New Biosecurity Threats Appear in Less Familiar Forms

Infectious diseases pose a threat from multiple avenues—naturally occurring events such as outbreaks, accidental incidents like lab errors, and intentional acts of bioterrorism. Globalization, growing populations, and increasing encroachment of humans onto animal habitats have increased the risk for spillover and natural outbreaks. From the laboratory side, the threat is a mixture of biosecurity and biosafety. Biosecurity measures are those that seek to protect the organisms from nefarious actors, while biosafety practices look to protect investigators (or the public) from accidental exposures. The Ebola outbreak in 2014 and 2015, the Zika virus epidemic of 2015 and 2016, findings of smallpox vials in National Institutes of Health laboratory freezers in 2014, and continual lab errors involving mishandling and shipping of live select agents all highlight the threat of natural and accidental events. Although these recent occurrences have reinforced the need for preventive and responsive measures, the threat of bioterrorism can seem a bit distant; however, with advances in biotechnology and global travel, we must remain vigilant.

The 2001 Amerithrax attacks easily come to mind when discussing the threat of bioterrorism. Following the September 11, 2001, attacks, letters laced with anthrax added a new horror to the United States, a country that was already vulnerable. The Amerithrax attacks killed 5 individuals and sickened 17 and are considered the worst biological attacks in US history.

¹

The decontamination costs alone were estimated to be $320 million, and challenges with postexposure prophylaxis recommendations and compliance only added to the chaos.

²

Perhaps one of the most unexpected aspects of this attack was the conclusion that US Army Medical Research Institute of Infectious Diseases biologist and anthrax expert Bruce Ivins, PhD, was considered the most likely culprit (he later took his own life prior to charges being filed).

³

Typically, bioterrorism is thought of in terms of attacks like the ricin release by Aum Shinrikyo in the Tokyo subway and the poisoning of salad bars with Salmonella by the Rajneeshee cult in Oregon.

⁴

All these attacks involved fanatical groups and revealed deep-rooted challenges with the science of acquiring, growing, weaponizing, and disseminating complex biological weapons. The Amerithrax attacks were different because the anthrax was delivered in a fine powder that ensured easy inhalation exposure. Many were surprised that the threat came from not only a scientist but also an American researcher working at an infectious disease institute aimed at protecting the United States. Moreover, Dr. Ivins had the means and capacity to make the attack exponentially worse but simply had chosen not to.

³

It was during this time that significant gaps were found within the United States’ response to such an attack. Whether it was who was responsible for decontamination, physician capacity to diagnose agents likely to be used for bioterrorism, or the sensationalized news, numerous factors left the United States truly struggling to handle such an event.

⁵

The Amerithrax attacks gave insight into not only the poor American preparedness and response for bioterrorism but also a new source for weapons: skilled scientists.

Although there is always the potential for nonstate actors—ISIS, for example— to develop crude biological weapons, a more recent focus regarding biothreats has aimed at emerging technology.

⁶

The scientific capabilities and tacit knowledge of bioterrorism will ultimately affect the bioweapon, whether it be the selection of organism, the crude design or complex dissemination method, etc. The Amerithrax attacks gave us a small window into the capabilities of a nefarious individual with significant skills and knowledge in bacteria. Recent biotech advances have added a new spin to biothreats.

For example, the biotech industry is rapidly growing, bringing new technologies like synthetic biology, digital-to-biological converters, and gene-editing tools like CRISPR-Cas9 to the masses.

⁷

CRISPR can effortlessly be purchased online for $150, making the process significantly easier.

