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Introducing Günter Wagner: Evolution as a Creative Intellectual Endeavor

bridges vol. 11, September 2006 / News from the Network: Austrian Researchers Abroad
by Christian Hederer


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Even among the exclusive group of scientists working at America's most prestigious research institutions, Günter Wagner, professor of ecology and evolutionary biology at Yale University, is something of a rare species. Given his position, you might think that a scientific career of more than 20 years in several areas of influential, cutting-edge research is not that unusual. Less common, though, is the breadth of intellectual outlook he has retained despite a general trend towards ever narrower specialization: "Like in the days of the giants, Günter is a polymath whose intellectual curiosity extends far beyond the scope of his immediate research interests," says Robert Leclerc, a researcher at the "Wagner Lab," his main research unit. Karen D. Crow, another Lab researcher, agrees: "Dr. Wagner is able to recall information from a developmental, biochemical, and evolutionary perspective to fully evaluate the merit of an idea."

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wagnerportrait_small At the same time, graduate students and post-doc collaborators stress his abilities as an advisor in both intellectual and motivational terms. As Jutta Roth, a former post-doc researcher at the Lab, describes her experience: "I have never before worked with someone who gives his grad students and post-docs so much freedom when it comes to choosing research projects, and is so open to suggestions. And he has a rare gift for inspiring students . . . he supports them in finding the field of research that really rocks their world, even if that means that he loses a person to another research group."

But perhaps most important of all, Günter Wagner has a reputation for continuously driving research forward and for his readiness to foster investigations with the potential for challenging conventional scientific wisdom. "He likes to pursue ideas that are slightly beyond the current accepted theories because . . . scientists can become entrenched in what is currently accepted. Therefore new ideas need to be proposed and evaluated," says Karen Crow. Robert Leclerc adds: "Günter once told me that he enjoyed helping out the intellectual outcasts, and those out of the mainstream academic paths, because he thought that science needed people to shake up the establishment from time to time." In a sense, then, Wagner is applying a fundamental principle of his research field, evolutionary theory, to his own scientific domain: the fundamental role of innovation and creativity in all development.

Rupert Riedl, teacher and scientific innovator

Acquiring the intellectual foundations for advancing the frontiers of science is a long-term task, and Wagner was lucky enough to find a highly supportive environment for this in his native city of Vienna. It all started during his time at the College of Chemical Engineering, when his brother took him to a lecture series on evolution which featured, among others, Rupert Riedl, director of the Institute of Zoology at the University of Vienna. His fascination with this lecture persisted. After graduation, he took up studies in zoology and mathematical logic, and Riedl, whom he calls an "extraordinary and impressive intellectual personality," would exert a decisive influence on his thinking. Together with theoretical chemist Peter Schuster who, with Riedl, was Wagner's Ph.D. supervisor, and mathematician Karl Sigmund, Riedl was instrumental in keeping evolutionary theory at the University of Vienna at an internationally competitive level. Students such as Wagner, Walter Fontana, and Martin Nowak (the latter two now at Harvard University) bear testimony to his success. But Riedl's main significance, of course, does not lie in getting Austrian scientists to top US universities: He was a highly innovative thinker himself and decisively contributed to developing a "systemic view" of evolution, a way of looking at evolution that Wagner still alleges is the intellectual basis of his research today.

To see what this is about, let's take a very short look into the history of evolutionary theory. Modern evolutionary thinking started off with Charles Darwin's well-known On the Origin of Species by Means of Natural Selection (1859); but it took well into the 1940s for his account to be combined with other life science disciplines such as botany or paleontology into a rigorous theory of mutation and recombination at the genetic level. Evolution, at that time, was seen primarily as consisting of changes in gene frequencies from one generation to the next as a result of natural selection, random genetic drift, and gene flow (the transfer of genes between populations). That remained the scientific mainstream until the 1980s.

