Stem cells reverse blindness caused by chemical burns

Stem cells reverse blindness caused by chemical burns
Posted 6/24/2010 12:01 PM
By Alicia Chang, Associated Press

LOS ANGELES — Dozens of people who were blinded or otherwise suffered severe eye damage when they were splashed with caustic chemicals had their sight restored with transplants of their own stem cells — a stunning success for the burgeoning cell-therapy field, Italian researchers reported Wednesday.

The treatment worked completely in 82 of 107 eyes and partially in 14 others, with benefits lasting up to a decade so far. One man whose eyes were severely damaged more than 60 years ago now has near-normal vision.

“This is a roaring success,” said ophthalmologist Dr. Ivan Schwab of the University of California, Davis, who had no role in the study — the longest and largest of its kind.

Stem cell transplants offer hope to the thousands of people worldwide every year who suffer chemical burns on their corneas from heavy-duty cleansers or other substances at work or at home.

The approach would not help people with damage to the optic nerve or macular degeneration, which involves the retina. Nor would it work in people who are completely blind in both eyes, because doctors need at least some healthy tissue that they can transplant.

In the study, published online by the New England Journal of Medicine, researchers took a small number of stem cells from a patient’s healthy eye, multiplied them in the lab and placed them into the burned eye, where they were able to grow new
corneal tissue to replace what had been damaged. Since the stem cells are from their own bodies, the patients do not need to take anti-rejection drugs.

Adult stem cells have been used for decades to cure blood cancers such as leukemia and diseases like sickle cell anemia. But fixing a problem like damaged eyes is a relatively new use.

Researchers have been studying cell therapy for a host of other diseases, including diabetes and heart failure, with limited success.

Adult stem cells, which are found around the body, are different from embryonic stem cells, which come from human embryos and have stirred ethical concerns because removing the cells requires destroying the embryos.

Currently, people with eye burns can get an artificial cornea, a procedure that carries such complications as infection and glaucoma, or they can receive a transplant using stem cells from a cadaver, but that requires taking drugs to prevent rejection.

The Italian study involved 106 patients treated between 1998 and 2007. Most had extensive damage in one eye, and some had such limited vision that they could only sense light, count fingers or perceive hand motions. Many had been blind for years and had unsuccessful operations to restore their vision.

The cells were taken from the limbus, the rim around the cornea, the clear window that covers the colored part of the eye. In a normal eye, stem cells in the limbus are like factories, churning out new cells to replace dead corneal cells. When an injury
kills off the stem cells, scar tissue forms over the cornea, clouding vision and causing blindness.

In the Italian study, the doctors removed scar tissue over the cornea and glued the laboratory-grown stem cells over the injured eye. In cases where both eyes were damaged by burns, cells were taken from an unaffected part of the limbus.

Researchers followed the patients for an average of three years and some as long as a decade. More than three-quarters regained sight after the transplant. An additional 13% were considered a partial success. Though their vision improved, they still had some cloudiness in the cornea.

Patients with superficial damage were able to see within one to two months. Those with more extensive injuries took several months longer.

“They were incredibly happy. Some said it was a miracle,” said one of the study leaders, Graziella Pellegrini of the University of Modena’s Center for Regenerative Medicine in Italy. “It was not a miracle. It was simply a technique.”

The study was partly funded by the Italian government.

Researchers in the United States have been testing a different way to use self-supplied stem cells, but that work is preliminary.

One of the successful transplants in the Italian study involved a man who had severe damage in both eyes as a result of a chemical burn in 1948. Doctors grafted stem cells from a small section of his left eye to both eyes. His vision is now close to normal.

In 2008, there were 2,850 work-related chemical burns to the eyes in the United States, according to the Bureau of Labor Statistics.

Schwab of UC Davis said stem cell transplants would not help those blinded by burns in both eyes because doctors need stem cells to do the procedure.

“I don’t want to give the false hope that this will answer their prayers,” he said.

Dr. Sophie Deng, a cornea expert at the UCLA’s Jules Stein Eye Institute, said the biggest advantage was that the Italian doctors were able to expand the number of stem cells in the lab. This technique is less invasive than taking a large tissue sample from
the eye and lowers the chance of an eye injury.

“The key is whether you can find a good stem cell population and expand it,” she said.

