The untimely death of Neocles Leontis on December 8 came as a complete shock to the Bowling Green and Bowling Green State University communities. There has been an outpouring of personal messages telling about the many ways in which he touched people over the years. He was extraordinarily active, just off the charts, and I would encourage you to read the accounts of his life and his career, and let them inspire you, as I think he would have wanted. Here I have collected my memories of working with him over the last two decades on a variety of projects in scientific research and in other venues at BGSU and in Bowling Green. I lost a collaborator and a friend, but I can only be thankful for the time we had together.
I met Neocles in February of 1999 when he and my math/stat colleague Edsel Pena stopped by my office to invite me to lunch. I don’t know why. Who knew that that would lead to 21 years of us working together? I learned to never turn down an invitation to go to lunch!
The project that got us started was an idea from Neocles to analyze some RNA sequence data that he was working with. He was sure that a statistical analysis would help to identify interesting interactions that hold the RNA molecule together. This was perfect for an undergraduate mathematics major I knew who was looking for an idea for an interdisciplinary honors research project. She went on to earn a Goldwater scholarship and the project worked out well. Like bookends, in 2020 we were working with another Goldwater scholar, who is working on a project to understand covariation between positions in RNA and protein sequences. We’ve been very lucky to have such strong students to work with.
Neocles introduced me to the world of RNA bioinformatics, which sits somewhere between biology, chemistry, statistics, mathematics, and computer science. Over all these years, it was a perfect collaboration, where we learned to understand each other and communicate well, but had very different domains of expertise. Neocles brought up authentic scientific questions that he wanted answered, and we could bring any mathematical or statistical or computational method to bear on it. Some problems were easy, some were very hard, some are still not solved, but all were fun to work on.
Neocles was a central figure in the world of RNA 3D structure annotation and understanding. He and Eric Westhof, a giant in the field, wrote a seminal paper on RNA basepairs in 2001, introducing an annotation system that is nearly universally used, and, more importantly, promoting an explanation for why certain random mutations are observed in different species and why others are not. This was a first step in solving the sequence to 3D structure problem for RNA, and which we continued to pursue in many of our papers. The sequence to 3D structure problem is now nearly solved for proteins, by AlphaFold from Google, but not so close to being solved yet for RNA. Neocles also organized and led the RNA Ontology Consortium, getting NIH funding for the project, which established a controlled vocabulary for describing RNA 3D structures. But when he worked as an National Science Foundation program officer for two years, I took over from him as the Principal Investigator. Funny story: we organized a meeting Cambridge, England, in January, to follow up on a successful meeting in Cambridge from the previous year. But half the invitees bailed out, and eventually it came out that they were attending a different meeting at the same time in Hawaii. We couldn’t use the grant money to fly people from Cambridge to Hawaii. So we decided to have two meetings, one in Cambridge, the other in Hawaii, in January, covering different topics in RNA Ontology. Can you guess which one I was obliged to go to? Do you know how far north Cambridge is? The sun barely rises in January. It is dark all the time. I know this from personal experience. Neocles didn’t get to go to Hawaii, either.
In summer 2001, Neocles asked me to give short introductions to programming in a graduate chemistry course he was teaching on bioinformatics, so students could simulate genetic sequences and understand some of their statistical characteristics. This was one of many innovations in his teaching over the years. Neocles was always looking for new and better ways to get his students to think carefully and understand deeply. Before most people heard of 3D printing, he had ordered 3D printed molecules for his students to pass around and hold. He was constantly changing the way he taught his courses, always moving away from lecture and toward students working more actively. He made a simple game using small colored pieces of paper to represent molecules from our cells and had students exchange them with each other to simulate what happens in our metabolism. He went on to hire a programmer to make a web-based version of the game called MetabolismFun, which students thought was a lot more fun than listening to a lecture, and which immediately got them to think about metabolism from a very practical perspective. Unfortunately, the site is now defunct or I would point you there.
