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OCR for page 45
MIN CHUEH CHANG
October ~ 0, ~ 908-fune S. ~ 991
BY ROY O. GREEP
THE LIFE WORK OF Min Chueh Chang centered on a dis-
crete portion of the mammalian reproduction process,
the part that begins with the existence of male ant! female
free living gametes and ends with their successful union,
fertilization. In this sphere Chang was a world leacler, a
giant of his time. That, however, is only part of the fame
that is conjured up by the mention of his name. Actually,
Chang is best known in the public minct for his work on the
development of the oral contraceptive, "the Pill." The lat-
ter benefited millions of women and fomented a social/
sexual revolution. This freeing of the sexual act from the
threat of conception lecl to major changes in the way men
ant! women live together.
To bring these two related but very different aspects of
Chang's research into perspective, it is important to note
that of his forty-five years in research only five ~1951 through
1956) were spent in proving the effectiveness of certain
steroids in controlling fertility in laboratory mammals when
aciministered orally. This was his greatest contribution in
pragmatic terms.
This brief departure from Chang's abiding interest in
eggs ancl sperm themselves is in keeping with his recogni-
tion of the critical neec! for better means of controlling
45
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46
BIOGRAPHICAL MEMOIRS
human fertility. It is noteworthy that Chang's work on de-
veloping the Pill utilized fundamental information already
available. Except for the mode of administering the contra-
ceptive steroids, little was acicled to existing knowledge. On
the contrary, Chang's monumental work on fertilization was
purely an exercise in basic science for the purpose of gain-
ing new insight into the mechanism of fertilization. That
this turner! out to have great practical significance was, of
course, a personal satisfaction, but it was the plaudits of the
scientific community that pleasecI him most.
His life career is a story of triumph and disappointments,
perseverance and major accomplishments, accolades, inter-
national recognition, and, lastly, an element of what Peter
Meciawar recognized as chance. It was largely by chance
that Chang often found himself the right man at the right
place at the right time. This was especially true at Cam-
bridge University ~ ~ 939-45) and again at the Worcester Foun-
ciation for Experimental Biology (1951-561. Chang was aware
of these favoring circumstances. In an unpublished manu-
script titled "Reminiscences on the Study of Animal Repro-
duction en cl Association with Reproductive Biologists," Chang
wrote extensively, forthrightly, and illuminatingly on the many
preceptors and counselors to whom he was greatly in(lebtecl
for their material help, guidance, and encouragement.
Lastly, note need be made of the fact that Chang grew
up, as it were, with a newly founder! institution that pro-
viclec! him with the opportunity and the facilities to carry
out his extended program of research and to attain preemi-
nence in the world of science. Chang returnee! this favor by
leaving to the Worcester Foundation for Experimental Biol-
ogy a proud legacy of prestige and renown.
Not the least of what made Chang a notable and enclear-
ing character is that he was every inch a kind, generous,
fair-mincled, anc! gentle person whose integrity was a given.
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MIN CHUEH CHANG
PERSONAL HISTORY
47
Min Chuch Chang was born in Tai Yuan (Shanxi prov-
ince), China, ~ ~^ ~^^~ ~~ ~ ~
on ()ctober 1(), 19()~. His lather, a magistrate,
was able to provide him with a quality education, inclucling
in 1933, a bachelor's degree in animal psychology from
Tsing Hua University in Peking. Over the next few years of
turbulent times in China, Chang stayed at the university as
a teacher and made some original observations on the stain-
ing of nerve cells that gained publication in a prestigious
American journal.
