Monday, September 21, 2015

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.

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]


  1. I never met Emile Zuckerkandl in person, but he did call me up once (probably to remind me to turn in a review of Journal of Molecular Evolution on which I was late). I recall him as very polite, friendly and considerate, in a courteous old European way.

    When I spoke at a meeting in Vienna two months ago, I reminded the audience of two sons of Vienna who were great pioneers of work on molecular evolution and phylogenies -- Robert Sokal and Emile Zuckerkandl. Both fled, and fortunately both survived.

    1. I had the pleasure of meeting Emile Zuckerkandl when I gave talks at Stanford in 2001. As you say, Joe, he was "very polite, friendly and considerate, in a courteous old European way."

      What struck me even more was just how excited he was about science--about what people were doing and what they would do in the future. It was inspiring to see someone that old who was still incredibly excited about the future of science.

  2. Terrific post. As a non-scientist I had heard of Pauling and seen the name Zuckerkandl, but hadn't realized all Zuckerkandl had done. The whole complexity being the hallmark of natural processes is new to me, and one that makes perfect sense when you step back and think about it for a moment. Recently I've been blogging about the whole 'Darwinism' and the Discovery Institute's constant targeting of Darwin as if removing him from the whole Theory of Evolution would cause it to collapse. The latest DI shill, Denyse O'Leary has been rather vocal on that lately. Nice to know I am not off-base. Thanks!


  3. 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.

    And of course the exact opposite of the concept that motivates many toward a belief in higher powers: how could such inordinate complexity arise merely by chance and without intelligent design?

    Well, the answer lies in ideas like Neutral Constructive Evolution (for example), or as a person associated with Ford Doolittle’s lab remarked to me a few months ago, the idea that is otherwise known as the “shit happens” view of molecular evolution.

    1. 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.
      Can you think of a design specification for a bacteria...can self replicate...convert environmental energy to work...move and change directions almost would we simplify the current design?

    2. you are missing the point, I think. Go back to the original post from which that quotation was extracted and note the context.

    3. Thanks..I see your point. The only point I would add is that increased complexity with increased function should be expected. Until we really understand these architectures in detail it is hard to comment whether there is excess complexity or not. Living architectures have lots of capability that man made architectures do not. How much do we really understand of the core design of a bacteria, the design tradeoffs etc, which is much simpler then multicellular life.

    4. No doubt you make valid points. But I would add that the issue as to whether there is excess complexity in a system is one question, and probably a complicated one. But another question is the path by which complexity increases in the first place. The point often made is that incremental increases in complexity are often viewed as the consequence of improved functionality. The alternative view is that increases in complexity do not always do so and may be initially neutral and the result of certain contingent events. Of course, once an increase in complexity has been established, there is nothing to prevent the subsequent evolution of novel and diversified function in the constituent parts.

    5. The Achilles heel of all such arguments regarding the evolution of complex forms is that "complexity" is never defined. For particular instance, I find the interaction of cI, cro, and RNA polymerase at the Or promoter of phage lambda to be both elegant and, notably, very complex; but how does one quantify the lesser complexity of that model system to, say, the complexity of stem cells and resultant developmental outcomes? The latter seems, intuitively, to be more complex but is it really? If so, by how much?

      The bottom line: how does one measure the relative complexity of biological systems? Unless or until that question is answered, any discussions seem to me fruitless.

    6. Interesting points and questions, Scott, and with your points and questions in mind I have a request for everyone, especially creationists.

      Arrange the following into a list with the most complex biological entity (or biological 'system') at the top of the list: lichen, a butterfly, a current male human, a current female human, a male human that lived 50,000 years ago, a female human that lived 50,000 years ago, a bristlecone pine tree, a Venus flytrap, a dandelion, a honey bee, a Komodo dragon, a dragonfly, a beetle, a mantis shrimp, an orb weaver spider, a gorilla, a blue whale, a virus, a bower bird, a crow, a hummingbird, a platypus, Staphylococcus aureus, an amoeba, an onion, Hymenoepimecis argyraphaga, Dicrocoelium dendriticum, Ophiocordyceps unilateralis, Sacculina carcini, a wood frog (Rana sylvatica), frogs in the Dendrobatidae family, a cancerous cell, a Spinosaurus, a pterodactyl, a bat, an octopus, a current Coelacanth, a Coelacanth that lived 70 million years ago, a current African elephant, a Columbian Mammoth, the fairy fly Kikiki huna, and Tiktaalik roseae.

