By Gary Evans, Medical Writer

It’s astonishing in retrospect — as blatant violations in human research so often are — that women in New Zealand diagnosed with an increasingly clear precursor to cervical cancer were left untreated and uninformed in an unethical study that continued for two decades. Predictably, some of them followed a downward spiral to disease and death in a manner similar to the African-American men with untreated syphilis in the infamous Tuskegee Experiment in the United States.

The so-called “Unfortunate Experiment” at National Women’s Hospital in Auckland, NZ, was finally halted after a press exposé1 in 1987 led to the formation of a board of inquiry that produced a damning report. The Cartwright Report2 concluded that the experiment that began in 1966 at the hospital was an egregious ethical breach by both the principal investigator and the administration that enabled him. The late gynecologist Herbert Green, MD, began the trial to test his conviction that carcinoma in situ (CIS) was not predictive of progression to invasive cervical cancer. Thus, some women diagnosed with CIS by Green were not treated nor informed about their condition, but rather followed to see if they developed cancer. A disturbing corollary to the main study was that Green was found to have performed cervical smears on newborn girls without consent of their parents in an apparent attempt to show that abnormal cell growth was present at birth.

“An analysis of Dr. Green’s papers points to misinterpretation or a misunderstanding of some data on his part, and on occasion, manipulation of his own data,” the Cartwright Report concluded. “The inference to be drawn from Dr. Green’s 1966 proposal and published papers is that CIS will progress to invasive cancer in only a very small proportion of patients, if at all. This inference is incorrect and reliance on it has been dangerous for patients. … It was an attempt to prove a theory that lacked scientific validity and little attention was given to ethical considerations.”

Medical staff who cautioned against the trial at the onset or who tried to stop it later were outvoted and essentially ignored by other faculty and administration, who were strangely blind to the ethical lapses and clinical outcomes of the horrific experiment. The board of inquiry found “no reason” for faculty and administration to overlook “basic ethical and scientific information that was then available” as the trial continued.

“The fact that the women did not know they were in a trial, they were not informed that their treatment was not conventional, [and] they received little detail on the nature of their condition, were grave omissions,” the board of inquiry reported. “The responsibility for those omissions extend to all those who approved the trial, knew or ought to have known of its mounting consequences and its design faults, and allowed it to continue.”

The “failures” cited in the report included that the experiment was counter to generally accepted standards of treatment at the onset, and that it was allowed to continue even as the incidence of invasive cancer rose in the patient population. There was a hierarchical authoritarian work culture that allowed the trial to continue even after dissenting faculty published data on the rising cervical cancer rates of untreated women in 1984.3

There appears to be no official agreement on the number of women who died because they were not treated and subsequently developed full-blown cervical cancer. There is no doubt that some died because of the experiment, and 19 patients sued and were compensated in an out-of-court settlement. By the time of the Cartwright inquiry, Green was in his mid-70s and was deemed too ill to be charged. His administrative supervisor was censured and fined by the New Zealand Medical Council.

IRB Advisor asked Ronald W. Jones, MD, a retired National Women’s OB/GYN faculty member and one of the principal authors of the aforementioned 1984 paper, whether in hindsight he wished he had taken the story directly to the lay press to create the public outcry that eventually halted the trial.

“I have spent much of my life anguishing over this question,” says Jones, who has written a book4 that gives an insider’s view of the experiment and the academic culture that allowed it. “I cannot speak on behalf of my two, long-dead colleagues [who tried to stop the experiment]. I came a generation after them and Green’s experiment had been underway for seven years when I joined the staff, from England, as a complete outsider, and I was unaware of it. I was the youngest member of the staff and anxious to establish a permanent contract in the prestigious National Women’s Hospital. For some years, I was largely ignorant of the experiment and its evolving outcome.”

