Author Archives: Matthew Tontonoz
The recent decision by the U.S. Centers for Disease Control and Prevention (CDC) to endorse circumcision as a prophylactic measure against disease has once again drawn media attention to America’s most controversial surgery. In draft guidelines issued in December, the CDC emphasized that the most up-to-date medical science indicates clear health benefits of circumcision—including a 50%-60% reduced risk of female-to-male HIV transmission, a 30% reduced risk of transmission of the human papilloma virus (HPV), and lower risk of urinary tract infections during infancy. On the basis of these data, the CDC is recommending that health care workers counsel uncircumcised adolescent boys and men, as well as the parents of newborn males, on the potential benefits and risks of circumcision. The guidelines are currently undergoing a 45-day review period, during which the CDC is actively soliciting feedback.
The CDC guidelines follow similar pronouncements made by the American Academy of Pediatrics (AAP). In 2012, the AAP’s “Task Force on Circumcision” issued a revised policy statement and technical report, which concluded that the health benefits of circumcision outweigh the risks, and argued that the procedure should be reimbursed by insurance.
These recent “favorable” reviews of circumcision by the CDC and the AAP come at a time when peer medical organizations in other Western countries are moving in the exact opposite direction. Medical organizations in England, Canada, Australia, Finland, Denmark, Sweden, the Netherlands, and Germany all oppose routine infant circumcision on medical grounds. Several national medical organizations go further and suggest that infant circumcision constitutes a violation of human rights.
It’s not just on policy matters that the U.S. differs from other nations. The strange truth is that the U.S. is the sole country in the world where a large majority of its male population is routinely circumcised at birth for non-religious reasons. According to the World Health Organization, approximately 30% of the world’s males are circumcised. Of these, most (69%) are Muslim men living in Asia, the Middle East, and North Africa; less than 1% are Jewish men; and the rest (13%) are non-Muslim, non-Jewish men living in the United States.
How did the U.S. come to be so out of step with the rest of the world on this issue? America has a long and peculiar relationship with circumcision, and it is impossible to understand the CDC’s and the AAP’s positions without appreciating that history.
Circumcision, or removal of the foreskin from the penis, is the most common surgical procedure performed in the United States. More than a million newborn males are circumcised by doctors every year. You might think, given these numbers, that circumcision has sound scientific logic behind it. You would be wrong. In 1971, when the rate of neonatal circumcision in the U.S. was near its peak of around 80-90%, the American Academy of Pediatrics concluded that, “there are no valid medical indications for circumcision in the neonatal period.”
To be sure, various health benefits have been proposed over the years, but none that has ever stuck. In the midst of the latest debate about HIV transmission and other risks, it is easy to forget that circumcision has long been, in America, a cultural practice looking for a medical justification.
As medical historian David Gollaher shows in his engaging book Circumcision: A History of the World’s Most Controversial Surgery, the American medical fascination with the procedure can be traced to the enthusiasm of a New York-based orthopedic surgeon named Lewis Sayre. In the 1870s, Dr. Sayre—who would go on to become president of the American Medical Association—developed a theory about the value of circumcision in treating muscle paralysis. The theory depended on the then-popular notion of reflex neurosis, which held that many diseases were caused by persistent stimulation of the nervous system by “irritation.” Dr. Sayre believed that by removing the foreskin he could eliminate one form of this “irritation” and thereby relieve the paralysis. (Interestingly, this was also the basis for removing a woman’s ovaries to combat hysteria and backache.) Sayre’s intervention, which he first performed on a 5-year-old boy suffering from leg paralysis, was the beginning of the American medical appropriation of what had been a primarily religious ritual.
What Sayre began, other physicians continued with gusto. Circumcision was used to treat conditions as varied as asthma, epilepsy, hernia, and indigestion. When reflex neurosis eventually fell out of medical fashion as an explanation for illness, other uses were found for the procedure. Increasingly, doctors said circumcision could prevent a number of conditions, including venereal diseases like syphilis and gonorrhea, masturbation, and cancer.
Integral to this new emphasis on prevention was the emergent germ theory of disease, which linked numerous deadly diseases to microbes. Americans became obsessed with germs during this period, pursuing cleanliness with an almost religious zeal. And in this pursuit, the genitals were found “filthy by association” (89). Smegma, the oily white substance that accumulates under the foreskin in uncircumcised males, was increasingly seen as a source of contamination, and the area itself became a kind of breeding ground for disease. Circumcision, American doctors thought, made patients cleaner (85).
