Dual-use research and the H5N1 bird flu: Is restricting publication the solution to biosecurity issues?
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Science and Public Policy Advance Access published September 27, 2013 Science and Public Policy (2013) pp. 1–14 doi:10.1093/scipol/sct064 Dual-use research and the H5N1 bird flu: Is restricting publication the solution to biosecurity issues? Sabrina Engel-Glatter* Institute for Biomedical Ethics, University Basel, Bernoullistrasse 28, 4055 Basel, Switzerland. *Corresponding author. Email: email@example.com. Recent studies altering the host range of the H5N1 bird flu virus have refueled intense debates over the potential misuse of academic life science research. To curtail the bioterrorism threat, it has been suggested that dissemination of the research results and methodology should be restricted. However, doubts have been raised over the suitability and effectiveness of this measure. Using the H5N1 studies as an example, this paper summarizes the main arguments of the debate. Particular attention is paid to the issue of the tacit knowledge required to replicate published life science research results, which has so far received limited attention. Taking into account the importance of tacit knowledge for life science research, it is argued that preventing publication of the methodology does not decrease the threat of bioterrorism. Keywords: dual-use research of concern; life science research; biosecurity; tacit knowledge; inﬂuenza. 1. Introduction to include non-state actors in late 2001, raised doubts over its effectiveness to address the current challenges Since the anthrax attacks in 2001, the dual-use potential of and initiated this controversial debate (McLeish and life science research has been intensely discussed. Fears of Nightingale 2007; Tucker 2002). published research ﬁndings serving as a blueprint for The concerns have been publicly discussed after selected building biological weapons have especially troubled US scientiﬁc papers on pathogenic viruses were published, policy-makers (Malakoff 2001). Initially, the term dual-use including a paper on an engineered mousepox virus that applied to engineering and information technologies and overcomes vaccine protection (Jackson et al. 2001), a pub- related knowledge that may be used for both peaceful and lication describing the ﬁrst de novo synthesis of a pathogen military purposes with little or no modiﬁcation (Hall 1965; (the poliovirus) (Cello et al. 2002), a study identifying Panel on Scientiﬁc Communication and National Security virulence factors that distinguish the causative agent of 1982). The rapid advances of life science research in recent smallpox, variola virus, from its close relative, vaccina years have pushed its experiments, results, and related virus (Rosengard et al. 2002), a paper characterizing the technologies into the center of the dual-use debate. reconstructed 1918 Spanish inﬂuenza pandemic strain Long before the misuse potential of life science research (Tumpey et al. 2005), and recent studies on mutated received so much public attention, the development, pro- versions of the H5N1 bird ﬂu (Herfst et al. 2012b; Imai duction and stockpiling by state actors of bacteriological et al. 2012). To prevent deliberate misuse of such published and toxic weapons had been banned internationally by the knowledge, there have been calls for tighter regulations 1972 Bioweapons and Toxin Convention (BTWC). and restrictions on academic research and the dissemin- However, the apparent ease with which life science know- ation of research results (Tucker 2002; Wallerstein 2002, ledge develops and diffuses is perceived to have widened Resnik and Shamoo 2004; Gaudioso and Salerno 2004; the range of actors with the potential to develop bio- van Aken 2006). In addition, a variety of international weapons from state actors to non-state actors. The and local policy measures have been implemented. For anthrax attacks, and the failure to reinforce the BTWC example, the US government has deﬁned a list of ‘select ß The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org
2 of 14 . S. E. Glatter agents’ with the potential to pose a severe threat to both any attempts to determine the pandemic potential of the human and animal health, to plant health, or to animal virus remain speculative. It is this unknown potential, or and plant products.1 US government regulations control in other words, our ignorance about the implications of research with, and transfer of, these ‘select agents’.2 releasing the virus into the environment, that leads to the Further measures include: publication guidelines for disagreement amongst virology experts on whether the journals to pre-screen potentially sensitive publications mutated H5N1 virus and the related experiments can (Atlas et al. 2003), US government oversight of research truly be termed ‘dangerous’ (Palese and Wang 2012; projects and possible classiﬁcation of sensitive research,3 Bouvier 2012; Inglesby et al. 2011; Morens et al. 2012). the implementation of screening guidelines for synthetic With this in mind, a ﬁxed list of ‘dangerous technologies DNA orders from ofﬁcial providers for sequences and pathogens’ and ‘experiments of concern’, although encoding select agents and toxins,4 and the establishment helpful, appears to be of limited use to deﬁne which type of codes of conduct for scientists.5 of research may pose a threat to public health and safety. In an attempt to address concerns over life science A more ﬂexible perspective on dual-use technology and research and to ﬁnd a formal deﬁnition of dual-use ‘dangerous science’ is needed to ensure that policy research, the US National Academies published the measures keep up with the rapid developments in life highly inﬂuential report ‘Biotechnology Research in an science research and secure the beneﬁts of academic Age of Terrorism’ (National Research Council 2004). research. This different perspective on the development The so-called Fink report6 deﬁnes dual-use research of of life science research and its impact on the dual-use concern (DURC) as: debate has been discussed amongst sociologists (McLeish and Nightingale 2007; Vogel 2008; Tucker 2011). . . . research that, based on current understanding, can be However, it has not yet found its way into the public reasonably anticipated to provide knowledge, products, or debate over dual-use research. By using the controversially technologies that could be directly misapplied to pose a threat to public health and safety, agricultural crops and debated H5N1 studies as a case study, this paper will em- other plants, animals, the environment, or material. phasize the impact of an alternative perspective on the dominant biosecurity discourse and highlight how an In addition, the report deﬁned seven categories of ‘experi- alternative view of ‘dangerous’ life science research may ments of concern’ to be scrutinized when designing research alter the prioritization of policy responses. programs and publishing sensitive results. These include: Furthermore, in the light of an alternative perspective, (1) to render a vaccine ineffective this paper will evaluate the effectiveness of one key policy (2) to create resistance to therapeutically useful antibi- measure: restricting dissemination of the research method- otics or antiviral agents ology. It has been argued that the potential dangers and (3) to enhance the virulence of a pathogen or render a disastrous consequences of academic research demand the non-pathogen virulent implementation of precautionary measures such as restrict- (4) to increase the transmissibility of a pathogen ing publication (Osterholm and Relman 2012; Kuhlau (5) to