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Proposing that Darwin's principle works at the molecular level


The importance of understanding life at the molecular level
Manfred Eigen Scientist
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Now we come to the question of life, and...

[Q] When did you start to think about 'life'?

Yes, one of the main results of these studies was that we found that enzymes are optimal catalysts. What does optimal mean? Optimal does not necessarily mean that they are the fastest possible, because an enzyme has not only to take care of a fast turnover - it has to be specific. So in fact in an enzymatic reaction you have two contradicting processes, namely you want to do the reaction as fast as possible. But, on the other hand, the reaction should be specific. The enzyme should accept only it's very specific substrate, and a substance which is similar to it should not be accepted, because otherwise the life process would get mixed up. So, to be specific means it has to make a strong bond, and a strong bond means a slow reaction. If something is very fixed, then it takes a longer time to break it apart. So you see the two contradicting things. First of all the enzyme and the substrate have to combine. They usually do that diffusion-controlled, so that's a very rapid process. We found many enzymes where that speed is given by the diffusion-controlled reaction. Wonderful if this could also be the total speed. But now comes this binding... must be very strong, so that something which is similar can dissociate before the reaction takes place. So in order to get it specific, you need a sufficiently strong binding, and then you need the turnover from the substrate into the reaction product, which I said could appear in several steps involving the enzyme changing its conformation, has to bring all the reacting groups in an optimal contact to this.

So, what are the requirements, then? Well, they should combine rapidly, that's diffusion-controlled. Now before they can come apart, there should be the turnover. On the other hand, the reaction... the substrate coming apart, doesn't have to be much slower than the turnover, because otherwise when this is very slow the product wouldn't come apart again. And when we look at an enzyme reaction, and we have studied many of them, they always were an optimal combination of these various requirements. So we ask the question: how come? How did nature manage? The biologists among us said, 'This is Darwinian explanation, survival of the fittest.' We said, 'Wait, wait, Darwin developed his principle for living organisms.  These are molecules. How do the molecules know?' So we had the feeling we should understand more about life at the molecular level.

Nobel Prize winning German biophysical chemist, Manfred Eigen (1927-2019), was best known for his work on fast chemical reactions and his development of ways to accurately measure these reactions down to the nearest billionth of a second. He published over 100 papers with topics ranging from hydrogen bridges of nucleic acids to the storage of information in the central nervous system.

Listeners: Ruthild Winkler-Oswatitch

Ruthild Winkler-Oswatitsch is the eldest daughter of the Austrian physicist Klaus Osatitsch, an internationally renowned expert in gas dynamics, and his wife Hedwig Oswatitsch-Klabinus. She was born in the German university town of Göttingen where her father worked at the Kaiser Wilhelm Institute of Aerodynamics under Ludwig Prandtl. After World War II she was educated in Stockholm, Sweden, where her father was then a research scientist and lecturer at the Royal Institute of Technology.

In 1961 Ruthild Winkler-Oswatitsch enrolled in Chemistry at the Technical University of Vienna where she received her PhD in 1969 with a dissertation on "Fast complex reactions of alkali ions with biological membrane carriers". The experimental work for her thesis was carried out at the Max Planck Institute for Physical Chemistry in Göttingen under Manfred Eigen.

From 1971 to the present Ruthild Winkler-Oswatitsch has been working as a research scientist at the Max Planck Institute in Göttingen in the Department of Chemical Kinetics which is headed by Manfred Eigen. Her interest was first focused on an application of relaxation techniques to the study of fast biological reactions. Thereafter, she engaged in theoretical studies on molecular evolution and developed game models for representing the underlying chemical proceses. Together with Manfred Eigen she wrote the widely noted book, "Laws of the Game" (Alfred A. Knopf Inc. 1981 and Princeton University Press, 1993). Her more recent studies were concerned with comparative sequence analysis of nucleic acids in order to find out the age of the genetic code and the time course of the early evolution of life. For the last decade she has been successfully establishing industrial applications in the field of evolutionary biotechnology.

Tags: Enzymes, optimal catalysts, substrate, diffusion-control, molecular biology, Charles Robert Darwin

Duration: 3 minutes, 54 seconds

Date story recorded: July 1997

Date story went live: 24 January 2008