Category Archives: Education

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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Fun in Philadelphia

Madeleine and I just spent a few magical days in Philadelphia, where I was inducted into the American Philosophical Society. While I had heard of the APS, and knew it had a long history, I didn’t know very much about it until a few years ago, when I heard about some colleagues being elected.

The APS was founded in 1743 by Benjamin Franklin, making it the oldest learned society in the United States, and making this the 275th anniversary year. George Washington was a member. Thomas Jefferson was a member. In fact, Jefferson was President of the APS while he was also serving as Vice President and President of the United States. Barrack Obama is another member. In other words, there’s a bit of history associated with the APS.

Our hotel was almost next door to the APS, including the Benjamin Franklin Hall (with the auditorium where the meeting was held) as well as the museum and library. (More on those later.) Here’s the view from our hotel room the evening we arrived. Yes, that’s Independence Hall, where the Declaration of Independence was approved on July 4, 1776.

Independence Hall at night

The highlights of the meeting for me are almost beyond description, but here’s an attempt.

The people: From colleagues across all fields to the staff and officers of the APS, everyone was exceptionally welcoming to Madeleine and me. (Partners and spouses are as much a part of the meeting as the members.) I got to see some longtime friends from the field of evolutionary biology including David and Marvalee Wake; I got to chat with people from other fields who I’ve met before, but rarely get to see, including population biologist Joel Cohen and geneticist Michael Young; I got to meet people for the first time including APS President Linda Greenhouse, an expert on the Supreme Court, and her husband Eugene Fidell, who works in military law. And many other warm, welcoming, and interesting people.

The talks: There were several talks each day, across a wide range of fields, and they were uniformly lively and interesting. You can see the full program here, and I’ll just mention some of them that especially caught my fancy. Two talks on the history of the US census (Margo Anderson) and on political fights over its implementation (Kenneth Prewitt). Three talks on new technologies used to give voice to the voiceless (Rupal Patel), on interpreting interactions between police and motorists (Dan Jurafsky), and on future cameras that can reveal with extraordinary resolution a fingerprint on an object in a still life photo or capture the image reflected in a subject’s gaze (Shreer Nayar). Toni Morrison received the 2018 Thomas Jefferson Medal for Distinguished Achievement in the Arts, Humanities, and Social Sciences; while she could not attend, a moving letter of acceptance was read on her behalf. Bryan Stevenson received the 2018 Benjamin Franklin Medal for Distinguished Public Service and he gave an inspiring, hard-hitting, beautiful, and moving talk about his childhood and his life’s work for social justice, emphasizing the importance of proximity, memory, empathy, and persistence. You can—and really should—hear his talk on memory and justice. (The award starts at ~35 minutes, followed by a short acceptance speech, and then his hour-long talk at ~42 minutes. Set aside the time; you won’t be disappointed.)

The Treasures: Wow. The APS library includes over 13 million manuscripts, many of extraordinary historical and scientific importance. The amazing staff of the APS, including Library Director Patrick Spero and Museum Director Merrill Mason, pulled out some of the original treasures for us to see. Among them: Thomas Jefferson’s final draft of the Declaration of Independence, with his marginal comments showing the changes that were made (to Jefferson’s consternation) in order to secure approval from Congress. The only document signed by the first four US Presidents: Washington, Adams, Jefferson, and Madison. All four were members of the APS, and they signed pledges to contribute financially to a cross-continental scientific survey of the flora by André Michaux, a French botanist. Although this expedition was eventually stymied by politics, it was a precursor to Lewis and Clark. Speaking of which, another treasure we got to see was one of the journals of the Lewis and Clark expedition, with a beautiful, tiny, hand-drawn map of Cape Disappointment. On the science side, we saw Charles Darwin’s draft of the title page of The Origin of Species, which he had originally titled “An abstract of an Essay on the Origin of Species and Varieties Through Natural Selection.” We also got to see a notebook of the physicist John Wheeler, with his illustration of gravitational collapse producing a “black hole”—this was especially exciting because Wheeler was a mentor of Madeleine’s stepfather, also a theoretical physicist. As I said, wow! The APS has some of these items on display at their Museum, and you can see some of these treasures online as well.

Another treasure: Another great pleasure was spending time with my wonderful friend and MSU colleague Jack Liu. Jack holds the Rachel Carson Chair in Sustainability, and his work focuses on the complex interactions between people and the environment—from protecting pandas and their special habitat in China, to the effects of divorce on energy consumption in American households. As we rode together to and from airports, I learned Jack’s own inspirational story: from a tiny village in China to becoming the first member of his family to attend college; his experience learning English almost from scratch while a doctoral student at the University of Georgia; and becoming the first person from MSU ever elected to the American Philosophical Society.

Jack and me at APS Nov 2018

[Here’s a picture of Jack Liu and me standing below portraits of Franklin and Washington in the APS Auditorium.]

Signing the book at APS

[Here’s a picture that Jack took of me “signing the book” during my induction into the APS.]

Greeting from Linda Greenhouse

[This one, which Jack also took, shows me being officially welcomed by Linda Greenhouse, the APS President, after Robert Hauser (at left), the Executive Officer, has read a statement about my work.]

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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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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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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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