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ROBERT KHO-SENG LIM
October 15, 1897-July 8, 1969
BY HORACE W. DAVENPORT
ROBERT K. S. LIM lived two lives. In the first, he was
a physiologist with research interests in the control of
gastric secretion and the neurophysiology of pain. He estab-
lishecl Western physiology in China while teaching at the
Peking Union Medical College.
In his second life, Robert K. S. Lim organized medical
relief corps and trainee! doctors, nurses and technicians to
meet the needs of China at war. He supervised meclical ser-
vices on the field] of battle from the Great Wall to the retreat
with Stilwell through the Burmese jungle. He built hospitals
and meclical schools on MainIanc! China and on Taiwan, and
after the war he rebuilt his country's meclical education and
medical research. He was "one of the great men of China,"*
the abundantly clecoratec] Lieutenant General in the Army
ant! Surgeon General of the Republic of China.
In both lives, Robert K. S. Lim was the vivacious, gen-
erous, charming, energetic, athletic and artistic man who
spoke with a Scottish burr and was universally known as
Bobby.
Robert Lim's ancestors came to Singapore from Fukien
Province in southwestern China. The surname means a small
* B. Tuchman, Stilwell and Me American Experience in China, 1911-45 (New York:
Macmillan, 1970).
281
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282
BIOGRAPHICAL MEMOIRS
forest represented by two trees, ant! the present official trans-
literation of the charcter is Lin. Although the Lim family, like
many from their province, retained the old spelling, R. K. S.
Lim sometimes appears in the indexes of books about war in
China and in library catalogs as R. K. S. Lin.
Robert Lim's father, Lim Boon Keng, dic3 so well as a poor
boy at the Raffles Institution in Singapore that he won the
Queen's Scholarship to Edinburgh University where he grad-
uated in medicine. He worker! briefly with W. B. Harcly in
Cambridge, and together they published a paper in the
Journal of Physiology* on the origin and function of leucocytes
in the frog. On returning to Singapore, I.im Boon Keng
practiced medicine, but he was also active in public affairs in
China as well as in Singapore. He was a Legislative Council-
lor, and in 1911 he was appointed Medical Advisor to the
Chinese Ministry of the Interior. The next year he became
physician and confidential secretary to Sun Yat-sen. He rep-
resented his country at meetings in Paris and Rome, ant! in
1923, with the help of a millionaire friend, he established the
University of Amoy. Lim Boon Keng married Margaret
Tuan-Keng Wong, one of the first Chinese women to be
eclucated in the United States, and they had four sons, the
oldest being Robert Kho-seng. Lim Boon Keng (lied at the
vernerable age of eighty-eight in Singapore.
Bobby Lim was born in Singapore on October 15, IS97.
His father sent Bobby to ScotIancl when he was eight years
old. The boy was in the charge of his father's apothecary, who
was also an itinerant lay preacher, and in moving from parish
to parish, Bobby's education was more peripatetic than
substantial. Later, Bobby attended Watson's School in Ectin-
burgh where he prepared for the University. At the outbreak
of the First World War, Lim volunteered! and was assigned to
*journal of Physiology, 15(1894):361-74.
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ROBERT KHO-SENG LIM
283
the Indian Army in France as a warrant officer. His job was
to drill recruits, and the young sons of Maharajas who had
joined the colors objected to being ordered arounc! by a
young "Chinaman." In 1916, Lim was allowed to return to
Edinburgh for medical studies, ant! he receiver! the M.B. and
Ch.B. degrees in 1919.
In the Medical School of Edinburgh University, Lim
quickly established himself as a protege of Sir Edward
Sharpey-Schafer, the Professor of Physiology, and as an
undergraduate he worked in the Physiology Laboratory on
problems suggested by Sharpey-Schafer. Immediately upon
graduation, he was appointed Lecturer in Physiology with
responsibility for teaching histology. The next year Lim pre-
sented the results of his research to earn the Ph.D.
