Scitech  The avian flu controversy

Assessing the risks and benefits of studying H5N1

On January 23, news broke that researchers working with the deadly avian flu virus had lifted their self-imposed moratorium. Forty scientists signed a letter, published in both Nature and Science, announcing resumption of work that would determine the genetic mutation necessary to permit the virus to transmit between humans. “Because the risk exists in nature that an H5N1 virus capable of transmission in mammals may emerge,” the authors wrote, “the benefits of this work outweigh the risks.”

As of February 1, the World Health Organization (WHO) reported 615 human cases of H5N1 worldwide. Of those infected, 364 died. The virus does not pass easily between humans, but the death rate has raised fears within the scientific and medical community that if it were to become easily transmissable, avian flu could spark a global pandemic worse than the 1918 Spanish flu.

In late 2011, the furor over avian flu took a turn. Two studies, one led by Dr. Ron Fouchier of Erasmus Medical Centre in the Netherlands, and another lead by Dr. Yoshihiro Kawaoka at the University of Wisconsin at Madison, reported lab-made variants of H5N1 that were readily transmissible in mammals. The U.S. government flagged the work as “dual use,” signifying that the findings could be used not only for academic progress, but also for the more sinister purpose of developing bioterrorist weapons. The public went into uproar, with some arguing that the research should never have been done.

In the midst of the controversy surrounding this label, Fouchier, Kawaoka, and 37 other scientists announced a voluntary moratorium on H5N1 research. “We recognize that we and the rest of the scientific community need to clearly explain the benefits of this important research and the measures taken to minimize its possible risks,” they wrote last January.

A year later, the scientists declared that the goals of the moratorium had been met, citing policy reviews conducted in Canada, the Netherlands, and the U.S., as well as technical consultations hosted by WHO and the U.S. Department of Health and Human Services. These consultations were carried out largely by scientists in conjunction with government representatives, with the aim of alleviating public fears.

Whether their goal to increase public support was successful is debatable; the decision to continue the research was met with controversy. Proponents of the work fear that without continued study, an H5N1 pandemic could catch us unprepared. Detractors fear that developing mutant strains with added capabilities could actually increase the risk of a pandemic, should the new virus escape.

For some, these worries are exaggerated. “The chances of one of these viruses coming out of these labs is relatively unlikely,” Dr. Brian Ward, associate professor at McGill’s Centre for the Study of Host Resistance, told The Daily. To minimize the risk, WHO recommends enhanced biosafety level 3 (BSL-3+) in labs working with the virus. In Canada, only labs with biosafety level 4 (BSL-4), which include air locked entries and shower exits, are permitted to work with H5N1.

Ward conceded that with “human nature being what it is, the more labs doing this, the more likely someone […] could have access to these things and release them intentionally.”  But, as long as the number of labs doing this work is limited, the risk is minimal. “There are several labs that work with smallpox [for example], and we haven’t had any evil person releasing smallpox.”

In fact, the last fatal case of smallpox, in 1978, was the result of an accidental leak from a research lab. After that, a research moratorium on wild-type smallpox was imposed. Every stock of the virus was destroyed or transferred to two BSL-4 labs: one in the United States and one in Russia. The final stocks were meant to be destroyed decades ago, but both the U.S and Russia demurred. In 2011, the international community agreed that the risks inherent in smallpox research outweighed the benefits and again called for the virus to be destroyed. Despite this pressure, these stocks remain.

The history of smallpox makes the threat easy to assess. In the case of avian flu, we’re stuck with guesses and projections. The main fear is that, as the wild virus circulates, it could mutate into something catastrophic, as H1N1 did in the pandemic of 1918.

To this day, scientists are unsure why the 1918 flu strain was so deadly.  Researchers have no samples of the virus, and modern descendants are not nearly as virulent. This lack of knowledge makes it difficult to evaluate the chance of repeating history. “We don’t have anything to hang our hats on,” Dr. Dalius Briedis, associate professor in the Department of Microbiology and Immunology, pointed out to The Daily. “In the past 100 years or so, this has only happened once. It’s one of these low probability, high risk events.”

The possibility of H5N1 becoming transmissible outside the lab is certainly real. Each of the mutations that Fouchier identified in his lab-made strains already exists in nature. If viruses with key mutations were to recombine, the result would be a human transmissible virus. “If you say this is only a 1 in a billion chance,” Ward said, “well, you have a billion birds and a few billion pigs and seven billion people, so statistically the chances are not bad.”

On the other hand, it’s possible that a transmissible strain may not be as deadly. Fouchier’s mutant virus was lethal in ferrets, but only when it was passed from ferret to ferret via syringe. When the contagion was passed through airborne droplets, it wasn’t lethal.

So the question remains, does the risk of a natural pandemic outweigh the risk of a man-made one? The debate left the scientific community divided. After a year of consultations and debates, a full consensus still hasn’t been reached. Ward noted, however, that, “in the end, the split wasn’t 50/50.  The large majority of the world’s scientists fall on the side of the line where releasing this [research] is not a bad thing.”

Briedis, for one, remains unconvinced. “I do not think that it’s wise research to do,” he said.  “I personally would not have gotten involved in doing it, and I would have attempted to sway people from doing it.” But, he added, “the academic ambitions of individual researchers are not to be underestimated.  If there’s something interesting to be done, generally someone somewhere will end up doing it.”

As biotechnology moves forward, we may see more and more cases like this. The consultation process has clearly set a precedent for how scientists deal with controversy in the public eye. But one questions the effectiveness of such an insular decision process in gaining public trust. While the attempts to address public fears are a step in the right direction, lingering fears about the release of a supervirus suggest that more transparency is needed.