Original article from: Scientific American posted on April 12, 2017. by Helen...
Testimony of Seth Jaffe on Behalf of Boston University in Connection with Proposed Ordinance on BSL-4 Research in the City of Boston
This testimony addresses the scope of the review of potential risks posed by the National Emerging Infectious Diseases Laboratories (NEIDL) and the assessment of that review by two separate panels of experts, as well as by federal and state court judges. The heart of the review is the final supplemental risk assessment (FSRA)1 I performed by the National Institutes of Health (NIH). The review of the NEIDL was by far the most comprehensive ever performed for a biological research facility. In fact, in this writer’s experience over more than 25 years, the review performed for this facility and the independent assessment provided for that review may be the most comprehensive I have seen for any facility of any kind.
Including appendices, the FSRA runs approximately 2,000 pages. There is an additional response to comments that runs almost 700 pages. The risk assessment was reviewed by two separate teams of independent scientists and engineers. The first group of reviewers was a Blue Ribbon Panel convened by the NIH to provide guidance in the development of the risk assessment. The Blue Ribbon Panel may be the most distinguished panel of experts on infectious disease and public health ever assembled.2 In reviewing the draft final SRA, the BRP concluded that:
This study is unprecedented in its scope, breadth and complexity, and utilized widely accepted validated methods. The scenarios described in the risk assessment used real live data and experience to the maximum extent possible.
With that in mind the Blue Ribbon Panel believes that this is the most scientifically sound rigorously conducted study that is possible at this point.
AR, pp. 674-75. In short, the world’s leading experts in infectious disease reviewed the risk assessment for the NEIDL and concluded that the review wasn’t just pretty good. It wasn’t just good enough. It was “unprecedented” and it was the “most scientifically sound rigorously conducted study that is possible.”
To provide yet another level of independent review, the NTH engaged the National Research Council (NRC), which formed a “Committee on Continuing Assistance to the National Institutes of Health on Preparation of Additional Risk Assessments for the Boston University NEIDL” (the NRC Committee). The NRC Committee also included prominent infectious disease researchers, as well as experts in risk assessment.3
It is important to emphasize that these experts were not rubber stamps for the NIH. In fact, the NRC Committee’s involvement in the development of the FSRA began in 2007 at the request of the Secretary of EOEEA. AR , pp. 53-54, 838. Over the subsequent four years, the NRC Committee met with the BRP at key milestones in the FSRA’s development, provided feedback and constructive criticism, voiced concerns, and submitted at least four written reports containing extensive suggestions for how the FSRA could be improved. AR, pp. 53-55, 664-787, 837-839, 841, 881, 1557-1570. In December 2011, following its review of the “90%” or penultimate draft of the risk assessment, the NRC Committee concluded that:
It is clear that the NIH and the Blue Ribbon Panel have gone to unprecedented lengths to improve the risk assessment for the NEIDL and have made substantial advances…. It is the Committee’s view that no further advice from this group would be useful nor should it be required.
AR, p. 1570. By the time the FSRA was finalized in July 2012, the NRC Committee’s remaining comments had been addressed. Compare AR, pp. 1557-1570 to AR, pp. 1579-4294.
In addition to these thorough expert reviews, the FSRA and the SFEIR then received two additional layers of review; first administrative, and then judicial. The administrative review was by the Secretary of EOEEA, who has the obligation under the MEPA statute to certify whether the SFEIR complied with MEPA. The secretary provided the required certificate on March 1, 2013.4 The Secretary’s certificate helpfully lays out the history of the environmental review of the project, including the decision by the prior Secretary to engage the NRC Committee and the role that the NRC played in reviewing the FSRA over time.
As the Secretary’s certificate noted, both the BRP and the NRC Committee had substantial input into the preparation of the Draft Supplementary Risk Assessment. The final joint meeting of the BRP and the NRC was convened on November 2, 2011, to review the 90% Risk Assessment (the 90% Draft)…. The 90% Draft, with the exception of issues noted during the final joint meeting was, as named, 90% or substantially complete. Consensus was reached among the BRP, NRC, and Tetra Tech regarding the final content of the Supplementary Risk Assessment.
