2008: April 14th Good News (Naked Nomad Leaves Multi-million Dollar Estate to Sister, Anthrax Nasal Spray Vaccine Effective in Early Tests, more...)

Hello all,

Well, I am not quite finished unpacking, but the hard stuff is pretty much done. I am waiting on a bookshelf to shelve my books, and I still have to organize a few of the closets, but I can now live quite normally, and unpack more at leisure. This means I've finally got some time! So, here I am, posting again for you. :)

Today I'd like to draw your attention to two intriguing stories. One is about a man who was covered in warts that had been growing for so long he became known as "tree man. The story is about the recent successful removal of his warts. The other is about the man who fell into the Mt St. Hellens Crater, and lived to tell of it. Both are incredibly interesting in their own way.

Anyway, I hope that you all enjoy today's posts. I'm very happy to be able to post them for you.



Today's Top 5:
1. Blood Stem Cells May Repair Heart (Times of India)
2. Hope is Free at This Shop (Denver Post)
3. Tree Man 'Who Grew Roots' Hopes to Marry After 4lb of Warts Removed (Telegraph UK)
4. Man Fell into St. Helens, Lived to Tell Tale (Seattle Times)
5. Naked Nomad Victor Flanagan Leaves Multi-million Dollar Estate to Sister (News.com AU)

Honorable Mention:
1. Norway's King Opens New Opera House (BBC)
2. "Extinct" Plants Found in Remote Australia (Yahoo news)
3. Cancer Therapy Without Side Effects Nearing Trials (wired.com)
4. Magic Goes on as Tokyo Disneyland Turns 25 (Yahoo news)
5. Nose Spray Anthrax Vaccine Effective In Early Tests (Science Daily)


Today's Top 5:

1. Blood Stem Cells May Repair Heart
http://timesofindia.indiatimes.com/Blood_stem_cells_may_repair_heart/articleshow/2950063.cms
14 Apr 2008, 0633 hrs IST,PTI

HOUSTON: Researchers at University of Texas Southwestern Medical Centre have for the first time used drug-treated blood stem cells to repair heart damage in an animal model, results that may lead to methods for healing injuries from cardiac diseases.
In the study, researchers screened about 147,000 molecules to find one that could transform human blood stem cells into a form resembling immature heart cells.
When they implanted blood stem cells activated by this compound into injured rodent hearts, the human cells took root and improved the animal’s heart function.
"The clinical potential is enormous," said Dr Jay Schneider, assistant professor of internal medicine and senior author of the study, which appears online this week and in a future issue of the Proceedings of the National Academy of Sciences.
Despite medical advances in treating and preventing heart attacks, once the heart is damaged it cannot repair itself, said Dr Schneider, a cardiologist.
"Heart attack is a man-made problem," he said. "It's a function of increased longevity and atherosclerosis, which have occurred at no other time in human evolution."
In the first stage of the study, which involved mouse stem cells, the researchers screened some 147,000 compounds in UT Southwestern's Small Molecule Library to see which ones would activate genes known to be at work in the early stages of heart development.
They initially sifted out about 1,600 compounds, but narrowed their focus to a related group of molecules, among the most potent and easy to make, called Shz for sulfonyl-hydrazone.




2. Hope is Free at This Shop
http://www.denverpost.com/news/ci_8914445
By William Porter
Denver Post Columnist
Article Last Updated: 04/14/2008 12:09:29 AM MDT

