To Defend Against Flu, Make It Deadly
Researchers want to create a more contagious and deadly version of the avian influenza virus, H7N9, which causes severe respiratory illness in humans as well as death.
In a letter jointly published today in Nature and Science, influenza expert Ron Fouchier of the Erasmus Medical Center in the Netherlands and professor of virology Yoshihiro Kawaoka University of Wisconsin-Madison together with twenty other scientists in the field outlined five general research areas they plan to investigate.
The scientists say their experiments could shed light on how the virus works, how it develops resistance to drugs and how it might adapt to jump from poultry, where it originates, to humans. That information could lead to a life-saving vaccine that prevents a worldwide pandemic.
But some scientists think that telling the world about the experiments ahead of time is a bad idea. They say the letter will just stoke unwarranted fears about necessary research and potentially create public pressure to roadblock valuable science.
Fouchier and Kawaoka wrote the letter to forestall the kind of controversy that followed similar experiments they did in 2011 on the bird flu virus H5N1. This variety of influenza originated in birds, most likely chickens, but jumped to humans, especially to those handling infected birds. So far only about 600 people have come down with H5N1 because the virus is not capable of efficiently spreading itself to human hosts. But when it does, it's deadly. To date, 60 percent of those infected have died and that's why health officials at the Centers for Disease Control and Prevention are worried. If H5N1 mutates into a strain that's easily transmissible between humans, millions of people could die.
In their experiments on H5N1, Fouchier and Kawaoka made the harmful virus more contagious, although paradoxically it became less deadly. Nonetheless, fears about the possible use of the research data to make biological weapons prompted a self-imposed, yearlong moratorium on certain kinds of flu research that lasted until January 2013.
Now Fouchier, Kawaoka, and other researchers want to do a similar thing with H7N9, another potentially dangerous avian influenza virus, and they want the world to know what they're doing and why.
"We wanted to be transparent," Kawaoka told DNews. "We learned from H5N1 experience that there were many misunderstandings about our research. By publishing this statement, we hope to help the public understand what we are doing and why; we also explain the precautions we take and the oversight we operate under to conduct our research."
What they want to do is genetically modify the H7N9 virus in a variety of ways to uncover the functions of its genes -- research that involves so-called "gain of function" experiments. In the letter to Nature and Science, the researchers outlined five different areas they'd like to study: the virus's potential to adapt to different hosts, its drug resistance, its ability to mutate, its potential to become pathogenic and how to develop effective vaccines.
A technician carries out a test on a suspected infected sample using the H7N9 bird flu virus test.REUTERS/Stringer/Corbis
The individual experiments are unspecified but for example, in one study a team of scientists might genetically modify the virus to make it transmissible through the air. Right now, the virus is likely acquired from touching the mucus or feces from infected chickens, and is not passed along to other humans through sneezing or coughing. (As a side note, there is at least one isolated case in China, reported today in the British Medical Journal, of a woman who may have caught the disease from her father. Both died.)
While engineering the H7N9 virus to become airborne makes it potentially more infectious, it gives scientists direct evidence about what it takes for the virus to reach this harmful stage. "For some questions we are asking, gain of function experiments are the only way to obtain correct answers," Kawaoka said.
Instead of being forced to wait and see how many people die during a flu outbreak, scientists would already know which genetic changes make a given flu dangerous. That would make vaccine production a lot easier -- and even allow them to pre-empt a deadly outbreak, if they saw certain mutations.
Without that information, health authorities can only react to flu outbreaks, losing lives in the time it takes to develop a vaccine or anti-viral drug. "It takes six months to get a vaccine in gear," said Dr. Walter Orenstein, professor at Emory University School of Medicine and one of the signatories. "With 'gain of function' studies, we can determine what it would take to make a flu dangerous; we could make a vaccine and store it."
But some in the field think that nuance will get lost on the wider public.
"All this will do is engender horror and debate among those who do not understand the value of gain-of-function research," said Vincent Racaniello, a professor of microbiology and immunology at Columbia University. "No matter how much you explain this work, the H5N1 debacle instilled fear in the world and it will never go away."
"Gain of function is almost always accompanied by loss of function -- gain something, lose something. In the case of H5N1, gain of aerosol transmission in ferrets was accompanied by loss of virulence. It's always that way, which is why gain of function experiments are not a problem. But the world doesn't understand this, and the 'dual use research of concern' proponents -- those who want to prevent certain kinds of research -- don't understand it either."
Blocking the research out of fear would actually make it more difficult to defend against it should it be used to make a biological weapon. Since the changes in the virus that make it deadly are so specific, only researchers with the unique knowledge acquired from gain of function experiments would likely understand how to counter it. And that would lead to quick development of an antiviral agent or a vaccine. "If Dr. Evil did something like that, we'd be ahead of the game," Orenstein said.
"The issue is to lay out on the table that yes there, are risks but also major benefits," he said. "Nothing in life is without risk."