⁸

A tool that can easily edit DNA like a pair of scissors with a copy and paste has the potential to prevent mosquitoes from transmitting malaria and to remove chronic conditions from humans. Gene editing also has the capacity for gene drive, which allows genetic traits to be quickly passed down through generations. The potential for CRISPR is endless, and yet it has many scientists worried. The ease of use and access, not to mention very limited federal oversight, could have unintended effects due to a garage-biohacker’s tinkering around with DNA. Jennifer Doudna, PhD, one of the inventors of CRISPR, expressed her worry about this very act, noting, “I think there’s sort of the potential for unintended consequences of gene editing in people for clinical use. How would you ever do the kinds of experiments that you might want to do to ensure safety? ”

⁹

Although CRISPR has made gene editing easier and more accessible, there also exists the hazard of dual-use research of concern (DURC), like that of gain-of-function research (GoF). DURC is life sciences research that, despite its good intentions, has the capacity to be directly misapplied to pose a threat to humans, animals, the environment, agriculture, etc. The recent news that a Canadian research team reconstituted horsepox with little specialized knowledge, mail-ordered DNA fragments, and $100,000 highlights the DURC debate.

¹⁰

Although the research has yet to be published, the concern is not only that this process could be applied to reconstitute smallpox but also that the research was not flagged in the review process for risks related to dual-use research. The horsepox experiment points out the possibility that such work can be done and that even at the most structured level, proper risk review is not being done.

¹¹

Moreover, such an experiment raises concerns for lowering the barriers to experiments using smallpox and normalizing DURC in a manner that could be dangerous.

GoF is one of the most common examples of DURC. Experiments with GoF involve increasing the virulence, transmissibility, or host range of pathogens. Although this research is performed to better understand current diseases and what it would take for them to evolve to have more pandemic potential, this research inherently worries many in the research community because of the risk of accidental release or intentional misuse by a nefarious actor. This first became an issue in 2012 when 2 research teams genetically modified H5N1 viruses to transmit efficiently between mammalian hosts to show the genetic mutation needed for the virus to sustain human-to-human transmission.

¹²

The concern over this research led to a federal moratorium’s halting funding for such experimentation until guidance could be developed.

¹³

What do CRISPR and DURC have to do with bioterrorism? In a word, everything. The growing biotech industry makes the science of genetic engineering easier and more accessible, while DURC means that research with pathogens of pandemic potential poses both a biosecurity and biosafety risk. Imagine a lab failure, which history proves can happen, that results in the release of a strain of H7N9 that has been modified to be easily transmitted among people or a strain of Neisseria meningitis that is highly resistant to antibiotics. This becomes even more relevant as the dramatic increase in biodefense activities and in the number of biosafety level 4 labs continues.

¹⁴

Moreover, imagine that this incident is not an accident; rather, it has occurred because of a person with bioterrorist ambitions who acquired access to these labs or even an insider threat like Bruce Ivins. The truth is that the threat of bioterrorism is no longer beholden to the state program or cultish group with a makeshift lab in their garage but may also include a DIY biohacker or laboratory worker with nefarious intent.

How can we, as infectious disease practitioners, prepare or respond? First, knowledge is key. It is crucial to understand the threats, whether they are a natural outbreak, a lab breach you read about, or even just a review of the signs and symptoms of organisms we tend to worry about but may not see in the United States (such as severe acute respiratory syndrome, Middle East respiratory syndrome, anthrax, etc). Researchers should also consider the implications of their work and take the necessary review processes to ensure the proper biosecurity measures are taken.

Second, as simple as it sounds, practice vigilant infection control. That’s right—hand hygiene, personal protective equipment use, rapid isolation of potentially infectious patients, and working with your infection prevention and control (IPC) resources. Fundamentally, these practices will provide the first and most vital line of defense against the exposure and spread of a disease.

Third, keep an open communication channel with those IPC resources and your local public health department. If something seems off, say something. You are without a doubt the most vital part of identifying patients with unusual or concerning disease presentations. Every outbreak begins with someone asking questions and knowing when to bring in additional resources. Consider a surge of patients with the same symptoms during an off time of year or with symptoms of a rare disease. Although the surge could be a flu epidemic, or the result of a crowd from a major sporting event being exposed to a food-borne pathogen, it could also be something more sinister. By touching base with public health officials, you allow them to start investigating.

