Tag Archives: evolution

Is the LTEE breaking bad?

Michael Behe has written a third book, Darwin Devolves, that continues his quixotic effort to overturn evolutionary biology. Nathan Lents, Joshua Swamidass, and I wrote a book review for Science. (You can find an open-access copy here.) As our short review states, there are indeed many examples of evolution in which genes and their functions have been degraded, sometimes conferring an advantage to the organism. However, Behe’s book largely ignores the ways by which evolution generates new functions. That’s a severe problem because Behe uses the evidence for the ease of gene degradation to support his claim that our current understanding of the mechanisms of evolution is inadequate.

This is my third in a series of posts delving into various issues where I think Behe’s logic and evidence are weak. These weaknesses undermine his position that the known mechanisms of evolution are inadequate to explain life as we see it in the fossil record and in the diversity of living species. Let me be clear: there is still much to learn about the intricacies of how evolution works, both in terms of a better understanding of the general mechanisms and unraveling all the fascinating particulars of what happened along various lineages. However, I don’t see much chance of future research upending the central role of natural selection—operating over vast time along with mutation, drift, and recombination (including various forms of horizontal gene transfer)—in creating new functions that spark the diversification of life. By contrast, Behe accepts that natural selection occurs, but he treats it almost entirely as a degradative process that weakens and destroys functions. To explain all the new functions that have arisen during evolution (and he accepts the fact that evolution has occurred for billions of years), Behe appeals to an “intelligent agent” who somehow, mysteriously has added new genetic information into evolving lineages.

In my first post, I explained why Behe’s “first rule of adaptive evolution” doesn’t imply what he says it does about evolution writ large. In particular, his overarching thesis confuses frequency over the short run with lasting impact over the long haul of evolution. In my second post, and building on the work of others, I examined a specific case involving polar bears, which Behe argued showed adaptations resulting from degradative evolution. He apparently regarded the case as so compelling that he used it as the lead example in his book, but a careful review of the science suggests an alternative explanation, in which gene function actually improved.

In this post, I examine Behe’s interpretation of findings from a long-term evolution experiment (LTEE) with E. coli bacteria that has been running in my lab for over 30 years. In short, the LTEE represents an ideal system in which to observe degradative evolution, and indeed we’ve seen examples of such changes. However, Behe overstates his case by downplaying or dismissing evidence that runs counter to his thesis.

III. Evolution of functionality in the LTEE

Recall what Behe calls “the first rule of adaptive evolution: break or blunt any functional gene whose loss would increase the number of a species’ offspring.” In support of that rule, Darwin Devolves pays considerable attention to the LTEE. Behe skillfully uses it to build his case that unguided evolution produces adaptations (almost) exclusively by breaking or blunting functional genes. The implication is that constructive adaptations—those that do not involve breaking or blunting genes—require an “intelligent agent” who has introduced new genetic information, by some mysterious process, into certain lineages over the course of life’s history.

Am I surprised that Behe uses the LTEE as one of the centerpieces of Darwin Devolves? No, not at all. Does the LTEE provide strong support for his argument? No, it does not. The LTEE fits the bill for Behe because it’s just about the best case possible to showcase his rule. But just as loss of sight in cave-dwelling organisms is a special case that won’t tell us how eyes evolved, one must be careful when extrapolating from this experiment to evolution writ large. (I say this even though the LTEE is my scientific “baby” and has been a useful model system for studying some aspects of evolution.)

The LTEE was designed (intelligently, in my opinion!) to be extremely simple in order to address some basic questions about the dynamics and repeatability of evolution, while minimizing complications. It was not intended to mimic the complexities of nature, nor was it meant to be a test-bed for the evolution of new functions. The environment in which the bacteria grow is extremely simple. The temperature is kept constant at 37C, the same as our colons where many E. coli live. The LTEE “host” is an Erlenmeyer flask, not an animal with an immune system and other defenses. There are no antibiotics present, no competing species, and no viruses that plague bacteria in nature. And the culture medium contains a single source of energy that the ancestral bacteria can use, namely the sugar glucose. In contrast, E. coli lineages have endured and adapted over millions of years to countless combinations of resources, competitors, predators, toxins, and temperatures in nature.

