I HAD BEEN EXCITED by the idea of asking the FDA and OHRP to help with prenatal dex not only because I believed those agencies would have the power to do something the medical societies couldn’t, but also because I had imagined impartial and well-informed investigators—those accountants on white horses. Hard as I had tried to look for evidence that our read of the situation might be wrong, I could never be completely objective. A team of government investigators, on the other hand—they would go in as the ultimate scholars, without allegiances, conflicts of interest, loyalties, agendas, or relationships that might complicate their thought patterns.
Because I had believed this, I had told myself that, whatever the agencies found, I would simply accept it. If they found we were right, well, that would be very satisfying, because then rigorous scientific practices might finally begin around this intervention. Researchers—including Maria New—would know that freedom of inquiry entails a responsibility for just research practices. The CAH-affected families might finally have their rights respected, especially the right not to be subject to experimentation without their consent, and other researchers watching might be more inclined to stick to the rules about informed consent. If the government investigators looked at the facts and somehow found we were wrong, well, accepting that judgment would show that we were putting ourselves second to the truth, the universe was functioning right, and we were behaving ethically.
Nevertheless, I never really believed they could find that there was nothing wrong with this picture. How could so many people, so many medical practitioners and researchers, looking at it and being outraged, be completely wrong about what seemed so obviously to be an ethical travesty befalling these families? Even if you didn’t care about intersex rights the way I did, you had to see how wrong this was. Yet so the government had ruled: we had no case. For someone like me, who had journeyed a long way to come to the firm belief that following the evidence is the most important ethical principle in democracy, the government’s findings meant that not only had I been wrong, but perhaps I had behaved unethically.
Of course, that’s what the AJOB guys, especially Larry McCullough, were saying everywhere they could. One might think that, having studied by now so many researchers who’d been accused on the national stage of unethical transgressions, I might have had some sense of how to manage my own condition in the days just after the one-two punch of AJOB and the feds’ nonfinding. Instead I could only watch myself experience the progression of emotions brought about by being labeled an unethical researcher: feeling by turns disgusted with myself and utterly wronged, alternately hiding and lashing out, having a sense of mental house arrest, and general catastrophizing. Mostly I felt as if I had utterly failed the families involved. On that shocking day in early September when the Feds and AJOB aligned to write us off, it was as if something cracked in my brain. Over the next few weeks, it felt like the crack just kept getting wider.
Well, when you get what feels like a diagnosis of terminal cancer, it helps to have friends who point out that you’re not dead yet. That job fell to Aron, Ellen, and Anne. The main thing they did was to point out over and over again, until it clicked, that while the government said they didn’t find anything worth pursuing according to their investigation and a narrow reading of the regulations, that didn’t mean we’d actually been wrong about the ethics. It certainly didn’t mean we were wrong to do what we had done to try to protect these families’ rights and health. Aron asked me this: How often in the history of major medical ethical travesties has the government, when called upon to act, done the right thing the first time around? I couldn’t think of a single case. Some people in the FDA had given Frances Kelsey a hard time on thalidomide, and it had taken thirty years after the finding that DES causes cancer in prenatally exposed humans for the FDA to withdraw approval of its use in humans—and then only because the drugmaker had finally asked the FDA to do so. Maybe government agencies weren’t superhuman after all. Maybe I had just been incredibly naive.
Aron also hinted that, when trying to understand where to go from here, instead of looking to stories like Chagnon’s and Bailey’s—wherein the odds had been long that the truth would ever get sorted out in public—I should look instead to what I had learned in my research from people who had persevered in their work on their own in spite of being accused of being enemies of the people. As a result, although I had become a science historian partly out of my adoration of Stephen Jay Gould, the arch-critic of sociobiology, now I found myself looking to Gould’s nemesis, Harvard naturalist Edward O. Wilson, for professional and psychological guidance. The year before the dex disaster, when I was researching Napoleon Chagnon’s story, Nap had bugged me to talk to Wilson, both because of how Wilson had helped Nap get through the Tierney tunnel, and because of what Wilson himself had been through for his vigorous defense of sociobiology, a field that had greatly offended many on the left. I still had my notes from a phone interview with Wilson in which he had talked to me about how he’d weathered being maligned and kept his focus on the big picture of his scholarship, scholarship aimed at helping lay people understand themselves.
To be honest, before I talked to Wilson that day for nearly two hours, it had never occurred to me that he could have really suffered. He seemed to me too famous, too stately, too smart, too polished to have ever had his feathers seriously ruffled by anyone. Yet when I spoke with him, Wilson movingly described what it felt like to be repeatedly, publicly accused by his Harvard colleagues, Richard Lewontin and Gould, of promoting a dangerous right-wing science in his quest to help humans understand their own nature. Lewontin and Gould denounced Wilson’s work on sociobiology, for example accusing him in a group open letter to the New York Review of Books of “join[ing] the long parade of biological determinists whose work has served to buttress the institutions of their society by exonerating them from responsibility for social problems.” This letter made clear what Wilson’s kind of biological determinism had led to historically: anti-immigration laws, sterilization laws, and ultimately “the eugenics policies which led to the establishment of gas chambers in Nazi Germany.” At Harvard, positioning themselves under the banner of Science for the People, Gould and Lewontin, along with lesser-known scientific critics, had opposed Wilson’s alleged science against the people. A group called the Committee Against Racism (CAR) aggressively protested Wilson’s “racist lies” on the Harvard campus. In 1977, riffing on the criticisms of Gould and Lewontin, a CAR flyer warned, “Sociobiology, by encouraging biological and genetic explanations for racism, war and genocide, exonerates and protects the groups and individuals who have carried out and benefitted from these monstrous crimes.”