alter the host range of a pathogen et al. 2011; Resnik 2013). Thus, besides outlining a differ- (6) to enable the evasion of diagnostic/detection ent perspective on the potential dangers of dual-use life modalities science research, this paper will summarize the main argu- (7) to enable the weaponization of a biological agent or ments of the dual-use debate around the H5N1 case and toxin make use of the precautionary principle (PCP) to evaluate whether preventing publication of the methodology of This paper will outline that categorizing and focusing on DURC is an effective tool to decrease the bioterrorism ‘dangerous technologies and pathogens’ reﬂects a limited threat. perspective on the dual-use dilemma. As McLeish and Nightingale (2007) pointed out, an unambiguous deﬁnition of ‘dangerous’ cannot be agreed upon as this: 2. Research on highly virulent, possibly . . . is not a descriptive term that denotes the property of some- human transmissible, H5N1 influenza thing but an expressive term that refers to how we think about virus strains the possible implications of the properties of something. Two recent studies on the H5N1 bird ﬂu have intensiﬁed As a result, different people, even experts, will evaluate the the international debate over DURC. They describe a set dangerousness of technologies and pathogens differently. of mutations necessary for the highly virulent H5N1 bird This is reﬂected by the current discourse around two ﬂu virus to transmit amongst mammals, possibly humans studies on the highly virulent H5N1 bird ﬂu virus. (Herfst et al. 2012b; Imai et al. 2012). The H5N1 case Researchers have mutated the virus so that it can spread raised concerns for several reasons: the bird ﬂu virus is amongst mammals via aerosol (Herfst et al. 2012b; Imai highly virulent, it is listed on the select agent and toxin et al. 2012). However, as no human studies are desirable, list, and the performed experiments can be allocated to
Dual-use research and the H5N1 bird flu . 3 of 14 category 5 (to alter the host range of a pathogen) of the aggressive control programs, and to adapt current Fink report. pandemic preparedness plans (Kawaoka 2012; Fouchier When submitted to the journals Nature and Science for et al. 2012a, 2013). publication, the editors referred the two studies to the However, the NSABB experts had initially decided that National Advisory Board for Biosecurity (NSABB). the beneﬁts of the study would not outweigh the risks of Established by the US government as a result of the publication (Berns et al. 2012). The main risks in publish- Fink report, the NSABB provides advice, guidance and ing both papers in full were described as twofold. First, the leadership regarding biosecurity oversight of DURC in results and methodology of the H5N1 studies, if published, the USA.7 Its decisions are, however, not legally binding. could be directly misapplied by others to pose a threat to For the ﬁrst time, the NSABB had voted against the pub- public health and safety (biosecurity risk). In particular, lication of the methodological details in order to prevent the possibility of synthesizing the ﬂu mutant strains based ‘those who would seek to do harm’ from replicating the on published sequences and the identiﬁed mutations raised experiment.8 The board had concluded that the harms of concern. The NSABB members Osterholm and Relman fully publishing these results exceeded the beneﬁts of pub- argued that: lication (Berns et al. 2012). Two crucial aspect may have . . . reverse engineering and synthesizing a mutant A/H5N1 inﬂuenced the board’s so far unique decision: the ofﬁcial virus strain will be easier for many scientists if they have World Health Organization estimate for the case fatality access to the complete methods and results of the two rate of H5N1 avian inﬂuenza of around 60% (Beigel et al. research efforts and do not need to surmise the steps of the 2005)9, and misunderstandings of technical details investigators. (Osterholm and Relman 2012)16 (Morens et al. 2012).10 Hence, fears of potentially disas- trous consequences for public health resulting from an Second, research with the virus could result in an uninten- unintended or intended release of the engineered H5N1 tional release into the environment (biosafety risk).17 In strains were particularly strong (Berns et al. 2012). order to mitigate the biosecurity and biosafety risks To allow time for evaluating the risks and beneﬁts of the associated with publication, the board had suggested research, the inﬂuenza research community proposed a redacting the papers and excluding any description of the three-month voluntary moratorium11 on research methodology (Berns et al. 2012). However, the effective- involving highly pathogenic avian inﬂuenza H5N1. ness of partially restricting or even preventing publication During that time, the pros and cons of publishing the was repeatedly questioned. manuscripts were intensely discussed by scientiﬁc and The main argument used in favor of publishing the security experts, the NSABB, the WHO and the US gov- research in full was the necessity to share the research ernment. Finally, a majority vote of 6 to 1212, strongly results in the wider scientiﬁc community to ensure free opposed by the NSABB member Michael and open science. Withholding the methodology has T. Osterholm,13 led to the revision of the NSABB’s been criticized as unethical, and as an assault on the decision resulting in full publication of the two papers openness, accessibility and quality of scientiﬁc research (Herfst et al. 2012b; Imai et al. 2012). The research mora- (Bouvier 2012; Racaniello 2012). It was argued that torium proposed by the inﬂuenza community was omitting the methods from the manuscripts presents a extended beyond the originally proposed three months to barrier for researchers to engage in further research provide time for further evaluation of biosafety14 and thereby limiting the scientiﬁc output essential to combat biosecurity15 concerns (Fouchier et al. 2012a). The the natural pandemic threat of inﬂuenza viruses (Palese research ﬁnally commenced one year later in January and Wang 2012; Morens et al. 2012; Kawaoka 2012; 2013 (Fouchier et al. 2013). Perez 2012; Faden and Karron 2012; Casadevall and Shenk 2012). In contrast, it was claimed that, although the results are valuable, publishing the results would not 3. To publish or not to publish? bring about any additional beneﬁt for pandemic prepared- Fouchier and Kawaoka, the two corresponding authors ness as resources to detect the virus and support programs of the studies, defended conducting, publishing and for a number of the H5N1 endemic countries are often continuing the work on mammalian transmissible H5N1 lacking (Osterholm and Relman 2012). virus strains by emphasizing the beneﬁts of their work Furthermore, it was argued that publishing the papers and by stressing the importance of their research for in full may result in more laboratories working with the pandemic preparedness. Their proof-of-principle experi- virus, possibly some with insufﬁcient safety standards, ments show that few mutations could enable the virus thereby increasing the chance of an unintentional release to be transmitted via aerosols amongst mammals, (Inglesby et al. 2011; Osterholm and Henderson 2012). possibly humans, while maintaining virulence (Herfst Other opponents of publishing claimed that sharing the et al. 2012b; Imai et al. 2012). According to the authors, results and methodology with a small group of selected the study highlighted the need to monitor H5N1 outbreaks experts would be sufﬁcient to secure beneﬁcial outcomes in poultry with more urgency, to implement more (Osterholm and Relman 2012; Fouchier et al. 2012b).
