In the United States, four out of ten people will have cancer in their lifetimes. [1] Worldwide, the figures are a little better, “about 1 in 5 people develop cancer in their lifetime, approximately 1 in 9 men and 1 in 12 women die from the disease.” As the American Cancer Society notes, lifestyle, environmental factors and family history can increase or decrease the risk of getting cancer.
Before the 20th Century, surgery was the only treatment for cancer. Radiation therapy came into being in the early 1900s after the discovery of X-rays and radium. Those with cancers of the blood had no treatment. Chemotherapy is a phenomenon of the late 1940s and 1950s.
What is really amazing though, are the number of people living today who have survived cancer.Since 1991, when smoking rates began to drop in the US, with newer treatments and earlier detection, there has been an 33% drop in cancer death rates overall.
Treating Acute Lymphocytic Leukemia with Chemotherapy
One treatment success story is Acute Lymphocytic Leukemia (ALL) in children. ALL is a cancer of white blood cells produced in the bone marrow. Normally, bone marrow produces red and white blood cells and platelets. In ALL, abnormal and immature white blood cells take over the bone marrow so that no other blood cells can be produced. Without the production of red blood cells, the children become anemic. Then, the abnormal white blood cells cannot fight infections, while the lack of platelets makes it impossible for the body to stop bleeding. Before 1950, if a child got acute lymphocytic leukemia (ALL), that child died. Only 3 percent of children survived. Once diagnosed, within about eight weeks, they bled to death. [2]
Dr. Sidney Farber
Seeing the horror firsthand, Dr. Sidney Farber, a pathologist working in Boston, thought that folic acid might help these children. At the time—1948— the medical world had discovered that folic acid could help people with pernicious anemia.
In this environment of blood, fatality and devastation, he cautiously decided to treat patients in the last stages of the disease with folic acid. Unfortunately, this did not cure the children. It made things worse. But Dr. Farber didn’t give up.Using the knowledge gained from this effort, Dr. Farber treated children sick with ALL with an antagonist of folic acid called aminopterin ( related to methotrexate). In biochemistry, an antagonist is a substance that interferes with or stops the action of another element.
Aminopterin chemotherapy worked. The children actually experienced remission of their cancer. Sadly, it was a temporary remission, but it was something. [3]
Farber’s work got the ball rolling.
The Need for Money
Cancer, however, was not a word used in polite conversation. In fact, the use of the word “cancer” was actually prohibited on radio, the predominant medium of the day. An influential woman named Mary and her advertising magnate husband, Albert Lasker, brought the word “cancer” out in the open.
Mary and Albert Lasker
Albert contributed his understanding of advertising, the media, and money. The early loss of a dear mother figure from cancer fueled Mary’s determination to forward research for cancer.
Things started happening.
In 1943, Mary approached the American Cancer Society (ACS). Finding the ACS a small and ineffectual organization, with a tiny budget of $102,000, Mary went on a fund-raising mission. First, she engaged the Reader’s Digest to publish three small articles on the need for more research to find a cure for cancer and with a request for money for the ACS. ACS’s 1944 budget increased to over $300,000. Then, in 1945 Mary raised $4 million, requiring $1 million of that money to be devoted for research.
Albert, though, knew that $1 million would not be enough. He understood the need for more money knowing that only through government support could real progress occur. He encouraged Mary to advocate for federal funding of the National Cancer Institute (NCI). By 1947, the couple, along with Dr. Farber, persuaded Congress to increase funding to NCI from $1.75 million in 1946 to more than $14 million in 1947. [4]
Increased funding began to help the research effort. Dr. Emil Freireich, “recognized as a founding father of modern clinical cancer research,” praised both Farber and Lasker, “My personal adviser was Sidney Farber. Farber was the godfather of the NIH. He worked with Mary Lasker to get the money and create the legislation.” With funding, NCI hired Freireich and several other founding fathers of oncology research. [2]
Freireich’s Contributions to ALL Treatment with Chemotherapy
Overcoming hurdles from established scholars is the backdrop to many of Freireich’s efforts. One of the first he faced involved platelets. This occurred because Freirech believed that stopping the bleeding/hemorrhaging that killed children with ALL, would allow the children to actually receive treatment.
