The Role of Chemistry in History

Introduction to Quinine | Properties of Quinine | A brief History of Quinine | History affects Quinine | Quinine affects History | Quinine and Third World Countries | Undesired Effects of Quinine | Substitutes of Quinine | Conclusion

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Intro | Chemistry | Origin | Affects History | History affects  | Poor Countries | Undesired Effects  | Substitutes | Conclusion

Soldiers taking daily dose of quinine

Colonization:

• Without quinine, the colonization of many African and Asian countries would not have been possible.

• Malaria is very common in these areas and therefore European powers relied heavily on their supplies of quinine to keep them under control.

Gin and Tonic:

• Gin and Tonic was introduced by the Birtish East India Company in India, in the 18th century.

• Tonic water contains quinine and is used to prevent malaria.

• Because tonic water was very bitter, gin was added to make the water more palatable.

• This has become and still is a popular drink

Second World War:

• The discovery of the source of quinine, the Cinchona tree, has created very profitable commerce for countries like Bolivia, Ecuador, Peru and Colombia. They banned the export of the tree in order to monopolize the commerce.

• Species of the tree were eventually smuggled out. In 1861, the Dutch bought a pound of the species known as Cinchona Ledgeriana from an Australian trader named Charles Ledger.

• The species turned to be the most most productive with quinine level as high as 13% compared to the usual 3%. C. Ledgeriana was cultivated in Java.

• In 1940, the quinine molecule tipped the scale of the war as Germany attacked the Netherlands to confiscate the entire European stock of quinine.

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Intro | Chemistry | Sources | Affects History | History affects  | Poor Countries | Undesired Effects  | Substitutes | Conclusion

•  Natural Source: The Cinchona Tree
  • It was not generally known which plant Quinine came from.
  • In 1735, a French botanist discovered the source as Cinchona tree.
  • Harvesting the bark of Chinchona then became major industry.
  • High demand  and low supply drove prices up.
  • Isolating and identifying the molecule became a big research field.

“High in the Andes, between three thousand and nine thousand feet above sea level, there grows a tree whose bark contains an alkaloid molecule, without which the world would be a very different place today”.

Napoleon’s Buttons: P.332

• Synthetic Makeup:

“No matter how much the evidence points to the correctness of a proposed structure, to be absolutely sure it is correct, you have to synthesize the molecule by an independent route”.

Napoleon’s Buttons: P.340

• • Quinine is belived to be first  isolated in 1792, maybe in its impure form.
  • In 1820, French researchers Joseph Pelletier and Joseph Caventou identified and purified quinine.
  • Structure of quinine not fully understood until 2oth century.
  • First attempts to synthetize were unsuccessful.
  • In 1856, English chemist William Perkin combined allyltoluidine with 3 oxygens to make quinine.
  • He thought: 2C₁₀H₁₃N + 3O = C₂₀H₂₄N₂O₂ + H₂O.
  • Instead, he made “mauve” and a lot of “money”.
  • In 1944 Robert Woodward and William Doering of Harvard presumably completed the synthesis of quinine.
  • They were able to convert a quinoline derivative into a molecule that, allegedely, was successfully transformed into quinine in 1918.
  • The report about this earlier work, however, could not be ascertained.
  • Finally, in 2001, Gilbert Stork from Columbia University and coworkers were able to synthesize quinine by going through all the steps themselves

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Intro | Chemistry | Sources | Affects History | History affects  | Poor Countries | Undesired Effects  | Substitutes | Conclusion

Malaria, which comes from the Italian mal aria meaning bad air, is a disease caused by a microscopic parasite transmitted from one patient to another by the anopheles mosquito. References to this disease can be found in written records of China, India and Egypt dating from as far back as thousands of years.  Believed to be perhaps the greatest killer of humanity of all time, malaria remains a big concern especially in third world countries where it claims millions of lives every year. The first effective treatment against this disease is quinine, a natural white crystalline alkaloid extracted from the cinchona bark. Thanks to its medicinal properties, quinine has saved millions of lives and has had a tremendous impact on the history of the world as we know it.

