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.