A Leap of Faith, Part 2

My wife, infant son, and I moved to Amherst the first weekend of April 1982. A beautiful snow fell on Sunday. Then, early on Monday morning, my new boss Bruce Levin cross-country skied by the old house we were renting, knocked on the door, and asked me when I’d be coming to the lab!

I had much to learn, of course. I remember learning how to use a pipettor from a technician in Bruce’s lab, and how exciting it was to estimate the number of cells in a flask (typically many millions or even billions). That estimation is done not by counting the cells directly, but instead involves precisely diluting small amounts through a series of test tubes, each tube containing a large, known volume of a sterile solution. At the end of the dilution series, one takes a tiny amount from the final tube and spreads it across an agar plate. The plate is then incubated for a day or so, during which time each of the few hundred cells that survived the dilutions grows into a separate colony. A colony is a clump of millions of cells that can be seen with the naked eye, unlike the individual cells that can be seen only by using a microscope. One counts the colonies on the plate and, using that number and the dilutions that one made, one can then back-calculate the density of cells in the original flask.

In my first effort at this most basic procedure, I did three replicates from the same flask. I was thrilled when I counted the colonies on the first two plates, and the numbers differed by only a few percent. The third plate, however, differed by perhaps a factor of two, which meant I had done something wrong—maybe I’d let an air bubble into the pipettor’s tip, displacing some of the liquid—and I realized the importance of attention to details.

A little later, while I was still learning the ropes, Bruce had me perform a more complicated experiment to measure the rate at which a certain virus, called T6, adsorbs to and infects E. coli cells. The experiment required a lot of repetitive dilutions and plating of samples that I had to process quickly and accurately. The basic idea is that free viruses should decline in number over time as more and more of them enter cells. (This decline continues only until the first viruses to infect cells have had enough time to produce the next generation of viruses, hence the need to process the samples quickly.) Alas, my experiment was a total failure. What was I doing wrong? I think Bruce had me repeat the experiment, with the same lousy outcome. Though he never said it, perhaps he would regret hiring me. After all, given my lack of experience, Bruce had also taken a leap of faith.

After my second failure, Bruce checked his notes about the particular strain that we were using. As it turned out, he had given me a strain of E. coli that was resistant to T6! Hence, there were no infections, and that explained my failed experiments. Later on, I was able to use the same protocol to measure the rate at which a different virus, T2, adsorbed to and infected E. coli.

Oh, and what about my experiment to look for evolutionary changes that compensated for the cost of bacterial resistance to infection by viruses? That’s what I had proposed in my letter to Bruce asking about a postdoc. I never got to that experiment while I was in Bruce’s lab. However, it provided the seed for a project that I eventually conducted as an early-career faculty member at the University of California, Irvine.

[Bacterial colonies growing on agar plates. Photo credit: Brian Baer, MSU.]

A Leap of Faith, Part 1

I did my graduate work at the University of North Carolina, Chapel Hill, in what was then called the Department of Zoology. I had several important and formative experiences during those years: clear advice from my advisor, Nelson Hairston (1917-2008), about the value of well-designed experiments in ecology; an eye-opening course on the integration of ecological and evolutionary perspectives, taught by Janis Antonovics (then at Duke University, just a few miles from UNC); an abysmal failure in my own attempt at an experiment with praying mantises; an enlightening collaboration with a fellow grad student, Phil Service; and a dissertation project on the effects of forest clearcutting and competition on beetles in the mountains of southwestern North Carolina.

Although that dissertation project was reasonably successful, I realized it was not a good fit to my skills and interests. Many of my fellow students were excellent naturalists with a love for the organisms they studied. While I enjoy being outdoors, I’m not a naturalist. Instead, I’m intrigued by the conceptual questions that biologists ask about the living world. And as my graduate work moved forward, I realized that questions about evolution, including especially the mechanisms and dynamics of evolution, interested me most. However, the beetles I was studying were not well-suited to those questions. So how could I pursue my interests?

While we were finishing our doctoral projects, Phil and I spent a lot of time discussing potential systems for studying evolution. As he moved on in his career, Phil chose to study evolution using fruit flies, a long-standing model system for studying genetics. I recalled an undergrad course I had taken, where we learned about elegant experiments done with microbes, including one by Salvador Luria and Max Delbrück that showed mutations happen at random, not in response to selection.

Meanwhile, the graduate students and faculty at UNC had a seminar in which we discussed recent papers in the field of ecology. One week we read a terrific paper by Lin Chao, Bruce Levin, and Frank Stewart titled “A complex community in a simple habitat: an experimental study with bacteria and phage.” I forget who chose that paper for our seminar, but I owe that person a debt of gratitude. 