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Introduction to Paclitaxel | From Tree to Taxol | Paclitaxel and Cancer Treatment | Inside Paclitaxel: Physical Characteristics | Paclitaxel: Effective or Too Costly? | Paclitaxel’s Affect on History | History’s Affect on Paclitaxel | References

Cragg, G.M. et al. (1993). ‘The taxol supply crisis: New NCI policies for handling the large-scale production of novel natural product anticancer and anti-HIV agents.’ Journal of Natural Products 56, 1657-1668.

Gentry, H.S. & Hadley, Diana. (1995). ‘Listening to my mind’: Howard Scott Gentry’s recollections of the Rio Mayo Journal of the Southwest, 37, 178-245.

Goodman, J. & Walsh, V. (2001). The story of taxol: Nature and politics in the pursuit of an anti-cancer drug. Cambridge, UK: Cambridge University Press.

Horwitz, S.B. (1994). ‘How to make taxol from scratch.’ Nature, 367, 593-594.

Horwitz, S.B. & Horwitz, M.S. (1973). ‘Effects of camptothecin on the breakage and repair of DNA during the cell cycle.’ Cancer Research, 33, 2834-2836.

Horwitz, S.B. et al. (1982). ‘Taxol: A new probe for studying the structure and function of microtubules.’ Cold Spring Harbor Symposium on Quantitative Biology, 46, 219-226.

Kingston, D.G.I. (1995). ‘History and chemistry.’ In McGuire & Rowinsky Paclitaxel in cancer treatment. New York, NY: Marcel Dekker, Incorporated.

Kinghorn, A.D. & Balandrin, M.F. (Eds.). (1993). Human medical agents from plants. Washington, DC: American Chemical Society.

Kumar, N. (1981). ‘Taxol-induced polymerization of purified tubulin.’ Journal of Biological Chemistry 256, no. 20, 10435-10441. 

McGuire, W.P. & Rowinsky, E.K. (Ed.). (1995). Paclitaxel in cancer treatment. New York, NY: Marcel Dekker, Incorporated.

Nicolaou, K.C., Dai, W.-M. & Guy, R.K. (1994). Chemistry and biology of taxol. Angewandte Chemie International Edition English, 33, 15-44.

Ringel, Israel. (1995). ‘Molecular mechanisms.’ In McGuire & Rowinsky Paclitaxel in cancer treatment. New York, NY: Marcel Dekker, Incorporated.

Suffness, M. (Ed.). (1995). Taxol: Science and applications. New York, NY: CRC Press.

Suffness, M. & Wall, M.E. (1995). Discovery and development of taxol. In Suffness, M. (Ed.), Taxol: science and applications. Boca Raton, FL: CRC Press, 3-25.

Wani, M.C. et al. (1971). ‘Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia.’ Journal of the American Chemical Society, 93, 2325-2327.

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Introduction to Paclitaxel | From Tree to Taxol | Paclitaxel and Cancer Treatment | Inside Paclitaxel: Physical Characteristics | Paclitaxel: Effective or Too Costly? | Paclitaxel’s Affect on History | History’s Affect on Paclitaxel | References

Paclitaxel’s development might be seen as a microcosm of external historical events and ideologies that have affected not only the biochemical world but history in general. For instance, paclitaxel’s development came during a period of increased fervor in finding a cure for cancer, an incredibly important field that continues today. Moreover, environmentalists, developing from the 1970s in particular, became more aware of different man-made impacts on the environment, notwithstanding paclitaxel’s synthesis. Thus, one sees the impact that external ideologies and events may have on the cancer treatment world, a top-down effect. Finally, serendipity, an undefinable but significant role in the production of many drugs throghout history, has also affected paclitaxel. Paclitaxel, a result of a wide-ranging look for cancer treatments through plants, came realtively out-of-nowhere, when the botanist Arthur S. Barclay discovered taxol in 1962. Through these devlopments outside of paclitaxel, one sees that history has affected paclitaxel most likely more than paclitaxel has affected history, a comment on the power of external ideas and events over internal ideas such as paclitaxel’s unique history.