Like dozens of secondhand shops in Denver, Safari Seconds Thrift Store boasts an array of used clothes, kitchenware, cast-off appliances, old magazines and baby strollers whose former occupants are now ready for driver's ed.
But sales at Safari Seconds benefit a special group: They are refugees who have relocated here, fleeing war and political strife from Somalia to Southeast Asia.
"We're principally a refugee resettlement program," said Jennifer Gueddiche, director of the African Community Center, the sponsoring organization.
Its name notwithstanding, the center serves refugees from all nations, up to 500 in any given year. Aided by federal funding, the center provides job training and language instruction for newcomers.
Most importantly, it helps set them up with housing and housewares.
For many refugees, it is the first stability they have encountered.
Fadumo Yusuf, who lived in Somalia when the nation's first civil war broke out in 1991, arrived in Denver nearly two years ago.
"We had terrible problems in Somalia," she said. "It was so very bad. Here, it is safe."
Yusuf works at the store, a cavernous warren at 410 Broadway. She processes items and brings order to the rows of packed shelves.
Working the cash register on Friday afternoon was Abdul Rakeem, a refugee from Afghanistan. "This is where I learned to speak English," he told me. "Right here. It has meant so much to me."
When many refugees arrive, they are traumatized by the horrors they have endured. Working in the store brings a sense of normalcy and self-worth.
"We had one woman who came from Burma with five children, one severely disabled," said staffer Julia Paul. "She had huge anxiety issues. But she's been in the training program for five months, and it's made a huge difference.
"Watching these people go through this transformation is amazing."
The store opened in 2005, partly with funding from the Denver Office of Economic Development.
For all the good the operation has done for the refugees, when you talk with the store's volunteers, it becomes clear that the benefits are a two-way street.
"I feel close to these people in a way that I wouldn't in a regular job," said Shauna Agan, a store staffer. "We have big community dinners every Tuesday night."
"These people are truly deserving of compassion," Gueddiche said. "They are people just like us whose lives were disrupted because they're the wrong tribe or they voted for the wrong person in an election."
Despite its unique mission, Safari Seconds chugs along much like other businesses. This month features an "overstock blowout sale."
The store will soon expand, moving into an adjacent optical shop. Along with an additional 1,600 square feet, this will give the store a Broadway storefront and greater visibility.
That will mean more shoppers. And just maybe, more volunteers to help the refugees.
Gueddiche isn't in lock step with everything the federal government does, but she is a champion of its resettlement program.
She said, "I really do think it's one of the things this nation can be proudest of."
William Porter's column runs Monday, Wednesday and Friday. Reach him at 303-954-1977 or wporter@denverpost.com



3. Tree Man 'Who Grew Roots' Hopes to Marry After 4lb of Warts Removed
http://www.telegraph.co.uk/news/main.jhtml?xml=/news/2008/04/11/wtreeman111.xml
By Adam Lusher, Marianne Kearney and Aji Ramyakim
Last Updated: 7:46am BST 14/04/2008

The 'Tree Man of Java’ is hoping to get married after doctors performed four major operations to hack away the bark-like tissue sprouting from his hands and feet.
For 20 years Dede Koswara lived covered in warts with huge tree-like growths encasing his limbs.
Today Dede, whose plight was highlighted on the Telegraph website, can once more use his hands and walk without pain.
He can see the outline of his toes for the first time in over a decade after medics cut more than 4lbs of warty horns from his legs and feet.
He has also become a sudoko addict now medics have cut growths from his hands allowing him to hold a pen.
Dede, 37, now hopes that he will resume a normal life after two more operations to graft undamaged skin onto his hands, feet and face.
Speaking from an Indonesian hospital, he said: "What I really want first is to get better and find a job. But then, one day, who knows? I might meet a girl and get married."
Dede’s ordeal began when he was 15 and cut his knee in an accident. A small wart developed on his lower leg and spread uncontrollably.
Eventually he had to give up work as a builder and fisherman, and scratch a living in a traveling freak show. His wife of ten years left him as it became impossible for him to support her and their two children.
Late last year, however, Dede’s plight was highlighted on Telegraph.co.uk and in a Discovery Channel documentary.
The documentary team took American dermatology expert Dr Anthony Gaspari to Indonesia to see if he could find a cure.
Dr Gaspari, of the University of Maryland, concluded Dede’s affliction was caused by the Human Papilloma Virus (HPV), a fairly common infection usually causing only small warts.
Dede’s problem was that he has an extremely rare immune system deficiency, leaving his body unable to contain the warts. The virus was therefore able to "hijack the cellular machinery of his skin cells", ordering them to produce massive amounts of the substance causing tree-like growths known as "cutaneous horns".
Indonesian health officials have suggested that the mysterious immune problem may occur in as few as 200 people worldwide.
Dede's counts of a key type of white blood cell were so low that Dr Gaspari initially suspected he may have the Aids virus.
Immediately after the documentary was aired, a row seemed to be brewing over Dede’s treatment. The Indonesian government was worried that Dr Gaspari had taken blood and tissue samples abroad without official authorisation.
This was resolved, and Dr Gaspari has revisited Indonesia to meet the health minister Dr Siti Fadilah Supari. He is now liaising with the doctors caring for Dede at the Hasan Sadikin Hospital in Bandung, West Java.
Dr Lily Sulityowati, from the Indonesian Health Department, said: "Once Dr Gaspari met with the minister and explained all, we were happy to work with him."
Dede went under the knife for his first operation in January. In the most recent operation, in March, doctors removed growths on his feet. The medics are now trying to ensure that the warts don’t grow back.
Dede is taking vitamin A tablets to boost his immune system, and Dr Gaspari is hoping to get expensive anti-viral medicine available only in the US.
Dr Rachmat Dinata, the skin specialist leading the Indonesian doctors, said the final phase of operations should be completed in around three months. They will take skin from Dede’s back and thigh and graft it onto damaged areas.
Dr Dinata said: "There is still a high risk that there will be a recurrent growth of warts. So far, though, there has been some thickening of the skin, but no recurrent warts. Dede is very happy. Hopefully he will be able to socialise and work again."
For now, Dede is passing the time in hospital doing sudoko puzzles. Skin grafts on his hands will allow him better movement in his fingers, but he can already punch numbers into a telephone and talk to friends.
His father Ateng, 72, said: "You can see the form of his 10 toes now. He can wear flip flops. He loves doing sudokos. He is in good condition."
Ateng added: "The first priority is to get cured and get a job, but as a father, of course I want my son to remarry. He is a normal guy and he is still a young man."