This obsession with cleanliness was class inflected. At the turn of the century, as millions of immigrants from southern and Eastern Europe poured into U.S. cities, circumcision became one important way that middle class Americans distinguished themselves from poor, dirty immigrants. In fact, Gollaher suggests that it was this meaning of circumcision as a mark of “civilization” that enshrined it in American popular culture (106-107).
That Americans’ germ obsession didn’t simply call for more vigorous cleaning with soap and water, Gollaher attributes to the increasing popularity of surgery as a discipline at the end of the 19th century. The development of antisepsis and anesthesia, “dramatically lowered the threshold for using the scalpel (97),” he notes. With these advances, it became increasingly feasible to prescribe circumcision as a prophylactic measure against disease.
Doctors’ new enthusiasm for prophylactic circumcision notwithstanding, it’s unlikely that the procedure would have ever become routine if it required adolescent boys and men to agree to genital surgery. As Gollaher ruefully notes, “The ultimate popularity of circumcision depended not on convincing normal men to undergo the ordeal of surgery, but on targeting a group of patients who could not object” (100). Infant circumcision proved to be the perfect solution. By 1920, neonatal circumcision performed by doctors in hospitals was standard procedure in America (105).
“The ultimate popularity of circumcision depended not on convincing normal men to undergo the ordeal of surgery, but on targeting a group of patients who could not object.”
The situation in England was similar to that in the U.S. for the first half of the 20th century; Sayre was widely read in England, too. But by World War II, things began to change. After the war, as Britain began creating its system of national “cradle-to-grave” health insurance coverage, the cost-benefit ratio of various medical procedures became a central concern. And, it turns out, circumcision didn’t make the cut. A British doctor, Douglas Gairdner, who reviewed the issue in 1949 found that scientific understanding of the foreskin was woefully inadequate; little research had ever been done on its normal development, including the time it takes for the foreskin to fully separate from the head of the penis and become retractable. This was remarkable, since one of the most common indications for circumcision since the late 19th century had been “phimosis,” or the abnormal adhesion of the foreskin to the underlying glans. Doctors in both America and Britain believed that the foreskin was normally—that is, in healthy infants—separate from the glans at birth; when it was not, circumcision was indicated. But Gairdner discovered that no one had bothered to find out what happened to the foreskin when it was left alone. Contrary to common wisdom, Gairdner found that boys differed widely in the time it took for the foreskin to naturally separate from the glans—anywhere from birth to 3 years. Circumcision as a treatment for so-called “adherent prepuce” before this time was therefore unnecessary. The National Health Service agreed, and in the years following the circumcision rate in Britain fell, from about 33% in 1948 to less than 10% today, with most of those being done for religious reasons.
Things were very different in the United States. Lacking a national heath care system concerned with cost-containment, the U.S. was not forced to conduct similar cost-benefit analyses of circumcision. Health insurance companies were happy to provide reimbursement for the procedure, and doctors were content to continue to collect payments for performing it. Technical innovations also made the procedure simpler, allowing it to be performed by obstetricians rather than by surgeons. As a result, circumcision became even more common.
The neonatal circumcision rate peaked in the U.S. in the late 1960s, at around 80-90%. Since then, the procedure has been slowly declining—in part due to the skepticism of parents who no longer place blind faith in the medical establishment and in part due to the profession’s own writings.
Risks vs. Benefits
In 1971, the American Academy of Pediatrics issued its first policy statement on circumcision, declaring that there were “there are no valid medical indications for circumcision in the neonatal period.” It issued this same view again in 1975 and 1977. In 1989, the AAP shifted course, finding now that there were some potential benefits of circumcision, including a reduced risk for urinary tract infections, yet still it refrained from recommending routine circumcision of infants. In 1999, the AAP policy statement on circumcision read, “Existing scientific evidence demonstrates potential medical benefits of newborn male circumcision; however, these data are not sufficient to recommend routine neonatal circumcision.”
The AAP’s most recent policy statement, issued in 2012, went further than it had in previous years, arguing that the health benefits of newborn male circumcision outweigh the risks. What happened in the interim to tip the scales? Most important were several influential epidemiological studies conducted in Kenya, Uganda, and South Africa, which showed that circumcision greatly reduced the rate of female-to-male HIV transmission. Specifically, the studies showed that the rate of female-to-male HIV transmission was reduced by 50%-60%, from about 2.5% to 1.2%, in areas where HIV transmission occurs mainly through heterosexual sex. Though the AAP still declined to endorse routine neonatal circumcision on the basis of this evidence, it did say that if parents elected to have it performed, then it should be covered by third-party reimbursement.
