The first use of the term “hormone” can be traced back to Britain. In 1905, Ernest H. Starling, professor in physiology at University College in London, introduced the concept of hormones:
These chemical messengers…or “hormones” as we may call them, have to be carried from the organ where they are produced to the organ which they affect, by means of the blood stream, and the continually recurring physiological needs of the organism must determine their production and circulation through the body.
(Starling 1905)
The concept of hormones as potent substances regulating physical processes in organisms implied a drastic change in the paradigm of physiology. Edward Schaefer, professor at University College in London, evaluated this shift as follows:
The Old Physiology was based, as we have seen, on nervous regulation; the New Physiology is based on chemical regulation.. The changes of physiology which have resulted from this knowledge constitute not merely an advance in degree but an alteration in characte.. We must in future explain physiological changes in terms of chemical regulation as well as nervous regulation.
(Edward Schaefer as cited in Medvei 1983:339)
The “New Physiology” enabled scientists to conceptualize the development of organisms in terms of chemical agencies, rather than just nervous stimuli. The chemical messengers believed to originate from the gonads (sex glands) were designated sex hormones, with male sex hormone designating the secretion of the testis and female sex hormone designating ovarian secretion. With the introduction of the concept of sex hormones scientists suggested that they had found the key to understanding what made a man a man and a woman a woman. In the General Biological Introduction to the first textbook of sex endocrinology, Sex and Internal Secretions, the French-Canadian zoologist Frank R. Lillie evaluated this rapidly expanding research field:
One of the most interesting and promising lines of experimental biological investigations of the present century has been in the biology of sex. It has been discovered that sex characteristics in general are subject to certain simple mechanisms of control that operate throughout the life history, and which determine whether male or female characters shall develop in the individual…. The mechanisms of control are exceedingly simple compared with the sex machinery itself.. This book deals predominantly with a method of control of sex characters which is especially characteristic of vertebrates including man, mediated by hormones circulating in the blood. Of these, the specific internal secretions of the testis, or male sex hormone, and the specific internal secretion of the cortex of the ovary, or female sex hormone, are the most important, and probably occur in all vertebrates.
(Lillie 1939:5-6)
In the same textbook Lillie described the function of sex hormones:
As there are two sets of sex characters, so there are two sex hormones, the male hormone controlling the “dependent” male characters, and the female determining the “dependent” female characters.
(Lillie 1939:11)
Sex hormones were thus conceptualized as the chemical messengers of masculinity and femininity.
To what extent were these developments linked to any prescientific ideas? The idea of testes and ovaries as agents of masculinity and femininity can be traced back to several periods in which these ideas emerged, prior to the hormonal era.
The idea that the ovaries are in one way or another related to female sexual development can be traced back as far as Aristotle. In his History of Animals Aristotle wrote that “the ovaries of sows are excised with the view of quenching in them sexual appetites and of stimulating growth in size and fatness” (Aristotle as cited in Corner 1965:3). Aristotle was referring here to the custom of removing ovaries in domestic animals, a widespread practice among European fanners in the Middle Ages, that seems to have been kept in use till the late nineteenth century. The idea that the ovaries are somehow linked to female sexuality remained, however, for a long time restricted to the domain of agricultural practices (Corner 1965:4).
Let us first focus our attention on the prescientific precursors of the concept of male sex hormones, before tracing how the idea of ovaries as agents of femininity became incorporated in the life sciences. The idea that the male gonads are the seat of masculinity is a very old one. From the earliest times, the testis has been linked with male sexuality, longevity and bravery. Greeks and Romans used preparations made from goat or wolf testes as sexual stimulants. The seventeenth century brought a revival of these ancient ideas of virility. In this period, the prescientific idea of testes as agents of masculinity became for the first tune incorporated into medical science. European reformers, like the physician Paracelsus, used testes extracts in the treatment of “imbecility of the instruments of generation.” The official pharmacopoeia of the London College of Physicians of 1676 gave directions for the extraction of animal reproductive organs as a treatment for numerous illnesses and as sexual stimulants. In the eighteenth century, belief in the testis as the controller of virility was abandoned to the realm of folk-wisdom and quackery. By 1800, testicular extracts had disappeared from the official pharmacopoeias in Europe. The belief in the testis as agent of masculinity remained, however, very much alive in popular culture. Although the medical profession strongly disapproved of testicular therapy, potions made from testis extracts were among the wares of eighteenth-century quacks and were quite popular all over Europe.3
How did the pre-ideas of testes and ovaries as seats of masculinity and femininity become integrated into the modern life sciences? The most conspicious actor in advocating the doctrine of the gonads was the French physiologist Charles-Edouard Brown-Sequard. In 1889, Brown-Sequard addressed his colleagues at the Societe de Biologie in Paris, reporting the results of self-medication in which he had treated himself with injections prepared by crushing guinea-pigs’ and dogs’ testicles, resulting in “a marked renewal of vigour and mental clarity.” He also reported the practices of a midwife in Paris, who treated women with the filtered juice of guinea-pigs’ ovaries for “hysteria, various uterine affections, and debility due to age” (Corner 1965:5). On this occasion Brown-Sequard suggested that the testes produced a secretion that controlled the development of the male organism. These “internal secretions” might be discovered by using extracts in treatment for certain diseases.4 Brown-Sequard’s advocacy gave rise to a renewed interest in the 1890s in what was now called “organotherapy”: the use of extracts of animal organs as therapeutic agents.5
The scientific community reacted for the most part with hostility to Brown — Sequard’s claims. In their eyes the clock was being put back to the dark ages of quackery. On the other hand, Brown-Sequard, as the successor to Claude Bernard at the College de France, was considered a distinguished neurophysiologist (Hamilton 1986:12,15). Moreover, Brown-Sequard’s ideas harmonized with Victorian notions of masculinity. He suggested that the secretions of the testis were present in the seminal fluid containing sperm. In this manner, Brown-Sequard linked his ideas to the then popular notion that loss of semen, through sexual intercourse or, even worse, masturbation, was weakening the male. Brown-Sequard’s claims thus not only reflected prescientific ideas about the power of the testis that can be traced back to early civilization, but also reflected the sexual assumptions of Victorian days (Hamilton 1986:16).