Before talking to Wilson, I’d thought it couldn’t have been so bad before the Internet. But of course Lewontin and Gould were famous and beloved by the Left. They could rapidly publish almost anything they wanted about Wilson and his science, and with fewer venues for public debate, each of these attacks had a big impact. As I discussed with him how easily an individual’s research and public identity could be distorted, Wilson told me he could relate: “Gould and Lewontin could do something like that, change your identity to evil.”
I had asked Wilson if there had ever been a group of colleagues who had actively defended him at Harvard. He answered:
No. Unfortunately, no. In fact, I had several close friends in the Organismic and Evolutionary Biology Department who would sometimes speak to me and just say they were sorry it was happening. One was my close colleague Bert Hölldobler. We were working all the time together in the lab and field. We would spend long periods of time talking about it and trying to figure it out, trying to understand Lewontin. He gave me his unstinting support, and made it clear to Lewontin and others. But no one else said anything or did anything. I think they kind of weren’t one hundred percent sure about me. They thought maybe there was something to what Lewontin or Gould were saying. No one [except Hölldobler] ever offered any sympathy or any kind of help. I know at one point Lewontin had unleashed some outrageous statement and [Harvard biologist] Ernst Mayr read it and he spoke to Lewontin and asked, “Why are you doing this? Why are you attacking Ed all the time?” And the response Mayr reported to me was that Lewontin said in effect, well, it’s just my nature or personality.
I asked Wilson to share the advice he would give to a younger scholar caught in his position, knowing one’s motives and research were being widely distorted in the public sphere. At the time, I had no idea I’d be finding solace in his response only a year later. He answered:
I think I would tell him or her to ignore it. Pay attention, I mean, and respond if there is some really scurrilous thing being said. But, as much as possible, ignore it, and keep working. And you’ll win in the end. I know it isn’t easy during fights. I always said to myself, “Don’t get into a pissing contest with a skunk.” Looking back, if you ask me, what I most resent about all that period, I think the answer, the older I get, the farther behind this gets, as it recedes, I must resent the amount of time I wasted. I spent countless hours talking with journalists writing stories about this. They’d come to me and say, “Well, Professor Lewontin just said so-and-so, Professor Gould just said so-and-so.” Or, “I’ve read in the latest thing that they’ve said this. What do you say to that?” they’d ask me. I couldn’t sit by and let them say something that was in fact declaring me a racist and a proto-Nazi. I couldn’t say, “No comment.” I just wasted enormous amounts of energy and just pure time I could have used for something much more valuable. So my advice would be, this too shall pass. Ignore it as much as you can. Conduct yourself with dignity and with courtesy and let it pass.
Looking back at this interview with Wilson, hoping that I would someday again feel capable of helping people through my work, I drafted marching orders for myself: Stop thinking the press will get it right. Stop thinking you need them to get it right. Keep working for the long term. Disengage from the immediate fight and focus on knowing more, knowing as much as you can.
But in the short term, how to work past my sense of having failed at protecting the rights of families affected by CAH and intersex? For that, I found a possible answer in the survival advice I’d also collected the year before dex from the famous psychology researcher Elizabeth Loftus. Today Loftus is generally recognized as having been right—that human memory is fallible and that you can actually implant false “memories” in a person. However, in the late 1990s, Loftus had found herself in very deep trouble over her work challenging recovery of repressed memories of alleged child sexual abuse. She and a colleague, Melvin Guyer of the University of Michigan, had decided to research the index case of recovered memory. They had ended up gathering evidence that suggested that the poster child for repressed memory of childhood sexual abuse, a woman identified in the 1997 case study as Jane Doe, almost certainly did not experience the childhood sexual abuse at the hands of her mother that had been described in the context of an ugly custody battle. Loftus and Guyer had used public documents and interviews to make their case that the girl’s “memories” of abuse likely resulted from suggestions made to Jane Doe when she was a child, not from actual events.
Before Loftus and Guyer could publish, Jane Doe—whose real name is Nicole Taus—made formal complaints, saying her privacy was being violated. As one might expect, people who believed they had recovered memories and psychiatrists engaged in memory recovery angrily rallied against Loftus and Guyer. Eventually cleared by their universities, the two went on to publish their exposé, but Taus proceeded to litigation. Given that Loftus and Guyer had employed conventional investigative journalistic methods and had not even published Taus’s real name you would think the case would have been quickly dismissed. But as the claims and counterclaims became ever more complex, the suit survived, making it all the way to the California Supreme Court—and taking over a great chunk of the researchers’ lives.
