Andreas Radbruch: keeping order amidst chaos of the immune system

<ic:message key='Bild vergrößern' />

Andreas Radbruch, as the Scientific Director of the German Rheumatism Research Centre (DRFZ) in Berlin, is taking care of the stepchild rheumatology. Source: DRFZ

02.02.2007  - 

Andreas Radbruch shares the dream of many immunologists: The Scientific Director of the German Rheumatism Research Centre (DRFZ) in Berlin is hoping to help sufferers of immune-related diseases with therapies which not only treat the symptoms, but actually get to the root of the problem and promise a cure. So far, in view of the complex interaction of the huge variety of cells and signal materials in the body’s immune defence system, such a cure is not yet available. Radbruch is hoping to change this and, piece-by-piece, he is bringing order to this molecular confusion. But the 54-year-old is not only busy in the realm of science: he has also acted as godfather in the establishment of two German biotech companies.

After school, Andreas Radbruch was unsure about what he would choose to study at university. Of course, biology had always fascinated him, but he was hesitant –concentrating exclusively on the plant and animal world did not seem exciting enough, and studying medicine was not in his nature. To make the decision more difficult, he was also fascinated by archaeology. Ultimately, he opted for biology in what was a pragmatic decision: The future prospects seemed much more promising.

Unravelling a mystery in the immune system with the help of molecular genetics

Once at university, it became clear to Radbruch where his priorities lay. He wanted to know what was going on behind the outer appearances of an organism and in doing so he discovered the world of genetics. The young student had luck: During his studies, Radbruch ended up at the renowned Institute of Genetics at the University of Cologne and, in professor Klaus Rajewsky, he found a Mentor who could open up the world of immunology for the eager student. "At that time, the complexity of the immune system was still completely mysterious - only after the breakthroughs made in molecular genetics did we have the tools we needed to unravel these mysteries ", remembers Radbruch. Rajewsky immediately inspired the young biologist who, in the meantime, has also become an expert in the field. In the past decades, Radbruch has substantially contributed to a better understanding of the molecular processes behind the human immune system and has shed light on the interaction of defence cells, which identify and tackle intruders in the body such as bacteria or viruses. Here, his foremost interest was in two particular families of defence cells in the white blood cell group - the so-called t-cells and b-cells.

Why does the equilibrium of the immune system go off course?

As a basic researcher, Radbruch has investigated the role that both of these families play in the immune system - on a molecular level and in every detail. For example, how certain signal molecules from t-cells enable b-cells to produce protein materials (the antibodies), which then go on to attach themselves to harmful intruders. And how these markings again attract an arsenal of secondary workers from the immune system, which attack and kill the exciter. When Radbruch describes these processes, you can see that he’s still fascinated: "The body can adjust to every kind of pathogen and is able to produce millions of different antibodies." The scientist has long been interested in shedding light on the genetic background to this variety and in finding out why this equilibrium sometimes goes out of kilter. "In former times, immunologists focused on either b-cells or about t-cells. Today, we know that both function via a complex interaction and the production of antibodies by b-cells is simply not conceivable without the regulating effects of t-cells", explains Radbruch. At the same time, he is also greatly interested in the so-called memory cells: These develop from b-cells and t-cells and are the basis for what experts call immunological memory - the immune system’s ability to recognise past intruders and to tackle them with the appropriate weapons.

Illuminating the role of immunological memory

Above all, the native of Lower Saxony wants to find out why the immune system sometimes allows itself to be misled, releasing ‘auto antibodies’ that attack the body and cause chronic inflammations - for example in sufferers of chronic diseases such as rheumatoid arthritis. For some time now, Immunologists such as Radbruch have been shedding light on how these complex autoimmune reactions actually proceed on molecular level. For example, challenging the long-held dogma that autoantibody-producing b-cells are extremely short-lived, Radbruch, together with colleagues, proved that such plasma cells, in the right conditions, can survive for months or even years in the bone marrow and infected tissue. As the researchers demonstrated, these cells continue to produce specific antibodies intended for long-eliminated intruders, and in doing so, clearly play a substantial role in chronic immune illnesses as well as in immunological memory.

