Reply to Michael Behe’s gentle comment

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

Here is his comment, and my reply follows.

Behe comment 18-Feb-2019

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tiktaalik

 

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Happy birthday, Charles and Abe

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

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

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

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

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

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

LTEE flasks repeating

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

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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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Thank you, Neerja

Neerja Hajela has worked with me for over 22 years as a technician and lab manager. She is extremely skillful, diligent, organized, and dedicated in her work. On top of all that, she is a wonderfully kind and warm person. Now, this is her last week before she retires.

It’s impossible to put into words all that Neerja has done for me, for everyone in the lab, for the LTEE, and for my collaborators. But let me mention a few of the things she has done.

By keeping the lab running in a smooth and orderly fashion, Neerja has enabled me to spend more of my time thinking about science, writing papers, giving talks, etc., etc. We scientists sometimes complain that we have too much to do, and so we joke that we want to clone ourselves. Well, I’ve done better—I’ve had Neerja.

Those of us with labs know that our institutions take laboratory safety very seriously, as well they should. Neerja runs such a tight ship that, on many occasions after inspecting our lab, the safety officers have made comments to the effect that they wish all labs were as neat, clean, organized, and safety-conscious as ours.

One of the challenges of the long-term evolution experiment (LTEE) with E. coli is freezer management. We now have over 30 years of samples, spread over half a dozen freezers, which provide a record of past evolution. Neerja has overseen this ever-growing collection with extraordinary care and dedication. The samples provide critical backups that allow us to restart the LTEE from a recent milestone when mishaps occur, and they provide unique research materials such as when new technologies emerge. A case in point: Michael Desai wrote me a few years ago with a request. In essence, he wanted all of the LTEE samples for metagenomic sequencing. All of them—from each population and every generation with saved samples. Since I started the LTEE in 1988, we’ve always saved duplicate samples, with one of them being a backup to be opened only in an emergency. I could send Michael the backups, perhaps, but that didn’t seem like a good idea. So I decided we should make additional sets by going into the ~1500 key samples spread over several freezers; taking a subsample of each and culturing it to produce a larger sample; splitting the new culture into ten sub-cultures; and freezing those to provide a new set for Michael as well as other sets for collaborators and institutions. It took Neerja many months to accomplish all of this, but as always, she did it with great skill and care. (Oh, and you can read about the results of Michael’s request here.)

Last, but surely not least, Neerja has done more of the daily transfers of the LTEE than anyone else. She performed her first LTEE transfer on February 5, 1996, and since then she has done well over 4,200 daily transfers. (Thanks to Zachary Blount, who went through the LTEE lab notebooks for its 30th birthday.) And when Neerja hasn’t done the transfers herself, she has organized who else is responsible for each and every day’s transfers.

Thank you, Neerja, for all that you have done for me, for everyone in the lab, for the LTEE, and for science. Everyone in the lab joins me in wishing you and Ravindra all the very best in your retirement and new home!

 

Neerja Hajela 13-Mar-2017[Neerja Hajela]

Neerja doing transfers 30-July-2018[Here’s Neerja doing yesterday’s LTEE transfer]

Neerja pointing to entries from 1996 & 2018[Neerja pointing at two of her LTEE entries: her first transfer on February 5, 1996, and the one from yesterday July 30, 2018. The lab notebooks in the background record the daily transfers since she joined the lab.]

Neerja's first LTEE entry from 1996[Close-up of Neerja’s first entry.]

LTEE protocol[Neerja’s protocols for the LTEE, mounted in the lab, so nobody makes a mistake]

Neerja enforcing discipline[And in case that doesn’t work, here’s Neerja enforcing lab discipline]

LTEE transfer board[The LTEE transfer board from earlier this year]

Tanush tower 2017[Horsing around Tanush’s plate tower]

Neerja in lab, May 2017[Neerja making copies of freezer samples]

Neerja and Rich[Neerja and me]

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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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Thirty years is NOT enough

On second thought, let’s get on with the plan for the LTEE to run for at least 50,000-squared generations!

We’re over 1/50,000th of the way there already!

And just a modest donation away! (A few million dollars in an endowment account is all it would take to keep the LTEE going into perpetuity. Contact me if you’d like to fund the experiment when it gets passed along to the next scientist, and the next, and the next, and …)

 

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