Riedl's approach, elaborated during the 1970s, doesn't take issue with the validity of population genetics. However, it does add a new level to the analysis: the evolution of body plans and "morphological characters" such as limbs or organs. Riedl's motivation for doing this was his insight - now firmly established in empirical terms - that the relation between genes and morphological characters is not one-way (i.e., genes translate into characters that are then subject to natural selection) but interdependent. By being constructed in a certain way, organisms limit the possibilities of how, and whether, genes are "expressed" in certain characters. Thus, Wagner calls morphological characters the "institutions" or sets of rules in evolution. They are shaped and influenced by individual behavior (the "genes") as well as putting restrictions on that behavior themselves. And just as the evolution of rules, such as a constitution or social conventions, cannot be reduced to individual behavior, the evolution of morphological characters, such as the structure of a hand, cannot be fully analyzed in terms of gene frequencies.

As is true for many scientific innovations, the essential idea of the systems approach was both straightforward and revolutionary, opening up an entire new field of research. What are the evolutionary reasons for the remarkable resilience of morphological characters, given constant underlying genetic variation? Exactly how does evolutionary innovation on the "macro level" - e.g., the development of complex organs and specialization within organisms - come about? How does the development of an organism work - from a single cell to an embryo to an adult - and how can it be explained in evolutionary terms? The latter question is the core of a new field, evolutionary developmental biology, known as "evo devo," which has become one of the most vibrant in biological science. Wagner's contribution in bringing those questions to the forefront of research was substantial, as pointed out by James M. Cheverud, a collaborator of Wagner's at the Washington University School of Medicine: "Dr. Wagner was instrumental in bringing evolutionary genetics together with development and morphology. While evolution and development is now a popular field of research, Dr. Wagner's efforts as early as 25 years ago provided much of the conceptual framework needed for this unification."

Yale, outside the box

Wagner received his Ph.D. from the University of Vienna in 1979, held several temporary research positions in Germany and the US, and became a tenured associate professor at the University of Vienna in 1990. The decisive turning point of his career came in 1991, when, shortly before finishing his Habilitation (a second dissertation, following the doctorate), he received an invitation to give a presentation at a biology seminar at Yale University. "Although the event officially did not have any relation to recruiting activities, it very soon became clear to me that the conversations with various people I had were actually job interviews . . . A couple of weeks after the event, I received another call from Yale asking me to send my resumé." He did, and Yale offered him a full professorship. In view of the lack of prospects for reaching a comparable position in Austria or Germany anytime soon, he accepted.

Given his new employer's formidable reputation, Wagner's account of research conditions at Yale is remarkably cautious. He stresses that to support his activities he is partly dependent on fund-raising, which is notoriously hard, particularly in basic research, where the rate of federal funding has reached a stunningly low 8 percent this year. Financing is a problem not only in terms of quantity but also of continuity. Moreover, this environment generates pressure for conformity and tends to crowd out exactly those risky and creative lines of research that Wagner deems so important. As Vincent Lynch, another researcher at the Wagner Lab, points out, the Yale factor hardly mitigates this problem because its high profile generates a lot of pressure to be successful, that is, to continuously publish and receive credit from the scientific community.

In spite of these constraints, however, allowing for intellectual variation is a major organizing principle of the Wagner Lab. It is definitely not a conventional laboratory where the everyday routine of specialized research takes its course: The researchers (graduate students and post-docs) are a diverse crowd, with past collaborators that include a theoretical physicist as well as the more common population geneticists and zoologists. The problems tackled are theoretical as well as empirical, with substantial effort directed into quantitative modeling. And a substantial amount of "thinking outside the box" is indeed on the research agenda.


Canalization and the intricacies of being different

One example of creative collaboration is the interaction between theory and empirical research. Being immersed in both areas, Wagner's work repeatedly demonstrates the potential of theoretical development to shake up the way empirical observations are interpreted.