From research conducted on Japanese survivors of the atomic bomb, he learned that radiation destroyed platelets in the body and that those survivors died of hemorrhaging. Freireich connected the dots and realized that children with ALL did not have platelets to stop their bleeding. To prove this, Freireich mixed platelets from his blood with those of his ALL patients. Their bleeding stopped. [2]
Blood transfusions given to ALL patients helped ease their suffering. Freireich realized that patients with ALL were being given old blood, blood stored for more than 48 hours, to replace the blood that they were losing. Platelets die after 48 hours of storage. Freireich had to convince the establishment at NCI to provide newer blood to the children. His premise pushed against prevailing wisdom and numerous publications by colleagues in the field of hematology. Yet, once the children received blood that had living platelets, children with ALL did not die of hemorrhage. They were able to be treated with chemotherapy.
Using techniques he had learned in conducting clinical trials in infectious diseases, Freireich created clinical studies for ALL. Lessons from infectious disease trials included combating infections from several angles with different drugs. Could combination treatments work on ALL?
Dr. Freireich thought it might.
They tried combinations of 6MP, methotrexate, and prednisone. But Freireich faced what Farber had faced before him temporary remission. They would get the children into remission, but after some time the leukemia would come back. Freireich used the term “minimal residual disease”—a concept that is part of the lexicon of oncology today— to describe what happened with the children. Even though most of the cancer had been destroyed, some of the cancer was still left in the body and came back.[2]
Then Dr. Irving Johnson at Eli Lily approached Freireich with vincristine, a drug derived from periwinkle. Dr. Freireich convinced his superiors at NCI to allow him to try the new drug, saying, “I’ve got children on the ward right now that are dying, who have no hope for living. What harm is there in doing it?” Of the 11 children who were given vincristine, seven achieved remission of their ALL.
“I said to myself, ‘Wow! This is something,” Freireich remembered. With this success, he created a new protocol—a strategy of treatment— called VAMP for children with ALL. VAMP stands for vincristine, amethopterin (another name for methotrexate), mercaptopurine, and prednisone. As he stated in an interview, “They finally allowed me to treat brand-new, untreated children with this regimen. This is the most famous chemotherapy in the history of chemotherapy. We treated 17 consecutive children, and 16 of those 17 children responded immediately, in 2 or 3 weeks.” He remembered thinking,
“Could we possibly, with this enormously potent combination, cure leukemia?” [2]
With the “powerful 4-drug combination that induced remission,” Freireich and his colleagues decided to try something further, the first adjuvant therapy. “It was the first time we treated people who had no disease on the assumption that they had disease….We proved that treatment when the patients were in remission
could prolong remission.” [2]
The development of combination therapies to treat ALL and other cancers is one of the greatest successes in cancer research. Through funding by the federal government, ALL cancer survival rates for children are at 90% overall. [5]
References:
[1] https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf
[2] MD Anderson Cancer Center (2021, Oct 27). Cancer History Project. Emil J. Freireich Interviews. https://cancerhistoryproject.com/primary-source/emil-j-freireich-interviews/
[3] Kohn, K. Chapter 5: The methotrexate story: folic acid analogs.Drugs Against Cancer: Stories of Discovery and the Quest for a Cure. https://discover.nci.nih.gov/kohn/book/drugs_against_cancer_chapter5_v220719dj3.pdf
[4] Wallace, L. (2015). Catalyst for National Cancer Act: Mary Lasker https://laskerfoundation.org/catalyst-for-the-national-cancer-act-mary-lasker/
[5] https://www.cancer.org/cancer/types/leukemia-in-children/detection-diagnosis-staging/survival-rates.html
