Article in Science / Biology & Nature / Biotechnology
NIH funded research on the deadly bird flu virus. The current situation has unfortunately placed the publishing community in a dilemma of either creating a barrier to research that leads to a vaccine or either providing a how-to manual to terrorists.
 
 
 

A pandemic is one of the biggest challenges in public health. One can only imagine if the bird flu, polio, anthrax, Ebola, Legionnaire’s disease, smallpox, or SARS could create the deadliest scenario in history. Currently, the H5N1 bird flu, which first surfaced in Hong Kong in 1997 killing six people, is of special interest to public health officials.

The bird flu does not frequently infect humans, but in nature it can spread from birds to mammals. The virus has not acquired the mutations enabling the spread from mammal to mammal potentially leading to a pandemic. In order to better understand mammal to mammal transmission, NIH funded research which led to creating five mutations in two genes producing a highly transmissible form of the virus.

Wearing respirators and full body suits, the researchers introduced the virus in to the nasal passages of ferrets which subsequently infected other ferrets through airborne transmission. Understandably, news of the H5N1 bird flu research raised public concerns. What is at stake here is that compared to the 2.5 percent mortality rate of the 1918 Spanish influenza which killed roughly 50 million people, according to the World Health Organization the H5N1 bird flu virus has a roughly 60 percent mortality rate.

Bird Flu Research Fallout

When research has consequences of this magnitude, it is the responsibility of governments and public health officials to take proactive steps. Subsequently, several developments have taken place. The fallout includes a moratorium on research and censorship on publishing the details of the research.

Going forward in a new age of biosecurity risks, governments and public health officials must consider the possibility of a pandemic created by human manipulation of these deadly viruses. What if the mutated viruses accidentally escaped from the lab? Some basic scientific research has dual use applications. As one can use research on nuclear energy for nuclear weapons, they can also use research on viruses for bioweapons. What if terrorists were able to steal the viruses from a lab?

H5N1 bird flu research is not the first case where policy makers and health officials evaluated the risks and benefits of biological research. At the 1975 Asilomar Conference, leaders in the genetic engineering field met to discuss how to wisely proceed with research inside the laboratory. Scientists developed self-imposed safety guidelines for lab research. After adopting a voluntary code of self-governance, the technology has remained harmless.

Similarly, both teams of scientists involved with the bird flu research have agreed to suspend their research indefinitely. Interestingly, media coverage reveals that the researchers used Biosafety Level Three (BSL-3) labs, not BSL-4 which has the highest containment rating. What is it that the average citizen is supposed to take from this message, pandemics killing millions of people are not the worst possible scenario?

In preparing vaccines for the next pandemic created by natural causes, cooperation among researchers by sharing their findings in public databases, articles, e-mails, and conferences will in theory provide faster results. NIH‘s Public Access Policy mandates that funded research is placed in the public database PubMed. A bill introduced in the House, The Research Works Act H.R. 3699, aims to reverse NIH’s policy.

Past Dual Use Biological Research

As genome sequencing and synthesizing technologies became more affordable and powerful, researchers have performed research on deadly organisms and published the research details. In 2001, Australian scientists reported in the Journal of Virology that while developing a contraceptive vaccine to control rodent populations, researchers had inserted a gene for an immune system protein into a mousepox virus. This unexpectedly made the normally mild virus lethal in mice, even to those that were naturally resistant to mouse pox or that they had vaccinated against it.

Then, in 2002 a group of researchers at SUNY led by virologist Eckard Wimmer, assembled a DNA template for the RNA poliovirus using a published nucleotide sequence from the internet and from customized mail order oligonucleotides, DNA sequences 50-100 base pairs long. The synthesized poliovirus caused paralysis in animals confirming that scientists could recreate the deadly virus from its nucleotide sequence. Commenting on the potential for terrorism, Wimmer said the process is so tedious that terrorists would find it much easier to use an existing virus found in nature.

In prior research on influenza viruses, scientists were extremely interested in the 1918 pandemic created by the Spanish influenza virus which killed an estimated 50 million people. Most people have some immunity to the 1918 virus because they have exposure to more recent strains partially derived from it. However, the CDC reports even with current vaccines and antiviral drugs, it is possible that a new strain of the virus could potentially kill over 100 million people. So, scientists began searching for answers to several puzzling questions. What are its origins? Why was it so lethal? Why did some waves of the virus target healthy people while other waves target the most vulnerable; the young, elderly, and infirm? Nearly half of the victims were in the 20-40 age group. Why do some viruses hit at certain times of year? Why was the death rate much higher than expected?

Scientists went directly to the pathogen that was so destructive during the 1918 pandemic for answers. Jeffery Taubenberger of the U.S. Armed Forces Institute of Pathology attempted to sequence the virus, but preserved tissue samples from victims which were stored at his institute had degraded. Fortunately, researchers were able to recover viral RNA from lung tissue samples found in an Inuit woman preserved in the northern Alaska permafrost. In 2005, a group of scientists were able to determine the genetic sequence of the responsible pathogen including its eight genes.

The U.S. Centers for Disease Control and Prevention (CDC) used the genetic sequence to synthesize the virus in the laboratory. After the researchers created a synthetic virus, in a matter of days it killed mice and chicken embryos in the lab. In a controversial move, the federal government labs placed Taubenberger’s viral sequence in an online database maintained by NIH. After deliberating on covering the story the editors of Nature and Science also decided to publish articles giving the details of how scientists sequenced and brought to life the lethal virus. Both journals decided the benefits of publication outweighed the risks. According to Donald Kennedy, the former editor-in-chief of Science, scientists needed access to the research as they try to develop vaccines and antiviral medications against potential future pandemic agents.

