The 7 Sexes: Biology of Sex Determination

By Elof Axel Carlson

What makes us male or female? A geneticist explains the history of scientific research into human sexuality and reproduction.

In this book, geneticist and science historian Elof Carlson tells the incredible story of the difficult quest to understand how the body forms girls and boys. Carlson’s history takes us from antiquity to the present day to detail how each component of human reproduction and sexuality was identified and studied, how this knowledge enlarged our understanding of sex determination, and how it was employed to interpret such little understood aspects of human biology as the origin of intersex births.

“Reveals the various scientific advances, in both methods and understanding, that allowed researchers to identify anatomical structures, gametes, sex hormones, sex chromosomes, and ultimately, a firm comprehension of the genetics of sex. . . . This scientific story of discovery is quite fascinating.” —Barbara Baumgartner, Washington University, St. Louis

• Language: English
• Publisher: Open Road Integrated Media
• Release date: Feb 12, 2013
• ISBN: 9780253006547

Book preview

The 7 Sexes

The 7 Sexes

BIOLOGY OF SEX DETERMINATION

ELOF AXEL CARLSON

This book is a publication of

Indiana University Press

601 North Morton Street

Bloomington, Indiana 47404-3797 USA

iupress.indiana.edu

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© 2013 by Elof Axel Carlson

All rights reserved

No part of this book may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying and recording, or by any information storage and retrieval system, without permission in writing from the publisher. The Association of American University Presses’ Resolution on Permissions constitutes the only exception to this prohibition.

The paper used in this publication meets the minimum requirements of the American National Standard for Information Sciences—Permanence of Paper for Printed Library Materials, ANSI Z39.48–1992.

Manufactured in the United States of America

Library of Congress Cataloging-in-Publication Data

Carlson, Elof Axel.

The 7 sexes : biology of sex determination / Elof Axel Carlson.

p. cm.

Includes bibliographical references and index.

ISBN 978-0-253-00645-5 (cl : alk. paper) — ISBN 978-0-253-00654-7 (eb)

1. Sex determination, Genetic. I. Title. II. Title: Seven sexes.

QP278.5.C37 2013

612.6—dc23

2012030688

1  2  3  4  5    18  17  16  15  14  13

Dedicated to Alfred Charles Kinsey (1894–1956)

who changed the discussion of human sexuality from ignorance

and tradition to scientific findings.

CONTENTS

List of Tables

List of Figures

Preface

1 Introduction

2 Wild Guesses in an Era of Scientific Ignorance

3 The Ancient World

4 Monotheistic Religious Interpretations

5 The Descriptive Embryology of Male and Female Development

6 The Discovery of the Egg in Higher Eukaryotes

7 The Discovery of Sperm in Higher Eukaryotes

8 The Discovery of Sex Hormones

9 Ploidy Levels and Sex Determination

10 The Discovery of Sex Chromosomes

11 The Balance Theory of Sex Determination

12 The Discovery of Sex in Microorganisms

13 The History and Interpretations of Hermaphrodites and Intersexes

14 Dosage Compensation and the Sex Chromosomes

15 The Discovery of Human Sex Chromosome Conditions

16 The Seven Sexes of Humans

17 The Identification and Role of Sex-Determining Genes

18 The History of Homosexuality

19 The History of Behavioral Gender Assignment

20 The Evolution of Sex Determination

21 What Does It Mean to Have an Assigned Sex?

22 The Quest for a Unified Theory of Sex, Gender, and Sexuality

Afterword

Appendix: Secondary Literature and the Relation of Biology to Sex and Gender

Glossary

Notes

Index

LIST OF TABLES

LIST OF FIGURES

PREFACE

Every aspect of the history of sexuality is controversial. Eating, fashion, sports, occupation, or political outlook can be discussed freely in public, even by those who disagree. There is not the same intensity of unease that accompanies these aspects of our lives as it does sexuality. A major reason for this unease comes from religion. Religions, especially the monotheistic ones, have long held strong opinions on sex, mostly regulating sexual behavior and often describing transgressions as abominations, sins, or moral crimes leading to the fury of God or those representing God’s views. A second reason for treating sexuality with fear, guilt, or embarrassment stems from our psychology. For Freudian psychiatrists, sexuality was the basis for all neurotic and psychotic conditions they interpreted or tried to help. Whether we treat psychiatric approaches with respect or disapproval as a healing science, we usually repress our sexual thoughts in public settings, and are awkwardly aware of the passing or fleeting moments of erotic awareness that shove themselves into our minds at inappropriate times. A third reason is cultural. Each community develops its own ideas about the differences in sexual behavior expected of males and females. These ideas sometimes reflect religious views, but often have their own expression in how we behave in our daily lives as men and women in society, which limits aspects of sexual behavior in public—from kissing, holding hands, exposing parts of our bodies without clothing, or hiding most of them, especially those parts usually associated with our sexual identification.

