A cast taken from an ancient Greek intaglio gem depicts a physician examining a patient while Asclepius, the god of healing, stands nearby holding the symbol of medicine, a snake coiled round a staff.

Hulton Archive/­Getty Images

adAfterSmallInset

Introduction to How Human Experimentation Works

­It is the fourth century B.C. and Herophilus, the father of anato­my, raises his surgical blade to gleam in the Egyptian sun. All around him, physicians from throughout the Mediterranean crowd in to witness his incision, strain to see as he bends his instrument to the task ahead. Already, they have learned so much about the physiology of the eye, have plunged the mysteries of human viscera.

Once more, the master parts flesh, enters the bloody maze of arteries and muscle. With each incision, the body beneath writhes with agony, strains against the cords that bind him to the operating table -- for he is no mere cadaver, but a living, breathing test subject. Herophilus continues his examination, oblivious to the condemned prisoner's muffled screams. The scholars discuss the study of the exposed poroi or nerves, even as they spark with unimaginable torment.

­It was a time of great learning in the ancient world, and Alexandria was the very center of it. The Ptolemy family had established a museum or "house of muses" for the advancement of science and literature. The family's findings helped fill the legendary Library of Alexandria and, for a time, the city served as a redoubt against an ignorance-shadowed world. The ban against the dissection of cadavers was lifted.

For a period of approximately 50 years, even the tabooed practice of human vivisection became common practice. After all, scholars could learn only so much from a study of the dead. In an age when blood vessels were still thought to carry air, they needed to open living bodies to their scientific scrutiny. Why shouldn't the forsaken lives of the condemned benefit generations to come?

Herophilus allegedly dissected nearly 600 live prisoners, earning his place in medical history with his various discoveries. Yet, even at the time, many critics expressed unease about vivisection, regardless of the rewards. His writings were lost forever in A.D. 272, when the city's great library was gutted by fire.

As we stare back through the ages, Herophilus hardly stands as a distant flicker of moral quandary. Rather, history snakes with countless and unsettling examples of human experimentation.

­Modern society stands mere decades removed from some of the worst examples of unethical experimentation. Even today, medical science continues to advance on the backs of human test subjects.

In this 1751 woodcut, the anatomical dissection of a convicted murderer takes place in the surgeon's hall. In the 18th century, only the bodies of executed criminals could legitimately be used for this purpose.

Hulton Archives/­Getty Images

adAfterSmallInset

Why Experiment on Humans?

­The issue of human experimentation generally comes down to a basic fact: When science deals directly with humans, you have to study humans -- eventually. It's that simple. Whether you're looking to heal ailments and injuries, build a safer automobile or design a deadlier weapon, you may need to test human thresholds for disease, stress and injury.

A few other options (and ethical obstacles) tend to present themselves before you take Herophilus' lead and start cutting into convicted felons. If your experiment absolutely demands the use of a human subject, you can always fall back on the dead variety. Even without function, you have form. The famed father of anatomy himself used them for much of his research.

To break new ground, medical pioneers often had to depend on the bodies of executed criminals or steal corpses from graves and gibbets. Body snatching became a growth industry in 19th century, as medical schools required fresh bodies for young surgeons to practice on. Today, researchers and students can more easily obtain access to legal medical cadavers.

Sometimes, scientists require a living subject -- a working model. In many cases, they turn to the rest of the animal kingdom. In the past century alone, chimps, rabbits and other animals have aided in everything from polio research and space exploration to cosmetics and bioweapons testing.

Moral and ethical dilemmas aside, there are two key problems with animal research. First, a rabbit can only provide behavioral and physiological feedback. Even the brightest primate can't fill out a Q&A. Second, you're working with a nonhuman species, making it difficult or impossible to study certain human-specific diseases, ailments and scenarios.

Self-experimentation has often proved a very successful (and foolhardy) means of scientific inquiry. Numerous scientists have purposely infected themselves with disease or parasites to get a firsthand take on the subject matter. Pierre and Marie Curie earned the 1903 Nobel Prize in physics for their radiation research, which involved taping hazardous radium salts to their skin.

Yet self-experimentation has its limits. Herophilus couldn't have performed his own vivisection, much less 600 separate procedures on himself. After all, an experiment is just one phase in the scientific method -- there's no sense in dying halfway through. Plus, how do you retain functionality and objectivity if you're suffering from the very plague you hope to cure?

That leaves human experimentation, and all the negative connotations that come with it.

A man views a wall listing the names of 800 out of an estimated 10,000 victims of Nazi experiments as a memorial titled 'Man with Sheet' created by Australian artist Ron Mueck crouches silently at the Medical History Museum in Berlin.

