Human subject research includes experiments (formally known as interventional studies) and observational studies. Human subjects are commonly participants in research on basic biology, clinical medicine, nursing, psychology, and all other social sciences. Humans have been participants in research since the earliest studies. As research has become formalized the academic community has developed formal definitions of "human subject research", largely in response to abuses of human subjects.
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In biostatistics or psychological statistics, a research subject is any object or phenomenon that is observed for purposes of research. In survey research and opinion polling, the subject is often called a respondent. In the United States Federal Guidelines a human subject is a living individual about whom an investigator conducting research obtains 1) Data through intervention or interaction with the individual, or 2) Identifiable private information (32 CFR 219.102.f). (Lim,1990)
Aulus Cornelius Celsus, author of an encyclopedia which survived in part as De Medicina, which introduced the Latin term cancer, discussed at length the pros and cons of human and animal medical experimentation.
Human subject research experiments were recorded during vaccination trials in the 18th century. In these early trials, physicians used themselves or their slaves as test subjects. Experiments on others were often conducted without informing the subjects of dangers associated with such experiments.
A famous example of such research were the Edward Jenner experiments, where he tested smallpox vaccines on his son and neighbourhood children. In an instance of self-experimentation, European physician Johann Jorg swallowed 17 drugs in various doses to record their properties.[1]
In the 20th century, as the progress of medicine began to accelerate, the concept of the various codes of ethics of scientific disciplines changed dramatically, and the treatment of research subjects along with it.
Walter Reed's experiments to develop an inoculation for yellow fever led these advances. Reed's vaccine experiments were carefully scrutinized, however, unlike earlier trials.[2]
Infamous cases of human subjects abuse in the 20th century were conducted during World War II by the Imperial Japanese Army (Unit 731 in China) and the Nazis, the latter an example of research involving prisoners which came to light in the Nuremberg Doctors' Trial and led to the Nuremberg Code of ethical conduct for human subjects research. Research in the second half of the 20th century has been characterized by increasing attempts to protect human subjects through national agencies, institutional ethical review boards, and informed consent.
Strict policies now exist when a human being is the subject of an experiment. These evolved over time after particularly horrid abuses (and even atrocities) on human subjects: such as research involving prisoners, research on slaves and servants, and research on family members. In some notable cases, doctors have performed experiments on themselves when they have been unwilling to risk the well-being of others. This is known as self-experimentation.
Unit 731, a department of the Imperial Japanese Army located near Harbin (then puppet state of Manchukuo, in northeast China), experimented with prisoner vivisection, dismemberment, bacteria inoculation and induced epidemics on a very large scale from 1932 onward through the Second Sino-Japanese war. With the expansion of the empire during World War II, many other units were implemented in conquered cities such as Nanking (Unit 1644), Beijing (Unit 1855), Guangzhou (Unit 8604) and Singapore (Unit 9420). After the war, Supreme commander of occupation Douglas MacArthur gave immunity in the name of the United States to Shiro Ishii and all members of the units in exchange for all of the results.[3] The United States blocked Soviet access to this information; some unit members were judged by the Soviets during the Khabarovsk War Crime Trials.
At the end of the war, 23 Nazi doctors and scientists were put on trial for the unethical treatment of concentration camp inmates, often used as research subjects with fatal consequences (see Nazi human experimentation). Out of those 23, 15 were convicted, 7 were condemned to death, 9 received prison sentences from 10 years to life, and 7 were acquitted (see the Doctors' Trial).[4]
De-classified documents of the National Archives revealed that during the 1930s and 1940s, the British Army allegedly used hundreds of British and native British Indian Army soldiers as "guinea pigs" in their experiments to determine if mustard gas inflicted greater damage on Indian skin compared to British skin. It is unclear whether the trial subjects, some of whom were hospitalised by their injuries, were all volunteers.[5] Fort Detrick in Maryland was the headquarters of US biological warfare experiments. Operation Whitecoat involved the injection of infectious agents to observe their effects in human subjects.[6]
In Sweden, the Vipeholm experiments were conducted, where mentally handicapped test subjects were exposed to large amounts of sugar to induce dental caries. In the United Kingdom (voluntary) human experimentation at Porton Down in the 1950s, led to the death of Ronald Maddison.
