Thursday, April 12, 2012

I called Paul Berg is Stanford today to get his perspective since he was so involved in a leadership role in the Asilomar situation in the 1970s. We had a great conversation as we discussed the similarities and differences between then and now. I pointed out and he agreed that there is still today “scientific hubris” on the part of some people. Ron Fouchier showed that early on. Hopefully now he is “cured”. However, Paul emphasized (as I feel) that the issue with bioterrorists is really a non-issue. He is concerned about sloppy science and public trust. He said that in the 1970s there was little concern about “germ warfare”. I told him that that is the biggest difference from todfay when biodefense and biosecurity is a cottage interested with people (Ingesbly et al) and Agencies (DHS) who think about and work on this full time. In addition, there are the biodefense “Beltway Bandits”. This “Biosecurity intimidation” matches the “Scientific Hubris”. More amazing shit. Mike Osterholm wrote a letter to Amy Patterson with a cc to the entire NSABB membership excluding the ex officio members saying that he feels that the NSABB meeting was “rigged’ by us to come up with the outcome that happened. I truly believe that he is traying to cover his ass that the NSABB completely missed the point of the transmissibility. This is similar to the Nature issue from yesterday. In addition, he disingenuously mentioned to Amy in the e-mail that he does not want this to be a public statement and does not want it to leak even though he copied about 50 people. Give me a break!!!! See letter below. NSABB letter final 41212.pdf April, 13, 2012 – It has leaked 12 hours after it was sent. There is no way that Mike did not know it would leak since he sent it to so many people. It has appeared on the Nature website and in and “Science Insider” article by Jon Cohen. It is clear to me that Mike Osterholm is bipolar. If you look at the letter, it is crazy. He keeps referring to “anonymous” influenza researchers who are not involved in transmissibility research who say that the research should not have been done. In the Science Insider piece, Susan Ehrlich, another NSABB member says that she agrees with Mike. She is a complete goof-ball, having spoken with her at the NSABB meeting. Mike goes on in the letter to say that the NIH did not invite any experts on surveillance or non-transmission influenza experts, even though he requested this. We checked all of the files and he never made any such requests. He asked for a security briefing that said that there was no credible terror threat with H5N1. This is not what he wanted to hear and so he said that the briefing was useless. BTW, it was given by the CIA and the NIA. He also states that according to discussions at the March 29-30 NSABB meeting, Ron Fouchier already has the necessary mutations to create a ferret-transmissible virus that do not require passage. Since Mike absolutely knew that this letter would leak, he has egregiously violated the confidentiality agreement of the NSABB. This together with the paranoid statement of Mike Imperiale that he was uncomfortable because he thought that the NIAID would not fund his grant if he voted to not publish makes me certain that the NSABB as it is presently constituted is fatally flawed. As you can imagine, the press and bloggers are having a field day with this. I am astounded that Helen Branswell (Canadian Press) was more interested in why she was not given the leaked document than she was in the fact that the very leaking of the document reflects the craziness of some people on the NSABB. This whole process has circumvented our plan to coordinate with the Dutch our release of the NSABB recommendations since Mike in effect has made public the “minority vote” before the actual majority vote to publish. Remember, the committee voted 18-0 to publish the Kawaoka manuscript and 12-6 to publish the Fouchier manuscript.

