Should scientists be allowed to create extremely aggressive and highly infectious influenza viruses? Dutch virologists have done it and, in the process, triggered a fierce debate over the risks of bioterrorism and the potential release of deadly viruses.
The 17th floor of the Erasmus Medical Center in the Dutch city of Rotterdam certainly doesn't look like the kind of place that could pose a threat to global security. A disco ball hangs from the ceiling in the hallway in front of the elevators, and a bar with a golden beer tap stands in the corner of the conference room.
Everything in this 1960s high-rise building evokes the charm of student life, including the door to Room 17.73, which is covered with colorful stickers. But some view the scientist who sits behind that door as a threat to mankind.
Ron Fouchier, a giant of a man at more than two meters tall (6'6"), has dark circles under his eyes. His life has been stressful lately. "They want to paint me as a homicidal idiot," he says heatedly. He is referring, most of all, to a powerful institution from the United States, the National Science Advisory Board for Biosecurity (NSABB).
In his work Fouchier, a virologist, uses the methods of a branch of research that is as booming as it is controversial. Synthetic biology employs targeted manipulation through genetic engineering to construct new organisms. The 45-year-old's research has even set off alarm bells at the World Health Organization (WHO). This week, Fouchier will appear before an international panel of experts at the WHO to explain his experiments.
Fouchier is attracting so much attention because he has created a new organism. And although it is tiny, if it escaped from his laboratory it would claim far more human lives than an exploding nuclear power plant.
The pathogen is a new mutation of the feared bird flu virus, H5N1. In nature, this virus, which kills one of every two people infected, has not yet been transmitted from humans to humans. So far, a relatively small number of people have caught the virus from poultry, and 336 people have died.
Scientific Wake-Up Call
For years, experts feared that the adaptable virus could soon mutate from being primarily a bird killer to a highly infectious threat to humans. But as the years passed and this did not happen, many hoped that it might not even be possible, and some of the fears subsided.
But now Fouchier's experiments have given the research community a wake-up call. The scientist performed only a few targeted manipulations on the genetic material of the ordinary H5N1 virus and, to make the virus even more dangerous, he repeatedly transmitted it from one laboratory animal to the next.
"In the end, the virus became airborne," the Dutch scientist explains. From then on Fouchier's ferrets, animals that most closely resemble humans when it comes to influenza, transmitted the virus to each other without direct contact, through tiny droplets of saliva and mucus.
Many scientists are particularly impressed by the fact that, at almost the same time, another research team also managed to produce a bird flu virus that could be transmitted via airborne respiratory droplets. To achieve this, virologist Yoshihiro Kawaoka of the University of Wisconsin combined the avian flu virus with the swine flu virus. The newly created superbug is highly infectious, however not particularly dangerous to the ferrets Kawaoka used in his experiments.
Articles Not Published The scientific community anxiously anticipated learning about the details of the experiments. What exactly had Fouchier and Kawaoka done? How had Fouchier manipulated the bird flu virus? And, most of all, must the medical community now fear that the natural bird flu virus will develop in similar ways? Scientists hoped to find answers to these questions in findings that were to be published in the scientific magazines Nature and Science.
But the articles were not published. Officials from the NSABB had called the magazines' executive editors to prevent their publication. Because of the potential risk that the newly created bird flu viruses could be used as biological weapons, the organization asked the journals not to publish Kawaoka's and Fouchier's results, or at least not in their entirety.
This suddenly puts Fouchier at the center of an explosive controversy over biosecurity and academic freedom. Should scientists be allowed to create artificial viruses and bacteria, even if they are dangerous to human beings? What safety standards should be applied to their work? And should their controversial results be published, or is the risk too great that they will be misused as instructions to make biological weapons?
The debate has caused two opposing worlds to collide. The virologists, on the one side, suspect that the bioterrorism watchdogs are being paranoid. The terrorism experts, on the other, feel that the scientists are simply naïve.
'A Door Has Been Pushed Open'
The NSABB censorship came as a shock to most influenza researchers. "I've never seen anything like this," says Hans-Dieter Klenk, an influenza expert in the German city of Marburg. His colleague Stephan Ludwig, a virologist at the University of Münster in northwest Germany, sees the move as a threat to scientific freedom. "A door has been pushed open here that won't be so easy to close again," he says.
For many of the scientists, the idea that terrorists could misuse their viruses as weapons is simply absurd. "If I wanted to kill a lot of people, I would rent a truck, fill it with gasoline and fertilizer and blow it up," Fouchier says testily. Reinhard Burger, president of Berlin's Robert Koch Institute, Germany's federal institution for disease control and prevention, says: "I think the risk of misuse by terrorists is low."