In the tradition of British physiology, microscopic anat-
omy came within the purview of the Physiology Department,
and Lim cleveloped skill in histological techniques and obser-
vations. His first major publication was a study of the his-
tology of tadpoles whose development had been accelerated
by being fed thyroid. This paper is notable for Limes draw-
ings. Lim had considerable skill as a draughtsman, and he
tract transiently wanted to be an artist before his father per-
suaclecl him to try medicine first. He continued to illustrate
his papers with clelicate drawings. The best example is Lim's
paper, published in 1922,* on the microscopic anatomy of
the gastric mucosa. The paper is distinguished by its smooth
style, by its thoroughness baser! on wide observation and
meticulous attention to detail, and by its correlation of struc-
ture with function.
him carried the microscopic anatomy of the gastric mu-
cosa almost as far as it could be carried until the advent of
electronmicroscopy. In fact, he carried it a little further than
*Quarterly Journal of Microscopical Science, 66(1922): IS7-2 12.
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284
BIOGRAPHICAL MEMOIRS
the resolution possible in light microscopy warranted, for in
papers publishes] later from China he described how mito-
chondria dissociate cluring secretion into a free lipid which
condenses to form the Golgi apparatus and a remainder
which either catalyzes or enters into the secretion.
Lim described the structure of the stomach, because he
was aIreacly studying its function. The results were reported
in a flood of papers in 1923.
At this time research in gastrointestinal physiology was in
the doldrums. In Russia, Pavlov had turned to the study of
conditioner] reflexes, and in the United States, Walter
B. Cannon had stopped work on the mechanical factors of
digestion when he discovered he had been burned by X-rays.
Cannon's observation on the supposes! relation between gas-
tric motility and the sensation of hunger had been taken up,
without any notable results, by A. J. CarIson, whose reputa-
tion rests more on his picturesque behavior than on his
scientific accomplishments. CarIson's industrious pupil,
Andrew C. Ivy, was just beginning his long career.
In 1902 William Bayliss ant! Ernest H. Starling had estab-
lishec! the fact that a hormone from the upper intestinal
mucosa, secretin, could stimulate pancreatic secretion, but no
progress had been maple in purifying the hormone or in
delineating its role in the course of digestion. Ec~kins had
shown, by methods very similar to those of Bayliss ant!
Starling, that extracts of the gastric antral mucosa stimulate
secretion of acid by the oxyntic mucosa, and he had postu-
latec! that his extracts contained a hormone which he called
gastrzn. Unfortunately for E6kins, the two subsequent
discoveries—that crude tissue extracts always contain his-
tamine ant! that histamine stimulates acid secretion were
generally interpreted to mean that E6kins had made a
luclicrous mistake.
This conclusion, which was to trouble gastroenterology
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ROBERT KHO-SENG LIM
285
for another fifty years, was not accepted by Robert Lim. He
repeated E6kins's experiments with no significant improve-
ment, and he found that extracts of the pyloric mucosa, but
not extracts of other tissues, stimulate acid! secretion. Rec-
ognizing that the crucial test of a gastric hormone wouIc! be
demonstration of it in gastric venous blooct, Lim unsuccess-
fully tried to finct acid-stimulating properties in blooc! drawn
from clogs digesting a meal.
Lim became interested] in the properties of pyloric secre-
tion. With his colleague, N. M. Dott, Lim prepared, in a
two-stage operation, a pouch of the gastric antrum devoid of
oxyntic mucosa. Dott probably contributed much of the
surgical skill, for he published separately on operative tech-
niques. The pouch was found to secrete a viscid, alkaline
secretion containing a proteolytic enzyme active in acid but
not in alkaline solution. A dog with such a pouch was reacly
for the next step: the demonstration that stimulation of the
pouch causes acid secretion by the remote oxyntic mucosa,
but Lim did not do the experiment.
In the autumn of 1922, lLim applied to the China Medical
Board of New York for a fellowship to enable him to study in
European and American universities. His application was im-
mediately welcomed by Roger S. Greene, the Board's Secre-
tary. Greene knew Lain Boon Keng by reputation, and the
day before he received Lim's letter he had been toIcl about
Lim by the Chinese Minister to the United States. Greene
asked Lim whether, if he received a fellowship, he wouIct be
willing to take a year's appointment at the Peking Union
Medical College.
