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A Critical Review of Behe's Darwin's Black Box

by David Ussery

(Printout of this review may run several pages)

A Critical Review of Behe's Darwin's Black Box
by David Ussery
Associate Research Professor at the Danish Technical University in Denmark
Introduction and comments by Larry Flammer


Life, at the molecular level, is too complex to have simply evolved. This is the premise of a popular 1996 book by Michael Behe: Darwin's Black Box: The Biochemical Challenge to Evolution. Another biochemist, David Ussery, challenges that idea in an excellent and thorough critique of Behe's book, written in July, 1998 for Bios magazine (an undergraduate magazine for Biology majors). Click here for full text, off-site, (with animated illustrations). What follows are some telling excerpts from that review, including some useful "gee-whiz" biochemical bits which might surprise you, and probably amaze your students, posted here with the author's kind permission. My occasional comments and condensations will be bracketed and in boldface.

It is interesting to note that the reviewer (Ussery) grew up in Arkansas and admits that he was an ardent Creationist by the age of 14, but then gradually came to believe that perhaps the creationists didn't have ALL the answers. His research has involved bacterial genetics, bacterial pathogenesis, and currently deals with the relationship between DNA sequence and cell structures.


Many of my biologist friends tell me that few "modern biologists" believe that Darwinian gradualism on its own can fully explain evolution - that most of them agree that there are aspects of punctuated evolution mixed with the more slow gradualistic evolution. I had expected the book to deal more with this, or perhaps to discuss some of the new ideas concerning origins of complexity in terms of "self organization" systems, instead of a general debunking of natural selection altogether. This review is my own personal response to Behe's "biochemical challenge to evolution".

Behe says "Yet for the Darwinian theory of evolution to be true, it [modern biochemistry] has to account for the molecular structure of life. It is the purpose of this book to show that it does not." (page 25)

Molecular biology [or "modern biochemistry"] DOES indeed provide a very convincing basis for describing the evolution of life, at the molecular level, contrary to the central thesis of Michael Behe's book. It is the purpose of this review to have a careful look at Behe's arguments, and to point the reader towards evidence that biochemistry CAN in fact account for the origins of the complex molecular structures of life.

The basic premise of the book is that "Biochemistry has pushed Darwin's theory to the limit. It has done so by opening the ultimate black box, the cell, thereby making possible our understanding of how life works." Basically, life is so complicated, Behe claims, that it MUST have been created by divine intelligence, or at any rate gradual evolution could not possibly have created such complex systems, and most scientists ("biochemists") know this but are just too proud or embarrassed to admit the obvious fact of intelligent design. [Behe invokes a conspiracy theory from within the scientific community, a theory which is not substantiated in my experience in the world community of molecular biologists, as I will show.]

One recurrent theme in the book is the concept of "irreducible complexity", for which the household mousetrap is used as an example. The argument goes something like this: You need at least 5 essential components for the mousetrap to work - a platform, holding bar, spring, catch, and hammer. If any of these are missing, the mousetrap fails to work. Perhaps this analogy works for things built by humans, but I think it is very dangerous and misleading to try and extend it to molecules - in this case, biochemical systems and evolution. Why? [See the full text for the expansion on this point.]

[Behe repeatedly and grossly overstates data bearing on the degree of complexity of various systems, and completely ignores the thousands of research articles published which describe in detail how such complex systems could very well have evolved, often providing very compelling evidence to support that idea. Behe generally claims that little or no such work has been done, in spite of the abundant evidence to the contrary available to anyone who can do a quick web search of PubMed! Behe simply didn't do his homework! Several specific examples are included in the full text of the review.]


