Galileo's Middle Finger (24 page)

By the time I got home the next day, I had a full-blown fever and a terrible cough, a cough that got worse and worse over the next several days. (It turned out to be pertussis. My doctor had forgotten to vaccinate me.) As I fell in and out of sleep, I kept thinking back to the one hostile question I’d gotten at HBES, from a man who accused Bailey of being offensive in his work. He had asked me, near the end of our session, whether I thought that perhaps the Galilean personality I was describing also applied to me. I had answered promptly: yes.

And now I knew, better than ever.
Yes.
Pugnacious, articulate, politically incorrect, and firmly centered in the belief that truth will save me, will have to save us all. Right in the fight but never infallible. Yes, I thought: In Chagnon, I have met the ghost of Galileo. And he is me. He must be all of us.

A
S
I
LAY
about recovering from whooping cough in late 2009, reflecting on all I had learned in my journeys, I had a vision of how much
easier
social justice work around scientific research might become if it
were
consistently evidence-based. Scientists, the vast majority of whom I now understood to care deeply about social justice, would have to respect evidence-based activism. Maybe if everybody just agreed to discuss what we really knew—rather than imagining, assuming, and suspecting based on loyalties to particular theories or persons—disputes could be sorted out peaceably. Researchers and advocates could come together, look at the facts, and—as in the case of climate change, AIDS research, and intersex care—the great majority of researchers and activists would agree on what had happened and what needed to happen. The light of many minds would show a way forward. After carefully investigating and getting reasonable people to see what had actually happened in the Bailey and Chagnon cases, I felt downright optimistic that if we all simply agreed to talk through what we knew and didn’t know,
true
cases of injustice would be relatively easy to spot, expose, stop, and ultimately prevent.

As if by providence, at that moment—just as I was feeling tremendous clarity about what activism should and shouldn’t look like—a small group of my old intersex-rights allies, including a couple of clinicians with whom I’d remained close, called me to ask me to help with an ongoing travesty of justice. The crux of the matter was this: A major clinician-researcher in the intersex field (someone we all knew well) had been
promoting a high-risk drug regimen
to pregnant women who, along with their mates, were genetic carriers for a particular intersex condition, one caused by elevated levels of androgens in female children. The idea behind the intervention was this: If, through genetic screening, a clinician identified a woman as being at risk of having a daughter with this condition, then as soon as the woman got pregnant, a doctor would start dosing her with the steroid dexamethasone. If all went as planned, the dexamethasone would dampen the effect of the androgens, preventing intersex development in the daughters.

The major proponent of this fetal intervention,
Dr. Maria New
—a distinguished member of the National Academy of Sciences and a charismatic pediatric endocrinologist still actively working in her eighties—was going directly to the support groups for families with this condition to strongly
recommend the intervention
to them. She was selling parents on this “treatment” by claiming that “with nearly 20 years’ experience, the treatment has been
found safe for mother and child
.” This wording made it sound as though the Food and Drug Administration (FDA) had approved this use, when the FDA hadn’t. While doctors are allowed to prescribe drugs “off-label,” i.e., for uses the FDA has not approved, doing so means acting without the benefit of extensive FDA review of a use. In fact, the medical-scientific literature was utterly devoid of well-controlled
studies of efficacy and long-term safety
of prenatal dexamethasone for intersex prevention. Doctors didn’t know
what
the intervention really did in the long term, although many were very worried; dexamethasone was being used specifically because it had the power to cross the placenta and permanently alter the course of fetal development. Indeed, lab-based studies of prenatal dexamethasone exposure in animals, including nonhuman primates, suggested that dexamethasone exposure could shift fetal development in deeply unpredictable ways, including by
changing brain development
.

