Thursday, September 3, 2009

Surface Restoration

Engineers restore high-resolution photos of the moon.

By Katherine Bourzac

The images of the moon’s surface taken by five NASA Lunar Orbiter satellites in 1966 and 1967 are still among the most detailed ever made. The original analog data, beamed down to Earth to plan landing sites for the Apollo missions, was recorded on magnetic tapes that collected dust for decades and were nearly discarded.

Photo by: Daniel Hennessy


http://www.technologyreview.com/computing/23188/?a=f



Sleep Analysis at Home

By TR Editors

If you've ever wondered how much sleep you actually got during a restless night, a new home-use device may have the answer. Users sleep wearing a headband fitted with a sensor that monitors electrical activity in the brain. Physicians use similar data gathered from EEGs to diagnose sleep disorders, but EEG studies are usually conducted in dedicated sleep clinics. In the home device, the headband sends data wirelessly to a bedside unit resembling an alarm clock, which records and displays the user's sleep patterns. The data can be uploaded to a website that allows users to track sleep statistics and gives suggestions for how to improve sleep.



Product: Zeo Personal Sleep Coach

Cost: $400

Source: MyZeo.com

Company: Zeo


http://www.technologyreview.com/biomedicine/23204/

Saturday, August 29, 2009

In Vino Veritas

Winemakers disappointed by organic methods have turned to biodynamics as the purest route to wine that's true to soil, grape, and climate.

By Corby Kummer

For years the question in winemaking was how technology could make wine better. This was especially true if the wine was Californian. When California cabernet sauvignon bested the best of Bordeaux--in a legendary blind tasting, the "Judgment of Paris," convened by the English wine merchant Steven ­Spurrier--it was a moment of great national pride at the time of America's Bicentennial, and it was achieved in part because California winemakers had used technology in ways tradition-bound French winemakers would not. As California wine became respectable, Silicon Valley millionaires bought vineyards in Napa and Sonoma counties. California wine and tech soon enjoyed a happy marriage.

Insectaries are natural habitats for beneficial insects that control pests. The Benziger Family Winery’s main insectary is planted with more than 50 kinds of plants and flowers.
Credit: Benziger Family Winery
RESOURCES:
Benziger Estate v.2006 Tribute
Sonoma Mountain
14.5% alcohol
$80.00
www.benziger.com

Two generations of winemakers came out of the University of California at Davis armed with the latest knowledge of clones, viticulture, and gas chromatography. With their chemical toolbox, they could fix any flaw--a dry year, overripe grapes left on the vine a day or two too long, sour wine. The descendants of the original Hungarian and Italian immigrants who first planted grapes in Napa and Sonoma may have been slow to sign on to the new methods, but not the high-tech grandees who were living the California dream by buying land and putting their names on bottles of wine. New money is always attracted to old vineyards (even if California's vineyards aren't really that old).

Like most activities the very rich are drawn to, winemaking is highly subject to fashions. The current fashion is a practice that was far on the fringes even 10 years ago: biodynamic farming, ever so much more authentic and true to nature than plain old organic. It's the realization of what an increasingly vocal minority of winemakers, particularly in France, began calling for in the 1980s--utterly unmanipulated wines, with no corrections, no adjustments, no filtering, and no chance to compensate for a mistake made during the growing season.

That true reflection of the air, rain, sun, and soil of a place is what's meant by terroir, the cachet-laden term being slapped on every local food these days. Biodynamic farming, says the studiedly eccentric, preternaturally persuasive California winemaker Randall Grahm, "is the royal road to terroir."

This approach sounds completely in tune with Slow Food, the movement (about which I wrote a book) that since the 1980s has called for a return to growing and production methods dictated by nature, place, and subsistence economics. These are the methods that gave rise to the world's great artisan foods and wines in the centuries before artisan was needed to indicate "nonindustrial," when organic was the default.

Biodynamic principles in fact predate organic farming, although both were reactions to the rise of nitrogen-laced fertilizers in the early 20th century. In 1924, the Austrian-­born philosopher Rudolf Steiner gave a series of lectures on farming as it related to anthroposophy, the movement he founded upon Goethe's scientific works. Anthroposophy attempts to unite science, the arts, and the spiritual and invariably views the part in the context of the whole, up to and including the cosmos. It survives in applied "daughter forms" that include the Waldorf schools--and biodynamic farming.

