Vaccination
Intervention
Child receiving an oral polio vaccine
ICD-9-CM	99.3-99.5

Vaccination is the administration of antigenic material (a vaccine) to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens. The efficacy of vaccination has been widely studied and verified; for example, the influenza vaccine,^[1] the HPV vaccine,^[2] and the chicken pox vaccine^[3] among others. In general, vaccination is considered to be the most effective method of preventing infectious diseases. The active agent of a vaccine may be intact but inactivated (non-infective) or attenuated (with reduced infectivity) forms of the causative pathogens, or purified components of the pathogen that have been found to be highly immunogenic (e.g., the outer coat proteins of a virus). Toxoids are produced for the immunization against toxin-based diseases, such as the modification of tetanospasmin toxin of tetanus to remove its toxic effect but retain its immunogenic effect.^[4]

Smallpox was likely the first disease people tried to prevent by purposely inoculating themselves with other types of infections.^[5] In 1718, Lady Mary Wortley Montagu reported that the Turks had a tradition of deliberately inoculating themselves with fluid taken from mild cases of smallpox, and that she had inoculated her own children.^[6] Before 1796 when British physician Edward Jenner tested the possibility of using the cowpox vaccine as an immunization for smallpox in humans for the first time, at least six people had done the same several years earlier: a person whose identity is unknown, England, (about 1771); a Mrs. Sevel, Germany (about 1772); a Mr. Jensen, Germany (about 1770); Benjamin Jesty, England, in 1774; a Mrs. Rendall, England (about 1782); and Peter Plett, Germany, in 1791.^[7]

The word vaccination was first used by Edward Jenner in 1796. Louis Pasteur furthered the concept through his pioneering work in microbiology. Vaccination (Latin: vacca—cow) is so named because the first vaccine was derived from a virus affecting cows—the relatively benign cowpox virus—which provides a degree of immunity to smallpox, a contagious and deadly disease. In common speech, 'vaccination' and 'immunization' in general have the same colloquial meaning. This distinguishes it from inoculation, which uses unweakened live pathogens, although in common usage either is used to refer to an immunization. The word "vaccination" was originally used specifically to describe the injection of smallpox vaccine.^[5][7]

Vaccination efforts have been met with some controversy since their inception, on scientific, ethical, political, medical safety, religious, and other grounds. In rare cases, vaccinations can injure people and, in the United States, they may receive compensation for those injuries under the National Vaccine Injury Compensation Program. Early success and compulsion brought widespread acceptance, and mass vaccination campaigns were undertaken, which are credited with greatly reducing the incidence of many diseases in numerous geographic regions.

Mechanism of function[link]

In the generic sense, the process of artificial induction of immunity, in an effort to protect against infectious disease, works by 'priming' the immune system with an 'immunogen'. Stimulating immune response, via use of an infectious agent, is known as immunization. Vaccinations involve the administration of one or more immunogens, which can be administered in several forms.

Polio vaccination started in Sweden in 1957.

Some vaccines are administered after the patient already has contracted a disease. Vaccinia given after exposure to smallpox, within the first three days, is reported to attenuate the disease considerably, and vaccination up to a week after exposure likely offers some protection from disease or may modify the severity of disease.^[8] The first rabies immunization was given by Louis Pasteur to a child after he was bitten by a rabid dog. Subsequent to this, it has been found that, in people with uncompromised immune systems, four doses of rabies vaccine over 14 days, wound care, and treatment of the bite with rabies immune globulin, commenced as soon as possible after exposure, is effective in preventing the development of rabies in humans.^[9] Other examples include experimental AIDS, cancer and Alzheimer's disease vaccines. The essential empiricism behind such immunizations is that the vaccine triggers an immune response more rapidly than the natural infection itself.

Most vaccines are given by hypodermic injection as they are not absorbed reliably through the intestines. Live attenuated polio, some typhoid and some cholera vaccines are given orally to produce immunity based in the bowel.

Adjuvants and preservatives[link]

Vaccines typically contain one or more adjuvants, used to boost the immune response. Tetanus toxoid, for instance, is usually adsorbed onto alum. This presents the antigen in such a way as to produce a greater action than the simple aqueous tetanus toxoid. People who get an excessive reaction to adsorbed tetanus toxoid may be given the simple vaccine when time for a booster occurs.

In the preparation for the 1990 Gulf campaign, Pertussis vaccine (not acellular) was used as an adjuvant for Anthrax vaccine. This produces a more rapid immune response than giving only the Anthrax, which is of some benefit if exposure might be imminent.

They may also contain preservatives, which are used to prevent contamination with bacteria or fungi. Until recent years, the preservative thiomersal was used in many vaccines that did not contain live virus. As of 2005, the only childhood vaccine in the U.S. that contains thiomersal in greater than trace amounts is the influenza vaccine,[1] which is currently recommended only for children with certain risk factors.^[10] Single-dose Influenza vaccines supplied in the UK do not list Thiomersal (its UK name) in the ingredients. Preservatives may be used at various stages of production of vaccines, and the most sophisticated methods of measurement might detect traces of them in the finished product, as they may in the environment and population as a whole.[2]

Vaccination versus inoculation[link]

Many times these words are used interchangeably, as if they were synonyms. In fact, they are different things. As doctor Byron Plant explains: "Vaccination is the more commonly used term, which actually consists of a "safe" injection of a sample taken from a cow suffering from cowpox... Inoculation, a practice probably as old as the disease itself, is the injection of the variola virus taken from a pustule or scab of a smallpox sufferer into the superficial layers of the skin, commonly on the upper arm of the subject. Often inoculation was done "arm to arm" or less effectively "scab to arm"...^[11]

Vaccination began in the 18th century with the work of Edward Jenner.^[12][13][14]

Types[link]

All vaccinations work by presenting a foreign antigen to the immune system to evoke an immune response, but there are several ways to do this. The four main types that are currently in clinical use are as follows:

1. An inactivated vaccine consists of virus or bacteria that are grown in culture and then killed using a method such as heat or formaldehyde. Although the virus or bacteria particles are destroyed and cannot replicate, the virus capsid proteins or bacterial wall are intact enough to be recognized and remembered by the immune system and evoke a response. When manufactured correctly, the vaccine is not infectious, but improper inactivation can result in intact and infectious particles. Since the properly produced vaccine does not reproduce, booster shots are required periodically to reinforce the immune response.
2. In an attenuated vaccine, live virus or bacteria with very low virulence are administered. They will replicate, but locally or very slowly. Since they do reproduce and continue to present antigen to the immune system beyond the initial vaccination, boosters may be required less often. These vaccines may be produced by passaging, for example, adapting a virus into different host cell cultures, such as in animals, or at suboptimal temperatures, allowing selection of less virulent strains, or by mutagenesis or targeted deletions in genes required for virulence. There is a small risk of reversion to virulence, which is smaller in vaccines with deletions. Attenuated vaccines also cannot be used by immunocompromised individuals. Reversions of virulence were described for a few attenuated viruses of chickens (infectious bursal disease virus, avian infectious bronchitis virus, avian infectious laryngotracheitis virus [3], avian metapneumovirus [4])^[15]
3. Virus-like particle vaccines consist of viral protein(s) derived from the structural proteins of a virus. These proteins can self-assemble into particles that resemble the virus from which they were derived but lack viral nucleic acid, meaning that they are not infectious. Because of their highly repetitive, multivalent structure, virus-like particles are typically more immunogenic than subunit vaccines (described below). The human papillomavirus and Hepatitis B virus vaccines are two virus-like particle-based vaccines currently in clinical use.
4. A subunit vaccine presents an antigen to the immune system without introducing viral particles, whole or otherwise. One method of production involves isolation of a specific protein from a virus or bacterium (such as a bacterial toxin) and administering this by itself. A weakness of this technique is that isolated proteins may have a different three-dimensional structure than the protein in its normal context, and will induce antibodies that may not recognize the infectious organism. In addition, subunit vaccines often elicit weaker antibody responses than the other classes of vaccines.

