University of California: In Memoriam, 1988

Choh Hao Li, Biochemistry: San Francisco


1913-1987
Professor of Biochemistry and Experimental Endocrinology, Emeritus
Emeritus Director of the Laboratory of Molecular Endocrinology

The death of Professor Choh Hao Li in Berkeley, California, in late November 1987 brought to an end an era of slightly over 52 years of intimate association with the University of California. In 1938 when he began his own research on the isolation and purification of the anterior pituitary hormones, none of the six then known anterior pituitary hormones had been identified chemically. The following years covered a period of unparalleled advances in the isolation and chemical assessment of a large group of pituitary protein and peptide hormones. By the time of Professor Li's death, all of the original six anterior pituitary hormones had been chemically identified, their amino acid sequences determined, and one of them, human growth hormone, was being sold for clinical use after synthesis by recombinant DNA technique. Professor Li was the major contributor to all of this and furthermore he and others had discovered, chemically identified, and synthesized a variety of peptide hormones other than the six originally attributed to the anterior lobe, subserving a wide group of physiological functions.

Professor Li was born in Canton, China (Guangzhou), the fourth of 14 children of Kan Chi Li and Mew Shing Twui. He graduated from Pui Jing High School in Canton and then attended the University of Nanking where he received a B.S. degree in chemistry in 1933. From that year until the summer of 1935 he was an instructor in chemistry and during these years he conducted research leading to his first scientific paper published in 1935. When Professor Li received the Nichols medal from the American Chemical Society in March, 1979, in his acceptance speech entitled, Faith and Fate: My Personal Experiences, he recounted briefly how he applied for graduate work in the United States at the Universities of California and Michigan and how he was turned down by the University of California


89
but accepted by Michigan. En route to Michigan, he stopped in Berkeley to visit his older brother, Choh Ming Li, who was then completing his Ph.D. in economics. His brother insisted that he, C.H., should see Professor G.N. Lewis, Dean of the College of Chemistry in Berkeley. C.H. had brought with him a reprint of his article in the Journal of American Chemical Society of which Professor Ward V. Evans of Northwestern University was senior author. Since Ward Evans was known to Lewis, Lewis decided to accept C.H. as a graduate student on probation for one semester. Thus began his long association with the University of California.

In June of 1938 Li received a Ph.D. degree in chemistry from the University of California and that summer he became a research associate in the Institute of Experimental Biology, having been recruited by Herbert M. Evans to join the group of chemists and biologists engaged in a joint effort on the isolation, purification, chemical identification and biological studies of the anterior pituitary hormones. From that time on, until literally a few weeks before his death, Li continued to be active in research, always in a hands-on fashion. When he began his tenure in the Institute of Experimental Biology all of the six then known pituitary hormones were thought to be protein in nature but none had been purified to the point of either biological or chemical purity. The methods of determining whether protein preparations were pure and a single molecular species were primitive 50 years ago compared to methods now available. In the forefront of the methods then becoming available, was ultra-centrifugation and the determination of the electrophoretic pattern obtained through the use of the Tiselius apparatus. It was typical of his ability to recognize and use new methodology that Li personally constructed a Tiselius apparatus in the Institute of Experimental Biology where it served him well for many years.

Before the mid-1940s Li had isolated a protein preparation which was apparently homogenous and possessed high adrenocorticotropic (ACTH) activity. He also obtained an increasing body of experimental evidence leading to his view that this protein was possibly a carrier of, or precursor for, much smaller peptide molecules containing ACTH activity. This culminated in 1954 with the isolation from sheep pituitaries of a smaller molecule named α-ACTH which was not only a more potent stimulator of the adrenal cortex but also possessed other activities, producing fat mobilization and having melanocyte stimulating (MSH) activity (i.e., the darkening of skin in certain vertebrates due to the dispersion of pigment in melanocytes). Subsequently he demonstrated that α-ACTH was a 39-amino acid peptide. Because it contained more than just ACTH activity, a search was undertaken to identify the part of the molecule possessing these different activities. This was successful and resulted in the synthesis of a 19-amino acid peptide with potent ACTH activity.

