Category Archives: Science

Thank you, Neerja

Neerja Hajela has worked with me for over 22 years as a technician and lab manager. She is extremely skillful, diligent, organized, and dedicated in her work. On top of all that, she is a wonderfully kind and warm person. Now, this is her last week before she retires.

It’s impossible to put into words all that Neerja has done for me, for everyone in the lab, for the LTEE, and for my collaborators. But let me mention a few of the things she has done.

By keeping the lab running in a smooth and orderly fashion, Neerja has enabled me to spend more of my time thinking about science, writing papers, giving talks, etc., etc. We scientists sometimes complain that we have too much to do, and so we joke that we want to clone ourselves. Well, I’ve done better—I’ve had Neerja.

Those of us with labs know that our institutions take laboratory safety very seriously, as well they should. Neerja runs such a tight ship that, on many occasions after inspecting our lab, the safety officers have made comments to the effect that they wish all labs were as neat, clean, organized, and safety-conscious as ours.

One of the challenges of the long-term evolution experiment (LTEE) with E. coli is freezer management. We now have over 30 years of samples, spread over half a dozen freezers, which provide a record of past evolution. Neerja has overseen this ever-growing collection with extraordinary care and dedication. The samples provide critical backups that allow us to restart the LTEE from a recent milestone when mishaps occur, and they provide unique research materials such as when new technologies emerge. A case in point: Michael Desai wrote me a few years ago with a request. In essence, he wanted all of the LTEE samples for metagenomic sequencing. All of them—from each population and every generation with saved samples. Since I started the LTEE in 1988, we’ve always saved duplicate samples, with one of them being a backup to be opened only in an emergency. I could send Michael the backups, perhaps, but that didn’t seem like a good idea. So I decided we should make additional sets by going into the ~1500 key samples spread over several freezers; taking a subsample of each and culturing it to produce a larger sample; splitting the new culture into ten sub-cultures; and freezing those to provide a new set for Michael as well as other sets for collaborators and institutions. It took Neerja many months to accomplish all of this, but as always, she did it with great skill and care. (Oh, and you can read about the results of Michael’s request here.)

Last, but surely not least, Neerja has done more of the daily transfers of the LTEE than anyone else. She performed her first LTEE transfer on February 5, 1996, and since then she has done well over 4,200 daily transfers. (Thanks to Zachary Blount, who went through the LTEE lab notebooks for its 30th birthday.) And when Neerja hasn’t done the transfers herself, she has organized who else is responsible for each and every day’s transfers.

Thank you, Neerja, for all that you have done for me, for everyone in the lab, for the LTEE, and for science. Everyone in the lab joins me in wishing you and Ravindra all the very best in your retirement and new home!

 

Neerja Hajela 13-Mar-2017[Neerja Hajela]

Neerja doing transfers 30-July-2018[Here’s Neerja doing yesterday’s LTEE transfer]

Neerja pointing to entries from 1996 & 2018[Neerja pointing at two of her LTEE entries: her first transfer on February 5, 1996, and the one from yesterday July 30, 2018. The lab notebooks in the background record the daily transfers since she joined the lab.]

Neerja's first LTEE entry from 1996[Close-up of Neerja’s first entry.]

LTEE protocol[Neerja’s protocols for the LTEE, mounted in the lab, so nobody makes a mistake]

Neerja enforcing discipline[And in case that doesn’t work, here’s Neerja enforcing lab discipline]

LTEE transfer board[The LTEE transfer board from earlier this year]

Tanush tower 2017[Horsing around Tanush’s plate tower]

Neerja in lab, May 2017[Neerja making copies of freezer samples]

Neerja and Rich[Neerja and me]

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Ralph Evans

Ralph Evans was an exceptionally talented young scientist and wonderful human being. He joined Bruce Levin’s lab as a doctoral student while I was a postdoc in that lab. Bruce and I met Ralph at the joint meeting of the Genetics Society of America, the Society for the Study of Evolution, and the American Society of Naturalists, which was held in St. Louis in June of 1983. That was an historic conference for anyone who studies microbial evolution because several leaders in that nascent field—including Bruce, Dan Dykhuizen, Dan Hartl, and Barry Hall—arranged a session to discuss the future of the field. Among other things, that session led to the organization of the Gordon Research Conference on Microbial Population Biology; the first of those conferences was held in 1985 and chaired by Bruce.