4. Man Fell into St. Helens, Lived to Tell Tale
http://seattletimes.nwsource.com/html/localnews/2004347113_fall14m.html
Monday, April 14, 2008 - Page updated at 12:38 AMBy Marsha King

Mount St. Helens National Volcanic Monument From his hospital bed in Portland, a banged-up but lucky John Slemp said he'd snowmobiled to that exact same spot on Mount St. Helens at least four times before Saturday.
But this time was special — a welcome-home ride with his son, who is just back from serving a year in Iraq.
It turned out to be history-making.
Slemp, a longtime driver for UPS in the Portland area, is the first person known to have fallen into the crater of Mount St. Helens.
Saturday afternoon, after snowmobiling up to the west crater rim, he and his son, Jared, and a buddy parked their machines. Then Slemp and his son crawled on all fours to within 20 feet of the edge of a snow cornice that overhung the crater.
The cornice gave way. The buddy pulled Jared back, but Slemp fell 100 to 200 feet before landing on the crater's inside slope, then slid on his hands and knees to the bottom. The snow cushioned his fall, but he estimated he was traveling 40 mph at times while descending a total of 1,300 to 1,500 feet.
"It just gave way," Slemp said of the cornice. "I didn't have a chance to do anything."
But knowing he might be buried under snow, he did have the presence of mind to put a hand over his mouth to keep an air passage open and keep one hand up so he might be found.
"I was thinking clearly," added Slemp, 52. "I never really went into major shock."
Slemp, a Damascus, Ore., resident who has been riding snowmobiles for 20 years, was wearing a helmet, sturdy boots and riding bibs, which probably helped save his life, rescue officials said. It's legal to ride in that area, a rescue official said, but it's not recommended for anyone other than an expert.
Outside of closed areas, snowmobiles are allowed around the mountain when snow depths are sufficient to shelter the ground surface, said Peter Frenzen, Mount St. Helens monument scientist.
But people need to be cautious, he added. When the wind blows snow over a precipice or side of a ridge, it tends to cantilever out in a cornice or overhang.
"You have to determine where the real rim is and if you're on something substantial, not something hanging out in space," Frenzen said.
"I've encountered parties of climbers having lunch on cornices," he said.
Snowmobiling also is not a casual undertaking on Mount St. Helens. Riders can damage their machines or roll because the terrain is so steep, Frenzen said.
Slemp calls himself more extreme than the average trail rider. His "sled," or snowmobile, is built to climb hills.
When Slemp landed at the bottom, he said his first instinct was to try to climb back up. But loose snow carried him back down, so he tried to crawl over to a steam vent to stay warm.
Above the crater, his son and the friend called out on a battery-operated, two-way radio. A man in Mossyrock, Lewis County, happened to have the same kind of radio turned on and called the Sheriff's Office.
North Country Emergency Medical Service's volcano rescue team was contacted about 5:30 p.m. and flew two paramedics to the crater. They helped Slemp into their helicopter.
The rescue guys "were incredible," said Slemp. "I couldn't believe they got there that fast."
Tom McDowell, North Country EMS director, said Slemp "got his legs battered up, got rolled and bumped around a bit."
Slemp was flown to Yacolt, Clark County, then went by ambulance to a Portland hospital, where he learned he'd suffered torn knee ligaments.