The third example of irreducible complexity has to do with how proteins are transported within a cell. Believe it or not, I think Behe even UNDERSTATES the level of complexity here! For example, when he describes the synthesis of a protein that is to be targeted to the lysosome (page 107), Behe mentions that going all the way from the cytoplasm to the lysosome requires BOTH gated transport, and vesicular transport. This is indeed quite complicated - he doesn't even talk about the fact that most mRNAs are originally made much longer than needed - sometimes more than 100 times longer. Then, after the "pre-mRNA" is read, intervening sequences (sometimes more than a hundred) are spliced out, (different sections are snipped out in cells in different tissues) by a special RNA/protein (snRNP) complex called a "spliceosome". Sometimes, the message is further EDITED by changing the sequence at certain positions (!). This PROCESSED mRNA is what is then EXPORTED outside of the nucleus, using a little mechanical motor that moves along a microtubule, to the cytosolic face of the Endoplasmic Reticulum (ER - not the free cytoplasm), where it is translated. It doesn't float out. The cells are very crowded inside. The newly formed peptide chain is then threaded into the ER lumen, where it undergoes the first round of post-translational modification. Then vesicles containing the protein bud from the ER to the cis Golgi, and then subsequently go through the Golgi stack, where further protein modifications (such as glycosylation) occur. And then eventually it winds up in the lysosome. Yes, so far I agree with Behe - this is indeed a VERY complicated system. Is this system then an example of "irreducible complexity"? Are all the parts necessary? In a review of protein transport, the authors state that some proteins can direct their own secretion - that is, no transport proteins are necessary. Although these proteins do not use gated transport, they provide an example of a simple system that could well be the precursor to vesicular transport.

However, many of the proteins involved in transport have molecular "ancestors" in the form of ABC transporters in bacteria. Here you have a bacterial protein which has three different parts, or domains, which can be modified to fill the needed role in a more complicated system. The original proteins exist in bacteria, which are much smaller and have less complex intracellular structures than eukaryotes. Why doesn't Behe talk about this large family of bacterial transporters that are also found in eukaryotes? Here is a perfect example of the very type of molecular evolution he is talking about, and yet he never mentions it. If you are looking for the "simplest mousetrap", it would make sense to look at these systems in bacteria.

I kept waiting to see what Behe had to say about the self-organization of nucleic acid bases. If you were to take some Adenine, for example, and throw it into solution, it would self associate, and form a HELIX. This is the SAME type of self assembly that Behe readily discusses for liposomes and even for ribosomes (although he seems a bit surprised: "Incredibly, the ribosomes are self assembling"). There is nothing "magic" about how the bases stack on top of each other, it is just pure and simple chemistry - due to the hydrophobicity of the bases. The bases are merely seeking a thermodynamic minimum. Perhaps this has somehow not made it to the introductory level biochemistry textbooks, but it is certainly well known, and of course has direct bearing on the possible evolutionary origins of RNA and DNA. (For a reference see Calladine & Drew's wonderful book UNDERSTANDING DNA - The Molecule and How it Works and/or visit my "DNA is like Coca-Cola" web page). If free bases stack on their own and form a helix, it is not too difficult to envision simple molecular linkers connecting them together. The free bases, and necessary "linkers" to form a primitive type of polymeric nucleic acid, can be formed from simple inorganic material plus a bit of sunlight.

He [Tom Cech, a world-class biochemist] has done what good scientists do - designed a hypothesis in terms of simple questions that can be addressed experimentally, and then tested this with experiments. Sometimes you are "right" (e.g., the experiment works and validates the predictive power of your theory), and sometimes you're wrong - but scientists are willing to TEST their ideas. Of course what also must happen is that OTHER people must be able to reproduce ("test") your results. The hypothesis was the following: ribosomes are made of a mixture of RNA and protein. Is it possible that at one time ribosomes consisted ONLY of RNA, and no proteins? If this were true, you should be able to find an RNA molecule (or set of molecules) which could combine with the present rRNA and be capable of synthesizing proteins - with no ribosomal proteins required. They designed an "in vitro evolution" set of experiments, and found the necessary RNA, and got it to work. This is a pretty major advance in terms of understanding possible molecular mechanisms for the origins of a complex system - the synthesis of proteins.

Tom Cech also presented the crystal structure for a self splicing RNA. The amazing thing is that, when he compared this to an enzyme, they looked similar. Basically, in order to catalyze a chemical reaction, you just need to be able to have the right chemical groups in the right place, and the rest is just "scaffolding" - it often doesn't matter WHAT the size or shape of the material is, so long as the reactive groups are properly localized.

