Dr. Johan Hutlin at the Minuteman Project, giving an interview, October 17, 2005



http://www.cbsnews.com/stories/2005/10/ ... 7888.shtml

U.S. A Step Behind Bird Flu

CBS) Good news: scientists have not only reconstructed the genetic sequence of the 1918 flu virus, which killed as many as 50 million people, they've learned that it was a bird flu that jumped to humans who then passed it on to each other.

Bad news: there are a lot of similarities between the 1918 virus and the new flu that's killed millions of birds, and at least 60 of the 116 people who've gotten it as it's begun to march across Asia. It's those similarities that have driven this past week's alarming headlines, CBS News correspondent Martha Teichner reports.

"The world is obviously unprepared or inadequately prepared for the potential of a pandemic," says Health and Human Services Secretary Michael Leavitt.

Leavitt was a speaker at an international conference on flu preparedness in Washington attended by 80 nations. Some of whom it seems are way ahead of us in stockpiling the antiviral drug Tamiflu. So if a pandemic is truly on the way, the United States won't have enough.

No doubt, recalling Hurricane Katrina the president was all over the flu issue at his news conference talking about quarantines.

And who best to be able to effect a quarantine: one option is the use of a military that's able to plan and move.

On Friday, President Bush met with drug company officials, urging them to speed up production of flu vaccine.

So why the urgency and why now?

"The lethal capacity of this virus is very, very high, so it's a deadly virus that humans have not been exposed to before. That's a very bad combination," says Dr. Irwin Redlener, director of the National Center for Disaster Preparedness at Columbia University.

"We're only missing one more piece before it becomes a pandemic and that is the ability to be transmitted from person to person as opposed to simply from birds or fowl to humans," Redlener explains.

Which is exactly what happened in the 1918 flu.

Half a million Americans died of it. Maybe 20,000 die in a normal flu season.

In WWI, more soldiers died of the flu than on the battlefield. Living together in close quarters, they were literally attacked in their beds. They got the sniffles one day and were often dead the next.

"People described military camps: they say the bodies were stacked up like cordwood," New York Times science writer Gina Kolata says.

Kolata wrote a book about the 1918 flu. "Never in the recorded history of the world has an infectious disease killed so many people in such a short time," Kolata says.

Most vulnerable were children under 15 and adults between the ages of 20 and 40. For every one person who died, something like 100 got sick.

We told you it was good news that scientists have managed to recreate the 1918 flu. Here's why:

"We can take these genes and sequence them," microbiologist Adolfo Garcia-Sastre says.

Using its genetic signature to clone the virus, Garcia-Sastre and his colleagues at Mt. Sinai school of Medicine in New York are on the verge of determining exactly how a virus mutates and turns deadly, triggering a pandemic.

"We'll be able to predict this type of events," Garcia-Sastre says. Garcia-Sastre added that his team hopes to predict not only when the virus might jump from bird to man and then man to man, but also the lethalness of the flu.

Researchers argue that any risk caused by recreating the virus is offset by what can be learned, but none of this would even be happening if it weren't for an amazing medical detective story.

"This process has been a nine-year effort from that first moment," Dr. Jeffrey Taubenberger says.

Taubenberger, a molecular biologist at the Armed Forces Institute of Pathology in Washington was the lead detective: the man who tracked down the 1918 flu virus and then mapped its genome.

"What we're doing is analyzing a virus right out of the lungs of people who died in the prime of their lives, soldiers who were just in their 20's when they died," Taubenberger explains.

Why soldiers? In a way, thanks to President Lincoln, he became interested in what soldiers were dying of. So, from that day to this, tissue samples have been collected for study. There are now five million little wax blocks and 30 million slides.

When we first met Dr. Taubenberger in 1999, he explained that he had thought, maybe, somewhere in this amazing archive, he could find a sample that contained the 1918 flu virus.

He found not one, but two.

Enter Dr. Johann Hultin, a retired pathologist from San Francisco. In 1951, he had tried and failed to extract the virus from flu victims frozen into the ground in Alaska. The technology simply wasn't sophisticated enough then, but when Hultin read about Taubenberger's discovery, he tried again.

This time he found the bodies decomposed. All except one.

"That was a great moment. Like that," Hultin snaps his finger, "I knew it."

The virus in the lung tissue matched the two soldiers', proving it was the 1918 flu.