5. Naked Nomad Victor Flanagan Leaves Multi-million Dollar Estate to Sister
http://www.news.com.au/story/0,23599,23536001-421,00.html
By Mark SchliebsApril 14, 2008 01:00pm

A MAN who rejected possessions and walked around Australia naked has been declared dead, leaving his sister to inherit an estate worth millions of dollars.
Victor Flanagan, also known as the “Naked Nomad”, was declared “presumed dead” in the Supreme Court in Perth last week – more than a decade after he last spoke to his sister.
The West Australian reported that a multi-million dollar beachfront property near Busselton would be left to his sister, Violet Georgina Jenkins. Flanagan had inherited the property after their father’s death.
Mrs Jenkins told the court that she last spoke to Flanagan in 1996, while he was living in Papua New Guinea, the newspaper reported.
He had relocated to PNG after years of wandering around outback Australia naked – except for a sarong he would wear when walking through towns and a pair of thongs for when there were too many prickles on the road.
Mrs Jenkins said loggers at a remote camp found a dying Caucasian man lying in a canoe – without any clothing – and that she believed it was her brother.
The man’s body had been buried in a mass grave in the PNG city of Lae, where other unidentified people were laid to rest, she said.
Supreme Court Justice Andrew Beech ruled that it was fair to say Flanagan, who would have turned 57 this year, was dead.
“It is to be expected that he would have been in contact with (Mrs Jenkins) if he were still alive,” Justice Beech said.
In the March newsletter from environmental awareness group The Great Walk, Flanagan was described as “a gentle man who walked this earth with love and care for the environment around him”.
“He walked barefoot from Perth to Papua New Guinea, becoming known as the Naked Nomad, making the news in his plight to share his truth with the outside world,” the newsletter said.
In 1995, Flanagan told a reporter that his naked adventures had attracted a lot of interest from travellers and police, but many were willing to give him and his dog food and water.
“When I get hungry I hold out my plate and when I get thirsty I hold out my bottle for water for me and my dog,” Flanagan said.
He said his goal was simply to be in touch with nature.


Honorable Mention:

1. Norway's King Opens New Opera House
http://news.bbc.co.uk/2/hi/europe/7344874.stm
Saturday, April 12th, 2008

Visitors can walk up the opera house's sloping stone roof from the fjord
Norway's King Harald V has opened the country's national opera house in Oslo at a gala performance attended by royalty and other national leaders.
The $835m (£424m) white marble landmark on the shore of the Oslo Fjord in the heart of the capital fulfils a long-held dream for local music fans.
The 1,350-strong audience on Saturday included German Chancellor Angela Merkel and Denmark's Queen Margrethe.
The opera house is the largest cultural centre built in Norway in 700 years.
The Norwegian parliament's decision to approve its construction in 1999 ended more than 120 years of debate and waiting for a national opera house.
From the outside, the most striking feature is the sloping stone roof, made up of 36,000 fitted pieces, which seems to rise from the water of the fjord.
It has been described by the Norwegian architects, Snoehetta, as a "fifth wall", designed so visitors can walk up the gentle incline to the top, and look out over the city and the fjord.
The inside of the 1,000-room building has been lined with crafted woodwork and decorated with about $12m of art.
"Innermost in the Oslo Fjord, the opera house rises as a new and monumental landmark," said King Harald at the inaugural concert on Saturday evening.
"This house for many generations to come will be filled with music, dance and song."
The director of Norwegian Opera & Ballet, Bjoern Simonsen, said the building would "change the way the world sees us, and the way we see ourselves".