Kurt Vinion/Getty Images News/­Getty Images

adAfterSmallInset

The Dark Side of Science: Unit 731 and Nazi Germany

­Human experimentation doesn't have to be an exercise in cruelty, yet we're not even a century removed from some of the more deplorable acts -- cases that could easily rival and even surpass the alleged crimes of Herophilus and his colleagues.

As in ancient Alexandria, scientists and doctors have often turned to the disenfranchised when the need for test subjects arises. After all, we experiment on animals by telling ourselves that the greater good outweighs the desires of a few lesser creatures. History has shown us where this line of thinking can lead when we see other humans as the lesser creatures in question.

J. Marion Sims is widely considered the father of gynecology and even became the president of the American Medical Association in 1876. Yet Sims developed his experimental surgeries by testing them on African slaves, often without anesthesia.

The United States often turned to prisoners for medical tests, such as the 1906 cholera experiments in the Philippines and the 1915 pellagra experiments in Mississippi. Poor and orphaned children suffered similar fates. In 1908, three Philadelphia physicians infected several orphans with tuberculosis, permanently blinding several. Between 1919 and 1922, Dr. Leo Stanley injected 656 prisoners at San Quentin Prison with animal testis trying to slow or reverse ageing [source: Lunenfeld]. Before the 1970s, roughly 90 percent of all pharmaceutical products were tested on prisoners [source: Proquest].

Yet when it comes to experiments on captives and prisoners, few examples resonate as strongly as the experiments conducted by the Nazis during World War II on Jews, gypsies and other targeted individuals. The doctors conducted cruel and often lethal experiments into wartime injury treatment generally by inflicting said injury on a captive patient. They froze victims to research hypothermia, placed them in compression chambers to test the effects of high-altitude flight. They also conducted brutal sterilization experiments in the name of racial superiority.

Similarly, Japan's infamous Unit 731 reportedly killed more than 10,000 Chinese, Korean and Russian prisoners of war to research and develop biological weapons. They infected inmates and performed vivisections on them, all in an attempt to craft even deadlier weapons out of disease.

­How are we suppose­d to process such atrocities? And what do we do with the data gleaned from degradation and torture?

Japanese soldiers stand guard over eight Chinese prisoners in Mongolia during the Imperial Army's 1941 Winter Hygienic Research program.

­AP Photo/Kyodo News

adAfterSmallInset

Wisdom Out of Suffering: Learning from Human Experimentation

­Humanity continues to m­arch on through the years, bound to the linear procession of time. Any sober, honest glance back at the path we've traveled is often as horrifying as it is wondrous. Our collective history bristles with atrocity. We can't separate ourselves from it without also draping ourselves again in the cloak of ignorance.

Much the same can be said of science. While it continues to light the way to the future, portions of its momentum were purchased through horrible deeds. But what can we do? No one is arguing that we throw out everything we know about human anatomy in penance for Herophilus' vivisections.

Allied scientists faced such a dilemma at the end of World War II. What were they to do with Unit 731's medical findings on disease? Regardless of the methods used to obtain it, the information was valuable. It was like pondering a gold coin fetched from a vat of boiling oil. Were the U.S. scientists simply to flip it back into the searing pitch? Rather than see the information fall into the hands of the Russians, the U.S. bargained with the Japanese officers responsible: immunity from war crime prosecution in exchange for the ill-gained data [source: McNaught]. The officers were even given stipends.

Similar concerns have arisen concerning Nazi documents leftover from the Holocaust. With no regard for the welfare of their test subjects, German scientists at Dachau subjected victims to extremely low temperatures -- often resulting in death. Yet the Nazis also used these experiments to determine the best method of reviving hypothermia patients in tubs of hot water. Hypothermia researchers later insisted that the data was valuable, no matter how deplorable the methods used to obtain it.

Many critics argue that by using the data, we validate the crimes. Yet purely logistical criticisms arise as well. Can we trust Nazi doctors who sought politically motivated results, such as those that "proved" German racial superiority? In many cases, the experiments lacked proper methods and protocol. The subjects themselves, selected from the death camps, tended to be imperfect specimens to begin with, already suffering from malnourishment and psychological trauma.

­Sometimes, however, the victims of atrocity have managed to obtain useful data from the conditions brought on by their tormenters. Jewish doctors documented starvation in the Warsaw ghetto -- notes that later aided the study of hunger-associated disease [source: NOVA].

President Clinton and Vice President Al Gore recognize Herman Shaw, 94, a Tuskegee Syphilis Study victim, during a news conference in 1997.