A number of other vaccine strategies are under experimental investigation. These include DNA vaccination and recombinant viral vectors.

History[link]

Jenner's handwritten draft of the first vaccination.

It is believed likely that some form of inoculation was developed in India or China before the 16th century.^[5] Scholar Ole Lund comments: "The earliest documented examples of vaccination are from India and China in the 17th century, where vaccination with powdered scabs from people infected with smallpox was used to protect against the disease. Smallpox used to be a common disease throughout the world and 20% to 30% of infected persons died from the disease. Smallpox was responsible for 8% to 20% of all deaths in several European countries in the 18th century. The tradition of inoculation may have originated in India in 1000 BCE."^[16] The mention of inoculation in the Sact'eya Grantham, an Ayurvedic text, was noted by the French scholar Henri Marie Husson in the journal Dictionaire des sciences me`dicales.^[17] Almroth Wright, the professor of pathology at Netley, further helped shape the future of vaccination by conducting limited experiments on the professional staff at Netly, including himself. The outcome of these experiments resulted in further development of vaccination in Europe.^[18] The Anatolian Ottoman Turks knew about methods of inoculation. This kind of inoculation and other forms of variolation were introduced into England by Lady Montagu, a famous English letter-writer and wife of the English ambassador at Istanbul between 1716 and 1718, who almost died from smallpox as a young adult and was physically scarred from it. She came across the Turkish methods of inoculation, consenting to have her son inoculated by the Embassy surgeon Charles Maitland in the Turkish way. Lady Montagu wrote to her sister and friends in England describing the process in details. On her return to England she continued to propagate the Turkish tradition of inoculation and had many of her relatives inoculated. The breakthrough came when a scientific description of the inoculation operation was submitted to the Royal Society in 1724 by Dr Emmanual Timoni, who had been the Montagu's family physician in Istanbul. Inoculation was adopted both in England and in France nearly half a century before Jenner's famous smallpox vaccine of 1796.^[19]

Since then vaccination campaigns have spread throughout the globe, sometimes prescribed by law or regulations (See Vaccination Acts). Vaccines are now used against a wide variety of diseases besides smallpox. Louis Pasteur further developed the technique during the 19th century, extending its use to killed agents protecting against anthrax and rabies. The method Pasteur used entailed treating the agents for those diseases so they lost the ability to infect, whereas inoculation was the hopeful selection of a less virulent form of the disease, and Jenner's vaccination entailed the substitution of a different and less dangerous disease for the one protected against. Pasteur adopted the name vaccine as a generic term in honor of Jenner's discovery.

A doctor performing a typhoid vaccination in Texas, 1943.

Prior to vaccination with cowpox, the only known protection against smallpox was inoculation or variolation (Variola - the Smallpox viruses) where a small amount of live smallpox virus was administered to the patient; this carried the serious risk that the patient would be killed or seriously ill. The death rate from variolation was reported to be around a tenth of that from natural infection with Variola, and the immunity provided was considered quite reliable. Factors contributing to the efficacy of variolation probably include the choices of Variola Minor strains used, the relatively low number of cells infected in the first phase of multiplication following initial exposure, and the exposure route used, via the skin or nasal lining rather than inhalation of droplets into the lungs.

Consistency would suggest the activity should have predated Jenner's description of an effective vaccination system, and there is some history relating to opposition to the older and more hazardous procedure of variolation.^[20] In modern times, the first vaccine-preventable disease targeted for eradication was smallpox. The World Health Organization (WHO) coordinated the global effort to eradicate this disease. The last naturally occurring case of smallpox occurred in Somalia in 1977.

Maurice Hilleman was the most prolific of inventors of vaccines. He developed successful vaccines for measles, mumps, hepatitis A, hepatitis B, chickenpox, meningitis, pneumonia and Haemophilus influenzae bacteria.^[21]

In 1988, the governing body of WHO targeted polio for eradication by 2000. Although the target was missed, eradication is very close. The next eradication target would most likely be measles, which has declined since the introduction of measles vaccination in 1963.

In 2000, the Global Alliance for Vaccines and Immunization was established to strengthen routine vaccinations and introduce new and under-used vaccines in countries with a per capita GDP of under US$1000. GAVI is now entering its second phase of funding, which extends through 2014.

Society and culture[link]

Poster for vaccination against smallpox.

In an attempt to eliminate the risk of outbreaks of some diseases, at various times several governments and other institutions have instituted policies requiring vaccination for all people. For example, an 1853 law required universal vaccination against smallpox in England and Wales, with fines levied on people who did not comply. Common contemporary U.S. vaccination policies require that children receive common vaccinations before entering public school.

Beginning with early vaccination in the nineteenth century, these policies were resisted by a variety of groups, collectively called anti-vaccinationists, who object on scientific, ethical, political, medical safety, religious, and other grounds. Common objections are that vaccinations do not work, that compulsory vaccination represents excessive government intervention in personal matters, or that the proposed vaccinations are not sufficiently safe.^[22] Many modern vaccination policies allow exemptions for people who have compromised immune systems, allergies to the components used in vaccinations or strongly held objections.^[23]

In countries with limited financial resources, limited coverage is a major problem causing unnecessary morbidity and mortality.^[24] More affluent countries are able to subsidize vaccinations for at-risk groups, resulting in more comprehensive and effective cover. In Australia, for example, the Government subsidizes vaccinations for seniors and indigenous Australians.^[25]

Public Health Law Research,^[26] an independent organization, reported in 2009 that there is insufficient evidence to assess the effectiveness of requiring vaccinations as a condition for specified jobs as a means of reducing incidence of specific diseases among particularly vulnerable populations;^[27] that there is sufficient evidence supporting the effectiveness of requiring vaccinations as a condition for attending child care facilities and schools.;^[28] and that there is strong evidence supporting the effectiveness of standing orders, which allow healthcare workers without prescription authority to administer vaccine as a public health intervention aimed at increasing vaccination rates.^[29]

Allegations of vaccine injuries in recent decades have appeared in litigation in the U.S. Some families have won substantial awards from sympathetic juries, even though most public health officials have said that the claims of injuries were unfounded.^[30] In response, several vaccine makers stopped production, which the US government believed could be a threat to public health, so laws were passed to shield makers from liabilities stemming from vaccine injury claims.^[30]

Vaccination-autism controversy[link]

One of the most noteworthy allegations of vaccine-induced injury is the MMR vaccine controversy. A 1998 paper by Andrew Wakefield, originally published in The Lancet, presented supposed evidence that the MMR Vaccine (an immunization against measles, mumps and rubella that is typically first administered to children before their first birthday) was linked to the onset of autism spectrum disorders.^[31]

