“Inconvenient Truths” in the Pursuit of Scientific Knowledge and Public Health

(See the major article by Barash and Arnon on pages 183–91 and Dover et al on pages 192–202, and the editorial commentaries by Popoff on pages 168–9 and Hooper and Hirsch on page 167.)

In this issue of The Journal of Infectious Diseases, a group of scientists and physicians from a state public health laboratory present a discovery with important scientific, public health, and security implications, and a difficult dilemma [1, 2]. Their identification of a novel, eighth botulinum neurotoxin (BoNT) from a patient with botulism expands our understanding of Clostridium botulinum and BoNT diversity, C. botulinum evolution, and the pathogenesis of botulism, but it also reveals a significant public health vulnerability. This new toxin, BoNT/H, cannot be neutralized by any of the currently available antibotulinum antisera, which means that we have no effective treatment for this form of botulism. Until anti-BoNT/H antitoxin can be created, shown to be effective, and deployed, both the strain itself and the sequence of this toxin (with which recombinant protein can be easily made) pose serious risks to public health because of the unusually severe, widespread harm that could result from misuse of either [3]. Thus, the dilemma faced by these authors, and by society, revolves around the question, should all of the information from this and similar studies be fully disseminated, motivated by the desire to realize all possible benefits from the discovery, or should dissemination of some or all of the information be restricted, with the goal of diminishing the probability of misuse?

In the early 1980s, Dale Corson, who was president emeritus of Cornell University, led a now-famous study at the US National Academy of Science that culminated in a report entitled Scientific Communication and National Security [4]. The committee explored the growing tension between the principle of openness in science and consequent concerns about national security, which assumed prominence in US public discourse with the development of the atomic bomb and then served as the basis for vigorous debate at the time of their study during the height of the cold war. The report is remembered for having drawn a sharp, “bright” line between scientific information whose communication deserves strict control, that is, national security classification, and information that should be freely disseminated. The committee recommended a long-term national strategy of “security by accomplishment,” to be achieved through a vigorous and open research enterprise. It reminded readers about the “inherent limits on the feasibility and effectiveness of controls,” especially when pursued in the domain of basic scientific research. The persuasive arguments of the Corson committee about a bright line shaped national policy and were cited in President Reagan's National Security Decision Directive 189, which declared in 1985 that “to the maximum extent possible, the products of fundamental research remain unrestricted …[W]here the national security requires control, the mechanism for control of information generated during federally-funded fundamental research … is classification.” [5] This policy has been reaffirmed by subsequent presidential administrations.

What is less well appreciated is that the Corson report also discussed “a small ‘gray area’ of research activities for which limited restrictions short of classification are appropriate” [4]. The Corson committee offered 4 criteria to define research for which communication ought to be limited (all of which must be met): (1) research with dual use or military applications, (2) research with a short time to such applications, (3) research when dissemination could give short-term advantage to adversaries, and (4) research when the information was believed not to be already held by adversaries. They then suggested that classification was not appropriate in all such circumstances, and that there might be other mechanisms of control. As an alternative mechanism, the committee recommended a form of voluntary prepublication control exercised by the investigator. Of interest, given recent political debates, they cited a successful early experiment in voluntary prepublication control for manuscripts dealing with cryptography, involving academia and the National Security Agency.

The Corson “gray area” was largely ignored in subsequent years, in part because there were few concrete and compelling examples of work that might fit in this category and, in part, because the practical aspects of a nonclassification information control mechanism were, and remain, profoundly challenging. Yet, the ongoing revolution in the life sciences now forces us to confront an uncomfortable reality: The same process by which we gain further understanding of biology, invent powerful methods for reengineering genomes and organisms, and derive critical solutions to the problems that ail us and our planet is a path that will predictably generate new and increasingly substantial risks [6]. An important case study in 2012 involved the deliberate engineering of highly pathogenic avian influenza viruses with enhanced properties of transmissibility [7, 8]. The scientific outcome was easily anticipated as it was the stated and intended goal of the investigators, but the risks of the proposed experiments were not widely discussed ahead of time, nor were alternative scientific approaches or risk mitigation strategies. When the National Science Advisory Board for Biosecurity, of which I am a member, initially recommended to the US government, after careful assessment of the risks and benefits, that some of these scientific results not be widely disseminated, the absence of a mechanism, other than classification, for limited distribution of the information confounded policy makers. The need for such a mechanism now deserves renewed serious deliberation and wider discussion, because we are inadequately served by just 2 options, that is, unrestricted dissemination and classification. Some information from life sciences research has an unusually high likelihood of immediately enabling irresponsible or malevolent persons to do grave harm to society, and deserves some control. Yet, classification may not be appropriate, because the burdens of working within the classified environment might hinder needed countermeasure work, or the criteria for national security classification might not be met, such as in the current case where the information is not owned by, produced by or for, or under the control of the US government [9]. A mechanism for short-term, limited distribution is needed while risk mitigation measures are devised (eg, therapies and vaccines), even though the control of distribution will be far from perfect.

The 2 articles in this issue of JID [1, 2] highlight an important alternative mechanism for management of risk in life sciences research, albeit an imperfect one, and take us back to 1982, to Dale Corson and colleagues. The authors of these articles, believing that the sequence information of BoNT/H poses an immediate and unusually serious risk to society, and that the information was unlikely to be already in the hands of those who would seek to do harm, decided to exercise voluntary prepublication control and to withhold this specific information. The more general and less risky aspects of the information were submitted for publication to alert the public to the discovery. This investigator-initiated strategy has merit and deserves careful consideration, but some major caveats should be noted. First, this strategy offers only short-term benefits, as data generated in today's highly interconnected world will inevitably become disseminated. (Corson's “inherent limits on the effectiveness of controls” are even more apparent today.) Given current capabilities in gene synthesis and expression, possession of the sequence is tantamount to possession of the toxin. Therefore, for this strategy to make sense, every effort should be made to exploit this temporary benefit, and to promote immediate, rapid development of an effective countermeasure, that is, anti-BoNT/H antisera. In fact, studies to inform countermeasure development are well under way. Second, this approach poses significant danger to the research enterprise in general if decisions to adopt this approach are made casually, arbitrarily, or frequently. However, I agree with the actions of the authors in this specific case. Although government officials may have participated in a discussion about these papers, to my knowledge relevant stakeholders outside the government were not involved. Going forward, decisions should be based on the best available guidance from experts representing broad, diverse constituencies, including nonscientist representatives of the public, and should be made in a transparent manner.

As more powerful techniques are used to explore the natural world [1, 2] and generate novel biological diversity [7], benefits and risks will both multiply and magnify. And the “gray area” will expand. Voluntary controls may have worked reasonably well for the field of cryptography in the early 1980s because, as the Corson committee remarked, the field was relatively small, its dual use features were obvious, and at the same time, the National Security Agency had high technical competence and an interest in promoting open science. Today's world of the life sciences is much more challenging and consequential.

The life sciences encompass a large number of disciplines and practitioners around the globe, with disparate purposes. Therefore, more expansive, balanced, and dispassionate discussion will be needed, and it must include difficult questions, such as whether there are experiments that should not be undertaken because of disproportionately high risk. In addition, as suggested by Corson et al., we need to make controls more workable, improve the factual basis for decisions on whether and when to exercise such controls, and improve mutual understanding between the government and the scientific community. Finally, for voluntary controls to play a useful role in the management of problematic information in the “gray area,” scientists will first need to recognize their ethical and moral responsibilities to society in the pursuit of knowledge [10]. Scientists have obligations to society that involve more than blind pursuit of information. Like clinicians, scientists have an obligation to do no harm.