Li, Choh Hao

Biographical Statement

Summary

Born April 21, 1913 in Canton China, Choh Hao Li received a B.S. (Chemistry) from the University of Nanking and taught there for two years before coming to U.C. Berkeley in 1935. After receiving his Ph.D. in Physio-organic Chemistry from Berkeley in 1938 he went to work as a Research Assistant in Herbert McLean Evan's Experimental Biology Laboratory advancing to lecturer and then through Assistant and Associate Professor. In 1950 he was made full professor and became the first director of the newly created Hormone Research Laboratory (HRL). Li moved with the HRL to the University of California San Francisco campus in 1967. He officially retired in 1983, but as emeritus professor, from 1983 until his death in 1987, he headed the Laboratory of Molecular Endocrinology.

During his career, Li received at least 25 scientific awards and 10 honorary degrees, and published 1,100 scientific articles with over 300 collaborators. He also chaired numerous symposia, served on local, national, and international advisory boards and edited several scientific journals and books.

A pioneer in the field of bio-chemistry, Li devoted his professional life to unlocking the secrets of the pituitary gland. He was either the first, or one of the first, to identify and/or purify eight of the nine hormones of the anterior pituitary. The identification, purification and later synthesis of Human Growth Hormone (HGH) or somatatropin, and the identification of beta-endorphin were his two most widely recognized achievements, but he also worked on ACTH (corticotrophin), the gonadotropins --leuteinizing hormone (LH) and follicle stimulating hormone (FSH), thyrotropin, prolactin, melanocyte stimulating hormone (MSH), and lipotropin. His last accomplishment was the identification and purification of insulin-like growth factor I. While not a clinician or directly involved in clinical research, Li's discoveries had direct clinical impact, especially in the areas of growth and fertility.

Family

One of 11 children of a Cantonese industrialist, Li grew up in a family that stressed education. All of his siblings attended college, many going on to advanced study, and at least three spending some time in the United States. His elder brother Choh-Ming Li, received a doctorate in Economics from U.C. Berkeley and later became the Vice-Chancellor of the Chinese University in Hong Kong and was considered for a UN education post. Another brother, Choh-Luh, was a neurosurgeon at the National Institute for Health (NIH), in Bethesda, Maryland, and a third brother, Choh Hsien, was director of Minneapolis-Honeywell Corporation's research division. Li met his future wife, Shen Hwai Lu (Annie), in 1931 at the University of Nanking. They married in 1938, after he had received his doctorate and convinced her to pursue graduate studies in the United States. She received her masters in Agricultural Economics from U.C. Berkeley when their eldest child was two. Mrs. Li reported that C.H. discussed the titles, introductions and conclusions of his papers with her, allowing her to make suggestions and briefed her on the daily happenings at the laboratory. He worked 6 or 7 days a week until he was in his in his mid-fifties and she convinced him to cut back to 5 days so that they could spend their weekends in the country. They had three children all of whom received professional degrees. Their son, Wei-i, became a doctor, and daughters Anne-si and Eva, a veterinarian and an environmental designer.

Choh Hao Li became a naturalized U.S. citizen in 1955.

Education

Li graduated from Pui Ying High School in Canton in 1929, at sixteen years of age, and went on the University of Nanking where he received his bachelors degree in 1933. After teaching two years at Nanking (1933-35) he applied for admission to graduate schools in the United States. The University of California at Berkeley where his older brother Choh-Ming was attending was his first choice. However he did receive immediate acceptance into the U.C. program, because the Dean, Gilbert Newton Lewis was skeptical of Li's Chinese undergraduate degree. The University of Michigan at Ann Arbor did accept him. On his way East to Ann Arbor Li stopped at Berkeley to visit his brother and make one last try at admittance. Li showed Dean Lewis his first scientific paper in English, recently published in the Journal of the American Chemical Society (JACS). The paper's senior researcher, Ward V. Evans of Northwestern University, was known and respected by Lewis, and subsequently Li was admitted to the program on six months probation. Three years later, in 1938, Li received his doctorate degree.