"The long-term goal would be to apply this information in a way that ultimately might be able to prevent a pandemic from ever happening again," Taubenberger says.

But what if it does? A copy of a Bush administration plan for dealing with a flu pandemic was just leaked to the New York Times. It outlines a worst case scenario: 1.9 million Americans dead and 8.5 million hospitalized.

It talks about a domestic vaccine production capacity of 600 million doses within 6 months, more than 10 times the present capacity.

"There is an h5n1, an avian flu, bird flu vaccine. They first made a two million dose batch and now they're doing a 20 million dose batch," says Doris Bucher.

A far cry from 600 million. Bucher heads a lab at the New York Medical College that creates flu vaccines.

"The thing about flu is that it's so mutable," Bucher says.

Which is why making a vaccine requires tailoring it precisely to whatever form the flu virus finally takes and that requires time, months we may or may not have.

"We started from zero five weeks ago to all this hot, hot spotlight on pandemic flu, but we're not going to be ready," Dr. Irwin Redlener says.

If we're lucky, it won't happen. At least, not this year, and we buy ourselves time to be ready. We can only hope.
© MMV, CBS Broadcasting Inc. All Rights Reserved.
------------------------

A few weeks before his 73rd birthday, Johan Hultin left his Nob Hill home to go hunting in a remote and frozen Alaskan graveyard for the deadliest killer in human history.

The Indiana Jones of the scientific set, Hultin was hell-bent on uncovering the secrets behind one of the world's most baffling natural disasters, a flu virus that felled tens of millions of people in the waning days of World War I,

then promptly vanished.

Hultin had visited the Alaskan burial ground once before - 46 years earlier as a graduate student working on his doctoral thesis.

His mission was the same both times: to find the virus living in frozen bodies, to root out the genetic mystery of the 1918 influenza pandemic, a catastrophic outbreak little known to the general public but one that to this day haunts the medical community.

But in his first foray to the distant cemetery, Hultin found no trace of the mutant killer bug, a failure that would bedevil him for four decades.

Four years ago, he decided to try again.

On his solitary expedition, the San Francisco physician carried just one tool: a pair of garden clippers borrowed, without permission, from his wife.

Implausibly, Hultin succeeded.

He found, buried in the subarctic permafrost, a corpse containing remnants of the elusive 1918 virus. The tissue Hultin retrieved from that corpse is now helping federal researchers unlock the microscopic secrets behind the pandemic.

"I knew it, I knew the virus was there," Hultin exulted. "That was one of the great days for me."

He's had many others.

A restless and wildly curious spirit, the 77-year-old iconoclast is not only a respected scientist, but also a carpenter, inventor and even an automotive safety designer.

He's also somewhat of a prophet when it comes to bioterrorism. Half a century before biological warfare became part of the daily vernacular, Hultin started worrying about the potential of weaponized pathogens - and established a special lab to study anthrax and other deadly organisms.

"I just wanted to be ready," he says in characteristic understatement.

Though Hultin is a forensic pathologist by profession, he's as much at home scaling mountains as he is peering into a microscope. Now retired, Hultin travels the globe with the energy of a college backpacker on spring break.

Last year, with only the help of his similarly intrepid wife, Eileen, he painstakingly restored an ancient labyrinth in western Iceland, lugging hundreds of heavy stones rebuilding the historic maze.

This year he went on an extended hike in England. Then Turkey. Next up: Siberia in the spring.

"I'm going to settle down when I get old," Hultin says. "I have to do these things now. I'm afraid the warranty will run out."

Insatiably inquisitive, he's spent his life searching for "things . . . that offer a steep learning curve." No matter where his passions or projects have taken him, Hultin has followed a simple credo: never quit.

Born in Sweden, he immigrated to the United States in 1949, and earned a master's degree in microbiology at the -University of Iowa.

In 1950, curiosity led him into what was then an arcane study of anthrax, clostridium botulinum, and other poisonous agents. With the blessing of officials at the University of Iowa, Hultin set up a one-man diagnostic lab - during his spare time - to study freeze-dried samples of anthrax and other bacteria, testing them on mice and guinea pigs.

"I was worried that anthrax and other organisms could be used against us," Hultin says. "I wanted to be able to diagnose it in the lab."

Neighbors and friends scoffed. Biowarfare, they said, was mere science fiction.

