Meet the Prize Medal 2025 Winner, Professor Richard Lenski

25 March 2025

Each year, the Microbiology Society awards the Microbiology Society Prize Medal to an outstanding microbiologist who is a global leader in their field and whose work has had a far-reaching impact beyond the field of microbiology.

Ahead of the Prize Medal 2025 lecture, early career member James Croxford interviewed Professor Richard Lenski to learn more about his career and how it feels to win a Microbiology Society prize.
 

What advice would you give to early career researchers who want to pursue bold, long-term projects like the LTEE, but feel constrained by time or resources?

I’m always cautious about giving general advice, because people are different in their individual temperaments, fields of research, the type of lab they're in and so on. At the same time, research almost always advances incrementally. Individuals must find a way to balance their long-term goals with the day-to-day business of being a scientist. So, it’s important to be flexible. That being said, while flexibility is key, dreaming big is just as crucial!

I transitioned from my graduate studies doing fieldwork with insects to a postdoc in microbiology because, despite knowing little about microbes, I realised their tractability suited the fundamental scientific questions that fascinated me. That's one example of being willing to change course in order to find ways to make your dreams happen.

People often ask me about the Long-Term Evolution Experiment, wondering if I ever envisioned it lasting this long, and the answer is no. I had done some shorter-term evolution experiments, but I called the LTEE long term after just a year, when it reached 2000 generations. It’s now run for over 37 years and more than 80,000 generations. Great students, collaborators, and emerging technologies—like genome sequencing—help keep projects fresh. Maintaining deep interest in your work is just as crucial.

In many of your papers, you highlight the simplicity of the LTEE as one of its key strengths. Do you think simplicity is a general hallmark of successful experiments, or is it unique to the LTEE?

It's hard to give universal advice. Although, I would say I think it often helps for experiments to be simple. In the case of the LTEE, it’s meant that we've had core metrics, things that we've followed since the early days—like measuring fitness in competition assays—that have stood the test of time. It enhances reproducibility and makes troubleshooting easier. You can't always simplify, however.

For example, I think about people studying natural microbial communities. I do think there's room to simplify, but it’s much more difficult given the complexities. Also, how appropriate is a mouse model for a human infection?  It’s hard to know at first, so you have to be willing to put the work in to start with to then know where you can go on to simplify. My advice would be to simplify, when possible, but recognise that some systems demand complexity. If you're interested in studying a natural system, you have to include the features that are relevant to the questions you're asking. So, start simple, but be prepared to explore as deeply and intricately as the questions demand.

What was it like handing over such significant ownership of the LTEE to Jeff Barrick, and how did it feel to see someone else continuing your vision?

The short answer is it feels great! A lot of biology is about continuity. Jeff is superbly talented, and he’s got great leadership skills. He was a postdoc in my lab and really drove us into getting started with genomics. Nowadays, genomics seems so obvious, but 20 years ago it was too expensive and hard to do. I think it's just amazing to have his talents brought to the LTEE.

The bigger picture is that while we are mortal beings, science is immortal. Science is a way of understanding nature—and I hope it will persist as long as humanity does. Seeing the LTEE continue for another generation of scientists is amazing and a dream come true. I'm sure it contributes to scientific knowledge in the present, but it’s nice having a completely fresh set of eyes on it for the future. Hopefully, to explore some new questions in different ways.

I'm a little bit of a technophobe, but so many people, including Jeff, have been able to answer tough questions utilising new technologies. Over the years, researchers have brought new questions and with those new questions, new approaches to the long-term lines. It's kept the research fresh and broadened it, which has meant that out of its simplicity, complexity has come from collaborations.

How have the findings from your work influenced practical applications in other fields like medicine, biotechnology, or computational biology?

It's a tremendous honour to think of my work having the impact on labs like your own, but it’s hard to know how to answer this question. I think most importantly, and it's not unique to the LTEE, the idea of experimental evolution has contributed to a growing awareness among microbiologists that evolution is this ongoing process. It's not something that only happened in the past and can be ignored. Even when you're trying to preserve strains, say by storing them in stabs or slants, evolution is happening, and we need to be aware of that. Evolution isn’t just a thing of the past; it's happening all the time!