As it was, Jones claims that he was treated with derision and contempt for publishing the 1984 paper that exposed the ongoing experiment by concluding that the fate of some of the patients showed that “CIS of the cervix had a significant invasive potential.” The bitterness of some toward him for exposing the situation has resurfaced again with publication of his book, Jones says.

“Had I gone to the media when we published our [1984] paper I would certainly have been blackballed from my own country,” he told IRB Advisor in an email interview. “As it was, I became persona non grata soon after the government set up the Committee of Inquiry. Some professional colleagues have refused to speak to me from that time.”

Indeed, there are those who have disagreed with aspects of the Cartwright Report and raised questions about whether Green’s work was accurately portrayed by critics like Jones.

“The value and strengths of a democratic process are that credible and verifiable opposing opinions should be able to be expressed without prejudice — and be open to public debate. However, in revisiting the Unfortunate Experiment, this is not possible,” wrote Graeme H. Overton, FRCOG, FRCS, a consultant associated with National Women’s Hospital from 1960-1999.5 “Contrary opinions are not welcome, are seldom printed, and invoke demeaning criticism rather than discussion. In New Zealand, revisiting the Unfortunate Experiment is a minefield inviting self-destruction.”

A Cautionary Tale

It has been decades since the study was halted, posing the question whether the Unfortunate Experiment is a historical curiosity or a highly relevant incident germane to the current oversight of IRBs.

“I think everybody should know this story, even beyond IRBs — anyone who is involved in research in any way,” says Carl Elliott, MD, PhD, a bioethicist at the University of Minnesota. “If you talk to anybody who has ever worked in an academic health center, this sort of very authoritarian, hierarchal culture is still very much intact. The kind of things that Ron Jones describes at National Women’s Hospital didn’t seem all that unique to me when I was reading them.”

That same culture was insular, certainly not conducive to whistleblowers coming out against colleagues, he said.

“The effort to file internal complaints, keep things in-house and within academic medicine did no good,” Elliott said. “They could not imagine that this would happen. They assumed that those efforts were going to make a difference. It was not possible for people, [Jones and colleagues thought] to actually see what was going on — that these women were dying — and do nothing about it. Yet, that’s what happened.”

In the broader context of other human research debacles, the Unfortunate Experiment has really never received widespread attention outside of New Zealand, he says.

“In bioethics in America — and to some extent, the U.K. — there is a sort of standard canon of research disasters that every introductory medical ethics student is taught, starting with Tuskegee, Willowbrook, prison research, and so on,” Elliott says. “Nobody seems to pay any attention to this one.”

One of the lessons to be learned is that in the wake of the Unfortunate Experiment, New Zealand adopted rigorous and transparent oversight of human research, he adds. This action compares favorably to the more muted response in the U.S. to such incidents, he says.

“They had a disaster on the scale of Tuskegee, but unlike the U.S. they actually tried hard to fix it and they did all these very sensible things,” Elliott says. “[These include] a public judiciary inquiry, making the researchers answer for themselves publicly, and they put in an oversight system. And they haven’t had anything similar in 30 years. The Cartwright inquiry had a lot of credibility. It was clearly intended to come to a resolution that was satisfying to the public, the victims, and the people who were afraid that the same thing could happen to them.”

While unethical research trials often are exposed and then fade from thought, the experiments of Tuskegee in the U.S. and National Women’s in New Zealand still resonate in their respective countries.

“The reason they do, I think, is because they both piggybacked onto these larger social movements,” Elliott says. “When Tuskegee [was revealed] it was kind of an example of what people in the civil rights movement were demonstrating against. It was the same with the women’s movement in New Zealand. It became representative of a whole range of oppressive practices against women.”

‘Complete Silence’

In contrast, other episodes of unethical research affect a disparate and marginalized group who may have little more in common than a disease or diagnosis. Again, Elliott maintains that the New Zealand travesty has not been on the radar in the U.S., but perhaps Jones’ book, Doctors in Denial: The Forgotten Women in the ‘Unfortunate Experiment,’ will change that. IRB Advisor interviewed Jones about his book and the legacy of the experiment.

