Representing Science to My Representative

My research is funded by the National Science Foundation, including the BEACON Center for the Study of Evolution in Action. BEACON is one of a dozen or so NSF Science and Technology Centers. Today, our Representative in the US Congress, Mike Bishop, came to BEACON for 40 minutes to discuss our center—what we do, what impacts our work has, and so forth.

It was something of a “fire hose” for Mr. Bishop, with several presenters trying to convey a lot of information very quickly.  However, he was engaged and asked thoughtful questions.  I think he left with an understanding of the importance of scientific and engineering research, including how fundamental curiosity-driven research can lead to applications.

I had 10 minutes to show him my lab and explain what we do and why.  When I make a short presentation like this one, I often write out a version in advance.  I don’t read it or memorize it by any means. However, writing it out helps get my thoughts in order—removing details that aren’t important, ordering ideas into a narrative, reminding me of what I most want to convey.

I’m sure I was not as clear or coherent as the text that follows.  I offer it here because it conveys the points I tried to make in the few minutes that I had as a representative of science speaking with a representative of the people.

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I want to show you one of the experiments in my lab.  We call it the long-term evolution experiment. It’s an unusual experiment because it’s been running for over 27 years.  And we keep it going because it’s been a scientific goldmine leading to new discoveries about how bacteria change over time.

It’s important that we understand bacteria and how they evolve for many reasons. Bacteria are best known because some of them can cause dangerous infections. But many of them protect us against infections—if our guts were not filled with harmless bacteria, then the dangerous ones would have a much easier time getting established in our bodies. Some bacteria also provide nitrogen to plants and perform other essential functions in the environment, including degrading some of the wastes that we produce.  And some bacteria are the workhorses of biotechnology.

To give one example of why bacterial evolution is so important:  If bacteria didn’t evolve, we would have defeated nearly all the pathogenic bacteria on Earth with antibiotics.  But they do evolve and become resistant to our drugs, and so the pharmaceutical industry has to spend billions of dollars trying to keep up with the evolving bacteria and viruses by developing new drugs to treat infections.

It’s possible to see evolution-in-action in bacteria, like we do here, for several reasons.

• Their populations are huge.  The number of bacteria in just one of these little flasks is comparable to number of people in the United States.
• They grow really fast.  Every day, there are about 7 generations of bacteria in each of the flasks.  So each day we see the great-great-great-great-great grandkids, so to speak, of the bacteria that were in our flasks yesterday. After 27 years, the experiment has run for over 63,000 generations.
• And one more important thing about bacteria. We can freeze them and bring them back to life, and so we’ve got a frozen fossil record of the experiment.

When I started the experiment in 1988, there was no human genome project, and not even a single bacterial genome had been sequenced.  Now we go into our freezers and sequence the bacterial genomes to see how their DNA is changing over time.

The work we’ve done in this curiosity-driven experiment has inspired others who are using similar ideas and approaches to understand the rates and mechanisms of how bacteria evolve.

I’ll give two quick examples that show how our NSF-supported fundamental science gets translated into applications that are important for security and health.

First, you remember the anthrax letter attacks on Congress that occurred right after the 9/11 attacks. In the first few days after the anthrax attacks, I was contacted by the Defense Threat Reduction Agency for advice on how to identify the source of the strain used in that bioterrorism, and how to distinguish it from other related strains. And in the months that followed, I was asked for and provided advice to the FBI and other agencies investigating the attacks. Tracking the source of microbes in outbreaks—whether natural or terroristic in origin—requires understanding how they change over time.

Second, my colleague Prof. Martha Mulks studies bacteria that colonize the lungs of people with cystic fibrosis (CF).  There are about 30,000 people with this disease in the US alone.  It’s an inherited disease that makes people susceptible to lung infections and, unfortunately, those infections kill many kids and young adults with CF.  Some of the bacteria that infect the diseased lungs are not pathogens to most of us—they’re bacteria that live in soil and on plants, but when they get into the lungs of CF patients they evolve and adapt to that new environment. They also evolve resistance to the antibiotics that are meant to get rid of them. How exactly the various bacteria change to become better adapted to the CF lung environment is not known. Luckily, though, Martha Mulks and other foresighted scientists and clinicians have kept frozen samples of these bacteria over the years—just like we’ve done with the long-term experiment I described a moment ago. Now the BEACON Center is supporting work by a graduate student, Elizabeth Baird, who will analyze the DNA from old and new samples and apply some of the same approaches and methods that we’ve used and developed for the laboratory experiment to see how the bacteria have changed—how they have become resistant to antibiotics and otherwise adapted to the environment of the lungs of people who suffer from cystic fibrosis.

The bottom line is that the fundamental, curiosity-driven research that the National Science Foundation supports is also an engine for future applications—often ones that we may not even have dreamed of—as well as a training ground for the talented and dedicated young people who you can see working all around us in this lab and throughout the BEACON Center.

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Rep. Mike Bishop (MI-08) and me in the lab.  [Photo: Danielle Whitaker, MSU.]

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Through the Wormhole with Science Communication

As a scientist, I spend a lot of my time trying to communicate subtle ideas and complex results to other scientists who, to a first approximation, share my interests and vocabulary. When I’m not doing that, I also spend a fair bit of time teaching students who are learning about science and, in some cases, trying to become scientists.

But it can be fun and interesting to step outside the usual communication channels by trying to explain our scientific research to people who aren’t scientists or students.

Last fall, I was invited to explain our research on the show Through the Wormhole with Morgan Freeman. The show’s director Tony Lund spoke with me at length by phone, asking questions about scientific concepts, our work, my personal interests, etc.