By 2003, we were working together to advise PhD students, and by 2005 we were meeting regularly as the BGSU RNA Group. Over the years, we worked together to advise nine PhD students in Biology or Photochemistry, four PhD students in Statistics, and many undergraduates and even some high school students. Neocles loved bringing new students into group meetings. Discussions always started out at the level appropriate for the student with the least background, giving us all practice explaining our work in the simplest possible terms. He always told new students, if there is a term we’re using that you don’t understand, stop us and let’s make sure you understand. Many of his students have written to me in recent days to say what a huge impression he made on them and on the trajectory of their careers. He was devoted to his students and they knew it.
In 2008, our first joint paper was published, on motif searches in RNA 3D structures. This paper formed the basis for most of our subsequent work. Over the years, we published 27 papers together, with our students and with dozens of co-authors from around the world. Many of the papers are steps on the way to solving the RNA sequence to 3D structure problem. Neocles introduced us to google docs, which allowed us to simultaneously draft and edit papers and proposals; once in a while, our group meetings consisted of five people sitting around the big table in 132 Overman, quietly tapping away, sweeping through the article, then sweeping through again to check each other’s drafts and edits. For whatever reason, it usually worked best for me to write the first draft, then Neocles would work it over, and over, until it was right. “Good writing is rewriting,” he would say. We worked together for so many years, every meeting was like a continuation of some previous conversation that had been momentarily interrupted, though days or weeks had gone by.
In 2010, our first joint NIH grant proposal was funded, then renewed in 2014, and a few months ago another four years were funded, all with Neocles as the Principal Investigator. These 12 years of funding are a collaboration with Helen Berman and others at the Nucleic Acid Database at Rutgers University. Every week, our annotation pipeline runs automatically on new RNA 3D structures and posts annotations at rna.bgsu.edu, which are then picked up by other groups around the world. Neocles told me a few years ago that he just wanted to get another four years of support for the group before he retired, so it would be in good shape. But he never showed any signs of actually retiring! Of course we’ll carry on, but that won’t be easy without his driving force and expertise behind the work.
In 2011, Neocles read about research on activity-based teaching in Physics classes called POGIL, for Process Oriented Group Inquiry Learning. This method gave results one standard deviation higher than traditional physics teaching, on the same traditional exams. In brief, pick the 25 key topics from your course and design activities for students to work through in groups to really understand them, and don’t worry so much about the other 100 topics you usually whip through in class. The idea was perfect for a new course I was teaching, Math 3280, “How to write proofs” and now I’ve taught that course successfully four times with the POGIL method. Neocles was always looking for new approaches that were supported by research, and had an uncanny ability to find what he was looking for. In 2011-2012, Neocles and Steve Cady organized a faculty learning community called the Innovative Teaching Group, which I joined. As Neocles wrote at the time, “Focus is innovation and assessment — the idea of Evidence-based practice which is now being promoted also by NSF. They are dangling big money for universities that will take this up in a serious manner.” This was followed up by campus-wide events to showcase innovative teaching methods. No one workshop revolutionizes teaching across a university, but every push in a good direction helps.
Neocles had incredible intellectual intensity. When he got interested in a subject, he not only read the New York Times and Scientific American level description, but went on to read research papers in the area to really understand the science behind it. Again, he had an uncanny ability to identify the right things to read. He must have read very quickly, judging by the sheer number of things he would read, and then he was very good at getting to the main point and being able to explain that to other people. Neocles loved books. As long as I’ve known him, whatever city he went to, he would actively seek out high quality book stores and buy new books, on whatever subject, read them insanely quickly and then give them away to students or anyone else who he figured would benefit from reading them. He simply inhaled books. Most recently, he bought several copies of a book on the coronavirus and distributed them to the students in our group. And that is on top of a steady stream of emails and texts with links to articles and videos on topics in science and climate change. I could never figure out how he managed to read so much, and watch videos, and listen to podcasts, and talk with so many people. Now and then, for weeks in a row, Neocles would read the daily news in French from Le Monde, to keep his French up. And his German was solid as well. Wow.
