In the 1940s childhood leukaemia was a death sentence. Very little was understood about this blood cancer, especially its occurrence in children, and no treatments were available.
The discovery of chemotherapy
A big breakthrough came in the 1940s after a chemical spillage of mustard gas during World War II, when American scientists noticed a significant lowering of the white blood cell counts of its victims.
It seemed that nitrogen mustard, the chemical in mustard gas, was effective at stopping rapidly dividing cells. Scientists then went on to test this in mice with lymphoma and found it to be effective, leading to its use in patients. Although this effect only lasted a few weeks it was a big step forward in the realisation that drugs could be used to treat cancer.
At this time there were also attempts to treat children with arsenic and radiotherapy. Although arsenic is no longer used for the more common types of leukaemia, derivatives of the chemical have more recently been introduced into the treatment of a rare subtype, acute promyelocytic (APL), for both adults and children with much success.
By the 1950s, childhood leukaemia was still untreatable and most children died soon after their diagnosis.
People blamed all sorts of factors for causing the disease in children, from dirty drinking water to car fumes, all of which are unfounded. At this time it was believed that childhood leukaemia was incurable, so studies aimed at finding a cure were considered very controversial.
The first anti-leukaemia drug
In the meantime Dr Sidney Farber, a US scientist, noticed that folic acid was incredibly effective in making leukaemia cells grow. We now know that this is because it stimulates the metabolism of DNA.
Dr Farber successfully tested folic-acid reducing drugs, called anti-folates, to treat leukaemia. These became the first drugs to induce remission in children with leukaemia and are still used in the treatment of acute lymphoblastic leukaemia (ALL) today, in the form of a drug called methotrexate.
Around this time scientists also began developing a different group of drugs called purine analogues. These were designed to block DNA copying within cancer cells to stop them from growing, and therefore destroying them. This resulted in 6-mercaptopurine; a drug introduced in the 1960s which is still used during maintenance therapy, the final stage in the treatment of childhood leukaemia.