The Peking Union Medical College had been developed
by the China Medical Board with an endowment from the
Rockefeller Foundation. In 1915 the Board, with the advice
of W. H. Welch and Simon FIexner, tract bought the mis-
sionary-foundecI Union Medical College in Peking anct had
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286
BIOGRAPHICAL MEMOIRS
begun to build a medical school along Western lines.* 'rhe
aims of the school were "to give medical education compara-
ble with that provident by the best mectical schools in the
United States and Europe, through..."! an undergraduate
curriculum and through graduate training in research and
practice. Emphasis was always on quality, and pressure from
the Chinese government for quantity was firmly resisted. The
stated goal of those responsible for the College was to have
Western medical science taken over by the Chinese people so
that it became part of their national life. The suggestion that
Lim consider an appointment at P.U.M.C. was an example of
the Boards continued search for competent Orientals.
Lim replied that the chief object in his life was to return
to China to teach physiology and to clo research there as
efficiently as it was being done in the West. However, he
cautiously refused to commit himself completely to P.U.M.C.
without assurances of an acloquate salary and a senior
appointment.
Him received the fellowship, and he came to the United
States in the autumn of 1924. Although the China Medical
Board tract suggested that I,im study in two departments,
those of Joseph ErIanger in St. Louis and A. J. CarIson in
Chicago, Lim worked only in the Department of Physiology
of the University of Chicago. That laboratory was the only
one in the country with a current reputation in gastro-
intestinal physiology. Most of the work was being clone by a
*The administrative history of P.U.M.C. is fully described in M. E. Ferguson,
China Medical Board and Peking Union Medical College (New York: China Medical
Board of New York, Inc., 1970). The records of the China Medical Board and of
P.U.M.C. are now in the Rockefeller Archive Center, North Tarrytown, New York.
Copies of letters relating to Lim have been made available to me through the
courtesy of the Center's Director and Associate Director, I. W. Ernst and I. W. Hess.
The educational and scientific program of P.U.M.C. is described in J. Z. Bowers,
Western Medicine in a Chinese Palace (New York: The Josiah Macy, Jr. Foundation,
1972). Bowers is wrong in identifying Lim's first wife as Sharpey-Schafer's daughter.
tFerguson, p. 44.
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ROBERT KHO-SENG LIM
287
team uncier A. C. Ivy, and Lim was put to work as a member
of the team. Research was on the control of gastrointestinal
secretion and motility, and dogs with chronically prepared
pouches and fistulas were usecI. In one stucly in which Lim
participated, the entire stomach was separated from the
esophagus and duodenum, and macle into a pouch draining
to the body surface. The vagus nerves hac! been cut, ant!
cephalic stimuli could not affect the pouch through them.
The pouch's secretion could be collected, and thereby the
efficacy of stimuli could be cleterminecI. Because the distal
end of the esophagus had been anastomosed to the proximal
end of the cluodenum, the clog could eat naturally. With such
a preparation, Ivy, Lim and McCarthy found that mixed
meals, meat extracts and milk stimulated gastric secretion
after a latent period of one or more hours. Fats fee! inhibited
basal or continuous secretion.
This team, and indeec! all such teams for many years, was
dominated by Ivy; Lim, as a visiting fellow, cannot be held
responsible for the conclusions of papers bearing his name.
He can only be juciged by the use to which he later put what
he had Earned in Chicago. The paper just cited lamely con-
cludec! that stimulation of gastric secretion by foocI in the
intestine must result from some vascular response. More-
over, ". . . our work proves that E6kins' pyloric hormone
theory is utterly inadequate; that there is either no hormone
mechanism, or, if one, that the whole gastro-intestinal tract is
involved."* What Lim thought when he eventually saw this
paper in print is unknown, but it seems unlikely that he, who
tract only recently published several papers of his own af-
firming the existence of gastrin, hacl abruptly changed his
mincI.
* A. C. Ivy, R. K. S. Lim, and J. E. McCarthy, "Contributions to the Physiology of
Gastric Secretion. II. Intestinal Phase of Gastric Secretion," Journal of Experimental
Physiology, 15(1925):55-68.
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288
BIOGRAPHICAL MEMOIRS
Having received a satisfactory appraisal of Lim from A. J.
