Bioidentical Hormones Urine Therapy Ancient China

MEDIEVAL PREPARATIONS

OF URINARY STEROID HORMONES

by

LU GWEI-DJEN AND JOSEPH NEEDHAM

(References indicated by superior figures are to the Chinese characters opposite pages iI8 and I I9.)

Introduction

OUR knowledge of the endocrine functions of the sexual organs of man and

mammals is an acquisition of comparatively recent date. Endocrinology as a

whole indeed does not go back beyond the beginning of the present century.

By the end of the twenties a great deal of important knowledge about the

endocrine secretions of the testis and ovary, the placenta and the adrenals had

been attained, as may be seen in the collective work Sex and Internal Secretions,

edited by Edgar Allen I 1932. The same period had seen the establishment of

the correct formula of the steroid ring system by Wieland, Windaus, Diels,

Bernal, Rosenheim and King; and this opened the way for the sweeping

advances in the field of androgens and oestrogens which have taken place

since then.* We are now familiar with a large number of substances of androgenic

and oestrogenic activity naturally occurring in the body, and we are also

able to make use of derivatives of these substances which do not naturally

occur in Nature but which may have very useful properties for our purposes.

Since the knowledge of the steroid sex hormones is thus such a characteristic

achievement of modern science, it seems hardly believable that in any phase of

ancient or medieval science it should have been possible to make preparations

which possessed activity of this kind. Nevertheless, we have recently come upon

a corpus of material which indicates that this was accomplished by the Chinese

iatrochemists between the tenth and the sixteenth centuries A.D. Guided by

theories of traditional Chinese type, not of course the same as those of modern

science, and using urine as their starting-point, they succeeded in preparing

mixtures of androgens and oestrogens in relatively purified form and employing

them in medicine. The classical discovery of Aschheim & Zondek in 1927 that

pregnancy urine contains rich amounts of steroid sex hormones,t and the subsequent

discoveries of the presence of similar substances in urine from other

sources, was thus anticipated by many centuries in these Chinese empirical

preparations. In the present paper we wish to set forth the evidence which we

have found.+~

On the androgens see especially Dorfran & Shipley.

t It very soon became the chief source of supply for biochemists; cf. Veler & Doisy's paper, and

Allen, pp. 44o, 483; also Brools et al., p. I I I.

The stem of romanization of Chinese characters in this paper follows that of Wade-Giles with

the substitution of an 'h' for the aspirate apostrophe.

We are greatly indebted to Dr. Roger Short of the Department of Veterinary Science at Cambridge

and to Dr. Hal Dixon of the Biochemical Department, as well as to Prof. H. Breuer, for much kind help

and valuable advice.

We wish to record with great gratitude generous financial assistance received from the Wellcome

Trust.

IOI

Lu Gwei-Djen and Joseph Needham

The Sexual Organs in Chinese Medicine

Before proceeding further it will be desirable to say a few words about the

sexual organs in Chinese medical thought and practice. The secondary sexual

characteristics were recognized as connected with the testis in quite ancient

times. As in all other civilizations, castration was undertaken very early, in man

for social reasons (eunuchism), and in animals both for medicinal purposes and

for gastronomy, because gelded animals were found to put on fat and to give

a more tender meat. The simple physiological experiment of castration thus

taught the Chinese very early that the beard and other characters of virility

were connected in some way with the presence of the testes. Intersexes also

aroused much interest and were catalogued in the Hsi ruan Lul of Sung Tzhu,'

the founder of forensic medicine, in A.D. 1247. This book, entitled The Washing

Away of Wrongs (i.e. False Charges), is the oldest treatise on legal medicine in

any civilization, and it was natural that attention should be paid in it to various

forms of hermaphroditism.* By the sixteenth century A.D., Li Shih-Chen8 in his

great pharmacopoeia, the Pen Tshao Kang Mu4 (1596), has an elaborate discussion

of ten principal forms of hermaphroditism.t The interest of the Chinese

was aroused very early also in sex-reversals. From the beginning of the Former

Han dynasty (third century B.C.) cases are reported, for example in the

Lun H6ng6 (Discourses Weighed in the Balance)+ of the famous skeptic Wang

Chhung,6 written about A.D. 8o. These sex-reversals, where persons predominantly

male turned into persons mainly female in character and vice versa,

were taken note of naturally for prognostication purposes, like other unusual

phenomena, celestial or terrestrial. For this reason many cases of similar change

in animals as well as man were recorded in the dynastic histories under the

heading of 'strange events'; § and there are plenty of case reports in the

memorabilia of private scholars. I

So far as we know, the Chinese were not particularly early in the use of testicular

tissue as a therapeutic agent in cases of hypogonadism, sexual debility,

impotence, spermatorrhoea, and female affections such as dysmenorrhoea,

leucorrhoea, etc. The practice was first emphasized in a book entitled Lei Cheng

Phu Chi Pen Shih Fang10 (Classified Fundamental Prescriptions of Universal

Benefit) printed in A.D. I253, and attributed to an eminent physician, Hsu ShuWei,"'

who flourished in A.D. 1132. The testes of animals such as the sheep, pig

and dog were used either desiccated, raw or comminuted with hot wine. Other

thirteenth-century books describe the treatment, e.g. the Chi Sing Fang12

(Prescriptions for the Preservation of Health), written by Yen Yung-Ho"' about

1267; after that time it became a current method in Chinese therapeutics.¶

The use of testis tissue as a drug goes back far in medical history; it appears in

* Chap. I, pp. 32aff. The material was in part older, since Sung Tzhu based his work on three still

earlier books now lost.

t Chap. 52, pp. 43aff. Hereinafter abbreviated to PTKM. Study continues today in China on modern

lines; cf. Liu Pen-Li et al.

$ Chap. 7 (Forke tr., vol. I, p. 327).

§ E.g. Chhien Han Shu,7 chap. 27 BA, pp. 2oaff.; chap. 27 CA, p. x8b; Hou Han Shu," chap. 27, p. 8a;

Hsin Thang Shu,9 chaps. 34 to 36 passim.

11 Cf. Laufer. Further references will be given in "Science and Civilization in China" (hereinafter

abbreviated to SCC), vol. vs.

¶ See PTKM, chap. 50A, pp. 13a, 2ia, b, 30b, 43a.

I02

Medieval Preparations of Urinary Steroid Hormones

the Hippocratic corpus, in Dioscorides (c. A.D. 6o),* and among the Indian

writings, especially the Sulruta-samhita, sometime between the second and fifth

centuries A.D.t As early as 135 B.C. Nicander recommended the use of the

testes of hippopotamus. There is no reason to think that such medication would

have been valueless. Although testosterone is inactivated in the liver, administration

per os may have been reasonably effective, provided sufficient quantities

were given to the patient.