Indeed, the LTEE environment is so extremely simple that one might reasonably expect the bacteria would evolve by breaking many existing functions. That is because the cells could, without consequence, lose their abilities to exploit resources not present in the flasks, lose their defenses against absent predators and competitors, and lose their capacities to withstand no-longer-relevant extreme temperatures, bile salts, antibiotics, and more. The bacteria might even gain some advantage by losing these functions, if doing so saved time, energy, or materials that the cells could better use to exploit the limited glucose supply.

And just as one would expect, the bacteria have diminished or lost various abilities during the LTEE. For example, all 12 populations lost the ability to use another sugar, called ribose, and they gained a small but measurable competitive advantage as a result. Similarly, half of the lines evolved defects in one or another of their DNA repair systems, which led to hypermutability. While hypermutability resulted from a loss of function at the molecular level, it produced a slight gain in terms of the rate at which those lineages adapted to their new laboratory environment. There are undoubtedly many functional losses that have occurred during the LTEE, some that have been described and others not.

If that was all there were to the story, I might say that Behe’s portrayal was correct, but that he had missed the point—namely, that of course evolution often involves the loss of functions that are no longer useful to the organism. Biologists have known and understood this since Darwin.

But there is more to evolution than that, not only in nature but, as it turns out, even in the simple world of the LTEE. We’ve discovered cases where beneficial mutations evolved in genes that encode proteins that are essential, not dispensable, including ones involved in synthesis of the cell envelope and in structuring DNA so that it can be copied, transcribed, and packed into the tiny space of a cell. We’ve also found genes in which mutations occur repeatedly near key interfaces of the encoded proteins, in ways that imply the fine-tuning of protein functions to the LTEE environment, rather than degradation or loss of those functions.

In Darwin Devolves, Behe asserts (p. 344) that “it’s very likely that all of the identified beneficial mutations worked by degrading or outright breaking the respective ancestor genes.” He includes a footnote that acknowledges our work that suggests the fine-tuning of some protein functions, but there he writes (p. 609): “More recent investigation by Lenski’s lab suggests that mutations in a small minority (10 of 57) of selected E. coli genes may not completely break them but rather, as they put it, ‘fine-tune’ them (probably by degrading their functions).” Why does Behe assert that fine-tuning of genes occurred “probably by degrading their functions”?

Perhaps it’s because this assertion supports his claim, but more charitably I suspect the underlying reason is similar to the problematic inferences that got Behe into trouble in the case of the polar bear’s genes. That is, if one assumes the ancestral state of a gene is perfect, then there’s no room for improvement in its function, and the only possible functional changes are degradative. In my post on the polar bear case, I explained why the assumption that a gene is perfect (or nearly so) makes sense in certain situations. However, that assumption breaks down when an organism encounters a new environment, where the optimal state of a protein might differ from what it was before. Perhaps, for example, a mutation that would have slightly reduced an essential protein’s activity in the ancestral environment slightly improves its activity in the new environment. As I explained earlier, the LTEE environment differs from the conditions that E. coli experienced before being brought into the lab. It would be surprising if some proteins couldn’t be fine-tuned such that their activities were improved under the particular pH, temperature, osmolarity, and other conditions of the LTEE. It is unreasonable to simply assume that fine-tuning mutations “probably” degrade functions when evolving populations—whether of bacteria or bears—encounter new conditions.

The adaptation in the LTEE that has garnered the most public attention, though, is far less subtle. (The attention grew enormously after I had an email exchange with Andrew Schlafly, who runs the “Conservapedia” website.) After more than 30,000 generations, one of the 12 lines evolved the ability to consume citrate in an oxygen-rich environment—something that E. coli normally cannot do. Citrate, it turns out, has been a potential source of carbon and energy in the culture medium ever since the LTEE started. (The citrate is there, despite the inability of E. coli to import it from the medium, because it chelates iron and, in so doing, makes that micronutrient available to the cells.)