Amy P. Patterson, M.D. Associate Director for Science Policy National Institutes of Health Office of Science Policy, OD, NIH Building 1, Room 103 9000 Rockville Pike Bethesda, MD 20892 Dear Amy, We all realize that the National Science Advisory Board for Biosecurity (NSABB) is currently in “uncharted scientific and public policy waters” with the request by the United States Government (USG) to review and make recommendations regarding publication of manuscripts from Dr. Ron Fouchier and colleagues and Dr. Yoshihiro Kawaoka and colleagues reporting their respective research methods and results related to the transmissibility of H5N1 in mammals. As a member of the NSABB, I appreciate the extensive efforts by the Board over the past six months to provide this comprehensive review and to make recommendations based on the previous extensive work of the Board to define dual-use research of concern (DURC.) It has been a gratifying professional and personal experience for me to work with such a dedicated group of scientific and policy leaders with a common purpose of both enabling the ongoing critical life science research that provides answers to some our most challenging health and environmental issues and at the same time protecting the world from potential catastrophic outcomes resulting from similar research. It has been two weeks since the NSABB meeting of March 29-30 where the Board was requested by the USG to reconsider our previous decision recommending the redaction of both the above referenced manuscripts before publication. During this time I have given considerable thought to the way the meeting was conducted and the subsequent decision by the NSABB to change its recommendation to full publication of both manuscripts without redaction. While we all realize any effort by the NSABB members and staff to arrive at a “Solomon-like” decision regarding the dissemination of the methods and results included in these manuscripts will be questioned by those who do not agree with the outcome, there is also a critical consideration for establishing precedence for how the NSABB will move forward with similar complex issues in the future. It is for this reason I share this letter with the NSABB members and the National Institutes of Health (NIH) Office of Biotechnology Activities (OBA) staff that support the Board’s work. The views in this letter are mine and mine alone; I have not communicated with members of the NSABB or staff since the meeting. I write this letter in the spirit of moving forward and with an understanding of how the recent events related to the H5N1 influenza manuscript review informs us on why the USG-NSABB process for evaluating DURC issues must fundamentally change to both protect life science research and the risk to the public of such research. For the record, I voted at the meeting to approve the full publication of the Kawaoka manuscript and the continued requirement of redaction of the Fouchier manuscript. First, I believe that the agenda and speakers for the March 29 and 30th NSABB meeting as determined by the OBA staff and other USG officials was designed to produce the outcome that occurred. It represented a very “one sided” picture of the risk-benefit of the dissemination of the information in these manuscripts. The agenda was not designed to promote a balanced reconsideration of the manuscripts. While I don’t suggest that there was a sinister motive by the USG with regard to either the agenda or invited speakers, I believe there was a bias toward finding a solution that was a lot less about a robust science- and policy-based risk-benefit analysis and more about how to get us out of this difficult situation. I also believe that this same approach in the future will mean all of us, including life science researchers, journal editors and government policy makers, will just continue to “kick the can down the road” without coming to grips with the very difficult task of managing DURC and the dissemination of potentially harmful information to those who might intentionally or unintentionally use that information in a way that risks public safety. Merely providing a “minority report” in the final findings and recommendations of the meeting does nothing to address the fundamental issues of how the risk and benefits were determined, described, and considered at the meeting. For example we heard from Dr. Fouchier that he has already identified an additional mutation (not included in his current manuscript) that results in ferret-to-ferret transmission (mammalian transmission) without the need for repeated passage of the virus in ferrets. This work, which may have been supported by NIH funds, surely must be considered as a candidate for the next manuscript to be before the NSABB for review. What scientific and policy issues will differ with this “incrementally changed manuscript” compared with the issues we just considered? If such work represents only incremental changes in results from previously approved work, will the Board ever find a bright line for redacting publication and all the issues that go with that decision? For you to better understand my concerns, I will detail specific examples of how I believe the agenda and selected speakers resulted in the one-sided risk-benefit analysis that I described above. I will use in part the general considerations and conclusions in the April 11th draft NSABB findings and recommendations document as the framework for these points. The data in the newly revised manuscripts are immediately and directly enabling. There was no objective review provided by a disinterested subject matter expert that addressed the current state of the art regarding the proliferation and use of reverse genetics technology that can incorporate the methods and results presented in the current manuscripts to allow those who would not have the ready expertise or resources to more easily repeat these experiments. The implications of doing such work, even by well-meaning scientists who do not have adequate biosafety measures in place, should have been reviewed. The subject matter experts that addressed this issue at the meeting have a real conflict of interest in that their laboratories are involved in this same type of work and the results of our deliberations directly affect them, too. The same