Michael Osterholm, the most prominent member of the NSABB, completely disagrees. "I don't think it's a question of whether terrorists will use infectious pathogens to kill innocent civilians," he says. "It's just a question of when and how they do it."
Osterholm can feel confident that he has support from the highest levels of the US government. Last December, US Secretary of State Hillary Clinton made a surprise appearance at the annual biological weapons convention in Geneva. Such a high-ranking US official had not attended the event in decades.
Clinton spoke of "warning signals," even "evidence" that al-Qaida was trying to recruit "brothers with degrees in microbiology or chemistry." "The nature of the problem is changing," she told the delegates. "A crude, but effective, terrorist weapon can be made by using a small sample of any number of widely available pathogens, inexpensive equipment and college-level chemistry and biology."
To buy some time in the face of so much opposition, 39 influenza researchers from around the world began a 60-day moratorium on all research related to controversial viruses at the end of January. "We realize that organizations and governments around the world need time to find the best solutions for opportunities and challenges that stem from the work," the scientists wrote in an open letter published in Nature.
But the scientists are deeply divided over what exactly these solutions should look like. While some would prefer not to make any changes, Richard Ebright, a molecular biologist at Rutgers University, proposes making research with artificially produced bird flu viruses subject to strict regulation, as is the case with pox viruses.
But if such regulation is imposed, it will have to apply to more than avian flu viruses. Similarly controversial experiments have also been conducted with other pathogens:
-- In 2001, a mouse pox virus that was 100-percent fatal was accidentally created in an Australian laboratory. The genetic makeup of the killer virus was published.
-- In 2005, scientists at Stanford University calculated that a terrorist attack with botulinum toxin in milk could kill 568,000 people. The Bush administration tried in vain to prevent the paper from being published.
-- Nature recently published instructions on how to create the plague virus.
-- The influenza virus that caused the devastating Spanish Flu in 1918 has been completely recreated.
But security authorities only seem to be getting uneasy now, as they suddenly ask themselves a fundamental question: How great is the risk that such pathogens could escape from the laboratory, and that scientists would trigger precisely the devastating pandemic that they are in fact trying to prevent with their research?
Differing Safety Levels
Most virologists feel that the risks are justifiable. "We have set up a laboratory here that has three separate physical barriers," Fouchier insists. The core of the laboratory consists of wardrobe-sized boxes outfitted with glass windows, each containing four cages of ferrets.
Two pairs of black rubber gloves are poking into the boxes. "Before we take swabs from the animals or inject viruses into the nostrils, we put steel gloves on over the rubber gloves," says Fouchier. For security reasons, he is not even willing to provide the exact location of the laboratory.
The low pressure in the boxes provides additional protection, because it is intended to ensure that even in the event of a leak, no viruses will escape. In addition, everything that leaves the boxes is disinfected with acetic acid in a safety area.
"And if I did infect myself, we have isolation wards in the adjacent hospital," Fouchier explains. "It's practically impossible for one of my team members to accidentally take the virus along into the Rotterdam subway."
Nevertheless, not even Fouchier can deny that pathogens have escaped from highly secure laboratories. The "Russian flu" of 1977 may have been triggered by a lab virus. SARS, a respiratory disease, almost returned when laboratory workers became infected with the coronavirus during their work. A scientist in Chicago even died of SARS in 2009.
Hundreds of new virus laboratories have been established worldwide in recent years, and highly dangerous pathogens are used in a large share of these laboratories. "The risk of a virus being released accidentally is considerable," says critic Ebright.
That, says Ebright, is why future research involving bird flu viruses should only be done in laboratories with highest so-called biosafety level, BSL-4. Currently only the second-highest level, BSL-3, is required. During their experiments, Fouchier and Kawaoka only wore lab coats and breathing masks, not the "spacesuits" that virologists wear when they are working with pathogens like the Ebola virus.
'An Early Warning System'
Fouchier would prefer to take things a step further and send his pathogen to other labs around the world. "We are at the very beginning, and we need as many scientists and their ideas as possible, so that we can understand why this new virus is so contagious," he says.
In the end, whether the experiments with Fouchier's super-flu virus will continue or possibly be stopped altogether will probably not be determined by issues of safety, but by their potential benefits.
The situation is clear to Fouchier. Using his killer virus, he wants to find out which mutations in the genome are responsible for the extreme infection rates. "We'll know where to look in the future," says the virologist, who hopes that his research will allow him to develop an "early warning system for pandemics."
But this is precisely what others see as an illusion, noting that the monitoring of poultry and especially pigs, in which new viruses develop with particular frequency, is still far too incomplete. A colleague who knows Fouchier's work very well says that the experiments are "nothing more than a piece of the puzzle." Translated from the German by Christopher Sultan