In the end, they prevailed. Because Loftus’s story had already been so well documented, what I had wanted to know most from Loftus when we had talked was how she had survived and continued to advocate for those wrongly accused through allegedly recovered memories. Now in my dex mess, I had advice from her to make my own. Some of her strategies seemed obvious: You keep working, you pay good lawyers, and you hold trustworthy friends and colleagues near. But one of her strategies had surprised me: She told me that during the worst years, she took up the habit of watching the Lifetime television network. She explained that the same basic story in different guises runs over and over again on Lifetime, the story of a woman facing tremendous adversity who somehow sticks it out and survives. Loftus’s approach made her philosophy clear: If you think you’re working for the greater good, you take the knocks and keep working, doing good research to figure out reality. You stop worrying about yourself. And so—staying firmly focused on the work that matters—you survive.
Knowing there probably wasn’t going to be a good historian who would do the work to tell me what actually happened with the whole prenatal dex scene, I realized that what Aron was telling me was right: I had to stop acting like a beaten dog and act like a professional historian. I had to treat this like a new major historical project, and I had to have the patience to work on it as long as it took to figure it out. As I made findings, I would have to present and publish them in scholarly arenas and in the mainstream press, so that people could see the evidence I’d found and help bring justice to bear. It might take several years, but this project was important enough to give years, because this really did look like DES all over again, even as to the reluctance of the government to stop the travesty, recalcitrance in the name of letting individual doctors decide what is best for their patients, no matter the science, no matter the ethics. If I did this work right—if I focused on truth and justice and not on my own misery—eventually I would help the CAH- and intersex-affected families and the ethical medical researchers, as I had originally set out to do.
So I crawled out of my hole and pulled myself forward. I started by carefully looking into the characters in the drama. I put out a series of feelers to find new leads. I tracked medical conferences and the medical literature to find any new data. I corresponded with strangers who sent me information, among them several mothers who wrote to tell me what they had been through with Maria New. (Such stories were only “anecdotal evidence,” but they gave me leads.) I learned how to use the Freedom of Information Act (FOIA) to get copies of New’s grants and information on the federal investigations we had initiated. When the OHRP FOIA office wouldn’t give me what I asked for and the FDA FOIA office wouldn’t even acknowledge my written requests, I hired a lawyer and sued the government. Meanwhile, when I had nothing new on dex on my plate to analyze, I kept up my reputation as a researcher and health and science writer by working on side projects. In private, I distracted myself with pro bono, confidential, medical-history-recovery work for individuals who had been medically traumatized, work that made me think I had some use to the universe, even if it ultimately turned out that I had been all wrong about dex. And day by slow day, week by slow week, I pressed on with investigatory historical research into dex.
After a few years of steady work, I could finally see clearly what had happened with dex. I could finally see where we’d been right, where we’d been wrong, and where we’d perhaps been played.
• • •
AS WE HAD FEARED, prenatal dex did turn out to be a story of how layers upon layers of medical research protection systems can fail—and fail even around the group recognized to be the most vulnerable: human fetuses. As we hadn’t fully understood, prenatal dex also turned out to be a story of what results when you get a perfect storm of beneficent intentions, professional loyalties, gut-level fears of sexual anomalies, unmanaged conflicts of interest, and mindless bureaucratic paper-pushing. To my horror, prenatal dex also turned out to be something of an ethics canary in the modern medical mine; whereas I had assumed at the outset of my investigations that prenatal dex would always be a story of exception, over the years I learned that in fact the same story of failed protections—and failure of truly informed consent—may well be playing out in clinics all over the United States.
That’s the short version of what I discovered in those three years of work. Here’s the slightly longer one:
Maria New’s main NIH grant, a grant to study many forms of and treatments for various adrenal disorders, had been consistently funded all the way back to the 1970s. When the idea of using prenatal dexamethasone to prevent virilization in CAH-affected females came along in the mid-1980s, New successfully rolled the intervention into her multiarmed grant renewal applications, thereafter using prenatal dex to give the NIH more reason to fund her work. She started offering prenatal dexamethasone for CAH through her Cornell clinic in 1986, and right around that time, presumably because she planned to publish on the intervention, she sought and obtained Cornell research ethics committee (IRB) approval to study what happens when you dose pregnant women and their fetuses with dexamethasone starting very early in pregnancy to try to prevent intersex in the female offspring. These pregnancy drug trials were not rigorous, in spite of the fact that the goal was to have the drug cross the placenta and change fetal development, in spite of the fact that seven out of eight of the offspring exposed in the first few weeks of embryonic development could stand no benefit and would assume all the risks. There was no placebo control, and no blinded assessments of results. In the mid-1990s, Maria New’s team published some results, comparing girls who had been exposed to prenatal dexamethasone to sisters who had not; they claimed that this showed the intervention worked.
Contrary to what I had thought when we sent our complaints to the feds, New did seem to have consistently gotten IRB approval at Cornell for studies of prenatal dexamethasone for intersex prevention. However, New’s IRB applications at Cornell, which I obtained via FOIA, throw up multiple red flags, flags which apparently did not attract the notice of the IRB members. For example, in 1985, in New’s first Cornell IRB application to include (among many other endocrinological studies) a plan to study the use of prenatal dexamethasone for CAH starting at two to four weeks of gestation, New did not check the “special populations” boxes on the front page of the form to indicate that her subject population would include pregnant women and fetuses. Checking those important header boxes would normally have set off special layers of review. Checking those boxes would have ensured that absolutely everyone in charge of managing research subject protections knew that, deeper in the packet, there was a plan for fetal experimentation—and yet as New renewed her IRB approvals each year, no one serving on the Cornell IRB seems to have noticed these “special groups” boxes were not being checked. It took sixteen years for someone to notice.
