The birth of chemotherapy drugs

This is the 3819th article of Da Yi Xiao Hu

Speaking of chemotherapy, I believe everyone is familiar with it. It is well known to the public as the main way to treat cancer. However, do you know how chemotherapy drugs were born?

The birth of nitrogen mustard, the earliest chemotherapy drug used in clinical practice, can be traced back to World War II. On the night of December 2, 1943, at the port of Bari, Italy, Allied ships were unloading tens of thousands of tons of strategic materials. However, what was unexpected was that the port of Bari, with its weak air defense measures, was heavily bombed by Nazi German bombers.

This air incident was called "the Pearl Harbor of Europe". Materials show that the air raid on Bari Port was the most serious air raid on the European continent suffered by the Allies, and it was also the most serious chemical gas leak in history, with the highest number of deaths and injuries. Because among the ships sunk was a Liberty ship named John Harvey, which carried 2,000 M47 mustard gas bombs. Speaking of mustard gas, I believe everyone has heard of it. The Japanese invaders secretly stationed Unit 731 in Northeast China to conduct gas research and testing, and used mustard gas in battles such as the Battle of Songhu, the Battle of Xuzhou, and the Battle of Hengyang, killing nearly 10,000 Chinese soldiers and civilians.

There is a saying that goes: Great inventions are always created inadvertently. This incident made people observe that the bone marrow cells of men exposed to mustard gas were obviously depleted, so some scientists put forward such a hypothesis: since mustard gas can reduce the number of bone marrow cells, can it inhibit the proliferation of white blood cells in patients with leukemia or lymphoma? So scientists launched relevant research, but the results were regrettable. Mustard gas itself had no effect on cancer cells and was extremely toxic to normal cells. However, scientists held a firm belief and kept transforming mustard gas. Finally, they replaced the sulfur in mustard gas with nitrogen and synthesized a compound similar to mustard gas - nitrogen mustard. Nitrogen mustard is much less toxic than mustard gas. After years of continuous experiments, in 1943, pharmacologists Alfred Gilman and Louis Goodman of Yale University in the United States successfully conducted a clinical trial of lymphoma treatment using nitrogen mustard, which opened the prelude to modern tumor chemotherapy.

From the birth of the first chemotherapy drug for the treatment of cancer to the present, mankind has gone through a long journey of more than 70 years. From mustard gas to the emergence of the first chemotherapy drug, nitrogen mustard, the birth process of chemotherapy drugs presents us with the thinking and methods of developing new chemotherapy drugs. This method is to find a drug that can have a toxic effect on cancer cells, and then continuously transform its molecular structure to obtain a chemotherapy drug that is highly toxic to cancer cells but has little effect on normal cells. Although chemotherapy drugs have made great progress in the advancement of medicine. But it is undeniable that chemotherapy is still a painful process to this day, so there is still a long way to go in exploring new chemotherapy drugs.

Author: Shanghai Fifth People's Hospital Affiliated to Fudan University

General Surgery Nail and Breast Specialty Group

Dr. Li Yujin