From a Ram’s Testicle to Modern Radiotherapy: How Invisible Rays Became a Safe Weapon

Radiotherapy’s First Brave and Dangerous Years, the Discovery of Fractionation, and the Invisible Ray’s Transformation into a Weapon

The first tumor treatments, months after Röntgen’s discovery

The medical imaging value of X-rays was clear (day 81); more surprising was how quickly their use for treatment began. Röntgen announced his discovery in December 1895, and in the first months of 1896 physicians in different parts of the world were already applying X-rays to skin diseases and tumors. An ironic historical fact: X-rays were initially used more for treatment than diagnosis — contrary to a modern reader’s intuition.

The central dilemma of early radiotherapy

In the first decade of the 1900s, radiotherapy faced a central problem. Physicians tended to deliver the highest possible radiation dose in one sitting to destroy the tumor. The logic was simple: “the more radiation, the more dead tumor”. But the result was often disastrous. Even if a single large dose killed the tumor, it severely burned healthy tissue along its path, particularly the skin, caused necrosis or tissue death, and left nonhealing wounds and permanent damage. The tumor might shrink, but the treatment itself seriously harmed the patient.

The problem was biological, and no one yet understood its mechanism. Its solution would also come from a biological observation, arising from a wholly unexpected experimental subject.

Claudius Regaud and the foundational experiment of radiobiology

From the basement X-ray unit to clinical radiotherapy

The person who applied Regaud’s laboratory discovery to actual patients was his brilliant colleague at Institut Curie, Henri Coutard (1876-1950). Coutard’s story is interesting: during the First World War he headed the radiology service of a military hospital on the Eastern Front, while also serving in Marie Curie’s mobile X-ray units, the “petites Curies” (day 82). After the war, he joined Institut Curie and began working in an X-ray unit in its basement.

Coutard applied Regaud’s fractionation principle to head and neck cancers, especially cancers of the larynx and pharynx. He spread treatment courses over weeks, delivered small daily doses, and meticulously observed skin and mucosal reactions. He systematically described radiation side effects, introducing the terms “radioepidermitis” for radiation-induced skin peeling and “radioepithelitis” for the radiation reaction of the oral and pharyngeal mucosa. He also made a crucial observation: different tumors have different sensitivities to radiation — they do not respond identically to the same dose. This formed the basis of the modern concept of “radiosensitivity.”

Coutard continually refined his approach. Initially, he delivered large daily doses at a low dose rate to small tumors. When he reduced the daily dose for larger tumors, he found that a low dose rate was no longer needed. This led to the “simple fractionation” technique: small fraction sizes at a relatively high dose rate. Around 1930, leading radiotherapists in Zurich (Schinz), Vienna (Holzknecht), and other centers adopted it.

The First International Congress of Radiology

In London in 1925, at the First International Congress of Radiology, Claudius Regaud formally presented the fractionation principle and Institut Curie’s “French school” approach to the international scientific community. This began the acceptance of fractionated radiotherapy as a global standard. Paris’s Institut Curie, the institution born from Marie Curie’s discovery of radium, had also become the center of world radiotherapy. Its “French school,” formed by Regaud, Coutard, Antoine Lacassagne, and others, defined the basic clinical principles of modern radiation oncology in the 1920-1930s.

More powerful rays, deeper tumors

The biggest technical limitation of early radiotherapy was its low beam energy: soft X-rays could not reach deep tumors. This limitation was overcome in the middle of the 20th century:

The institutionalization of radiotherapy in Turkey

Modern radiotherapy’s arrival in Turkey progressed alongside the Republic’s healthcare advances. During the first half of the 20th century, radium tubes and kilovoltage X-ray units were installed; from the middle of the 20th century, cobalt-60 devices were established in university hospitals and major urban hospitals. Linear accelerators subsequently spread. Today, IMRT, SBRT, and modern image-guided radiotherapy are routinely delivered at many centers across Turkey.

In contemporary oncology, radiation oncology is one of three main pillars alongside surgery and medical oncology. Organ-preserving chemoradiotherapy for head and neck cancer, directly descended from Coutard’s laryngeal patients in 1922; postoperative adjuvant radiotherapy for breast cancer; SBRT for prostate cancer: all are current extensions of the fractionation principle born from a ram’s testicle. A radiation oncologist at the table for every case discussed by multidisciplinary tumor boards is today’s expression of this 100-year lineage.

This article is day 83 of the Cancer History in 365 Days Series. The birth of radiotherapy — turning invisible rays into a controlled cancer treatment after Röntgen’s discovery of X-rays (day 81) and the Curies’ discovery of radium (day 82) — is the foundation of radiation oncology, one of modern oncology’s three main pillars. Claudius Regaud’s fractionation principle and Henri Coutard’s clinical application transformed radiotherapy from dangerous trial and error into a precise science that destroys tumors while sparing healthy tissue. This principle remains the basis of all modern radiotherapy, including IMRT, SBRT, and proton therapy. Early radiotherapy’s tragic price — radiation damage to pioneering physicians and overdose complications in patients — led to modern radiation safety science. This sensitive subject is presented in balanced, informative language for readers anxious about radiation. The article takes a historical, popular perspective and provides no treatment guidance. All dates, names, and scientific information were verified using Regaud and Coutard’s original publications, the Bernier-Hall-Giaccia history in Nature Reviews Cancer (2004), the Connell-Hellman perspective in Cancer Research (2009), Springer’s history of radiation biology (2023), and modern academic sources.