­AP Photo/Doug Mills

adAfterSmallInset

Experimenting on Unknowing Subjects

­We tend to place a great deal of trust in our physicians. With that trust comes the understanding that they won't secretly experiment on us. But there was a time when entering a teaching hospital as a patient might result in not only the procedure you needed, but also whatever the students needed to practice that week [source: Roach].

While the prospect of receiving an unmerited appendectomy at no extra cost may seem horrifying enough, more shameful experiments litter medical history. In 1932, the U.S. Public Health Service began its 40-year Tuskegee study of syphilis. During this time, African-Americans who sought treatment for the disease were deceived. Instead of administering proper medical attention, the doctors allowed their conditions to worsen in order to better study the illness. The U.S. military also tested unsuspecting patients, exposing citizens to germ warfare agents and LSD in the '50s and '60s. Various U.S. radiological tests also used unknowing subjects, injecting hospital patients with plutonium and feeding radioactive cereal to mentally disabled children [source: Proquest].

Human trials became increasingly essential to the pharmaceutical industry as the U.S. Food and Drug Administration began requiring stricter testing of new drugs in the 1930s. In 1966, the National Institutes of Health (NIH) established the NIH Policy for Protection of Research Subjects. This measure established review boards to monitor human experimentation. To this day, U.S. colleges and universities that perform any kind of human experimentation also have institutional review boards, or IRBs.

Subsequently, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (later the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research) entered the picture to refine the laws and practices surrounding human experimentation.

Throughout the 20th century, medical laws raced to keep pace with human experimentation -- often falling troublingly behind. For instance, 1964's Helsinki Declaration by the World Medical Association allowed for experimentation on incapacitated and incompetent individuals so long as legal guardians gave written consent.

­Yet, even sheathed with the protection of signed written consent, human testing continues to bring­ up ethical concerns.

A doctor examines a patient in a drug study conducted by RapidTrials, a company known for finding ways to avoid delays in clinical trials, one of the most expensive parts of developing new products.

­AP Photo/Mark Stehle

adAfterSmallInset

Modern Clinical Drug Trials

Walk into a Phase I U.S. clinical trial for a new drug and you'll likely find something between a frat house rec room and a hospital. Far from suffering, most of the test subjects would likely be busy watching TV or blasting through a few video games. As it turns out, catheters, needles and the occasional invasive surgical procedure don't really spoil a good time, especially when you're getting paid for it.

­These mini-vacations for science can last anywhere from days to weeks and can pay in the thousands of dollars. Sometimes they're even held in hotel rooms. Phase I clinical trials typically involve otherwise healthy (though generally not gainfully employed) individuals. In this stage, researchers try to pinpoint dangerous side effects and potential complications. Phase II trials deal with dosing and efficiency, while Phase III trials enlist the help of actual patients to compare the experimental treatment to conventional ones, placebos or both.

A great deal of money and time go into these tests because pharmaceutical companies have a limited window to get a new drug out on the market and profit from it. U.S. drug patents only last 20 years; if a new medication is tied up in testing for a decade, then it will only have 10 moneymaking years left in it. While the companies themselves are frequently criticized for their commercialism, it does take a considerable financial investment to see a medical discovery all the way to the point where it can help patients -- even with limited or no human testing. Due to financial or logistical reasons, many potential medical breakthroughs don't even make it through the experimental period, which may be why researchers dub it "the valley of death."

Pharmaceutical companies used to rely more on university research facilities or teaching hospitals -- which, in turn, gave them access to students who might appreciate a spring break full of experimental psychotropic drugs and repeat viewings of "The Wall." The downside to this, however, was that it introduced academic bureaucracy into an already highly regulated process. The FDA required the tests to be supervised by an institutional review board, and these were generally staffed by university faculty.

­To streamline this ordeal, pharmaceutical companies now deal largely with commercial contract research organizations, which handle all the testing. In a 2008 article in The New Yorker, Carl Elliot described the resulting situation as a subculture of guinea pigs -- they even have their own publications, detailing which studies have the best pay and perks.

A test subject sits in a body composition assessment machine called a bop pod at Fort Campbell Army Base's Injury Prevention and Performance Enhancement Laboratory in Fort Campbell, Ky.

AP Photo/Jeff Adkins

adAfterSmallInset

Cash Money for Human Guinea Pigs

­P­aying human test subjects is a reality many view as unavoidable. While ­afflicted individuals­ might line up for the possible benefits of Phase III testing, Phase I testing tends to require healthy specimens. Like it or not, most of these individuals aren't going to volunteer without financial compensation.