Chang's brilliance of mind and unbounded! curiosity dicI
not go unnoticed. In 1938 he was encouraged to compete
in a national examination for a few much-prized fellow-
ships to study abroacl and he won. He opted for a year of
study in agricultural science at Edinburgh University. At
year's ens! the chilly climate and his perception of some
bias against foreigners were not to his liking. An appealing
invitation from Arthur Walton to join him in research on
ram spermatozoa at Cambridge University was glaclly ac-
cepted. This was in keeping with Chang's newfound! inter-
est in reproductive biology, a departure from his initial in-
tent on a career in behavioral psychology. There uncler
Walton's tutelage ant! association with such other greats as
Sir John Hammonc! and F. H. A. Marshall, Chang became
engrossed in research. On the basis of his multiple observa-
tions on the effect of testicular cooling and various hor-
monal treatments on the respiration, metabolism, anti sur-
vival of sperm in rabbits and some farm animals, Chang was
awardect a Ph.D. degree in animal breeding by Cambridge
University in ~ 961.
The options available to Chang at that time included
returning to China and sharing in the suffering of his par-
ents anc! friends. Fortunately, counselors at Cambridge pre-
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48
BIOGRAPHICAL MEMOIRS
veiled upon him to remain there. With the exigencies im-
posed by WorIcl War II, the best that could be provided was
maintenance support en cl limiter! opportunities for research.
At war's end Chang again was torn between returning to
China or finding elsewhere an outlet for his study of fertil-
ity. He sought and was granted a one-year fellowship with
Gregory Pincus to learn the technique of in vitro fertiliza-
tion before returning home. At the time of Chang's arrival
in the United States, Pincus was at Clark University with
Hudson Hoaglanct, ant! the two of them were in the process
of founding the Worcester Foundation for Experimental
Biology in Shrewsbury, Massachusetts, just outside Worces-
ter. Chang was given a room at the newly creates! founcia-
tion, and he often toil with some clelight how he server! as
night watchman. It was soon evident to Pincus ant] Chang
that they were an effective team with many common inter-
ests in the broacI field of reproductive biology. Moreover,
they almost immecliately formed a warm, personal, and en-
during relationship. It was there that Chang wouIc! spencI
the remainder of his illustrious and rewarding career in
research on matters relating to mammalian fertility.
As funds for support of research on reproduction be-
came increasingly available after micI-century, Chang's labo-
ratory began to attract a cacire of highly competent young
investigators who today are clistinguished leaders in basic
ant! clinical research on reproduction. In Chang's labora-
tory they were mainly left to their own crevices except that
Chang was always at hand for helpful guidance ant! advice
when needled. Among the group of approximately 100 fel-
lows and associates, singling out any for mention risks the
sin of omission, but mention of a few will illustrate the
ctistinction of the group as a whole: J. M. Beclforcl, C. R.
Austin, R. Yanagimachi, M. R. J. Harper, Y. Toyo(lo, R. H. F.
Hunter, i. H. Marston, T. Twamatsu, and H. Miyamoto. With
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MIN CHUEH CHANG
49
this concentration of expertise in Chang's special fielcT, his
laboratory became an international crossroad. An unend-
ing influx of distinguishecl visitors was a significant factor
in establishing the Worcester Foundation for Experimental
Biology as an important biomedical research center.
Chang's work habits were incredible. He personified what
is clubbed a workaholic. His quest for better understanding
of the intricate series of sequential physiological mecha-
nisms involved in the fertilization of mammalian ova was
the dominant en c! consuming factor in his life. Some mea-
sure of the intensity of his labors will be evident from the
fact that at the peak of his productivity he was publishing
up to nineteen papers annually all in first-rate, peer-re-
viewed journals en cl all reporting substantive findings. Chang
was by his own admission a patient and persevering type of
investigator. He hac! long-range goals toward which he
planned his experimentation assicluously. The strong likeli-
hood of gaining substantive new information from each
carefully clesigned experiment was a contributing factor to
his prolific procluctivity. Chang's bibliography lists 347 pa-
pers, of which he was sole author of Il2 and senior author
of another 38. Most scientists will agree that such procli-
gious effort comes at the expense of time with the family,
cultural pursuits, and reflections on broader issues within
and outsit e science.