The AAP’s revised policy statement generated quite a bit of media attention. The big news, judging from the American press coverage, was the impact the AAP’s conclusion could have on reversing what some saw as the “alarming” reduction in the number of circumcisions being performed in the U.S. These advocates predicted a “health-care doomsday” marked by a “steep rise in infections and medical-related spending if circumcision rates continue to fall.” In recent years, 18 states have eliminated Medicaid coverage for routine neonatal circumcision, citing lack of medical justification. What that means in many cases is that poor families who lack private medical insurance, and must pay out of pocket, elect not to have it done. For circumcision advocates, the AAP’s statement provides hope that state Medicaid programs will be forced to cover the procedure and American boys will no longer be denied access to it.
Among circumcision opponents, the AAP report also generated passionate responses, though these seem not to have gotten as much press coverage (to judge from popular matches in a Google search).
Circumcision opponents—which include groups such as Intact America, Stop Infant Circumcision and Doctors Opposing Circumcision—level several different arguments against the procedure. First, they doubt the medical rationale, pointing out, for example, that urinary tract infections in uncircumcised newborns are rare (incidence of 0.7%, according to the CDC), and when they do occur can be treated with antibiotics. They also note that rates of STDs, including HIV, are actually higher in the U.S., where circumcision is very common, than in many countries in Europe, like Sweden, Finland, and Denmark, where it is essentially nonexistent.
While not necessarily disputing the findings of the African HIV studies, circumcision opponents do doubt the relevance of these findings to the American context. In the U.S., most new cases of HIV transmission occur between homosexual men. There is no evidence that circumcision reduces risk of HIV transmission in this population (something that the CDC and AAP freely admit). Moreover, circumcision alone does not prevent HIV transmission to either men or women; condoms are still required for that. Advocating circumcision as a way to curb HIV transmission when the U.S. has both the highest rates of circumcision and the highest rates of HIV infection in the industrialized world strikes many critics as misguided.
What about cancer? The rate of penile cancer is exceedingly rare (just under 1 case in 100,000 men per year in the U.S., which translates into a lifetime risk, for any man, of 0.07%, according to the CDC). Circumcision opponents acknowledge that circumcision does lower a man’s risk of getting the condition. Removing one-third to one-half of the skin of the penis, it turns out, is an effective way to protect against contracting what is, after all, a skin cancer. Nevertheless, performing surgery on newborns to prevent such a rare cancer does not, to opponents, rise to the level of medical justification. As Gollaher notes in his book, “A high percentage of skin cancers eventually develop on the nose. But this has not led physicians to recommend prophylactic rhinoplasties” (145).
The American Cancer Society (ACS) agrees that infant circumcision is not a valid or effective measure to prevent penile cancer. “Although infant circumcision can lower the risk of penile cancer,” the ACS website notes, “based on the risk of this cancer in the US, it would take over 900 circumcisions to prevent one case of penile cancer in this country.”
What’s more, penile cancer is caused by infection with the human papilloma virus (HPV). Though neither the CDC nor the AAP documents mention it, there are safe and effective vaccines to prevent HPV infection. And the vaccines, unlike circumcision, offer strong protection against HPV infection.
The second, and closely related, argument opponents raise is ethical. They argue it is unethical to perform a medically unnecessary operation on a human who is not old enough to consent to it. Because most of the purported benefits of circumcision (with the exception of a reduced risk of UTIs) apply only to sexually active individuals, the decision to circumcise or not can be postponed to when the individual is old enough to decide for himself. Removing healthy tissue from an infant, critics say, represents a violation of the Hippocratic oath: primum non nocere. First, do no harm.
(For their part, circumcision advocates invoke their own ethical arguments, likening not circumcising to not vaccinating.)
To many critics, what is most galling about the CDC and AAP guidelines is that they completely ignore the value of having an intact foreskin. Very little attention is paid to the natural function of the foreskin, or to the foreskin as a source of pleasure. Nor are the risks of the procedure—including partial or complete amputation of the penis—ever properly acknowledged.
“Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious.”
