Follow Your Nose!

"Very often in the course of scientific experimentation a totally unexpected observation is made that is either unrelated or only incidentally related to the problem under immediate investigation. When it captures the attention of an alert, inquisitive mind, this observation may open the door for an entirely new study that is often more fruitful than that of the original design."

• –Earl Stadtman

The living organism is like a well-maintained chemical factory: a number of organic compounds are incessantly produced and degraded, while various inorganic materials—non-carbon compounds, metals, and minerals-are consumed, to keep the system alive. Almost all chemical reactions in this factory are catalyzed by protein molecules called enzymes. As catalysts, enzymes speed up enormously (10-billion-fold) the rate of specific biochemical reactions.

Enzymes are thus the key to understanding "metabolism," which is a highly integrated and regulated process of biochemical reactions. This process is usually manifest in a sequence of multiple reactions, rather than of a single one, to form a "metabolic pathway," and survival of an organism is possible only within the narrow limits of "metabolic regulation." Therefore, the two main goals of biochemists studying metabolism are: (1) to map out metabolic pathways by identifying important intermediates—substances that are produced or used in the sequence of reactions but are not considered final products—and isolating the enzymes involved; and (2) to elucidate the ways in which biochemical reactions are regulated.

Thressa and Earl have explored the metabolism of fatty acids, amino acids, and proteins, taking advantage of enzymes extracted from both bacterial and mammalian cells. At NIH, they have always been allowed to choose their own research topics, and often, their keen attention to unexpected experimental results has paid off with important discoveries leading to new fields of study. To those looking for a promising research subject, their advice is simple and direct: "Follow your nose!"