Life on earth would be impossible without the presence of plants. Since the dawn of humanity, functions; from producing life-maintaining oxygen, to being a source of food and shelter for humans and animals. In addition, they also act as nature’s medical cabinet, hosting a variety of compounds possessing medicinal value.
A historical perspective
Photo by Marion Botella on Unsplash
In an era without antibiotics and modern medical techniques, mankind relied on plants for cures against various diseases. Common kitchen spices such as ginger, pepper, clove, cinnamon, nutmeg, and cardamom, were used by ancient physicians to treat colds, fevers, bruises, and more. Ancient medicinal cures utilising various plant parts are still used to great effect in Asian and African continents. Thus, it is not surprising to see modern-day medical chemists direct their attention to the plant world in an attempt to unearth novel ways to combat various disease
One of the deadliest diseases afflicting mankind is cancer. The disease, known to affect both humans and animals, can be caused due to unlucky genetics to bad lifestyle choices. Despite the miraculous advancements in medicine, the dynamic nature of cancer makes it one of the leading causes of deaths in people of all ages.
Over the years, scientists have been waging a heated war against cancer. Chemotherapy, radiotherapy, gene therapy, surgery etc., are some of the common arrows in the cancer-treatment quiver. One of the key strategies to combat the disease was developed in the United States of America (USA) in the late 20th century. A scientist duo from the Research Triangle Institute (RTI), USA, played a central role in the discovery of two key anti-cancer drugs. Before diving into their spectacular finding, let us take a brief look at the disease they were targeting.
Cancer: The silent killer
To truly comprehend the danger of cancer, one needs to understand how the disease afflicts us. Our body comprises of trillions of cells, each of which has a designated task to perform. The code determining these tasks is written into our DNA (deoxy-ribonucleic acid). One of the tasks directed by the DNA is cell division, i.e., the regulated production of new cells from existing cells. At times, due to some damage to our DNA, the signal for regulated cell division can be scrambled. This can cause cells to divide indiscriminately, and thus, the disease condition called cancer develops.
Cancer Cells got no chill whatsoever!
Cancer can afflict any cell of the body, including blood cells. The condition allows for the unchecked production of abnormal cells that are impervious to regulatory commands. The cells sometimes form solid masses called tumors, which can be benign or malignant. While benign tumours can be detected and treated with relatively more ease, malignant tumour cells are extremely dangerous. They have the ability to travel through the body and convert other normal cells into cancerous cells causing extensive spread and acceleration of the disease
Our Natural Pharmacy
In the 1960s, The National Cancer Institute (NCI), USA, began a novel program that screened plants for compounds with anti-cancer properties. The institute formed a partnership with a research group from the newly established Natural Products Laboratory at the RTI.
The group headed by veteran medicinal chemists Dr. Monroe Wall and Dr. Mansukh Wani. screened various plant compounds for their study. One of the compounds that caught their interest came from the bark of Camptotheca acuminate, a tree native to China. The scientists named the compound Camptothecin and observed that cancer cells treated with it were destroyed. Despite its promising anti-cancer property and the group’s interest in developing it as a drug for clinical trials, camptothecin proved to be difficult to handle. The compound was insoluble in water causing roadblocks in the drug development process. Efforts were made to create suitable variants of camptothecin, but these weren’t effective cancer cell killers and the drug trials were abandoned.
Dr. Mansukh Wani (Left) and Dr. Monore Wall © RTI International / Wikimedia Common
The Wall-Wani duo were also responsible for the discovery of the more popular drug, Taxol. The targeted compound, was isolated after years of cumbersome research from the bark of the Taxus brevifolia, the Pacific yew tree. The experiments conducted by the researchers indicated that the compound had tumour destruction properties. It halted cell division and growth of cancer cells, leading to their eventual death. Despite promising experimental data, the drug development hit a snag due to the high manufacturing cost of Taxol. The bark from one Pacific yew tree provided enough compound for just a single dose of the drug. This coupled with the extremely slow growth rate of the tree raised concerns about its extinction since the removal of its bark killed the whole tree.
Revolution in cancer treatment
Both camptothecin and taxol had immense potential as prospective anti-cancer drugs, but the cumbersome isolation of these compounds from their plants and their subsequent issues in the chemical process of drug development stymied the interests of pharmaceutical companies.
Taxol’s potential as a viable anti-cancer drug gained traction after Dr. Susan Band Horowitz in 1977 decided to accept NCI’s request to study the intriguing plant compound. Her group reinforced Taxol’s anti-cancer properties with various experiments and unearthed the underlying process that made it so deadly to cancer cells. Their study published in 1979 helped NCI set the stage for the unencumbered development and testing of Taxol as a drug against cancer.
The pharma-company Bristol-Meyers Squibb, circumvented the Taxol manufacturing issue by deriving the compound from the needles of Taxus baccata, the common yew tree which was widely and easily grown across the North-American continent. The drug is now widely used against breast, ovarian, skin and lung cancer.
In the same vein, camptothecin was given a new lease of life in the late 1980s. A research team from Johns Hopkins University detailed the unique mechanism by which the compound acted as a destructive poison to cancer cells. This study reignited the scientific community’s interest in camptothecin and new strategies were identified to solve the solubility problem and create an effective drug. Camptostar and Hycamtin were drugs developed from camptothecin by Pfizer and GlaxoSmithKline respectively. Both drugs are widely used in the treatment of colon and ovarian cancer.
Conclusion
In the scientific and medical circles, camptothecin and Taxol have been hailed as miracle compounds with extremely effective anti-cancer properties. The drugs generated from the two compounds have undergone refinement over the years and are still a staple in chemotherapy strategies against cancer. Their distinctive and one-of-a-kind mechanisms of action against cancer cells have proved beneficial in creating treatment strategies for cancer patients whose cells have developed resistance against other chemotherapy drugs.
Dr. Wall and Dr. Wani, the forces driving the discovery of these live-saving drugs, faced extensive ridicule and criticism for their focus on plant-derived solutions for cancer treatment. The duos grit, perseverance, and ingenuity helped propel their work forward despite the many hurdles in their journey. Their discoveries have saved the lives of numerous people around the world. In the words of Dr. Wall, “Cancer is not one, but several hundred diseases and will require many different types of agents. Undoubtedly, there are other highly active natural products from plant, marine, and fungal sources as yet unknown which, when discovered, will have therapeutic value.”
#Note: Cover Photo by Picture Seeker on Unsplash