And here is where I think Behe [a protein biochemist] really misses the point. Throughout the book he almost leaves me with the impression he's looking for an explanation for the evolution of complex PROTEIN systems. Well, complex protein systems don't evolve, and proteins don't evolve, but DNA sequences do. In fact, when examined at the molecular level, evolution can be seen to occur in "jumps" sometimes! These sudden, major changes occur through the introduction of new genetic material (i.e., DNA sequences) which had been previously either non-existent, or present but not able to express itself. Where do the extra DNA sequences come from? Often through copies of itself, or gene duplication, or from other organisms, via any one of a variety of mechanisms, such as transposable elements, viruses, and homologous recombination. This is not some postulated, theoretical mechanism - this is something that can be seen to happen VERY OFTEN in every organism we have ever looked at - this is why individuals are unique - why you are different from me. So really, if you want to know about molecular evolution (the theme of this book!), it makes perfect sense to talk about changes in the DNA sequence, which can result, of course, in changes in the protein sequence and can also affect whether the protein gets made at all, and how much of it gets made.

In order for evolution to occur, you need the following three things: a system of inheritance, variation within that system, and some sort of selection. In the above case, Cech made the variation artificially, such that you had perhaps more than a million different sequences from which to choose. What is the variation like in "the real world"? To exaggerate Behe, if you dare to change a single amino acid in a protein, you could destroy its function. However, using the same "classic" example of the hemoglobin gene and sickle cell anemia, it is easy to ask the question: how much variability can you have within the protein? Behe readily admits that you see a bit of a change between the hemoglobin of horse and humans. In fact, you can have different amino acids for MOST of the positions of the hemoglobin proteins, but ONLY A CERTAIN FEW positions are so important that they cannot be changed. Thus, it is NOT a case of certain death if you change ANY of the amino acids. Furthermore, the "step-by-step" gradual changes you see in the amino acid sequence of the hemoglobin protein can be explained quite simply and logically by gradual evolution. I think Behe concedes this point - he's interested in the evolution of complex systems. But my point is that even within complex systems, you have a tremendous amount of variation within a population of organisms, and hence the potential for change by natural selection.

How much variation is there in the DNA sequence? I was quite surprised to learn of the enormous variance between humans. One out of every thousand males has an extra X chromosome, and a similar number (one out of a thousand) of males have an extra Y chromosome. About one out of every thousand females only have one X-chromosome, instead of two. If you were to have a look at the DNA sequence for any two human beings, there would be more than a MILLION base pair (bp) differences between them! Many humans carry major chromosome translocations, where part of the arm of one chromosome has broken off and been attached to another chromosome. Think about this - there are roughly 3,000,000,000 bp in the human genome. Even if you were to copy this at an error rate of only one in a million, which is pretty close to what happens in the real world, then you will still get 1000 bp differences EVERY time the cell divides. All humans started out as a single cell, which divides many times over - hence the DNA sequence is quite diverse, even within different cells from the same person! How can we possibly survive all this variation? Most (about 98%) of the DNA in humans does not code for proteins, so we can take quite a bit of deterioration in sequence and still live. Furthermore, the mutations (changes in DNA sequence) are not in fact completely random, but somewhat localized to regions that are not as essential for life.

There are many well documented cases of new species arising from large scale changes in the DNA sequences. For example, in simple cases, the chromosomes get duplicated. This is the likely origin of trout fish - if you examine the trout cells, they contain FOUR copies of each chromosome of a smaller related fish, rather than the expected "normal" two copies. This extra set of genetic material not only make the trout larger than their ancestors, but gives them extra space to change and adapt with. This happens very often with plants, although complete polyploidy is much less common in animals. This is how many plants have obtained such large genomes - some more than a thousand times the size of the human genome!