Chinese medicine was perhaps more original in the use of the human placenta

for therapy; after all the richest source of oestrogens. § How far back this goes

we are not quite sure, but Li Shih-Chen tells usil that the use of human placenta

was first mentioned in the Pen Tshao Shih 1P4 pharmacopoeia written by Chhen

Tshang-Chhi15 about A.D. 725. At first it was not greatly used, but during the

Ming period (fourteenth century onwards) it came into prominence, and was

prescribed habitually for all such affections as are considered to benefit by the

administration of oestrogens at the present day. The placenta was much studied

by Wu Chhiul8 towards the end of the fifteenth century in his Chu ChSng

Pien 117 (Resolution of Diagnostic Doubts)-; he, like other physicians of the Yuan

and the Ming, invariably prescribed placental tissue, desiccated or boiled down

in wine,T combined with a variety of herbal drugs. Some of these are known

today to have quite powerful effects on smooth muscle, blood-pressure, etc.**

The oral route is often considered inefficient for oestrogens, but there can be no

doubt that real effects would have been produced if enough material was

given.t t As in the case of the testis, placentas of animals, especially the horse

and cat, were also employed."

One little indication occurs here which links the use of the placenta with the

iatrochemical studies on urine which are the main subject of this paper. In

discussing the placenta, Li Shih-Chen quotes first from a Tan Shu20 concerning

the theory of the use of the placenta and the choice of the best specimens for the

purpose. It is probable that Tan Shu here is a generic term meaning books on

iatrochemical medicines, and not the name of a specific work, for it cannot be

found in Li Shih-Chen's own bibliography.1111 If this is so, there is here an

interesting link with the iatrochemists, descendants of the alchemists of the

Thang and Sung who developed the urinary fractionation methods now to be

discussed.

* Gunther ed. p. 102; Berendes, vol. i, pp. 194, 294; Brooks et al., p. 23.

t Bhishagratna ed., vol. iI, pp. 512ff. + Berendes, vol. I, p. 274. § Allen, p. 456.

11 PTKM, chap. 52, pp. 36a, b, 37a, b.

¶ Such a treatment, like refluxing with aqueous alcohol, would liberate the steroid hormones, both

free and conjugated, from the cells.

** E.g. tu-chwngU (Eucommia ulmoides), and tang-kuei" (Angelicapolymorpha).

tt Oestrogenic components can in certain circumstances be well absorbed per os (cf. Allen, pp. 908,

9IO); progesterone not so. The famous experiments of Brown-S6quard in I889, so often regarded as

the foundation of endocrinology, sought to overcome the difficulties of the oral route by the injection

of glycerol extracts of testis tissue; they were thus distinctly less subtle than the ancient Chinese methods

of fractionating urine, and indeed also less convincing, since 'the validity of the results has not been

substantiated' (Allen, p. 88I), while the Chinese preparations were in widespread use.

4+ PTKM, chap. 50B, p. 20a; chap. 51A, p. 36b.

111 Asearchin the catalogues of the Taoist Patrology (Tao Tsang)2 which contains so many aIchemical

books, reveals only one which contains both these characters in its title, a Tan Tao Pi Shu" (Secret

Book of the Tao of Elixirs); but this is not in either of the main collections, and we have not been able

to see it. We suspect that it is in any case a late work, and not what Li Shih-Chen was referring to.

I03

Lu Gwei-Djen and Joseph JNeedham

Proto-Endocrinology in Chinese Medical Theory

Elsewhere we expect to give a thorough study of the theories of Chinese

physiology, pathology and medicine throughout antiquity and the Middle

Ages.* These are the basis of the characteristic conceptions of traditional

Chinese medicine still today. Our conviction is that such an extended study will

demonstrate that the Chinese medical theory-structure was remarkably congruent

with the fundamental conception of endocrinology, namely that the

organs of the body exert important effects upon one another.

In the first place, the principal viscera were analogized with the elements.

As is generally known, Chinese natural philosophy from the fourth century B.C.

onwards thought in terms of five elements (unlike the Greek four): Metal,

Water, Wood, Fire and Earth.t The whole of Nature was considered as being

the theatre of a continual succession of changes in the Five Elements, changes

which proceeded according to certain systems of mutual inter-relations. One

such system was the Mutual Production Order, a particular succession according

to which each element generated the next one in a series. Similarly, another

cyclical succession was that known as the Mutual Conquest Order, in which in

a different succession each element conquered or destroyed its neighbour,

according to a particular succession. Since the viscera were analogized with the

Five Elements the conception of constant interactions between them lay very

near to the physiological thought of the ancients.

Besides the Five Elements, however, there were also the two fundamental

forces in the universe, Yin and Yang, originally corresponding to brightness

and darkness, the male and the female, etc., but here particularly relevant in

that the physiological thinkers used them so often in a sense very similar to that

which we have in mind when we speak of stimulus and inhibition. Thus the

medieval Chinese physicians had no difficulty in conceiving of a stimulatory

action of one organ on another and also an inhibitory one.

Furthermore, there was a third feature in classical Chinese physiological

thought which helped the conception of interactions within the body as a whole.

This is what one might call a circulation-mindedness. Although medieval

Chinese physiology had no such precise conception of a circulation of the blood

in the blood-vessels as was brought to perfection by William Harvey, nevertheless

it did not share in the old Greek and medieval Western ideas of 'tides' in

the blood. Chinese thought envisaged a steady circulation throughout the body

of chki23 (pneuma) and blood.+ The distinction between arterial and venous

blood had indeed been appreciated as early as the Former Han period, when

the Huang Ti Nei Ching,24 the earliest medical classic, was compiled.§ Consequently

it was not only easy on general element-theory to imagine the action

of one organ upon another, but it was also easy to see how it could come about

because of the perpetual circulation going on within the body.

* SCC, vol. vT.

t See SCC, vol. II, pp. 232ff., 253ff.

+ As yet there is no adequate treatment of this subject in a Western language, but we intend to give

one in SCC, vol. vi; meanwhile the reader may be referred to the papers of Liang Po-Chhiang;

Kapferer; and Huard & Huang Kuang-Ming.

§ The loCuS classicus is Ling Shu,'5 chap. 39; cf. also Su Win,2' chaps. 27, 39.

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Medieval Preparations of Urinary Steroid Hormones

In I849 A. A. Berthold* made his classical experiment of transplanting the

testis in the cock to the abdominal cavity; he found that it was vascularized

but not innervated in its new position, and he was thus able to prove that the

caponized cock would remain a cock, a fully male animal, when the testis was

able only to contribute something to the blood-stream. The thought behind

Berthold's experiment-the foundation of modern endocrinology, though not

followed up for sixty years afterward-has been investigated by Forbes, but it

still remains somewhat obscure. It probably originated from the old Greek

theory of pangenesis, according to which particles from all the organs of the body

went to form the corresponding organs in the embryo.+ As interpreted in the

eighteenth century by men such as Maupertuis, Buffon and de Bordeu,§

this theory supposed that every organ (even if it had an obviously external

secretion also) contributed specifically and characteristically to the bloodstream,

not only for the purpose of forming the sexual products but also for all

kinds of purposes. This then was probably the mainspring of Berthold's experiment.