The consent forms that the Cornell IRB approved for New’s prenatal dex work also minimized the risks of this experiment in shocking ways. Any woman who did sign them could not legitimately be said to have given informed consent to put herself and her offspring into this experiment. Instead of describing the risks as essentially unknown, the 1985 consent form approved by Cornell described potential harms of dexamethasone exposure as “transient and reversible suppression of the maternal and fetal adrenal gland.” A pregnant woman reading this description would have reasonably assumed any harm from prenatal dex would be—well, transient and reversible, especially given how the form went on to emphasize the relatively low dose and that “pregnant women and fetuses treated to date with this regimen have not experienced complications.” There is no way, given the high risks, the unknowns, and the extremely controversial status of this intervention, Cornell should ever have allowed such a reassuring description as put forth in this form. But problems with the consent forms persisted year after year, including in that they did not contain appropriately updated information about findings of possible harm to mothers and children from prenatal dex. As late as 2004, Cornell’s IRB was still approving consent forms that reassured pregnant women that prenatal dexamethasone “has been shown to be safe for the fetus” even while the supposed point of the study was to determine “long-term safety of prenatal treatment.”
New repeatedly boasted to the NIH that a strength of her research team was that her clinic had far more CAH-affected and dex-exposed patients to use as research subjects than any other researcher. By her own admission, she had this advantage of numbers specifically because offering prenatal diagnosis and dex treatment brought CAH-affected families to her door. In her 2001 grant renewal application, for example, she told the NIH, “The prenatal diagnosis and treatment program has provided a new source of patients with CAH, adding about 15 patients per month. Clearly we are in a position to expand the [clinic’s] database to provide sufficient patients to answer the [medical research] queries relevant to CAH.” That particular NIH application included a table describing human subjects under the research arm called “prenatal dx [i.e., diagnosis] and treatment in families at risk.” The total number of her research subjects for that study aim is stated as 2,144. So prenatal dex wasn’t just a boon in and of itself in terms of clinic and research income; prenatal dex allowed New a big boost in numbers of CAH-affected people who could then be used to obtain research funding for studies beyond prenatal dex.
To get and maintain her NIH funding for experimentation involving exposing fetuses to dexamethasone, New had to show that she had Cornell’s IRB’s approval for such studies. As noted above, it appears that, indeed, she consistently got Cornell’s IRB’s approval for studies that would have involved pregnant women, and that she then reported to the NIH the IRB approvals. Keep in mind she didn’t have to show the NIH signed consent forms from the mothers she was naming as subjects, or even the blank consent forms—just IRB approval to enroll subjects. The NIH would have assumed that the human subjects she was talking about in her grants had been properly enrolled—that they had signed well-vetted forms that meant they had been fully and honestly informed about potential benefits and risks before agreeing to become experimental subjects.
For many years, New’s work chugged along, approved and funded annually. By 1996, the NIH was specifically funding New to study whether prenatal dexamethasone for CAH could “succeed” in making CAH-affected females, in effect, more likely to be straight and interested in becoming mothers. No one at the NIH seems to have raised a question about whether this was a reasonable goal of clinical care or medical research.
In August 2001, the young, Greek pediatric endocrinologist Kyriakie Sarafoglou was hired to work in the pediatric research program at Cornell’s medical school. Under a new national program designed to provide on-site monitors for big NIH study locations, Sarafoglou was employed on NIH money as a “research subject advocate,” overseeing patient safety at Cornell’s Children’s Clinical Research Center. Only a few months into that job, Sarafoglou realized she was seeing all sorts of problems with the $23 million NIH grant for which New was the principal investigator, including financial and ethical irregularities. For example, Sarafoglou noted concerning irregularities on New’s IRB materials. Sarafoglou first tried raising the alarm within Cornell. This led to an internal investigation that found nothing especially concerning. The internal Cornell report, which I obtained via FOIA, praised Maria New for her storied career and suggested Sarafoglou needed replacing.
Unsatisfied with Cornell’s response, Sarafoglou contacted the OHRP with her concerns, documenting them with thousands of pages of internal paperwork. Although OHRP proceeded to investigate, the agency did so at the usual glacial pace, perhaps because Sarafoglou had sent huge quantities of evidence of systemic problems in Cornell’s pediatric research. With the investigation ultimately involving the Department of Justice, things got hot, and Sarafoglou was given notice that her position was being terminated. About a year after she had called on OHRP to investigate, Sarafoglou sent an anguished message to the agency: “It seems that my academic career is over. I just wish I had [had] the foresight to know the pain to me and damage to my career that filing with OHRP would cause.”
