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The nocebo effect appears to have a specific biological substrate. A group of 15 men whose wives suffered from terminal cancer participated in a small perspective study. After their wives' deaths, the men experienced severe grief that caused immunodepression. The spouses' lymphocytes for a period of time after their wives' deaths responded poorly to mitogenes. Grief had assaulted their immune system. The study proposed that grief and grief-induced immunodepression resulted in high- level mortality of the specific group.° reported in 1957 when a new wonder drug, Krebiozen, held promise as the final solution to the cancer problem. A patient with metastatic tumours and with fluid collection in his lungs, who demanded the daily intake of oxygen and the use of an oxygen mask, heard of Krebiozen. His doctor was participating in Krebiozen research and the patient begged him to be given the revolutionary drug. Bent by the patient's hopelessness, the doctor did so and witnessed a miraculous recovery of the patient. His tumours melted and he returned to an almost normal lifestyle. The recovery didn't last long. The patient read articles about Krebiozen's not delivering what it promised in cancer therapy. The patient then had a relapse; his tumours were back. His doctor, deeply affected by the aggravation, resorted to a desperate trick. He told his patient that he had in his possession a new, improved version of Krebiozen. It was simply distilled water. The patient fully recovered after the placebo treatment and remained functional for two months. The final verdict on Krebiozen, published in the press, proved the drug to be totally ineffective. That was the coup de grace for the patient, who died a few days later.” Th a nf tha m a nf tha A short history of a small miracle Krebiozen's not delivering what it promised in cancer therapy. The term placebo (meaning "I shall please") was used in The patient then had a relapse; his tumours were back. His mediaeval prayer in the context of the phrase Placebo Domino ("I doctor, deeply affected by the aggravation, resorted to a desperate shall please the Lord") and originated from a biblical translation trick. He told his patient that he had in his possession a new, of the fifth century AD.’ During the 18th century, the term was improved version of Krebiozen. It was simply distilled water. adopted by medicine and was used to imply preparations of no The patient fully recovered after the placebo treatment and therapeutic value that were administered to patients as "decoy remained functional for two months. The final verdict on drugs". The term began to transform in 1920 (Graves *), and Krebiozen, published in the press, proved the drug to be totally through various intermediate stages (Evans and Hoyle, 1933°; ineffective. That was the coup de grace for the patient, who died Gold, Kwit and Otto, 1937'°; Jellinek, 1946'') was fully a few days later."’ transformed in 1955 when it finally In spite of the melodrama of the claimed an important portion of the Krebiozen case, there is no single case therapeutic effect in general. Henry K. or personal testimony that can denote Beecher, in his 1955 paper "The or prove a therapy to be effective. Powerful Placebo", attributed a rough Positive or negative thinking Statistical studies, not personal percentage of 30 per cent of the overall war . testimonies, can verify a proposed therapeutic benefit to the placebo seems to be a decisive risk therapy's effectiveness, and well- effect.” factor for every treatment, planned studies are able to concur that In certain later studies, the placebo the placebo phenomenon has somatic effect was estimated at even higher, at perhaps even more important properties. 60 per cent of the overall therapeutic than medical intervention. One such study was implemented in outcome. In a recent review of 39 1997. The two study groups consisted studies regarding the effectiveness of of patients with benign prostatic antidepressant drugs, psychologist Guy hypertrophy. One group took actual Sapirstein concluded that 50 per cent medication while the control group of the therapeutic benefits came from the received placebo treatment. The placebo effect, with a poor percentage of 27 per cent attributed to placebo recipients reported relief from their symptoms and even drug intervention (fluoxetine, sertaline and paroxetine). Three amelioration of their urinary function.'* A placebo has also been years later Sapirstein, along with a fellow psychologist Irving reported to act as a bronchodilator in asthmatic patients, or to Kirsch, processed the data from 19 double-blind studies regarding have the exact opposite action—respiratory depression— depression and reached an even higher percentage of therapeutic depending on the description of the pharmacological effect the results attributed to the placebo effect: 75 per cent of depression researchers gave to the patients and therefore the effect the therapies or ameliorations were placebo induced!'* patients anticipated.” Hrobjartsson and Ggtzsche (2001 '*, 2004'*) doubted the A placebo proved highly efficient against food allergies and, effectiveness of the placebo phenomenon, attributing it solely to subsequently, impressively effective in the sinking of the subjective factors of human psychology. And indeed, there is biotechnologies on the stockmarket. How could that be? Peptide a major aspect of the placebo effect related to psychology. In two Therapeutics Group, a biotech company, was preparing to launch studies where placebos were exclusively administered, the on the market a novel vaccine for food allergies. The first reports placebo effect seemed to be effected from the subject's perception were encouraging. When the experimental vaccine reached the of the applied therapy, i.e., two placebo pills were better than one, clinical trials stage, the company's spokesperson boasted that the bigger pills were better than smaller, and injections were even vaccine proved effective in 75 per cent of the cases—a percentage better.'° that usually suffices to prove a drug's effectiveness. But the good The placebo induced a reaction not only to the therapy but also news didn't last long. The control group, given a placebo, did to its form, suggesting that the placebo phenomenon is shaped almost as well: seven out of 10 patients reported getting rid of according to the personal symbolic universe of the patient. their food allergies. The stock value of the company plunged by Before the placebo response occurs, human perception has 33 per cent. The placebo effect on food allergies created a nocebo already interpreted the applied therapy and has prepared a certain effect on the stockmarket!*° In another case, a genetically response to it. It would appear that not only chemical but also designed heart drug that raised high hopes for Genentech was non-chemical stimuli participate in the motivation of the human clobbered by a placebo.” organism towards therapy. As aptly put by science historian Anne Harrington, placebos are But is the placebo reaction solely a psychological phenomenon "ghosts that haunt our house of biomedical objectivity and expose or does it have additional tangible somatic effects? the paradoxes and fissures in our own self-created definitions of One of the more dramatic events regarding placebo therapy was the real and active factors in treatment". Positive or negative thinking seems to be a decisive risk factor for every treatment, perhaps even more important than medical intervention. 28 = NEXUS JUNE — JULY 2007 www.nexusmagazine.com