A woman being treated with docetaxel chemotherapy for breast cancer. Cold mittens and wine coolers are placed on her hands and feet to reduce harm to her nails.

Chemotherapy primarily refers to the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen. Certain chemotherapy agents also have a role in the treatment of other conditions, including ankylosing spondylitis, multiple sclerosis, Crohn's disease, psoriasis, psoriatic arthritis, rheumatoid arthritis and scleroderma.

The most common chemotherapy agents act by killing cells that divide rapidly, one of the main properties of most cancer cells. This means that chemotherapy also harms cells that divide rapidly under normal circumstances: cells in the bone marrow, digestive tract, and hair follicles. This results in the most common side-effects of chemotherapy: myelosuppression (decreased production of blood cells, hence also immunosuppression), mucositis (inflammation of the lining of the digestive tract), and alopecia (hair loss).

Newer anticancer drugs act directly against abnormal proteins in cancer cells; this is termed targeted therapy and, in the technical sense, is not chemotherapy.

History[link]

Sidney Farber is regarded as the father of modern chemotherapy.

The first use of drugs to treat cancer was in the early 20th century, although it was not originally intended for that purpose. Mustard gas was used as a chemical warfare agent during World War I and was discovered to be a potent suppressor of hematopoiesis (blood production).^[1] A similar family of compounds known as nitrogen mustards were studied further during World War II at Yale University.^[2] It was reasoned that an agent that damaged the rapidly growing white blood cells might have a similar effect on cancer. Therefore, in December 1942, several patients with advanced lymphomas (cancers of certain white blood cells) were given the drug by vein, rather than by breathing the irritating gas.^[2] Their improvement, although temporary, was remarkable.^[3][4] Concurrently, during a military operation in World War II, following a German air raid on the Italian harbour of Bari, several hundred people were accidentally exposed to mustard gas, which had been transported there by the allied forces to prepare for possible retaliation in the event of German use of chemical warfare. The survivors were later found to have very low white blood cell counts.^[5][6] After WWII was over and the reports declassified, the experiences converged and led researchers to look for other substances that might have similar effects against cancer. The first chemotherapy drug to be developed from this line of research was mustine. Since then, many other drugs have been developed to treat cancer, and drug development has exploded into a multibillion-dollar industry, although the principles and limitations of chemotherapy discovered by the early researchers still apply.^[7]

[edit] The term chemotherapy

The word "chemotherapy" without a modifier usually refers to cancer treatment, but its historical meaning is broader. The term was historically used for non-oncological references, such as the use of antibiotics (antibacterial chemotherapy). The first modern chemotherapeutic agent was arsphenamine, an arsenic compound discovered in 1909 and used to treat syphilis.^{[citation needed]} This was later followed by sulfonamides (sulfa drugs) and penicillin. Other uses that have been termed chemotherapy are the treatment of autoimmune diseases such as multiple sclerosis, dermatomyositis, polymyositis, lupus, rheumatoid arthritis.^{[citation needed]}

Principles[link]

This unreferenced section requires citations to ensure verifiability.

Cancer is the uncontrolled growth of cells coupled with malignant behavior: invasion and metastasis. Cancer is thought to be caused by the interaction between genetic susceptibility and environmental toxins.

In the broad sense, most chemotherapeutic drugs work by impairing mitosis (cell division), effectively targeting fast-dividing cells. As these drugs cause damage to cells, they are termed cytotoxic. Some drugs cause cells to undergo apoptosis (so-called "self-programmed cell death").

Scientists have yet to identify specific features of malignant and immune cells that would make them uniquely targetable (barring some recent examples, such as the Philadelphia chromosome as targeted by imatinib). This means that other fast-dividing cells, such as those responsible for hair growth and for replacement of the intestinal epithelium (lining), are also often affected. However, some drugs have a better side effect profile than others, enabling doctors to adjust treatment regimens to the advantage of patients in certain situations.

As chemotherapy affects cell division, tumors with high growth fractions (such as acute myelogenous leukemia and the aggressive lymphomas, including Hodgkin's disease) are more sensitive to chemotherapy, as a larger proportion of the targeted cells are undergoing cell division at any time. Malignancies with slower growth rates, such as indolent lymphomas, tend to respond to chemotherapy much more modestly.

Drugs affect "younger" tumors (i.e., more differentiated) more effectively, because mechanisms regulating cell growth are usually still preserved. With succeeding generations of tumor cells, differentiation is typically lost, growth becomes less regulated, and tumors become less responsive to most chemotherapeutic agents. Near the center of some solid tumors, cell division has effectively ceased, making them insensitive to chemotherapy. Another problem with solid tumors is the fact that the chemotherapeutic agent often does not reach the core of the tumor. Solutions to this problem include radiation therapy (both brachytherapy and teletherapy) and surgery.