Copyright 2010 The Associated Press. All rights reserved.

Ancient human remains found in Israel

By DANIEL ESTRIN, Associated Press Daniel Estrin, Associated Press
Mon Dec 27, 6:13 pm ET
JERUSALEM –

Israeli archaeologists said Monday they may have found the earliest evidence yet for the existence of modern man, and if so, it could upset theories of the origin of humans.

A Tel Aviv University team excavating a cave in central Israel said teeth found in the cave are about 400,000 years old and resemble those of other remains of modern man, known scientifically as Homo sapiens, found in Israel. The earliest Homo sapiens remains found until now are half as old.

“It’s very exciting to come to this conclusion,” said archaeologist Avi Gopher, whose team examined the teeth with X-rays and CT scans and dated them according to the layers of earth where they were found.

He stressed that further research is needed to solidify the claim. If it does, he says, “this changes the whole picture of evolution.”

The accepted scientific theory is that Homo sapiens originated in Africa and migrated out of the continent. Gopher said if the remains are definitively linked to modern human’s ancestors, it could mean that modern man in fact originated in what is now Israel.

Sir Paul Mellars, a prehistory expert at Cambridge University, said the study is reputable, and the find is “important” because remains from that critical time period are scarce, but it is premature to say the remains are human.

“Based on the evidence they’ve cited, it’s a very tenuous and frankly rather remote possibility,” Mellars said. He said the remains are more likely related to modern man’s ancient relatives, the Neanderthals.

According to today’s accepted scientific theories, modern humans and Neanderthals stemmed from a common ancestor who lived in Africa about 700,000 years ago. One group of descendants migrated to Europe and developed into Neanderthals, later becoming extinct. Another group stayed in Africa and evolved into Homo sapiens — modern humans.

Teeth are often unreliable indicators of origin, and analyses of skull remains would more definitively identify the species found in the Israeli cave, Mellars said.

Gopher, the Israeli archaeologist, said he is confident his team will find skulls and bones as they continue their dig.

The prehistoric Qesem cave was discovered in 2000, and excavations began in 2004. Researchers Gopher, Ran Barkai and Israel Hershkowitz published their study in the American Journal of Physical Anthropology.

If an island state vanishes, is it still a nation?

By CHARLES J. HANLEY, AP Special Correspondent Charles J. Hanley, Ap Special Correspondent
Mon Dec 6, 2:27 pm ET

CANCUN, Mexico – Encroaching seas in the far Pacific are raising the salt level in the wells of the Marshall Islands. Waves threaten to cut one sliver of an island in two. “It’s getting worse,” says Kaminaga Kaminaga, the tiny nation’s climate change coordinator.

The rising ocean raises questions, too: What happens if the 61,000 Marshallese must abandon their low-lying atolls? Would they still be a nation? With a U.N. seat? With control of their old fisheries and their undersea minerals? Where would they live, and how would they make a living? Who, precisely, would they and their children become?

For years global negotiations to act on climate change have dragged on, with little to show. Parties to the 193-nation U.N. climate treaty are meeting again in this Caribbean resort, but no one expects decisive action to roll back the industrial, agricultural and transport emissions blamed for global warming — and consequently for swelling seas.

From 7,000 miles (11,000 kilometers) away, the people of the Marshalls — and of Kiribati, Tuvalu and other atoll nations beyond — can only wonder how many more years they’ll be able to cope.

“People who built their homes close to shore, all they can do is get more rocks to rebuild the seawall in front day by day,” said Kaminaga, who is in Cancun with the Marshallese delegation to the U.N. talks.

The Marshallese government is looking beyond today, however, to those ultimate questions of nationhood, displacement and rights.

“We’re facing a set of issues unique in the history of the system of nation-states,” Dean Bialek, a New York-based adviser to the Republic of the Marshall Islands who is also in Cancun, told The Associated Press. “We’re confronting existential issues associated with climate impacts that are not adequately addressed in the international legal framework.”

The Marshallese government took a first step to confront these issues by asking for advice from the Center for Climate Change Law at New York’s Columbia University. The center’s director, Michael B. Gerrard, in turn has asked legal scholars worldwide to assemble at Columbia next May to begin to piece together answers.

Nations have faded into history through secession — recently with the breakup of the former Yugoslavia, for example — or through conquest or ceding their territory to other countries.

