Emile Zuckerkandl and the 50th anniversary of the birth of molecular evolution

Emile Zuckerkandl (1922-2013) and Linus Pauling (1901-1994) published a paper on the evolution of proteins back in 1964. The original paper was published first in a Russian translation. The English version appeared in 1965 and that paper marks the beginning of the field of molecular evolution (Zuckerkandl and Pauling, 1965a).

Dan Graur has a nice post: Happy Birthday Molecular Evolution! You’re 50 Years Old. I stole the photo from Dan's post. It shows Linus Pauling (left) and Emile Zuckerkandl (right) in Japan in 1986.

Most of you have heard of Linus Pauling—he won two Nobel Prizes—but you've probably not heard of Emile Zuckerkandl. That's a shame because he made significant contributions to the field of molecular evolution. Those early papers (Zuckerkandl and Pauling, 1965a; Zuckerkandl and Pauling, 1965b; Zuckerkandl and Pauling, 1965c) were remarkably insightful.

One of my graduate students, Sharon Shtang, was so impressed with the "Evolving Genes and Proteins" paper that she quoted from it at the beginning of her Ph.D. thesis. The authors were commenting on the, then novel, use of amino acid sequences in proteins to demonstrate evolution. They were worried that some people would think this was overkill since evolution was a well-established fact. They said ... [On Beating Dead Horses]

Some beating of dead horses may be ethical, where here and there they display unexpected twitches that look like life.

This is an obvious reference to creationism.

Emile Zuckerkandl was the editor-in-chief of the Journal of Molecular Evolution, a position of great influence in the field. A special symposium on "Junk DNA: the role and the evolution of non-coding sequences" was organized by the International Society of Molecular Evolution (ISME) in 1997 in his honor.

To devote the ISME Symposium to Emile Zuckerkandl was natural for several reasons. The first one was to celebrate a lifetime of activity in the new field of Molecular Evolution. The second reason was his long-standing interest in the non-coding DNA of eukaryotes, a subject to which he has given much thought, as witnessed by a number of important publications. The third reason is that the Journal of Molecular Evolution has agreed to be the official Journal of the International Society of Molecular Evolution. The last, but not the least, reason was to pay tribute to a personal style which has the special charm of things disappearing. In the words of Dan Graur, a rejection letter by Emile Zuckerkandl could be more pleasant and memorable than an acceptance letter by the editor of another journal.
                                                                                   (G. Bernardi, 1997)

Emile Zuckerkandl was an opponent of Intelligent Design Creationism and he wrote several papers on the subject. I want to show you a few quotations from a paper he published in 2006 on "Intelligent design and biological complexity" to give you a flavor of his style and intellect (Zuckerkandl, 2006).

To give themselves an edge, the “creationists"—the dominant stripe of anti-evolutionists in the United States—have decided some years ago (Pennock, 2003) to dress up in academic gear and to present themselves as scholars who rise in defense of a legitimate alternative scientific theory, intelligent design. Clearly, in the US it is not sufficient to laugh off this disguise. Creationists have proven to exert a sometimes decisive influence on the American political process and thereby on world history. Their educational and political militancy, linked to erroneous beliefs, are weighty reasons to keep them in check....

One ought to get out of the way two related misapprehensions that scientists often help nourish through their own use of vocabulary. One is that biological evolution, even nowadays, is a theory. The other is that biological evolution is merely, or primarily, “Darwinism”, namely, an “ism”, a doctrine, with Darwin playing for “believing” scientists a role to some extent comparable to that of a prophet. Not accidentally, these two misapprehensions start the whole discussion on the wrong foot—the only foot on which promoters of intelligent design can get around. The two biased characterizations are cherished by nearly every proponent of intelligent design, because desirably one of the points, evolution as a theory, reduces science to incertitude, and the other, evolution as an "ism," reduces it in practice to an unscientific belief. Thus, the mere way of using words permits intelligent designers to assert implicitly before any discussion starts: the only real difference between you and us is that we are sure of what we say!....

The field of evolution still includes theories, theories about particular evolutionary processes, but as to the question whether evolution occurred, there are more positive lines of evidence for this mostly past phenomenon, one may venture to guess, than for other past occurrences, say, for the past reality of George Washington, and yet people refrain from considering the evidence for George Washington as the basis for a George Washington theory. Historical facts are established as facts on the basis of converging evidence. The combined effect of independent historical pieces of evidence is synergistic. It is the product rather than the sum of the components of the evidence that determines the solidity of the evidence — a circumstance that “intelligent designers” do not consider. Some of the facts, in isolation, would not by themselves be convincing enough; collectively they are overwhelmingly so. Few historical facts are based on more evidence from more distinct sources than evolution is, which, in addition—as an extra-bonus, one might say—is supported by contemporary experimentation and the observation of contemporary processes (for example, in the field of bacterial evolution, ....

