Chemist Manfred Weiss manages the MX beamlines at BESSY II in Berlin-Adlershof, Germany. Here, researchers and pharmaceutical companies study the structure of crystalline molecules and discover triggers of disease – mostly in the search for new medicines.
He still clearly remembers the call that came in at 4 a.m.: Manfred Weiss was the scientist on standby in case of problems, and on the other end of line were the scientists currently experimenting at one of his beamlines. “We’re finished. Everything went well, thank you,” they informed the sleepy chemist. This was a few years ago and it still makes Weiss smile to think back to it: “It was so out of the blue.”
This scene says a lot about the job of Manfred Weiss, who is responsible for experiments in the field of macromolecular crystallography at the electron storage ring BESSY II: about the fact that his team is on call around the clock to supervise and help scientists who come from all over the world to conduct their experiments here; and about how satisfied the users are, that they feel a natural urge to say thank you, even in the middle of the night.
Discovering why protein molecules in the human body “go crazy”
From the three MX beamlines that the team supervises, it’s just a few steps through the HZB cafeteria and past the stairwell to Manfred Weiss’s office. Piles of paper rising high on his desk give physical form to the mountain of work Weiss and his colleagues have to cope with. Research groups and companies come from all over the world to study their crystallized protein samples in the X-ray light of BESSY II. These proteins reveal their structure under the special radiation here. This is of great importance in pharmaceutical research, for example. Once the scientists have discovered which protein molecules in the human body “go crazy” in a certain disease (as Manfred Weiss puts it), they look for substances that will dock targetedly onto those specific molecules and perform their active function there. To identify these drug candidates, the researchers have to determine exactly what structure they assume when joined to the target protein – and that is exactly what macromolecular crystallography is for.
“I entered this field of research at just the right time”
As Manfred Weiss talks about his work, we detect a slight southern German accent. Now 55, Weiss grew up in Baden-Württemberg, in the southwest. He was the first of his family to go to university, “and I have the accent as a souvenir. You never really lose it,” he says. With a laugh, he adds: “The only Baden-Württemberger who can speak proper High German is [controversial comedian] Harald Schmidt.” As a student, Weiss remained true to his origins; he enrolled in Freiburg University and quickly took to structural biology, which was still in its infancy at the time. “I entered this field of research at just the right time,” Manfred Weiss says in retrospect.
Before completing his diploma, he spent one year at a partner university in the USA. After earning his doctorate, he took a postdoc position in Los Angeles. “That was more out of curiosity than career planning,” he laughs meekly. He was lured by the opportunities in the USA, which were considerable at the time: it was around the mid-1990s, and macromolecular crystallography was in its most strongly expanding phase. After the German researchers Johann Deisenhofer, Robert Huber and Hartmut Michel had won the Nobel Prize in 1988, the importance of the field had since become widely recognised. The Nobel laureates were the first to elucidate the structure of a membrane protein – the photoreactive centre – with the same groundbreaking method that Manfred Weiss used shortly afterwards for his doctoral thesis, in which he determined the structure of a pore-forming membrane protein.
Switching from user to beamline operator
While he worked in the US, research groups dedicated to macromolecular crystallography mushroomed everywhere throughout Germany. One of these groups was situated in Jena at what was then called the Institute of Molecular Biotechnology. In 1996, Weiss returned to Germany for a position at that Institute. Five years later, he swapped sides, so to speak: “I basically went from beamline user to beamline operator,” he says with a grin. While he did still study his own samples, his main duties were now to support colleagues at the beamlines operated by the European Molecular Biology Laboratory (EMBL) at the Deutsche Elektronen-Synchrotron (DESY) in Hamburg. And when Manfred Weiss took the position at HZB in 2009, it was with the exact same responsibilities.
10 years ago, measurements took the whole night. Now 10 minutes
There is a knock at the door and a PhD student pokes his head in through the door. “Hey, I never got a dosimeter, and have to get down to the experimental cabin,” he says. And that’s just one more of the things that come with the job, Manfred Weiss chuckles. His team comprises twelve employees, so there is always something that needs seeing to. They have developed into a well-oiled team and, together, they accomplish a gigantic workload: of all biological structures elucidated in Germany, two thirds can be attributed to the three MX beamlines in Adlershof. “The advancements are insane,” Manfred Weiss says, shaking his head. “When I was working on my thesis, it would take a whole night to run measurements on a crystal. Now, we can do it in ten, fifteen minutes, max.” This acceleration is all thanks to a higher degree of automation, better detectors and, not least, the years of accumulated experience of all those involved. And, of course, the stability of BESSY II: “Those who apply to us for 24 hours of beamtime really do get 24 hours,” Manfred Weiss says bluntly. It is extremely rare for experiments to be interrupted due to technical problems. Nearly 3,000 protein structures have been elucidated at the MX beamlines to date, making them by far the most productive in Germany.
Research groups come even from Israel
Naturally, word of this reliability gets around among the users, and the beamlines are heavily overbooked. Approximately 120 research groups come regularly, 40 percent of which are from Germany, and the rest from many countries of Central and Eastern Europe, Scandinavia and even Israel. Corporate clients, too, visit regularly to study new candidates for active ingredients. “I don’t exactly know what they do; they often keep that information pretty secret, so that the competition won’t catch wind of it,” says Manfred Weiss. Once these experiments are up and running, he turns his attention to his next lot of duties, but sometimes wonders what molecules they might be currently working on. Who knows: maybe the foundations have already been laid here for a groundbreaking cancer medicine – maybe even sometime around 4 a.m., while Manfred Weiss sleeps with his phone by the pillow, forever on call should anything happen to go wrong.
written by Kilian Kirchgessner; translated by Peter Gregg.