Wakefield was accused of fabrication of data after attempted replications of his experiment did not support a link between vaccination and autism spectrum disorders.^[32] It was also later revealed that Wakefield's research had been funded by litigants against vaccine manufacturers, bringing to light a conflict of interest that would have prevented the paper's initial publication.^[33] The article was partially retracted in 2004 by Wakefield's co-authors,^[34] and was fully retracted by The Lancet in 2010.^[35] Andrew Wakefield has since been struck from the Medical Register, and can thus no longer legally practice medicine in the United Kingdom.^[36]

Wakefield's research is an often-cited example of pseudoscience due to its inability to be replicated, deliberate manipulation of data, and conclusions being driven by personal interest, meeting several of the pseudoscientific criteria outlined by Michael Shermer's Baloney Detection Kit.^[37] Psychologist Keith Stanovich addresses the case of the vaccination-autism link briefly in his 2009 book How to Think Straight About Psychology.^[38] Stanovich states that the MMR vaccine is administered around the same time in an infant's development that autism spectrum disorders are typically diagnosed, which may have led to the fallacious belief in an illusory correlation between the vaccine and the onset of autism. This suggestion is supported by the fact that the link was first observed by parents, who went on to sue vaccine manufacturers, and not by health professionals or scientists who would have been trained not to make such an error.

Routes of administration[link]

Air France Vaccinations Centre in the 7th arrondissement of Paris

A vaccine administration may be oral, by injection (intramuscular, intradermal, subcutaneous), by puncture, transdermal or intranasal.^[39]

See also[link]

Medicine portal

• List of vaccine topics
• H5N1 flu vaccine clinical trials
• Influenza vaccine
• Immunization
• Immunization during pregnancy
• Vaccination and religion
• Vaccination of cats
• Vaccination of dogs
• Vaccine trial

References[link]

External links[link]

Wikimedia Commons has media related to: Vaccinations

• U.S. government Vaccine Research Center: Information regarding preventive vaccine research studies
• The Vaccine Page links to resources in many countries.
• Immunisation Immunisation schedule for children in the UK. Published by the UK Department of Health.
• CDC.gov - 'National Immunization Program: leading the way to healthy lives', US Centers for Disease Control (CDC information on vaccinations)
• CDC.gov - 'Mercury and Vaccines (Thimerosal)', US Centers for Disease Control
• Immunize.org - Immunization Action Coalition' (nonprofit working to increase immunization rates)
• WHO.int - 'Immunizations, vaccines and biologicals: Towards a World free of Vaccine Preventable Diseases', World Health Organization (WHO's global vaccination campaign website)
• Health-EU Portal Vaccinations in the EU
• History of Vaccines Medical education site from the College of Physicians of Philadelphia, the oldest medical professional society in the US

This article uses bare URLs for citations. Please consider adding full citations so that the article remains verifiable. Several templates and the Reflinks tool are available to assist in formatting. (Reflinks documentation) (October 2011)

Usage of lethal injection for the death penalty in the United States.

  State uses only this method.

  State uses this method primarily but has secondary methods.

  State has previously used this method, but does not today.

  State has never used this method.

* U.S. Military: only lethal injection * Federal government: lethal injection as a primary method; retains secondary methods

Lethal injection is the practice of injecting a person with a fatal dose of drugs (typically a barbiturate, paralytic, and potassium solution) for the express purpose of causing the immediate death of the subject. The main application for this procedure is capital punishment, but the term may also be applied in a broad sense to euthanasia and suicide. It kills the person by first putting the person to sleep, and then stopping the breathing and heart in that order.

Lethal injection gained popularity in the twentieth century as a form of execution intended to supplant other methods, notably electrocution, hanging, firing squad, gas chamber, and beheading, that were considered to be more painful. It is now the most common form of execution in the United States of America.

The concept of lethal injection as a means of putting someone to death was first proposed on January 17, 1888, by Julius Mount Bleyer,^[1] a New York doctor who praised it as being cheaper than hanging.^[2] Bleyer's idea, however, was never used. The British Royal Commission on Capital Punishment (1949–53) also considered lethal injection, but eventually rejected it after pressure from the British Medical Association (BMA).^[2]

On May 11, 1977, Oklahoma's state medical examiner, Jay Chapman, proposed a new, less painful method of execution, known as Chapman's Protocol: "An intravenous saline drip shall be started in the prisoner's arm, into which shall be introduced a lethal injection consisting of an ultra-short-acting barbiturate in combination with a chemical paralytic."^[3] After the procedure was approved by anesthesiologist Stanley Deutsch, Reverend Bill Wiseman introduced the method^[4] into the Oklahoma legislature, where it passed and was quickly adopted (Title 22, Section 1014(A)). Since then, until 2004, thirty-seven of the thirty-eight states using capital punishment introduced lethal injection statutes.^[3] On August 29, 1977,^[5] Texas adopted the new method of execution, switching to lethal injection from electrocution. On December 7, 1982, Texas became the first state to use lethal injection to carry out capital punishment, for the execution of Charles Brooks, Jr..^[6]

The People's Republic of China began using this method in 1997, Guatemala in 1998, the Philippines in 1999, Thailand in 2003, and the Republic of China (Taiwan) in 2005.^[7] Vietnam reportedly now uses this method.^[8] The Philippines has since abolished the death penalty.

Nazi Germany's T-4 Euthanasia Program used lethal injection as one of several methods to destroy what the Nazi government dubbed "life unworthy of life".

Lethal injection has also been used in cases of euthanasia to facilitate voluntary death in patients with terminal or chronically painful conditions. Both applications have used similar drug combinations.^[9]

Procedure in China executions[link]

The People's Republic of China used to exclusively execute prisoners by means of shooting, but has been changing over to lethal injection in recent years. The specific lethal injection procedures, including the drug or drugs used, are a state secret and not widely known.^[10] In at least some cases, prisoners facing death by lethal injection have been sedated at a prison, then placed inside an execution van that is disguised to look like a regular police van.^[11]

Procedure in U.S. executions[link]

The condemned person is strapped onto a gurney; two intravenous cannulae ("IVs") are inserted, one in each arm. Only one is necessary to carry out the execution; the other is reserved as a backup in the event the primary line fails. A line leading from the IV Line in an adjacent room is attached to the prisoner's IV, and secured so the line does not snap during the injections.

The arm of the condemned person is swabbed with alcohol before the cannula is inserted.^[12] The needles and equipment used are also sterilized. There have been questions about why these precautions against infection are performed despite the purpose of the injection being death. There are several explanations: cannulae are sterilized during manufacture, so using sterile ones is routine medical procedure. Secondly, there is a chance that the prisoner could receive a stay of execution after the cannulae have been inserted, as happened in the case of James Autry in October 1983 (he was eventually executed on March 14, 1984). Finally, it would be a hazard to prison personnel to use unsterilized equipment.

Following connection of the lines, saline drips are started in both arms. This, too, is standard medical procedure: it must be ascertained that the IV lines are patent, ensuring the chemicals do not mix in the IV lines and occlude the needle, preventing the drugs from reaching the subject. A heart monitor is attached so prison officials can determine when death has occurred.