Sequencing the genomes of the citrate-using lineage revealed an unusual mutation—a physical rearrangement that brought together regulatory and protein-coding sequences in a new way—and genetic experiments demonstrated that mutation was responsible for this gain of function. In the line that gained the ability to consume citrate, the rearrangement involved duplicating a particular DNA segment; additional experiments showed that other types of rearrangements could also generate this ability. Even now, after more than 70,000 generations, none of the other LTEE populations has managed to evolve this new ability, despite its great benefit to the bacteria. This difficulty reflects several factors: (i) the low rate of occurrence of the necessary rearrangement mutations; (ii) the fact that efficient use of citrate requires certain additional mutations; and (iii) the absence of other, more highly beneficial mutations that could out-compete early, weakly beneficial citrate-using mutants.

To his credit, Behe does write about the lineage that evolved the ability to consume the citrate. However, he dismisses it as a “sideshow” (p. 365), because he refuses to call this new capability a gain of function. Instead, Behe writes (p. 362) that under his self-fulfilling scheme “the mutation would be counted as modification-of-function—because no new functional coded element was gained or lost, just copied.” In other words, Behe won’t count any newly evolved function as a gain of function unless some entirely new gene or control region “poofs” into existence.

But that’s not how evolution works—unless you believe, as Behe apparently does, that God or some other “intelligent agent” intervened to insert new genetic information into various lineages during the course of history. (Suffice it to say that I don’t regard this as a scientifically useful hypothesis, because I don’t think it can be tested.) Evolutionary biology doesn’t require that new genes poof into existence. Instead, old genes and their products are coopted, modified, and used in new ways—a process called exaptation. For example, crystallin proteins in the lenses of our eyes derive from proteins that performed other functions. At a larger physical scale, the wings of birds and bats derive from the forelimbs of their four-legged ancestors, which in turn derive from fins of fishes.

In short, Darwin Devolves presents a biased picture of the LTEE’s findings. Behe is overly confident in asserting that the vast majority of beneficial mutations have degraded functions, when the functional effects of most of these mutations have not been measured under relevant conditions. In any case, the experiment was designed to address issues other than molecular functionality, with the environment deliberated constructed to be as simple as possible. And yet, having closed the door on nearly all opportunities for new functions to evolve, a striking example arose in a tiny flask after a mere decade or two.

[This image shows some of the LTEE populations in their flasks. The one in the center is more turbid because the bacteria have reached a higher density after they evolved the ability to consume citrate in the culture medium.  Photo credit: Brian Baer and Neerja Hajela.]

LTEE lines centered on citrate #11

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Reply to Michael Behe’s gentle comment

Michael Behe posted a kind, brief comment on my previous post. As I began to write my reply, I realized his comment and my reply would interest many readers, and hence this separate post.

Here is his comment, and my reply follows.

Behe comment 18-Feb-2019

Good day, Mike (if I may): Thank you for your kind words. I do appreciate the fact that you remain upbeat about my lab’s research, and much other work that you describe in your writings, even though I disagree with the “big picture” that you take from the evolution literature.

I find it interesting and personally enjoyable (despite some frustrations as well) that evolution remains such a “hot” topic. That’s true scientifically, with many extraordinary discoveries in recent years—from fossils like Tiktaalik and Archaeopteryx [edit: this one was discovered long ago, but it’s better understood now] to the DNA-based evidence that Denisovans and Neanderthals contributed to the genomes of many of us living today. It’s also the case that evolution remains “hot” for many non-scientists, and that’s wonderful. Whether for secular or religious reasons, we humans are deeply interested in where we came from and how we came about. In my own small way, I take pleasure in knowing that my lab’s research helps people get a glimpse of how evolution works.

I’m concerned, though, when these scientific and religious perspectives get intertwined and confused, even when they concern those big, important questions that interest all of us. I get even more concerned when I see what I regard as non-scientific ideas (such as “intelligent agents” introducing “purposeful design” by unstated and untestable means) being used to undermine the admittedly imperfect (and always subject to revision) understanding of evolution that science provides to those who want to learn. And I am most disturbed when these confusions appear to be part of a deliberate “wedge” strategy with ulterior sociopolitical motives. People will undoubtedly have diverse views about whether scientific explanations are adequate and/or satisfying ways to understand the world, but I see danger in trying to undermine scientific methodology and reasoning to advance religious beliefs and political goals.

