Other References

Radiobiology's Contribution to Radiotherapy: Promise or Mirage? Failla Memorial Lecture
Henry S. Kaplan
Radiation Research, Vol. 43, No. 2 (Aug., 1970), pp. 460-476

Some historical data on radiotherapy

  • 1895: Wilhelm Conrad Röntgen in Würzburg (Germany) discovers X-rays.
  • 1895: First therapeutic attempt to treat a local relapse of breast carcinoma by Emil Grubbe (Chicago)
  • 1896: Discovery of natural radioactivity by Henri Becquerel in Paris
  • 1896: First use of X-Rays for stomach cancer by Victor Despeignes (Lyon - France)
  • 1896: Irradiation of a skin tumour in a 4-year-old by Léopold Freund (Vienna - Austria)
  • 1897: Thomson identifies the electrons for creating X-Rays
  • 1898: Discovery of radium by Pierre et Marie Curie in Paris
  • 1899: First real proof of cure by X -Rays ( two pictures taken at an interval of 30 years)
  • 1901: First therapeutic use of radium for skin 'brachytherapy' by Dr Danlos (Hôpital Saint-Louis - Paris)
  • 1903: First scientific description of the effect of radiotherapy on lymphoma nodes (Drs Senn et Pusey)
  • 1904: First treaty on radiotherapy by Joseph Belot in Paris
  • 1905: Discovery of the sensitivity of seminoma to X-Ray by Antoine Béclère in Paris
  • 1913: Institut du Radium by Marie Curie-Sklodowska and Claudius Regaud
  • 1915The atomic model by Ernest Rutherford (Cambridge - UK) : radioactive active disintegration - Development of RX tubes
  • 1920: Structuration of French Radiotherapy by Marie Curie-Sklodowska: Institut du Radium
  • 1921: Foundation of the Institut du Cancer in Villejuif (Institut 'Gustave Roussy' - who was a pathologist) with the brachytherapy unit of Jean Pierquin, Georges Richard and Simone Laborde.
  • 1930: Institut Curie works on fractionation (Claudius Regaud, Henri Coutard, Antoine Lacassagne).
  • 1932: Discovery of neutrons by Sir James Chadwick (Cambridge UK)
  • * 1934: Death of Marie Curie from pernicious anaemia (myelodysplasia)
  • 1934: Discovery of artificial radio-elements by Irène andFrédéric Joliot-Curie (Paris)
  • 1934: Publication of 23% cure rate in head and neck cancer by X-Rays ( Dr Henri Coutard - Institut Curie)
  • 1936: François Baclesse (Institut Curie) begins his work on conservative treatment of breast cancer
  • 1948: first ZOE nuclear reactor (Frédéric Joliot) : productions of artificial radioelements
  • 1951: First cobalt installation (Victoria Hospital - London - Ontario)
  • 1952: First linear accelerator (Henry S. Kaplan in Stanford - California)
  • 1960: The 'Paris system' for brachytherapy with afterloading (Bernard Pierquin)
  • 1973: Scanner invention par G.N. Hounsfeld (UK)
  • 1990: First use of scanner and computers for IMRT
  • 2000: One in two cured cancer patients owes his/her recovery, at least partly to radiotherapy


Interestingly enough, the therapeutic potential of x-rays was demonstrated even earlier. After noting pealing of his hands exposed to x-rays, a medical student in Chicago named Emil Grubbe convinced one of his professors to allow him to irradiate a cancer patient, a woman named Rose Lee, suffering from locally advanced breast cancer. By doing so, Grubbe became the World’s first Radiation Oncologist.

No longer responding to medical treatments, Ms. Lee benefited greatly from Grubbe’s intervention, demonstrating the potential value of x-ray treatments. In a few short years, patients throughout the United States and Europe were undergoing Radiotherapy.


At first, Radiotherapy was delivered primarily in a limited number of treatments. A Professor at the Radium Institute in Paris name Claude Regaud (1870-1940), however, recognized that treatment may be better tolerated and more effective if delivered more slowly with modest doses per day over several weeks.

This approach, known as fractionation, is one of the most important underlying principles in Radiation Therapy. To this day, fractionation lies at the heart of many treatment programs currently used in Radiation Oncology.


