Quick—what's the first thought that pops into your head when you hear the word "experiment"? Odds are that what did not bubble up was the image of a 16th-century Italian nobleman who lived for 30 years on a platform suspended from a large straight-beam balance. But it should have. Historians of medicine consider Santorio Santorio—aka Santorio Santorii, aka Sanctorius of Padua—the first physician to have knowingly submitted his theoretical speculations to the rigor of experimental testing that today is taken for granted. By living on the balance, he was able to weigh himself against his daily intake of food and liquids, and his combined expulsions, leading him to the discovery of the insensible perspiration that wafts from our bodies.

Signore Santorio is far from the only self-experimenter to have left a mark on science. Sir Isaac Newton left a mark on the back of his eyelids, nearly blinding himself at age 22 by staring at the sun for too long in a mirror to study the after-images it left on his retinas. Early chemists were known for tasting their distillations, a habit that may have cut short the life of Carl Wilhelm Scheele, the 18th-century German-Swedish chemist who discovered chlorine and co-discovered nitrogen and oxygen; he died at age 44 from suspected heavy metal poisoning. And in what is probably the most famous case of self-experimentation, Australian physician Barry James Marshall downed the contents of a Petri dish laden with Helicobacter pylori bacteria to demonstrate that the microbe caused ulcers, sharing the 2005 Nobel Prize in Physiology or Medicine with J. Robin Warren for his self-experiment.

The practice is common enough among biomedical researchers that a full accounting would take volumes—a good starting point is the 1987 book by physician–journalist Lawrence Altman, entitled Who Goes First? The Story of Self-Experimentation in Medicine. To showcase the variety of reasons that a researcher (or daughter of a researcher or filmmaker) would opt to self-experiment as well as the problems of ethics and data interpretation that may crop up as a result, Scientific American is presenting an eight-part series on some of the most fascinating modern exemplars of the self-experimental method.

Day 1:

Self-Styled Cyborg Dreams of Outwitting Superintelligent Machines

Kevin Warwick wired his nervous system into the Internet and his wife; now he's out to become one with The Matrix

Day 2:

Filmmaker Gained Weight to Prove a Point about Portion Size

Morgan Spurlock turned an extreme Big Mac Attack into a public health wake-up call

Day 3:

Malaria Vaccine Maven Baits Irradiated Mosquitoes with His Own Arm

Stephen Hoffman has given years of sweat—and lots of blood—on his quest to stop a global killer.

Day 4:

To Purge Binges, Alcoholic Cardiologist Self-Prescribed an Obscure Drug

Olivier Ameisen had tried everything to dry out; then he heard about baclofen

Day 5:

Can 200,000 Hours of Baby Talk Untie a Robot's Tongue?

Deb Roy and his family are risking their privacy so that someday computers might understand human speech

Day 6:

Self-Experimenter Freed Himself from Insomnia, Acne and Love Handles

Seth Roberts says the key to self-help lies in the scientific method

Day 7:

Daughter of MRI Researcher Offered Her Brain for Virtual Dissection

Sasha Giedd would have been the only girl in high school with a time-lapse movie of her developing brain, until the IRB caught wind of it

Day 8:

Psychedelic Chemist Explores the Surreality of Inner Space, One Drug at a Time

Alexander Shulgin endured a government crackdown and bone-melting hallucinations in pursuit of new mind-bending compounds