Among the highlights of that 1983 conference was meeting Ralph Evans. Ralph was from Texas, and he had done his undergraduate studies at Rice University. He was in graduate school at the University of Minnesota working in ecology. But after Ralph heard about this new field, he was determined to join it. I can still recall chatting with Ralph after the discussion session about the exciting things one could do with microbes to understand ecology, evolution, and infectious disease. I forget the exact timing, but Ralph soon joined Bruce’s lab at the University of Massachusetts, Amherst (with the blessing of Peter Abrams, his advisor at Minnesota). Ralph and I talked about science pretty much every day from his arrival in the lab until I left to join the faculty at the University of California, Irvine, in the late summer of 1985.

Ralph and I not only shared scientific interests, but Ralph and his wife Barbara (Bard as he called her) became wonderful friends with my wife Madeleine and me. Ralph had a soft Texas drawl, a gentle sense of humor, and a kind and sweet demeanor. He took a special liking to our toddler son Daniel—I still remember all of us walking in a snowy field as Ralph pulled Daniel in a sled. We even shared a washing machine with Ralph and Bard—they owned the machine but had no place to put it, while we had the space and a great need for one!

Tragically, as Ralph was pursuing his doctoral research, he was struck with an aggressive and ultimately lethal brain cancer. He and Bard battled through it together. She joined him in the lab to help with his work, and we sent a then-new-fangled watch that had an alarm setting to help Ralph remember when to do the next step of his experiments. Ralph had a remission, and we all had high hopes when he set off to do a postdoc with Dan Dykhuizen at Stony Brook. Alas, the cancer returned. I gave a talk at Stony Brook and got to say goodbye to Ralph, but not really—for he was in the hospital and non-responsive.

In loving memory of Ralph, and in recognition of the areas of science that most interested him, Madeleine and I have established the Ralph Evans Award. To honor Ralph’s legacy, the award may be given to either a postdoctoral researcher or senior graduate student in the Department of Microbiology and Molecular Genetics here at MSU for important contributions to the understanding of microbial evolution and its underlying ecological and genetic processes.

Thank you, Ralph, for your friendship and inspiration.

[Bruce with three of his UMass graduate students—Lone, Judy, and Ralph—in the late 1980s.]

Bruce, Lone, Judy, and Ralph

[Group photo from the first GRC on Microbial Population Biology: Bruce is front and center, and Ralph is near the back, center-left with a big smile.]

Group photo from 1985 GRC

[Ralph (far left) at a party at Bruce’s home in Amherst in the summer of 1985.]

amherst-goodbye-party-summer-1985[Here Madeleine and I are with Zachary Blount, who received the inaugural Ralph Evans Award.]

Zack, me, Madeleine 2018 Ralph Evans award

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Thirty years is NOT enough

On second thought, let’s get on with the plan for the LTEE to run for at least 50,000-squared generations!

We’re over 1/50,000th of the way there already!

And just a modest donation away! (A few million dollars in an endowment account is all it would take to keep the LTEE going into perpetuity. Contact me if you’d like to fund the experiment when it gets passed along to the next scientist, and the next, and the next, and …)

 

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Ex Laboratorium

The E. coli long-term evolution experiment, or LTEE for short, is approaching its 30th birthday, which will be on February 24th, 2018.

In honor of all the people who have worked on this project, I thought it would be neat to commission a special, but shareable, piece of art. Given the history of science and my own interest in old books, I decided that a bookplate would be appropriate for that.

So the next challenges were deciding what to depict, and who to make the image. I wondered what a smart, curious, but evolutionarily distant organism—like a cephalopod—would think about the LTEE. Who could make an image both interesting and aesthetically pleasing around that idea?

As Stephen Jay Gould wrote in his book Wonderful Life, the evolution of life—like our own individual lives—is often contingent on chance events. And luckily I stumbled via Twitter on TAOJB—The Art Of Jo Brown—during the “Inktober” one-ink-drawing-each-day-of-October event. You can see Jo’s 31 compositions from 2017 here. Looking at her website, I also discovered that she made wonderful images of cephalopods! So I wrote Jo and commissioned a work to celebrate the LTEE’s upcoming birthday!