Steiner's followers argue that Sir Albert Howard, the British botanist who pioneered organic agriculture after observing Indian farming practices, Lord Northbourne, the agronomist who coined the term organic farming in his 1940 book Look to the Land, and the publisher J. I. Rodale, who popularized it in the United States, were simply building on and codifying his ideas. As organic farming is now defined in government standards, however, the important things are what you don't do: apply chemical pesticides and fertilizers to crops and soil. But farmers can draw on a whole range of nonchemical surrogates for the chemical correctives they give up. It takes three years to gain full organic certification, as the land detoxes, and then it's relatively straightforward.

Biodynamic, though--that's really hard. Steiner, who gave his lectures on the home farm of a count who had an estate in what is now Poland, viewed farms as living, unified organisms that should be completely self-sustaining. Maintaining that standard means paying daily attention to exactly what's happening in your vineyard and your dirt. It means not buying the pest fighters and fertilizers that still get delivered every season to organic farms. It means constantly rebuilding soil for the future. It means not planting a good portion of your land at all--and if you're in Sonoma or Napa, that's some of the most expensive farmland on earth--and raising cows, sheep, goats, chickens, and the other animals that keep a farm thriving and independent.

A biodynamic label can differentiate a wine from the passel that are already organic. But the term hasn't quite reached the point of conferring bragging rights. Also standing in the way of status is the hippie image. Biodynamic farming involves using sprayed applications meant to encourage growth and keep pests in check, composts infused with various herbs in homeopathic quantities, and a bunch of shamanistic, ridiculous-­sounding "preparations" based on a too-literal reading of what Steiner, observing life on Central European farms, mentioned in his few writings on farming.

The Benziger Family Winery, in Glen Ellen, is a postcard-perfect biodynamic farm, and the people who run it speak with the air of calm longtime converts--unlike several winemakers I talked to on a recent visit to Sonoma and Napa, who were slightly scary. When it comes to hearing about some biodynamic practices--burying manure in a cow horn in autumn and digging it up in spring; burying oak bark in a goat's skull; using stags' bladders and cows' intestines as casings for herbs; planting and picking on "root, leaf, flower, and fruit days" shown on lunar farming calendars covered with zodiac symbols--it can be hard to tell the difference between calm and zealotry.

Glen Ellen is a relic of an era when a family of normal means could buy a beautiful piece of land and grow grapes. Mike and Mary Benziger bought the property in 1980 with the help of Mike's father, Bruno, a wine and spirits importer. Bruno and his wife moved there a year later, and other siblings followed. It was "quite mediocre" wine, Mike Benziger says, that made them change their farming ways: "We'd killed what would have been native yeasts"--the naturally occurring organisms long beloved of sourdough-bread bakers and now of winemakers--"through years of using herbicides, so we had to add lab yeasts." The soil was "very like dirt balls or talc," and was strangely quiet: "You just heard the wind in the vines. It was a green desert." Now, Mike says, the soil is "almost cakelike--like brownies."

The view as Mike talks, from a hillside vineyard across to another hill, is a patchwork of zinfandel vines, lavender, rosemary, and olive trees. Demeter, the international certification program for biodynamic farming (it has branches in 43 countries), requires that 10 percent of a farm's land be uncultivated--not as much as the percentage that would have to be wild, or reserved for grazing, in a truly self-sufficient farm, but enough to scare off farmers who profit from a single crop, however much they dislike monocropping.

Although many biodynamic vineyards do not have enough cows to make all the manure they need (and are thus not the truly closed system that is the biodynamic ideal), the ­Benzigers' three cows are sufficient to their needs. They also raise sheep that clean fields by eating weeds, and grow vegetables that renew soil by providing cover crops--and provide beautiful purslane, lamb's-quarter lettuce, and fresh peas to be sold to Ubuntu, an organic vegetarian restaurant in downtown Napa that is the talk of the food world. And this being a postcard, the farmer who delivers those vegetables is a photogenic straw-hatted college grad married to a former cook at Chez Panisse (and who, by complete chance, tested recipes for my book on Slow Food).