Shortly after Chang arrived in the United States he mar-
riect an American-born Chinese woman, Isabelle Chin, whom
he met by chance in the Yale University library. Their three
chiTciren inclucle two daughters, Claudia Chang Tourtellotte,
head of the anthropology department at Sweet Briar Col-
lege in Sweet Briar, Virginia; Pamela O'Malley Chang, an
architect and civil engineer in San Francisco, California;
and a son, Francis Hugh Chang, director of a health center
in Boston, Massachusetts.
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50
BIOGRAPHICAL MEMOIRS
Chang was neither a family man in the usual sense nor a
closing father. In his private life he was a Confucian scholar
and held to the principles of strict discipline for himself
ant! his son and mate dominance of the marital relation-
ship. Much credit must be given to Chang's talented wife
for her willing acquiescence in the role of a Confucian wife
as her part in enabling Chang to develop his full potential
unhindered by domestic concerns. On Chang's behalf it
can be saict that he followed the cultural traditions of his
Asian background in a Western setting yet retained the pro-
founcl respect of his family.
In his later years Chang traveled extensively to many parts
of the world to participate in meetings devoted to his spe-
cial fielcI of investigation. Such attendance was almost al-
ways as an invitec! speaker. His distinguished accomplish-
ments were otherwise recognizes! by numerous honors ant!
awards. A partial list includes the Albert Lasker Awarc! (1954),
Ortho Mecial and Award by the American Fertility Society
(1961), Hartman Award by the Society for the Study of
Fertility (1971), Frances Amory Prize by the American Acad-
emy of Arts and Sciences (1975), Wippman Scientific Re-
search Awarc! by the Planned Parenthood Federation of
America ~ ~ 987), and election to membership in the Na-
tional Academy of Sciences in 1990.
PROFESSIONAL HISTORY
A cletailed account of Chang's experimental work as cle-
pictecl in nearly 350 publications is far beyond accommocla-
tion here. A look at some of his major accomplishments
must suffice. Chang's life work involved a series of highly
interrelated projects. The first dealt with the metabolism,
motility, and fertilizing capacity of ram sperm. This was
closely tier! to a concurrent attempt to improve the effec-
tiveness of artificial insemination in farm animals. It being
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MIN CHUEH CHANG
51
wartime this had the prospect of increasing food produc-
tion. Once the war ended and Chang had moved to the
United States, he was able to take up a quest that he had
had in mind for some time namely, fertilization of ova
outside the mammalian body (in vitro fertilization). To that
end he sought first to understand why sperm from the epi-
didymis or ejaculate were motile but incapable of penetrat-
ing ova.
Chang's competence in reproductive biology was occa-
sioned by having to understand, and to manipulate, the
reproductive status of the host animals from which he ob-
tained male and female gametes. Tt was with this background
that he was eminently qualified to meet the challenge of
evaluating, on a virtually emergency basis, a wide range of
steroidal compounds as potential orally active antifertility
agents in the early ~ 950s.
In his initial studies on eggs and sperm Chang carried
out a variety of experiments mainly to acquire expertise in
the techniques involved and to gain a thorough knowledge
of the field. He examined the motility and fertilizing capac-
ity of sperm taken from different areas of the mate repro-
ductive tract, with special attention to sperm from various
parts of the epididymis. Out of this came the finding that
cooling by simply applying ice to the scrotum caused severe
disintegration of sperm from the Tower end of the epididy-
mis. This is now a generally recognized phenomenon known
as cold shock. It occurs in a critical range of temperatures
(13°-0°C) and results in a breakdown of membrane struc-
ture and function. Chang showed that sperm subjected to
deep freezing must be protected by a cryoprotective agent
found in egg yolk. Chang's original observation on cooling
led to a massive study of cold shock. Obversely, Chang found
that exposure of unfertilized rabbit ova to elevated tem-
peratures destroyed their fertilizability.