The early French Radiation Oncologist Henri Coutard (1876-1950) pioneered the use of fractionated Radiotherapy in a wide variety of tumors. Of note, he reported impressive results using this approach in patients with locally advanced laryngeal (voice box) cancers. His seminal 1934 report of the outcome of these patients is still quoted today.


Despite their promise, an important limitation of the early x-ray machines was their inability to produce high energy, deeply penetrating beams. It was thus difficult to treat deep-seated tumors without excessive skin reactions.


Many early advocates of Radiation Therapy thus relied instead on the placement of radioactive sources in close proximity or even within the tumor, a technique known as brachytherapy [Brachytherapy]. In many tumors, for example cervical and uterine cancers, brachytherapy became the mainstay of treatment (as it so remains to this day).


Following World War II, England became the primary focus for Radiotherapy research. Founded by Ralston Patterson (1897-1981), the Holt Radium Hospital was quickly recognized as a world renowned center for radiation treatment and research.

Through his careful clinical observations, Patterson established the optimal treatment approaches for a wide variety of tumors undergoing external beam radiotherapy. Together with the noted Physicist Herbert Parker, Patterson developed the basic principles underlying brachytherapy prescription, the so-called “Patterson-Parker Rules”.

By the 1960s, the epicenter of Radiation Oncology began to shift to the United States, primarily due to the immigration of many noted European radiotherapists. An exciting development was the introduction of high energy (megavoltage) treatment machines, known as linear accelerators or linacs. Such machines were capable of producing high energy, deeply penetrating beams, allowing for the very first time treatment of tumors deep inside the body without excessive damage to the overlying skin and other normal tissues.


A prototype linac was developed by Henry Kaplan and his colleagues at Stanford University. The first patient treated using this machine was a child with retinoblastoma (a cancer of the eye). Treatment was highly successful for more than 40 years later, this patient remained free of disease with good vision.


Subsequently, many noteworthy Radiation Oncologists made enormous contributions to the field of Oncology. Malcolm Bagshaw, also of Stanford University, demonstrated the curative potential of Radiation Therapy in prostate cancer. Today, based in part on his ground breaking work, radiotherapy is recognized as a mainstay in the treatment of prostate cancer.


Gilbert Fletcher of the MD Anderson Cancer Center established optimal treatment regimens in a wide variety of tumor sites including head and neck cancers and cervical cancer.


Samuel Hellman, the founding Chair of the Joint Center for Radiation Therapy (Harvard University), who trained UCSD Radiation Oncologists Dr. Arno Mundt and Dr. Kevin Murphy, was instrumental in establishing breast conserving therapy (the use of lumpectomy plus radiation instead of mastectomy) as the treatment of choice for women with breast cancer.


The Right to Kill
Monday, Nov. 18, 1935

"Five times have I taken a life… . "The first case was a newborn child, clearly doomed to imbecility. With the squeeze of my finger and thumb, I had taken a life. "In the second case, the child was born without a skullcap. "The third case was that of a farmer suffering from an incurable and agonizing disease. He died clasping my hand, and murmuring, 'God bless you, doctor.' "The fourth case was a man suffering from the same disease and unable to eat, drink or sleep. He was in agony beyond the torment of the damned. He also died with a smile on his face and with his hand in mine. "The fifth case [had] the same disease.* I had no hesitation in ending his life." The author of this confession, printed last week in the London Daily Mail, added that his conscience had never stabbed him, that he would act similarly in similar circumstances, that he would willingly face "any tribunal in the land." He was described as a kind-eyed, elderly country doctor. His statement was "anonymous." But whatever the facts behind the Mail's fat story, it could hardly have aroused more controversy had it been printed as a signed and sworn affidavit in the solemn Times. Medical bigwigs on two continents last week spoke their minds as to the rightness or wrongness of murder for mercy. Pungent, voluble Dr. Morris Fishbein, editor of the American Medical Association's Journal, observed that the average doctor frequently faces the problem, that when it is a matter between him and his patient he may generally decide it in his own way without interference. The Rockefeller Institute's famed Nobel Prizeman Alexis Carrel declared that sentimental prejudice should not obstruct the quiet and painless disposition of incurables, criminals, hopeless lunatics.

Dr. Henri Coutard, chief of staff of Paris' Curie Institute: "Men born crippled or feeble-minded have been responsible for some of the great works of art. Why should their lives be taken?"

Dr. William Alanson White of Washington, No. 1 U. S. practicing psychiatrist: "Dangerous business."