"People would tell me I was wrong," Hultin shrugs. "I -didn't pay attention.

Other scientists around me had no doubt that it would come sooner or later."

It would take 51 years but Hultin - to his regret - would be proved right. In the nation's first deadly confrontation with bioterrorism, five people were killed and a dozen sickened in anthrax attacks in October and November, a frightening assault on a country already reeling from the terrorism of Sept. 11.

"I knew it was coming, I -didn't think it would take this long," Hultin says ruefully.

Yet, far more grievous harm may lie ahead, he thinks.

"It's a very dangerous new world we are entering into," Hultin says.

"Theoretically, one can design organisms specifically for biowarfare, diseases we have never seen before. They can be made antibiotic-resistant, viral agents that could be spliced with the genetic code for ebola or smallpox and spread easily like influenza from person to person," he says. They could cause terrible devastation.

"This is highly sophisticated work, but we have to be aware of the potential. It may not come tomorrow or the day after or the next year but it could come.

"We should not live in fear," he says, "but live with fear and do whatever we can to use fear as a propellant to protect ourselves."

Propelled by the same curiosity that had driven him to study anthrax, Hultin in 1951 decided to tackle the mystery behind the 1918 flu virus, the most dangerous virus the world has ever seen, he says.

The number of casualties is forever unknown: Epidemiologists from the 1920s put the death toll at 21 million, a number generally acknowledged to be an undercount.

"It was a plague so deadly that if a similar virus were to strike today, it would kill more people in a single year than heart disease, cancers, strokes, AIDS and Alzheimer's disease combined," says Gina Kolata in her acclaimed book,

"Flu - The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus that Caused It."

Writes Kolata, "The epidemic affected the course of history É killing more Americans in a single year than died in battle in World War I, World War II, the Korean War and the Vietnam War."

The virus struck with appalling speed, devastating those seemingly least susceptible - young adults. Victims, fine at sunup, would be near death by nightfall.

During one particularly dreadful five-week span in October and November of 1918, 2,021 people died in San Francisco alone.

"Moving-picture" houses were shuttered. Gauze masks were compulsory in San Francisco and elsewhere with violators subject to arrest - mask-wearing was "a patriotic duty for every American citizen," proclaimed California's then- governor, William D. Stephens. The San Francisco Board of Supervisors, displaying the contrariness that would characterize it for decades to come, voted against mandatory masking, contending it was ruinous to business and added to public hysteria.

Remarkably, as swiftly as it emerged, the virus retreated, leaving behind a chilling puzzle that continues to confound scientists who are convinced a similar pandemic will someday strike again.

"The 1918 virus demonstrates that an influenza virus can be devastating," says Dr. Ann Reid, a microbiologist at the Armed Forces Institute of Pathology in Maryland who has been working on the baffling bug since 1995.

"There could be a similar sequence of events that could lead to a new, emergent virus that could be just as lethal. But until we know more about the 1918 virus, we -won't know where to look."

Young Hultin, as a graduate student in 1951, had a plan: If he could find ice-bound traces of tissue containing the virus, it would allow scientists to reconstruct the genetic makeup of the virus.

His target: Brevig Mission Alaska, a village ravaged by the pandemic. Of 80 residents, 72 died, all within five days, a mortality horrific by any measure.

For nearly two weeks, in frigid weather, Hultin dug through a mass grave on the outskirts of the village. His was a mission fraught with potential peril - if the virus was alive, he might unleash it again.

"This was a great adventure for a little boy from Sweden. I had never spoken to Eskimos before," Hultin says. "I thought I was going to find the virus alive, I really did."

Adhering to the most stringent safeguards of the time, Hultin recovered lung tissue from four bodies. But the tissue came up short, there was no way to trace the lethal influenza from it.

"All the dreaming was gone," says Hultin. "We could not grow the virus, it would not replicate itself."

The virus waited through the decades as Hultin moved on with his life.

After graduating from the University of Iowa College of Medicine and working at the Mayo Clinic, Hultin in 1957 - by then a husband and father of four - bought a rusty, five-ton cattle truck for $250, strapped on all his belongings and moved with his family to Marin County.

Over the next three decades, he worked at several Bay Area hospitals, including St. Mary's in San Francisco and Los Gatos Community Hospital.