4 of 14 . S. E. Glatter Table 1. H5N1 debate: Summary of arguments for and against publication of research methodology Pro publishing Reference Contra publishing Reference Beneﬁts for pandemic Fouchier et al. 2012b; Herfst et al. 2012a; Knowing the results (mutations) Osterholm and preparedness: public health Perez 2012; Palese and Wang 2012; is sufﬁcient (no enhancement Relman 2012 threat of H5N1 strains Kawaoka 2012; Morens et al. 2012 of disease surveillance or (mammalian transmission, countermeasure availability maintenance of virulence), expected in the near future) enables monitoring of current H5N1 strains for critical mutations, need for enhancement of current preparedness plans ‘Nature is more inventive than men’ Accessibility of the methodology Herfst et al. 2012a; Perez 2012; Palese and Access to the complete methods Osterholm and through textbooks and other Wang 2012; Morens et al. 2012 and results makes it easier for Relman 2012 open sources such as published scientists to synthesize a mutant papers A/H5N1 virus strain (increase in bioterrorism threat through easier access) Need for trained experts and Palese and Wang 2012; Racaniello 2012; Replication not difﬁcult in Zimmer 2012 high-tech research facilities to Fouchier 2012 technological terms replicate results Sharing the results in the wider Racaniello 2012; Bouvier 2012 Sufﬁciency of sharing the results Osterholm and scientiﬁc is a basic requirement with a small group of selected Relman 2012; for scientiﬁc endeavor (value experts, even beneﬁt of that Fouchier et al. of free science) is questionable 2012c; Osterholm and Henderson 2012 Prerequisite for ensuring quality Bouvier 2012 of scientiﬁc research by enabling post-publication peer-review and replication (value of high quality in science) Barrier for researchers to continue Perez 2012; Palese and Wang 2012; Encouragement for more labs Osterholm and the research, need for Kawaoka 2012; Morens et al. 2012; to initiate dual-use research Henderson 2012; publication to ensure Bouvier 2012; Faden and Karron 2012; on H5N1 (increase of the Inglesby et al. further research and Casadevall and Shenk 2012 biosecurity and biosafety threat) 2011 prospective beneﬁts This has been rejected for the same reasons as restricting when the possible outcomes and their respective publication (Morens et al. 2012). It was also criticized on probabilities are known. the grounds that, while providing a main barrier to With regards to the H5N1 case, especially at the time of research, the measure would be futile in the long term, publication, the likelihood with which the risks and given that the methodology can be found in virology beneﬁts of the research will come to pass is unknown. textbooks (Palese and Wang 2012; Morens et al. 2012; For example, to estimate the likelihood of misuse one Perez 2012; Herfst et al. 2012a) (for a summary of the needs access to information on the degree of training, arguments see Table 1). intentions, ﬁnancial, and personnel resources of potential bioweaponeers. Such knowledge is, however, not publicly available. It will be held by intelligence and security 4. DURC and the precautionary principle experts, if anyone has access to it at all (Selgelid 2009). Several groups, including the WHO and the NSABB, have Furthermore, as Rappert (2008) pointed out, risk and proposed adopting risk–beneﬁt analysis when addressing beneﬁts will be open to a considerable amount of interpret- DURC issues.18 This recommendation has been followed ation. This is reﬂected in the discourse on the H5N1 case. throughout the discourse around the H5N1 studies. For example, experts do not agree on how ‘dangerous’ the However, as pointed out by Andrew Stirling, a risk mutated virus would be to human health, because data expert, under conditions of uncertainty and ignorance from the ferret model cannot be directly extrapolated to risk–beneﬁt analysis fails (Klinke et al. 2006; Stirling and the human context (Bouvier 2012; Racaniello 2012; Fauci Scoones 2009). It is traditionally used for routine risks, and Collins 2012).