can be said about the attendees and outcome of the February World Health Organization consultation. In short, it was the “involved influenza research community” telling us what they should and shouldn’t be allowed to do based on their interested perspective. Such a perspective is very important and should be included in this discussion, but it shouldn’t be the only voice. As director of one of the five NIH-supported centers of excellence in influenza research and surveillance, I can speak with firsthand knowledge and experience that the voice of an important group of senior influenza researchers not doing similar mutation/transmission work was not heard regarding this issue. I personally tried to have their voices represented at the meeting. They were not invited. One of them wrote me a very clear and compelling comment on the potential for the information in one of the manuscripts to be immediately and directly enabling. He stated; “I am an influenza virologist myself, and we routinely create viral mutants in my lab using reverse genetics, so I have a good sense of the technical issues involved. As such, I can recognize that some outspoken researchers in our field have been under-representing the increased risk that would be entailed by full publication of the specific mutations versus the current situation where only the general outline of the ferret-passage scheme is known. A ferret-passage experiment is expensive and technically demanding, and could only be done by a handful of labs in the world. Once the mutations are public, individuals in my lab (or many other labs) could generate the mutants in a few weeks given several thousand dollars for gene synthesis. I remain agnostic about what is the best policy going forward. I recognize that there also important potential benefits from this research, and think that research along these lines does have valid scientific and public-health justifications. But these benefits need to be carefully weighed against the real risks, and I am definitely concerned that there has been a rush to judgment for full publication within our own research community.” I have talked with many similarly minded influenza researchers from around the world who agree with the above statement. Yet these voices were notably absent in the NSABB deliberations. The data may benefit public health and surveillance efforts. The Board received no formal or informal presentation from those on the front lines of H5N1 animal surveillance and control. Specifically, no one with H5N1 virus surveillance and control expertise from either the Food and Agriculture Organization (FAO) or the World Organization for Animal Health (OIE) were invited to participate. I have discussed with officials from both organizations the implications of sharing the mutation data; the general response indicated that such information without major new resources and government commitment to active animal surveillance and control would not fundamentally change current surveillance and control practices in most of the endemic H5N1 countries. Yet, there was a series of very general and unsubstantiated statements made by others invited to the meeting who are not involved in the day-to-day animal surveillance activities in the H5N1 endemic countries (including the authors) as to the benefits of making the mutational data available for this purpose. Our NIH-supported center of excellence is supporting surveillance for H5N1 virus in domestic animals in one of the H5N1 endemic countries; our surveillance researchers have told us that the finding of an H5N1 virus with specific mutational changes in poultry would not result in widespread culling activities unless the birds are sick. Immediate culling is supposed to be the standard protocol now for the control of H5N1 virus, but resources for a number of the H5N1 endemic countries are often lacking to detect the virus or support programs. The voice of these and similar on-the-ground experts was missing from our discussion regarding the benefit of making these mutation data general available. Setting aside the fact that surveillance experts noted above were not invited as subject matter experts, it is notable that current news sections in both Science and Nature have published a series of articles on the controversy of using the H5N1 virus mutation information for surveillance and control purposes. Several of these stories were well researched, with numerous interviews with some of the experts I noted above. Their conclusions were consistent with my comments above regarding the utility of making the mutation data from these studies generally available and the impact on the control of H5N1 infection in poultry. None of these news stories were referenced in the meeting (except by me) or provided as important background information leading to a more complete risk-benefit analysis. There was no discussion as to the limited number (and time from sampling to testing) of H5N1 viruses sequenced from endemic countries or how to improve that situation in the endemic countries before the release of the mutation data could yield even remote benefit. The most important aspect of the results in these two studies on surveillance and control has already been accomplished; namely alerting the world to the possibility that H5N1 influenza virus surely can become a mammalian-transmitted virus and poses real pandemic potential. We must be much better prepared to respond to a possible H5N1 influenza pandemic than we are today. Publication of the full study methods and result of either manuscript will not enhance this conclusion. Finally, I believe it was unfortunate that Dr. Smith was able to present the work on the population-based mutational changes in H5N1 viruses without an opportunity for others in the influenza field to provide commentary. Since Dr. Fouchier was a coauthor of the work, it hardly represented an unbiased view of H5N1 virus genetics. Was the manuscript that Dr. Smith presented peer-reviewed? While I appreciate that he is a leading influenza researcher, for the sake of balance others without a primary interest in these manuscripts should have led this discussion. Security considerations and the risk of malevolent applications of the mutation data. One of the most disturbing aspects of the meeting was the