It got worse. Even while Dr. New was describing this use as safe and effective, openly taking credit for having gotten over six hundred pregnant women to follow this prenatal regimen, and boasting that she had at Mount Sinai School of Medicine in New York “
the only clinic in the United States
which routinely provides this service,” she was
at the same time
taking National Institutes of Health (NIH)
funding to study, retrospectively
, what had really happened to children and mothers who had been exposed. To get the NIH funding, Dr. New told the agency something very different from what she said in her public promotions of prenatal dex: “The long-term effects of dexamethasone on the children who received it as fetuses and on mothers who were exposed to it while they were pregnant
have not been determined
.
” She told the NIH that her
large “accumulated” clinical population
of exposed women and children made her especially well positioned to do this research.

Telling pregnant women a fetus-altering drug is “safe and effective” and then using them to get grants to see if it really
is
safe or effective? The failure of ethics in this case seemed so appalling and so obvious to me that it seemed a perfect case study of how to spot and stop a true and significant case of abuse of research subjects. And it involved the very issue around which most of my work had revolved: the often-harmful, non-evidence-based medical quest to “normalize” children. Here again was a situation where doctors, motivated by not-unreasonable fears of social stigma, were driving forth an unscientific and even unethical system of treatment—in this case, risking the health of pregnant women and their babies, completely outside of modern scientific standards for pharmaceuticals. Indeed, after I did a little more reading and investigating, the situation seemed so clear that I thought we could and should use this as a demonstration of evidence-based social justice protest—a model of how you appropriately use evidence, the press, and the Internet to reign in abusive research. This case could serve to show scientists why activists were very reasonable to still be vigilant about ethics violations—because terrible abuse really was happening to some vulnerable subjects—and to show activists why and how we should work to push for better evidence. Moreover, because the researchers calling for my help were calling me in
as
an activist, I thought this would be a great example of collaborative work between the two camps.

Yes, it would be relatively easy! The source of our outrage, the reason for our collaboration across the researcher-activist divide—it would all be obvious to everyone. The press, the universities, and the government would do what they’re supposed to do. People weighing in on the Internet would behave well. Everyone would see that
this
is how you do it: You push together for the truth.

Looking back, I’m guessing I was high on cough medicine. That said, even if I hadn’t been, I would have taken on this cause. It was too important to say no. This was one quest for pediatric “normalization” run completely amok. And although this work—which I guessed at the outset would take only three months—ended up consuming the next three years of my life, nearly crushing my reputation and my spirit, it did end up teaching me the last things I needed to learn from my long journey: how badly most people want simple stories of male and female, nature and nurture, good and evil; how the Internet has gutted the Fourth Estate; how the government is made up of fallible and occasionally disappointing humans; and why, more than ever before, democracies must aggressively protect
good
research.

 • • • 

A
T THIS POINT
in my intellectual development, after witnessing the personal consequences to individuals attacked for controversial research, to say that I was reluctant to call out a single researcher would have constituted a substantial understatement. But after my colleagues brought this case to my attention, I poked around and could quickly see why they were focusing specifically on Maria New. Dr. New, I realized uncomfortably, had made herself the eight-hundred-pound gorilla of prenatal dexamethasone for intersex prevention. She really stood alone. There had been a number of major pediatric researchers, including prominent physicians with whom I had for years argued over intersex care,
trying to put a stop
to her misleading promotion of this intervention as having been found safe and effective. A quick search confirmed why they were a bit frantic: There remained
a complete absence of any properly controlled scientific studies
demonstrating efficacy or safety in humans. There hadn’t even been any animal modeling of this use published. The animal studies that
had
looked at prenatal dexamethasone were designed simply to find adverse effects of prenatal exposure to dexamethasone in general; no animal studies had been published specifically looking at whether you really could stop intersex development via prenatal dosing with steroids. The number-one rule of pharmaceutical research? Before you touch a human,
see if the intervention works in animals
. This was
especially
true for fetal experimentation. Yet such animal modeling hadn’t been done, and New’s retrospective sampling methodology suggested that the results of her NIH-funded study would be of low scientific quality. While what she was doing didn’t appear to be illegal according to FDA prescribing rules,
ethically
it was extremely problematic.