Career

Anti-Asian sentiment was strong during the Depression, making jobs and housing difficult to find for a young Chinese man. Biologist Herbert Evans took an interest in the young chemist and offered him a tiny work space in the Basement of his Experimental Biology Laboratory (EBLl) in the Life Sciencees Building at Berkeley. At the EBL, Evans was beginning to explore the workings of the pituitary galnd and Li's chemistry background was essential for the success of the research. However, this cooperation between Chemistry and Biology was new and his biologist lab-mates reportedly did not know what to make of Li and left him to his own devices. It was during these early years with Dr. Evans that Li developed the techniques necessary to isolate hormones from the brain and identify their chemical structure. This research paved the way for a series of discoveries which greatly increased scientific knowledge and had a profound effect on the understanding and treatment of a variety of diseases and conditions.

Li's first success came in 1940 when he isolated luteinizing hormone, the first hormone from the anterior pituitary, which along with follicle stimulating hormone, is important in sexual development and fertility. With his isolation of bovine growth hormone (1944) Li began to receive notice. During this period he advanced from Research Associate (1938) to Lecturer in Chemical Morphology (1942), becoming Assistant Professor of Experimental Biology in 1944. Li became an Associate Professor in 1947 the same year he received the CIBA Award in Endocrinology. In 1948 he received a John Simon Guggenheim Memorial Foundation Fellowship, which he appied to fund research under the direction of Arne Tiselius at the University of Uppsala in Uppsala, Sweden. Tiselius had won the 1948 Nobel Prize for Chemistry for his work with separating the proteins in the blood stream. He also developed equipment and techniques for separation of proteins and became the leader in protein chromatography. Li was originally supposed to spend six months in Sweden and then return to Berkeley, however, while at Uppsala, Li extended his stay.

Fearing Li's loss, UC administrators acted quickly to meet his research needs. Li returned to Berkeley in 1950 as a full Professor with joint appointments in the newly created Berkeley Biochemistry Department and the San Francisco Experimental Endocrinology Department. At the same time he was named Director of the newly designated Hormone Research Institute. Li maintained strong ties with Tiselius and two future directors of University of Uppsala departments, Dr. C.A. Gemzell, Chairman (1959-72) Department of OB/GYN and Dr. Jerker Porath, Director Institute of Biochemistry, trained under Li at the HRL. The isolation of human growth hormone in 1955 and the successful synthesis of human growth hormone in 1971 confirmed Li's place in scientific history. The direct clinical applications of growth hormone in the treatment of children with hypo-pituitary dwarfism drew Li into cooperation with clinical trials and publicity of these discoveries provoked floods of letters to Li and the HRL.

The University of Chicago attempted to recruit Li in the late 1950s, but he remained with the University of California. In 1967 both the lab and his professorial affiliations moved from Berkeley to San Francisco. The change in location appears to have had little or no effect on the laboratories focus or function. Li continued to unlock the secrets of the pituitary. He and his lab were responsible for the isolation and amino acid sequencing of prolactin (ovine) which stimulates milk production, the semi-synthesis of ovine corticotrophin and the total synthesis of human ACTH (adrenocorticotropin) which were important in the treatment of inflammatory disease before the development of cortico-steroids, the isolation and sequencing of lutropin (ovine and human) and thyrotropin (human), and the isolation, sequence determination and synthesis of b-melanotropin or b-MSH (porcine, bovine and camel), as well as the discovery, isolation, structure and synthesis of corticotropin-inhibiting peptide.