Knowing the relation of the testes to the secondary sexual characteristics,

he thought that it might be possible to demonstrate that their action was

mediated by the blood-stream alone. And it was. From what has been said

above it will be clear that the implicit content of the medieval Chinese medical

conceptions was rather similar, in that the Five Viscera were in constant

communication with each other through the circulatory systems of the body.1j

What was particularly remarkable about the Chinese practices from the

tenth century A.D. onwards was the fact that they based themselves on the belief

that the contributed 'virtues' of the blood were in part transmitted to the

urine. The urine could therefore be regarded as a valuable source of some of

these precious qualities. The traditional doctrine of Chinese medicine is summed

up by Li Shih-Chen in his Pin Ts/lao Kang Mu (I596), where he says that the

nutrient essentials (jen chih ching chhi27) circulating in the body divide into two

fractions, the lighter fraction (chiing cht28) forms the blood, and the grosser

fraction (cho chJ29) forms the chhi; then the grosser part of the lighter fraction

forms the urine, while the lighter part ofthe grosser fraction forms the secretions.

For this reason the urine must be considered as 'of the same category as'

(thung 1630) the blood. This was a fundamental doctrine, for the conception

of categories was of wide-ranging implication in Chinese medieval natural

philosophy. Elsewhere we have studied the doctrine of categories in relation

with medieval Chinese alchemy, where it was also highly important.¶ Essentially

it provided a further cross-classification other than the basic division of

all things and events in the world into Yin and Yang. A multitude of texts bear

witness that particular processes will only occur if the reacting substances are

either of the same or of a different category, but knowledge of the categories

one must have.

* Biography by Rush.

t The converse demonstration with the ovary was due to Knauer and Halban-but not till I900.

Cf. Needham, pp. 39ff.; Meyer, pp. 86ff.; Russell. The theory, characteristic of the Hippocratic

and Democritean schools, was combated by Aristotle.

§ See Neuburger; Rolleston.

11 For the wider aspects of medieval Chinese proto-endocrinology, see Needham & Lu Gwei-Djen,

PEC. ¶g See Ho Ping-Yu & Needham: CAT.

105

Lu Gwei-Djen and Joseph Needham

The use of the urine as a starting-point for medicinal preparations can therefore

in no way be dismissed as merely superstitious 'Dreckapotheke'. On the contrary,

there was good theoretical ground for it in medieval Chinese eyes, and it

is remarkable to reflect how far this intuition has been justified by the assured

findings of modem biochemical science. Moreover, it is clear that what the

Chinese were looking for in urine was a substance or substances which would

give the kind of results that the androgens and oestrogens give when administered

today. This will be apparent from the quotations of texts given below.

The Empirical Background

The use of urine as a medicament, especially for sexual debility and related

disorders, goes back a very long way ini Chinese history. The Hou Han Shu

(History of the Later Han dynasty) has a short biography of three Taoist adepts

who lived towards the end of the second century A.D. It must be remembered

that the attitude of ancient Taoism to sex was philosophical and medico-scientific

rather than ascetic in the ordinary Western sense. Among the paths

to the attainment of material immortality, sexual techniques took their place

beside diet, gymnastic exercises, control of the breathing, heliotherapy and

ascesis as understood in the West. The passage is as follows:*

Kan Shih'1 and Tungkuo Yen-Niens [Comm. The Han Wu JNei Chwan33 (Secret History of

(Emperor) Wu of the Han) says that his (Tungkuo's) style was Kung-Yu'4.] and Feng ChunTa;'

these three were all adepts (or magic,fang shih"). They were all expert at following

the techniques ofJung Chh& g7 in commerce with women.t They could also drink urine and

sometimes used to hang upside down. They were careful and sparing of their seminal essence

and (inherited) cMi, and they did not boast with great words of their powers. What Kan

Shih, (Tso) Yuan-Fang8"+ and (Tungkuo) Yen-Nien could do was recorded by (Tshao)

Tshao8' who asked them about their art and tried to practise it.§

[Comm. Tshao Chih's!011 Pien Tao Lunl' (On Taoism, True and False) says: 'Although Kan

Shih was old, yet he looked young. All the magicians and adepts flocked to him, but he talked

much and showed them little. His words were unorthodox and strange. I myself once dismissed

my retainers and talked alone with him, asking him with kindness and courtesy what

exactly it was that he practised. He said "My teacher's name was Han Ya.4" With this master

I once made gold in the southern regions; on four occasions we threw away into the sea several

tens of thousands of catties of gold." He also said "In the time of (Shen) Chu-Liang' (i.e.

500 B.C.)¶ barbarians came from the western regions bringing tribute of incense, mir cloth

belts and jade-cutting knives; I often regretted that I did not get some of them." He also said

"In the countries west of the Chu-Shih"' kingdom, people cut open the backs of new-born

children and take out their spleens in the hope that they will eat less and be more aggressive."**

He also said "If you take a pair of carp (fishes) five inches long, put a certain drug into one of

* Chap. I12B, p. i8a.

t A semi-legendary figure associated both with sexual physiology and calendrical science. Cf. van

Gulik.

Alchemist and thaumaturgist, A.D. I55 to 220 or a little later. Like the other three, a frequenter

of the court of the founder of the (San Kuo) Wei Kingdom.

§ The founder, and posthumously the first emperor, of the (San Kuo) Wei Kingdom; celebrated as

a military leader, and interested in many aspects of technology.

11 Third son of Tshao Tshao, famous writer and poet, much inclined to Taoism and interested in

natural history. 1¶ A sympathetic feudal lord with whom Confucius once conversed when on his travels, builder of

one of the most ancient of Chinese reservoir dams for irrigation water.

** The Han histories describe two Chu-Shih kingdoms, one anterior and one ulterior (from the

Chinese point of view), the former centered on Turfan, the latter on Guchen, but both in modern

Sinkiang. See Teggart, p. 212; McGovern (under Gushi).

io6

Medieval Preparations of Urinary Steroid Hormones

them and throw it into boiling fat, the drug will make it violently move its tail and gills and

leap about wildly up and down as if it were sporting in the abyss. But by this time the other

one will be cooked and can be eaten." I often asked him whether (these things) could be tested.

He said that this drug was ten thousand miles away and one must go beyond the frontiers to

get it. "If you don't go yourself", said he, "you won't get it." (Kan Shih) said many other things

but I cannot recall them all; I mention only the strangest. If he had lived in the time of Chhin

Shih Huang" or Han Wu Ti"6 he would have been counted among (the great adepts such as)

Hsui Fu'7 and Luan Ta.'48]*

Feng (Chun-Ta) was called the Blue Ox Master (Chhing Niu Shih49). [Comm. The Han Wu

Nei Cluan says that he was a Kansu man. He began by eating huang-lien"t and after more than

fifty years he entered the Niao-Chu Mountains"6a and consumed metallic mercury. After more

than a hundred years he returned to his native village looking like a young man of twenty. He

always rode on a blue ox, which was why he was called the Blue Ox Taoist. If he heard of

anyone who was ill or dying, whether he knew him or not, he quickly gave him drugs, which

he kept in a tube of bamboo tied to his waist. Sometimes he practiced acupuncture on the

patients, who incontinently recovered, but he never revealed his names. He heard that Lu

Nu-Seng'1 had got hold of the Five-Mountain Map, and year after year he asked for it but he

could never obtain it. (Lu)+ would only counsel moderation. When he was over 2oo years old

he (Feng) went away into the Yuan-Chhiu Mountains.]