Over time, cancer cells become more resistant to chemotherapy treatments. Recently, scientists have identified small pumps on the surface of cancer cells that actively move chemotherapy from inside the cell to the outside. Research on p-glycoprotein and other such chemotherapy efflux pumps is currently ongoing. Medications to inhibit the function of p-glycoprotein are undergoing testing as of 2007 to enhance the efficacy of chemotherapy.

Treatment schemes[link]

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (July 2009)

There are a number of strategies in the administration of chemotherapeutic drugs used today. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms.

Combined modality chemotherapy is the use of drugs with other cancer treatments, such as radiation therapy or surgery. Most cancers are now treated in this way. Combination chemotherapy is a similar practice that involves treating a patient with a number of different drugs simultaneously. The drugs differ in their mechanism and side effects. The biggest advantage is minimising the chances of resistance developing to any one agent.

In neoadjuvant chemotherapy (preoperative treatment) initial chemotherapy is designed to shrink the primary tumor, thereby rendering local therapy (surgery or radiotherapy) less destructive or more effective.

Adjuvant chemotherapy (postoperative treatment) can be used when there is little evidence of cancer present, but there is risk of recurrence. This can help reduce chances of relapse. It is also useful in killing any cancerous cells that have spread to other parts of the body. This is often effective as the newly growing tumours are fast-dividing, and therefore very susceptible.

Palliative chemotherapy is given without curative intent, but simply to decrease tumor load and increase life expectancy. For these regimens, a better toxicity profile is generally expected.

All chemotherapy regimens require that the patient be capable of undergoing the treatment. Performance status is often used as a measure to determine whether a patient can receive chemotherapy, or whether dose reduction is required. Because only a fraction of the cells in a tumor die with each treatment (fractional kill), repeated doses must be administered to continue to reduce the size of the tumor.^[8] Current chemotherapy regimens apply drug treatment in cycles, with the frequency and duration of treatments limited by toxicity to the patient.^[9]

Types[link]

The majority of chemotherapeutic drugs can be divided in to alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumour agents.^[10] All of these drugs affect cell division or DNA synthesis and function in some way.

Some newer agents do not directly interfere with DNA. These include monoclonal antibodies and the new tyrosine kinase inhibitors e.g. imatinib mesylate (Gleevec or Glivec), which directly targets a molecular abnormality in certain types of cancer (chronic myelogenous leukemia, gastrointestinal stromal tumors). These are examples of targeted therapies.

In addition, some drugs that modulate tumor cell behaviour without directly attacking those cells may be used. Hormone treatments fall into this category.

Alkylating agents[link]

Alkylating agents are so named because of their ability to alkylate many nucleophilic functional groups under conditions present in cells. Cisplatin and carboplatin, as well as oxaliplatin, are alkylating agents. They impair cell function by forming covalent bonds with the amino, carboxyl, sulfhydryl, and phosphate groups in biologically important molecules.^[10]

Other agents are mechlorethamine, cyclophosphamide, chlorambucil, ifosfamide.^[10] They work by chemically modifying a cell's DNA.

Anti-metabolites[link]

Anti-metabolites masquerade as purines ((azathioprine, mercaptopurine)) or pyrimidines—which become the building-blocks of DNA. They prevent these substances from becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. They also affect RNA synthesis. Due to their efficiency, these drugs are the most widely used cytostatics.

Plant alkaloids and terpenoids[link]

These alkaloids are derived from plants and block cell division by preventing microtubule function. Microtubules are vital for cell division, and, without them, cell division cannot occur. The main examples are vinca alkaloids and taxanes.

Vinca alkaloids[link]

Vinca alkaloids bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules (M phase of the cell cycle). They are derived from the Madagascar periwinkle, Catharanthus roseus (formerly known as Vinca rosea). The vinca alkaloids include:

• Vincristine
• Vinblastine
• Vinorelbine
• Vindesine

Podophyllotoxin[link]

Podophyllotoxin is a plant-derived compound that is said to help with digestion as well as used to produce two other cytostatic drugs, etoposide and teniposide. They prevent the cell from entering the G1 phase (the start of DNA replication) and the replication of DNA (the S phase). The exact mechanism of its action is not yet known.

The substance has been primarily obtained from the American Mayapple (Podophyllum peltatum). Recently it has been discovered that a rare Himalayan Mayapple (Podophyllum hexandrum) contains it in a much greater quantity, but, as the plant is endangered, its supply is limited. Studies have been conducted to isolate the genes involved in the substance's production, so that it could be obtained recombinantly.

Taxanes[link]

The prototype taxane is the natural product paclitaxel, originally known as Taxol and first derived from the bark of the Pacific Yew tree. Docetaxel is a semi-synthetic analogue of paclitaxel. Taxanes enhance stability of microtubules, preventing the separation of chromosomes during anaphase.

Topoisomerase inhibitors[link]

Topoisomerases are essential enzymes that maintain the topology of DNA. Inhibition of type I or type II topoisomerases interferes with both transcription and replication of DNA by upsetting proper DNA supercoiling.

