Editor’s note: In 2020, Michael Behe published A Mousetrap for Darwin, a collection of his essays and responses to critics. Professor of biochemistry Laurence Moran argued that Behe had misinterpreted evidence and had misunderstood the significance of chloroquine resistance. This is the first in a two-part response.

In 2007, biochemist Michael Behe had the temerity to ask a question — a question that should have been asked with repeated and urgent sincerity by all biologists since the ink from Darwin’s quill first dried on his manuscript: What can evolution actually accomplish?

The question is at once reasonable and utterly crucial to the evolutionary story. Yet, for the most part it has been ignored in the history of evolutionary thought. The deeply held assumption of nearly all evolutionists is that evolution can do everything. After all, we’re here aren’t we! So there is little point in even asking the question. To be sure, occasional lip service has been paid to this inquiry over the decades, but such efforts typically descend into a question-begging exercise that simply assumes evolution must have this great creative power. Again, we’re here, and so even if we don’t understand the precise mechanisms of evolution, even if we’re still trying to fill in the details, even if there is some as-yet-undiscovered evolutionary mechanism, evolution simply must have this great creative power.

Paleontologist Stephen Jay Gould famously used this tactic, arguing that even if we don’t understand exactly how evolution works, we must still regard evolution as a fact, because, well, things have evolved. Phillip Johnson rightly called out Gould for this self-serving circular attempt to prop up evolution, with Johnson’s careful analysis revealing that Gould’s “fact” of evolution turned out to mean nothing more than the theory.

Unsatisfied with circular evolutionary arguments and lazy reasoning, Behe decided to pose his question to the real-world data. What does the actual evidence show about what evolution can do? Behe approached the problem from a number of angles, the most well-known being his analysis of the appearance of chloroquine resistance in the unicellular malaria parasite Plasmodium falciparum.

Lots and Lots of Cells

In brief, Behe noted that the anti-malarial drug chloroquine had been far more successful against the parasite than many other drugs, with resistance to chloroquine arising only in one out of approximately 10^20 parasite cells, as estimated by immunologist Nicholas White, a well-known expert in malaria research. It’s hard for us to grasp such a number, but for comparison’s sake, astronomers estimate there are only between 10^11 and 10^12 stars in our Milky Way galaxy.

Although the molecular details of chloroquine resistance remained fuzzy at the time of Behe’s 2007 book, The Edge of Evolution, based on the malaria data then available Behe suggested that chloroquine resistance might well require two coordinated mutations. A single point mutation (as had been seen with some other drugs) or a series of individually beneficial mutations should have arisen much more frequently than White’s 10^20 estimate. The data, Behe noted, simply did not fit with such approaches, so a more parsimonious explanation was that two coordinated mutations were required.

Evolutionists, predictably, were upset. Jerry Coyne and Sean Carroll asserted that Behe had to be wrong, just on the principle of the thing. In essence, they argued that oh, yes, chloroquine resistance can too come about by a series of single beneficial step-by-step point mutations. That such a claim flatly contradicted the data was beside the point.

Not lost on careful observers was the irony that Behe had proposed that Plasmodium could in fact acquire two coordinated mutations via evolutionary means. Yet intent on maintaining the lore of “one small step at a time for evolution,” Coyne and Carroll eschewed Behe’s offer of two coordinated mutations. In a creative albeit bizarre kind of reverse-gamble, they wagered, “We’ll see your two mutations and raise it to one!”

Over the next several years, arguments went back and forth, and more ink was spilled by the debaters than by a clumsy apprentice at the print shop. Yet despite the nitpicking of definitions, the fights over math, and the repeated accusations that Behe must not understand how evolution really works, those of us who watched the battle of wits from the sidelines noticed that Behe’s basic question remained awkwardly unanswered by his critics: How much can evolution really accomplish?

Moran and the Luck of the Draw

One of the more engaged critics of Behe’s argument was Dr. Larry Moran, professor of biochemistry at the University of Toronto. Moran seems to be on board with the broader evolutionary narrative, but does not consider himself to be a Darwinist. Not long before Behe published The Edge of Evolution, Moran posted a detailed description of his views on his Sandwalk blog titled “Evolution by Accident.” Moran laid out the case for a non-Darwinian view of evolution, building on Jacques Monod’s argument that “pure chance…is at the very root of the stupendous edifice of evolution,” as well as Gould’s famous replay-the-tape-of-life analogy.

