Tags Posts tagged with "Richard Sever"

Richard Sever

From left, John Inglis and Richard Sever. Photo from CSHL

By Daniel Dunaief

Scientists rarely have people standing at their lab door, waiting eagerly for the results of their studies the way the public awaits high-profile verdicts.

That, however, changed over the last 16 months, as researchers, public health officials, school administrators and a host of others struggled to understand every aspect of the basic and translational science involved in the Sars-Cov2 virus, which caused the COVID-19 pandemic.

With people becoming infected, hospitalized and dying at an alarming rate, businesses closing and travel, entertainment and sporting events grinding to a halt, society looked to scientists for quick answers. One challenge, particularly in the world of scientific publishing, is that quick and answers don’t often mesh well in the deliberate, careful and complicated world of scientific publishing.

The scientific method involves considerable checking, rechecking and careful statistically relevant analysis, which is not typically designed for the sharing of information until other researchers have reviewed it and questioned the approach, methodology and interpretation.

The pandemic changed that last year, increasing the importance of preprint servers like bioRxiv and medRxiv at Cold Spring Harbor Laboratory, which provide a way for researchers to share unfiltered and unchecked information quicker than a scientific review and publishing process that can take months or even years.

The pandemic increased the importance of these preprint servers, enabling scientists from all over the world to exchange updated research with each other, in the hopes of leading to better basic understanding, diagnosis, treatment and prevention of the spread of the deadly virus.

The importance of these servers left those running them in a bind, as they wanted to balance between honoring their mission of sharing information quickly and remaining responsible about the kinds of information, speculation or data that might prove dangerous to the public.

Richard Sever and John Inglis, Assistant Director and Executive Director of Cold Spring Harbor Laboratory Press, created pandemic-specific criteria for work reporting potential Covid-19 therapies.

“Manuscripts making computational predictions of COVID-19 therapies are accepted only if they also include in vitro [studies in test tubes or with live cells] or in vivo [studies in live subjects] work,” the preprint directors wrote in a recent blog. “This restriction does not apply to non-covid-19 work.”

Inglis and Sever continue to decline research papers that might cause people to behave in ways that compromise public health.

“We are simply doing our best to tread carefully in the early days of clinical preprints, as we gain experience and bias our actions toward doing no harm” the authors wrote in their blog.

In the first few months after the pandemic hit the United States, the pace at which scientists, many of whom pivoted from their primary work to direct their expertise to the public health threat, was the highest bioRxiv, which was founded in November of 2013, and medRxiv, which was started in June of 2019, had ever experienced.

These preprint servers published papers that wound up leading to standards of care for COVID-19, including a June research report that appeared on June 22nd in medRxiv on the use of the steroid dexamethasone, which was one of the treatments former President Donald Trump received when he contracted the virus.

The rush to publish information related to the virus has slowed, although researchers have still posted over 16,000 papers related to the virus through the two pre-print servers. MedRxiv published 12,400 pandemic-related papers since January of 2020, while bioRxiv published over 3,600.

At its peak in late March of 2020, medRxiv’s abstract views reached 10.9 million, while downloads of the articles were close to five million.

Currently, bioRxiv is publishing about 3,500 papers a month, while medRxiv put up about 1,300 during a month. Close to 60 percent of the medRxiv papers continue to cover medical issues related to the pandemic.

The numbers of page views are “not anywhere near the frenzy of last year,” Inglis said in an interview. 

With the volume of papers still high, people can receive alerts from the preprint servers using parameters like their field of interest or word searches.

“The real question is how to sort out the gold from the dross,” Inglis said. While some people have suggested a star system akin to the one shopping services use, Inglis remained skeptical about the benefit of a scientific popularity contest.

“Have you looked at the stuff [with four or five stars] on Amazon? It’s one thing if you’re buying a widget, but it’s different if you’re trying to figure out what’s worthwhile science,” he said.

Other organizations have reviewed preprints, including the Bloomberg School of Public Health at Johns Hopkins.

“By sheer diligence, the [Johns Hopkins team] go into medRxiv mostly and simply pick out things they think are striking,” Inglis said. 

At the same time, a team of researchers led by Nicolas Vabret, Robert Samstein, Nicolas Fernandez, and Miriam Merad created the Sinai Immunology Review Project, which provides critical reviews of articles from the Cold Spring Harbor Laboratory preprint sites. The effort ranks COVID-related preprints according to their immunological relevance. Fernandez created a dedicated website to host and integrate the reviews. The group also worked with Nature Reviews Immunology to publish short weekly summaries of preprints, according to a comment piece in that journal.

BioRxiv and medRxiv were founded on the belief that early sharing of results as preprints would speed progress in biomedical research, better equipping scientists to build on each other’s work.

“My team is proud to have contributed to the response to this worldwide human tragedy,” Inglis said. “We’re also glad we made the decision to set up a separate server for health science, in which the screening requirements are different and more stringent.”

Inglis explained that the pre-print servers have “learned a lot in the past year” about providing information during a crisis like the pandemic. “If another pandemic arose, we’d apply these learnings and respond immediately in the same way.”

