Adrenaline has enormous cultural significance as a molecule associated with medically important stress and with excitement, anger, and terror. Adrenaline flows in an adventurer ascending a sheer cliff or in a young violinist debuting at Carnegie Hall. A shot of adrenaline empowers superhuman feats in emergencies. Risk takers seeking dangerous recreations are adrenaline junkies who enjoy repetitive adrenaline rushes. On the other hand, an adrenaline surge during a bitter argument may precipitate a heart attack or scare us to death.

Many widely held views about adrenaline are popular extrapolations of scientific research done by Walter Cannon at Harvard Medical School....

In the fairy tale about the three bears, Goldilocks tastes Papa Bear’s porridge and finds it far too hot, while Mama Bear’s porridge proves much too cold. Happily for Goldilocks, Baby Bear’s porridge is just right. This represents an example of what’s often known as the Goldilocks Principle, reflecting the desirability of an appropriate balance that avoids extremes. As we will see, the Goldilocks Principle applies as much to adrenaline as it does to porridge. In this chapter, as we begin our multifaceted discussion of adrenaline, we concentrate on the dire effects of too much or too little adrenaline, along...

By the nineteenth century, biomedical scientists generally believed that the body’s various functions were integrated by the brain alone, through the signals sent along nerve pathways to the peripheral organs. This widely accepted paradigm delayed appreciation of hints pointing to the existence of invisible chemicals released into the blood that also influenced the function of distant organs. Now we know that these chemicals, called hormones, secreted by endocrine glands, are vitally important. Just over a century ago, the putative existence of hormones remained shrouded in uncertainty and controversy. We now live in a hormone-empowered culture, familiar with the raging sex...

In the early 1890s, numerous medical journals reported both the benefits of thyroid extracts in myxedema and Brown-Séquard’s rejuvenation claims. Then, as now, many physicians were enthusiastic—and sometimes uncritical—early adopters of novel therapeutic strategies, and so the use of animal extracts in patients expanded considerably. This prompted an editorial in the influential British Medical Journal in 1893 warning about a “possible epidemic of universal injections . . . often upon no better evidence than quacks produce for their ‘cures.’”

At about the same time, however, George Oliver, a thoughtful physician in private practice, was conducting bold experiments with...

The Oliver and Schäfer experiments pointed to the existence of a chemical in the adrenal medulla that markedly raised blood pressure. Unmasking its identity presented a challenging biomedical problem that attracted ambitious scientists. We now know that adrenaline constitutes only about 0.1 percent of the weight of the adrenal glands, a tiny fraction of the total material, which made identifying it something like looking for a needle in a haystack.

More than a century ago scientists had very few clues about substances in the adrenal medulla and only rudimentary methods for isolating chemicals. In 1856, Alfred Vulpian discovered that iron-based...

Adrenal extracts and then adrenaline moved rapidly from the laboratory to the bedside. The initial infectious enthusiasm for adrenaline contributed to physicians prescribing this new drug in highly fanciful and futile efforts to combat disease. Physicians learned only gradually and inconsistently from anecdotal experience about adrenaline’s efficacy and serious adverse effects. This chapter describes both the rational and the indiscriminate incorporation of adrenaline into medical practice. These stories, carried through to the present, illustrate the advances that have been made over the past century in the systematic evaluation of the safety and efficacy of drugs, as well as limitations in...

When compared with injections of adrenaline, activation of sympathetic nerves has many similar actions on organs throughout the body. The dazzling explanation for their comparable effects emerged only after much hard work, and it had broad implications for understanding the inner workings of the nervous system and for the invention of powerful drugs. Sorting out how the companion parasympathetic nerves activated target organs posed an analogous challenge. The resolution of both questions involved the astonishing demonstration that sympathetic and parasympathetic nerve endings release chemicals called neurotransmitters that move across the narrow gap from nerve endings to cells in target organs....

In the first several de cades of the twentieth century, physiologists identified the most prominent effects of adrenaline on major organs such as the heart and lungs. Elucidating the mechanisms underlying these actions presented highly attractive scientific problems that proved very difficult to solve. The explanations required discovering and unraveling intricate, submicroscopic actions that adrenaline has on specific molecules in cells that make up organs. This broad field of research is now known as signal transduction biology, the investigation of how the arrival of a signal such as adrenaline at cells is transduced biochemically into responses within cells. There was...

Adrenaline operates only on cells that have adrenergic receptors; by sliding into these intricate structures like a key, adrenaline unlocks each receptor’s capacity to set in motion cascades of signals. The hypothesis that drugs interact with specific receptors emerged at the end of the nineteenth century. However, skepticism about the existence of receptors gave way only relatively recently, under the weight of increasingly powerful experimental evidence. Research over the past hundred years addressing adrenaline action has played a pivotal role in recognizing that drug and hormone receptors are concrete molecules that have specific biochemical effects in cells.

The hypothesis that...

Early twentieth-century chemists seized the opportunity to synthesize structurally related analogs of adrenaline; pharmacologists evaluated these new substances in elaborate, time-consuming animal experiments. Some of these compounds partially reproduced or inhibited the actions of adrenaline. A number of interesting drugs emerged, providing either novel therapies for disease or serving as useful pharmacological tools that helped unravel the fundamental biology of the autonomic nervous system. Throughout the first half of the twentieth century, limited understanding of how adrenaline activated cellular responses hindered the invention of drugs with highly selective actions. In the second half of the century, Ahlquist’s framework of α...

At just the right dose, adrenaline connotes excitement, vigor, and thrills. On the other hand, overflowing adrenaline heralds fear, anger, and even death. Similarly, many of the ways adrenaline has been portrayed over the years in popular media involve its capacity to increase strength and to boost the flavor and intensity of emotional responses; other allusions draw upon its ability to trigger heart attacks.

The most fashionable facets of adrenaline have changed considerably over the last hundred years. The first story in the New York Times involving adrenaline appeared on the front page on Sunday, January 18, 1903. The article...