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Charles Robert Richet used poison from a sea anemone like this one in his experiments on allergies.

Accidental Discoveries
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Allergy
Charles Robert Richet, a French physiologist, made several experiments testing the reaction of dogs exposed to poison from the tentacles of sea anemones. Some of the dogs died from allergic shock, but others survived their reactions and made full recoveries.

Weeks later, because the recovered dogs seemed completely normal, Richet wasted no time in reusing them for more experiments. They were given another dose of anemone poison, this time much smaller than before. The first time the dogs' allergic symptoms, including vomiting, shock, loss of consciousness, and in some cases death, had taken several days to fully develop. But this time the dogs suffered such serious symptoms just minutes after Richet administered the poison.

Though Richet was puzzled by what had happened, he realized he could not disregard the unexpected result of his experiment. Later, he noted that his eventual conclusions about the dogs' affliction were "not at all the result of deep thinking, but of a simple observation, almost accidental; so that I have had no other merit than that of not refusing to see the facts which presented themselves before me, completely evident."

Richet's conclusions from his findings came to form the theoretical basis of the medical study and treatment of allergies. He eventually proved that there was a physiological state called anaphylaxis that was the antithesis of prophylaxis: When an allergic subject is exposed to an allergen a second time, he or she is even more sensitive to its effects than the first time. Instead of building immunity to the substance through exposure (prophylaxis), the allergic subject's immunity becomes greatly reduced.

In 1913 Richet received a Nobel Prize for his discovery and articulation of diseases of allergy.

Frederick Banting (above) and John MacLeod discovered insulin, the elusive substance that regulates blood-sugar levels in the body.

Insulin
Frederick G. Banting, a young Canadian doctor, and Professor John J.R. MacLeod of the University of Toronto shared a Nobel Prize in 1923 for their isolation and clinical use of insulin against diabetes. Their work with insulin followed from the chance discovery of the link between the pancreas and blood-sugar levels by two other doctors on the other side of the Atlantic decades earlier.

In 1889, German physicians Joseph von Mering and Oscar Minkowski removed the pancreas from a healthy dog in order to study the role of the pancreas in digestion. Several days after the dog's pancreas was removed, the doctors happened to notice a swarm of flies feeding on a puddle of the dog's urine. On testing the urine to determine the cause of the flies' attraction, the doctors realized that the dog was secreting sugar in its urine, a sign of diabetes. Because the dog had been healthy prior to the surgery, the doctors knew that they had created its diabetic condition by removing its pancreas and thus understood for the first time the relationship between the pancreas and diabetes.

With more tests, von Mering and Minkowski concluded that a healthy pancreas must secrete a substance that controls the metabolism of sugar in the body. Though many scientists tried in vain to isolate the particular substance released by the pancreas after the Germans' accidental discovery, it was Banting and MacLeod who established that the mysterious substance was insulin and began to put it to use as the first truly valuable means of controlling diabetes.

Dr. George N. Papanicolaou, who devised the "Pap" smear test for cancer, examines a slide in his laboratory in 1958.

Pap smear
Dr. George Nicholas Papanicolaou's chance observation, while doing a genetic study, of cancer cells on a slide containing a specimen from a woman's uterus spawned the routine use of the so-called "Pap smear," a simple test that has saved millions of women from the ravages of uterine cancer.

In 1923, Papanicolaou undertook a study of vaginal fluid in women, in hopes of observing cellular changes over the course of a menstrual cycle. In female guinea pigs, Papanicolaou had already noticed cell transformation and wanted to corroborate the phenomenon in human females. It happened that one of Papanicolaou's human subjects was suffering from uterine cancer.

Upon examination of a slide made from a smear of the patient's vaginal fluid, Papanicolaou was astonished to discover that abnormal cancer cells could be plainly observed under a microscope. "The first observation of cancer cells in the smear of the uterine cervix," he later wrote, "gave me one of the greatest thrills I ever experienced during my scientific career." Papanicolaou quickly realized that doctors could administer a simple test to gather a sample of vaginal fluid and test it for early signs of uterine and other cancers.

Penicillium mold (enlarged here many times) is a fungus that differs little from one that appears on bread in warm, humid weather.

Penicillin
The identification of penicillium mold by Dr. Alexander Fleming in 1928 is one of the best-known stories of medical discovery, not only because of its accidental nature, but also because penicillin has remained one of the most important and useful drugs in our arsenal, and its discovery triggered invaluable research into a range of other invaluable antibiotic drugs.

While researching the flu in the summer of 1928, Dr. Fleming noticed that some mold had contaminated a flu culture in one of his petri dishes. Instead of throwing out the ruined dish, he decided to examine the moldy sample more closely.

Fleming had reaped the benefits of taking time to scrutinize contaminated samples before. In 1922, Fleming had accidentally shed one of his own tears into a bacteria sample and noticed that the spot where the tear had fallen was free of the bacteria that grew all around it. This discovery peaked his curiosity. After conducting some tests, he concluded that tears contain an antibiotic-like enzyme that could stave off minor bacterial growth.

Six years later, the mold Fleming observed in his petri dish reminded him of this first experience with a contaminated sample. The area surrounding the mold growing in the dish was clear, which told Fleming that the mold was lethal to the potent staphylococcus bacteria in the dish. Later he noted, "But for the previous experience, I would have thrown the plate away, as many bacteriologists have done before."

Instead, Fleming took the time to isolate the mold, eventually categorizing it as belonging to the genus penicillium. After many tests, Fleming realized that he had discovered a non-toxic antibiotic substance capable of killing many of the bacteria that cause minor and severe infections in humans and other animals. His work, which has saved countless lives, won him a Nobel Prize in 1945.

Keep that mind open
For all you would-be Nobel Prize-winners, remember the one trait that tied all these lucky strikers together: openmindedness. As the American physicist Joseph Henry once noted, "The seeds of great discoveries are constantly floating around us, but they only take root in minds well prepared to receive them."

Lexi Krock is editorial assistant of NOVA Online.

Photos: (1-7) Corbis Images.

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