• Some type I topoisomerase inhibitors include camptothecins: irinotecan and topotecan.

• Examples of type II inhibitors include amsacrine, etoposide, etoposide phosphate, and teniposide. These are semisynthetic derivatives of epipodophyllotoxins, substances naturally occurring in the root of American Mayapple (Podophyllum peltatum).

Cytotoxic antibiotics[link]

These include:

• actinomycin
• anthracyclines
  • doxorubicin
  • daunorubicin
  • valrubicin
  • idarubicin
  • epirubicin, which also inhibit topoisomerase II
• other cytotoxic antibiotics
  • bleomycin. Bleomycin acts in unique way through oxidation of a DNA-bleomycin-Fe(II) complex and forming free radicals, which induce damage and chromosomal aberrations.
  • plicamycin
  • mitomycin

Newer and experimental approaches[link]

Isolated infusion approaches[link]

Isolated limb perfusion (often used in melanoma), or isolated infusion of chemotherapy into the liver or the lung have been used to treat some tumours. The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumor sites without causing overwhelming systemic damage. These approaches can help control solitary or limited metastases, but they are by definition not systemic, and, therefore, do not treat distributed metastases or micrometastases.

Targeted delivery mechanisms[link]

Specially targeted delivery vehicles aim to increase effective levels of chemotherapy for tumor cells while reducing effective levels for other cells. This should result in an increased tumor kill and/or reduced toxicity.

Specially targeted delivery vehicles have a differentially higher affinity for tumor cells by interacting with tumor-specific or tumor-associated antigens.

In addition to their targeting component, they also carry a payload - whether this is a traditional chemotherapeutic agent, or a radioisotope, or an immune-stimulating factor. Specially targeted delivery vehicles vary in their stability, selectivity, and choice of target, but, in essence, they all aim to increase the maximum effective dose that can be delivered to the tumor cells. Reduced systemic toxicity means that they can also be used in sicker patients, and that they can carry new chemotherapeutic agents that would have been far too toxic to deliver via traditional systemic approaches.

Nanoparticles[link]

Nanoparticles have emerged as a useful vehicle for poorly soluble agents such as paclitaxel. Protein-bound paclitaxel (e.g., Abraxane) or nab-paclitaxel was approved by the U.S. Food and Drug Administration (FDA) in January 2005 for the treatment of refractory breast cancer. This formulation of paclitaxel uses human albumin as a vehicle and not the Cremophor vehicle used in Taxol. Nanoparticles made of magnetic material can also be used to concentrate agents at tumour sites using an externally applied magnetic field.

Electrochemotherapy[link]

Electrochemotherapy is the combined treatment in which injection of a chemotherapeutic drug is followed by application of high-voltage electric pulses locally to the tumor. The treatment enables the chemotherapeutic drugs, which otherwise cannot or hardly go through the membrane of cells (such as bleomycin and cisplatin), to enter the cancer cells. Hence, greater effectiveness of antitumor treatment is achieved. Clinical electrochemotherapy has been successfully used for treatment of cutaneous and subcutaneous tumors irrespective of their histological origin.^{[11][12][13][14][15][16][17]} The method has been reported as safe, simple and highly effective in all reports on clinical use of electrochemotherapy. According to the ESOPE project (European Standard Operating Procedures of Electrochemotherapy), the Standard Operating Procedures (SOP) for electrochemotherapy were prepared, based on the experience of the leading European cancer centres on electrochemotherapy.^[13][18] Recently, new electrochemotherapy modalities have been developed for treatment of internal tumors using surgical procedures, endoscopic routes or percutaneous approaches to gain access to the treatment area.^[19][20]

Dosage[link]

This unreferenced section requires citations to ensure verifiability.

Dosage of chemotherapy can be difficult: If the dose is too low, it will be ineffective against the tumor, whereas, at excessive doses, the toxicity (side-effects, neutropenia) will be intolerable to the patient. This has led to the formation of detailed "dosing schemes" in most hospitals, which give guidance on the correct dose and adjustment in case of toxicity. In immunotherapy, they are in principle used in smaller dosages than in the treatment of malignant diseases.

In most cases, the dose is adjusted for the patient's body surface area, a measure that correlates with blood volume. The BSA is usually calculated with a mathematical formula or a nomogram, using a patient's weight and height, rather than by direct measurement.

Delivery[link]

This unreferenced section requires citations to ensure verifiability.

Most chemotherapy is delivered intravenously, although a number of agents can be administered orally (e.g., melphalan, busulfan, capecitabine). In some cases, isolated limb perfusion (often used in melanoma), or isolated infusion of chemotherapy into the liver or the lung have been used. The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumour sites without causing overwhelming systemic damage.