The smaller changes, such as gene duplications, are also well documented. Transposable genetic elements can splice themselves in and out of genomes, creating duplicate copies of genes, and also causing problems for the genomic organization and stability of organisms. At the level of bacteria, it is possible to look at complete genomes, and see which regions have come from bacterial viruses. A bacterial virus is really quite simple: a small piece of DNA and a protein coat. That's all. Pretty simple. Yet this is a very powerful mechanism of introducing genetic change in bacteria. Similarly, eukaryotic viruses can bring foreign DNA sequences (e.g., from other organisms) into human cells. So the genetic information is varied and constantly changing.

Michael Behe's book reminds me of a cartoon, where a scientist has filled the blackboard with equations, and then he says, in exasperation, "Then a miracle occurs!". The question is - must God necessarily be restricted in the method of creation, such that the only options are ones that science has not (yet) explained? Is it possible that God could use natural processes to create life? I think that, in fact, this line of belief has been held by Jews and Christians for more than 3000 years. It is only very recently, within the last few hundred years, when scientists disproved spontaneous generation, that some theologians decided to try and hook their theology to the shifting sands of modern science - and this has been a source of problems ever since. Presently the trend of Darwin bashing is limited mainly to the U.S. - I have spoken with many people here in Europe who attend synagogue or church regularly, and all of them have no problems accepting science (including Darwinian evolution) and their view of God. Very few of them have even HEARD of the "creationism" common in many parts of the U.S.

For the few readers that have made it this far into the review, I want to try and put "The Biochemical Challenge of Evolution" into perspective. Behe is opposed to Darwinian evolution, but claims he's no creationist - he also realizes that there is evidence the world is older than 10,000 years. He even makes a bolder statement: "Further, I find the idea of common descent (that all organisms share a common ancestor) fairly convincing, and have no particular reason to doubt it...." (page 5). (This is a major concession for many of my traditional creationist friends in Arkansas.) If one believes in "common descent", then this might create a bit of a puzzle in terms of the intelligent design argument. Is the "intelligent design" only visible at the molecular level, and not to be readily seen at the organismal level? If you allow for the evolution of complex systems from simpler systems in anatomy, for example, at what point could you say intervention by the Intelligent Designer must occur? Last December (1997), I watched a debate considering whether creationism should be treated equally with evolution in the public schools. The side FOR creationism included Michael Behe and William F. Buckley; on the "evolutionist" side was Michael Ruse, among others. (Michael Ruse is in fact a Christian who has written an excellent book, But is it Science? about evolution vs. creationism.) Darwin's Black Box had a very favorable write up in Christianity Today (presenting Behe as an anti-evolutionist), and has received much positive attention from many in the religious community, who delight in his attacks on gradual evolution. I know that Behe would not consider himself a creationist - but here he is, on the debate team arguing that Creationism should be taught in the schools. I want to stress once again that I am not opposed to anyone wanting to express their religious belief. But I do have real problems with people who want to somehow use science to make their invisible God, "visible", and then insist on teaching this doctrine as "science" in the public schools. My point is that for the life of me, I cannot understand why so many people consider it a necessary part of their BELIEF in an all-powerful God to put restrictions on the method of creation. They say that God could not have used evolution - and not only that, but they won't allow anyone to teach evolution as "science" because of their theological objections. But I'm straying from the topic here. Behe, to his credit, spends most of the book arguing from a factual perspective. So surely the best thing is to judge the book on the facts.

"Over the past four decades modern biochemistry has uncovered the secrets of the cell" (page 232). I think perhaps he should be a bit more realistic and say something like "over the past four decades, molecular biology has begun to uncover some of the secrets of the cell." If I didn't know anything about biochemistry, it sounds like we presently almost have fully solved how the cell works.

In another example, on page 175, he says "In the late 1970s, quick and easy methods became available for sequencing DNA..." This needs to be put into a broader perspective. Imagine that you are in the Library of Congress, and you've just learned how to distinguish the letters of the English alphabet, at a rate of a few minutes for each letter. Do you think you're ready to tackle the total meaning of all the books in the library and their origins? I suppose one could argue about what "quick" means, but if one were to decipher the DNA sequence of a single human cell, at the rate of the total world output in 1979, it would take more than 4,000,000 years! In fact, about 6 or 7 years later the U.S. government launched a 20 year project to sequence the human genome (see the previous review in Bios magazine), and has invested heavily in technology to speed up the sequencing process (at a cost of more than $200,000,000 a year - this is more than was spent on the Apollo space project!). By 1989, the ability to sequence had grown such that it would take a "mere" thousand years or so to sequence a human genome. Presently, in 1998, this same task would take about 50 years, and within a year or two, it is possible that one could read the entire DNA sequence from a single human cell, in perhaps a few hours!