John Inglis. Photo courtesy of CSHL

By Daniel Dunaief

In the post COVID-19 world, the pace of science and, in particular, scientific publishing has changed, giving researchers a sense of urgency to share information that might lead to preventions, treatments and cures.

Cold Spring Harbor Laboratory has produced two preprint research services, bioRxiv and MedRxiv, that complement the longer peer-reviewed path to publication.

After numerous scientists restructured their labs to contribute to the growing body of knowledge and information about COVID-19, these researchers turned to preprint services to share the results of their work and the evolution of their thoughts on how to defeat the virus.

“It’s absolutely unprecedented for scientists to drop what they are doing and switch their focus to something completely new to aid society and mankind in general,” said John Inglis, the co-founder of bioRxiv and one of the members of joint management group for medRxiv.

MedRxiv, which started in June of 2019, helped provide the scientific community with an outlet for their health science research, with the caveat that the results haven’t received a thorough peer review, as they might in the New England Journal of Medicine, Cell, or other periodicals.

The number of preprint research papers has climbed dramatically this year, as scientists race to get their results from the bench to the server. The number of papers in bioRxiv increased to 88,268 in June from 71,458 in January. The increase at the newer medRxiv is much more dramatic, climbing from 953 in January to 7,541 in June.

The number of pandemic related papers on medRxiv and bioRxiv in total is 6,458, with 5,133 on medRxiv and 1,325 on bioRxiv.

Pandemic-related papers account for close to 70 percent of the new research published on medRxiv since January 1st, while the percentage of virus-related papers on bioRxiv is 6.2%, in large part because bioRxiv includes numerous other subject areas, including ecology, bioinformatics, plant biology and zoology.

The world has taken notice of all these papers, with page views peaking in April for medRxiv to almost 11 million for the month.

While the papers aren’t peer reviewed, the managers of these sites urge readers to remain cautious in their interpretation and use of these findings, while the scientific community continues to duplicate any encouraging or compelling results.

“We remind people all the time that these are preprints,” Inglis said, as the site has numerous reminders about the early nature of the findings. “They are preliminary reports and should not guide clinical practice or be reported as established information. That’s a battle we’re still fighting.”

The peer review process has also picked up some speed, as journals, inundated with potential game-changing material, have been accelerating the process of reading and reviewing papers. The median time between posting an article on bioRxiv and publication in a journal before the pandemic was nine months. Some papers in medRxiv have been published in journal in as few as 35 days.

For medRxiv, the screening process requires an ethics statement, a funding statement, and any potential conflicts of interest. These requirements are “all far more familiar in medical publishing than in scientific publishing,” said Inglis.

At bioRxiv, which recently introduced a competing interest statement as well for authors, freelancers and a group of Principal Investigators look at everything before it posts, to make sure it’s science and that it’s not dangerous. The screeners turn the manuscripts back to the team if they have any concerns.

“We felt, early in the pandemic, that it was necessary to make sure we have people with expertise in outbreak science,” Inglis explained. “We brought on volunteers.”

According to Inglis, the percentage of manuscripts that scientists submit, but that bioRxiv doesn’t publish, is between 5 and 10 percent, while that figure is closer to 20 to 25 percent for medRxiv.

Inglis said numerous scientists have done some modeling based on public data, but that the preprints don’t accept those papers unless they contain additional research.

The preprint management team was “worried about the indiscriminate use of these models to guide public policy,” he said.

Additionally, the team excluded manuscripts that might be dangerous to human health or human-health related behavior. They didn’t want people to rush out and take something that, theoretically, might help, but that hasn’t received sufficient testing. A treatment might block a receptor, but also have significant side effects.

Inglis said the team of people who work at the preprints, which includes five full-time preprint-platform dedicated staff members and seven other CSHL staff with other responsibilities, including the founders, tech developers and production staff, worked seven days a week, with long working days to meet the increased need and demand.

People working on this effort “are not doing it because they are getting rich or handsomely acknowledged.” An arduous job with thousands of papers, the staff are working out of a “sense of purpose and mission,” Inglis explained.

The Chan Zuckerberg Initiative and CSHL provide financial support for these preprints. The research community has shared their appreciation for these preprints and CSHL generously acknowledges the work of the staff.

Inglis and Richard Sever co-founded bioRxiv. MedRxiv is managed by Sever and Inglis in collaboration with Professors Harlan Krumholz and Joe Ross from Yale and Dr. Theo Bloom and Claire Rawlinson from BMJ, which was originally called the British Medical Journal.

Inglis said numerous papers have become game-changers in the battle against the virus, including a study from two weeks ago in the United Kingdom on dexamethasone, a steroid that was proven effective in severe cases of COVID-19. Indeed, just recently, a Bethesda hospital became the first in the nation to use the steroid to combat the virus.

The team working in preprints at CSHL appreciates the opportunity to contribute to the public health crisis.

Inglis is pleased with how the community trusted the preprints with their work, while numerous members of the community helped screen manuscripts and provide advice about how to react to the needs of the pandemic.