Depending on the patient, the cancer, the stage of cancer, the type of chemotherapy, and the dosage, intravenous chemotherapy may be given on either an inpatient or an outpatient basis. For continuous, frequent or prolonged intravenous chemotherapy administration, various systems may be surgically inserted into the vasculature to maintain access. Commonly used systems are the Hickman line, the Port-a-Cath, and the PICC line. These have a lower infection risk, are much less prone to phlebitis or extravasation, and abolish the need for repeated insertion of peripheral cannulae.

Harmful and lethal toxicity from chemotherapy limits the dosage of chemotherapy that can be given. Some tumors can be destroyed by sufficiently high doses of chemotherapeutic agents. However, these high doses cannot be given because they would be fatal to the patient.

Adverse effects[link]

Chemotherapeutic techniques have a range of side-effects that depend on the type of medications used. The most common medications affect mainly the fast-dividing cells of the body, such as blood cells and the cells lining the mouth, stomach, and intestines. Common side-effects include:^[21]

• Depression of the immune system, which can result in potentially fatal infections. Although patients are encouraged to wash their hands, avoid sick people, and take other infection-reducing steps, about 85% of infections are due to naturally occurring microorganisms in the patient's own gastrointestinal tract (including oral cavity) and skin.^[22] This may manifest as systemic infections, such as sepsis, or as localized outbreaks, such as Herpes simplex, shingles, or other members of the Herpesviridea.^[23] Sometimes, chemotherapy treatments are postponed because the immune system is suppressed to a critically low level.
• Fatigue. The treatment can be physically exhausting for the patient, who might already be very tired from cancer-related fatigue. It may produce mild to severe anemia. Treatments to mitigate anemia include hormones to boost blood production (erythropoietin), iron supplements, and blood transfusions.
• Tendency to bleed easily. Medications that kill rapidly dividing cells or blood cells are likely to reduce the number of platelets in the blood, which can result in bruises and bleeding. Extremely low platelet counts may be temporarily boosted through platelet transfusions. Sometimes, chemotherapy treatments are postponed to allow platelet counts to recover.
• Gastrointestinal distress. Nausea and vomiting are common side-effects of chemotherapeutic medications that kill fast-dividing cells. This can also produce diarrhea or constipation. Malnutrition and dehydration can result when the patient does not eat or drink enough, or when the patient vomits frequently, because of gastrointestinal damage. This can result in rapid weight loss, or occasionally in weight gain, if the patient eats too much in an effort to allay nausea or heartburn. Weight gain can also be caused by some steroid medications. These side-effects can frequently be reduced or eliminated with antiemetic drugs. Self-care measures, such as eating frequent small meals and drinking clear liquids or ginger tea, are often recommended. This is a temporary effect, and frequently resolves within a week of finishing treatment.
• Hair loss. Some medications that kill rapidly dividing cells cause dramatic hair loss; other medications may cause hair to thin. These are most often temporary effects: hair usually starts to regrow a few weeks after the last treatment, sometimes with a tendency to curl, resulting in "chemo curls." Permanent hair loss can result from some standard chemotherapy regimens. Scalp cooling offers a means of preventing both permanent and temporary hair loss.

Damage to specific organs is possible:

• Cardiotoxicity (heart damage)
• Hepatotoxicity (liver damage)
• Nephrotoxicity (kidney damage)
• Ototoxicity (damage to the inner ear), producing vertigo
• Encephalopathy (brain dysfunction)

Immunosuppression and myelosuppression[link]

Virtually all chemotherapeutic regimens can cause depression of the immune system, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells, and platelets. Anemia and thrombocytopenia, when they occur, are improved with blood transfusion. Neutropenia (a decrease of the neutrophil granulocyte count below 0.5 x 10⁹/litre) can be improved with synthetic G-CSF (granulocyte-colony-stimulating factor, e.g., filgrastim, lenograstim).

In very severe myelosuppression, which occurs in some regimens, almost all the bone marrow stem cells (cells that produce white and red blood cells) are destroyed, meaning allogenic or autologous bone marrow cell transplants are necessary. (In autologous BMTs, cells are removed from the patient before the treatment, multiplied and then re-injected afterward; in allogenic BMTs, the source is a donor.) However, some patients still develop diseases because of this interference with bone marrow.

In Japan, the government has approved the use of some medicinal mushrooms like Trametes versicolor, to counteract depression of the immune system in patients undergoing chemotherapy.^[24]

Chemotherapy-induced nausea and vomiting (CINV)[link]

Nausea and vomiting are two of the most feared cancer treatment-related side-effects for cancer patients and their families. In 1983, Coates et al. found that patients receiving chemotherapy ranked nausea and vomiting as the first- and second-most-severe side-effects, respectively. Up to 20% of patients receiving highly emetogenic agents in this era postponed, or even refused, potentially curable treatments.^[25] Chemotherapy-induced nausea and vomiting (CINV) are common with many treatments and some forms of cancer. Since the 1990s, several novel classes of antiemetics have been developed and commercialized, becoming a nearly universal standard in chemotherapy regimens, and helping to successfully manage these symptoms in a large portion of patients. Effective mediation of these unpleasant and sometimes-crippling symptoms results in increased quality of life for the patient and more efficient treatment cycles, due to less stoppage of treatment due to better tolerance by the patient, and due to better overall health of the patient.

