Chance, discoveries

The immense importance of Si in transistor technology stems from the chance discovery of the effect in Ge at Bell Telephone Laboratories, New Jersey, in 1947, and the brilliant theoretical and practical development of the device by J. Bardeen, W. H. Brattain and W. Shockley for which they were awarded the 1956 Nobel Prize for Physics. A brief description of the physics and chemistry underlying transistor action in Si is given in the Panel (p. 332). 

It is interesting to note that one of the founders of modern psychiatry, Kraepelin, listed only nine substances that were available for the treatment of psychiatric illness in the 1890s. These were opium, morphine, scopolamine, hashish, chloral hydrate, a barbiturate, alcohol, chloroform and various bromides. Later Bleuler, another founder of modern psychiatry, added paraldehyde and sodium barbitone to the list. Thus psychopharmacology is a very recent area of medicine which largely arose from the chance discovery of chlorpromazine by Delay and Deniker in France in 1952, and of imipramine by Kuhn in Switzerland in 1957. 

The first inhibitors of flavin-dependent MAO that were developed for clinical use were hydrazines and hydrazides. The chance discovery that the antitubercular drug, 4-pyridine carboxylic acid hydrazide (isoniazid, 40), was also a potent MAO inhibitor led to the development of the related drug, iproniazid (41), used for the treatment of depressive illness. Although this compound demonstrated remarkable antidepressant action, its clinical value was seriously compromised by side effects [19]. 

The antidepressant properties of these earlier antidepressants were chance discoveries. Imipramine was first developed as a potential antipsychotic, but when Kuhn (2) tested the clinical efficacy of this agent, he found that it only benefited depressed schizophrenic patients. This observation prompted him to test it in patients who were suffering from melancholia. Iproniazid was developed as an antitubercular drug, but the observation that euphoria was a side effect led George Crane ( 3) to conduct clinical trials, which found it useful in purely depressed patients. A year later, Nathan Kline ( 4), following up on this observation, reported positive results when he administered iproniazid to another depressed group. 

For many years, cosmochemistry depended on the chance discovery of meteorites - either witnessed falls and serendipitous finds, or the dogged determination of a few private collectors who systematically searched for them. That changed in 1969, when Japanese explorers in Antarctica led by Masaru Yoshida stumbled onto meteorites exposed on bare ice. American geologist William Cassidy immediately recognized an opportunity, and with support from the National Science Foundation he mounted a joint expedition with the Japanese to the Allan Hills region of Antarctica in 1977 to recover meteorites. This was the first of many expeditions, sponsored by the National Science Foundation and headed first by Cassidy and later by Ralph Harvey, that have returned to Antarctica every year to collect meteorites (Fig. 1.11). The Japanese have operated a parallel field program in... 

Serendipity—or chance discovery—is the scientist s best friend. The mentally prepared scientist, that is. As Louis Pasteur wisely stated, In the field of observation, chance favors the prepared mind. Of course, entrepreneurial opportunism plays its part in this story, too, because the pharmaceutical companies that held the rights to these agents were able to mobilize both the clinical trials needed to demonstrate efficacy and the marketing machinery to make the drugs widely available. 

The Swiss biochemist Albert Hofmann discovered the hallucinogenic effects of LSD-25 by accident when he was working to synthesize molecules akin to ergota-mine for the treatment of peripheral autonomic dysfunction. In a rush of what scientists call serendipity (or chance discovery) Hofmann realized that he had stumbled upon a far more important effect LSD acted in the brain itself, altering its chemistry in the direction of psychosis and of dreaming. Descriptions of these effects upon his mind are given in the text. (Courtesy of the Albert Hofmann Foundation)... 

Fascinating stories illustrating how many scientific advances are made by chance discovery when an investigator is keen enough to recognize the significance of the discovery. 

What role did chance discovery play in the history of polymers Cite some examples. 

As with any scientific endeavor, chance discovery played an important role in the development of polymers. In all cases, however, there was a scientist with an open and innovative mind who was ready to recognize and take advantage of a chance observation. Charles Goodyear accidentally tipped sulfur into heated natural rubber to discover vulcanized rubber. Christian Schobein inadvertently wiped up a nitric acid spill with a cotton rag to discover nitrocellulose. Jaques Brandenberger thought of cellophane as he observed the accidental stains on tablecloths. Also, as was discussed in Chapter 1, Teflon was discovered upon the unexpected disappearance of a chemical in a gas cylinder that Roy Plunkett was compelled to saw in half. 

In the early days of automated synthesis there was a fear amongst researchers that it would reduce the chances of serendipity. However, experience has now shown that, when used in sensible way, the, automation of the design, synthesis and test cycle can increase significantly the odds of chance discoveries of new compound that have attractive properties to the company in unforeseen ways. 

In complete contrast to the chance discovery of lindane, Muller s discovery of the insecticidal activity of DDT in 1939 was the culmination of a more or less rational application of experience and intuition in the development and improvement of existing moth-proofing agents based on chlorinated benzenes. 

The protocol leading to the unsaturated 1,1 -hydroxy-binaphthyl saturated NHC was a chance discovery, enabled by an aqueous workup procedure. The yield is only moderate (40%) and has to be separated from the main product, the targeted bis-imidazolium salt (51%). A better synthesis for this ligand might be desirable, although the saturated NHC equivalent is readily available [18,86,88,89]. 

Topic Chance Discoveries Sci Links code HW4139... 

Chance discoveries Sometimes, when a scientist plans research with a specific goal in mind, he or she will conduct experiments and reach a conclusion that is expected. Sometimes, however, the conclusion reached is far different from what was expected. Some truly wonderful discoveries in science have been made unexpectedly. 

Even in today s more rational drug discovery environment, it may be said that serendipity is one of the medicinal chemist s best friends. Of course, serendipity alone cannot provide a drug it requires someone to recognize the opportunity and capitalize on it. As demonstrated by Sternbach and his colleagues, when chance discoveries fall into the hands of open-minded and persistent scientists, the results can be remarkable. 

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