Interestingly, though infant circumcision in the U.S. is now routinely done under local anesthesia, this is a relatively recent development. It was not until 1987 that infant pain was taken seriously by doctors. Before that, anesthesia was rarely used (Gollaher, 136).
A third common critique is to accuse American doctors of cultural bias. When the AAP’s 2012 report came out, pediatricians in Europe and Canada took the opportunity to issue a published response, entitled “Cultural Bias in the AAP’s 2012 Technical Report and Policy Statement on Male Circumcision.” The article, co-authored by 38 physician representative of societies of pediatrics, pediatric surgery, and pediatric urology from 19 countries, argues that the purported benefits of circumcision do not rise to the level of medical justification, and certainly not before someone is old enough to consent. But the authors also make the point that this same evidence has been reviewed by doctors in other parts of the world where the conclusions reached were exactly the opposite of physicians in America. “Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious,” they write.
The AAP responded, essentially accusing their European and Canadian counterparts of being biased in the other direction, owing to the cultural norm of non-circumcision in these regions.
Sometimes the critiques can get quite personal. A published commentary on the AAP report written by the group Doctors Opposing Circumcision accuses the members of the AAP’s Task Force on Circumcision of bias verging on outright corruption. The commentary names several members of the task force and lists their potential conflicts of interest, including strong religious beliefs in favor of the procedure, economic incentive in the promoting it, and, in one case, deriving financial income from a medical practice devoted to treating boys with circumcision-related problems. Lest it go unnoticed, an additional potential source of bias is noted: “It appears that no member of the task force had a foreskin.”
* * *
To anyone interested in learning more about the peculiar history of circumcision in America I heartily recommend Gollaher’s book. It provides a valuable context within which to view the recent controversy over the health benefits of prophylactic circumcision. I’ll leave you with an interesting “thought experiment,” courtesy of Gollaher. Imagine, he says, that circumcision never caught on in America—that it was more like Norway in this respect. Now imagine that at a meeting of the American Academy of Pediatrics a doctor proposes in a talk that the genitals of all baby boys should be operated upon in order to achieve marginally lower incidences of urinary tract infections and perhaps a lower risk of STDs in adulthood. No one in his or her right mind would take him seriously, leading Gollaher to conclude, “If routine medial circumcision didn’t exist today, no one would dare to invent it.”
American Academy of Pediatrics Task Force on Circumcision (2012). Male circumcision [Technical Report]. Pediatrics. 130(3). [link]
Centers for Disease Control and Prevention (2014). Recommendations for providers counseling male patients and parents regarding male circumcision and the prevention of HIV infection, STIs, and other health outcomes. [link]
Earp, B. D. (2012). The AAP report on circumcision: bad science + bad ethics = bad medicine. Practical Ethics. University of Oxford. [link]
Earp, B. D. (2014). Do the benefits of male circumcision outweigh the risks? A critique of the proposed CDC guidelines. Frontiers in Pediatrics, in press. [link]
Frisch, M. et al. (2013). Cultural Bias in the AAP’s 2012 Technical Report and Policy Statement on Male Circumcision. Pediatrics. 131;796-800. [link]
Morris, B. J., Bailis, S. A., Wiswell, T. E. (2014). Circumcision Rates in the United States: Rising or Falling? What Effect Might the New Affirmative Pediatric Policy Statement Have? Mayo Clin Proc. 89(5); 677–686. [link]
Svoboda, J. S. & Van Howe, R. S. (2013). Out of step: fatal flaws in the latest AAP policy report on neonatal circumcision. J Med Ethics. Published Online First: doi:10.1136. [link]
World Health Organization/UNAIDS (2007). Male Circumcision. Global Trends and Determinants of Prevalence, Safety and Acceptability. Geneva, Switzerland: World Health Organization. [link]
In the winter of 1899, the Viennese medical doctor Sigmund Freud wrote to his good friend Wilhelm Fliess about a topic close to his heart: “Now for bisexuality! I am sure you are right about it. I am accustoming myself to the idea of regarding every sexual act as a process in which four persons are involved.”
Fliess—an ear, nose, and throat doctor practicing in Berlin—was a proponent of the idea that humans were bisexual, retaining within their bodies traces of anatomical structures and physiological processes that more properly defined the opposite sex. Freud was quite taken with Fliess’s idea, and eagerly incorporated it into his developing psychoanalytic understanding of sexuality.
