Placebo, a historical perspective

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Abstract

Substances and interventions with no specific therapeutic effect have been in use since the dawn of history. The term placebo has first been mentioned in the Scriptures, but it was not until the 19th century that it appeared in a medical context. Although lay people like Voltaire, and physicians such as Sir William Osler, have raised the possibility that much of what physicians did had no specific therapeutic effect, this notion was not shared by the public at large or by the medical profession. It was only by the end of the 18th century that a placebo-controlled trial has been conducted, repudiating the therapeutic effect of mesmerism. The advent, in the late 1940s, of effective treatments, which also had serious adverse effects, made the distinction between placebo and putative, active drug effects more relevant and urgent, and cleared the way for double-blind, randomized, placebo-controlled trials. This in turn triggered an ethical debate on the use of placebo, both in research and in clinical practice. Anthropologists, sociologists, physiologists, and medical researchers are all focusing their efforts on understanding the mechanism, role and modulating factors of placebo.

Introduction

The term placebo defines a therapy which is used for its non-specific psycho-physiological or presumed effect, but is without actual effect on the condition being treated. Placebo response is the difference between the non-specific beneficial response and that attributed to the natural history. Placebo effect is the (beneficial) effect which is derived from the context of the encounter – the rituals, the settings, and the clinician/healer-patient relationship – which is common to all treatments, as distinguished from therapeutic benefits, produced by the specific or characteristic pharmacological or physiological effects of an active compound or intervention. The first mention of “placebo” is in St. Jerome's mistranslation of the first word of the ninth line of Psalm 116. The Hebrew for “I will walk before the Lord”, was translated by him into “Placebo Domino in regione vivorum” (“I shall please the Lord in the land of the living”) (Jacobs, 2000). Pleasing has a central meaning to the notion of placebo: placebo is associated with the pleasing of the patient by the therapist, of the therapist by the patient, or both.

Since very few treatments with recognized and consistent beneficial effects have existed until the beginning of the 20th century, the history of medicine is the history of placebo. Effective placebo remedies have been ubiquitous in all societies and cultures, from the ancient Egypt (Shapiro and Shapiro, 1997) to today's multi-billion-dollar alternative medicine (Singh and Ernst, 2008). From crocodile dung poultices, practiced by ancient Egyptians, to acupuncture, practiced today at the top medical centers all over the world, the placebo effect continues to be a trusted ally to the practicing clinician and an unavoidable hindrance to the clinical investigator.

Section snippets

Ancient times (B.C.)

Dating back to 2100 B.C, In Babylonia and Assyria, we find that the modus operandus of the sorcerer (ashipu) and the physician (asu) was based on providing patients with empathy and comfort along with the “specific” remedy, thus taking full advantage of the placebo effect (Shapiro and Shapiro, 1997). The Egyptians were pioneers in writing medical texts, using medical terminology, exploring anatomy, and keeping records of procedures such as applying splints and bandages (Estes, 1989, Majno, 1975

The first eighteen centuries

Galen's Pharmacopeia, with its 820 remedies, has dominated treatment for 1500 years and disappeared only in the 19th century, under pressure from the emerging scientific approach to medicine. Galen's Pharmacopeia included any substance and mixture made of plants, bacteria, worms, reptiles, fish, human organs, tissue, bones powder, excretion, or extract in any phase, with or without the involvement of force majeure, magic, witchcraft, or any other intentional or unintentional action. Faulty

The 19th century—a few steps closer to modern medicine

Enter the 19th century and the medical dictionary. Robert Hooper in Quincy's Lexicon-Medicum, defined placebo as “an epithet given to any medicine adapted more to please than benefit the patient” (Hooper, 1811). The century was marked by several scientific developments, beginning with the study of pathological anatomy and of physiology, and the birth of modern pharmacology (Modell, 1976).

Despite these scientific advances, in 1858, in a grotto near by Lourdes, France, a 14-year-old peasant girl

The 20th century—placebo and medicine as we know it

Surgery on the battlefields of WWII provided the anesthesiologist Henry Beecher with the opportunity to observe that when the supply of morphine has run out, plain saline solution might be an effective substitute to control pain. He summarized his observations on the placebo effect in a series of articles published in the 50s and 60s, claiming that up to 40% of the therapeutic effect of any intervention is due to the placebo effect (Beecher, 1955, Beecher, 1961, Lasagna et al., 1954). He

Placebo-good or bad? real or fake?

Since the 14th century, placebo has been associated with fakery, as demonstrated in the Latin prayers for the dead. Singers of placebo are paid mourners, or mourners falsely claiming a relation to the deceased in the hope of getting a share of the funeral meal (Aronson, 1999). In the Canterbury Tales, the sycophantic servant is called Placebo (Shapiro, 1968). It was Voltaire who pointed out how physicians employing the placebo effect took credit for the healings, which were the outcome of the

Role of the funding source

The Joseph Sagol Neuroscience Center at Sheba Medical Center Israel.

Contributors

None.

Conflict of interest

Authors report no financial interests or conflicts of interests in this research.

Acknowledgment

Safra Nimrod for the language editing.

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