If we want to trace how the prescientific idea of the ovaries as the seat of femininity became integrated into the center of the life sciences, we have to direct our attention to another place: the gynecological clinic. It was through changes in medical practice that the prescientific idea of ovaries as agents of femininity became incorporated into scientific theory and practice. Until the mid-nineteenth century, medical scientists studying the female body focussed their attention primarily on the womb. The uterus was known several millennia before the ovary (the “female testicle”) was described as an anatomic unit.6 Scientists located the essence of femininity in the uterus. Beginning in the middle of the nineteenth century, medical attention gradually shifted from the uterus to the ovaries. The ovaries came to be regarded as the essence of femininity itself: the study of these organs would lead to an understanding of woman’s whole being, including all women’s diseases. (Gallagher and Laqueur 1987:27). In gynecological textbooks the ovary was described as “the organ of crisis which is missing in the male body.” This shift from the uterus to the ovaries provided the gynecological profession with their own “paradigm-specific” organ which enabled them to delineate the boundaries between gynecology and obstetrics, the profession that focused primarily on the uterus (Honegger 1991:82-83).
In this period the role of the ovaries was not yet described in terms of chemical substances, but rather in the then popular terms of regulation by the nervous system. Gynecologists were the first to introduce the idea that ovaries secreted chemical substances that regulate the development of the female body (Medvei 1983:215). They were already familiar with the changes in the body that followed the removal of ovaries, due to the widespread medical practice of surgical operations for the removal of the ovaries in the late nineteenth century (Corner 1965:4; T. Laqueur 1990:176). Two Viennese gynecologists, Emil Knauer and Josef Halban, described the secretion of chemical substances by the ovaries as early as 1896 and 1900. Gynecologists were thus the first to recognize the relevance of Brown-Sequard’s theory of “internal secretions” to the female sex glands.7 This branch of the medical profession came under the spell of the glands because of their therapeutic promises. Gynecologists were particularly attracted to the concept of female sex hormones because it promised a better understanding and therefore greater medical control over the complex of disorders in their female patients frequently associated with the ovaries, such as disturbances in menstruation and various diseases described as “nervous” in medical literature. Moreover, by linking female disorders to female sex hormones, “women’s problems” remained inside the domain of the gynecologists.
THE EMERGENCE OF SEX ENDOCRINOLOGY
In the first decade of the twentieth century, the study of sex hormones developed into a major field of research that became known as sex endocrinology.8 The concept of sex hormones as agents of masculinity and femininity functioned as a paradigm, focusing previously scattered research around a generally accepted theory. Compared with gynecologists, physiologists were relatively slow to recognize the relevance of the theory of internal secretions for the sex glands. One of the main reasons for this was the association of the sex glands with human sexuality and reproduction, an area that previously had been taboo in biomedical research. This negative association was reinforced by the therapeutic claims of Brown-Sequard about the effects of testis extracts on the sexual activity of men, claims that caused a controversy among clinicians and laboratory scientists. Physiologists who took up the study of ovary and testes preparations did so cautiously, avoiding association with these therapeutic claims. Obviously, the subject was more legitimate for gynecologists (Borell 1985:2).9
After the turn of the twentieth century, physiologists also gradually came under the spell of the gonads. Schaefer’s laboratory in London was one of the first physiological laboratories that took up the study of the ovaries (Borell 1985:13). The physiologists were particularly interested in the study of the glands because the concept of hormones provided a new model for understanding the physiology of the body. In the first decade of the twentieth century, physiologists included the study of the ovaries and testes as a branch of general biology (Corner 1965:7). Hereby the traditional borders between two different groups of actors—the physiologists and the gynecologists— changed drastically. Before the turn of the twentieth century the study of ovaries, particularly in relation to female disorders, had been the exclusive field of gynecologists. With the introduction of the concept of sex hormones, laboratory scientists explicitly linked female disorders with laboratory practice, thus entering a domain that had traditionally been the reserve of gynecologists. Whereas gynecologists were particularly interested in the functions of the ovaries in order to control all kinds of disorders ascribed to ovarian malfunction, physiologists had a broader interest in the role of the ovaries and testes in the development of the body.