His final major discovery while at HRL grew out of his labs isolation, in 1964, of sheep lipotropin which had powerful lipid-mobilizing properties. It also appeared to be a precursor of b-MSH. Li felt that there was more to this protein than was immediately obvious. In 19__ he first discovered that lipotropin could be cleaved to yield b-endorphin, a protein with morphine-like effects first isolated by Li from camel pituitaries and later human and other species. This led to two new fields of research, the defining of "pro-hormone" precursors, and the study of endorphin and the enkephalins. b-endorphin sparked a whole new area of clinical research and cooperation. It was hoped that b-endorphin would help with pain relief since camels who produce relatively large amounts of this protein are almost totally impervious to pain. It was also investigated as a possible treatment for drug addiction, depression, and schizophrenia.

He retained his professorships and directorship until his "retirement" in 1983 when William Rutter became Director of the HRL, and shifted the laboratories focus towards biochemistry/biophysics. Li was then given his own Molecular Endocrinology Laboratory which he ran until his death from Cancer in 1987. His last major accomplishment, the identification and purification of insulinlike growth factor I in 198_ took place at the Molecular Endocrinology lab and he was awarded his final honor --the Pierce Award at the Tenth American Peptide Symposium in 1987 just months before his death.

Other awards and honors earned by Li during his life include the California Section Award of the American Chemical Society (1951), the Francis Amory Septennial Prize of the American Academy of Arts and Sciences (1955), a Gold Medal from the Minister of Education of the Republic of China (1958), the first Lasker Award for Basic Medical Research (1962), the Golden Plate Award from the American Academy of Achievement (1964), a Gold Medal from the City of Milan, Italy (1967), the University Medal in Liege, Belgium (1968), the City of Hope National Medical Center Award (1969), the Modern Medicine Distinguished Achievement Award (1970), a Scientific Achievement Award from the American Medical Association (1970), the National Award of the American Cancer Society (1971), the Nicholas Andry Award from the Association of Bone and Joint Surgeons (1972), the Lewis Price of the American Philosophical Society (1977), the Nichols Medal of the American Chemical Society (1979), a Science Award from the Academia Santa Chiara, Genoa, Italy (1979), the Koch Award of the Endocrine Society (1981), the Heyrovsky Gold Plaque of Honor for Achievement in Chemistry from the Czechoslovakia Academy of Sciences (1982) and the Luft Medal of the Swedish Society of Endocrinology (1986).

He also received awards from a number of Chinese-American organizations including the Chinese-American Citizen Alliance (1961), the Chinese Society of Engineers (1965), the Chinese-American Physicians Society (1977), The Shoong Foundation (1980), the Chinese Hospital of San Francisco, the American Chinese Medical Society (1983) and the Mid-America Chinese Science and Technology Association (1984).

Though nominated at least twice for the Nobel prize, this highest of scientific awards eluded him, though he was invited to nominate a candidate for the 1957 Nobel for Physiology and Medicine. He nominated Dr. Charles Huggins. Li was also active on the prize committees for the Lasker (1970, 1975, 1979, and 86) and Amory Prizes (1977, 1979, 1981-87) as well as serving on grant review committees for the American Cancer Society (1971-83).

Li's association with the University of California spanned more than five decades, during which he served as mentor to a number of students who went on to prominent scientific careers including several department heads. Alumni of the HRL include: Dr. Yehudith Birk, Hebrew University, Israel; Dr. R.D. Cole, University of California Berkeley, Dr. Laszlo Graf, Institute of Drug Research, Budapest, Hungary; Dr. C.Y. Lee, Chinese University, Hong Kong; J.E. Leonis, University of Brussels, Belgium; Dr. Lin Ma, Vice-chancellor, The Chinese University of Hong Kong; Dr. T.B. Lo, National Taiwan University; Dr. N.R. Moudgal, Indian Institute of Science, Bangalore, India, Dr. Willem Oelofsen, University of Port Elizabeth, South Africa; Dr. Brian T. Pickering, University of Bristol England; Dr. R.S. Schwyzer, Swill Federal Institute of Technology, Zurich; and Dr. P.G. Squire, Colorado State University.