Certificate, p. 5. The Secretary then went on to note the conclusion by the BRP that the risk assessment was “the most scientifically sound rigorously conducted study that is possible at this point.” Certificate, p. 5.
The Secretary then reviewed the contents and conclusions of the risk assessment, including the qualitative and quantitative assessments of the 13 pathogens chosen for study, the alternatives analysis, and the mitigation measures implemented at the NEIDL. After reviewing all this information, the Secretary’s Certificate concluded that the SFEIR complied with MEPA.
Next, we turn to the judicial review of the thoroughness of the environmental assessment of the NEIDL. Because the project has been funded by NIH, the NEIDL is subject to the National Environmental Policy Act, or NEPA, and NIH’s approval of the FSRA was thus subject to judicial review. After three rounds of briefing, oral argument, and a review of the extensive record, Chief Judge Patti Saris of the District Court for the District of Massachusetts issued an opinion on September 30, 2013 in which she concluded that the environmental review of the NEIDL was adequate, complied with NEPA, and supported NIH’s conclusions that the risks posed by the facility “are extremely low to not reasonably foreseeable.” Saris Opinion, p. 75.5
Because Judge Saris’s review of the record was so thorough and complete, it is worth discussing in some detail. Judge Saris addressed each chapter of the FSRA, summarized its contents, reviewed the opinions provided by the BRP and NRC with respect to each chapter, and stated her conclusions regarding the validity of the FSRA analysis. This testimony will discuss the important issues raised in Judge Saris’s review of the risk assessment; certain issues were not actually the subject of any significant debate, and will not be addressed here.
After briefly summarizing the introduction, Judge Saris then reviewed Chapter 2, which addresses the design and operations of the NEIDL. She noted several key issues:
- The building space is designed with a number of features to ensure the
security of the BSL-4 space. These include:
- The BSL-4 space is physically separate (a “box within a box”) to ensure that
the physical integrity of the BSL-4 space is not compromised if an incident
affects the rest of the building. Saris opinion, p. 12; SFRA, pp. 2-4, 2-10.
- The use of air locks and negative pressure to ensure that air from the BSL-4
space cannot exit the BSL-4 space into the rest of the NEIDL. Saris opinion,
p. 12; SFRA, pp. 2-8, 2-10.
- The use of two high-efficiency particulate air (HEPA) filters to ensure that
the air returning from the BSL-4 space is clean. Saris opinion, p. 12; SFRA,
- The BSL-4 space is physically separate (a “box within a box”) to ensure that
- The “culture of safety,” to ensure the everyone associated with NEIDL
operations, always puts safety first. Saris opinion, p. 12.
- Review of select agent research by the federal Centers for Disease Control
(CDC); Saris opinion, pp. 12-13.
- The two-person rule, which minimizes or eliminates the risk that BSL-4
pathogens could be removed from the NEIDL by rogue scientists, by
requiring two researchers present for any BSL-4 research. Saris opinion,
- The physical security measures (described here in Mr. Robbins’s testimony).
Saris opinion, p. 13.
- The public safety and emergency response capabilities at the Boston site,
which are much more extensive than those available in non-urban locations.
Judge Saris then addressed Chapter 3, which provided details on the characteristics of the pathogens studied in the risk assessment. Judge Saris noted that the BSL-3 agents such as pneumonic plague, 1918 H1N1 Influenza Virus, and SARS-associated Coronavirus are spread through airborne transmission. She then pointed out that the NRC pane1,6 after reviewing Chapter 3, stated that:
some agents handled in BSL-3 facilities may present more serious potential risks than BSL-4 agents.
Agents are categorized for BSL-4 containment because they cause deadly disease for which there is no treatment, not because they are highly infectious and cause widespread disease.
Saris Opinion, pp. 14-15.
Chapter 4 of the SFRA describes the process by which specific scenarios for potential releases were considered in the risk assessment. As Judge Saris noted, the risk assessment initially considered more than 300 different scenarios. It then narrowed those down to 34 different categories of scenario, finally reduced to five scenarios intended to provide upper bounds for the potential risks from NEIDL operations. Those five scenarios included:
- a centrifuge release, in which a centrifuge tube breaks and a pathogen is released into the air;
- a needle stick, in which a lab worker breaks his skin with a needle so that the pathogen enters his body;
- an earthquake, including the maximum reasonably foreseeable event that would cause total collapse of the BioLab building and release all of pathogens;
- an aircraft crash into the BioLab; and
- malevolent acts, such as a terrorist attack.7
As Judge Saris noted, the probability of an earthquake or airplane accident that could cause a pathogen release was less than one every 10,000 years. Saris opinion, p. 17.
