Was the study that created the hybrid COVID-19 virus too risky? | | Chemistry

This week, Twitter erupted in outrage over research that supposedly created the Frankenstein COVID-19 virus. A version of SARS-CoV-2, it combines the now ubiquitous, rapidly spreading but relatively mild variant, Omicron, with a more deadly strain. From the beginning of the pandemic. The lab-made virus killed him in 80% of the mice that infected it, whereas the unmodified Omicron variant of him did not. preprint Posted online on Oct. 14 by researchers at Boston University (BU).

“totally irresponsible” When “this is madnesscritics tweeted, raising concerns that a hybrid virus known as a chimeric virus could escape a laboratory and cause a deadly outbreak. Richard Ebright, a molecular biologist at Rutgers University in Piscataway , pointed to the workfunded in part by the National Institutes of Health (NIH) and conducted at the National Institute of Emerging Infectious Diseases, BU.

Officials at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) expressed concern: To tell statistics Her division was unaware of the particular experiment. She said she likely should have done a special review of her NIH-funded GOF study, which creates so-called enhanced potential pandemic agents. However, a BU official said: NIH funds were not used directly They are in “continuous dialogue” with NIAID.

But some virologists took to Twitter to argue that the study wasn’t as surprising as it first appeared. They also noted that other researchers had published results of similar experiments that did not raise similar concerns. It is not clear that it will be significantly different from virus research.

Here’s a quick guide to controversy.

What did the BU researchers do and why?

They took the gene for the omicron surface or spike protein that SARS-CoV-2 uses to enter cells and added it to the genome of the ‘backbone’ virus. Shortly after the pandemic first broke out in Wuhan, China in early 2020. The aim was to analyze whether the omicron spike protein explains why it is less pathogenic. The answer could lead to improved diagnostic testing for COVID-19 and better ways to manage the disease, say the preprint authors.

Somewhat surprisingly, the hybrid virus caused death in 8 out of 10 infected mice, whereas Omicron-infected mice became sick but did not die. This suggests that mutations that reduce Omicron’s virulence must involve changes in proteins other than the spike protein, the authors say.

What are study critics saying?

They question the scientific value of the study and argue that its potential risks and benefits were not properly considered before it was conducted.

Under current U.S. government policy, proposals to conduct “reasonably anticipated” federally funded experiments that would make an already highly virulent and contagious virus more dangerous would It will be subject to special scrutiny. BU says the experiment did not meet its criteria (see below). However, some researchers believe so.They found that the new hybrid was less lethal to mice than the original Washington variety, but probably more contagious.

Some scientists have also questioned the relevance of this research to protecting human health. They note that findings made in mice often do not translate to humans. Given such limitations, the argument for doing this work “generally doesn’t feel very convincing to me.” murmured Francois Ballou, a virologist at University College London.

Some researchers also feel that the public should have more say in such research. Broad Institute gene therapy researcher Alina Chan, an outspoken critic of the GOF study, said: called research “I’m a little worried” because she fears the effects if the hybrid virus leaks to Boston, where she lives. (BU says the experiment was approved by community representatives and biosafety committees, including Boston’s Public Health Commission.)

what is the objection?

The study was “much less surprising” than some might suggest. murmured Virologist Stuart Neal of King’s College London emphasized that the hybrid virus is less deadly than the original Washington strain.

It was also tested in mice that are “highly susceptible” to SARS-CoV-2, because the receptors that SARS-CoV-2 uses to enter human cells are designed to be packed into lung cells. Neil said. Scientists shoved large amounts of virus into mouse noses, much higher than humans normally encounter. mortality rate of about 1%.

Neal also said it was reassuring that the experiments were conducted in a Biosafety Level 3 (BSL-3) laboratory with a series of sealed doors, negative pressure cabinets, and workers in protective clothing. says. This is far from the safety precautions found in the safest BSL-4 laboratories, reserved for highly deadly pathogens such as the Ebola virus.

Florian Kramer, a virologist at the Icahn School of Medicine in Mount Sinai, said the experiment was of little concern because similar hybrid SARS-CoV-2 variants had already emerged naturally and later faded into the background. thinking about. For example, one such naturally occurring virus featured her Omicron spike protein in the backbone of the Delta strain. “Mother Nature already did it in humans some time ago, but nobody cared,” he said. murmured.

Did the experiment have to undergo more rigorous scrutiny?

BU says it does not believe the study meets federal review standards. [backbone] SARS-CoV-2 virus strain or what makes it more dangerous. In fact, this study lowered the risk of viral replication,” he said in a statement. Today, the BU added that NIAID funding will only be used for “tools and platforms,” ​​and that the BU is not required to report research.

Emily Abelding, head of the NIAID division that funded the work, said the hybrid virus experiment was not listed in BU’s grant proposal or progress report. had informed NIAID of the plan, the institute would likely have referred it for review.

In the past, however, the NIAID has considered similar studies ineligible for review. For example, officials ruled out a study that created chimeras of a particular bat her coronavirus, a distant relative of SARS-CoV-2.In that case, the agency I got it Researchers did not expect the hybrid virus to be more contagious or more pathogenic than the original virus.

Other groups have performed experiments similar to the BU study but have not been reviewed. study A study conducted at the U.S. Food and Drug Administration also created a hybrid of Omicron and an early SARS-CoV-2 variant with essentially the same results. Most of the infected mice died.And earlier this year, a privately funded team in Texas report We created similar COVID-19 chimeras to test the vaccine.

The work was met with “no problem” by GOF critics, Krammer said. Some say the reaction to the BU experiment was different. That’s because, rather than simply noting that the hybrid virus is still lethal even when the Omicron spike protein is replaced, the researcher emphasized an 80% mouse lethality rate in a preprint summary. . It “wasn’t the wisest launch of a preprint” murmured Erasmus University Medical Center virologist Marion Koopmans blamed the BU team for a “communication” error. Even Chan laments, “Her one line taken out of context could lead to an explosive headline.”

what’s next?

dust up ongoing review Federal oversight policy against risky GOF research by a panel called the National Scientific Advisory Board for Biosecurity (NSABB). September, NSABB Task Force issued A draft report recommending expanding the review policy to wipe out some types of research and some pathogens that are currently exempt. Also, experts from all sides of the GOF debate say the review criteria need to be made clearer. The government is expected to announce new rules as early as next year.