The intravenous injection is usually a series of drugs given in a set sequence, designed to first induce unconsciousness followed by death through paralysis of respiratory muscles and/or by cardiac arrest through depolarization of cardiac muscle cells. The execution of the condemned in most states involves three separate injections (in sequential order):

1. Sodium thiopental or pentobarbital^[13]: ultra-short action barbiturate, an anesthetic agent capable of rendering the prisoner unconscious in a few seconds.
2. Pancuronium bromide: non-depolarizing muscle relaxant, causes complete, fast and sustained paralysis of the skeletal striated muscles, including the diaphragm and the rest of the respiratory muscles; this would eventually cause death by asphyxiation.
3. Potassium chloride: stops the heart, and thus causes death by cardiac arrest.

Lethal injection room in the San Quentin State Prison in California

The drugs are not mixed externally as that can cause them to precipitate. Also, a sequential injection is key to achieve the desired effects in the appropriate order: administration of the barbiturate is essential to minimize physical distress during the process; the infusion of the muscle relaxant induces complete paralysis but not unconsciousness, and the injection of a highly concentrated solution of potassium chloride can cause severe pain in the site of the IV line as well as along the punctured arm.

The intravenous tubing leads to a room next to the execution chamber, usually separated from the offender by a curtain or wall. Typically a prison employee trained in venipuncture inserts the needle, while a second prison employee orders, prepares and loads the drugs into the lethal injection syringes. Two other staff members take each of the three syringes and secure them into the IVs. After the curtain is opened to allow the witnesses to see inside the chamber, the condemned offender is then permitted to make a final statement. Following this, the warden will signal that the execution may commence, and the executioner(s) (either prison staff or private citizens depending on the jurisdiction) will then manually inject the three drugs in sequence. During the execution, the condemned's cardiac rhythm is monitored. Death is pronounced after cardiac activity stops. Death usually occurs within seven minutes, although the whole procedure can take up to two hours, as was the case with the execution of Christopher Newton on May 24, 2007. According to state law, if a physician's participation in the execution is prohibited for reasons of medical ethics, then the death ruling can be made by the state Medical Examiner's Office. After confirmation that death has occurred, a coroner signs the condemned’s death certificate.

In three states (Delaware, Illinois and Missouri) there is a lethal injection machine designed by Massachusetts-based Fred A. Leuchter that comprises two components: the delivery module and the control module. Two staff members each have a station in which they key the machine on and depress two stations buttons to be ready in case of mechanical failure. Each person presses one station button on the console which travels to a computer which starts all three injections electronically. The computer then deletes who actually started the syringes so that participants are not aware if their syringe contained saline or one of the drugs necessary for execution (to assuage guilt in a manner similar to the blank cartridge in execution by firing squad). The delivery module has eight syringes. The end syringes containing saline, syringes 2, 4, 6 containing the lethal drugs for the main line and syringes 1, 3, 5 containing the injections for the back-up line. The system was used in New Jersey before the abolition of the death penalty in 2007. Illinois previously used the computer, and Missouri and Delaware use the manual injection switch on the delivery panel.^[14]

In 2011, after pressure by activist organizations, the manufacturers of sodium thiopental and pentobarbital halted supply of the drugs to U.S. prisons performing lethal injections and required all resellers to do the same.^[13]

Drugs[link]

Conventional lethal injection protocol[link]

Typically, three drugs are used in lethal injection: sodium thiopental is used to induce unconsciousness; pancuronium bromide (Pavulon) to cause muscle paralysis and respiratory arrest; and potassium chloride to stop the heart.^[15]

Sodium thiopental[link]

• Lethal injection dosage: 2-5 grams

Sodium thiopental (US trade name: Sodium Pentothal) is an ultra-short acting barbiturate, often used for anesthesia induction and for medically induced coma. The typical anesthesia induction dose is 3–5 mg/kg. Loss of consciousness is induced within 30–45 seconds at the typical dose, while a 5 gram dose (14 times the normal dose) is likely to induce unconsciousness in 10 seconds.

A full medical dose of Thiopental reaches the brain in about 30 seconds. This induces an unconscious state. Within 5 to 20 minutes only 15% of the drug remains in the brain, with the rest redistributed to the rest of the body.

The half-life of this drug is about 11.5 hours,^[16] and the concentration in the brain remains at around 5-10% of the total dose during that time. When a 'mega-dose' is administered, as in state-sanctioned lethal injection, the concentration in the brain during the tail phase of the distribution remains higher than the peak concentration found in the induction dose for anesthesia. This is the reason why an ultra-short acting barbiturate, such as thiopental, can be used for long-term induction of medical coma.

Historically, thiopental has been one of the most commonly used and studied drugs for the induction of coma. Protocols vary for how it is given, but the typical doses are anywhere from 500 mg up to 1.5 grams. It is likely that this data was used to develop the initial protocols for state-sanctioned lethal injection, according to which one gram of thiopental was used to induce the coma. Now, most states use 5 grams to be absolutely certain the dosage is effective.

Barbiturates are the same class of drug used in medically assisted suicide. In euthanasia protocols, the typical dose of thiopental is 1.5 grams, the Dutch Euthanesia protocol indicates 1-1.5 grams or 2 grams in case of high barbiturate tolerance.^[17] The dose used for capital punishment is therefore about 3 times more than the dose used in euthanasia.

Pancuronium bromide (Pavulon)[link]

• Lethal injection dosage: 100 milligrams

Pancuronium bromide (Trade name: Pavulon): The related drug curare, like pancuronium, is a non-depolarizing muscle relaxant (a paralytic agent) that blocks the action of acetylcholine at the motor end-plate of the neuromuscular junction. Binding of acetylcholine to receptors on the end-plate causes depolarization and contraction of the muscle fiber; non-depolarizing neuromuscular blocking agents like pancuronium stop this binding from taking place.

The typical dose for pancuronium bromide in capital punishment by lethal injection is 0.2 mg/kg and the duration of paralysis is around 4 to 8 hours. Paralysis of respiratory muscles will lead to death in a considerably shorter time.

Other drugs in use are tubocurarine chloride and succinylcholine chloride.

Pancuronium bromide is a derivative of the alkaloid malouetine from the plant Malouetia bequaertiana. [1]

Potassium chloride[link]

• Lethal injection dosage: 100 mEq (milliequivalents)

Potassium is an electrolyte, 98% of which is intracellular. The 2% remaining outside of the cell has great implications for cells that generate action potentials. Doctors prescribe potassium for patients when there is insufficient potassium, called hypokalemia, in the blood. The potassium can be given orally, which is the safest route; or it can be given intravenously, in which case there are strict rules and hospital protocols on the rate at which it is given.

The usual intravenous dose is 10-20 mEq per hour and it is given slowly since it takes time for the electrolyte to equilibrate into the cells. When used in state-sanctioned lethal injection, bolus potassium injection affects the electrical conduction of heart muscle. Elevated potassium, or hyperkalemia, causes the resting electrical potential of the heart muscle cells to be lower than normal (more positive). Without a negative resting potential, cardiac cells cannot generate impulses that lead to contraction.

Depolarizing the muscle cell inhibits its ability to fire by reducing the available number of sodium channels (they are placed in an inactivated state). ECG changes include faster repolarization (peaked T-waves), PR interval prolongation, widening of the QRS, and eventual sine-wave formation and asystole. Cases of patients dying from hyperkalemia (usually secondary to renal failure) are well known in the medical community, where patients have been known to die very rapidly, having previously seemed to be normal.

Potassium chloride is also used in certain abortions to terminate pregnancies. (See, e.g., Justice Anthony Kennedy's description in the U.S. Supreme Court's opinion in Gonzales v. Carhart [2].)

