"There isn't one 'single right way' for a career - and it doesn’t have to be a straight line"

Maren Nattermann, Research Group Leader at the Max Planck Institute for Terrestrial Microbiology, on Marjory Stephenson (1885–1948): pioneer of chemical microbiology, whose work on bacterial metabolic physiology established the field as an independent discipline

She shaped an entirely new scientific discipline, wrote the book that defined it for decades, and became one of the first two women ever elected Fellows of the Royal Society after nearly 300 years of male-only membership: Marjory Stephenson, the pioneer of chemical microbiology.

Marjory Stephenson was born in Burwell, Cambridgeshire in 1885, the youngest of four children. Her father, a farmer and surveyor, fascinated by the “new sciences” that captivated Victorian England, encouraged her early curiosity. Recognised as exceptionally gifted, she won a scholarship to Berkhamsted High School for Girls – one of the few schools then offering science to girls – and in 1903 entered Newnham College, Cambridge, to read Natural Sciences: Chemistry, Physiology and Zoology.

Because at the time, women were barred from most university laboratories and libraries, she and her classmates conducted experiments in the Balfour Biological Laboratory for Women and a small chemistry lab at Newnham. On completing her studies in 1906, she received only a " title to a degree", not a degree itself, since women were still denied full degrees at Cambridge. Financial limits ended her hopes of studying medicine, and she spent several discouraging years teaching domestic science before joining biochemist R. H. A. Plimmer’s group at University College London. There she studied fat metabolism and intestinal enzymes.

During the First World War, Stephenson volunteered with the Red Cross in France and Greece, developing enzyme‑enriched diets for soldiers who could not digest ordinary rations and supervising the preparation of more than two million meals. For her services, she was awarded an MBE.    

In 1919, she returned to Cambridge to join the lab of Frederick Gowland Hopkins, affectionately known as "Hoppy", whose concept of "dynamic biochemistry", the idea that metabolism is a continuous chemical process rather than a static system, matched her own experimental approach. While many bacteriologists still classified microbes by shape, Stephenson saw them as sophisticated chemical machines, designing precise experiments to prove it: Using precisely defined growth media – feeding bacteria known chemical recipes and tracking exactly what they consumed and excreted – she laid the groundwork for the modern study of microbial metabolism. 

In 1928, together with Leonard Stickland, Stephenson achieved a methodologically groundbreaking advance: in cell-free extracts, that is, outside living cells, they isolated the enzyme hydrogenase from bacteria such as Escherichia coli and proved that it can activate molecular hydrogen and make it usable for energy processes. In doing so, they showed that bacterial metabolism can be studied with the same biochemical methods as that of animal or plant cells – an assumption that may seem obvious to us today, but was anything but at the time, and one that became foundational to modern bioenergetics. Three years later, around 1931–1932, Stephenson and Stickland characterised formic hydrogenlyase (also called formate hydrogen lyase), an enzyme system that splits formic acid into hydrogen and carbon dioxide and plays a key role in bacterial energy metabolism in the absence of oxygen.

The most consequential observation of those years, however, was a different one. Stephenson discovered that bacteria produce certain enzymes only when the corresponding substrates are present in their environment, as if they could flexibly adjust their biochemistry to the resources available. She called this phenomenon “enzyme adaptation.” Today we know it as enzyme induction, the principle that genes can be switched on or off depending on environmental conditions: a concept that became one of the foundations of molecular biology. Jacob and Monod, who received the Nobel Prize in 1965, built directly on Stephenson’s insights.

Her defining achievement came in 1930 with the publication of her monograph Bacterial Metabolism. At a time when microbiology was still largely a medical discipline concerned with identifying disease-causing germs, Stephenson reimagined bacteria as living chemical laboratories, dynamic systems whose internal reactions could reveal the fundamental processes of life. Her book became the field’s cornerstone, serving as the standard global textbook for over two decades and laying the methodological foundation for modern biochemical research.   

