The most mysterious and important of all biological molecules was a family of substances called proteins. When Pauling decided to enter the field, scientists had been at work trying to unravel their secrets for almost two hundred years, and still relatively little was known. It was clear that proteins were involved in every biological reaction and formed an important part of almost every structure within living organisms. It was known that life could not exist without them. They seemed to be the very key to what constituted "life" (many researchers believed that genes, the stuff of heredity, were made of protein). Yet their basic structure defied study.

One set of problems arose from the fact that proteins took many forms. Structures as different as hair is from blood, or the horn of a cow from the skin of a jellyfish, were all made of protein. More confusion came from their dizzying array of abilities. Proteins somehow caused "ferments" that could change substances into other substances. Proteins were built into structures, like feathers and connective tissue. Proteins called enzymes catalyzed biological reactions. Proteins called antibodies conferred immunity. Other proteins were fashioned into fingernails. How could one class of biomolecules do all these things?

Then there was proteins' unusual ability to change properties and appearance. Take eggs, for instance: when raw, the albumen of a chicken egg is a clear gel; when beaten, a fluffy meringue; when heated, a tasty omelet. Proteins were difficult to separate from one another, tough to purify, hard to preserve, easy to destroy, and almost impossible to study in detail. Researchers could not even agree on names for the many forms they took. The riot of names common around the turn of the twentieth century is a testament to how little researchers understood: fibrin, casein, albuminous bodies, protoplasm, peptones, hemipeptones, antipeptones, albumoses, colloids, enzymes, gelatins, ferments, globules, glutens, and on and on. Attack after attack was made on their mysteries, from many angles. One theory after another was proposed to explain their nature. None of them was satisfactory.

By Pauling's time, however, many decades of chemical study had yielded a small treasury of important facts. It was known, for instance, that all proteins seemed to be made from twenty or so smaller building blocks called amino acids. Each amino acid had the same backbone: an amino group at one end, connected to a carboxyl group at the other via a central carbon atom. Various side groups and structural peculiarities gave each of the twenty a particular flavor.

The questions remained: How did these amino acids join together to create active proteins, and how did the final structure of these proteins confer such a range of abilities? In the first years of the twentieth century, the great German organic chemist Emil Fischer put forward the idea that amino acids were connected to each other through what he called a peptide bond formed end-to-end between a carboxyl group on one amino acid, and the amino group on another. Two amino acids linked in this way formed what Fischer called a dipeptide. Three formed a tripeptide. He strung together as many as fourteen amino acids in his laboratory into a chain-like molecule that began to show the properties of a natural protein. The general term Fischer used for this type of structure was "polypeptide."

As Linus Pauling dove into the field of biological molecules, he read everything he could find on proteins and came to believe that Fischer's ideas made good chemical sense. Amino acids, he thought, were likely to join together to form long chains.

But how did these long chains of amino acids achieve the many forms and functions of proteins?