This last point is very important. In order to appreciate the evidence for evolution you have to look at the "big picture" and not individual experiments or data on particular events. Intelligent Design Creationists don't do this. Instead, they concentrate on casting doubt on particular aspects of evolution (e.g. the Cambrian explosion) as if discrediting this one point would call into question the whole idea of evolution. Jonathan Wells even wrote an entire book about this fallacy (Icons of Evolution") and so have other Intelligent Design Creationists.

Unfortunately, this mistake isn't confined to creationists. We see the same problem with many of the opponents of junk DNA. They think that evidence of one or two functional transposons, for example, is sufficient to ignore all the other evidence that most of our genome is junk.

As to “Darwinism”, however monumental a person's contribution to a field of science may have been, if the contribution remains monumental—and Darwin's does—its perdurability, after a century and a half, suggests that what started out as someone's theory (though on evolution Darwin was neither first nor alone) has meanwhile been transformed into an established field of science or discipline. When this has happened it is time routinely to refer to the field rather than to its originators. The basis of an established scientific field is not questionable: too many competent, critically minded people working in a number of subfields and analyzing phenomena at a number of levels have contributed to it, with their results supporting one another within a large body of scientific knowledge. A field would have collapsed long since, were it not based on extant phenomena. The flood of creationist references to a particular scientist rather than to a field of science conveniently tends to hide this fact from view. Advocates of intelligent design have taken on more than they usually wish to admit: biological science, not just a scientist and a “clique” of his followers....

We know why creationists use the term "Darwinism" and "Darwinist." They've been told many times that there's more to evolution than Origin of Species but they refuse to change their ways. Ironically, they often proclaim victory whenever an evolutionary biologist proposes a non-Darwinian way of looking at evolution.

Consider something designed by an intelligence: what would its general distinctive character be, as contrasted with products of nature? Would it be increased complexity? No, it would on the contrary be increased simplicity! This pertinent remark, made and discussed by Glenn Ross (2005), removes a basic misunderstanding that is traditionally cultivated by creationists and intelligent designers. Though relative simplicity does occur in nature at certain levels (e.g., in crystals)—if we consider the hierarchical plane of phenomena encountered in every day life it is simplicity that is much of the time a hallmark of actual intelligent design....What should surprise us is not the universally present complexity of natural structures and processes; it is the fact that the human mind can cut through extremely high interaction complexities by showing that they conform to relatively simple relationships, which the connoisseurs experience as “beautiful”.

This is a new idea to me. It's very profound. The complexity we see in the biological world is very unlike what an intelligent designer would have created. Our experience with designed objects suggests that the simplest objects that can do the job are the best design. That's not what we see in living organisms where useless complexity—especially in eukaryotes—is the rule. It's like Rube Goldberg designed the spliceosome, transcription complexes, the inner ear, and the human reproductive organs. The new idea (for me) is that complexity is not the mark of humans design or engineering—simplicity and elegance are the signatures of intelligent design.

For those of us who look at the "big picture," the idea that new species can arise by simply changing the way genes are regulated is old hat. The advances in developmental biology ("Evo_Devo") in the last quarter of the 20th century left little doubt that this is rule in biology. That's why most of us are not surprised that humans and fruit flies share so many genes and we are not surprised that the number of new genes in humans or mammals is not large.

Creationists, on the other hand, think that you need new genes in order to get new species. They also think that each species has a large number of unique genes (so-called "orphan" genes) and that evolution isn't capable of making so many new genes in such a short period of time. Because their view of evolution is so flawed, they think they've discovered a "gotcha" that discredits all of evolution.

Here's how Emile Zuckerkandl describes this fallacy ...

For the minority of “intelligent designers” who have any true interest in biology it will thus be important to realize that much of the evolution of biological forms is primarily attributable, not to new types of genes carrying out new kinds of physicochemically defined functions (such as for example those of hemoglobin to bind oxygen reversibly), but to regulatory changes in the genes (cf. Zuckerkandl, 2005) and to new relations among regulatory genes. The effects of such processes are expressed as changes in quantities of otherwise identical gene products and in the timing and location of the manufacture of these products....

... the era designated as that of the Cambrian explosion may well have been a period of relatively rapid evolution. The “intelligent designers'” theme song is that the unaided powers of nature were exceeded here in that too many “novel proteins” had to be invented over too short a time. By novel proteins are understood proteins with a completely novel structure and function. In reality—a disappointment for intelligent designersmdash;comparatively little structural novelty in proteins is required to make markedly different organisms. Functional novelty originates mostly from sequences or components of sequences that, in other ways, had already made functional sense for geological ages, and are mostly only moderately modified in their structure, though, to emphasize it again, at times greatly modified in their regulation and regulatory connections. Thus, the Cambrian explosion, to the extent to which it took place, probably was not based on the sudden appearance of an important proportion of radically new proteins, but rather on a rapid variation and differentiation among regulatory networks.

