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Going Against the Grain

CREDIT: Denis Gebauer

The desire to discover something new is certainly one of the most important motivators for scientists. But Denis Gebauer, who is now 34, got more than he bargained for during his Ph.D. at the Max Planck Institute of Colloids and Interfaces in Potsdam, Germany. He built a new experimental setup to try and understand the formation of calcium carbonate -- a mineral with relevance to chemistry, geology, biology, climate change, and industry -- and soon was confronted with measurements that didn’t make sense according to the conventional view of crystallization.

“It’s always difficult to decide if the data that you’ve generated are representative, or if not understanding the data is due to your setup.” -- Denis Gebauer

At first, Gebauer doubted his results. He subjected them to aggressive experimental scrutiny and discussed them extensively with colleagues. Eventually, he concluded that his measurements showed something real. “This finding opens up an entirely new view on crystallization,” writes Helmut Cölfen, Gebauer’s former Ph.D. supervisor, in an e-mail to Science Careers. Last month, Gebauer was awarded a Heinz Maier-Leibnitz Prize from the German Research Foundation for his “ground-breaking discoveries which revolutionised the scientific perspective of nucleation and crystallization.”

A departure from the classical approach

Gebauer originally planned to study medicine. He shadowed a family friend, a physician at the Hannover Medical School, who advised him to study biochemistry. “He said my interest would be much more into that direction, which I think was a very good advice,” Gebauer says.

While studying for a bachelor’s degree in biochemistry at Leibniz Universität Hannover, Gebauer found that what he enjoyed most was physical chemistry. “I liked the insight into very fundamental mechanisms that are … not as complex as perhaps elaborate biological systems are,” Gebauer says. He went on to obtain a M.Sc. degree in biochemistry, doing his final-year thesis at the university’s Institute of Physical Chemistry and Electrochemistry, studying the kinetics of silica formation through the polycondensation of silicic acid. Some algae are able to extract silicic acid from ocean waters to form silica as a way of building an exoskeleton, so Gebauer also looked at the role of proteins on in vitro silica formation.

Gebauer was fascinated that nature could produce chemical compounds that are much simpler than biological molecules and yet “still direct and control the formation mechanisms in a very sophisticated manner,” Gebauer says. He realized that there was still much to discover about how nature accomplished this.

After graduating in 2005, Gebauer joined Cölfen’s group at Max Planck seeking a Ph.D. in physical chemistry. Nicole Gehrke, a former Ph.D. student in the lab, had recently managed to fill a biological matrix with mineral to reproduce nacre, a composite, iridescent, calcium carbonate–rich material formed in the inner shell of some mollusks and commonly known as mother of pearl. At first, Gebauer's Ph.D. project was to characterize the physicochemical aspects underlying such crystallization. “I actually never got to the stage to do that ... because we found something else,” he says.

Gebauer began his work by building an experimental setup that would allow him to detect the presence of the various chemical species as he brought the solution to supersaturation. Almost immediately, he started seeing things that didn't make sense. “During the instrument calibrations and test measurements, he always detected that calcium was missing in a calcium carbonate assay,” writes Cölfen, who now works at the University of Konstanz. “Since the calcium cannot disappear, I always believed in some sort of artifact and sent him back to the lab.” But, “after several months and the x-th modification of the experiment, I ran out of ideas … [on] which experimental artifact could be responsible for this. I suggested to him to look at the solution in an analytical ultracentrifuge, a very powerful instrument, which is able to show the components even in very complex mixtures.”

According to the classical theory of crystallization, calcium carbonate nuclei form spontaneously and then fall apart until they reach a critical size, after which they serve as nucleation clusters that can grow into crystals. Contrary to this textbook view, Cölfen and Gebauer found that the calcium ions were missing in their assays because they had formed minute, stable calcium carbonate clusters, prenucleation.