The standard medicines that are used to suppress the immune system do not have an effect on these cells and Radbruch now hopes that his realizations will lead to new treatment strategies. What's more, it is Radbruch’s opinion that treatments should concentrate by design on the immune cells themselves, and not only attack the huge number of messenger signals existing in the immune system. To date, the first successes in this area have only been achieved using a fairly radical method. In this, patients who are no longer responding to conventional treatment for particularly aggressive forms of rheumatoid diseases such as Systemic Lupus Erythematosus or multiple sclerosis have their auto-aggressive immune system almost entirely destroyed by chemotherapy or by antibodies which act against the blood cells in question. Following this, the immune system is built up once more using the patient’s own stem cells. In the majority of individuals who are given such treatment, the illness disappears completely. However, as this treatment also renders the patients temporarily unprotected against infection by pathogens, it is only really suitable for the seriously ill.

Vision: targeted treatment eliminates only disease provoking cells

Radbruch is therefore pursuing a vision of a ‘cell treatment’ that only eliminates the disease provoking cells and leaves the rest of the immune system untouched. In doing so, the scientist has set his sights high: Illnesses that are a result of misdirected reactions of the immune system should not only have their symptoms treated, but should actually be treated at the root of the problem, thereby providing a cure. In the mid 90’s and with this aim as motivation, Radbruch left his research establishment after twenty years in Cologne and moved to Berlin to become Scientific Director of the German Rheumatism Research Centre (DRFZ). "I am not one of those people who are constantly looking for a new job. I want to move things forward and persistently work towards developing something important”, says the 54-year-old. For Radbruch, 1996 was the beginning of a completely new chapter: today he is the coordinator of 120 rheumatism researchers with a broad background of disciplines. All are working under a single roof and all have a common aim. "Rheumatology is often considered to be something of a stepchild and basic research is not considered interesting enough to be commercial relevant for the pharma industry. But this is exactly why we want to do it here", he says.

In 2006 Radbruch took a big step forward: The DRFZ was admitted to the Leibniz Scientific Society. This was an acknowledgment of the research centre as an efficient scientific institute, bringing with it no small measure of financial security. Today, the DRFZ is able to profit above all through the close proximity to other research and clinical institutes such as the Charité, the Max Planck Institute for Infection Biology or the Technical University of Berlin. On top of this, the DRFZ has established itself as an important member of the Germany-wide national ‘Rheumatology Competence Network’. "Ten years ago, there wasn’t a single special immunological research network funded by the German Research Foundation in Berlin. Today, there are three, and two more are in preparation. Now that’s a development!” says Radbruch.

Acting as godfather of two biotech start-ups

Radbruch has not only given his body and soul to research, but his working group has also acted as incubator for profit-generating ideas and in such a way has advanced methodological developments above all. For example, at the end of the 80's, one of his graduates developed a method of separating cells using anti-bodies attached to magnetised particles. This led to the establishment of Miltenyi Biotech GmbH in 1989. "Before this method was developed, getting the same results took an eternity. The new procedure emerged in large part from our impatience", remembers Radbruch. In the meantime, this technique is part of the standard repertoire of most laboratories and the company, with more than 800 employees, is one of the largest biotech companies in Germany. In 1998, Radbruch acted as godfather for yet another start-up: This time during the founding of amaxa GmbH by two of his doctorands who had specialised in the development of gene transfer technologies. And would he ever choose to set up a company himself? Radbruch shakes his head. He sees himself as anchored in science and wants to create momentum from the side of research, as well as in a commercial direction. This is how he thinks purpose will be best fulfilled. "To successfully found a company and bring it to the market, you've got to give it your absolute dedication and live for the company alone. It doesn't leave much time for anything else."