  4. The journal that Emile Zuckerkandl was editor-in-chief of was Journal of Molecular Evolution, not Molecular Evolution.

    Dan Graur, in his blog post, attributes to Christian Anfinsen the invention of the phrase Molecular Evolution because he wrote a book entitled The Molecular Basis of Evolution in 1959. Now this is the kind of historical issue that typically leads to endless discoveries of earlier and earlier uses, ending up with Aristotle or the ancient Babylonians.

    I did, in some searches in Google Books, find the phrase "molecular evolution" in the title of this paper by Sidney Fox, a pioneer in studies of the Origin Of Life:

    Fox, S.W. 1953. A correlation of observations suggesting a familial mode of molecular evolution as a concomitant of biological evolution. American Naturalist 87: 253-256.

    But of course we can find the phrase "molecular evolution" within papers even earlier. In a JSTOR search I found a couple of hits from 1874 - 1926 that seem not be intended as describing biological evolution, but rather the origin of the earliest molecules. The first hit that is biological I get the year before Fox, in:

    F. H. McCutcheon. 1952. The viewpoint and progress of comparative vertebrate physiology. The Scientific Monthly, Vol. 74, No. 5 (May, 1952), pp. 297-302.

    (see page 299, top of right column).

    These uses seem to be part of the field of "comparative biochemistry" which preceded the study of molecular evolution. People as central to molecular evolution as Walter Fitch and Allan Wilson got their start in comparative biochemistry.

    1. Thanks for catching the typo. I fixed it.

    2. By the way, Larry, in spite of my long-winded stuff above, I basically agree that the origin of the field of "molecular evolution" is near the time of Zuckerkandl and Pauling's papers. I would put it at 1962, when they published their first paper discussing differences among species in their hemoglobin sequences. There is a great discussion of the history of their work here. Their 1962 paper is this one:

      Zuckerkandl, E. and L. Pauling. 1962. Molecular disease, evolution, and genetic heterogeneity. pp. 189--225 in Horizons in Biochemistry, ed. M. Kasha and B. Pullman. Academic Press, New York.

      The earlier uses of the phrase "molecular evolution" are really discussions of comparative biochemistry, where they are talking about the evolution of biochemical systems that do or do not have particular metabolites.

      So happy 53rd anniversary to the field of molecular evolution!

    3. I don't think it really matters what date we choose as long as it's reasonable. You could choose any number of dates but it seems reasonable to pick one between 1960 and 1965. I think 1965 is as good as any and since it's arbitrary let's just agree on that date.

      I'm happy to gove a lot of credit to Zuckerkandl and Pauling but let's not forget Emanuel Margoliash who was there from the beginning.

      Margoliash, E. (1963) Primary structure and evolution of cytochrome c. Proc. Natl. Acad. Sci. USA 50:672-679

    4. Would be interested, in a future post, to hear your thoughts as a biochemist on the role of the study of comparative biochemistry in the development of molecular evolution. I have heard that Allan Wilson first got interested in evolutionary approaches to biochemistry when he read the book by Ernest Baldwin on that topic.

    5. Biocemistry textbooks in the 1940s. 50s, and 60s tended to emphasize comparative biochemistry—comparing plants and animals, for example. The goal was to teach the "big picture" view of biochemistry. That's how I was taught in the 1960s. I think it made biochemists and molecular biologists more interested in evolution.

      The situation today is very different. Undergraduate biochemistry courses in most countries are more like human physiology courses. Photosynthesis has disappeared from most courses because teachers know nothing about it (and don't care). In some countries (USA) the courses are designed to prepare students for admission to medical school. Students rarely hear about evolution and they only learn about fuel metabolism in humans.

      I think this explains the narrow-minded views of recent generations of scientists who have never heard of photosystems, the glyoxylate shunt, neutral mutations, cell wallls, or bacteriophage lambda.