Based on what I found when I FOIA’ed the OHRP investigation Sarafoglou initiated in 2003, it appears a major point of concern was IRB records at Cornell that made no sense. External reviewers looking at Cornell’s pediatric research records found misleading consent forms as well as “at least one protocol in which a significant number of subjects were enrolled an [sic] on whom no documentation of informed consent could be found.” One reviewer concluded that, although the people at Cornell clearly cared about children, “The IRB members interviewed did not appear to have a thorough understanding of the additional protections for children as subjects of research.” In an angry memo that seems to have been written by Sarafoglou, someone complained that New was claiming “130 or 160 patients have been accrued each year [to New’s IRB-approved CAH studies] but [there is] not one single dropout or patient studied under another protocol,” a virtual impossibility. Yet the records from Cornell show New reporting to her IRB, in her annual applications for renewal, that not a single potential subject refused to be in, withdrew from, or had a complaint about her IRB-approved study protocol. Moreover, in a letter to her IRB, New claimed with regard to a study on prenatal dex for CAH that, “To our knowledge, there have been no adverse events in patients due to studies performed,” even while she cited in that letter a publication she had co-authored which had reported adverse events for exposed mothers and their offspring! Incidentally, all medical researchers know that IRB-reportable “adverse events” include any medical problems while in the study, not only those you can pin to the intervention. So what are the odds studies involving subjects who are pregnant women and developing fetuses would not involve any reportable adverse events? Again, this is virtually impossible.
From 2003 to 2005, in response to Sarafoglou’s whistleblowing, OHRP ultimately undertook a massive review of Cornell pediatric research. OHRP found so many problems, they took the extraordinary step of requiring review by Cornell’s IRB of all active pediatric research at Cornell. One of the projects about which OHRP had pointed questions at that time was New’s supposed research on prenatal dexamethasone for CAH. In a letter dated May 24, 2004, OHRP asked Cornell to “Please clarify whether the subjects described in the Journal of Clinical Endocrinology and Metabolism [1995 publication] entitled ‘Extensive Personal Experience: Prenatal Treatment and Diagnosis of Congenital Adrenal Hyperplasia[’]. . . were enrolled in a research study. If they were, please provide a copy of the complete IRB-approved protocol for these studies.” What OHRP was asking was not just whether Cornell’s IRB had given New permission to do a study, but whether she had actually had the hundreds of pregnant women research subjects enrolled in a formal study by signing the consent forms. After a lot of back-and-forth in which Cornell said they were having trouble finding the records, and in which Cornell reminded OHRP that New was now gone from Cornell, OHRP just decided to stop tracking what had happened to the pregnant women given dex. They just had too much else to sort out.
This is troubling—OHRP dropping the question of the ethics of the matter. But what is more troubling is that when, in response to OHRP’s inquiries, a Cornell administrator asked New about the pregnant women mentioned in that publication, New wrote back a curt memo informing the Cornell IRB rep that, “Prenatal diagnosis and treatment is a standard procedure at the patient’s request and has been performed in France since 1981 and in our lab since 1986.” In other words, she was stating that so far as she was concerned prenatal dex wasn’t experimental—so it didn’t require consent to research. It was “standard” practice given because patients “requested” it.
This, I think, may explain why I can’t find anything, in all the records, indicating actual enrollment numbers for pregnant women in IRB-approved trials of prenatal dex. Although she got IRB approval for fetal research as required to obtain NIH funding, in practice, New seems to have treated dex as “a standard procedure [performed] at the patient’s request.” Although OHRP would later tell us that “written informed consent (which included disclosure of risks) was obtained from subjects for participations in these studies,” I can’t find any consent forms that appropriately disclosed risks, and I can’t find any direct confirmation of enrollment of pregnant women into consented research for intersex prevention. All we have is Cornell’s word to OHRP that they looked into it and nothing had gone wrong. Recall that Cornell’s internal investigation in 2002 also said nothing had gone wrong, and when OHRP came and did a real site investigation, they found much evidence to the contrary.
If Cornell’s IRB administrators had audited their pediatric researchers’ records prior to Sarafoglou’s complaints, they might have picked up that the pregnant women being named in New’s publications might not have given appropriately informed consent to research. But it appears that no such auditing occurred at Cornell’s Children’s Clinical Research Center (CCRC), a unit for which New herself served as director. Via FOIA, I have obtained extensive records and correspondence on IRB review of pediatric research at Cornell during this period, and I can find no reference to any audits—the kinds of inquiries that would have checked to see if people were actually signing consent forms—until Sarafoglou’s complaints. The extensive OHRP correspondence resulting from the 2003-2005 investigation also makes no mention of regular internal audits, as one would expect if such audits had occurred. And the previously mentioned angry whistleblowing memo specifically decried the complete absence of regular audits, seeming to confirm that no pediatric research at Cornell was being audited during this period to ensure appropriate consent practices:
[New’s IRB protocol] like all the protocols performed in the CCRC has never been through a SAC [scientific advisory committee] review or an IRB audit . . . The Dean’s Office and IRB may indicate to regulatory agencies that Cornell has made “numerous corrective actions” or are “developing new procedures for the IRB” or “initiating an audit program” . . . But these are EMPTY WORDS that do not reflect the reality at Cornell. If Cornell really bothered to perform all the things they say they will when denying charges to regulatory agencies, don’t you think they would have at least properly audited a few protocols in the CHILDREN’S clinical research center, especially protocols begun before 1998.