In 1945, Stephenson and crystallographer Kathleen Lonsdale broke new ground as the first women ever elected Fellows of the Royal Society, ending 285 years of all-male membership. Tellingly, a slight adjustment was necessary: on her nomination form, "him" had to be crossed out and replaced with "her." That same year she helped found the Society for General Microbiology, later serving as its second president.

Beyond the lab, Stephenson was known for her "Cambridge school" of bacterial chemistry, through a culture of methodological innovation and collegial collaboration. An exceptionally supportive and loyal mentor, she was modest about her own achievements, yet notably generous with credit, often allowing students to publish first-author papers without her name. In his obituary of Stephenson, British microbiologist and biochemist Donald Woods – one of her former students and close collaborators – recalled her teaching philosophy: "Infection, not instruction, is the way to teach."  

Shortly before her death from cancer on December 12, 1948, she was appointed Cambridge’s first Reader in Chemical Microbiology. That same year, Cambridge finally granted women the full degrees long denied them.

Maren Nattermann, what first sparked your interest in biochemistry? Was there a specific moment or experience that defined your path?

I actually started my biochemistry studies simply because I’d taken chemistry and biology in high school. When it came time to choose a major, I just combined the two  – without really knowing what I was getting myself into. In Heidelberg, my programme was so chemistry-heavy, I didn't even see a biochemistry lecture until the third semester.

But that shift from pure chemistry to biochemistry turned out to be exactly right for me. It was absolutely fascinating to see how the fundamental rules of chemistry apply to metabolism, and how nature – through enzymes – finds solutions for reactions that, in classical chemistry, would require extreme conditions. Nature does it all at room temperature, in water, and at a neutral pH. You hardly ever see that in conventional chemistry.

What specifically drew you into your current field of research?  

My group’s research focusses on enzymatic cofactors, which are small molecules that assist in catalysis. My fascination with these “helper molecules” started when I was working on a cofactor called thiamine pyrophosphate (TPP) during my master's thesis. TPP allows for what we call an "umpolung" reaction, a polarity inversion. Depending on their position in a molecule, carbon atoms tend to have either a positive or negative character; an "umpolung" is when that character is reversed. This enables TPP to facilitate reactions that would otherwise be virtually impossible.

I found it intriguing from the start, partly because TPP is so effective that it’s even used in conventional chemistry for these reactions. Working with cofactors is just exciting because they use all sorts of chemical tricks to assist enzymes. Plus, I always find it funny when I walk past the vitamins in a drugstore and try to remember which vitamin corresponds to which cofactor (thiamine is B1!).

What motivates you during the difficult phases, when results are slow to come or experiments don't go as planned?

To be honest? I just push through and keep going. Neither motivation nor frustration changes the simple fact that sometimes, an experiment just isn’t working. People call research a rollercoaster for a reason.

I do believe it is important to allow yourself to be frustrated. I’ve definitely headed straight home after a failed experiment because I was too annoyed to keep going. I found that the day after, it’s a lot easier to try again.

In 1930, Marjory Stephenson published Bacterial Metabolism – the first systematic textbook on microbial biochemistry, which served as the "bible" of the field for over 20 years. How does this work still influence your research or your understanding of the discipline today?

I find it telling that if you Google that title today, her work no longer appears first; instead, you find a book from the 1980s on the same topic. Textbooks probably go out of style quickly because the field grows so fast. Many of the pioneers of biochemistry rarely appear in modern textbooks anymore – unless they won a Nobel Prize or had a metabolic pathway named after them. This is especially true for women, who already had to fight for visibility in their own time. So we’ve lost a certain appreciation for the visionaries who uncovered everything we now take for granted, all without our modern experimental methods.

In the field of metabolism specifically, we tend to forget that it’s possible to describe enzymes or even entire pathways without being able to "see" into the cell the way we do today through DNA and RNA sequencing, proteomics, and metabolomics.

Which of Stephenson's discoveries do you consider particularly influential today?