Secondary neoplasm[link]

Development of secondary neoplasia after successful chemotherapy and/or radiotherapy treatment can occur. The most common secondary neoplasm is secondary acute myeloid leukemia, which develops primarily after treatment with alkylating agents or topoisomerase inhibitors.^[26] Survivors of childhood cancer are more than 13 times as likely to get a secondary neoplasm during the 30 years after treatment than the general population.^[27] Not all of this increase can be attributed to chemotherapy.

Infertility[link]

Some types of chemotherapy are gonadotoxic and may cause infertility.^[28] Chemotherapies with high risk include procarbazine and other alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil, and chlormethine.^[28] Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin.^[28] On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycin and dactinomycin, and antimetabolites such as methotrexate, mercaptopurine, and 5-fluorouracil.^[28]

Patients may choose between several methods of fertility preservation prior to chemotherapy, including cryopreservation of semen, ovarian tissue, oocytes, or embryos.^[29] As more than half of cancer patients are elderly, this adverse effect is only relevant for a minority of patients.

Teratogenicity[link]

Chemotherapy is potentially teratogenic during pregnancy, especially during the first trimester, to the extent that abortion usually is recommended if pregnancy in this period is found during chemotherapy.^[30] Second- and third-trimester exposure does not usually increase the teratogenic risk and adverse effects on cognitive development, but it may increase the risk of various complications of pregnancy and fetal myelosuppression.^[30]

In males previously having undergone chemotherapy or radiotherapy, there appears to be no increase in genetic defects or congenital malformations in their children conceived after therapy.^[30] The use of assisted reproductive technologies and micromanipulation techniques might increase this risk.^[30] In females previously having undergone chemotherapy, miscarriage and congenital malformations are not increased in subsequent conceptions.^[30] However, when in vitro fertilization and embryo cryopreservation is practised between or shortly after treatment, possible genetic risks to the growing oocytes exist, and hence it has been recommended that the babies be screened.^[30]

Neurological adverse effects[link]

Reported are cytotoxic-induced neuropathy causing pain^[31] or paralysis. Some patients report fatigue or non-specific neurocognitive problems, such as an inability to concentrate; this is sometimes called post-chemotherapy cognitive impairment, referred to as "chemo brain" by patients' groups.^[32]

Other side effects[link]

In particularly large tumors, such as large lymphomas, some patients develop tumor lysis syndrome from the rapid breakdown of malignant cells. Although prophylaxis is available and is often initiated in patients with large tumors, this is a dangerous side-effect that can lead to death if left untreated.

Less common side-effects include red skin (erythema), dry skin, damaged fingernails, a dry mouth (xerostomia), water retention, and sexual impotence. Some medications can trigger allergic or pseudoallergic reactions.

Specific chemotherapeutic agents are associated with organ-specific toxicities, including cardiovascular disease (e.g., doxorubicin), interstitial lung disease (e.g., bleomycin) and occasionally secondary neoplasm (e.g., MOPP therapy for Hodgkin's disease).

Occupational precautions[link]

Healthcare workers exposed to antineoplastic agents take precautions to keep their exposure to a minimum. There is a limitation in cytotoxics dissolution in Australia and the United States to 20 dissolutions per pharmacist/nurse, since pharmacists that prepare these drugs or nurses that may prepare or administer them are the two occupational groups with the highest potential exposure to antineoplastic agents. In addition, physicians and operating room personnel may also be exposed through the treatment of patients. Hospital staff, such as shipping and receiving personnel, custodial workers, laundry workers, and waste handlers, all have potential exposure to these drugs during the course of their work. The increased use of antineoplastic agents in veterinary oncology also puts these workers at risk for exposure to these drugs.^[33]

In other animals[link]

Chemotherapy is used in veterinary medicine similar to in human medicine.^[34]

See also[link]

• Anti-Cancer Drugs (journal)
• Chemotherapy regimens
• Experimental cancer treatments
• Safe Handling of Hazardous Drugs
• National Comprehensive Cancer Network
• Radiotherapy
• Chemo brain
• Radiation induced cognitive decline
• Cancer-related fatigue

References[link]

External links[link]

• Search for chemotherapy trials
• American Cancer Society - Chemotherapy

James Randi
Born	Randall James Hamilton Zwinge (1928-08-07) August 7, 1928 (age 83) Toronto, Ontario, Canada
Nationality	Canadian American
Occupation	Magician, illusionist, writer, skeptic
Religion	None (atheist)[1]
Website
www.randi.org