He also received honorary degrees from 10 Universities. Including three in 1971, the year that the synthesis of Human Growth Hormone was announced (University of the Pacific, Marquette University and Saint Peter's College ). The other degrees were from the Catholic University of Chile (1962), Chinese University of Hong Kong (1970), University of Uppsala, Sweden (1977), University of San Francisco (1978), Long Island University (1979), University of Colorado (1981), and the Medical College of Pennsylvania (1982).

Li is credited with being an excellent teacher who encouraged the free flow of ideas within his laboratory. Hew was always ready to play devil's advocate and pressed his students and associates to be creative as well as able to back up there opinions. More than one student wrote Li, after leaving his lab, that they missed the openness and independent working conditions that Li provided.

Professional Activities

Beyond his academic and lab duties Li was very active in the wider scientific community serving on the Scientific Advisory Board for the Sloan Kettering Institute for Cancer Research, New York (1952-55), and as Scientific Advisor for the Children's Cancer Research Foundation, Boston (1963-73), in the United States. He was also active in promoting the study of science and specifically Biochemistry in China through his service on the advisory boards of two Chinese Institutions. He served on the Academic Advisory Board of the Chinese University of Hong Kong (1963 -87), and as Chairman of the Advisory Board (1971-77), then as Corresponding Member (1979-83) and finally again as Chairman (1983-87) of the Institute of Biological Chemistry of the Academia Sinica in Taipei, Taiwan,

He also served chairman or president for a number of national and international scientific symposia including the International Symposium on Protein and Polypeptide Hormones, Liege, Belgium (1963), Conference on Glycoproteins with Hormonal Activities, National Institutes of Health (1971), Second International Symposium on Growth Hormone, Milan Italy (1971), Symposium on Gonadotropins, Bangalore, India (1973), International Symposium on Growth Hormone and Related Peptides, Milan, Italy (1975), 12th Miles International Symposium on Peptide Hormones, Baltimore (1979), and the International Symposium Growth Hormone and Other Biologically Active Peptides, Milan Italy (1979). At the time of his death he was making plans to attend yet another international event, the centennial celebration at the Catholic University in Santiago, Chile, hosted by his long-time associate Hector R. Croxatto.

Publishing is an integral part of modern academic scientific practice and Li published with a vengeance, authoring or co-authoring over 1000 papers during his career and collaborated with at least 300 other scientists. He also shared his knowledge through a variety of editorial activities. He Edited Hormonal Proteins and Peptides, volumes 1-11, (Academic Press Inc.) 1973-83. There are no documents relating to his editing of vol 13 (1987). And he co edited Methods in Medical Research, volume 3, 1950 and Perspectives in the Biochemistry of Large Molecules, Supplement I, Archives of Biochemistry and Biophysics, 1962, was Section Editor of Amino Acids, Peptides and Proteins, Chemical Abstracts, 1960-63 and Specialist Subject Editor for the International Encyclopedia of Pharmacology and Therapeutics (Pergamon Press) 1975-77. He served first as Co-associate Editor (1969-76) and then as Editor-in-Chief (1977-87) for the International Journal of Peptide and Protein Research, as well as serving on editorial advisory boards for both Scientific and Popular journals such as the Archives of Biochemistry and Biophysics (1959-68, 1985-87), General and Comparative Endocrinology (1961-66), Molecular Pharmacology (1965-68), Family Health (1969-82), Current Topics in Experimental Endocrinology (1969-87), and Biopolymers (1979-86).

Li was also actively involved in the creation of Pituitary Banks, in an attempt to insure an adequate amount of human pituitaries for both research and clinical uses. The lack of adequate supplies of pituitaries from which to extract human growth hormone for the treatment of more than a token number of dwarf children was a major motivating factor in the push to synthesize the hormone.

In order to insure the funding of his work Li and Alice Fordyce of the Lasker Foundation organized the Hormone Research Foundation around 1968. Li served as President of the Foundation until his death.