I am fascinated – with all due bias – by her work on formate hydrogenlyase, because I’ve worked extensively on formate metabolism myself. Her research comes from an era when enzyme reactions had to be demonstrated without purifying the enzymes – meaning they couldn’t be fully separated from the cell.

For example, in her experiments, formate had to be added to the nutrient medium just to get the enzyme to be produced in the first place. Every experiment had to be designed so that the observations could only be explained by the presence (or absence) of the specific enzyme. That required a level of experimental control we hardly need today. Our entire understanding of metabolism is built on these works. Reading these old publications is a bit like watching someone assemble a puzzle when many pieces are still missing. It’s simply impressive.     

And honestly, I’d love to one day write in one of my own papers: This "figure [...] needs no further comment" (Stephenson and Stickland, Biochem. J. 1932).

What made Stephenson a pioneer of "Chemical Microbiology"?

Research like Marjory Stephenson’s shows us that the biochemistry of supposedly "simple" microbes is incredibly fascinating and highly complex. She conducted research on E. coli, which is probably the best-known microbe in our field – we almost forget other microbes exist. She proved that under certain conditions, this organism produces hydrogen.

Why is this discovery of hydrogen production so significant?

The fact that hydrogen is produced E. coli under certain conditions – and, perhaps more importantly, not under others – demonstrates metabolic flexibility: one of the core principles of biochemistry. In nature, if you only know one way to survive, you usually don't last long.

Microbes, in particular, must act lightning-fast when their environment changes. They must have escape routes so they don't accidentally poison themselves through their own metabolic processes. Marjory Stephenson’s discovery of "formate hydrogenlyase" is exactly one of these "problem-solving" mechanisms of nature. What she gave us was a way of looking at enzymes that remains fundamental to our discipline: you have to see the smallest, microscopic detail, but always within the context of the entire metabolism.

She also coined the term "adaptive enzymes." What was the significance of that?

Adaptation is a cornerstone of evolution; organisms adapt to their environment to avoid being out-competed. When we hear the word “adaptation”, we often think of DNA, because DNA is what is passed down through generations. But our genetic code changes over generations – not exactly minute by minute. The much faster adaptations required for day-to-day survival are something the cell surrounding the DNA needs to deal with – the metabolism and enzymes.

Can you give an everyday example of this?

Take glucose: when I eat it, all the alarm bells in my body go off – it’s a signal for a high dose of available calories. But food doesn’t stay in our bodies forever. We have to react quickly. A signal goes out: "Sugar, now!", and the metabolism reacts immediately – transporters and enzymes from sugar metabolism are activated. This allows us to get as much as possible out of the short time the sugar is present.

Does this principle of speed also apply to the microbes Stephenson studied?

Absolutely. The same principle applies to single-cell organisms – though for them, the challenge isn’t just how long food is available – it’s competition. Whoever reacts the fastest eats the most: something that anyone with siblings knows all too well!

Metabolism as a whole is adaptive. A single "adaptive enzyme" is usually highly specialized and isn't normally needed. In fact, it would be an enormous waste of energy to have it ready all the time. You don’t set out the fine china just for a bowl of pasta – it stays in the cupboard, waiting to be used with pride once a year. Adaptive enzymes are only produced or activated when circumstances demand it.

What Marjory Stephenson proved with formate hydrogenlyase is that it is active when you grow E. coli on a medium with formate – but not when you don't. The formate acts as a signal: "Turn on my metabolic pathway!" Only then does the enzyme convert the substance.

What distinguishes Stephenson's approach from modern laboratory work?

What I love about her work is that she could have just left it at that: formate present, enzyme on; formate absent, enzyme off. But she didn't. She looked at the entire metabolic environment of the enzyme. Since she knew that E. coli could produce formate from sugar, she tested feeding the bacteria sugar instead of formate – and sure enough, the enzyme switched on as well.

She describes this test in her publications almost as an afterthought. I find it incredibly charming how she presents it as completely self-evident:

"The introduction of glucose […] also results in the production of […] formic hydrogenlyase. As it is well known, (glucose is) […] decomposed by Bact. coli with production of formic acid, so this phenomenon is sufficiently explained." (Stephenson and Stickland, 1932)

How far does the legacy of these "adaptive enzymes" reach into today's research?