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52
BIOGRAPHICAL MEMOIRS
Early in his career Chang was intrigued by the prodigal-
ity of sperm production and macle several observations on
the effect of the number of sperm on fertilization of ova.
He once estimated that the human male produces about ~
billion sperm for every egg releaser! by the female gonads.
He found that of approximately 200 million sperm clepos-
ited in the rabbit vagina by ejaculation or artificial insemi-
nation barely ~ percent make it past the cervical barrier to
the uterine cavity and only about 5,000 find their way past
the utero-tubal junction. Fewer still reach the site of fertili-
zation in the outer segment of the oviduct.
Earlier literature cIaimec! that fertilization required the
presence of what were termec! swarms of sperm in contra-
distinction to vanguards. The belief was that large numbers
of sperm were necessary to release a Tytic agent that would
dispel the follicular cells surrounding the oocyte, the cu-
muTus oophorus, ant! corona radiate. Chang showed that it
is the physiological integrity of an incliviclual sperm that is
important for fertilization. He also found that a single sperm
can penetrate the cumulus mass of cells and reach the zone
pellucida, a thick mucoprotein membrane enveloping the
ovum. Each sperm head carries an attacher! packet, the
acrosome, containing hyaluronidase, which is releasect by
the acrosome at the site of fertilization and was believer! to
effect the clispersal of cumulus cells. Chang found that the
number of sperm at the site was far too few to accomplish
this event. Adcling hyaluroni(lase to sperm suspensions clic!
not prove to be beneficial. Chang also clisproved an alleger!
claim that phosphorylatec3 hespericlin, a hyaluroniciase in-
hibitor, had an antifertility action when aciministerecl orally.
Since large numbers of sperm are of no benefit to fertili-
zation, their production in astronomical numbers through-
out reproductive life posed a challenge to Chang. He pos-
ited that every population of sperm is comprised of some
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Representative terms from entire chapter:
chueh chang
MIN CHUEH CHANG
53
that are strong and others weak, morphologically defective,
or aged. Since only the strongest of the strong reach the
site of fertilization, Chang held that the more sperm enter-
ing the female reproductive tract the more this would pro-
vide for greater variation in the recombination of genes.
Chang also did a large amount of work on the local mi-
lieu of sperm. He wanted to understand the effect of the
very different environmental factors to which sperm are
exposed during their Passage through the enididYmis and
~ . ~ ~ ~ .. am. ~ ... .
ascent ot the female reproductive tract. the tert~l~z~ng ca-
pacity of rabbit epididymal sperm was not benefited by sus-
nension in rabbit seminal Plasma as compared to Rin~er's
or Tyrode's solution. On the matter of osmolaTity, Chang
and Thorsteinsson found that rabbit sperm could tolerate
without ill effect on either motility or fertility half the strength
or twice the strength ot longer s solution at neutral pH.
They also found that sperm couIcl survive a wide range of
pH at isotonicity namely, from 5.57 to 10.94! That is for-
tuitous since sperm often encounter a wide range of pH in
the human vagina.
Sperm deposited in the rabbit vagina on mating reach
the fallopian tubes within minutes and await the arrival of
ova for fertilization ten to twelve hours later. In a fateful
experiment Chang deposited ejaculated sperm in the tubes
to coincide with the arrival of ova. Fertilization failed. Test-
ing his speculation that the waiting period was the crucial
factor, Chang next deposited sperm in the tubes six to eight
hours before the arrival of ova and obtained fertilization.
This finding that soerm must undergo an incubation ne-
· ,1 , ,1 r ~~ ~ 1 ,~
0 1
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54
BIOGRAPHICAL MEMOIRS
sense of disappointment. A year later Austin named this
phenomenon sperm capacitation—a term now in wide use
by reproductive biologists ant! clinicians.