Cow horns are filled with manure and buried through the winter to create biodynamic preparation 500, which promotes root growth.
Credit: Benziger Family Winery

The Benzigers are quick to point out that they use satellite imagery and sophisticated soil analysis and winemaking technology to verify their low-tech methods. The high-tech-low-tech seesaw they boast about--and also the high-tech money that finances low-tech methods all through Sonoma and Napa--is on equally scenic display at DaVero, a farm just outside Healdsburg, the Napa-fying but not completely Napafied main town of Sonoma County. DaVero is kept alive by the money its owner, Ridgely Evers, made developing QuickBooks software. Its chief product is olive oil, and it leaves much more than the required 10 percent of its land open--60 percent, Evers claims.

Evers gives at least one compelling reason for paying to be certified as biodynamic rather than organic: it's good marketing. Biodynamics can fulfill the promise that organics make but don't fulfill: as Evers succinctly summarizes it, food that's "sustainably and responsibly farmed near where you live." That, indeed, is the idea that started Slow Food in the 1980s and made it into an international movement in the '90s, and that made locavore the New Oxford American Dictionary's 2007 word of the year. And it's the promise that got buried in the years leading up to the USDA's National Organic Program (NOP), which finally set a single national standard for organic certification after years of state-by-state definitions. "They didn't codify best practices," Evers says, in an undiplomatic summary of what many farmers think of the USDA's approach. "Lobbying organizations came in, and now the NOP is so far from what people think organic means as to be a joke."

Many of the vineyard owners and farmers I talked to called biodynamic the new organic. And unlike early organic-farming associations, Demeter is taking no chances that the standards it's using will be watered down. It has registered a trademark in the United States on the word biodynamic itself. Now its work will be to make consumers understand the meaning of biodynamic farming and its stricter-than-organic rules.

Interest in biodynamic farming is growing, chiefly among winemakers. Disillusion with big industry's encroachment on organics and desire for a marketing edge have led Demeter's U.S. membership to triple in the past five years, according to Elizabeth Candelario, Demeter USA's marketing director.

One reason winemakers are more drawn to the biodynamic label than the organic is that they outright reject organic winemaking methods (though not organic farming methods). "The organic law in the U.S. is not sustainable for winemaking," says Larry Stone, a legendary sommelier who is now pursuing his boyhood dream of winemaking as the general manager of the very successful Napa winery Rubicon, owned by Francis Ford Coppola. The problem, he explains, is that the standards for organic wine were written at the same time that high sulfite levels in salad bars were causing health problems. So the permitted levels of sulfites in wine--10 parts per million--are much lower than the European standard of about 50 parts per million. Good news for migraine sufferers who think sulfites are triggers. Bad news for red-wine makers: "It's almost impossible to make wines, especially red wines, that can withstand the ravages of oxidation after a year," Stone says. Thus the great disparity between the number of organic vineyards and the number of organic wines. Biodynamic standards for sulfites are in line with European ones for organic wine--which gives Demeter a big market opportunity.

But is it even possible to tell that a wine is biodynamic? In particular, does biodynamic wine taste any better?

You won't find reason to suppose so in the winemaking itself. Biodynamic certifiers dictate no loony methods for making wine, though the calendar for propitious times to make it--those leaf and fruit days--strikes many winemakers as superstitious. The winemaker's skill, or lack of it, determines the taste of any wine. And so, of course, does the quality of the vineyard.

But the argument that biodynamic farming produces better-tasting grapes is easy to make and easier to test. Chefs including Jeremy Fox, at Ubuntu, say that biodynamically grown fruits and vegetables are more likely than organic ones to taste of themselves--that elusively pure and focused flavor cooks always pursue. When Jim Fetzer, part of a family that has adopted the slogan "The Earth-Friendly Wine," converted its 160 acres to biodynamic practices to sell grapes to the Fetzer winery (now owned by a conglomerate), Benziger and others called them the most beautiful grapes they'd ever seen.

The wines Benziger makes from grapes grown in its own biodynamic vineyards are highly regarded--particularly the Benziger Estate Sonoma Mountain V.2006 Tribute, a cabernet blend the winery introduced five years ago as a "tribute" to biodynamic farming. It has a surprisingly shy nose for a wine that, as is the California custom, is a high 14.5 percent alcohol. It is delicate on the palate, too, because it includes cabernet franc, merlot, and petit verdot, and far cleaner and less oaky than the California norm. Tribute is deceptively luscious; it's so clean in the nose and light on the tongue that only after a while does the deep fruit creep up on you and make you want more, much more--very unlike the usual brassy, heavy, overripe California cab. It's not cheap (about $80 in retail stores), but the French style will appeal even to timid merlot drinkers. Is Tribute so good because of the sympathetic family's beautiful property and admirable farming methods? Maybe. It's certainly because they know how to make wine.