Dual-use research and the H5N1 bird flu . 5 of 14 In order to address the challenges associated with Along these lines, Resnik (2003) argues that: DURC, the bioethicists Kuhlau et al. (2011) have . . . the principle can be scientiﬁc provided that (1) the threats proposed to make use of the PCP as a ‘rule of choice’ addressed by the principle are plausible threats, and (2) the with regards to DURC: precautionary measures adopted are reasonable. When and where serious and credible concern exists that He proposes to use epistemic criteria to determine whether legitimately intended biological material, technology or know- a threat is plausible and to use practical considerations to ledge in the life sciences pose threats of harm to human health and security, the scientiﬁc community is obliged to develop, determine whether a response to a threat is reasonable. implement and adhere to precautious measures to meet the Considering the ignorance of risks and beneﬁts concern. associated with DURC studies such as the H5N1 research, the PCP could be a useful tool to analyze the Correspondingly, the NSABB members Osterholm and reasonableness of preventing or banning the publication Relman have, in the light of the potentially disastrous of results and methods as a precautionary measure. consequences associated with the release of a human trans- When applying the PCP using Resnik’s and Sandin’s missible H5N1 virus, suggested to err in favor of ‘do no framework, there are two main questions to answer. harm’. They proposed to make: First, how plausible are the threats associated with pub- lishing the H5N1 studies? Second, is censorship a reason- . . . use of the precautionary principle when approaching the able mean to address the threat and prevent possible issue of DURC. (Osterholm and Relman 2012) negative consequences? In order to determine whether publishing the H5N1 The PCP is designed for making practical decisions under papers in full presents a reasonable threat, one needs to uncertainty when no reliable quantitative data is available. discuss whether the engineered H5N1 strain could, in prin- It was originally created as a way to respond to environ- ciple, cause a disastrous pandemic and whether the H5N1 mental risks (Goklany 2001). For example, the PCP has publications could easily be misused by those who seek to been used to address issues such as: global warming, in- do harm. In this context, the PCP does not specify the tensive dichlorodiphenyltrichloroethane (DDT)19 use, and degree of scientiﬁc evidence required to determine what the commercialization of genetically modiﬁed food. The a reasonable threat might be. To solve this issue, Sandin principle has often been criticized for being too vague, et al. (2002) proposed to use a degree of evidence in overly risk-averse and an unscientiﬁc approach to qualitative terms such as ‘scientiﬁcally supported strong decision-making due to a lack of a scientiﬁc basis suspicions’ to evaluate the threat. (Brombacher 1999; Gray and Bewers 1996). Contrasting Thus, what is the scientiﬁc evidence supporting the sus- this critique, risk experts argue that under conditions of picion that engineered H5N1 strains could pose a reason- uncertainty,20 ignorance21 and ambiguity22 sound scientiﬁc able threat to human health? To begin with, it is true that methods of risk assessment have in any case little justiﬁca- the H5N1 virus infects humans, although transmission tion (Stirling 2007; Hoffman-Riem and Wynne 2002). It is between humans remains limited (Yang et al. 2007). under these conditions that the PCP can be viewed as a Another source of concern is the ofﬁcial mortality rate of general normative guide for policy-makers to acknowledge about 60% (Beigel et al. 2005).23 Virology experts, such the beneﬁt of doubt (Stirling 2007). as Palese, Bouvier, and Taubenberger believe the rate to be The critique of the PCP may also be related to the fact overestimated (Bouvier 2012; Palese and Wang 2012).24 that the principle does not deﬁne which types of hazards it The true case fatality rate of the unmodiﬁed H5N1 virus applies to, what level of (scientiﬁc) evidence is required, is estimated to be between 1% and 33% (Li et al. 2008; which preventive measures should be taken and with Morens et al. 2012). In comparison, the fatality rate of the what force they are recommended (Sandin et al. 2002). 1918 pandemic virus was estimated to be 2.5% (Li et al. However, Sandin, a bioethicist, argues that the PCP does 2008). The worst human inﬂuenza pandemic in history so not contradict science and has recommended establishing far, raged from 1918 to 1919 and claimed an estimated the following criteria when deciding whether to use the 50 million lives (Taubenberger and Morens 2006). PCP (Sandin et al. 2002; Sandin 2009): However, even if the true mortality rate of the mutant virus strains was much below the rate of the 1918 virus, An action A is precautionary with respect to something pandemic spread of a deadly H5N1 variant would be a undesirable U, if and only if 1) A is performed with the cause for signiﬁcant public health concern. intention of preventing U, 2) the agent does not believe it to Further data comes from the animal model in which be very likely that U will occur if A is performed, and 3) the agent has externally good epistemic reasons a) for believing human inﬂuenza viruses cause inﬂuenza-like illness that U might occur, b) for believing that A will in fact at (Maher and DeStefano 2004). Ferrets are susceptible to least contribute to the prevention of U, and c) for not believing infection with the mutated H5N1 virus. According to the that it to be certain or very likely that U will occur if A is two studies, the virus can be transmitted amongst ferrets performed. via aerosol while maintaining virulence (Herfst et al.
6 of 14 . S. E. Glatter 2012b; Imai et al. 2012). Hence, the mutant virus has the reports covering the H5N1 case, for example by the New potential to infect and spread amongst humans. However, York Times (Zimmer 2012). it should be noted that the results of these infection studies Indeed, as has been pointed out, life science research has cannot be used directly to predict the transmissibility and evolved rapidly over the past decades. The emergence of pathogenicity of the virus in humans (Bouvier 2012; gene technology, the development of high-throughput Morens et al. 2012; Racaniello 2012; Fauci and Collins DNA synthesis and DNA sequencing machines, the com- 2012). pletion of the human and other genome projects have sig- In conclusion, the threat is plausible: it is possible that niﬁcantly enhanced research efﬁciency and opened new the virus could cause a pandemic that would be devastat- possibilities. However, by taking this view, two important ing to the world’s population, although there is no (and aspects are overlooked. First, it ignores the signiﬁcant there will not be) concrete scientiﬁc evidence available. ﬁnancial means and trained specialists required to operate Next, the second question needs to be answered: is pre- these new technologies. For example, to ensure constant venting or restricting publication a reasonable response access to this vital scientiﬁc and technological expertise to the threat of misuse? Would it signiﬁcantly contribute and to help to rationalize institutional resources, more to the prevention of the feared consequences? and more so-called ‘core service facilities’ are being estab- lished at major universities with a life science