Whatever she told the mothers, New consistently led the NIH to believe prenatal dex was experimental. Odds are NIH wouldn’t have funded it if she’d told them it was standard of care. The portrayal of dex as experimental for grant-getting purposes didn’t change when, shortly after leaving Cornell, Maria New landed herself a position as a pediatric endocrinologist at Mount Sinai School of Medicine, across New York City. In 2006, in a research progress report to the NIH from her position at Mount Sinai, New assured the NIH that, even though she had left Cornell, her research on fetuses continued unabated: “The prenatal diagnosis and treatment program has galloped ahead so that we have now diagnosed and[/]or treated 768 fetuses.” She specifically referred to fetuses being “treated” with prenatal dex at Mount Sinai as part of her research progress. Because NIH funding requires proof of IRB approval for grant-funded experiments, New got a letter from the head of Mount Sinai’s IRB to give to the NIH, indicating Mount Sinai’s IRB had approved the study of “prenatal diagnosis and treatment.” This letter was signed by the same administrator who told the OHRP in response to our complaints that there was no fetal experimentation of this kind occurring at Mount Sinai.
It is possible that what happened at Mount Sinai is what I think happened at Cornell: New obtained IRB approval for a study of prenatal dex to show to the NIH, as the NIH would have required to fund her prenatal dex studies, but pregnant women given dex for CAH virilization prevention were, at Mount Sinai, probably treated like patients, not asked to sign consent to fetal research. This seems to be confirmed by what that Mount Sinai administrator told OHRP in response to our complaints: “the decision as to whether to treat prenatally with dexamethasone or not was made by the patient and her physician,” not under the auspices of an IRB-approved trial. So even though New very specifically represented to the NIH that these pregnant women and fetuses were human subjects of her research at Mount Sinai, they were probably afforded no protection by an IRB, because they were “just” patients when they were offered dex.
Some might wonder, how did New even manage to get hired at Mount Sinai after the NIH and OHRP investigations of her work at Cornell? Just after she had to relinquish her leadership positions and income at Cornell, New had written to the NIH asking for money to support herself under the NIH Merit Award System. New pleaded to her friends at the NIH that, “As I am no longer Chairman of Pediatrics, Chief of Pediatric Endocrinology, and Program Director of the CCRC, I have much more time to devote to the research,” and added, “This is a hard time for me and I am deeply appreciative of your consideration.” Noting that “her circumstances changed abruptly this year when she had to relinquish” her leadership positions “and the salaries entailed in these positions,” her colleagues on the NIH staff “enthusiastically support[ed]” giving her the award and writing her a big check. The NIH kept funding her. With a big active NIH grant, and with a brand new Merit Award to her name, Mount Sinai probably saw Maria New as the goose that would keep laying golden eggs. The NIH-Cornell fraud settlement was only announced after New was safely ensconced at Mount Sinai, and by then, OHRP had dropped its questions about her research ethics. So, without any official blemish on her name, she just moved over to Mount Sinai and “galloped ahead” on prenatal dex. Continuing to advertise the intervention as “having been found safe for mother and child,” she drew in more and more families to her relocated clinic. Because she had so many more CAH-affected research subjects than anyone else, the NIH kept funding her. According to one medical school administrator who looked at what I found (one to whom I happen to be married), Maria New seems to have invented a perpetual motion machine of NIH funding.
I think it is fair to summarize what happened this way: The pregnant women given dexamethasone under Maria New’s guidance may never have understood they were in a high-risk experiment, and the NIH may never have understood they weren’t. Most of the pregnant women, like those who told their stories to the Time reporter, probably thought they were taking a drug that was safe and effective, not experimental. And the NIH, being shown by New the official IRB approval for her studies and being told about the “progress” of fetal treatment research, probably assumed that all the women were being actively enrolled in careful experiments that would be meticulously overseen by the medical schools’ IRBs. Because the medical schools’ IRBs appear never to have audited New’s practices—at least until the investigations at Cornell—they do not seem to have been keeping careful track of what was going on.
It is quite possible that the problem of blurring the line between clinical care and human experimentation in Cornell’s pediatric unit went beyond Maria New. Internal minutes from Cornell’s IRB show that, after Sarafoglou raised the alarm, a member of the IRB who had simply been signing off on New’s annual renewals said this: “one of the issues the Program Review Committee is reviewing is the blurring of patient care vs. research and whether patients are being told which procedures are part of their care and which are part of the research.”
• • •
THAT’S WHAT I NOW BELIEVE happened with New’s work on prenatal dex. Given that I was able to figure all this out—given that I learned all this chiefly through obtaining government records through the Freedom of Information Act (FOIA)—why didn’t the government do something when we made our complaint in 2010? That is a tale in and of itself.
Recall that it was late 2009 when my allies called me to help. In February 2010—not realizing there had ever been an OHRP investigation into New’s work on prenatal dex—Ellen Feder, I, and thirty of our colleagues appealed to the FDA and OHRP.
About three months later, AJOB released the target-article manuscript by Larry McCullough and Frank Chervenak attacking us as “unethical” and “transgressive” for our calls for a federal investigation. FOIA confirmed that, as I had suspected, Larry McCullough had sent the AJOB manuscript to OHRP while that agency was deciding what to do with our complaints. In his cover letter, McCullough told OHRP, “We hope that your [sic] will take our critique into account in your deliberations.” None of the authors’ conflicts of interest were disclosed to OHRP. For the target article, McCullough listed Baylor College of Medicine as his only affiliation. As it turns out, he also had two other active, paid faculty positions: at the medical schools of Cornell and Mount Sinai. The Cornell chair of Obstetrics, Frank Chervenak, coauthor of the target article, did not mention to OHRP that he had served as “key personnel” on Maria New’s NIH grant.
