The movie Dying to Survive was a hit, and let everyone know about an anti-cancer drug, Gleevec. Gleevec can treat leukemia, but the high price makes appall. Movies have attracted unprecedented attention from the whole society.
In fact, in the history of fighting leukemia, there is a drug that is greater than Gleevec, and that is "Vincristine". Under normal circumstances, patients will first receive chemotherapy by intravenous injection of vincristine. If the recovery effect is good, doctors will recommend taking targeted drug Gleevec. Therefore, Gleevec is a bit like an additional oral drug, and the more important drug, vincristine, has been ignored by everyone because of its relatively low price. From the point of view of medical importance or popular science cognition, it is necessary to introduce vincristine to everyone.
Vinblastine is an alkaloid extracted from Catharanthus roseus, and its discovery can be described as an accident. Catharanthus roseus, which originated in Madagascar, is a small flower of Apocynaceae, with two kinds of white and pink. Around 1750, the famous botanist Linnai discovered and named Catharanthus roseus. Because of its beautiful colors and long seasons, it was introduced to all parts of the world by gardeners and exhibited various herbal cultures. In Britain, India, China, Mexico and other places, people have used the traditional knowledge of Catharanthus roseus to treat diabetes, dysentery and other diseases.
Chemical structure of Catharanthus roseus and vincristine
Catharanthus roseus is toxic, but for terminally ill patients, taking it in small doses is generally nothing. Especially before the invention of insulin, many diabetic patients had almost no cure, and a dead horse was a living horse doctor. Many folks are popular to use Catharanthus roseus and leaves to make tea, and there is such a culture all over the world.
Robert Noble, a Canadian doctor, is a medical scientist who studies diabetes. His brother Clark Noble (who made a great contribution to the discovery of insulin) heard that "Jamaicans use Catharanthus roseus as tea to treat diabetes", so he told Robert the news and sent him some samples. Like most pharmacologists, Robert obtained information from folk medicine, then confirmed it by scientific methods, and then isolated effective compounds to develop new drugs.
By injecting Catharanthus roseus extract into the blood of mice and rabbits, they found that Catharanthus roseus could not actually lower the blood sugar concentration. In other words, Catharanthus roseus has no therapeutic effect on diabetes at all. However, something magical happened. Careful experimenters found that injection of sterilized Catharanthus roseus extract would lead to liver and kidney abscess in mice. Since there is no bacterial infection, how can mice get abscess? Further research found that the original Catharanthus roseus extract destroyed the immune system of mice, and further research found that Catharanthus roseus extract directly destroyed hematopoietic cells in the spinal cord, thus reducing the ability to be responsible for immunity in the blood.
The ingredients in Catharanthus roseus can kill white blood cells. The keen Robert soon realized this important discovery. Catharanthus roseus extract can not treat diabetes, but it is likely to have therapeutic effect on leukemia. Now we know that leukemia is canceration and abnormal bone marrow due to special reasons, resulting in abnormal white blood cell proliferation.
Robert Noble (right) and Charles Beer (left).
Aware that Catharanthus roseus has a potential therapeutic effect on leukemia, keen Robert invited another chemist, Charles Beer, to join in and set out to separate the special components from Catharanthus roseus. In 1958, they finally got an active alkaloid and named it Vinblastine. At the same time, Robert and Beer were studying Catharanthus roseus with Eli Lilly, a famous American pharmaceutical company. Later, the two teams cooperated in research and development, and successfully launched Vincristine, which we are now familiar with. Vinblastine has better anticancer effect than vinblastine, and now it is the first choice chemotherapy drug for leukemia, especially for acute lymphoblastic leukemia, Hodgkin’s lymphoma and other cancers.
The mechanism of vincristine is that it can attach to microtubules and inhibit mitosis. Many cancers are caused by uncontrolled cell division and rapid reproduction, so vincristine is widely used in chemotherapy to treat cancer. The side effects of vincristine are quite great, the most obvious ones are hair loss, constipation, walking disorder and headache. But in order to live a few more years, these side effects are nothing. My father is a leukemia patient, so I have a special affection for this "ordinary" floret. My father injected vincristine many times, and with the help of this magic medicine, he lived for two more years. Leukemia patients will attack normal tissues maliciously because of the increase of white blood cells, so they will feel pain all over, especially at the joints. On his deathbed, my father took morphine, a painkiller, which was not very effective. In order to return to his hometown in Dali smoothly, he took a little vincristine to stop the pain and finally died at home with dignity.
Therefore, I have a strong motivation, explosive emotions and an irresistible sense of responsibility in writing this article. Although Catharanthus roseus is now a common plant that can be seen everywhere, people may not know about vincristine and the outstanding contribution of this unique plant in Africa. Catharanthus roseus is a natural spirit given to us by God, and it blooms the most beautiful flowers in the world.
Biosynthesis process of vinblastine and vincristine (via science)
Once vinblastine was discovered, it was quickly put into the market and became a hot star anticancer drug. However, the content of vincristine in Catharanthus roseus plants is extremely low, and only about 500 kilograms of dry leaves can extract 1 gram of vincristine. In the early stage of research and development, the price of vincristine was also staggering, worth millions of dollars per kilogram.
In order to obtain anticancer drugs more quickly and efficiently, scientists have been making efforts. The first is whether it can be mass-produced by simulating biosynthesis. This has always been a huge problem, and scientists have been exploring and studying it for more than 60 years. In 2016, a Japanese research team analyzed the synthesis, transportation and regulation of vinblastine in leaves (PNAS 2016), and the process was very complicated. Recently, Science published another article, saying that two key enzymes and functional genes controlling the synthesis of vinblastine have been found, and we have a further understanding of this anticancer drug in nature.
(Original title: Vincristine: another "magic medicine" not mentioned in Medicine God, written by Liu Guangyu, a researcher at Xishuangbanna Tropical Botanical Garden of China Academy of Sciences)