2. "Extinct" Plants Found in Remote Australia http://news.yahoo.com/s/nm/20080412/sc_nm/australia_extinct_dc
Fri Apr 11, 11:51 PM ET

MELBOURNE (Reuters) - Two plants that were thought to have been extinct since the late 1800s have been rediscovered in far northern Australia, according to an official report released on Saturday. The Queensland state government's State of the Environment report said the two species were found on Cape York, in tropical far north Queensland.
"The Rhaphidospora cavernarum, which is a large herb that stands about one and a half meters high, has reappeared," state climate change minister Andrew McNamara told Australian Broadcasting Corp radio.
"It hasn't been seen in Queensland since 1873," he said.
He said the second plant that has reappeared, another herb called Teucrium ajugaceum, was last seen in 1891.
The report was produced from research by more than 100 academic and government experts.
"The rediscovery of two presumed extinct plant species has seen a decline in this category, with a corresponding increase in the endangered category," the report said.
It said more than 50 plant species new to science are discovered and described in Queensland every year and there are more than 12,000 native plant species known to science in the state.
(Reporting by Victoria Thieberger; Editing by Jerry Norton)




3. Cancer Therapy Without Side Effects Nearing Trials
http://www.wired.com/medtech/health/news/2008/04/kanzius_therapyB
By Jennifer Laloup 04.13.08 1:00 PM

A promising new cancer treatment that may one day replace radiation and chemotherapy is edging closer to human trials.
Kanzius RF therapy attaches microscopic nanoparticles to cancer cells and then "cooks" tumors inside the body with harmless radio waves.
Based on technology developed by Pennsylvania inventor John Kanzius, a retired radio and TV engineer, the treatment has proven 100 percent effective at killing cancer cells while leaving neighboring healthy cells unharmed. It is currently being tested at M.D. Anderson Cancer Center in Houston.
“I don’t want to give people false hope,” said Dr. Steve Curley, the professor leading the tests, “but this has the potential to treat a wide variety of cancers.”
Modern cancer treatments like radiation and chemotherapy have proven remarkably effective at treating many cancers, especially in combination, but are plagued with toxic side effects. These treatments kill healthy cells as well as cancerous ones.
Kanzius RF therapy is noninvasive, and uses nontoxic radio waves combined with gold or carbon nanoparticles, which have a long history of medical use.
Since the mid-1980s, scientists have been trying to create new medical therapies to take advantage of their tiny size. Nanoparticles made of gold, carbon and other materials can move through the bloodstream and through cell walls, allowing for efficient drug delivery, or to act like a homing devices for research purposes.
However, questions about the safety of nanoparticles are largely unanswered. Nonetheless, the potential of nanoparticles to create novel treatments has become a central thrust of many fields of medicine, including oncology.
At M.D. Anderson, Curley's research team is working on coating microscopic gold nanoparticles with cancer-seeking molecules. The proteins act as a filter that ensures nanoparticles attach only to cancerous cells in the body.
“We’re looking into gold because it is FDA-approved and has a track record of being tolerated in humans,” said Dr. Christopher Gannon, assistant professor at the Cancer Institute of New Jersey, who collaborated with M.D. Anderson.
When the gold nanoparticles are inside the malignancy, a blast from a radio-frequency generator causes them to heat and cook the cancer cells.
In trials with animal and human cells, the RF treatment destroyed 100 percent of malignant cells injected with nanoparticles, without harming surrounding healthy tissue.
A study in the November 2007 issue of the journal Cancer showed that tumor cells infused with nanoparticles and exposed to the electromagnetic field of the RF generator died within 48 hours of treatment, with no noted side effects.
A study in the Journal of Nanobiotechnology in January 2008 showed that destruction of human pancreatic cancer cells was 100 percent effective — again producing no noticeable side effects.
“We know it has the potential to work well,” said Gannon. "It’s just a matter of making the details work."
The problem is finding cancer-seeking molecules that are attracted to cancer cells but leave healthy cells alone.
Curley's team has identified a targeting molecule, c225 , which is FDA-approved. While c225 is present in many cancer cells, it also occurs in healthy cells.
“It will depend on the type of cancer and the targeting molecules attached to the nanoparticles,” Curley said.
The radio-frequency generator was invented by Kanzius, who underwent chemotherapy in 2003 and 2004 for leukemia. Kanzius declined to be interviewed for this story, citing an exclusive agreement with CBS News. 60 Minutes has scheduled a segment about Kanzius RF therapy for Sunday.
“His device helped inspire us to create the targeted nanoparticles to make it a fully functional clinical device,” said Gannon.
Kanzius is now working on a larger CT-scanner-sized device that will help scientists test larger subjects by this summer — and pave the way for human trials.
Curley, who described himself as the "ultimate skeptic," thinks the treatment is only a few years away.
"The best-case scenario is that we would be able to clinical trials within three years,” he said.


