The Accidental Idea
From the chance discovery of quinine as a malaria treatment in the 17th century to Alexander Fleming’s accidental encounter with penicillium mold in 1928, some of medicine’s most important advances have occurred through serendipity or error.
Call them happy accidents. Still, inadvertent discoveries would be nothing without keen, creative minds knowing what to do with them. As Louis Pasteur famously said, “In the field of observation, chance favors only the prepared mind.” Here are some legendary accidental breakthroughs in science, and some lesser-known ones that have emerged recently from the prepared minds of Cedars-Sinai researchers.
In September 1928, about to leave for a vacation, Alexander Fleming piled a number of his Petri dishes to the side of his workbench so that his colleagues could use it. When he sorted through the dishes upon his return, one of them caught his attention. A mold was growing in it. While that was not so unusual, what was remarkable was that the mold had killed the bacteria that had been growing in the dish. Fleming discovered that the mold contained an agent that became so famous it was virtually synonymous with antibiotics for a long time: penicillin. Twelve years later, during World War II, two Oxford scientists—Howard Florey from Australia and Ernst Chain, a German refugee—figured out how to isolate and mass produce the drug, which was urgently needed as disease spread like wildfire among wounded soldiers on the battlefields of Europe. In 1945, Fleming, Florey, and Chain shared the Nobel Prize in Physiology or Medicine.
High Blood Pressure Vaccine
Plaque on your teeth is bad enough—nobody likes a trip to the dentist. But plaque in your arteries can be deadly. Healthy arteries have smooth inner walls, and blood flows through them easily. But many people end up with clogged arteries from a buildup of plaque, which can reduce blood flow—or block it altogether. Atherosclerosis, as the condition is known, increases the risk of heart attack and stroke. Prediman K. Shah, MD, director of the Division of Cardiology at the Cedars-Sinai Heart Institute, and his colleague, Kuang-Yuh Chyu, MD, PhD, have been working on a vaccine against plaque. Testing his vaccine on mice, Dr. Shah saw promising results. But his research team member Tomoyuki Honjo, MD, also saw something that nobody was prepared for: The vaccine caused a sharp drop in blood pressure in a model of high blood pressure in mice—and, if it has the same effect on humans, we may have a vaccine not only against arterial plaque but also against high blood pressure, a development that would save countless lives. The anti-plaque vaccine is awaiting FDA permission to enter Phase 1 of a clinical trial.
Antioxidants & Cancer
You’ve heard it before: Antioxidants are good for you—so good, in fact, that you probably can’t get too much of them. Eduardo Marbán, MD, PhD, director of the Cedars-Sinai Heart Institute, did not set out to prove otherwise. He didn’t plan to study antioxidants at all. But while working on cardiac stem cell therapies, he found something unexpected. Because stem cells are often grown in Petri dish cultures composed of 20 percent oxygen—a much higher level than cells growing in human tissue— they can develop abnormalities that make them unusable to researchers. To correct the problem, Dr. Marbán’s team added very high doses of antioxidants to the stem cells. They weren’t prepared for what they discovered: The cells ended up with genetic abnormalities that create a predisposition to cancer. While antioxidants are good for you, supplementing far above the recommended amount isn’t just unnecessary—it may be outright dangerous.
In 1889, German physicians Joseph von Mering and Oskar Minkowski removed the pancreas from a healthy dog in order to study the role of the pancreas in digestion. Several days after the operation, 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, 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. Frederick G. Banting and John J.R. MacLeod later established that the mysterious substance was insulin, and they began to put it to use as the first truly effective means of controlling diabetes
In 1956, Wilson Greatbatch, an assistant professor in electrical engineering at the University of Buffalo, was working on a device to record heart rhythms. He reached into a box for a 10,000-ohm resistor to finish a circuit—but grabbed a 1-megaohm resistor instead and installed it before realizing his error. The circuit pulsed for 1.8 milliseconds, then stopped for one second. Then it repeated. Greatbatch had accidentally built a circuit that produced intermittent electrical impulses—the timing and rhythm of which perfectly matched a human heartbeat. Recognizing the extraordinary potential of his device, he began experimenting on ways to shrink the equipment and make it safe for implantation. With only $2,000 in savings, and a family to feed, Greatbach eventually left the University of Buffalo to work full-time on this research. His wife, Eleanor, was similarly devoted to his success. She patiently shock-tested hundreds of the pacemaker’s transistors by tapping them with pencils. After extensive testing, it was implanted in 10 human patients in 1960. Greatbatch’s prolific career as an inventor continued until his passing in September 2011 at the age of 92. His legacy lives on, in the hearts of more than 2 million people in the U.S. with a pacemaker.
Breaking the Blood-Brain Barrier
In 1987, Keith Black, MD, was enjoying a big reputation for his research on swelling in the brain, a common repercussion of strokes and brain tumors. The young physician had shown that leukotrienes—molecules found in white blood cells—contributed to such swelling, and that it could be prevented with drugs that block leukotriene formation. The discovery brought him international attention, National Institutes of Health funding, and a laboratory at UCLA. There was just one glitch: He couldn’t replicate his own research. Baffled, he finally figured out that he’d simply gotten better at injecting animal models with leukotrienes, no longer injuring the surface of their brains in the process. The molecules could penetrate damaged, but not normal, brain tissue. The implications were astounding: He had found the key to selectively opening the blood-brain barrier—the brain’s most important protection, which prevents anything water-soluble from percolating through. His discovery solved the biggest obstacle to targeting tumors with chemotherapy drugs. Dr. Black has continued this work at Cedars- Sinai, where he is chairman of the Department of Neurosurgery. In 2008, he showed that erectile-dysfunction drugs also allow chemotherapy drugs to better cross the blood-brain barrier.
From alarming headlines to monster microbes in movies, few things in medicine have captured the popular imagination like superbugs—bacteria that are resistant to antibiotics. One of the scariest examples is methicillin-resistant staphylococcus aureus (MRSA). George Liu, MD, launched a new era in treating MRSA after an intern accidentally left traces of bleach on a test tube. Dr. Liu noticed that the bacteria culture in it stopped growing— the bleach had stripped the culture of its gold-colored pigment. Recalling that MRSA contains the same pigment, he wondered if whatever destroyed the pigment in his test tube might also destroy it in MRSA. It did. The process that creates that pigment also creates cholesterol, so the next step was to test anti-cholesterol drugs against the staph. An intern’s mistake, coupled with a doctor’s curiosity, means we may finally have a weapon against one of the fastest-spreading bacterial strains around.
The fastest-selling drug in history was discovered without its makers knowing what it would be used for. In the small English town of Sandwich, Pfizer researchers were working on a drug they hoped would relax blood vessels. The objective was to find a treatment for angina, a painful condition in which the heart muscle does not receive enough blood and oxygen due to constricted coronary arteries, the heart’s blood vessels. Researchers tested some 1,500 compounds before they found the one they thought they were looking for. To their dismay, initial trials showed that the drug was ineffective. While Pfizer considered shelving the project, the doctor in charge pointed out a curious side effect: Many of the men participating in the trial reported penile erections. As it turns out, the drug did relax blood vessels—just not in the heart. Viagra® (sildenafil citrate) is today the standard pharmaceutical treatment for erectile dysfunction.