The Doctor at the MDC

What do short fingers and high blood pressure in common? And how bad is salt really for our health? Fred Luft is more than a researcher, he is a physician as well. Now, he celebrated his 75th birthday.

The early spring sun provides little warmth. We stand on the long balconies imagining bygone days when patients enjoyed time here underneath colorful marquees. For just a moment, they savored the time away from the hospital environment. "The laboratories behind us used to be four-bed rooms,” Friedrich Luft points out. The former nurses station now serves as my office and right in front, in the wing with the mural relief from DDR times, used to be the ORs."

The presence of medical history still lingers in the buildings now housing the Experimental and Clinical Research Centers (ECRC). From the very beginning, basic research and patient care linked up tightly in this place. Very early, way back in the 1920, the neuroscientists Oskar and Cécile Vogt established the hospital right next to their laboratory building. "These scientists had a visionary concept, which gathered inspiration from bedside to bench and from bench to bedside,“ emphasizes Friedrich Luft. In his opinion, it is the only way to do molecular medicine. This never changes.

Even though the hospital wings are long since closed, twelve outpatient clinics of the large teaching hospital Charité are still present. Many patients come to participate in trials. "Among other equipment, we have an indirect calorimetry chamber. It is the only one of its kind in Germany. Another chamber allows us to simulate the oxygen conditions at high altitude," Friedrich Luft tells us. Pride swings in his voice. "Being a physician was my great passion," the 75-year old reminisces. He feels that "there is nothing better than finding out why people get sick".

Friedrich Luft turned into the American Fred Luft

In 2007, Friedrich Luft was appointed head of the ECRC as interface between the Charité and the Max Delbrück Center. Room by room, he turned the former patient quarters into research space. The latest addition is a new stem cell laboratory to the ECRC facilities. Starting in May, yet another partial demolition and reconstruction will take place. Soon, the Berlin Institute of Health will move into the new space.

At his birth in Berlin on March 04, 1942, nature may have given Friedrich Luft equal amounts of extra skepticism and curiosity. After the Nazis denied his father tenure at the Charité, the Luft family left Berlin. In 1947, they moved to the USA. At the time, the need for scientists was great in the USA. For example, the father served as director of the Lovelace Respiratory Institute in Albuquerque where the first astronauts trained for their mission. Friedrich Luft grew up as Fred Luft in the USA. He studied biology in Colorado Springs and medicine in Philadelphia.

While many of his fellow graduates joined the US National Institutes of Health, Fred Luft completed his internship at the Indiana School of Medicine and specialized in internal medicine. From 1975 to 1989, he held a nephrology professorship at the Indiana School of Medicine. "What a streak of luck," wrote Detlev Ganten, the founding director of MDC,  a few years ago about the early career of his colleague. This early experience deepened his already pronounced interest in patient-oriented research, in hypertension and the consequences of salt consumption on the metabolism.

The Remarkable Fate of a Turkish Family

In this Turkish family, hypertension was transmitted with extreme values. Image: Hakan Toka

In 1984, a sabbatical in Detlev Ganten's laboratory brought Friedrich Luft to the University of Heidelberg. This sabbatical became a stepping stone for his return to his birth place Berlin. In 1992, Detlev Ganten invited Friedrich Luft to join the just established MDC. At the MDC, Friedrich Luft headed a molecular genetics group working on cardiovascular diseases. From 1993 to 2010, he was also Chief Physician for Internal Medicine and Nephrology at the Franz-Volhard Clinic.

Friedrich Luft always treasured for the extraordinary, the challenging cases. There was for example the man whose circulation worked as it should providing the man kept lying down flat. However, upon standing up, his blood pressure dropped precipitously so that the man would almost faint. He lacked a certain enzyme. Then there is the remarkable fate of a Turkish family. The family originated in a village near the Black Sea. Whenever a child was born in the village, the relatives first examined the baby's fingers. If the fingers did not grow properly and the hands remained diminutive, the relatives predicted an early death.

As early as in the 1970s, a Turkish physician named Nihat Bilginturan discovered a family with hereditary hypertension up to the extreme value of 270/160 mm Hg. However, his paper was forgotten until Thomas Wienker rediscovered it in the 1990s while he was preparing a talk at MDC. Friedrich Luft was excited immediately.

 

Different growth of fingers in one family. Image: Sylvia Bähring

"Such projects never disappear."

Usually, diseases that affect a large part of the population, are triggered by subtle interactions between many genes and the environment. Finding these genes is very hard. By contrast, in this family, a single gene anomaly caused the hypertension. The scientists around Friedrich Luft hoped that it might be easier to zoom in on this one. Little did they know that they would work with the family and project for more than twenty years. It took scientists until 2015 to find a mutated form of the enzyme PDE3A as culprit for the hypertension in the studied family. It regulates not only blood pressure, but also affects bone growth. They published their results in the scientific journal 'Nature Genetics'.

At the time, Friedrich Luft considered the gene found and the problem solved. "It's time to retire," said Friedrich Luft jokingly. "Still, such projects do no disappear." His group has modified the gene in animals and is investigating whether they would develop hypertension. Besides, the discovery brought many families with similar conditions to his attention. The group looks at their genome as well. Jointly with structural biologists at the MDC, the group now establishes the three-dimensional shape of the modified proteins. They want to find out how the modified protein interacts with other proteins. The scientists want to elucidate the disease mechanism and see whether repair is possible.

"Scientific work is often like searching for a black cat in a dark room – and not even knowing whether the cat is there," muses Friedrich Luft. Only in a long arduous process, all the unknown and initially ignored factors will make their presence known. Curiosity drives Friedrich Luft to more discoveries. What does he envision for the MDC? "I like to see the MDC do justice to its unique mission and continue its collaboration with clinicians who are ready to perform excellent basic research."


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