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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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Thirty years is enough

The LTEE has run for over 30 years and almost 70,000 generations. It’s time to shut it down, as of today.

It’s been a hell of a lot of work, and we have almost nothing to show for it. As some astute commentators have noted around the web, the creatures in the flasks are still just bacteria—creatures, just as they were created.

If you read the first LTEE paper*, you’ll see we predicted the bacteria should become yeast by about 5,000 generations, nematodes at 15,000 generations or so, and fruit flies by 30,000 generations, maybe 35,000 at the outside.

After that, we’d have to stop the experiment anyhow, because we wouldn’t be able to freeze and bring them back alive any longer.

Plus, we’d have to get IRB approval for human experimentation if we ran it much past 50,000 generations.

Well, we’ve given the LTEE all this time, and still … they’re just bacteria. I guess we’ve proven that Charles Darwin was wrong after all.

As an astute reviewer pointed out when we submitted that first paper, “I feel like a professor giving a poor grade to a good student …” I should’ve listened and quit way back then. It would’ve saved everyone a lot of time and effort.

Now it’s going to be a hell of a lot of work next week emptying the freezers and autoclaving all those samples.

*Lenski, R. E., M. R. Rose, S. C. Simpson, and S. C. Tadler. 1991. Long-term experimental evolution in Escherichia coli. I. Adaptation and divergence during 2,000 generations. American Naturalist 138: 1315-1341.

 

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What Was I Thinking?

The LTEE has run for over 10,000 days and almost 67,000 generations. It’s time to shut it down, as of today.

It’s been a hell of a lot of work, and we have almost nothing to show for it. As some astute commentators have noted around the web, the creatures in the flasks are still just bacteria—creatures, just as they were created.

If you read the first LTEE paper*, you’ll see we predicted the bacteria should become yeast by about 5,000 generations, nematodes at 15,000 generations or so, and fruit flies by 30,000 generations, maybe 35,000 at the outside.

After that, we’d have to stop the experiment anyhow, because we wouldn’t be able to freeze and bring them back alive any longer.

Plus, we’d have to get IRB approval for human experimentation if we ran it much past 50,000 generations.

Well, we’ve given the LTEE all this time, and still … they ’re just bacteria. I guess we’ve proven that Charles Darwin was wrong after all.

As an astute reviewer pointed out when we submitted that first paper, “I feel like a professor giving a poor grade to a good student.”  I should’ve listened and quit way back then. It would’ve saved everyone a lot of time and effort.

Now it’s going to be a hell of a lot of work next week emptying the freezers and autoclaving all those samples.

* Lenski, R. E., M. R. Rose, S. C. Simpson, and S. C. Tadler. 1991. Long-term experimental evolution in Escherichia coli. I. Adaptation and divergence during 2,000 generations. American Naturalist 138: 1315-1341.

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63,000 Strong

Ever wonder about those big numbers posted in a window in that tall building on the east side of Farm Lane, across from the entrance to the MSU Dairy Store?

Right now, the digits read 63000. That’s the number of generations in an experiment that’s been running in my lab for over a quarter century.

We call it the LTEE, which stands for the Long-Term Evolution Experiment. There are 12 populations of E. coli bacteria in the experiment, and they all started from the same strain.

Every day—weekends and holidays included—a member of my team takes 1% of the cells in each population and puts them in a flask with fresh food. Over the next 24 hours, the population grows 100-fold and then runs out of food. These dilutions and renewals go on day after day, week after week, month after month, year after year, decade after decade. I hope the experiment will continue long after I’m gone, so that someday someone can write “and century after century.”

Bacteria grow by binary fission: 1 cell makes 2 cells, 2 cells make 4, 4 make 8, etc. So the 100-fold growth in the fresh medium represents about 6.6 doublings, or generations, every day. (There’ve been some interruptions since the LTEE began in 1988, but not many.)

Now consider a bacterial cell that gets a mutation in its DNA that lets it acquire more food and grow a little faster. That cell will leave more descendants than its competitors—that’s adaptation by natural selection. Over time, the bacteria are becoming stronger and fitter in their flask-worlds.

By watching the 12 populations evolve, we can answer questions about the dynamics and repeatability of evolution in a group of organisms—bacteria—that are essential for life on Earth as well as important players in health and disease. We measure the growth rates of the bacteria, we sequence their DNA, and we see just how much evolution can achieve even in short order.

Oh, about the sign. Zachary Blount is a talented postdoc who works on this project, and he likes to have fun with science. He put up the window display which, if you look closely, has a picture of Charles Darwin on the left, “The E. coli Long-Term Evolution Experiment” over the number, and “Generations and Counting” to the right. Every 1,000 generations or so, Zack updates the sign.

63K window

[Photo credit: Zachary D. Blount]

Note:   This piece first appeared at eastlansing.org after an invitation from Alice Dreger to explain the numbers in the window to our community.

