Fatal Immunity and the 1918 Flu Virus

Jan. 17, 2007— -- The flu virus that killed roughly 50 million people worldwide in 1918 is alive and still very deadly. New research sheds light on how the 1918 Spanish flu virus might have killed so many people so quickly -- and opens new horizons for researchers who hope to avoid a flu pandemic today.

Scientists regenerated the 1918 virus Jurassic-Park-like from a frozen corpse two years ago. Now scientists have discovered that the regenerated virus can kill monkeys much as it killed humans in 1918, by kicking the immune system into dangerous overdrive, which ultimately kills the infected host.

A group of researchers infected one group of monkeys with the 1918 virus, and one group of monkeys with a conventional human flu virus -- called the K173 virus. Within 24 hours, each of the 1918-virus-infected animals became visibly ill, according to the study report.

The report is published in today's issue of the journal Nature.

The monkeys were depressed, the study authors report, and didn't want to eat or drink. They coughed, sniffled and were euthanized within eight days of infection because their symptoms were so severe.

Monkeys infected with the K173 virus didn't show serious signs of a flu infection. Those animals were also euthanized within eight days of infection.

A Fast-Moving and Powerful Virus

When doing autopsies of the 1918 flu and K173 infected monkeys, scientists could see to what extent the 1918 flu virus had ravaged the monkeys it infected.

Scientists easily recovered the 1918 flu virus from the throat and nasal cavities of the infected animals, and found in some monkeys that the virus had spread to the heart and spleen. Their lungs were covered in lesions, and the infected lung tissue -- which covered 60 or even 90 percent of the lung within six to eight days after infection -- was filled with watery and bloody liquid.

The lungs of monkeys infected with the K173 virus had actually begun to heal themselves within six to eight days after infection. The autopsy proves that the 1918-virus-infected monkeys were very sick when they were put down.

The 1918 Spanish flu was the deadliest human plague of the 20th century. The pandemic was unusually severe, causing upward of 40 million deaths worldwide -- including 675,000 Americans. Most of the victims were healthy people in the prime of life.

So what makes the 1918 flu virus so much more deadly than, for example, the K173?

Scientists discovered that the 1918 flu virus is so aggressive -- it multiplies and spreads quickly throughout the body -- that it causes the immune system to overreact.

"The [1918 flu] virus causes more destructive damage to the body and does so early in infection because it changes the body's immune response," said Dr. William Schaffner, professor and chairman of the department of preventive medicine at the Vanderbilt University School of Medicine.

In the face of the 1918 flu virus, the immune system becomes "less effective," Scahffner said.

"Some parts of the immune system are depressed and work less hard, but other parts become unregulated and work harder."

In other words, the 1918 flu virus somehow corrupts our only defense against it.

Answers to a Medical Mystery

The finding finally answers the question of what made the 1918 virus so deadly.

"After all, the 1918 strain killed tens of millions of people and it had to be able to do something that other viruses cannot do," said Philip Alcabes, an infectious-disease epidemiologist and associate professor of public health at Hunter College, City University of New York.

But the research does not tell us anything specific about contemporary flu strains, like the H5N1 avian flu virus that has infected birds and some humans in several Asian countries.

Scientists fear that the H5N1 virus -- or some yet-unknown virus -- will soon explode into a pandemic.

"While [this report] is a reminder that a flu virus can develop extraordinary virulence under certain circumstances, there is no reason to expect that circumstances [if we had a pandemic today] will resemble those in 1918," said Alcabes.

The research does suggest some "distant goals on the horizon," said Schaffner.

"This is basic science. It doesn't immediately suggest a new therapy against the H5N1 virus, but it suggests new ways for scientists to look at or study that virus," he said.

Bottom line -- new research on the regenerated 1918 flu virus shows just how deadly the virus really is. The new research could eventually lead scientists to a new therapy, to a new way of treating deadly flu viruses.

But while scientists continue to study the deadly regenerated virus, is there any way the virus could escape? Just like the Jurassic Park DNA slipped out of science's control, could we have a real life 1918 flu pandemic back on our hands?

Probably not. So don't call Steven Spielberg yet.

Security Measures

The 1918 virus is studied in a biosecurity level-four laboratory -- the highest level of security possible for a scientific lab.

"Biosecurity" refers to special security measures designed to prevent the loss, theft, misuse, diversion or intentional release of pathogens or toxins, such as the 1918 flu virus.

A level-four lab is equipped with special airlock entry, shower exits and secure waste disposal. Scientists have to wear special suits and breathe filtered air. A level-four lab is "a highly contained, elaborately guarded laboratory. It is the ultimate guarded laboratory," said Schaffner.

So the virus should be safely under lock and key there, excepting an unforeseen disaster.

"We are never sure. It is a continuing challenge," Said Dr. Ann Marie Kimball, director of the Asia Pacific Economic Cooperation Emerging Infections Network and a professor at University of Washington School of Public Health and Community Medicine.

Despite the unavoidable uncertainty, there is little reason to worry that the 1918 flu will come back.

"Any virus in a laboratory could, in theory, escape but … to the best of my knowledge, the laboratory involved here is a most responsible one," said Dr. Don Henderson, resident scholar at the Center for Biosecurity at the University of Pittsburgh Medical Center and dean emeritus at the Johns Hopkins Bloomberg School of Public Health. Henderson is a former adviser on bioterrorism to president Bush and led the World Health Organization's campaign against smallpox in the 1960s.

Should scientists be working with such a deadly virus?

"My answer would be an unequivocal yes," said Henderson.

"We need to learn all we can about pathogens in order to develop means of our own for prevention or therapy."