After receiving our letters of concern, the FDA gave the job of the prenatal dex investigation to a physician-ethicist named Robert “Skip” Nelson. As I figured out much too late to do anything about it, not only was Nelson serving on the AJOB editorial board (with Larry McCullough), but he was also actively negotiating a new AJOB journal editorship in chief for himself, for a new offshoot journal called AJOB-Primary Research. Just to be clear, he was in negotiations with AJOB while he was running the federal investigation that AJOB was being used to undermine. Nelson’s new editorship came with a fancy title and ten thousand dollars a year, to hire an editorial assistant. In the e-mail exchange in which he informed his ethics supervisors that he was planning to accept this position with AJOB, Nelson said he hoped it would allow him to get an adjunct faculty appointment at Georgetown University’s ethics unit, but never mentioned what role the journal was playing in the FDA investigation he had been given to run. Remember the “coincidence” of AJOB officially publishing the McCullough et al. target article just as the federal findings were made public? E-mails discovered via FOIA suggest that Nelson, by then working for both FDA and AJOB, was keeping track of when the federal findings would be released.
Nelson’s behaviors would be less concerning if what he had represented in his official findings had been factually accurate. In one of the most important revelations of the whole federal investigation, in the name of the FDA, Nelson had told everybody that Maria New sought and obtained an IND (investigational new drug) exemption from the FDA in 1996 for a study using prenatal dexamethasone to prevent virilization in female fetuses. This would have meant that way back in 1996, a high-ranking physician at the FDA had reviewed the intervention and had formally decided that it was not risky enough to require significant FDA review before proceeding.
This seemed almost impossible—the FDA giving a pass on an experiment meant to try to change fetal development, with seven of eight fetuses deriving no possible benefit? When Nelson made the claim in 2010, we all believed it. When I obtained a copy of the 1996 exemption letter, however, I found that it actually refers to a very different thing. It refers to a proposal from Maria New “to utilize dexamethasone to treat pregnant women with a [sic] congenital adrenal hyperplasia.” Based on this wording, it looks quite possible that what New was proposing to the FDA in 1996 was to use dexamethasone on pregnant women who themselves had CAH; women with CAH often need to have their disease treated during pregnancy, to maintain their own health, and dexamethasone can be used to treat the disease. In other words, the exemption was probably not, as Nelson claimed, for a study of “the administration of dexamethasone during pregnancy for the purpose of preventing virilization in females with congenital adrenal hyperplasia.” It appears to have been meant for a study of using dexamethasone during pregnancy for the purposes of maintaining the health of pregnant women who themselves had CAH. That’s presumably why the physician at the FDA didn’t flip out at what New had proposed to do without full FDA review. What was most likely being proposed wasn’t a fetal engineering experiment!
When I contacted the physician who had signed the letter back in 1996, he had no recollection of the matter. But for his part, in 2010, Nelson knew full well there was no documentation to support his public misrepresentation of the letter. In internal communications, Nelson told OHRP staff that the single vague FDA letter was the only record of all this, so they could know no more than what the letter said. He explained to OHRP that any related documentation (which would have explained exactly what New had proposed) had been shredded during an FDA move. But in his 2010 memo to OHRP and the public, rather than providing what the IND exemption letter actually said—that New had been given an exemption to study “dexamethasone to treat pregnant women with a [sic] congenital adrenal hyperplasia”—he made it look as though the FDA had already reviewed prenatal dexamethasone for virilization prevention in 1996 and had found it to be nothing especially concerning.
If OHRP had done a full investigation in 2010—if the agency had bothered to look up its own 2003 investigation at Cornell, as I later did—I think it would have found as much reason to be concerned as we had. Instead, an e-mail obtained via FOIA of the 2010 investigation shows the head of OHRP thanking Nelson for suggesting that OHRP rely on his work. That is what OHRP did—relied largely on Nelson for OHRP’s conclusions.
OHRP was not alone in heavily relying on Nelson’s review. A couple of months after the federal findings emerged, AJOB published a piece by Maria New extensively quoting Nelson’s FDA memo and concluding, “The recent reports by the Office of [sic] Human Research Protections and the FDA therefore make crystal clear that my research on prenatal treatment of CAH is and always has been both legally and ethically proper at every level.” The article included no disclosure of the FDA official’s (Nelson’s) relationship with AJOB. When we asked AJOB to make this disclosure and to correct New’s article’s title to make clear that the federal government had not “vindicated” the intervention, the editors refused. Thanks to Nelson and the rest of the AJOB editorial team, the medical literature continues to include a supposedly peer-reviewed article that says that the FDA has vindicated prenatal dexamethasone for CAH.
When we set out to petition the FDA, I felt sure that the agency would at least stop Maria New from advertising prenatal dexamethasone for CAH as having “been found safe for mother and child,” because the language seemed to be the kind you’re only allowed to use for FDA-approved drug indications. New is subject to no such limitation. Thanks to a loophole New is still driving a truck through, only two classes of people—employees of a drug’s maker and researchers with active FDA investigator status—are prohibited from advertising an off-label use as “safe and effective.” Because New doesn’t have appropriate FDA investigator status for this intervention, she isn’t subject to the prohibition. Under current regulations, if you unethically study a drug use, you can also unethically advertise it. As a Hail Mary play, I tried appealing to the “bad-ad” division of the FDA. The staff of that division never even acknowledged my letter.
