In the wake of an experiment to see if a mutated form of the H5N1 bird flu could be made transmissible to humans, a pair of biologists are now speaking out about the potential risks posed by such endeavors; they say there's a much greater chance that these viruses could escape from the lab than we've been led to believe.
The purpose of these so-called "gain of function" experiments are to create and manipulate new potential pandemic pathogens (PPPs). They're designed as a kind of pre-emptive strike against viruses before they mutate into something dangerous. For example, experiments by Ron Fouchier at Erasmus medical centre in Rotterdam and Yoshihiro Kawaoka and his team at the University of Wisconsin-Madison determined that H5N1 is as little as one stabilizing mutation away from becoming human-transmissible. With this knowledge, scientists can not only anticipate the mutation before it happens in the wild, but also begin the arduous process of developing vaccines.
But as Harvard's Marc Lipsitch and Yale's Alison Galvani argue, it's simply not the worth the risk. As they write in their PLos Medicine report:
There is a quantifiable possibility that these novel pathogens could be accidentally or deliberately released. Exacerbating the immunological vulnerability of human populations to PPPs is the potential for rapid global dissemination via ever-increasing human mobility. The dangers are not just hypothetical. The H1N1 influenza strain responsible for significant morbidity and mortality around the world from 1977 to 2009 is thought to have originated from a laboratory accident.
And by "quantifiable" the authors calculate that if 10 high-containment labs in the U.S. performed gain of function experiments for 10 years, there's a 20% chance of at least one person becoming infected. This infected person could then unwittingly (or deliberately) serve as patient zero, spreading the disease more widely and spawning a global pandemic.
Moreover, they say there are safer and more ethical approaches to this kind of medical research, such as comparisons of seasonal human flu strains and other respiratory viruses that have made the leap from animals into humans. Lipsitch and Galvani say that future experiments
should be assessed on the basis of their marginal benefits, compared to those of safer approaches. In the case of influenza, given the higher throughput and lower cost of alternatives, we believe the benefits of alternative approaches will be greater than those of novel PPP experimentation, yet without the risks–thereby negating the justification for taking such risks. Similarly, careful consideration should be given to analyses of novel PPP experiments beyond the study of influenza, as these are proposed. Funders and regulators should evaluate the balance of risks and benefits before further novel PPP experiments are undertaken.
The PLoS report has since been rejected by Fouchier and Kawaoka. As reported in The Guardian:
Fouchier said the authors were wrong on both points they made – that alternative experiments could provide answers about the transmissibility of viruses, and that the risk of an outbreak or pandemic was high.
"The research agenda they propose is important and currently ongoing, but alone will never lead to solid conclusions about mammalian adaptation and transmission: the proof of the pudding will need to come from gain-of-function studies using infectious viruses. This is why the department of health and human services has approved our research, taking into account all ethical, safety and security issues, and weighing the risks of the research against the benefits," Fouchier said.
He said the authors had misinterpreted published data to arrive at their risk of someone picking up a virus in the laboratory. "The truth is that scientific research has never triggered a virus pandemic." Lipsitch and Galvani point out that a flu strain that spread around the world from 1977 to 2009 was probably released in a laboratory accident.
Kawaoka was similarly unimpressed with the report. "The authors imply that gain-of-function studies are going on without proper reviews. This is not so and suggests they do not understand how highly regulated this work is and the approvals and planning required to conduct this research," he said. "This commentary lists many experiments they think we should be doing. We are doing many of those experiments already."
Read the entire study at PLoS Medicine: "Ethical Alternatives to Experiments with Novel Potential Pandemic Pathogens."
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