From surgeries without anesthesia to clinical trials performed overseas, the history of human experimentation is riddled with stomach-turning moments.

The path to the modern understanding of medicine was paved with the misfortune of many people subjected to medical testing without their consent.

Prisoners, soldiers, the poor, and the mentally ill have historically born the brunt of misguided medical testing. (Among the worst was live dissection without anesthesia.)

While these atrocities did not go unpunished, some led to medical discoveries that saved thousands of lives.

Before its eradication in 1979, smallpox was a deadly virus unique to humans, often referred to as “the scourge of mankind.

In 1796, Edward Jenner, an English doctor, noticed that dairymaids seemed to be protected against smallpox because of their contact with cowpox, a milder virus that affected cow udders.

Jenner took samples of matter from inside a dairymaid’s hand lesion and injected it into an unknowing 8-year-old boy, James Phipps. In the following days, Phipps developed a fever, lost his appetite, and felt discomfort in his armpit. However, he soon recovered.

Two months later, Jenner injected Phipps with the smallpox virus. While it might have killed the boy, he was unfazed. From this experiment, Jenner created the first smallpox vaccine, which stems from the Latin word for cow.

While Jenner is credited with saving more lives than any other human being, his test on Phipps wouldn’t pass modern experimental standards because the young boy did not consent to the testing, nor did his parents.

From 1918 to 1922, inmates at California’s San Quentin State Prison were subjected to numerous medical procedures, including receiving transplanted testicles from recently executed prisoners. During the research, headed by Dr. Leo L. Stanley, many men received transplanted sex organs from rams, goats, and boars.

Tuberculosis treatments were also tested on prisoners in exchange for clemency, and 400 inmates of Stateville Correctional Center in Illinois were exposed to malaria in the hope of finding a cure. In this book Life Plus Ninety-Nine Years, inmate Nathan Leopold wrote “no one squawked. They all took it like men.”

Up until the 1960’s, about 90 percent of pharmaceutical research was done on prison inmates, as drug companies needed large pools of test subjects. Prison inmate testing ended in the 1970’s.

From 1956 to 1970, children with cognitive and intellectual disabilities held at the Willowbrook State School in Staten Island, N.Y., were given hepatitis so that doctors there could track the spread of the viral infection and how it responded to gamma globulin injections. More than 700 children were infected. The school was closed in 1987 after public outcry about overcrowding and the filthy conditions.

Beginning in 1932, the Tuskegee experiment was a 40-year clinical research study carried out by the Public Health Service at the Tuskegee Institute in Alabama.

Nearly 400 hundred of the 600 poor, rural sharecroppers who took part were never told they had syphilis, nor treated for it. Instead, they were given “free healthcare,” meals, and burial money as researchers studied how untreated syphilis progressed.

Besides violating the ethical rules of consent, the study was unnecessary because in 1947 penicillin was found to be adequate to treat the disease.

The Public Health Service also carried out a similar experiment in Guatemala where nearly 700 men and women in institutions and prisons were unknowingly infected with syphilis and gonorrhea.

As far back as ancient Greece, live dissection has been used as a form of medical exploration. Now considered to be torture, the practice has a dark history, predominantly during WWII.

Japan’s infamous Unit 731, led by Lt. Gen. Shirō Ishii, kept a secret 150-building complex near Harbin, China. There, an estimated 10,000 people were subjected to medical, biological, and chemical weapons testing.

There, prisoners of war along with Russian and Chinese citizens were operated on without anesthesia, had limbs amputated to study blood loss, were injected with animal blood, spun to death, and infected with gonorrhea, syphilis, plague, cholera, smallpox, and other fatal diseases.

Ishii and other Unit 731 leaders were given immunity in exchange for the data they gathered during the experimentation.

One of the most infamous wartime medical criminals was Josef Mengele, a Nazi physician at the Auschwitz concentration camp in what is today Poland, known as “the Angel of Death.”

Mengele was obsessed with twins, performing painful and often deadly experiments on Jewish and gypsy twins to study heredity and the genetic origins of disease. He was also fascinated with heterochromia, or different colored irises. He and other concentration camp doctors would inject children’s eyes with chemicals, amputate limbs, and perform various surgeries without anesthesia.

From 1945 to 1946, many Nazi leaders were prosecuted for their crimes during the Nuremberg Trials. This led to the establishment of the Nuremberg Code, a 10-point guideline for research ethics, the first point of which is that the subject must consent to the research.

Mengele evaded U.S. authorities by living in South America until his death in 1979, the same year an investigative journalist exposed the Tuskegee experiments.

Following that revelation, the U.S. Department of Health and Human Services published Ethical Principles and Guidelines for the Protection of Human Subjects of Research, which outlines what experiments can be done on humans in the U.S.

The U.S. has a strict policy on what kinds of medical experiments can be carried out on U.S. soil, but many drugs intended for Americans use data from experiments conducted overseas.

Since 2008, the National Institutes of Health (NIH) has reported 58,788 experimental drug trials involving humans in 173 countries, a 2,000 percent increase since 1990, according to a report by Vanity Fair.

Many of these trials are being conducted in countries with large numbers of illiterate and poor people, who often give their consent with a thumbprint or “X.” The countries with the highest number of clinical trials, according to Vanity Fair, include the Russian Federation, Romania, Thailand, Bangladesh, and the Ukraine.