dual-use research. i am paul keim, the acting chair of the national science advisory board for biosecurity. i appreciate the opportunity to speak to you about dual-use research and in particular about the board's activities and our recent evaluation of two scientific papers concerning the avian h5n1 virus. it's been recognized for many years that science and technology can be used for both good purposes and bad. it is this two-sided coin that we refer to as dual-use research. the problem is that all biological research can be construed as having potential bad applications, as well as their good ones. the nsabb created a new term, dual-use research of concern or durc, as we've been saying, to distinguish normal research from that with high potential to be misused. the parameters defining durc would include the magnitude any of danger, and the immediacy of any threat balanced against the overall benefits of the work. over the last eight years, the board has advised u.s. government on best practices and policy approaches for the -- for research communication, personnel reliability standards, codes of conduct and international engagement for issues associated with durc. the board is recognized a good policy needs to protect us from scientific misuse and protect the scientific enterprise from

being overburdened with unnecessary regulation. both are essential for our country to be safe, productive and to remain a global leader. the national science advisory board for biosecurity is comprised of well respected scientists, lawyers, infectious disease experts, scientific editors and public health experts. we have an eight-year track record of protecting academic freedom while seeking policy recommendations that will minimize the misuse of biological sciences research. with that in mind, recognize the significance for the board's unanimously recommended against the publication two of scientific papers in november of 2011 due to their potential to be misused. the u.s. government asked the board to review two nih-funded studies reporting mutations that allowed a highly dangerous bird flu virus to transmit from one ferret to another. by a split vote, the board

instead recommends to the government that key elements of the studies not be published and only redacted papers were acceptable for general distribution. these recommendations were based upon the board's finding that if this avian influenza virus acquires the capacity for human to human spread, and retained its current virulence, the world could face a pandemic of significant proportions. the risk for public harm to be of unusually high magnitude. the board has published its recommendations to the u.s. government along with its rational. importantly, we pointed out that an international discussion was needed amongst multiple societal components to develop policy on this arena of high consequence durc. i would further note in the few months since the recommendations were released there's an a flurry of u.s. and international meetings to discuss the risks and benefits of these experiments. the research issues and policy consequence are now commonly known in being debated. this continuing global conversation is important for the scientific endeavor and for our biosecurity. in late march 2012, the u.s.

government task nsabb with reviewing revised versions of the two original manu scripts. this was coupled with a face-to-face meeting to the board could hear directly from the investigators about their search. in this meet, the board received nonpublic information about the risks and benefits of the research from the international public health and research community as well as from the united states government intelligence community. in a classified briefing from national intelligence council and national counterterrorism center representatives, the board heard and an assessment of the risk for misuse and of the global political ramifications associated with these papers. the details of these briefings are classified, but i can tell you that many of the board were left with the impression that the risk of misuse did not appreciably increase with full publication and there's a high likelihood of undesirable political consequences to not publishing.

in addition, the u.s. government has recently issued new policy guidelines targeting high consequence durc. this was based upon the nasbb's own definition of durc and seven categories of experiments that warrant special consideration and targeting particular high-consequence pathogens. it is in this context the board arrived at different recommendations for the revised manuscripts. one paper was unanimously recommended for full publication while the other recommended by a split vote of 12-6. and balancing the risks against the benefits of the revised manuscripts and the context of additional information and new u.s. government policy, the board shifted its position. in my opinion, the split vote is highly significant and signals that the board still believes that there is great potential for misuse of information generated by these types of experiments.

the majority of the board members vote forward publication but they were clearly still troubled by this research and its potential to be misused. it is fair to say the board believes that these types of experiments will arise again and that these issues are not fully settled. as one board member noted, we have only kicked this can down the road and we'll be dealing with it again in the future. it is critical that we establish policy that intensely monitors high potential durc research from cradle to grave in order to protect us from misuse, but also to free low potential durc research from onerous regulations. we must be careful we don't destroy the scientific enterprise as we protect against a misuse of some research. thank you. >> thanks very much, dr. keim. let me ask you while the phrase is in my mind. what did you mean when you said we refer to undesirable political consequences from not publishing? >> well, so this was in the classified briefing, and so in this environment, we can't talk about it in detail, but there are many international collaborative projects going on in public health to try to control and predict and

understand influenza pandemics. many of those political agreements are very fragile and i think it's fair to say that not releasing this information was seen as having a detrimental effect upon those fragile -- >> understood. okay. thank you. final witness is dr. thomas ingelsby, chief executive officer and director, center for biosecurity, university of pittsburgh medical center. welcome back. >> mr. chairman, thank you for the chance to speak to you today. i am the director for the center for biosecurity of upmc. i am an infectious disease physician by training and have seen many patients with influenza die, despite excellent medical care in american hospitals. for many years, my center colleagues and i have been studying avian and pandemic flu and the public health actions that need to be taken to protect us from those challenges. and like all of you, i am deeply concerned that h5n1 is a major