It is also used in cardioplegia (cardo-Heart; plegia-paralysis) solutions used to arrest the heart during cardiac surgeries performed on a heart-lung machine.

New lethal injection protocols[link]

The Ohio protocol, developed after the incomplete execution of Romell Broom, ensures the rapid and painless onset of anesthesia by only using sodium thiopental and eliminating the use of Pavulon and potassium as the second and third drugs, respectively. It also provides for a secondary fail-safe measure using intramuscular injection of midazolam and hydromorphone in the event intravenous administration of the sodium thiopental proves problematic.^[18]

Primary: Sodium thiopental, 5 grams, intravenous Secondary: Midazolam, 10 mg, intramuscular, and hydromorphone, 40 mg, intramuscular

The brief for the U.S. courts written by accessories, the State of Ohio implies that they were unable to find any physicians willing to participate in development of protocols for executions by lethal injection, as this would be a violation of the Hippocratic Oath, and such physicians would be thrown out of the medical community and shunned for engaging in such deeds, even if they could not lawfully be stripped of their license.^[18]

On December 8, 2009, Kenneth Biros became the first person executed using Ohio's new 1-drug execution protocol. He was pronounced dead at 11:47 a.m. EST, 10 minutes after receiving the injection. On September 10, 2010, Washington became the second state to use the single-drug Ohio protocol with the execution of Cal Coburn Brown.^[19] Currently, Ohio and Washington are the only states that use the single drug method.

After sodium thiopental began being used in executions, Hospira, the only American company that made the drug, stopped manufacturing it due to its use in executions.^[20] The subsequent nationwide shortage of sodium thiopental led states to seek for other drugs. Pentobarbital, a drug often used for animal euthanasia,^[21] was used as part of a three drug cocktail for the first time on December 16, 2010, when John David Duty was executed in Oklahoma.^[22] It was then used as the drug in a single drug execution for the first time on March 10, 2011, when Johnnie Baston was executed in Ohio.^[23]

Euthanasia protocol[link]

Euthanasia can be accomplished either through oral, intravenous, or intramuscular administration of drugs. In individuals who are incapable of swallowing lethal doses of medication, an intravenous route is preferred. The following is a Dutch protocol for parenteral (intravenous) administration to obtain euthanasia, with the old protocol listed first and the new protocol listed second:

First a coma is induced by intravenous administration of 1 g thiopental sodium (Nesdonal), if necessary, 1.5-2 g of the product in case of strong tolerance to barbiturates. Then 45 mg alcuronium chloride (Alloferin) or 18 mg pancuronium bromide (Pavulon) is injected. In order to ensure optimal availability, these agents are preferably given intravenously. However, there are substantial indications that they can also be injected intramuscularly. In severe hepatitis or cirrhosis of the liver, alcuronium is the agent of first choice.^[24]

Intravenous administration is the most reliable and rapid way to accomplish euthanasia and therefore can be safely recommended. A coma is first induced by intravenous administration of 20 mg/kg thiopental sodium in a small volume (10 ml physiological saline). Then a triple intravenous dose of a non-depolarizing neuromuscular muscle relaxant is given, such as 20 mg pancuronium bromide or 20 mg vecuronium bromide (Norcuron). The muscle relaxant should preferably be given intravenously, in order to ensure optimal availability. Only for pancuronium dibromide are there substantial indications that the agent may also be given intramuscularly in a dosage of 40 mg.^[24]

A euthanasia machine may allow an individual to perform the process alone.

Constitutionality in the United States[link]

In 2006, the Supreme Court ruled in Hill v. McDonough that death-row inmates in the United States could challenge the constitutionality of states' lethal injection procedures through a federal civil rights lawsuit. Since then, numerous death-row inmates have brought such challenges in the lower courts, claiming that lethal injection as currently practiced violates the ban on "cruel and unusual punishment" found in the Eighth Amendment to the United States Constitution.^[25] Lower courts evaluating these challenges have reached opposing conclusions. For example, courts have found that lethal injection as practiced in California,^[26] Florida,^[27] and Tennessee^[28] is unconstitutional. On the other hand, courts have found that lethal injection as practiced in Missouri,^[29] Arizona,^[30] and Oklahoma^[31] is constitutionally acceptable. On September 25, 2007, the United States Supreme Court agreed to hear a lethal injection challenge arising from Kentucky, Baze v. Rees.^[32] In Baze, the Supreme Court addressed whether Kentucky's particular lethal injection procedure comports with the Eighth Amendment and will determine the proper legal standard by which lethal injection challenges in general should be judged, all in an effort to bring some uniformity to how these claims are handled by the lower courts.^[33] Although uncertainty over whether executions in the United States would be put on hold during the period in which the United States Supreme Court considers the constitutionality of lethal injection initially arose after the court agreed to hear Baze,^[34] no executions took place during the period between when the court agreed to hear the case and when its ruling was announced, with the exception of one lethal injection in Texas hours after the court made its announcement.^[35]

On April 16, 2008 the Supreme Court rejected Baze v. Rees thereby upholding Kentucky's method of lethal injection in a majority 7-2 decision.^[36] Ruth Bader Ginsburg and David Souter dissented.^[37] Several states immediately indicated plans to proceed with executions.

Ethics of lethal injection[link]

The American Medical Association believes that a physician's opinion on capital punishment is a personal decision. Since the AMA is founded on preserving life, they argue that a doctor "should not be a participant" in executions in any form with the exception of "certifying death, provided that the condemned has been declared dead by another person"[3]. Amnesty International argues that the AMA's position effectively "prohibits doctors from participating in executions."^[38] The AMA, though, does not have the authority to prohibit doctors from participation in lethal injection, nor does it have the authority to revoke medical licenses, since this is the responsibility of the individual states.

Typically, most states do not require that physicians administer the drugs for lethal injection, but many states do require that physicians be present to pronounce or certify death.

From Delaware law (Title 11, Chapter 42, § 4209)[Excerpt] "the administration of the required lethal substance or substances required by this section shall not be construed to be the practice of medicine and any pharmacist or pharmaceutical supplier is authorized to dispense drugs to the Commissioner or the Commissioner's designee, without prescription, for carrying out the provisions of this section, notwithstanding any other provision of law." State law allows for the dispense of the drugs/chemicals for lethal injection to the states DOC without a prescription.