But “no country has ever physically disappeared, and it’s a real void in the law,” Gerrard said during an interview in New York.

The U.N. network of climate scientists projects that seas, expanding from heat and from the runoff of melting land ice, may rise by up to 1.94 feet (0.59 meters) by 2100, swamping much of the scarce land of coral atolls.

But the islands may become uninhabitable long before waves wash over them, because of the saline contamination of water supplies and ruining of crops, and because warming is expected to produce more threatening tropical storms.

“If a country like Tuvalu or Kiribati were to become uninhabitable, would the people be stateless? What’s their position in international law?” asked Australian legal scholar Jane McAdam. “The short answer is, it depends. It’s complicated.”

McAdam, of the University of New South Wales, has traveled in the atoll nations and studied the legal history.

As far as islanders keeping their citizenship and sovereignty if they abandon their homelands, she said by telephone from Sydney, “it’s unclear when a state would end because of climate change. It would come down to what the international community was prepared to tolerate” — that is, whether the U.N. General Assembly would move to take a seat away from a displaced people.

The 1951 global treaty on refugees, mandating that nations shelter those fleeing because of persecution, does not cover the looming situation of those displaced by climate change. Some advocate negotiating a new international pact obliging similar treatment for environmental refugees.

In the case of the Marshallese, the picture is murkier. Under a compact with Washington, citizens of the former U.S. trusteeship territory have the right to freely enter the U.S. for study or work, but their right to permanent residency must be clarified, government advisers say.

The islanders worry, too, about their long-term economic rights. The wide scattering of the Marshalls’ 29 atolls, 2,300 miles (3,700 kilometers) southwest of Hawaii, give them an exclusive economic zone of 800,000 square miles (2 million square kilometers) of ocean, an area the size of Mexico.

The tuna coursing through those waters are the Marshalls’ chief resource, exploited by selling licenses to foreign fishing fleets. “If their islands go underwater, what becomes of their fishing rights?” Gerrard asked. Potentially just as important: revenues from magnesium and other sea-floor minerals that geologists have been exploring in recent years.

While lawyers at next May’s New York conference begin to sort out the puzzle of disappeared nations, the Marshallese will grapple with the growing problems.

The “top priority,” Kaminaga said, is to save the isthmus linking the Marshalls’ Jaluit island to its airport, a link now swept by high tides.

Meantime, a lingering drought this year led islanders to tap deeper into their wells, finding salty water requiring them to deploy emergency desalination units. And “parts of the islands are eroding away,” Kaminaga said, as undermined lines of coconut palms topple into the sea.

This week in Cancun and in the months to come, the Marshalls’ representatives will seek international aid for climate adaptation. They envision such projects as a Jaluit causeway, replanting of protective vegetation on shorelines, and a 3-mile-long (5-kilometer-long) seawall protecting their capital, Majuro, from the Pacific’s rising tides.

Islanders’ hopes are fading, however, for quick, decisive action to slash global emissions and save their remote spits of land for the next century.

“If all these financial and diplomatic tools don’t work, I think some countries are looking at some kind of legal measures,” said Dessima Williams, Grenada’s U.N. ambassador and chair of a group of small island-nations. Those measures might include appeals to the International Court of Justice or other forums for compensation, a difficult route at best.

In the end, islanders wonder, too, what will happen to their culture, their history, their identity with a homeland — even to their ancestors — if they must leave.

“Cemeteries along the coastline are being eroded. Gravesites are falling into the sea,” Kaminaga said. “Even in death we’re affected.”

NASA Unveils Arsenic Life Form

By Rachel Ehrenberg, Science News

When cooking up the stuff of life, you can’t just substitute margarine for butter. Or so scientists thought.

But now researchers have coaxed a microbe to build itself with arsenic in the place of phosphorus, an unprecedented substitution of one of the six essential ingredients of life. The bacterium appears to have incorporated a form of arsenic into its cellular machinery, and even its DNA, scientists report online Dec. 2 in Science.

Arsenic is toxic and is thought to be too chemically unstable to do the work of phosphorus, which includes tasks such as holding DNA in a tidy double helix, activating proteins and getting passed around to provide energy in cells. If the new results are validated, they have huge implications for basic biochemistry and the origin and evolution of life, both on Earth and elsewhere in the universe.