Based on our conversation, Tony came up with several ideas for scenes to film, both inside and outside the lab. The people in my lab group organized the props and materials that we would need to film the scenes, and several of them also had cameo roles in the various scenes.

Tony then came to MSU, along with veteran cameraman Max Miller. They spent over 12 hours with me, filming scenes in a studio and the lab, and asking countless questions on and off camera. I was impressed by the combination of creativity and attention to detail they brought to this work. For me, it was both exciting and exhausting.

Tony then had to take the hours of film and edit it all down to just a few minutes, while adding interesting visuals and preparing the script for the distinctive style and perspective of the show’s host and narrator, Morgan Freeman.

You can see the fruit of everyone’s labor here, in this four-minute segment: Evolution is Like Poker.

My lab’s portion of the show ran a bit longer than this clip, but this is the bulk of it. A lot of time and effort went into making those few minutes of the show, but I think it was well worth it. I understand the show has over a million viewers, and I hope some of them will have a better understanding of evolution, our place in nature, and the joy of science.

So thanks Tony Lund, Max Miller, Morgan Freeman, Kim Ward in MSU’s communication office, everyone who helped with logistics and production, and all the members of the team, past and present, who have kept the LTEE going … and going … and going.

One of the Challenges—and Privileges—of Working at a Major Research University

Today is going to be difficult, but it should be interesting. There are not one, not two, but three seminars that I really want to—and will (or meant to*)—attend. They are scattered all across campus, with none in my building. I’ll also meet with one of the speakers–though I’d have liked to meet with all three if only I had unlimited time. The seminars are by:

• Lee Spector, speaking on “The Future of Genetic Programming” for the College of Engineering;
• Eugene Koonin, speaking on “Viruses and Transposons as Drivers of the Evolution of Life” for the Department of Biochemistry and Molecular Biology; and
• J. J. Emerson, speaking on “Evolution and Novelty: Exploring Adaptation from the Perspectives of Experimental Evolution and Population Genomics” for the Ecology, Evolutionary Biology and Behavior Program.

So I won’t get much of my own work done today. That’s one of the challenges—and one of the privileges!—of being at a top university like MSU, which attracts visiting speakers in so many areas that interest me. *End-of-day edit: Did I mention that having so many seminars to attend was a challenge? Ah yes, it’s in the title and at the end. Well, as it so happens, I screwed up reading my schedule today and so only made it to two of the three talks.

[This photo shows the Beaumont Tower on the MSU campus.  It was taken in May 2006 by Jeffness; it is from Wikipedia and shown here under the indicated Creative Commons license.]

Questions from Jeremy Fox about the LTEE, part 1

EDIT (23 June 2015): PLOS Biology has published a condensed version of this blog-conversation.

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Over at the Dynamic Ecology blog, Jeremy Fox asked me some interesting questions about the history, philosophy, and science of the E. coli long-term evolution experiment. Perhaps mistakenly—in terms of time management, not my interest!—I agreed to try to answer them … though over what time frame, I’m not sure. Anyhow, here is Jeremy’s first question followed by my (very) short and (too) long answers.

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• When you first started the LTEE, did you consider it to be a low risk or high risk experiment? Because I could see arguing both ways. In some ways, it’s low risk, because one can imagine lots of different possible outcomes, all of which would be interesting if they occurred. But in other ways, it’s high risk–I imagine that many of the interesting outcomes (including those that actually occurred!) would’ve seemed unlikely, if indeed they’d even occurred to you at all. Or did you not worry much about the range of possible outcomes because the experiment was basically a lottery ticket? “This’ll be cheap and not much work, let’s just do it and see what happens. Something really cool might happen, but if it turns out boring that’s ok because it wasn’t a big investment.”

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The short answer: Life was good, and I wasn’t thinking about risk. Or as they say about investing: it’s better to be lucky than smart!

The long, non-linear* answer: I’d already had success with some shorter duration, more traditionally designed experiments (e.g., Lenski, 1988), and so it wasn’t a total shot in the dark—that is, I knew the LTEE would yield data. I also knew, though, that it was an unusually abstract, open-ended, and non-traditional experiment, and that it might not appeal to some people for those reasons. But I loved (and still do) the seemingly simple (but in reality complex) questions, issues, and hypotheses that motivated the LTEE.

I never thought of the LTEE project as a “lottery ticket”, but some follow-up work that grew out of it had that feel.** And, oddly enough, there was one lottery-ticket aspect of the research early on, although that reflected a lack of preparation rather than a well-conceived feature.***

Maybe I was overly confident, but I’d also say that I was pretty sure the outcomes—whatever they might be—would be “cool.” The questions were intriguing, and there hadn’t been many, if any, previous attempts to answer them quite so directly. Data would be forthcoming, and even if the results weren’t definitive, I felt there would be some interest in trying to interpret whatever data emerged.**** Plus, I knew enough about what would happen—based on the experiments I had already done—that I was confident that the data and analyses would be informative with respect to at least some of my questions. Also, the use of microbes to study evolution in action was still uncommon, so the novelty of the approach would ensure some interest among my colleagues—although let me emphasize that Lin Chao, Dan Dykhuizen, Barry Hall, and Bruce Levin, among others, had already demonstrated the power of using microbes for experimental studies of evolutionary questions.*****

I should also say, in case it’s not obvious, that I had no idea or intention that the experiment would continue for anywhere near as long as it has lasted—nor that it might, I now hope, be running long after I’m gone. I had previously performed some experiments that lasted several hundred generations, and as I saw the dynamics and thought about the math behind the dynamics, I realized that over those time scales I might be seeing the effects of only one or two beneficial mutations as they swept to fixation. That hardly seemed satisfactory for experiments to explore the structure of the fitness landscape. So I decided the experiment should run for 2,000 generations, over which time I expected there would be at least several fixations of beneficial mutations in each population (and I was right), and that would deserve calling it long-term. That would take a little less than a year, given the 100-fold dilution and 6.6 generations of re-growth each day.