In addition to an image, bookplates often say “from the library” or “ex libris” (Latin for “from the books”) followed by the owner’s name. I also decided that, instead of ex libris, mine would say “ex laboratorium” with my name.

But that presented another problem, because I want to give some of the bookplates to people who might like them with their own names. So I’ve asked Jo to make a second version that says ex libris along with a blank area for the recipient to write his or her name.

After Jo’s art is complete, I’ll have a printer use her drawings to make bookplates. I’ll give a few to anyone who has ever done an LTEE transfer and/or coauthored a paper based on the LTEE with me! Please let me know if you read this and are one of those folks.

I’ll also eventually post the images here, but for now you can watch Jo’s twitter feed as she shows her progress on executing the design!

ADDED on Nov. 29:  Here are links to Jo’s work in progress including one that shows steps along the way toward the first version and time-lapse videos of her drawing the second version. And the final one shows the two versions completed! Wow & wow!!

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Time fleas, with apologies to Jonathan Swift

Over on twitter, Kyle Card posted a photo of Halloween in the Lenski lab. That prompted Morgan Feeney to reply: “You mean you don’t all dress up as different generations of the LTEE? I am SHOCKED.”

 

And that got me thinking about Jonathan Swift’s rhapsody on fleas:

So nat’ralists observe, a flea

Has smaller fleas that on him prey;

And these have smaller fleas to bite ’em.

And so proceeds ad infinitum.

 

With apologies to Swift, here’s my rhapsody to the LTEE:

So ‘lutionists observe, a cell

Had older cells from which it came;

And these had older cells beget ’em.

So life proceeds and don’t forget em.

 

LTEE flasks repeating

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The Philosophers’ Way

Sometimes we forget … forget to take a break, forget to go outside, and forget to reflect on our individual and collective pasts.

After an intense three days of talks at EMBO—hearing about exciting work by diverse and superb biologists in 13-minute chunks (plus Q&A); seeing dear friends Santiago Elena, Sebastian Bonhoeffer, and Roy Kishony; and making new friends, too—I’ve got the weekend to work quietly and explore Heidelberg.

Yesterday I took the beautiful hike known as Philosophenweg, or the Philosophers’ Way. After crossing the river Neckar, a quick right on Ladenberger Strasse, then the walk up past the grand houses and physics buildings before the gardens that overlook the river, old city, and castle perched in the hills across the way. There were also intriguing and enticing paths into the woods above, but I didn’t take them yesterday.

I returned this morning, despite the chill and overcast sky. The Philosophers’ Way was as scenic as yesterday, but I hardly lingered and hustled up the path to do some exploring in the woods today, hopefully before the rain began.

Off the main path, it soon became very quiet and beautiful in a different way—no longer the dramatic views across the river, and instead the smells, sounds, and colors of autumn in a beautiful forest. The sights and sounds of leaves falling and crunching under foot, and the smells of leaves, branches, and trees returning to the soil.

The slopes and colors and smells reminded me—not exactly, but close enough—of days long past when I hiked and worked in the forests of the Nantahala mountains in North Carolina. I’d be willing to bet there are a lot of carabid beetles in the woods above the Philosophers’ Way. And they have been walking through these woods far longer than the philosophers.

As I walked up and up, there were lots of paths, and at many of the intersections old stones with names, all unfamiliar to me. In particular, this one—Thingstätte—caught my attention. It seemed kind of funny, but maybe in a dark way. I wondered what it meant, and so I took a picture to remind me to look it up when I returned to the city.

Thingstatte

My mind also wandered to these woods, and to history. There weren’t any markers of battles or massacres, but what did happen here in the 1930s and 1940s? With friends and family about 20 years ago, I went on a peaceful walk in the lovely forests near Krakow, where we came upon markers for sites of executions during the Second World War. And the violence of man (and it’s almost always men) against humanity continues—from crazed gunmen shooting on happy crowds to suicide bombers, genocidal wars, and even the threat of nuclear war.