When a patient died after a car accident, Hultin became obsessed with automotive safety, and devoted spare hours to the task for more than a dozen years. Starting with the family car, he tinkered with the seat belts, seat backs, shoulder harnesses, adding surplus aircraft seats, dashboard padding.

By today's sleek standards, Hultin's brainchild was an ungainly behemoth, looking like an early SUV led by a snowplow, actually a giant set of detachable bumpers. Still, what Hultin's cars may have lacked in grace, they compensated for in safety.

In 1964, he won an auto safety award "for lifesaving achievement in the service of health." In 1968, the U.S. Department of Transportation commissioned him to set up a unit of automotive safety engineering at Stanford Research Institute.

While trying to make the roads safer, Hultin became a proficient mountain climber. At an age when most climbers would have hung up their crampons, Hultin insisted on an employment clause guaranteeing him time off every year to make one major trek.

In 1982 when he was 57, he became the oldest person to ski Mustagh Ata, in China. While descending the nearly 25,000-foot peak, Hultin became separated from his fellow skiers. With nightfall, his peril mounted - if he fractured a leg, if he fell into a crevice, he'd never be found. For hours, amid the darkness and solitude on the vast expanse of snow, Hultin precariously skied, guided only by instinct and the light of a few stars. Finally, at 2 a.m., he found his way to camp.

"It was a tough spot to be in," he remembers. "You -can't imagine how cold the damn thing was."

In 1985, when Hultin was 60, he married his second wife, Eileen (he'd divorced in 1973), and vowed to give up mountain climbing after she agreed to "let me do one more."

On his final ascent, he reached the summit of a never-before-climbed Pakistan mountain, Karakoram, now dubbed "Old Codger's Peak."

"I'm married to a very wonderful, eccentric man," says Eileen Hultin, a retired docent at Stanford University. "I knew when I married him, there was no curtailing his desire for adventure. It's a very exciting life. I never know what to expect next."

Hultin formally retired from Los Gatos Community Hospital in 1988, whimsically choosing as his final workday Dec. 21, the shortest day of the year.

Retirement gave Hultin more time for another long-standing project.

For 32 years, he's been building a cabin in Alpine County, about 40 minutes from the rural hamlet of Arnold - building not a mere woodsy shack but a precise replica of a 14th century Norwegian mountain dwelling called Vastveit Loftet.

Hultin first saw that structure, now housed in a Swedish museum, when he was about 10 years old.

"It was strikingly beautiful to me," he says. "I never forgot it."

Hultin built it all, felling the timbers (his 1963 Christmas card shows his kids astride a giant log), installing the plumbing. A perfectionist, he built the chimney three times before he was satisfied. The front door took four tries.

Hultin's wooden masterpiece should stand 800 years, not just a random guess - he's studied the science of wood erosion.

"I've been accused, or complimented, of thriving on adversity," Hultin says.

"I've asked myself what is the satisfaction in this house? It's not to own it or use it, but it's in the building process, to see the house coming out of my hands."

Despite his accomplishments, Hultin's long-ago failure in Alaska continued to nag at him.

In 1997, he learned of the work of a government scientist, Dr. Jeffrey K. Taubenberger, a molecular pathologist at the Armed Forces Institute of Pathology who was attempting to map the 1918 virus using minute specimens collected in 1918 and embedded in wax.

Hultin wrote a cordial, stupefying letter: Would Taubenberger be interested in tissue if Hultin could dig it up? Stunned, Taubenberger said yes.

Hultin set out alone for Alaska a week later.

Ironically, at the same time, a similar, considerably higher-profile expedition was under way on a remote Norwegian island some 800 miles from the Arctic Circle.

Led by Kirsty Duncan, a young geographer at the University of Windsor and the University of Toronto, the mission was to determine if the bodies of seven young miners, who'd crossed the Norwegian Sea in 1918 in search of work, contained frozen remnants of the killer virus.

According to "Flu," by New York Times reporter Gina Kolata, Duncan believed the bodies might yield answers, but the project was rife with uncertainty. If the bodies had been buried in an area subject to melting and refreezing, hope of finding the virus would vanish - the influenza virus was delicate, if exposed to room temperature for even one hour it would die.

Duncan put together an impressive, well-financed team including world-class scientists from England, Canada and the U.S. The costly project, taking about four years to plan, generated worldwide publicity and debates over the potential danger of releasing live flu viruses from the bodies of the long- dead miners.