But the problem is, what will we do with this information? Currently, we don't even know for sure how many proteins are made in humans - nor are we really sure how to figure out exactly where the genes start and stop. But even if we were to know the SEQUENCE of all the proteins, it is still very difficult to figure out the structure and function of these proteins. For example, we have known (some of) the sequence for the gene that causes cystic fibrosis, for nearly 10 years. The full DNA sequence for this one single human gene is larger than the size of the ENTIRE genome of many bacteria! Presently, the best evidence is that this gene codes for a protein which is a chloride channel, or perhaps regulates a channel, but we still aren't sure of the structure nor do we know exactly how this protein works. We probably know more about the bacterium Escherichia coli than we do any other organism - and yet when the complete sequence was published last year, about a third of the proteins were known, a third had been postulated to exist, and the remaining third was totally unexpected - we're not even sure how many of these are "real"! ["DEEP IGNORANCE":] In my opinion we understand such a tiny fraction of the wonders of life. We're not even sure how many genes humans have - nor is it even completely clear how we will be able to figure out where all the genes are! We still have a long way to go, a lot more to explain. So I don't think we've "uncovered the secrets of the cell" yet - a few perhaps, but certainly not even the majority. Once we understand our present state of ignorance, it is a bit more forgivable to see that people haven't proposed in detail the evolution of these complex systems. Please - give us a chance to define the systems well enough to know what's there, before we worry too much about explaining molecular evolution in gradualistic, step-by-step detail!

He UNDERSTATES the vast amount of literature on molecular evolution that can readily be found, through simple searches. For example: "Molecular evolution is not based on scientific authority. There is no publication in the scientific literature - in prestigious journals, specialty journals, or books - that describes how molecular evolution of any real, complex, biochemical system either did occur or even might have occurred." (page 185). In the five specific examples of "irreducible complexity", I entered the search terms suggested, and came up with several hundred articles about the evolution of these systems, in a matter of a few minutes. Once again - please don't take my word for it - have a look for yourself! As far as books go, I have a book called Molecular Evolution, by Wen-Hsiung Li (Sinauer Associates, Inc., Publishers, Sunderland Massachusetts, U.S.A., 1997, 487 pages). This book is all about molecular mechanisms of evolution, which includes a section on "Concerted Evolution of Multigene Families", which provides detailed specifics of the evolution of biochemical systems. Perhaps another good book along these lines would be Molecular Biology and Evolution of Blood Group and Mhc Antigens in Primates, which deals with one of Behe's specific examples of irreducible complexity (this is only one of several books about evolution of the immune system). Go to and type in "Molecular Evolution" and see what you can find. Try PubMed for research articles on specific topics. The truth is out there.

Behe is quite critical of the Journal of Molecular Evolution, because most of the articles (85%, he reckons) deal with analysis of biological sequences, and hence somehow don't REALLY deal with evolution. However, as I've stated above, evolution can be thought of as merely selection for a change in the DNA sequence. So by this definition of evolution (which by the way is a very good "working definition" in that it consistently yields good results when tested), if one wants to understand evolution at the molecular level, it makes PERFECT SENSE to look at tiny changes in DNA sequences, which could result in changes in the amino acid sequence of proteins, which could affect their shape and hence their structure and function. I just had a glance at this week's issue of J.Mol.Evolution, and found two articles dealing with the evolution of the immune system, and an article about the evolution of the eye. All three of these are from areas of "irreducible complexity", where scientists have allegedly not been publishing. PLEASE, don't trust me - click on the link and check it out for yourself!

