Sometimes, experiments in the name of scientific progress are deeply, unequivocally unethical. They may or may not provide game-changing detail on the topic they’re investigating, but the treatment of their subjects can range from the disturbing to the outright criminal.

The US is no exception to that. Although it’s one of the world’s best sources of scientific research, it has, in the past, featured a variety of experiments that no one in their right mind would agree should ever be replicated in any form. Some are conducted by rogue individuals, but many were government-sanctioned at the time – and they’ve taken place at home, and abroad.

Although there’s a depressingly long list in which to choose from, here’s a handful of examples that’ll haunt you long after you’ve stopped reading this article.

1 – The American Nuclear Guinea Pigs

A report, published in 1986 by the Committee on Energy and Commerce at the US House of Representatives, is titled: “Three Decades Of Radiation Experiments On US Citizens.” As you’d expect, it’s not a pleasant read.

Uncovered documents revealed that, since the 1940s, the US government knowingly engaged in “frequent and systematic use of human subjects” as guinea pigs for radiation experiments. Beginning in the 1940s, these are partly put down to scientific ignorance on the subject, but those in the 1960s/70s are a different matter.

It details a variety of trials, which would convey “little to no medical benefit” to the subjects, in which the effects of radiation exposure on human biology were studied. Whether it was ingested, inhaled, injected or placed in proximity, the subjects chosen to become “nuclear calibration devices” were seen as “expendable” by the scientists in charge.

These included “the elderly, prisoners, hospital patients suffering from terminal diseases or who might not have retained their full faculties for informed consent.” In fact, it appears plenty weren’t given a chance to consent. These experiments were kept secret, and families of the victims were intentionally deceived.

The individual examples are mortifying. From 1953 to 1957, terminal brain tumor subjects were injected with uranium in an attempt to find out when kidney damage began. In 1956, the US Air Force sent manned planes through radiation clouds at atomic bomb test sites to see if the crew were affected.

In the late 1960s, prisoners at two facilities had their testes bombarded with X-rays to see how it affected their fertility. In one particularly galling example, 102 subjects in the early 1960s were fed real fallout particles scavenged from the infamous Nevada Test Site.

The recommendation of Congress was to identify the victims and compensate them, but the irreversible damage, in almost every case, had already been done.

2 – Operation Top Hat

Although formalized guidelines in the post-Second World War period prevented American researchers from engaging in unethical tests on volunteers, this sometimes only applied on paper. A “loophole” meant that certain types of experiments didn’t require approval, and one labeled a “local field exercise”, certainly infringed on multiple human rights.

Taking place at Fort McClellan in Alabama in 1953, it involved the Chemical Corps, a US Army branch that is trained to deal with biological, radiological, and nuclear weapons. Without being informed or allowed to give their consent, members were exposed to mustard gas and several nerve agents – although it remains unclear what ultimately happened to them.

3 – The Guatemala Syphilis Experiment

Syphilis is a deeply unpleasant infection, one that’s usually transmitted sexually. Although occasionally asymptomatic, hosts normally experience skin growths around the vulva in women or the anus in both men and women, along with skin rashes, headaches, fevers, swollen glands, and joint pain.

It can usually be killed off with a course of antibiotics, but if left untreated, it can lead to strokes, meningitis, symptoms of dementia, heart problems, blindness, and even death through complications.

We know a lot more about it now than we did in the 1940s, which is partly why an experiment, coordinated by the American and Guatemalan governments at the time, was set into motion. Between 1946 and 1948, during the Truman and Arevalo administrations of the respective nations, hundreds of people in Guatemala were infected with the bacteria without their consent, and without being told.

These unwitting subjects included prison inmates, mental patients, conscripts, and orphans who were otherwise healthy. They were then given antibiotics to treat it, and researchers studied both the infection and the treatment methods in detail. In total, around 1,300 people were infected with a range of venereal diseases, but syphilis was the primary topic of investigation.

They were infected in a range of ways, including through the use of syphilis-infected prostitutes. Some had bacterial samples poured into cuts they had on their arms, faces or genitals. Sometimes, when all else failed, they were infected through a spinal puncture.

Although many were cured after getting their antibiotics treatment, many weren’t – just 700 were treated with antibiotics. In one case, a mentally ill woman who had been infected was clearly dying, but remained in the study nevertheless. Eventually, she experienced an agonizing death, one of around 83 casualties of the experiments.

The results of the experiments were never published. The study only came to light in 2010 after a research paper by a professor of medical history at Wellesley College began to uncover these experiments.

The Obama administration apologized to Guatemala, whose government eventually accused the US of crimes against humanity before issuing its own apology to its citizens. Two massive inquiries were launched by the US, and a presidential panel concluded that the scientists at the time were fully aware that what they were doing was unethical.

This wasn’t even the first or last experiment of its kind. The junior US Public Health Service officer that led the Guatemala experiments at the time, Dr John Cutler, also joined in on the future Tuskegee syphilis experiment, where hundreds of black American men were intentionally not treated for syphilis. This lasted for 40 years, only ending in 1972.

Cutler died in 2003, and never apologized for his work.

4 – The Holmesburg Prison Experiments

Dr Albert Kligman is a person whose medical legacy will forever live in infamy. He died back in 2010, aged 93, and an obituary in The New York Times noted that, in the plus column, his dermatological research led to the development of widely used acne medication Retin-A.

It also points out that his prolific scientific career also involved direct experiments at Philadelphia’s Holmesburg Prison, whose sinister practices divided experts, both at the time and to this day.

Between 1951 and 1974, inmates here were paid to test a range of product prototypes, substances and ingredients – primarily those involving the skin – by various pharmaceutical companies and government agencies, many of which were run by Kligman. At the same time, various skin infections were tried out on the prisoners, including the herpes virus and athlete’s foot.

According to a book on the subject, Kligman once said of the prison and its inmates: “All I saw before me were acres of skin. It was like a farmer seeing a fertile field for the first time.” It was from these experiments that Retin-A was developed.

Experiments went beyond dermatology. Prisoners were also subjected to tranquilizers, psychotropic drugs and environmental pollutants, such as the highly toxic dioxin group of chemicals. Dioxin is also found in Agent Orange, an incredibly dangerous chemical used by the US military as part of its herbicidal warfare program during the Vietnam War.

The experiments were terminated in 1974. At the turn of the millennium, 300 former inmates attempted to sue the doctor, the University of Pennsylvania, and the marketer of Retin-A (Johnson & Johnson) over what they’d been through during these experiments. The legal action failed, as by then too much time had passed, and according to US law, no prosecution case could be brought.

In the US, until the early 1970s, around 90 percent of pharmaceuticals were tested on inmates. Cases like Holmesburg ultimately led to federal restrictions on human test subjects, but there is always a danger of history repeating itself.

Back in 2006, a federal panel of medical advisers recommended that the government loosen these restrictions once more, as long as such experiments provided a benefit to the prisoners and the wider community.