Min Chiu Li
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Min Chiu Li (; 1919–1980) was a Chinese-American oncologist and cancer researcher. Li was the first scientist to use
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
to cure widely
metastatic Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
,
malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
cancer.


Early life and education

Born in China, Li studied at Mukden Medical College in present-day Shenyang. Li came to the United States in 1947 for medical training at the
University of Southern California , mottoeng = "Let whoever earns the palm bear it" , religious_affiliation = Nonsectarian—historically Methodist , established = , accreditation = WSCUC , type = Private research university , academic_affiliations = , endowment = $8.1 ...
, but was unable to return to his home country due to the Chinese Revolution. Li served as a resident at Chicago's Presbyterian Hospital (now
Rush University Medical Center Rush University Medical Center (Rush) is an academic medical center in the Illinois Medical District neighborhood of Chicago, Illinois. It is the flagship hospital for the Rush University System for Health, which includes Rush Oak Park Hospital a ...
) and from 1953 to 1955 worked as a Damon Runyon Fellow at Memorial Hospital (now
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center (MSK or MSKCC) is a cancer treatment and research institution in the borough of Manhattan in New York City, founded in 1884 as the New York Cancer Hospital. MSKCC is one of 52 National Cancer Institute– ...
) in New York City. In 1955, Li accepted a position as an assistant
obstetrician Obstetrics is the field of study concentrated on pregnancy, childbirth and the postpartum period. As a medical specialty, obstetrics is combined with gynecology under the discipline known as obstetrics and gynecology (OB/GYN), which is a surgic ...
in the laboratory of Roy Hertz at the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
(NCI). Li took the job primarily to avoid being drafted into the US military during the
Korean War , date = {{Ubl, 25 June 1950 – 27 July 1953 (''de facto'')({{Age in years, months, weeks and days, month1=6, day1=25, year1=1950, month2=7, day2=27, year2=1953), 25 June 1950 – present (''de jure'')({{Age in years, months, weeks a ...
, but became obsessed with finding a cancer cure after watching patients die in terrible pain from
choriocarcinoma Choriocarcinoma is a malignant, trophoblastic cancer, usually of the placenta. It is characterized by early hematogenous spread to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also c ...
, a cancer of the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...
.