Chang and his associates proceeded to show that capaci-
tation was a general phenomenon occurring among all mam-
maTian species stucliect. They found that the duration of the
waiting perioc! varies! somewhat among species: rabbit, five
to six hours; rat, four to five hours; mouse, one hour; goIclen
hamster, two to three hours; and sheep, one and one-half
hours. They also fount! that sperm could acquire capacita-
tion in the uterus as well as the tubes. An exciting exten-
sion of capacitation came with the discovery by Chang in
1957 that capacitated sperm exposed to either seminal plasma
or bloocl serum from the same species or from other spe-
cies lost their capacitation, an event termed decapacitation.
This factor was found by Bedford ant! Chang to be a high-
molecular-weight substance that adheres to the surface of
sperm and is removable by centrifugation at ~ 05,000 times
g. Taking this one step further, they found that clecapacitatec3
sperm could be recapacitated by placing them back in the
uterus or tubes.
In a 1958 study of the possible influence of the hormonal
status of the female rabbit reproductive tract on the capaci-
tation of sperm, Chang found that ejaculated sperm placed
in the uteri of pseuclopregnant or progesterone-treated rabbits
failecl to become capacitated. In striking contrast, sperm
placed in the fallopian tubes of these rabbits diet become
capacitated. Capacitation was also achiever! in the uteri of
immature or ovariectomizec! rabbits with or without estro-
gen treatment.
Chang's mastery of capacitation did not prove to be the
Holy Grail. He could not have been unaware that by the
discovery of capacitation he was one step closer to the achieve-
ment of in vitro fertilization. Back in 1945 Chang's main
MIN CHUEH CHANG
55
purpose in coming to the Worcester Foundation was to learn
the technique of in vitro fertilization from Gregory Pincus.
As early as 1935 Pincus claimed to have obtained living
young from rabbit eggs fertilizer! in vitro and returnee! to
the floe. Doubts as to the authenticity of this report lin-
gerecI, and Chang working in Pincus's laboratory was not
able to repeat those inklings. This opener! an intense and
competitive search for a solution to this important prob-
lem. In 1954 Thibault and associates reported early embry-
onic clevelopment in eggs fertilized in vitro. Chang's crown-
ing achievement came in 1959 with his demonstration that
eggs from a black rabbit fertilized in vitro by capacitated
sperm from a black male ant! transferred to a white female
resulted in the birth of a litter of black young. This evi-
clence seemed beyond question, and was, but some skepti-
cism persisted for a while.
The circumstances that allowocl in vitro fertilization in
rabbits proved to be species specific. For many years, Chant
en c! his students continued to define the varying specific
-r ~
~ .
v
· ._
conditions required for in vitro fertilization in several spe-
cies. To wit, in 1963, Yanagimachi ant! Chang reported the
first successful fertilization of golden hamster eggs in vitro.
They user! Tyrocle's solution, containing glycine and sperm
capacitated in the uterus. Next came the in vitro fertiliza-
tion of mouse ova incubated in bovine follicular fluicI, as
reported by Iwamatsu and Chang in 1969, and in the same
year Pickworth and Chang succeeder! in fertilizing Chinese
hamster eggs in vitro. In 1973-74 Miyamoto ant! Chang and
Toyoda and Chang reported fertilization of rat eggs in vitro,
ant! in ~ 978 Hanocia et al. accomplishec! the same for
deermouse eggs.
In an extension of this study of in vitro fertilization,
Yanagirnachi and Chang (1963) found penetration of rab-
bit ova by sperm taken from the epidiclymis, thus showing
56
BIOGRAPHICAL MEMOIRS
that capacitation had occurred in vitro. In 1973 Miyamoto
and Chang observed fertilization of mouse eggs by in vitro
capacitated sperm, and a year later Toyodo and Chang made
similar observations on rat sperm capacitated in a chemi-
cally defined medium.
It was on the basis of this animal data that Steptoe, Bravister,
and Edwards were able to achieve in vitro fertilization of
human ova. Later, the landmark birth on July 25, 1978, of
the world's first test-tube baby, Louise Joy Brown, in Oldham,
England, was recorded by Steptoe and Edwards.