Controversy[link]

Opposition[link]

Awareness[link]

Opponents of lethal injection believe that it is not actually painless as practiced in the United States. Opponents argue that the thiopental is an ultra-short acting barbiturate that may wear off (anesthesia awareness) and lead to consciousness and an uncomfortable death wherein the inmate is unable to express their discomfort because they have been rendered paralyzed by the paralytic agent.^[39]

Opponents point to the fact that sodium thiopental is typically used as an induction agent and not used in the maintenance phase of surgery because of its short acting nature. Following the administration of thiopental, pancuronium bromide is given. Opponents argue that pancuronium bromide not only dilutes the thiopental, but (since the inmate is paralyzed) also prevents the inmate from expressing pain. Additional concerns have been raised over whether inmates are administered an appropriate level of thiopental owing to the rapid redistribution of the drug out of the brain to other parts of the body.^[39]

Additionally, opponents argue that the method of administration is also flawed. They state that since the personnel administering the lethal injection lack expertise in anesthesia, the risk of failing to induce unconsciousness is greatly increased. In reference to this problem, Jay Chapman, the creator of lethal injection, said, "It never occurred to me when we set this up that we’d have complete idiots administering the drugs."^[40] Also, they argue that the dose of sodium thiopental must be customized to each individual patient, not restricted to a set protocol. Finally, the remote administration results in an increased risk that insufficient amounts of the lethal injection drugs enter the bloodstream.^[39]

In total, opponents argue that the effect of dilution or improper administration of thiopental is that the inmate dies an agonizing death through suffocation due to the paralytic effects of pancuronium bromide and the intense burning sensation caused by potassium chloride.^[39]

Opponents of lethal injection, as currently practiced, argue that the procedure employed is designed to create the appearance of serenity and a painless death, rather than actually providing it. More specifically, opponents object to the use of Pancuronium bromide, arguing that its use in lethal injection serves no useful purpose since the inmate is physically restrained. Therefore the default function of pancuronium bromide would be to suppress the autonomic nervous system, specifically to stop breathing.^[39]

Research[link]

In 2005, University of Miami researchers, in cooperation with an attorney representing death row inmates, published a research letter in the medical journal The Lancet. The article presented protocol information from Texas and Virginia which showed that executioners had no anesthesia training, drugs were administered remotely with no monitoring for anesthesia, data were not recorded and no peer-review was done. Their analysis of toxicology reports from Arizona, Georgia, North Carolina, and South Carolina showed that post-mortem concentrations of thiopental in the blood were lower than that required for surgery in 43 of 49 executed inmates(88%); 21 (43%) inmates had concentrations consistent with awareness.[4] This led the authors to conclude that there was a substantial probability that some of the inmates were aware and suffered extreme pain and distress during execution. The authors attributed the risk of consciousness among inmates to the lack of training and monitoring in the process, but carefully make no recommendations on how to alter the protocol or how to improve the process. Indeed, the authors conclude, "because participation of doctors in protocol design or execution is ethically prohibited, adequate anesthesia cannot be certain. Therefore, to prevent unnecessary cruelty and suffering, cessation and public review of lethal injections is warranted."

Paid expert consultants on both sides of the lethal injection debate have found opportunity to criticize the Lancet article. Subsequent to the initial publication in the Lancet, three letters to the editor and a response from the authors extended the analysis. The issue of contention is whether Thiopental, like many lipid-soluble drugs, may be redistributed from blood into tissues after death, effectively lowering thiopental concentrations over time, or whether thiopental may distribute from tissues into the blood, effectively increasing post-mortem blood concentrations over time. Given the near-absence of scientific, peer-reviewed data on the topic of thiopental post-mortem pharmacokinetics, the controversy continues in the lethal injection community and in consequence, many legal challenges to lethal injection have not used the Lancet article.

In 2007, the same group that authored The Lancet study extended its study of the lethal injection process through a critical examination of the pharmacology of the barbiturate thiopental. This study published in the online journal PloS Medicine [5] confirmed and extended the conclusions made in The Lancet article and go further to disprove the assertion that the lethal injection process is painless. To date these two studies by the University of Miami team serve as the only critical peer-reviewed examination of the pharmacology of the lethal injection process. These findings also appear true to be further supported by increased reporting of problematic lethal injections in the United States.

Single drug[link]

The execution can be painlessly accomplished, without risk of consciousness, by the injection of a single large dose of a barbiturate.^[41] By this logic, the use of any other chemicals is entirely superfluous and only serves to unnecessarily increase the risk of pain during the execution. Another possibility would be the infusion of a powerful and fast-acting narcotic, such as fentanyl, which would ensure comfort while suppressing the victim's respiratory drive.

When sodium pentobarbital, a barbiturate used in animal euthanasia, is administered in an overdose, it causes rapid unconsciousness. Respiratory arrest follows next, through paralysis of the diaphragm and collapse of the lungs. The drug would then suppress cardiac activity, thus causing death.

Cruel and unusual[link]

On occasion, there have also been difficulties inserting the intravenous needles, sometimes taking over half an hour to find a suitable vein.^[42] Typically, the difficulty is found in convicts with a history of intravenous drug use.^{[citation needed]} Opponents argue that the insertion of intravenous lines that take excessive amounts of time are tantamount to being cruel and unusual punishment. In addition, opponents point to instances where the intravenous line has failed, or where there have been adverse reactions to drugs, or unnecessary delays during the process of execution.

On December 13, 2006, Angel Nieves Diaz was not executed successfully in Florida using a standard lethal injection dose. Diaz was 55 years old, and had been sentenced to death for murder. Diaz did not succumb to the lethal dose even after 35 minutes, necessitating a second dose of drugs to complete the execution. At first, a prison spokesman denied Diaz had suffered pain, and claimed the second dose was needed because Diaz had some sort of liver disease.^[43] After performing an autopsy, the Medical Examiner, Dr. William Hamilton, stated that Diaz’s liver appeared normal, but that the needle had been pierced through Diaz’s vein into his flesh. The deadly chemicals had subsequently been injected into soft tissue, rather than into the vein.^[44] Two days after the execution, then-Governor Jeb Bush suspended all executions in the state and appointed a commission “to consider the humanity and constitutionality of lethal injections.”^[45] The ban was lifted by Governor Charlie Crist when he signed the death warrant for Mark Dean Schwab, July 18, 2007.^[46] On November 1, 2007 the Florida Supreme Court unanimously upheld the state's lethal injection procedures.^[47]

A study published in 2007 in the peer-reviewed journal PLoS Medicine suggested that "the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable".^[48]

The execution of Romell Broom was abandoned in Ohio on September 15, 2009, after prison officials failed to find a vein after 2 hours of trying on his arms, legs, hands and ankle. This has stirred up intense debate in the United States about lethal injection.^[49]

Support[link]

Commonality[link]

The combination of a barbiturate induction agent and a nondepolarizing paralytic agent is used in thousands of anesthetics every day. Supporters of the death penalty argue that unless anesthesiologists have been wrong for the last 40 years, the use of pentothal and pancuronium is safe and effective. In fact, potassium is given in heart bypass surgery to induce cardioplegia. Therefore, the combination of these three drugs is still in use today. Supporters of the death penalty speculate that the designers of the lethal injection protocols intentionally used the same drugs as used in every day surgery to avoid controversy. The only modification is that a massive coma-inducing dose of barbiturates is given. In addition, similar protocols have been used in countries that support euthanasia or physician-assisted suicide. [6]

Anesthesia awareness[link]

Thiopental is a rapid and effective drug for inducing unconsciousness, since it causes loss of consciousness upon one circulation through the brain due to its high lipophilicity. Only a few other drugs, such as methohexital, etomidate, or propofol have the capability to induce anesthesia so rapidly. (Narcotics such as Fentanyl are inadequate as induction agents for anesthesia.) Supporters argue that since the thiopental is given at a much higher dose than for medically-induced coma protocols, it is effectively impossible for the condemned to wake up.

Anesthesia awareness occurs when general anesthesia is inadequately maintained, for a number of reasons. Typically, anesthesia is induced with an intravenous drug, but maintained with an inhaled anesthetic given by the anesthesiologist (note that there are several other methods of safely and effectively maintaining anesthesia). Barbiturates are used only for induction of anesthesia and these drugs rapidly and reliably induce anesthesia, but wear off quickly. A neuromuscular blocking drug may then be given to cause paralysis which facilitates intubation, although this is not always required. The anesthesiologist has the responsibility to ensure that the maintenance technique (typically inhalational) is started soon after induction to prevent the patient from waking up.

