(CNN) -- The Tuskegee syphilis experiment of the 20th century is often cited as the most famous example of unethical medical research. Now, evidence has emerged that it overlapped with a shorter study, also sponsored by U.S. government health agencies, in which human subjects were unknowingly being harmed by participating in an experiment.
Research from Wellesley College professor Susan Reverby has uncovered evidence of an experiment in Guatemala that infected people with sexually transmitted diseases in an effort to explore treatments.
The U.S. government apologized for the research project on Friday, more than 60 years after the experiments ended. Officials said an investigation will be launched into the matter.
The Tuskegee and the Guatemala studies show what National Institutes of Health Director Francis Collins called a "a dark chapter in the history of medicine."
As unethical as the methods were, the basic research questions behind both studies were highly relevant at the time, said Peter Brown, medical anthropologist at Emory University. Research in Guatemala focused on the powers of penicillin; in Tuskegee, researchers wanted to know the natural history of syphilis.
"In a racist context, they thought [syphilis] might be different in African-Americans; the real unethical part in my mind had to do with denial of treatment and, most importantly, the denial of information about the study to the men involved," he said.
In 1926, syphilis was seen as a major health problem, according to the Centers for Disease Control and Prevention; in 1928, about 25 percent of black employees at the Delta Pine and Land Company of Mississippi had tested positive for syphilis, according to Tuskegee University. A charity called the Julius Rosenwald Fund came to the U.S. Public Health Service to start a project to improve the health of African-Americans in the South.
But in 1929, the Great Depression began, and the Rosenwald Fund had to cut its funds for the treatment program.
The director of the U.S. Public Health Service, Dr. Taliaferro Clark, proposed salvaging the project by investigating the course of untreated syphilis.
Getting African-Americans to participate was not a challenge; most African-Americans did not have access to medical care at that time and the study provided free health exams, food and transportation, according to Tuskegee University.
But none of the patients who had syphilis was told that he carried the condition, and doctors did not give the patients sufficient treatment. Instead they were told they would get treatment for "bad blood," a phrase that connoted a variety of illnesses including syphilis, anemia and fatigue, the CDC said.
The Tuskegee study, which began in the early 1930s, consisted of 399 African-American men with syphilis and 201 without, according to the CDC. The Tuskegee Institute partnered with the Public Health Service for an experiment that was supposed to last 6 months. Instead it lasted about 40 years.
While the Tuskegee study was still going in the 1940s, other efforts that would never meet today's medical ethics standards were going on elsewhere. The Public Health Service did research at a U.S. prison in 1944 that involved injecting inmates with gonorrhea, Reverby said. That project was abandoned, and the Public Health Service turned to Guatemala to more closely examine syphilis and in what ways penicillin could treat or prevent it, Reverby said in documents posted on her website.
"The whole fact that the Public Health Service was very aware about the ethical problems is very characteristic of American international health policy at the time, which was very condescending to other countries," Brown said.
It turns out that a physician at the Public Health Service, Dr. John C. Cutler, participated in both the Guatemala and the Tuskegee experiments. Cutler came to the Tuskegee project in the 1960s, according to Reverby, and continued to defend it even in the 1990s, long after it ended. Cutler died in 2003 at age 87.
The Guatemala syphilis research involved 696 subjects who came from the Guatemala National Penitentiary, army barracks and the National Mental Health Hospital, according to Reverby's research. These subjects did not give direct permission to participate. Instead, the authorities signed them up. There were also 772 patients exposed to gonorrhea and 142 subjects exposed to chancres, according to a CDC report.
Unlike the Tuskegee project, these participants were given the diseases as part of the experiment.
"The doctors used prostitutes with the disease to pass it to the prisoners (sexual visits were allowed by law in Guatemalan prisons) and then did direct inoculations made from syphilis bacteria poured onto the men's penises or on forearms and faces that were slightly abraded when the 'normal exposure' produced little disease, or in a few cases through spinal punctures," Reverby wrote.
Many people wrongly believe that the Tuskegee study involved injecting subjects with syphilis, according to a 2008 study led by Ralph Katz of the NYU College of Dentistry. His survey found that more than 60 percent of both whites and blacks said they believed study subjects were injected with syphilis.
Another important difference between the studies is that the subjects in Guatemala received penicillin after getting the sexually transmitted disease, Reverby wrote, although it's not clear whether everyone was cured.
In Tuskegee, on the other hand, the Public Health Service made sure that the subjects with syphilis did not get treatment from elsewhere. During World War II, draft boards agreed to lift the requirement of syphilis treatment for study participants, according to Tuskegee University.
Tuskegee study subjects continued to be excluded when the Public Health Service began giving other patients penicillin to treat syphilis in 1943. The agency set up Rapid Treatment Centers to treat the disease in 1947, helping to lower the overall syphilis rate; study subjects were still not treated, according to the CDC.
The Guatemalan study ended when "it proved difficult to transfer the disease and other priorities at home seemed more important," according to Reverby's paper. Cutler was told go back to the United States, she said. There he went on to work on an inoculation study at Sing Sing Prison in Ossining, New York, from 1953 to 1956, and later to Tuskegee. As for the participants in the Guatemalan study, there was some follow-up laboratory testing and observation until the early 1950s, the CDC said.
Tuskegee experiments stopped on a more dramatic note: in 1972 when Peter Buxton, who also worked for the Public Health Service, relayed information about the experiment to a reporter. By that time, 28 men had died of syphilis and 100 others had died of related complications. As a result of the experiment, at least 40 wives contracted syphilis and 19 children had it from birth.
The exposure of the study sparked congressional hearings in 1973 that led to a total overhaul of the Health, Education and Welfare rules concerning work with human subjects. A class-action lawsuit resulted in an out-of-court settlement of $10 million, with the U.S. government promising lifetime medical benefits and burial services to all study subjects still living. This program later expanded to include wives, widows and children.
President Bill Clinton publicly apologized to the victims of the Tuskegee experiments in an emotional speech in 1997, in which he said the study was shameful and racist.
"The people who ran the study at Tuskegee diminished the stature of man by abandoning the most basic ethical precepts. They forgot their pledge to heal and repair. They had the power to heal the survivors and all the others and they did not. Today, all we can do is apologize," he said at a ceremony at the White House.
Because of the ethical guidelines that all research institutions must follow, these kinds of studies would not happen in the United States today, Brown said.