H5N1 Research Discussed in Special Session at ASM

Troy Brown

February 29, 2012

February 29, 2012 (Washington, DC) — A panel of prominent scientists expressed their agreement with steps taken so far regarding the publication of controversial research results on the H5N1 influenza virus at a session hastily convened today at the American Society for Microbiology (ASM) meeting on biodefense and emerging diseases. The ASM organized the extra session to provide time for the discussion of recent recommendations by the US National Science Advisory Board for Biosecurity (NSABB).

Late last year, the NSABB asked researchers from the Netherlands and the United States to publish only limited information about their research in Science and Nature, respectively, because of concerns that the research could be replicated and used for bioterrorism.

The early-morning meeting was scheduled because this issue has generated intense debate on all sides. Some believe the research should be published in full, some feel the research is not really all that sensitive because there is a low likelihood of it being used for bioterrorism, and others believe the research is so dangerous that it should not have been done in the first place.

Concerns about biosafety issues have led some to call for the research to be conducted in biosafety level 4 (BSL-4) laboratories instead of the BSL-3 laboratories where much of the research is currently performed. The wide range of opinions has made it difficult to reach any kind of consensus.

On February 16 and 17, the World Health Organization (WHO) held a meeting in Geneva, Switzerland, with 22 researchers, medical publishers, and other individuals directly involved with the research, to discuss issues related to its dissemination. The participants decided that the research must continue because it is critical, and that it should ultimately be published, in part because they say it would be extremely difficult to develop a system for disseminating it only to those with a legitimate need.

The dispute has been featured prominently in several science journals including Science, Nature, and mBIO, and it has been covered extensively in the mainstream media as well. On February 24, mBIO commissioned 3 commentary articles by experts in the field in an effort to provide a forum for airing differing opinions.

Record Attendance for Early Meeting

Paul Keim, PhD, chair of the NSABB, moderated today's meeting. He began by noting what he called record attendance at a meeting held that early in the day: 7:15 am. Dr. Keim described the events that led to the advisory board's recommendation and introduced the panel.

"We recommended to the US government that the papers be modified, and the results and experimental details be redacted, so somebody with malevolent intent could not exactly replicate the results," explained Dr. Keim. "That was a recommendation that went back to the US government; the US government then accepted those recommendations and went back to the journals and to the investigators," he said.

Dr. Keim explained that because the research is still confidential, it would not be discussed in detail at this meeting. Nevertheless, he said, "I assure you there are many things to talk about because of these recommendations."

Setting the Record Straight

Ron A.M. Fouchier, PhD, from Erasmus MC in Rotterdam, the Netherlands, is 1 of the researchers whose work has come under scrutiny. He described the experiments his team conducted and the questions his research is attempting to answer.

"These viruses have caused hundreds and hundreds of millions of poultry deaths, and on occasion these viruses have also been transmitted to various mammals, including cats, dogs, pigs, [and] tigers, and importantly, they have spread to humans," he said. "From 1997 onward, the question has been in the influenza community, as well as the public health community on the whole: Can this virus go airborne, and can this virus ever trigger a pandemic?"

Dr. Fouchier explained that they conduct their research in a BSL-3 facility with a low-pressure, high-efficiency particulate air (HEPA) filter room, and that all research is carried out in class 3 biosafety cabinets and class 3 isolator units, with many conditions similar to those seen in BSL-4 laboratories.

Dr. Fouchier added that there are 2 misperceptions being circulated in the mainstream media. The first is that the disease spreads quickly. "If one were going to deduce anything [about] the efficiency of spreading, we would have to conclude that this virus does not spread yet like a pandemic or a seasonal influenza virus," he noted.

"The second misconception is that the virus would be highly lethal if it would ever come out," he said. He added that although the virus is highly pathogenic for chickens, this is not the case with mammals. "In mammals, it is known that if we infect ferrets with very, very high doses, and put it straight down into the lungs of the animals, yes, the animals with the virus will drop dead, and they will do it by around day 3," he said. "But if we inoculate ferrets or other mammals by an intranasal route, the animals generally do not get sick at all. They might get a little bit of flu, but they don't die," he added.

"This virus, although it is highly lethal to chickens, and highly lethal if you put it directly down, at high titers, in the lower respiratory tract, it is certainly not highly lethal if ferrets start coughing and sneezing on one another," Dr. Fouchier said.

In addition, he added, most humans would be protected by cross-protective immunity, acquired by previous infection with seasonal influenza.

He concluded that the research needs to continue, but with proper protective measures.

NSABB Recommendations

Michael T. Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota School of Public Health in Minneapolis, described the position of the NSABB on this issue.

He said that the NSABB believes in full publication of research, and that its decision was reached after "many hundreds of hours of conference calls and question and answer sessions." He said that even though its members all have strong opinions, the vote for recommendations was unanimous.

They looked at the risks and benefits of full publication and recommended "that the conclusions of the manuscripts be published, but without experimental details and mutation data that would enable replication of the experiments," he said.

"Trust me, we looked very carefully at both sides of this issue," said Dr. Osterholm.

"I think it's fair to say that these are probably the 2 most famous unpublished manuscripts in modern science history," he said.

Recent discussions about the accuracy of case fatality estimates is a diversion, he said, and noted that this was never a major consideration of the NSABB's deliberations.

"Because the NSABB found that there was significant potential for harm in fully publishing these results and that the harm exceeded the benefits of publication, the board therefore recommended that the work not be fully communicated in open forum," said Dr. Osterholm.

Government Response to the Recommendations

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), discussed the US government's response to the NSABB's recommendations.

The National Institutes of Health (NIH) believes this research is important, said Dr. Fauci. The NIH is concerned with research about a wide range of influenza issues, including the development of therapeutics, he added. Numerous agencies, including the NIH and the US Centers for Disease Control and Prevention, were involved in developing a strategic preparedness plan that involves multiple components from surveillance to research, including vaccines and the development of antivirals.

Dr. Fauci agreed with Dr. Fouchier's observation that the NIH is very interested in this type of research. He described the NIH/NIAID research review and oversight process as "a dynamic process with multiple steps." The research process involves internal review, as well as consultation with outside experts including blue ribbon committees, he explained.

He added that the NIH accepted the recommendations of the NSABB.

Noting that "there was more said in the press than at the scientific level," Dr. Fauci said they determined that a timeout was the best way to move forward. He expressed concern that this whole process is being perceived as a "US-centric process, and a US government–centric process," as they supported the WHO meeting in Geneva.

Science's Response to the Recommendations

Bruce Alberts, PhD, editor-in-chief of Science, described the events that took place at the journal. He explained that much discussion has taken place regarding this issue, saying that more than 25 conference calls have occurred among the authors, Science, and Nature, and that he has collaborated closely with Phil Campbell of Nature.

He added he supports the NSABB and their decision, saying that he believes the NSABB is the best organization to be making these decisions. Although they knew this day would eventually come, there was no formal process for managing the process, he said. Reiterating his formal statement made late last year, he said, "Our response will be heavily dependent on the steps taken by the NSABB and/or by the US government or by the WHO to set forth a written transparent plan so that any information that is submitted for publication will be provided to all those responsible scientists who request it as part of a legitimate effort to improve public health and safety."

He said that the NSABB will be meeting again to discuss this further. "It's my intention to try to comply with the NSABB recommendations, provided they have a mechanism for selective access to the redacted information by those with a need to know," he said.

The authors have disclosed no relevant financial relationships.

ASM Biodefense and Emerging Diseases Research Meeting. Presented February 29, 2012.