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Does Behe’s “First Rule” Really Show that Evolutionary Biology Has a Big Problem?

Michael Behe has a new book coming out this month called Darwin Devolves. Nathan Lents, Joshua Swamidass, and I wrote a review of that book for the journal Science. (You can also find an open-access copy of our review here.) It provides an overview of the problems we see with his thesis and interpretations. As our review states, Behe points to many examples of evolution in which genes and their functions have been degraded, but he largely ignores the ways that evolution generates new functions and thereby produces complexity. That’s a severe problem because Behe uses the evidence for the ease of gene degradation to support his overarching implication that the current scientific understanding of the mechanisms of evolution is inadequate and, consequently, the field of evolutionary biology has a “big problem.”

I won’t attempt to summarize Behe’s entire book nor our short review, as people can read those for themselves if they want. Instead, I hope to accomplish three things in this post and two more that will follow. In this first post, I explain why Behe’s so-called “first rule of adaptive evolution” does not imply what he says it does about evolution writ large. In the second post, I’ll discuss whether my long-term evolution experiment (the LTEE for short) does or doesn’t provide strong support for Behe’s position in that regard. In my third post, I’ll explain why I think that Behe’s positions, taken as a whole, are scientifically untenable.

I. Behe’s “First Rule of Adaptive Evolution” Confounds Frequency and Importance

Behe’s latest book is centered around what he calls “The First Rule of Adaptive Evolution: Break or blunt any gene whose loss would increase the number of offspring.” As he wrote in an immediate, dismissive response to our review: “The rule summarizes the fact that the overwhelming tendency of random mutation is to degrade genes, and that very often is helpful. Thus natural selection itself acts as a powerful de-volutionary force, increasing helpful broken and degraded genes in the population.”

Let’s work through these two sentences, because they concisely express the thrust of Behe’s book. The first sentence regarding “the tendency of random mutation” is not too bad, though it is overly strong. I would tone it down as follows: “The tendency of random mutation is to degrade genes, and that is sometimes helpful.” My reasons for these subtle changes are that: (i) many mutations are selectively neutral or so weakly deleterious as to be effectively invisible to natural selection; (ii) while loss-of-function mutations are sometimes helpful to the organism, I wouldn’t say that’s “very often” the case (though it may be in some systems, as I’ll discuss in part II); and (iii) even those degradative mutations that are not helpful on their own sometimes persist and occasionally serve as “stepping stones” on the path toward new functionality. This last scenario is unlikely in any particular instance, but given the prevalence of degrading mutations it may nonetheless be important in evolution. (This scenario does not fit neatly within the old-fashioned caricature of Darwinian evolution as only proceeding by strictly adaptive mutations, but it is certainly part of modern evolutionary theory.)

Behe’s next sentence then asserts the power of the “de-evolutionary” process of gene degradation. This is an unjustifiable extrapolation, yet it is central to Behe’s latest book. (It’s not the sort of error I would expect from anyone who is deeply engaged in an earnest effort to understand evolutionary science and present it to the public.) Yes, natural selection sometimes increases the frequency of broken and degraded genes in populations. But when it comes to the power of natural selection, what is most frequent versus most important can be very different things. What is most important in evolution, and in many other contexts, depends on timescales and the cumulative magnitude of effects. As a familiar example, some rhinoviruses are the most frequent source of viral infections in our lives (hence the expression “common cold”), but infections by HIV or Ebola, while less common, are far more consequential.

Or consider an investor who bought stocks in 100 different companies 25 years ago, of which 80 have been losers. Ouch? Maybe not! A stock can’t lose more than the price that was paid for it, and so 20 winners can overcome 80 losers. Imagine if that investor had picked Apple, for example. That single stock has increased in value by well over 100-fold in that time, more than offsetting even 80 total wipeouts all by itself. (In fact, research on the stock market has shown the vast majority of long-term gains result from a small minority of companies that, like Apple, eventually become big winners.)