focus (Sa 2008).25 Those facilities are operated by staff scientists 5. The role of tacit knowledge with various backgrounds and expert training ranging Many scientists have argued that preventing publication from bioinformatics to molecular biology, chemistry and of the results and methodology does not prevent misuse. engineering. They argued that even if the methodology was omitted Second, the non-technological component of research is from the paper, an individual with the relevant training overlooked. In addition to sophisticated machines and would be able to repeat the experiments. For example, technologies, there are many more steps involved when Fouchier and colleagues, stated that their methodology performing life science research. These often require very can be found in many virology textbooks (Herfst et al. speciﬁc expertise and technical skills of the individual re- 2012a): searcher that can only be learned through constant Individuals with bad intentions do not need to read the details practice and observation of peers. Hence, even if ‘labora- in our manuscript because the methods for creating similar tory processes have become more automated’ as Chyba viruses have already been published widely. (2006) pointed out, it does not follow that ‘less and less tacit knowledge is needed’ to conduct life science research. A similar argument was used by Wimmer (2006): Tacit knowledge was, and still is, an important factor not . . . all methods used for the synthesis of poliovirus were pub- only for the success of life science research, but for science lished long before the experiment was conceived. Thus, we and technology in general. neither described new technologies to synthesize DNA nor The term tacit knowledge was ﬁrst coined by Polanyi invented novel methods to convert cDNA into infectious who deﬁned it as: viral RNA. . . . things that we know but cannot tell. (Polanyi 1962) This argument contrasts the current discourse about DURC, which assumes a direct correlation between Since the 1960s much research has been done on the technological advances in the life sciences and an increased concept of tacit knowledge. Different forms have been threat of bioterrorism. By focusing on the ease of diffusion deﬁned including somatic-limit and collective tacit know- of knowledge and technologies, socio-technical aspects of ledge,26 which are widely accepted, for example in the ﬁeld biotechnology such as tacit knowledge, complexity and of economics, psychology, and education. contingency are overlooked and possible challenges are Scholars have attempted to describe and measure the disregarded, thus leading to the perception of an increased impact of tacit knowledge on the success of academic threat (Vogel 2008). Moreover, relying on this linear model endeavors and the translation of academic knowledge into of technical change may lead to a false prioritization of industrial applications (Leonard and Insch 2005; Somech policy measures and an inappropriate focus on high-tech and Bogler 1999; Zucker et al. 2002). For example, Harry research (McLeish and Nightingale 2007; Vogel 2008; M. Collins, a social scientist, has presented an insightful Leitenberg 1999). analysis of the importance of tacit knowledge for scientiﬁc Chyba (2006) has compared the rapid development of research in physics (Collins 2001). He described the attempt life science technologies to the evolution of computer of Western researchers to repeat experimental results pub- power. He argued that the pace of development will lished by Russian scientists during the Cold War. Only in make DNA synthesis and other biotechnologies increas- the 1990s, after closely observing how the experiments were ingly available to individuals with only basic scientiﬁc performed, did the Western researchers succeed in skills. This view was repeatedly presented in media replicating the results. Collins drew the following
Dual-use research and the H5N1 bird flu . 7 of 14 conclusions from his ﬁeld observations: In order to success- rare? Could the lack of capabilities be a main reason? fully replicate an experimental result, researchers ﬁrst have Previous studies on failed and successful attempts to to understand and acknowledge the importance of tacit develop bioweapons provide possible answers. Two knowledge. Second, they have to trust the validity of the studies illustrating the impact of socio-technical aspects results, and third they need to know how difﬁcult a proced- on bioweapons have been presented by Ouagrham- ure is, meaning how much patience with trial and error is Gormley and Vogel (2010) and by Leitenberg (1999). required (Collins 2001). Ouagrham-Gormley and Vogel (2010) show that a The concept of tacit knowledge has not yet gained much substantial part of the Soviet smallpox bioweapon devel- attention in the biosecurity debate within life science opment program was unable to create a workable biolo- research. Tucker (2011) and Vogel (2008) are among the gical weapon even though they had substantial expertise, few who have highlighted the importance of tacit know- resources, time, infrastructure and even detailed protocols ledge used by life scientists during experimentation. In the at their disposal. They highlight: context of life science research, Tucker (2011) deﬁnes ‘tacit . . . the local and personal character of bioweapons know- knowledge’ as knowledge: ledge, specialized skills, and scientiﬁc know-how, which . . . that cannot be transmitted in writing but must be gained cannot be transferred easily from one person to another and through years of hands-on experience in the laboratory. from one location to another. (Ouagrham-Gormley and Vogel 2010) Tacit knowledge plays, as Tucker (2011) recognizes, a central role when aiming to determine the biosecurity They also concluded that depending on the social context, risks associated with life science research. tacit knowledge plays an important role not only on the One of the few studies on tacit knowledge in the life individual, but also on the communal level (collective tacit sciences has been conducted by Kathleen Vogel. It knowledge). As the most effective policy recommendation involved members of the Wimmer group who published to prevent former Soviet weaponeers working in the USA the ﬁrst de novo synthesis of a virus (Cello et al. 2002; from selling their knowledge, they suggested separating Vogel 2008). The group revealed that the most difﬁcult them from one another in order ‘to allow the BW-related part of the poliovirus synthesis was not the partially auto- skills to decay over time’. mated DNA synthesis. Instead, it was the construction of Leitenberg, a security expert, reached a similar conclu- the virus: the production of the virus components, the sion on the importance of tacit knowledge for biological assembly of those components into virus particles, and weapons construction. Despite extraordinary ﬁnancial ﬁnally the incorporation of the virus’ synthetic genetic resources, access to modern equipment, despite sufﬁcient material. According to the group, these steps, although time and the fact that there were individuals with graduate around for more than 20 years ‘. . . require specialized la- and postgraduate training amongst their members, the boratory know-how and practices only obtained by religious Japanese Aum Shinrikyo group failed to training, care, and attention to detail [and are difﬁcult produce and disperse botulinum toxin or Bacillus anthracis even for experienced