General anesthesia is not maintained with barbiturate drugs. An induction dose of thiopental wears off after a few minutes because the thiopental redistributes from the brain to the rest of the body very quickly. However, it has a long half-life, which means that it takes a long time for the drug to be eliminated from the body. If a very large initial dose is given, little or no redistribution takes place (since the body is saturated with the drug), which means that recovery of consciousness requires the drug to be eliminated from the body, which is not only slow (taking many hours or days), but unpredictable in duration, making barbiturates very unsatisfactory for maintenance of anesthesia.

Thiopental has a half-life of approximately 11.5 hours (however, the action of a single dose is terminated within a few minutes by redistribution of the drug from the brain to peripheral tissues) and the long acting barbiturate phenobarbital has a half-life of approximately 4–5 days. It contrasts towards the inhaled anesthetics have extremely short half-lives and allow the patient to wake up rapidly and predictably after surgery.

The average time to death once a lethal injection protocol has been started is about 7 – 11 minutes.^[50] Since it only takes about 30 seconds for the thiopental to induce anesthesia, 30–45 seconds for the pancuronium to cause paralysis, and about 30 seconds for the potassium to stop the heart, death can theoretically be attained in as little as 90 seconds. Given that it takes time to administer the drug, time for the line to flush itself, time for the change of the drug being administered, and time to ensure that death has occurred, the whole procedure takes about 7–11 minutes. Procedural aspects in pronouncing death also contribute to delay and, therefore, the condemned is usually pronounced dead within 10 – 20 minutes of starting the drugs. Supporters of the death penalty say that a huge dose of thiopental, which is between 14 - 20 times the anesthetic induction dose and which has the potential to induce a medical coma lasting 60 hours, could never wear off in only 10 to 20 minutes.

Dilution effect[link]

Death penalty supporters state that the claim that pancuronium dilutes the sodium thiopental dose is erroneous. Supporters argue that pancuronium and thiopental are commonly used together in surgery every day and if there were a dilution effect, it would be a known drug interaction.

Drug interactions are a complex topic. Some drug interactions can be simplistically classified as either synergistic or inhibitory interactions. In addition, drug interactions can occur directly at the site of action, through common pathways or indirectly through metabolism of the drug in the liver or through elimination in the kidney. Pancuronium and thiopental have different sites of action, one in the brain and one at the neuromuscular junction. Since the half-life of thiopental is 11.5 hours, the metabolism of the drugs is not an issue when dealing with the short time frame in lethal injections. The only other plausible interpretation would be a direct one, or one in which the two compounds interact with each other. Supporters of the death penalty argue that this theory does not hold true. They state that even if the 100 mg of pancuronium directly prevented 500 mg of thiopental from working, there would be sufficient thiopental to induce coma for 50 hours. In addition, if this interaction did occur, then the pancuronium would be incapable of causing paralysis.^{[citation needed]}

Supporters of the death penalty state that the claim that the pancuronium prevents the thiopental from working, yet is still capable of causing paralysis, is not based on any scientific evidence and is a drug interaction that has never before been documented for any other drugs. Supporters of the death penalty question if this is an invented false claim.

Single drug[link]

Amnesty International, Human Rights Watch, the Death Penalty Information Center, and other anti-death penalty groups have not proposed a lethal injection protocol which they believe is less painful. Supporters of the death penalty argue that the lack of an alternative proposed protocol is testament to the fact that the painfulness of the lethal injection protocol is not the issue. Instead supporters argue that the issue is the continued existence of the death penalty, since if the only issue was the painfulness of the procedure, then Amnesty International, HRW, or the DPIC should have already proposed a less painful method.

Regardless of an alternative protocol, some death penalty opponents have claimed that execution can be less painful by the administration of a single lethal dose of barbiturate. Supporters of the death penalty, however, state that the single drug theory is a flawed concept. Terminally ill patients in Oregon who have requested physician-assisted suicide have received lethal doses of barbiturates. The protocol has been highly effective in producing a painless death, but the time to cause death can be prolonged. Some patients have taken days to die, and a few patients have actually survived the process and have regained consciousness up to three days after taking the lethal dose.^[51] In a Californian legal proceeding addressing the issue of the lethal injection cocktail being "cruel and unusual," state authorities said that the time to death following a single injection of a barbiturate could be as much as 45 minutes.^[52]

Scientifically, this is readily explained. Barbiturate overdoses typically cause death by depression of the respiratory center, but the effect is variable. Some patients may have complete cessation of respiratory drive, whereas others may only have depression of respiratory function. In addition, cardiac activity can last for a long time after cessation of respiration. Since death is pronounced after asystole and given that the expectation is for a rapid death in lethal injection, multiple drugs are required; specifically potassium chloride to stop the heart. In fact, in the case of Clarence Ray Allen a second dose of potassium chloride was required to attain asystole. The position of most death penalty supporters is that death should be attained in a reasonable amount of time.

Supporters of the death penalty agree that the use of pancuronium bromide is not absolutely necessary in the lethal injection protocol. Some supporters believe that the drug may decrease muscular fasciculations when the potassium is given, but this has yet to be proven.^{[citation needed]}

See also[link]

Law portal

• Capital punishment in the United States
• Euthanasia
• Execution chamber

Notes[link]

References[link]

• Bean, Matt (June 8, 2001). "Lethal injection—the humane alternative?". Court TV. http://www.courttv.com/news/mcveigh_special/botched_ctv.html. 
• Liptak, Adam (October 7, 2003). "Critics Say Execution Drug May Hide Suffering". New York Times. http://query.nytimes.com/gst/health/article-page.html?pagewanted=all&res=9A06E7DF113CF934A35753C1A9659C8B63. 
• "Prisoners 'aware' in executions". BBC News. 14 April 2005. http://news.bbc.co.uk/2/hi/health/4444473.stm. 
• Kevin Bonsor. "How Lethal Injection Works". HowStuffWorks.com. http://people.howstuffworks.com/lethal-injection.htm. Retrieved 2005-09-03. 
• Koniaris, Leonidas G. et al. (2005). "Inadequate anesthesia in lethal injection for execution". The Lancet 365 (9468): 1412–1414. DOI:10.1016/S0140-6736(05)66377-5. PMID 15836890. 

External links[link]

• Lethal Injection Web-Based Clearinghouse
• CapitalPunishmentUK.org

Bill Gates
Gates at the World Economic Forum in 2007
Born	William Henry Gates III (1955-10-28) October 28, 1955 (age 56) Seattle, Washington, United States
Residence	Medina, Washington, United States
Nationality	American
Alma mater	Harvard University (dropped out)
Occupation	Chairman of Microsoft Co-Chair of the Bill & Melinda Gates Foundation CEO of Cascade Investment Chairman of Corbis
Years active	1975–present
Net worth	US$ 61 billion (2012)[1]
Board member of	Berkshire Hathaway
Religion	None (Agnostic[2][3])
Spouse	Melinda Gates (m. 1994) «start: (1994)»"Marriage: Melinda Gates to Bill Gates" Location: (linkback:http://en-wiki.pop.wn.com/index.php/Bill_Gates)
Children	3
Parents	William H. Gates, Sr. Mary Maxwell Gates
Signature
Website
Bill Gates

William Henry "Bill" Gates III (born October 28, 1955 in Seattle, Washington)^[4] is an American business magnate, computer programmer and philanthropist. Gates is the former chief executive officer (CEO) and current chairman of Microsoft, the world’s largest personal-computer software company he co-founded with Paul Allen. He is consistently ranked among the world's wealthiest people^[5] and was the wealthiest overall from 1995 to 2009, excluding 2008, when he was ranked third;^[6] in 2011 he was the wealthiest American and the second wealthiest person.^[7][8] During his career at Microsoft, Gates held the positions of CEO and chief software architect, and remains the largest individual shareholder, with 6.4 percent of the common stock.^[9] He has also authored or co-authored several books.