global threat. i have been opposed to the publication of the fouchier manuscript. just as it kills ferrets when instilled into their tracheas this engineered virus also kills ferrets the same way. so there's no evidence that i've seen publicly presented that this engineered virus would have less virulence than h5n1 would. were it to cause a human infection it could acquire new virulence properties. if it led to human infection, we can't rule out the chance it would lead to high case fatality and spreading epidemic, difficult to stop. there are others in the scientific and health communities who share this concern. that said, i appreciate that a deliberative process has taken place in the last six months.

the majorities of nsabb members, u.s. government agencies and the journal "science" have decided that this work should be published. i'm concerned about this, but i recognize this decision has been made. so now it's time to look ahead and anticipate the future of h5n1 transmissibility research which scientists are poised to pursue. here are some brief thoughts on benefits and risks of further pursuing this line of research. will further engineering h5n1 transmission improve surveillance? genetic mutation data is not widely collected in avian flu surveillance systems. very few sequences are analyzed in realtime.

the prescribed response would still be the same. culling of infected birds, all flocks, regardless of the mutations of the virus. until we have a surveillance system in place that collects far more genetic sequence, does so in time frames meaningful and have value to lead to additional action if the field, this research seems unlike three practically improve surveillance. nor is this research necessary to making h5n1 vaccines for reasons i explain in my written testimony. what could go wrong with transmissible h5n1? could an accident occur? biosafety at modern labs is generally excellent. accidents are uncommon and most pathogens have little for societal spread. but the accidental escape could result in catastrophe. although it's uncommon, accidents do happen and 1977, h1n1 caused a mini pandemic probably from a lab escape. nine years ago during sars at least three incidents in which researchers working in labs accidentally infected themselves with sars. i'm not meaning to single out laboratorians for criticism, mistakes are made by all types of professionals, doctors, pilots, rocket scientists, all of us. because we're human. we have detected the possibility

of human error into our research. can we assure it won't be replicated and deliberately misused? we can hope they won't have the competence or intention to pursue this but can't accurately predict the chances this will be replicated by a malevolent scientist somewhere in the world or a terrorist group. what happens if a transmissible h5 starts to spread. as much as a billion people or more. the case fatality rate of database is nearly 60% as you indicated. if a strain with that fatality rate were engineered hundreds of millions of people's lives would be at risk. if a strain with that fatality rate were engineered, hundreds of millions of peoples lives would be at risk. so what should be done about the research going forward? first, i would extend the moritorium discussed. the reason many agree are still valid.

before proceeding we should have more confidence this research will lead to practical benefits and we should look for other benefits that don't require engineering. if this work is allowed to continue, we should limit it to the smallest number of labs. my understanding is the u.k. and canada have decided it can only be done in b4 labs. we should have these discussions in an open transparent way. second, let's decide if there are red lines that shouldn't be crossed. for example, should increased transmissable strains be so we can understand the genex of those problems. the u.s. should continue to strengthen its pandemic prepardness efforts. universal flu vaccine, new anti-virals.

preparing for pandemic is critically important. let me turn to the policy for dual use of concern recently announced. this is a good step towards addressing the controversy. the success of the policy will depend upon how it's implemented. in my written testimony, i pro might recommendations for success of the policy and i highlight four of them here. number one, implement effectively at the local level. scientists, institutions and biosafety institutions will be crucial to the success of this policy. this is new territory for them so training and education will be key. they'll need new members and a clear process for elevating concerns. two, learn from experience. this process will need to evolve as we learn. i understand that the review of the portfolio found ten experiments warranted further risk management. it would be a valuable learning tool for the science community to understand these ten cases. what caused the concerns?

how were the risks mitigated? it would be useful to learn as much as we can from the risk management process. how were risks assessed? going forward, the success of the durc policy will depend on these issues. third, attend to the regulatory burden. this new policy will add another process to be navigated by a scientific community that's already navigated. we have to make sure we don't impose such a regulatory burden that scientists can't continue their important work. to this end, i recommend asking to examine the existing regulatory burdens on u.s. scientists. and last, reaffirm the rule of nassb. it deserves a lot of credit. for its work. nassb members have done substantial public service and prepared valuable guidelines and spent energy, intellect and time on this debate. independent and strong nsabb could have an important role in durc policy implementation

going forward, i hope the nsabb will rarely be in the position of getting invited in process after manuscripts have? been submitted. i think we all agree in this room -- the process should happen early in the research process. to conclude, scientists who research influenza and infectious diseases are working to better the world. the u.s. needs to continue supporting entrepreneurial and talented scientists with the best ideas. at the same time, we need to acknowledge there are rare situations where the consequences of accidents, special processes are needed to manage the public. this new durc policy is a good step in that direction. >> thanks, doctor. help us just to, lay public, including me. when we hear about accidental escape of pathogens from laboratories, we get alarmed. talk more about it.