For instance, a common observation in biology is that the variance of phenotypes in a population that carries a major mutation or is subject to environmental stress is larger than the variance in the corresponding "wild-type" population (i.e., one without mutation or environmental stress). Since most of this additional variance has a genetic basis, it follows that the wild-type population must have a certain amount of underlying genetic variance that is not expressed in the phenotype. This used to be interpreted as the consequence of selection for reduced phenotypic variability in the wild-type - its canalization or "genetic robustness" against mutations. Intuitively, given a stable selection environment, it seems evolutionarily advantageous to stick to well-tried solutions instead of tinkering around with new mutations. However, in a paper with J. Hermisson, Wagner showed that this cannot stringently be concluded from the evidence; rather, the observed increase in phenotypic variance is a generic property (that is, it pertains to large classes of models or groups) of genetic systems under fairly general conditions, and does not require canalization as a necessary condition. This forces experimentalists and theorists alike to rethink the interpretation of their results - creative theoretical reasoning at its best.

Given Wagner's interest in advancing theory, perhaps it is no coincidence that one of his fundamental topics is the very question of novelty - and its mirror image, homology - in evolutionary processes. Variation, that is, the generation of novelty, is one of the fundamental building blocks of evolutionary theory, and it is quite surprising that it has not been operationalized as a mathematically rigorous concept. This is partly due to the fact that the mathematical tools to capture the nature of novelty and innovation are only recently becoming available. Wagner has done a considerable amount of work to drive these forward.

The analysis of novelty is also a building block in tackling one of the most vexing questions in evolutionary biology: How is it possible that complex adaptations such as specialized organs - and ultimately, our own species, homo sapiens sapiens - evolved from a principally random, "unguided" evolutionary process? As Wagner explains, the long-term trend towards increasing complexity in natural evolution is in part just a statistical artifact. Complexity is bounded below but, in principle, does not have any upper limit, so the probability that more complex structures will evolve over time is substantial. Another factor is "ratchet effects". Once a developmental line is established (e.g., by the emergence of a new species) starting from a certain complexity level, it is statistically more probable that complexity will increase rather than decrease. But none of these results, of course, implies any deterministic necessity to add complexity - for example, artificial life models often show a reproductive advantage for less complex agents. In sum, this is a field where a lot of ground remains to be explored.

Understanding the choreography of organismic development

Wagner says that empirical work now takes the bulk of the time that he can invest in research, between his administrativechalcides-embryo_small obligations as holder of a Chair, the editor-in-chief of the Journal of Experimental Zoology, and a member of the editorial boards of various other journals. While empirical work may be less glorious than fundamental theory, it still offers opportunities to embark on the road less taken, something Wagner does not hesitate to do if he sees the potential for breaking new ground.

One example is the study of protein function in evolutionary developmental biology. Proteins are among the most important organic substances and regulate a whole spectrum of essential body functions. The building blocks of proteins are amino acids, with the amino acid sequence determining a protein's specific function. Investigating how the production of many different proteins is organized, leads back to the role of genes. Basically, the DNA of an organism can be differentiated into genes and so-called "regulatory regions." Genes contain the information that cells translate into proteins, the amino acid sequence of the protein - and thereby its function - being determined by the base sequence of the gene. Regulatory regions affect when and where a certain gene is activated leading to formation of a protein, in short, to gene expression.

An essential finding of evolutionary developmental biology is that all investigated animals so far share the same "tool kit" of developmentally important genes. This is particularly remarkable for a special class of genes called Hox genes, which play a major role in regulating embryonic development. The base sequence of Hox genes turns out to be very similar in different species, e.g., a fruit fly (where they were first identified) and a mouse. Since a fruit fly and a mouse look quite different (even to a non-biologist) their differences must be founded on the developmental process of the organism. Basically, there are two scenarios that could account for the differences in the body plans of fruit flies and mice:


  • expression of a similar gene differs due to differences in regulatory regions; or
  • regulatory regions are similar, but protein functions - and, by implication, the underlying base sequence of the gene - are different.

hox5front_smallWhether scenario 1 or 2 is utilized makes a big difference in evolutionary terms: If there's a mutation in a regulatory region, but the base sequence of the gene doesn't change, a protein just gets expressed at a different time or place in the organism which (depending on the specific case) may have a very restricted impact on the organism as a whole. However, if there is a mutation in the base sequence of the gene, this will affect all regions of the organism where this gene is expressed. Therefore, from an evolutionary point of view, it appears likely that organisms with mutations in regulatory regions (Scenario 1) have a greater chance of surviving, which is one of he reasons why evo devo research focuses mainly on these. Empirical examples for changes in protein functions (Scenario 2) are, so far, rare. However, as Jutta Roth points out, despite the advances in recent research, the enormous complexity of organismic development is still not well understood, so it is important to keep looking at a variety of mechanisms instead of focusing on just one. In keeping with this, the study of protein function is an important topic for empirical research in the Wagner Lab.

