We know a lot about the human body, what’s in there, how it works, and how to heal it when it’s sick. But of course this wasn’t always so. It’s really only been in the last few centuries that scientists have been able to explore and experiment on humans. I mean rats and mice may be a good place to start down on the road to new discoveries, but after a point, to really learn about humans, you have to try stuff out on humans. 

And as you might expect, human testing is currently, and has always been, a tricky business. At their best, researchers have searched for life-saving cures and treatments for uncomfortable and deadly conditions. At their worst, human studies have edged into dark curiosity-satisfying torture-experiments that yielded few useful results. When it comes down to it, the science performed on humans has ranged from good, to bad, to very, VERY ugly.

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Way back in the day, physicians like Aristotle got most of their information about our bodies from a combination of dissecting other animals' bodies, and guesswork. But you can study monkeys and pigs all you want and not get a very good picture of what’s really going on all up in here. So one of the very earliest uses of the human body in science was the simple study of human anatomy. 

For more than a thousand years, it was one of the most controversial areas of scientific research. This may, in some part, be because ethically speaking, anatomical study got off to a very bad start. Around 2,300 years ago, Greek physicians Herophilus and Erasistratus got to see the inside of human bodies when they obtained permission to carry out live dissections, or vivisections on criminals.

Herophilus was also the first known person to perform autopsies and his descriptions of the nervous, digestive, reproductive and cardiovascular systems remained important, and in some cases singular, until the middle ages. But working on human bodies, living or dead, was widely considered taboo. Many contemporaries considered Herophilus to be a sadistic butcher, and people thought poking through the guts of even a dead person would anger the gods. 

By the time Roman law came along, human dissections of all types were banned, and the taboo of studying the human body remained in place for the next 1600 years. It wasn’t until the late 15th century when Michelangelo, Leonardo da Vinci and Antonio Pollaiolo started making secret anatomical drawings of cadavers, that the scientific mind began once again to probe our inner workings.

Still, human anatomy wasn’t taught in universities until the mid 1620s and dissection was regarded warily even then. It wasn’t until England's Murder Act of 1752 that the surgeons in that country were allowed to dissect the bodies of executed criminals. But it was around this time when scientists were finally able to address the essential questions of what goes where inside us, that the idea of actually experimenting on people became at least thinkable. 

Perhaps the most famous and important early example of human experimentation is the origin of the smallpox vaccine. In 1796, English doctor Edward Jenner was seeing a lot of smallpox patients. Lots of pus, lots of dying. He started thinking about the folk adage that people who caught cowpox couldn’t catch smallpox. Cowpox is a mild viral infection seen in cows, and other than getting some pussy pox on your udders, it wasn’t so bad. Milk maids sometimes caught cowpox on their hands in particular after milking infected udders, and while it made them feel nasty, it wasn’t a big deal. 

So one spring day, Dr. Jenner got a patient with cowpox on her hands, and he’s all ”Aha, an opportunity! To infect an unsuspecting human.” Then, the gardener's eight year old son walked by. Jenner scratched up little Jimmy’s arm and rubbed some pus in there. The kid got mildly ill with cowpox, but was fine a week later. Jenner then knew cowpox could be passed from person to person, as well as from cow to person, and presumably cow to cow. 

But the big question was about smallpox, so, Jenner infected the boy again, this time by injecting the smallpox pathogen into him. What?! And to his, the kid’s, and presumably the gardener’s great relief, he was immune. Just to be sure though, Jenner then tested his methods on other neighborhood kids, including his own infant son.

Eventually, the medical community and the public accepted what Jenner had discovered, a vaccine, from the Latin for cow, ”vacca”. In the end, Jenner made history, and luckily, no humans were maimed or killed in the process. It’s a good example of successful human medical experimentation. Other cases are more complicated, in fact, this case is kind of more complicated because if he had failed, he would have just been murdering people. 

But let's look at the case of Alabama doctor J. Marion Sims, originally lauded as the ”father of gynecology”, history isn’t sure what to make of him now. In the mid 1800s, Sims discovered how to operate on collapsed uteruses and how to close up fistulas, or tears in inner tissues suffered during childbirth. These were serious problems that killed or made miserable many women at the time, and Sims pioneered the operation that fixes them. But, he tested his technique on slave women, often without anesthetic, even after such drugs became widely available. He operated on one woman at least 30 times. 

Sad to say, the practices on human subjects didn’t improve much in the 20th century, when many doctors conducted their experiments on prisoners, poor folks, soldiers and mental patients. Some of this work had good intentions, but some of it was just weird. Like back in 1920, when a resident physician at San Quentin prison in California tried to revitalize older men by implanting them with the testicles from younger, executed convicts, and even livestock [disgusted noises]. 

Of course, no one did evil experimentation quite like the Nazis, except maybe their equally morally bereft Japanese counterparts in the infamous Unit 731 secret research unit during World War II. I’ll let you research these atrocities if you want yourself, but suffice to say there were many trials involving vivisections without anesthetic; forced sterilization; exposure to extreme temperatures, deadly pathogens and chemicals and other totally, TOTALLY messed up stuff. 

