Category Archives: Science

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.

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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.

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In Other News

Today is the 34th birthday of the LTEE, which I started on February 24, 1988. 

With the invasion of Ukraine, however, it’s not a day to celebrate.

 The LTEE will move to the capable lab and hands of Jeff Barrick this Spring, after all 12 lines have reached 75,000 generations.

Over the decades, several lines fell behind others due to cross-contamination (or concerns about the possibility), which we detected by examining the alternating Arabinose marker and seeing the resulting colony colors on TA plates. Those lines were then restarted from whole-population samples, but they would be 500 generations behind the others (or a multiple of 500 generations behind in some cases).

The picture above shows red and white colonies growing on TA agar in a Petri dish. The red colonies cannot grow on the sugar arabinose that is part of the TA medium, while the white ones can use arabinose. Half of the LTEE lines started from red colonies (Ara–1 to Ara–6), and half started from white colonies (Ara+1 to Ara+6). We alternate the red and white lines each day during their propagation. That way, if cross-contamination occurs, we can detect it by the presence of bacteria that make colonies that are the wrong color. We check colonies before every periodic freeze of the LTEE. These days, with DNA sequencing, we can also use derived mutations that are unique to each lineage to check whether a putative contamination event is real or not. (Indeed, in some populations, especially those that evolved hypermutability, the colony markers don’t work like they did when the LTEE started.) If we confirm that a cross-contamination event has occurred, we restart the affected population from the last frozen sample of that population.

So today, Devin Lake will propagate the last two lagging populations. Our lab will continue to propagate them until they, too, reach 75,000 generations. The last one should reach that goal in late May.

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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!

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Vinyl

Who remembers the old LP record albums?  They were made of vinyl, and music was recorded by etching tiny variations along a spiral groove. You put an LP onto a turntable, and you set the stylus with a fine needle into the groove. As the turntable rotated, the needle vibrated according to those tiny variations along the groove. And by amplifying that analog signal, music emanated from your speakers.    

The LP replaced an earlier format that used shellac instead of vinyl. The older format rotated on the turntable at 78 rpm, and a 12-inch diameter record allowed for only about 5 minutes of music per side. The vinyl LP allowed finer etching along a narrower groove, and these albums turned at 33 and 1/3 rpm. This technology allowed over 20 minutes of music to be recorded on each side of the disc. Hence the acronym LP, which stands for “long play.”

Why am I telling you this? I started the LTEE on February 24, 1988. A year on our planet is about 365.25 days, and so a century is 36,525 days. There have been 12,175 days from February 24, 1988, until today. That’s exactly one third of a century.

The LTEE has now revolved around our sun 33 and 1/3 times!  I think that qualifies as an LP.

An old LP album cover …
even older than the LTEE
.

Writing in the lab notebook on the occasion of the LTEE circling the sun 33 and 1/3 times.

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The Next Time

As we continue to fight the current covid pandemic caused by the SARS-CoV-2 virus, it’s not too early to begin thinking about the next pandemic.  I’ve been mulling this over for a while, and I was prompted to write this post by a twitter thread from Michael Baym.

Michael wrote about some work that he and Kaylee Mueller started, early in the pandemic, to develop a rapid colorimetric assay for covid.  They decided to curtail their work, however, when the personal risk of continuing to work in the lab seemed too great. But Michael is now wisely looking ahead, thinking about what science can do to respond even more quickly to the next pandemic.

Last February, as most of the world was just waking up to the threat posed by covid, I wrote a post with words of wisdom for pandemic preparedness. The words were written by a former Secretary of the US Department of Health and Human Services, Michael O. Leavitt, in 2007, who at that time was especially concerned about the potential for an influenza pandemic. He said: “Everything we do before a pandemic will seem alarmist. Everything we do after a pandemic will seem inadequate. This is the dilemma we face, but it should not stop us from doing what we can to prepare.”

So congratulations, and thanks, to Michael and all the others who are looking ahead. But really, all of us need to look and think ahead, using our hearts as well as our minds

Almost exactly a year ago, I was very worried about how hard this country would be hit by the pandemic.  I wrote:  “I think it is entirely possible, maybe even likely, that Europe will get hit harder by the coronavirus than China has been hit, and the US may get hit even harder than Europe.” 

I suggested that a number of epidemiological and sociopolitical issues would contribute to the United States being especially hard hit by the pandemic.  Among the former, “China’s outbreak started from a single point source in Wuhan … The US, meanwhile, has gotten many independent seeds both from China and from Europe … hundreds or even thousands of smoldering embers at first, most growing unseen and uncontained …”  Among the latter, “here in the US, we have deep social divisions, widespread skepticism of expertise (often fed by those divisions), an extremely complex political landscape with federal, state, & municipal layers of government … and many independent-minded people who are inclined to disregard advice and instructions—a wonderful attitude some of the time, but an exceptionally dangerous attitude during a pandemic.”

My worries about the next pandemic have been leaning to the problems of social division and disregard for evidence.  As terrible as this pandemic has been, the next one could be worse … even much worse.  How will people react if the next pandemic is 10 times more deadly than covid?  What if the next outbreak causes disproportionate mortality in kids or young adults?  Would the (mostly) right-wing denialists still refuse masks? Would anti-vaxxers (on the left & right) still oppose vaccination?

So, Michael Baym is right to be thinking ahead, as was Michael O. Leavitt. As a nation, we need to commit resources to support science (including the basic sciences that lead to breakthroughs in medicine) as well as our often neglected public-health system.  But we also need to find ways to come together as people, to overcome the sometimes willful ignorance, and to discuss things in a meaningful, non-conspiratorial way. 

Science and public-health workers can only do so much. The rest is up to all of us to protect ourselves, our families, and our communities from covid … and from the next pandemic … and from ourselves.

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How NOT to Write a Response to Reviewers

Last year I outlined my strategy for writing a response to reviewers.  It was intended primarily for early-career scientists, and the strategy I outlined was most relevant for a paper that had generally positive reviews.

One piece of my advice was to try to view every comment as constructive, even if you disagree with it. Reviewers are often mistaken on some points; indeed, one of the major benefits of the review process is that it calls attention to where we, as authors, have not explained ourselves clearly to the reader.

In my experience as an author and editor, it is pretty rare for a reviewer to say things that are truly hostile or otherwise inappropriate. However, it does occasionally happen that reviewers are unfair. 

I’ve blogged previously about one particularly aggressive and unconstructive review that my coauthors and I received. It was a harsh critique of the very first paper on the long-term evolution experiment with E. coli.  Fortunately, the other reviewer was very positive, and the editor requested a revision.

For some time I’ve thought about posting my response to that negative review. However, I thought the response was perhaps somewhat ill-tempered and overly long. Now, more than 30 years later, if I were advising a young scientist facing a similar review, I’d probably say: “Forget revising it for that journal. Just move on and try again elsewhere.”  But I didn’t do that myself, and I guess it worked out alright in the end.

Without further ado, here’s the response to that reviewer. (You can click on the image for each of the 4 pages to enlarge it.)


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