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2017年09月05日 临床话题, 基本知识 暂无评论

12 Key Accidental Discoveries in Medicine

Steven Rourke | August 8, 2017 | Contributor Information 

The path to medical discovery tends to follow a scenic route, one that takes unforeseen twists and turns to arrive at surprising destinations, well off the beaten track. In the following slides, we explore some of science's most unlikely findings and celebrate the scientists whose brilliant minds, sense of intellectual adventure, and keen powers of observation helped change the course of medicine.

Images from Wikimedia

Protozoa and Bacteria (1676): Antony van Leeuwenhoek

Contribution: Helped lay the foundations for bacteriology and protozoology

"These little animals to my eye were more than ten thousand times smaller than…the water flea or water-louse, which you can see alive and moving in water with the bare eye." 

—Letter 18, sent to the Royal Society of London for Improving Natural Knowledge in 1676 [1]

Antony van Leeuwenhoek (1632-1723), originally a trader of fabric during the Dutch Golden Age, is considered one of the founders of bacteriology and protozoology for the discoveries he made using his extraordinarily powerful homemade microscopes. [1-3] He may have originally built microscopes to examine the quality of cloth, [2] but they also allowed him to satisfy his abundant curiosity [3] by providing the means to examine a jolly combination of commonplace substances, including stagnant rain water, "hog's tongue," fleas, dung, and semen. [1,2]At a time of remarkable discovery and trade, his experiments were apparently originally motivated in part by the desire to discover what made peppercorns hot.

Van Leeuwenhoek seems to have come close to understanding the role of bacteria in disease and the process of heat pasteurization—both while examining the plaque from his teeth. He described "round" (cocci), "rod-shaped" (bacilli), and "spiral-shaped" (spirochetes) bacteria [2] and corresponded with the Royal Society in London for over 50 years. [1,3]

Images from iStock; Wikimedia (inset of Davy)

Nitrous Oxide (1799): Humphry Davy

Contribution: Provided a basis for the eventual uptake of anesthesia in surgery

"The pleasurable sensation was at first local, and received in the lips, and about the cheeks. It gradually, however, diffused itself over the whole body, and in the middle of the experiment, was as intense and pure as to absorb existence." 

—Humphry Davy [4]

By all accounts, Humphry Davy (1778-1829) was a brilliant, original-minded researcher of humble origins who apprenticed with a surgeon-apothecary and, through his remarkable intelligence and self-promotional savvy, became president of Britain's Royal Society [5] and one of the most celebrated scientists in the early 1800s. [1,4-7]

While a young researcher, Davy isolated several gases, including nitrous oxide. Later, as the superintendent of experiments at the Pneumatic Society of Bristol, [4] he hoped these might provide treatment for consumption. [5] He conducted exhaustive, meticulously documented "self-experiments," which earned him the respect of the scientific establishment, a wide following, famous friends, and fortune. [1,4] Apparently on the basis of how nitrous oxide relieved the pain in his gums, Davy predicted that it would become an anesthesia for surgery—though it took a further 50 years for his prediction to come true. [1,4] Davy was also a pioneer in electrochemistry; discovered magnesium, calcium, strontium, and barium; and invented the Davy lamp for miners. [6]

Images from iStock; Wikimedia (inset of Jenner)

Vaccination (1796): Edward Jenner

Contribution: Helped create the theory and practice of vaccination, leading to the eradication of smallpox in 1980

"Thank God, I cannot take it, for I have had cowpox."

—Milkmaid in England, late 1700s [2]

Folklore in the English countryside at the end of the 18th century held that those who had been sick with cowpox did not contract smallpox, one of the prevalent diseases of the time, which was fatal in up to 40% of cases. [2]

Alongside other, well-known scientific pursuits—which included the study of cuckoos, [1,2] angina pectoris and heart attacks, [1] and paleontology and geology [1]—the country doctor Edward Jenner (1749-1823) was keenly interested in establishing the connection between these two diseases and paid close heed to country beliefs. He was not the first scientist to be aware of the connection between cowpox and smallpox. [8-10] Preventive immunization against smallpox was described in Ming Dynasty China, [2] India, [1] and Africa, [8] and variolation was practiced in the Ottoman Empire. [2] However, through his painstaking scientific rigor, Jenner is credited with creating the first vaccine and with laying the foundations for immunology. [1,2,8-10]

To create his rudimentary smallpox vaccine, Jenner collected fluid from the cowpox sore on the hand of a milkmaid and, through a superficial incision, applied it into the arm of an 8-year-old boy. After 6 weeks, he inoculated the boy with the smallpox virus, which failed to produce a reaction, hence showing immunity. [2]

Images from iStock; Wikimedia (inset of Koch)

Selective Culturing of Bacteria (1881): Robert Koch

Contribution: Helped establish bacteriology as a scientific discipline and led to the identification of the bacterial causes of many diseases