It goes much further than one may think. To turn adaptive enzymes on and off, a biochemical switch is put in front of the gene that serves as their blueprint. This switch is responsive to a certain compound and will flip in its presence. These genetic control elements are called “operators”, and they are one reason why it's so much easier for us to produce and isolate enzymes in the lab today. If I place a gene behind an operator that responds to a known substance (usually a specific sugar), I can send a very clear signal to the bacterium: "Start producing this enzyme right now!" And remarkably, it usually does.

Where do you see concrete progress for women in your discipline today, and where do structural or cultural hurdles remain?

I do see real progress in biochemistry. Structural hurdles are slowly being dismantled — or at least the effort is there. I’m quite new to my leadership position, and it only became clear to me on my way to becoming a research group leader what a balancing act it is: to specifically support and encourage women to stay in research without giving them the feeling that their gender is the basis of their career.

How do you personally manage to balance professional and private demands? What strategies would you recommend to young female scientists?

I have the privilege of being able to work from home quite a bit now. For me, that means one hour less of commuting and fewer distractions during work itself. By starting earlier, I find I’m faster with my tasks and can finish earlier. Getting up every two or three hours to do a few household chores is almost meditative. That leaves the evening free for my private life.

Of course, it’s not simple if you have to be in the lab all day. But I would still advise people to listen to themselves early in their careers to find out how they work most efficiently. Experience shows that this saves a lot of frustration.

Do you have an example of such a personal rhythm?

When it comes to experiments, I’m very much a morning person. If I force myself to start an experiment in the afternoon, it drains an incredible amount of mental energy that I could better use elsewhere. My rhythm was always: plan experiments the evening before, go straight to the lab in the morning and start pipetting, and only then do the measuring, evaluating, and documenting.

What is your advice for young researchers still searching for their own rhythm?

You should really listen to yourself and ask honest questions. At what time of day can I focus best on reading, when on writing? When do I make the fewest mistakes in data analysis? Do I have a "post-lunch slump"? Do I want to chat with colleagues in the morning, or do I want to dive straight into work? These are a thousand little things we often don't pay attention to, but they can really make life easier. Of course, there are deadlines, meetings and experiments that can't be shifted. But having a somewhat regulated "normal state" in lab work really helps. Unless, of course, you work best when things are a bit chaotic. But that’s also a valid insight.

Which female role models – historical or contemporary – personally inspire you?

I find it hard to relate to historical figures as role models because our life circumstances are so fundamentally different. Today, I have the privilege of being surrounded by excellent female researchers of all ages. Because of that, I hear many different perspectives on my research or my plans when I ask for advice – but I also see how varied the paths in research can be. It can be very reassuring to remember that there isn't one "single right way" for a career, and it doesn't always have to be a straight line.

What advice would you give to young women aspiring to a scientific career?

Everyone feels insecure sometimes. Everyone has doubts – even the people you’d never suspect, the ones who are incredibly successful. The trick isn't to stop having self-doubts, but to learn how to handle them. Often, it’s good to just do things. Just apply for the position, just write the email, just ask the question.

I know, of course, that "just" isn't actually that easy. But my motto is: "The very worst they can do is say no". That’s how I got my current position. I applied because I knew this chance wouldn't come again. It took a lot of effort for me to overcome my own hesitation, but it was absolutely the right decision.  

For International Women's Day 2026, the campaign motto is "Give to Gain." What does this mean to you personally?

For me, "giving" is a fundamental requirement of being in a leadership position. Supporting early-career researchers is simply part of the job. While the "gain" that comes from that investment shouldn't be taken for granted, I’ve found that it often follows naturally.  

Is there anything else you would like to say in closing?

Thank you for the chance to share! I truly hope that my perspective can be of use to others.

Maren Nattermann, thank you so much for this interview