Gates is one of the best-known entrepreneurs of the personal computer revolution. Gates has been criticized for his business tactics, which have been considered anti-competitive, an opinion which has in some cases been upheld by the courts.^[10][11] In the later stages of his career, Gates has pursued a number of philanthropic endeavors, donating large amounts of money to various charitable organizations and scientific research programs through the Bill & Melinda Gates Foundation, established in 2000.^[12]

Gates stepped down as chief executive officer of Microsoft in January 2000. He remained as chairman and created the position of chief software architect. In June 2006, Gates announced that he would be transitioning from full-time work at Microsoft to part-time work, and full-time work at the Bill & Melinda Gates Foundation. He gradually transferred his duties to Ray Ozzie, chief software architect, and Craig Mundie, chief research and strategy officer. Gates's last full-time day at Microsoft was June 27, 2008. He remains at Microsoft as non-executive chairman.

Early life[link]

Bill Gates was photographed by the Albuquerque, New Mexico police in 1977 after a traffic violation (details of which have been lost over time).

Gates was born in Seattle, Washington, to William H. Gates, Sr. and Mary Maxwell Gates. His parents are of English, German, and Scots-Irish descent.^[13][14] His father was a prominent lawyer, and his mother served on the board of directors for First Interstate BancSystem and the United Way. Gates's maternal grandfather was J. W. Maxwell, a national bank president. Gates has one elder sister, Kristi (Kristianne), and one younger sister, Libby. He was the fourth of his name in his family, but was known as William Gates III or "Trey" because his father had the "II" suffix.^[15] Early on in his life, Gates's parents had a law career in mind for him.^[16] When Gates was young, his family regularly attended a Congregational church.^[17][18][19]

At 13 he enrolled in the Lakeside School, an exclusive preparatory school.^[20] When he was in the eighth grade, the Mothers Club at the school used proceeds from Lakeside School's rummage sale to buy a Teletype Model 33 ASR terminal and a block of computer time on a General Electric (GE) computer for the school's students.^[21] Gates took an interest in programming the GE system in BASIC, and was excused from math classes to pursue his interest. He wrote his first computer program on this machine: an implementation of tic-tac-toe that allowed users to play games against the computer. Gates was fascinated by the machine and how it would always execute software code perfectly. When he reflected back on that moment, he said, "There was just something neat about the machine."^[22] After the Mothers Club donation was exhausted, he and other students sought time on systems including DEC PDP minicomputers. One of these systems was a PDP-10 belonging to Computer Center Corporation (CCC), which banned four Lakeside students—Gates, Paul Allen, Ric Weiland, and Kent Evans—for the summer after it caught them exploiting bugs in the operating system to obtain free computer time.^[23]

At the end of the ban, the four students offered to find bugs in CCC's software in exchange for computer time. Rather than use the system via Teletype, Gates went to CCC's offices and studied source code for various programs that ran on the system, including programs in FORTRAN, LISP, and machine language. The arrangement with CCC continued until 1970, when the company went out of business. The following year, Information Sciences, Inc. hired the four Lakeside students to write a payroll program in COBOL, providing them computer time and royalties. After his administrators became aware of his programming abilities, Gates wrote the school's computer program to schedule students in classes. He modified the code so that he was placed in classes with mostly female students. He later stated that "it was hard to tear myself away from a machine at which I could so unambiguously demonstrate success."^[22] At age 17, Gates formed a venture with Allen, called Traf-O-Data, to make traffic counters based on the Intel 8008 processor.^[24] In early 1973, Bill Gates served as a congressional page in the U.S. House of Representatives.^[25]

Gates graduated from Lakeside School in 1973. He scored 1590 out of 1600 on the SAT^[26] and enrolled at Harvard College in the autumn of 1973.^[27] While at Harvard, he met Steve Ballmer, who later succeeded Gates as CEO of Microsoft.

The Poker Room in Currier House at Harvard University, in which Bill Gates and Steve Ballmer formed Microsoft

In his sophomore year, Gates devised an algorithm for pancake sorting as a solution to one of a series of unsolved problems^[28] presented in a combinatorics class by Harry Lewis, one of his professors. Gates's solution held the record as the fastest version for over thirty years;^[28][29] its successor is faster by only one percent.^[28] His solution was later formalized in a published paper in collaboration with Harvard computer scientist Christos Papadimitriou.^[30]

Gates did not have a definite study plan while a student at Harvard^[31] and spent a lot of time using the school's computers. Gates remained in contact with Paul Allen, and he joined him at Honeywell during the summer of 1974.^[32] The following year saw the release of the MITS Altair 8800 based on the Intel 8080 CPU, and Gates and Allen saw this as the opportunity to start their own computer software company.^[33] He had talked this decision over with his parents, who were supportive of him after seeing how much Gates wanted to start a company.^[31]

Microsoft[link]

BASIC[link]

MITS Altair 8800 Computer with 8-inch (200 mm) floppy disk system

After reading the January 1975 issue of Popular Electronics that demonstrated the Altair 8800, Gates contacted Micro Instrumentation and Telemetry Systems (MITS), the creators of the new microcomputer, to inform them that he and others were working on a BASIC interpreter for the platform.^[34] In reality, Gates and Allen did not have an Altair and had not written code for it; they merely wanted to gauge MITS's interest. MITS president Ed Roberts agreed to meet them for a demo, and over the course of a few weeks they developed an Altair emulator that ran on a minicomputer, and then the BASIC interpreter. The demonstration, held at MITS's offices in Albuquerque was a success and resulted in a deal with MITS to distribute the interpreter as Altair BASIC. Paul Allen was hired into MITS,^[35] and Gates took a leave of absence from Harvard to work with Allen at MITS in Albuquerque in November 1975. They named their partnership "Micro-Soft" and had their first office located in Albuquerque.^[35] Within a year, the hyphen was dropped, and on November 26, 1976, the trade name "Microsoft" was registered with the Office of the Secretary of the State of New Mexico.^[35] Gates never returned to Harvard to complete his studies.

Microsoft's BASIC was popular with computer hobbyists, but Gates discovered that a pre-market copy had leaked into the community and was being widely copied and distributed. In February 1976, Gates wrote an Open Letter to Hobbyists in the MITS newsletter saying that MITS could not continue to produce, distribute, and maintain high-quality software without payment.^[36] This letter was unpopular with many computer hobbyists, but Gates persisted in his belief that software developers should be able to demand payment. Microsoft became independent of MITS in late 1976, and it continued to develop programming language software for various systems.^[35] The company moved from Albuquerque to its new home in Bellevue, Washington on January 1, 1979, after the former rejected his loan application.^[34]