The association of urine with sexual activity therefore goes back to a very

early time in Chinese history, and if here we find it towards the end of the

second century A.D. it is highly probable that it was a Taoist art which could be

found in the second century B.C. also. Jung Chheng, the semi-legendary master of

the arts of sex and hygiene applied to longevity, was considered a man of this

time if not of the Warring States period (fifth to third centuries B.C.). The connection

with alchemy is here of course very evident and impressive. The curious

legendary adumbration of endocrinological operations is entertaining in the

context of Berthold's discovery, but hardly relevant, except in so far as it may

indicate physiological experimentation on the part of the Han Taoists. The case

of Feng Chun-Ta also illuminates the intimate relations between Taoism and

medicine.

A thousand years later one comes across the same belief and practice. Chu

Chen-Heng52 says in his PeAn Tshao ren I Pu I53 (Revision and Amplification of

the General Ideas of the Pharmacopoeia), written about A.D. 1350:§

I once attended an old woman over eighty years of age who gave an appearance of being

about half that seniority. In reply to my questioning she explained why she thought she had

had such good health. She had once suffered from a severe illness and had been instructed to

take human urine, and this she had done for more than forty years. Who could maintain

therefore the old belief that the property of urine is algorific, and that it could not be taken

for a long time? All such cases of yin hsi4" (impotence, sexual debility, eremosis, excess Yang of

burning feverish type, etc.) which no medicine can benefit will take a turn for the better if urine

is administered.11

* Chhin Shih Huang Ti was the first emperor of China unified under the first dynasty, the Chhin

(r. 221 to 210 B.C.); he sent Hsu Fu to find the isles of the immortals in the Eastern Ocean. Han Wu Ti

was the greatest of the Han emperors (r. 141 to 87 B.C.); he was served by many Taoist adepts, among

whom Luan Ta is remembered for his connection with the history of magnetical science; cf. SCC,

vol. IV, pt. I.

t Coptis tecta, a very bitter herb. + Another of Tshao Tshao's thaumaturgical experts.

§ Chu Chen-Heng (I280 to 1358) was one of the 'four famous physicians of Chin and Yuan'.

1I Quoted in PTKM, chap. 52, p. 15a. Some of the technical terms in this passage (and in those

which follow) have been developed by us to aid in the translation of medieval Chinese medical texts,

and will be fully explained in SCC, vol. vI.

107

Lu Gwei-Djen and joseph Needham

An intermediate date is represented by Chhu Chheng,55 a physician who

died in A.D. 501. In his remaining writings we read that the urine is valuable

because it has styptic properties.

When the throat has lesions, the patient coughs up blood and this may lead to death. The

throat will not tolerate anything on its walls, so that an object as tiny as a hair will cause a

severe cough. The more the coughing continues the worse the breathing will be, so that it is

essential to stop it. If urine is taken the condition is nearly always cured, but if algorific drugs

are given none of the patients gets better.*

We do not know what property of urine such styptic effects could be due to,

but there can be no doubt that throughout the centuries between Kan Shih

and Chu Chen-Heng urine was used medicinally. Li Shih-Chen says that it has

the property of leading forth from the body pathological influences.

Human urine is moderately calorigenic and not algorific. Urine entering the stomach is

absorbed, carried upwards to the lungs along with the pneuma of the spleen (phi chih chhi57), and

downwards to the 'water-passage' (shui tao58) to enter the urinary bladder.t This is the same

route through which it passed once before. For this reason it can lead the (undue) heat (yin

huoll), the cause of the illness, downwards to be excreted.",

In the light of all this it was perfectly natural that the sediments and natural

precipitates ofthe urine should arouse great interest among the Chinese medical

naturalists at an early time. While it seems that the appearance of the urine was

never rated so highly for the purposes of diagnosis as it was in the West,§

nevertheless it was thought that the sediments might contain very important

substances. The naturally occurring sediment was called nipai hsin60 orjen chung

pai,61 and the first evidence of its use occurs in the Thang period. Li Shih-Chen

says that it was first mentioned in the Thang Pen Tshao,62 and though this is not

extant today, we can confirm what he says by the manuscript of the Hsin Hsiu

Pen Tshao63 (Newly Reorganized Pharmacopoeia) 11 of A.D. 659, which was conserved

in Japan. The reference to ni pai hsin is there very clear. Possibly the

earliest account of its use, in this case for curing severe diarrhoea in infants,

occurs in the Chhien Chin rao Fang64 (Thousand Golden Remedies) by the great

Sui and Thang physician Sun Ssu-Mo about A.D. 650. In the fourteenth century

Chu Chen-Heng said that the

urinary precipitate has the property of leading out the (undue) heat affecting the liver, the

three coctive regions (san chiao"6), and the bladder, by way of the urine. This is because it was

itself originally excreted through the bladder and urinogenital tract.¶

Li Shih-Chen in the sixteenth century repeats the statement.** He says that

* Chhu Chhing I Shus", cit. PTKM, chap. 52, p. i6a.

t On p. I5a the 'water passage' is identified with the Ian min,"a structure which we recognize as

the colic valve at the junction of the ileum with the caecum and colon. Here the intestinal contents

were thought to separate into two portions, the aqueous part passing to the kidneys and the bladder,

while the solid residues continued towards the anus. The work of concentration of the contents was thus

symbolically located at a particular place. + Loc. cit.

§ For a brief account of ancient and medieval urinoscopy see Mettler, pp. 293ff.

CChap. 15, p. 189. 1 PTKM, chap. 52, p. iga. ** Lc. cit.

io8

Medieval Preparations of Urinary Steroid Hormones

jen chungpai makes the hsiang hou" (primary heat)* descend, and disperses static blood. This

is because of its saline property which enables it to benefit the hsia (chiao"6) (lower coctive

region) and to travel along with the blood.

Thus we have another principle, that of yin tao,67 leading something out by the

same way that it previously came itself. This brings us to the purification of the

urinary precipitates. Who would guess that one would have to look for them

in the Chinese pharmacopoeias under the names of chkiu shih68 (autumn

mineral) and chhiu ping69 (autumn ice, i.e. crystals)?t

The Iatro-Chemical Preparations

Writing about A.D. 1586, Li Shih-Chen tells us that urinary precipitate can

keep the blood in motion, greatly help sexual debility, bring down heat, kill parasites, and

disperse poisons; but the princes and wealthy patricians disliked using it because they considered

it unhygienic. So the iatrochemists (fang shih) began to purify the sediment, making

first chhiu shih and later on chhiu ping. For this they used two methods, the rang Ien70 and the

rin lien.71+

According to Li Shih-Chen the term chkiu shih was first mentioned in the Pen

Tshao Ming Ckhuan72 (Ignorance about the Pharmacopoeia Dissipated) produced

by Chhen Chia-Mo78 in A.D. 1567. Chhen Chia-Mo emphasized the value

of the product in many sexual and systemic disorders. However, Li goes on

to say:

The term was really first used by the Huai Nan TZU74 book.§ (Liu An748) named one of his

elixirs (tan) chhiu shih, to express its white colour and its solidity. Recently people have purified

the urinary precipitates (jen c/ung pai) to a white substance which is also called ch/iu shih, to

indicate that like the urine itself it is derived from the excess of the nutrient essentials (ching

chhi). The iatrochemists repeat the process of sublimation (shUng ta ), and the best product is

called chhiu ping. The idea (of the initial concentration) was derived from the evaporation of

sea-water in the production of salt. Indeed there are adepts who place (certain) salts in the

reaction-vessel and apply heat to obtain a substitute or imitation product. It is important to

know the difference between the real product and the false one.