For example, when we first started to get into the genomics around 2006, we had to sequence our ancestor strain, which was an E. coli B strain, not a K12 strain. It turns out to be a strain that's widely used in biotechnology. Another group, led by Bill Studier, was also using E. coli B as a protein production strain. When he heard that we were sequencing our derivative, he reached out to compare results. We knew they both came from the Luria-Delbrück lineage, which was confirmed by our analysis. They were closely related, but what was really cool and unexpected is that by comparing the genome sequences, we could identify which mutagens different labs had used. It was recorded in the papers, for example, which markers they had selected to help keep track of some of their phenotypes of interest. It was really like the bacteria themselves were lab notebooks. As a scientist, you do your best to record everything. Even if you make a mistake, there's a good chance the microbes will remember it in their genomes! I think there's a good lesson here about really being attentive to storage and details of strains.

Another example on the medical side is one of my all-time favourite papers that came from a big group led by Tammy Lieberman and Roy Kishony. Clinicians had stored strains of a Burkholderia that came from a clinical outbreak among cystic fibrosis patients. Lieberman and colleagues' analysis was beautiful—in some ways, it resembled the LTEE. They had additional challenges because they had to do all this within a phylogenetic framework. First, they had to figure out the transmission network of the infections. Then, they were able to use both genomic and some phenotypic analyses to really dig in and show that evolution was surprisingly repeatable, which is very similar to some of the results that we've seen with the LTEE. It was really gratifying to see that even in these complicated real-world scenarios, some of the lessons and approaches we had been developing on the long-term lines were fruitful.

I recently gave a talk at a Cancer Grand Challenges Conference. There’s increasing interest in the LTEE among cancer biologists. Like the LTEE, cancers are asexual cell lineages undergoing mutations, competition and evolution. It’s really nice to think my work is also having an impact on that.

Your work with the Long-Term Evolution Experiment has had an incredible impact on evolutionary biology. As you reflect on its progress, what are the next big questions you hope to explore, either in the LTEE or in other areas of your research?

Papers don't always present findings in strict chronological or evolutionary order. Therefore, I should find some way, whether it's a scientific monograph or a really long review article on the LTEE, to try and consolidate all of the knowledge we’ve gained so far in one place.

We’ve seen a lot of repeatability and parallelism in the LTEE, much more than I expected at the outset. One big question is how much contingency and subtle divergence underlies all this outward parallelism? For example, I would love to examine the effects of extensive, genome-wide recombination between lineages. Are they becoming incipient species, with emerging barriers to gene exchange? I think what we would need is a way of doing free genome-wide recombination between pairs of strains. What if we could just create a thousand recombinant strains of population number one and population number two, so that each one had about 50% of each parent? Would they be just about as fit as both parents, suggesting that they're mostly evolving in parallel? Or are there so many subtle genetic differences accumulating between them, so that if you were to hybridise them, you'd end up with a lot of really misfit organisms? I think this will be a big challenge. Interestingly, one observation from the LTEE is that the bacteria appear to be evolving in a way that makes them more difficult to manipulate.

I’d also really like to see a detailed analysis of the dynamic coupling of genomic and phenotypic evolution. Genomics has just advanced so much since the LTEE started, to a point that I never dreamed would be possible. I think it would be really exciting if metabolomics got to the same point. Clearly, huge advances are being made in the field of metabolomics, but the nice thing about sequencing is that it’s just as easy to measure any base pair. Whereas with metabolites, some of them are at very low levels. We’d not only need to measure metabolite levels over evolutionary time, but also see if they are having their effects in stationary phase, exponential growth, or coming out of lag. The challenge is to see and quantify pools and fluxes of minor as well as major metabolites.

How have societies like the Microbiology Society supported your work or helped foster a sense of community within the field of microbiology?

I’ve tended to be pretty spread out across scientific societies, so my participation has varied. Early in my career, I was more involved with evolution-related societies, as I felt a bit like an outsider or imposter in microbiology. Over time though, I’ve really become integrated into both communities, both of which have been wonderfully supportive. As a scientist, you may have one home or many, depending on what fits your needs. So, they're super important, especially for young scientists, really for all scientists. They perform incredibly important roles, for example with meetings and journals. However, societies are facing huge challenges, including managing open access, finding reviewers when everybody is submitting more papers, and securing funding when people can access journals online without being members. I sincerely hope that societies like the Microbiology Society, which play such crucial roles, continue to thrive in the years ahead.

Notes from interviewer:

It was a real pleasure to interview Professor Richard Lenski and hear his thoughts on long-term research, collaboration and the evolution of the LTEE. His insights were both thoughtful and engaging, it was fascinating to learn more about how his work continues to shape different areas of science. I really appreciated his candid reflections on the challenges and surprises that come with long-term experiments, as well as his advice for early-career researchers. I hope others find this conversation as interesting and inspiring as I did. I thank Professor Lenski for sharing his time and perspectives with myself and the Microbiology Society.