Chapter 5 of the FSRA addressed potential risks associated with transportation of the pathogens.8 As Judge Saris noted, BSL-4 pathogens are required to be triple-packed. The bottom line, as summarized by Judge Saris, is.that even a single public infection caused by a transportation accident is likely to occur less than once in one million years. Saris opinion, p. 20. This conclusion in the risk assessment was endorsed without reservation by the NRC. “The committee believes that the chapter on transportation is thorough and has no concerns with the content.” Administrative Record, at p. 1567. Indeed, literally no evidence was presented to NIH in the course of the risk assessment, or to the federal or state courts during those proceedings, from which one could rationally conclude that the transportation of BSL- 4 pathogens to the NEIDL poses any plausible risk.
Chapter 6 of the FSRA addresses the potential risk associated with malevolent acts. It was based on the analysis contained in a “threat assessment,” which is a “controlled document” under the provisions of the Public Health Security and Bioterrorism Preparedness and Response Act of 2002. Saris opinion, p. 21. The threat assessment concluded that the risk associated with a potential pathogen release resulting from a malevolent act was less than that posed by an earthquake. Judge Saris reviewed the threat assessment and concluded that it “adequately analyzes the risks of malevolent acts at the three locations, and The full suite of precautions intended to ensure safe transportation of pathogens was addressed in Mr. Robbins’s testimony.
The heart of the risk assessment consists of Chapter 8, which addresses the risk of initial infection, and Chapter 9, which addresses the risk of secondary infection.9 Of course, members of the public are not at risk of initial infection from accidents inside the building such as needle sticks. In those scenarios, the risk to the public results only from potential secondary infections.
The risk to the public from the maximum reasonably foreseeable earthquake scenario was once every 100,000 years, associated with Rift Valley Fever Virus, a BSL-3 pathogen. The highest risk for a BSL-4 pathogen was from Ebola Virus, at once per six (6) million years. Saris opinion, p. 28; AR, pp. 2604-2606.
Chapter 9 addresses the risk of secondary infection, following an initial infection resulting from an incident in the NEIDL, such as an unreported needle stick. As Judge Saris noted, the risk assessment “concludes that the probability of secondary infections is so low that none is likely to occur for any of the pathogens over the proposed 50-year life of the BioLab.” Saris opinion, p. 29. In fact, the risk assessment concluded that the highest frequency of secondary infection would be for Yersinia pestis, which causes pneumonic plague, which is expected to occur 518 years to 18,000 years. Yersinia pestis is a BSL-3 agent. The most frequent secondary infection for a BSL-4 agent was for Ebola virus, predicted to every 550 years to 16,000 years.
Chapter 11 of the SFRA summarized the conclusions from the prior chapters, concluding that “the risk of infections or deaths resulting from accidents or malevolent acts at the BioLab are generally very low to only remotely possible.”10 Saris opinion, p. 33.
After reviewing the criticisms concerning the risk assessment conclusions made by opponents, Judge Saris rejected them all. First, she noted that the risk assessment did not ignore issues related to mass transit and did not ignore any data on the subject. Saris opinion, pp. 46-47. In fact:
to quantify secondary transmission rates for outbreaks of 1918 H1 N1 influenza virus and SARS-associated Coronavirus in urban areas, the NIH used infection data from historical outbreaks from the published literature. Much of this data came from large cities around the world with mass transit systems, such as Beijing, Singapore, and Toronto. See id. at L-82, L.3.4.1, L.3.5.1; see also AR Doc. 246 at 179-80 (“The branching process model does consider the probability that one person could spread the pathogen to many others. Those probabilities that we’re using for SARS Coronavirus are based on what actually happened in outbreaks that occurred. There were no outbreaks in Boston, but outbreaks did occur in large cities where public transportation exists.”)(Comments of NIH modeling consultant Dr. Damon Toth).