In The Better Angels of Our Nature, Steven Pinker tells us the world is becoming less violent. But Peter Turchin warns us that history is nonlinear—it can come in waves, sometimes constructive but other times violent and destructive. I sure hope Pinker is right.

About that Thingstätte above Philosophenweg. It’s a large amphitheater in the woods, built by and for the Nazis. It was opened in 1935 with a speech by Joseph Goebbels, who called it “National Socialism in stone.” I’m glad that I turned around before I got there …

Can we all turn around now? Let’s take The Philosophers’ Way back from the brink, and get on with studying the amazing world that we all share.

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You gotta know when to hold ‘em

I was honored and humbled to speak at the Doctoral Hooding Ceremony last weekend at the University of North Carolina at Chapel Hill. I received my Ph.D. there in 1982. It was great to be back in Chapel Hill, seeing some old friends and making many new ones.

There was also one of those interesting small-world connections: UNC Chancellor Carol Folt is an ecologist. I first met Carol when she was an assistant professor at Dartmouth and I was commuting from Amherst, where I was a postdoc, to Dartmouth, to teach evolution as a sabbatical replacement for one semester. Carol is such a positive person, always smiling, and an energetic chancellor.

Anyhow, I had never given a talk like this before, so it was a challenge to prepare. Here’s what I had to say to new doctorates; maybe some of you will find it useful as well.

~~~ ~~~ ~~~

Let me begin by congratulating all of the new PhDs and recipients of other doctoral degrees. Each of you climbed a mountain that no one before you had ever climbed. That’s what made it a doctorate — your original research leading to new knowledge.

My remarks today are about constancy versus change, and about luck versus skill. They turn out to be core themes in the research I do, and they also have a lot to do with life, including the decisions we make in our professional careers.

Speaking of constancy, some things hardly seem to change. I got my degree here in 1982. And who won the NCAA men’s basketball title that year? Yep, it was the Tar Heels, just like this year.

Of course, there have also been a lot of changes since I was a student. Music, for example. When we went to the bar, we had these awesome communal listening devices, called jukeboxes. You didn’t even need headphones to hear the music.

Kool & the Gang’s “Celebration” was hot then — and it’s still a great song if you’ve got a party tonight! Cross-over country music was big, too.

Kenny Rogers had a hit called “The Gambler”, about advice from an old poker player. You’ve probably heard it. It goes like this:

“You got to know when to hold ‘em, Know when to fold ‘em, Know when to walk away, Know when to run.”

Of course, the song is about life, using poker as a metaphor. Just as in our careers and lives, poker requires making decisions in the face of uncertainty.

I had a lot of very good luck at Carolina. I went to a party where I happened to meet Madeleine, a graduate student in the School of Public Health, who is now my wife.

However, I also faced some difficulties, and while I managed to get through them, they led me to change the direction of my research.

I came to UNC to study ecology, which focuses on species and their interactions in nature. I got interested in biology when I took a non-majors course as an undergraduate at Oberlin College, and I saw the sweep of discoveries from molecular biology to vertebrate evolution.

As I contemplated graduate school, I focused on ecology because it was filled with interesting and unanswered questions that, to my naïve self back then, seemed like they wouldn’t be too hard to study.

Many ecologists are superb naturalists, including Nelson Hairston, my advisor here at Carolina, who loved the salamanders he studied, and who knew their biology inside and out.

Or Charles Darwin, who was fond of beetles. On a collecting trip, he already had two beetles he wanted, one in each hand, when he came upon a third that he also wanted to keep. He was so in love with his beetles that he popped one into his mouth to free up a hand. Well, it turns out that the one he put in his mouth was a bombardier beetle. To escape predators, they combine and squirt out two chemicals in an explosive exothermic reaction. Needless to say, Darwin lost all three of those beetles.*

As a kid, I loved being outdoors, hiking and playing sports. But I wasn’t a naturalist; I didn’t know very much about any particular group of animals or plants. At least partly because of that lack of familiarity with organisms in the wild, my first efforts at doing ecological research were failures.

Let me give one example, because it’s kind of funny — at least in hindsight. I tried to do a field experiment using praying mantises. I reared batches of them in the lab from egg cases, and then released them on small plots with two treatments. I had painstakingly cleared the vegetation around each plot by hand to keep the mantises where I put them. Well, the next time I went to see how they were doing, I couldn’t find a single one! Maybe some birds were watching me when I released the mantises, wondering: “What is this crazy guy doing?” before gobbling them up. I have no idea what happened, but that experiment was a total bust.