Phages are viruses that infect bacteria, and the paper provided an elegant demonstration of the interplay of ecological and evolutionary processes on a time scale of a few weeks. It documented the coevolution of E. coli and a virus, called T7, that can infect and kill the bacteria. The authors showed that the bacteria evolved resistance, then the virus evolved the ability to infect the resistant cells, and finally the bacteria evolved resistance to the viruses with the extended host range. Moreover, they showed that virus-sensitive and virus-resistant host genotypes coexisted because the sensitive types were better competitors for the limiting resources in the environment. That paper and others by Bruce Levin cemented my interest in using microbes to study evolution in action.

In March of 1981, about a year before I defended my dissertation, I wrote Bruce to ask if he would consider me for a postdoctoral position in his lab. I admitted I had no experience working with microbes, but I proposed an experiment. His team’s work showed that bacteria that evolved resistance to phage were outcompeted by their sensitive progenitors when those viruses were not present. I wondered whether the tradeoff was an unavoidable metabolic cost, or whether bacteria could evolve compensatory changes that reduced the cost of resistance. My proposed experiment suggested a way to look for such compensatory changes.

Bruce invited me to visit his lab and give a talk at the University of Massachusetts, Amherst, that spring. I remember him greeting me when I got off a bus at the town square and being surprised by just how young he looked. Although he was 40 years old and a full professor, Bruce could easily have passed for an undergrad. More importantly, I recall our intense discussions over the next two days with Bruce at a chalkboard, writing equations that described the growth of various interacting microbes, and using terms that I barely understood.

Despite my limited experience and knowledge of microbiology, Bruce offered me a postdoctoral position in his lab. I was thrilled, but also worried about doing research in a new field where I lacked experience and knowledge. Nonetheless, I took that leap of faith. And I’m so glad I did.

[Nelson Hairston after his retirement from UNC (left) and Bruce Levin in the mid-1980s (right).]

The Bacterial Allstars

I wrote about Stephen Jay Gould’s book, Wonderful Life, in a previous post. While that book wasn’t an inspiration for starting the LTEE, I often quote passages from it when I give talks on the LTEE, because those passages frame the big-picture question about the repeatability of evolution.

I first heard Gould speak at a multi-day conference in Irvine, California, in 1994. The conference was on Tempo and Mode in Evolution, with the talks celebrating and building upon the ideas in a landmark 1944 book of that same title written by the paleontologist George Gaylord Simpson (1902-1984).

Gould’s talk began with several pictures of dramatic newspaper headlines that read something like these:  Darwin Hammered, Darwin Rejected, and Darwin Trounced Yet Again. I remember nodding in agreement about the lack of respect for Charles Darwin and his ideas in the press, and I’m sure many of the others in attendance did as well.

But then Gould turned the tables to reveal his sly humor. These were all headlines from the sports section of Boston newspapers about ill-fated outings by Danny Darwin, who pitched for the Red Sox. Gould was not only an expert on fossils; he was an aficionado of baseball as well. In fact, he wrote many interesting and scientifically minded essays about baseball including, for example, a memorable piece on the extinction of the .400 hitter in his book Full House. (And see this interview with Gould on that subject.)

I had hoped to meet Gould at this meeting, or at least I hoped he might hear me speak when I gave a talk about the LTEE. (Here’s a link to the paper that I covered in my talk.) Alas, Gould gave his talk and then left the conference before my talk, and before I could meet him.

Luckily, though, I met Gould when he came to MSU, first as a commencement speaker in 1999, and then in 2000 when he gave a public lecture here. On that second visit, I served as one of his hosts. When I picked Gould up at the airport, I brought along two Lansing Lugnuts caps.  The Lugnuts are a local minor-league baseball team. I explained to Gould that I’d have liked to take him to a Lugnuts game, but the season had ended before his visit. I gave him one of the caps, and I asked if would autograph the other cap as a souvenir for me.

Gould hesitated for a moment. He explained he had been asked to autograph books by Darwin and others. He would sign books that he had authored, but nothing else. When he looked at the Lugnuts cap, however, he realized this was a different kind of request. And so, he signed it: “To the bacterial allstars, Stephen Jay Gould.” Now that’s a souvenir!

Gould and I also had the chance to have a meal together, just the two of us. We discussed our shared interest in the repeatability of evolution, and how our disparate study systems—fossils and flasks—could shed light on that fascinating question.

Sadly, Gould died just two years later. However, he managed to complete a massive volume, The Structure of Evolutionary Theory, shortly before his death. That 1400-page tome included a recounting of the history of evolutionary thought—informed by Gould’s collection of rare old books—as well as a synthesis of modern research in evolutionary biology from his perspective.  I was pleased and honored that he discussed the LTEE at several places in that book.