Cancer research

Li began to treat his choriocarcinoma patients with an
antifolate Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionin ...
chemotherapy drug called methotrexate. A decade earlier
Sidney Farber Sidney Farber (September 30, 1903 – March 30, 1973) was an American pediatric pathologist. He is regarded as the father of modern chemotherapy for his work using folic acid antagonists to combat leukemia, which led to the development of other c ...
had discovered that injecting
folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
into children with
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
accelerated the progress of the disease. Farber hypothesized that leukemia could be treated with a folate antagonist, a drug with a molecular structure similar to that of folic acid which would bind to the folate receptors in cancer cells, preventing them from receiving the folic acid they needed. Farber was able to use a drug of this type,
aminopterin Aminopterin (or 4-aminopteroic acid), the 4-amino derivative of folic acid, is an antineoplastic drug with immunosuppressive properties often used in chemotherapy. Aminopterin is a synthetic derivative of pterin. Aminopterin works as an enzyme inh ...
, to achieve a temporary remission in childhood leukemia. In the early 1950s, Jane C. Wright used methotrexate, a less toxic drug of the same type, to treat
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...
. Between 1953 and 1955, while still at Sloan Kettering, Li and his colleagues experimented with using methotrexate as a cancer treatment. Although they were unable to demonstrate any improvement in patient health, the team made one important finding: When patients were being treated with methotrexate, urine levels of the hormone
human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantatio ...
(hCG) dropped steadily. Li hypothesized that the patients' tumors were secreting hCG, and as a result, that the level of hCG in a patient's urine could be used to measure the effectiveness of a particular treatment. In 1955, after moving to the National Cancer Institute, Li had the opportunity to test his hypotheses. Li's first patient was the 24-year-old wife of a U.S. Navy dental technician. A lesion in one of her lungs had ruptured, filling her
chest cavity The thoracic cavity (or chest cavity) is the chamber of the body of vertebrates that is protected by the thoracic wall (rib cage and associated skin, muscle, and fascia). The central compartment of the thoracic cavity is the mediastinum. There ...
with blood and air (a condition known as hemopneumothorax) and leaving her near death. After consultation with
pharmacologist Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemic ...
Paul Condit, Li administered a single 10 mg dose of methotrexate. Defying expectations, the patient survived through the next day, at which point Li administered a 50 mg dose. Over the next several days, Li noted slight improvements in the patient's hCG levels, but they soon climbed again. Concluding that the 50 mg dose of methotrexate had provided some temporary benefits, Li decided to try four daily doses of 25 mg. The patient improved enough that within three weeks she was able to sit up in a chair. Li repeated the regimen of daily doses and, although she had several complications brought on by the toxicity of the drugs, including
leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of in ...
, diarrhea and
stomatitis Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration. In its widest meaning, stomatitis can have a multitude of different cau ...
, the patient continued to improve. Within four months she was "normal without evidence of disease." Li treated two additional patients with choriocarcinoma that had metastasized to the lungs and achieved similar results: complete remission within four months. During his work with these three patients Li tried varying the amount of methotrexate given to the patients and the frequency of the doses. He concluded that a dose of 100–125 mg given every day for four or five days was more effective than a single, larger dose. Li and his colleagues found that methotrexate eliminated the visible tumors in patients whose choriocarcinoma had metastasized. However, Li noted that the patients' blood tests continued to show an elevated level of hCG. Although the patients did not exhibit what doctors traditionally considered "clinical evidence of cancer", such as tumors, Li continued to treat them with chemotherapy based on their elevated hCG levels. The National Cancer Institute administration disapproved, feeling that by continuing treatment Li was experimenting on his patients and unnecessarily poisoning them with the chemotherapy drug. In 1957, the NCI fired Li and he returned to Sloan Kettering. However, Li was ultimately vindicated. Those patients whose methotrexate treatment was stopped once the visible tumors disappeared inevitably relapsed, while the patients who continued to be treated until their hCG levels returned to normal were cured. Fellow cancer researcher Emil Freireich described Li's insight, that cancer was likely to recur in patients if a chemical
tumor marker A tumor marker is a biomarker found in blood, urine, or body tissues that can be elevated by the presence of one or more types of cancer. There are many different tumor markers, each indicative of a particular disease process, and they are used in ...
was found, as an "extraordinarily important new principle in cancer treatment". Before the work of Li and his colleagues, 90% of women who developed choriocarcinoma died within a year. Today, with chemotherapy, choriocarcinoma can be cured in almost every case without surgery. Li made several subsequent contributions to cancer research. In 1960, he demonstrated that metastatic
testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an ...
could be treated with chemotherapy, and in 1977, he showed that the use of
fluorouracil Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pan ...
in addition to surgery improved the survival rates of patients with colon cancer. In the 1970s, Li served as Director of Medical Research at New York's
Nassau Hospital Nassau may refer to: Places Bahamas *Nassau, Bahamas, capital city of the Bahamas, on the island of New Providence Canada *Nassau District, renamed Home District, regional division in Upper Canada from 1788 to 1792 *Nassau Street (Winnipeg), ...
and later as Professor of Medicine at
Loma Linda University School of Medicine Loma may refer to: Geography United States * Loma, Colorado * Loma, Montana * Loma, Nebraska * Loma, North Dakota Other countries * Loma, Ladakh, a town in Ladakh, India * Loma (woreda), a district in Southern Nations, Nationalities, and P ...
.


Recognition

Li received the
Lasker-DeBakey Clinical Medical Research Award Lasker-DeBakey Clinical Medical Research Award is one of four annual awards presented by the Lasker Foundation. The Lasker-DeBakey award is given to honor outstanding work for the understanding, diagnosis, prevention, treatment, and cure of diseas ...
for his work in 1972 and, in 1975, was appointed Chairman of the National Cancer Research Committee of Taiwan's
National Science Council The National Science and Technology Council (NSTC; ) is a statutory agency of Executive Yuan of the Republic of China (Taiwan) for the promotion and funding of academic research, development of science and technology and science parks. NSTC is ...
.


References


Citations


Sources

* * * * * * * * * {{DEFAULTSORT:Li, Min Chiu 1919 births 1980 deaths Cancer researchers Chinese emigrants to the United States Keck School of Medicine of USC alumni People from Shenyang Scientists from Liaoning Loma Linda University faculty Educators from Liaoning 20th-century American physicians American academics of Chinese descent Recipients of the Lasker-DeBakey Clinical Medical Research Award