Brain drain and the point of no return

Being at the same time an émigré from the European world of science and what Peter Stadler, a long-term collaborator of Wagner's and professor of bioinformatics at the University of Leipzig, calls "one of today's most important theoretical biologists," Wagner seems to be a classical case of "brain drain" from Europe to the US, which has recently has become such a big issue in science policies. Has he ever regretted his step of permanently moving to the US? His answer is somewhat hesitant at this point: "You know, after six or seven years your perspectives become more American than Austrian . . . You reach a certain point of no return, and by now I have almost certainly passed that point," he says, adding: "Well, that's how things turn out . . ." As to the quality of life in his new home, the city of New Haven, CT (where Yale is located) was not exactly the coziest place imaginable when Wagner first arrived. Regularly at dusk, as he recalls, the noise of handgun fire started to reach an intensity that he had only experienced previously during his compulsory service in the Austrian army. Since then, however, police pressure on gangs has risen substantially and the university is strongly engaged in neighborhood development.

How, then, does Wagner view the European - and specifically Austrian - university system? Again, the decisive question of creativity in science comes to the fore: He stresses that a crucial difference between the US and Austria lies in the opportunities for young researchers to work as independent investigators after obtaining their Ph.D.s, a phase of their intellectual development often considered the most productive and innovative in a natural scientist's lifetime. Contrary to the US, the institutional environment for achieving such an independent position at this stage is virtually absent in Austria. Moreover, in contrast to the US, tenure track positions in Austria have been virtually abolished. Wagner sees this as a demand for mobility at the wrong point; whereas mobility makes sense at the undergraduate and Ph.D. levels, he feels that, having undergone a rigorous selection procedure, scientists should be able to take a long-term perspective at a specific institution where they can gradually develop their work.

Regardless of these problems, though, Wagner has a generally positive view of education systems in Austria and Europe, citing his own experience: "The University of Vienna offered me a lot of freedom and, while I was selective about my intellectual environment, perfectly enabled me to build up the international reputation needed to become a Yale professor." He does not see any problem with generating young talent in Europe as long as schools and universities maintain their current levels. "Research and education policies should not primarily focus on regaining emigrated European scientists, but on offering better perspectives for the young generation," he says. So perhaps some creative European minds, as yet unknown, will in fact find attractive alternatives to the path that Günter Wagner chose back in 1991.


The author, Christian Hederer, has been an economist at the Austrian Federal Ministry of Economics and Labor since 2004, spending July-September 2006 at the OST as a visiting expert. His main field is European economic policy, with an emphasis on the Lisbon Strategy for Growth and Development, research and innovation policy, and labor market policy.

Related sources

The main source for the article was an interview conducted with Prof. Wagner on Aug 17, 2006. My special thanks to Jutta Roth for generously spending her time on introducing me into the intricacies of empirical evo devo research.

Homepage of Prof. Günter Wagner at Yale:

Homepage of Wagner Lab: http://pantheon.yale.edu/%7Egpwagner/index.html

Orr, H. Allen 2005: Turned On. A Revolution in the Field of Evolution? The New Yorker, 10/17/2005.

Laubichler, Manfred D. / Wagner, Günter 2004: Rupert Riedl and the re-synthesis of evolutionary and developmental biology: body plans and evolvability. Journal of Experimental Zoology Part B: Mol Dev Evol. 302B:92-102.

Hermisson, Joachim / Wagner, Günter 2004: The Population Genetic Theory of Hidden Variation and Genetic Robustness. Genetics 168: 2271-2284 (December)

Gibson, Greg / Wagner. Günter 2000: Canalization in Evolutionary Genetics: A Stabilizing Theory? BioEssays 22: 372-380.



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