It’s a Wonderful Life

I’ve sometimes been asked whether the idea of the LTEE was inspired by Stephen Jay Gould’s book, Wonderful Life. In this bestseller, Gould put forward the idea of “replaying” evolution to explore the idea of whether evolution is repeatable. He wrote (page 48): “I call this experiment ‘replaying life’s tape.’ You press the rewind button and, making sure you thoroughly erase everything that actually happened, go back to any time and place in the past—say, to the seas of the Burgess Shale. Then let the tape run again and see if the repetition looks at all like the original.”  However, Gould then went on to say: “The bad news is we can’t possibly perform the experiment.”

Gould (1941-2002) was a paleontologist as well as an historian of science and prolific author, and he had in mind replaying life’s tape on a planetary scale over millions of years. The Burgess Shale is a geological formation in western Canada that contains fossils from about 500 million years ago. The fossils include exceptionally well-preserved early animals, many of which have body plans that are unlike any modern animals. Building on his thought experiment of replaying life’s tape, Gould pondered the potential outcomes: “If each replay strongly resembles life’s actual pathway, then we must conclude that what really happened pretty much had to occur. But suppose that the experimental versions all yield sensible results strikingly different from the actual history of life? What could we then say about the predictability of self-conscious intelligence? or of mammals?”

Of course, Gould’s experiment is impossible at a paleo-planetary scale. But at a more modest scale, one of the main goals of the LTEE is to study the repeatability of evolution. And so, I often quote from Wonderful Life when I’m giving talks about the experiment. Thus, it’s only natural that someone might wonder if Gould’s book had inspired me to start the LTEE.

In fact, though, Wonderful Life was published in 1989—a year after the LTEE began. I think I first heard about it when Mike Travisano shared some passages with me that were relevant to a paper we were writing on the roles of adaptation, chance, and history in evolution.

So, while Gould and I were thinking about similar issues, we were imagining them at vastly different scales. It’s one of the fascinating aspects of evolution that these broad categories of causality—adaptation by natural selection, chance events from mutations to asteroid impacts, and the effects of past history on future opportunities—play out at these different scales.

I was lucky to meet Gould and discuss these issues with him several years later, as I’ll describe in a future post.

New Beginnings

Greetings on this winter solstice!  The winter solstice marks a sort of new beginning, as the days become longer for the next half year, before then becoming shorter until the cycle is repeated. 

Every day, the E. coli populations in the long-term evolution experiment (LTEE) experience a cycle of renewed resources and growth followed by depletion of their food and then waiting for the next transfer event. 

On a much longer timescale, the LTEE also experiences cycles as it is passed from one scientific generation to the next. With that in mind, we’ve made a new website that reflects the beginning of the second scientific generation of the LTEE, as the populations and responsibility for their sustenance will soon pass from my lab to that of the new director, Jeff Barrick.

On this website, you can get an introduction and quick overview of the LTEE including how it works, its goals, some of the key findings, and plans for its future.  You can see a timeline of the experiment with some of the milestones and key events in its history.  You can read, watch, and listen to a few of the news stories about the LTEE.  You can find resources including protocols and links to important datasets.  You can search and find links to the publications that report findings from the LTEE itself as well as descendant experiments that have used the LTEE lines. And last, but not least, you can see the talented people who’ve done and are doing the work behind the LTEE, including propagating the populations, performing analyses, analyzing data, and reporting the findings.

We’ve probably missed some papers, and we know that we’re still missing photos for some participants. We’ve also only scratched the surface of reporting past news.  So please let one of us know if you find someone or something LTEE-related that you’d like to see included on this website.  For now, enjoy the new beginnings as seasons and generations continue onward!

Revisiting Telliamed

I started this blog, Telliamed Revisited, back in August of 2013, after attending a conference at which a colleague emphasized the value of social media in science.

I recall being questioned on Twitter by someone who expressed skepticism whether my blog would last or quickly be dropped. (Hey, I had already been running the LTEE for a quarter of a century at that point, so you’d think I’d get a little slack.) Anyhow, I said I didn’t really know, and that this blog was a personal experiment in communication.  In any case, I’ve now kept it up for six years, but with only occasional posts … about 100 in total so far.

If you want to follow a regular blog that is focused on science and related issues, I highly recommend Dynamic Ecology.  Jeremy Fox, Meg Duffy, and Brian McGill discuss interesting issues multiple times almost every week.  Impressive!