In pursuing better procedures for the isolation of ACTH, Li and his collaborators isolated two new substances which clearly were different


90
from either ACTH itself or MSH. Both were larger than ACTH and contained lipolytic as well as MSH activity. The larger of the two molecules isolated in 1964 was named beta-lipotrophin (β-LPH). Professor Li had long been active in comparative studies of pituitary hormones from different animal species and about 10 years later in searching for β-LPH from camel pituitaries, he succeeded in isolating a unique 31-amino acid peptide fragment of β-LPH. When two pentapeptides from the brain which competed with morphine for binding sites in the nervous system were found, it was noted that the amino acid sequence of one of them, methionine-enkephalin, was part of both the 31-amino acid peptide and β-LPH. Because of these identities the 31-amino acid peptide was tested and found to have potent opioid-like properties being several times more active than morphine as a pain reliever. It was named β-endorphin (a contraction of endogenous morphine) and subsequently was shown to be present in many animal species, its primary molecular structure being strongly conserved in evolution. All this work relating to the hormonal activities of substances related to ACTH is a major part of the corpus of knowledge leading to the current belief that the pituitary produces a large molecule, proopiomelanocortin, which can be processed into many smaller peptides with varied activities.

In the early 1940s Li obtained a highly purified and potent preparation of bovine growth hormone. This, by all standards, was the most active and purified growth hormone preparation yet to be obtained anywhere in the world. Thus began a long, protracted period of research directed at elucidation of the amino acid sequence of growth hormone from cattle and other species. Of prime importance was his isolation of human growth hormone in 1956 and later the determination of its structure, since it was known that humans do not respond to growth hormone of any species other than man or the higher primates. This culminated in the synthesis of human growth hormone both by chemical means and by recombinant DNA technology. Concomitantly with much of the work on growth hormone isolation and structure, was the comparable work on lactogenic hormone or prolactin. Growth hormone preparations, even when highly purified to apparent homogeneity exhibited significant prolactin activity and these two hormones have a high degree of chemical similarity. The question of whether growth hormone itself had intrinsic prolactin activity was never satisfactorily answered until human growth hormone was synthetically prepared. The synthetic hormone continues to exhibit both activities which appear to distinguish it from growth hormone isolated from other vertebrate species.

At the time Li joined the staff of the Institute of Experimental Biology in 1938, most endocrinologists would have agreed that there were two gonadotropic hormones in the anterior pituitary. One was concerned primarily with the stimulation of growth of follicles in the ovary and the other with stimulation of the interstitial tissue and perhaps conversion of follicles to


91
corpora lutea. Li's first paper in 1939 dealt with the characterization of these gonadotropic hormones by their sugar content. Over the years, work continued on the isolation, purification, and chemical characterization of these gonadotropins. In a sense this work reached its culmination with the recognition in 1964 of the two-chain dissociable nature of the gonadotropic hormones. A comparable structure is known to be present in thyrotropic hormone; thus all three are closely related chemically and all are glycoproteins. The last decade of work in his laboratory demonstrated an increasing interest in substances such as somatomedin which is thought by many to be a mediator of growth hormone activity in the intact animal.

Li was generous in providing hormone preparations he had made to fellow workers worldwide. He also was generous in acknowledging the contributions of his students, post-doctoral fellows, and laboratory staff. In surveying his bibliography it is not unusual to find laboratory technicians among the co-authors of many papers. With the establishment of his own laboratory, the Hormone Research Laboratory, in Berkeley in 1950 and later in San Francisco, C.H. Li nurtured an environment which in many respects was very much like a family. The family, representing senior staff, post-doctoral scientists, students, and technical staff numbered 200 or more over the years. These people came from not only the United States, but from every continent in the world. Becoming an Emeritus Professor and retiring as Director of the Hormone Research Laboratory in 1983 was not an occasion for his becoming inactive. Rather, he established yet another laboratory, the Laboratory of Molecular Endocrinology at UCSF where he could continue his hands-on research style with somewhat fewer administrative duties.