One of our most important sources for the preparation of the hormones in

* This term usually refers to the heat of the cardiac region, but it is also applied to that of the urinogenital

system (cf. SCC, vol. iv, pt. I, p. 65). In Chinese medical literature, heat, fire and Yang are

interchangeable.

t There can be little doubt that the name derives from the fact that a long process gave rise to a white

product, for autumn is the climax of the yearly cycle of life and white was the colour of autumn in the

system of symbolic correlations (cf. SCC, vol. ii, pp. 262, 263, and vol. iv, pt. i, p. i ). Modern Western

students of Chinese materia medica have had a tradition of translating it simply as 'urea', but in the

light of the evidence here presented, this is quite untenable. Smith's explanation (I87I, p. 224) made

clear that the product as he knew it was simply the total urinary solids, but Giles' dictionary (I892,

no. 2302), adopted the bald identification, and so did Read (I93I, no. 419), who ought to have known

better. Curiously Smith adds that the substance is 'often kept in kitchens, to soften fresh meat required

for immediate use', for it.is indeed true that strong urea solutions denature proteins and bring them

into solution.

PTKM, chap. 52, p. 20b.

§ This work is one of the great classics of Chinese history of science; it was compiled about 125 B.C.

by a group of naturalists gathered by Liu An, the Prince of Huai-Nan. There is no mention of chhiu

shih in the text as we have it today; a solitary reference to 'autumn drugs' occurs in chap. 19, p. 14b,

but it has to do with something else.

I09

Lu Gwei-Djen and Joseph Xeedham

relatively purified form is a book called the Shui run Lu76 (Water and Clouds

Record) by a famous scholar, Yeh Meng-Te77 (A.D. I077 to 1I48). Another

work of about the same time refers to the preparations, namely the So Sui Lu78

(Fragments from the Ring of Jade) by an unknown author, probably of the

late eleventh century. This work says:

The property of chhiu shi/h is saline; it travels (in the body) along with the blood. When taken

it has the effect of reducing the (normal) equilibrium of Water over Fire, i.e. it weakens the

renal-urinogenital system so that it cannot balance the cardiac-respiratory system. So continual

use of the substance gives rise to pathological thirst.*

After quoting this, Li Shih-Chen goes on to say:

This is because it is a processed product with properties verging on the calorific. It is often

taken by lascivious people, who use it to further their unrestrained desires; the result is that

eremotic heat (hsa rang78&) is set at large, and the renal-urinogenital system and the seminal

secretion (chen shui7@) quite exhausted. How could there not be thirst in such conditions?

Besides people sometimes add Yang (calorific) drugs to intensify the aphrodisiac effect (hsieh

hUo79a). Therefore only those who suffer from internal eremotic algor in the umbilical region

and impotence (tan thien hsu lIbg"0) should take it. Look at those suffering from urinary gravel

and stone; in such patients the element of Water is weak and Fire is very strong, so naturally

there is evaporation and precipitation with the formation of calculi. This occurs by exactly the

same principle as is used in making chhiu shih from urine.

Here we have a strong indication that the products which were available in

Li Shih-Chen's time, as also apparently in the Sung, were of considerable

hormonal activity, even though perhaps this was difficult to control. His acute

account of the formation of urinary calculi is worth notice in passing.t The

Shui run Lu says that:

The best preparations are the products of two different processes of purification, one Yin

and one Yang. The rang lien process is designed to obtain the Yin concealed in the Yang,

for it condenses as heat is applied (in evaporation). It dissolves in water (a Yin entity) and

returns to formlessness (wu tMil), yet it retains its special properties (wei"9). It is like the broken

line in the kua L13.§

The rin lienlI process is designed to obtain the Yang concealed in the Yin, for

it precipitates when water is added to it. When dried in the sun it becomes glossy and changes

no more. In this case the (original) special properties (wei) are lost and the substance (chih83)

remains. It is like the solid line in the kua Khansm.1

Both substances came originally from the heart and the renal-urinogenital system (including

the sex organs) yet had once been flowing in the small intestine.... To take these substances

can be beneficial for those two systems (or organs), indeed they are the essentials for the

maintenance of a healthy life....**

* PTKM, chap. 52, pp. 20b, 21a.

t Gallstones and bezoars were instanced as examples of the concretive or aggregative forces in nature

by the Neo-Confucian philosophers in Sung times, when discussing the formation and dissipation of

souls; cf. Wieger, p. 215. + The text says ho lien,"°& but the meaning is the same.

* One of the symbolic trigams in the 'Book of Changes' (see SCC, vol. II, P. 313).

The text says shui liun," but the meaning is the same.

¶ One of the symbolic trigrans in the 'Book of Changes' (see SCC, vol. ii, p. 313).

** PTKM, chap. 52, p. 2ia, b.

I I0

Medieval Preparations of Urinary Steroid Hormones

We come now to a description of the six main preparation methods given in

the Pin Tshao Kang Mu.

Method I

This method is the simplest as it is the oldest. It is quoted by Li Shih-Chen

from a Ching ren Liang Fang84 (Valuable Tried and Tested Prescriptions). There

were several books of this name in the Yuan and early Ming periods (fourteenth

and fifteenth centuries), one by Lu Shang-Chhing,85 and we do not

know from which of them Li Shih-Chen took his account. However, it is

possible to show that the method goes back much earlier than this, because the

Chhung Hsiu Ching-Ho Cking Lei PEn Tshao86 (Reorganized Pharmacopoeia) of

A.D. 1249 quotes it* from a Ching ren Fang87 (Tried and Tested Prescriptions) of

still earlier date. Although this book is lost, the details of its publication are

known.t Its preface dates it at A.D. 1025 and its author was Chang Sheng-Tao.88

Other prescriptions of this physician, restorative for people on the point of

death, are quoted in various editions of the Hsi ruan Lu. Since Chang ShengTao

flourished at the beginning of the eleventh century, it is very probable

that his method for making chhiu shih was already quoted in the first edition of

the ChEng Lei PEn Tshao issued by Thang Shen-Wei89 in I Io8.

The title of the method is Chhiu Shih Huan ruan Tan.90 Its description is as

follows:

... Take ten tan'l or more (over 150 gallons) of men's urine and put it in a large evaporating

pan (kuo#2) in an empty room. Fix on top of it a deep earthenware still (shen wa ching9s) and

lute them together with paper, lime and straw, so that no steam comes out when it has dried.