Of course, propagating the lines for 2,000 generations was one thing—running the competitions to measure fitness, analyzing the data, writing the paper, responding to reviews, all that took longer. So while the experiment began in February 1988, the first paper (Lenski et al., 1991) was not submitted until August 1989, resubmitted September 1990, accepted that November, and finally published in December 1991. Meanwhile, the LTEE itself continued and the generations ticked by. The baseline work of keeping the populations going is not that onerous—yes, somebody has to attend to the transfers every day, but once a lab team reaches a moderate size, it’s not too hard to arrange. And I lived next to the campus in Irvine, so it wasn’t hard for me to come in on the weekends and holidays … and my wife still loves me, and my kids recognized my face ;>)

You also wondered whether some of the interesting possible and actual outcomes had occurred to me when I started. Definitely not! I had made a strategic decision to make the environment of the LTEE very simple in order to eliminate, or at least reduce, certain complications (especially frequency-dependent interactions and clonal interference). And while I think my planning kept these complications from getting out of hand, the tension between the simplicity of the experimental design and all the complications has definitely been part of its interest. That tension, along with time, the evolutionary potential of the bacteria, and the smart, talented, creative** and hard-working students and colleagues have made the LTEE what I call “the experiment that keeps on giving.”

Footnotes

*Hey, that’s what footnotes are for, right?

**I’ve thought that way about some follow-on work that uses the LTEE lines, but not about the project as a whole. Here are a couple of examples of “lottery tickets” that people suggested to me, and that won big. A former postdoc Paul Sniegowski, now on the faculty at Penn, wanted to know whether the actual mutation rate itself might be evolving in the LTEE populations. Bingo! Several lines evolved hypermutability and so, curiously enough, the first mutations we ever mapped affected the mutation rate itself (Sniegowski et al., 1997). Another example: Dominique Schneider is a molecular microbiologist in Grenoble, and we’ve collaborated for over 15 years. He thought we should look at whether DNA topology—the physical supercoiling inside the cell—might have changed in the LTEE lines. Well, I thought to myself, why would it change? But Dom’s lab will do all the work, so sure, why not look? And it turns out, sure enough, that DNA supercoiling changed repeatedly in the LTEE lines (Crozat et al., 2005), and it even led us to discover a gene not previously known to affect supercoiling (Crozat et al., 2010). There’s a lesson here, by the way—work with people who are smarter, who have different interests, and who have different skills than oneself.

***I actually started two versions of the LTEE—not one experiment with two proper treatments, but two separate experiments that differed in terms of both the starting strain and the environment. Unlike the successful LTEE, I hadn’t done any previous evolution experiments with the other ancestral strain and environment. Anyhow, I soon stopped the other version when the populations evolved a phenotype that made it very difficult to work with them. In brief, the populations evolved to make pinprick-sized colonies that were next-to-impossible to count in the assays we use to measure fitness. Who needed that headache! So, in a way, I guess I had two lottery tickets: I hadn’t done the relevant prior work for one of them, whereas the one that paid off was actually a pretty strategic gamble.

****I was at UC Irvine when I started the LTEE, and Michael Rose was one of my colleagues there. His work on the evolution of aging—postponed senescence—in fruit flies (e.g., Rose 1984) was an inspiration in terms of the importance and power of long experiments. We also spent a lot of time discussing fitness landscapes, the alternative perspectives of Sewall Wight and R. A. Fisher about the dynamics on those landscapes, and what experiments might tell us. Michael didn’t design, direct, or do the lab work for the first LTEE paper, but he helped me clarify my thinking and write the first paper on the LTEE (Lenski et al., 1991). Perhaps more importantly, his interest in the questions and issues made me realize that other smart people would also be interested.

*****I used to complain, mostly in jest, that “Evolutionary biologists say I’m asking the right questions, but studying the wrong organism, and microbiologists tell me I’m studying the right organism but asking the wrong questions.” I got that sort of response occasionally, but many people from both fields were very interested and encouraging. For example, I remember David Wake telling me, after one of my first talks about the LTEE, how much he liked both the questions and the approach.

References

Lenski, R. E. 1988. Experimental studies of pleiotropy and epistasis in Escherichia coli. II. Compensation for maladaptive pleiotropic effects associated with resistance to virus T4. Evolution 42: 433-440.

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.

Sniegowski, P. D., P. J. Gerrish, and R. E. Lenski. 1997. Evolution of high mutation rates in experimental populations of Escherichia coli. Nature 387: 703-705.

Crozat, E., N. Philippe, R. E. Lenski, J. Geiselmann, and D. Schneider. 2005. Long-term experimental evolution in Escherichia coli. XII. DNA topology as a key target of selection. Genetics 169: 523-532.

Crozat, E., C. Winkworth, J. Gaffé, P. F. Hallin, M. A. Riley, R. E. Lenski, and D. Schneider. 2010. Parallel genetic and phenotypic evolution of DNA superhelicity in experimental populations of Escherichia coli. Molecular Biology and Evolution 27:2113-2128.

Rose, M. R. 1984. Laboratory evolution of postponed senescence in Drosophila melanogaster. Evolution 38: 1004-1010.