With hindsight, I was lucky that this project failed right away. The treatment effect I was looking for would probably not have given a significant outcome, even if the mantises had stayed put. So even failures can sometimes be valuable, by keeping us from wasting time—and by forcing us to change direction.

Maybe some of you had failed projects, too, before you found your bearings. It’s a normal part of science and scholarship, though it’s upsetting when it happens.

I had another project that also failed. But this second failure led me to the study system that became my dissertation, which was about the effects of forest cutting and competition on a certain group of insects, called ground beetles.

I loved being outdoors in the mountains of western North Carolina, although the frequent rainstorms often flooded the traps that I used to catch the beetles, drenching both the beetles and me. But this project, at last, was successful, leading to my dissertation and some papers.

But I also had doubts that this line of research was a good fit for my interests and skills. Maybe some of you are at similar points in your career.

I’m sure some of you have found work that you hope to continue for the rest of your life. If so, that’s terrific and more power to you.

Others of you might be pondering or even planning a change—using your degree and experience, but setting off in a new direction. Maybe not right away, but perhaps keeping an eye out for some opportunity that better fits your own skills and interests.

In my case, an exciting opportunity dawned in a graduate reading group, when we read a paper about the coevolution of bacteria and viruses that attack bacteria. Even though I had no experience in microbiology, I wrote the head of that lab with an idea for a project related to the paper, and—lucky for me—he hired me as a postdoc.

Before I started my new position, I was worried about working in an area where, once again, I had no experience. Well, I soon discovered that I enjoyed the work. I wasn’t good at it right away, but I liked the rhythm of a microbiology lab. Unlike praying mantises, the bacteria stayed put in their flasks. Unlike the beetles in the mountains, there weren’t any rainstorms in the lab. And sometimes you could see the results of an experiment the very next day.

Down the road, there were more hurdles. In my first year of looking for a faculty position, I applied for dozens of jobs. I got one interview and no offers. Meanwhile, the grant that funded my research wasn’t renewed, and I had a growing family to support. I even thought about leaving science — and I would have if Lady Luck hadn’t come through for me yet again.

The grant was renewed on the second try, and in my second year on the job market I got two offers. So I headed out to Irvine, California, where I started a project that continues to this day.

The project is an evolution experiment. In fact, the experiment was set up to address the same themes as my talk today—luck and skill, constancy and change—although in a scientific context, rather than a personal one.

In evolution, genetic mutations are random events, while the process that Darwin discovered—adaptation by natural selection, sometimes called “survival of the fittest”—multiplies the best competitors across the generations. I wanted to see how luck and skill—that is, mutation and selection—would play out if we could watch evolution over and over and over.

So I set up 12 populations of E. coli bacteria, all started from the same genetic stock, and I put them in identical flasks, with identical food, the same temperature, etc.

I wanted to know: Would they all change and adapt in the same way, showing the power of natural selection to shape life? Or would each population evolve along a different path, highlighting the importance of random mutation?

One thing that makes bacteria great for this experiment is that we can freeze samples and then later revive them as living cells. In essence, our freezers are time-travel machines for the bacteria, allowing us to directly compare and even compete bacteria that lived at different times.

You’ve all heard about our close relatives, the Neanderthals, who went extinct about 40,000 years ago. Some of you might know that their DNA has been recovered from fossils, allowing their genomes to be analyzed. It’s even been discovered that most of us have stretches of Neanderthal DNA in our own genomes.

But despite these amazing advances, we don’t really know what the Neanderthals were like and how similar they would be to us, if they were raised in our world. How well would they play chess, or music, or basketball? What topics would they choose for their dissertations? What would they talk about if they were at this podium?