security briefing on the evening of March 29th. It was one of them most incomplete and, dare I say, useless classified security briefings I’ve ever attended. For the past 20 years, I have held security clearances in my work with international and national bioterrorism, including a top secret clearance in my role as a special assistant to HHS Secretary Tommy Thompson from 2001 to 2004. I have served as a briefer for some of our leading government officials during that time. I do understand threat assessment and the limitations and strengths of intelligence. I realize I’m limited in to what I can share here because of the classified nature of the briefing, but in short the briefing we received can be summed up by saying “We don’t know much about anyone wanting to use this information for malevolent reasons, so it’s probably not a risk.” I would agree that few persons in the terrorism and intelligence worlds see this as a primary or even secondary weapon of choice for international terrorism for all the obvious reasons. But the absence of any discussions regarding international or national rogue scientists or irresponsible researchers not using adequate biosafety to conduct “now enabled work” was a major flaw in the briefing. These types of scientists are exactly the ones who would benefit immensely in conducting work of serious concern with the recipe and methods defined in fully published manuscripts. There was no discussion of eco-terrorists whose single purpose is to disrupt animal production activities. A release of a mammalian-transmitted H5N1 virus in swine would devastate that industry even if limited illness occurred because of the public relations issue of “killer bird flu virus in pigs.” I can’t think of a worse scenario than having H5N1 virus circulating widely in swine with a critical reassortment likely to occur and human transmission not far off. The briefing (or the meeting as a whole) did not cover the historical perspective of why influenza virus is truly different than any Class A pathogen we worry about because of it the consequences of its accidental release and our inability to stop transmission once it occurs in the community. As bad as an accidental release of variola virus, Bacillus anthracis, Yersinia pestis, or SARS virus might be, we could—based on agent transmissibility, incubation period, clinical recognition and countermeasures—effectively stop a global pandemic from occurring. We can’t do that with influenza virus. There is no margin for error. We need look no further than the reemergence of H1N1 in 1977, after a 20-year absence from global circulation. Our group has been actively investigating the return of H1N1 in 1977, and based on that work we are convinced it leaked out of a Russian lab that was working on a live-attenuated H1N1 virus vaccine. Again, none of this information was addressed in the risk assessment overview. I am particularly concerned about this aspect of the two days of deliberations, because I heard several members remark how the security briefing had a substantial impact on their decision of how to vote. The use of the mutation data to enhance countermeasure preparedness. Although this issue came up several times in terms of the importance for sharing the mutation data for the development of countermeasures (vaccines and antiviral drugs), there were no datarelated presentations addressing this issue. Again the Science and Nature news stories of the previous three months did an outstanding job of researching the claim that the mutation data were critical in developing and deploying H5N1 countermeasures. The authors of the articles interviewed a number of global experts in the area of influenza countermeasures; they concluded there was no immediate benefit to countermeasure development or production as a result of the availability of the mutation data. At no time was this information presented to the Board by a disinterested expert. A previous decision. Throughout the discussion of the current review of the two manuscripts, the issue surrounding the NSABB’s approval of publication of the 1918 H1N1 virus paper in 2005 has been raised as precedence for how we might proceed in this situation. I want for the record to be clear that I firmly believe we made a mistake in approving the publication of the 1918 virus paper. At the time I was one of the supporters of publication. We reasoned that the 1918 H1N1 virus, if it were to accidently escape or be intentionally released, would cause little public health consequence because of the previous circulation of H1N1 influenza virus prior to 1958 and again since 1977. We believed that the vast majority of the world’s population would have sufficient crossprotective immunity to prevent any kind of H1N1 influenza pandemic as experienced in 1918. Well, with the appearance of A(H1N1)pdm09, we now realize there was virtually no populationbased immunity to either the new H1N1 virus or the closely related virus, the 1918 H1N1 strain. The exception was for those who had experienced H1N1 infection prior to the early 1950’s when those circulating strains in humans did provide cross protection. Had someone taken the published data on the 1918 virus mutations, they could have created a virus that, had it been even accidently released, could have caused a pandemic much as the A(H1N1)pdm09 virus did. I share this observation not to be critical of the 2005 NSABB decision, as I was part of that decision. Rather, it’s to remind us that you can’t unring a bell. Any decisions that the NSABB makes with regard to the influenza issue may possibly have farreaching and yet unrecognized implications, like the 1918 virus situation. Summary In short, the NSABB March meeting should be a very important learning experience for the USG, the journal editors, and life scientists in general as to the need for a much more effective system to address DURC issues. One primary lesson that I believe is critical: The Board must involve disinterested subject matter experts to provide technical advice. I believe that the relative lack of subject matter expert input from those without a direct interest in the Board’s decision be viewed critically by the larger policy and life science communities as the decision is debated over the upcoming days. As I stated before, I believe our