Many grape growers in both valleys are sold. David Bos, a young farmer with midwestern roots and the evangelical air of the religion major he once was, extols the advantages of biodynamics; all five of the vineyards owned by Grgich Hills, the Napa winery he works for, are Demeter-certified. "People ask if it makes economic sense," he said when he took me to one, near Yountville in Napa. (Several farmers said their initial changeover to biodynamics cost them a few thousand dollars an acre over several years.) "But we've seen biodynamics heal our vineyards." Using biodynamic methods, he rescued a blighted vineyard other growers would have torn up. Now, grapes from that vineyard are part of his esteemed Yountville cab. "We've been making 300 to 400 cases a year," he says. "We sell it only through our tasting room, and it sells out at $135 a bottle."

Vintage '70s farmers move quickly from the realm of the practical to the spiritual. Michael Sipiora, for instance, farms at Quintessa, a spectacular property on the Silverado Trail. He knows wine; he farmed the vineyards at Stag's Leap before joining the conservation-minded couple who own Quintessa, Valeria and Agustin Huneeus. The difference between organic and biodynamic, he told me, lies in "energy." He went on to talk about Steiner's levels of consciousness: the "etheric" level of plant life, the "astral" level of the animal kingdom, the cosmic and telluric levels of energy we share with animals, the "eagle" level attained by humans.

Sipiora buries crystals and "puts intent" on them. Water--"the great messenger"--is his main theme. His pride is the "flow form," a cascading fountain with double bowls on each level that spins water in opposite "vortexes," charging it with energy; he pipes that water around the property. He makes many of Steiner's preparations himself--valerian, stinging nettle, and chamomile are basic components--and what he can't grow on the property, he buys from the Josephine Porter Institute in Virginia: stag's bladder, oak bark for burying in skulls.

This kind of cultishness drives Aaron Pott crazy. Pott is a winemaker and consultant (formerly for Quintessa) who is planting his own vineyard. He studied at both UC Davis and the University of Burgundy and worked at two chateaux in Bordeaux, so he is familiar with New World and Old. He first encountered biodynamic farming in France and learned more when Quintessa expanded its biodynamic program. He calls many biodynamic preparations "ludicrous" and "medieval."

The problem, he says, is that Steiner wrote little on grapes (just half a page in his agricultural lectures), and his knowledge of farming was based on his experiences in chilly Central Europe--entirely removed from the climate of Napa and Sonoma. Many of the preparations aim to encourage ripening of grapes, whereas in California, overripening is the concern.

Pott doesn't dismiss biodynamics altogether. "The tenets I like," he says, "are those things that say--the way Steiner actually said--'Look at everything that's around you. Use preparations that work. These are things that work for me in the middle of Germany.' You see what's naturally occurring on your farm and use those techniques." Pott crushed leaves of the agave plant, whose interior stays moist in the desert, and sprayed them on vines to prevent sunburn--and "lo and behold, it worked." Why don't others adapt Steiner's philosophy to such pragmatic effect, and discard what is clearly unsuitable to their own climate? He shrugs. "Why don't Christians follow the teachings of Christ?"

In the end, it comes down to faith. Scientific studies comparing organic and conventional farms have shown that organic farms have better soil quality, according to John Reganold, a soil scientist at Washington State University. But studies comparing the soil on biodynamic and organic farms show "mixed results," he says. He has compared soil from adjacent biodynamic and organic vineyards and seen no difference; and although a chemical analysis of grapes revealed some differences, in a blind tasting of merlot wines from those vineyards, wine tasters were stumped. Still, Reganold is an advocate: "Biodynamic farmers observe and are in contact with the crop more often than conventional growers." And, of course, he likes that biodynamic farmers care so much about the soil.

If biodynamic means only that the soil the grapes were grown in will be better for generations to come, that's all right. "There's no money in winemaking, let me tell you," says Jim Fetzer, whose family stayed in property development and grape growing after selling its winery. The money is in the land. Given the undisputed benefits biodynamic farming has for the life of soil, maybe it's a good investment after all.

Corby Kummer is a senior editor at the Atlantic and the author of The Joy of Coffee and The Pleasures of Slow Food.




http://www.technologyreview.com/biomedicine/23201/

A Beacon to Guide Cancer Surgery

A modified virus makes cancer cells fluoresce to better identify tumors.

