Serendipity effect

The subsequent advance was rather fortuitous and rested more with serendipity than with scientific logic. A search was made for cheaper more effective replacements for casein hydrolysate. Amongst the tested materials was com steep liquor (CSL). CSL is a by-product of the manufacture of starch from maize kemals. Whole maize is incubated in warm water, at 50°C acidified with SO2. Thermophilic bacteria hydrolyse proteins and other components of the kemals, thereby loosening the starch granules. These are removed, leaving behind the steep liquor which is used to treat further maize kemals. Ultimately, the liquor is too viscous to re-use and the liquor is concentrated and used as cattle feed. It was this material that was used for penicillin fermentation. Surprisingly, the yield of penicillin increased by a further 5-10 fold giving yields of 50-100 ig ml. 

Examples abound regarding the role of serendipity in the discovery of new therapeutic approaches, which on closer examination usually turned out to be the result of clinicians paying attention to unexpected clinical effects rather than discounting them. For example, lithium was tried first for hypertension, chlorpro-mazine was initially developed as an anesthetic, and imipramine was originally regarded as an antihistamine and an antipsychotic agent. Without astute clinical observations, these drugs would not have found their niche, nor would clozapine have been revived for the benefit of millions of the most difficult to treat schizophrenic patients. Other examples include the expanded indications of newer... 

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

In a classic case of serendipity, cisplatin (PLATINOL ), a key component of the combination therapy which revolutionised treatment of testicular cancer [ 1 ], was uncovered fortuitously in the 1960s during studies on the effect of an electric current on the growth of E. coli [ 17,18]. Cell division was inhibited not by the electric current but by production of a platinum complex from the... 

The discovery of unusual physical or chemical properties in multicomponent systems demands the isolation and chemical and physical characterization of the single component which is responsible for the observed effect. In many instances the resulting search is less than systematic and depends more on serendipity than on careful experimentation. As an example, many of the early attempts to discover the compound responsible for superconducting transition temperatures in the 90K range were sometimes haphazard when viewed in terms of synthetic techniques. 

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)... 

Two communications on propene polymerization by non-metallocene catalysts that include DFT/MM calculations have been recently published [60, 61]. They deal with group 4 bidentate non-cyclopentadienyl complexes. In the first communication [60], the topic addressed is the fact that a C2-symmetric precatalyst of titanium leads to a syndiotactic polymer, contrary to observations of metallocene catalysts. The chirality at the metal center is found to play a key role in the stereocontrol of the process. The second communication [61] addresses the fact that a C2-symmetric precatalyst of zirconium very similar to the previous one produces an isotactic polymer, finds out that it is due to a complicated concourse of synergic steric and electronic effects, and emphasizes the key role that serendipity still plays in the design of new catalysts. 

Serendipity occurs all the time in science. People like Fleming must be applauded. The famous discovery of penicillin by Fleming in 1928 is a well-known story. Fie noticed the effect of a mould killing bacteria. The derivatives of penicillin must be some of the greatest discoveries ever made in medical science. We now know that there are a series of penicillin derivatives based upon the structure shown in Figure 14.5. 

Paracetamol owes its development to serendipity. In 1888 a pharmacist in Vienna made a fateful error. In response to a request from two physicians for a chemical called naphthalene to treat a patient with a parasitic infection of the gut, he mistakenly gave them a chemical called acetanilide. This was found to be very effective at reducing the temperature of the patient due to the fever. Although it proved to be too toxic for large-scale use as a drug, this discovery eventually led to the development of paracetamol, a related chemical. 

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