Fill the evaporating basin 70 per cent or 8o per cent full with urine and heat from below. Set a

man to watch it. If (there is too much, then) gradually add cold urine, until dry. This (residue)

is jen chung pai. Place some of this in a (closed) container (a reaction-vessel, i.e. the ku chill

apparatus, ju hao kuan tzu nei, jufa ku chiM ) in a stove and heat with charcoal. About 2 or 3

ounces (of sublimate) will be obtained. Grind this to a powder, mix with dates, to make pills

the size of a mumg (lu tou)" bean.§ For each dose take five to seven pills with warm wine or

soup before breakfast ... 11

Here then the entire dried solids of the urine were used. Besides the obvious

urates, uric acid, phosphates, sulphates and other inorganic salts, there would

be the steroid glucuronides and sulphates. After the simple procedure of

evaporation, the entire fatty powder is placed in the sublimatory and the active

steroids carefully sublimed. It is a well-known fact that hormones of the steroid

class sublime unchanged below their melting-points, at temperatures varying

between 1300 and 2io0C.,** and there can be no doubt that this was the

* Chap. I5, p. 365-

t See Okanishi Tameto, pp. 972, 1138.

t Weights and measures changed considerably through Chinese dynastic history, but their movements

are well enough charted. The volume measure tou, sometimes translated peck, has often been

loosely rendered gallon (as in Giles' dictionary) because it comprised ten shbzgla or 'pints', but in

fact the absolute value of the 'pint' varied greatly in different centuries (see Wu Chheng-Lo, Table I3,

p. 58). Here we are concerned with the Sung and Ming periods; in the former the tan of ten tou was

equivalent to I4-5 of our gallons, in the latter to 23-6 gallons.

§ Phaseolus mungo, the mung bean, or gram.

1I PTKM, chap. 52, p. 2ia.

** See Kassau; Breuer & Kassau. Up to 260°C. there is no decomposition at all, and many compounds

will still sublime almost without loss up to 3000.

III

Lu Gwei-Djen and Joseph Needham

technique employed, because the term ku chi is found in alchemical and technological

writings with the meaning of sublimatory.* Since the entire solids of the

evaporated urine were taken for sublimation, the process must have been rather

a messy one, and it is not surprising that in the following centuries various

methods of preparation were worked out which got rid of many of the urinary

constituents before sublimation was attempted. This we shall see in the following

examples.

Method 2

This method, together with the following one, derives from Yeh Meng-Te's

Shui run Lu. This is clearly a Sung work, for Li Shih-Chen referst to its author

both under his ordinary name and under his hao or courtesy name, Yeh ShihLin.Y00

Since this scholar was living towards the end of the Northern Sung and

through the years of re-establishment of the dynasty in the South after the fall

of the capital, Khaifeng, to the Chin Tartars in A.D. I I26, one might be near

the truth in dating his prescriptions about A.D. i i io. He must have been one of

the younger members of the entourage of virtuosi of Hui Tsung, the last

effective emperor of the Northern Sung, in a court very similar in many ways

to that of Rudolf II at Prague later on, or Alfonso el Sabio in Castile at the end

of the following century.+ The first method is entitled rang Lien Fa.100

Use over io tan of urine (more than 150 gallons) in wooden buckets. For each tan (14.5

gallons) of urine add one bowlful of the juice of soap-beans (tsao chia chihl01). Stir energetically

with a bamboo stick hundreds of times. When the precipitate has settled, decant off the clear

fluid and keep the precipitate (ni pai hsin). Combine all the precipitates (with some liquid) into

one bucket, stir as before and allow to settle. Take one or two tou102 of the concentrated

mixture and filter. Place the precipitate in a kuo (large evaporating basin) and evaporate to

dryness. Scrape it out, grind it fine, and take up as much as possible of it by boiling with water.

Filter through paper over a bamboo sieve. Again evaporate to dryness and repeat these processes

several times until the precipitate becomes as white as snow. Then put it into an earthenware

container (sublimatory) (sha ho ku chi'03), seal tightly and heat until the sublimate

condenses. If the heating does not at first complete the sublimation, repeat the process once

or twice more until the colour of the product is like that of lustrous jade. Grind this to a fine

powder and place it in another container where it should be heated gently for seven days and

seven nights. Then take it out and spread it (on paper) laid on the ground, to get rid of the

noxious effects due to the heating. Finally mix the powder with dates to make (small) pills the

size of a wu(-thwig"04) seed.§ Thirty pills should be taken daily with warm wine before breakfast.

Here we have an extraordinarily interesting procedure. It is hard to believe that

the use of saponins for preparing steroids could anticipate by so many centuries,

* The nomenclature is delicate here, for the term can also mean a still, i.e. a vessel with a side-tube.

In Thien Kung Khai WU97 (The Exploitation of the Works of Nature) by Sung Ying-Hsing98 (A.D. i637)

ku chi is clearly a sublimatory for making vermilion (chap. i6, p. 2b) but it is shown near by as a still

for distilling mercury (p. 5b, descr. p. 2a). The illustration is reproduced in Ho Ping-Yu & Needham,

LEC, Fig. 52, cf. pp. 82ff., iooff. See further Tshao Yuan-Yu, pp. 43, 52 (pp. 78, 85).

t PTKM, chap. 52, pp. 2ob, 22a. Chinese literature contains one other book of the same title, by a

Ming pharmacist, Yang Po99, but Li Shih-Chen could hardly have been mistaken in a matter of this

kind.

X See SCC, vol. iv, pt. 2, pp. 50I ff., or Needham, Wang & Price, pp. 124ff.

§ Sterculia platanifolia, not to be confused with the thung-oil tree Akuritesfordii.

11 PTKM, chap. 52, p. 21b.

112

Medieval Preparations of Urinary Steroid Hormones

not merely decades, the classical discovery of Windaus in I909 that digitonin

precipitates many sterols quantitatively.* One of those so precipitated, indeed,

is an androgen, namely dehydro-epi-androsterone, and we know today that the

saponins will precipitate all the 3,B-hydroxy steroids. The precise action of

digitonin is well known, but one cannot be so sure about the action of the

various saponins contained in the soap-beans from Gleditischia sinensis, the

characteristic vegetable detergents used in China for hygienic purposes all

through the Middle Ages.t All one can be sure of is that they would precipitate

certain varieties of steroids.

Besides the addition of the saponins in this method of Yeh Meng-Te, there

was also the addition of proteins in the soap-bean juice. This is important

because it is known that all urinary steroids will precipitate with the protein

precipitate if one is present. This raises the question of the frequency of renal

lesions in the population of medieval China. It seems very likely that in every

collection of large amounts of urine as described in these preparations one at

least of the donors in the batch would quite probably have been excreting some

protein, and a small amount would be quite enough to produce the effects of

the precipitation of steroids. We suspect that schistosomiasis was widespread in

medieval China, and that in itself would be a possible cause of proteinuria.

Then there is the extraction of the total precipitate with boiling water. A

possible explanation would be that all the conjugated steroids were taken down

in the precipitate, but when the protein present was denatured by the boiling

water all would come out in the solution except the 3fl steroids which had been

firmly combined with the saponin. We may be here in the presence of an ancient

empirical method of partial separation of androgens from oestrogens.

Another feature of this method is of course the complete removal of soluble

solids in the urine, such as urea, by the use only of the first precipitate. A great

quantity of soluble salts will also be discarded at this stage. One notices too the

gradual elimination of the urinary pigments. Finally the reference to the sublimate

as resembling lustrous jade is, as already mentioned, a strong indication

that the glittering pearly appearance of crystalline steroids was being observed.

Method 3

This is the second method of Yeh Meng-Te in his Shui run Lu, dating from

about A.D. I I IO. It is called Ein Lien Fa,10", and like the previous method refers

back to the two types of separation, the theory of which was discussed in the

same book (p. I io above).