Back to the experiment with bacteria: We’ve seen many parallel changes in the bacteria across the 12 replicate populations, showing that natural selection can sometimes make evolution predictable, despite the randomness of mutation. But we’ve also seen differences emerge, including in one lineage a surprising new ability to grow on a resource that other E. coli cannot use. And using new technologies that didn’t exist when the experiment was started, we’ve sequenced hundreds of genomes to find the mutations in samples from across the generations and populations, allowing us to test the repeatability of evolution at the level of the DNA itself.

I sometimes call it “the experiment that keeps on giving.” I originally intended the experiment to run for 2,000 generations, which would take about a year. Well, today it’s been running for almost 30 years, and the bacteria have been evolving for 67,000 generations.

This experiment keeps on giving because the bacteria keep evolving in interesting and sometimes unexpected ways, and because students bring new questions and ideas to the project. My hope is that it will continue long after I’m gone.

While the experiment gets a lot of nice press and compliments these days, there have been some obstacles along the way, as there always are in life and science.

When the first paper was submitted, one reviewer was very negative and even hostile. That reviewer wrote: “I feel like a professor giving a poor grade to a good student” — ouch! — without any suggestions for how to improve it. In fact, the reviewer even wrote: “This paper has merit and no errors, but I do not like it.” Well, I wasn’t going to fold — I liked the cards in this hand. So I wrote a rebuttal, and the paper was accepted. In fact, it went on to receive the journal’s award for best paper of the year.

A second obstacle was one of my own making. I came across another experimental system that I found fascinating, and still do — artificial life in the form of computer programs that can replicate themselves and evolve. At the time, I thought maybe the long-term experiment with bacteria had run its course. Well, unlike in poker, when you face important decisions in your research and career, you can ask other people for advice. It’s a good thing, because I was able to have my cake and eat it, too. Everyone told me: “Don’t end the experiment with bacteria. It’s too valuable.” So my lab has kept it going and it has continued to be a scientific gold mine.

Along the way, some creationists have criticized our work. Some don’t believe our results, while others believe us but say: “See, they’re still only bacteria” — as though any scientist would expect to see worms or monkeys or whatever emerge from this experiment.

There can be many reasons for misunderstandings between scientists and the public: problems of education, politics, and communication. The third problem — communication — is one that we can strive to overcome by explaining our work not only to our close colleagues, but also to the general public.

A couple of years ago I had a wonderful opportunity to communicate science to a broad public audience. I was asked by the producer of “Through the Wormhole with Morgan Freeman” to do a segment about our research on bacteria for that show.

One of the scenes had me playing poker with a few of my students. It shows how the effect of a random event—a particular card in a game of poker—depends on the context in which it occurs. The same is true in evolution. A particular mutation that might be advantageous in one species could be detrimental or even lethal in another.

Let’s have a look**:

“When there was a Queen and a King of Hearts on the table and you have the 10 and Ace of Hearts in your hand, you are set up to potentially make a Royal Flush, the most powerful hand in poker. All you need is for the final card to be the Jack of Hearts.”

I’ve been lucky in life. I was born to parents who nurtured me. I was born in a nation dedicated to life, liberty, and the pursuit of happiness. And like those of you receiving your degrees today, I was fortunate to get a superb education here at Carolina.

The French scientist Louis Pasteur — who in the 1800s disproved spontaneous generation, invented what we now call pasteurization, and developed the first rabies vaccine — said: “chance favors the prepared mind.”

Thanks to your Carolina education, and the hard work that brought you here today, you have a prepared mind. You will encounter many uncertainties, probably some obstacles, and hopefully some terrific opportunities as the cards of life are dealt to you.

Play them well: Know when to hold them, know when to fold them. And sometimes you won’t really know what to do, so you’ll just have to give it your best shot.

Thank you, and congratulations again to all of you receiving your doctoral degrees today.

~~~ ~~~ ~~~

*This story is told in the autobiographical chapter of The Life and Letters of Charles Darwin, edited by his son Francis Darwin. I should have checked the source instead of relying on my memory, as Darwin says he lost only two of the three beetles.  The details of the bombardier beetle’s chemical defense system were worked out in the 1960s by Thomas Eisner and others.

**Thanks to Tony Lund, who produced the television show, for also making the short clip that I showed in my talk. You can see a longer clip here.

 

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