According to Behe, "... evolutionary biology is stuck in the same frame of mind that dominated origin-of-life studies in the early fifties, before most experiments had been done: imagination running wild. Neither of Darwin's starting points - the origin of life, and the origin of vision - has been accounted for by his theory. Darwin never imagined the exquisitely profound complexity that exists even at the most basic levels of life." (page 173).

First, I don't think that it is fair to say that hardly any experiments had been done before the 1950's, or to imply that evolution is based purely on imagination. Second, there's been a considerable amount of literature on both the origin of life and the origin of vision. This is more Behe's OPINION that Darwinian evolution doesn't account for these two points. I would encourage the curious readers to check out Richard Dawkin's The Blind Watchmaker, (or Climbing Mount Improbable or River Out of Eden) and decide for themselves. Also, there's a quite good article by a Swedish group, in which the gradual, step-by step evolution of the eye is considered in detail. Finally, and more to the point, the complexities of biochemistry are not that much greater than the complexities of organisms. Just think about the numbers - there are about [1.4 million different known, categorized species, but it is very likely this number is less than 10% ] of the total species that exist in nature [(which could be anywhere between 10 and 100 million, according to E.O. Wilson in The Diversity of Life)]. Darwin's theory of evolution was such an accomplishment because it allowed a simple explanation for how all this diversity and complexity has arisen, and continues to arise. His "explanation" was natural selection - which is a mechanism that has been tested and found to work experimentally; evolution by natural selection has enormous explanatory powers about the origins of life. Yes, it is true that Darwin didn't fully understand HOW this mechanism worked, but - and here is where I beg to differ with Michael Behe - we DO understand now the mechanisms by which evolution work, at the level of molecular genetics, as for example the evolution of the eye. But this does not at all counter the evidence of evolution from numerous observations at the species level. Over the years, I have accumulated my own personal library of more than a hundred books on documented examples (and possible mechanisms) of biological evolution. I think that it is quite true that biological systems are indeed very complicated at the organismal level, but it's also true that "nothing in biology makes sense except in the light of evolution" (Theodosius Dobzhansky).

Finally, in my admittedly biased opinion, he SETS UP A FALSE DICHOTOMY - if there are indeed complicated systems that scientists can't presently explain the origins of, then it must be that there was a "Great Designer" who is responsible. Hidden in this argument is the idea that if we CAN explain the origins of life, then there is no need or reason for the existence of God. This sounds a bit like the "vitalist" theories of the past, which held God is what we don't understand. I can choose to look at the wonders of nature and believe in God or not - but I don't feel that I am necessarily FORCED to believe or not to believe. I have a choice in the matter. I get the feeling Behe thinks we DON'T really have a choice - that anyone with half a brain who sees how complicated biochemistry is, MUST believe in a Creator God.

In many senses Darwin's Black Box has a flavor which is similar to many of the more traditional creationists books - an appeal to ignorance of the subject matter. To someone who knows only a little bit about biochemistry, (indeed, the intended audience) this book could sound like a devastating attack on Darwinian evolution by natural selection. Unfortunately, it was quite tortuous for me to read. The subject matter has the POTENTIAL for a very good book, but I was continually frustrated by his distorted portrayal of molecular biology. It is my own opinion that, upon closer inspection, his "biochemical challenge to evolution" vaporizes to essentially a restatement of the traditional creationist attack on Darwinian gradualism: life is so complicated - it HAS to have been created by a divine intelligence. This is a matter of belief, either I can choose to believe that God created life, or I can choose not to believe this - but to say that science FORCES me to believe one way or the other denies my free will. "Inferring that biochemical systems were designed by an intelligent agent is a humdrum process that requires no new principles of logic or science" (page 193). Most molecular biologists would agree that many biochemical systems appear to be designed (i.e., optimized energetically, as Stuart Kauffman has put it so well)- but they would argue that it is selective pressure from "nature" or the environment which is responsible for the design. For a scientist to say that "a miracle must have happened" is not a routine (or valid scientific) explanation.

Over the years, I have accumulated my own personal library of evolution/creationism books, with more than a hundred books on documented examples (and possible mechanisms) of biological evolution. Please check it out at <>.