IRB Advisor: In your book, you describe the rudimentary nature of Dr. Green’s research, which lacked a protocol, a team approach, and had no clear hypothesis. Just to clarify, at the time of the study, were there no requirements for ethical review by some kind of institutional review board?

Jones: You are correct that Green’s research had no “clear hypothesis,” but careful reading of his words and writing does give a reasonably clear idea of his thinking. At the fateful 1966 meeting, which approved his study, the minute secretary recorded his “aim is to attempt to prove that carcinoma in situ [of the cervix] is not a premalignant disease.” While institutional review boards did not exist in New Zealand in 1966, the Hospital Medical Committee acted as a de facto ethics committee. Any change in hospital policy or medical practice required approval by this committee.

IRB Advisor: You note in your book that a discussion of the Unfortunate Experiment at a medical meeting in Florida in 1978, and even your published article in 1984, failed to stop the experiment. Can you comment on this?

Jones: It caused a stir within the walls of the meeting room in Florida, but nary a ripple reached New Zealand. Despite prepublication copies of the [1984] paper being given to all members of the National Women’s Hospital senior medical staff, there was not the slightest sound, whimper, or muffled comment outside the walls of the hospital following the publication of our paper. Complete silence! Seemingly everyone was paralyzed by the bad news.

IRB Advisor: That is rather extraordinary. Were the powers that be bound to a “false dogma” of sorts to protect the hospital’s reputation and prevent exposure to liability?

Jones: Years before, in 1975, an in-house “whitewash” committee had examined complaints by [two faculty members] about the outcome of Green’s experiment, but failed to address the central issue — patient safety. Of the 29 cases [of women with cancer] referred to the subcommittee, more than half were excluded without a reason being recorded for doing so. Of the remainder, all of whom had developed invasive cancer, the committee stated that “the staff members have acted with personal and professional integrity, but it is not within the terms of reference of the committee to comment on the outcome of the trial to which the agreed policy applies.”

The committee noted that “the effect of continuation of this trial depended on the staff concerned subjugating personality differences in the interest of scientific inquiry.” In essence, professional loyalties were more important to the committee than the welfare of the patients in Green’s study. Liability was not an issue as New Zealand had introduced, in 1966, a no-fault Accident Compensation Act, which removed litigation except in rare circumstances.

IRB Advisor: In your opinion, could something like the Unfortunate Experiment in New Zealand occur again in another country?

Jones: My answer to this question is a qualified “yes.” I do not know about the USA, but New Zealand ethics committees reach their decisions by consensus. In my story, only one man, [the late] Dr. McIndoe, argued against Green’s experiment in the first instance and he was overruled by the hospital hierarchy. I do not think we can say that such an experiment could never happen again. Professional loyalties and human frailties weaken good decision-making.

REFERENCES

1. Coney C, Bunkle P. An Unfortunate Experiment at National Women’s. Metro June 1987:47-65.

2. The Cartwright Report. The Report of the Committee of Inquiry into Allegations Concerning the Treatment of Cervical Cancer at National Women’s Hospital and Other Related Matters. New Zealand, 1988.

3. McIndoe WA, McLean MR, Jones RW, et al. The Invasive Potential of Carcinoma In Situ of the Cervix. Obstetrics and Gynecology 1984;64(4):451-458.

4. Jones, RW. (2017) Doctors in Denial: The Forgotten Women in the ‘Unfortunate Experiment’ Dunedin, New Zealand. Otago University Press.

5. Overton GH. The 1987 National Women’s Hospital (NWH) ‘Unfortunate Experiment’. Accusations of unethical experiments and undertreatment, resulting in excess deaths from cervical cancer. Facts and fables. NZ J Med 2010; 123(1319): Available at: http://bit.ly/2iFfglv. Accessed Dec. 8, 2017.