From this overview of the entire spectrum of Chang's
Investigational program, it is evident that the central and
constant objective was understanding the detailed circum-
stances involved in the process of sperm penetration and
fertilization of mammalian ova. Such was the fabric of his
illustrious career.
In the twilight of his career Chang became disturbed by
the confusion and controversy appearing in the literature
as a result of disagreement as to what chances are to be
~ ,
. . . .. . .
a
considered part ot the capacitation process. Capacitation as
ori~inallv clefined both by Austin and Chant in 1951 in-
O
. . ~ . .
eluded all the changes that enable sperm to penetrate eggs.
Over the years a variety of structural and chemical changes
in the sperm during the capacitation were described, some
being considered as components of the capacitation pro-
cess, others not. The bulk of the controversy centered on
whether the acrosome reaction was a separate feature or a
part of capacitation. Among those holding that capacita-
tion was simply a preliminary that enabled the acrosome
reaction to occur were several of Chang's former colleagues,
most notably Bedford' Austin, and Yanagimachi. In a review
article on capacitation published in ~ 984, Chang argued
forcefully at some length as to why the original definition'
which includes all the changes that enable a sperm to pen-
MIN CHUEH CHANG
57
etrate the egg, should be retained. He dealt strictly with the
facts on a totally impersonal basis. It was an elegant appeal
to await full understanding of what happens to sperm dur-
ing that still ever so puzzling waiting period.
PERSONAL COMMENTS BY THE AUTHOR
Chang was an easily recognized figure, tall and slimly
built with a copious head of dark hair tinged with gray. His
twinkling eyes and ready smile were prominent features of
his friendly greetings. Despite being a man of illustrious
international stature, the impression he gave was that of a
genuinely modest and somewhat humble man. He always
seemed to look up to whomever he met on a casual basis.
Albeit meeting Chang was always a welcome and delightful
experience. Despite this self-effacement, Chang had a nor-
mal healthy ego and took justifiable pride in his own ac-
complishments.
One of Chang's most endearing attributes was his won-
derful sense of humor. Before an audience his quick wit
and facile repartee often had his audience in stitches. This
was aided by an unusual feature in his manner of speaking,
a rapid motion of the lower jaw. This made it appear that
his often pithy and sometimes pungent quips were being
ushered out with gnashing of teeth.
Chang was sensitive to any personal slight or any over-
sight of his scientific work. The aftermath of the discovery
of the oral contraceptive was particularly nettlesome. As
have indicated elsewhere Journal of Andrology, Nov.-Dec.
1992), "Chang sometimes figured in the series of clinical
reports on these field trials but not to the extent that seemed
deserving. Certainly there was no intent to downplay his
role in this remarkable development and with the passage
of time Chang came into his rightful dues as a co-founder
of the Pill. It is much to Chang's credit that he never wa-
58
BIOGRAPHICAL MEMOIRS
vered in his admiration ant! respect for his benefactor, Gre-
gory Pincus."
In a final review summarizing his extensive studies, Chang
noted rather pointedly and with some understatement that,
"We have achieved a good deal towards the unclerstancting
of mammalian fertilization by simple biological experimen-
tation." In this age of high technology and molecular prob-
ing, this may give encouragement to some who would as-
pire to extent! the frontiers of knowledge by other means.
Chang was by any measure an extraordinary person. His
mastery of the phenomenon of capacitation took six years
of unrelenting effort. His demonstration of-in vitro fertili-
zation in a mammal took fourteen years. Such tenacity has
become a rarity in biomedical research clue to the tenuous-
ness of financial support. Chang's rise to prominence as a
Chinese scholar (luring a perioc! of political unrest and so-
cial upheaval at home was also out of the ordinary by a
wide, nay very wicle, margin. Similarly, his contributions to
human welfare are on a scale matched only by the few whose
names are legencI.
