Scientists seek ethics review of H5N1 gain-of-function research

Mar 29, 2013 (CIDRAP News) – A group of scientists acting under the aegis of a vaccine research advocacy organization has asked President Obama's bioethics committee to evaluate the ethics of experiments designed to increase the transmissibility of H5N1 avian influenza viruses.

The Foundation for Vaccine Research (FVR), a privately funded group that seeks to increase funding for vaccine research, argues that manipulating viruses to make them more deadly than they are in nature is "morally and ethically wrong," and that the ethical questions have been pushed aside in recent debate. Such experiments have been dubbed gain-of-function research.

The foundation made its request yesterday in a letter to Amy Gutmann, PhD, chair of the Presidential Commission for the Study of Bioethical Issues (PCSBI). The commission is a White House advisory committee that was set up in 2009. So far it has mostly addressed topics assigned to it by the president or federal agencies, but it can also address topics of interest to its own members, according to information on its Web site.

The FVR letter was signed by the group's chair, Simon Wain-Hobson, PhD; its executive director, Peter Hale, and 15 other scientists. The list includes such prominent names as Paul A. Offit, MD, of the Children's Hospital of Philadelphia; Marc Lipsitch, PhD, of the Harvard School of Public Health; Sir Richard Roberts, PhD, of New England Biolabs, a 1993 Nobel laureate; and Michael J. Imperiale, PhD, of the University of Michigan, a member of the National Science Advisory Board for Biosecurity (NSABB).

Wain-Hobson authored a Nature commentary this week that called for a halt to research designed to make viruses more transmissible, pending a thorough public discussion and independent risk assessment. The stated aim of such research on H5N1 is to identify which mutations might render the virus capable of spreading readily among humans, so that scientists could tell if the natural virus is starting to evolve in a dangerous direction.

Controversy over H5N1 research erupted in late 2011 when two groups of flu researchers revealed plans to publish studies involving lab-modified H5N1 viruses that could spread by air among ferrets. The NSABB objected to publishing the full details of the studies, but after a series of discussions, clarifications, and revisions, the two papers were published in May and June 2012. The studies were led by Ron Fouchier, PhD, of Erasmus Medical Center in the Netherlands, and Yoshihiro Kawaoka, DVM, of the University of Wisconsin.

Amid the controversy, a group of 40 prominent flu researchers announced a moratorium in January 2012 on further H5N1 gain-of-function research. The group called off the moratorium on Jan 23 of this year, saying the pause had allowed time for scientists to explain the potential benefits of the research and for governments and others to review relevant policies.

A spokeswoman for the PCSBI, Hillary Wicai Viers, acknowledged that the commission received the FVR's request but declined to comment on it further.

"Dr. Amy Gutmann, Chair of the Presidential Commission for the Study of Bioethical Issues, received the letter from the Foundation for Vaccine Research late Thursday afternoon," Viers told CIDRAP News via e-mail. "The Commission has not yet seen the letter though it looks forward to the opportunity to review the opinions of these distinguished scientists."

The letter calls on the commission to "consider the ethical issues raised by H5N1 gain-of-function research, especially experiments to increase the transmissibility of H5N1 viruses so they can be transmitted between humans as easily as the seasonal flu." H5N1 has a fatality rate of about 60% in confirmed cases, but it does not spread readily from person to person.

The accidental release of a lab-generated, human-transmissible H5N1 virus could "cause a global pandemic of epic proportions that would dwarf the 1918 Spanish flu pandemic that killed over 50 million people," the FVR letter says.

The foundation canvassed "a cross-section of life scientists" and found that most of them believed that manipulating a virus in the lab to make it more lethal is morally and ethically wrong.

Hale said the group has talked with close to 200 scientists, most of them virologists, about the issue since February 2012. "A large majority of them share all of these concerns, excluding the influenza people," he told CIDRAP News.

The letter says that more gain-of-function studies on H5N1 and other viruses are on the way. A Chinese group is working with H5N1, and a Dutch group is expanding its H5N1 studies to include work with the H7N7 avian flu virus and has plans for similar research with the SARS coronavirus. Also, German scientists recently did experiments to see what it would take for canine distemper virus to spread from dogs to humans, the letter states.

Echoing concerns explained in the letter, Hale said, "It's become apparent over the past 15 months that the whole ethics issue has been brushed under the carpet. The talks on ethics have been on the margin."

He said the FVR thought White House officials or the Department of Health and Human Services (HHS) would ask the PCSBI to examine the ethics of the research, "but nobody did, and there was a vacuum there. That's why we did it."

The foundation feels that it's both appropriate and necessary for the commission to review the issue, given that the US government has funded most gain-of-function studies so far, the FVR letter says.

Hale said the steps taken by the federal government so far don't fully address the ethics of gain-of-function research. Among those steps, in February the National Institutes of Health announced a framework to guide decisions on funding for research designed to create H5N1 viruses capable of respiratory transmission in mammals. At the same time, the White House Office of Science and Technology Policy released a draft policy requiring federal agencies to routinely review the risks of funded studies involving 15 high-risk pathogens.

Hale said the FVR has reason to think the commission may be receptive to the request.

"We wouldn't have proceeded unless we knew in advance there was an excellent chance the commission would take up this issue," he said. "We can't think of an ethical issue that's more deserving to be looked at."

He said the foundation understands that most requests to the commission come from the White House or HHS, but one petition came from the National Biodefense Science Board.

According to information on the PCSBI Web site, the group is assigned topics by the president and federal departments, but it also can "choose a topic to study based on issues of interest to the members."

The commission has issued five reports so far. The most recent one, issued Mar 19, deals with the question of anthrax vaccine trials in children.

The FVR wants to see an independent risk assessment of gain-of-function research, Hale said. "It really is astonishing that 12 to 15 months into this debate we still don't have an indepenpent risk assessment." He added that the Government Accountability Office has been getting calls from lawmakers seeking such an assessment.

The FVR is primarily funded privately by its own board members, but it has received support from foundations, such as the Bill and Melinda Gates Foundation, for specific events, according to Hale.

See also:

Mar 27 CIDRAP News item about Nature commentary by the chair of the FVR

Feb 21 CIDRAP News story about federal policies on dual-use H5N1 research

Jan 23 CIDRAP News story about end of research moratorium

PCSBI site

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