Chemotherapy

Cancer treatment before the middle of the twentieth century meant the knife or the X-ray beam, and both worked only on tumors that had stayed put. Once the disease had spread through the body, physicians had nothing to offer but morphine and honesty. The idea that a drug circulating in the bloodstream might hunt malignant cells wherever they had gone was not new — Paul Ehrlich had imagined a magic bullet decades earlier — but no compound had ever managed it. The one that finally did came out of chemical warfare.

Two lines of evidence converged. At Yale in 1942 the pharmacologists Louis Goodman and Alfred Gilman, working under an army contract on chemical weapons, injected a nitrogen mustard compound into a patient whose lymphoma had stopped responding to radiation. The tumors shrank dramatically, then came back. The work stayed classified for years. Then on December 2, 1943, German bombers struck the Italian harbor of Bari and sank an American ship secretly carrying mustard gas. An army physician, Stewart Alexander, examined the injured and reported that the agent had specifically destroyed white blood cells and bone marrow.

The second breakthrough came in Boston. Sidney Farber, a pathologist at Children's Hospital, reasoned that if folic acid fed the runaway cell division of childhood leukemia, a chemical that blocked folic acid might starve it. In 1947 and 1948 he gave aminopterin to sixteen children with acute leukemia, and ten of them went into remission — the blood cleared and the children got out of bed. Every one of them relapsed and died. Farber published his results in 1948 over objections from colleagues who thought raising such hope so briefly was a cruelty.

What turned remissions into cures was combination. Beginning in the late 1950s, researchers at the National Cancer Institute gave several drugs at once, each attacking the cell by a different route, at doses that pushed patients to the edge of what a body could survive. Methotrexate cured metastatic choriocarcinoma in 1956, the first time any drug had cured a spreading solid tumor. Regimens for childhood leukemia and Hodgkin lymphoma followed, and survival for children with the commonest leukemia went from near zero to roughly ninety percent. The bargain was brutal and largely still is — a treatment that damages every dividing cell in the body, and merely damages the malignant ones more.