How global research was contaminated

Call it the retraction that shook the coronavirus world.

On June 4, the Lancet, the British medical journal that’s one of the most prestigious scientific publications in the world, withdrew a paper that had been one of the most consequential in the novel field of coronavirus studies.

The peer-reviewed paper, which the Lancet had published on May 22, said treating COVID-19 with the antimalarial drugs chloroquine or hydroxychloroquine raised the heartrelated death risk for COVID-19 patients in the hospital without showing any benefit.

The lead author of the paper, which employed a worldwide database of 96,000 patients from nearly 700 hospitals on six continents, was a highly regarded Harvard cardiac surgeon.

The findings were so striking they prompted researchers in the U.S. and abroad, including the World Health Organization, to halt studies of the antimalarials immediately, citing the risk of heart problems.

But questions had been raised about that database almost within hours of the paper’s publication. Its retraction was followed shortly by the retraction of another paper drawn from the same database and published by the similarly prestigious New England Journal of Medicine.

The retractions are being depicted by defenders of the peer-review system of scientific publishing as evidence that the system works — the papers were published, they were subjected to painstaking scrutiny through normal scientific give-and-take, and were retracted as soon as their shortcomings were exposed.

Isn’t that how the scientific method is supposed to work?

Well, no. The whole point of peer-review, through which submitted papers are subjected to learned examination by panels of experts in their field, is to catch shortcomings before publication.

In this case, lead author Mehreep R. Mehra of Harvard has acknowledged he didn’t have direct access to the patient database itself, but was relying on an analysis by the database’s owner, a curious Chicago company called Surgisphere. When he sought access to the database after publication, he was refused.

“We can no longer vouch for the veracity of the primary data sources,” Mehra and two of his three co-authors said in their retraction statement. The name of the third co-author, Surgisphere CEO Sapan S. Desai, doesn’t appear on the statement.

It’s self-evident neither the Lancet nor NEJM had their eyes on the ball here.

“This isn’t a story about a bad co-author,” says Leigh Turner, a bioethicist at the University of Minnesota. “There were some pretty significant breakdowns occurring within the journals.”

Worse, the breakdowns fed politically inspired skepticism about coronavirus research in general and research into the antimalarials specifically. The chief culprit in this effort to undermine science is President Trump, who turned the use of the antimalarials as treatments for the pandemic into a partisan cause.

Sure enough, Trump’s reelection campaign exploited the publication fiasco for its own purposes. The original study, the campaign asserted, “was gleefully promoted by the mainstream media in an attempt to discredit and attack President Trump.”

Noting Trump has often been accused of waging a “war on science,” the campaign crowed: “The actual war on science was being waged by the people behind the study and The Lancet.”

The inadequacies of peer review have been understood for some time.

“Yes, this is a wake-up call,” says Ivan Oransky, whose Retraction Watch website tracks withdrawals of research papers, of the Lancet and NEJM retractions. “But we’ve had the wake-up call for years.”

In perhaps the most notable reversal of judgment of a scientific paper, the Lancet in 2010 retracted a study by British researcher Andrew Wakefield purporting to link autism to the measles, mumps and rubella (MMR) vaccine.

But the retraction only came 12 years after the Lancet had published the study, which has been conclusively debunked. In the interim Wakefield’s research had come under heavy scientific fire.

Soon after the retraction, Wakefield lost his license to practice medicine in Britain. But he remains a prominent figure in the anti-vaccine movement and his debunked paper fuels antivaccine activity to this day.

The Lancet also supported Paolo Macchiarini, an Italian surgeon whose claim to have developed a stem cell-engineered artificial trachea had been widely touted, including an admiring special report by NBC News anchor Meredith Vieira. The claim was eventually deemed to be the product of unethical and deceptive work.

“Paolo Macchiarini is not guilty of scientific misconduct,” the Lancet declared in 2015, citing a finding by the Karolinska Institute, where Macchiarini held a research position. “Dragging the professional reputation of a scientist through the gutter of bad publicity ... was indefensible,” the Lancet opined.

Three years later, when the Karolinska reversed itself, so did the Lancet, with a headline reading:

“The final verdict on Paolo Macchiarini: guilty of misconduct.” The journal also retracted two papers by Macchiarini that had been published in 2011 and 2012.

By those standards, the retractions of the coronavirus papers happened with lightning speed. But given the politically charged environment and the global desperation for a treatment for COVID-19, the original papers were especially damaging to respect for the scientific process.

The retractions threatened to undermine the credibility of the first large objective study of the antimalarial drugs as treatments for COVID-19. That’s a study of 821 subjects who had been exposed to the virus either in their households or at work as healthcare professionals or first responders, and were then treated either with hydroxychloroquine or a placebo.

This study, led by the University of Minnesota and published by the New England Journal on June 3, found the drug was useless in preventing infection by the coronavirus.

“It is now clear to me that in my hope to contribute this research during a time of great need, I did not do enough to ensure that the data source was appropriate for this use,” he told me by email. “For that, and for all the disruptions — both directly and indirectly — I am truly sorry.” Yet is that enough? A lot is riding on their transparency, because without that, why should anyone trust anything they publish?