The chance discovery of different-colored growths on a slice of potato left in the lab—subsequently identified as different colonies of bacteria—led Robert Koch (1843-1910) to create a revolutionary method to selectively culture bacteria. [1,2] Until this point, bacteria had been studied in liquid "broths," in which it was impossible to isolate bacteria. Koch proposed the use of a solid growth medium—inspired by the famous potato but derived from seaweed, and contained within a shallow jar that was designed by his colleague, the famous Julius Petri—as the new vehicle in which to isolate, study, and identify bacteria. [1,2]

Alongside his contemporary Louis Pasteur, Robert Koch was one of the brightest minds of 19th-century science whose influential work also contributed significantly to the germ theory of disease and the identification of the pathogens that cause anthrax, typhoid, meningitis, leprosy, tetanus, syphilis, and tuberculosis—for which he won the Nobel Prize in 1905. [1,2,4,11-13]

Images from iStock; Wikimedia (inset of Roentgen)

The "X-ray" (1895): Wilhelm Roentgen

Contribution: Established new paradigms in diagnosis and treatment while creating new research disciplines and revolutionizing physics and medicine

"I didn't think, I investigated."

—Wilhelm Roentgen [14]

In this famous slice of scientific lore, the physicist Wilhelm Roentgen (1845-1923) noticed a mysterious green glow when experimenting on cathode rays in a vacuum tube in the presence of a rudimentary photosensitive plate. [4,15] Roentgen subsequently noted the penetrative properties of the "x-rays," a previously unknown type of radiation. [16] The well-known photo that illustrates his article reveals the bones of his wife's hand. [1,4]

Roentgen's discovery had wide-ranging consequences for several disciplines [1,2,4,14-16] and earned Roentgen the 1901 Nobel Prize in Physics. [16] For the first time in history, it became possible to view the inside of the body without conducting surgery.

The harmful effects of exposure to "x-rays" were discovered shortly thereafter.

Images from iStock; Wikimedia (inset of Fleming)

Penicillin (1928): Alexander Fleming

Contribution: Provided effective treatment for bacterial infections and ushered in the age of antibiotics [1,2,4,17]

The discovery of the antibiotic properties of penicillin is the stuff of sometimes disputed [2] medical mythology—a tale that brings together a chain of chance occurrences or fortuitous coincidences, like the plot of an improbable novel.

After a 2-week vacation, Alexander Fleming (1881-1955) observed that Staphylococcus aureus had thrived in a petri dish that had been left at room temperature—except in areas that had been contaminated, totally by chance, by airborne spores of Penicillium[1,2,4] In subsequent experiments, Fleming noted that Penicillium notatum not only controlled bacterial growth, but also killed the bacteria, which was not the case with other species of penicillium. [1,2]

Once he had published his findings, Fleming set them aside. It took the subsequent research of Ernst Chain and Howard Florey to realize the full potential of penicillin. All three shared the Nobel Prize in Physiology or Medicine in 1945 for "for the discovery of penicillin and its curative effect in various infectious diseases." [18] Penicillin went into large-scale pharmaceutical production in the 1940s. [19]

Image from Science Source; Wikimedia (inset of Minkowski and Mering)

The Pancreas/Diabetes Connection (1889): Oskar Minkowski and Joseph von Mering

Contribution: Paved the way for the discovery of insulin and the management of diabetes

A discovery frequently hinges on the accidental meeting of the right minds, as was the case when Oskar Minkowski (1858-1931) and Joseph von Mering (1849-1908) crossed paths in the library at the University of Strasbourg in 1889. It was a chance meeting in which the discussion of pancreatic enzymes ultimately led to the establishment of the role of the pancreas in diabetes. [4,20-22]

After surgical removal of a dog's pancreas—a procedure undertaken by Minkowski to test one of von Mering's hypotheses and one considered impossible at the time [23]—the team noted the dog's thirst and its copious, sugary (glucose-loaded) urine. [4,23] They subsequently showed that hyperglycemia could be prevented in a depancreatized dog by subcutaneous implantation of a section of pancreas, and identified the role of the pancreas in maintaining glucose homeostasis. [20]

Images from Science Source; University of Wisconsin-Madison Archives (inset)

Warfarin (1940): Karl Paul Link and Mark Arnold Stahmann

Contribution: Formed the basis for widespread use of oral anticoagulants to prevent clotting

The discovery of warfarin was the result of a chain of events, starting with the serendipitous meeting in 1933 of a Wisconsin farmer—who was seeking an explanation for why his cows were hemorrhaging to death—and a young agricultural chemist at the Experiment Station at University of Wisconsin in Madison, Karl Paul Link (1901-1978). It also relied on the low-key tenacity of another influential biochemical researcher, Mark Arnold Stahmann (1914-2000). [2,4,24,25]

Link discovered that coumarin—present in the cows' spoiled sweet clover feed—caused bleeding and, after 7 years of study, proposed that the spoiling process transforms coumarin into dicumarol, which in turn interferes with the clotting properties of vitamin K. [2] Link, working alongside his lab manager Mark Arnold Stahmann, synthesized several coumarin variants[2,4]—though he rejected one analogue of dicumarol, which he considered too potent for human use. [24]

Warfarin—named after the Wisconsin Alumni Research Foundation, [26] and patented by Stahmann [24]—was instead marketed as rat poison. Highly potent, and with a delayed onset of action, it was found to be safe for human use after the total recovery of a young Navy recruit who had attempted suicide by ingesting it. [2,4]

Warfarin, marketed as Coumadin, is taken daily by approximately 2 million Americans to prevent clotting events. [2] Although heparin and streptokinase were discovered earlier, [2] it was arguably warfarin that launched the era of oral anticoagulants.