MIN CHUEH CHANG
SELECTED BIBLIOGRAPHY
1940
59
With A. Walton. The effects of low temperature and acclimatization
on the respiratory activity and survival of ram spermatozoa. Proc.
R. Soc. Lond. (Series B) 857 ~ 129 ~ :517-27.
1943
Disintegration of epididymal spermatozoa by application of ice to
the scrotal testis. i. Exp. Biol. 20~1~:16-22.
1947
Effects of testis hyaluronidase and seminal fluids on the fertiliza-
tion capacity of rabbit spermatozoa. Proc. Soc. Exp. Biol. Med. 66:51-
54.
1950
Further study of the role of hyaluronidase in the fertilization of
rabbit ova in vivo. Science 112 (2900) :118-19.
1951
Fertilizing capacity of sperm deposited in the fallopian tube. Nature
168:697.
Fertilization in relation to the number of spermatozoa in the fallo-
pian tubes of rabbits. Estratto das 2°Fascicolo Speciale (7~:918-25.
1953
With G. Pincus. The effects of progesterone and related compounds
on ovulation and early development in the rabbit. Acta Physiol.
Latinoam. 3 (2-3) :177-83.
1955
Development of fertilizing capacity of rabbit spermatozoa in the
uterus. Nature 175: 1036.
1956
With G. Pincus et al. Studies of the biological activity of certain 19-
nor steroids in female animals. Endocrinology 59:695-707.
60
BIOGRAPHICAL MEMOIRS
1957
A detrimental effect of seminal plasma on the fertilizing capacity of
sperm. Nature 179:258-59.
1958
With T. Thorsteinsson. Effects of osmotic pressure arid hydrogen-
ion concentration on the motility and fertilizing capacity of rab-
bit spermatozoa. Fertil. Steril. 9~6~:510-20.
Capacitation of rabbit spermatozoa in the uterus with special refer-
ence to the reproductive phases of the female. Endocrinology 63~5~:619-
28.
1959
Fertilization of rabbit ova in vitro. Nature 184:466-67.
1960
With D. M. Hunt. Effects of in vitro radiocobalt irradiation of rabbit
ova on subsequent development in viva with special reference to
the irradiation of maternal organism. Anat. Rec. 137~4~:511-20.
1962
With }. M. Bedford. Fertilization of rabbit ova in vitro. Nature
193 (4818) :898-99.
1963
With R. Yanagimachi. Fertilization of hamster eggs in vitro. Nature
200 (4903) :281-82.
1964
With R. Yanagimachi. In vitro fertilization of golden hamster ova. {.
Exp. Zool. 156~3~:361-76.
1966
With M. I. K. Harper. Effects of ethinyl estradiol on egg transport
and development in the rabbit. Endocrinology 78~4~:860-72.
1968
In vitro fertilization of mammalian eggs. [. Anim. Sci. 27 (Suppl. 1 ) : 15-
22.
MIN CHUEH CHANG
1969
61
With S. Pickworth. Fertilization of Chinese hamster eggs in vitro. I.
Reprod . Fertil. 1 9: 371 -74.
With T. Iwamatsu. In vitro fertilization of mouse eggs in the pres-
ence of bovine follicular fluid. Nature 224:919-20.
1971
With T. Iwamatsu. Factors involved in the fertilization of mouse
eggs in vitro. I. Reprod. Fertil. 26:197-208.
1973
With H. Miyamoto. In vitro fertilization of rat eggs. Nature 241:50-
52.
1974
With Y. Toyoda. Fertilization of rat eggs in vitro by epididymal sper-
matozoa and the development of eggs following transfer. J. Reprod.
Fertil. 36:9-22.
With H. Miyamoto and Y. Toyoda. Effect of hydrogen-ion concen-
tration on in vitro fertilization of mouse, golden hamster and rat
eggs. Biol. Reprod. 10:487-93.
1984
The meaning of sperm capacitation. A historical perspective. [. Androl.
5 (it) :45-50.
