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Richard Lenski and Citrate Hype — Now Deflated

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Dishonesty comes in degrees, from the white lie told to spare another’s feelings to criminal fraud for one’s own financial gain. Somewhere in the middle lies hype in science. Certainly a bit of innocent, accentuate-the-positive spinning of research results can help a scientist catch people’s attention. Unfortunately, that can escalate into hucksterism that seriously exaggerates the importance of the work.

Most scientists aren’t even tempted to try it, because most areas of research aren’t sexy enough to pull it off. It is a problem, however, for those who work on topics that catch the news media’s attention: cures for cancer; cloning; grand theories of the universe; and, of course, evolution.

Which brings us to Michigan State’s Richard Lenski. As longtime readers of Evolution News and Views well know, to study evolution, for more than 25 years Lenski’s lab has continuously grown a dozen lines of the bacterium E. coli in small culture flasks, letting them replicate for six or seven generations per day and then transferring a portion to fresh flasks for another round of growth. The carefully monitored cells have now gone through more than 60,000 generations, which is equivalent to over a million years for a large animal such as humans. (It’s dubbed the Long Term Evolution Experiment — LTEE.) As I’ve written before, the work itself is terrific. However, the implications of the work are often blown seriously out of proportion by a cheerleading science news media eager for stories to trumpet.

In 2008 Lenski’s group reported that after more than 15 years and 30,000 generations of growth one of the E. coli cell lines suddenly developed the ability to consume citrate, which for technical reasons had been present in the liquid culture medium. Later work by the Michigan State team showed the ability was due to the duplication and rearrangement of a gene for a protein that normally imports citrate into the cell, but only when no oxygen is present. The mutation allowed the protein to work when oxygen was present, as it was throughout the LTEE.

It was an interesting, if modest, result — a gene had been turned on under conditions where it was normally turned off. But the authors argued it might be pretty important. In their paper they wrote that the mutant’s ability could be the result of “historical contingency” — that is, a rare, serendipitous event that might alter the course of evolution. They also remarked that, since an inability to use citrate in the presence of oxygen had been a characteristic used to help define E. coli as a species, perhaps the mutation marked the beginning of the evolution of a brand new species.

One scientist who thought the results were seriously overblown was Scott Minnich, professor of microbiology at the University of Idaho and — full disclosure — a colleague of mine as a Fellow at Discovery Institute’s Center for Science & Culture. Minnich knew that decades ago the microbiologist Barry Hall had isolated an E. coli mutant that could also use citrate after only a few weeks of growth (also cited in Lenski’s paper), and that other studies had shown mutants could be isolated rapidly if they were selected directly — that is, if they were grown where the only available food source was the selecting substrate such as citrate, rather than a mixture of the selecting substrate plus glucose, as in Lenski’s experiment.

So Minnich’s lab re-did the work under conditions he thought would be more effective. The bottom line is that they were able to repeatedly isolate the same mutants Lenski’s lab did as easily as falling off a log — within weeks, not decades. In an accompanying commentary highlighting the Idaho group’s paper in the Journal of Bacteriology, the prominent UC Davis microbiologist John Roth and his colleague Sophie Maisnier-Patin agreed that Lenski’s “idea of ‘historical contingency’ may require reinterpretation.”

Richard Lenski was not pleased. Although in a response on his blog he acknowledged up front that the Idaho group’s science was “fine and interesting,” he insisted that yes the mutation was too historically contingent. Roth and Maisner-Patin’s comments to the contrary supposedly represented “a false dichotomy.” After all, historical contingency just “means that history matters,” and whether Lenski’s cells developed the mutation clearly depended on how they had been treated in his lab. Ipso facto, it was contingent.

But of course it’s vacuous to say simply that “history matters.” Any near-certain outcome can be prevented if necessary conditions for it to occur aren’t present. A ball will always roll down a hill — unless someone puts a barrier in front of it. The fact that the Minnich lab easily and repeatedly obtained the same results with multiple bacterial strains and growth conditions shows they are not some special example of historical contingency, if that phrase has any nontrivial meaning at all. Rather, under the right conditions it’s a humdrum, repeatable result.

Lenski also tried to split hairs over the question of speciation. He faulted Minnich for writing skeptically of Lenski’s citrate mutation, “This was interpreted as a speciation event.” Lenski countered that in their initial paper his group had only been wondering out loud if the mutant would “eventually become” a distinct species. It’s a process, not an event, you see. But Minnich’s group had cited two publications in their paper that backed up their take on things. The first was a review paper where Lenski himself described the experiment and then remarked coyly, “That sounds a lot like the origin of species to me. What do you think?” (Wink, wink, nudge, nudge.)

The second was Elizabeth Pennisi’s puff piece in Scienceon the LTEE in 2013 where she wrote (presumably after consulting with Lenski) “because one of E. coli‘s defining characteristics is the inability to use citrate for energy in the presence of oxygen, the citrate-consuming bacteria could be seen as a new species.” If Lenski plays fast and loose with the public’s perceptions of his work, he shouldn’t complain when he’s called on it.

In a disgraceful move, Lenski impugned Scott Minnich’s character. Since he’s a “fellow of the Discovery Institute” sympathetic with intelligent design, the skeptical discussion in Minnich’s paper (which underwent thorough peer review by an excellent journal that chose to highlight it with commentary from eminent scientists) “suggests an ulterior nonscientific motive.” (Apparently Lenski himself can speculate about all sorts of grand possibilities, ulterior-motive free.) You see, the Idaho scientists had the temerity to write, “A more accurate, albeit controversial, interpretation of the LTEE is that E. coli‘s capacity to evolve is more limited than currently assumed.”

Well, perhaps someone personally involved in the work might see unending possibilities. But what should an objective observer call a situation where the exact same mutations occur time and time again? — Limitless? Where a problem has no other solution except the one found? — Flexible? Where deletion of either of the genes (citT or dctA) involved in the mutation prevents citrate utilization, as Minnich’s group showed? — Resourceful? Where none of the other thousands of genes in the cell can substitute? — Inventive? Where even the easily obtainable mutation has apparently been of little use in nature? Earth-shaking?

With regard to citrate evolution, the Minnich lab’s results have revealed E. coli to be a one-trick pony. And, as I’ve written previously, in other respects Lenski’s own work has shown that E. coli evolves in his lab overwhelmingly by damaging loss-of-function and decrease-of-function mutations.

If that isn’t “more limited than currently assumed,” it’s close enough. The take-home lesson is that, although the unvarnished work itself is great, the hype surrounding the LTEE has seriously misled the public and the scientific community. It’s far past time that a pin was stuck in its balloon.

Photo: Richard Lenski, by Brian Baer, Michigan State University [CC BY-SA 4.0], via Wikimedia Commons.