientific Council of the Paul Ehrlich Foundation on 14 March 2023 at 5.00 pm at the Paulskirche in Frankfurt.

Pictures of the prize winner and detailed background information – “What Mitochondria Tell Us” – can be downloaded from: www.paul-ehrlich-stiftung.de

the Paul Ehrlich and Ludwig Darmstedter Early Career Prize, First awarded in 2006, it is presented once a year by the Paul Ehrlich Foundation to a young scientist working in Germany for outstanding achievements in the field of biomedical research. The prize money of €60,000 must be used for research-related purposes. University professors and senior scientists at German research institutions are eligible to nominate candidates. Award winners are selected by the Foundation Board on the recommendation of an eight-member selection committee.

the Paul Ehrlich Foundation It is a legally affiliated institution that is faithfully run by the Society of Friends and Donors of Goethe-University. The honorary president of the Foundation, which was founded by Hedwig Ehrlich in 1929, is Prof. Dr. Katja Becker, President of the German Research Foundation, who also appoints the elected members of the Foundation Council and Board of Trustees. The Chairman of the Scientific Board of the Paul Ehrlich Foundation is Prof. Dr. Thomas Boehm, Director of the Max Planck Institute for Immunology and Epigenetics in Freiburg, and the Chair of the Board of Trustees is Prof. Dr. Jochen Maas, Director General for Research and Development, Sanofi-Aventis Deutschland GmbH. As President of the Association of Friends and Donors of Goethe University, Prof. Dr. Wilhelm Bender is also a member of the Scientific Council of the Paul Ehrlich Foundation. The Rector of Goethe University is also a member of the Board of Trustees in this capacity.

Goethe University It is a research-oriented university in the European financial center Frankfurt am Main. Founded in 1914 with private funding, primarily from Jewish sponsors, the university has since made pioneering achievements in the fields of social sciences, sociology, economics, medicine, quantum physics, brain research, and business law. It gained a unique level of autonomy on January 1, 2008 by returning to its historical roots as a “foundation university”. Today, it is one of the three largest universities in Germany. Together with the Technical University of Darmstadt and the University of Mainz, it is a partner of the University of Rhine-Main strategic interstate alliance. Internet: www.uni-frankfurt.de