Last, don’t stop what you’re doing. Infectious disease threats present from all angles—natural, accidental, or as acts of bioterrorism—but they all require identification, isolation, and treatment from practitioners. The field of infectious disease and public health isn’t for the weary, and every person is vital to global health security.

Ms. Popescu is a hospital epidemiologist and infection preventionist with Phoenix Children’s Hospital in Phoenix, Arizona. She is currently a PhD candidate in Biodefense at George Mason University, where her research focuses on the role of infection prevention in facilitating global health security efforts.

References

1. US Federal Bureau of Investigation. Amerithrax or anthrax investigation. www.fbi.gov/history/famous-cases/amerithrax-or-anthrax-investigation. Published May 17, 2016. Accessed June 17, 2017.
2. Bresnitz, EA. Lessons learned from the CDC’s post-exposure prophylaxis program following the anthrax attacks of 2001. Pharmacoepidemiol Drug Saf. 2005;14(6):389-391. doi:10.1002/pds.1086.
3. AMERITHRAX INVESTIGATIVE SUMMARY. Released Pursuant to the Freedom of Information Act. February 19, 2010. https://www.justice.gov/archive/amerithrax/docs/amx-investigative-summary.pdf. Accessed October 24, 2017.
4. Koblentz, Gregory D. Living weapons: biological warfare and international security. Ithaca: Cornell University Press, 2011
5. Cosgrove SE, Perl TM, Song X, Sisson SD. Ability of physicians to diagnose and manage illness due to category A bioterrorism agents. Arch Intern Med. 2005;165(17):2002-2006. doi:10.1001/archinte.165.17.2002.
6. Khaniejo N. Use of chemical and biological weapons by Daesh / ISIS. CBW Magazine: Journal on Chemical and Biological Weapons. 2016;9(3). http://www.idsa.in/cbwmagazine/use-chemical-and-biological-weapons-by-daesh-isis. Accessed June 21, 2017.
7. Boles KS, Kannan K, Gill J, et al. Digital-to-biological converter for on-demand production of biologics. Nat Biotechnol. 2017;35(7):672-675. doi: 10.1038/nbt.3859.
8. Vasiliou SK, Diamandis EP, Church GM, et al. CRISPR-Cas9 system: opportunities and concerns. Clin Chem. 2016;62(10):1304-1311. doi: 10.1373/clinchem.2016.263186.
9. Wood M, Velasco P. Crispr inventor worries about the unintended consequences of gene editing. Marketplace website. www.marketplace.org/2017/06/16/tech/crispr-inventor-worries-about-unintended-consequences-gene-editing. Published June 16, 2017. Accessed June 21, 2017.
10. Kupferschmidt K. How Canadian researchers reconstituted an extinct poxvirus for $100,000 using mail-order DNA. Science. June 2017. doi:10.1126/science.aan7069.
11. Koblentz GD. The de novo synthesis of horsepox virus: implications for biosecurity and recommendations for preventing the reemergence of smallpox. Health Secur. August 24, 2017. doi: 10.1089/hs.2017.0061.
12. Schnirring L; Center for Infectious Disease Research and Policy. Work continues on policies for ‘gain of function’ research. www.cidrap.umn.edu/news-perspective/2015/10/work-continues-policies-gain-function-research. Published October 2, 2015. Accessed June 21, 2017.
13. David MalakoffJan. 23, 2013 , 1:00 PM, 20 2017 S, 19 2017 S. H5N1 Researchers Announce End of Research Moratorium. Science | AAAS. http://www.sciencemag.org/news/2013/01/h5n1-researchers-announce-end-research-moratorium. Published July 26, 2017. Accessed September 20, 2017
14. Koblentz G, Lentzos F; International Law and Policy Institute. 21st century biodefence: risks, trade-offs & responsible science. http://nwp.ilpi.org/?p=5488. Published November 2016. Accessed June 18, 2017.