 

Science and Religion: Vive la Différence

[This post is the text of a talk that I presented on October 18, 1998, in East Lansing, Michigan, as part of a forum on “Our Evolving World: Challenge to Mind and Spirit.” This document is in the public domain and may be used without charge and without permission, provided the source is acknowledged.]

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Preface

Let me begin by thanking Glenn Johnson and Lars Clausen for inviting me to participate in this forum, and Philip Hefner for providing a thoughtful and thought-provoking view of the relation between religion and science in his book, “The Human Factor: Evolution, Culture and Religion” (Fortress Press, Minneapolis, 1993).

Pastor Clausen suggested that I begin by telling you briefly about my own research. I work in evolutionary biology, a field of study that seeks to understand the history and mechanisms by which life on Earth has changed during the past several billion years. Most of you probably first associate the study of evolution with dusty fossils, many of which demonstrate the existence of species that no are no longer alive today. Certain fossils provide striking evidence for evolution because the fossils have combinations of morphological traits that are no longer present in living organisms, yet were predicted from an evolutionary theory of relationships among modern-day species. For example, scientists have found fossil birds with exquisite feathers and hind-limbs like those of modern birds, but which also have teeth, clawed digits on their fore-limbs, and a long vertebral tail like their reptilian ancestors. Some of you may also know about the evidence for evolution that exists within the genes of all living organisms, including ourselves. The myriad similarities and differences among the genes of different organisms provide a material basis for evaluating the evolutionary relationships among all organisms, from bacteria to humans. These genetic similarities and differences enable scientists to determine which species are more closely related than others, using much the same logic and material that is used to establish paternity in lawsuits. The information in these genes provides independent support for the evolutionary derivation of birds from reptilian ancestors. By digging out fossil bones and sequencing genes using molecular methods, scientists can reconstruct historical events.

But I suspect that few of you think of evolution as an on-going process, one with consequences in our lifetime. And yet, evolution is happening all around us, sometimes with tangible repercussions for human welfare. Consider many disease-causing bacteria that have recently evolved resistance to the antibiotics that we use to treat infections. For example, Staphylococcus aureus, which is often acquired in hospitals following surgery, can cause potentially lethal infections; some strains of this species are now resistant to all but one of the antibiotics that were once available for its treatment. By the same token, many agricultural pests have evolved resistance to pesticides that we began using only in our lifetime. Indeed, while much of the public may regard evolutionary biology as abstract and far-removed from our present lives, in fact a substantial component of the costs of medicine and agriculture reflects an arms-race with our biological enemies. While we seek to control or eradicate diseases and pests using chemicals and other methods, these enemies are evolving genetic defenses against our best weapons. The evolution of these defenses by our natural enemies causes illness and economic devastation, and it forces us to spend more money to develop new means of combat.

And because evolution is occurring in the world around us, it is possible to perform experiments on evolution, just as one can in the fields of chemistry and physics. What is required for these experiments are organisms, such as bacteria, that have rapid generations and large populations, so that one can observe — on the time-scale of a student’s doctoral dissertation, for example — evolutionary changes that require many generations and that depend on infrequent genetic events. In my laboratory here at MSU, graduate students and I have monitored some 20,000 generations in bacterial populations that have been propagated for about ten years as part of one long-running experiment.

This experimental approach enables us to address certain evolutionary questions that would be difficult to resolve using a retrospective (historical) approach, such as studying fossils or comparing genes of living organisms. For example, on the theoretical side, how repeatable is evolution? That is, what are the relative roles of chance — from random mutation — and necessity — reflecting natural selection — during evolution? To address this question, we measure changes that take place when several initially identical populations of bacteria evolve in parallel in identical laboratory environments. On the applied side, are bacteria that have evolved resistance to antibiotics inferior to sensitive bacteria when they compete for resources, and hence for reproductive success, in the absence of antibiotic? If so, then this suggests that we may prevent, or at least slow, the spread of antibiotic-resistant bacteria by more judicious use of antibiotics.

One of the intriguing and powerful features of bacteria for this evolutionary research is the fact that they can be stored frozen, in a state of suspended animation. These frozen bacteria can be later revived to allow direct comparison, and even competition, with their own evolutionary descendants. Imagine if we could resurrect our own ancestors — from ten-thousand or a million generations ago — and then challenge them to a game of chess, or in the struggle for existence.

My students and I perform these experiments because we find them fascinating, and because evolution is a critically important process in the world in which we live. It is a process that has shaped our own being, yet it can also confound our efforts to shape the world for our well-being.

Response to Hefner’s Theological Theory of the Created Co-Creator

When Dr. Johnson told me that the focus of this forum would be the dialogue between science and religion, I listened politely but cautiously. I was pleased to hear this would not be another debate about evolution versus creation, and therefore would not pit science against religion. But as the magnitude of responding to Dr. Hefner has dawned on me, I’ve almost come to wish that this were a debate about evolution and creation! At least then it would be easy for me to disagree with another speaker’s position, and to feel that I had some expert knowledge to contribute.

Instead, my problem is this: I am a scientist, one with no special knowledge of either theology or philosophy. And yet I must respond to a distinguished theologian who has thought long and hard about the relationship between science and religion, and who has built on subtle philosophical underpinnings. So I begin by admitting that I am in over my head and hoping that I can swim, or at least dog-paddle, across this vast lake. Nonetheless, I do welcome this opportunity to respond, in order to express my admiration for Dr. Hefner’s work, but also to convey my own view of the relationship between science and religion. My view is somewhat different from the harmonious and integrated vision put forward by Dr. Hefner.