James Randi (born Randall James Hamilton Zwinge; August 7, 1928^[2]) is a Canadian-American stage magician and scientific skeptic^[3][4] best known as a challenger of paranormal claims and pseudoscience. Randi is the founder of the James Randi Educational Foundation (JREF). Randi began his career as a magician named The Amazing Randi, but after retiring at age 60, he began investigating paranormal, occult, and supernatural claims, which he collectively calls "woo-woo".^[5]

Although often referred to as a "debunker", Randi rejects that title owing to its perceived bias, instead describing himself as an "investigator".^[6] He has written about the paranormal, skepticism, and the history of magic. He was a frequent guest on The Tonight Show Starring Johnny Carson and was occasionally featured on the television program Penn & Teller: Bullshit!. The JREF sponsors The One Million Dollar Paranormal Challenge offering a prize of US$1,000,000 to eligible applicants^[7] who can demonstrate evidence of any paranormal, supernatural or occult power or event under test conditions agreed to by both parties.^[8]

Early life[link]

Randi was born in Toronto, Ontario, Canada, and has a younger brother and sister.^[9] He took up magic after seeing Harry Blackstone, Sr^[10] and reading magic books while spending 13 months in a body cast following a bicycle accident. He confounded doctors who expected he would never walk again.^[11] Although a brilliant student, Randi often skipped school, and he dropped out of high school at 17 to perform as a conjurer in a carnival roadshow.^[12] In his twenties, Randi posed as a psychic to establish that they were actually doing simple tricks and briefly wrote an astrological column in the Canadian tabloid Midnight under the name "Zo-ran," by simply shuffling up items from newspaper astrology columns and pasting them randomly into a column.^[13][14] In his thirties, Randi worked in Philippine night clubs and all across Japan.^[15] He witnessed many tricks that were presented as being supernatural. One of his earliest reported experiences is that of seeing an evangelist using a version of the "one-ahead"^[16] routine to convince churchgoers of his divine powers.^[17]

Career[link]

Magician[link]

Randi worked as a professional stage magician, or "conjurer" as he prefers to be called,^[18] and escapologist beginning in 1946, initially under his birth name, Randall Zwinge, and then as The Amazing Randi. Early in his career, Randi was part of numerous stunts involving his escape from jail cells and safes. On February 7, 1956, he appeared live on The Today Show, remaining in a sealed metal coffin submerged in a hotel swimming pool for 104 minutes, breaking what was said to be Houdini's record of 93 minutes.^[19][20]

Randi was the host of The Amazing Randi Show on New York radio station WOR in the mid 1960s.^[21] This radio show, which filled Long John Nebel's old slot with similar content after Nebel went to WNBC in 1962, had frequent pro-paranormal guests, including Randi's then-friend James Moseley. Randi, in turn, spoke at Moseley's 1967 Fourth Congress of Scientific Ufologists in New York City,^[22] stating, "Let's not fool ourselves. There are some garden variety liars involved in all this. But in among all the trash and nonsense perpetrated in the name of Ufology, I think there is a small grain of truth."^[23]

Randi also hosted numerous television specials and went on several world tours. Then Randi appeared as "The Amazing Randi" on a television show titled Wonderama from 1967 to 1972,^[24] and as host of a failed revival of the 1950s children's show The Magic Clown in 1970.^[25] In the February 2, 1974, issue of Abracadabra (a British conjuring magazine), Randi defined the magic community, saying, "I know of no calling which depends so much upon mutual trust and faith as does ours." In the December 2003 issue of The Linking Ring, the monthly publication of The International Brotherhood of Magicians, Points to Ponder: Another Matter of Ethics, p. 97, it is stated, "Perhaps Randi's ethics are what make him Amazing" and "The Amazing Randi not only talks the talk, he walks the walk."

During Alice Cooper's 1973–1974 tour, Randi performed as the dentist and executioner on stage,^[26] and designed and built several of the stage props, including the guillotine.^[27][28] Shortly after that, in February 1975, Randi escaped from a straitjacket while suspended upside-down over Niagara Falls in the winter on the Canadian TV program World of Wizards.^[29]

Randi was once accused of actually using "psychic powers" to perform acts such as spoon bending. James Alcock relates this incident, which occurred at a meeting where Randi was duplicating the performances of Uri Geller: A professor from the University at Buffalo shouted out that Randi was a fraud. Randi said, "Yes, indeed, I'm a trickster, I'm a cheat, I'm a charlatan, that's what I do for a living. Everything I've done here was by trickery." The professor shouted back: "That's not what I mean. You're a fraud because you're pretending to do these things through trickery, but you're actually using psychic powers and misleading us by not admitting it."^[30] The famous author and believer in spiritualism Arthur Conan Doyle had years earlier made a similar accusation against the magician Harry Houdini.^[31] A similar event involved Senator Claiborne Pell. Pell believed in psychic phenomena. When Randi demonstrated viewing a hidden drawing by using trickery, Pell refused to believe that it was a trick, saying, "I think Randi may be a psychic and doesn't realize it." Randi has consistently denied having any paranormal powers or abilities.^[32]