That mission ended in disappointment - the ground the miners were buried in had thawed and refrozen.

By contrast, Hultin's homespun expedition, which took mere days to plan, generated no publicity and cost $3,200, which Hultin himself paid.

In Alaska, he found the village had changed considerably, now with a post office and mayor. Hultin met with the village matriarch.

"She remembered hearing about my first visit," he says. "I told her it was a terrible day when that disease came to this village and now it is possible to prevent that by analyzing the lungs of the victims and to make a vaccine from the dead virus."

She called the mayor. Three hours later, the village council assembled to meet Hultin and hear his proposal. They granted permission to reopen the graveyard.

That very afternoon, Hultin started digging with the help of several young men.

"I could have done it myself, but it would have taken weeks, so I accepted their help," he says.

That night, and for the rest of his week in Alaska, Hultin slept on the floor of the village school.

"I was used to terrible conditions," he says. "I've slept in the snow for months. To go back to Alaska, to dig in the permafrost, by comparison it was a Sunday picnic."

Four days after opening the ground, Hultin discovered, seven feet deep, a woman's corpse. Fancifully, he dubbed her Lucy. Later he learned that Lucy had been an obese woman who died from the flu in her mid-20s.

Using his wife's pruning shears, Hultin opened Lucy's mummified rib cage. There he found two frozen lungs, the very tissue he n-eeded.

"Her lungs were magnificent, full of blood," Hultin says.

He removed the lungs, sliced them, placed them in preserving fluid. Then he and the village helpers replaced the graveyard sod.

There was just one last task for him before he left Alaska. On his first trip, 46 years earlier, the village cemetery had been marked by two large crosses. Those crosses were now gone. Hultin wanted to honor the memory of the dead, so he worked through the night in the school workshop building replicas of the crosses, one 11 feet tall, the other 7 feet. He installed them the next day, then flew home.

Back in his San Francisco kitchen, Hultin set out his specimen bottles containing Lucy and boxed them for shipping.

"I was afraid to send them all at once," he says.

So he shipped one box through UPS, one through Federal Express, another through the U.S. postal system.

Ten days later, the call came. The dumbfounded scientists, to their joy, had found in Lucy's lungs genetic material from the 1918 virus.

"When he wrote and said he would try to get more samples, it hardly seemed possible that all of the pieces could come together," says Dr. Reid of the Armed Forces Institute of Pathology. "It was incredible that he was able to do all this."

"Dr. Hultin is an amazing man, an inspiration to us. We were really thrilled when one (of his specimens) turned out to be positive."

Hultin is more modest.

"The virus sat and waited for me," he says. "Maybe it was good I -didn't find it before, technology -wasn't ready for it yet. Also, if I had found it, I would have become a famous person, my future would have been very narrow. I - didn't find it, so I had the chance to do other things."

Using Lucy's recovered tissue as their road map, scientists are mapping the virus' gene sequence. They've finished about a third of it.

Eventually, they hope to answer a near-century-old riddle: Where did the virus come from? Did it circulate for years or surface right before the pandemic?

"The really big question is why was this virus so much more lethal than other viruses?" ponders Reid. "It is possible that it had to do with people's immune systems in 1918, that they had an exposure system that made them especially vulnerable."

Whether the virus would be as lethal today is open to dispute. Some believe the advent of antibiotics and other health measures would lessen the impact. Others disagree.

Influenza, even in its relatively mild common form, is still a serious illness, causing on average 20,000 deaths in the U.S. annually, say the Centers for Disease Control. Yet it's not taken seriously enough, experts say.

"There's an acceptance that certain things happen and annual influenza outbreaks are something we are used to," says Dr. Ray Strikas, a medical epidemiologist with the CDC's National Immunization Program.

Strikas, like many others, believes another influenza epidemic is inevitable.

"The flu clock is ticking, we just -don't know when it's going to happen," he says. "Some say we are overdue. It should give us all pause.

"It was really impressive what Dr. Hultin did. You could argue that he took some chances with his own health. It's a theoretical concern when digging for frozen bodies that the virus could aerosolize. But many people -wouldn't have taken Dr. Hultin's initiative."

Last June, as part of his lifelong interest in the connection between food and chronic disease, Hultin took yet more initiative.

He traveled to southeast Turkey and found growing on the hillside of an extinct volcano 'Ãâ€