Carison, a recommendation which said that Lim made an
excellent impression even on those prejudiced against the
Chinese, the China Medical Board recommenclec! that Lim be
made an Associate Professor in physiology at P.U.M.C. In the
meantime, Lim's father hac! begun to organize the University
of Amoy, and he asked his son to build a mectical school from
scratch. In contrast with the superb school, hospital, and staff
being completecl in Peking, Amoy had no buildings and no
faculty, but young Lim conic! have at least the title of Profes-
sor. To get him for Peking, the P.U.M.C. made him a Visiting
Professor with no increase in salary over that previously
offered. In September of 1925 the trustees of the school
made him Head of the Department of Physiology.
By the time Lim arrived in Peking in 1924, the builclings
of P.U.M.C. had been completed. The preclinical and clinical
clepartments, a hospital, and faculty residences occupied the
site of a Prince's palace. The Prince's name of Wu sounder!
much like the Chinese word for oil, anct P.U.M.C. was known
to the Chinese as the Oil Prince's Palace. Lim occupied a fully
equipped Physiology Department, and during his tenure
from 1924 to 1938 he hacl a staff of seven professionals, five
of them Oriental. The China Medical Board sent visiting pro-
fessors to P.U.M.C., and the list is an honor roll of American
meclical science. In ~ 935 both Anton I. Carison ant] Walter B.
Cannon were Visiting Professors of Physiology.
him establishecl a vigorous research program in collabora-
tion with many colleagues and students. He foun~lec! the
Chinese Physiological Society, and the Society began publica-
tion of the Chinese Journal of Physiology. I.im was managing
editor, and he published many papers in the journal. He also
organized a Peking branch of the Society for Experimental
Biology and Medicine which gave him the opportunity of
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ROBERT KHO-SENG LIM
289
publishing summaries of his work in a journal more easily
accessible to Western physiologists.
By means of transplanted ant! perfused stomachs, Lim
stuclied gastric metabolism and the control of secretion. His
most important result was the demonstration that feeding
olive oil inhibits secretion by a transplanter! pouch of the
stomach. In the process of preparation, the gastric tissue
forming the pouch was totally separated from the donor dog,
and it was therefore completely extrinsically clenervated. The
inhibitory influence of fat feeding must have been carried by
the blood, and Lim showed that fat absorbed into the lymph
was not responsible. Lim coined the word enterogastrone for
the putative hormone, and he shower! that it is probably
different from the hormone cholecystokinin which had
recently been identiBlecl by Ivy. Lim attempted to purify
enterogastrone, but he succeeded no better than many after
him. Today, it appears that the inhibitory property of entero-
gastrone is only one of the properties of a number of poly-
peptides extractable from the intestinal mucosa. Although
the hormonal mechanism clescribed by Lim indubitably
exists' his name for it is being discarded.
Working with pupils ant! colleagues from other depart-
ments, Lim clid three other substantial pieces of physiological
research at P.U.M.C. He found a presser center in the lateral
parts of the floor of the IVth ventricle between the levels of
the acoustic strict and the inferior fovea. Stimulation of the
center electrically or by iontophoresis of acetylcholine elicits
typical and complete sympathetic responses. The efferent
pathway goes unilaterally clown the ventrolateral columns of
the spinal cord, and through it both sympathetic neurones
and the adrenal medulla are excited. Stimulation of the
central end of the cut sciatic nerve has its familiar presser
effects mediated by the center Lim described. In a thorough
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290
BIOGRAPHICAL MEMOIRS
comparative study, Lim demonstrates! that a similar presser
response follows stimulation of corresponding parts of the
medulla in fish, amphibians, reptiles, birds, and eight species
of mammals.
Lim's efforts to identify circulating hormones released
from the gastrointestinal mucosa made him a master of the
techniques of cross circulation and vivi-perfusion. In vivi-
perfusion, an organ removed from a donor animal, usually a
dog, is perfused by way of the carotid arteries anc! jugular
veins of another animal. The perfusing animal is frequently
unanesthetized, its vessels being isolated uncler local anes-
thetic. Lim used this method to study humoral transmission
in the central nervous system. In this case, the organ per-
fused was the severed head of a donor dog. Stimulation of the
central ens! of the vagus nerves of the perfused heat! is fol-
lowed by a small and brief fall in the blooct pressure of the
perfusing dog and then by a large and prolonged rise in its
blooc! pressure. Lim showed, using standarct pharmacologi-
cal and physiological methods, that the response is me(li-
ated by acety~choline liberates! by the perfused head. The
transient fall in blood pressure is the direct effect of acetyI-
choline on the cardiovascular system, and the rise is caused by
epinephrine liberatecl from the adrenal medulla under the
stimulus of acety~choline.