Pharmaceutical giant Pfizer came under fire in 2001 for allegedly testing meningitis drugs on Nigerian children.[7]
In Israel, a former worker of Negev Nuclear Research Center filed lawsuit, claiming that employees of the Center were given drinks with uranium without medical supervision and without obtaining written consent.[8]
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In a 1966 paper noted anesthesiologist Henry K. Beecher described 22 published medical studies where patients had been experimented on with no expected benefit to the patient.[9] In one study, for example, patients infused with live cancer cells had been told they were receiving "some cells" without specifying that they were cancer. Though identities of the authors and institutions had been stripped, the 22 studies were later identified as having been conducted by mainstream researchers and published in prestigious journals within approximately the previous decade. The 22 cases had been selected from a set of 50 that Beecher had collected, and he presented evidence that studies he considered unethical were even more widespread and represented a systemic problem in medical research rather than exceptions.[9][10] Though Beecher had been writing about human experimentation and publicizing cases that he considered to be bad practice for nearly a decade, it was a 1965 briefing to science writers and the 1966 paper that finally earned widespread news coverage and stimulated public reaction.[10][11] The paper has been described as "the most influential single paper ever written about experimentation involving human subjects."[12] The Office for Human Research Protections credits this paper as "ultimately contributing to the impetus for the first NIH and FDA regulations."[13]
In addition to documenting the extent of problems in human subjects research, Beecher was instrumental in formulating the solutions. One common aspect to many of Beecher's cases was that some experimental subjects, such as military personnel and mentally handicapped children in institutions, were not in a position to freely decline consent.[10] Beecher believed that rules requiring informed consent were not by themselves sufficient, as truly informed consent was an unattainable ideal. He worked both in defining the rules and conditions for informed consent and in establishing institutional review boards as an additional layer of oversight regarding research protocols.[10][11]
U.S. scientific researchers infected hundreds of Guatemalan mental patients with sexually transmitted diseases from 1946 to 1948. Researchers from the U.S. Public Health Service conducted experiments on 696 male and female patients housed at Guatemala's National Mental Health Hospital. The scientists injected the patients with gonorrhea and syphilis—and even encouraged many of them to pass the disease on to others. The experiments were done in conjunction with the Guatemalan government. The US Public Health Service carried out the experiments under the guise of syphilis inoculations. When some of the inmates did not contract the disease, the researchers created abrasions on the inmate's body and poured the bacteria into the abrasion. When that failed, they injected the disease straight into the inmates' spines. In 2010 these experiments were revealed by Susan Reverby of Wellesley College who was researching a book on Tuskegee experiments. This led to Secretary of State Hillary Clinton issuing an official apology.[14] President Barack Obama apologized to President Álvaro Colom who had called these experiments 'a crime against humanity'.[15]
Herophilos, the "father of anatomy" and founder of the first medical school in Alexandria, was described by the church leader Tertullian as having performed surgery on at least 600 live prisoners.[16] In recent times, the wartime programs of Nazi Dr. Josef Mengele, Shiro Ishii, founder of the Japanese military Unit 731, and Dr. Fukujiro Ishiyama at Kyushu Imperial University Hospital, conducted surgery on concentration camp prisoners in their respective countries during World War II.[17]
In November 2006, Doctor Akira Makino confessed to Kyodo news having performed surgery and amputations on condemned prisoners, including women and children in 1944 and 1945 while he was stationed on Mindanao.[18] In 2007, Doctor Ken Yuasa testified to The Japan Times that he believes at least 1,000 persons working for the Shōwa regime, including surgeons, did surgical research in mainland China.[19]
The use of the term vivisection when referring to procedures performed on humans almost always implies a lack of consent. Human volunteers can consent to be subjects for invasive experiments which may involve, for example, the taking of tissue samples (biopsies), or other procedures which require surgery on the volunteer. These procedures must be approved by ethical review, and carried out in an approved manner that minimizes pain and long term health risks to the subject.[20]
Several experiments have been conducted on consenting volunteers whose ethical nature is now considered questionable. Following exposure of these experiments, rules regarding informed consent have been tightened.
Various guidelines have been proposed for governing different aspects of human subject research. Among the most influential of these guidelines are the Nuremberg Code, the Declaration of Helsinki, and the Belmont Report.