recent experience is just the beginning, not the end of this type of scientific and policy conflict. As a said to Dr. Collins toward the conclusion of the March meeting, I wouldn’t want to be in his shoes sitting before a Congressional hearing trying to explain why the NSABB and likely the USG supported the full Fouchier publication when we heard at the meeting that he has done more work and found one additional mutation that now confers H5N1 transmissibility between mammals without ferret passage. How will we justify one more “incremental finding paper” that now is a pretty complete cookbook when we didn’t recommend redaction for the vast body of his work? If we believe redaction of the current manuscript is problematic in terms of international agreements, I think the next mutation paper will prove to be the straw that breaks the camel’s back. It is unfortunate that the current NSABB action just kicked the can down the road to the next manuscript. I hope these comments are helpful as the NSABB moves forward. As someone who will soon be rotating off the Board after 7 years of service, I believe now, more than ever, of its importance. Thank you for the honor and opportunity to participate. Sincerely, Michael T. Osterholm, PhD, MPH Director, Center for Infectious Disease Research and Policy Director, Minnesota Center of Excellence for Influenza Research and Surveillance Professor, Division of Environmental Health Sciences, School of Public Health Adjunct Professor, Medical School Cc: NSABB Members NSABB Staff MEMORANDUM OF UNDERSTANDING Between UNITED STATES DEPARTMENT OF HEALTH AND HUMAN SERVICES, NATIONAL INSTITUTES OF HEALTH And THE UNITED STATES MARSHALS SERVICE I. PARTIES This Memorandum of Understanding (MOU) sets forth the understanding of the obligations and goals of the United States Department of Health and Human Services (HHS), National Institutes of Health (NIH), and the United States Marshals Service (USMS) relating to protective services for Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases prior to and after his retirement from federal service. II. PURPOSE The purpose of this MOU is to define the roles, responsibilities, and actions necessary to secure and protect Dr. Anthony Fauci under this MOU and the fiscal year Reimbursable Agreement (RA). III. AUTHORITY For USMS: 1. 28 United States Code (U.S.C.) §§ 561(b), 566(e)(1) 2. 28 Code of Federal Regulation (C.F.R.) § 0.111(e) 3. USMS Directive 10.1, Judicial Security For HHS NIH: 1. 42 U.S.C. § 282 2. 15 U.S.C. § 1535 IV. FUNDING AND REIMBURSEMENT Funds transferred to the USMS by HHS NIH will be utilized for the sole purpose of the protective services provided to Dr. Anthony Fauci and will include, but not be limited to, the following: 1. Salaries and benefits for assigned Deputy United States Marshals (DUSM) and administrative support personnel, including reasonable and necessary overtime pay. 2. Reasonable and necessary travel costs for Temporary Duty personnel. 3. One leased and equipped limousine and follow car used for the transportation and security of Dr. Anthony Fauci. 4. Leased vehicle and fuel for one vehicle for each DUSM assigned to the protective detail. 5. Necessary law enforcement equipment for operational use. 6. Other ancillary costs as identified, documented by USMS, and mutually agreed upon in advance by HHS NIH and the USMS. The RA accompanying this MOU identifies the actual cost of the services to be provided. All expenses incurred by USMS related to this agreement must be reasonable, necessary, mission related, and documented. Funding for the following items will be paid for directly by HHS NIH: 1. All travel and per diem expenses for permanent security detail members related to the protective mission will be paid for by HHS NIH. 2. Other ancillary costs as identified, documented by USMS, and mutually agreed upon in advance by HHS NIH and the USMS. V. USMS PROTECTIVE SERVICES PROVIDED 1. The protective services provided will continue upon the execution of this MOU and the effective transfer of funds as stipulated in the accompanying RA, as well as future fiscal year RAs, subject to periodic assessment as outlined below. The number of reimbursable positions and other costs identified in the RAs are based on USMS protective service requirements, experience and methodology, in addition to USMS operational requirements at the HHS NIH. At least each fiscal year hereafter, and as frequently as the USMS deems appropriate, the USMS will conduct a threat assessment to determine, in its discretion, whether USMS authorities allow for continued protection and, if so, future protective requirements, if any. HHS NIH will be consulted and provide recommendations regarding protective requirements, but the USMS retains final authority regarding the extent of protective requirements and the continuing need and authority for protective services. Permanent security detail members are not HHS NIH employees and at all times during the term of this MOU will remain USMS personnel and operate under the supervision of the USMS. 2. Personal Security briefing, including occasional threat-based briefings, will be provided by a USMS Chief Inspector DUSM or designee assigned to HHS NIH. The initial briefing on USMS protective services will include, but not be limited to, USMS protective service policy 10.1 and 28 USC 566(e)(I)(A). The initial briefing will be provided to Dr. Anthony Fauci and his immediate family. Dr. Anthony Fauci and his immediate family will be given a copy of USMS Publication #94 (Offsite Security Handbook). 3. Protective services will be provided for Dr. Anthony Fauci. The level of support will be based on the USMS assessment. At any time, threat-based circumstances exist, additional personnel may be added to or removed from the protective detail as agreed upon by the Deputy Director for Management, NIH (or their designee) and the USMS. 4. The USMS will monitor and mitigate threats against Dr. Anthony Fauci. This includes access to, and use of, the USMS Office of Protective Intelligence, Threat Management Center, and other USMS protective investigations resources as required. The USMS Detail Chief Inspector will meet regularly with the Deputy Director for Management, NIH (or their designee) to discuss security services and threat management.