Meanwhile, alarming data were emerging from a Swedish research team that had been tracking children there carefully from the start of prenatal dexamethasone exposure straight through later childhood.
The Swedish data
suggested that prenatally exposed children were showing increased rates of problems with memory and with social anxiety—signs that the intervention might have adverse brain effects. And the rest of their bodies?
The Swedish group had found
cases of growth failure and of delayed psychomotor development among the children prenatally exposed, suggesting unintended effects on the rest of the body as well.

Dr. New had not been studying the effects of exposure nearly as carefully as the Swedish team, even though she had taken credit for exposing well over
fifteen times
as many mothers and children. I did the math to figure how many pregnant women per month might be getting sucked in to this unethical cycle of ill-informed “treatment” and federal follow-up research grants, knowing the frequency of the condition at issue (somewhere
between 1 in 10,000 and 1 in 15,000
births) and knowing that New’s clinic
drew patients from around the world
. It could be a dozen per month. Then I mentally put myself in the position of these pregnant women, most of whom would know only what was told to them by the intervention’s reassuring promoter. Then I thought about what New was doing—telling the families the intervention had been found safe while using previously exposed families to get NIH funding to see if it was safe.

Then I went back to my friends’ central question: What should we do?

You’d think that if anybody was qualified to answer the question
How do you stop a scientific researcher?
, it would’ve been me at that moment. The problem was that my work had only uncovered all the
wrong
ways to do it. What the hell was the
right
way?

 • • • 

T
O UNDERSTAND HOW
my colleagues and I were processing this scene, one needs first to know a little biochemistry, a little developmental biology, and a little history.

In spite of what popular culture might lead you to believe, males and females usually make the same types of hormones. In addition to making the hormones usually associated with their sexes, male bodies also make the “female hormone” estrogen and female bodies also make the “male hormone” testosterone. What determines male and female biology is, in part, the different
levels
of sex hormones that usually occur in males and females during sex development. Being estrogen-heavy will usually make you more female-typical, while being testosterone-heavy will usually make you more male-typical.

Ovaries equal more estrogen, and testes equal more testosterone. That’s why most females are feminine and most males are masculine. But again contrary to pop culture’s representations of sex, the ovaries and testes aren’t the only organs in the human body that produce sex hormones. Some sex hormones are also made by our adrenals, a pair of glands that sit just above our kidneys. These glands make androgens, a group of hormones sometimes called masculinizing hormones: androgens can push the development of sex differentiated-tissues (like genital tissue, breast tissue, and some brain cells) in a more male-typical direction during sex development, even if you have ovaries. Perhaps you already see where this is going: There exists a condition called congenital adrenal hyperplasia (CAH) that results in higher-than-normal levels of androgens. If CAH occurs in a genetically
female
fetus, in spite of the fact that the fetus has XX chromosomes, ovaries, and a uterus, the higher-than-normal level of androgens can lead that fetus to be born masculinized in terms of genital appearance. CAH is, in fact, the
most common cause of congenital ambiguous genitalia
in genetic females.

The reason it’s impossible to know the efficacy of prenatal dexamethasone for CAH without a blinded, controlled drug treatment trial—something that has never been done—is because there is actually
substantial natural variation
in genital formation of CAH-affected females, ranging all the way from nearly typical female to nearly typical male. The natural variation among XX children with CAH means that a child with the condition may be born with a typical clitoris, a large clitoris, or in very extreme cases even one that has the urethra running part or all the way through it, just like a penis. The labia majora may be separated in the typical female fashion or may be joined at birth, looking much like a male scrotum. The XX child with CAH may have a normal vagina, may have a vagina that will not allow normal menstruation and vaginal intercourse, or in very rare cases may be essentially missing a vagina altogether. Sometimes a CAH-affected XX child will have something called a urogenital sinus, wherein the urethra and vagina develop in such a way that they meet, creating the potential for urine and menses backwash and subsequent infections.