In his famous Three Essays on the Theory of Sexuality, first published in 1905, Freud called bisexuality the “decisive factor,” and stated that, “without taking bisexuality into account I think it would scarcely be possible to arrive at an understanding of the sexual manifestations that are actually to be observed in men and women.” The idea remained central to his thinking until his death, in 1939.
Coming from the person who brought you penis envy, castration anxiety, and a never-ending parade of cigar jokes, such a credulity-straining notion as bisexuality might seem to belong in the historical dustbin alongside such Victorian fads as phrenology and mesmerism. After all, if recent commentators are to be believed, Freud was a crackpot pseudoscientist with a bit of a cocaine habit.
So it is with great interest that I have been following the work of Harvard neurobiologist Catherine Dulac, whose research is putting a modern a spin on some frankly Freudian notions. Back in 2007, Dulac and colleagues published a remarkable article in the journal Nature, showing that female mice can essentially be turned into behavioral males by altering their sense of smell. A female mouse with a genetic mutation that alters receptors in the vomeronasal organ, which detects pheromones, behaves in a manner indistinguishable from a male, eagerly chasing and attempting to mount fellow female mice. As the team reported, “These findings suggest a new model of sexual dimorphism in which the effector circuits of both male and female behaviours exist in the brain of each sex.” In other words, mice brains are bisexual.
Dulac and her colleagues reported being “flabbergasted” by these results, by how easy a female could be turned into a male, with just a small change in the sense of smell. But from a developmental and evolutionary perspective, she says, the results make a lot of sense. “Males and females have essentially the same genome,” she notes. “So you want to construct one template for brain, and then you kind of tilt it one way or another for better expression of the male phenotype or the female phenotype. But that doesn’t mean that you construct two different brains with entirely different circuits.”
Without taking bisexuality into account I think it would scarcely be possible to arrive at an understanding of the sexual manifestations that are actually to be observed in men and women.”
This week, Dulac and colleagues published another paper in Nature, a companion piece of sorts, showing that male mice contain within their brains a fully functioning behavior circuit for a typically female activity: mothering. Male mice with a genetic mutation that impairs vomeronasal functioning behave in a way toward pups that is characteristic of normal females—retrieving pups, building nests, and grooming pups. “They basically behave exactly like mom,” says Dulac. “The only thing they cannot do is lactate.”
What is going on here? Don’t these result contradict everything we know about the nature of sex differences in the brain?
The standard view of sexual differentiation of the brain is that hormones, principally testosterone and estrogen, sculpt male and female brains in a manner similar to the way they sculpt physical sexual anatomy, producing mutually exclusive phenotypes—male or female, but not both. But recent work in neuroscience is showing that this model is a bit too simplistic. Hormones undoubtedly play an important role in shaping sex-typical behavior, but the analogy with the reproductive organs has blinded us to the ways in which brains are more complex, and not so easily divided into two separate camps.
“The concept of a ‘male brain’ and a ‘female brain’ went out the window with that study,” Dulac has said.
Our modern ideas of sexual differentiation of the brain go back to a key paper, published in 1959, by William C. Young and colleagues at the University of Kansas. This paper—cited hundreds of times since it was published—has reached canonical status in the world of behavioral endocrinology. What Young and colleagues showed was that if they administered testosterone prenatally to female guinea pigs they could permanently alter the behavioral repertoire of the animal as an adult. A female treated with testosterone would, when stimulated with testosterone as an adult, display more male-typical (mounting) behavior than a control animal. When stimulated by estrogen and progesterone as an adult, she would display less female-typical (back arching) behavior (called ‘lordosis’ in the jargon of behavioral endocrinology).
Young and colleagues interpreted their results to mean that the brain was “organized” by hormones much in the same way that hormones organize the body, to be later “activated” by the same hormones at puberty. A few years earlier, in 1950, a French researcher, Alfred Jost, had worked out the hormonal control of anatomical sex determination. “Male” hormones like testosterone were necessary for male sexual anatomy to develop and to suppress the development of female structures, which developed as the default pathway when these hormones were not present. Young and colleagues took that model and applied it to the brain. The result was the creation of the organizational/activational hypothesis that has proved foundational to subsequent work in behavioral endocrinology and neurobiology.
Only it’s wrong. Unlike the reproductive system, where one set of structures clearly develops and the other clearly degenerates, the brain appears to retain both male and female circuits, albeit with one usually being dormant, or masked.