By Courtney Humphries


Removing tumors from cancer patients always brings uncertainty. Surgeons fear that cells they don't spot and remove might re-emerge. Researchers have been looking for ways to make cancer cells visible so that none is left behind. Some of these strategies rely on injecting fluorescent probes or nanoparticles like quantum dots that will attach to the surface of cancer cells. Now a company is working on technology that makes cancer cells fluoresce from the inside out. The approach, developed by San Diego-based company AntiCancer, in partnership with scientists at Okayama University in Japan, uses a virus that infects cancer cells to integrate a fluorescence gene into tumors. The result is cancer that permanently glows, which the company hopes would allow surgeons to remove tumors with more precision and to monitor any cancer that re-emerges.

A bright idea: Mice carrying tumors from human colon cancer cells were given a virus that causes cancer cells to fluoresce. Researchers were able to visualize the dispersed tumors (in green) and remove them surgically. The small intestine is shown in red.
Credit: Hiroyuki Kishimoto and Robert M. Hoffman, AntiCancer

To make cancer cells fluoresce, the researchers used a virus called OBP-401, a modified cold virus that can enter all cells but will only replicate in those that have activated telomerase, an enzyme that is expressed in cancer cells and allows them to divide indefinitely. Normally a cell can only divide a limited number of times before dying, because at every division it loses part of its telomeres, caps of DNA at the ends of chromosomes that keep the genome stable. But cancer cells can keep dividing because telomerase replaces the telomeres every time the cell divides.

The OBP-401 virus had been developed as an anticancer therapy. Here, the researchers modified the virus to carry green fluorescent protein (GFP), a protein derived from jellyfish that fluoresces in blue light. When the virus is injected into an animal, the gene becomes active in cells that express telomerase. Robert Hoffman, president of AntiCancer and a surgeon at the University of California, San Diego, explains that GFP is permanently integrated into the genome of cancer cells, making this technology fundamentally different from approaches that rely on attaching a fluorescent particle to a protein on the surface of cancer cells. Hoffman believes that by creating a genetic marker, the approach "takes advantage of the tumor biology more effectively."

In a recent paper in the Proceedings of the National Academy of Sciences, Hoffman's team used the virus to illuminate tumors in mice that were scattered throughout the body. During surgery to remove the tumors, they could visualize them by exposing tumors to light of the proper wavelength and looking through a filter that picks up GFP fluorescence. "In principle it should pick up any cancer cell," says Hoffman. The team has not yet reached single-cell precision, but they are able to see and remove small cancerous areas that would otherwise be invisible.

Although new cancers that form after the virus is delivered would not be fluorescent, Hoffman says that any of the original cancer that began to grow again should still express GFP, allowing clinicians the opportunity to monitor the results of the surgery over time.

Hisataka Kobayashi, a scientist in the molecular imaging program at the National Cancer Institute, says the advantages of this method are that it very specifically targets cancer cells and makes it possible to monitor the cancer over time. The method also allows for flexibility; for instance, a gene that would cause the cancer cells to kill themselves could be added to the virus along with GFP, pairing imaging with treatment.

Kobayashi says that one of the key questions of the technology is safety. Giving patients a virus carrying a gene for imaging is very similar to giving them a gene to correct a disease, he says, and consequently "all the problems with gene therapy apply to this method." Many gene therapy approaches have been stalled because of immune reactions to the treatment. However, Lily Wu, a scientist at the University of California, Los Angeles, who develops cancer therapies, points out that similar gene therapy treatments for cancer have so far been found safe in clinical trials, whereas safety "is still not determined for other synthetic vectors such as quantum dots." Wu believes that this method offers several advantages over other ways of labeling tumors but says that it will require a more thorough quantitative analysis to demonstrate its effectiveness.

Hoffman says AntiCancer hopes to complete further safety testing that will allow it to bring the technology into clinical trials. Although fluorescence in mice can be visualized throughout the body, in humans the task will be more difficult, because the light scatters easily and doesn't penetrate very far into tissues. For that reason, the researchers envision this technique being used during surgery where the tumor can be seen directly.



http://www.technologyreview.com/biomedicine/23311/

Quantum Cryptography for the Masses

A new partnership will make quantum cryptography more widely available.

By Duncan Graham-Rowe


Quantum cryptography could finally hit the mainstream thanks to a deal that will allow customers to adopt the technology without having to install dedicated optical fibers.