Today, it’s impossible to view any of these experiments as anything more than torture thinly veiled as medical research. When the war ended, and the world learned what the Nazi researchers had done, the Nuremberg war trials began, and from them we got the Nuremberg Code, a set of international rules, outlined to protect human test subjects. The code, I know, revolutionary stuff, stated that the subject's voluntary consent without coercion is essential. Surprise! Really, did it take us that long to figure that out?! 

Also that the subject can end treatment at any time, that only licensed professionals should carry out treatments, and they should terminate their study if the subject is in danger. But, many US doctors believe that these rules only apply to war crimes and apparently not their own research. So a boom in prison populations combined with the rise of pharmaceutical and health care industries, led to tons of corporate and federally-funded experiments on prisoners. By the 1960s at least half of states in the country allowed medical testing on prisoners, and about 90 percent of all pharmaceutical testing happened there. 

Meanwhile, some doctors were taking liberties outside of prisons too. In 1963 Dr. Chester Southam injected cancer cells into around 20 elderly and infirm patients at the Jewish Chronic Disease Hospital in Brooklyn, to see if their bodies would reject the cells the same way healthy bodies did. The patients were not asked for permission, they weren’t even told what was happening. Around that same time, word got out that researchers were infecting mentally disabled children with viral hepatitis at Staten Island's Willowbrook Institution to test new treatments. The researchers found that the disease could be blocked with injections of the blood protein gamma globulin, but conditions were so inhumane that the institution was shut down, hardly a shining victory for science. 

The final straw came in 1972 when news of the notorious 40-year old Tuskegee experiment hit the press. The study began in 1932, when the public health service of Macon County, Alabama and the Tuskegee Institute wanted to observe the effects of untreated syphilis. In exchange for free meals, medical exams and burial services, nearly 400 poor, syphilitic African American men enrolled in the study and were told they were being treated for ”bad blood”. They were not informed that they had syphilis, they were never treated for it, even after penicillin became the standard cure in 1947. Instead, the researchers observed how the disease progressed and ultimately killed over the years. Meanwhile, many of the men went home and inadvertently infected their families.

Combined, these stories proved to much for the public, and the government got involved. By the mid-1970s the U.S banned all outside research in federal prisons and cracked down on human subject experimentation. In response, many research outfits and drug companies simply moved their operations overseas. In 2008, the U.S Department of Health and Human Services estimated that as much as 65 percent of clinical trials of federally regulated drugs were done in foreign countries, virtually none of those tests were closely monitored.

Now none of this is to say that a lot of good, life-saving treatments haven’t come out of human testing, virtually all of the big ones from blood transfusions to vaccines to organ replacements to space exploration had to be tested on humans at some point. It’s just that experimenting on humans can be a slippery slope, and that’s why, in recent decades, some researchers have avoided this sticky wicket of experimentation on other people by experimenting on themselves. Bruce Banner style.

The tradition of self-experimentation probably most famously began with the amazing husband and wife team of Pierre and Marie Curie, who in the early 1900s exposed themselves to lots and lots and LOTS of radiation while researching the elements they had discovered, uranium and radium. Pierre, for instance, strapped radium salts to his arm for several hours and then observed the resulting burn change over the course of several weeks. They were constantly sick, tired and in pain, but the Curies' research ushered in the use of radiation in medicine, and earned both of them a Nobel prize, and unfortunately, eventually killed Marie. 

Taking a cue from the Curies decades later in the mid 1980s, Australian doctor Barry Marshall and pathologist Robin Warren, sought to refute the theory that stomach ulcers were caused by lifestyle factors like stress and poor diet. They believed that the bacterium Helicobacter pylori was the culprit. To test this theory, Marshall decided to take one for the team. Fearing that the hospital's ethics committee and his wife would shoot his idea down if he asked, he just knocked back a petri dish and swallowed a healthy dose of the bacteria. 

Four days later he started puking and develop some serious death-breath. Biopsies confirmed that the bacteria had taken up shop in his stomach, and that he had contracted gastritis, which eventually may lead to ulcers. But the yuck-factor eventually paid off, Marshall and Warren earned the 2005 Nobel price for medicine for their breakthrough contributions, and probably a stern talking to from Mrs. Marshall.

Speaking of unhappy guts and self-testing, in 2004 Dr. David Pritchard strapped some larva to his arm to infect himself with parasitic hookworms to prove that the presence of these gut parasites significantly decreased the symptoms of autoimmune diseases. While doing fieldwork in Papua New Guinea in the late 1980s Pritchard noticed that the natives infected with hookworms were largely unaffected by illnesses like asthma and seasonal allergies. He theorized that somehow, the worm switched off the immune system response, and in the process the immune system didn’t overreact with allergic symptoms. 

Before he could get approval from regulators in Britain to recruit wheezy, sneezy volunteers he used himself as the subject and learned some important stuff. It turns out 50 hookworms are too many and make you sick, but ten is just the right amount to avoid intestinal discomfort and allergy symptoms. Soon he had a steady stream of human test subjects knocking on his door, inviting worms to get cozy in their intestines. 

Hopefully, in addition to learning more about our physical selves, we’ve also learned more about our moral selves. There will likely always be a need for some level of human testing, a lab rat simply can’t stand in for everything. But researchers and regulators alike can take one very old piece of advice because Hippocrates really did have it right, ”primum non nocere”, ”first do no harm”.

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