  5. An outstanding post worth rereading several times. Thank you, Larry.

  6. Molecular evolution must prove itself on scientific evidence like all claims for evolution.
    Did they do this? or just add the obvious idea that there wasv evolution at the molecular level? it could only be that way if evolution was true!
    What did they accomplish exactly!
    Are they saying they see evolution going on in molecular operations now? No. They said it was a PAST event. RIGHT! Thats the word.
    i think its just comparative molecular concepts that they hypothesized on and was accepted.
    They were foreigners and did not understand creationism. They attack iD/YEC on scholarship and the usual accusations. Their profiling is way off.
    anyways if their evidence for molecular evolution is no better then the rest of evidence for evolution then I see no threat.
    I don't myself have interest at such atomic levels but I'm sure ID /YEC thinkers can deal with this.
    To intellectually impress me they must do better then in their profiling of creationists.
    Its you guys heros. Not ours.
    Where are the Nobel awards for iD thinkers? YEC too.!

    1. I don't have anything useful to add to this excellent post. That said, I do want to note that I find the juxtaposition of posts from Joe Felsenstein, Richard Lenski and...Robert Byers in the same comment thread to be jarring almost beyond description!

    2. Where are the Nobel awards for iD thinkers? YEC too.!

      It's tough to nail this down, but since you perpetually predict the downfall of evolution to be 15 years in the offing, I predict the first creationist Nobel Prize to be perpetually about 40 or so years in the future (unless Jesus returns in the meantime, in which case Jesus would get the award immediately I suspect, and not any particular creationist). As I say, it's tough to nail down.

    3. ...universal common ancestry by molecular phyogenetics was formally tested, actually.

      Douglas L. Theobald, "A formal test of the theory of universal common ancestry", Nature 465, 219–222, doi:10.1038/nature09014

      Universal common ancestry (UCA) is a central pillar of modern evolutionary theory1. As first suggested by Darwin2, the theory of UCA posits that all extant terrestrial organisms share a common genetic heritage, each being the genealogical descendant of a single species from the distant past3, 4, 5, 6. The classic evidence for UCA, although massive, is largely restricted to ‘local’ common ancestry—for example, of specific phyla rather than the entirety of life—and has yet to fully integrate the recent advances from modern phylogenetics and probability theory. Although UCA is widely assumed, it has rarely been subjected to formal quantitative testing7, 8, 9, 10, and this has led to critical commentary emphasizing the intrinsic technical difficulties in empirically evaluating a theory of such broad scope1, 5, 8, 9, 11, 12, 13, 14, 15. Furthermore, several researchers have proposed that early life was characterized by rampant horizontal gene transfer, leading some to question the monophyly of life11, 14, 15. Here I provide the first, to my knowledge, formal, fundamental test of UCA, without assuming that sequence similarity implies genetic kinship . I test UCA by applying model selection theory5, 16, 17 to molecular phylogenies, focusing on a set of ubiquitously conserved proteins that are proposed to be orthologous. Among a wide range of biological models involving the independent ancestry of major taxonomic groups, the model selection tests are found to overwhelmingly support UCA irrespective of the presence of horizontal gene transfer and symbiotic fusion events. These results provide powerful statistical evidence corroborating the monophyly of all known life.

    4. They were foreigners and did not understand creationism.


    5. Right after Dave Carlson mentions jarring juxtapositions, we get a comment from SRM referring to Jesus and using the phrase "tough to nail down." Ho ho!

  7. "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. Logical fallacy: you cannot demonstrate evolution."

    She probably wanted to please her supervisor, Larry Sandwalk? The evolving genes and proteins are merely changing, not evolving. They already have function and changes are allowed within that function. Genes and proteins without function would not be genes and proteins.

  8. Very nice blog - the writing of Zuckerkandl is very stylish, and to the point as well.

    I most like the final quote at the end:
    "a proper generalized nondoctrinal education regarding the nature of the world's phenomena combined with the teaching of ethical behavior."

    Indeed !

    Reading the comments from creationists on this blog, we're not quite there yet ...

    1. And you will never get there, Eelco...btw ...Are you Eelco, the dutch kosmologist? My friend...who wrote a negative review on my book before it even had been published? So far for ethical behavior.