researchers] (Vogel 2008). That the (Leitenberg 1999; Ballard et al. 2001). Leitenberg reconstruction or recovery of a pathogen would currently concluded that: require someone ‘skilled in the art’ has been supported by . . . the experience of the Aum is therefore in marked contrast other experts including the NSABB Working Group on to the legion of statements by senior US government ofﬁcials Synthetic Genomics.27 In the context of the H5N1 and other spokesmen claiming that the preparation of biolo- studies, Palese and Wang argue that the generation of en- gical agents and weapons could be carried out in ‘kitchens’, gineered H5N1 based on the published raw sequence ‘bathrooms’, ‘garages’, ‘home breweries’, and is a matter of would require: relative ease and simplicity. . . . (i) access to a sophisticated laboratory setting, (ii) proﬁ- In a related study from 1995, the sociologists McKenzie ciency in relevant concepts of molecular biology, and (iii) ex- and Spinardi (1995) highlighted the importance of socio- perience with laboratory methods related to viruses. (Palese technological aspects with regards to nuclear weapons and Wang 2012) development. In their analysis based on interviews with nuclear weapons designers and computing experts, they The author of one of the criticized H5N1 studies has used a emphasized that: similar argument: . . . tacit knowledge is also crucial to nuclear weapons It takes a lot of knowledge, together with perhaps ten years of development. training and a well-equipped high containment lab, even to reproduce our work. (Fouchier 2012) Thus, the work of Ouagrham-Gormley and Vogel, Leitenberg, and McKenzie and Spinardi indicates that: In his simplistic portrait of biotechnology research, Chyba (2006) nevertheless raised an important question: . . . Because tacit knowledge is transmitted person to person, Why is it that modern bioterrorist attacks28 have been so there are greater barriers to the spread of competence than
8 of 14 . S. E. Glatter the traditional view might lead us to expect. (McKenzie and knowledge needed to reproduce the experimental results, Spinardi 1995) the task may pose signiﬁcant hurdles even for specially Another aspect to be considered in this context is the trained individuals. accessibility of bioweapons material. Rather than buying Two possible conclusions can be drawn from this state-of-the-art laboratory equipment and investing great analysis. Unskilled individuals or groups do not possess the explicit and tacit knowledge currently needed to make ﬁnancial resources and time to synthesize a virus from use of the published methodology of the H5N1 studies and scratch, pathogens more suited for a bioweapon could, reproduce the results. On the other hand, omitting the for example, be stolen or isolated from the wild and sub- methodology would signiﬁcantly delay, but not prevent, a sequently modiﬁed to turn it into a category A bioterror- skilled team of speciﬁcally trained scientists with the will, ism agent as deﬁned by the US Center for Disease enough time, the right equipment and sufﬁcient ﬁnancial Control29 (Herfst et al. 2012a; Tucker 2003). Moreover, resources from replicating the H5N1 study results. With a study by Suk et al. (2011) suggests that instead of this in mind, prohibiting dissemination of the methodology ‘high-tech’ activities, ‘low tech’ activities may be especially could be regarded as ineffective in reducing the bioterror- attractive to bioterrorists: ism threat and as a result may be considered an unreason- Contamination of food and water, and direct injection/appli- able response to the biosecurity threat of DURC. cation of a pathogen, all have much lower technical hurdles and might be expected to be rather more successfully deployed. 6. Discussion Indeed, in 1984, followers of Bhagwan Shree Rajneeshee, an Indian guru, deliberately contaminated salad bars at ten This paper outlines that prohibiting publication of the restaurants in the USA with salmonella resulting in 754 methodology and results is not a reasonable response to individuals with food poisoning (Wheelis et al. 2006). the uncertain biosecurity threat. It contrast a recent Furthermore, many scientists have pointed out that analysis published by Resnik (2013) who argues that: although ferrets are a good model for human inﬂuenza . . . re-dacted publication would have been a reasonable infection, the results may not be directly applicable to response to the threats posed by the controversial H5N1 humans as the potential for the transmission and lethality papers if not for practical and legal problems. of engineered H5N1 in humans is unknown (Bouvier 2012; Morens et al. 2012; Racaniello 2012; Fauci and Collins Resnik seems to support the common assumption that the 2012). Consequently, bioterrorists run the risk of discover- papers: ing that the mortality and transmission rates of the engin- . . . provide terrorists with a recipe for making a bioweapon. eered strains are comparable to a seasonal inﬂuenza after having invested much time and resources in replicating the However, I would question that assumption and argue that H5N1 experiments. replicating the H5N1 experiments is not very easy for in- Thus, it seems that attempting to replicate published dividuals or groups with minimal training, or even for dual-use results may pose more challenges than the trained specialists. Neither is replicating the H5N1 common discourse reﬂects. Considering the importance studies the most suitable and easiest way to obtain a bio- of tacit knowledge, an individual with only minimal weapon. However, for individuals with specialty know- training should not be able to repeat the experiments ledge in inﬂuenza virology, this will not provide a real even if the methodology was published. The more barrier. With enough time and resources at hand, they pressing question is how easily could a professional virolo- do not need to rely on the short methods section in the gist replicate the results and produce sufﬁcient amounts of H5N1 papers, but will be able to combine their expert the virus? First, withholding the methodology would likely knowledge with textbook methodology in order to repli- result in a need for more time for ‘trial and error’. Another cate the experiments. factor that comes into play is the form and length of the Although replicating the results of the H5N1 studies is methodology sections in papers. The explanations in such doable for trained individuals even without access to the sections are usually short and of limited depth due to space methodology, omitting this information will provide a limitations, besides only providing information on explicit barrier for well-intentioned scientists. As the current knowledge. Commonly, researchers exchange more system of academic research is built on openness and the detailed protocols or even visit each other in their exchange of study results, classiﬁcation of results and laboratories to be able to replicate published results. potential funding cuts may divert scientists to other Furthermore, tacit knowledge may be essential for research ﬁelds. Prohibiting publication may even impose translating or adapting technologies to a new environment, new risks. As Sandin et al. (2002) point out, the PCP not only on an individual level, but also on a communal should also: level (Ouagrham-Gormley and Vogel 2010). In summary, . . . be applied to precautionary measures prescribed by the depending on the degree of training and the tacit principle itself.