Author[link]

Randi is author of Conjuring (1992), a biographical history of noted magicians. The book is subtitled: Being a Definitive History of the Venerable Arts of Sorcery, Prestidigitation, Wizardry, Deception, & Chicanery and of the Mountebanks & Scoundrels Who have Perpetrated these Subterfuges on a Bewildered Public, in short, MAGIC!. The book selects the most influential magicians and explains their history in the context of strange deaths and careers on the road. This work expanded on the 1976 book Houdini, His Life and Art, co-authored with Bert Randolph Sugar, which focused on Houdini and his cohorts. Randi also wrote a children's book in 1989 titled The Magic World of the Amazing Randi, which introduced children to magic tricks. In addition to his magic books, he has written several educational works about the paranormal and pseudoscientific. These include biographies of Uri Geller and Nostradamus as well as reference material on other major paranormal figures. He is currently working on A Magician in the Laboratory, which recounts his application of skepticism to science,^[33] though in January 2011, he expressed doubts as to whether it would be finished. James Randi has since confirmed the that the book will be sent to publishers by May 20, 2012.^[34] He is a member of the all-male literary banqueting club the Trap Door Spiders, which served as the basis of Isaac Asimov's fictional group of mystery solvers the Black Widowers.^[35]

Skeptic[link]

Randi entered the international spotlight in 1972 when he publicly challenged the claims of Uri Geller. Randi accused Geller of being nothing more than a charlatan and a fraud who used standard magic tricks to accomplish his allegedly paranormal feats, and he supported his claims in the book The Truth About Uri Geller.^[17][36] Geller sued Randi for $15 million in 1991 and lost.^[37] Geller's suit against the Committee for Scientific Investigation of Claims of the Paranormal (CSICOP) was thrown out in 1995, and he was ordered to pay $120,000 for filing a frivolous lawsuit.^[38]

Randi was a founding fellow and prominent member of CSICOP.^[39] During the period when Geller was filing numerous civil suits against him, CSICOP's leadership, wanting to avoid becoming a target of Geller's litigation, requested that Randi refrain from commenting on Geller. Randi refused and resigned. However, he still maintains a respectful relationship with the group and frequently writes articles for its magazine.

Randi has gone on to write several books criticizing beliefs and claims regarding the paranormal.^[40] He has also demonstrated flaws in studies suggesting the existence of paranormal phenomena; in his Project Alpha hoax, Randi revealed that he had been able to orchestrate a three-year-long compromise of a privately funded psychic research experiment.^[41] The hoax became a scandal and demonstrated the shortcomings of many paranormal research projects at the university level.

Randi has appeared on numerous TV shows, sometimes to directly debunk the claimed abilities of fellow guests. In a 1981 appearance on That's My Line, Randi appeared opposite psychic James Hydrick, who claimed that he could move things with his mind and demonstrated this ability on live television by apparently turning a page in a telephone book without touching it.^[42] Randi, having determined that Hydrick was surreptitiously blowing on the book, arranged packaging peanuts (polystyrene foam shapes) on the table in front of the telephone book for the demonstration, preventing Hydrick from demonstrating his abilities, which would have been exposed when the blowing moved the packaging.^[43] Many years later, Hydrick admitted his fraud.^[44]

Randi was awarded a MacArthur Foundation Genius award in 1986. The money was used for Randi's comprehensive exposé of faith healers, including Peter Popoff, W.V. Grant and Ernest Angley. When Popoff was exposed, he was forced to declare bankruptcy within the year.^[45]

In 1988, Randi tested the gullibility of the media by perpetrating a hoax of his own. By teaming up with Australia's 60 Minutes program and by releasing a fake press package, he built up publicity for a spirit channeler named Carlos who was actually artist Jose Alvarez, a friend of Randi's. Randi would tell him what to say through sophisticated radio equipment. The media and the public were taken in, as no reporter bothered to check Carlos's credentials and history, which were all fabricated. The hoax was exposed on 60 Minutes; Carlos and Randi explained how they pulled it off.^[46][47]

In the book The Faith Healers, Randi explains his anger and relentlessness as arising out of compassion for the helpless victims of frauds. Randi has also been critical of João de Deus (John of God), a self-proclaimed psychic surgeon who has received international attention.^[48] Randi observed, referring to psychic surgery, "To any experienced conjurer, the methods by which these seeming miracles are produced are very obvious."^[49]

In 1982, Randi verified the abilities of Arthur Lintgen, a Philadelphia physician who is able to determine the classical music recorded on a vinyl LP solely by examining the groove on the record. However, Lintgen does not claim to have any paranormal ability, merely knowledge of the way that the groove forms patterns on particular recordings.^[50]