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Erdös with a non-kosher side of Bacon

Erdös number

Paul Erdös was a prolific and important mathematician. He also had hundreds of collaborators from around the world who coauthored papers with him.

Years ago, Casper Goffman explained an idea, called the Erdös number, that describes the “collaborative distance” between Erdös and someone else, where that distance is defined by the smallest number of steps based on coauthored papers. Erdös himself has an Erdös number of 0, while the 511 mathematicians who wrote papers with Erdös have an Erdös number of 1. One of these people is Persi Diaconis, a professional magician and Stanford mathematician specializing in probability theory.

Over 9,000 people have Erdös numbers of 2, meaning they wrote a paper with one or more of Erdös’s coauthors but never wrote a paper with Erdös himself.  Two of these people are Berkeley professors Bernd Sturmfels, in the field of algebraic geometry, and Lior Pachter, a computational biologist.  (Sturmfels coauthored three papers with Diaconis, and he wrote other papers with two more people with Erdös numbers of 1.  Pachter wrote several papers with mathematician Daniel Kleitman, an Erdös coauthor.)

In 2007, I coauthored a paper with Pachter and Sturmfels in which we analyzed epistatic interactions to describe the geometric structure of a fitness landscape:

Beerenwinkel, N., L. Pachter, B. Sturmfels, S. F. Elena, and R. E. Lenski. 2007. Analysis of epistatic interactions and fitness landscapes using a new geometric approach. BMC Evolutionary Biology 7:60.

So that paper gives me an Erdös number of 3.

Bacon number

A group of students later came up with the idea of a Bacon number, a Hollywood version of the Erdös number that equals the smallest number of film links separating any other actor from Kevin Bacon. (Bacon had been previously described as the “center of the Hollywood universe” after a 1994 interview in which he said he worked with everybody in Hollywood or someone who’s worked with them, according to Wikipedia.)

So Kevin Bacon has a Bacon number of 0, while actors who have appeared in a film with him have Bacon numbers of 1. An actor who appeared in a film with any actors who appeared with Bacon, but not in a film with Bacon himself, have a Bacon number of 2.

Morgan Freeman has a Bacon number of 1 based on a 2013 documentary film called “Eastwood Directs: The Untold Story.” (You missed that one? Me, too.) Well, a couple of weeks ago, I appeared in an episode of the show “Through the Wormhole with Morgan Freeman.”

Erdös-Bacon number

Now there’s a really special number called the Erdös-Bacon number, which is the sum of a person’s Erdös and Bacon numbers. Not many people have an Erdös number, and not many have a Bacon number. And very few people have an Erdös-Bacon number because you have to have written a math or science paper and appeared in a film, and of course with known connections to Erdös and Bacon along both paths.

Cornell mathematics professor Steven Strogatz has an Erdös-Bacon number of just 4, having appeared in a TV documentary film with Kevin Bacon called “Connected: The Power of Six Degrees.” Of course, that film is about the very sort of mathematical links we’re talking about here!

So someone just suggested to me that I now have an Erdös-Bacon number of 5. If so, that would put me ahead of such luminaries as Carl Sagan and Richard Feynman! Awesome!!

The fine print

As I was looking into this exciting possibility, I discovered a website called “The Oracle of Bacon.” It seems to be the semi-official arbiter of Bacon numbers, and it says: “We do not consider links through television shows, made-for-tv movies, writers, producers, directors, etc.”

That documentary about Clint Eastwood, with both Morgan Freeman and Kevin Bacon in it, apparently doesn’t qualify.  So Morgan Freeman’s Bacon number rises to 2 (via many different paths through his many major films).

Even worse, though, my Bacon number evaporates entirely, since my link to Kevin Bacon goes through my appearance on a television show with Morgan Freeman.

So there you have it. I have an officially non-kosher Erdös-Bacon number of 5.

I guess I can live with that.

