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Birth of Tamoxifen

In 1896, the then famous cancer surgeon Dr. George Beatson found that he could extend the lives of women with breast cancer by surgically removing their ovaries - a major oestrogen source. This finding revealed the clue that oestrogen was involved in the growth and development of breast cancer. Over the next five decades, researchers experimented with a variety of oestrogen-like chemicals to treat breast cancer. But the side-effects of these chemicals were too severe for widespread use. By the mid 1960s, the researchers almost completely lost their interest in this concept.

In the current era, researchers at ICI (now AstraZeneca) in the UK were investigating the effects of various oestrogen-like chemicals on animals with the aim of finding new contraceptives as part of the company's contraceptive research programme. Tamoxifen was synthesized in 1962, but its promising results in animal studies were not supported in humans, where the drug boosted fertility, rather than the reverse. It was in fact an oestrogen antagonist and was considered a useless drug. However, the biologist Arthur Walpole the one who synthesized tamoxifen thought that it could be useful in testing oestrogen-sensitive breast cancer and having the oncologist Mary Cole as a partner in the Christie hospital in Manchester, UK, they started testing tamoxifen in 46 women with metastatic breast cancer in 1969. They found significant improvement in 10 patients with a tangible reduction in tumor volume and lung metastases. Importantly, the treatment had a very low incidence of side-effects compared to standard therapy of that time. In 1973, Craig Jordan in Massachusetts, US showed that the tumors with positive oestrogen receptors were responding to this new drug. Tamoxifen was first approved for the treatment of postmenopausal women with metastatic breast cancer in 1973 in the UK and in the US in 1977. ICI pharmaceuticals Division in 1978 received the Queen's Award for technological achievement because tamoxifen was the first antiestrogen developed for the treatment of advanced breast cancer. Later, tamoxifen was also found to prevent breast cancer.

Sources:

Scowcroft H. Tamoxifen - incremental progress, massive impact. Cancer Research UK (blog); Nov 2008Bryan J. From breast cancer treatment to prevention: the story of tamoxifen. PJ; Feb 2009Sardi PC. Tamoxifen: 50 years later… long live the king.

Discovery of Morphine

Last year, morphine celebrated its 200th anniversary as an analgesic (first distributed for public use in 1817). Derived from the seedpods of the poppy, opium (Papaver somniferum) has been used since several thousands of years back. A 6000 year old Sumerian tablet speaks of it and it became famous to the point where Egyptian pharaohs had it placed in their tombs. By the 700s AD, opium use had spread to India, China and Arabia.

In early 19th century, the young uneducated curious boy Freidrich Wilhelm Adam Serturner (1783 - 1841) a pharmacist assistant watched frustrated physicians complaining about the unpredictability of opium to his boss, who could only ask his suppliers for better quality. Realizing that the problem would never be remedied until dosages could become standard-ized, Friedrich sought to isolate the active ingredient in opium, from which predictable and reliable doses could then be produced.

Working in the evenings on the pharmacist's old equipment, Friedrich eventually isolated a yellow-white crystal after submerging it in ammoniated water. The substance isolated was identified as an alkaloid (the first ever alkaloid isolated from a plant source) with the then available knowledge.

After conducting animal experiments and adjusting the dosages, Friedrich named his new drug for the Greek god of dreams, Morpheus, but to keep it consistent with standard drug naming policy, it was named as morphine.

However Friedrich's discovery was not welcomed by medical community due to his lack of credentials and poor methodology. Discouraged Friedrich kept aside his discovery for years until he treated himself successfully with morphine when he developed toothache. Finding it safe, he tested his product among local children and confirmed the safety and efficacy subjectively. It was then his second round of experiment started with French physician Francois Magendie who published a paper on morphine's analgesic and sedative properties in 1817 followed by companies marketing morphine for medical use.

After 200 years of successful use, morphine continues to stay at the top of WHO analgesic ladder for severe pain. Truly a quantum leap in the history of medicine!

Sources: The invention of morphine. www.todayifoundout.com [online accessed, 08 Mar 2018] , Even today, morphine remains a popular opioid analgesic. PJ [online, 16 Apr 2013]

Source: CMC Pharmacy Bulletin, a publication of the Pharmacy Service (DISH), CMC, Vellore