History of Leukemia
Discovery of
Leukemia
Generally, the ancient Greeks are credited with being
the first to recognize cancer some time in the 4th or 5th
century B.C.E. (Greaves, 2000). In 1932, Louis Leakey discovered a
mandible in Kenya of Australopithecus or Homo erectus
that George Stathopolous believes was a malignant tumor and may have
been Burkitt's lymphoma, a common cancer of the jaw in contemporary
east Africa. The bones of a dinosaur that may have had cancer have
been found from 150 million years ago (Greaves, 2000).
Leukemia was not officially diagnosed until 1845,
when John Hughes Benett diagnosed it in Edinburgh (Greaves, 2000).
Other European physicians in the 19th century observed
that their patients had abnormally high levels of white blood cells,
and they called the disease “weisses blut,” meaning “white
blood.” The term “leukemia” that is used now comes from the
Greek words “leukos” and “heima,” also meaning “white
blood” (Leukemia and Lymphoma Society, 2005). In 1913, four types
of leukemia were classified: chronic lymphocytic leukemia, chronic
myelogenous leukemia, acute lymphocytic leukemia, and
erythroleukemia. In 1970, it was first confirmed that some patients
could be cured of leukemia, and by the 1980s and 1990s the cure rates
for leukemia were around 70% (Pui, 2003).
Although
cancer was less common before the twentieth century, humans have been
getting cancer for a long time. Some explanations for the increase
during the twentieth century are that more people are surviving who
would have died of infectious disease, and that in the past many
times cancer may not have been properly diagnosed (Greaves, 2000).
William Harvey's recognition of the circulatory system of the blood
and Gaspae Aselli's explanation of the lymphatic system were
important for the diagnosis and understanding of cancer (Greaves,
2000). In the 19th and 20th centuries,
physicians first began recognizing that certain factors could
increase the risk of developing cancer. In the 1920s, Hermann Muller
recognized that ionizing radiation could cause mutations in DNA that
contributed to cancer (Greaves, 2000).
The increase of childhood leukemia in
modern times may be lifestyle-related. In developed countries,
families are usually smaller and hygiene has improved. Infants are no
longer exposed to infections at an early age (Greaves, 2000). Our
immune systems have evolved to respond to infections shortly after
birth, usually through the mother's antibodies during breast-feeding.
The immune systems of children exposed at later ages, without having
confronted microbes at an earlier age, may not respond as well. These
children may have increased risk of developing leukemia. The
incidence of leukemia is higher among more industrialized nations,
and in those nations among people of higher socioeconomic status,
because these people are living in an environment that is least like
the environment humans evolved to fit. People in these privileged
positions are exposed to more pesticides and chemicals, and fewer
infectious diseases, than other people.
History of Leukemia Treatment
Arsenic
Historically, one of the most common treatments for
leukemia was arsenic. This cure is mentioned in the ancient Ramayana
of India, and was used by Hippocrates (460-370 BC), who gave cancer
its name, from the Greek term "carcinos" or "karkinos"
for crab (Waxman and Anderson, 2001). In the 18th century, Thomas
Fowler created what became known as "Fowler's Solution," a
combination of arsenic trioxide and potassium bicarbonate, which
"became a standard remedy to treat anemia, Hodgkin's disease,
and leukemia"(Waxman and Anderson, 2001). Arsenic became the
primary therapy for leukemia, used up to the early 20th century, when
it fell out of favor with the advent of radiation therapy (Waxman and
Anderson, 2001). In 1865, a German physician named Lissauer used
Fowler's solution to treat chronic myelocytic leukemia (Burns, 2004).
In the 1970s in China, arsenic was revived as a treatment for acute
promyelocytic leukemia. Today, some researchers continue to
investigate arsenic as an effective treatment for leukemia.
Radiation Therapy
In
the early 20th century, leukemia was considered an incurable, chronic
disease. Around 1897, after the discovery of radiation, studies
showed that x-rays could reduce the size of tumors: "it was
discovered that daily doses of radiation over several weeks would
greatly improve therapeutic response" (American Cancer Society).
After medical investigation, "x-ray radiation for patient
therapy moved into the clinical routine in the early 1920s"
(Imaginis). Shortly after becoming widely used, radiation was shown
to be a cause as well as a cure for leukemia. According to the
American Cancer Society, "many early radiologists used the skin
of their arms to test the strength of radiation from their
radiotherapy machines, looking for a dose that would produce a pink
reaction (erythema) that looked like sunburn.” This was considered
an accurate measure of the dose, called the "erythema dose."
Unfortunately, but unsurprisingly, many of these early radiologists
came down with leukemia (American Cancer Society).
Chemotherapy
Until after World War II, there were no adequate
treatments for leukemia. One of the most important treatments for
cancer, chemotherapy, actually developed from an agent of chemical
warfare used by the Germans during WWI, mustard gas, which attacks
rapidly-dividing white blood cells. Scientists discovered the
tumor-fighting effects of mustard gas when a group of soldiers during
WWII accidentally came in contact with mustard gas and "were
later found to have very low white blood cell counts" (American
Cancer Society). This led to the invention of chemotherapy, a more
targeted approach to nitrogen mustard exposure.
In
the 1940s there were new treatments, such as aminopterin, first used
by Sidney Farber of Boston to treat acute childhood leukemia.
Aminopterin is a compound related to folic acid that can be found in
ALL patients in remission. Aminopterin prevents the DNA replication
in tumor cells. After the discovery of aminopterin, "other
researchers discovered drugs that blocked different functions
involved in cell growth and replication. The era of chemotherapy had
begun" (American Cancer Society).
George Hitchings (1905-1998) and Gertrude Elion
(1918-1999) used rational drug design to create 6-mercaptopurin, the
first truly effective leukemia drug. By 1950, the pair had combined
diaminopurine and thioguanine, which disrupted DNA synthesis by
replacing adenine and guanine. "Elion later substituted an
oxygen atom with a sulfur atom on a purine molecule, thereby creating
6-mercaptopurine (also known as 6-MP)" (Bowden). Despite these
new treatments, leukemia was not conquered. Many patients entered
remission, but they later relapsed and died. Elion researched the
drug intensively, with the result that today therapy uses 6-MP in
combination with other drugs, and continues during remission.
DNA
The greatest advances of the 20th century took place
with the advent of the discovery of DNA by James Watson and Francis
Crick. This led to a greater understanding of the detailed mechanisms
of cancer, answering some questions and leading to a number of
others. In addition to the environmental risk factors, “as our
understanding of DNA and genes increased, [scientists] learned that
it was the damage to DNA by chemicals and radiation or introduction
of new DNA sequences by viruses that often led to the development of
cancer" (American Cancer Society). In the future, genetic
analysis may prove to uncover new treatments for diseases like
leukemia.
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References
Cited
Created by Shannon McGlauflin, Jolene Munger, and
Rebecca Nelson, 2005.