But if Kevin Bacon, Morgan Freeman, or any of their Hollywood friends invites me to appear in a real film, I’ll probably accept!

~~~

Note:  It looks like Steven Strogatz’s Erdös-Bacon number of 4 is also compromised because his Bacon number is through a TV movie.  You need to use non-default settings for it to show up on The Oracle of Bacon website.  But maybe it’s less non-kosher, since it was a TV movie, not just a TV show.

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Tiny Things that Live in Little Bottles

As I mentioned in my previous post, it can be a fun challenge to explain your scientific research to people who aren’t scientists.

A week or so ago I came across a website that challenges you to explain something complicated using only the thousand most commonly used words.

So here’s my effort about our long-term evolution experiment with E. coli:

My team works with really tiny things that live in little bottles. We watch the tiny things change over time – over a really long time. The tiny things that do the best have learned to eat their food faster and faster, before the other guys can eat their lunch, so to say.  Well, the tiny things don’t really learn, but it’s kind of like learning – and even better, the best ones pass along what they learned to their kids.  A really cool guy came up with the idea of how this works more than a hundred years ago. My team’s work shows he got it pretty much right. But there’s a lot of stuff he didn’t know, and we’re figuring that out, too.

Several other biologists followed up including Nicole King, Graham Coop, and Josie Chandler (the links are to the simple-words-only descriptions of their own research).

Give it a try, and add your contributions in the comments below!

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A Day in the Life of …

Today was a great day – busy and wonderful. Pretty typical, I’m happy to say, though a bit busier than usual but all of it great.

Woke up to beautiful Spring day in East Lansing and walked 1.7 miles to work at MSU.

Did the usual email stuff.

Worked on getting ready for teaching for a class on evolutionary medicine taught by my colleague Jim Smith. Today’s focus will be the paper by Tami Lieberman et al. on the evolution of Burkholderia dolosa in cystic fibrosis patients during an outbreak in Boston. Last night I re-read the paper for the umpteenth time, and I still enjoyed it. Today I organized a series of questions for the students – a very interactive and smart group – around three parts.

Part I: Some background about CF, the inheritance of this disease, the frequency of the disease, how that frequency allows one to estimate the frequency of carriers, why the allele might be so common (not understood), side questions about sickle-cell anemia and why it’s so prevalent, and why, if it’s inherited, the paper we read is all about infections.

Part II: Preparing slides so we could work our way, figure by figure and panel by panel, through all of the main points in Lieberman et al.  (Reminder: Explain to students how scientific papers are often written around figures.  Once the figures and tables are there, then start on the results, etc.)

Part III: Follow up questions about the paper, the system, the interface of epidemiology and evolutionary biology, prospects for the future of this field and the students’ careers (most in this class are premed, many with a research bent), etc. And whatever questions they might want to ask of me.

Sometime in the middle of doing all that: Chatted with second-year grad student Jay Bundy, who is reading some of Mike Travisano’s terrific earlier papers on the LTEE. Specifically, why do we sometimes express fitness as a ratio of growth rates (measured in head-to-head competitions) and sometimes as a difference in growth rates?

Also in the middle of doing all that: Had phone conversation with former Ph.D. student Bob Woods, now also an M.D. specializing in infectious disease, about a faculty job offer he has (congrats, Bob!), some of the issues he needs to clarify or negotiate, and some of the amazing work he’s now doing on the population dynamics and evolution of nasty infections.

Email from grad student Mike Wiser that our paper, submitted to PLOS ONE, has been officially accepted. We had posted a pre-submission version at bioRxiv – now it’s gone through peer-review and revisions and is accepted for publication. Congrats, Mike!

Got a draft of the fourth and final chapter of Caroline Turner’s dissertation. The first three chapters are in great shape. Congrats, Caroline! With teaching looming, I had only time to review the figures, tables, and legends on this one, and made some small suggestions. On to the text tomorrow … It’s a beautiful body of work on two fascinating aspects of the interplay between ecology and evolution that have emerged in the LTEE and another evolution experiment that Caroline performed. Stay tuned for these papers!

Took a phone call from an MSU colleague who has friend with a child in high school who is interested in microbiology, who is visiting MSU, and who wanted to see the lab. Yikes, I gotta run teach! But postdoc Zack Blount kindly agreed to give a guided tour as I headed off to teach.  Thanks, Zack!

Beautiful day continues as I walk to teach in another building. Touch base with Jim Smith about what I plan to cover.

Two straight hours of teaching (one 5-minute break) in an overly hot room. Almost all of it interactive, with me asking questions and the students conferring in small groups and then responding. Very interactive, very bright students! The two hours were nearly up, with little time for my third, post-paper set of questions. But all of the students stayed (despite the beautiful weather, hot room, and the dinner hour at hand) an extra 15-20 minutes for a couple of my questions and some great ones from them about the LTEE and the future prospects for microbial evolution in relation to medicine.

It’s 6:20 pm: I’m mentally exhausted but equally invigorated. Beautiful Spring day continues as I walk home. I’m greeted by our lovely hound, Cleopatra. Exercise and feed her. Then an even more lovely creature, Madeleine, returns home and I greet her.

Check email before dinner. Find that paper with grad student Rohan Maddamsetti and former postdoc Jeff Barrick has been provisionally accepted, pending minor revisions, at Genetics. We posted a pre-submission version of that paper, too, at bioRxiv. Though we still need to do some revisions, I think it’s fair to offer congrats to Rohan and Jeff, too!

Time to crack open a bottle of wine and have some dinner. Fortunately, some of the pre-packaged dinners are pretty tasty and healthy, too, these days ;>)

Refill wine glass. Sit down and start to write a blog on a day in the life of …

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