“What our results show,” says Dulac, “is that the brain of a male animal is geared towards expressing preferentially male-specific behavior, but there are a number of silent circuits that are still there. And that in some circumstances can be revealed—for example, when you remove vomeronasal input.”
Scents and Sensibility
Dulac didn’t start her career in neurobiology planning to overturn the textbook view of sexual differentiation. She was far more interested in how the brain interprets sensory information such as smell. Growing up in France, the daughter of two literature professors, Dulac discovered Proust at an early age, and was captivated by the role that smell—of a madeleine cookie, for example—played in Proust’s semiautobiographical novel A Remembrance of Things Past. After completing her Ph.D. in developmental biology at the University of Paris, she did her postdoc with Richard Axel at Columbia. Axel’s lab was famous for discovering oderant receptors in the brain, and Dulac decided that she wanted to find the receptors for another type of sensory cue: pheromones, the molecules detected by the vomeronasal organ in mice and other rodents. Ten years of painstaking work later, she did.
Now, as Chair of the Molecular and Cell Biology department at Harvard and a Howard Hughes Medical Institute Investigator, Dulac has turned to investigating the role of pheromones in orchestrating sexual behavior. That pheromones play a role in sexual behavior in mice is not itself surprising. Such chemical cues are known to trigger amorous behavior in a wide range of vertebrate animals, including, some researchers believe, humans. But what Dulac’s research seems to show is that chemical cues may go ever deeper than the perfume that sets animal desire aflutter; they may also, in some sense, determine an animal’s sexual identity.
When Dulac’s 2007 article came out, everyone’s first question seemed to be: what does this mean for humans? Does this work help to explain transsexuality or homosexuality in people? Dulac herself is quick to say that she and her colleagues are not psychologists, and they don’t know what relevance, if any, their work on mice has for humans. But it stands to reason that humans, being animals, may have bisexual brains as well. “The ability to behave both like a male and a female is extremely conserved throughout evolution,” says Dulac. “We see it in insects, fish, lizards, and mammals…it would be very surprising if humans are different.”
The Bisexual Brain
Not long after Dulac published her 2007 paper, she got an e-mail from a fellow biologist, David Crews, whom she had never met, but who was particularly interested in her results. Crews, a behavioral endocrinologist at the University of Texas-Austin, studies the neural and hormonal control of sex behavior in whiptail lizards, among other organisms. One species of whiptail lizard is all female and reproduces parthenogenically—that is by cloning; there are no anatomical male lizards in this species and females reproduce by laying diploid eggs that do not require fertilization. Yet the lizards still copulate, with one female lizard performing the female-typical role, and the other female lizard performing the male-typical role.
Crews has found that the brain circuits that light up in the brain of a female lizard playing the male role is the same circuit that lights up in the brain of male non-parthenogenic whiptail lizards. In other words, lizard brains are bisexual.
What intrigued Crews about Dulac’s results was they provided neurobiological support for behavioral observations of animals stretching back decades. It has long been recognized in the field of animal behavior that animals of one sex occasionally display the behavior of the other sex. The animal psychologist Frank Beach, for example, first wrote about this topic in 1940, and continued to write about it for the next 40 years. He noted in 1949 that bisexual behavior had been observed in the “rat, guinea pig, rabbit, golden hamster, porcupine, short-tailed shrew, marten, dog, cat, lion, sow, cow, sheep, horse, rhesus monkey, baboon, and chimpanzee.” Crews and a select few other biologists have worked diligently to keep Beach’s legacy alive, but among mainstream biologists this view has largely been forgotten.
Dulac attributes that forgetfulness to the spectacular discovery of sex hormones and their influence on behavior. The role of hormones in gearing a young male brain towards male behavior or a female brain towards female behavior is, she says, “indisputable.” Perhaps understandably, this momentous discovery had the effect of deflecting attention away from how the brains of males and females might be similar to how they are different. And this at exactly the time in American culture—the 1950s—when gender norms were becoming more stringently defined. As the feminist biologist and historian of science Anne Fausto-Sterling wryly notes in her book Sexing the Body: Gender Politics and the Construction of Sexuality: “By 1959, a new rodent emerged that was distinctly heterosexual and far more bound by gender roles than were Beach’s rats.”
That shift was unfortunate, because it has blinded us to ways that males and females are more similar than they are different. As an example of how a focus on difference can blind researchers to what is otherwise staring them in the face, Crews points to the history of our understanding of the hormone progesterone, long thought to be a specifically “female” hormone.