Using the same vivi-perfused preparation, but one in
which the life of acety~choline was not prolonge(1 by eserine,
Lim found that when afferent fibers of the vagus nerve are
stimulated there is also a pressor response, but one which is
abolished by extirpation of the donor's pituitary glancI. Fur-
thermore, bloocl draining the perfused head also contains an
oxytocic and an anticliuretic principle. Lim, returning to his
histological methods, found that exhaustion of the reflex is
correlate(1 with disappearance of secretory granules from the
posterior pituitary gland, and that the reflex returns when
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ROBERT KHO-SENG LIM
297
Corresponding Member, Royal Academy of Sciences, Bologna,
1932
Member, Permanent Commission for Biological Standardization,
League of Nations, 1935
Counsellor, Academia Sinica, 1936
Foreign Associate, National Academy of Sciences, Washington,
1942; Member, 1955
Honorary Member, American Gastroenterological Association,
1946
Honorary Fellow, American College of Surgeons, 1947
Member, Permanent Committee of the International Congress of
Physiology, 1947
Honorary Member, Association of Military Surgeons of the United
States, 1948
American Society for Pharmacology and Experimental Therapeu-
tics, 1952
Society of Toxicology, 1963
Fellow, American College of Clinical Pharmacology and Chemo-
therapy, 1964
MILITARY RECORD
Warrant Of firer, Indian Army, 1914- 1916
Lieutenant, RAMC,1919
Field Director, Chinese Red Cross Medical Relief Commission,
North China, 1933
Director, Chinese Red Cross Medical Relief Corps, 1937-1943
Inspector General of Medical Service, Chinese Army, 1942,1944
Deputy Surgeon General, Chinese Army, 1944~1945
Surgeon General and Lieutenant General, Chinese Army, 1945-
1949
D E C O. RA T. I O N S
Great Britain: 1914-1915 Star; General Service Medal, Victory
Medal, 1918
United States: Legion of Merit, Officer Grade, 1943; Medal of
Freedom with Silver Palms, 1946
Republic of China: Kan Ching Medal; Chung Ching Medal; Sheng
Li Medal; Yun Hui Order, 1st Class; Victory Medal, 1945
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298
BIOGRAPHICAL MEMOIRS
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OCR for page 301
ROBERT KHO-SENG LIM
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1932
With T. Kosaka, S. M. Ling, and A. C. Liu. On the mechanism of
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1933
With T. Kosaka. On the mechanism of the inhibition of gastric
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Observations on the mechanism of the inhibition of gastric function
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1934
With A. C. Liu and l. C. Yuan. Quantitative relationships between
the oxyntic and other gastric component secretions. Chin. I.
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1935
With H. C. Chang, T. P. Feng, S. M. Ling, A. C. Liu, T. C. Loo, and
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1936
With H. C. Chang. A simple method of mechanically stimulating
the carotid sinus receptors. Chin. I. Physiol., 10:29-32.
With T. H. Sub and C. H. Wang. The effect of intracisternal appli-
cations of acetylcholine and the localization of the presser
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myelencephalic sympathetic centre. I. The effect of stimulation
of the presser area on visceral function. Chin. l. Physiol.,
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With S. M. Ling, A. C. Liu, and I. C. Yuan. Quantitative relation-
ships between the basic and other components of pancreatic
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1937
With M. P. Chen, S. C. Wang, and C. L. Yi. On the question of a
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myelencephalic sympathetic centre. IV. Experimental localiza-
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sion of nerve impulses at central synapses. I. Sinus and vagus
afferent nerves. Chin. l. Physiol., 12: 1-36.
With Y. M. Lu. On the question of a myelencephalic sympathetic
centre. V. Comparative study of location of myelencephalic
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With H. C. Chang, K. F. Chia, and C. H. Hsu. A vagus-post-
pituitary reflex. I. Pressor component. Chin. I. Physiol., 12:
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1938
With H. C. Chang, K. E. Chia, and C. H. Hsu. Humoral transmis-
sion of nerve impulses at central synapses. II. Central vagus
transmission after hypophysectomy in the dog. Chin. J. Physiol.,
13: 13-32.
