1957 Nobel Prize in Physiology or Medicine — Bovet and Receptor-Blocking Drugs

What You Will Learn in This Article

You will understand how Daniel Bovet established a new pharmacological category called “receptor antagonists” by successively creating a series of synthetic drugs, including antihistamines, curare-based muscle relaxants, and sulfa drugs, and why this approach is now a major component of pharmacology textbooks.

Beyond Common Sense — Drugs Don’t Only Come from Nature

Today, we commonly think of drugs as being of two types: “those derived from nature and those synthesized.” Penicillin is a natural product (1945 Nobel Prize), aspirin is a modified natural product, and most new drugs today are completely synthetic.

Until the mid-20th century, this balance was completely different. Most antibiotics came from screening natural products (Waxman, 1952), and anesthetics were also mostly natural alkaloids. It was uncommon for purely synthetic drugs to gain clinical significance.

Bovet was one of the key figures who reversed this balance. The success of the various series of synthetic drugs he created in clinical practice demonstrated that “a non-natural, synthetic approach can become the mainstream in drug development.” This demonstration has determined the direction of the pharmaceutical industry for the past half-century.

In the language of CS, what Bovet did was synthesize a mock object that does not exist in nature and precisely fit it into a specific interface. Examples include antihistamines, which bind to histamine receptors but do not transmit signals, and curare-based drugs, which bind to acetylcholine receptors and block muscle contraction signals. These were synthetic molecules designed to mimic the structure of natural ligands but with reversed function.

The Zeitgeist — The Beginning of Space Exploration and European Integration

1957 was a year in which several major trends of the late 20th century began.

In March, the Treaty of Rome was signed, creating the European Economic Community (EEC). This is the root of today’s European Union (EU). The treaty, in which six countries – West Germany, France, Italy, the Netherlands, Belgium, and Luxembourg – resolved to form a customs union and a common market, became the cornerstone of European integration for the following half-century.

On October 4, the Soviet Union launched Sputnik 1. The first artificial satellite. This event triggered the US space development program (NASA was established in 1958) and the US science education reform (NDEA 1958). This was the moment when the “Space Age” symbolically began.

At the same time, several synthetic drugs were already being successfully introduced into clinical practice. Antihistamines became the standard of care for allergies, muscle relaxants became essential tools in anesthesiology, and chlorpromazine (1952) became the first antipsychotic drug in psychiatry. The Nobel Committee’s selection of Bovet was recognition of the individual who created the theoretical roots of these various trends.

In the context of Korean history, 1957 was a year in which the political fissures in the late Lee Seung-man regime deepened. The seeds of the March 15th rigged election were being sown, which would lead to the April 19th Revolution.

Bovet — A Laboratory Across Two Continents

Daniel Bovet was born in Fribourg, Switzerland. After studying biology at the University of Geneva, he moved to Paris and joined the Pasteur Institute. The Institute’s chemotherapy department was the stage for several key discoveries at the time. He then moved to the Italian National Health Institute (Istituto Superiore di Sanità) in Rome in 1947 and spent the rest of his life there.

His methodology was systematic synthesis and screening. He observed that certain natural ligands bind to specific receptors and trigger specific reactions, and then synthesized and screened a series of similar compounds with different structures but different functions. The drugs he created through this method belonged to various categories.

Sulfa Drugs

During his time at the Pasteur Institute in Paris (around 1935), he made his first major discovery. He showed that the antibacterial effect of Prontosil, discovered by the German scientist Domagk (see 1939 Nobel Prize), was actually due to the fact that this compound is broken down into sulfanilamide in the body. This discovery laid the theoretical foundation for the expansion of the sulfa drug series and opened up a crucial class of antibiotics before the penicillin era.

Antihistamines

Around 1937, Bovet’s team synthesized the first clinically useful antihistamine. It was already known that histamine is a mediator of allergic reactions, and Bovet discovered compounds that bind to histamine receptors but do not cause a reaction. This marked the establishment of a new pharmacological category called “receptor antagonists.”

Since then, pyrilamine, promethazine, and subsequent generations of non-sedating antihistamines (loratadine, cetirizine, etc.) have been developed. The drugs we take today for seasonal allergies are all descendants of this series.

Muscle Relaxants

In the late 1940s, Bovet’s team developed synthetic analogs of curare alkaloids. Curare is a natural product used by South American indigenous people as an arrow poison, which blocks acetylcholine receptors at the neuromuscular junction and causes muscle relaxation. Natural curare was limited in its clinical use because its composition was not consistent and its supply was difficult, but Bovet’s team created synthetic analogs such as succinylcholine and gallamine, making clinical standardization possible.