This dilemma has existed for more than a century. In 1903, a New York physician stirred up ethical debate when he offered $5,000 to any man or woman willing to cut an ear off for his studies. Is it ethical to purchase a slice of another individual's health, even with the greater good in mind? Despite all the cozy accoutrements and oversight, paid test subjects put their health and even their lives on the line in sometimes painful or degrading clinical trials. After all, Phase I tests exist to help identify harmful side effects. If your bottle of medication says that it might result in bowel control problems or suicidal thoughts, you can bet that someone received a paycheck for experiencing them at some point.

Plus, there's the concern that the resulting guinea pig lifestyle winds up appealing to a particular segment of the general population. In some cases, the individuals are professional test subjects, moving from one to another like a jobless Phish fan trailing a never-ending tour. In other cases, the test ranks are occupied by some of the very underprivileged classes preyed upon in less ethical times: the poor, the mentally handicapped and even undocumented immigrants.

Contract research organizations have also come under fire for their oversight and staffing. University institutional review boards placed more emphasis on curtailing overzealous academics, in addition to testing ethics. For-profit review boards, however, answer to the market's need for speed, which has resulted in overlooked ethical concerns such as unsafe testing environments and unlicensed medical staff members. The FDA on the other hand largely places more emphasis on data inspections and reportedly inspects only 1 percent of clinical trials [source: Elliot].

Meanwhile, headlines continue to document the role of human embryonic stem cells in experimentation. While these highly versatile cells may play a huge role in the development of cures for various diseases and even ageing, many oppose the destruction of human embryos to get them.

In one form or another, human experimentation is as old as human curiosity. We learned that fire burned beca­use we tested ­it. As scientific research continues, the challenge is to keep the fla­mes in check.

­Explore the links on the next page to learn even more about scientific experimentation. ­

adAfterSmallInset

Lots More Information

adLastPage

Sources

  • "Ancient surgery: Alexandria." Channel 4. 2009. (March 17, 2009)http://www.channel4.com/history/microsites/H/history/a-b/ancientsurgery5.html
  • Beagley, Sharon. "Where Are the Cures?" Newsweek. Nov. 10, 2008. (March 17, 2009)http://www.newsweek.com/id/166856
  • Elliot, Carl. "Guinea-Pigging." The New Yorker. Jan. 1, 2008. (March 17, 2009)http://www.newyorker.com/reporting/2008/01/07/080107fa_fact_elliott
  • Harris, Eleanor. "Eight scientists who became their own guinea pigs." New Scientist. March 11, 2009. (March 17, 2009)http://www.newscientist.com/article/dn16735-eight-scientists-who-became-their-own-guinea-pigs.html?DCMP=OTC-rss&nsref=online-news
  • Longrigg, James. "Greek Rationale Medicine." Routledge. 1992.http://books.google.com/books?id=qD6G9R_-1UMC&pg=PA190&lpg=PA190&dq=vivisection+alexandria+account&source=bl&ots=Dfu9t_cG5A&sig=xUSLDKWh3NwCSyV-CfZoQUkDWOk&hl=en&ei=rn26SdW4OdTFtgeDk-ziDw&sa=X&oi=book_result&resnum=1&ct=result#PPP1,M1
  • Lunenfeld, Bruno, et al. "Textbook of Men's Health and Ageing: 2nd Edition." CRC Press. 2008http://books.google.com/books?id=9vEeMOwKY4AC&pg=PA5&lpg=PA5&dq=San+Quentin+Prison+took+part+in+testicular+transplant+experiments&source=bl&ots=EXzW5JjQk8&sig=VaiYKGZGUWKVGnClpMz2-UDOg9c&hl=en&ei=GGi-SbWKCMi0tweww-z3Cw&sa=X&oi=book_result&resnum=10&ct=result#PPR12,M1
  • "Medical Ethics Timeline." ProQuest. 2009.
  • "Results of Death-Camp Experiments: Should They Be Used?" NOVA Online. October 2000. (March 17, 2009)http://www.pbs.org/wgbh/nova/holocaust/experiments.html
  • Roach, Mary. "Stiff: The Curious Lives of Human Cadavers." W.W. Norton & Company. 2003.
  • Rodgers, Joann Ellison. "Guinea Pig Nation." Psychology Today. February 2009. (March 17, 2009)http://www.psychologytoday.com/articles/pto-20081215-000004.xml
  • "Unit 731: Japan's biological force." BBC News. Feb. 1, 2002. (March 17, 2009)http://news.bbc.co.uk/2/hi/programmes/correspondent/1796044.stm

­