Of Microbes and Grandfathers

The antibiotic penicillin is one, as well as the painkiller morphine, and so too artemisinin, the antidote to malaria – all three of these are so-called specialized metabolites, metabolic products that bacteria, plants, fungi and animals create but which they don’t require for their immediate survival, unlike sugars or amino acids, for example. This is why they used to be called “secondary metabolites” – but in the meantime it has become quite clear that they are anything but secondary. Not for those creatures that utilize them for such things as defense and communication, and certainly not for us humans who make use of specialized metabolites as medicines, flavorings and insecticides, among many other things. 

Research on the complexity of these specialized metabolites is only in its infancy. According to Rachel Gregor, chemist and Fellow at the Wissenschaftskolleg’s College for Life Sciences, “Micro-organisms in particular are the source of new chemistry that we have hitherto failed to recognize, not to mention understand.” Gregor obtained her doctorate in Israel at the Ben-Gurion University of the Negev before her academic career took her to the Massachusetts Institute of Technology, supported by the Simons Foundation and the Center for Chemical Currencies of a Microbial Planet. By then she had long since moved beyond the limits of classical chemistry, and today her field of research is the specialized metabolites produced by marine micro-organisms. She is exploring exactly how they create these substances and how they utilize them to interact and communicate. She is especially interested in those microbial communities that subsist on so-called marine snow – particles from the surface layers that sink to the depths and serve as food for many organisms.

“My paternal grandfather was a chemist and my father also studied chemistry,” says Gregor. “I don’t exactly know what finally led me to chemistry, but natural science has always fascinated me.” She briefly flirted with synthetic chemistry. “I actually started in an organic chemistry lab with synthetic chemistry. I synthesized a couple of molecules at the beginning of my PhD and it was very hard. In retrospect, it just wasn’t for me. I remember getting very annoyed back then when a friend of mine said, ‘You know, bacteria are much better at synthesizing molecules than we are.’ But these days I agree. I mean, bacteria really are the master synthetic chemists.”

So she started to work on micro-organisms and their ability to synthesize chemicals. First she worked on the gut microbiome in animals and then she dove into the world of marine micro-organisms, at least in the figurative sense, for Gregor admits to a certain fear of the ocean. “I can’t scuba dive and I’m not a strong swimmer, those unknown depths are a bit scary.” This hasn’t lessened her fascination with marine micro-organisms. “Working on the ocean has always seemed, like, I can’t believe I get paid for this! It’s such a privilege. It’s the same feeling you get when you’re looking at the sea, just that feeling of expansiveness and possibility and this whole big vast unknown.”

In the laboratory freezer, those samples of micro-organisms isolated from seawater all look the same at first – white tubes with serial numbers on them – but only until Rachel Gregor brings them back to life. “When you spread them out in a culture dish, they often show beautiful pigments – orange, yellow, pink or maroon. And they smell very different. Usually not so good, but sometimes very pleasant. That alone gives you some idea of the diversity with which you’re dealing in every drop of seawater.” Using genomes of the micro-organisms, researchers can estimate the potential that an organism has for producing chemicals. 

Yet the multiplicity of micro-organisms and their products is not the best fit for science’s current disciplinary boundaries. “When biologists and chemists set to work,” says Gregor, “there are built-in limits to their scientific purview and what they can research with the methods they have at their disposal. Rather than all that colorful, exotic variety to be found out there, biologists are mostly interested in simple metabolites that are already known from human metabolism. Chemists are always finding new compounds, but they are chiefly interested in their applications. They test the substances for their activity, for instance on a range of different cancers and infections, and if a substance doesn’t work then it is recorded in the literature and forgotten.”

To transcend these boundaries, Rachel Gregor shuttles between disciplines. She is interested in the organisms, their products, their way of life and also the role they play in the environment. “It’s about a better understanding of the world of marine micro-organisms and finding a way to manufacture new medicines, for example. And if we better understand how these creatures live, we can also cultivate communities of micro-organisms that produce useful substances for us.”