In order to appreciate the correctness of this view, Intelligent Design Creationists would have to immerse themselves in the scientific literature and learn about development and molecular biology. They aren't going to do this.

In fairness, there are far too many scientists who haven't done it either. I recommend the book "Endless Forms Most Beautiful" by Sean Carrol (the biologist).

The concept of evolution as a tinkerer is usually attributed to François Jacob (Jacob, 1977; Jacob, 1994) [see Evolution as tinkering].

Jacob said, "Natural selection has no analogy with any aspect of human behavior. If one wanted to use a comparison, however, one would have to say that this process resembles not engineering but tinkering, bricolage we say in French." The French word "bricolage" is actually a much better word because it conveys the concept of an amateur putting something together by trial and error.

Many molecular biologists and evolutionary biologists are familiar with the concept (more "big picture") but unless you are immersed in the subject it seems quite strange. Here's how Zuckerkandl puts it ...

Francisco Ayala (2004) has written: “…The ‘design’ of organisms is not ‘intelligent’, but rather quite incompatible with the design that we would expect of an intelligent designer or even of a human engineer, and so full of dysfunctions, wastes, and cruelties as to unwarrant its attribution to any being endowed with superior intelligence, wisdom, and benevolence.” ...

One may point to some relatively new reasons for making the judgment that intelligent design is a false solution of nature's riddles. These relatively new reasons, again, reside in observations made at the level of the informational macromolecules and their interactions. The observations in question definitely do not suggest that living systems have been built up thanks to the insights and decisions of a master engineer. Rather, the observations testify to a vast amount of continuous tinkering by trial and error with macromolecular interactions. The results of this tinkering are often retained when they can be integrated into the organism's functional whole. But why would God tinker? Doesn't He know in advance the biological pathways that work? Isn't a tinkering God one who loudly says “I am not”? And why would He say so if He existed?

Sandwalk readers are familiar with the argument from ignorance and the "god of the gaps" because of the creationists who frequent the comments section of the blog. Emile Zuckerkandl is also familiar with those fallacies but he expresses himself so much better than the rest of us ...

Predictably, whenever a scientific answer is not yet in, religiously minded metaphysicians rush to fill the void. From the zones they try to occupy within the world of phenomena, science without fail has chased them in the end, yet they do not learn their lesson. People of “faith” invariably plant their flag on territory toward which science is marching but that it has not yet reached. In the end, metaphysics just as invariably has to pack its bags—beginning with the interpretation of the rainbow's origin.

I'm a big fan of teaching critical thinking. Zuckerkandl seemed to be somewhat pessimistic about the possibilities of success!

The least one should be able to expect from any intelligent design of nature and from an intelligent origin of human intelligence is that beings supposed to be modeled in the image of an all-enveloping superhuman intelligence be endowed with a good dose of what is called the critical mind. It is the form of mind whose use made it possible, for example, to put a human on the moon. An Intelligence that made this human and that made this moon would have had to be endowed with its own brand of this form of mind. Yet, humans, this higher Intelligence's alleged pet creatures, in regard to their participation in the critical mind, appear in general to be a basket case. This is a serious failure of the higher powers; probably an irreparable flaw. Good “nurture” would help, however: a proper generalized nondoctrinal education regarding the nature of the world's phenomena combined with the teaching of ethical behavior.

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Bernardi, G. (1997) Forward Gene:ix-x [doi: 10.1016/S0378-1119(97)88693-3]

Jacob, F. (1977) Evolution and Tinkering. Science 196:1161-1166. [JSTOR]

Jacob, F. (1994) from The Possible and the Actual, reprinted in Evolution Extended, Connie Barlow ed. MIT Press, Cambridge, MA (USA) 1994.

Zuckerkandl, E. (2006) Intelligent design and biological complexity. Gene, 385:2-18. [doi: 10.1016/j.gene.2006.03.025]

Zuckerkandl, E., and Pauling, L. (1965a) Molecules as documents of evolutionary history. Journal of theoretical biology, 8:357-366. [PDF]

Zuckerkandle, E., and Pauling, L. (1965b) Evolving Genes and Proteins, eds. Bryson, V. & Vogel, H. J.(Academic, NY), 97-116. [PDF]

Zuckerkandl, E., and Pauling, L. (1965c) Evolutionary divergence and convergence in proteins. Evolving genes and proteins, 97:97-166. [PDF]