4. Magic Goes on as Tokyo Disneyland Turns 25
http://news.yahoo.com/s/afp/20080413/lf_afp/lifestylejapanleisureentertainmentdisneyland_080413033729
by Miwa Suzuki
Sat Apr 12, 11:37 PM ET

MAIHAMA, Japan (AFP) - The Japanese are having fewer children and Disneylands abroad face problems, but the magic has not dimmed here where Mickey and friends are marking 25 years with fans as loyal as ever. Tokyo Disneyland opened in the suburbs of the Japanese capital on April 15, 1983 as the company's first theme park outside the United States.
Built on reclaimed land in Tokyo Bay dubbed "Maihama" -- a Japanese take on Miami Beach near Florida's Disney World -- the resort has sprawled out to include hotels, a shopping mall, an aqua park and soon a permanent Cirque du Soleil.
"The moment I arrive at Maihama Station, my heart starts singing with its legs doing dance steps," said Toshiko Sugano. "I turn 58 next month, so I'll have to come back to celebrate."
She was spending the day at Disneyland with her 31-year-old daughter and 54-year-old sister, all still enchanted since they first came a quarter century ago.
"It's a totally different world here, away from real everyday life," the elder Sugano said.
Her daughter, Izumi, a Disney maniac who has visited the park more than 100 times, teased her mother over how much she has warmed to the characters.
"She was initially taken aback when Mickey put his arm around her shoulder. Now she springs towards Mickey if she finds him," Izumi said.
As Japan's birth rate sinks to one of the world's lowest, Tokyo Disneyland has already set its sights on people like the Suganos, the generation who grew up admiring Disney cartoons on television and took their children to the park at the opening.
Oriental Land Co. Ltd., the Japanese company that runs the park under a license contract with the Walt Disney group, in March launched a cut-rate pass for visitors aged 60 or older.
Sugano is determined to get one. "It's two more years to go. Knowing that I'll be able to get it, it's quite nice getting old," she said.
Takashi Fujisawa, 31, came all the way from Japan's northernmost island of Hokkaido with his wife and three-year-old son. It was his second visit after the first trip 16 years ago with his parents.
"I feel strange coming back here as a father bringing a son myself," he said, carefully adjusting the position of a baby stroller to take pictures of the sleeping boy with Cinderella Castle in the background.
The number of visitors to Disneyland and DisneySea, the water park opened in 2001, has stood at record levels of around 25 million in recent years, up from 9.9 million people in Disneyland's first year.
Since 1983 a total of 436 million people have visited the two parks that sit next to the megalopolis.
Visits have become such a rite of passage that Disneyland even holds a traditional coming-of-age ceremony for 20-year-olds each year with Mickey and Minnie.
Oriental Land puts annual revenue from theme parks at 285 billion yen (2.8 billion dollars) -- a far cry from the performances of other overseas Disneylands.
Hong Kong government figures showed in December that visitor numbers at Hong Kong Disneyland fell up to 23 percent in its second year of operation.
Visitors to the 15-year-old Euro Disney hit a record of 14.5 million in 2007 but the operation was still in the red for a sixth straight year.
Tokyo Disneyland benefits from being in a nation that widely embraces US pop culture and commonly accepts grown-ups, particularly women, pursuing the same hobbies and fashions as children.
Hideki Nakagawa, a sociology professor at Nihon University, said going to Disneyland has turned into a "fashion in itself" in Japan, with frequent visitors collecting Disney items.
"You feel superior if you go there many times, while it makes others feel they must go as well," he said.
As it looks ahead, Disneyland is hoping to become more of a true "resort," persuading adults not only to come and visit but to stay for a few days as well.
Tokyo Disney Resort's latest on-line promotion offers "romantic night views" at DisneySea, with pictures showing a couple who turn 60 this year strolling and dining at the park.
"It's been a long time since I last talked with my husband this much. Next time I come, I want a package to stay," the woman in the advertisement says as she clings to her husband's arm.