In the same vein, even if many more mutations destroy functions than produce new functions, the latter category has been far more consequential in the history of life. That is because a new function may enable a lineage to colonize a new habitat or realm, setting off what evolutionary biologists call an “adaptive radiation” that massively increases not only the numbers of organisms but, over time, the diversity of species and even higher taxa. As one example, consider Tiktaalik or some relative thereof, in any case a transitional kind of fish whose descendants colonized land and eventually gave rise to all of the terrestrial vertebrates—amphibian, reptiles, birds, and mammals. That lineage left far more eventual descendants (including ourselves), and was far more consequential for the history of life on Earth, than 100 other lineages that might have gained a transient advantage by degrading some gene and its function before eventually petering out.

Asteroid impacts aren’t common either, but the dinosaurs (among other groups) sure felt the impact of one at the end of the Cretaceous. (There remains some debate about the cause of that mass extinction event, but whatever the cause its consequences were huge.) Luckily for us, though, some early mammals survived. Evolution often leads to dead ends, sometimes as a consequence of exogenous events like asteroids, and other times because adaptations that are useful under a narrow set of conditions (such as those caused by mutations that break or degrade genes) prove vulnerable over time to even subtle changes in the environment. It has been estimated that more than 99% of all species that have ever existed are now extinct. Yet here we are, on a planet that is home to millions of diverse species whose genomes record the history of life.

Summing up, Behe is right that mutations that break or blunt a gene can be adaptive. And he’s right that, when such mutations are adaptive, they are easy to come by. But Behe is wrong when he implies these facts present a problem for evolutionary biology, because his thesis confuses frequencies over the short run with lasting impacts over the long haul of evolution.

[The picture below shows the Tiktaalik fossil discovered by Neil Shubin and colleagues.  It was posted on Wikipedia by Eduard Solà, and it is shown here under the indicated Creative Commons license.]

Tiktaalik

 

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Happy birthday, Charles and Abe

Charles Darwin was born into wealth and privilege in England 210 years ago, while across the ocean on the same day Abraham Lincoln was born to a poor family in Kentucky.

Besides the coincidence of their birthdays, there are other interesting connections. Lincoln is known, of course, for preserving the Union and freeing slaves through the Emancipation Proclamation. But Lincoln also signed the law that established the National Academy of Sciences, which provides pro bono scientific advice to the federal government. And while Darwin is known for his work on evolution, he was also a prominent overseas voice in the abolitionist movement. During the voyage of HMS Beagle, Darwin had a heated argument with the captain, Robert FitzRoy, who defended the institution of slavery.

Darwin was onboard the ship as a gentleman naturalist, but the voyage was far from easy. Planned as a 2-year expedition, it was almost 5 years before 27-year-old Darwin returned to England in 1836. He was frequently seasick and, back home, often ill. Nevertheless, his observations, specimens, and notes laid the groundwork for his thinking that culminated with On the Origin of Species in 1859. That book presented Darwin’s evidence for descent with modification (what we now call evolution), and it put forward a mechanism—natural selection—that explains how species acquire traits that fit them to their environments.

Many of us first encounter the idea of evolution as children, when we see pictures or fossils of dinosaurs and other long-ago creatures. But evolution isn’t confined to the past; it continues to occur all around us. Some ongoing evolution causes problems for our health and wellbeing, such as pathogenic microbes evolving resistance to antibiotics. In many cases, though, evolution is used to solve problems in agriculture, biotechnology, and engineering. For example, Frances Arnold won a 2018 Nobel Prize in Chemistry for her work using evolution to generate valuable enzymes with improved and even new functions.

In my lab, we study evolution in action using bacteria, taking advantage of their rapid generations. We can freeze and later revive living cells, allowing us to compare organisms from different generations—in essence, time travel! In an ongoing experiment I started in 1988, we’ve watched 12 populations of E. coli evolve for over 70,000 generations. We can quantify the Darwinian process of adaptation by natural selection, and we’ve sequenced the bacteria’s genomes to understand the coupling between adaptation and genotypic evolution. We’ve even seen the emergence of a new metabolic function that transcends the usual definition of E. coli as a species.

It’s amazing just how much evolution has taken place during a few decades in these small flasks. It leaves me with awe at what evolution has achieved over the last four billion years on our planet … and with wonder about what more will unfold in the fullness of time.

LTEE flasks repeating

This post was written for the National Academy of Sciences Facebook page, where it also appears.

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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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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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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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