does that normally happen? infection of workers? or -- >> yes. in all the cases i mentioned and other cases, that is typically the way that people, an infection would escape a lab. the laboratory would get infected. usually when they get infected they don't spread it to anybody else. so the risk really is is to the person working in the laboratory. >> i assume that all the regulations both before and after march 29th were intent on limiting the possibility of exposure to personnel. >> definitely, mr. chairman. in general and specifically in the two cases that were discussing as prototypes here today, the two laboratory, one in wisconsin were very, very highly qualified. inspected multiple times and given a rating of meet or exceed

the kind of standards we're talking about. >> let me ask you first about the two laboratories that were the subject of this concern to the extent that you can. why was the ultimate decision unanimous in the case of wisconsin and then mixed in the case of irasmus? >> the underlying science and approach they took for doing these experiments was different. a they did lump together a lot. one of the approach was viewed as having a greater biological control of the risks. it's one of the aspects we have instituted across the board in in biosafety experiments across the united states, which is to try to do these in a context that's less dangerous. for example, if we do an experiment where we're going to add a gene to something, usually we like to do that with a pathogen that has been disarmed before we get there. so, distinguishing the do groups

and their approaches, i would say that was the biggest difference is, one, worked in a platform if you will, that was viewed as less risky. not as virulent than the other one which was taking really the wild type, the raw material from nature, then changing the transmissability on that platform. >> if i understand that difference had more to do with the scientific decisions of each team as owe posed to differing levels of safety standards they were operating under in their respective institutions or countries. >> so as dr. foucher pointed -- so as dr. fauci pointed out, both institutions were heavily regulated and reviewed. both exceeded the requirements for biological safety that we have in place for these types of experiments. >> okay, dr. kiem and dr. fauci,

i want to give you an opportunity to respond to the dissent in the letter which was, i gather, originally a confidential letter and then was leaked from -- from michael ostraholm in his criticism of the nsabb decisions and to some extent, not totally reflected by dr. engelsby, but also dr. engilsby expressing some concern about the decision. dr. keim, why don't you begin? >> first off on the committee, we are again a board of 25 high ly qualified individuals and we rarely agree upon anything. >> sounds like congress. >> i know. awe although we may not be highly qualified. >> i must say we actually embrace this dissent and weep use it and we cherish the different members and their opinions and it's true for this

particular example as well. i did, this was in fact, a letter that was meant for an internal type of a process for us to understand in a retrospective fashion what we had done and what we had come through and it was as such, i view it as a very constructive type of communication. it was unfortunate that it was leaked and it became part of the public dialogue. it makes it harder to have a constructive and proactive type conversation there. many things you said are worth examining. one point that he makes in the letter is in fact there was a bias in the witness list. i think that -- that is true. the primary witnesses that we brought in were -- were, briefers that we brought unfin this hearing were investigators themselves. they're inherently by yals lly. we brought in a second investigator collaborating with them and working on how you use this information for

surveillance purposes. again somebody who would loike o see their work publishes and sees benefits clearer than the risks. i don'tchairman. we are scientists on this board, and what we do is look at scientific data and other scientists work and we can be very critical of that and so the biases inherent in those types of witnesses i think was not a problem for us. so we in fact i think dealt with that very well, were able to ask very tough questions of the investigators over a series of time. dr. f uchet was in front of us for two hours with lots of intense question and answering about that. i think those biases were something the board could deal with quite well. one part that was clearly not -- was independent of all of the other aspects of the science was the intelligence briefing. this was a briefing that was set up by the u.s. government intelligence community, and we came into that as scientists and

pretty much took this on faith that what we were hearing the assessments of the risks and the political consequences were fact. that was an environment where the board is perhaps a little bit naive. we don't have the capability to look behind these assessments. the briefing was held at the secret level, and we were only able to ask so many questions. they were quite confident and that briefing in fact suggested to us that in fact the risks were minimal and the political consequences, again, were great, and i think that had a great effect upon the board. that's one aspect of dr. osterholm's letter that is an attribute of the process itself. this was never set up as a point-counter point, so we didn't have time in the six hours we had witnesses in front of us to have everybody in the world there, but the most important witnesses that we did have were inherently biassed.