5. Nose Spray Anthrax Vaccine Effective In Early Tests
http://www.sciencedaily.com/releases/2008/04/080411175427.htm
ScienceDaily (Apr. 12, 2008)

Early studies show that a new mucosal vaccine against anthrax has the potential to provide military personnel with more effective and efficient protection against a “popular” bioweapon, according to a study published in the journal Clinical and Vaccine Immunology (CVI). With the new vaccine, researchers sought to take two steps at once, fine-tuning its ingredients and delivering it by nose spray instead of injection.
Anthrax is caused by Bacillus anthracis, a bacterium that forms seed-like structures called spores capable of reproducing the organism despite tremendous punishment. In recent years, anthrax has become a top choice as a biological warfare agent, according to the U.S. Department of Defense (DOD), because its spores can easily become airborne. It can be spread by mailed packages, missiles or crop-dusting planes. It can travel downwind for hundreds of miles and stay lodged in soil for decades. Following the Sept. 11, 2001, attacks, terrorists mailed letters coated with anthrax spores to 22 U.S. men and women, five of whom died. Saddam Hussein developed anthrax spore-filled weapons, and Boris Yeltsin said the former Soviet Union had a biological weapons program that dwarfed that of pre-war Iraq.
The U.S. military requires personnel in high-risk areas to be vaccinated with the only FDA-licensed human anthrax vaccine, BioThraxTM, produced by BioPort Corporation/Emergent Defense Operations. It was approved by the U.S. Food and Drug Administration in 1998, and about 1.8 million U.S. personnel have been vaccinated since then, according the Department of Defense. Those vaccinated are intended to receive a series of six shots, and then an annual booster shot. While 1.8 million have been vaccinated since 1998, just seven million doses have been handed out.
“Our study found that a mucosal delivery system promises to add a second layer of immune protection against anthrax by priming the disease-fighting cells in mucous membranes lining the nose along with those in the blood, and with just three doses,” said Mingtao Zeng, Ph.D., assistant professor within Department of Microbiology and Immunology at the University of Rochester Medical Center, and a study author along with Qingfu Xu, also at the medical center. “That, along with the addition of newly precision-designed vaccine components, should represent important steps in the race to provide troops with stronger protection in a vaccine that is easier to use.”
The study was in mice, but much of the evidence behind the currently approved vaccine was collected in animals as well. In a challenge common to many lines of vaccine research, it is “obviously unethical to test anthrax vaccines in humans using the real pathogen.”
In arguing for the value of the currently available vaccine, the military cites a CDC study from the 1950s where an older version of the current vaccine protected mill workers when both “skin” (cutaneous) and “lung” (inhalation) anthrax infections outbreak at their workplace. In the study, 25 out of 754 unvaccinated workers got infected with skin anthrax, while just one of 379 vaccinated workers got infected. During that study, five of the unvaccinated workers unexpectedly developed inhalation anthrax as well, and four of them died. None of the vaccinated workers developed inhalation anthrax. The same vaccine also protected 95 percent of monkeys and 97 percent of rabbits in other studies. The U.S. Food and Drug Administration has certified, and re-certified, that the current vaccine is safe and effective.
Despite these proofs, some critics argue that there has never been a large-scale study of the currently approved vaccine in humans, raising questions about how well the current vaccine would protect against a modern-day, weaponized version of anthrax. A few former soldiers are involved in lawsuits with the military because they refused to be injected with the vaccine, which they did not believe to be safe. The current vaccine was formulated before the revolution in molecular biology in the 1980s. Today, vaccines are designed “rationally,” based on precise understanding of molecular pathogenesis and protein structures. Older vaccines contained a mix of ingredients that were not always precisely defined.
Given these questions, vaccine designers worldwide have been seeking to design a vaccine made up of a more precise combination of the Bacillus anthracis antigens. In the latest attempt, the current study sought to improve on the current vaccine in two ways: deliver it mucosally and fine-tune its ingredients. Membranes lining the mouth, nose, and throat secrete mucus, a thick coating that protects these surfaces as they interact with the outside world. Mucosal membrane has its own set of disease-fighting cells concentrated in mucosa-associated lymphoid tissue (MALT) that are related to, but separate from, the immune cells operating in the bloodstream, lymph nodes and spleen.
Researchers believe a vaccine administered via the mucosal surface might prime both sets of immune cells, providing two layers of protection, and a very strong effect in the membranes that would be directly exposed to airborne anthrax spores. Vaccines injected by needle may prime only the systemic immune system. In addition, mucosal vaccination is painless, making it convenient for vaccine administration even when multiple doses are required, researchers said.
