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The science of serendipity

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In the age of computer-aided drug design, many believe accidental discoveries in the natural sciences and medicine are a thing of the past. However, and fortunately, that is not the case.

Dr. Klaus Duffner | Germany

Even now random observations and unforeseen failures open up completely new paths to groundbreaking innovations. For such unintentional discoveries, the scientific world has a special term: "serendipity". The word is derived from an oriental fairy tale. On their adventurous travels three Princes of Serendip – an old name for Sri Lanka – constantly made discoveries they had not been looking for. However, serendipity goes beyond pure coincidence, since only those who recognize an opportunity can turn surprises into discoveries. The following scientists worked in their fields for years and were, therefore, able to consider the value of happenstance. Their particulary talent was the ability to recognize serendipity and capitalize on it.

X-rays – a strange glow
A single event can be decisive, and a number of momentous discoveries can be pinned to a certain date or even time of day. Such was the case with physicist Wilhelm Conrad Röntgen, who on the evening of 8 November 1895, was conducting an experiment with a Crookes tube (a vacuum tube in which cathode rays propagate in a straight line without a magnetic field) at the University of Würzburg, Germany. When he applied voltage, a fluorescent paper that happened to be lying around in the darkened room suddenly began to glow. Röntgen tried to prevent the disturbing glow with black cardboard – in vain. Soon he realized that certain materials, such as bone and metal, were less permeable to this "X radiation," and lead blocked it completely. Using a photo plate mounted behind his wife’s hand, he was able to depict her internal tissues tissues – one of the first x-ray images ever taken. The accidental discovery and, later, thorough study of X-rays earned Röntgen the Nobel Prize for Physics in 1901.

Penicillin – lid forgotten
The research of the Scottish bacteriologist Alexander Flemming was marked by his experiences during World War I. More soldiers had died in the trenches from wound infections than from combat injuries. The breakthrough search for a cure was due to a coincidence. When Fleming left for the summer holidays in August 1928, he forgot to close the lid on his staphylococci Petri dishes. When he returned to his laboratory at St Mary’s Hospital in London on 28 September, he noticed that mold had grown in one of the dishes. But wherever the fungus had come into contact with the staphylococci, the bacteria had disappeared. Flemming cultivated the fungus and found that it was secreting an antibacterial poison. However, more than a decade elapsed before this poison, later known as penicillin, could be produced in large enough quantities to be used as an antibiotic. Flemming, who together with two other bacteriologists received the Nobel Prize in 1946, remained modest throughout his life. Asked about his great discovery, he said: "Nature created it. I just stumbled upon it."

Genetic fingerprint – runs in the family
On 10 September 1984 in his laboratory at Leicester University in Great Britain, biochemist Alec John Jeffreys was continuing his research on what is known as mini-satellite DNA. Mini-satellites are sections in the human genome that consist of variable repetitions of a short DNA sequence. Jeffreys examined blood samples from several members of the same family, side by side. He noted that the mini-satellite DNA images could be individually assigned to each person like a barcode. Family relations could also be seen – the more agreement, the closer the relationship. Jeffreys immediately recognized the importance of his discovery. He had found what we now call the genetic fingerprint. Today it is impossible to imagine criminal investigations, as well as paternity tests, without the genetic fingerprint of DNA profiles.

PDE-5 inhibitors – unexpected side effects
In 1989 two British researchers Peter Ellis and Nick Terret were looking for a drug to prevent heart attacks and other cardiovascular disorders. They were focusing on the active substance and vasodilator sildenafil. After two years of study sildenafil’s efficacy for coronary disease could still not be proved, but the drug had an unexpected side effect: Male participants had more erections, and the erections persisted. Sildenafil had inhibited the enzyme phosphodiesterase-5 (PDE-5), and the concentration of the secondary messenger substance cGMP in the erectile tissue of the penis remained high, which in turn led to dilation of the vessels and produced unexpected and durable erections. One of the most common causes of erectile dysfunction to date, namely constricted blood vessels and insufficient blood supply to the penis, could now be treated pharmaceutically.

Today the accidentally discovered side effect has made PDE-5 inhibitors one of the world’s most widely used drugs.

Hemangioma – suddenly shrinking
The bright red, rubbery birthmark on the nose of the newborn had grown rapidly and was already beginning to press on the baby’s trachea. Hemangioma is a nodule of extra blood vessels in the skin, and although in 2007 pediatrician Christine Léauté- Labrèze from the University Hospital in Bordeaux had started treatment with systemic corticosteroids, the treatment had not been successful. Instead, at the age of three months the baby also developed a serious heart muscle disorder, so therapy with the beta-blocker propranolol was initiated. Just a few days later something completely unexpected happened: The conspicuous growth changed color from red to purple and became softer. Within a few weeks it began to shrink. When the beta-blocker was discontinued at 14 months, the hemangioma had almost completely disappeared.

Nine more children with problematic facial hemangiomata were soon cured in the same manner. For doctors, for parents and above all for thousands of children, this random observation from southern France has been one thing above all: a great stroke of good fortune.

Giant viruses – stuck in the bacterial sieve
In 2003 at a British clinic Didier Raoult from the Université de la Méditerranée in Marseille was not searching for viruses but for a special type of bacteria: legionellae. When Raoult examined the contents of a bacteria filter more closely, he discovered previously unknown giant viruses, and they were to turn some existing ideas about viruses upside down. With a length of 0.4 μm and containing about 900 genes, they were not only considerably larger than all known viruses, and larger than many bacteria as well, but also a kind of hybrid organism that included the ability to produce proteins. Such giant micro-organisms had already been seen by researchers in the 1990s, but they had been thought to be new bacterial species. Didier Raoult not only found the organisms but also identified them as megaviruses. Since then an entire spectrum of even larger virus giants has been described. Their study indicates that the line between viruses and bacteria, between lifeless and alive, is now fluid. A completely new chapter of virology was started, by chance.

Dr. Klaus Duffner

Dr. Klaus Duffner | Germany

Scientific Journalist
Medizin & Wissen Freiburg

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