“People had worked on progesterone for years and they were driven by this idea that is pro-gestational, hence the name, and it’s a female hormone,” says Crews. “But in fact males show this enormous diurnal rhythm of progesterone.”
And the hormone has an important role in male behavior. Crews explains that a male rat who is castrated (i.e., has its testes removed so it cannot produce testosterone) and then given testosterone will mount a female, but he’s not quite as good as an intact male. Partly, he says, that’s because females don’t like these castrated hormonal impostors as much. But if castrated males are given both testosterone and progesterone they become indistinguishable from intact males. “So progesterone, a ‘female-like’ hormone, is in fact important in male sexual behavior,” says Crews.
By 1959, a new rodent emerged that was distinctly heterosexual and far more bound by gender roles than were Beach’s rats.”
To make sense of her counterintuitive findings, Dulac began reading extensively about sexual behavior in other species. That’s when she started to see evidence of bias. “The textbooks always show sexually dimorphic areas,” Dulac points out. “You have these areas in the preoptic area [of the hypothalamus] that are so much bigger in males than in females. That’s a very classical example. Well, as it turns out, this is true for the guinea pig but if you look in the mouse it’s not true at all. And if you look at dozens of animal species, mammalian species, it’s not true. So what is shown is the most extreme example of sexually dimorphism.”
Moreover, the size of the sexual dimorphism does not closely parallel differences in behavior. Even in species without large sex dimorphisms in the brain, there are still males and females that behave like males and females.
“I think this illustrates very well that we don’t know what we’re talking about when we correlate some anatomical trait of the brain to a particular function of the brain. We just don’t know.”
Dulac has been surprised by the backlash her work has generated. “I got a lot of hate e-mails from neuroendocrinologists who said the idea that we were presenting is completely, completely wrong.” says Dulac. “I just didn’t realize the uproar that our work would generate, frankly.”
To a great many scientists, the organization/activational paradigm of sexual differentiation is an established fact. Researchers have built entire careers on this paradigm. So it’s perhaps not surprising these researchers might not take kindly to work that threatens to rock the boat.
For others less invested in the organizational/activation paradigm, Dulac’s work may hold important clues to understanding gender and sexuality. Norman Spack, an endocrinologist at Boston Children’s Hospital/Harvard Medical School, is one scientist who found Dulac’s work particularly illuminating. Spack, who co-founded the gender management clinic at Boston Children’s, invited Dulac to speak at endocrinology grand rounds at Harvard Medical School back in 2007. After her talk, Spack shared with Dulac his interest in her research.
As Dulac explains, when Spack started to work in the gender management clinic, he expected to see mainly teenagers troubled by their gender identity. Instead, he encountered very young children, ages 3 and 4, who would come in saying, “I know I’m not a girl” or “I know I’m not a boy.” Gender identity seemed to have nothing to do with sexual behavior, and it raised the question of how gender identity could get “mixed up” in a person’s brain. Dulac’s work offered a suggestive answer.
“The idea is that in the brain you might have both components,” says Dulac. “And there is one that corresponds to your biological sex that is the set of circuits that are normally activated. And maybe sometimes the activation goes wrong.”
At a time when transgender has become culturally salient, and fluid gender roles are increasingly the norm for both men and women, at least in Western countries, it is perhaps not surprising that Dulac’s work has caught the attention of non-scientists as well. Several high-profile national news articles were published just this week on her recent Nature paper showing that male mice have brain circuits that enable them to be maternal. Even Dulac has experienced this heightened popular interest first-hand: “When I tell that story to my friends, men in particular love the story because they see themselves as very good dads and so they are really happy to have the right neurons that enabled them to be as good as mom.” But why was it considered so shocking?
Of Mice and Men
The scientist who perhaps did the most to champion the organization/activational hypothesis in the context of humans was the endocrinologist Milton Diamond. Back in 1959, Diamond was a graduate student in William Young’s lab at the University of Kansas. Young’s work on guinea pigs had a profound impact on him and he has spent much of his subsequent career championing a biological perspective on gender and sexual orientation over and against more environmentalist notions, such as those promulgated by the sexologist John Money, of Johns Hopkins.