This requires that microbiology, chemistry, ecology and both pure and applied research all work in close cooperation. And that is exactly Rachel Gregor’s next project – her time at the Wissenschaftskolleg is in fact a way station en route to Canada where she is currently setting up her first laboratory. Starting in March 2025, the MicroChemEco Lab at the University of Toronto will bring together researchers from all three disciplines. “My lab will be part of the Department of Chemical Engineering & Applied Chemistry, where I feel very comfortable,” she says now gazing pensively out the window of the Wissenschaftskolleg’s library at a certain green garden bench. This bench is used not only for breaks to reflect and converse, it also adorns the background image of the College of Life Sciences’ “Call for Applications.” Gregor was lured from MIT to the Grunewald by the image of this bench, captioned with the enticing legend: Gain Time to Think. “I was immediately struck by that,” she says. “The lab has a very strong gravitational pull. There are always more experiments to do, you’re never finished, plus I was still busy with job applications, so a break in the action to stop and think was really very tempting.” 

But she also learned that this time for reflection, particularly the collaborative thinking with other Fellows, can be very disorienting. At the Wissenschaftskolleg, Rachel Gregor actually wanted to compile an index of marine micro-organisms and the molecules they produce. Yet simply finding the organizing principles for such diversity is a challenge. It begins with the question of whether there are actually species in the world of micro-organisms. After all, species are typically defined by their ability to beget fertile offspring, yet micro-organisms don’t have sex but instead create identical copies of themselves through cell division. Nonetheless, micro-organisms can also exchange genes with each other, which scientists call “horizontal gene transfer.”

As a chemist, Rachel Gregor planned to classify the variety of organisms according to the products they make: “This would enable us to prioritize research on new compounds – for example if the same chemicals were produced by entirely different, distantly related bacteria.” But this project likewise proved to be complicated. And the philosophers and science theoreticians at the Wissenschaftskolleg made things no easier for her. “My project has definitely evolved since I’ve been here,” she says. “At first I wanted to do a meta-analysis, a study of the literature, to obtain as much information as possible on chemical diversity in interactions between micro-organisms. But after talking with so many people here, particularly from the history and philosophy of science, I realized that I had to fine-tune my thinking about just how the categories I use determine the work I do.”

For instance, antibiotics are chemicals that have a particular biological function in common, a function that is of interest to us humans. “But that’s not a chemical category,” explains Gregor. “The antibiotics don’t necessarily have shared chemical properties. And if you chose a chemical category, some of the substances in this category are antibiotics and some are not. I ask myself what the proper perspective is for considering all this – what is the most informative way of categorizing? Is ‘antibiotics’ a useful category? I just got a book by Foucault from the library that other Fellows here recommended to me – very different than my usual scientific journals.”

The Wissenschaftskolleg’s library staff not only found specialized literature for Rachel Gregor but something else entirely – the childhood home of her maternal grandfather Hugo Münsterberg. He was born in 1916 in Berlin, where he grew up and whence he fled from the Nazis in 1935 to the United States. “He was half-Jewish and got expelled from the Gymnasium for expressing anti-Nazi opinions,” says Gregor. “And the family was able to send him to the USA a month later because his mother was an American citizen. He died when I was five, so I can barely remember him.”

Hugo Münsterberg, nephew of the famous psychologist of the same name, became a renowned art historian. “My siblings and I have always been interested in our family history, and when I got here it all felt so alive. It made me think about how it was for him to leave Berlin, a city he continued to love all his life, and my own relationship with the two cities that have always felt like home to me, New York and Tel Aviv. With help of the library staff I began to do research. We discovered that his birth certificate no longer exists, but we were able to find other records – and his house – just a 20-minute ride away!” Rachel Gregor had brought an address with her, yet she couldn’t find the house belonging to the address, so she thought the buildings had been destroyed. “But the houses in this street had been renumbered after the war and we discovered it is still there.“ She was also able to drop in for a visit because it’s currently a hotel. “It was great having the library researchers to help me. You know, I’m a researcher, but not that kind of researcher. This stuff is completely inaccessible to me. It’s a real joy delving into it all.”

Rachel Gregor will now be carrying forward her real research in Toronto. Will proximity to the Great Lakes shift her interest to freshwater organisms? “A lot of people have asked me that. I think yes, honestly, my research will be shaped by the place that I’m in. I can certainly imagine having some Great Lakes projects.” In any case she has not yet investigated bacteria in the Halensee, right next to the Wissenschaftskolleg. “Maybe if I was here in the summer, I’d be more tempted to explore the lake.” 

Whether salt or fresh water, that little known and barely understood chemical diversity is everywhere to be found. “Because I do research in ecology, lots of people think that I want to save the world. I wouldn’t say I’m saving the world, but I want to understand it, and use that understanding to do what I can to improve our lives in whatever small way.”