Dual-use research and the H5N1 bird flu . 9 of 14 Less scientiﬁc research may mean a lack of crucial know- This analysis does not conclude that we should ignore ledge for pandemic preparedness necessary to address the DURC problem, as it would not be a reasonable threats imposed by future natural human H5N1 pandemics. response to the threat. Preventing terrorists and states For example, the development of counter-measures (e.g. from using bioweapons is important. The DURC vaccination) may be prevented, thereby precluding society problem calls for a more detailed investigation of the from obtaining the beneﬁt of the research. This is especially biosafety and biosecurity risks associated with DURC worrisome as the prospective of beneﬁts for public health that includes a fact- and case-based assessment of the po- are the motivation of such research and justiﬁcation for tential for misuse. In this respect, the H5N1 papers could public funding. In their analysis of the case, the bioethicists be regarded as a wake-up call for the scientiﬁc community. Faden and Karron (2012) refer to a: Although the dual-use issues associated with life science research have been discussed for the last decade, the . . . moral obligation to ensure that the results of that research H5N1 example illustrates how the restriction of research are used to help reduce risks to global health. funding and publication could become a reality in the near There are further risks from limiting scientiﬁc openness. For future. In response to the H5N1 case, the US government example, sharing the results is a prerequisite for responsible has issued a new policy that allows research funding pro- conduct in science as peer review signiﬁcantly contributes to posals sent to government agencies to be screened for ensuring the quality of the research and the research teams. DURC. It also allows for the classiﬁcation of research Preventing this mechanism might have a negative impact results and the restriction of funding of research that on the quality of the research and thus may increase the raises concerns.31 However, how research proposals will likelihood of viral escape from the laboratory. be evaluated, that is how risks and beneﬁts will be Regarding the biosafety concerns associated with a assessed and who will evaluate the proposals, remains higher number of researchers working with the engineered unclear.32 Major differences in assessment of the term strains—this issue may better be solved through enhanced ‘dangerous’ in association with DURC might either biosafety regulations than through censoring the research, result in the underestimation of risks and threats or may given the potential negative implication of censorship. lead to the restriction of legitimate academic research. Although it was discussed that enhanced Biosafety Level Thus, it has become more important than ever for the 3 (BSL 3) conditions are sufﬁcient (Casadevall aned Shenk scientiﬁc community to address public concerns over 2012; Herfst et al. 2012a), Imperiale and Hanna (2012) DURC by establishing a transparent governance sys- proposed using BSL4 conditions until more evidence is tem (see Miller and Selgelid (2008) for an overview of available on the danger of the virus. A further biosafety possible options). measure would be to plan ahead and use a less virulent Governance options that restrict and control access to strain of the H5N1 virus. In fact, one of the two labs, in research results, as for example proposed by experts from which the controversial H5N1 studies have been per- the Center for International and Security Studies at formed, did decide to use less virulent strains for their ex- Maryland (Steinbruner et al. 2007), may not be useful in periments (Imai et al. 2012). the light of the analysis presented above. For ensuring In contrast to censorship, education and personnel oversight, the WHO has been suggested as an ideal gov- screening to identify individuals with malicious intentions ernance body (Fouchier et al. 2012b). However, based on may be more reasonable and effective measures to mitigate decades of experience with regulating smallpox research, biosecurity risks. For example in the USA, the Public Health the WHO may not be the ideal choice to prevent deliber- Security and Bioterrorism Preparedness and Response Act ate misuse of DURC due to ﬁnancial and political (PL107-188) from 2002 requires that persons seeking to dependencies and a strong inﬂuence of the pro-research possess, use, or transfer agents and toxins listed on the fraction (Tucker 2006). ‘select agents and toxins’ list must undergo registration and Nevertheless, the scientiﬁc community has a duty to must have a legitimate need to handle or use such agents and consider the negative implications of their research and toxins.30 Finally, secrecy is an ineffective tool of prevention. thus must ﬁnd a way to address and possibly regulate Before publication, the information on the H5N1 experi- DURC issues (Kuhlau et al. 2008). As has been repeatedly ments had been available to many scientists and the editors suggested, scientists should receive education in bioethics of the two journals. Even if the US-based journal, Science, and familiarize themselves with ‘experiments of concern’ as had been forced to follow the original NSABB recommen- deﬁned by the Fink report and the BTWC (Dando et al. dation to not publish the methodology, the UK-based 2008; Pearson and Mahaffy 2006; Rappert et al. 2006). If Nature could have (and did) proceed with publication. possible, plans to mitigate potential risks, for example There are many other journals and editors who do not fall intensiﬁed security measures and personnel training and under US legislation and may be willing to publish such screening, must be prepared before the results of DURC manuscripts. Redaction of the papers would thus not be ef- are communicated to the public. fective in reducting the threat as it would not prevent dissem- However, scientists will not be able to ensure that their ination of the sensitive knowledge. research will never be misused. Thus, it is important that
