Who is the “Father of Cancer chemotherapy” and how did he change the landscape of Cancer treatment?
In the 1940s, the understanding of the treatment of Cancers, including a blood Cancer called Acute Lymphoblastic Leukaemia (ALL), was extremely limited. [1] Despite the fact that there were experiments in treating Cancers with toxic substances such as nitrogen mustard (mustard gas) with limited success [2], there was no primary treatment for ALL and palliative care was the main option. [1] At the same time, ALL was the most common leukaemia in children. This “swiftly lethal” Cancer caused a lot of suffering for its patients, while doctors did not believe that an “antileukemic drug” could be devised. [3]
ALL starts in the bone marrow. There, different blood cells are made from stem cells. The stem cells develop specific traits as they differentiate into different types of cells, so that they can perform their function properly (so that red blood cells can carry oxygen and white blood cells can protect your body). In case of ALL, bone marrow makes too many white blood cells that are not fully developed and differentiated. These cells cannot perform any particular function and are called blasts. Because these blasts can grow and divide quickly, they flood the blood, bone marrow and lymph nodes, preventing normal blood cells from functioning properly and new, normal cells from developing. This causes people with ALL to become more susceptible to infections and develop anaemia, easy bruising and slow recovery. [4]
Nutritional research before and during WWII has identified that folic acid (folate) was essential for bone marrow to maintain a healthy number of blood cells to prevent anaemia. [1,3] Sydney Farber, born in Buffalo, New York, in 1903, knew about this and the basics of the ALL. Although his job mainly involved lab work and not dealing with patients, he couldn’t stand the suffering. In his small laboratory in the Children’s Hospital, Boston, he decided to test the effect of giving children folic acid, hoping this could help make more normal blood cells. The results, however, turned out to be a disaster. Folic acid accelerated the development of ALL. After quickly stopping the trial and infuriating the doctors with the results, Farber started to work on his mistakes. His new idea was to use an antifolate. A molecule similar to folic acid in its structure, but actually useless to cells. Using his connections with a chemist, Y. SubbaRow, he acquired differentantifolates and began a new trial. [3]
In December 1947, he administered aminopterin (a name of an antifolate) to a two-year-old Robert Sandler who had recently fallen sick with ALL. The results were astonishing. The number of blast cells in his blood dropped significantly. Robert's appetite returned. His alertness increased. He became more active. There were still Cancer cells remaining in Robert's body, but his symptoms vanished. This was a breakthrough that prompted Farber to start administering aminopterin to other children with ALL in the hospital. [4]
There was 1 problem with these remissions, however. After a few months, the Cancer inevitably returned (relapsed). Thesymptoms reappeared, and the blast cell counts skyrocketed again. Robert Sandler died in 1948, after responding to the treatment for only a few months. Although lengthening the life of a person for a few months might seem like a modest achievement, there are two aspects that need to be kept in mind. First of all, even a few months of prolonged life can mean a ton for a patient. Moreover, a few months for ALL was like an eternity. Secondly, it was the effect of Farber’sfindings that he published in June 1948 that had a huge effect on the future of cancer treatment. Although initially perceived with scepticism, it proved a point. Cancer could be treated with a chemical drug. Many future oncologists would cling to this idea when making new chemotherapy regimens. [4]
Farber, however, didn’t stop there. Farber’s belief that Cancer could be treated led him to collaborate with the Variety Club to create a charity that could help fund Cancer research. Farber and Bill Koster (one of the Variety Club members) selected Einar Gustafson as a representative of the charity. To protect Einar’s identity, they called him ‘Jimmy’ and the organisation - ‘Jimmy Fund’. After broadcasting Jimmy’s story, money from different people and philanthropies poured into the charity. Raising more than 200,000$ allowed the Jimmy Fund to lay the foundations for what later became known as Jimmy Fund Hospital, where children with different cancers would be treated. [1]
Finally, Farber helped Mary Lasker, another philanthropist, to boost federal funding for Cancer research, ultimately leading to the National Cancer Act being passed by the USA in 1971, which Declared War on Cancer and helped tosubstantially increase the funding for Cancer research. [1] Moreover, Farber also played a pivotal role in helping Mary Lasker reform the American Society for Control of Cancer into the American Cancer Society, transforming the purpose of the institution from publishing manuscripts by oncologists to raising enormous funds for Cancer research through charity.[3]
There were many key players in the ‘War on Cancer”. Although everyone who helped and is helping to defeat cancer is important, Farber was likely to be the one who revolutionised the field and saved a lot of people.
References:
Kumar Upadhyay A, Prakash A, Kumar A, et al. (August 31, 2024) Dr. Sidney Farber (1903-1973): Founder of Pediatric Pathology and the Father of Modern Chemotherapy. Cureus 16(8): e68286. doi:10.7759/cureus.68286
DeVita VT, Chu E. A History of Cancer Chemotherapy. Cancer Research [Internet]. 2008 Oct 30;68(21):8643–53. Available from: https://aacrjournals.org/cancerres/article/68/21/8643/541799/A-History-of-Cancer-Chemotherapy
Mukherjee, S. (2010). The emperor of all maladies: a biography of cancer. Large print ed. Thorndike Press.
Cancer Research UK. What Is Acute Lymphoblastic Leukaemia (ALL) | Cancer Research UK [Internet]. www.cancerresearchuk.org. 2021. Available from: https://www.cancerresearchuk.org/about-cancer/acute-lymphoblastic-leukaemia-all/about