>> interesting. if you had to do it over again, would you try to -- >> i would do many things different, mr. chairman. one is i would probably make sure this was being -- a lot of, of the being done before it ever came to the board. we were brought the papers under a tight timeline back in october. >> right. >> in retrospect the amount of time it took and the timeline we were on was much too tight. the process and the number of hours we put in to reviewing the two papers was massive. it is clear the new government policy identifying durc early on will be critical for moving much of this evaluation earlier on. >> it is a very important point. i agree with you that the dissent even to some extent the bias is not of itself of concern, particularly in scientific debate and discussion, but obviously from a homeland security point of view

we're concerned about the impact, and am i right that you're essentially to the best of your ability providing assurances that information is not going to be released in the two studies, particularly in the fash study that would significantly increase the risk of deliberate or accidental release of modified h5 n 1. >> the both was confident in the oak apaper and unanimous and in the f ucher it was split and 12-6 and i would say in this type of board process each of us had to weigh the evidence. i mean, there were great uncertainties in this type of research, a very small number, relatively small number of ferrets were used in the sperms, so understanding the biological properties of these viruss is not 100% certain. we don't know everything there is about these and so these 20

board members had to weigh the evidence as best they could, and i will tell you you won't find a better group of people to do this. this board is extremely qualified and able to do this and worked very hard at understanding the risks and benefits and came to a split vote on the f ucher paper. >> doctor, do you want to respond to the osterholm complaints? >> sure. with regard to the letter, as you probably know, because i am sure that your staff or you have a copy of the letter, there were several issues that were brought up in there. i have to say that i agree with of the things that dr. kooim said. this is a strong board, a really good board. with he worked with them a long time and i don't think they will be significantly influenced what

they might perceive as bias. if they did as paul has done in the past if you have an issue with something, you bring it up. the letter was sent to the executive secretary of the nsabb who is at the nih, dr. patterson. we have responded on a point by point basis to everything in that letter. we would be more than happy to make that response available to you so that you can see the point by point discussion. again, there were important issues about looking forward. there were several things in there that i must say quite frankly, mr. chairman, i actually disagree with, one of which was the concern about the security briefing as you know. i have a great deal of trust in the director of the national intelligence to tell us what we need to know, so that's just one example. the idea as you mentioned about the picking of people who would be on, we did not get any

indication from dr. osterholm of people he wanted to see there that weren't there so rather than ti it for tat on that, i have to say for the record i disagree with many of the things in his letter. >> i appreciate that directness, and i thank you for it. do you have a reaction to dr. i think always suggestion that the moratorium be extend and had if so for how long. >> i totally agree with an extension of the moratorium. the critical issue is for how long. >> right. >> this is a voluntary moratorium, and i think that's something that the public needs to understand. this is a voluntary moratorium on the part of the scientific community. i had discussions with the influenza assign tiss and encouraged them and they actually to their credit and to

the discussion that dr. kooim himself had in the nssab, this is something they agreed upon. exactly when to call it off, i think we have to see how we can have and we're very actively involved in pushing forward the principles and the implementation of the march 29th government wide durc policy. that will have an important impact that we can feel comfortable we can go on. as long as people understand the principles and the implementation mechanisms of how you address durc, several of the labs involved understand that now. we need to make sure that's broadly understood. i definitely agree with that. i just want to make one point of minor disagreement if you want to call it that with what my esteemed colleague says that if we only looked at the short-term benefit of research, we wouldn't do a lot of research at the nih because you very often have a

situation where it is incremental and you build up into something that really becomes important, so although i understand the point is being made if you look at what immediate benefit of those mutations will have us right now, sure, you can say that there isn't a lot of surveillance capabilities, of high sequencing, et cetera, but the incremental accumulation of knowledge is one of the fundamental principles that the nih research agenda is built upon. i think there is a little bit of a disagreement on that. i don't think you need to have an absolute immediate benefit for research not to be ultimately important to do and publish. >> do you want to respond? >> i actually completely agree with what you just said. i don't think we disagree on that. i agree that fundamental research and understanding biological principles is critical, and it is part of the science mission, and i think this is just one very specific and rare example where i think the bar for what is perceived with this line of research

should be beyond a deeper fundamental understanding of biology. in general, i think i completely agree that the test for basic science shouldn't be whether it has practical benefits in the next year, but in this case there has been a lot of the proponents of the research have been arguing for urgent practical benefit, and in my view i just haven't seen a compelling case for that. >> ask you, dr. f auci and anybody else that wants to answer, in some sense it is a question at the margins when considering future research that would be seen as durc, dual use research of concern, can you imagine instances in which you would conclude that research should not be undertaken under any circumstances? >> i do. i don't think -- i think it would be scientific