At that point, the main scientific challenge Gebauer faced was “to design and perform experiments which truly prove the nature of the clusters,” Cölfen writes. “This was especially difficult since many analytical techniques -- even when using synchrotron radiation -- come to their limit when characterizing the very small clusters which are additionally only present in small quantities.” Gebauer designed a number of clever experiments, Cölfen writes, and based on the finding of stable prenucleation clusters, proposed a new mechanism for calcium carbonate crystallization in a paper in Science in December 2008.

So important and unorthodox a finding can be especially challenging for a junior scientist. “It’s always difficult to decide if the data that you’ve generated are representative, or if not understanding the data is due to your setup,” Gebauer says. It took him at least half a year of tweaking before he felt sufficient confidence in his data. Then, he found himself with a lot of data that didn’t appear to make sense and felt pulled in many directions.

When, eventually, he was able to explain his observations, he found himself in the middle of a controversy. “Denis’s results about the prenucleation clusters were initially discussed and questioned a lot,” Cölfen writes. “The crystallization community … is a bit conservative. So there are well-known scientists that challenge your ideas and you have to defend your theory all the time.” Gebauer says this was always done in a friendly manner, and he was able to make it through -- and eventually change people's minds -- because he had already considered many of the objections people would raise. The detection of the clusters by an independent group using cryo-electron microscopy helped convince the community, Cölfen adds.

Returning to the classical (career) path

After obtaining his Ph.D. in June 2008 -- and winning his university’s prize for the best dissertation in natural sciences -- Gebauer stayed at the Max Planck Institute of Colloids and Interfaces for 6 months, working with Markus Antonietti, the institute’s director, exploring the mode of action of common antiscalants using his quantitative setup. Calcium carbonate “is not only a biomineral, it’s also the [scaling] that forms in your laundry machine or in the dishwasher,” Gebauer explains.

Gebauer then went on to do a 2-year postdoc with Niklas Hedin in the Department of Inorganic, Physical, and Structural Chemistry (now the Department of Materials and Environmental Chemistry) at Stockholm University. There, he used his nonclassical crystallization theory to study the formation of early structures in amorphous calcium carbonate, getting these structures to develop in the absence of any additives for the first time. “This prestructuring … appears to be … very important when it comes to the [later] evolution of polymorphic structures,” he says.

Gebauer returned to Germany in January 2011, rejoining Cölfen's lab at Konstanz to prepare his “habilitation” diploma -- a second research thesis that allows scientists to teach in Germany. “What I am doing now is more the very classical version” of the academic career path in Germany, whereby you strive for a couple of years to build your own research lines and team within the group of a renowned scientist and then compete for a permanent university position. There are other routes these days, but “I myself did it that way because I didn’t want to change subject.”

Today, Gebauer is working on understanding the early stages of calcium carbonate crystallization in more detail. He is also turning his attention toward broadening the concept of nonclassical nucleation to other minerals. He has initiated collaborations with theorists to simulate the formation of prenucleation clusters and come up with a predictive model of which minerals his theory may apply to. “What I would hope is, there’s something like a consistent model that would include this prenucleation concept into a hopefully quantitative theory of nucleation,” he says.

His theory is still debated, but “many people realize its value for explaining observations, for example, ... in studies dealing with bio- and biomimetic mineralization,” Gebauer says. In any case, “The classical theory of nucleation has turned out to be off-target by several orders of magnitude in some systems when it comes [to] quantitative predictions." There are many corrections to the theory, he says, but until now, they "never challenged the fundamental assumptions,” Gebauer adds. “The new findings show that the fundamental assumptions have to be revisited.” Ultimately, the implications could include the development of novel antiscalant strategies, the ability to design new synthetic materials, the control of crystal properties, or a better understanding of CO2 sequestration in sediments, which is relevant to climate change.

While Gebauer may have found his niche topic primarily out of luck, he was able to develop a career in it due to his commitment to skepticism and a thoroughly analytical approach. “The textbook view can be the suitable approach for some systems. But you have to be aware that it's not necessarily always the case, especially when it comes to complex systems.”

Elisabeth Pain is contributing editor for Europe.