Many awards and honors came to C.H. Li for his scientific work. He was the recipient of 10 honorary degrees from universities both in the United States and abroad. He received 28 honors and awards among which was the Koch Award from the Endocrine Society, the Luft Medal from the Swedish Society of Endocrinology, and the Lasker Award. He was fellow or member of 14 societies, six of which were foreign. Among them was his honorary membership in the Harvey Society of New York as well as his membership in the National Academy of Sciences. He was much sought after for visiting professorships and lectureships, of which he held 17. Prominent among these was the first Herbert M. Evans Memorial Lectureship and the Faculty Research Lectureship at the University of California, San Francisco. He was also the first Geschwind Memorial Lecturer at the University of California, Davis. Li was on numerous advisory boards for a wide variety of activities such as the Sloan Kettering Institute for Cancer Research and the First and Second International Symposia on Growth Hormone, of which he was President. He had also been designated as the Honorary President of the 8th International Congress of Endocrinology


92
held in Kyoto, Japan in 1988. True to his heritage, Li was very much personally involved as a member of the Advisory Board of the Chinese University of Hong Kong as well as Academica Sinica and the National Science Council of Taiwan. He not only published over 1,000 scientific papers, but was also an indefatigable editor of many journals, and series of books such as the Academic Press Hormonal Proteins and Peptides.

C.H. Li met Annie Lu of Nanchang, Kiangsi Province, in the Fall of 1931 when both were students at the University of Nanking. Annie Lu was a freshman in the Department of Agricultural Economics in the School of Agriculture. They dated until 1935 and then continued in correspondence during the period of graduate studies by C.H. in Berkeley while she stayed at Nanking completing her B.S. degree and becoming an instructor. In 1938 she was admitted for graduate work at both Cornell and UC Berkeley and upon her arrival at the Berkeley train station they met again and they were married October of that year. She continued graduate work in Berkeley and received an M.A. degree in Agricultural Economics. Although she was not a scientist they were full partners in his research. “He would show her the draft of his papers for her to read the introductions and the conclusions.” He also discussed titles of papers with her and daily briefed her about happenings in the laboratory. The couple had three children, Wei-i Li, a cardiac surgeon, Ann-Si Li, a veterinarian, and Eva Li, an architect. C.H. Li and Annie built their final home in Berkeley near the Arlington Circle and it was here that their children matured. Later they built and extensively used, a small retreat on the shores of Bodega Bay. They were among the most gracious of hosts in their home, at dinners arranged by them for visitors at local restaurants, or at formal banquets for international meetings. Their aesthetic tastes were cosmopolitan and both their home and Dr. Li's university office pleased the eye with fine examples of artistic work from both East and West. C.H. himself did things with his hands other than building scientific equipment or things for his home. He liked classical music and for a considerable period of time, took cello lessons from one of the premier teachers of the East Bay.

Professor Li left an enormous legacy of accomplishments to the world of science as well as a standard of continuous discipline of organization and hands-on personal involvement in research. As a friendly, humane person of wide interests, he is mourned by his family, his students, his colleagues, and his associates throughout the world.


Ergo vivida vis animi pervicit
--Lucretius

Leslie L. Bennett David Chung Harold Papkoff E. Leong Way

About this text
Courtesy of University Archives, The Bancroft Library, University of California at Berkeley, Berkeley, CA 94720-6000; http://bancroft.berkeley.edu/info
http://content.cdlib.org/view?docId=hb967nb5k3&brand=calisphere
Title: 1988, University of California: In Memoriam
By:  University of California (System) Academic Senate, Author
Date: 1988
Contributing Institution:  University Archives, The Bancroft Library, University of California at Berkeley, Berkeley, CA 94720-6000; http://bancroft.berkeley.edu/info
Copyright Note:

Transmission or reproduction of materials protected by copyright beyond that allowed by fair use requires the written permission of the copyright owners. Works not in the public domain cannot be commericially exploited without permission of the copyright owner. Responsibility for any use rests exclusively with the user

University of California Regents

Academic Senate-Berkeley Division, University of California, 320 Stephens Hall, Berkeley, CA 94720-5842