A good place to begin my reply is with a cartoon featuring Frank and Ernest, which appeared a few months ago (August 2, 1998). Ernest asks “What do you think of the idea of humans evolving, Frank?” To which Frank replies “I think it’s worth a try.” Instead of the familiar image about life emerging from the primordial ooze, or our descent from apes, this cartoon strikes us as funny because it depicts evolution in a forward-looking fashion, rather than the typical backward view. In fact, it does so at two different levels, at least for me. First, it is forward-looking in the literal sense of suggesting a future course of action. Second, Frank seems to be conveying the progressive view that not all is well with the world as it is, that humans bear some responsibility for the problems, and that therefore a new course of action is necessary.

I think this cartoon captures an important component of Dr. Hefner’s thesis. In his own words, and I quote, “… in the situation to which biocultural evolution has brought us … the life not only of the human species, but of the entire planetary ecosystem is made to depend on a great wager going well. This wager is that the cultural systems of information that the co-creator fashions will interface with the natural systems and with the global human culture so as to promote survival and a wholesome future.” Dr. Hefner then suggests that “… the wager is not going well. The cultural systems of information are not meshing adequately enough with other systems, and calamity is the prospect.” He therefore proposes “…revitalization of our mythic and ritual systems, in tandem with scientific understandings, so as to reorganize the necessary information. This may help us to put our world together …”

In a nutshell, I share Dr. Hefner’s profound concern for the future welfare of our species and planet. I agree with him that our species has evolved the unique ability to make decisions that profoundly influence the future of the world in which we live. And I share his view that this decision-making ability imposes — on all of us — a tremendous responsibility to do what it takes to ensure a wholesome future for our species and planet.

As an academic who values creative synthesis, in a world where narrow specialization has become the norm, I admire Dr. Hefner’s effort to integrate scientific and religious perspectives. But I am also troubled by the idea of integrating two such different ways of knowing. To clarify the reason for my discomfort, I must present my own views of the relationship between science and religion.

Evidence and Faith

What is the difference between science and religion? I think it is fair to say that one important difference is that science is based on evidence, whereas religion depends on faith. From some philosophical quarters, this distinction has been criticized as naïve, because science (like religion) also depends on certain fundamental beliefs that cannot be tested within the scientific enterprise. For example, science presumes that there is some correspondence between the material universe and our sensory perceptions of it. But science cannot actually prove that the world in which we live is “real” as opposed to a phantasm of our befuddled senses. I will admit, grudgingly, that I cannot prove the material reality of that wall behind me. But I invite anyone who doubts this assertion to try walking through the wall during the next break. Therefore, I will cling to the common-sense view that this distinction between science and religion — between reliance on evidence and faith — is an important one. (As a further complication to this distinction, some religious persons also claim evidence for their beliefs, as witnessed in recent days by thousands of pilgrims who visited a farm in Georgia last week to await a message they said was from the Virgin Mary. One of the pilgrims said he had on other occasions personally met both Jesus and God, and that they looked similar, except that God has more white hairs in his beard than does Jesus. But this religious evidence — unlike that required by science — cannot be reproduced or replicated on demand for a skeptic.)

While I hold to this difficult distinction between evidence and faith — indeed because I make this distinction — I would maintain that the existence of a supernatural God lies outside the realm of scientific inquiry. Science can only address natural forces in the material universe. In our work as scientists, we must assume that what we observe obeys natural laws, and that no supernatural force or being plays tricks with our experiments. Otherwise, interpretation of nature becomes arbitrary. This basic assumption applies to all scientific fields, from nuclear physics and inorganic chemistry to molecular genetics and evolutionary biology. Science therefore is unable to prove, or disprove, the existence of a supernatural God. Thus, while science is based on evidence and religion depends on faith, the two can coexist compatibly in our lives precisely because of their essential difference.

Yet despite the compatibility of science and religion at some level, science places constraints on what a religious person can believe about God, if that person also accepts a scientific world view. Let me emphasize that I don’t mean that science is infallible. Scientific claims are always liable to revision as new evidence, and even new ideas, emerge. Nonetheless, those of us who accept the validity of the scientific enterprise assume that science tends to converge toward some objective truth, even if convergence sometimes involves taking a step back before seeing the way to move two steps forward. Despite this inherent uncertainty of science, those who accept both science and religion as two sources of truth generally allow their understanding of science to constrain their personal vision of God the Creator.

For example, if a religious person accepts the scientific evidence that the Earth is several billion years old, and that all organisms including humans have evolved from a common ancestor, then that person must also accept the view that God the Creator was extremely subtle in the acts of creation, much more so than is indicated by a literal interpretation of Genesis or creation stories of most other religions. Within these scientific bounds, and recognizing the inability of science to answer questions about the supernatural, one might still imagine very different reasons for God’s subtle creativity: Perhaps God is playful and has allowed all nature the freedom to follow a path that is unknown even to God; or perhaps God is willful and directed the laws of natural creation so that they would lead to some ultimate purpose. But it would be in striking conflict with the scientific evidence to suggest that God the Creator took such direct actions as the creation stories would have us believe, if we take them as the literal truth.

Thus, one view of the relationship between science and religion is this: Science can say something about what God the Creator has done to bring about creation. This view is certainly not a new one. Over the centuries, and continuing to the present, many scientists have justified their studies on the ground that they are seeking the truth about the universe in which we live, one that God created and ultimately gave us the powers to explore. What better way to understand and even worship God than to investigate and understand God’s creation? The view that science provides insight into God’s creation, and by extension into God, seems to me entirely sensible — provided that one believes in the existence of God the Creator.