Light box: id Quantique's Cerberis quantum key distribution system (bottom) with two link encryption units (above) is now widely available over dark fiber networks.
Credit: id Quantique

Quantum cryptography--a means of keeping secrets safe by using light particles to help scramble data--has been commercially available for several years. But the technology has only been practical for governmental or large private-sector organizations that can afford to have their own point-to-point optical fiber that the technology requires. But under the new deal, struck between Siemens IT Solutions and Services in the Netherlands and Geneva, Switzerland-based id Quantique, any organizations or individuals wanting state-of-the-art data security will be able to buy the complete package of quantum cryptography and cable.

For the commercial development of quantum cryptography it's a significant step, says Seth Lloyd, an expert in the subject and a professor at MIT. "It makes it a lot more commercially viable. The fiber is by far the most expensive part," he says.

Quantum cryptography is a method that seeks to solve the problem of how to securely send cryptographic keys between two parties by encoding them within light particles, or photons. It allows the parties to share a random--and so almost unbreakable--key without fear of third-party interception. If anyone does try to eavesdrop on the key exchange, the mere act of observing the photons changes them, making the attack detectable.

But for this quantum key distribution (QKD) to work, the same photons transmitted by one party have to be received by the other. This means that unlike most optical fiber data signals, which are periodically amplified by repeaters to boost the signal, quantum keys can only be sent through dedicated, unamplified, point-to-point fibers.

Telecom companies have spent the last few years installing precisely this kind of fiber, but for entirely different reasons, says Lloyd. Known as dark fiber, this is essentially extra capacity that has been laid in bulk to accommodate future growth.

Some companies lease this dark fiber for their own secure data connections, but for the most part it's just laying there waiting for deployment, says Andrew Shields, head of Toshiba Research Europe's Quantum Information Group in Cambridge, U.K. "For quantum key distribution, this is a godsend. There is all this dark fiber in the ground right now that's not being used."

In the new deal, Siemens SIS will offer id Quantique's QKD system over Siemens' existing dark fiber. "It's important from a commercial point of view that companies like Siemens, a global player, are showing an interest in this technology," says Grégoire Ribordy, co-founder and CEO of id Quantique. "There's potential to really accelerate commercial development."

Initially it will only be made available to Dutch customers, says Feike van der Werf, sales director of Siemens SIS, but in time may be deployed more widely. "I see this as the first step in the switch to quantum-based security," says Charlotte Rugers, a security consultant with Siemens SIS.

In essence, this deal means that for the first time QKD will be commercialized and marketed like standard IT services, says Ribordy. Dark fiber has become so prevalent that in some countries you have fiber direct to your home, he says. At the moment it is still not widely used, mainly by organizations that really care about security. But in theory this new deal means that even individuals could adopt the technology, "if you were really paranoid," he says.

This is an important step that should help bring QKD into the mainstream, says Shields. Previously customers were forced to source their own dark fiber, either through laying it themselves or getting a telecom to provide it, but this new deal allows them to buy the complete, scalable package. Although some bigger companies may have their own dark fiber, for smaller companies it would make it easier to adopt the technology, he says. "There are people out there using it but mostly it's to assess the capability, rather than using it to hide their secrets."

It will still be expensive. Besides the $82,000 price tag for a pair of id Quantique's QKD boxes, the cost of dark fiber remains high, because the customer will have to bear the cost of at least two fibers--one for the QKD and the other with which to send the encrypted data once keys have been exchanged. Normally, the cost of each fiber is offset by having dozens of customers share it, says Shields. But QKD customers will be unlikely to want to share their cables. "I think in the longer term we will need to see QKD integrated with normal telecom fibers." But for now this isn't possible, he says. Quantum signals are very weak and classical data signals are very strong, so there is a danger they will be drowned out. Once this problem has been solved, QKD should become even more attractive, he says.


http://www.technologyreview.com/computing/23317/?a=f



Friday, August 28, 2009

Changing A Cell's Biological Battery

A new method tested in monkeys for replacing mitochondrial DNA could one day prevent devastating diseases.

By Lauren Gravitz


Mitochondrial diseases, which affect as many as one in 4,000 people, can impair muscles, nerves, even entire organ systems, and have no known cure. Now, in a breakthrough study, Oregon researchers replaced defective mitochondrial DNA with that from a healthy donor. The first subjects, four baby monkeys, are pushing the envelope on the ethical debate that surrounds bioengineering.