Building Blocks
The purpose of the human immune system is to recognize and destroy invading organisms, and to remember and fight against them should they invade again. Without causing an actual infection, vaccines introduce weakened or detoxified versions of disease-related molecules to the system, which remembers them for next time. Once researchers confirm the kind of immune response needed to achieve protection, they can choose for inclusion in a multi-component vaccine the key antigens that trigger the strongest immune response. The immune system reacts, not to the presence of a whole bacterium or virus, but instead to specific proteins (antigens) on the surface of, or secreted by, the pathogen that reveal its identity.
Past studies have shown that anthrax kills by secreting three toxic proteins that cause the breakdown of key immune cells, and ultimately, the death of cells and tissues. Paradoxically, those same toxins, if changed slightly, may represent the best vaccine building blocks. The toxins are protective antigen (PA), lethal factor (LF), and edema factor (EF). PA binds to receptors on the outer surface of immune cells called macrophages and forms a pore through which LF and EF can enter the cells. Once inside, LF signals for the cell to self-destruct, and EF causes a damaging inrush of fluid (e.g. inflammation). Since macrophages remove toxins from the body, their death causes a quick build-up of toxins fatal to cells.
Because PA plays such a central role in anthrax infection, human immune systems have evolved to recognize it well. However, it cannot cause disease itself until combined with LF or EF, and thus, makes the perfect vaccine ingredient. The current vaccine consists primarily of PA, with some undefined quantities of LF and EF, injected into the bloodstream. The re-designed study vaccine too has the biologically active portion of PA, PA63, as its first building block.
In the study’s key innovation, Zeng’s team next added a detoxified version of LF to PA63 to create an even stronger immune response. Past research has shown researchers can eliminate LF’s toxicity by using molecular biology techniques to substitute out one of its amino acid building blocks. Detoxified mutant LF (mLF) was first assembled more than a decade ago in the lab of Stephen H. Leppla, Ph.D., acting lab chief at the Laboratory of Bacterial Diseases within the National institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Although first assembled a decade ago, no one had yet looked at whether it would make a good component for a candidate anthrax vaccine. The hope was that detoxified mLF could be safely administered into a host, and that the host’s immune system would still recognize the detoxified version.
For the experiments, the team divided thirty-two mice into four groups of eight. Each group received a nasal spray three times over four weeks that contained either PA alone, detoxified mLF alone, a combination of PA and mLF at the same doses or an inactive control solution. The animals were then subcutaneously challenged with B. anthracis Sterne spores.
In a dramatic result, all mice vaccinated with the combination vaccine (60 µg PA63/30 µg mLF) were protected against anthrax spore exposure and survived. Just 60 percent of those vaccinated with only PA63 survived, and just 30 percent of those receiving mLF alone. All control animals inoculated with saline died within 5 days of spore challenge.
Reflecting the survival results, intranasal vaccination with the combination PA63/mLF elicited significantly higher antibody responses against PA or LF than vaccination with the same amount of individual PA63 or mLF at all time points measured (P values < 0.05). The data suggested that PA63 and mLF have a mutual enhancement effect, researchers said, in terms of evoking an immune response. Two types of immune system cells, T cells and antibodies, enable the system to “remember” bacterial incursions, and levels of each were followed closely.
To see if intranasal mucosal vaccination with the combination vaccine elicited mucosal immune protection, the team measured anti-PA and anti-LF antibody levels in saliva, nasal wash, and other mucosal samples from vaccinated animals. Three doses of 60 µg of PA63/30 µg mLF resulted in considerably higher levels of mucosal anti-PA and anti-LF antibody responses than vaccination with either PA63 or mLF alone.
In addition, modern, protein-based vaccine work like the current study uses for experiments only specific and detoxified proteins that resemble those created by the bacteria, not the whole, anthrax-causing organism, making it much safer to work with. Should the new combination be approved for use in humans in the future, it would be much easier, safer and less expensive to manufacture for the same reason, researchers said.
“This study was the first to demonstrate that the detoxified anthrax lethal toxin could be used as an effective mucosal anthrax vaccine without any adjuvant,” Zeng said. “Other antigens such as N-terminal fragment of edema factor, spore-associated glycoprotein, capsular poly-gamma-d-glutamic acid and various pieces of B. anthracis have also shown promise as candidate vaccine components, and a future vaccine may contain some of them along with the ones we tested here.”
Adapted from materials provided by University of Rochester Medical Center.