Images from Dreamstime; Ridley Eye Foundation (inset of Ridley)

Intraocular Lens (1949): Harold Ridley

Contribution: Provided a technique to prevent one of the chief causes of blindness

As an ophthalmology surgeon during World War II, Dr Nicholas Harold Lloyd Ridley (1906-2001) examined the eyes of a Royal Air Force pilot, Gordon Cleaver, which had been damaged by plastic shards. In follow-up examinations, Ridley noticed that the pilot's eyes had not reacted adversely to the presence of the plastic. [4] Armed with this observation and years of subsequent research, in 1949, during cataract surgery, Ridley replaced a (consenting) patient's cataract by an implanted plastic lens, in what was considered a highly controversial and daring operation. The success of the procedure paved the way to vastly improved outcomes in cataract surgery. [4,27,28]

Although it was initially angrily disputed, cataract surgery with intraocular lens implantation has been performed millions of times worldwide and has transformed the care of eyes and the practice of ophthalmology. [27-29]

Images from iStock; Wikimedia (inset of Sternbach)

Benzodiazepines (1959): Leo Sternbach

Contribution: Created an effective class of drugs with antianxiety and relaxing properties

The chemist Leo Sternbach's (1908-2005) decision to reinvestigate tricyclic compounds that he had isolated during his study of dyestuffs [2] at the University of Krakow on the eve of World War II ultimately led to the discovery of the benzodiazepine class of drugs, including diazepam (Valium). [2,4]

In the 1950s, at his lab at Hoffman-LaRoche in New Jersey, Sternbach and his team studied tens of compounds, which all turned out to be biologically inactive. However, in a theatrical twist of fate, one sample—which had kicked around the lab without complete testing and was saved from destruction at the last minute—turned out to have extraordinary tranquilizing characteristics. The drug chlordiazepoxide (Librium)—and a whole new class of drugs, the benzodiazepines—came into being. [2,4,30] Diazepam followed in 1963. [2,4,30] It was the most prescribed drug in the United States from 1969 to 1982, [31] with peak annual sales of $600 million. [4] Approximately 30 benzodiazepines—prescribed for anxiety, muscle relaxation, sleep disorders, anesthesia, and epilepsy—are currently in use around the world.

After an illustrious research career that included 241 patents, Sternbach was named one of the most influential Americans in the 20th century by US News & World Report. [31]

Images from Science Source; Radiological Society of North America (inset of Dotter)

Percutaneous Transluminal Angioplasty (1963): Charles Dotter

Contribution: Formed the basis of interventional radiology

Radiologist Charles Dotter (1920-1985) was a giant of 20th-century medicine, considered by many to be the "father" of interventional radiology. [32,33] In 1963, he pioneered the "dottering" technique, based on his observations from an accident during a diagnostic catheter study: When he jammed his catheter through an arterial obstruction, he found that he had dislodged the blockage. [2,32]

Percutaneous transluminal angioplasty was perhaps Dotter's most important contribution to medicine; however, he also created several other interventional techniques, including flow-directed balloon catheterization, the double-lumen balloon catheter, the safety guidewire, the concepts of percutaneous arterial stenting, and stent grafting—to name only a few. [32,33]

In creating interventional radiology, Dotter paved the way for Andreas Gruentzig's work in coronary angioplasty and the growth of interventional cardiovascular techniques. [2,32,33]

Images from iStock; Wikimedia (inset of Marshall and Warren)

Helicobacter pylori in Gastritis and Peptic Ulcer Disease (1982): Barry Marshall and Robin Warren

Contribution: Revolutionized the diagnosis and treatment of gastritis and peptic ulcer disease while identifying one of the most prevalent bacterial infections in the world

"I happened to be there at the right time."

—Robin Warren [2]

The identification of Helicobacter pylori and its role in peptic ulcer disease relied on an improbable chain of incidents—most important, the chance meeting of compatible minds, and agar plates left to incubate for much longer than intended. [2,4]

Despite vocal, quasi-universal disbelief in their "outrageous" theory, Barry Marshall (b. 1951) and Robin Warren (b. 1937), working together at the University of Western Australia in Perth, showed that one of the most common causes of gastric ulcers was an unknown bacterium. The bacterium, which the team had originally thought to be part of the genus Campylobacter, was eventually identified—thanks to an inadvertently extended incubation period over a long holiday weekend—to be an entirely new genus. [2,4]

Marshall and Warren showed that Helicobacter pylori is a cause of gastric ulcers and that it can be successfully treated with antibiotics. Their discovery flew in the face of accepted medical knowledge and earned them the Nobel Prize in Physiology or Medicine in 2005. [2,4,34]

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