Born of science: Spindler, a baby rhesus macaque, is one of only four monkeys born with DNA from three parents.
Credit: Nature
Multimedia
video Watch how the researchers create a fertile egg.

Mitochondria are often called the cell's power plants--the tiny organelles are responsible for energy production, and there can be hundreds to thousands of them in a single cell. They also contain their own DNA. Unlike nuclear DNA, which is a unique combination of both parents' genomes, mitochondrial DNA (or mtDNA) is passed down through the mother, is derived almost exclusively from her egg, and typically remains unchanged from one generation to the next. Mutations in a woman's mtDNA are inherited by her child, and so far there has been no way to cure these conditions or stop their transmission.

Now, Shoukhrat Mitalipov and his colleagues at Oregon Health & Science University in Beaverton, OR, have found a way to get rid of mutant mtDNA. Using a process similar to cloning, they first harvested a fertile egg. Then, when the egg was undergoing cell division, they removed a set of its chromosomes and inserted them into an egg harvested from another female, one that already had its nucleus removed. In essence, the enucleated egg provided a set of mitochondrial chromosomes, while the transferred nuclear chromosomes provided the main genetic material for development. Other researchers have attempted similar processes, but previous efforts couldn't prevent mutant mitochondria from tagging along to the new egg.

The researchers avoided this problem by carefully isolating chromosomes during a very specific and segregated process of cell division, in which nuclear DNA is tied up into an elliptical spindle. "Our whole technique comes to efficiently separating the two different types of DNA that [mammals] carry, and to separate them very cleanly," Mitalipov says. "We believe this can be used to prevent transmission of mutated mitochondrial DNA...[and] correct for mitochondrial DNA mutations in children even before they're born."

To date, there are 200 to 250 known disease-causing mutations in mitochondrial DNA, and they occur in as many as one in 4,000 people. The syndromes vary in severity, with symptoms ranging from muscle weakness and loss of motor control to diabetes, liver disease, and developmental delays. Many die before ever reaching adulthood. "The patients carrying these types of mutations don't have the same options for genetic counseling," Mitalipov says, since any mutation a woman has will be passed to her egg. "Currently, her only options are using donated eggs or adopting a child."

"It's an important study, and it's the only approach that I can think by which you could render a family free of risk of their offspring developing a mitochondrial DNA disease," says Douglas Wallace, a mitochondrial DNA researcher at the University of California, Irvine. Because mitochondrial DNA is self-replicating, the technique allows for a way to "swap" healthy versions for mutant ones without genetic alterations.

But therein also lies the rub. Many researchers and ethicists alike balk at the idea of making genetic changes to the germline, ones that fundamentally affect an egg or sperm and will be passed along to the next generation. While swapping out mitochondrial DNA may not qualify as the kind of germline engineering people have in mind when they worry about made-to-order babies--with certain traits like intelligence or eye color specifically engineered--it edges toward that shaky ethical ground.

Two babies from three parents: Mito and Tracker, baby rhesus macaque twins, are the first to have DNA from three parents--nuclear DNA from their mother and father, and mitochondrial DNA from a second female monkey, which they inherited through her donated egg.
Credit: Nature


"The technique that they used, transferring a chromosomal spindle to get new mitochondria to power the egg, seems completely ethical and defensible," says Arthur Caplan, a bioethicist at the University of Pennsylvania. "But while this technique doesn't have much use outside of fixing problems in the mitochondria, it does open the door a tiny bit on germline engineering." Because it's using a self-contained part of the cell, he notes that it's not what people typically have in mind when they talk about tinkering with germline genetics. "But by cracking open the door, it puts the principle of never doing germline engineering into dispute."

David Magnus, who heads Stanford University's Center for Biomedical Ethics, agrees that most of society's germline engineering concerns don't apply in this case. But he does point out that the procedure would lead to, essentially, three parents instead of two, "making legal and social arrangements more complicated," he says. "What happens if the mitochondrial donor decides, down the road, that she should have some parental rights to the offspring?"