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Introduction to Paclitaxel | From Tree to Taxol | Paclitaxel and Cancer Treatment | Inside Paclitaxel: Physical Characteristics | Paclitaxel: Effective or Too Costly? | Paclitaxel’s Affect on History | History’s Affect on Paclitaxel | References

Paclitaxel is a remarkably controversial, yet effective drug for fighting the mitotic processes in cancer cells. As such, paclitaxel has affected the direction of cancer research due to its relatively high success rate, particularly with ovarian cancer. Moreover, history has shown that paclitaxel’s very means of discovery was fraught with ecological concerns, associated with its success, as well as institutional and political problems. The effectiveness of paclitaxel may represent its crux as well: the success of the molecule has spurred competing chemists into a battle over the rights to the cancer treatment, one that has often involved serious legal and governmental legislation. Taxol is also used in other procedures, such as in vitro fertilization, used to affect the cell microtubules.

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Introduction to Paclitaxel | From Tree to Taxol | Paclitaxel and Cancer Treatment | Inside Paclitaxel: Physical Characteristics | Paclitaxel: Effective or Too Costly? | Paclitaxel’s Affect on History | History’s Affect on Paclitaxel | References

Paclitaxel has always been the center of attention between scientists and researchers looking for a viable solution/drug for certain types of cancers, however, the drug has also been the center of attention for evironmentalists (and rightly so) for its ecological affects on the pacific yew tree populatioon of the Pacific Northwest. During phase II trials, an abudence of bark samples were needed to work on the synthesis of the cancer treating drug: an alarm bell for environmentalists to commence fighting against scientists and researchers, appealing to the government to limit the use of tree bark in paclitaxel’s synthesis.

Currently, pacltaxel is devloped through an improved method of plant cell fermentation which limits the amount of energy used and retain the effectiveness of the drug produced. This is a result of environmentalists demanding a resolution from the government in 1993, making the production of paclitaxel more ecologically-friendly in its nature.

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Introduction to Paclitaxel | From Tree to Taxol | Paclitaxel and Cancer Treatment | Inside Paclitaxel: Physical Characteristics | Paclitaxel: Effective or Too Costly? | Paclitaxel’s Affect on History | History’s Affect on Paclitaxel | References

• Paclitaxel works to inhibit mitosis in quickly multiplying cells in the body (cancer cells in particular).

• Upon injection of the drug, paclitaxel interfers with the beta subunit of tubulin, an important part of the microtubule that facilitates cell division and construction.

• Moreover, when paclitaxel bonds with this specifc part of the microtubules, the cell goes through characteristics that are irregular and affect the division of the cell in mitosis.

• Once mitosis is started, the microtubules position themselves for division and seperation into the emerging ‘new’ cell; however, the paclitaxel has already bonded to the microtubule and created a surpluss of microtubules (in contrast to other mitotic inhibitors that attach to tubulin and disassemble the microtubules), and thus, the cell undergoes apoptosis (cell death).

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Introduction to Paclitaxel | From Tree to Taxol | Paclitaxel and Cancer Treatment | Inside Paclitaxel: Physical Characteristics | Paclitaxel: Effective or Too Costly? | Paclitaxel’s Affect on History | History’s Affect on Paclitaxel | References

In 1979, Susan B. Horwitz’s publication on the true intermoleculear features of taxol, including the mitotic inhibition caused by the molecule upon injection, created a new interest in the molecule. The 80’s produced the first phases of efforts to analyze the affects of paclitaxel as a cancer treatment, which began preliminary trials in 1984. By 1988, phase II trials were underway, meaning an inceases in the amount of pacific yew tree bark needed to synthesize the molecule.

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