Anyhow, reflecting on my blog experiment as we head into a new decade, I was interested to see which of my posts had been viewed most often.  Here are the top 10:

• A Blast from the Past
• On the Evolution of Citrate Use
• Does Behe’s “First Rule” Really Show that Evolutionary Biology Has a Big Problem?
• Resources for People Interested in Learning about Evolution
• Luria and Delbrück, 1943, Genetics
• An Alternative to Schekman’s Boycott of Luxury Journals
• Fifty-Thousand Squared
• Thirty years is enough
• Zachary Blount on “Ham on Nye” Debate, Follow-up #3
• The Ten Commandments of Statistical Inference

Here are five more that are among my own favorites, but which didn’t make the top 10:

• On Time and Space
• If
• When We’re Sixty Four (Thousand)
• Questions from Jeremy Fox about the LTEE, part 1
• Favorite Examples of Evolution

Also, if you’re wondering about the name of this blog, see the following post:

• Telliamed: Indian Philosopher or French Missionary?

Last but not least, Happy New Year—and New Decade—to one and all!

Coach Izzo and me

Chalk up another great year for the Michigan State men’s basketball team and coach Tom Izzo. The Spartans were co-champions of the Big10 and won the conference’s grueling tournament. And in the NCAA’s March Madness, they made it all the way to the Final Four, knocking out the top-seeded team in the process.

Being a fan of this team got me thinking: Coach and I have a lot in common. We’ve both been doing our jobs, mostly at MSU, for a long time. Coach Izzo came here as a part-time assistant in 1983, becoming head coach in 1995. I was on the faculty at UC-Irvine starting in 1985, before moving here in 1991.

But the real similarities are deeper and more important:

First and foremost, we’ve both been fortunate to be surrounded by talented and hard-working students who listen to our ideas, experiment with them, develop them in their own ways, and translate them into meaningful outcomes—winning big games and making new discoveries.

That’s not to say there aren’t frustrations along the way: games lost, grants and papers rejected, grinding practice on the court and repetition in the lab, and even occasional conflicts. But our students are usually resilient—they overcome those setbacks and frustrations, and they go on to productive lives as players and coaches, researchers and teachers, and other careers as well.

We also both had mentors who helped us start our own careers. In Coach Izzo’s case, one mentor was Jud Heathcote, the previous head coach who hired him as an assistant. My mentors included my doctoral advisor, Nelson Hairston, and my postdoctoral supervisor, Bruce Levin. Coach Izzo and I also had friends who helped shape our careers early on: Steve Mariucci, who went on to become an NFL coach; and Phil Service, who did important work on life-history evolution.

Coach Izzo and I also both benefitted, I think, from early successes—again, largely due to our students—that helped establish our reputations, allowing us to retain our jobs and thrive by recruiting more talented, hard-working students. For Tom Izzo, it was players like Mateen Cleaves, Charlie Bell, and Mo Peterson who took the Spartans to the Sweet 16 in his 3^rd year as head coach and to the Final Four the next year, and who won the 1999-2000 National Championship. For me, the early students included Judy Bouma, Felisa Smith, John Mittler, Mike Travisano, Paul Turner, and Farida Vasi, and postdocs Toai Nguyen and Valeria Souza.

Coach Izzo has also had assistant coaches and staff, who I imagine do a lot of the heavy lifting. While some might eventually become head coaches of their own teams, many others labor in relative obscurity. In a similar vein, I’ve had outstanding lab managers including Sue Simpson, Lynette Ekunwe, and—for over 20 years, before retiring last year—Neerja Hajela.

Coach Izzo and I have both had deep benches—students who helped the team succeed without being in the limelight themselves. For Coach Izzo, they include the walk-ons and others who see limited action in games, but who compete against the starters every day in practice, helping everyone become even better. I think of three undergraduates who joined my lab when it was just getting started in Irvine (all Vietnamese refugees, by the way) who asked if they could work in my lab. Trinh Nguyen, Quang Phan, and Loan Duong prepared media and performed experiments like some incredible three-brained, six-handed machine, setting a high standard for everyone who followed in their footsteps.

Coach Izzo and I are nearly the same age. Retirement might be easier, but neither of us is ready for that. It’s too much fun when you’ve got talent to encourage and guide like Cassius Winston, Joshua Langford, Nick Ward, Xavier Tillman, and Aaron Henry—and on my team Jay Bundy, Kyle Card, Nkrumah Grant, Minako Izutsu, and Devin Lake.

Of course, there’s more that Coach Izzo and I have in common—we were lucky to be born into circumstances that allowed us to pursue our dreams without the obstacles that many others face.

Last but not least, Coach Izzo and I have had supportive partners who’ve accepted our peculiar obsessions and the long hours and frequent travel that our work entails.

Go Green! Go Students!!