With H. C. Chang and Y. M. Lu. Humoral transmission of nerve
impulses at central synapses. III. Central vagus transmission
after hypophysectomy in the cat. Chin. I. Physiol., 13:3~48.
With M. P. Chen, S. C. Wang, and C. L. Yi. On the question of a
myelencephalic sympathetic centre. VI. Syndrome of lesions of
the myelencephalo-spinal sympathetic neurons. Chin. I. Phys-
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With S. C. Wang and C. L. Yi. On the question of a myelencephalic
sympathetic centre. VII. The depressor area a sympatho-
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With H. C. Chang, W. M. Hsieh, and T. H. Li. Humoral transmis-
sion of nerve impulses at central synapses. IV. Liberation of
acetylcholine into the cerebrospinal fluid by afferent vague.
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1939
With H. C. Chang, J. J. Huang, and K. J. Wang. A vagus-post-
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acetylcholine. VI. The liberation of acetylcholine from nerve
trunks during stimulation. Chin. I. Physiol., 14:19~26.
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nerve trunks and its synthesis in vitro. Chin. }. Physiol.,
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With H. C. Chang, K. F. Chia, and J. J. Huang. A vagus-post-
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1956
With M. H. Pindell, H. G. Glass, and K. Rink. The experimental
evaluation of sedative agents in animals. Ann. N. Y. Acad. Sci.,
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1958
With O. E. Fancher. The sedative and contrasedative activity of
the two geometric isomers of 2-ethylcrotonylurea. Arch. Int.
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1960
With M. N. Carroll. Observations on the neuropharmacology of
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Visceral receptors and visceral pain. Ann. N. Y. Acad. Sci.,
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1961
With K. G. Rink, H. G. Glass, and E. Soaje-Echague. The evaluation
of cumulation and tolerance by the determination of A-ED50s
and C-ED50s. Arch. Int. Pharmacodyn. Ther., 130:336-53.
1962
With F. Guzman and C. Braun. Visceral pain and pseudoaffective
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With Soaje-Echague. Anticonvulsant activity of some carbinylureas.
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1964
With F. Guzman, C. Braun, G. D. Potter, and D. W. Rodgers.
Narcotic and non-narcotic analgesics which block visceral pain
evoked by intra-arterial injection of bradykinin and other
algesic agents. Arch. Int. Pharmacodyn. Ther., 149:571-88.
With F. Guzman, D. W. Rodgers, K. Goto, C. Braun, G. D.
Dickerson, and R. I. Engle. Site of action of narcotic and non-
narcotic analgesics determined by blocking bradykinin-evoked
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Animal techniques for evaluating hypnotics. In: Animal and Clinical
Pharmacologic Techniques in Drug Evaluation, ed. J. H. Nodine
and P. E. Siegler, vol. 1, pp. 291-97. Chicago: Year Book
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1965
With G. D. Dickerson, R. i. Engle, F. Guzman, and D. W. Rodgers.
The intraperitoneal bradykinin-evoked pain test for analgesia.
Life Sci., 4: 2063-69.
1966
A revised concept of the mechanism of analgesia and pain. In: Pain,
ed. R. S. Knighton and P. R. Dumke, pp. 117-54. Boston: Little,
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1967
With D. G. Miller, F. Guzman, D. W. Rodgers, R. W. Rodgers, S. K.
Wang, P. W. Chao, and T. W. Shih. Pain and analgesia eval-
uated by the intraperitoneal bradykinin-evoked pain method in
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1968
With F. Guzman. Manifestations of pain in algesia evaluation in
animals and man. In: Pain, ed. A. Soulairac, }. Cahn, and I.
Charpentier, pp. 119~52. London: Academic Press.
1969
With G. Krauthamer, F. Guzman, and R. R. Fulp. Central nervous
system activity associated with the pain evoked by bradykinin
and its alteration by morphine and aspirin. Proc. Natl. Acad. Sci.
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1970
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Representative terms from entire chapter:
biographical memoirs