The same unease applies to the scientific study of sexuality. Each generation learns something more about the biology, psychology, or cultural history of sexuality. Society itself changes in the way it regards children born with sex disorders, just as it does for those born with birth defects not associated with sex. Since the 1980s, terms like mongoloid idiocy, juvenile amaurotic idiocy, and gargoylism have yielded to neutral terms like Down syndrome, Tay-Sachs syndrome, and Hurler syndrome. In a similar way, older terminology in the scientific literature is yielding to a new vocabulary for the twenty-first century. All forms of human hermaphroditism are now referred to as intersexuality. The generic term disorders of sex development (DSDs) or differences of sex development is gradually replacing older terms like male pseudohermaphrodite (46,XY DSD), female pseudohermaphrodite (46,XX DSD), true hermaphrodite (ovotesticular DSD), XX male sex reversal (46,XX testicular DSD), and XY female sex reversal (46,XY complete gonadal dysgenesis).¹ These new terms may be easier and more descriptive for the scientist to use, but they are more difficult for parents of such children when describing their child’s condition to relatives and friends. Some may still have an alienating connotation and may be subject to further descriptive changes, or eventually they may be switched to neutralizing eponyms—as in Turner syndrome (for the human 45,X syndrome) or Klinefelter syndrome (for the 47,XXY syndrome).

In this history, I will use the older terms as they were in use at the time, but in the final chapters I will use the old or new terms (with their alternate terminology in brackets) so readers will not have to flip back and forth to Table 22.2 to know what is being discussed. Sexuality is a huge topic, and while all aspects of sexuality enter into the discussion of sex determination to some extent, the main emphasis in this book is the history of the biological processes that deal with the mechanisms and events that lead normally to male or female offspring. The term sex differentiation applies to the various components of our sexuality and how they are formed after the initial sex-determining event occurs. For humans, that initiating event is the union of an X- or Y-bearing sperm with an X-bearing egg. We have an XY sex-determining mechanism. It is not universal. I describe the other major forms of sex determination that occur in plants, animals, and even microbes. But once initiated, the differentiation process may also be elaborate—involving the formation of the gonads, the formation of the internal genitals, and the formation of the external genitals. What we see at birth and assign to a gender (legally restricted on birth certificates to male or female) is often limited to the external genitals. If we see a penis and scrotum, we assign a male status to the child. If we see the clitoris, labia, and a vaginal opening, we assign a female status. On occasion (and it is very rare) there will be an inconsistency in our expectations. The baby boy may be XX instead of XY; the baby girl may be XY instead of XX. That would not have been an issue before the 1960s because human sex chromosomes were not easily identified before that decade. But it becomes an issue for the person who learns of this reversal of expectations and it might lead to self-doubts, confusions about one’s gender, and other troubling thoughts.

This book follows the history of sex determination with an emphasis on how all the biological aspects have been interpreted since antiquity and how, piecemeal and in not a particularly logical order, the story of our sex determination and sex differentiation has been worked out to understand how we produce baby boys or baby girls. It also follows the history of anomalies of birth, how these were interpreted in the past, and how present day society sees them (often still with controversy). It brings in the evolution of sexual systems, a concept that did not exist before the Darwinian revolution that extended biological studies to prehistoric times.

A reproductive system also requires a nervous system for its performance. In heterosexual couples, it usually involves some maturation, usually in the teen years, a courtship bringing a couple together, an act of sexual intercourse, and, for the duration of one’s conscious life, the presence of a gender, male or female, as an adult in society. These behavioral aspects were the only ones that could be addressed before there were biological views of sex. They generated the popular literature on sex, which is abundant, as well as religious views of what is permissible and what is taboo. In the last chapters of this book, I attempt to show how the biological and the behavioral approaches independently arrived at a similar conclusion. They both reject a concept that there are only two sexes, male and female, established at conception.

The idea for this project arose when I moved from Stony Brook University to Bloomington, Indiana. I had taught a course on the biology of human sexual reproduction (Biology 300) at Stony Brook University for about ten years before my retirement. I had thought about the history of this topic, but was too busy teaching and running the Honors College to do the research required for it. Bloomington is the home of Indiana University and the Kinsey Institute for Sex Research, which is located in Morrison Hall on the IU campus. I made good use of the Kinsey Institute library after writing an initial draft of the book that laid out the broad outline of what I wanted to cover. I thank Liana Zhou, the Head Librarian, and Shawn Wilson the Public Services manager, for their assistance and warm welcome to the Kinsey Institute Library. I also thank Mark Robison at the Reference Desk, Wells Library, Indiana University, for help tracing dates and full names.