Money is credited with formulating the concept of “gender identity” as a distinct aspect of sexual identity, separate from genetic or hormonal sex and largely independent of them. Gender identity developed after birth and was conditioned by anatomy and the chosen sex of rearing. In the 1960s and 1970s, Diamond wrote numerous articles criticizing Money’s notion of “psychosexual neutrality” at birth, arguing that prenatal and postnatal hormones left indelible effects on brain development that could not be overridden by childrearing.
Diamond appeared to have finally won the argument, in 1997, when he and a colleague, Keith Sigmundson, published an exposé of a famous Money case involving a 7-month-old boy who had been sex-reassigned as a girl after a botched circumcision left him without a functional penis. For years, Money had presented this individual—known in the literature as John/Joan—as indisputable evidence in support of his theory of gender identity: that a boy could be turned into a girl through surgery and childrearing; that nurture trumped nature. But as Diamond and Sigmundson discovered when they later tracked down the patient, the sex change was anything but an unequivocal success: the patient never fully accepted her feminine gender role and eventually underwent a (second) sex change operation to restore her male body, eventually marrying a woman and adopting her children. The shocking, and sad, details of the case were later recounted by journalist John Colapinto in his 2000 book As Nature Made Him: The Boy Who Was Raised as a Girl.
These days, partly as a result of such findings, the pendulum has swung back toward biology. But the question can legitimately be posed: which biology? It’s common for people to speak of biology as if it’s a self-evident singularity. But as research like Dulac’s shows, biology can hold surprises.
Take the example of the menstrual cycle. In the 1970s, Milton Diamond and others argued that male and female brains developed in a “mutually exclusive” way, such that an individual either has the capacity for monthly hormonal cycling (i.e., the female pattern) or for tonic, non-cyclic hormone release (the male pattern)—but not both. This was a logical corollary of the organization/activational model of brain development modeled on sexual anatomy, which Diamond had pushed so strongly. The only problem with hypothesis was that it was never actually tested. When researchers did finally investigate the situation, they found out the hypothesis was wrong.
In 1986, the American endocrinologists Reid Norman and Harold Spies found that male macaque monkeys, implanted with ovaries from a female, could support a cyclic 28-day menstrual cycle, complete with ovulation. In other words, their “male” brains could function in a completely typical “female” pattern in terms of hormone release from the pituitary—cyclic rather than tonic. Research conducted in humans by the Dutch endocrinologist Louis Gooren has likewise shown that men and women do not differ in this way.
Which is not to suggest that males and females do not differ in important ways. The question for researchers is, to what extent do those differences emerge against a background of shared or parallel circuitry? “I think that there’s no doubt that the brain from males and from females are different. I think that the idea is that they are not dramatically different,” says Dulac.
Does all this mean that Freud was right—that bisexuality is important for understanding human sexuality? Not so fast. Even if it were the case that humans share with mice, lizards, and—indeed—every other animal species studied the conservation of brain circuits underlying male-typical and female-typical reproductive behaviors, there would be no easy extrapolation into the realm of human sexual identity. “Humans have sophisticated behavioral control systems,” says Dulac, “and so it’s possible that those circuits are even more silent or masked than in other species.”
Nevertheless, this work is certainly suggestive, and seems to rattle some seemingly self-evident notions about sexual difference.
“I think that if you look across history in different civilization you can see that women can be warriors and men can take care of their offspring. So I think that there are examples all over of men and women doing—being able to do—a huge repertoire of behaviors in general. I think the fact that they do not in practice doesn’t mean that they are unable to.”
Crews is more blunt: “I see my work as making the point that everybody is inherently bisexual,” Crews said. “That’s the nature of life. There are extremely few sex-specific traits.”
More to Explore
- Kimchi, Tali, Jennings Xu, and Catherine Dulac (2007) A functional circuit underlying male sexual behaviour in the female mouse brain. Nature 448(7157):1009-1014.
- Wu, Zheng, et al. (2014) Galanin neurons in the medial preoptic area govern parental behaviour.” Nature 509(7500):325-330.
- Crews, David (2012) The (Bi)sexual brain. EMBO reports. July 27.
- Fausto-Sterling, Anne. (2000) Sexing the Body: Gender Politics and the Construction of Sexuality. New York: Basic Books.
- Colapinto, John. (2000) As Nature Made Him: The Boy Who Was Raised as a Girl. Toronto: HarperCollins.
- Jordan-Young, Rebecca M. (2010) Brain Storm: The flaws in the science of sex differences. Cambridge: Harvard University Press.