    2. So you, Peter Borger, use a false name to post your creationist utterings here, and make false accusations at the same time ? I never wrote a review of your book - just a one-line warning that it is a creationist book, not a science book (as the webshop was claiming). A warning is not the same as a review. You had already published many bits and bobs of that book online, so don't whine about my warning: that was (and still is) most certainly correct.

      PS: your reply just confirms my last statement above - how sad (and boring).

    3. Eelco, it is you, old chap!

      I did not publish anything of my book before 2009. It is also not a creationist's book. It is anti-Darwinian. That is all. You believed -- and probably still do -- that Darwin is all there is. Back in 2005-2009, I showed you several times that you were wrong.

      Disclosing my pseudonym, here, is pathetic. So far for Eelco's ethics. Have a nice day.

    4. "I did not publish anything of my book before 2009."

      Sure you did. On your blog, including excerpts. Which were all obviously creationist.

      And I fear that you are the one that keeps going on about Darwin - you seem to be stuck for about 150 years or so ?

    5. "Disclosing my pseudonym, here, is pathetic. "

      That was already done earlier on this blog (by another Peter) - nothing to do with me. And it is not just a pseudonym: you go to great lengths to hide your actual name (something that is *not* common amongst creationists !), especially at (although not all traces are erased, it seems). No idea why ...

      But it seems to be you who keeps on going on about me (Eelco) - why all this interest in me ? I don't find myself interesting at all, and the readers here won't find my person very interesting either ... so why do *you* keep going on about who I am ? I fail to see the interest.

      Although I am happy to report that my wife and son still find me very interesting. Lucky me. But who else would care ?

    6. Genes...without function would not be genes....

      Torborg discovers pseudogenes! Creationism marches on! Congratulations, in another 50 years or so maybe you'll "discover" genetic drift.

    7. judmarc, Borger also recently learned why differences in mutation rates and genome size must be taken into account before trying to extrapolate data from bacterial experiments to other life forms. It almost looks as if a creationist was evolving in real time!

  9. I had several email exchanges with Zuckerkandl back in early 2006 and enjoyed his gentleman style very much.

    The real date for the start of molecular evolution should be 1962-1963 with these three papers. The 1965 paper has not a single data table and figure.
    Zuckerkandl E, Pauling L. Molecular disease, evolution, and genetic
    heterogeneity. In: Kasha M, Pullman B, eds. Horizons in Biochemistry.
    New York: Academic Press, 1962
    5 Margoliash E. Primary structure and evolution of cytochrome c. Proc
    Natl Acad Sci USA, 1963, 50: 672–679

    Nonetheless, unhappily we found ourselves determined to spoil the party. The original molecular clock hypothesis was grossly mistaken. Here is an abstract of a paper we have just submitted.

    The Genetic Equidistance Phenomenon at the Proteomic Level

    Denghui Luo and Shi Huang

    The field of molecular evolution started with the alignment of a few protein sequences in the early 1960s. Among the first results found, the genetic equidistance result has turned out to be the most unexpected. It directly inspired the ad hoc universal molecular clock hypothesis that in turn inspired the neutral theory. Unfortunately, however, what is only a maximum distance phenomenon was mistakenly transformed into a mutation rate phenomenon and became known as such. Previous work studied a small set of selected proteins. We have now performed proteome wide studies of 7 different sets of proteomes involving a total of 15 species. All 7 sets showed that within each set of 3 species the least complex species is approximately equidistant in average proteome wide identity to the two more complex ones. Thus, the genetic equidistance result is a universal phenomenon of maximum distance. There is a reality of constant increase in complexity during evolution. These results provide additional lines of evidence for the recently proposed maximum genetic diversity (MGD) hypothesis.

    1. Shi Huang is a member of an interesting group of people calling themselves 'The Third Way' ( ), who seem to think people either believe in creationism or neo-Darwinism. As the latter does not exist (science does not do -isms, as Zuckerkandl clearly said as well), and science usually does not involve believe, I find this a bit odd.

      Obviously there has been much progress since the neo-darwinian New Synthesis and all that, as is common in the scientific endeavour, so their main gripe is that 'people' do not seem to realise that. But all this progress is in succession of the neo-darwinian New Synthesis, it is not something completely new, so I think the term 'Third Way' is somewhat misleading.