Saris opinion, p. 47.
Judge Saris then also rejected the assertion that the operation of BSL-4 laboratories pose any greater risk to the public than BSL-3 laboratories already operating in Boston.
Of the 13 pathogens studied in the FSRA, all of the highly transmissible airborne ones, such as the 1918 H1 N1 influenza virus and SARS-associated Coronavirus, are BSL-3 pathogens, and none are BSL-4. In other words, the most deadly viruses which understandably cause the greatest public concern are unlikely to be transmitted on public transportation through airborne contact, such as coughing or sneezing. Instead, according to the best current scientific knowledge about the BSL-4 pathogens discussed in the FSRA, it is believed that an infected person must have direct bodily contact with an individual to transmit the disease.
As this Court previously pointed out, because eleven BSL-3 laboratories already exist in the Boston area, the BioLab only poses a unique risk to Boston residents due to its inclusion of BSL-4 pathogens. See Doc. No. 36 at 3 n.1, 4; see also Tr-Valley CAREs v. Dep’t of Energy, 671 F.3d 1113, 1119 (9th Cir. 2012) (“There are more than 1,350 BSL-3 laboratories in the United States. Common examples of BSL-3 facilities include hospital surgical suites, laboratories associated with medical schools, and university research laboratories.”). Therefore, even if Boston’s mass transit system would increase the potential infection rate of the public, this risk would likely pertain primarily to the BSL-3 pathogens, which are already being studied elsewhere in Boston, and does not justify enjoining NIH’s funding to construct the BioLab’s BSL-3 or BSL-4 laboratory.
Saris opinion, p. 50.
Judge Saris then summarized the scope of the review of the risk assessment by the BRP and the NRC. It is worth reproducing in full:
The BRP and NRC Committee spent considerable time reviewing and critiquing the report to ensure it adequately addressed the risks of permitting research of BSL-3 and BSL-4 pathogens at the Boston site. Over the four years it took to draft the FSRA, the BRP met nine times, held 25 teleconferences, met with the NRC Committee six times, and conveyed its findings to the NIH in four meetings with the NIH Advisory Committee to the Director of NIH. In reviewing the final report, the BRP concluded that:
This study is unprecedented in its scope, breadth and complexity, and utilized widely accepted validated methods. The scenarios described in the risk assessment used real live data and experience to the maximum extent possible. With that in mind the Blue Ribbon Panel believes that this is the most scientifically sound rigorously conducted study that is possible at this point.
AR. Doc. 371 at 11-12.
Since its initial letter in 2007 finding the first draft of the FSRA to be “not sound and credible,” the NRC Committee issued updated letter reports in 2008, April 2010, September 2010, and December 2011.
The NRC Committee remained critical of the FSRA’s methodology throughout the drafting process. For example, the September 2010 letter concluded that the NRC Committee “could not endorse as scientifically and technically sound the illustrative analyses presented.” AR. Doc. 650 at 7. At that time, the committee found that the “the analyses presented did not represent a thorough assessment of the public health concerns.” Id. However, in its final December 2011 letter, the NRC Committee concluded that the NIH responded to many of its concerns and stated:
The [FSRA] is now closer to reaching its goal of being “scientifically and technically sound” and, in general, addresses the concerns raised in the original NRC review of the “DSRASSA” document in 2007. While there are many approaches to preparing a risk assessment and in some aspects the Committee would have used approaches other than those found in this draft, this is no reason to fault the document. It is clear that NIH and the Blue Ribbon Panel have gone to unprecedented lengths to improve the risk assessment for the [BioLab] and have made substantial advances. . . . It is the Committee’s view that no further advice from this group would be useful nor should it be required.
Saris opinion, pp. 35-37.
In sum, the risk assessment performed for the NEIDL was “unprecedented.” It comprehensively assessed the potential risks from operation of the NEIDL and concluded that the risk of even one public infection over the operating life of the NEIDL ranged from extremely low to not remotely possible. The data and analysis contained in the risk assessment was thoroughly reviewed by separate independent panels. Those panels included some of the world’s leading experts in infectious disease, as well as experts in risk assessment and risk communication, and public health. Both panels endorsed the conclusions of the risk assessment. The Secretary of EOEEA concluded that the risk assessment complied with state law. Chief Judge Saris concluded that it complied with federal law.