The concept of hormones triggered a new experimental approach in laboratory science. At the turn of the twentieth century scientists began to search actively for the chemical substances in the sex glands using the techniques of castration and transplantation. In this surgical approach, scientists removed ovaries and testes from animals like rabbits and guinea- pigs, cut them into fragments, and reimplanted them into the same individuals at locations other than their normal positions in the body. With these experiments scientists tested the concept of hormones as agents having control over physical processes without the mediation of nervous tissue. In transplantation the nervous tissue of the glands was dissected, so the effects of the reimplanted glands on the development of the organism had to take place through another medium, such as the blood (Borell 1985).
The acceptance of the hormonal theory in the biological sciences was facilitated by the fact that it fitted into a major debate among biologists about the sexual development of organisms. In the 1910s, the topic of sexual development was most controversial, particularly between physiologists and geneticists. Physiologists at that time suggested that the determination of sexual characteristics is affected by environmental and physiological conditions during the development of the embryo. Geneticists suggested however that sex is irrevocably fixed at conception by nuclear elements: the sex chromosomes.10
With the introduction of the concept of sex hormones, sex endocrinologists claimed they had found the missing link between the genetic and the physiological models of sex determination. In 1916, Frank Lillie provided arguments for the role of sex hormones as well as sex chromosomes in the sexual development of higher animals by studying intersexes in cows. Lillie looked at the anatomical characteristics of the freemartin, the sexually abnormal co-twin of a male calf, usually possessing female as well as male external genitalia. Lillie suggested that the freemartin, a “natural experiment,” is genetically female but that “a powerful blood-born chemical produced in the male had altered the sex that the genes intended for the freemartin”. Lillie thus suggested that “the intentions of the genes must always be carried through by appropriate hormones developed in the gonad.”11
This suggestion provided geneticists and sex endocrinologists with arguments to demarcate the fields of the two young sciences with respect to the study of sex, a demarcation coined with the concepts of sex determination and sexual differentiation. Geneticists focussed on the study of sex determination, defined in Sex and Internal Secretions as “the establishment of internal conditions leading to the development of one or the other set of sex characters”. Sex endocrinologists restricted their research to the study of sexual differentiation: “the development of sexual characteristics in the course of the individual’s life history.” Lillie described this demarcation of the domains of genetics and sex endocrinology as follows:
It is clear that we must make a radical distinction between sex determination and sex differentiation. In most cases the factors of sex determination are chromosomal, and subject to the usual laws of Mendelian inheritance…. In the higher vertebrates, the mechanism of sex differentiation is taken over by extracellular agents, the male and the female sex hormones.
(Lillie 1939:7-8)12
In the early decades of the twentieth century sexual development came thus to be defined as the result of two processes: sex determination regulated by genetic factors, and sexual differentiation influenced by hormonal factors.
In the 1920s, biochemists became involved in the study of sex hormones. Following advances in organic chemistry in the late 1910s, the surgical approach of transplanting gonads was replaced by chemical extraction of the gonads. The introduction of the chemical approach into the study of sex hormones was—compared with other fields—somewhat belated. This delay was partly due to technical problems. In the 1910s, biochemists were preoccupied with proteins. In this period the biochemists had “neither the incentive nor the information” to enter the field of sex hormone research. This situation changed in the 1920s when lipid chemistry emerged as a new line of inquiry in biochemistry. In the 1920s, sex hormones were classified as steroids, a class of substances that could be extracted with the same solvents applied in extracting lipids, thus providing biochemists with both the information and the tools to enter the study of sex hormones (Long Hall 1975:83).
In addition to clinicians and laboratory scientists, the emerging field of sex endocrinology also attracted a third group to the scene: the pharmaceutical industry. The manufacturing of extracts from animal organs offered a new and promising line of production. Pharmaceutical companies started producing ovary and testes preparations, and not without success. At the turn of the century the advertising pages of medical journals were full of recommendations for the prescription of these preparations under a wide variety of trade names, indicating a flourishing trade in “biologicals” (Corner 1965:6). Many researchers involved in the study of sex hormones worked in close cooperation with pharmaceutical companies. This issue will be dealt with in further detail in Chapter 4.