      Interesting as well is their last paragraph on their 'rationale' page ( ), just in case the creationists here get too exited about this 'Third Way'.

    2. Gnomon = Shi Huang, Eelco.

      Are you the dutch kosmologist, who branded my book at as creationism before it was published and in the shops (judging by the cover), while it merely was anti-Darwinian?

    3. Did not see his confirmation, above. He is the kosmologist.

    4. while it merely was anti-Darwinian?

      You're so stupid that you think that's convincing, like we don't know what the creatard agenda is.

    5. The problem with the Third Way of Evolution is that it does not exist. Sure, there is a web site there, with statements by about 49 scientists, which they have agreed to have posted on the web site. If they all had similar theories, this would be a major Third Way, worth serious discussion.

      But alas, the owner of the web site has miscounted. There are actually Ways 3 Through 51 there. Each of the listed scientists resolutely marches off in a different direction, with no hint of a consensus about what the Third Way is.

      I don't think there is even a Second Way, since creationism is not a "way of evolution".

    6. Peer Terborg (false name) " ... before it was published "

      No, *after* it was published (same month). I posted my warning on the webshop selling the book. Which still is a creationist book, not a science book.

      And yes, I am a cosmologist - so what ? I fail to see the relevance of that fact.

      You work at a hospital in Zurich: which is also irrelevant.

      The arguments matter, not the persons.

    7. Joe, all good points. Reading the blurb that accompanies each person, they do seem to form a rather odd collective ...

    8. Gnomon,
      1. how do you define 'complexity' in organisms?
      2. How do you measure it ?
      3. Could you give an example of a list of organisms sorted by increasing complexity ?
      4. I (still) don't understand what you try to tell us...

    9. Simple. Compare the two approaches to study evolution. One ignores complexity. The other engages it even if imperfectly (use number of cell types to quantify complexity). Now ask yourself, which approach is better or has a chance to eventually succeed? If one thinks human is no more complex than HIV or bacteria, he surely would pick approach one. But then he is clearly not at the level of Aristotle in terms of intuitive power and really should have no business in being in the thinking profession or the hard science, the foundation of which is intuition or axiom. Regarding your question 3, Aristotle had it largely right and you can go read him.

    10. Why do you think there are only two approaches to study evolution ? That sounds like a false dichotomy to me ...

  10. Its not easy to take on esteemed leaders in a subject close to the heart of posters here. However they are asserting that there was/is molecular evolution. Separate and secondary point they took shots at ID and/or creationism .
    I heard of Pailing in something that got a nobel prize.
    their attacks on iD is just strange wrong and would persuade no one these days.
    Did they prove their had been molecular evolution??
    They said it was about past events. How did they contribute to evidence for evolution at the genetic levels.??
    In all these things i always find its just about comparaitive analysis based on presumptions of evolution. Yet not demonstrating evolution itself.
    Why would it be so late in the 1960's ito discover this?
    It couldn't be the guess their was molecular evolution. It MUST be some demonstration of how it would/did work. Yet my hunch is its the same comparative models they make like these tree models for evolution.
    Time will sort out truth and error on these matters.

    1. "their attacks on iD is just strange wrong and would persuade no one these days."

      They are convincing as ever, so your statement is wrong here. They do express themselves more stylishly than most, though :)

      "Time will sort out truth and error on these matters."

      That is a platitude.

  11. Crime Scene Investigation (CSI), complex specified information (CSI), and now "Compound Structure Identification" (CSI):

  12. Does anyone know of a photo of Emanuel Margoliash that one can find on the web? Despite a lot of searching I've never managed to find one.

  13. @Athel C-B:. I can't find a photo of him online either. You might try his son Dan Margoliash, who is a faculty member of the Department of Organisms Biology and Anatomy at the University of Chicago.

    1. "Anatomy and Organismal Biology" might make the search a little easier. Speaking of which, I once had a sign on my office door declaring it to be the Department of Anatidae and Oxyural Biology.

    2. Thanks, both. I'm trying what you suggest.

    3. The trubbel iz I can spel but I cannt tipe.