Blow that whistle at your own risk

The image of a lone scientist standing up for integrity against a pharmaceutical giant seems romantic and compelling. But to haematologist Nancy Olivieri, who went public when the company sponsoring her drug trial for a genetic blood disorder tried to suppress data about harmful side effects, the experience was as unglamorous as it was damaging and isolating. “There’s a lot of people who fight for justice in research integrity and against the pharmaceutical industry, but very few people know what it’s like to take on the hospital administrators” too, she says.

Now, after more than 30 years of ostracization by colleagues, several job losses and more than 20 lawsuits — some of which are ongoing — Olivieri is still amazed that what she saw as efforts to protect her patients could have proved so controversial, and that so few people took her side. Last year, she won the John Maddox Prize, a partnership between the London-based charity Sense about Science and Nature, which recognizes “researchers who stand up and speak out for science” and who achieve changes amid hostility. “It’s absolutely astounding to me that you could become famous as a physician for saying, ‘I think there might be a complication here,’” she says. “There was a lot of really good work that we could have done that we wasted a lot of years not doing because of all this.”

Olivieri didn’t set out to be a troublemaker. As a young researcher at the University of Toronto (UT), Canada, in the 1980s, she worked with children with thalassaemia — a blood condition that prevents the body from making enough oxygen-carrying haemoglobin, and that causes a fatal build-up of iron in the organs if left untreated. She worked her way up to become head of the sickle-cell-disease programme at the city’s Hospital for Sick Children (SickKids). In 1989, she started a clinical trial at SickKids to test a drug called deferiprone that traps iron in the blood. The hospital eventually brought in a pharmaceutical company called Apotex, based in Toronto, Canada, to co-sponsor the study as part of regulatory requirements.

Disappointment, defiance and data

A few years into the trial, Olivieri found evidence that deferiprone was raising some patients’ liver iron to dangerous levels and increasing their risk of heart disease. She was disappointed: she’d sincerely hoped the drug would help her young patients. But when she took her concerns to Apotex in 1996, the company pointed to a confidentiality clause in the contract that it had signed with the research hospital.

Apotex told Olivieri not to publish her findings or notify patients without the company’s permission. It then abruptly shut down the trial, even pulling deferiprone from the hospital pharmacy’s shelves, and threatened to sue her if she went public.

Olivieri published her results anyway in The New England Journal of Medicine¹ and told her patients what she’d found. When Apotex continued to threaten her with legal action, she sought help from SickKids and UT. But both institutions sided mostly with Apotex — a decision she thinks was influenced by the company’s donations to the institutions. Her case drew wide media attention in Canada as SickKids, UT and Apotex publicly questioned her integrity, casting her as unreliable and an unethical scientist. (SickKids declined to comment for this article, because its leadership has changed since the events. UT and Apotex have not responded to Nature’s requests for comment.)

The geneticist who uses science to free parents wrongly convicted of killing their children

There were practical consequences, too. In 1999, SickKids removed Olivieri from her position as head of the sickle-cell-disease programme and reported her to the College of Physicians and Surgeons of Ontario (CPSO) for misconduct in how she had communicated with the institution and patients — a move that could have resulted in her medical licence being revoked. Fighting Apotex’s legal threats — along with several of her own suits against media outlets and individuals that she says libelled her — nearly bankrupted her, she says. As a result of her whistle-blowing, the coming years would be a roller coaster of highs and lows that would forever alter the trajectory of her career.

Arthur Schafer, a bioethicist at the University of Manitoba in Winnipeg, says the institutions followed a familiar playbook by attacking Olivieri’s credibility. “Her career was blighted,” he says. Still, he was impressed by her ferocity. “On one hand, she’s an incredibly strong character,” he says. “But I don’t think anyone could have survived as an isolated heroic figure.”

Olivieri certainly felt isolated. Rumours swirled around the research hospital as people whom she had once considered colleagues and friends accused her of hiding data, advancing her career through sexual favours and stealing from grants. She says she received hate mail, including an anonymous letter calling her “unethical” and a “pig” that was DNA-traced to a former collaborator at SickKids and UT. “It was real academic warfare,” she says.

A ‘gang’ helps to push back

John Dick, a stem-cell biologist at UT who had worked with Olivieri at SickKids, recalls sensing an unusually hostile vibe when Olivieri gave a presentation at a haematology conference in 1997. When Olivieri explained the situation, Dick and a handful of other researchers decided to help her out. According to Dick, none of them knew Olivieri well or had any stake in the deferiprone study. “We basically realized this was a real affront to academic freedom,” Dick says.

Olivieri says their volunteer “gang”, which included Schafer, spent up to six hours a day between 1998 and 2002 responding to lawsuits, organizing a media strategy and corresponding with other scientists for support. Olivieri doesn’t miss those days, but was impressed with the camaraderie. “We were really fighting and working for something,” she says.

