In the course of the 1920s and 1930s, great progress was made in the study of the intermediary reactions by which sugar is anaerobically fermented to lactic acid or to ethanol and carbon dioxide.
I did help to set up an undergraduate course in medicinal chemistry and made progress in modelling and analysing pharmacological activity at the tissue level, my new passion.
But sequence comparisons simply can't account for the development of complex biochemical systems any more than Darwin's comparison of simple and complex eyes told him how vision worked.
My laboratory uses evolution to design new enzymes. No one really knows how to design them - they are tremendously complicated. But we are learning how to use evolution to make new ones, just as nature does.
We are seeing the cells of plants and animals more and more clearly as chemical factories, where the various products are manufactured in separate workshops.
If a potato can produce vitamin C, why can't we? Within the animal kingdom only humans and guinea pigs are unable to synthesize vitamin C in their own bodies. Why us and guinea pigs? No point asking. Nobody knows.
I feel now, as we did then, that for an effective approach to the problem of nucleic acid biosynthesis, it was essential to understand the biosynthesis of the simple nucleotides and the coenzymes and to have these concepts and methodology well in hand.
In teaching, I wanted to offer a general pharmacology course based on chemical principles, biochemical classification and mathematical modelling. In the event I achieved neither of my ambitions.
A logical extension of our work on glycogen was to investigate the formation of starch in plants.
It's nice to be able to look at one protein, but life is driven by the interactions between proteins, so it's really essential to be able to see multiple proteins at a time to understand these interactions.
Finally, to the theme of the respiratory chain, it is especially noteworthy that David Kellin's chemically simple view of the respiratory chain appears now to have been right all along-and he deserves great credit for having been so reluctant to become involved when the energy-rich chemical intermediates began to be so fashionable. This reminds me of the aphorism: 'The obscure we see eventually, the completely apparent takes longer'.
So I set out to study the oxidation system in the potato, which, if damaged, causes the plant to turn brown. I did this in the hope of discovering, through these studies, the key to the understanding of adrenal function.
The identification of the genes which determine biological phenomena and the study of the control they exert on these phenomena has proven to be the most successful approach to a detailed understanding of the mechanism of biological processes.
We are loping sequences of chemical conversions, acting ourselves converted. We are twists of genes acting ourselves twisted; we are wicks of burning neuroses acting ourselves wicked. And nothing to be done about it. And nothing to be done about it.
We allowed ourselves to become particularly interested in research into the appearance of intermediate products of sugar decomposition during cell-free fermentation.