Dr. Max Cutler, Chicago cancer specialist: "We do not have the moral right."

Emotional Britons have been excited about "mercy killing" since the pardon acquittal of Mother May Brownhill for poisoning and asphyxiating her imbecile son Dennis (TIME, March 11). Lord Moynihan of the Royal College of Surgeons is pushing the "Right to Die" movement, backed by the Earl of Listowel and Lord Denman, onetime Governor General of Australia. Last week Lord Moynihan deprecated the Mail story as a cheap advertisement, said his group would put his proposition sensibly to the British public in December, try to get a permissive bill through Parliament.

*Presumably cancer.


Cancer Research 31 (6) June 1971

Claudius Regaud (1870 - 1940), professor of histology at the University of Lyon, was a distinguished exponent of radiobiology and curietherapy and the founder of the Radium Institute (Institut du Radium) of the University of Paris in 1906. He developed original staining techniques and wrote a thesis on the lymphatics of the testes (Les vaisseaux lymphatiques du testicule. Compt. Rend. Soc. Biol., 49 659-661, 1897).

Regaud became an early student of Emile Roux at the Pasteur Institute. This led him to research on the effects of ionizing radiations on various tissues; with Blanc he discovered the varied radiosensitivity of the testicular tubular cells (Action des rayons X sur les diverses generations de la lignee spermatique. Extreme radiosensibilite des spermatogonies a ces rayons. Compt. Rend. Soc. Biol., 61: 163-165, 1906).

With Nogier he studied radiophysiological effects on irradiated skin and described moist radioepidermitis (Les Effects produits sur la peau par les hautes doses de rayons X. Arch. d'Elect. Med.. 20: 321-334, 1912). In 1912, he was chosen to organize the biomedical services of the Radium Institute in a twin building to the one in which Madame Curie pursued her physicochemical research. Mobilized by World War I, he recruited his future collaborators (Lacassagne, Coutard, Ferroux, Monod, and Roux-Berger). With Debierne he developed an early system of radium dosimetry (Sur l'emploie de I'emanation condenseen tubes cbs et sur le dosage en millicuries d'truits. Compt. Rend. Acad. Sci., 161: 422-424, 1915). Using the ram testes as an experimental model, he proved the advantage of a dose of radiation fractionated in ten days over a greater total dose administered in a single exposure (Influence de la dure d'irradiation sur les effects determines dans le testicule par le radium. Compt. Rend. Soc. Biol., 86: 787-790, 1922). This observation on the time-dose relationship became the most important radiobiological contribution to modern radiotherapy. Regaud was also responsible for the development of gadgets (Colpostat, Columbia paste) and of techniques of interstitial and intracavitary radium therapy which have been widely accepted.

Henri Coutard (1876-1950), radiotherapist of the Radium Institute of Paris, the Chicago Tumor Institute, and the Penrose Cancer Hospital of Colorado Springs, did early work on the utilization of radium emanation (Sur l'amanation du radium et son utilisation therapeutique. Congress of the Association Francaise pour l'Advancement des Sciences, Nimes, August 1912); in 1919, he joined the staff of the Radium Institute. With a single piece of radiological equipment and interchangeable tubes, he studied experimental radiophysiology and radiodiagnosis and practiced radiotherapy. In 1922, he described the mucous membrane reaction which he named radioepithelitis (Sur les delais d'appantion et d'evolution des reactions de la peau, et des muqueuses de la bouche et du pharynx, provoquCes par les rayons X. Compt. Rend. Soc. Biol., 86: 1140-1141, 1922).

He originated the radiographic study of the larynx (Note preliminaire sur la radiographic du larynx normal et larynx cancereux. J.Radiol. d'Electrol., 8: 461-465, 1924). Refusing to accept the theoretical limitations of Regaud's fractionation, Coutard dared to extend the daily irradiation of patients to periods of several weeks. His unprecedented results in the treatment of cancer of the larynx attracted world-wide attention (Considerations sur le cancer de la bande et de la cavite ventriculaire du larynx. Ann. des MaI. de l'Oreille, 46: 467-521, 1927). This method was dubbed the protracted-fractional treatment. His contributions are now indistinguishably incorporated into the everyday practice of radiotherapy (Principles of X-ray Therapy of Malignant Diseases. Lancet, 2: 1-12, 1934). Coutard was primarily responsible for placing radiotherapy on a clinical footing.

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