In the Century of Science theme The Mystery of Reproduction, Science News explores the history of advanced reproductive technologies (ART) like in vitro fertilization (IVF).

Throughout the world, ART leads to over 9 million births each year. However, before these reproductive technologies became mainstream, scientists had a lot to learn about how reproduction worked—and I mean, A LOT.

The first working hypothesis for the age-old question "Where do babies come from?" was that microscopic, pre-made humans were inside either semen or menstrual blood. Even those humans would be too small to enjoy the <link explore whats-here exhibits colleen-moores-fairy-castle>Fairy Castle!

It wasn't until 1876 that early embryologists used sea urchin embryos to show that babies definitely come from both sperm and egg. But how that happened and how in the world an embryo ultimately became a baby was a field full of creative, fun and—at times—bizarre experiments.

Gregory Pincus was an American biologist studying reproduction in rabbits at Harvard in the 1930s. Fascinated by how chemicals in the body could play a part in reproduction, Pincus was the first to figure out the hormone cycle that gives rise to a mature egg every month. Once he understood that hormones controlled the potential for reproduction in the body, Pincus and his colleague E.V. Enzmann set out to recreate the whole process outside the body. These experiments are the foundation for all IVF that occurs today.

Pincus and Enzmann pulled out immature eggs from a female rabbit and washed the eggs in a cocktail of hormones to bring them to maturity. Adding in rabbit sperm, the matured eggs became rabbit embryos and were implanted into the uterus of a third, unrelated rabbit. One month later—bing, bang, boom—out came the first IVF babies: a litter of rabbits!

Pincus continued his work at Harvard for several years, pushing the boundaries of just how much power hormones could have over reproduction. In one of his most infamous experiments, later named "Franken-bunny," Pincus used only hormones—no sperm needed!—to "fertilize" a rabbit egg.

The "fertilized" embryo eventually grew into a bunny that graced the cover of Look magazine in 1937. This form of reproduction is called parthenogenesis and happens naturally in a variety of animal species, including some bees, fish, reptiles, amphibians and, very rarely, in birds.

Speaking of amphibians, salamanders provided the key to understanding how the embryonic ball of cells morphs into a baby. In the 1920s, Hans Spemann and Hilde Mangold were trying to answer the <link explore whats-here exhibits you-the-experience the-exhibit your-beginning prenatal-development>embryo-to-baby question through transplantation experiments in salamander embryos.

Using a microscope, a tweezer and a fine needle, Spemann and Mangold systematically sliced small parts off one embryo and grafted them onto a second embryo. In one of these experiments, Spemann and Mangold's grafted embryo grew into not one, but two salamander larvae attached at the belly. This chunk of transplanted cells became known as the "organizer" as this experiment showed it was enough to "organize" the formation of an entire individual. Spemann went on to win the Nobel Prize in 1935 for this weird but wildly important experiment.

Our understanding of reproduction has come a long way from Franken-bunnies and two-headed salamanders. Moving forward, the next frontier isn't so much about how reproduction works, but how can we get it to work in new ways.

While the sea urchin experiments of 1876 showed that both sperm and egg are definitely required to make a baby, new research is showing that's not exactly true. Scientists around the world are deconstructing the boundary between eggs and sperm, producing healthy mice pups from the merger of two eggs and (not-so-healthy) mice pups from two sperm.

While these types of experiments could pave a whole new avenue of artificial reproductive technologies—and a whole new chapter to the "Where do babies come from?" question—the potential for that is decades away. Yet, offspring from double-egg and duo-sperm pairings are incredibly useful in medicine as their genes hold a trove of information about disorders caused by genetic anomalies in eggs and sperm.