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SWEDEN REMAINS THE only place where prenatal dexamethasone for CAH has been studied using a prospective, long-term tracking approach with full ethics board oversight and informed consent throughout. Just two months after the U.S. agencies decided our letters of concern were unfounded, the Swedish clinical researchers studying prenatal dex were so alarmed by their results that they went to their ethics committee to tell them they would no longer provide the intervention in Sweden even if a woman was willing to sign up for a prospective clinical trial. They shut it down.
The Swedish group continues to track those already dosed. In a study of forty-three children given prenatal dex for CAH, results show that in the quest to sex-normalize the females, boys who are “accidentally” exposed may be genitally and behaviorally feminized. This study also confirmed earlier findings of impaired verbal working memory in exposed children who turned out not to have CAH. In terms of major side effects among the forty-three children tracked, researchers documented a total of eight “severe adverse events.” This is an astonishingly high rate, albeit one that requires a larger study to establish whether these problems were caused by the drug. The “events” included growth disorders like the one described by the American mother in the Time magazine article, a mood disorder requiring hospitalization, and three cases of mental retardation. (Just to be clear: 7 percent of the prenatally exposed children in this prospective cohort have mental retardation. That’s about ten times the normal rate.) In response to these findings, the Swedish team has declared it “unacceptable that, globally, fetuses at risk for CAH are still treated prenatally with DEX without follow-up.”
In 2012, two years after we made our complaints to the feds, New’s research group, led by Heino Meyer-Bahlburg, published a retrospective convenience-sample study of prenatal dexamethasone for CAH. The group looked at cognitive function in sixty-seven children prenatally exposed, including eight CAH-affected girls and fifty-nine boys and CAH-unaffected girls, a tiny portion of the number of children New told the NIH she has had in her prenatal treatment studies. While the new study’s finding “contributes to concerns about potentially adverse cognitive after effects of such exposure,” in sharp contrast to the Swedish data, this study by New’s group found some positive outcomes in terms of brain function—i.e., the exposed children appeared to do better on some measures than children never exposed! The paper noted that the result was confusing, and considered what it might mean. Among those considerations was not the most obvious possibility: the sample was highly skewed.
FOIA provided us a copy of the design for the retrospective follow-up study to be carried out with Heino Meyer-Bahlburg. This is how I discovered that the design specifically stated as one of the “exclusion criteria for all groups” this: “mental impairment which prevents understanding of questionnaire.” In Sweden, 7 percent of those exposed show mental retardation. In the United States, those who may be significantly cognitively damaged by the drug won’t even make it into the study.
In the United States, pregnant women offered prenatal dexamethasone for CAH remain essentially unprotected by the Office for Human Research Protections and the Food and Drug Administration. Doctors who believe the intervention is safe and effective can even advertise it as such. (Maria New still does.) If an American mother or her child is harmed by it, the family’s only recourse is to sue. In order to win such a lawsuit, the family would need to prove that the harm was caused by the prenatal dexamethasone. Without high-quality scientific studies of the intervention—prospective, long-term studies involving large enough numbers of subjects to show statistical significance—this would be almost impossible.
Back in September 2010, when I was acting like a beaten dog in response to the federal findings—before I took another three years to figure out what really happened—my dex-worried friend David Sandberg at the University of Michigan said to me something very useful: The people we’ve always really cared about are the mothers and the children, not Maria New. We can’t stop her, but maybe we can make sure everyone knows the truth. David asked me to keep working, specifically to see if I could make sure there wasn’t a single obstetrician, genetic counselor, or pregnant woman considering prenatal dexamethasone for CAH who didn’t know that this drug use is experimental and dangerous.
This is not how informed consent is supposed to work, but as I write, if you Google “prenatal dexamethasone for CAH,” that’s the message you get. The top hit is a scholarly article I coauthored with Ellen Feder and Anne Tamar-Mattis documenting what really happened in the history of this intervention. The second hit is a support group page discussing the “controversy.” The third hit is a report I cowrote for the medical news literature letting doctors know that prenatal dex continues to be considered experimental and in need of IRB oversight. The fourth is the Time magazine article. The fifth is the Swedish report of harm. The sixth is the Bioethics Forum article in which we documented New’s use of prenatal dex to try to prevent lesbianism and tomboyism.
The seventh is an article I wrote for The Atlantic. It’s about how I discovered by accident, from a pregnant woman writing to me, that fertility doctors are using dexamethasone on their pregnant IVF (in vitro fertilization) patients on the hunch that it might prevent miscarriages. As was the case with diethylstilbestrol (DES), there is no evidence that dexamethasone is effective or safe for miscarriage prevention. There are no studies of this use. I tried to find an investigative health reporter willing to research and write this story. Finding none, I did it myself. My editor at The Atlantic had previously told me—while we were having coffee literally in the shadow of the Watergate Hotel—that I should avoid investigative work. He said The Atlantic’s Health section simply didn’t have the resources to support it. Perhaps because he has an MD, he published this one anyway.
What do you do when you realize the Fourth Estate is dying, and there are no accountants on white horses in Washington? The answer now seems obvious to me: You work harder. You find compatriots in the ivory tower—the kind of people who don’t mind difficult questions that may take years to answer and that might get you in a heap of trouble—and you work, together, as long and as hard as you can.