Balinese government officials prepare to cull chickens as a precautionary measure to prevent the spread of bird flu, at a market in Denpasar, Bali, Indonesia on April 26. (Firdia Lisnawati/AP) 
 
 The journal Nature, after much debate and delay, on Wednesday published a paper in which scientists describe how they engineered a part of the deadly H5N1 “bird flu” virus to become more transmissible in mammals. 
 
 The research, led by Yoshihiro Kawaoka of the University of Wisconsin, was one of two experiments that a federal advisory panel had asked journals to hold off publishing because the papers might provide a how-to guide for terrorists or mischief-makers. The panel later dropped its objections after it became clear the engineered viruses were less virulent than had been feared. 
 
 Since it emerged in Hong Kong in 1997, H5N1 influenza has killed millions of chickens, mostly in Asia. People are rarely infected, but when that happens they are likely to die. Since 2003 there have been 602 human cases and 355 deaths. 
 
 In the lab, Kawaoka started with an H5N1 strain that had killed several people in Vietnam in 2004. He isolated the gene for “hemagglutinin,” which is most responsible for contagiousness. He put into it two mutations that allow the flu virus to attach more easily to cells in a person’s throat. 
 
 He then combined that doctored gene with the “normal” genes from the strain of H1N1 flue that caused the human flu pandemic in 2009. Two more mutations in hemagglutinin appeared during lab experiments and after ferrets — which stand in for people in flu studies — were infected with the virus. 
 
 Together, the four mutations made the engineered virus transmissible through the air, although it didn’t kill the ferrets who caught it, or even make them very sick. Whether “wild” bird flu virus containing them would be both contagious and deadly isn’t known. 
 
 However, the experiment has given scientists an idea of what mutations to look out for — which was the purpose of the research from the beginning. 
 
 One of the mutations is already widespread in H5N1 strains circulating in the Middle East. Some of those strains also carry a mutation in a different gene that makes growth in human cells easier. 
 
 “These viruses may be several steps closer to those capable of efficient transmission in humans and are of concern,” Kawaoka and his colleagues wrote in their Nature article. 
 
 A second paper, by Dutch scientist Ron A. M. Fouchier, that made a more contagious bird flu virus using other methods, is awaiting publication at the journal Science. 
 
 The National Science Advisory Board for Biosecurity, a panel of independent experts that advises the federal government, in December asked the two journals to hold off publishing the papers while researchers and governments thought about how to handle this kind of research. In late March the board looked at the experiments more closely and said it no longer opposed publication. ||||| A poultry seller in Vietnam, which is still struggling with new cases of bird flu. (Hoang Dinh Nam, AFP/Getty Images / ) 
 
 In a long-awaited study that helped prompt a contentious debate over the wisdom of conducting research that has the potential to help as well as harm, scientists reported Wednesday that they had engineered a mutant strain of bird flu that can spread easily between ferrets — a laboratory animal that responds to flu viruses much as people do. 
 
 That means that bird flu has "the potential to acquire the ability to transmit in mammals," said University of Wisconsin virologist Yoshihiro Kawaoka, who led the study. 
 
 Only a few mutations were necessary for the transformation, he added, which suggests that a more contagious strain of bird flu could emerge on its own without targeted prodding by scientists in the lab. 
 
 Kawaoka's discovery, published online after a months-long delay by the journal Nature, dampens hopes that the deadly H5N1 virus simply wasn't capable of becoming a highly contagious bug in mammals, including humans. 
 
 He and his team developed a hybrid bird flu virus that combined an H5 hemagglutinin gene — which helps viruses bind to host cells — with genes from 2009's pandemic H1N1 flu, also known as swine flu. 
 
 Using a sort of selective breeding to favor flu strains whose H5 protein could bind with human rather than bird host cells, the researchers developed a version of the virus with four mutations in its H5 that sickened ferrets. 
 
 The pathogen traveled in respiratory droplets through the air to infect ferrets in adjacent cages. It did not kill any of the animals used in the study. 
 
 Richard Webby, a virologist at St. Jude Children's Research Hospital in Memphis, Tenn., said that the changes in the virus Kawaoka's team identified had all been seen before, but that scientists had not recognized that together they could make a flu virus spread more easily among mammals. 
 
 "It's a great place to start looking for exactly what's going on," he said, noting that researchers still don't understand how changes in host organisms affect transmissibility. 
 
 The publication of Kawaoka's paper comes after months of debate over his research and experiments conducted in the lab of Dutch virologist Ron Fouchier, who has also developed strains of bird flu that can pass between ferrets. 
 
 The worry, voiced by biosecurity experts, was that nefarious-minded people could use details provided in the papers to turn bird flu into a biological weapon of sorts and inflict widespread harm. 
 
 In the last 15 years or so, the H5N1 virus has killed millions of chickens and ducks. Very few people — 602, according to the latest World Health Organization estimate — have been infected since the latest outbreak in 2003, but 355 of them died. That has fueled concerns that a contagious strain of the virus could spawn a pandemic, potentially causing millions of deaths around the world. 
 
 Fear that a pandemic strain could emerge in nature prompted scientists to study its potential to mutate, so that they could monitor new variants as they arise and get a head start on developing a vaccine and treatment. The National Institutes of Health helped fund Kawaoka's and Fouchier's studies in high-security labs. 
 
 When the scientists were ready to publish their results, critics said the research could be used as a recipe for bioterrorism — assuming a dangerous strain of the virus wasn't stolen directly from a laboratory. 
 
 A U.S. government advisory panel recommended in November that Nature as well as Science, the journal that planned to publish Fouchier's research, remove sensitive details from the papers. It was an unprecedented step. 
 
 The journals agreed to delay publication and virologists put their H5N1 research on hold while the scientific and security communities debated their next steps. Ultimately, the advisory panel decided the papers were safe to publish, but the release of Kawaoka's research — and the expected publication shortly of Fouchier's — won't mark the end of the conversation, scientists said. 
 
 "There are still a lot of unknowns about how this will be dealt with going forward," Webby said. 
 
 In the meantime, Kawaoka said he hoped his research would help public health workers trying to fight the spread of H5N1 by suggesting useful mutations to incorporate in vaccines or to track as the virus spreads. 
 
 One of the mutations his team identified is already circulating in viruses in the Middle East and Asia, he said. 
 
 eryn.brown@latimes.com
– The journal Nature has published a controversial paper describing how University of Wisconsin scientists created an airborne strain of H5N1—aka "bird flu"—that was transmissible in mammals. A federal panel had asked Nature not to publish the study, and a similar one from a Dutch virologist, fearing they might provide a handy DIY guide for bioterrorists, the Washington Post reports. They eventually dropped their objections, however, once they realized that the more-contagious virus was also less deadly. Researchers added two mutations to a deadly H5N1 strain, mixed in some swine flu genes, and released it on a group of ferrets. The ferrets caught the virus easily—but didn't die or even get very sick. The research was conducted to understand how the virus might mutate in nature—and indeed, scientists say the process was simple enough to occur naturally, the LA Times reports. "It's a great place to start looking for exactly what's going on," says one virologist.