Significantly, the risk assessment concluded that the risk of public infection resulting from operation of the NEIDL was actually greatest for a BSL-3 agent, Yersinia pestis, which causes pneumonic plague. Similarly, the risks associated with potential releases of other BSL-3 agents, SARS and HIN1 influenza, were also greater than the risk related to Ebola, a BSL-4 pathogen.
While the opponents of the NEIDL have raised a variety of objections to the NEIDL, none of those objections stand up to scientific scrutiny, as explained by Judge Saris. More importantly, none of the criticisms of the risk assessment go to the fundamental conclusion that any potential risk to the public from the operation of a BSL-4 facility is no greater than — and almost certainly less than — the risks posed by operation of a BSL-3 laboratory. Thus, there is no rational basis on which one could conclude that a prohibition on BSL-4 research in Boston is necessary or appropriate to protect the public health. In the absence of such a rational basis, enactment of the bylaw would be arbitrary and capricious and the bylaw would not withstand judicial review.
This Council should reject the notion that it is necessary to ban BSL-4 research in order to protect public health or welfare. Instead, the Council should take pride in the fact that Boston Public Health Commission has the sophistication necessary to regulate the NEIDL, in conjunction with other City of Boston agencies, and the federal Centers for Disease Control. No other BSL-4 laboratory in the United States (none of which have resulted in public infection after more than 700,000 person hours of operation) — is regulated as stringently as the NEIDL will be by the BPHC. That stringent regulation, combined with the numerous safeguards built into the design and construction of the NEIDL, will ensure that the NEIDL can fulfill its mission to find vaccines and cures for infectious diseases
without leading to even a single public infection over the life of the NEIDL.
- As the Council may be aware, the NEIDL has been subject to review under the Massachusetts Environmental Policy Act (MEPA). On March 1, 2013, the Secretary of the Office of Energy and Environmental Affairs (EOEEA) issued a certificate stating that the supplemental final environmental impact report (SFEIR) filed by Boston University with respect to the NEIDL complied with MEPA. That decision was appealed by certain residents of Boston. As part of that appeal, the Commonwealth prepared an administrative record (AR) for the SFEIR. That administrative record includes the SFRA prepared by NIH. The entire AR prepared by EOEEA is attached hereto as Exhibit 1.
- See biographical sketches of BRP Members, attached hereto as Exhibit 2.
- See biographical sketches of NRC Committee members, attached hereto as Exhibit 3.
- The Secretary’s certificate is attached hereto as Exhibit 4.
- A copy of Judge Saris’s opinion is attached hereto as Exhibit 5.
- Gary Smith, Chief of the Section of Epidemiology and Public Health at the University of Pennsylvania, who reviewed the chapter for the NRC Committee, described it as “an incredibly substantial chapter.”Administrative Record, p. 690.
- Transportation events were considered separately. See below.
- The full suite of precautions intended to ensure safe transportation of pathogens was addressed in Mr. Robbins’s testimony.
- Chapter 7 of the risk assessment addressed the potential that any of the pathogens could become established in the environment, if released. This chapter has not been the subject of public debate or contention and will not be discussed here.
- It is important to remember that the NEIDL would not be the first BSL-4 facility operating in the United States. Indeed, several of the existing laboratories are located in densely populated areas, including the Georgia State and CDC BSL-4 laboratories located in Atlanta, and federal facilities located in Frederick, Maryland. As stated in the FSRA, there has not been a single public infection resulting from almost 700,000 hours of operation of existing BSL-4 laboratories. AR, p. 2229. As the FSRA notes: “Mlle zero numerator of infections among laboratorians and the huge denominator of exposure hours make it impossible to provide a number for ‘risk of infection’ to either laboratory workers or outside communities. Nevertheless, that number must be vanishingly small.” Id.
Seth D. Jaffe (BBO# 548217)
Foley Hoag LLP
155 Seaport Boulevard
Boston, Massachusetts 02210
Attorneys for Trustees of Boston University and Boston Medical Center Corporation
Dated: April 16, 2014