Over the years, we attended RNA research meetings in Ann Arbor, Columbus, Indianapolis, Madison, Seattle, Stanford University, Rutgers University, Cancun, Mexico, Cambridge, England, and a beautiful little resort town in the Pyrenees called Benasque, Spain for small meetings on RNA bioinformatics. While there, we hiked several hours up a pass and a few steps into France. In Cambridge, we had lunch in the pub where Watson and Crick used to meet when they were puzzling out the 3D structure of DNA, and visited the botanical garden at the site of Newton’s apple tree. (Neocles loved botanical gardens.) Neocles explained his strategy for finding his way around a new city: just start walking until you get lost, and by the time you find your way back to your hotel, you know the city!
Neocles took great interest in students. Once, a student visiting with a group from Ukraine so impressed him that he figured out how to get her funded to come to BGSU as an undergraduate, where she did very well, and then went on to earn a PhD in science education. In the last year, a student we both worked with was sent to prison, and Neocles took great interest in his condition there and conditions in other prisons in the state, noting that prisoners really don’t have any chance to escape the coronavirus once it starts to spread, they aren’t even provided with soap unless they can buy it themselves, and it’s very hard to send them reading materials. He corresponded with other prisoners and then passed along their concerns to newspapers in the state to try to get some improvement in prison conditions.
Neocles had an activist mentality. It was never enough for him to be aware of the problems in the world, he wanted to change the world for the better. On climate change, for example, as early as 2012, he was campaigning in the City of Bowling Green and with BGSU to install district-wide geothermal heating for sections of the city and at BGSU. He visited a similar installation at Ball State University, gave a well-researched Town and Gown talk, and met with people at BGSU to try to push this forward. My memory from the time is that electric rates were too high relative to natural gas prices for this to be financially viable, but it was certainly the right thing to do, and now we are many more years behind where we should be. By 2014, he was working with Columbia Gas to specifically focus on Bowling Green for their low-cost energy audit program, where they come to your house, use thermal imaging equipment to find air leaks and poor insulation, and then provide real discounts on getting the work done. And he actively recruited people in town to get those audits done, and any followup work. This would improve the comfort of their home, reduce their heating bills, and reduce their carbon footprint. The program still exists, google “columbia gas ohio home energy audit.” All this in addition to giving talks around campus on climate change. In the last few years, he worked with Citizens Climate Lobby in Perrysburg to organize entries in the Bowling Green and Perrysburg parades with electric cars and handouts about how people can reduce their carbon footprint. He invited me to give a few talks at Kiwanis and other places about electric cars. As others have noted, he ran against an incumbent on city council for the Democratic nomination, researched how to run an optimal modern campaign, won, and served on the Bowling Green City Council for nearly a year, pushing for changes on rental regulations and the city’s coronavirus response. He was a very active activist!
In 2012, he started reading about the impact of diet on long-term health, and together with Karyn Smith we organized a wellness program that met several times to help people learn how to eat differently. We organized a potluck and set up a wiki to direct people to research articles and recipes. Enduring lessons from the experience: it’s very hard for people to change how they eat, even when they are motivated to do so, and it’s very hard to get conclusive data about long-term health benefits of eating one way or another, because it’s so hard to do long-term randomized trials. Still, it seems that there are dramatic benefits to eating carefully over a long period of time, and he would consider it a dereliction of duty if he kept that knowledge to himself.
Neocles was always excited to share something he had just learned. His last text to a student and me read “Next week I’ll show you the key role played by proline mutations in production of new vaccines! Very cool. Thanks to NIH research American socialist state rises to the rescue once again!” He explained just a bit to me, that people designing coronavirus vaccines needed to alter the messenger RNA of the coronavirus spike protein so that, when expressed in human cells, it would nevertheless take the same shape as it does on the surface of the virus so the immune system would be able to recognize it. But you can’t do that work without a strong foundation in basic research that was developed over many years; the only reason we have a vaccine so quickly is that so much basic research on mRNA vaccines was done before 2020. Neocles always spoke up for federal funding of scientific research; scientific research is a common good that we all benefit from supporting with our tax dollars.
Neocles was a visionary, an idealist, an activist, and a true friend these 21 years. I was extremely lucky to work with him for so many years and on so many projects. He was a devoted son, brother, husband, and father. My heart just aches for what could have been, now that he is gone.
Craig L. Zirbel
Professor of Mathematics and Statistics
Bowling Green State University
December 13, 2020