Science and Religion: Vive la Différence

I now want to suggest a slightly different view of the relationship between science and religion. It is an evolutionary view of their relationship within our culture that I personally find both plausible and liberating, in contrast to the scientific constraints that are placed on religious belief according to the previous view. As I explain this view, it should be apparent that there is an important shift in what I mean by religion from the way that I have used it previously, a shift from an emphasis on God the Creator to an emphasis on human morality. Importantly, this shift neither confirms nor denies the existence of God; instead, this view simply accepts the scientific impossibility of settling that issue.

While I am not a historian or a theologian, I think the case can be made that many religions have historically (and probably prehistorically) been conflicted between two distinct functions. On the one hand, religions have often sought to provide explanations about the natural world — how it came into being, and especially our own place or purpose in the world. The stories from Genesis of the creation in six days, and of the tower of Babel leading to different languages, are two familiar examples. On the other hand, religions have also sought to direct actions by explaining which behaviors were morally acceptable and which were not, and often prescribing rewards and punishments (in this life or beyond) to encourage moral behavior. The ten commandments and the parables of Jesus are examples in which religion gives moral direction. Thus, many religions, in an intellectual sense, have served two masters — understanding our place in nature and giving moral guidance.

But these two functions of religion sometimes come into conflict with one another, especially with the emergence of science as another way of explaining the natural world. This conflict has run both ways, with religious groups sometimes challenging scientific findings as heretical, and scientists (or individuals who usurped science) sometimes suggesting that their knowledge gave them special authority over issues of morality. As examples of the former, consider the trial and imprisonment of Galileo by the church for stating that the Earth revolved around the Sun; and the effort today of some fundamentalist groups to impose their creationist beliefs on the science curriculum in public schools. As examples of the latter, industrialists of the Victorian era sought to use Darwin’s principle of natural selection to justify their exploitation of the poor and weak. And Nazis borrowed pseudoscientific theories of racial differences as a supposed rationale for the irrational genocide of the Holocaust.

By viewing science and religion as two descendants of ancient religion, we can take comfort from the fact that these two interwoven realms of ancient religion — explanation of the natural world, and moral direction — continue to be present in our lives today. Moreover, by separating these two realms of understanding, each is freed from the binding constraints of the other. No longer must science be squeezed through the filter of any religious doctrine; and no longer must religion depend on justification in the natural world, which is often ruthless and unforgiving of mistakes.

Let me make it clear that I don’t believe these two realms must be kept absolutely separate. For example, we may use scientific data to inform the ethical course of action in medical practice. So, too, we need scientific information about our impact on nature, in order to weigh the moral consequences of alternative behaviors with respect to the health of our planet and all its inhabitants. And religious persons may wish to integrate a scientific understanding of the natural world into their religious framework in order to promote morality that is maximally consistent with a wholesome future, as exemplified by Dr. Hefner. By the same token, scientists ought not ignore the moral implications of their work, for example, with regard to methods of warfare or the impact of discoveries on the environment. Moreover, scientists may investigate the evolutionary origins of certain moral and religious beliefs, such as prohibitions against incest or dietary laws. And scientists may take spiritual pleasure in expanding our knowledge of the universe, whether to satisfy curiosity or to promote a wholesome future by informing effective decisions within a moral framework.

But my important point is this: Our understanding of the material world no longer depends on its agreement with any religious faith. At the same time, our moral dimension has the freedom to develop, perhaps enlightened by — but without fear of contradiction by — the natural world, which seems usually to favor selfishness over true altruism.

Conclusion

My discomfort with Dr. Hefner’s theological theory boils down to this: He weaves science and religion together so tightly as to blur the boundary between them, at least in my own reading. In a sense, he uses scientific evidence to support his religious faith; he uses what is known to support the unknowable. But this could be a hazardous enterprise. I think the same facts of evolution — with the perpetual struggle for existence and genetic rewards for selfishness — could just as easily be used to support a religion that both Dr. Hefner and I would find repugnant.

So I respect Dr. Hefner’s faith, and I admire his inclusive religious tone, even as he holds fast to the tenets of his faith. And I applaud his use of science and religion together to promote a more wholesome future for our species and our planet. But I cannot endorse his theological theory of the created co-creator, just as I could not agree with any theological theory that seeks scientific support for a matter of religious faith. Science depends on internal consistency, whereas religions span an enormous range of mutually incompatible beliefs. Some believe that God is embodied in nature, whereas others believe that God exists outside the material universe. Some believe that morality evolved from within nature, whereas others believe that morals are transcendent. Some preach tolerance, while others claim divine support for intolerance toward outsiders. Some look forward to life after death, others fear life after death, while still others view this life as the only one we have. Some even welcome the idea of an apocalypse, while others hope for generations without end.

Science can never settle these differences in faith. While individual scientists may hold diverse religious beliefs, or none at all, science is a way of knowing about the material universe only. Having evolved into two distinct cultural functions — two different ways of knowing — we can hope that science and religion together promote a wholesome future. Let the dialogue continue between science and religion. Mais vive la différence.

Postscript

I’ve spoken about the roles of science and religion in providing explanation of our place in nature and giving moral direction, but I’ve not said much about spirituality. The following poem is from a book that was written by my late mother and published a few years ago. To me, it shows the deep spirituality that can arise out of a material view of life.

---

THE FIRST GIFT

—being comprised of DNA and shared in the

first cell division, 3 to 4 billion years ago.

Take this. It’s part of me

and everything I know

about this emergent art

of getting by.

Since what I am survived

this long, this place,

my information may enable you

to live a little.

— Jean Lenski (Genesis, 1993, St. Andrews College Press)

---

This cartoon is © by Thaves  (http://frankandernest.com/cgi/view/display.pl?98-08-02). It is shown here under the doctrine of fair use.

