Posted by: Adam Kay | December 24, 2012

Pandemic in the Periphery: How Dangerous the Search for a Cure Could Be

Students in Dr. Jill Manske‘s class (BIOL 467- Emerging Infectious Diseases) completed a semester-long project on dual use research (life sciences research that yields information with the potential to be misused to threaten public health or national security) and the case of influenza A virus subtype H5N1. As part of  the project, the class wrote an informal opinion piece. Here it is!

Pandemic in the Periphery:

How Dangerous the Search for a Cure Could Be

Edward Aika, Daisy Alfaro, Erica Bye, Terese Heighway, Abby House, Ashton Johnson, Brandilyn Reak, Toni Teague, Linda Thomas, Paul Zerfas

21 December, 2012

Department of Biology, University of St. Thomas

Introduction to Influenza: The Common Misconception of the Common “Flu”
Through modern advancements in both science and technology, researchers have been able to stand toe-to-toe with some of the world’s deadliest infectious diseases. Like a zookeeper walking into the lion exhibit, we have developed a sense of invincibility while handling these diseases. We must be careful though. There is always that one rare occasion when the zookeeper pays with his life by encountering nature too closely. High-risk agents and toxins are no different. By playing God in the laboratory, we often forget that we are handling nature. Whether through ignorance or intention, there exists an ever-present possibility that our creative capacity exceeds our foresight. Unfortunately, discussion and action are already too late. Toying and experimentation with these high-risk agents have been done and sent for publishing. More work is in progress. But, with what, you may be asking? This work does not involve work with history’s notably notorious killers, like smallpox or the plague. It involves a virus that the body’s defenses normally fight off. It often gets mislabeled as several common symptoms of other illnesses. It involves the virus that everyone loves to shrug off as no big deal: INFLUENZA. And now, we have a bigger problem on our plate than we ever imagined.

According to the CDC, seasonal influenza infects the respiratory tract of roughly 5-20% of the U.S. population.1 Vaccines and antivirals help prevent complications and severe infection, allowing for us to sleep at night. More often than not, those infected are down for a week but return even more resilience to the flu without a second thought. However, very few laymen know the potential behind the flu’s biology. More specifically, the strain of influenza that has come to be known as the “the bird flu”, H5N1, packs more punch than otherwise known. The World Health Organization has reported an unfathomable mortality rate of 60% for those infected with highly pathogenic avian influenza H5N1 (HPAI H5N1).2 Fortunately, we can breathe at least one sigh of relief. Thanks to differing receptors on our cell surfaces, HPAI H5N1 is unable to sustain human-to-human transmission, and infection is reserved for those who intimately handle infected birds. But we can’t celebrate just yet. Mother Nature always finds a way to “one-up” us. One weapon in her arsenal is the capability for genetic recombination. We all remember the 2009 H1N1 influenza pandemic as being globally widespread. In terms of its virulence, however, its bark was worse than its bite. However, let’s say, for instance, that only one little cell is introduced to both the H1N1 strain and the H5N1 strain. Let’s expand that further and suppose that the two strains decide to do a genetic tango. A switch and a swap, and voilà: now, we have a new virus with swine flu’s bark and bird flu’s bite. Now that bigger deal just became a scary reality. However, you might be convincing yourself, “Mother Nature takes her time! We’ll be fine.” To that, two men named Ron Fouchier and Yoshihiro Kawaoka would say, “Are you so sure about that?”

“And then the first ferret sneezed…”: How Ron Fouchier and Yoshihiro Kawaoka Amplified the Concern

Ron Fouchier and Yoshihiro Kawaoka demonstrated just how scary H5N1 can be when they independently conducted research with this menacing virus and tried to get their papers published. However, it was not so simple to share with the world what they had created. Both papers were labeled as “dual use research of concern” or DURC. This means that the risks associated with their work could potentially outweigh the benefits. In other words, the research was super super super dangerous despite the potential of obtaining ground-breaking results. This term, DURC, may not be one that many people in the scientific community are familiar with. Even experts disagree on what defines DURC and how the Fouchier and Kawaoka papers should be published. Therefore, we first need to understand what makes these experiments unique as well as why scientists were so concerned with releasing this information.