“This is an amazing result, a striking, very important and astonishing result — if true,” says molecular chemist Alan Schwartz of Radboud University Nijmegen in the Netherlands. “I’m even more skeptical than usual, because of the implications. But it is fascinating work. It is original, and it is possibly very important.”

The experiments began with sediment from eastern California’s Mono Lake, which teems with shrimp, flies and algae that can survive the lake’s strange chemistry. Mono Lake formed in a closed basin — any water that leaves does so by evaporation — making the lake almost three times as salty as the ocean. It is highly alkaline and rich in carbonates, phosphorus, arsenic and sulfur.

Led by Felisa Wolfe-Simon of NASA’s Astrobiology Institute and the U.S. Geological Survey in Menlo Park, California, the researchers cultured microbes from the Lake Mono sediment. The microbes got a typical diet of sugar, vitamins and some trace metals, but no phosphate, biology’s favorite form of phosphorus. Then the team started force-feeding the critters arsenate, an analogous form of arsenic, in greater and greater quantities.

One microbe in particular — now identified as strain GFAJ-1 of the salt-loving, mostly marine family Halomonadaceae — was plucked out and cultured in test tubes. Some were fed loads of arsenate; others got phosphate. While the microbes subsisting on arsenate didn’t grow as much as those getting phosphate, they still grew steadily, doubling their ranks every two days, says Wolfe-Simon. And while the research team couldn’t eliminate every trace of the phosphate from the original culture, detection and analytical techniques suggests that GFAJ-1 started using arsenate as a building block in phosphate’s place.

“These data show that we are getting substitution across the board,” Wolfe-Simon says. “This microbe, if we are correct, has solved the challenge of being alive in a different way.”

Arsenic sits right below phosphorus in the periodic table and so, chemically speaking, isn’t that different, Wolfe-Simon notes. And of the six essential elements of life — carbon, hydrogen, nitrogen, oxygen, phosphorus and sulfur (aka CHNOPS) — phosphorus has a relatively spotty distribution on the Earth’s surface. If a microbe in a test tube can be coerced to live on arsenic, perhaps life’s primordial home was also arsenic-rich and life that used phosphorus came later. A “shadow biosphere” of arsenic-based life may even exist unseen on Earth, or on some lonely rock in space.

“It isn’t about arsenic, and it isn’t about Mono Lake,” says Wolfe-Simon. “There’s something fundamental about understanding the flexibility of life. Any life, a microbe, a tree, you grind it up and it’s going to be CHNOPS. But we have a single sample of life. You can’t look for what you don’t know.”

Similarities between arsenic and phosphorus are also what make the element so poisonous. Life often can’t distinguish between the two, and arsenic can insinuate itself into cells. There, it competes with phosphorus, grabs onto sulfur groups, or otherwise gums up the works, causing cell death. Some microbes “breathe” by passing electrons to arsenic, but even in those cases the toxic element stays outside the cell.

Researchers are having a hard time wrapping their minds around arsenate doing the job of phosphate in cells. The ‘P’ in ATP, the energy currency for all of life, stands for phosphate. And the backbone of the DNA double helix, the molecule containing the genetic instructions for life, is made of phosphate. Basic biochemistry says that these molecules would be so unstable that they would fall apart if they were built with arsenate instead of phosphate.

“Every organism that we know of uses ATP and phosphorylated DNA,” says biogeochemist Matthew Pasek of the University of South Florida in Tampa. He says the new research is both fascinating and fantastic. So fantastic, that a lot of work is needed to conclusively show exactly how the microbe is using arsenate.

Both phosphate and arsenate can clump up into groups, and with their slightly negative electric charge, slightly positive DNA would be attracted to such clumps, says Pasek. Perhaps the arsenic detected in the DNA fraction was actually a nearby clump that the DNA wrapped itself around, he speculates.

The microbe may be substituting for phosphate with discretion, says geochemist Everett Shock of Arizona State University in Tempe, using arsenic in some places but not others. But Shock says the real value of the work isn’t in the specifics. “This introduces the possibility that there can be a substitution for one of the major elements of life,” he says. Such research “stretches the perspective. Now we’ll have to see how far this can go.”

For an audio report go here or download the mp3.