To 4 or 5 tan of urine (58 to 72-5 gallons) in large earthenware vats add half its volume of

rainwater and stir a thousand times. Allow to settle. Discard the clear solution and keep the

precipitate (ni pai hsin). Repeatedly wash with rainwater, stir and allow to settle until no disagreeable

odour remains and the precipitate resembles putty or face cream (nifin105). Let it

dry in the sun, scrape it up and grind it. Then mix with milk from the mother of a male baby

* The protective action of cholesterol in saponin haemolysis was thus explained; and the digitonin

precipitation method was immediately applied (Windaus, QBC) to the assay of free and esterified

cholesterol in biological entities such as the normal or diseased kidney.

t See Needham & Lu Gwei-Djen, HYG, pp. 458ff.

I 13

Lu Gwei-Djen and Joseph Needham

into a paste (kao'°") or fatty-like ointment and dry this in very hot sunshine. By this procedure

one obtains the life-giving essentials of the sun (thaiyang chen chhil07). Repeat this nine times

and then mix with dates to make pills. Twenty of these should be taken at midday with warm

wine.*

This is one of the two methods which begins by diluting the urine. It might at

first sight be thought possible that this would help to precipitate lipoidal or

steroidal constituents, but since the steroids are all in the form of soluble

conjugates, it seems unlikely that this would happen. We are not clear as to the

purpose of the dilution, but at any rate it would have done no harm, since it

would help to remove soluble substances such as urea and salts. In what way

the conjugates were got into the precipitate in this method we are not clear.

Perhaps the description accidentally omits some protein precipitant. In any case

it is interesting that here no sublimation was involved. The fact that the precipitate

was of a fatty consistency and taken up in milk fat is also appropriate

enough if free steroids were present, but unless the urine sources had included

cases of lipuria, such as may occur in diabetes, it is not easy to understand why

the eventual precipitate should have been so fatty in nature. One thing at any

rate is probable, namely that these two methods of Yeh Meng-Te would have

yielded different groups of active urinary steroids, perhaps giving another

separation of androgens from oestrogens. The fact that one of his methods was

considered Yang and the other Yin gives us a rather strong hint that differences

of just this sexual nature had in fact been observed by the physicians who used

these preparations.

Method 4

The next two descriptions are taken from two books of formularies of the early

Ming period (fifteenth century). They both stem from local surgeries or

pharmacies, exactly where in China we do not know. The first, entitled Chhiu

Ping Ju Fin Wan,108 from a book called I Chen Thang Ching ren Fang'09 (Tried

and Tested Prescriptions of the True-Centenarian Hall) was the work of a

writer known only to us by his family name, Mr. (or Dr.) Yang.'10 The text is

as follows:

One bucketful each of the collected sediment (ni pai hsin) from the urine of boys and girls

(dulng nan thung nill) is used.t Heat the evaporating pan containing the sediment with

mulberry firewood and evaporate until dry. Remove the residue and place it in one bucket

of river water. Mix well until as much as possible is dissolved. Filter and evaporate the filtrate.

Repeat the same procedure seven times. By then the residue is as white as frost. Next it is

usual to collect i catty of the frost-like residue and place it in an earthenware jar. Cover with

an iron lid the shape of an oil lamp, and apply salt-mud lute to make it tight. Heat the jar

during the space of the burning of three bundles of incense-sticks to sublime (s/zng ta) the

substance. At this stage you will see that the chhiu shih has become as white as jade. Grind the

product and repeat the procedure. Very gradually sponge cold water on to the cover, care

being taken in the process, for with too much cooling the product will not volatilize, and with

* PTKM, chap. 52, p. 2Ib.

t This must mean an initial volume of at least 400 gallons. The age implied here would be, in the

most natural acceptation of the text, under about fifteen, for the Jei Ching defines the marriageable

age as sixteen for boys and fourteen for girls. But it may mean unmarried or virgin boys and girls in

the sense of the usages of the writer's own time, i.e. up to about eighteen or so.

I 14

Medieval Preparations of Urinary Steroid Hormones

too little cooling it will not condense.* Carry out the process from the chhen double-hour

(7-9 a.m.) until the wei double-hour (i-3 p.m.). Then take away the fuel and let the vessel

cool. The substance which has collected under the cover is chhiu ping, ice-like (glossy), tasteless

and pleasant-smelling. This substance is the (best) pure essence of the chhiu shih.t When taken

it is beneficial for the liquid of the renal-urinogenital system, restoring urinary and sexual

normality; it fortifies the vital resistance (yuan ang113) and also drives down the heat which

produces phlegm (than huoll3) in the thoracic region. The residue is ordinary chhiu shih,

saline and bitter in property like burning meat. In this there is some slight benefit when taken.+

Here again we see processes of purification carried out so that the very soluble

substances such as urea and some salts, together with the pigments, are first

discarded; and the conjugates then progressively separated from urates, inorganic

salts, denatured proteins, etc., less soluble than themselves. The

sublimation process is more clearly described and directions are given that the

sublimation should be repeated. Apparently some active substances remained

in the residue which did not sublime. One assumes that the active steroid

conjugates were carried down with small amounts of protein at the beginning

of the operation and passed thereafter into the extracts of the successive residues

until sublimation.

Method 5

This method comes from a book of about the same date as the previous

formulary. It is entitled Pao Shou Thang Ching ren Fang"4 (Tried and Tested

Prescriptions of the Protection of Longevity Hall), the author of which was Liu

Sung-Shih.116 The name of the medicament prepared was Chhiu Shih Wu Ching

Wan."16 The text runs as follows:

Select boys and girls§ free from any illness as the donors of the urine. They should be bathed

and their clothes changed. They should be provided with innocuous food and soup, but one

should avoid giving them foods with rank and pungent smells, such as leeks, onions, garlic,

ginger, etc., or other things which have an acrid property. When sufficient urine, about I tan

(23-6 gallons) has been collected from each group in one vat (kang117), add half its own volume

of water, stir, and collect the precipitate (jen chung pai). Place this in an earthenware reaction

vessel (wa kuanll8) from Yang-chhengll8S. Make the opening airtight with the lute (a mixture

of salt and mud) and use iron wire (or netting) to fix it in the stove. Heat during the space of

one bundle of incense-sticks, and repeat the heating seven times, securing with fresh wire

each time. Then take weighed equal portions (of the sublimate) from the male and female

urine precipitates thus treated. Mix and grind together. Dissolve the material in river water

and filter through seven layers of paper. Evaporate to dryness and obtain the chhiu shih which

is snow-white in colour. Add to this good sweet thick milk and mix. Leave it in the open air

to absorb the sun during the daytime and the dew at night, in order to acquire the essence of

the sun and the glory of the moon. After it has been dried further add more milk for forty-nine

days. Preserve it as an ingredient for prescriptions.11

Here the directions about the treatment of the urine donors are interesting, and

the details of the sublimation are much the same as before. At first sight it seems

* An inversion in the text has been corrected here.

t It will be noticed that the term chhiu ping seems to be reserved for preparations which have sublimed

repeatedly.

+ PTKM, chap. 52, p. 22a.