For the most part, I agree with Moran’s assessment of the randomness of evolution, my primary quibble being that Moran doesn’t go far enough in recognizing the role of chance in the evolutionary narrative, specifically in the case of so-called selective events. Upon careful analysis, Darwin’s selection mechanism also collapses to a largely chance-based affair, and so the effort to distance oneself from the shadow of Darwin by embracing random evolution is, to a large extent, a distinction without a difference. Yet that is a nuance and a discussion for another time, should I ever have the honor of the proverbial drink at the pub with Moran.

The key point for readers here is that armed with his chance-centered view of evolution, Moran dove into the debate with Behe over chloroquine resistance. The backs and forths between Moran and Behe (and by their supporters and detractors) throughout the summer of 2014 were too numerous to detail here. Then, following several years of relative peace (at least on this particular front), the battle began anew.

In part to silence the spurious accusation that he doesn’t respond to his critics, in November 2020 Behe published A Mousetrap for Darwin, a collection of his numerous rebuttals to critiques of his three prior books. Included in Mousetrap are several responses to Moran. Moran quickly penned a hurried response on his Sandwalk blog arguing, in essence, that Behe was both wrong about how chloroquine resistance came about and had misinterpreted the mechanisms of evolution.

Behe’s Misunderstanding or Misunderstanding Behe?

Significantly, Moran acknowledges the main thrust of Behe’s argument, noting that:

Behe has correctly indentified [sic] an extremely improbably evolution event; namely, the development of chloroquine resistance in the malaria parasite. This is an event that is close to the edge of evolution, meaning that more complex events of this type are beyond the edge of evolution and cannot occur naturally. [Emphasis added.]

This is a very important acknowledgement, and a reader of The Edge of Evolution might well say to Moran, “Welcome aboard!”

Instead, Moran’s main disagreement (coaxed along at various times by P. Z. Myers, Kenneth Miller, and company) seems to be that Behe has misunderstood how malaria resistance came about. Moran acknowledges that “none of us have a serious problem with this guesstimate [1 in 10^20 malaria-cell replications], but several of us have objected to the way Behe interprets it.”

Flashing back to 2007, we remember Behe had suggested that the simplest explanation for the extreme rarity of resistance to chloroquine was that at least two coordinated mutations were required. This was in stark contrast to the drug atovaquone, for example, which required but a single point mutation, and against which resistance arose faster than the average person could learn to pronounce “Plasmodium falciparum.”

Casey Luskin observed that much indignation was brought to bear by some of Behe’s critics for Behe’s use of the word “simultaneous,” but it was clear to any thoughtful reader of The Edge of Evolution that Behe had never claimed that the two mutations had to arise at the same moment in one fell swoop, such as in the exact same reproduction cycle. His point was simply that the two mutations needed to eventually be together at a particular point in time in a particular cell to confer the needed benefit, regardless of precisely when the mutations arose or which mutation came first. Unlike some of Behe’s critics, Moran, to his credit, granted Behe’s point about the mutations having to be together simultaneously to provide the needed benefit. Moran’s concern was more about the possible routes to chloroquine resistance.

What Guesses Were Reasonable?

It was not at all clear in 2007 — my understanding is that it is still not completely clear — exactly which mutational routes are available to Plasmodium in humans in the wild, nor all the other factors or nuances that might bear on the problem. Moran himself notes that “there are lots of complications and many unknown variables” and that we can “provide estimates” but “can’t give precise calculations.”

The best anyone could do while waiting for more definitive research in 2007 was to make an educated guess as to the exact pathway(s) to resistance. The question is, what guesses were reasonable in light of the malaria data?

Then in 2014, an important paper by Summers et al. shed additional light on the development of chloroquine resistance. Although limited to experiments involving frog oocytes in the lab, this research provided solid experimental evidence detailing the specific mutations involved. The researchers identified two initial routes to chloroquine resistance, with additional mutations leading to “the attainment of full transport activity.” Behe’s critics pounced on this as a possible chink in Behe’s argument, grasping onto the possibility that there might be various ways to achieve chloroquine resistance, including from combinations of more than two mutations.

Behe for his part correctly noted that, if anything, the new research supported his primary argument. Indeed, one of the key takeaways of Summers et al. is that chloroquine resistance is a multi-mutational event, with both of the identified routes to resistance requiring “a minimum of two mutations” to get started. Behe’s 2007 prediction that chloroquine resistance did not result from a series of individually beneficial mutations, but required a multi-mutational event, turned out to be correct. Yet critics still asserted that the key take-home lesson was elsewhere to be found.

In the second part of this response, we’ll examine the data and the implications of chloroquine resistance for the broader evolutionary story.