Then in 2006, James Randerson, a science reporter with The Guardian, investigated if it was possible to order the biological parts necessary for synthesizing a deadly virus. [1] Acting responsibly, Randerson contacted synthetic biologist Drew Endy for advice on the story. For safety reasons, they discussed a slightly altered partial sequence of the smallpox virus. The reporter then ordered the partial sequence via the internet to see what would happen. The supplier delivered the sequences not aware it coded for a destructive organism. In response, similar to Wimmer, a group of scientists and policy analysts disclosed in a report financed by the Alfred P. Sloan Foundation, that terrorists would find it easier to work with naturally occurring pathogens than synthesizing them.

In these cases, science journals decided the benefit of publication, potentially developing vaccines and antiviral medications, outweighed the risks. In addition, an Alfred P. Sloan Foundation report determined that terrorists would find it easier to work with naturally occurring pathogens than synthesizing them.

Fisking Anti-Censorship Arguments

Dual use biological research requires oversight on a case by case basis. Until H5N1 bird flu research, the public’s concerns did not faze the scientific and publishing communities enough to pause and rethink strategies for disseminating information. The current situation has unfortunately placed the publishing community in a dilemma of either creating a barrier to research that leads to a vaccine or either providing a how-to manual to terrorists.

The U.S. National Science Advisory Board for Biosecurity (NSABB), created after the 2001 anthrax attacks, asked two major science journals not to publish the key details of the bird flu experiments, rather edited versions. The NSABB decided that in publishing the full details of the research the potential risk is high and outweighs the benefits.

Even with the possibility of creating a pandemic, some analysts have argued in favor of publishing the full details of the research. Their arguments include science requires transparency and openness to operate [2], the ability to publish cutting edge science papers is important in the recruitment of researchers and the process of vetting scientists is too complicated [3], and that censorship will encourage theft and hacking [4].

However, history reveals physicists have had restricted dissemination of their work for decades. Take, for example, the Manhattan Project. Also, the Defense Department and NASA’s space program currently operate successfully without openness and transparency. With censored physics research, it was possible to successfully recruit the best and brightest physicists leading to groundbreaking results in defense, space exploration, and nuclear engineering.

Policy makers have used Presidential Executive Orders and Acts of Congress to restrict information from the general public. In the vetting process, the Atomic Energy Act of 1954 made it possible for the U.S. government to allow private companies to obtain restricted technical information and exchange information with foreign nations through multiple levels of security clearance. [5]

It is not only the right of the government to censor or classify certain information, but its duty to protect the general welfare of its citizens. To ensure compliance with restricted access, those responsible for the unauthorized disclosure of classified information are accomplices and held accountable for any terrorist’s acts.

It is not obvious why the average person wants to know the technical details of making destructive viruses or even needs to know. It is, however, obvious why terrorists would want to know. Given the magnitude of the consequences of a pandemic created either naturally or by humans, censorship or redacted publication of the research until safeguards and countermeasures are in place for any high risk scenarios relating to public health is a wise decision.

The Future of Dual Use Biological Research

Public health officials and policy makers are now in the unenviable position of deciding how to move forward not only with H5N1 bird flu research, but setting a precedent for future dual use biological research. Adequate oversight will require international cooperation and flexibility in the oversight of funding, censorship, and biosafety.

Although the details of the bird flu research will temporarily remain secret, contrary to the NSABB’s recommendations a panel of WHO experts has concluded that the benefits of public access to the details of the bird flu research outweigh the risk of bioterrorism. [6] Paul Keim, chair of the NSABB, hopes to develop a protocol that enables sharing the research with responsible scientists who request it. With sensitive physics research, censorship of technical information varied in its duration and the NSABB could follow this successful strategy and release the research details at the appropriate time.

Prior to funding dual use biological research, it is NIH’s responsibility to take more proactive steps in anticipating the public’s reaction. In order to address public concerns, before funding and performing research on these deadly viruses it is important that mechanisms are in place to ensure research labs provide maximum biosafety precautions and for disseminating the details of the research. Security analyst Lynn Klotz suggests that in the future the first step is to have an advisory panel discuss and agree that performing the dual use research is actually a good idea.

Notes

[1] James Randerson. Revealed: the lax laws that could allow assembly of deadly virus DNA. The Guardian. June 14, 2006. http://www.guardian.co.uk/world/2006/jun/14/terrorism.topstories3

[2] Ronald Bailey. Bird Flu Censorship is Not a Good Idea. Reason. January 23, 2012.

http://reason.com/blog/2012/01/23/is-bird-flu-research-censorship-a-good-i

[3] Peter Palese. Don’t Censor Life-Saving Science. Nature. 481:115. 2012.

http://www.nature.com/news/don-t-censor-life-saving-science-1.9777

[4] Rob Carlson. Censoring Science is Detrimental to Security. January 9, 2012.

http://www.synthesis.cc/infectious-disease

[5] Arvin Quist. 1993. Security Classification of Information. Oak Ridge National Laboratory.

http://www.fas.org/sgp/library/quist/index.html

[6] Denise Grady. Despite Safety Worries, Work on Deadly Flu To Be Released. The New York Times.

February 17, 2012. http://www.nytimes.com/2012/02/18/health/details-of-bird-flu-research-will-be-released.html


 

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