Fouchier himself stated that the mutated H5N1 virus is “probably one of the most dangerous viruses you can make”…one of the MOST DANGEROUS viruses you can make. When Fouchier “mutated the hell out of H5N1”, it eventually became airborne transmissible between ferrets. “This is very bad news, indeed,” stated Fouchier. Great. Furthermore, his findings suggest that this mutated H5N1 virus may also be airborne transmissible between other mammals. And yes, we are other mammals. This wouldn’t be such bad news if the virus had required an extensive amount of mutations. But the fact that Kawaoka and Fouchier were able to transmit the virus literally through sneezing ferrets with as little as four or five mutations means that evolution may outsmart us more quickly than we originally thought possible.

This may be especially true considering this research on HPAI H5N1 has come to a screeching halt. What was initially a 60-day voluntary moratorium agreed upon by influenza researchers including Fouchier and Kawaoka, has been dragged out for almost a year. So as Fouchier and Kawaoka’s mutated H5N1 viruses sit untouched in the research facilities, H5N1 may be growing wings in the wild.

The Double Edged Sword of Dual Use Research of Concern

An organic chemistry final could go without a hitch, provided you’ve taken the time to study endlessly in the Leather Room, attend all review sessions, and even bring out your artistic side in crafting a rather colorful set of study guides. OR, the final could end in an incredible failure because of one freakishly simple aspect: you forgot to set an alarm and slept through the exam. This is DURC.

Dual use research of concern is research that could potentially be used to cause widespread harm to the general public. DURC does not exist simply because it is guaranteed to lead to an adverse outcome (i.e. the Viral Villain walks out of the lab with a vial of mutated H5N1 and single-handedly launches a pandemic). However, DURC exists because of the possibility of the research to be used to do harm. This is one side of the double-edged sword.

On the other “edge”, DURC may still lead to groundbreaking results. Kawaoka and Fouchier are essentially trying to predict evolution. The thought is that if we can get a few steps ahead of evolution, we may be able to detect extremely dangerous H5N1 strains in the wild and respond to them. How would we respond? By having a specifically tailored vaccine and/or treatment ready for use. In this case, dual use research of concern could be incredibly beneficial.

However, we need to remind ourselves that these potential benefits, such as a fantastic H5N1 vaccine, do not “solve” the risks that are still involved. It is still entirely possible that the Viral Villain could launch his pandemic. Therefore, we need to analyze this double-edged sword. In the hands of science, which side of the sword will come swinging down to land on the chicken’s head? Hopefully, we all agree. After all, we’d still like to pass our organic chemistry final.

Education: The Intellectual Vaccine to This Potential Danger
            So what does any of this information about DURC’s “double-edged sword” mean to the average college student? Well, in short, it means a lot. We feel that one of the greatest tools available to both the scientific community and the general public in combating the dangers of conducting DURC is to educate those who are about to enter into the field, such as us science nerds.

The first step is to realize that DURC even exists. From this point, educational materials, such as instructional yet entertaining YouTube videos, should be used to further inform students. Rather than conducting classes in which massive amounts of material are memorized and later dumped onto a final exam, students should be encouraged to view research through a different lens. Students should be able to recognize the benefits AND the risks of a research project and how this could impact both science and the general public. By maintaining this mindset throughout our undergraduate research careers, we will be able to move into our future careers with a broader sense of understanding and preparedness toward DURC. Long story short: we need to avoid scientific tunnel vision.

So here’s the point: the goal is to start with small steps. We need to inform. We need to educate. We need to practice. With these humble beginnings, we will develop a greater awareness of just how important it is to understand our responsibility to perform safe yet pivotal research. Let’s do this. Challenge yourself. Change our world.

 More detailed information about this issue as well as access to the report is available upon request. 

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