This is, of course, getting way ahead of the science itself. Much more must be done before the procedure is approved. The new technique has only been applied in nine rhesus macaques, three of which became pregnant (one with twins)--a 33 percent success rate that appears to mirror that of regular in vitro fertilization in human patients. And since the seemingly healthy offspring have not yet reached reproductive age, Mitalipov and his colleagues don't yet know whether the procedure has genetic implications they've not yet uncovered. The procedure will also need to be refined, tested in more than nonhuman primates and at other research facilities before human trials can begin. (The Oregon lab is known for very high success rates that other labs can rarely duplicate.)

Researchers in Britain, at the University of Newcastle upon Tyne, have reportedly done something similar in human embryos, but have yet to publish their results and would not comment on Mitalipov's research.

The Oregon researchers believe they may be ready to apply for clinical trials in two to three years, but much depends on funding and government approval. "This points the way to a technique--it doesn't provide a therapy," says UC Irvine's Wallace, who was the first researcher to discover disease-causing mutations in mitochondrial DNA. "It shows that the concept can work as one approach to treating mitochondrial DNA disease. And that's an incredible advance, since we have very little to offer these families right now."


http://www.technologyreview.com/biomedicine/23314/

New Type of Disappearing Ink

Nanoparticle inks that fade away in hours could be ideal for secure communications.

By Prachi Patel


Top-secret maps and messages that fade away to keep unwanted eyes from seeing them could be made with a new nanoparticle ink. Researchers at Northwestern University, led by chemical and biological engineering professor Bartosz Grzybowski, have used gold and silver nanoparticles embedded in a thin, flexible organic gel film to make the new type of self-erasing medium.

Timely disappearance: Metal nanoparticles that clump together and change color under ultraviolet light are used as an ink to create images. In visible light, the clumps break apart and the image fades away in nine hours.
Credit: Rafal Klajn

Shining ultraviolet light on the film through a patterned mask or moving an ultraviolet "pen" over it records an image on the film. In visible light, the image slowly vanishes. Writing on the medium takes a few tens of milliseconds, but the researchers can speed up the process by using brighter light. They can also tweak the nanoparticles to control how quickly the images disappear, anywhere from hours to a few days. The images vanish in a few seconds when they are exposed to bright light or heat.

The film can be erased and rewritten hundreds of times without any change in quality. It can be bent and twisted.

The technology, described in an online Angewandte Chemie paper, would be ideal for making secure messages, Grzybowski says. He also envisions self-expiring bus and train tickets. "It self-erases and there's no way of tracing it back," Grzybowski says. "Also this material self-erases when exposed to intense light, so putting it on a copier is not possible."

There have been previous reports of self-erasing media. In 2006, Xerox announced a paper that erases itself in 16 to 24 hours. These materials use photochromic molecules that rearrange their internal chemical structure when exposed to light, which changes their color. Typically, these molecules can only switch between two colors and they lose their ability to switch after a few cycles. Besides, says Grzybowski, the molecules are not bright so you need a large number to see any color change. "You have to put a kilogram of this into paper before you see something," he says.

Grzybowski and his colleagues make the self-erasing ink with 5-nanometer-wide gold or silver particles. They attach on the nanoparticles' surface molecules that change shape under ultraviolet (UV) light and attract each other. "They're like a molecular glue that you can regulate using light," he says. The unwritten films are red if they contain gold particles and yellow if they contain silver. The films can also be made of other colors, ranging from red to blue, by choosing nanoparticles of a different size. Particles exposed to light form clusters of a different color--the red film changes to blue and yellow changes to violet.

In the absence of light the clusters fall apart. How quickly they fall apart, erasing the writing, depends on the amount of gluelike particles on them.

You can write in different colors depending on how much light you put in--more UV light makes the particles form tighter clusters, which have a different color than looser clusters. The researchers were also able to write two images, one over the other, on the same film. All the nanoparticles do not get used to write the first image and can be used for the second image.

"The concept of using photostimulated reversible aggregation of gold or silver particles for self-erasing images is quite interesting and new," says Masahiro Irie, a chemistry professor at Rikkyo University in Tokyo who studies photochromic molecules. However, he believes that photochromic molecules might be better for practical self-erasing systems. Images or text written with the new inks might not have a high resolution because they require clusters of nanoparticles. Plus, the unwritten film is colored because of the nanoparticles, and it would be more desirable to have a colorless or white original film, he says.

But the flexibility and control that the new material offers makes it attractive. It is easy to control the speed of writing and erasure, as well as the color, Grzybowski says. He adds that the technology has drawn interest from a United Kingdom-based security firm.



http://www.technologyreview.com/communications/23316/