An Absence of Posts, an Abundance of Talks, and More

Dear Reader:  No, I have not given up on this blog.  But I’ve been busy, busy, busy!

In the last four weeks alone, I have traveled to the University of Arizona, Harvard University, Duquesne University, and Princeton University.  Besides giving talks at each place (two public lectures and two academic seminars, with cumulative audiences of well over a thousand people), I have met with dozens and dozens of amazing scientists, from graduate students and postdocs to faculty both young and old.  It’s been a blast:  an exhausting blast, but a blast all the same!

And next week?  I’m hosting four terrific colleagues from two continents who will work with me to begin making sense of hundreds of newly sequenced genomes from the LTEE.

Oh, and we have some more job searches starting next week.

And did I mention?  We just had a fascinating (if I may so myself) and complex paper come out today in Science (on-line express for now) on the most deeply divergent (i.e., oldest sustained polymorphism) of the 12 LTEE populations.  And no, it’s not about the citrate eaters from population Ara–3.

Plucain, J., T. Hindré, M. Le Gac, O. Tenaillon, S. Cruveiller, C. Médigue, N. Leiby, W. R. Harcombe, C. J. Marx, R. E. Lenski, D. Schneider.  2014.  Epistasis and allele specificity in the emergence of a stable polymorphism in Escherichia coli.  Science.

It’s population Ara–2 instead, where two lineages—dubbed the Larges (L) and Smalls (S)—have coexisted for several tens of thousands of generations.  In superb research led by Dr. Jessica Plucain that she did in the lab of my long-time collaborator (and dear friend!) Prof. Dom Schneider (Grenoble, France), Jessica led the work to identify—out of hundreds of mutations—three that are sufficient to allow a “constructed” S ecotype (i.e., the ancestor plus three derived alleles) to invade and stably coexist with the evolved L ecotype.  Ecological context and specific genetic interactions are key to establishing this “half” of the polymorphism … and the other “half” of the story— what makes the L ecotype special—might well turn out to be just as complex, or perhaps even more so.

The S and L types are especially challenging (even painful!) to work with because this population became a mutator very early on—before the two lineages diverged—and so there are many, many mutations to contend with; moreover, they make colonies on agar plates that are quite challenging to score and count.  So congratulations to Jessica, Dom, and other members of Dom’s lab for their perseverance in studying this extremely interesting population.

Also on the list of authors are Prof. Chris Marx and two members of his lab.  They performed metabolic analyses showing how the carbon fluxes through the central metabolism of the S ecotype have diverged from both the ancestor and the L ecotype.  Chris was a postdoc in my lab almost a decade ago, but most of his work (then and since) has been on experimental evolution using Methylobacterium, and so this is the first paper we’ve co-authored.

There was a production error, though, in the on-line version of our paper; the final sentence of the abstract was dropped (except for one word).  The abstract, in total, should read as follows:

“Ecological opportunities promote population divergence into coexisting lineages. However, the genetic mechanisms that enable new lineages to exploit these opportunities are poorly understood except in cases of single mutations. We examined how two Escherichia coli lineages diverged from their common ancestor at the outset of a long-term coexistence. By sequencing genomes and reconstructing the genetic history of one lineage, we showed that three mutations together were sufficient to produce the frequency-dependent fitness effects that allowed this lineage to invade and stably coexist with the other. These mutations all affected regulatory genes and collectively caused substantial metabolic changes. Moreover, the particular derived alleles were critical for the initial divergence and invasion, indicating that the establishment of this polymorphism depended on specific epistatic interactions.”

