If one were to try and identify what issue has most roiled the biomedical community in the past few months it is surely the effort to censor two papers describing genetic modifications of the H5N1 flu virus.

Background.  Last December, the U.S. National Science Advisory Board for Biosecurity (NSABB) was asked by the U.S. National Institutes of Health to look at two NIH-funded studies.  Both involved experiments in which scientists in the U.S. and the Netherlands showed that a form of the potentially deadly H5N1 influenza virus could be genetically tweaked so as to create a nastier, more lethal version, and one that could more easily cause airborne transmission between ferrets.  The ferret is an animal beloved of vaccine researchers partly for historical reasons but mainly because it sneezes; most vaccine experts agree that what can be transmitted through particles in the air between ferrets is very, very likely to be transmissible among humans.  High transmissibility between humans of a nasty version of pandemic flu could mean that someone could, alerted to the techniques used by the American and the Dutch research groups, create a highly contagious and lethal form of flu and put it to terroristic purposes.

The NSABB, appropriately alarmed by the potential for malice that might flow from this work, and charged by the U.S. government with keeping an eye out for any life science research “that may be misused to pose a biologic threat to public health and/or national security,” asked the journals Nature and Science, to which the two papers had been submitted, to redact certain key details about methodology and findings prior to publishing them.

This request led to a host of agitated behavior ranging from newspaper headlines screaming about the imminent creation of ‘Armageddon’ bugs, to the papers’ lead authors, after a lot of arm-twisting and jaw boning, agreeing to impose a moratorium on the publication process, to a high level meeting of flu experts convened by the WHO in Geneva blessing full publication, to the Dutch government imposing an ‘export’ ban on sending the Dutch paper outside the Netherlands on grounds of concern over national security.

It is no wonder the dispute over the fate of the pandemic flu papers commanded such intense attention.  The stew had an extraordinarily rich set of ingredients:  top experts in flu research, genetics and microbiology publicly yelling at one another; the editors of leading journals negotiating back and forth with high level government agencies about their right to print; a hefty dose of fear about horrific pandemics; a bevy of media more than willing to hit the end-of-times alarm button; and an extra big dollop of debate about the freedom of inquiry and the right to scientific free speech.  It has been quite a while since Lysenko, Julius and Ethel Rosenberg, and Galileo have been linked to a dispute over publication, but each made cameo appearances in the heat of the debate over the fate of the pandemic flu articles.

Unexpectedly, on March 30th, the NSABB reversed its decision.  The board said that, in light of some minor revisions to both papers and a clearer understanding of the non-lethal nature of the flu variants involved, Ron Fouchier, who led the Dutch group and Yoshihiro Kawaoka the American could publish their research in full.  And, at the same time, the National Institutes of Health Office of Biotechnology Activities posted on their website a brand new policy governing life sciences research that can be put to evil purpose or “dual use.”  Groups such as the Royal Society convened quite useful meetings to try and autopsy what had happened and bring a bit less mania to the discussion of censorship of potentially dangerous life sciences research.

Lessons From The Brouhaha

Despite an inauspicious beginning to the controversy, a number of important ethical and factual points emerged from the publication brouhaha.  These are especially important in that it is certain that controversy will arise in the future regarding the creation of more lethal and contagious flu viruses, as well as over the publication of information about other microbial agents that might be put to malicious purposes.

Why publish? First, why publish details about how to make nastier versions of the flu?  The answer is because the worst terrorist the world faces is nature.

Armed with more precise information of the meaning of genetic mutations or the processes by which a harmless microbe can evolve into one that is threatening to wildlife, domestic animals, or humans, better surveillance should be possible.  Knowing what mutations indicate greater transmissibility or virulence may be of help in preparing for a naturally occurring deadly pandemic.

Monitoring what is taking place naturally in wild birds, domestic poultry, pigs, and humans that might spell troubling genetic changes for possible pandemics allows for preventive action.  Poultry can be isolated or culled.  Humans can be moved, quarantined, isolated, warned to wear masks or take anti-viral medicines. Hospitals can begin to prepare for an influx of patients.  Pandemic plans can be launched.

Engineering and studying what makes microbes contagious and harmful also allows the stockpiling of vaccines and, through the creation of more precise “seed stock,” a quicker response to emerging pandemics or the detection of an accidental or deliberate release.  Conducting research keeps the world vigilant about pandemics — something that the recent decline in interest in flu pandemics in the wake of the rather mild H1N1 swine flu pandemic shows is a real public policy problem.

It’s too late to censor a paper being submitted to a journal. As for publishing the details of how to concoct horrific microbial agents, the fact is that by the time a manuscript is ready to go to a journal, censorship is utterly pointless.  Research teams involved in this type of work are large.  They exchange electronic information with each other and many non-team members.  They store details of their work on personal, easily hacked or stolen computers, in the cloud, in unencrypted emails, and in notes and in other discoverable ways.

After submission, editors and peer reviewers get a look at manuscripts, too, adding to the number of people who know all the details.  Redacting or restricting the publication of sensitive information in a paper that has made it to submission, much less publication in a journal, is pointless. A determined terrorist group or a 17 year-old moderately savvy computer hacker has plenty to work with by that point to find out whatever they want to know.  If security is wanted about the details of creating dangerous agents it will have to be imposed far sooner than blacking out sections of published journal articles.

The danger of inadvertent release. As is clear from the debate about publication of the details of bioengineered pandemic flu this bug is a poor choice of weapon for terrorists.  They are likely to kill a large number of themselves, their allies, and people they wish to bring to their cause, along with their perceived enemies.  Engineering nasty flu bugs is of concern for a very different reason: inadvertent escape due to accident.

Fouchier and Kawaoka assured the audience at the Royal Society meeting in early April that they worked under the tight biosafety conditions.  Each team works in a lab, which involves the use of a segregated air and water supply, multiple showers for workers, multiple airlocks, and pressure chambers or suits for workers.  Kawaoka noted that his lab was patrolled by his university’s police and had guards at the door.

This is somewhat — but only somewhat — reassuring.  Somewhat, because it is not at all clear that everyone anywhere in the world working with flu viruses or other pathogens will do so under secure conditions.  And only somewhat because it is not clear how employee screening, training, auditing, and counseling along with earthquakes, tornadoes, attacks by armed lunatics, hurricanes, floods, tsunamis and a host of other catastrophes play into worldwide planning and auditing of biolab safety.  The nuclear power generating industry gives some reason for concern about safety, as does the inability to arrive at minimal standards for the storage of radioactive waste.

Transparency, audit and omnipresent vigilance in dealing with dangerous microbes, natural or artificial, are moral and policy requirements.  Perhaps only a few, exceedingly secure places around the globe ought be doing work on bioengineering pandemic flu or other highly dangerous microbes. The world does not have any agreement that such a system ought to exist, much less have it firmly in place.  It should.