My wife Nedra Carlson, who spent 13 years as an in vitro fertilization embryologist, was a constant source of information on the early stages of fertilization and development. I also thank Mark Italiano for numerous discussions over the years on the varieties and interpretations of variations, differences, and disorders of the human reproductive system. I also thank my daughter, Christina Carlson, for rendering my sketches into the illustrations for this book.

Over the years I have benefitted from William Breneman’s graduate course in endocrinology, Ted Torrey’s course on embryology, and several courses of H. J. Muller, Tracy Sonneborn, and Ralph Cleland. I offer additional thanks for discussions with John Southin, Howard Diamond, J. Richard Whittaker, Abraham Krikorian, Paul Bingham, Robert Desnick, Greg Grabowksi, Ruth Cowan, John Gagnon, and Matthew Meselson. I thank Peter Gary for reading an earlier draft of this book.

I am grateful to the staff of IU Press for their enthusiasm and skills in producing this book. Robert Sloan, Editorial Director, was encouraging throughout, from my initial proposal to prepare this book. Angela Burton, managing Editor, kept me informed by email. Nancy Lightfoot, Project Director, and Bertolt Sobolik, Copy Editor, carefully edited my manuscript.

ELOF AXEL CARLSON

The 7 Sexes

1

Introduction

With rare exceptions, animals consist of sexually reproducing populations that are roughly half male and half female—at least that is a human perspective that is applied to other mammals, and generalized to all other animals. An observant individual will notice roaches mating rear end to rear end or horseshoe crabs on the beach in springtime mating with the male mounted on a female, reinforcing the idea that the image of human intercourse can be generalized. I can observe fruit flies mating in the same way without use of a microscope, and I can even tell which is male and which is female if I am looking at a solitary fruit fly resting on my finger.

But that idea of universality is undermined if I observe copulating earthworms, which seem to be engaged in some sort of symmetrical mutual engagement. The ambiguity of the earthworm’s hermaphroditism is also present in most flowering plants. Students learn that pollen bearing stamens are present in the same flower with female components—assigned scholarly names like stigma, style, and ovary—but that is also not universal.

Until the invention of microscopes in the 1660s, the world of the very small organisms—or parts of organisms, like cells—was closed off to human observation; almost all early ideas of sex determination are rooted in what could be seen with the unassisted eye. The two by two image of sexuality is reinforced in the story of Noah’s ark, but the story of sex determination in the Bible is puzzling to a reflective reader. Adam, clearly a functional male at creation, is given a companion out of his own rib and she is called Eve, but the special creation of the female is necessary only in the human species. Water, air, and land animals are created in Genesis equally as male and female (one assumes) in an indeterminate number with instructions to be fruitful and multiply; there is no second sex creation for the rest of life.

This book is a history of our ideas about sex determination—from ancient myths to present day molecular insights. I got interested in the history of human sexuality after teaching a course on the biology of human reproduction at Stony Brook University. Sometime around 1990, Ruth Cowan asked me if I knew anyone who could teach such a course for an undergraduate program she was developing. I volunteered to teach the course myself and spent a summer at the medical school library preparing the lectures and a text (unpublished) for it. The course was well received and I continued to teach it until I retired in 2001.

When there was no science, as we know it, speculation associated with religious writings prevailed on the determination of sex: Judaism, Christianity, and Islam drew their interpretations from the book of Genesis. Other religious traditions abound, which folklore scholars have studied using appropriate motifs of gender, sexual reproduction, twinning, hermaphroditism, and other variations. In the western tradition, the first scholarly attempts at studying sex determination are associated with Greek philosophers, but their insights are not very helpful because the tools of science were absent. Humans are adept at framing stories that explain complex reality as best as they can, but observation alone provides limited information.

The turning point in the history of sex determination arose with the introduction of the microscope when, for the first time, microscopic anatomy was revealed. It then took almost two centuries after cells were first named for the cell theory to emerge. Almost all of our present day knowledge of the biology of sex determination is relatively recent, primarily worked out in the twentieth century. For the duration of written history prior to the twentieth century, sex determination was embedded in religious traditions, taboos, and moral transgressions. Severe penalties could be imposed if those violating these norms were identified and tried by religious or secular courts.

Each component of human sexuality has its own history. The story of sperm, eggs, gonads, external genitals, internal genitals, sex in different stages of the life cycle, pregnancy, twinning, hormonal regulation, fertilization, alternation of haploid and diploid cellular states, the role of meiosis, sex chromosomes, and many other features of the complex events and developmental anatomy of reproduction was worked out and by the 1960s a fairly modern understanding was available. All that was lacking was a molecular interpretation of the way sex determination works, and that too yielded to studies in the last third of the twentieth century.