James Randi stated that Daniel Dunglas Home, who allegedly could play an accordion that was locked in a cage, without touching it, was caught cheating on a few occasions, but the episodes were never made public, and that the accordion in question was a one-octave mouth organ that Home concealed under his large moustache. James Randi writes that one-octave mouth organs were found in Home's belongings after his death.^[51] According to Randi 'around 1960' William Lindsay Gresham told Randi he had seen these mouth organs in the Home collection at the Society for Psychical Research.^[52] Eric Dingwall, who catalogued Home's collection on its arrival at the SPR does not record the presence of the mouth organs. According to Peter Lamont, the author of an extensive Home biography, "It is unlikely Dingwall would have missed these or did not make them public."^[53]

James Randi Educational Foundation (JREF)[link]

The offices of the JREF in Fort Lauderdale, Florida.

In 1996, Randi established the James Randi Educational Foundation (JREF). Randi and his colleagues update JREF's blog, Swift. Topics have included the mathematics of the one-seventh area triangle. Randi also contributes a regular column, titled "'Twas Brillig," to The Skeptics Society's Skeptic Magazine. In his weekly commentary, Randi often gives examples of what he considers the nonsense that he deals with every day.^[54]

He has regularly featured on many podcasts, including The Skeptics Society's official podcast Skepticality^[55][56] and the Center for Inquiry's official podcast Point of Inquiry.^[57] From September 2006 onwards, he has occasionally contributed to The Skeptics' Guide to the Universe podcast with a column titled "Randi Speaks."^[58] In addition, "The Amazing Show" is a podcast in which Randi shares various anecdotes in an interview format.

Views on religion[link]

In his essay "Why I Deny Religion, How Silly and Fantastic It Is, and Why I'm a Dedicated and Vociferous Bright", Randi, who identifies himself as an atheist,^[1] has stated that many accounts in religious texts, including the virgin birth, the miracles of Jesus Christ, and the parting of the Red Sea by Moses, are not believable. For example, Randi refers to the Virgin Mary as being "impregnated by a ghost of some sort, and as a result produced a son who could walk on water, raise the dead, turn water into wine, and multiply loaves of bread and fishes" and questions how Adam and Eve "could have two sons, one of whom killed the other, and yet managed to populate the earth without committing incest." He writes that, compared to the Bible, "The Wizard of Oz is more believable. And more fun."^[59] In An Encyclopedia of Claims, Frauds, and Hoaxes of the Occult and Supernatural, he looks at a variety of spiritual practices skeptically. Of the meditation techniques of Guru Maharaj Ji (Prem Rawat) he writes: "Only the very naive were convinced that they had been let in on some sort of celestial secret."^[60]

The One Million Dollar Paranormal Challenge[link]

The James Randi Educational Foundation (JREF) currently offers a prize of one million U.S. dollars to eligible applicants who can demonstrate a supernatural ability under agreed-upon scientific testing criteria. Similar to the paranormal challenges of John Nevil Maskelyne and Houdini, in 1964, Randi put up $1,000 of his own money payable to anyone who could provide objective proof of the paranormal.^[61] Since then, the prize money has grown to the current $1,000,000, and has formal published rules. No one has progressed past the preliminary test, which is set up with parameters agreed to by both Randi and the applicant. He refuses to accept any challengers who might suffer serious injury or death as a result of the testing.

On Larry King Live, March 6, 2001, Larry King asked Sylvia Browne if she would take the challenge and she agreed.^[62] Then Randi appeared with Browne on Larry King Live on September 3, 2001, and she again accepted the challenge.^[63] However, she has refused to be tested and Randi keeps a clock on his website recording the number of weeks that have passed since Browne accepted the challenge without following through.^[64] During Larry King Live on June 5, 2001, Randi challenged Rosemary Altea to undergo testing for the million dollars. However, Altea would not even address the question.^[65] Instead Altea, in part, replied "I agree with what he says, that there are many, many people who claim to be spiritual mediums, they claim to talk to the dead. There are many people, we all know this. There are cheats and charlatans everywhere."^[65] Then on January 26, 2007, Altea and Randi again appeared on Larry King Live. Once again, she refused to answer whether or not she would take the One Million Dollar Paranormal Challenge.^[66]

Starting on April 1, 2007, only those with an already existing media profile and the backing of a reputable academic were allowed to apply for the challenge.^[67] The resources freed up by not having to test obscure and possibly mentally ill claimants will then be used to more aggressively challenge notorious high-profile alleged psychics and mediums such as Sylvia Browne, Allison DuBois and John Edward with a campaign in the media.^[67]

JREF maintains a public log of past participants in the Million Dollar Challenge.^[68]

Legal disputes[link]

Randi has been involved in a variety of legal disputes but claims that he has "never paid even one dollar or even one cent to anyone who ever sued me."^[5] However, he says, he has paid out large sums to personally defend himself in these suits.