§ See note, p- 114, on this subject.

11 PTKM, chap. 52, p. 22b. This method became the most popular one after Li Shih-Chen's own

time, for one finds it constantly repeated in pharmacopoeias of the seventeenth and eighteenth centuries.

I "5

Lu Gwei-Djen and Joseph Needham

surprising that the text should speak of dissolving the sublimate in water, for if

this was composed of free steroids it could not go into solution. But it seems

likely that while the sulphate conjugation would be broken by the heating, the

glucuronide combination would not, and the sublimate would therefore be

composed of two parts, one water-soluble and one insoluble. If specific differences

existed between the hormones conjugated in different ways, this procedure

may possibly have been yet another quasi-empirical fractionation, producing

end-products of highly specific properties.

Method 6

The following description, the last which we shall quote, comes from the Pin

Tshao Ming Chhian of Chhen Chia-Mo, already mentioned (p. IO9), written in

A.D. 1567. His description says:

To make chhiu shih specimens of urine of boys* should be collected in the autumn. Add to each

earthenware vat (kang) o07 oz. of powdered calcium sulphate (gypsum, shih kao mol1l). Stir

well with a mulberry stick and allow the precipitate to settle. Discard the clear supernatant

fluid. Stir again and allow to settle. Repeat this two or three times. Then add to the precipitate

one bucket of autum dew water, stir and allow to settle. Repeat this again several times until

the impurities are removed and the precipitate is quite free from any salty taste. Filter the

precipitate on heavy paper placed over ashes, and allow it to sun dry. The light clear crystals

forming the upper part of the precipitate are collected, and this is chhiu shih, while the lower,

grosser layer is discarded.t

This seems to be rather a return to the second or blunderbuss method of Yeh

Meng-Te (Method 3 above). No sublimation process is used, but it is interesting

that calcium sulphate is added to begin with, an agent which would probably

assist the precipitation of the proteins and the steroid conjugates adsorbed upon

them. The procedure seems to end with a manual separation of the lighter from

the heavier part of the final precipitate. Chhen Chia-Mo has two curious

observations. He says that for male patients specimens from female urine should

be used and vice versa. He also criticizes practising physicians (shih i120) of his

own time and earlier who collect mixtures of all kinds of urine at any time and

precipitate with soap-bean juice, then dry the product and call it chhiu shih. He

regards this as a way of money-making which may have dangerous consequences.

For us, however, it is interesting in that it suggests that the saponin

method already introduced in the eleventh century must have been used a

great deal through the time elapsing between Yeh Meng-Te and Chhen

Chia-Mo.

Discussion and Conclusions

From all the foregoing material it is fairly clear that from the eleventh

century onwards the Chinese alchemists, physicians and iatrochemists were

earnestly looking in urine for substances of androgenic and oestrogenic property.

They had recognized its connection with the blood, and they felt that within it

could be found some of the virtues which the organs contributed to the blood

* See note, p. 1 14 on this subject. t PrKM, chap. 52, p. 2oa.

iI6

Medieval Preparations of Urinary Steroid Hormones

circulation. In our opinion they were successful in medieval times in making

quasi-empirical preparations of active substances with androgenic and oestrogenic

properties.

Of the six methods described herein, four involve a carefully controlled

sublimation at temperatures which would very probably have varied between

1200 and 300° C., in other words, just those which would bring about a sublimation

of the steroid hormones. Of course other substances would have sublimed

too; for example, cyanuric acid derived from any urea which was still present.

Cyanuric acid has no known effect in man but it has been shown to be antimalarial

in birds. Uric acid itself would have decomposed, gving rise to

ammonia and C02. The purification from urinary pigments preceded the

sublimation, but other substances present in small quantities, such as indole,

skatol, mercaptans, volatile fatty acids and non-steroidal phenols, would either

have been washed away or may have sublimed with the steroids. Since none of

them was in any way toxic that would not matter.

In two of the methods described there is a long series of precipitations and

evaporations before the material is brought to the sublimatory. In two cases

specific agents, soap-bean saponin and powdered calcium sulphate, are mentioned.

The significance of these has already been pointed out, the use of

saponin in particular being an extraordinary anticipation of modem practice.

Beside these, however, it is highly probable that small amounts of protein were

present in the urine, and the precipitation of this, whether by heat or by the

gypsum added, would without doubt have carried down the conjugated

steroids. The lipoproteins of the soap-bean would have had a similar function.

What the object was of the initial dilution recommended in some cases we do

not know, but it could have done no harm. The final end-product was no doubt

a very mixed one, consisting of steroids from the testis, ovary, adrenal cortex

and placenta; and it probably varied in accordance with the exact method of

fractionation used.

Some interest attaches to the precise directions about the age and sex of the

urine donors. We know today that androgen excretion reaches its maximum in

men about the age of twenty-five and in women also, though they excrete a

lesser amount. Conversely, maximum excretion of oestrogens occurs in girls

before twenty and in boys about eighteen, the latter, however, excreting only

about half as much as the former.* The word thung in the descriptions, though

originally meaning quite young boys and girls, may well mean here just unmarried

youths and girls of about eighteen or so. If maximum yields of the

steroid sex hormones were sought, it would have been somewhat quixotic to

insist on starting out with urine from boys and girls before puberty.

What is particularly striking is that in one at least of the methods the urine

from male and female sources was actually worked up separately and the

products later combined in equal proportions. From this it is very reasonable

to suppose that the Chinese physicians found, at least in late times, that quite

different effects could be produced by using the sublimates in varying proportions,

even wholly male or wholly female. One almost expects to find some

* Dorfinan & Shipley, pp. 259, 396ff., 4ooff.

I 17

Lu Gwei-Djen and Joseph Needham

reference to the urine of the mare, that spectacular source of sex hormones.*

And indeed it may perhaps have been used for preparing sublimed chhiu ping,

for it is in fact listed among the equine products of pharmaceutical value,t

though in connection with various other diseases.

All in all, the experimental preparation of mixtures of steroid sex hormones by

the Chinese during the Middle Ages and the sixteenth century must surely stand

as an extraordinary example of quasi-empirical anticipation of knowledge

acquired only in very recent times. When one considers that they totally lacked

the powerful methods of separation available today which depend upon the use

of many different organic solvents, one feels amazed at the ingenuity with which

they mastered their problem. In view of their theoretical presuppositions, one

might suppose that it would have been more logical to use blood rather than

urine as the starting-point, but here the difficulty of the presence of so much

protein would have presented itself acutely, and one may reasonably suppose

that while the handling of blood was beyond the powers of the medieval iatrochemists,

urine as a starting-point was much more manageable. And so at it

they went, with their 200 or 300 gallons, almost on a pharmaceutical manufacturing

scale, their evaporating basins, and their clever sublimatories-a

brilliant and courageous anticipation of the conscious biochemistry of our

own time.

*Brooks, et al., p. i i i; the classical paper is that of Hiusler in 1934.

t PTKM, chap. 50B, p. 23b. Elsewhere there is mention also of the pharmacological use of the

urine of the sheep and the cow.

Medieval Preparations of Urinary Steroid Hormones

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I20

Medieval Preparations of Urina?y Steroid Hormones

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121