In addition to the normal sequence of events leading to functional males and functional females copulating as heterosexual couples, a number of variations existed. Some involved rare ambiguities of genitals called, at the time, hermaphroditism, chimerism, or pseudohermaphroditism. Some involved equally rare disturbances of sexual development associated with sex chromosome aneuploidy. Some involved possible genetic or gestational conditions that led to changes in sexual orientation including homosexuality, which is especially of interest to society because of its wide prevalence.

Independent of these primarily biological changes, which could be worked out by scientists, there were changes in society’s views on gender roles. The rise of the women’s movement in the nineteenth century led to the achievement of social equality in the late twentieth century in most industrialized nations, including the United States.

Because human sexuality was so deeply connected to religious moral teachings, the scientific findings about human sexuality have been controversial; many are rejected either in courts of law, legislatures, or by public opinion. This is not surprising because the existence of a scientific understanding of human sex determination is almost entirely a consequence of findings that are less than a century old.

The study of comparative sex determination in animals, plants, and microbial organisms produces insights into the way genetic transmission takes place across the phyla. It also gives insights into the evolutionary history of sex determination. These insights do not have as much social impact as discoveries associated with human sex determination have. If we think about some essential insights into the human body and compare them to insights about sex determination, we begin to see why public understanding is so meager about our own sexuality. Gross anatomy, worked out by Andreas Vesalius (1514–1564), has been around for more than 400 years. Today, no one feels threatened by the idea that their bodies are composed of organs, bones, muscles, nerves, a vascular system, and other components they share with most animals. Similarly, the cell theory is almost 200 years old and we accept the reality that cells form tissues and that these tissues form our organs. Descriptive embryology is also about 200 years old and we are not threatened that we can follow a human life from a fertilized egg through blastocyst formation, implantation, embryonic tissue formation, and a cascade of developmental events that result in our organ formation and body symmetry.

Recency of discovery is only one factor in the lack of public understanding of human sex determination. The taboos associated with sexual knowledge are still strong in society. Because of this, it is poorly taught in K–12 education. Yet it will concern almost every individual who emerges out of childhood innocence and who is thrust into sexual life during the teen years. Morality tells us how to behave and it is proper that parents instruct their children. But if parents who are ignorant of the biology and chemistry of sex determination instruct their children, a lot of ignorance will be passed on.

We like to think, as scientists, that the more we know, the more options we have in a democratic society to explore what is best for ourselves, our families, and society. That is not borne out with public or religious sex education, which provides little of what is found in this book. If the truth shall make you free, why is that knowledge, hard won by science, shielded from most of humanity? That, of course, is not a question science asks. As scientists we provide information about the material universe we explore, describe, and interpret. It is up to society to use that knowledge, but it is frustrating nevertheless when it is ignored or rejected because it is inherently controversial to know our own sex determination.

Those involved in the feminist movements, and those who study gender and its shifting social and philosophic place in history, are using what I would call a top-down approach to sexuality that is very similar to experimental psychology. But biologists use a bottom-up approach: they want to understand how life works by following it from molecules, genes, cells, organs, and organisms through to evolution and society. The later chapters of this book try to relate these two approaches.

What you will not find in this book is a very popular approach called sociobiology, evolutionary psychology, or claims of an innate basis for most of that human activity that we call sexual behavior or gender identification. I discuss my guarded view of these approaches in the last two chapters.

What I hope I have achieved is a more detailed account of the history of the biology of sex determination and the historical changes in our views of human sexual differences in behavior. We have learned a substantial amount of knowledge about the processes of sex determination and differentiation and the underlying genetic and molecular events involved in those events. The same cannot yet be said for the genetic and molecular processes (if any) for human sexual and gender behavior.

2

Wild Guesses in an Era of Scientific Ignorance

Almost all of the topics taught in K–12 or undergraduate introductory science courses come from work published in the last two centuries. Before the nineteenth century, very little of the chemistry, biology, geology, astronomy, or physics (other than Newtonian) that is covered in a twenty-first century class had been discovered. Almost all of a medical school curriculum, with the exception of gross anatomy, is a product of work done in the past two centuries. However, humanity centuries ago had the same curiosity about life and the universe as those born today. One of the universally recognized experiences of all people born is that roughly half are males and about half are females. When it comes to classifying who is a male and who is a female at birth, almost every adult in the world will use the external genitals. In a male there are a penis and a scrotum containing two testes. In a female there is a vaginal passageway surrounded by labia and a clitoris. Except for rare occasions we do not see the genitalia of our fellow adult human beings. Usually we classify a person as male or female by characteristics such as body shape, the presence or absence of hair on the face, the length, distribution, and style of hair from the cranial part of the head, the bony structure of the limbs and face, the deepness or higher pitch of voice, the presence or absence of enlarged breasts, and the presence or absence of an Adam’s apple. To that, in most cultures,