10 of 14 . S. E. Glatter the research is conducted with the intention of beneﬁtting 7. National Science Advisory Board for Biosecurity the public. The peer review system of science, which can (2007), About NSABB accessed 11 stricted, needs to ensure that only such research is sup- September 2013. ported. Furthermore, the potential beneﬁts of the 8. National Institute of Health. Press statement on the research need to be explained to the public as best as NSABB review of H5N1 research, 2011 accessed 11 facts. Scientists will need to explain in their papers, and September 2013. possibly with accompanying media campaigns, the rele- 9. World Health Organization. FAQs: H5N1 inﬂuenza, vance and potential beneﬁts of their DURC to ensure Q1: What is H5N1? accessed 11 September 2013. 10. The Fouchier lab reported fatal infections of ferrets Acknowledgments following ‘intratracheal inoculation’ with the The author wishes to thank Anna Genske, Bernice Elger mutated H5N1 virus (Herfst et al. 2012b). However, and the anonymous reviewers for their valuable input. intratracheal inoculation is a method that: . . . is not directly relevant to viral transmissibility or Funding natural pathogenesis. [. . .] Inﬂuenza viruses that are otherwise considered to be of low pathogenicity This work was supported by the Forschungsfonds often induce severe and even fatal disease in University Basel and the Käthe-Zingg-Schwichtenberg animals when administered by this route. (Morens Fonds of the Swiss Academy of Medical Sciences. et al. 2012: 336) 11. A moratorium can be deﬁned as a period of time Notes during which a certain activity is not allowed. 1. The list includes a selection of viral, bacterial and 12. 14 April 2012, statement on NSABB’s recommenda- fungal species as well as toxins. An updated list of tions to the National Institute of Health on H5N1 select agents is accessible at accessed 11 September 2013. September 2013. 2. Uniting and Strengthening America by providing 13. See accessed 11 September 2013. Obstruct Terrorism (USA Patriot) Act, 2001 Public 14. Biosafety includes: Law 107–56, and the Public Health Security and . . . containment principles, facility design, practices Bioterrorism Preparedness and Response Act, 2002. and procedures to prevent occupational infections 3. National Institute of Health (2012) United States in the biomedical environment or release of the Government Policy for Oversight of Life Sciences organisms to the environment. (Nordmann 2010) Dual Use Research of Concern accessed 11 September 2013. . . . the sum of risk management practices in defense 4. US Government, Screening Framework Guidance for against biological threats’, which includes aversion Synthetic Double-Stranded DNA Providers, of biological terrorism and other disease breakouts. Department of Health and Human Services, Ofﬁce (Meyerson and Reaser 2002) of the Secretary Federal Register Vol. 74, p. 224 16. The press has also discussed how easily the results accessed 2012). 11 September 2013 17. See accessed 11 September 2013. Statement on biosecurity, Trieste, Italy accessed 11 September 2013. Just as scientists should weigh beneﬁts against 6. The report committee was headed by Professor Gerald the risks when deciding which projects to pursue, R. Fink, Professor of Genetics, Whitehead Institute, governments should be encouraged to do the same MIT, Boston, MA. when deciding which projects to fund.
Dual-use research and the H5N1 bird flu . 11 of 14 The NSABB (2007) stated that: Synthetic_Genomics.pdf> accessed 11 September 2013. The NSABB will [. . .] develop guidelines for the 28. According to the US Center for Disease Control: oversight of dual use research, including guidelines for the risk-beneﬁt analysis of dual use biological . . . a bioterrorism attack is the deliberate release of research and research results. viruses, bacteria, or other germs (agents) used to cause illness or death in people, animals, or plants. 19. DDT was extensively used as an insecticide in agricul- ( accessed 11 September 2013) 20th century. Today, due to concerns over its potential toxic side effects, intensive use of DDT is banned 29. The US Center for Disease Control separates bioter- worldwide. rorism agents into three categories, depending on how 20. Under the condition of uncertainty, possible outcomes easily they can be spread and the severity of illness or can be characterized, but the available information or death they cause. Category A agents are considered analytical models do not present a deﬁnitive basis for the highest risk, because they can be easily spread or assigning probabilities (Stirling 2007). transmitted from person to person, they result in high 21. Under ignorance neither probabilities nor outcomes death rates and have the potential for major public can be fully characterized (Stirling 2007; Collinridge health impact, they might cause public panic and 1980). social disruption, and they require special action for 22. Under the condition of ambiguity, outcomes are prone public health preparedness accessed 11 2007). September 2013. With a few exceptions, there are 23. World Health Organization. FAQs: H5N1 inﬂuenza, more steps required beyond the synthesis and replica- Q1: What is H5N1? (2012) accessed 11 September 2013. ization and dispersal of the pathogenic material 24. The mortality rate is based on diagnostically conﬁrmed (Tucker 2003). For example, the pathogen Bacillus cases of human H5N1 infections in hospitalized anthraces could be isolated from the wild as it is still patients in Southeast Asia. Due to a lack of epidemio- endemic amongst cattle, e.g. in Equatorial Africa. logic and virologic studies and limited access to health Infections are also sporadically detected in the USA care in rural areas, mild forms of infection may likely (see accessed 11 September 2013). However, viru- have retrospectively identiﬁed previously undetected lence varies amongst naturally occurring Bacillus asymptomatic infections (Beigel et al. 2005). anthraces strains, and environmental conditions deter- 25. For example, the Functional Genomics Center Zurich, mine the stability and hence the infectiousness of a joint state-of-the-art research and training facility of anthrax spores. Bioweaponeers would need to isolate the ETH Zurich and the University of Zurich, many strains to ﬁnd a suitable one, and would need to Switzerland, provides the latest technologies and stabilize the spores (Dragon and Rennie 1995). The expert support in genomics, transcriptomics, prote- same would be true for naturally occurring H5N1 omics, metabolomics, and bioinformatics accessed 11 September 2013. modiﬁed to adapt to humans as a host. 26. According to the social scientist Harry M. Collins, 30. According to the Public Health Security and somatic limit and collective tacit knowledge are Bioterrorism Preparedness and Response Act of experienced and acquired by humans through immer- 2002, Public Law 107–188, June 12, 2002, Sec. 351A, sion in society and guided practice: Somatic-limit tacit pp. 637ff. knowledge is deﬁned by the limited capacities and . . . the Secretary [. . .] shall include provisions to particular nature of the human brain and body, and ensure that persons seeking to register under such collective tacit knowledge regulations have a lawful purpose to possess, use, has to be known tacitly, because it is located in or transfer such agents and toxins. [. . .] The human collectivities and, therefore, can never be Secretary shall maintain a national database that the property of the any one individual. (Collins includes the names and locations of registered 2007) persons, the listed agents and toxins such persons are possessing, using, or transferring, and informa- 27. NSABB. Addressing biosecurity concerns related to tion regarding the characterization of such agents the synthesis of select agents (2006)
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