Two prominent haematologists, the late David Weatherall at the University of Oxford, UK, and David Nathan, now at the Dana-Farber Cancer Institute in Boston, Massachusetts, also stepped up in her defence (see ‘Quick-fire questions’). Olivieri says their support made a big difference: the institutions might be able to discredit her, but couldn’t do the same to these international experts.

In 2001, an independent report from the Canadian Association of University Teachers exonerated Olivieri, as did the CPSO medical board. She reached a settlement agreement with SickKids in 2002. She tried to move on — treating patients, conducting thalassaemia research at the nearby University Health Network (UHN) hospital in Toronto, and even getting a master’s degree in medical ethics at King’s College London in 2003, writing a thesis on medical whistle-blowers.

How restorative justice could help to heal science communities torn apart by harassment misconduct

But in 2009, the issue resurfaced again when the UHN replaced Olivieri as head of the thalassaemia programme at the end of her term. Her replacement began treating people with deferiprone, which was not yet licensed in Canada or registered in a clinical trial. Olivieri and her colleague Brenda Gallie, an ophthalmologist at SickKids, spent ten years going through medical records and concluded in a 2019 PLoS ONE publication² that the drug was causing significant harm to people at risk of liver complications — something that the UHN disputes.

Olivieri called for Canadian regulators, who licensed deferiprone in 2015 on the basis of the UHN’s data, to reconsider their decision. She alleges that the UHN data was incomplete and questions the legality of using unlicensed drugs in clinical trials.

In a statement, a UHN spokesperson said that the drug was administered under Canada’s Special Access Program, in which physicians can request to treat a patient with an unapproved drug. The spokesperson added that a 2019 internal review found that the treatments were appropriate, and that everyone who received deferiprone was made aware of Olivieri’s 2019 findings. Olivieri says she is still involved in legal disputes with the UHN over the issue, although she declined to elaborate because the case is ongoing. “I am never going to let this lie,” she says.

Trying to move on

Olivieri, who still works at the UHN as a senior scientist, has tried to continue her life outside the deferiprone ordeal. In addition to her clinical work, she is working with a Toronto-based organization that she co-founded with Weatherall, called Hemoglobal. Its mission is to provide treatment for children with blood disorders in Sri Lanka, where safe transfusions are difficult to come by. At the age of 54, she adopted a daughter, and she has started writing a book about her whistle-blower experiences.

Still, she says her story has had no happy ending. The US Food and Drug Administration (FDA) approved deferiprone in 2011, albeit as a last-resort treatment, despite having initially rejected it. Moreover, the decades-long experience left her disillusioned with clinical research, particularly the degree to which biotech companies can manipulate how studies are designed and reported. “It’s like a chlorinated pool compared to the ocean: it’s not the real thing,” she says.

Why Joe Biden’s bid to restore scientific integrity matters

And although she can finally sleep through the night without worrying about bankruptcy, Olivieri says that she is far from recovered. “We all can pretend that we’re emotionally healthy, and I’m probably one of the people who [has been] damaged the least,” she says. But “nobody who goes through this kind of thing ever really gets over it”.

Carl Elliott, a bioethicist at the University of Minnesota (UMN) in Minneapolis, agrees. “There’s a tremendous sense of disillusionment and isolation that goes with being a whistle-blower,” he says. In 2004, Elliott filed a complaint with the FDA and other agencies alleging poor research practices at the UMN after the suicide of a man who had been enrolled in an antipsychotic-drug trial there. Minnesota state investigators said that it was not possible to link the death directly to the study, but they found various ethical and conflict-of-interest problems with the study, and the UMN temporarily suspended all psychiatric research. Elliott says that Olivieri provided moral support. “There’s something uniquely helpful and reassuring to talk to someone who’s been through the same experience,” Elliott says. “Nancy is just outraged at your enemies, like ‘We’re gonna take the bastards down,’” he says. “It’s kind of what you need to hear.”

Elliott says it’s unusual for past whistle-blowers to jump into other whistle-blowing cases: most people retreat from public view once the experience has ruined their careers. “Nancy is kind of the opposite,” he says. “She’s really curious about other people’s troubles and eager to step in and help.”

Being a whistle-blower isn’t something to be taken lightly, Olivieri says: “You’re going to have to expect your life is going to implode and will never be the same.” She’s sceptical about policies that require researchers to report problems internally. Such practices, she thinks, serve mainly to protect the institutions. Instead, she says, the most important thing that a person can do is to gather allies, not only for moral support but also for credibility. “You really have to make sure you’re not alone,” she says.

Most of all, she cautions young researchers against signing deals with industry partners that control the scientists’ research programmes. Researchers who make the hard choice to speak up when problems arise, she says, “can’t expect people to say, ‘Why, aren’t you just wonderful?’ Because that’s not what happens to whistle-blowers.”