[Edited on 07-Mar-2014:  The on-line PDF at Science Express now has the complete abstract.]

~~~

The picture below shows Dom Schneider and Richard Lenski in Paris in 2013.  They are holding a petri dish that Jessica Plucain made to celebrate the 25th birthday of the LTEE.

Fifty-Thousand Squared

I’ve been thinking a lot about the long-term evolution experiment (LTEE) with E. coli lately – even more than usual.  One impetus has been the paper by Mike Wiser, Noah Ribeck, and me that appeared today (14-Nov-2013) in Science (online publication in advance of print).  Another reason is that I’m working on the competitive renewal for the NSF grant that funds this experiment.

The Experiment that Keeps on Giving

Both of these have got me thinking about the long-term fate of this long-term experiment.  Should the experiment continue?  For how long should it continue?  Who will take it over when (or before) I retire?  And after that person retires, then what?  How will they sustain it?  Will they rely on the usual competitive grants?  Would an endowment be more suitable?  How does one raise an endowment?

I like to say that the LTEE is the experiment that just keeps on giving.  Between the element of time, the inventiveness of the bacteria (even in their simple, confined, little flask worlds), and the many talented students, postdocs, and collaborators who have worked on the LTEE, there seems to be no end to the insights this experiment can provide into fundamental questions about evolution.  Why shouldn’t this experiment keep on giving, even after I’m gone?

When I started the LTEE in February of 1988, I had no idea that it would continue for more than 50,000 generations.  I had previously done some other experiments that went for a few hundred generations, and I intended this one to run for at least 2,000 generations.  That would deserve the “long-term” moniker.  Although we made some fitness measurements along the way, most of the hard work comes after a milestone is reached.  That’s when one begins the intensive assays to quantify the changes that occurred.  And while we performed those assays, we continued the daily transfers.  So by the time the first paper was prepared, submitted, reviewed, revised, and published in December of 1991, the LTEE was past 5,000 generations.  And so it has gone:  new milestones, new questions, new assays, new data, new analyses, and new papers.

And the new questions keep coming based on new hypotheses of students, postdocs, and collaborators (occasionally even me), new technologies such as genome sequencing, and new observations of what the evolving bacteria have done.

Fitness Unlimited

This latest paper is an interesting one because it uses our most old-fashioned assays – the kind that was the heart of the LTEE when it started, and which also formed the core of that first paper back in 1991.  That is, the results are based on measurements of relative fitness, coupled with new models – both descriptive and dynamical.  (Although this blog post emphasizes the descriptive model, the Science paper also presents new theory showing that the descriptive model can be derived from a dynamical model of evolution that incorporates two phenomena – clonal interference and diminishing-returns epistasis – that are known to occur in the LTEE and other studies of evolving asexual populations.)

Fitness is the central phenotype in evolutionary theory; it integrates and encapsulates the effects of all mutations and their resulting phenotypic changes on reproductive success.  Fitness depends, of course, on the environment, and here we measure fitness in the same medium and other conditions as used in the LTEE.  We estimate the mean fitness of a sample from a particular population at a particular generation by competing the sample against the ancestral strain, and we distinguish them based on a neutral genetic marker.  Prior to the competition, both competitors have been stored in a deep freezer, then revived, and acclimated separately for several generations before they are mixed to start the assay proper.  Fitness is calculated as the ratio of their realized growth rates as the ancestor and its descendants compete head-to-head under the conditions that prevailed for 500 … or 5000 … or 50,000 generations.

The exciting new result is that the fitness of these evolving bacteria shows no evidence of an upper bound or asymptote.  A two-parameter power law fits the data much better than does a two-parameter hyperbolic model.  According to both models, the rate of fitness increase decelerates over time, as it clearly does.  However, the power-law model has no asymptote, whereas the hyperbolic model has an upper bound.

Even more striking and important, to my mind, is that the models differ in their predictive power.  We fit these two models to truncated datasets that included only the first 20,000 generations of data and asked how well they predicted the fitness values observed over the next 30,000 generations of data.  The unbounded power law beautifully predicts the fitness trajectory that it had not seen, whereas the asymptotic hyperbolic model underestimated later measurements.  The underestimation of the asymptotic model becomes progressively worse as the temporal data are more and more truncated; that is, the evolving bacteria consistently pass right through the “limit” predicted from previous data.  By contrast, even with only 5000 generations of data, the power-law model very nicely predicts the fitness trajectory all the way out to 50,000 generations.

A Thought-Experiment

How long can this continue?  In our paper, we present the following thought-experiment.  I’ve overseen 50,000 generations of the LTEE in my scientific life; now imagine another 49,999 generations of scientists, each one overseeing 50,000 more bacterial generations. That’s 50,000^2 generations, or 2.5 billion generations in total.  (It will take about a million years to get there.)  You’re probably thinking that the unbounded power-law model must predict some crazy high fitness that would imply a ridiculously fast growth rate.

In fact, the power law predicts that fitness relative to the ancestor will increase from ~1.7 after 50,000 generations to ~4.7 after 2,500,000,000 generations.  If the bacteria eliminate the lag time associated with the transition from starvation to growth each day (which they have already largely done), then a fitness value of 4.7 implies that the bacteria will have to reduce their doubling time from the ancestor’s ~55 minutes to ~23 minutes.  That’s very fast given that the LTEE uses a minimal medium where cells must synthesize everything from glucose, ammonium, and a few other molecules.  But it’s not so fast that it suggests the bacteria would violate some biophysical constraint.  Indeed, some bacteria can grow twice that fast, albeit in a nutrient-rich medium.

What Does the Future Hold?

I’d really like science to test this prediction!  How often does evolutionary biology make quantitative predictions that extend a million years into the future?  Maybe the LTEE won’t last that long, but I see no reason that, with some proper support, it can’t reach 250,000 generations.  That would be less than a century from now.  If the experiment gets that far, I’d like to propose that it be renamed the VLTEE – the very long-term evolution experiment.

And this prediction about the future fitness trajectory is not the only – or even the main – reason to keep the LTEE going.  Some important things in evolution simply require a lot of time.  In my presidential address to the Society for the Study of Evolution this past summer, I highlighted three findings where it proved to be important that the LTEE had continued for many years (and, if I’d had more time, I could have added more to that list).  First, it takes a very long time series to distinguish between asymptotic and non-asymptotic fitness trajectories.  Second, it took over 30,000 generations before the most dramatic phenotypic change occurred in one of the populations, which evolved the ability to use citrate – which has been present in the medium of the LTEE throughout its duration – as a second source of energy.  Third, postdoc Zachary Blount is currently studying whether the refinement of that new function is leading to changes that would qualify the citrate users as a new, or incipient, species.

What other new traits might the bacteria evolve?  Could they evolve some means of genetic exchange?  Might the within-population competitive interactions ever take a turn toward predation?  Who knows?  Only time will tell – and only if we allow time, the bacteria, and future generations of scientists to do the work of evolution and science.

Some Additional Links

• Science Story by Elizabeth Pennisi on Richard Lenski and the LTEE
• Science Podcast Interview: Sarah Crespi with Richard Lenski
• MSU Press Release and Video Interview with Michael Wiser and Noah Ribeck
• NPR’s Nell Greenfieldboyce’s Report with Audio on the Morning Edition
• Carl Zimmer on The Loom Discusses this Story and his Previous Stories about the LTEE
• NewScientist‘s Bob Holmes Reports with Comments from Joachim Krug and John Thompson
• German Public Radio (Deutschlandfunk) and Lucian Haas Report in German
• George Dvorsky Blogs about our Findings at io9
• Wiser, M. J., N. Ribeck, and R. E. Lenski. 2013. Long-term dynamics of adaptation in asexual populations. Science 342: 1364-1367.