This development became a key element of modern general anesthesia. General anesthesia requires three elements: unconsciousness, analgesia, and muscle relaxation. Before the establishment of muscle relaxants, surgery was much more difficult, and Bovet’s synthetic muscle relaxants solved this problem.

The CS Framework of Mock Objects

Now let’s organize the pharmacological principles established by Bovet in the language of CS.

Various cells in the body have receptors, which are interfaces. When specific natural ligands (hormones, neurotransmitters, etc.) bind to these receptors, the cells receive signals and respond. This system is a precise counterpart to the API interface and client call. Receptor = API endpoint, ligand = client request, signal = response.

Receptor antagonists play the role of mock objects in this interface. They bind to receptors in a manner similar to natural ligands, but do not trigger signals. They also occupy the receptor, preventing the binding of the natural ligand. As a result, the entire signaling pathway through that receptor is inhibited.

The reason this approach is so powerful is its specificity. The natural system has many different receptors, each of which transmits different signals. A well-designed mock binds only to the specific receptor of interest and does not affect other receptors. This specificity is the key to minimizing side effects.

The occurrence of side effects can also be explained by this framework. Perfect specificity is impossible, so most receptor antagonists bind to some degree to other similar receptors besides the original target. This is the source of non-specific side effects. Much of today’s new drug development is focused on increasing this specificity.

A partial limitation of this CS framework: mock objects in software are usually used only in test environments, but receptor antagonists in pharmacology work in real production (the living body). This difference completely changes the weight of safety verification.

The Legacy That Continues Today

The receptor antagonist approach established by Bovet is now a major component of pharmacology.

Antihistamines (H1, H2, H3, H4 series) are used in allergies, gastric acid control, and sleep induction. β-blockers (propranolol, etc.) are a mainstay in the treatment of hypertension and arrhythmias. α-blockers are used in the management of benign prostatic hyperplasia and hypertension. ACE inhibitors and ARBs are key in the treatment of hypertension and heart failure. Opioid antagonists (naloxone, naltrexone) are used in the emergency treatment of opioid overdose.

Many anticancer targeted therapies also belong to this category. Breast cancer HER2 inhibitors (trastuzumab), chronic myelogenous leukemia BCR-ABL inhibitors (imatinib), and various lung cancer EGFR inhibitors. Each of these blocks the activity of a specific receptor or signaling molecule, inhibiting cancer growth.

Psychopharmacology is also largely based on this framework. Antipsychotics (dopamine D2 blockers), SSRIs (serotonin reuptake inhibitors), benzodiazepines (allosteric modulators of GABA receptors), etc. Each drug manipulates a specific neurotransmitter receptor or related system.

The theoretical root of all these series is the principle that “synthetic molecules that mimic the structure of natural ligands can block receptors,” and Bovet demonstrated this principle empirically.

Why It Matters

What Bovet’s story has left us with is the establishment of “an approach to manipulating nature from outside nature.”

Until the early 20th century, drug development relied largely on the discovery and purification of natural products. What Bovet and his generation established was an approach to designing new molecules that do not exist in nature and making them interact with natural systems. This shift has made possible the growth of the pharmaceutical industry over the past half-century. Most of the drugs we use today are synthetic drugs, and a significant portion of them are receptor antagonist series.

This principle is also repeated in the world of CS. The approach of designing artificial objects that do not exist in nature and making them interact with existing systems is one of the essential elements of software engineering. Mock objects, adapters, proxies, and middleware are all of this type of artifact. The principle that a designed component outside of nature can enable the expansion of a natural system is common to both worlds.

Another implication is that the establishment of a category makes knowledge expansion possible. When the category of “receptor antagonists” was created, new drugs that belong to that category were systematically developed. Each new drug could be discussed within the basic framework of being a synthetic molecule that binds to a specific receptor. This case reminds us that the creation of a category determines the organization of subsequent discoveries.

1957 Bovet Summary: Developed several series of synthetic drugs, including sulfa drugs, antihistamines, and curare-based muscle relaxants. Established the theoretical basis for the pharmacological category of “receptor antagonists.” This category is now a major component of pharmacology textbooks and forms the basis of various fields such as cardiovascular, psychiatric, anticancer, and anesthetic medicine.

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